Pediatrics

In a randomized controlled trial of close to 1,000 Ugandan children and youth with latent rheumatic heart disease (RHD), those who received monthly injections of penicillin G benzathine for 2 years had less disease progression than those who did not.

RHD, a valvular heart disease caused by rheumatic fever that develops after untreated Streptococcus pyogenes infection, is the most common acquired cardiovascular disease among children and young adults.

“It is clear that secondary antibiotic prophylaxis can improve outcomes for children with echo-detected rheumatic RHD,” co–lead author of the study, Andrea Z. Beaton, MD, said in an interview.

“There is huge potential here, but we are not quite ready to advocate for this strategy as a broad public health approach,” said Dr. Beaton, a pediatric cardiologist at Cincinnati Children’s Hospital Medical Center.

“We need to understand more the practical translation of this strategy to a low-resourced public health system at scale, improve [penicillin G benzathine] supply, and improve community and health care worker knowledge of this disease.”

Dr. Beaton presented the findings at the American Heart Association scientific sessions, and the study was simultaneously published in the New England Journal of Medicine on Nov. 13, 2021.

The GOAL trial – or the Gwoko Adunu pa Lutino trial, meaning “protect the heart of a child” – screened 102,200 children and adolescents aged 5-17. Of these kids and teenagers, 926 (0.9%) were diagnosed with latent RHD based on a confirmatory electrocardiogram.

“For now, I would say, if you are screening, then kids found to have latent RHD should be put on prophylaxis,” Dr. Beaton said.

“I think this is also a powerful call for more research [severely lacking in RHD],” to improve risk stratification, determine how to implement screening and prophylaxis programs, and develop new and better approaches for RHD prevention and care.

“This essential trial partially addresses the clinical equipoise that has developed regarding penicillin administration in latent RHD,” said Gabriele Rossi, MD, MPH, who was not involved with this research.

It showed that, out of the final 818 participants included in the modified intention-to-treat analysis, a total of 3 (0.8%) in the prophylaxis group had echocardiographic progression at 2 years, compared with 33 participants (8.2%) in the control group (risk difference, −7.5 percentage points; 95% confidence interval, −10.2 to −4.7; P < .001).

“This is a significant difference,” Dr. Rossi, from Médecins Sans Frontières (Doctors Without Borders), Brussels, said in an interview, noting that, however, it is not known what happens after 2 years.

The authors estimated that 13 children or adolescents with latent rheumatic heart disease would need to be treated to prevent disease progression in one person at 2 years, which is “acceptable,” he continued.

However, “screening, diagnosis, clinical follow-up, treatment, and program management [would] require substantial strengthening of health systems and the workforce, which is still far from being realizable in many African and low-income country settings,” Dr. Rossi noted.

Related study in Italy

Previously, Dr. Rossi and colleagues conducted a trial, published in 2019, that showed it was feasible to screen for asymptomatic RHD among refugee/migrant children and youths in Rome.

From February 2016 to January 2018, they screened more than 650 refugee/migrant children and adolescents who were younger than 18. They came largely from Egypt (65%) but also from 22 other countries and were often unaccompanied or with just one parent.

The number needed to screen was 5 to identify a child/youth with borderline RHD and around 40 to identify a child/youth with definite RHD.

Dr. Rossi noted that local resurgences of RHD have also been also documented in high-income countries such as Europe, Australia, New Zealand, Canada, and the United States, often among disadvantaged indigenous people, as described in a 2018 Letter to the Editor in the New England Journal of Medicine.

Dr. Beaton noted that a review of 10-year data (2008-2018) from 22 U.S. pediatric institutions showed that in the United States the prevalence of RHD “is higher in immigrant children from RHD endemic areas, but because of total numbers, more RHD cases than not are domestic.” Children living in more deprived communities are at risk for more severe disease, and the burden in U.S. territories is also quite high.
 

Screening and secondary prophylaxis

The aim of the current GOAL study was to evaluate if screening and treatment with penicillin G benzathine could detect and prevent progression of latent rheumatic heart disease in 5- to 17-year-olds living in Gulu, Uganda. The trial was conducted from July 2018 to October 2020.

“School education and community sensitization was done prior to the trial,” through radio shows or school-based education, Dr. Beaton explained. About 99% of the children/adolescents/families agreed to be screened.

The group has been conducting echo screening research in Uganda for 10 years, she noted. They have developed peer group and case manager strategies to aid participant retention, as they describe in an article about the study protocol.

The screening echocardiograms were interpreted by about 30 providers and four cardiologists reviewed confirmatory echocardiograms.

Two participants in the prophylaxis group had serious adverse events that were attributable to receipt of prophylaxis, including one episode of a mild anaphylactic reaction (representing <0.1% of all administered doses of prophylaxis).

Once children and adolescents have moderate/severe RHD, there is not much that can be done in lower- and middle-income countries, where surgery for this is uncommon, Dr. Beaton explained. Around 30% of children and adolescents with this condition who come to clinical attention in Uganda die within 9 months.
 

Further research

Dr. Beaton and colleagues have just started a trial to investigate the burden of RHD among Native American youth, which has not been studied since the 1970s.

They also have an ongoing study looking at the efficacy of a pragmatic, community-based sore throat program to prevent RHD.

“Unfortunately, this strategy has not worked well in low-to-middle income countries, for a variety of reasons so far,” Dr. Beaton noted, and the cost-effectiveness of this preventive strategy is questionable.

The trial was supported by the Thrasher Research Fund, Gift of Life International, Children’s National Hospital Foundation (Zachary Blumenfeld Fund and Race for Every Child [Team Jocelyn]), the Elias-Ginsburg Family, Wiley Rein, Philips Foundation, AT&T Foundation, Heart Healers International, the Karp Family Foundation, Huron Philanthropies, and the Cincinnati Children’s Hospital Heart Institute Research Core. Dr. Beaton and Dr. Rossi disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

In a randomized controlled trial of close to 1,000 Ugandan children and youth with latent rheumatic heart disease (RHD), those who received monthly injections of penicillin G benzathine for 2 years had less disease progression than those who did not.

RHD, a valvular heart disease caused by rheumatic fever that develops after untreated Streptococcus pyogenes infection, is the most common acquired cardiovascular disease among children and young adults.

“It is clear that secondary antibiotic prophylaxis can improve outcomes for children with echo-detected rheumatic RHD,” co–lead author of the study, Andrea Z. Beaton, MD, said in an interview.

“There is huge potential here, but we are not quite ready to advocate for this strategy as a broad public health approach,” said Dr. Beaton, a pediatric cardiologist at Cincinnati Children’s Hospital Medical Center.

“We need to understand more the practical translation of this strategy to a low-resourced public health system at scale, improve [penicillin G benzathine] supply, and improve community and health care worker knowledge of this disease.”

Dr. Beaton presented the findings at the American Heart Association scientific sessions, and the study was simultaneously published in the New England Journal of Medicine on Nov. 13, 2021.

The GOAL trial – or the Gwoko Adunu pa Lutino trial, meaning “protect the heart of a child” – screened 102,200 children and adolescents aged 5-17. Of these kids and teenagers, 926 (0.9%) were diagnosed with latent RHD based on a confirmatory electrocardiogram.

“For now, I would say, if you are screening, then kids found to have latent RHD should be put on prophylaxis,” Dr. Beaton said.

“I think this is also a powerful call for more research [severely lacking in RHD],” to improve risk stratification, determine how to implement screening and prophylaxis programs, and develop new and better approaches for RHD prevention and care.

“This essential trial partially addresses the clinical equipoise that has developed regarding penicillin administration in latent RHD,” said Gabriele Rossi, MD, MPH, who was not involved with this research.

It showed that, out of the final 818 participants included in the modified intention-to-treat analysis, a total of 3 (0.8%) in the prophylaxis group had echocardiographic progression at 2 years, compared with 33 participants (8.2%) in the control group (risk difference, −7.5 percentage points; 95% confidence interval, −10.2 to −4.7; P < .001).

“This is a significant difference,” Dr. Rossi, from Médecins Sans Frontières (Doctors Without Borders), Brussels, said in an interview, noting that, however, it is not known what happens after 2 years.

The authors estimated that 13 children or adolescents with latent rheumatic heart disease would need to be treated to prevent disease progression in one person at 2 years, which is “acceptable,” he continued.

However, “screening, diagnosis, clinical follow-up, treatment, and program management [would] require substantial strengthening of health systems and the workforce, which is still far from being realizable in many African and low-income country settings,” Dr. Rossi noted.

Related study in Italy

Previously, Dr. Rossi and colleagues conducted a trial, published in 2019, that showed it was feasible to screen for asymptomatic RHD among refugee/migrant children and youths in Rome.

From February 2016 to January 2018, they screened more than 650 refugee/migrant children and adolescents who were younger than 18. They came largely from Egypt (65%) but also from 22 other countries and were often unaccompanied or with just one parent.

The number needed to screen was 5 to identify a child/youth with borderline RHD and around 40 to identify a child/youth with definite RHD.

Dr. Rossi noted that local resurgences of RHD have also been also documented in high-income countries such as Europe, Australia, New Zealand, Canada, and the United States, often among disadvantaged indigenous people, as described in a 2018 Letter to the Editor in the New England Journal of Medicine.

Dr. Beaton noted that a review of 10-year data (2008-2018) from 22 U.S. pediatric institutions showed that in the United States the prevalence of RHD “is higher in immigrant children from RHD endemic areas, but because of total numbers, more RHD cases than not are domestic.” Children living in more deprived communities are at risk for more severe disease, and the burden in U.S. territories is also quite high.
 

Screening and secondary prophylaxis

The aim of the current GOAL study was to evaluate if screening and treatment with penicillin G benzathine could detect and prevent progression of latent rheumatic heart disease in 5- to 17-year-olds living in Gulu, Uganda. The trial was conducted from July 2018 to October 2020.

“School education and community sensitization was done prior to the trial,” through radio shows or school-based education, Dr. Beaton explained. About 99% of the children/adolescents/families agreed to be screened.

The group has been conducting echo screening research in Uganda for 10 years, she noted. They have developed peer group and case manager strategies to aid participant retention, as they describe in an article about the study protocol.

The screening echocardiograms were interpreted by about 30 providers and four cardiologists reviewed confirmatory echocardiograms.

Two participants in the prophylaxis group had serious adverse events that were attributable to receipt of prophylaxis, including one episode of a mild anaphylactic reaction (representing <0.1% of all administered doses of prophylaxis).

Once children and adolescents have moderate/severe RHD, there is not much that can be done in lower- and middle-income countries, where surgery for this is uncommon, Dr. Beaton explained. Around 30% of children and adolescents with this condition who come to clinical attention in Uganda die within 9 months.
 

Further research

Dr. Beaton and colleagues have just started a trial to investigate the burden of RHD among Native American youth, which has not been studied since the 1970s.

They also have an ongoing study looking at the efficacy of a pragmatic, community-based sore throat program to prevent RHD.

“Unfortunately, this strategy has not worked well in low-to-middle income countries, for a variety of reasons so far,” Dr. Beaton noted, and the cost-effectiveness of this preventive strategy is questionable.

The trial was supported by the Thrasher Research Fund, Gift of Life International, Children’s National Hospital Foundation (Zachary Blumenfeld Fund and Race for Every Child [Team Jocelyn]), the Elias-Ginsburg Family, Wiley Rein, Philips Foundation, AT&T Foundation, Heart Healers International, the Karp Family Foundation, Huron Philanthropies, and the Cincinnati Children’s Hospital Heart Institute Research Core. Dr. Beaton and Dr. Rossi disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

In a randomized controlled trial of close to 1,000 Ugandan children and youth with latent rheumatic heart disease (RHD), those who received monthly injections of penicillin G benzathine for 2 years had less disease progression than those who did not.

RHD, a valvular heart disease caused by rheumatic fever that develops after untreated Streptococcus pyogenes infection, is the most common acquired cardiovascular disease among children and young adults.

“It is clear that secondary antibiotic prophylaxis can improve outcomes for children with echo-detected rheumatic RHD,” co–lead author of the study, Andrea Z. Beaton, MD, said in an interview.

“There is huge potential here, but we are not quite ready to advocate for this strategy as a broad public health approach,” said Dr. Beaton, a pediatric cardiologist at Cincinnati Children’s Hospital Medical Center.

“We need to understand more the practical translation of this strategy to a low-resourced public health system at scale, improve [penicillin G benzathine] supply, and improve community and health care worker knowledge of this disease.”

Dr. Beaton presented the findings at the American Heart Association scientific sessions, and the study was simultaneously published in the New England Journal of Medicine on Nov. 13, 2021.

The GOAL trial – or the Gwoko Adunu pa Lutino trial, meaning “protect the heart of a child” – screened 102,200 children and adolescents aged 5-17. Of these kids and teenagers, 926 (0.9%) were diagnosed with latent RHD based on a confirmatory electrocardiogram.

“For now, I would say, if you are screening, then kids found to have latent RHD should be put on prophylaxis,” Dr. Beaton said.

“I think this is also a powerful call for more research [severely lacking in RHD],” to improve risk stratification, determine how to implement screening and prophylaxis programs, and develop new and better approaches for RHD prevention and care.

“This essential trial partially addresses the clinical equipoise that has developed regarding penicillin administration in latent RHD,” said Gabriele Rossi, MD, MPH, who was not involved with this research.

It showed that, out of the final 818 participants included in the modified intention-to-treat analysis, a total of 3 (0.8%) in the prophylaxis group had echocardiographic progression at 2 years, compared with 33 participants (8.2%) in the control group (risk difference, −7.5 percentage points; 95% confidence interval, −10.2 to −4.7; P < .001).

“This is a significant difference,” Dr. Rossi, from Médecins Sans Frontières (Doctors Without Borders), Brussels, said in an interview, noting that, however, it is not known what happens after 2 years.

The authors estimated that 13 children or adolescents with latent rheumatic heart disease would need to be treated to prevent disease progression in one person at 2 years, which is “acceptable,” he continued.

However, “screening, diagnosis, clinical follow-up, treatment, and program management [would] require substantial strengthening of health systems and the workforce, which is still far from being realizable in many African and low-income country settings,” Dr. Rossi noted.

Related study in Italy

Previously, Dr. Rossi and colleagues conducted a trial, published in 2019, that showed it was feasible to screen for asymptomatic RHD among refugee/migrant children and youths in Rome.

From February 2016 to January 2018, they screened more than 650 refugee/migrant children and adolescents who were younger than 18. They came largely from Egypt (65%) but also from 22 other countries and were often unaccompanied or with just one parent.

The number needed to screen was 5 to identify a child/youth with borderline RHD and around 40 to identify a child/youth with definite RHD.

Dr. Rossi noted that local resurgences of RHD have also been also documented in high-income countries such as Europe, Australia, New Zealand, Canada, and the United States, often among disadvantaged indigenous people, as described in a 2018 Letter to the Editor in the New England Journal of Medicine.

Dr. Beaton noted that a review of 10-year data (2008-2018) from 22 U.S. pediatric institutions showed that in the United States the prevalence of RHD “is higher in immigrant children from RHD endemic areas, but because of total numbers, more RHD cases than not are domestic.” Children living in more deprived communities are at risk for more severe disease, and the burden in U.S. territories is also quite high.
 

Screening and secondary prophylaxis

The aim of the current GOAL study was to evaluate if screening and treatment with penicillin G benzathine could detect and prevent progression of latent rheumatic heart disease in 5- to 17-year-olds living in Gulu, Uganda. The trial was conducted from July 2018 to October 2020.

“School education and community sensitization was done prior to the trial,” through radio shows or school-based education, Dr. Beaton explained. About 99% of the children/adolescents/families agreed to be screened.

The group has been conducting echo screening research in Uganda for 10 years, she noted. They have developed peer group and case manager strategies to aid participant retention, as they describe in an article about the study protocol.

The screening echocardiograms were interpreted by about 30 providers and four cardiologists reviewed confirmatory echocardiograms.

Two participants in the prophylaxis group had serious adverse events that were attributable to receipt of prophylaxis, including one episode of a mild anaphylactic reaction (representing <0.1% of all administered doses of prophylaxis).

Once children and adolescents have moderate/severe RHD, there is not much that can be done in lower- and middle-income countries, where surgery for this is uncommon, Dr. Beaton explained. Around 30% of children and adolescents with this condition who come to clinical attention in Uganda die within 9 months.
 

Further research

Dr. Beaton and colleagues have just started a trial to investigate the burden of RHD among Native American youth, which has not been studied since the 1970s.

They also have an ongoing study looking at the efficacy of a pragmatic, community-based sore throat program to prevent RHD.

“Unfortunately, this strategy has not worked well in low-to-middle income countries, for a variety of reasons so far,” Dr. Beaton noted, and the cost-effectiveness of this preventive strategy is questionable.

The trial was supported by the Thrasher Research Fund, Gift of Life International, Children’s National Hospital Foundation (Zachary Blumenfeld Fund and Race for Every Child [Team Jocelyn]), the Elias-Ginsburg Family, Wiley Rein, Philips Foundation, AT&T Foundation, Heart Healers International, the Karp Family Foundation, Huron Philanthropies, and the Cincinnati Children’s Hospital Heart Institute Research Core. Dr. Beaton and Dr. Rossi disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Because hepatitis C virus (HCV) infection is typically asymptomatic, its presence can easily be overlooked without appropriate screening efforts. For those screening efforts to be effective, they must keep pace with the changing demographic face of this increasingly prevalent but treatable disease.

Perhaps the most dramatic shift in HCV demographics in recent years has been the increase of infections among those born after 1965, a trend primarily driven by the opioid epidemic. In addition, data from the National Notifiable Diseases Surveillance System show that cases of diagnosed HCV doubled among women of childbearing age from 2006 to 2014, with new infections in younger women surpassing those in older age groups.

With such trends in mind, the Centers for Disease Control and Prevention broadened their recommendations regarding HCV in 2020 to include one-time testing in all adults aged 18 years and older and screening of all pregnant women during each pregnancy, except where the prevalence of infection is less than 0.1%, a threshold that no state has yet achieved.

The US Preventive Services Task Force (USPSTF) subsequently followed suit in their own recommendations.

The American Association for the Study of Liver Diseases/Infectious Diseases Society of America have long advocated for extensive expansion in their screening recommendations for HCV, including pregnancy.

Although the American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine did not immediately adopt these recommendations, they have since endorsed them in May 2021 and June 2021, respectively.
 

The hepatologist perspective

As a practicing hepatologist, this seems like an uncontroversial recommendation. Obstetricians already screen for hepatitis B virus in each pregnancy. It should be easy to add HCV testing to the same lab testing.

Risk-based screening has repeatedly been demonstrated to be ineffective. It should be easier to test all women than to ask prying questions about high-risk behaviors.

Given the increase of injection drug use and resultant HCV infections in women of childbearing age, this seems like a perfect opportunity to identify chronically infected women and counsel them on transmission and cure. And pregnancy is also unique in that it is a time of near-universal health coverage.

Let’s address some of the operational issues.

The diagnostic cascade for HCV can be made very easy. HCV antibody testing is our standard screening test and, when positive, can automatically reflex to HCV polymerase chain reaction (PCR), the diagnostic test. Thus, with one blood sample, you can both screen for and diagnose infection.

Current guidelines do not recommend treating HCV during pregnancy, although therapy can be considered on an individual basis. Linkage to a knowledgeable provider who can discuss transmission and treatment, as well as assess the stage of liver injury, should decrease the burden on the ob.gyn.

The impact on pregnancy is marginal. HCV should not change either the mode of delivery or the decision to breastfeed. The AASLD/IDSA guidance outlines only four recommendations for monitoring during pregnancy:

• Obtain HCV RNA to see whether the infection is active and assess liver function at initiation of prenatal care.
• Prenatal care should be tailored to the pregnancy. There is no modification recommended to decrease mother-to-child transmission (MTCT).
• Be aware that intrahepatic is more common with HCV.
• Women with have a higher rate of adverse outcomes and should be linked to a high-risk obstetrics specialist.

But of course, what seems easy to one specialist may not be true of another. With that in mind, let’s hear the ob.gyn. perspective on these updated screening recommendations.
 

The ob.gyn. perspective

Recent guidelines from the CDC, ACOG, and SMFM recommend universal screening for HCV in all pregnant women. The increased availability of highly effective antiviral regimens makes universal screening a logical strategy, especially to identify candidates for this curative treatment. What is questionable, however, is the recommended timing by which this screening should take place.

HCV screening during pregnancy, as currently recommended, provides no immediate benefit for the pregnant woman or the fetus/neonate, given that antiviral treatments have not been approved during gestation, and there are no known measures that decrease MTCT or change routine perinatal care.

We also must not forget that a significant proportion of women in the United States, particularly those with limited resources, do not receive prenatal care at all. Most of them, however, will present to a hospital for delivery. Consequently, compliance with screening might be higher if performed at the time of delivery rather than antepartum.

Deferring screening until the intrapartum or immediate postpartum period, at least until antiviral treatment during pregnancy becomes a reality, was discussed. The rationale was that this approach might obviate the need to deal with the unintended consequences and burden of testing for HCV during pregnancy. Ultimately, ACOG and SMFM fell in line with the CDC recommendations.

Despite the lack of robust evidence regarding the risk for MTCT associated with commonly performed obstetric procedures (for example, genetic amniocentesis, artificial rupture of the membranes during labor, placement of an intrauterine pressure catheter), clinicians may be reluctant to perform them in HCV-infected women, resulting in potential deviations from the obstetric standard of care.

Similarly, it is likely that patients may choose to have a cesarean delivery for the sole purpose of decreasing MTCT, despite the lack of evidence for this. Such ill-advised patient-driven decisions are increasingly likely in the current environment, where social media can rapidly disseminate misinformation.
 

Implications for pediatric patients

One cannot isolate HCV screening in pregnancy from the consequences that may potentially occur as part of the infant’s transition to the care of a pediatrician.

Even though MTCT is estimated to occur in just 5%-15% of cases, all children born to HCV viremic mothers should be screened for HCV.

Traditionally, screening for HCV antibodies occurred after 18 months of age. In those who test positive, HCV PCR testing is recommended at 3 years. However, this algorithm is being called into question because only approximately one-third of infants are successfully screened.

HCV RNA testing in the first year after birth has been suggested. However, even proponents of this approach concur that all management decisions should be deferred until after the age of 3 years, when medications are approved for pediatric use.

In addition, HCV testing would be required again before considering therapy because children have higher rates of spontaneous clearance.
 

Seeking consensus beyond the controversy

Controversy remains surrounding the most recent update to the HCV screening guidelines. The current recommendation to screen during pregnancy cannot modify the risk for MTCT, has no impact on decisions regarding mode of delivery or breastfeeding, and could potentially cause harm by making obstetricians defer necessary invasive procedures even though there are no data linking them to an increase in MTCT.

Yet after extensive debate, the CDC, USPSTF, AASLD/IDSA, ACOG, and SMFM all developed their current recommendations to initiate HCV screening during pregnancy. To make this successful, screening algorithms need to be simple and consistent across all society recommendations.

HCV antibody testing should always reflex to the diagnostic test (HCV PCR) to allow confirmation in those who test positive without requiring an additional blood test. Viremic mothers (those who are HCV positive on PCR) should be linked to a provider who can discuss prognosis, transmission, and treatment. The importance of screening the infant also must be communicated to the parents and pediatrician alike.

Dr. Reau has served as a director, officer, partner, employee, adviser, consultant, or trustee for AbbVie, Gilead, Arbutus, Intercept, and Salix; received research grants from AbbVie and Gilead; and received income from AASLD. Dr. Pacheco disclosed no relevant financial relationships.
 

A version of this article first appeared on Medscape.com.

Because hepatitis C virus (HCV) infection is typically asymptomatic, its presence can easily be overlooked without appropriate screening efforts. For those screening efforts to be effective, they must keep pace with the changing demographic face of this increasingly prevalent but treatable disease.

Perhaps the most dramatic shift in HCV demographics in recent years has been the increase of infections among those born after 1965, a trend primarily driven by the opioid epidemic. In addition, data from the National Notifiable Diseases Surveillance System show that cases of diagnosed HCV doubled among women of childbearing age from 2006 to 2014, with new infections in younger women surpassing those in older age groups.

With such trends in mind, the Centers for Disease Control and Prevention broadened their recommendations regarding HCV in 2020 to include one-time testing in all adults aged 18 years and older and screening of all pregnant women during each pregnancy, except where the prevalence of infection is less than 0.1%, a threshold that no state has yet achieved.

The US Preventive Services Task Force (USPSTF) subsequently followed suit in their own recommendations.

The American Association for the Study of Liver Diseases/Infectious Diseases Society of America have long advocated for extensive expansion in their screening recommendations for HCV, including pregnancy.

Although the American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine did not immediately adopt these recommendations, they have since endorsed them in May 2021 and June 2021, respectively.
 

The hepatologist perspective

As a practicing hepatologist, this seems like an uncontroversial recommendation. Obstetricians already screen for hepatitis B virus in each pregnancy. It should be easy to add HCV testing to the same lab testing.

Risk-based screening has repeatedly been demonstrated to be ineffective. It should be easier to test all women than to ask prying questions about high-risk behaviors.

Given the increase of injection drug use and resultant HCV infections in women of childbearing age, this seems like a perfect opportunity to identify chronically infected women and counsel them on transmission and cure. And pregnancy is also unique in that it is a time of near-universal health coverage.

Let’s address some of the operational issues.

The diagnostic cascade for HCV can be made very easy. HCV antibody testing is our standard screening test and, when positive, can automatically reflex to HCV polymerase chain reaction (PCR), the diagnostic test. Thus, with one blood sample, you can both screen for and diagnose infection.

Current guidelines do not recommend treating HCV during pregnancy, although therapy can be considered on an individual basis. Linkage to a knowledgeable provider who can discuss transmission and treatment, as well as assess the stage of liver injury, should decrease the burden on the ob.gyn.

The impact on pregnancy is marginal. HCV should not change either the mode of delivery or the decision to breastfeed. The AASLD/IDSA guidance outlines only four recommendations for monitoring during pregnancy:

• Obtain HCV RNA to see whether the infection is active and assess liver function at initiation of prenatal care.
• Prenatal care should be tailored to the pregnancy. There is no modification recommended to decrease mother-to-child transmission (MTCT).
• Be aware that intrahepatic is more common with HCV.
• Women with have a higher rate of adverse outcomes and should be linked to a high-risk obstetrics specialist.

But of course, what seems easy to one specialist may not be true of another. With that in mind, let’s hear the ob.gyn. perspective on these updated screening recommendations.
 

The ob.gyn. perspective

Recent guidelines from the CDC, ACOG, and SMFM recommend universal screening for HCV in all pregnant women. The increased availability of highly effective antiviral regimens makes universal screening a logical strategy, especially to identify candidates for this curative treatment. What is questionable, however, is the recommended timing by which this screening should take place.

HCV screening during pregnancy, as currently recommended, provides no immediate benefit for the pregnant woman or the fetus/neonate, given that antiviral treatments have not been approved during gestation, and there are no known measures that decrease MTCT or change routine perinatal care.

We also must not forget that a significant proportion of women in the United States, particularly those with limited resources, do not receive prenatal care at all. Most of them, however, will present to a hospital for delivery. Consequently, compliance with screening might be higher if performed at the time of delivery rather than antepartum.

Deferring screening until the intrapartum or immediate postpartum period, at least until antiviral treatment during pregnancy becomes a reality, was discussed. The rationale was that this approach might obviate the need to deal with the unintended consequences and burden of testing for HCV during pregnancy. Ultimately, ACOG and SMFM fell in line with the CDC recommendations.

Despite the lack of robust evidence regarding the risk for MTCT associated with commonly performed obstetric procedures (for example, genetic amniocentesis, artificial rupture of the membranes during labor, placement of an intrauterine pressure catheter), clinicians may be reluctant to perform them in HCV-infected women, resulting in potential deviations from the obstetric standard of care.

Similarly, it is likely that patients may choose to have a cesarean delivery for the sole purpose of decreasing MTCT, despite the lack of evidence for this. Such ill-advised patient-driven decisions are increasingly likely in the current environment, where social media can rapidly disseminate misinformation.
 

Implications for pediatric patients

One cannot isolate HCV screening in pregnancy from the consequences that may potentially occur as part of the infant’s transition to the care of a pediatrician.

Even though MTCT is estimated to occur in just 5%-15% of cases, all children born to HCV viremic mothers should be screened for HCV.

Traditionally, screening for HCV antibodies occurred after 18 months of age. In those who test positive, HCV PCR testing is recommended at 3 years. However, this algorithm is being called into question because only approximately one-third of infants are successfully screened.

HCV RNA testing in the first year after birth has been suggested. However, even proponents of this approach concur that all management decisions should be deferred until after the age of 3 years, when medications are approved for pediatric use.

In addition, HCV testing would be required again before considering therapy because children have higher rates of spontaneous clearance.
 

Seeking consensus beyond the controversy

Controversy remains surrounding the most recent update to the HCV screening guidelines. The current recommendation to screen during pregnancy cannot modify the risk for MTCT, has no impact on decisions regarding mode of delivery or breastfeeding, and could potentially cause harm by making obstetricians defer necessary invasive procedures even though there are no data linking them to an increase in MTCT.

Yet after extensive debate, the CDC, USPSTF, AASLD/IDSA, ACOG, and SMFM all developed their current recommendations to initiate HCV screening during pregnancy. To make this successful, screening algorithms need to be simple and consistent across all society recommendations.

HCV antibody testing should always reflex to the diagnostic test (HCV PCR) to allow confirmation in those who test positive without requiring an additional blood test. Viremic mothers (those who are HCV positive on PCR) should be linked to a provider who can discuss prognosis, transmission, and treatment. The importance of screening the infant also must be communicated to the parents and pediatrician alike.

Dr. Reau has served as a director, officer, partner, employee, adviser, consultant, or trustee for AbbVie, Gilead, Arbutus, Intercept, and Salix; received research grants from AbbVie and Gilead; and received income from AASLD. Dr. Pacheco disclosed no relevant financial relationships.
 

A version of this article first appeared on Medscape.com.

Because hepatitis C virus (HCV) infection is typically asymptomatic, its presence can easily be overlooked without appropriate screening efforts. For those screening efforts to be effective, they must keep pace with the changing demographic face of this increasingly prevalent but treatable disease.

Perhaps the most dramatic shift in HCV demographics in recent years has been the increase of infections among those born after 1965, a trend primarily driven by the opioid epidemic. In addition, data from the National Notifiable Diseases Surveillance System show that cases of diagnosed HCV doubled among women of childbearing age from 2006 to 2014, with new infections in younger women surpassing those in older age groups.

With such trends in mind, the Centers for Disease Control and Prevention broadened their recommendations regarding HCV in 2020 to include one-time testing in all adults aged 18 years and older and screening of all pregnant women during each pregnancy, except where the prevalence of infection is less than 0.1%, a threshold that no state has yet achieved.

The US Preventive Services Task Force (USPSTF) subsequently followed suit in their own recommendations.

The American Association for the Study of Liver Diseases/Infectious Diseases Society of America have long advocated for extensive expansion in their screening recommendations for HCV, including pregnancy.

Although the American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine did not immediately adopt these recommendations, they have since endorsed them in May 2021 and June 2021, respectively.
 

The hepatologist perspective

As a practicing hepatologist, this seems like an uncontroversial recommendation. Obstetricians already screen for hepatitis B virus in each pregnancy. It should be easy to add HCV testing to the same lab testing.

Risk-based screening has repeatedly been demonstrated to be ineffective. It should be easier to test all women than to ask prying questions about high-risk behaviors.

Given the increase of injection drug use and resultant HCV infections in women of childbearing age, this seems like a perfect opportunity to identify chronically infected women and counsel them on transmission and cure. And pregnancy is also unique in that it is a time of near-universal health coverage.

Let’s address some of the operational issues.

The diagnostic cascade for HCV can be made very easy. HCV antibody testing is our standard screening test and, when positive, can automatically reflex to HCV polymerase chain reaction (PCR), the diagnostic test. Thus, with one blood sample, you can both screen for and diagnose infection.

Current guidelines do not recommend treating HCV during pregnancy, although therapy can be considered on an individual basis. Linkage to a knowledgeable provider who can discuss transmission and treatment, as well as assess the stage of liver injury, should decrease the burden on the ob.gyn.

The impact on pregnancy is marginal. HCV should not change either the mode of delivery or the decision to breastfeed. The AASLD/IDSA guidance outlines only four recommendations for monitoring during pregnancy:

• Obtain HCV RNA to see whether the infection is active and assess liver function at initiation of prenatal care.
• Prenatal care should be tailored to the pregnancy. There is no modification recommended to decrease mother-to-child transmission (MTCT).
• Be aware that intrahepatic is more common with HCV.
• Women with have a higher rate of adverse outcomes and should be linked to a high-risk obstetrics specialist.

But of course, what seems easy to one specialist may not be true of another. With that in mind, let’s hear the ob.gyn. perspective on these updated screening recommendations.
 

The ob.gyn. perspective

Recent guidelines from the CDC, ACOG, and SMFM recommend universal screening for HCV in all pregnant women. The increased availability of highly effective antiviral regimens makes universal screening a logical strategy, especially to identify candidates for this curative treatment. What is questionable, however, is the recommended timing by which this screening should take place.

HCV screening during pregnancy, as currently recommended, provides no immediate benefit for the pregnant woman or the fetus/neonate, given that antiviral treatments have not been approved during gestation, and there are no known measures that decrease MTCT or change routine perinatal care.

We also must not forget that a significant proportion of women in the United States, particularly those with limited resources, do not receive prenatal care at all. Most of them, however, will present to a hospital for delivery. Consequently, compliance with screening might be higher if performed at the time of delivery rather than antepartum.

Deferring screening until the intrapartum or immediate postpartum period, at least until antiviral treatment during pregnancy becomes a reality, was discussed. The rationale was that this approach might obviate the need to deal with the unintended consequences and burden of testing for HCV during pregnancy. Ultimately, ACOG and SMFM fell in line with the CDC recommendations.

Despite the lack of robust evidence regarding the risk for MTCT associated with commonly performed obstetric procedures (for example, genetic amniocentesis, artificial rupture of the membranes during labor, placement of an intrauterine pressure catheter), clinicians may be reluctant to perform them in HCV-infected women, resulting in potential deviations from the obstetric standard of care.

Similarly, it is likely that patients may choose to have a cesarean delivery for the sole purpose of decreasing MTCT, despite the lack of evidence for this. Such ill-advised patient-driven decisions are increasingly likely in the current environment, where social media can rapidly disseminate misinformation.
 

Implications for pediatric patients

One cannot isolate HCV screening in pregnancy from the consequences that may potentially occur as part of the infant’s transition to the care of a pediatrician.

Even though MTCT is estimated to occur in just 5%-15% of cases, all children born to HCV viremic mothers should be screened for HCV.

Traditionally, screening for HCV antibodies occurred after 18 months of age. In those who test positive, HCV PCR testing is recommended at 3 years. However, this algorithm is being called into question because only approximately one-third of infants are successfully screened.

HCV RNA testing in the first year after birth has been suggested. However, even proponents of this approach concur that all management decisions should be deferred until after the age of 3 years, when medications are approved for pediatric use.

In addition, HCV testing would be required again before considering therapy because children have higher rates of spontaneous clearance.
 

Seeking consensus beyond the controversy

Controversy remains surrounding the most recent update to the HCV screening guidelines. The current recommendation to screen during pregnancy cannot modify the risk for MTCT, has no impact on decisions regarding mode of delivery or breastfeeding, and could potentially cause harm by making obstetricians defer necessary invasive procedures even though there are no data linking them to an increase in MTCT.

Yet after extensive debate, the CDC, USPSTF, AASLD/IDSA, ACOG, and SMFM all developed their current recommendations to initiate HCV screening during pregnancy. To make this successful, screening algorithms need to be simple and consistent across all society recommendations.

HCV antibody testing should always reflex to the diagnostic test (HCV PCR) to allow confirmation in those who test positive without requiring an additional blood test. Viremic mothers (those who are HCV positive on PCR) should be linked to a provider who can discuss prognosis, transmission, and treatment. The importance of screening the infant also must be communicated to the parents and pediatrician alike.

Dr. Reau has served as a director, officer, partner, employee, adviser, consultant, or trustee for AbbVie, Gilead, Arbutus, Intercept, and Salix; received research grants from AbbVie and Gilead; and received income from AASLD. Dr. Pacheco disclosed no relevant financial relationships.
 

A version of this article first appeared on Medscape.com.

WESTMINSTER, COLO. – Melissa Blatzer was determined to get her three children caught up on their routine immunizations on a recent Saturday morning at a walk-in clinic in this Denver suburb. It had been about a year since the kids’ last shots, a delay Ms. Blatzer chalked up to the pandemic.

Two-year-old Lincoln Blatzer, in his fleece dinosaur pajamas, waited anxiously in line for his hepatitis A vaccine. His siblings, 14-year-old Nyla Kusumah and 11-year-old Nevan Kusumah, were there for their TDAP, HPV and meningococcal vaccines, plus a COVID-19 shot for Nyla.

“You don’t have to make an appointment and you can take all three at once,” said Ms. Blatzer, who lives several miles away in Commerce City. That convenience outweighed the difficulty of getting everyone up early on a weekend.

Child health experts hope community clinics like this – along with the return to in-person classes, more well-child visits, and the rollout of COVID shots for younger children – can help boost routine childhood immunizations, which dropped during the pandemic. Despite a rebound, immunization rates are still lower than in 2019, and disparities in rates between racial and economic groups, particularly for Black children, have been exacerbated.

“We’re still not back to where we need to be,” said Sean O’Leary, MD, a pediatric infectious disease doctor at Children’s Hospital Colorado and a professor of pediatrics at the University of Colorado at Denver, Aurora.

Routine immunizations protect children against 16 infectious diseases, including measles, diphtheria and chickenpox, and inhibit transmission to the community.

The rollout of COVID shots for younger kids is an opportunity to catch up on routine vaccinations, said Dr. O’Leary, adding that children can receive these vaccines together. Primary care practices, where many children are likely to receive the COVID shots, usually have other childhood vaccines on hand.

“It’s really important that parents and health care providers work together so that all children are up to date on these recommended vaccines,” said Malini DeSilva, MD, an internist and pediatrician at HealthPartners in the Minneapolis–St. Paul area. “Not only for the child’s health but for our community’s health.”

People were reluctant to come out for routine immunizations at the height of the pandemic, said Karen Miller, an immunization nurse manager for the Denver area’s Tri-County Health Department, which ran the Westminster clinic. National and global data confirm what Ms. Miller saw on the ground.

Global vaccine coverage in children fell from 2019 to 2020, according to a recent study by scientists at the Centers for Disease Control and Prevention, the World Health Organization, and UNICEF. Reasons included reduced access, lack of transportation, worries about COVID exposure and supply chain interruptions, the study said.

Third doses of the DTP vaccine and of the polio vaccine decreased from 86% of all eligible children in 2019 to 83% in 2020, according to the study. Worldwide, 22.7 million children had not had their third dose of DTP in 2020, compared with 19 million in 2019. Three doses are far more effective than one or two at protecting children and communities.

In the United States, researchers who studied 2019 and 2020 data on routine vaccinations in California, Colorado, Minnesota, Oregon, Washington, and Wisconsin found substantial disruptions in vaccination rates during the pandemic that continued into September 2020. For example, the percentage of 7-month-old babies who were up to date on vaccinations decreased from 81% in September 2019 to 74% a year later.

The proportion of Black children up to date on immunizations in almost all age groups was lower than that of children in other racial and ethnic groups. This was most pronounced in those turning 18 months old: Only 41% of Black children that age were caught up on vaccinations in September 2020, compared with 57% of all children at 18 months, said Dr. DeSilva, who led that study.

A CDC study of data from the National Immunization Surveys found that race and ethnicity, poverty, and lack of insurance created the greatest disparities in vaccination rates, and the authors noted that extra efforts are needed to counter the pandemic’s disruptions.

In addition to the problems caused by COVID, Ms. Miller said, competing life priorities like work and school impede families from keeping up with shots. Weekend vaccination clinics can help working parents get their children caught up on routine immunizations while they get a flu or COVID shot. Ms. Miller and O’Leary also said reminders via phone, text or email can boost immunizations.

“Vaccines are so effective that I think it’s easy for families to put immunizations on the back burner because we don’t often hear about these diseases,” she said.

It’s a long and nasty list that includes hepatitis A and B, measles, mumps, whooping cough, polio, rubella, rotavirus, pneumococcus, tetanus, diphtheria, human papillomavirus, and meningococcal disease, among others. Even small drops in vaccination coverage can lead to outbreaks. And measles is the perfect example that worries experts, particularly as international travel opens up.

“Measles is among the most contagious diseases known to humankind, meaning that we have to keep very high vaccination coverage to keep it from spreading,” said Dr. O’Leary.

In 2019, 22 measles outbreaks occurred in 17 states in mostly unvaccinated children and adults. Dr. O’Leary said outbreaks in New York City were contained because surrounding areas had high vaccination coverage. But an outbreak in an undervaccinated community still could spread beyond its borders.

In some states a significant number of parents were opposed to routine childhood vaccines even before the pandemic for religious or personal reasons, posing another challenge for health professionals. For example, 87% of Colorado kindergartners were vaccinated against measles, mumps, and rubella during the 2018-19 school year, one of the nation’s lowest rates.

Those rates bumped up to 91% in 2019-20 but are still below the CDC’s target of 95%.

Dr. O’Leary said he does not see the same level of hesitancy for routine immunizations as for COVID. “There has always been vaccine hesitancy and vaccine refusers. But we’ve maintained vaccination rates north of 90% for all routine childhood vaccines for a long time now,” he said.

Dr. DeSilva said the “ripple effects” of missed vaccinations earlier in the pandemic continued into 2021. As children returned to in-person learning this fall, schools may have been the first place families heard about missed vaccinations. Individual states set vaccination requirements, and allowable exemptions, for entry at schools and child care facilities. In 2020, Colorado passed a school entry immunization law that tightened allowable exemptions.

“Schools, where vaccination requirements are generally enforced, are stretched thin for a variety of reasons, including COVID,” said Dr. O’Leary, adding that managing vaccine requirements may be more difficult for some, but not all, schools.

Anayeli Dominguez, 13, was at the Westminster clinic for a Tdap vaccine because her middle school had noticed she was not up to date.

“School nurses play an important role in helping identify students in need of immunizations, and also by connecting families to resources both within the district and in the larger community,” said Denver Public Schools spokesperson Will Jones.

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

WESTMINSTER, COLO. – Melissa Blatzer was determined to get her three children caught up on their routine immunizations on a recent Saturday morning at a walk-in clinic in this Denver suburb. It had been about a year since the kids’ last shots, a delay Ms. Blatzer chalked up to the pandemic.

Two-year-old Lincoln Blatzer, in his fleece dinosaur pajamas, waited anxiously in line for his hepatitis A vaccine. His siblings, 14-year-old Nyla Kusumah and 11-year-old Nevan Kusumah, were there for their TDAP, HPV and meningococcal vaccines, plus a COVID-19 shot for Nyla.

“You don’t have to make an appointment and you can take all three at once,” said Ms. Blatzer, who lives several miles away in Commerce City. That convenience outweighed the difficulty of getting everyone up early on a weekend.

Child health experts hope community clinics like this – along with the return to in-person classes, more well-child visits, and the rollout of COVID shots for younger children – can help boost routine childhood immunizations, which dropped during the pandemic. Despite a rebound, immunization rates are still lower than in 2019, and disparities in rates between racial and economic groups, particularly for Black children, have been exacerbated.

“We’re still not back to where we need to be,” said Sean O’Leary, MD, a pediatric infectious disease doctor at Children’s Hospital Colorado and a professor of pediatrics at the University of Colorado at Denver, Aurora.

Routine immunizations protect children against 16 infectious diseases, including measles, diphtheria and chickenpox, and inhibit transmission to the community.

The rollout of COVID shots for younger kids is an opportunity to catch up on routine vaccinations, said Dr. O’Leary, adding that children can receive these vaccines together. Primary care practices, where many children are likely to receive the COVID shots, usually have other childhood vaccines on hand.

“It’s really important that parents and health care providers work together so that all children are up to date on these recommended vaccines,” said Malini DeSilva, MD, an internist and pediatrician at HealthPartners in the Minneapolis–St. Paul area. “Not only for the child’s health but for our community’s health.”

People were reluctant to come out for routine immunizations at the height of the pandemic, said Karen Miller, an immunization nurse manager for the Denver area’s Tri-County Health Department, which ran the Westminster clinic. National and global data confirm what Ms. Miller saw on the ground.

Global vaccine coverage in children fell from 2019 to 2020, according to a recent study by scientists at the Centers for Disease Control and Prevention, the World Health Organization, and UNICEF. Reasons included reduced access, lack of transportation, worries about COVID exposure and supply chain interruptions, the study said.

Third doses of the DTP vaccine and of the polio vaccine decreased from 86% of all eligible children in 2019 to 83% in 2020, according to the study. Worldwide, 22.7 million children had not had their third dose of DTP in 2020, compared with 19 million in 2019. Three doses are far more effective than one or two at protecting children and communities.

In the United States, researchers who studied 2019 and 2020 data on routine vaccinations in California, Colorado, Minnesota, Oregon, Washington, and Wisconsin found substantial disruptions in vaccination rates during the pandemic that continued into September 2020. For example, the percentage of 7-month-old babies who were up to date on vaccinations decreased from 81% in September 2019 to 74% a year later.

The proportion of Black children up to date on immunizations in almost all age groups was lower than that of children in other racial and ethnic groups. This was most pronounced in those turning 18 months old: Only 41% of Black children that age were caught up on vaccinations in September 2020, compared with 57% of all children at 18 months, said Dr. DeSilva, who led that study.

A CDC study of data from the National Immunization Surveys found that race and ethnicity, poverty, and lack of insurance created the greatest disparities in vaccination rates, and the authors noted that extra efforts are needed to counter the pandemic’s disruptions.

In addition to the problems caused by COVID, Ms. Miller said, competing life priorities like work and school impede families from keeping up with shots. Weekend vaccination clinics can help working parents get their children caught up on routine immunizations while they get a flu or COVID shot. Ms. Miller and O’Leary also said reminders via phone, text or email can boost immunizations.

“Vaccines are so effective that I think it’s easy for families to put immunizations on the back burner because we don’t often hear about these diseases,” she said.

It’s a long and nasty list that includes hepatitis A and B, measles, mumps, whooping cough, polio, rubella, rotavirus, pneumococcus, tetanus, diphtheria, human papillomavirus, and meningococcal disease, among others. Even small drops in vaccination coverage can lead to outbreaks. And measles is the perfect example that worries experts, particularly as international travel opens up.

“Measles is among the most contagious diseases known to humankind, meaning that we have to keep very high vaccination coverage to keep it from spreading,” said Dr. O’Leary.

In 2019, 22 measles outbreaks occurred in 17 states in mostly unvaccinated children and adults. Dr. O’Leary said outbreaks in New York City were contained because surrounding areas had high vaccination coverage. But an outbreak in an undervaccinated community still could spread beyond its borders.

In some states a significant number of parents were opposed to routine childhood vaccines even before the pandemic for religious or personal reasons, posing another challenge for health professionals. For example, 87% of Colorado kindergartners were vaccinated against measles, mumps, and rubella during the 2018-19 school year, one of the nation’s lowest rates.

Those rates bumped up to 91% in 2019-20 but are still below the CDC’s target of 95%.

Dr. O’Leary said he does not see the same level of hesitancy for routine immunizations as for COVID. “There has always been vaccine hesitancy and vaccine refusers. But we’ve maintained vaccination rates north of 90% for all routine childhood vaccines for a long time now,” he said.

Dr. DeSilva said the “ripple effects” of missed vaccinations earlier in the pandemic continued into 2021. As children returned to in-person learning this fall, schools may have been the first place families heard about missed vaccinations. Individual states set vaccination requirements, and allowable exemptions, for entry at schools and child care facilities. In 2020, Colorado passed a school entry immunization law that tightened allowable exemptions.

“Schools, where vaccination requirements are generally enforced, are stretched thin for a variety of reasons, including COVID,” said Dr. O’Leary, adding that managing vaccine requirements may be more difficult for some, but not all, schools.

Anayeli Dominguez, 13, was at the Westminster clinic for a Tdap vaccine because her middle school had noticed she was not up to date.

“School nurses play an important role in helping identify students in need of immunizations, and also by connecting families to resources both within the district and in the larger community,” said Denver Public Schools spokesperson Will Jones.

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

WESTMINSTER, COLO. – Melissa Blatzer was determined to get her three children caught up on their routine immunizations on a recent Saturday morning at a walk-in clinic in this Denver suburb. It had been about a year since the kids’ last shots, a delay Ms. Blatzer chalked up to the pandemic.

Two-year-old Lincoln Blatzer, in his fleece dinosaur pajamas, waited anxiously in line for his hepatitis A vaccine. His siblings, 14-year-old Nyla Kusumah and 11-year-old Nevan Kusumah, were there for their TDAP, HPV and meningococcal vaccines, plus a COVID-19 shot for Nyla.

“You don’t have to make an appointment and you can take all three at once,” said Ms. Blatzer, who lives several miles away in Commerce City. That convenience outweighed the difficulty of getting everyone up early on a weekend.

Child health experts hope community clinics like this – along with the return to in-person classes, more well-child visits, and the rollout of COVID shots for younger children – can help boost routine childhood immunizations, which dropped during the pandemic. Despite a rebound, immunization rates are still lower than in 2019, and disparities in rates between racial and economic groups, particularly for Black children, have been exacerbated.

“We’re still not back to where we need to be,” said Sean O’Leary, MD, a pediatric infectious disease doctor at Children’s Hospital Colorado and a professor of pediatrics at the University of Colorado at Denver, Aurora.

Routine immunizations protect children against 16 infectious diseases, including measles, diphtheria and chickenpox, and inhibit transmission to the community.

The rollout of COVID shots for younger kids is an opportunity to catch up on routine vaccinations, said Dr. O’Leary, adding that children can receive these vaccines together. Primary care practices, where many children are likely to receive the COVID shots, usually have other childhood vaccines on hand.

“It’s really important that parents and health care providers work together so that all children are up to date on these recommended vaccines,” said Malini DeSilva, MD, an internist and pediatrician at HealthPartners in the Minneapolis–St. Paul area. “Not only for the child’s health but for our community’s health.”

People were reluctant to come out for routine immunizations at the height of the pandemic, said Karen Miller, an immunization nurse manager for the Denver area’s Tri-County Health Department, which ran the Westminster clinic. National and global data confirm what Ms. Miller saw on the ground.

Global vaccine coverage in children fell from 2019 to 2020, according to a recent study by scientists at the Centers for Disease Control and Prevention, the World Health Organization, and UNICEF. Reasons included reduced access, lack of transportation, worries about COVID exposure and supply chain interruptions, the study said.

Third doses of the DTP vaccine and of the polio vaccine decreased from 86% of all eligible children in 2019 to 83% in 2020, according to the study. Worldwide, 22.7 million children had not had their third dose of DTP in 2020, compared with 19 million in 2019. Three doses are far more effective than one or two at protecting children and communities.

In the United States, researchers who studied 2019 and 2020 data on routine vaccinations in California, Colorado, Minnesota, Oregon, Washington, and Wisconsin found substantial disruptions in vaccination rates during the pandemic that continued into September 2020. For example, the percentage of 7-month-old babies who were up to date on vaccinations decreased from 81% in September 2019 to 74% a year later.

The proportion of Black children up to date on immunizations in almost all age groups was lower than that of children in other racial and ethnic groups. This was most pronounced in those turning 18 months old: Only 41% of Black children that age were caught up on vaccinations in September 2020, compared with 57% of all children at 18 months, said Dr. DeSilva, who led that study.

A CDC study of data from the National Immunization Surveys found that race and ethnicity, poverty, and lack of insurance created the greatest disparities in vaccination rates, and the authors noted that extra efforts are needed to counter the pandemic’s disruptions.

In addition to the problems caused by COVID, Ms. Miller said, competing life priorities like work and school impede families from keeping up with shots. Weekend vaccination clinics can help working parents get their children caught up on routine immunizations while they get a flu or COVID shot. Ms. Miller and O’Leary also said reminders via phone, text or email can boost immunizations.

“Vaccines are so effective that I think it’s easy for families to put immunizations on the back burner because we don’t often hear about these diseases,” she said.

It’s a long and nasty list that includes hepatitis A and B, measles, mumps, whooping cough, polio, rubella, rotavirus, pneumococcus, tetanus, diphtheria, human papillomavirus, and meningococcal disease, among others. Even small drops in vaccination coverage can lead to outbreaks. And measles is the perfect example that worries experts, particularly as international travel opens up.

“Measles is among the most contagious diseases known to humankind, meaning that we have to keep very high vaccination coverage to keep it from spreading,” said Dr. O’Leary.

In 2019, 22 measles outbreaks occurred in 17 states in mostly unvaccinated children and adults. Dr. O’Leary said outbreaks in New York City were contained because surrounding areas had high vaccination coverage. But an outbreak in an undervaccinated community still could spread beyond its borders.

In some states a significant number of parents were opposed to routine childhood vaccines even before the pandemic for religious or personal reasons, posing another challenge for health professionals. For example, 87% of Colorado kindergartners were vaccinated against measles, mumps, and rubella during the 2018-19 school year, one of the nation’s lowest rates.

Those rates bumped up to 91% in 2019-20 but are still below the CDC’s target of 95%.

Dr. O’Leary said he does not see the same level of hesitancy for routine immunizations as for COVID. “There has always been vaccine hesitancy and vaccine refusers. But we’ve maintained vaccination rates north of 90% for all routine childhood vaccines for a long time now,” he said.

Dr. DeSilva said the “ripple effects” of missed vaccinations earlier in the pandemic continued into 2021. As children returned to in-person learning this fall, schools may have been the first place families heard about missed vaccinations. Individual states set vaccination requirements, and allowable exemptions, for entry at schools and child care facilities. In 2020, Colorado passed a school entry immunization law that tightened allowable exemptions.

“Schools, where vaccination requirements are generally enforced, are stretched thin for a variety of reasons, including COVID,” said Dr. O’Leary, adding that managing vaccine requirements may be more difficult for some, but not all, schools.

Anayeli Dominguez, 13, was at the Westminster clinic for a Tdap vaccine because her middle school had noticed she was not up to date.

“School nurses play an important role in helping identify students in need of immunizations, and also by connecting families to resources both within the district and in the larger community,” said Denver Public Schools spokesperson Will Jones.

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

Topical retinoids are a staple first-line treatment option cited in the American Academy of Dermatology’s most recent guidelines for the care of patients with acne, yet they are likely underused in today’s clinical practice.

A study of prescribing practices from 2012 to 2014 indicated that dermatologists prescribed retinoids for just 58.8% of acne cases, while nondermatologists prescribed them for only 32.4% of cases. “If the guidelines are telling us that we should use topical retinoids for almost all of our acne patients, why are we using them for half of the patients?” Emmy Graber, MD, MBA, asked during MedscapeLive’s annual Las Vegas Dermatology Seminar. “We have a lot of options today for topical retinoids,” she added, noting that, in the past few years, trifarotene cream 0.005% and new formulations of tazarotene lotion (0.045%) and tretinoin lotion (0.05%) have become available.

According to Dr. Graber, president of The Dermatology Institute of Boston, tazarotene has been considered the most efficacious topical retinoid but is generally the least well tolerated, while adapalene has often been considered to be one of the better-tolerated topical retinoids. “This is a broad generalization,” she said. “One should also take into account the concentration and formulation of the retinoid. Cutaneous adverse events increase in severity as the concentration increases regardless of the vehicle.” There are no studies comparing trifarotene with other topical retinoids, she added.

In two phase 2, double-blind, vehicle-controlled studies (PERFECT 1 and PERFECT 2), researchers randomized more than 2,400 patients with moderate facial or truncal acne to receive trifarotene cream or a vehicle for 12 weeks. The mean percent change from baseline in facial inflammatory lesions in the trifarotene-treated group was –54.4% and –66.2% in PERFECT 1, and PERFECT 2, respectively, while the mean percent change from baseline in facial noninflammatory lesions was –49.7% and –57.7%, respectively.

In addition, the mean percent change from baseline in truncal inflammatory lesions in the trifarotene-treated groups was –57.4% and –65.4%, respectively, while the mean percent change from baseline in truncal noninflammatory lesions was –49.1% and –55.2%, respectively.

The choice of vehicle may affect absorption of topical retinoids, and some formulations may increase skin hydration and decrease transepidermal water loss, “which is a good thing,” Dr. Graber said. “Also, vehicles aim to slow drug delivery over time while also making sure that the drug penetrates into the pilosebaceous unit.”

One recent advance is the honeycomb-like polymeric emulsion technology found in tretinoin 0.05% lotion and tazarotene 0.045% lotion. These formulations contain droplets of the tretinoin and tazarotene embedded in a honeycomb matrix with hydrating agents. “I think this is exciting and could enhance our patient compliance and tolerability,” she said. Another unique feature about these two products, especially the tretinoin product, is the very small particle size with this new formulation. “It’s small enough that it can penetrate down into the pilosebaceous unit,” which is different than with older formulations, in which the tretinoin “largely just sat on the surface of the skin and didn’t penetrate into the pilosebaceous unit.” In addition, she said, “there’s only 9% degradation of the tretinoin in UV light, compared to 72% degradation of standard tretinoin 0.025% gel, and with the new tretinoin formulation, there’s no degradation when used with benzoyl peroxide.”

Another new topical retinoid to consider is a fixed-dose combination of encapsulated benzoyl peroxide 3% and encapsulated tretinoin 0.1% cream (Twyneo), which was approved by the Food and Drug Administration in July 2021 for the treatment of acne in adults and children aged 9 years and older. “Typically, benzoyl peroxide and tretinoin cannot be mixed in the same tube to stability issues,” she said. “Here, each product is individually encapsulated in a silica shell so that they can be applied together.”

The approval was supported by positive results from two phase 3, randomized, double-blind, vehicle-controlled, multicenter studies (NCT03761784 and NCT03761810), in which Twyneo demonstrated efficacy and a favorable tolerability profile in patients aged 9 years and older with facial acne.

Another topical treatment option, dapsone, is now FDA approved for ages 9 and up, expanded from its initial indication for ages 12 and up. The new indication is based on a phase 4, multicenter, open-label study in which acne patients aged 9-11 years applied dapsone 7.5% gel once daily to the face and acne-affected areas on the upper chest, upper back, and shoulders for 12 weeks. After 12 weeks, facial acne was clear or almost clear in about 47% of patients. “Inflammatory, noninflammatory, and total lesions decreased from baseline, but there was a greater reduction in noninflammatory lesions, so if you have a very young patient with acne, now you can consider dapsone gel,” Dr. Graber said.

In August 2020, clascoterone cream became the first topical androgen receptor inhibitor approved for the treatment of acne in patients 12 years of age and older. It is a drug believed to address sebum and inflammation directly in the sebaceous gland and is structurally similar to dihydrotestosterone and spironolactone.

“This is a completely new drug category in acne,” she said. “Unlike all oral antiandrogen therapies, clascoterone cream can be used in both males and females with acne. It’s the first acne drug to have a new mechanism of action in almost 40 years, since isotretinoin was approved in 1982.”

In vitro, she continued, clascoterone competes with dihydrotestosterone for binding to the androgen receptor, inhibiting downstream signaling and leading to inhibited sebum production, reduced secretion of inflammatory cytokines, and inhibition of inflammatory pathways. Two phase 3 studies that led to its approval involved 1,440 patients with moderate to severe facial acne aged 9-58 years. The cream was applied twice a day for 12 weeks and treatment adherence was approximately 90%. The researchers found that clascoterone cream was significantly more effective than vehicle cream at achieving Investigator’s Global Assessment scores of 0 (clear) or 1 (almost clear), the definition of treatment success in the study, and reducing noninflammatory lesion and inflammatory lesion counts at week 12. “There were no safety issues noted during these studies, and clascoterone cream was well tolerated,” Dr. Graber said.

Dr. Graber disclosed that she is a consultant/adviser for Digital Diagnostics, Almirall, Hovione, Keratin Biosciences, La Roche Posay, Ortho Dermatologics, Sebacia, Sol-Gel, Verrica, and WebMD. She is also a research investigator for Hovione, Ortho Dermatologics, Sebacia, and she receives royalties from Wolters Kluwer Health.

MedscapeLive and this news organization are owned by the same parent company.

Commentary by Lawrence W. Eichenfield, MD

Acne vulgaris remains an issue of tremendous importance to preteens, teens, and young adults, with approximately 85% of individuals aged 12-24 being affected. Expanding options for topical treatments may help bring effective disease control. Dr. Graber pointed out that historically, pediatricians and other primary care practitioners utilize topical retinoids less often for acne care as compared with dermatologists or guidelines recommendations (either the AAP’s or AAD’s). There are now expanded options, including over-the-counter retinoids (adapalene 0.1% gel), generic and trade brand topical tretinoin products, prescription adapalene medications, older and recently approved tazarotene products, and a newer type of topical retinoid, trifarotene. Novel formulations and emulsion technology, as well as retinoid developed in combination products, give more options in patients down to 9 years of age. A novel topical anti-androgen, clascoterone, is in its own category, as the first topical “hormonal agent,” allowing hormonal therapy to be used for males as well as females (aged 12 years and up). A recent review in JAMA (2021 Nov 23;326[20]:2055-67) incorporates many of these newer medications into management suggestions, emphasizing that first-line therapies are topical retinoids, benzoyl peroxide, azelaic acid, or combinations of topicals, whereas in more severe disease, oral antibiotics such as doxycycline or minocycline, hormonal therapies such as combination oral conceptive agents or spironolactone, or isotretinoin are most effective.

Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children's Hospital-San Diego. He is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego. He disclosed that he has served as an investigator and/or consultant to AbbVie, Lilly, Pfizer, Regeneron, Sanofi-Genzyme, and Verrica.

A version of this article first appeared on Medscape.com.

This article was updated 6/18/22.

Topical retinoids are a staple first-line treatment option cited in the American Academy of Dermatology’s most recent guidelines for the care of patients with acne, yet they are likely underused in today’s clinical practice.

A study of prescribing practices from 2012 to 2014 indicated that dermatologists prescribed retinoids for just 58.8% of acne cases, while nondermatologists prescribed them for only 32.4% of cases. “If the guidelines are telling us that we should use topical retinoids for almost all of our acne patients, why are we using them for half of the patients?” Emmy Graber, MD, MBA, asked during MedscapeLive’s annual Las Vegas Dermatology Seminar. “We have a lot of options today for topical retinoids,” she added, noting that, in the past few years, trifarotene cream 0.005% and new formulations of tazarotene lotion (0.045%) and tretinoin lotion (0.05%) have become available.

According to Dr. Graber, president of The Dermatology Institute of Boston, tazarotene has been considered the most efficacious topical retinoid but is generally the least well tolerated, while adapalene has often been considered to be one of the better-tolerated topical retinoids. “This is a broad generalization,” she said. “One should also take into account the concentration and formulation of the retinoid. Cutaneous adverse events increase in severity as the concentration increases regardless of the vehicle.” There are no studies comparing trifarotene with other topical retinoids, she added.

In two phase 2, double-blind, vehicle-controlled studies (PERFECT 1 and PERFECT 2), researchers randomized more than 2,400 patients with moderate facial or truncal acne to receive trifarotene cream or a vehicle for 12 weeks. The mean percent change from baseline in facial inflammatory lesions in the trifarotene-treated group was –54.4% and –66.2% in PERFECT 1, and PERFECT 2, respectively, while the mean percent change from baseline in facial noninflammatory lesions was –49.7% and –57.7%, respectively.

In addition, the mean percent change from baseline in truncal inflammatory lesions in the trifarotene-treated groups was –57.4% and –65.4%, respectively, while the mean percent change from baseline in truncal noninflammatory lesions was –49.1% and –55.2%, respectively.

The choice of vehicle may affect absorption of topical retinoids, and some formulations may increase skin hydration and decrease transepidermal water loss, “which is a good thing,” Dr. Graber said. “Also, vehicles aim to slow drug delivery over time while also making sure that the drug penetrates into the pilosebaceous unit.”

One recent advance is the honeycomb-like polymeric emulsion technology found in tretinoin 0.05% lotion and tazarotene 0.045% lotion. These formulations contain droplets of the tretinoin and tazarotene embedded in a honeycomb matrix with hydrating agents. “I think this is exciting and could enhance our patient compliance and tolerability,” she said. Another unique feature about these two products, especially the tretinoin product, is the very small particle size with this new formulation. “It’s small enough that it can penetrate down into the pilosebaceous unit,” which is different than with older formulations, in which the tretinoin “largely just sat on the surface of the skin and didn’t penetrate into the pilosebaceous unit.” In addition, she said, “there’s only 9% degradation of the tretinoin in UV light, compared to 72% degradation of standard tretinoin 0.025% gel, and with the new tretinoin formulation, there’s no degradation when used with benzoyl peroxide.”

Another new topical retinoid to consider is a fixed-dose combination of encapsulated benzoyl peroxide 3% and encapsulated tretinoin 0.1% cream (Twyneo), which was approved by the Food and Drug Administration in July 2021 for the treatment of acne in adults and children aged 9 years and older. “Typically, benzoyl peroxide and tretinoin cannot be mixed in the same tube to stability issues,” she said. “Here, each product is individually encapsulated in a silica shell so that they can be applied together.”

The approval was supported by positive results from two phase 3, randomized, double-blind, vehicle-controlled, multicenter studies (NCT03761784 and NCT03761810), in which Twyneo demonstrated efficacy and a favorable tolerability profile in patients aged 9 years and older with facial acne.

Another topical treatment option, dapsone, is now FDA approved for ages 9 and up, expanded from its initial indication for ages 12 and up. The new indication is based on a phase 4, multicenter, open-label study in which acne patients aged 9-11 years applied dapsone 7.5% gel once daily to the face and acne-affected areas on the upper chest, upper back, and shoulders for 12 weeks. After 12 weeks, facial acne was clear or almost clear in about 47% of patients. “Inflammatory, noninflammatory, and total lesions decreased from baseline, but there was a greater reduction in noninflammatory lesions, so if you have a very young patient with acne, now you can consider dapsone gel,” Dr. Graber said.

In August 2020, clascoterone cream became the first topical androgen receptor inhibitor approved for the treatment of acne in patients 12 years of age and older. It is a drug believed to address sebum and inflammation directly in the sebaceous gland and is structurally similar to dihydrotestosterone and spironolactone.

“This is a completely new drug category in acne,” she said. “Unlike all oral antiandrogen therapies, clascoterone cream can be used in both males and females with acne. It’s the first acne drug to have a new mechanism of action in almost 40 years, since isotretinoin was approved in 1982.”

In vitro, she continued, clascoterone competes with dihydrotestosterone for binding to the androgen receptor, inhibiting downstream signaling and leading to inhibited sebum production, reduced secretion of inflammatory cytokines, and inhibition of inflammatory pathways. Two phase 3 studies that led to its approval involved 1,440 patients with moderate to severe facial acne aged 9-58 years. The cream was applied twice a day for 12 weeks and treatment adherence was approximately 90%. The researchers found that clascoterone cream was significantly more effective than vehicle cream at achieving Investigator’s Global Assessment scores of 0 (clear) or 1 (almost clear), the definition of treatment success in the study, and reducing noninflammatory lesion and inflammatory lesion counts at week 12. “There were no safety issues noted during these studies, and clascoterone cream was well tolerated,” Dr. Graber said.

Dr. Graber disclosed that she is a consultant/adviser for Digital Diagnostics, Almirall, Hovione, Keratin Biosciences, La Roche Posay, Ortho Dermatologics, Sebacia, Sol-Gel, Verrica, and WebMD. She is also a research investigator for Hovione, Ortho Dermatologics, Sebacia, and she receives royalties from Wolters Kluwer Health.

MedscapeLive and this news organization are owned by the same parent company.

Commentary by Lawrence W. Eichenfield, MD

Acne vulgaris remains an issue of tremendous importance to preteens, teens, and young adults, with approximately 85% of individuals aged 12-24 being affected. Expanding options for topical treatments may help bring effective disease control. Dr. Graber pointed out that historically, pediatricians and other primary care practitioners utilize topical retinoids less often for acne care as compared with dermatologists or guidelines recommendations (either the AAP’s or AAD’s). There are now expanded options, including over-the-counter retinoids (adapalene 0.1% gel), generic and trade brand topical tretinoin products, prescription adapalene medications, older and recently approved tazarotene products, and a newer type of topical retinoid, trifarotene. Novel formulations and emulsion technology, as well as retinoid developed in combination products, give more options in patients down to 9 years of age. A novel topical anti-androgen, clascoterone, is in its own category, as the first topical “hormonal agent,” allowing hormonal therapy to be used for males as well as females (aged 12 years and up). A recent review in JAMA (2021 Nov 23;326[20]:2055-67) incorporates many of these newer medications into management suggestions, emphasizing that first-line therapies are topical retinoids, benzoyl peroxide, azelaic acid, or combinations of topicals, whereas in more severe disease, oral antibiotics such as doxycycline or minocycline, hormonal therapies such as combination oral conceptive agents or spironolactone, or isotretinoin are most effective.

Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children's Hospital-San Diego. He is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego. He disclosed that he has served as an investigator and/or consultant to AbbVie, Lilly, Pfizer, Regeneron, Sanofi-Genzyme, and Verrica.

A version of this article first appeared on Medscape.com.

This article was updated 6/18/22.

Topical retinoids are a staple first-line treatment option cited in the American Academy of Dermatology’s most recent guidelines for the care of patients with acne, yet they are likely underused in today’s clinical practice.

A study of prescribing practices from 2012 to 2014 indicated that dermatologists prescribed retinoids for just 58.8% of acne cases, while nondermatologists prescribed them for only 32.4% of cases. “If the guidelines are telling us that we should use topical retinoids for almost all of our acne patients, why are we using them for half of the patients?” Emmy Graber, MD, MBA, asked during MedscapeLive’s annual Las Vegas Dermatology Seminar. “We have a lot of options today for topical retinoids,” she added, noting that, in the past few years, trifarotene cream 0.005% and new formulations of tazarotene lotion (0.045%) and tretinoin lotion (0.05%) have become available.

According to Dr. Graber, president of The Dermatology Institute of Boston, tazarotene has been considered the most efficacious topical retinoid but is generally the least well tolerated, while adapalene has often been considered to be one of the better-tolerated topical retinoids. “This is a broad generalization,” she said. “One should also take into account the concentration and formulation of the retinoid. Cutaneous adverse events increase in severity as the concentration increases regardless of the vehicle.” There are no studies comparing trifarotene with other topical retinoids, she added.

In two phase 2, double-blind, vehicle-controlled studies (PERFECT 1 and PERFECT 2), researchers randomized more than 2,400 patients with moderate facial or truncal acne to receive trifarotene cream or a vehicle for 12 weeks. The mean percent change from baseline in facial inflammatory lesions in the trifarotene-treated group was –54.4% and –66.2% in PERFECT 1, and PERFECT 2, respectively, while the mean percent change from baseline in facial noninflammatory lesions was –49.7% and –57.7%, respectively.

In addition, the mean percent change from baseline in truncal inflammatory lesions in the trifarotene-treated groups was –57.4% and –65.4%, respectively, while the mean percent change from baseline in truncal noninflammatory lesions was –49.1% and –55.2%, respectively.

The choice of vehicle may affect absorption of topical retinoids, and some formulations may increase skin hydration and decrease transepidermal water loss, “which is a good thing,” Dr. Graber said. “Also, vehicles aim to slow drug delivery over time while also making sure that the drug penetrates into the pilosebaceous unit.”

One recent advance is the honeycomb-like polymeric emulsion technology found in tretinoin 0.05% lotion and tazarotene 0.045% lotion. These formulations contain droplets of the tretinoin and tazarotene embedded in a honeycomb matrix with hydrating agents. “I think this is exciting and could enhance our patient compliance and tolerability,” she said. Another unique feature about these two products, especially the tretinoin product, is the very small particle size with this new formulation. “It’s small enough that it can penetrate down into the pilosebaceous unit,” which is different than with older formulations, in which the tretinoin “largely just sat on the surface of the skin and didn’t penetrate into the pilosebaceous unit.” In addition, she said, “there’s only 9% degradation of the tretinoin in UV light, compared to 72% degradation of standard tretinoin 0.025% gel, and with the new tretinoin formulation, there’s no degradation when used with benzoyl peroxide.”

Another new topical retinoid to consider is a fixed-dose combination of encapsulated benzoyl peroxide 3% and encapsulated tretinoin 0.1% cream (Twyneo), which was approved by the Food and Drug Administration in July 2021 for the treatment of acne in adults and children aged 9 years and older. “Typically, benzoyl peroxide and tretinoin cannot be mixed in the same tube to stability issues,” she said. “Here, each product is individually encapsulated in a silica shell so that they can be applied together.”

The approval was supported by positive results from two phase 3, randomized, double-blind, vehicle-controlled, multicenter studies (NCT03761784 and NCT03761810), in which Twyneo demonstrated efficacy and a favorable tolerability profile in patients aged 9 years and older with facial acne.

Another topical treatment option, dapsone, is now FDA approved for ages 9 and up, expanded from its initial indication for ages 12 and up. The new indication is based on a phase 4, multicenter, open-label study in which acne patients aged 9-11 years applied dapsone 7.5% gel once daily to the face and acne-affected areas on the upper chest, upper back, and shoulders for 12 weeks. After 12 weeks, facial acne was clear or almost clear in about 47% of patients. “Inflammatory, noninflammatory, and total lesions decreased from baseline, but there was a greater reduction in noninflammatory lesions, so if you have a very young patient with acne, now you can consider dapsone gel,” Dr. Graber said.

In August 2020, clascoterone cream became the first topical androgen receptor inhibitor approved for the treatment of acne in patients 12 years of age and older. It is a drug believed to address sebum and inflammation directly in the sebaceous gland and is structurally similar to dihydrotestosterone and spironolactone.

“This is a completely new drug category in acne,” she said. “Unlike all oral antiandrogen therapies, clascoterone cream can be used in both males and females with acne. It’s the first acne drug to have a new mechanism of action in almost 40 years, since isotretinoin was approved in 1982.”

In vitro, she continued, clascoterone competes with dihydrotestosterone for binding to the androgen receptor, inhibiting downstream signaling and leading to inhibited sebum production, reduced secretion of inflammatory cytokines, and inhibition of inflammatory pathways. Two phase 3 studies that led to its approval involved 1,440 patients with moderate to severe facial acne aged 9-58 years. The cream was applied twice a day for 12 weeks and treatment adherence was approximately 90%. The researchers found that clascoterone cream was significantly more effective than vehicle cream at achieving Investigator’s Global Assessment scores of 0 (clear) or 1 (almost clear), the definition of treatment success in the study, and reducing noninflammatory lesion and inflammatory lesion counts at week 12. “There were no safety issues noted during these studies, and clascoterone cream was well tolerated,” Dr. Graber said.

Dr. Graber disclosed that she is a consultant/adviser for Digital Diagnostics, Almirall, Hovione, Keratin Biosciences, La Roche Posay, Ortho Dermatologics, Sebacia, Sol-Gel, Verrica, and WebMD. She is also a research investigator for Hovione, Ortho Dermatologics, Sebacia, and she receives royalties from Wolters Kluwer Health.

MedscapeLive and this news organization are owned by the same parent company.

Commentary by Lawrence W. Eichenfield, MD

Acne vulgaris remains an issue of tremendous importance to preteens, teens, and young adults, with approximately 85% of individuals aged 12-24 being affected. Expanding options for topical treatments may help bring effective disease control. Dr. Graber pointed out that historically, pediatricians and other primary care practitioners utilize topical retinoids less often for acne care as compared with dermatologists or guidelines recommendations (either the AAP’s or AAD’s). There are now expanded options, including over-the-counter retinoids (adapalene 0.1% gel), generic and trade brand topical tretinoin products, prescription adapalene medications, older and recently approved tazarotene products, and a newer type of topical retinoid, trifarotene. Novel formulations and emulsion technology, as well as retinoid developed in combination products, give more options in patients down to 9 years of age. A novel topical anti-androgen, clascoterone, is in its own category, as the first topical “hormonal agent,” allowing hormonal therapy to be used for males as well as females (aged 12 years and up). A recent review in JAMA (2021 Nov 23;326[20]:2055-67) incorporates many of these newer medications into management suggestions, emphasizing that first-line therapies are topical retinoids, benzoyl peroxide, azelaic acid, or combinations of topicals, whereas in more severe disease, oral antibiotics such as doxycycline or minocycline, hormonal therapies such as combination oral conceptive agents or spironolactone, or isotretinoin are most effective.

Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children's Hospital-San Diego. He is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego. He disclosed that he has served as an investigator and/or consultant to AbbVie, Lilly, Pfizer, Regeneron, Sanofi-Genzyme, and Verrica.

A version of this article first appeared on Medscape.com.

This article was updated 6/18/22.

When parents of children with autism spectrum disorder (ASD) participating in the largest clinical trial of intranasal oxytocin to date came in for follow-up visits with investigators, they reported marked improvement in the children’s social functioning.

Kids who rarely communicated with their families began to interact more. Those who usually preferred to isolate themselves started joining their parents for meals. It all seemed so promising – until the data came in.

“Those sounded like real improvements to me, and it seemed like they increased over the period of the study,” lead investigator Linmarie Sikich, MD, an associate clinical professor of psychiatry with Duke University School of Medicine and the Duke Center for Autism and Brain Development, Durham, N.C., told this news organization. “Turns out it wasn’t oxytocin that was making that difference.”

Researchers found that after 24 weeks of daily treatment with intranasal oxytocin, there were no significant differences in social functioning between children who received active treatment and those in the placebo group.

The much-anticipated results were published online in The New England Journal of Medicine. To say that they are disappointing, Dr. Sikich said, is an understatement.
 

Increase in off-label use

Most studies in mouse models of ASD and small trials in children produced conflicting results, although there were modest improvements in social functioning associated with the use of intranasal oxytocin. Some clinicians were already prescribing it off label.

On the basis of this research and early feedback from parents of children, Dr. Sikich and colleagues were hopeful.

However, results from a rigorous, 5-year, $11.4 million randomized trial were negative. Yet, parents were convinced their child improved during the study, and there was a significant increase in off-label prescribing of a treatment her research says doesn’t work. What’s next for oxytocin?

Known as the “love hormone,” oxytocin is a neurotransmitter that is primarily synthesized in the hypothalamus. It plays a role in childbirth and lactation and is also involved in the regulation of social functioning and emotions. Research suggests low oxytocin levels are associated with diminished social functioning, regardless of ASD status.

Its potential as an autism therapy for children has been under study for a decade. Some findings link its use to improvements in core deficits associated with ASD, including repetitive behaviors, fixated or restricted interest, and social communication. A study published in 2020 showed that the treatment improved symptoms in high-functioning adults with ASD.

These were mostly small studies and were underpowered to reliably detect an effect of the therapy on social functioning. They often involved only a single dose of oxytocin. Some studies showed improvements, but others did not.

Still, interest in the treatment grew. Physicians began prescribing it for children with ASD, and parents began buying products containing oxytocin on the internet. Researchers feared this off-label use was becoming widespread, despite inconclusive evidence of efficacy.
 

High hopes

With support from a National Institutes of Health grant, Dr. Sikich and her team designed a phase 2, multicenter, randomized, double-blind, placebo-controlled study to determine whether the use of oxytocin in children with ASD works and is safe.

The challenges began before they even enrolled a single child. A number of behavioral assessment tools are used to measure social function in ASD, but there is no consensus on which one is best.

A simple blood test could determine how much oxytocin from the nasal spray was absorbed in the blood, but identifying how much made it to the brain would require fMRI, which is expensive and is challenging to use in this study population. Then there was the acquisition of the drug itself.

The Food and Drug Administration has approved intravenous oxytocin for inducing labor. Intranasal oxytocin is not approved for any indication and isn’t available commercially in the United States. Patients or researchers must secure the drug from a manufacturer in a country where it is approved or order it from a U.S. pharmacy that is capable of compounding IV oxytocin into an intranasal formulation.

The pharmacy in Switzerland Dr. Sikich planned to use couldn’t make enough for the study. Contracting with a compounding pharmacy in the United States was significantly more expensive and time consuming, but it was the researchers’ only option.

“If it hadn’t been something we expected to have a major benefit, I think we would have given up the project at multiple points along the line due to all of these challenges,” said Dr. Sikich.

In August 2014, with all the pieces finally in place, researchers began enrolling children aged 3-17 years. The final cohort included 290 participants with ASD, 146 in the oxytocin group and 144 in the placebo group. Of these, 48% had minimal verbal fluency, and 52% had fluent verbal speech.

Participants received daily synthetic oxytocin or placebo via a nasal spray for 24 weeks. The daily oxytocin dose was 48 IU for the first 7 weeks. After that, the dosage could be titrated to a maximum of 80 IU/d. The mean maximal total daily dose of oxytocin throughout the study was 67.6 ± 16.9 IU.
 

‘It just didn’t work’

Both study groups showed improvement in social withdrawal beginning at 4 weeks and continuing throughout the trial, as determined on the basis of caretakers’ responses on the Aberrant Behavior Checklist Modified Social Withdrawal Subscale, the study’s primary outcome measure.

Sociability and social motivation also improved in both groups, as measured by the Pervasive Developmental Disorders Behavior Inventory and the Social Responsiveness Scale.

But by the end of the trial, the difference between the groups in improvement of social function wasn’t significant (difference, -0.2 points; P = .61) after adjusting for age, verbal fluency, and baseline oxytocin level.

“We were so convinced that it would work,” Dr. Sikich said, “but it just didn’t.”

From observation, parents were also convinced the therapy was working. At the trial’s conclusion, fewer than half of caregivers correctly guessed whether their child was in the treatment group or the placebo group.

A lot of development changes can happen in a child over 6 months. It’s possible the improvements would have occurred regardless of the trial, Dr. Sikich said. Parents’ perceptions could also be a placebo effect. Their child was in a clinical trial of a drug they believed could improve social functioning, so in their mind, it did.

Caregivers received training in how to identify certain behavioral changes, which may have helped them spot an existing positive change they had previously overlooked. Or they may have worked with their child more intently as a result of their participation in the trial.

“People may start doing more things or doing them more intensively or purposefully, consciously or subconsciously, to try to help their child improve the skills or behaviors targeted by the active therapy in the study,” Dr. Sikich said. “These are things that might really help the child move forward which are completely separate from the medication being studied.”

The safety analysis offered more hopeful results. Only one serious adverse event from the treatment was reported: A 17-year-old participant taking a daily dose of 48 IU experienced a sedating effect while driving and had an accident.
 

Too soon to walk away?

Perhaps the most important take-away from the study is that even if it’s safe, intranasal oxytocin as it is currently used doesn’t work and clinicians shouldn’t prescribe it, said Daniel Geschwind, MD, PhD, director of the University of California, Los Angeles (UCLA) Center for Autism Research, who penned a commentary on the study and discussed the findings with this news organization.

“This study shows that using oxytocin the way it’s used in the community right now is not helping anybody, so why put a child through that?” added Dr. Geschwind, who also is a professor of genetics, neurology, and psychiatry at UCLA.

The trial highlights areas that need to be addressed in order to improve research in the field, he said. Establishing a consensus process to measure social functioning and figuring out a better way to access intranasal oxytocin would lead to studies that are more conclusive, comparable, and less expensive. Dr. Sikich agrees.

Despite the findings, Dr. Geschwind and other autism researchers say it’s too soon to walk away from oxytocin altogether, although it may be time to change the approach to autism research.

“We have to take a page from the playbook of modern medicine in other areas and begin to recognize that these syndromes are incredibly heterogeneous,” Dr. Geschwind says. “We can surmise, although we don’t know, that there might be different biological forms of autism that have different pathways involved that are going to respond differently to different medications.”

Calling the researchers’ efforts “heroic,” Karen Parker, PhD, an associate professor and associate chair of psychiatry and behavioral sciences at Stanford (Calif.) University, says efficacy trials such as this one are critical. However, Dr. Parker said in an interview, there are a number of questions that the study didn’t address.

The majority of medication dispensed in a standard intranasal device is sprayed into the back of the throat. Regular blood tests confirmed that oxytocin was getting into participants’ system, but, given how quickly oxytocin degrades in the blood, Dr. Parker said it’s hard to know just how much reached the brain.

It’s also unclear whether the results would have been different had the treatment been paired with behavioral therapy, an approach Dr. Parker suggests might benefit a subset of children with ASD.

A 2017 study from Dr. Parker’s lab found that children with ASD whose use of oxytocin at baseline was low derived greater benefit from synthetic oxytocin, something the new study failed to find. Still, Dr. Parker said, it’s possible oxytocin might increase social motivation and increase a child’s receptiveness to behavioral therapy.

“When you see a negative trial like this, it decreases enthusiasm for the therapy for autism in this context,” Dr. Parker said. “I hope people who are studying these syndromes will continue to explore oxytocin as a therapy.”

The study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development through the Autism Centers of Excellence Program and the Department of Psychiatry and Behavioral Sciences at Duke University. Full disclosures of the authors’ possible conflicts of interest are available online.

A version of this article first appeared on Medscape.com.

When parents of children with autism spectrum disorder (ASD) participating in the largest clinical trial of intranasal oxytocin to date came in for follow-up visits with investigators, they reported marked improvement in the children’s social functioning.

Kids who rarely communicated with their families began to interact more. Those who usually preferred to isolate themselves started joining their parents for meals. It all seemed so promising – until the data came in.

“Those sounded like real improvements to me, and it seemed like they increased over the period of the study,” lead investigator Linmarie Sikich, MD, an associate clinical professor of psychiatry with Duke University School of Medicine and the Duke Center for Autism and Brain Development, Durham, N.C., told this news organization. “Turns out it wasn’t oxytocin that was making that difference.”

Researchers found that after 24 weeks of daily treatment with intranasal oxytocin, there were no significant differences in social functioning between children who received active treatment and those in the placebo group.

The much-anticipated results were published online in The New England Journal of Medicine. To say that they are disappointing, Dr. Sikich said, is an understatement.
 

Increase in off-label use

Most studies in mouse models of ASD and small trials in children produced conflicting results, although there were modest improvements in social functioning associated with the use of intranasal oxytocin. Some clinicians were already prescribing it off label.

On the basis of this research and early feedback from parents of children, Dr. Sikich and colleagues were hopeful.

However, results from a rigorous, 5-year, $11.4 million randomized trial were negative. Yet, parents were convinced their child improved during the study, and there was a significant increase in off-label prescribing of a treatment her research says doesn’t work. What’s next for oxytocin?

Known as the “love hormone,” oxytocin is a neurotransmitter that is primarily synthesized in the hypothalamus. It plays a role in childbirth and lactation and is also involved in the regulation of social functioning and emotions. Research suggests low oxytocin levels are associated with diminished social functioning, regardless of ASD status.

Its potential as an autism therapy for children has been under study for a decade. Some findings link its use to improvements in core deficits associated with ASD, including repetitive behaviors, fixated or restricted interest, and social communication. A study published in 2020 showed that the treatment improved symptoms in high-functioning adults with ASD.

These were mostly small studies and were underpowered to reliably detect an effect of the therapy on social functioning. They often involved only a single dose of oxytocin. Some studies showed improvements, but others did not.

Still, interest in the treatment grew. Physicians began prescribing it for children with ASD, and parents began buying products containing oxytocin on the internet. Researchers feared this off-label use was becoming widespread, despite inconclusive evidence of efficacy.
 

High hopes

With support from a National Institutes of Health grant, Dr. Sikich and her team designed a phase 2, multicenter, randomized, double-blind, placebo-controlled study to determine whether the use of oxytocin in children with ASD works and is safe.

The challenges began before they even enrolled a single child. A number of behavioral assessment tools are used to measure social function in ASD, but there is no consensus on which one is best.

A simple blood test could determine how much oxytocin from the nasal spray was absorbed in the blood, but identifying how much made it to the brain would require fMRI, which is expensive and is challenging to use in this study population. Then there was the acquisition of the drug itself.

The Food and Drug Administration has approved intravenous oxytocin for inducing labor. Intranasal oxytocin is not approved for any indication and isn’t available commercially in the United States. Patients or researchers must secure the drug from a manufacturer in a country where it is approved or order it from a U.S. pharmacy that is capable of compounding IV oxytocin into an intranasal formulation.

The pharmacy in Switzerland Dr. Sikich planned to use couldn’t make enough for the study. Contracting with a compounding pharmacy in the United States was significantly more expensive and time consuming, but it was the researchers’ only option.

“If it hadn’t been something we expected to have a major benefit, I think we would have given up the project at multiple points along the line due to all of these challenges,” said Dr. Sikich.

In August 2014, with all the pieces finally in place, researchers began enrolling children aged 3-17 years. The final cohort included 290 participants with ASD, 146 in the oxytocin group and 144 in the placebo group. Of these, 48% had minimal verbal fluency, and 52% had fluent verbal speech.

Participants received daily synthetic oxytocin or placebo via a nasal spray for 24 weeks. The daily oxytocin dose was 48 IU for the first 7 weeks. After that, the dosage could be titrated to a maximum of 80 IU/d. The mean maximal total daily dose of oxytocin throughout the study was 67.6 ± 16.9 IU.
 

‘It just didn’t work’

Both study groups showed improvement in social withdrawal beginning at 4 weeks and continuing throughout the trial, as determined on the basis of caretakers’ responses on the Aberrant Behavior Checklist Modified Social Withdrawal Subscale, the study’s primary outcome measure.

Sociability and social motivation also improved in both groups, as measured by the Pervasive Developmental Disorders Behavior Inventory and the Social Responsiveness Scale.

But by the end of the trial, the difference between the groups in improvement of social function wasn’t significant (difference, -0.2 points; P = .61) after adjusting for age, verbal fluency, and baseline oxytocin level.

“We were so convinced that it would work,” Dr. Sikich said, “but it just didn’t.”

From observation, parents were also convinced the therapy was working. At the trial’s conclusion, fewer than half of caregivers correctly guessed whether their child was in the treatment group or the placebo group.

A lot of development changes can happen in a child over 6 months. It’s possible the improvements would have occurred regardless of the trial, Dr. Sikich said. Parents’ perceptions could also be a placebo effect. Their child was in a clinical trial of a drug they believed could improve social functioning, so in their mind, it did.

Caregivers received training in how to identify certain behavioral changes, which may have helped them spot an existing positive change they had previously overlooked. Or they may have worked with their child more intently as a result of their participation in the trial.

“People may start doing more things or doing them more intensively or purposefully, consciously or subconsciously, to try to help their child improve the skills or behaviors targeted by the active therapy in the study,” Dr. Sikich said. “These are things that might really help the child move forward which are completely separate from the medication being studied.”

The safety analysis offered more hopeful results. Only one serious adverse event from the treatment was reported: A 17-year-old participant taking a daily dose of 48 IU experienced a sedating effect while driving and had an accident.
 

Too soon to walk away?

Perhaps the most important take-away from the study is that even if it’s safe, intranasal oxytocin as it is currently used doesn’t work and clinicians shouldn’t prescribe it, said Daniel Geschwind, MD, PhD, director of the University of California, Los Angeles (UCLA) Center for Autism Research, who penned a commentary on the study and discussed the findings with this news organization.

“This study shows that using oxytocin the way it’s used in the community right now is not helping anybody, so why put a child through that?” added Dr. Geschwind, who also is a professor of genetics, neurology, and psychiatry at UCLA.

The trial highlights areas that need to be addressed in order to improve research in the field, he said. Establishing a consensus process to measure social functioning and figuring out a better way to access intranasal oxytocin would lead to studies that are more conclusive, comparable, and less expensive. Dr. Sikich agrees.

Despite the findings, Dr. Geschwind and other autism researchers say it’s too soon to walk away from oxytocin altogether, although it may be time to change the approach to autism research.

“We have to take a page from the playbook of modern medicine in other areas and begin to recognize that these syndromes are incredibly heterogeneous,” Dr. Geschwind says. “We can surmise, although we don’t know, that there might be different biological forms of autism that have different pathways involved that are going to respond differently to different medications.”

Calling the researchers’ efforts “heroic,” Karen Parker, PhD, an associate professor and associate chair of psychiatry and behavioral sciences at Stanford (Calif.) University, says efficacy trials such as this one are critical. However, Dr. Parker said in an interview, there are a number of questions that the study didn’t address.

The majority of medication dispensed in a standard intranasal device is sprayed into the back of the throat. Regular blood tests confirmed that oxytocin was getting into participants’ system, but, given how quickly oxytocin degrades in the blood, Dr. Parker said it’s hard to know just how much reached the brain.

It’s also unclear whether the results would have been different had the treatment been paired with behavioral therapy, an approach Dr. Parker suggests might benefit a subset of children with ASD.

A 2017 study from Dr. Parker’s lab found that children with ASD whose use of oxytocin at baseline was low derived greater benefit from synthetic oxytocin, something the new study failed to find. Still, Dr. Parker said, it’s possible oxytocin might increase social motivation and increase a child’s receptiveness to behavioral therapy.

“When you see a negative trial like this, it decreases enthusiasm for the therapy for autism in this context,” Dr. Parker said. “I hope people who are studying these syndromes will continue to explore oxytocin as a therapy.”

The study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development through the Autism Centers of Excellence Program and the Department of Psychiatry and Behavioral Sciences at Duke University. Full disclosures of the authors’ possible conflicts of interest are available online.

A version of this article first appeared on Medscape.com.

When parents of children with autism spectrum disorder (ASD) participating in the largest clinical trial of intranasal oxytocin to date came in for follow-up visits with investigators, they reported marked improvement in the children’s social functioning.

Kids who rarely communicated with their families began to interact more. Those who usually preferred to isolate themselves started joining their parents for meals. It all seemed so promising – until the data came in.

“Those sounded like real improvements to me, and it seemed like they increased over the period of the study,” lead investigator Linmarie Sikich, MD, an associate clinical professor of psychiatry with Duke University School of Medicine and the Duke Center for Autism and Brain Development, Durham, N.C., told this news organization. “Turns out it wasn’t oxytocin that was making that difference.”

Researchers found that after 24 weeks of daily treatment with intranasal oxytocin, there were no significant differences in social functioning between children who received active treatment and those in the placebo group.

The much-anticipated results were published online in The New England Journal of Medicine. To say that they are disappointing, Dr. Sikich said, is an understatement.
 

Increase in off-label use

Most studies in mouse models of ASD and small trials in children produced conflicting results, although there were modest improvements in social functioning associated with the use of intranasal oxytocin. Some clinicians were already prescribing it off label.

On the basis of this research and early feedback from parents of children, Dr. Sikich and colleagues were hopeful.

However, results from a rigorous, 5-year, $11.4 million randomized trial were negative. Yet, parents were convinced their child improved during the study, and there was a significant increase in off-label prescribing of a treatment her research says doesn’t work. What’s next for oxytocin?

Known as the “love hormone,” oxytocin is a neurotransmitter that is primarily synthesized in the hypothalamus. It plays a role in childbirth and lactation and is also involved in the regulation of social functioning and emotions. Research suggests low oxytocin levels are associated with diminished social functioning, regardless of ASD status.

Its potential as an autism therapy for children has been under study for a decade. Some findings link its use to improvements in core deficits associated with ASD, including repetitive behaviors, fixated or restricted interest, and social communication. A study published in 2020 showed that the treatment improved symptoms in high-functioning adults with ASD.

These were mostly small studies and were underpowered to reliably detect an effect of the therapy on social functioning. They often involved only a single dose of oxytocin. Some studies showed improvements, but others did not.

Still, interest in the treatment grew. Physicians began prescribing it for children with ASD, and parents began buying products containing oxytocin on the internet. Researchers feared this off-label use was becoming widespread, despite inconclusive evidence of efficacy.
 

High hopes

With support from a National Institutes of Health grant, Dr. Sikich and her team designed a phase 2, multicenter, randomized, double-blind, placebo-controlled study to determine whether the use of oxytocin in children with ASD works and is safe.

The challenges began before they even enrolled a single child. A number of behavioral assessment tools are used to measure social function in ASD, but there is no consensus on which one is best.

A simple blood test could determine how much oxytocin from the nasal spray was absorbed in the blood, but identifying how much made it to the brain would require fMRI, which is expensive and is challenging to use in this study population. Then there was the acquisition of the drug itself.

The Food and Drug Administration has approved intravenous oxytocin for inducing labor. Intranasal oxytocin is not approved for any indication and isn’t available commercially in the United States. Patients or researchers must secure the drug from a manufacturer in a country where it is approved or order it from a U.S. pharmacy that is capable of compounding IV oxytocin into an intranasal formulation.

The pharmacy in Switzerland Dr. Sikich planned to use couldn’t make enough for the study. Contracting with a compounding pharmacy in the United States was significantly more expensive and time consuming, but it was the researchers’ only option.

“If it hadn’t been something we expected to have a major benefit, I think we would have given up the project at multiple points along the line due to all of these challenges,” said Dr. Sikich.

In August 2014, with all the pieces finally in place, researchers began enrolling children aged 3-17 years. The final cohort included 290 participants with ASD, 146 in the oxytocin group and 144 in the placebo group. Of these, 48% had minimal verbal fluency, and 52% had fluent verbal speech.

Participants received daily synthetic oxytocin or placebo via a nasal spray for 24 weeks. The daily oxytocin dose was 48 IU for the first 7 weeks. After that, the dosage could be titrated to a maximum of 80 IU/d. The mean maximal total daily dose of oxytocin throughout the study was 67.6 ± 16.9 IU.
 

‘It just didn’t work’

Both study groups showed improvement in social withdrawal beginning at 4 weeks and continuing throughout the trial, as determined on the basis of caretakers’ responses on the Aberrant Behavior Checklist Modified Social Withdrawal Subscale, the study’s primary outcome measure.

Sociability and social motivation also improved in both groups, as measured by the Pervasive Developmental Disorders Behavior Inventory and the Social Responsiveness Scale.

But by the end of the trial, the difference between the groups in improvement of social function wasn’t significant (difference, -0.2 points; P = .61) after adjusting for age, verbal fluency, and baseline oxytocin level.

“We were so convinced that it would work,” Dr. Sikich said, “but it just didn’t.”

From observation, parents were also convinced the therapy was working. At the trial’s conclusion, fewer than half of caregivers correctly guessed whether their child was in the treatment group or the placebo group.

A lot of development changes can happen in a child over 6 months. It’s possible the improvements would have occurred regardless of the trial, Dr. Sikich said. Parents’ perceptions could also be a placebo effect. Their child was in a clinical trial of a drug they believed could improve social functioning, so in their mind, it did.

Caregivers received training in how to identify certain behavioral changes, which may have helped them spot an existing positive change they had previously overlooked. Or they may have worked with their child more intently as a result of their participation in the trial.

“People may start doing more things or doing them more intensively or purposefully, consciously or subconsciously, to try to help their child improve the skills or behaviors targeted by the active therapy in the study,” Dr. Sikich said. “These are things that might really help the child move forward which are completely separate from the medication being studied.”

The safety analysis offered more hopeful results. Only one serious adverse event from the treatment was reported: A 17-year-old participant taking a daily dose of 48 IU experienced a sedating effect while driving and had an accident.
 

Too soon to walk away?

Perhaps the most important take-away from the study is that even if it’s safe, intranasal oxytocin as it is currently used doesn’t work and clinicians shouldn’t prescribe it, said Daniel Geschwind, MD, PhD, director of the University of California, Los Angeles (UCLA) Center for Autism Research, who penned a commentary on the study and discussed the findings with this news organization.

“This study shows that using oxytocin the way it’s used in the community right now is not helping anybody, so why put a child through that?” added Dr. Geschwind, who also is a professor of genetics, neurology, and psychiatry at UCLA.

The trial highlights areas that need to be addressed in order to improve research in the field, he said. Establishing a consensus process to measure social functioning and figuring out a better way to access intranasal oxytocin would lead to studies that are more conclusive, comparable, and less expensive. Dr. Sikich agrees.

Despite the findings, Dr. Geschwind and other autism researchers say it’s too soon to walk away from oxytocin altogether, although it may be time to change the approach to autism research.

“We have to take a page from the playbook of modern medicine in other areas and begin to recognize that these syndromes are incredibly heterogeneous,” Dr. Geschwind says. “We can surmise, although we don’t know, that there might be different biological forms of autism that have different pathways involved that are going to respond differently to different medications.”

Calling the researchers’ efforts “heroic,” Karen Parker, PhD, an associate professor and associate chair of psychiatry and behavioral sciences at Stanford (Calif.) University, says efficacy trials such as this one are critical. However, Dr. Parker said in an interview, there are a number of questions that the study didn’t address.

The majority of medication dispensed in a standard intranasal device is sprayed into the back of the throat. Regular blood tests confirmed that oxytocin was getting into participants’ system, but, given how quickly oxytocin degrades in the blood, Dr. Parker said it’s hard to know just how much reached the brain.

It’s also unclear whether the results would have been different had the treatment been paired with behavioral therapy, an approach Dr. Parker suggests might benefit a subset of children with ASD.

A 2017 study from Dr. Parker’s lab found that children with ASD whose use of oxytocin at baseline was low derived greater benefit from synthetic oxytocin, something the new study failed to find. Still, Dr. Parker said, it’s possible oxytocin might increase social motivation and increase a child’s receptiveness to behavioral therapy.

“When you see a negative trial like this, it decreases enthusiasm for the therapy for autism in this context,” Dr. Parker said. “I hope people who are studying these syndromes will continue to explore oxytocin as a therapy.”

The study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development through the Autism Centers of Excellence Program and the Department of Psychiatry and Behavioral Sciences at Duke University. Full disclosures of the authors’ possible conflicts of interest are available online.

A version of this article first appeared on Medscape.com.

NEW ORLEANS – The increased use of digital screens for school during the COVID-19 pandemic may be causing convergence insufficiency in children, researchers say.

Although the long-term implications for current schoolchildren are not clear, convergence insufficiency sometimes persists for a lifetime, said Kammi Gunton, MD, interim chief of pediatric ophthalmology and strabismus at Wills Eye Hospital, Philadelphia.

“It’s important, if we use digital technology for education, that we are aware that it might contribute to increased eye symptoms in children,” Dr. Gunton told this news organization.

Dr. Gunton’s colleague, Jordan Hamburger, an MD candidate at Sidney Kimmel Medical College, Philadelphia, presented the finding at the American Academy of Ophthalmology 2021 Annual Meeting.

Convergence insufficiency is an impairment of binocularity. Symptoms include headaches while reading, words that seem to move around the page, blurriness, diplopia, and eye fatigue. It can be treated with exercise, prism glasses, or, rarely, surgery.

“We have some kids who improve with either time or maturity, then we have other patients who suffer from it for their entire lives,” Dr. Gunton said.

Previous research has linked the use of digital screens to convergence insufficiency, so when many schools shifted to distance learning for the pandemic, Dr. Gunton and her colleagues wanted to see whether it would have this effect on the students’ eyes.

They surveyed 110 healthy schoolchildren and adolescent students regarding eye symptoms before and after a day of virtual school. The mean age of the participants was 14 years (range, 10-17 years). The participants spent an average of 6.96 hours per day in virtual school. Forty-one percent also attended school in person part time. These students filled out the survey on days when they were in virtual school.

The participants answered questions on the Convergence Insufficiency Symptom Survey (CISS). The survey consists of 15 questions about eye complaints. On each question, the students rated symptoms from 0 to 4, with 4 indicating a severe symptom.

The average sum of the CISS scores rose from 5.17 before school to 9.82 after school, a statistically significant change (P < .001). Sixty-one percent of the participants reported an increase in convergence insufficiency symptoms.

Seventeen percent scored a total of at least 16, which is the threshold score considered suggestive of convergence insufficiency.

The researchers also found that, on average, the more hours each student spent in virtual school, the higher their CISS scores.

This makes sense, because reading requires convergence, Dr. Gunton said. The same problem might occur in traditional school if the students were looking at books all day instead of focusing on objects at various distances in their classrooms, such as the teacher or the whiteboard. “So, in the past, if you read a book, maybe you wouldn’t read for several hours, but now we’re asking children during virtual learning to stay on a device with the camera on,” she said.

Previous research has shown that people blink less when reading or using electronic devices, probably because of their increased concentration. This might explain symptoms such as burning and itching. Fifty-three percent of the students reported an increase in asthenopia symptoms.

The researchers would have liked to have compared the students in virtual school to a matched group of students in traditional school. However, almost all students were enrolled in virtual school when the study was conducted, making such a control difficult.

Although previous research has related virtual learning to myopia, as reported by this news organization, this study did not investigate myopia, and the researchers do not believe that convergence insufficiency causes myopia or vice versa.

Parents can help prevent convergence insufficiency during school by reminding their children to take breaks, Dr. Gunton said. She recommends the 20/20/20 rule: After 20 minutes of work that involves looking at objects nearby, students should take a 20-second break and look at something 20 feet away.

“I also think the take-home message is for parents to ask students if they’re having symptoms,” she said, “and if they hear complaints while kids are on the computers, to have them see an eye doctor and have an evaluation.”

Stephen Lipsky, MD, who wasn’t involved in the study, said he is seeing more cases of eye strain at Children’s Healthcare of Atlanta, where he is a consulting ophthalmologist.

“The study is very valuable in that it shines a light on the fact that these children do have symptoms, such as asthenopia or convergence insufficiency,” he told this news organization. “But I’m optimistic that with a return to more traditional learning, we will return the more traditional incidence of these problems.”

Dr. Gunton and Dr. Lipsky have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

NEW ORLEANS – The increased use of digital screens for school during the COVID-19 pandemic may be causing convergence insufficiency in children, researchers say.

Although the long-term implications for current schoolchildren are not clear, convergence insufficiency sometimes persists for a lifetime, said Kammi Gunton, MD, interim chief of pediatric ophthalmology and strabismus at Wills Eye Hospital, Philadelphia.

“It’s important, if we use digital technology for education, that we are aware that it might contribute to increased eye symptoms in children,” Dr. Gunton told this news organization.

Dr. Gunton’s colleague, Jordan Hamburger, an MD candidate at Sidney Kimmel Medical College, Philadelphia, presented the finding at the American Academy of Ophthalmology 2021 Annual Meeting.

Convergence insufficiency is an impairment of binocularity. Symptoms include headaches while reading, words that seem to move around the page, blurriness, diplopia, and eye fatigue. It can be treated with exercise, prism glasses, or, rarely, surgery.

“We have some kids who improve with either time or maturity, then we have other patients who suffer from it for their entire lives,” Dr. Gunton said.

Previous research has linked the use of digital screens to convergence insufficiency, so when many schools shifted to distance learning for the pandemic, Dr. Gunton and her colleagues wanted to see whether it would have this effect on the students’ eyes.

They surveyed 110 healthy schoolchildren and adolescent students regarding eye symptoms before and after a day of virtual school. The mean age of the participants was 14 years (range, 10-17 years). The participants spent an average of 6.96 hours per day in virtual school. Forty-one percent also attended school in person part time. These students filled out the survey on days when they were in virtual school.

The participants answered questions on the Convergence Insufficiency Symptom Survey (CISS). The survey consists of 15 questions about eye complaints. On each question, the students rated symptoms from 0 to 4, with 4 indicating a severe symptom.

The average sum of the CISS scores rose from 5.17 before school to 9.82 after school, a statistically significant change (P < .001). Sixty-one percent of the participants reported an increase in convergence insufficiency symptoms.

Seventeen percent scored a total of at least 16, which is the threshold score considered suggestive of convergence insufficiency.

The researchers also found that, on average, the more hours each student spent in virtual school, the higher their CISS scores.

This makes sense, because reading requires convergence, Dr. Gunton said. The same problem might occur in traditional school if the students were looking at books all day instead of focusing on objects at various distances in their classrooms, such as the teacher or the whiteboard. “So, in the past, if you read a book, maybe you wouldn’t read for several hours, but now we’re asking children during virtual learning to stay on a device with the camera on,” she said.

Previous research has shown that people blink less when reading or using electronic devices, probably because of their increased concentration. This might explain symptoms such as burning and itching. Fifty-three percent of the students reported an increase in asthenopia symptoms.

The researchers would have liked to have compared the students in virtual school to a matched group of students in traditional school. However, almost all students were enrolled in virtual school when the study was conducted, making such a control difficult.

Although previous research has related virtual learning to myopia, as reported by this news organization, this study did not investigate myopia, and the researchers do not believe that convergence insufficiency causes myopia or vice versa.

Parents can help prevent convergence insufficiency during school by reminding their children to take breaks, Dr. Gunton said. She recommends the 20/20/20 rule: After 20 minutes of work that involves looking at objects nearby, students should take a 20-second break and look at something 20 feet away.

“I also think the take-home message is for parents to ask students if they’re having symptoms,” she said, “and if they hear complaints while kids are on the computers, to have them see an eye doctor and have an evaluation.”

Stephen Lipsky, MD, who wasn’t involved in the study, said he is seeing more cases of eye strain at Children’s Healthcare of Atlanta, where he is a consulting ophthalmologist.

“The study is very valuable in that it shines a light on the fact that these children do have symptoms, such as asthenopia or convergence insufficiency,” he told this news organization. “But I’m optimistic that with a return to more traditional learning, we will return the more traditional incidence of these problems.”

Dr. Gunton and Dr. Lipsky have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

NEW ORLEANS – The increased use of digital screens for school during the COVID-19 pandemic may be causing convergence insufficiency in children, researchers say.

Although the long-term implications for current schoolchildren are not clear, convergence insufficiency sometimes persists for a lifetime, said Kammi Gunton, MD, interim chief of pediatric ophthalmology and strabismus at Wills Eye Hospital, Philadelphia.

“It’s important, if we use digital technology for education, that we are aware that it might contribute to increased eye symptoms in children,” Dr. Gunton told this news organization.

Dr. Gunton’s colleague, Jordan Hamburger, an MD candidate at Sidney Kimmel Medical College, Philadelphia, presented the finding at the American Academy of Ophthalmology 2021 Annual Meeting.

Convergence insufficiency is an impairment of binocularity. Symptoms include headaches while reading, words that seem to move around the page, blurriness, diplopia, and eye fatigue. It can be treated with exercise, prism glasses, or, rarely, surgery.

“We have some kids who improve with either time or maturity, then we have other patients who suffer from it for their entire lives,” Dr. Gunton said.

Previous research has linked the use of digital screens to convergence insufficiency, so when many schools shifted to distance learning for the pandemic, Dr. Gunton and her colleagues wanted to see whether it would have this effect on the students’ eyes.

They surveyed 110 healthy schoolchildren and adolescent students regarding eye symptoms before and after a day of virtual school. The mean age of the participants was 14 years (range, 10-17 years). The participants spent an average of 6.96 hours per day in virtual school. Forty-one percent also attended school in person part time. These students filled out the survey on days when they were in virtual school.

The participants answered questions on the Convergence Insufficiency Symptom Survey (CISS). The survey consists of 15 questions about eye complaints. On each question, the students rated symptoms from 0 to 4, with 4 indicating a severe symptom.

The average sum of the CISS scores rose from 5.17 before school to 9.82 after school, a statistically significant change (P < .001). Sixty-one percent of the participants reported an increase in convergence insufficiency symptoms.

Seventeen percent scored a total of at least 16, which is the threshold score considered suggestive of convergence insufficiency.

The researchers also found that, on average, the more hours each student spent in virtual school, the higher their CISS scores.

This makes sense, because reading requires convergence, Dr. Gunton said. The same problem might occur in traditional school if the students were looking at books all day instead of focusing on objects at various distances in their classrooms, such as the teacher or the whiteboard. “So, in the past, if you read a book, maybe you wouldn’t read for several hours, but now we’re asking children during virtual learning to stay on a device with the camera on,” she said.

Previous research has shown that people blink less when reading or using electronic devices, probably because of their increased concentration. This might explain symptoms such as burning and itching. Fifty-three percent of the students reported an increase in asthenopia symptoms.

The researchers would have liked to have compared the students in virtual school to a matched group of students in traditional school. However, almost all students were enrolled in virtual school when the study was conducted, making such a control difficult.

Although previous research has related virtual learning to myopia, as reported by this news organization, this study did not investigate myopia, and the researchers do not believe that convergence insufficiency causes myopia or vice versa.

Parents can help prevent convergence insufficiency during school by reminding their children to take breaks, Dr. Gunton said. She recommends the 20/20/20 rule: After 20 minutes of work that involves looking at objects nearby, students should take a 20-second break and look at something 20 feet away.

“I also think the take-home message is for parents to ask students if they’re having symptoms,” she said, “and if they hear complaints while kids are on the computers, to have them see an eye doctor and have an evaluation.”

Stephen Lipsky, MD, who wasn’t involved in the study, said he is seeing more cases of eye strain at Children’s Healthcare of Atlanta, where he is a consulting ophthalmologist.

“The study is very valuable in that it shines a light on the fact that these children do have symptoms, such as asthenopia or convergence insufficiency,” he told this news organization. “But I’m optimistic that with a return to more traditional learning, we will return the more traditional incidence of these problems.”

Dr. Gunton and Dr. Lipsky have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Mothers who use cannabis during pregnancy risk disrupting immune gene networks in the placenta and potentially increasing the risk of anxiety and hyperactivity in their children.

These findings emerged from a study led by Yasmin Hurd, PhD, a professor of psychiatry and director of the Addiction Institute at the Icahn School of Medicine at Mount Sinai, New York, and Yoko Nomura, PhD, a professor of behavioral neuroscience at Queen’s College, City University of New York, that was published online in Proceedings of the National Academy of Sciences.

The analysis assessed the effects of gestational maternal cannabis use on psychosocial and physiological measures in young children as well as its potentially immunomodulatory effect on the in utero environment as reflected in the placental transcriptome.

Participants were drawn from a larger cohort in a study launched in 2012; the investigators evaluated offspring aged 3-6 years for hair hormone levels, neurobehavioral traits on the Behavioral Assessment System for Children survey, and heart rate variability (HRV) at rest and during auditory startle.

The cohort consisted of 322 mother-child dyads and children with prenatal exposure to cannabis were compared with those having no exposure. The cohort consisted of 251 non–cannabis-using mothers and 71 cannabis-using mothers, with mean maternal ages in the two groups of 28.46 years and 25.91 years, respectively, The mothers gave birth at Mount Sinai and they and their children were assessed annually at affiliated medical centers in Mount Sinai’s catchment area.

For a subset of children with behavioral assessments, placental specimens collected at birth were processed for RNA sequencing.

Among the findings:

• Maternal cannabis use was associated with reduced maternal and paternal age, more single-mother pregnancies, state anxiety, trait anxiety, depression, cigarette smoking, and African American race.
• Hair hormone analysis revealed increased cortisol levels in the children of cannabis-using mothers, and was associated with greater anxiety, aggression, and hyperactivity.
• Affected children showed a reduction in the high-frequency component of HRV at baseline, reflecting reduced vagal tone.
• In the placenta, there was reduced expression of many genes involved in immune system function. These included genes for type I interferon, neutrophil, and cytokine-signaling pathways.

Several of these genes organized into coexpression networks that correlated with child anxiety and hyperactivity.

The principal active component of cannabis, tetrahydrocannabinol (THC), targets the endocannabinoid system in placental tissue and the developing brain, the authors noted. Exposure during pregnancy is associated with a range of adverse outcomes from fetal growth restriction to low birth weight and preterm birth.

“There are cannabinoid receptors on immune cells, and it is known that cannabinoids can alter immune function, which is important for maintaining maternal tolerance and protecting the fetus,” Dr. Hurd said. “It’s not surprising that something that affects the immune cells can have an impact on the developing fetus.”

“Overall, our findings reveal a relationship between [maternal cannabis use] and immune response gene networks in the placenta as a potential mediator of risk for anxiety-related problems in early childhood,” Dr. Hurd and colleagues wrote, adding that the results have significant implications for defining mental health issues in the children gestated by cannabis-smoking mothers.

Their results align with previous research indicating a greater risk for psychiatric illness in children with prenatal cannabis exposure from maternal use.

“While data are pretty limited in this realm, there are other studies that demonstrate a relationship between early child developmental and behavioral measures and cannabis use during pregnancy,” Camille Hoffman, MD, MSc, a high-risk obstetrics specialist and an associate professor at the University of Colorado at Denver, Aurora, said in an interview. “Our research group found children exposed to cannabis in utero at 10 weeks’ gestation and beyond were less interactive and more withdrawn than children who were not exposed.”

And THC remains in maternal breast milk even 6 weeks after usage stops.

The long-term effects of prenatal cannabis exposure remain to be determined and it is unknown whether the effects of gestational THC might attenuate as a child grows older. “We use early childhood measures in research as a proxy for the later development of diagnosed mental health conditions or behavioral problems,” Dr. Hoffman explained. “We know when we do this that not every child with an abnormal score early will go on to develop an actual condition. Fortunately, or unfortunately, other factors and exposures during childhood can change the trajectory for the better or worse.”

According to Dr. Hurd, child development is a dynamic process and epigenetic events in utero need not be deterministic. “The important thing is to identify children at risk early and to be able to go in and try to improve the environment they’re being raised in – not in terms of impoverishment but in terms of positive nurturing and giving the mother and family support.”

At the prenatal level, what’s the best advice for cannabis-using mothers-to-be? “If a woman doesn’t know she’s pregnant and has been using cannabis, taking extra choline for the remainder of the pregnancy can help buffer the potential negative impact of the cannabis exposure,” Dr. Hoffman said. The Food and Drug Administration and the American Medical Association recommend a dose of 550 mg daily. “The same is true for alcohol, which we know is also very bad for fetal brain development. This is not to say go ahead and use these substances and just take choline. The choline is more to try and salvage damage to the fetal brain that may have already occurred.”

This study was supported by the National Institute of Mental Health and the National Institute on Drug Abuse. The authors declared no competing interests. Dr. Hoffman disclosed no conflicts of interest with respect to her comments.

Mothers who use cannabis during pregnancy risk disrupting immune gene networks in the placenta and potentially increasing the risk of anxiety and hyperactivity in their children.

These findings emerged from a study led by Yasmin Hurd, PhD, a professor of psychiatry and director of the Addiction Institute at the Icahn School of Medicine at Mount Sinai, New York, and Yoko Nomura, PhD, a professor of behavioral neuroscience at Queen’s College, City University of New York, that was published online in Proceedings of the National Academy of Sciences.

The analysis assessed the effects of gestational maternal cannabis use on psychosocial and physiological measures in young children as well as its potentially immunomodulatory effect on the in utero environment as reflected in the placental transcriptome.

Participants were drawn from a larger cohort in a study launched in 2012; the investigators evaluated offspring aged 3-6 years for hair hormone levels, neurobehavioral traits on the Behavioral Assessment System for Children survey, and heart rate variability (HRV) at rest and during auditory startle.

The cohort consisted of 322 mother-child dyads and children with prenatal exposure to cannabis were compared with those having no exposure. The cohort consisted of 251 non–cannabis-using mothers and 71 cannabis-using mothers, with mean maternal ages in the two groups of 28.46 years and 25.91 years, respectively, The mothers gave birth at Mount Sinai and they and their children were assessed annually at affiliated medical centers in Mount Sinai’s catchment area.

For a subset of children with behavioral assessments, placental specimens collected at birth were processed for RNA sequencing.

Among the findings:

• Maternal cannabis use was associated with reduced maternal and paternal age, more single-mother pregnancies, state anxiety, trait anxiety, depression, cigarette smoking, and African American race.
• Hair hormone analysis revealed increased cortisol levels in the children of cannabis-using mothers, and was associated with greater anxiety, aggression, and hyperactivity.
• Affected children showed a reduction in the high-frequency component of HRV at baseline, reflecting reduced vagal tone.
• In the placenta, there was reduced expression of many genes involved in immune system function. These included genes for type I interferon, neutrophil, and cytokine-signaling pathways.

Several of these genes organized into coexpression networks that correlated with child anxiety and hyperactivity.

The principal active component of cannabis, tetrahydrocannabinol (THC), targets the endocannabinoid system in placental tissue and the developing brain, the authors noted. Exposure during pregnancy is associated with a range of adverse outcomes from fetal growth restriction to low birth weight and preterm birth.

“There are cannabinoid receptors on immune cells, and it is known that cannabinoids can alter immune function, which is important for maintaining maternal tolerance and protecting the fetus,” Dr. Hurd said. “It’s not surprising that something that affects the immune cells can have an impact on the developing fetus.”

“Overall, our findings reveal a relationship between [maternal cannabis use] and immune response gene networks in the placenta as a potential mediator of risk for anxiety-related problems in early childhood,” Dr. Hurd and colleagues wrote, adding that the results have significant implications for defining mental health issues in the children gestated by cannabis-smoking mothers.

Their results align with previous research indicating a greater risk for psychiatric illness in children with prenatal cannabis exposure from maternal use.

“While data are pretty limited in this realm, there are other studies that demonstrate a relationship between early child developmental and behavioral measures and cannabis use during pregnancy,” Camille Hoffman, MD, MSc, a high-risk obstetrics specialist and an associate professor at the University of Colorado at Denver, Aurora, said in an interview. “Our research group found children exposed to cannabis in utero at 10 weeks’ gestation and beyond were less interactive and more withdrawn than children who were not exposed.”

And THC remains in maternal breast milk even 6 weeks after usage stops.

The long-term effects of prenatal cannabis exposure remain to be determined and it is unknown whether the effects of gestational THC might attenuate as a child grows older. “We use early childhood measures in research as a proxy for the later development of diagnosed mental health conditions or behavioral problems,” Dr. Hoffman explained. “We know when we do this that not every child with an abnormal score early will go on to develop an actual condition. Fortunately, or unfortunately, other factors and exposures during childhood can change the trajectory for the better or worse.”

According to Dr. Hurd, child development is a dynamic process and epigenetic events in utero need not be deterministic. “The important thing is to identify children at risk early and to be able to go in and try to improve the environment they’re being raised in – not in terms of impoverishment but in terms of positive nurturing and giving the mother and family support.”

At the prenatal level, what’s the best advice for cannabis-using mothers-to-be? “If a woman doesn’t know she’s pregnant and has been using cannabis, taking extra choline for the remainder of the pregnancy can help buffer the potential negative impact of the cannabis exposure,” Dr. Hoffman said. The Food and Drug Administration and the American Medical Association recommend a dose of 550 mg daily. “The same is true for alcohol, which we know is also very bad for fetal brain development. This is not to say go ahead and use these substances and just take choline. The choline is more to try and salvage damage to the fetal brain that may have already occurred.”

This study was supported by the National Institute of Mental Health and the National Institute on Drug Abuse. The authors declared no competing interests. Dr. Hoffman disclosed no conflicts of interest with respect to her comments.

Mothers who use cannabis during pregnancy risk disrupting immune gene networks in the placenta and potentially increasing the risk of anxiety and hyperactivity in their children.

These findings emerged from a study led by Yasmin Hurd, PhD, a professor of psychiatry and director of the Addiction Institute at the Icahn School of Medicine at Mount Sinai, New York, and Yoko Nomura, PhD, a professor of behavioral neuroscience at Queen’s College, City University of New York, that was published online in Proceedings of the National Academy of Sciences.

The analysis assessed the effects of gestational maternal cannabis use on psychosocial and physiological measures in young children as well as its potentially immunomodulatory effect on the in utero environment as reflected in the placental transcriptome.

Participants were drawn from a larger cohort in a study launched in 2012; the investigators evaluated offspring aged 3-6 years for hair hormone levels, neurobehavioral traits on the Behavioral Assessment System for Children survey, and heart rate variability (HRV) at rest and during auditory startle.

The cohort consisted of 322 mother-child dyads and children with prenatal exposure to cannabis were compared with those having no exposure. The cohort consisted of 251 non–cannabis-using mothers and 71 cannabis-using mothers, with mean maternal ages in the two groups of 28.46 years and 25.91 years, respectively, The mothers gave birth at Mount Sinai and they and their children were assessed annually at affiliated medical centers in Mount Sinai’s catchment area.

For a subset of children with behavioral assessments, placental specimens collected at birth were processed for RNA sequencing.

Among the findings:

• Maternal cannabis use was associated with reduced maternal and paternal age, more single-mother pregnancies, state anxiety, trait anxiety, depression, cigarette smoking, and African American race.
• Hair hormone analysis revealed increased cortisol levels in the children of cannabis-using mothers, and was associated with greater anxiety, aggression, and hyperactivity.
• Affected children showed a reduction in the high-frequency component of HRV at baseline, reflecting reduced vagal tone.
• In the placenta, there was reduced expression of many genes involved in immune system function. These included genes for type I interferon, neutrophil, and cytokine-signaling pathways.

Several of these genes organized into coexpression networks that correlated with child anxiety and hyperactivity.

The principal active component of cannabis, tetrahydrocannabinol (THC), targets the endocannabinoid system in placental tissue and the developing brain, the authors noted. Exposure during pregnancy is associated with a range of adverse outcomes from fetal growth restriction to low birth weight and preterm birth.

“There are cannabinoid receptors on immune cells, and it is known that cannabinoids can alter immune function, which is important for maintaining maternal tolerance and protecting the fetus,” Dr. Hurd said. “It’s not surprising that something that affects the immune cells can have an impact on the developing fetus.”

“Overall, our findings reveal a relationship between [maternal cannabis use] and immune response gene networks in the placenta as a potential mediator of risk for anxiety-related problems in early childhood,” Dr. Hurd and colleagues wrote, adding that the results have significant implications for defining mental health issues in the children gestated by cannabis-smoking mothers.

Their results align with previous research indicating a greater risk for psychiatric illness in children with prenatal cannabis exposure from maternal use.

“While data are pretty limited in this realm, there are other studies that demonstrate a relationship between early child developmental and behavioral measures and cannabis use during pregnancy,” Camille Hoffman, MD, MSc, a high-risk obstetrics specialist and an associate professor at the University of Colorado at Denver, Aurora, said in an interview. “Our research group found children exposed to cannabis in utero at 10 weeks’ gestation and beyond were less interactive and more withdrawn than children who were not exposed.”

And THC remains in maternal breast milk even 6 weeks after usage stops.

The long-term effects of prenatal cannabis exposure remain to be determined and it is unknown whether the effects of gestational THC might attenuate as a child grows older. “We use early childhood measures in research as a proxy for the later development of diagnosed mental health conditions or behavioral problems,” Dr. Hoffman explained. “We know when we do this that not every child with an abnormal score early will go on to develop an actual condition. Fortunately, or unfortunately, other factors and exposures during childhood can change the trajectory for the better or worse.”

According to Dr. Hurd, child development is a dynamic process and epigenetic events in utero need not be deterministic. “The important thing is to identify children at risk early and to be able to go in and try to improve the environment they’re being raised in – not in terms of impoverishment but in terms of positive nurturing and giving the mother and family support.”

At the prenatal level, what’s the best advice for cannabis-using mothers-to-be? “If a woman doesn’t know she’s pregnant and has been using cannabis, taking extra choline for the remainder of the pregnancy can help buffer the potential negative impact of the cannabis exposure,” Dr. Hoffman said. The Food and Drug Administration and the American Medical Association recommend a dose of 550 mg daily. “The same is true for alcohol, which we know is also very bad for fetal brain development. This is not to say go ahead and use these substances and just take choline. The choline is more to try and salvage damage to the fetal brain that may have already occurred.”

This study was supported by the National Institute of Mental Health and the National Institute on Drug Abuse. The authors declared no competing interests. Dr. Hoffman disclosed no conflicts of interest with respect to her comments.

I was recently asked to see a 16-year-old, unvaccinated (against COVID-19) adolescent with hypothyroidism and obesity (body mass index 37 kg/m²) seen in the pediatric emergency department with tachycardia, O₂ saturation 96%, urinary tract infection, poor appetite, and nausea. Her chest x-ray had low lung volumes but no infiltrates. She was noted to be dehydrated. Testing for COVID-19 was PCR positive.¹

She was observed overnight, tolerated oral rehydration, and was being readied for discharge. Pediatric Infectious Diseases was called about prescribing remdesivir.

Remdesivir was not indicated as its current use is limited to inpatients with oxygen desaturations less than 94%. Infectious Diseases Society of America guidelines do recommend the use of monoclonal antibodies against the SARS-CoV-2 spike protein for prevention of COVID disease progression in high-risk individuals. Specifically, the IDSA guidelines say, “Among ambulatory patients with mild to moderate COVID-19 at high risk for progression to severe disease, bamlanivimab/etesevimab, casirivimab/imdevimab, or sotrovimab rather than no neutralizing antibody treatment.”

The Food and Drug Administration’s Emergency Use Authorization (EUA) allowed use of specific monoclonal antibodies (casirivimab/imdevimab in combination, bamlanivimab/etesevimab in combination, and sotrovimab alone) for individuals 12 years and above with a minimum weight of 40 kg with high-risk conditions, describing the evidence as moderate certainty.²

Several questions have arisen regarding their use. Which children qualify under the EUA? Are the available monoclonal antibodies effective for SARS-CoV-2 variants? What adverse events were observed? Are there implementation hurdles?

Unlike the EUA for prophylactic use, which targeted unvaccinated individuals and those unlikely to have a good antibody response to vaccine, use of monoclonal antibody for prevention of progression does not have such restrictions. Effectiveness may vary by local variant susceptibility and should be considered in the choice of the most appropriate monoclonal antibody therapy. Reductions in hospitalization and progression to critical disease status were reported from phase 3 studies; reductions were also observed in mortality in some, but not all, studies. Enhanced viral clearance on day 7 was observed with few subjects having persistent high viral load.

Which children qualify under the EUA? Adolescents 12 years and older and over 40 kg are eligible if a high risk condition is present. High-risk conditions include body mass index at the 85th percentile or higher, immunosuppressive disease, or receipt of immunosuppressive therapies, or baseline (pre-COVID infection) medical-related technological dependence such as tracheostomy or positive pressure ventilation. Additional high-risk conditions are neurodevelopmental disorders, sickle cell disease, congenital or acquired heart disease, asthma, or reactive airway or other chronic respiratory disease that requires daily medication for control, diabetes, chronic kidney disease, or pregnancy.³

Are the available monoclonal antibodies effective for SARS-CoV-2 variants? Of course, this is a critical question and relies on knowledge of the dominant variant in a specific geographic location. The CDC data on which variants are susceptible to which monoclonal therapies were updated as of Oct. 21 online (see Table 1). Local departments of public health often will have current data on the dominant variant in the community. Currently, the dominant variant in the United States is Delta and it is anticipated to be susceptible to the three monoclonal treatments authorized under the EUA based on in vitro neutralizing assays.

Implementation challenges

The first challenge is finding a location to infuse the monoclonal antibodies. Although they can be given subcutaneously, the dose is large and little, if any, time is saved as the recommendation is for observation post administration for 1 hour. The challenge we and other centers may face is that the patients are COVID PCR+ and therefore our usual infusion program, which often is occupied by individuals already compromised and at high risk for severe COVID, is an undesirable location. We are planning to use the emergency department to accommodate such patients currently, but even that solution creates challenges for a busy, urban medical center.

Summary

Anti–SARS-CoV-2 monoclonal antibodies are an important part of the therapeutic approach to minimizing disease severity. Clinicians should review high-risk conditions in adolescents who are PCR+ for SARS-CoV-2 and have mild to moderate symptoms. Medical care systems should implement programs to make monoclonal infusions available for such high-risk adolescents.⁴ Obesity and asthma reactive airways or requiring daily medication for control are the two most common conditions that place adolescents with COVID-19 at risk for progression to hospitalization and severe disease in addition to the more traditional immune-compromising conditions and medical fragility.

Dr. Pelton is professor of pediatrics and epidemiology at Boston University schools of medicine and public health and senior attending physician in pediatric infectious diseases, Boston Medical Center. Email him at [email protected].

References

1. Federal Response to COVID-19: Monoclonal Antibody Clinical Implementation Guide. U.S. Department of Health and Human Services. 2021 Sep 2.

2. Bhimraj A et al. IDSA Guidelines on the Treatment and Management of Patients with COVID-19. Last updated 2021 Nov 9.

3. Anti-SARS-CoV-2 Monoclonal Antibodies. National Institutes of Health’s COVID 19 Treatment Guidelines. Last updated 2021 Oct 19.

4. Spreading the Word on the Benefits of Monoclonal Antibodies for COVID-19, by Hannah R. Buchdahl. CDC Foundation, 2021 Jul 2.

I was recently asked to see a 16-year-old, unvaccinated (against COVID-19) adolescent with hypothyroidism and obesity (body mass index 37 kg/m²) seen in the pediatric emergency department with tachycardia, O₂ saturation 96%, urinary tract infection, poor appetite, and nausea. Her chest x-ray had low lung volumes but no infiltrates. She was noted to be dehydrated. Testing for COVID-19 was PCR positive.¹

She was observed overnight, tolerated oral rehydration, and was being readied for discharge. Pediatric Infectious Diseases was called about prescribing remdesivir.

Remdesivir was not indicated as its current use is limited to inpatients with oxygen desaturations less than 94%. Infectious Diseases Society of America guidelines do recommend the use of monoclonal antibodies against the SARS-CoV-2 spike protein for prevention of COVID disease progression in high-risk individuals. Specifically, the IDSA guidelines say, “Among ambulatory patients with mild to moderate COVID-19 at high risk for progression to severe disease, bamlanivimab/etesevimab, casirivimab/imdevimab, or sotrovimab rather than no neutralizing antibody treatment.”

The Food and Drug Administration’s Emergency Use Authorization (EUA) allowed use of specific monoclonal antibodies (casirivimab/imdevimab in combination, bamlanivimab/etesevimab in combination, and sotrovimab alone) for individuals 12 years and above with a minimum weight of 40 kg with high-risk conditions, describing the evidence as moderate certainty.²

Several questions have arisen regarding their use. Which children qualify under the EUA? Are the available monoclonal antibodies effective for SARS-CoV-2 variants? What adverse events were observed? Are there implementation hurdles?

Unlike the EUA for prophylactic use, which targeted unvaccinated individuals and those unlikely to have a good antibody response to vaccine, use of monoclonal antibody for prevention of progression does not have such restrictions. Effectiveness may vary by local variant susceptibility and should be considered in the choice of the most appropriate monoclonal antibody therapy. Reductions in hospitalization and progression to critical disease status were reported from phase 3 studies; reductions were also observed in mortality in some, but not all, studies. Enhanced viral clearance on day 7 was observed with few subjects having persistent high viral load.

Which children qualify under the EUA? Adolescents 12 years and older and over 40 kg are eligible if a high risk condition is present. High-risk conditions include body mass index at the 85th percentile or higher, immunosuppressive disease, or receipt of immunosuppressive therapies, or baseline (pre-COVID infection) medical-related technological dependence such as tracheostomy or positive pressure ventilation. Additional high-risk conditions are neurodevelopmental disorders, sickle cell disease, congenital or acquired heart disease, asthma, or reactive airway or other chronic respiratory disease that requires daily medication for control, diabetes, chronic kidney disease, or pregnancy.³

Are the available monoclonal antibodies effective for SARS-CoV-2 variants? Of course, this is a critical question and relies on knowledge of the dominant variant in a specific geographic location. The CDC data on which variants are susceptible to which monoclonal therapies were updated as of Oct. 21 online (see Table 1). Local departments of public health often will have current data on the dominant variant in the community. Currently, the dominant variant in the United States is Delta and it is anticipated to be susceptible to the three monoclonal treatments authorized under the EUA based on in vitro neutralizing assays.

Implementation challenges

The first challenge is finding a location to infuse the monoclonal antibodies. Although they can be given subcutaneously, the dose is large and little, if any, time is saved as the recommendation is for observation post administration for 1 hour. The challenge we and other centers may face is that the patients are COVID PCR+ and therefore our usual infusion program, which often is occupied by individuals already compromised and at high risk for severe COVID, is an undesirable location. We are planning to use the emergency department to accommodate such patients currently, but even that solution creates challenges for a busy, urban medical center.

Summary

Anti–SARS-CoV-2 monoclonal antibodies are an important part of the therapeutic approach to minimizing disease severity. Clinicians should review high-risk conditions in adolescents who are PCR+ for SARS-CoV-2 and have mild to moderate symptoms. Medical care systems should implement programs to make monoclonal infusions available for such high-risk adolescents.⁴ Obesity and asthma reactive airways or requiring daily medication for control are the two most common conditions that place adolescents with COVID-19 at risk for progression to hospitalization and severe disease in addition to the more traditional immune-compromising conditions and medical fragility.

Dr. Pelton is professor of pediatrics and epidemiology at Boston University schools of medicine and public health and senior attending physician in pediatric infectious diseases, Boston Medical Center. Email him at [email protected].

References

1. Federal Response to COVID-19: Monoclonal Antibody Clinical Implementation Guide. U.S. Department of Health and Human Services. 2021 Sep 2.

2. Bhimraj A et al. IDSA Guidelines on the Treatment and Management of Patients with COVID-19. Last updated 2021 Nov 9.

3. Anti-SARS-CoV-2 Monoclonal Antibodies. National Institutes of Health’s COVID 19 Treatment Guidelines. Last updated 2021 Oct 19.

4. Spreading the Word on the Benefits of Monoclonal Antibodies for COVID-19, by Hannah R. Buchdahl. CDC Foundation, 2021 Jul 2.

I was recently asked to see a 16-year-old, unvaccinated (against COVID-19) adolescent with hypothyroidism and obesity (body mass index 37 kg/m²) seen in the pediatric emergency department with tachycardia, O₂ saturation 96%, urinary tract infection, poor appetite, and nausea. Her chest x-ray had low lung volumes but no infiltrates. She was noted to be dehydrated. Testing for COVID-19 was PCR positive.¹

She was observed overnight, tolerated oral rehydration, and was being readied for discharge. Pediatric Infectious Diseases was called about prescribing remdesivir.

Remdesivir was not indicated as its current use is limited to inpatients with oxygen desaturations less than 94%. Infectious Diseases Society of America guidelines do recommend the use of monoclonal antibodies against the SARS-CoV-2 spike protein for prevention of COVID disease progression in high-risk individuals. Specifically, the IDSA guidelines say, “Among ambulatory patients with mild to moderate COVID-19 at high risk for progression to severe disease, bamlanivimab/etesevimab, casirivimab/imdevimab, or sotrovimab rather than no neutralizing antibody treatment.”

The Food and Drug Administration’s Emergency Use Authorization (EUA) allowed use of specific monoclonal antibodies (casirivimab/imdevimab in combination, bamlanivimab/etesevimab in combination, and sotrovimab alone) for individuals 12 years and above with a minimum weight of 40 kg with high-risk conditions, describing the evidence as moderate certainty.²

Several questions have arisen regarding their use. Which children qualify under the EUA? Are the available monoclonal antibodies effective for SARS-CoV-2 variants? What adverse events were observed? Are there implementation hurdles?

Unlike the EUA for prophylactic use, which targeted unvaccinated individuals and those unlikely to have a good antibody response to vaccine, use of monoclonal antibody for prevention of progression does not have such restrictions. Effectiveness may vary by local variant susceptibility and should be considered in the choice of the most appropriate monoclonal antibody therapy. Reductions in hospitalization and progression to critical disease status were reported from phase 3 studies; reductions were also observed in mortality in some, but not all, studies. Enhanced viral clearance on day 7 was observed with few subjects having persistent high viral load.

Which children qualify under the EUA? Adolescents 12 years and older and over 40 kg are eligible if a high risk condition is present. High-risk conditions include body mass index at the 85th percentile or higher, immunosuppressive disease, or receipt of immunosuppressive therapies, or baseline (pre-COVID infection) medical-related technological dependence such as tracheostomy or positive pressure ventilation. Additional high-risk conditions are neurodevelopmental disorders, sickle cell disease, congenital or acquired heart disease, asthma, or reactive airway or other chronic respiratory disease that requires daily medication for control, diabetes, chronic kidney disease, or pregnancy.³

Are the available monoclonal antibodies effective for SARS-CoV-2 variants? Of course, this is a critical question and relies on knowledge of the dominant variant in a specific geographic location. The CDC data on which variants are susceptible to which monoclonal therapies were updated as of Oct. 21 online (see Table 1). Local departments of public health often will have current data on the dominant variant in the community. Currently, the dominant variant in the United States is Delta and it is anticipated to be susceptible to the three monoclonal treatments authorized under the EUA based on in vitro neutralizing assays.

Implementation challenges

The first challenge is finding a location to infuse the monoclonal antibodies. Although they can be given subcutaneously, the dose is large and little, if any, time is saved as the recommendation is for observation post administration for 1 hour. The challenge we and other centers may face is that the patients are COVID PCR+ and therefore our usual infusion program, which often is occupied by individuals already compromised and at high risk for severe COVID, is an undesirable location. We are planning to use the emergency department to accommodate such patients currently, but even that solution creates challenges for a busy, urban medical center.

Summary

Anti–SARS-CoV-2 monoclonal antibodies are an important part of the therapeutic approach to minimizing disease severity. Clinicians should review high-risk conditions in adolescents who are PCR+ for SARS-CoV-2 and have mild to moderate symptoms. Medical care systems should implement programs to make monoclonal infusions available for such high-risk adolescents.⁴ Obesity and asthma reactive airways or requiring daily medication for control are the two most common conditions that place adolescents with COVID-19 at risk for progression to hospitalization and severe disease in addition to the more traditional immune-compromising conditions and medical fragility.

Dr. Pelton is professor of pediatrics and epidemiology at Boston University schools of medicine and public health and senior attending physician in pediatric infectious diseases, Boston Medical Center. Email him at [email protected].

References

1. Federal Response to COVID-19: Monoclonal Antibody Clinical Implementation Guide. U.S. Department of Health and Human Services. 2021 Sep 2.

2. Bhimraj A et al. IDSA Guidelines on the Treatment and Management of Patients with COVID-19. Last updated 2021 Nov 9.

3. Anti-SARS-CoV-2 Monoclonal Antibodies. National Institutes of Health’s COVID 19 Treatment Guidelines. Last updated 2021 Oct 19.

4. Spreading the Word on the Benefits of Monoclonal Antibodies for COVID-19, by Hannah R. Buchdahl. CDC Foundation, 2021 Jul 2.

How much did you get per tooth from the Tooth Fairy? How much do your children or grandchildren receive each time they lose a baby tooth? In my family the Tooth Fairy seems to be more than keeping with inflation. Has she ever been caught in the act of swapping cash for enamel in your home? Has she every slipped up one night but managed to resurrect her credibility the following night by doubling the reward? And, by the way, what does the Tooth Fairy do with all those teeth, and who’s funding her nocturnal switcheroos?

A recent study from the Center for Genomic Medicine at the Massachusetts General Hospital in Boston may provide an answer to at least one of those questions. It turns out some researchers have been collecting baby teeth in hopes of assessing prenatal and perinatal stress in infants.

Not surprisingly, teeth are like trees, preserving a history of the environment in their growth rings. The Boston researchers hypothesized that the thickness of one particular growth line referred to as the neonatal line (NNL) might reflect prenatal and immediate postnatal environmental stress. Using data and naturally shed teeth collected in an English longitudinal study, the authors discovered that the teeth of children whose mothers had a long history of severe depression or other psychiatric problems and children of mothers who at 32 weeks’ gestation experienced anxiety and/or depression were more likely to have thicker NNLs. On the other hand, the teeth of children whose mothers had received “significant social support” in the immediate postnatal period exhibited thinner NNLs.

Based on anecdotal observations, I think most of us already suspected that the children whose mothers had significant psychiatric illness began life with a challenge, but it is nice to know that we may now have a tool to document one small bit of evidence of the structural damage that occurred during this period of stress. Of course, the prior owners of these baby teeth won’t benefit from the findings in this study; however, the evidence that social support during the critical perinatal period can ameliorate the damage might stimulate more robust prenatal programs for mother and infants at risk in the future.

It will be interesting to see if this investigative tool becomes more widely used to determine the degree to which a variety of potential perinatal stressors are manifesting themselves in structural change in newborns. For example, collecting baby teeth from neonatal ICU graduates may answer some questions about how certain environmental conditions such as sound, vibration, bright light, and temperature may result in long-term damage to the infants. Most of us suspect that skin-to-skin contact with mother and kangaroo care are beneficial. A study that includes a survey of NNLs might go a long way toward supporting our suspicions.

I can even imagine that a deep retrospective study of NNLs in baby teeth collected over the last 100 years might demonstrate the effect of phenomena such as wars, natural disasters, forced migration, and pandemics, to name a few.

It may be time to put out a nationwide call to all Tooth Fairies both active and retired to dig deep in their top bureau drawers. Those little bits of long-forgotten enamel may hold the answers to a plethora of unanswered questions about those critical months surrounding the birth of a child.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

How much did you get per tooth from the Tooth Fairy? How much do your children or grandchildren receive each time they lose a baby tooth? In my family the Tooth Fairy seems to be more than keeping with inflation. Has she ever been caught in the act of swapping cash for enamel in your home? Has she every slipped up one night but managed to resurrect her credibility the following night by doubling the reward? And, by the way, what does the Tooth Fairy do with all those teeth, and who’s funding her nocturnal switcheroos?

A recent study from the Center for Genomic Medicine at the Massachusetts General Hospital in Boston may provide an answer to at least one of those questions. It turns out some researchers have been collecting baby teeth in hopes of assessing prenatal and perinatal stress in infants.

Not surprisingly, teeth are like trees, preserving a history of the environment in their growth rings. The Boston researchers hypothesized that the thickness of one particular growth line referred to as the neonatal line (NNL) might reflect prenatal and immediate postnatal environmental stress. Using data and naturally shed teeth collected in an English longitudinal study, the authors discovered that the teeth of children whose mothers had a long history of severe depression or other psychiatric problems and children of mothers who at 32 weeks’ gestation experienced anxiety and/or depression were more likely to have thicker NNLs. On the other hand, the teeth of children whose mothers had received “significant social support” in the immediate postnatal period exhibited thinner NNLs.

Based on anecdotal observations, I think most of us already suspected that the children whose mothers had significant psychiatric illness began life with a challenge, but it is nice to know that we may now have a tool to document one small bit of evidence of the structural damage that occurred during this period of stress. Of course, the prior owners of these baby teeth won’t benefit from the findings in this study; however, the evidence that social support during the critical perinatal period can ameliorate the damage might stimulate more robust prenatal programs for mother and infants at risk in the future.

It will be interesting to see if this investigative tool becomes more widely used to determine the degree to which a variety of potential perinatal stressors are manifesting themselves in structural change in newborns. For example, collecting baby teeth from neonatal ICU graduates may answer some questions about how certain environmental conditions such as sound, vibration, bright light, and temperature may result in long-term damage to the infants. Most of us suspect that skin-to-skin contact with mother and kangaroo care are beneficial. A study that includes a survey of NNLs might go a long way toward supporting our suspicions.

I can even imagine that a deep retrospective study of NNLs in baby teeth collected over the last 100 years might demonstrate the effect of phenomena such as wars, natural disasters, forced migration, and pandemics, to name a few.

It may be time to put out a nationwide call to all Tooth Fairies both active and retired to dig deep in their top bureau drawers. Those little bits of long-forgotten enamel may hold the answers to a plethora of unanswered questions about those critical months surrounding the birth of a child.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

How much did you get per tooth from the Tooth Fairy? How much do your children or grandchildren receive each time they lose a baby tooth? In my family the Tooth Fairy seems to be more than keeping with inflation. Has she ever been caught in the act of swapping cash for enamel in your home? Has she every slipped up one night but managed to resurrect her credibility the following night by doubling the reward? And, by the way, what does the Tooth Fairy do with all those teeth, and who’s funding her nocturnal switcheroos?

A recent study from the Center for Genomic Medicine at the Massachusetts General Hospital in Boston may provide an answer to at least one of those questions. It turns out some researchers have been collecting baby teeth in hopes of assessing prenatal and perinatal stress in infants.

Not surprisingly, teeth are like trees, preserving a history of the environment in their growth rings. The Boston researchers hypothesized that the thickness of one particular growth line referred to as the neonatal line (NNL) might reflect prenatal and immediate postnatal environmental stress. Using data and naturally shed teeth collected in an English longitudinal study, the authors discovered that the teeth of children whose mothers had a long history of severe depression or other psychiatric problems and children of mothers who at 32 weeks’ gestation experienced anxiety and/or depression were more likely to have thicker NNLs. On the other hand, the teeth of children whose mothers had received “significant social support” in the immediate postnatal period exhibited thinner NNLs.

Based on anecdotal observations, I think most of us already suspected that the children whose mothers had significant psychiatric illness began life with a challenge, but it is nice to know that we may now have a tool to document one small bit of evidence of the structural damage that occurred during this period of stress. Of course, the prior owners of these baby teeth won’t benefit from the findings in this study; however, the evidence that social support during the critical perinatal period can ameliorate the damage might stimulate more robust prenatal programs for mother and infants at risk in the future.

It will be interesting to see if this investigative tool becomes more widely used to determine the degree to which a variety of potential perinatal stressors are manifesting themselves in structural change in newborns. For example, collecting baby teeth from neonatal ICU graduates may answer some questions about how certain environmental conditions such as sound, vibration, bright light, and temperature may result in long-term damage to the infants. Most of us suspect that skin-to-skin contact with mother and kangaroo care are beneficial. A study that includes a survey of NNLs might go a long way toward supporting our suspicions.

I can even imagine that a deep retrospective study of NNLs in baby teeth collected over the last 100 years might demonstrate the effect of phenomena such as wars, natural disasters, forced migration, and pandemics, to name a few.

It may be time to put out a nationwide call to all Tooth Fairies both active and retired to dig deep in their top bureau drawers. Those little bits of long-forgotten enamel may hold the answers to a plethora of unanswered questions about those critical months surrounding the birth of a child.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

A series of sharp knocks on his driver’s side window startled Jason Burt awake.

It was the middle of the night on a Saturday in 2016. Burt was sleeping in his pickup truck in the parking lot of St. Jude Children’s Research Hospital in downtown Memphis, Tenn., where his 5-year-old daughter was being treated for brain cancer. He’d driven more than 500 miles from his home in Central Texas to visit her.

A St. Jude security guard peered into the truck and asked Burt what he was doing. Burt explained that his daughter and her mother, his ex-girlfriend, were staying in the hospital’s free patient housing. But St. Jude provides housing for only one parent. Burt, a school bus driver making $20,000 a year, told the guard he couldn’t afford a hotel. The guard let the exhausted father go back to sleep.

St. Jude would do no more to find him a place to stay.

“They were aware of the situation,” Burt said. “I didn’t push anything. I was just grateful she was getting treated and I was doing what I needed to do.”

St. Jude is the largest and most highly regarded health care charity in the country. Each year, the Memphis hospital’s fundraisers send out hundreds of millions of letters, many with heart-wrenching photographs of children left bald from battling cancer. Celebrities like Jennifer Aniston and Sofia Vergara sing the hospital’s praises in televised advertisements. This year, St. Jude’s fundraising reached outer space. The SpaceX Inspiration4 mission in September included a former St. Jude patient as a crew member.

Last year, St. Jude raised a record $2 billion. U.S. News & World Report ranked it the country’s 10th-best children’s cancer hospital, and St. Jude raised roughly as much as the nine hospitals ahead of it put together. It currently has $5.2 billion in reserves, a sum large enough to run the institution at current levels for the next four and a half years without a single additional donation.

St. Jude makes a unique promise as part of its fundraising: “Families never receive a bill from St. Jude for treatment, travel, housing or food – because all a family should worry about is helping their child live.”

But for many families, treatment at St. Jude does not relieve all the financial burdens they incur in getting care for their children, including housing, travel, and food costs that fall outside the hospital’s strict limits, a ProPublica investigation has found.

While families may not receive a bill from St. Jude, the hospital doesn’t cover what’s usually the biggest source of financial stress associated with childhood cancer: The loss of income as parents quit or take leave from jobs to be with their child during treatment. For many families, the consequence is missed payments for cars, utilities, and cellphones. Others face eviction or foreclosure because they can’t keep up with rent and mortgage payments.

Parents at St. Jude have exhausted savings and retirement accounts, borrowed from family and friends, or asked other charities for aid. ProPublica identified more than 100 St. Jude families seeking financial help through the online fundraiser GoFundMe, with half of the campaigns started in the past two years. We counted scores of other events like concerts and yard sales organized to help St. Jude families in need.

One family relied on a mixed martial arts fighter to help raise money for expenses like car repairs and cellphone bills, items that St. Jude would not cover. Another spent $10,000, originally saved to purchase a home, on costs related to treatment at St. Jude.

Only about half of the $7.3 billion St. Jude has received in contributions in the past five fiscal years went to the hospital’s research and caring for patients, according to its financial filings with the Internal Revenue Service. About 30% covered the cost of its fundraising operations, and the remaining 20%, or $1 of every $5 donated, increased its reserve fund.

Further, ProPublica found, a substantial portion of the cost for treatment is paid not by St. Jude but by families’ private insurance or by Medicaid, the government insurance program for low-income families. About 90% of patients are insured, bringing in more than $100 million in reimbursements for treatment a year. If a family shows up at St. Jude without insurance, a company hired by the charity helps them find it. St. Jude does cover copays and deductibles, an unusual benefit.

St. Jude spends about $500 million a year on patient services – a figure that includes all medical care and other assistance. Very little of what St. Jude raises from the public goes to pay for food, travel, and housing for families, the investigation found. Last year, it was 2% of the money raised, or nearly $40 million.

In written responses to ProPublica, lawyers for St. Jude and its fundraising arm, the American Lebanese Syrian Associated Charities, or ALSAC, emphasized that countless families have benefited from the charity provided since the hospital opened its doors in 1962.

“ProPublica should be celebrating St. Jude and ALSAC for their commitment to finding cures, saving children’s lives, and optimizing patient outcomes,” one of their letters said.

It is unquestioned that St. Jude has helped thousands of children and their families over the decades. Patients have offered scores of testimonials about the hospital’s generosity and care.

“This often comes as a huge relief to families who often expect to sell all their belongings just so their children can get the medical care and treatment they need to save their lives,” the hospital’s lawyers wrote. “St. Jude and ALSAC understand that this arrangement cannot cover all financial obligations of all families, nor can St. Jude or ALSAC shield families from all the financial and emotional effects” of a child’s illness.

St. Jude said it discloses the limits of its aid to families on its website and in material provided to those whose children are admitted to the hospital. That includes the rule Burt ran into, that the hospital covers the travel and housing costs of only one caregiver and one patient. For many families, the daily food budget is capped at $50. In some cases, hotel stays en route are provided only if families travel more than 500 miles to get to St. Jude.

St. Jude said its assistance is “based on guidelines to ensure fairness and responsible use of donor funds” and on remaining compliant with a federal anti-kickback statute that makes it a criminal offense to offer something of value to induce a medical referral. St. Jude declined to explain how the law affects the amount or type of financial assistance it provides to families.

“St. Jude has never promised anyone – neither patients nor the public in general – that it can solve all financial problems,” the letter said.

When parents need additional financial help, St. Jude’s social workers often send them to smaller charities or in some cases suggest that they apply for government aid.

They refer many to the Andrew McDonough B+ Foundation, which gives more than $2.5 million a year in grants to thousands of families of pediatric cancer patients at hospitals across the country to help cover rent, utilities, and other urgent expenses.

Joe McDonough, the foundation’s founder and president, said St. Jude families have the same money problems as families of patients at other children’s hospitals, even though he said St. Jude’s marketing creates the public perception that it alleviates these burdens.

“People say to me, ‘Why are you helping St. Jude families?’ ” McDonough said. “Well, what happens when a family lives in Augusta, Georgia, and they’re being treated at St. Jude? They still have to pay the rent on their apartment back in Augusta, Georgia. They still have to make their car payment. And it’s not my position to say whether St. Jude should be paying for all those expenses or not. I’m just explaining that it’s not a totally free ride.”

The help St. Jude provides to families may soon be increasing.

After ProPublica provided St. Jude with the findings of its reporting, the hospital informed families of a dramatic expansion in the assistance it will give to parents and other relatives during their kids’ treatment in Memphis.

Among the most significant changes are increasing travel benefits to two parents instead of one and covering regular trips to Memphis for siblings and other loved ones. St. Jude’s letter to parents said the changes take effect Nov. 15.

That would’ve made a big difference for Burt.

Burt’s daughter, whom ProPublica is not identifying at her mother’s request, was originally diagnosed with cancer in early 2015, when doctors discovered a tumor pressing against her brain stem. She had successful emergency surgery to remove the mass at Dell Children’s Medical Center in Austin, Texas. Medicaid and Dell Children’s covered the bill, but the family was still faced with the cost of her ongoing treatment.

“At that point I’m thinking: ‘What am I going to do? I guess I’m selling my house, whatever it takes,’” Burt recalled. “Honestly, that was probably a big deciding factor for St. Jude.”

St. Jude accepted Burt’s daughter into a clinical trial, and the family moved to the hospital’s patient housing in Memphis for several months. Both parents stopped working for a time, and people in their hometown raised cash to pay their bills.

Her cancer relapsed the following year with several new, inoperable brain tumors. Burt and his daughter’s mom broke up during that round of treatment, and financial problems piled up.

Burt said his credit score dropped so low that utility companies refused to set up service unless he first paid a deposit. One of the family’s cars was repossessed, he said. Burt’s 2005 Chevrolet Colorado pickup has 300,000 miles on it, many of them logged on trips from Texas to Memphis. When Burt’s daughter was at St. Jude for treatment or exams, he’d work all week, then visit on many weekends where he would spend Saturday night sleeping in the hospital parking lot.

He asked hospital officials if he could sleep in St. Jude’s housing, but they turned him down, he said.

Burt said he was happy with the care St. Jude provided. His daughter’s health is stable, he said, and brain scans taken during her September exam confirmed her two remaining tumors haven’t grown. But he’s still trying to recover financially.

“It’s five years now,” Burt said, “and I’m not completely caught up yet.”
 

A fundraising giant

St. Jude began with a fledgling entertainer praying for a career break.

When Danny Thomas, a comic and actor best known for the TV sitcom “Make Room for Daddy,” was struggling to earn a living in the late 1930s, the devout Roman Catholic went to church and asked for help from the patron saint of desperate cases, St. Jude Thaddeus. If he made it big, Thomas promised to build “a shrine where the poor and the helpless and the hopeless may come for comfort and aid,” according to a history published by ALSAC.

Within five years, Thomas became a star and worked to fulfill his promise by building a children’s hospital named after St. Jude and a fundraising organization to support it. Thomas, whose parents were Lebanese immigrants, recruited others who shared his Middle Eastern roots to help.

He used his fame to raise the hospital’s profile, appearing in ads for St. Jude and hosting fundraising events starring the likes of Elvis Presley and Sammy Davis Jr. Thomas’ daughter Marlo, herself a TV star, succeeded him in championing St. Jude.

Today, St. Jude is a specialty treatment and research center with about 5,700 employees and 73 beds. Other top children’s hospitals have more staff and beds, and they also treat more conditions.

Though St. Jude raises money across the world, most of its patients come from Tennessee and surrounding states. Patients from elsewhere are usually enrolled in clinical trials.

ALSAC, which handles St. Jude’s fundraising and investments, has 2,188 employees in Memphis and in 36 regional offices across the country. More than 400 of the fundraising arm’s employees are paid over $100,000, according to IRS filings. The charity takes in so much money each year that it regularly steers hundreds of millions of dollars in donations to reserve accounts, the filings show.

Overall, St. Jude’s reserve has grown by 58% over the past five fiscal years, during which it has added $1.9 billion to its investment accounts and shifted its portfolio toward financial products designed to generate bigger returns than stocks, bonds, and mutual funds traditionally deliver. The charity stowed more than a third of the new surplus, $688 million, in riskier private equity investments.

IRS rules do not limit the size of a nonprofit’s reserves, and experts on charitable finance differ on best practices.

St. Jude meets Better Business Bureau guidelines, which call for charities to maintain reserves of less than three times total expenses, but other experts expressed alarm that the hospital had accumulated such a large sum of money.

The size of the St. Jude reserve is “staggering,” said Laura Otten, the director of LaSalle University’s master program in nonprofit leadership. She said a typical reserve for a nonprofit the size of St. Jude is one to two years of expenses. Donors generally want to know their dollars are being put to work, she said.

The hospital said it needs a large reserve because its unique operating model relies on donations to fund annual operating costs. “[W]e are highly donor-dependent and subject to the economic driven vagaries of charitable giving,” the hospital said in a written response to ProPublica questions.

But the hospital’s reserve is already more than large enough to buffer against recessions and potential drops in donations, said Ge Bai, a professor of accounting and health policy at Johns Hopkins University. “They should be spending the money as aggressively as they raise it, but they seem to be hoarding,” Bai said.

The hospital said it is also raising billions to fund the construction of new housing and research space, although its plans do not currently include spending any of the reserve on new facilities.

St. Jude’s reserves have ballooned at a time when researchers, oncologists, advocates, and families complain about a dearth of funding for pediatric cancer studies nationally.

Dozens of other children’s hospitals across the country have research divisions devoted to pediatric cancer and enroll their patients in clinical trials for new drugs and procedures. They pay for research staff and studies in part with donations from their local communities, often competing directly against St. Jude. ALSAC has regional offices in several U.S. cities with elite pediatric cancer centers of their own, including Atlanta, Chicago, Denver, and Seattle.

Coury Shadyac, an ALSAC vice president and daughter of the organization’s CEO, Richard Shadyac Jr., oversees a team of 45 fundraisers along the West Coast “raising $300 million annually” for St. Jude, according to her LinkedIn profile. That’s $100 million more in donations than either Children’s Hospital Los Angeles or Seattle Children’s Hospital, two of the nation’s leading pediatric cancer institutions, received in fiscal year 2019, IRS disclosures show. But it’s only a small part of St. Jude’s fundraising haul.

ALSAC’s ubiquitous fundraising has led to concerns that it undercuts other hospitals’ campaigns. Some doctors interviewed by ProPublica said they have encouraged donors to give their money to hospitals closer to home.

David Clark, a pediatrician and former longtime chairperson of pediatrics at Albany Medical Center in New York, said St. Jude raises tens of thousands of dollars in his region that does little to benefit the children with cancer in his area since almost all are treated locally. ALSAC has a fundraising office located a few miles from Albany Medical.

“They think of every way they can to make money and the least amount of ways to spend it,” Clark said. “They deceive people into supporting something that is totally dishonest.”

Nearly all St. Jude solicitations feature the hospital’s patients – the children usually smiling and bald from treatment – along with the familiar promise that it never sends families a bill.

It’s a message that ALSAC has tested and researched to maximize donations. Donors appreciate the promise to never bill families, said Mary Kate Tolan, an ALSAC executive, in a podcast last year. She added that no parent should have to take out a second mortgage or lose their job because their child is being treated at St. Jude.

Alternative messaging to the no-bills promise did not “perform as well,” said Tolan, who develops emerging technologies for ALSAC. Tolan did not return requests for comment.
 

“Borrowing and begging”

Catherine Rainey thought she would be free of financial worry when her 2-year-old daughter Harlee was admitted to St. Jude last year.

“The first thing my dad said was: ‘Catherine, you have nothing to worry about. They raise billions of dollars. Anytime you have a problem, you tell them and they will take care of it,’ ” she said.

But like many families, the Raineys discovered that St. Jude’s charity came with limits on payments for expenses such as travel that could be bewildering.

Harlee ended up at St. Jude after first going to nearby Niswonger Children’s Hospital in Johnson City, Tenn., in October 2020. The doctors there discovered a cancerous mass attached to her right kidney. The hospital is a St. Jude affiliate, and the doctors recommended the toddler be treated in Memphis.

Rainey, a single mother of two young girls, had to leave her job as a nurse for months to be with Harlee at St. Jude. The loss of income quickly created problems. “My family, we don’t come from money,” she said. “We are not doctors and billionaires. We make it. That is it.”

St. Jude did provide food and housing on campus. But the hospital said it couldn’t help with the items that were causing Rainey to worry, including car payments, insurance, and cellphone bills.

Rainey’s boss set up a GoFundMe account to help make up some of her lost income. A small local charity, Kari’s Heart Foundation, also helped out by paying about $3,000 worth of phone bills and car payments, staving off repossession.

“It was just a bunch of borrowing and begging,” Rainey said of her experience while her daughter was treated in Memphis. “They acted like it was coming out of their own pocket.”

Harlee has checkups at St. Jude every three months that last about four days. The costs of travel to and from St. Jude put an additional strain on Rainey and Harlee. St. Jude is an eight-hour ride, without stops, from Rainey’s home in Appalachia, Va., a town of 1,432 people near the Kentucky border.

Rainey said her daughter generally can make it about two-thirds of the way, with frequent stops, before she has had enough. “When she is done, she is really done,” Rainey said. “She will scream, cry, and kick.”

In July, in advance of an August trip to Memphis, Rainey called the patient services department at St. Jude to see whether they could help pay for a hotel to break up the travel day — an expense Rainey said she could not afford.

To qualify for a hotel reimbursement, Rainey said, St. Jude told her she had to live more than 500 miles from Memphis. The ride from her home to the hospital is 530 miles (a measurement ProPublica confirmed with mapping tools). However, Rainey said, St. Jude told her it measured the trip from city limit to city limit and came up with a distance of 491 miles. Even using that metric, the distance is still more than 500 miles, ProPublica found.

When she challenged the hospital’s stance, Rainey said she was berated by a patient services representative.

“I was feeling pissed off, and I was crying,” Rainey said of the interaction. “You give up your whole life for your child, and they tell you don’t worry about anything, we will cover this and then they tell you to just push through the drive.”

Rainey did what she could to make the trip go smoothly: She configured a small table to extend across her daughter’s car seat, so Harlee could play with the coloring books, markers, and Play-Doh bought for the ride. She packed snacks and a cooler full of drinks. Since Harlee was still potty training, she brought extra towels and clothes for accidents. The final step was handing Harlee her Baby Yoda doll once she settled into her car seat. Rainey had sewed a port in the doll’s chest to mirror the one Harlee has in hers.

About three hours from Memphis, Harlee was crying inconsolably. Rainey pulled off the interstate and stopped at the first hotel she could find. She later learned it had been described in online reviews as “awful,” a “nightmare,” “disgusting,” and “horrible.”

“I didn’t know the area,” she said. “The hotel was garbage. It just made it worse.”

The drive home also required a hotel stop, but this time Rainey was able to find one that was cleaner. A $100 donation from a local charity helped to offset the cost.

Among the changes St. Jude is making is to reimburse families like Rainey’s, who live more than 400 miles from the hospital, for an overnight stay at a hotel when making the trip to Memphis.

Rainey said she was called by a St. Jude representative after ProPublica asked about her situation and was told the hospital would pay for her past hotel stays when traveling back and forth to St. Jude. The representative, Rainey said, also told her the hospital discovered the way it had been measuring mileage was inaccurate.

“I am not the only one,” Rainey said. “There are others. They should reimburse all the families.”

The anxiety of unpaid bills piling up, combined with caring for a child undergoing chemotherapy or radiation, takes a severe toll on parents and guardians, said Christopher Hope, a UPS driver who started a Memphis-based foundation after meeting St. Jude parents who were in financial crisis.

Hope’s small charity spent $12,000 last year to help families. Parents in St. Jude social media groups often refer families in need to it. The charity has helped families cover mortgage and car payments.

“I never knew anything about this until hearing about it from families,” Hope said. “All we hear is about kids and treatment, not the other side of it.”
 

“It’s not free”

In addition to charities like Hope’s, St. Jude families have repeatedly turned to fundraising sites and networks of their relatives, friends, and neighbors to help cover basic expenses while unable to work during their children’s treatment. Parents’ requests on fundraising sites are sometimes desperate pleas.

In January 2017, one father in North Carolina said he’d had to abandon a business venture to take time for his son to receive care at St. Jude. His income had plummeted. He asked friends to give as little as $10 to “at least make it possible to survive.”

This year, a mother in Memphis whose 1-year-old son receives care at St. Jude for sickle cell disorder ran out of medical leave and couldn’t work her shifts at a clothing distribution center. After the child had a flare-up in July requiring several days of treatment at the hospital, she said she returned home to find her power shut off. Sitting in a dark apartment, unable to pay her utility bills, she set up a GoFundMe campaign. She received less than $20 through the site; her relatives eventually pooled $350 to get her electricity restored.

Even parents with stable jobs and private health insurance often take on debt and need outside help.

When Taylr and Treg Murphy’s 17-year-old son Peyton was diagnosed with cancer and needed monthslong treatment at St. Jude in 2017, the entire family – mom, dad, sister, and brother – went with him, traveling from their home in Lafayette, La., to Memphis. Treg took a leave from his job at an oil mining company and Taylr, who works at her mother’s bakery, did the same.

“We knew that it was going to be a collective team effort,” Treg said. “Without even a discussion, we figured that if Peyton’s got to go for the surgery, we’re all going.”

Peyton had an enormous tumor that had grown out of his right femur and was crowding his knee. Rounds of chemotherapy appeared to have killed osteosarcoma cells elsewhere in his body. But he needed to undergo a procedure called limb-sparing surgery that would require weeks of recovery time at the hospital.

The hospital agreed to allow all five family members to stay for free at St. Jude if they bunked together in a single room. It assigned them a spot in Tri Delta Place, its hotel-like short-term patient residence on the campus. Tri Delta is set up for visits of up to seven days, according to the hospital’s guide for volunteers, but the Murphys were there for almost 50.

Taylr said the unit at Tri Delta had no oven or stove and St. Jude provided no grocery money, instead allotting them a $50-per-day credit at the hospital cafeteria, Kay Kafe – not enough to feed the family of five. As the weeks wore on, the Murphys split grilled cheese sandwiches and paid for food out of pocket.

After ProPublica asked about the hospital’s food allowances, St. Jude said it would increase them as part of the changes scheduled to go into effect this month. The hospital switched from a $50-a-day cap per family to providing $25 a day to each family member. For a family of four, that would double the food benefit. A weekly stipend given to families in long-term housing was increased to $150 from $125.

For the Murphys, it was the loss of their work income, more than out-of-pocket expenses, that put them into a financial hole as Peyton’s treatment went on. Treg’s employer couldn’t pay him during his long absences.

Fearful of being evicted or having their car repossessed, Taylr said she asked a St. Jude social worker for assistance. The social worker helped her apply for grants from other charities. Taylr said the B+ Foundation paid their rent one month, which ensured they’d have a home to return to.

In the years since his initial treatment, Peyton has gone back to St. Jude repeatedly for exams and surgeries to remove malignant growths in his lungs. Taylr and Treg have missed more work to bring Peyton to Memphis, costing them thousands of dollars more in income.

By the start of this year, Taylr and Treg said they were about $20,000 in debt and panicking. Dustin Poirier, a former UFC champion from their hometown, heard from a friend about Peyton and the family’s financial trouble. He donated $10,000 to them from his personal charity and in May hosted a local fundraiser that collected enough to pay off their credit cards.

St. Jude families sometimes commiserate about money problems with each other, Taylr said, but few are aware of the extent of the hospital’s unspent resources. The Murphys said they didn’t know St. Jude has more than $5 billion in reserve or that it continues to raise hundreds of millions of dollars in surplus donations each year.

“That’s just insane,” Taylr said. “That just blows my mind. When we first started getting treated, people would be like, ‘Oh, St. Jude covers everything, that’s awesome.’ That’s not how it works. People don’t understand that. I truly didn’t understand before I got into St. Jude.”

Taylr and Treg said the doctors at St. Jude are “amazing” and they’re grateful for their son’s care. But they bristled at the assumption that it was covered by the hospital’s charity. The family’s insurance paid a substantial part of the bills.

“It’s not free,” Taylr said. “My husband works very hard for the insurance we have – and they are billed.” The Murphys pay $12,000 in health insurance premiums each year.

Their struggle continues. Peyton’s cancer has relapsed, and he’s making regular trips with his mom or dad back to St. Jude for chemotherapy. The family is again applying for help from other charities.
 

Wiped out savings

The costs associated with care at St. Jude caused at least one family to stop going to Memphis altogether.

Last winter, Kelly Edwards was excitedly searching through Tulsa real estate listings after years of diligently saving $10,000 for a down payment on a house. She craved a permanent home for herself and the two young brothers she had taken in five years earlier at the behest of a family friend. She hoped to adopt the boys, now 13 and 9, who call her mom.

In February, the older boy, DJ, was lethargic and uninterested in his schoolwork. After several doctor visits, he was diagnosed with acute lymphoblastic leukemia at a Tulsa hospital. The cancer, referred to as ALL, is the most common type among children, with survival rates that exceed 90%. A day after his diagnosis, DJ and Edwards were driving six hours to Memphis for treatment at St. Jude, which is affiliated with the Oklahoma hospital.

The pair stayed for free at an independently operated Ronald McDonald House near St. Jude, and a weekly stipend from the hospital helped to pay for meals – aid that Edwards said was a blessing. DJ had health insurance through the Oklahoma Medicaid program.

But as with the Murphys, lost income soon put Edwards’ family into financial jeopardy. She works as a supervisor for a company that delivers packages for Amazon. After she used up two weeks of paid time off, she stopped getting paychecks. The bills, however, kept coming: rent, car payments, utilities. To that was added the $250 a week she paid a friend to stay with DJ’s younger brother and her two dogs in Tulsa.

Within four months, her house savings were wiped out. Edwards said she told her St. Jude social worker about her financial woes but got no additional help.

One of Edwards’ adult daughters started a GoFundMe campaign to help, bringing in just over $3,000. Edwards said she appreciated the aid but believes donations were kept low by the widespread perception that St. Jude families don’t have financial problems.

“Everyone hears that everything is taken care of by St. Jude,” she said. “That is not true, but everyone has that mentality.” She said someone she knew asked her “what is that money going for if St. Jude’s is paying for everything?”

DJ was scheduled to go back to St. Jude for three weeks of treatment in August, but Edwards decided she simply couldn’t afford it. “I don’t have the money to go back and forth,” she said. She worked with DJ’s local doctors and found that the hospital near her home in Tulsa could provide the same treatment he was scheduled to get in Tennessee.

The local treatment allowed her to continue working some shifts and to be at home with both of her boys. DJ is also happier when he is home, Edwards said.

Edwards and the boys are now living in a small house her brother owns just outside Tulsa. Late on a recent weekday afternoon, DJ slowly shuffled into the living room, exhausted from a day of chemotherapy treatment.

He is in the midst of a 20-week regimen where he receives the cancer-killing drugs every other day, just one phase of a nearly three-year treatment plan. He wore an orange knit hat, T-shirt, and shorts. He rubbed his eyes before asking a visitor, “How is your day going?” He smiled at the positive response. When he heard the family was eating steak for dinner, he eagerly jumped up to start helping in the kitchen. After they moved in, Edwards hung family portraits on the walls to make it feel homier. She doesn’t expect they will be moving again any time soon.

The dream of buying a home of their own is gone.

Former ProPublica reporter Marshall Allen contributed reporting. Kirsten Berg contributed research.

This story was originally published on ProPublica. ProPublica is a nonprofit newsroom that investigates abuses of power. Sign up to receive their biggest stories as soon as they’re published.

A series of sharp knocks on his driver’s side window startled Jason Burt awake.

It was the middle of the night on a Saturday in 2016. Burt was sleeping in his pickup truck in the parking lot of St. Jude Children’s Research Hospital in downtown Memphis, Tenn., where his 5-year-old daughter was being treated for brain cancer. He’d driven more than 500 miles from his home in Central Texas to visit her.

A St. Jude security guard peered into the truck and asked Burt what he was doing. Burt explained that his daughter and her mother, his ex-girlfriend, were staying in the hospital’s free patient housing. But St. Jude provides housing for only one parent. Burt, a school bus driver making $20,000 a year, told the guard he couldn’t afford a hotel. The guard let the exhausted father go back to sleep.

St. Jude would do no more to find him a place to stay.

“They were aware of the situation,” Burt said. “I didn’t push anything. I was just grateful she was getting treated and I was doing what I needed to do.”

St. Jude is the largest and most highly regarded health care charity in the country. Each year, the Memphis hospital’s fundraisers send out hundreds of millions of letters, many with heart-wrenching photographs of children left bald from battling cancer. Celebrities like Jennifer Aniston and Sofia Vergara sing the hospital’s praises in televised advertisements. This year, St. Jude’s fundraising reached outer space. The SpaceX Inspiration4 mission in September included a former St. Jude patient as a crew member.

Last year, St. Jude raised a record $2 billion. U.S. News & World Report ranked it the country’s 10th-best children’s cancer hospital, and St. Jude raised roughly as much as the nine hospitals ahead of it put together. It currently has $5.2 billion in reserves, a sum large enough to run the institution at current levels for the next four and a half years without a single additional donation.

St. Jude makes a unique promise as part of its fundraising: “Families never receive a bill from St. Jude for treatment, travel, housing or food – because all a family should worry about is helping their child live.”

But for many families, treatment at St. Jude does not relieve all the financial burdens they incur in getting care for their children, including housing, travel, and food costs that fall outside the hospital’s strict limits, a ProPublica investigation has found.

While families may not receive a bill from St. Jude, the hospital doesn’t cover what’s usually the biggest source of financial stress associated with childhood cancer: The loss of income as parents quit or take leave from jobs to be with their child during treatment. For many families, the consequence is missed payments for cars, utilities, and cellphones. Others face eviction or foreclosure because they can’t keep up with rent and mortgage payments.

Parents at St. Jude have exhausted savings and retirement accounts, borrowed from family and friends, or asked other charities for aid. ProPublica identified more than 100 St. Jude families seeking financial help through the online fundraiser GoFundMe, with half of the campaigns started in the past two years. We counted scores of other events like concerts and yard sales organized to help St. Jude families in need.

One family relied on a mixed martial arts fighter to help raise money for expenses like car repairs and cellphone bills, items that St. Jude would not cover. Another spent $10,000, originally saved to purchase a home, on costs related to treatment at St. Jude.

Only about half of the $7.3 billion St. Jude has received in contributions in the past five fiscal years went to the hospital’s research and caring for patients, according to its financial filings with the Internal Revenue Service. About 30% covered the cost of its fundraising operations, and the remaining 20%, or $1 of every $5 donated, increased its reserve fund.

Further, ProPublica found, a substantial portion of the cost for treatment is paid not by St. Jude but by families’ private insurance or by Medicaid, the government insurance program for low-income families. About 90% of patients are insured, bringing in more than $100 million in reimbursements for treatment a year. If a family shows up at St. Jude without insurance, a company hired by the charity helps them find it. St. Jude does cover copays and deductibles, an unusual benefit.

St. Jude spends about $500 million a year on patient services – a figure that includes all medical care and other assistance. Very little of what St. Jude raises from the public goes to pay for food, travel, and housing for families, the investigation found. Last year, it was 2% of the money raised, or nearly $40 million.

In written responses to ProPublica, lawyers for St. Jude and its fundraising arm, the American Lebanese Syrian Associated Charities, or ALSAC, emphasized that countless families have benefited from the charity provided since the hospital opened its doors in 1962.

“ProPublica should be celebrating St. Jude and ALSAC for their commitment to finding cures, saving children’s lives, and optimizing patient outcomes,” one of their letters said.

It is unquestioned that St. Jude has helped thousands of children and their families over the decades. Patients have offered scores of testimonials about the hospital’s generosity and care.

“This often comes as a huge relief to families who often expect to sell all their belongings just so their children can get the medical care and treatment they need to save their lives,” the hospital’s lawyers wrote. “St. Jude and ALSAC understand that this arrangement cannot cover all financial obligations of all families, nor can St. Jude or ALSAC shield families from all the financial and emotional effects” of a child’s illness.

St. Jude said it discloses the limits of its aid to families on its website and in material provided to those whose children are admitted to the hospital. That includes the rule Burt ran into, that the hospital covers the travel and housing costs of only one caregiver and one patient. For many families, the daily food budget is capped at $50. In some cases, hotel stays en route are provided only if families travel more than 500 miles to get to St. Jude.

St. Jude said its assistance is “based on guidelines to ensure fairness and responsible use of donor funds” and on remaining compliant with a federal anti-kickback statute that makes it a criminal offense to offer something of value to induce a medical referral. St. Jude declined to explain how the law affects the amount or type of financial assistance it provides to families.

“St. Jude has never promised anyone – neither patients nor the public in general – that it can solve all financial problems,” the letter said.

When parents need additional financial help, St. Jude’s social workers often send them to smaller charities or in some cases suggest that they apply for government aid.

They refer many to the Andrew McDonough B+ Foundation, which gives more than $2.5 million a year in grants to thousands of families of pediatric cancer patients at hospitals across the country to help cover rent, utilities, and other urgent expenses.

Joe McDonough, the foundation’s founder and president, said St. Jude families have the same money problems as families of patients at other children’s hospitals, even though he said St. Jude’s marketing creates the public perception that it alleviates these burdens.

“People say to me, ‘Why are you helping St. Jude families?’ ” McDonough said. “Well, what happens when a family lives in Augusta, Georgia, and they’re being treated at St. Jude? They still have to pay the rent on their apartment back in Augusta, Georgia. They still have to make their car payment. And it’s not my position to say whether St. Jude should be paying for all those expenses or not. I’m just explaining that it’s not a totally free ride.”

The help St. Jude provides to families may soon be increasing.

After ProPublica provided St. Jude with the findings of its reporting, the hospital informed families of a dramatic expansion in the assistance it will give to parents and other relatives during their kids’ treatment in Memphis.

Among the most significant changes are increasing travel benefits to two parents instead of one and covering regular trips to Memphis for siblings and other loved ones. St. Jude’s letter to parents said the changes take effect Nov. 15.

That would’ve made a big difference for Burt.

Burt’s daughter, whom ProPublica is not identifying at her mother’s request, was originally diagnosed with cancer in early 2015, when doctors discovered a tumor pressing against her brain stem. She had successful emergency surgery to remove the mass at Dell Children’s Medical Center in Austin, Texas. Medicaid and Dell Children’s covered the bill, but the family was still faced with the cost of her ongoing treatment.

“At that point I’m thinking: ‘What am I going to do? I guess I’m selling my house, whatever it takes,’” Burt recalled. “Honestly, that was probably a big deciding factor for St. Jude.”

St. Jude accepted Burt’s daughter into a clinical trial, and the family moved to the hospital’s patient housing in Memphis for several months. Both parents stopped working for a time, and people in their hometown raised cash to pay their bills.

Her cancer relapsed the following year with several new, inoperable brain tumors. Burt and his daughter’s mom broke up during that round of treatment, and financial problems piled up.

Burt said his credit score dropped so low that utility companies refused to set up service unless he first paid a deposit. One of the family’s cars was repossessed, he said. Burt’s 2005 Chevrolet Colorado pickup has 300,000 miles on it, many of them logged on trips from Texas to Memphis. When Burt’s daughter was at St. Jude for treatment or exams, he’d work all week, then visit on many weekends where he would spend Saturday night sleeping in the hospital parking lot.

He asked hospital officials if he could sleep in St. Jude’s housing, but they turned him down, he said.

Burt said he was happy with the care St. Jude provided. His daughter’s health is stable, he said, and brain scans taken during her September exam confirmed her two remaining tumors haven’t grown. But he’s still trying to recover financially.

“It’s five years now,” Burt said, “and I’m not completely caught up yet.”
 

A fundraising giant

St. Jude began with a fledgling entertainer praying for a career break.

When Danny Thomas, a comic and actor best known for the TV sitcom “Make Room for Daddy,” was struggling to earn a living in the late 1930s, the devout Roman Catholic went to church and asked for help from the patron saint of desperate cases, St. Jude Thaddeus. If he made it big, Thomas promised to build “a shrine where the poor and the helpless and the hopeless may come for comfort and aid,” according to a history published by ALSAC.

Within five years, Thomas became a star and worked to fulfill his promise by building a children’s hospital named after St. Jude and a fundraising organization to support it. Thomas, whose parents were Lebanese immigrants, recruited others who shared his Middle Eastern roots to help.

He used his fame to raise the hospital’s profile, appearing in ads for St. Jude and hosting fundraising events starring the likes of Elvis Presley and Sammy Davis Jr. Thomas’ daughter Marlo, herself a TV star, succeeded him in championing St. Jude.

Today, St. Jude is a specialty treatment and research center with about 5,700 employees and 73 beds. Other top children’s hospitals have more staff and beds, and they also treat more conditions.

Though St. Jude raises money across the world, most of its patients come from Tennessee and surrounding states. Patients from elsewhere are usually enrolled in clinical trials.

ALSAC, which handles St. Jude’s fundraising and investments, has 2,188 employees in Memphis and in 36 regional offices across the country. More than 400 of the fundraising arm’s employees are paid over $100,000, according to IRS filings. The charity takes in so much money each year that it regularly steers hundreds of millions of dollars in donations to reserve accounts, the filings show.

Overall, St. Jude’s reserve has grown by 58% over the past five fiscal years, during which it has added $1.9 billion to its investment accounts and shifted its portfolio toward financial products designed to generate bigger returns than stocks, bonds, and mutual funds traditionally deliver. The charity stowed more than a third of the new surplus, $688 million, in riskier private equity investments.

IRS rules do not limit the size of a nonprofit’s reserves, and experts on charitable finance differ on best practices.

St. Jude meets Better Business Bureau guidelines, which call for charities to maintain reserves of less than three times total expenses, but other experts expressed alarm that the hospital had accumulated such a large sum of money.

The size of the St. Jude reserve is “staggering,” said Laura Otten, the director of LaSalle University’s master program in nonprofit leadership. She said a typical reserve for a nonprofit the size of St. Jude is one to two years of expenses. Donors generally want to know their dollars are being put to work, she said.

The hospital said it needs a large reserve because its unique operating model relies on donations to fund annual operating costs. “[W]e are highly donor-dependent and subject to the economic driven vagaries of charitable giving,” the hospital said in a written response to ProPublica questions.

But the hospital’s reserve is already more than large enough to buffer against recessions and potential drops in donations, said Ge Bai, a professor of accounting and health policy at Johns Hopkins University. “They should be spending the money as aggressively as they raise it, but they seem to be hoarding,” Bai said.

The hospital said it is also raising billions to fund the construction of new housing and research space, although its plans do not currently include spending any of the reserve on new facilities.

St. Jude’s reserves have ballooned at a time when researchers, oncologists, advocates, and families complain about a dearth of funding for pediatric cancer studies nationally.

Dozens of other children’s hospitals across the country have research divisions devoted to pediatric cancer and enroll their patients in clinical trials for new drugs and procedures. They pay for research staff and studies in part with donations from their local communities, often competing directly against St. Jude. ALSAC has regional offices in several U.S. cities with elite pediatric cancer centers of their own, including Atlanta, Chicago, Denver, and Seattle.

Coury Shadyac, an ALSAC vice president and daughter of the organization’s CEO, Richard Shadyac Jr., oversees a team of 45 fundraisers along the West Coast “raising $300 million annually” for St. Jude, according to her LinkedIn profile. That’s $100 million more in donations than either Children’s Hospital Los Angeles or Seattle Children’s Hospital, two of the nation’s leading pediatric cancer institutions, received in fiscal year 2019, IRS disclosures show. But it’s only a small part of St. Jude’s fundraising haul.

ALSAC’s ubiquitous fundraising has led to concerns that it undercuts other hospitals’ campaigns. Some doctors interviewed by ProPublica said they have encouraged donors to give their money to hospitals closer to home.

David Clark, a pediatrician and former longtime chairperson of pediatrics at Albany Medical Center in New York, said St. Jude raises tens of thousands of dollars in his region that does little to benefit the children with cancer in his area since almost all are treated locally. ALSAC has a fundraising office located a few miles from Albany Medical.

“They think of every way they can to make money and the least amount of ways to spend it,” Clark said. “They deceive people into supporting something that is totally dishonest.”

Nearly all St. Jude solicitations feature the hospital’s patients – the children usually smiling and bald from treatment – along with the familiar promise that it never sends families a bill.

It’s a message that ALSAC has tested and researched to maximize donations. Donors appreciate the promise to never bill families, said Mary Kate Tolan, an ALSAC executive, in a podcast last year. She added that no parent should have to take out a second mortgage or lose their job because their child is being treated at St. Jude.

Alternative messaging to the no-bills promise did not “perform as well,” said Tolan, who develops emerging technologies for ALSAC. Tolan did not return requests for comment.
 

“Borrowing and begging”

Catherine Rainey thought she would be free of financial worry when her 2-year-old daughter Harlee was admitted to St. Jude last year.

“The first thing my dad said was: ‘Catherine, you have nothing to worry about. They raise billions of dollars. Anytime you have a problem, you tell them and they will take care of it,’ ” she said.

But like many families, the Raineys discovered that St. Jude’s charity came with limits on payments for expenses such as travel that could be bewildering.

Harlee ended up at St. Jude after first going to nearby Niswonger Children’s Hospital in Johnson City, Tenn., in October 2020. The doctors there discovered a cancerous mass attached to her right kidney. The hospital is a St. Jude affiliate, and the doctors recommended the toddler be treated in Memphis.

Rainey, a single mother of two young girls, had to leave her job as a nurse for months to be with Harlee at St. Jude. The loss of income quickly created problems. “My family, we don’t come from money,” she said. “We are not doctors and billionaires. We make it. That is it.”

St. Jude did provide food and housing on campus. But the hospital said it couldn’t help with the items that were causing Rainey to worry, including car payments, insurance, and cellphone bills.

Rainey’s boss set up a GoFundMe account to help make up some of her lost income. A small local charity, Kari’s Heart Foundation, also helped out by paying about $3,000 worth of phone bills and car payments, staving off repossession.

“It was just a bunch of borrowing and begging,” Rainey said of her experience while her daughter was treated in Memphis. “They acted like it was coming out of their own pocket.”

Harlee has checkups at St. Jude every three months that last about four days. The costs of travel to and from St. Jude put an additional strain on Rainey and Harlee. St. Jude is an eight-hour ride, without stops, from Rainey’s home in Appalachia, Va., a town of 1,432 people near the Kentucky border.

Rainey said her daughter generally can make it about two-thirds of the way, with frequent stops, before she has had enough. “When she is done, she is really done,” Rainey said. “She will scream, cry, and kick.”

In July, in advance of an August trip to Memphis, Rainey called the patient services department at St. Jude to see whether they could help pay for a hotel to break up the travel day — an expense Rainey said she could not afford.

To qualify for a hotel reimbursement, Rainey said, St. Jude told her she had to live more than 500 miles from Memphis. The ride from her home to the hospital is 530 miles (a measurement ProPublica confirmed with mapping tools). However, Rainey said, St. Jude told her it measured the trip from city limit to city limit and came up with a distance of 491 miles. Even using that metric, the distance is still more than 500 miles, ProPublica found.

When she challenged the hospital’s stance, Rainey said she was berated by a patient services representative.

“I was feeling pissed off, and I was crying,” Rainey said of the interaction. “You give up your whole life for your child, and they tell you don’t worry about anything, we will cover this and then they tell you to just push through the drive.”

Rainey did what she could to make the trip go smoothly: She configured a small table to extend across her daughter’s car seat, so Harlee could play with the coloring books, markers, and Play-Doh bought for the ride. She packed snacks and a cooler full of drinks. Since Harlee was still potty training, she brought extra towels and clothes for accidents. The final step was handing Harlee her Baby Yoda doll once she settled into her car seat. Rainey had sewed a port in the doll’s chest to mirror the one Harlee has in hers.

About three hours from Memphis, Harlee was crying inconsolably. Rainey pulled off the interstate and stopped at the first hotel she could find. She later learned it had been described in online reviews as “awful,” a “nightmare,” “disgusting,” and “horrible.”

“I didn’t know the area,” she said. “The hotel was garbage. It just made it worse.”

The drive home also required a hotel stop, but this time Rainey was able to find one that was cleaner. A $100 donation from a local charity helped to offset the cost.

Among the changes St. Jude is making is to reimburse families like Rainey’s, who live more than 400 miles from the hospital, for an overnight stay at a hotel when making the trip to Memphis.

Rainey said she was called by a St. Jude representative after ProPublica asked about her situation and was told the hospital would pay for her past hotel stays when traveling back and forth to St. Jude. The representative, Rainey said, also told her the hospital discovered the way it had been measuring mileage was inaccurate.

“I am not the only one,” Rainey said. “There are others. They should reimburse all the families.”

The anxiety of unpaid bills piling up, combined with caring for a child undergoing chemotherapy or radiation, takes a severe toll on parents and guardians, said Christopher Hope, a UPS driver who started a Memphis-based foundation after meeting St. Jude parents who were in financial crisis.

Hope’s small charity spent $12,000 last year to help families. Parents in St. Jude social media groups often refer families in need to it. The charity has helped families cover mortgage and car payments.

“I never knew anything about this until hearing about it from families,” Hope said. “All we hear is about kids and treatment, not the other side of it.”
 

“It’s not free”

In addition to charities like Hope’s, St. Jude families have repeatedly turned to fundraising sites and networks of their relatives, friends, and neighbors to help cover basic expenses while unable to work during their children’s treatment. Parents’ requests on fundraising sites are sometimes desperate pleas.

In January 2017, one father in North Carolina said he’d had to abandon a business venture to take time for his son to receive care at St. Jude. His income had plummeted. He asked friends to give as little as $10 to “at least make it possible to survive.”

This year, a mother in Memphis whose 1-year-old son receives care at St. Jude for sickle cell disorder ran out of medical leave and couldn’t work her shifts at a clothing distribution center. After the child had a flare-up in July requiring several days of treatment at the hospital, she said she returned home to find her power shut off. Sitting in a dark apartment, unable to pay her utility bills, she set up a GoFundMe campaign. She received less than $20 through the site; her relatives eventually pooled $350 to get her electricity restored.

Even parents with stable jobs and private health insurance often take on debt and need outside help.

When Taylr and Treg Murphy’s 17-year-old son Peyton was diagnosed with cancer and needed monthslong treatment at St. Jude in 2017, the entire family – mom, dad, sister, and brother – went with him, traveling from their home in Lafayette, La., to Memphis. Treg took a leave from his job at an oil mining company and Taylr, who works at her mother’s bakery, did the same.

“We knew that it was going to be a collective team effort,” Treg said. “Without even a discussion, we figured that if Peyton’s got to go for the surgery, we’re all going.”

Peyton had an enormous tumor that had grown out of his right femur and was crowding his knee. Rounds of chemotherapy appeared to have killed osteosarcoma cells elsewhere in his body. But he needed to undergo a procedure called limb-sparing surgery that would require weeks of recovery time at the hospital.

The hospital agreed to allow all five family members to stay for free at St. Jude if they bunked together in a single room. It assigned them a spot in Tri Delta Place, its hotel-like short-term patient residence on the campus. Tri Delta is set up for visits of up to seven days, according to the hospital’s guide for volunteers, but the Murphys were there for almost 50.

Taylr said the unit at Tri Delta had no oven or stove and St. Jude provided no grocery money, instead allotting them a $50-per-day credit at the hospital cafeteria, Kay Kafe – not enough to feed the family of five. As the weeks wore on, the Murphys split grilled cheese sandwiches and paid for food out of pocket.

After ProPublica asked about the hospital’s food allowances, St. Jude said it would increase them as part of the changes scheduled to go into effect this month. The hospital switched from a $50-a-day cap per family to providing $25 a day to each family member. For a family of four, that would double the food benefit. A weekly stipend given to families in long-term housing was increased to $150 from $125.

For the Murphys, it was the loss of their work income, more than out-of-pocket expenses, that put them into a financial hole as Peyton’s treatment went on. Treg’s employer couldn’t pay him during his long absences.

Fearful of being evicted or having their car repossessed, Taylr said she asked a St. Jude social worker for assistance. The social worker helped her apply for grants from other charities. Taylr said the B+ Foundation paid their rent one month, which ensured they’d have a home to return to.

In the years since his initial treatment, Peyton has gone back to St. Jude repeatedly for exams and surgeries to remove malignant growths in his lungs. Taylr and Treg have missed more work to bring Peyton to Memphis, costing them thousands of dollars more in income.

By the start of this year, Taylr and Treg said they were about $20,000 in debt and panicking. Dustin Poirier, a former UFC champion from their hometown, heard from a friend about Peyton and the family’s financial trouble. He donated $10,000 to them from his personal charity and in May hosted a local fundraiser that collected enough to pay off their credit cards.

St. Jude families sometimes commiserate about money problems with each other, Taylr said, but few are aware of the extent of the hospital’s unspent resources. The Murphys said they didn’t know St. Jude has more than $5 billion in reserve or that it continues to raise hundreds of millions of dollars in surplus donations each year.

“That’s just insane,” Taylr said. “That just blows my mind. When we first started getting treated, people would be like, ‘Oh, St. Jude covers everything, that’s awesome.’ That’s not how it works. People don’t understand that. I truly didn’t understand before I got into St. Jude.”

Taylr and Treg said the doctors at St. Jude are “amazing” and they’re grateful for their son’s care. But they bristled at the assumption that it was covered by the hospital’s charity. The family’s insurance paid a substantial part of the bills.

“It’s not free,” Taylr said. “My husband works very hard for the insurance we have – and they are billed.” The Murphys pay $12,000 in health insurance premiums each year.

Their struggle continues. Peyton’s cancer has relapsed, and he’s making regular trips with his mom or dad back to St. Jude for chemotherapy. The family is again applying for help from other charities.
 

Wiped out savings

The costs associated with care at St. Jude caused at least one family to stop going to Memphis altogether.

Last winter, Kelly Edwards was excitedly searching through Tulsa real estate listings after years of diligently saving $10,000 for a down payment on a house. She craved a permanent home for herself and the two young brothers she had taken in five years earlier at the behest of a family friend. She hoped to adopt the boys, now 13 and 9, who call her mom.

In February, the older boy, DJ, was lethargic and uninterested in his schoolwork. After several doctor visits, he was diagnosed with acute lymphoblastic leukemia at a Tulsa hospital. The cancer, referred to as ALL, is the most common type among children, with survival rates that exceed 90%. A day after his diagnosis, DJ and Edwards were driving six hours to Memphis for treatment at St. Jude, which is affiliated with the Oklahoma hospital.

The pair stayed for free at an independently operated Ronald McDonald House near St. Jude, and a weekly stipend from the hospital helped to pay for meals – aid that Edwards said was a blessing. DJ had health insurance through the Oklahoma Medicaid program.

But as with the Murphys, lost income soon put Edwards’ family into financial jeopardy. She works as a supervisor for a company that delivers packages for Amazon. After she used up two weeks of paid time off, she stopped getting paychecks. The bills, however, kept coming: rent, car payments, utilities. To that was added the $250 a week she paid a friend to stay with DJ’s younger brother and her two dogs in Tulsa.

Within four months, her house savings were wiped out. Edwards said she told her St. Jude social worker about her financial woes but got no additional help.

One of Edwards’ adult daughters started a GoFundMe campaign to help, bringing in just over $3,000. Edwards said she appreciated the aid but believes donations were kept low by the widespread perception that St. Jude families don’t have financial problems.

“Everyone hears that everything is taken care of by St. Jude,” she said. “That is not true, but everyone has that mentality.” She said someone she knew asked her “what is that money going for if St. Jude’s is paying for everything?”

DJ was scheduled to go back to St. Jude for three weeks of treatment in August, but Edwards decided she simply couldn’t afford it. “I don’t have the money to go back and forth,” she said. She worked with DJ’s local doctors and found that the hospital near her home in Tulsa could provide the same treatment he was scheduled to get in Tennessee.

The local treatment allowed her to continue working some shifts and to be at home with both of her boys. DJ is also happier when he is home, Edwards said.

Edwards and the boys are now living in a small house her brother owns just outside Tulsa. Late on a recent weekday afternoon, DJ slowly shuffled into the living room, exhausted from a day of chemotherapy treatment.

He is in the midst of a 20-week regimen where he receives the cancer-killing drugs every other day, just one phase of a nearly three-year treatment plan. He wore an orange knit hat, T-shirt, and shorts. He rubbed his eyes before asking a visitor, “How is your day going?” He smiled at the positive response. When he heard the family was eating steak for dinner, he eagerly jumped up to start helping in the kitchen. After they moved in, Edwards hung family portraits on the walls to make it feel homier. She doesn’t expect they will be moving again any time soon.

The dream of buying a home of their own is gone.

Former ProPublica reporter Marshall Allen contributed reporting. Kirsten Berg contributed research.

This story was originally published on ProPublica. ProPublica is a nonprofit newsroom that investigates abuses of power. Sign up to receive their biggest stories as soon as they’re published.

A series of sharp knocks on his driver’s side window startled Jason Burt awake.

It was the middle of the night on a Saturday in 2016. Burt was sleeping in his pickup truck in the parking lot of St. Jude Children’s Research Hospital in downtown Memphis, Tenn., where his 5-year-old daughter was being treated for brain cancer. He’d driven more than 500 miles from his home in Central Texas to visit her.

A St. Jude security guard peered into the truck and asked Burt what he was doing. Burt explained that his daughter and her mother, his ex-girlfriend, were staying in the hospital’s free patient housing. But St. Jude provides housing for only one parent. Burt, a school bus driver making $20,000 a year, told the guard he couldn’t afford a hotel. The guard let the exhausted father go back to sleep.

St. Jude would do no more to find him a place to stay.

“They were aware of the situation,” Burt said. “I didn’t push anything. I was just grateful she was getting treated and I was doing what I needed to do.”

St. Jude is the largest and most highly regarded health care charity in the country. Each year, the Memphis hospital’s fundraisers send out hundreds of millions of letters, many with heart-wrenching photographs of children left bald from battling cancer. Celebrities like Jennifer Aniston and Sofia Vergara sing the hospital’s praises in televised advertisements. This year, St. Jude’s fundraising reached outer space. The SpaceX Inspiration4 mission in September included a former St. Jude patient as a crew member.

Last year, St. Jude raised a record $2 billion. U.S. News & World Report ranked it the country’s 10th-best children’s cancer hospital, and St. Jude raised roughly as much as the nine hospitals ahead of it put together. It currently has $5.2 billion in reserves, a sum large enough to run the institution at current levels for the next four and a half years without a single additional donation.

St. Jude makes a unique promise as part of its fundraising: “Families never receive a bill from St. Jude for treatment, travel, housing or food – because all a family should worry about is helping their child live.”

But for many families, treatment at St. Jude does not relieve all the financial burdens they incur in getting care for their children, including housing, travel, and food costs that fall outside the hospital’s strict limits, a ProPublica investigation has found.

While families may not receive a bill from St. Jude, the hospital doesn’t cover what’s usually the biggest source of financial stress associated with childhood cancer: The loss of income as parents quit or take leave from jobs to be with their child during treatment. For many families, the consequence is missed payments for cars, utilities, and cellphones. Others face eviction or foreclosure because they can’t keep up with rent and mortgage payments.

Parents at St. Jude have exhausted savings and retirement accounts, borrowed from family and friends, or asked other charities for aid. ProPublica identified more than 100 St. Jude families seeking financial help through the online fundraiser GoFundMe, with half of the campaigns started in the past two years. We counted scores of other events like concerts and yard sales organized to help St. Jude families in need.

One family relied on a mixed martial arts fighter to help raise money for expenses like car repairs and cellphone bills, items that St. Jude would not cover. Another spent $10,000, originally saved to purchase a home, on costs related to treatment at St. Jude.

Only about half of the $7.3 billion St. Jude has received in contributions in the past five fiscal years went to the hospital’s research and caring for patients, according to its financial filings with the Internal Revenue Service. About 30% covered the cost of its fundraising operations, and the remaining 20%, or $1 of every $5 donated, increased its reserve fund.

Further, ProPublica found, a substantial portion of the cost for treatment is paid not by St. Jude but by families’ private insurance or by Medicaid, the government insurance program for low-income families. About 90% of patients are insured, bringing in more than $100 million in reimbursements for treatment a year. If a family shows up at St. Jude without insurance, a company hired by the charity helps them find it. St. Jude does cover copays and deductibles, an unusual benefit.

St. Jude spends about $500 million a year on patient services – a figure that includes all medical care and other assistance. Very little of what St. Jude raises from the public goes to pay for food, travel, and housing for families, the investigation found. Last year, it was 2% of the money raised, or nearly $40 million.

In written responses to ProPublica, lawyers for St. Jude and its fundraising arm, the American Lebanese Syrian Associated Charities, or ALSAC, emphasized that countless families have benefited from the charity provided since the hospital opened its doors in 1962.

“ProPublica should be celebrating St. Jude and ALSAC for their commitment to finding cures, saving children’s lives, and optimizing patient outcomes,” one of their letters said.

It is unquestioned that St. Jude has helped thousands of children and their families over the decades. Patients have offered scores of testimonials about the hospital’s generosity and care.

“This often comes as a huge relief to families who often expect to sell all their belongings just so their children can get the medical care and treatment they need to save their lives,” the hospital’s lawyers wrote. “St. Jude and ALSAC understand that this arrangement cannot cover all financial obligations of all families, nor can St. Jude or ALSAC shield families from all the financial and emotional effects” of a child’s illness.

St. Jude said it discloses the limits of its aid to families on its website and in material provided to those whose children are admitted to the hospital. That includes the rule Burt ran into, that the hospital covers the travel and housing costs of only one caregiver and one patient. For many families, the daily food budget is capped at $50. In some cases, hotel stays en route are provided only if families travel more than 500 miles to get to St. Jude.

St. Jude said its assistance is “based on guidelines to ensure fairness and responsible use of donor funds” and on remaining compliant with a federal anti-kickback statute that makes it a criminal offense to offer something of value to induce a medical referral. St. Jude declined to explain how the law affects the amount or type of financial assistance it provides to families.

“St. Jude has never promised anyone – neither patients nor the public in general – that it can solve all financial problems,” the letter said.

When parents need additional financial help, St. Jude’s social workers often send them to smaller charities or in some cases suggest that they apply for government aid.

They refer many to the Andrew McDonough B+ Foundation, which gives more than $2.5 million a year in grants to thousands of families of pediatric cancer patients at hospitals across the country to help cover rent, utilities, and other urgent expenses.

Joe McDonough, the foundation’s founder and president, said St. Jude families have the same money problems as families of patients at other children’s hospitals, even though he said St. Jude’s marketing creates the public perception that it alleviates these burdens.

“People say to me, ‘Why are you helping St. Jude families?’ ” McDonough said. “Well, what happens when a family lives in Augusta, Georgia, and they’re being treated at St. Jude? They still have to pay the rent on their apartment back in Augusta, Georgia. They still have to make their car payment. And it’s not my position to say whether St. Jude should be paying for all those expenses or not. I’m just explaining that it’s not a totally free ride.”

The help St. Jude provides to families may soon be increasing.

After ProPublica provided St. Jude with the findings of its reporting, the hospital informed families of a dramatic expansion in the assistance it will give to parents and other relatives during their kids’ treatment in Memphis.

Among the most significant changes are increasing travel benefits to two parents instead of one and covering regular trips to Memphis for siblings and other loved ones. St. Jude’s letter to parents said the changes take effect Nov. 15.

That would’ve made a big difference for Burt.

Burt’s daughter, whom ProPublica is not identifying at her mother’s request, was originally diagnosed with cancer in early 2015, when doctors discovered a tumor pressing against her brain stem. She had successful emergency surgery to remove the mass at Dell Children’s Medical Center in Austin, Texas. Medicaid and Dell Children’s covered the bill, but the family was still faced with the cost of her ongoing treatment.

“At that point I’m thinking: ‘What am I going to do? I guess I’m selling my house, whatever it takes,’” Burt recalled. “Honestly, that was probably a big deciding factor for St. Jude.”

St. Jude accepted Burt’s daughter into a clinical trial, and the family moved to the hospital’s patient housing in Memphis for several months. Both parents stopped working for a time, and people in their hometown raised cash to pay their bills.

Her cancer relapsed the following year with several new, inoperable brain tumors. Burt and his daughter’s mom broke up during that round of treatment, and financial problems piled up.

Burt said his credit score dropped so low that utility companies refused to set up service unless he first paid a deposit. One of the family’s cars was repossessed, he said. Burt’s 2005 Chevrolet Colorado pickup has 300,000 miles on it, many of them logged on trips from Texas to Memphis. When Burt’s daughter was at St. Jude for treatment or exams, he’d work all week, then visit on many weekends where he would spend Saturday night sleeping in the hospital parking lot.

He asked hospital officials if he could sleep in St. Jude’s housing, but they turned him down, he said.

Burt said he was happy with the care St. Jude provided. His daughter’s health is stable, he said, and brain scans taken during her September exam confirmed her two remaining tumors haven’t grown. But he’s still trying to recover financially.

“It’s five years now,” Burt said, “and I’m not completely caught up yet.”
 

A fundraising giant

St. Jude began with a fledgling entertainer praying for a career break.

When Danny Thomas, a comic and actor best known for the TV sitcom “Make Room for Daddy,” was struggling to earn a living in the late 1930s, the devout Roman Catholic went to church and asked for help from the patron saint of desperate cases, St. Jude Thaddeus. If he made it big, Thomas promised to build “a shrine where the poor and the helpless and the hopeless may come for comfort and aid,” according to a history published by ALSAC.

Within five years, Thomas became a star and worked to fulfill his promise by building a children’s hospital named after St. Jude and a fundraising organization to support it. Thomas, whose parents were Lebanese immigrants, recruited others who shared his Middle Eastern roots to help.

He used his fame to raise the hospital’s profile, appearing in ads for St. Jude and hosting fundraising events starring the likes of Elvis Presley and Sammy Davis Jr. Thomas’ daughter Marlo, herself a TV star, succeeded him in championing St. Jude.

Today, St. Jude is a specialty treatment and research center with about 5,700 employees and 73 beds. Other top children’s hospitals have more staff and beds, and they also treat more conditions.

Though St. Jude raises money across the world, most of its patients come from Tennessee and surrounding states. Patients from elsewhere are usually enrolled in clinical trials.

ALSAC, which handles St. Jude’s fundraising and investments, has 2,188 employees in Memphis and in 36 regional offices across the country. More than 400 of the fundraising arm’s employees are paid over $100,000, according to IRS filings. The charity takes in so much money each year that it regularly steers hundreds of millions of dollars in donations to reserve accounts, the filings show.

Overall, St. Jude’s reserve has grown by 58% over the past five fiscal years, during which it has added $1.9 billion to its investment accounts and shifted its portfolio toward financial products designed to generate bigger returns than stocks, bonds, and mutual funds traditionally deliver. The charity stowed more than a third of the new surplus, $688 million, in riskier private equity investments.

IRS rules do not limit the size of a nonprofit’s reserves, and experts on charitable finance differ on best practices.

St. Jude meets Better Business Bureau guidelines, which call for charities to maintain reserves of less than three times total expenses, but other experts expressed alarm that the hospital had accumulated such a large sum of money.

The size of the St. Jude reserve is “staggering,” said Laura Otten, the director of LaSalle University’s master program in nonprofit leadership. She said a typical reserve for a nonprofit the size of St. Jude is one to two years of expenses. Donors generally want to know their dollars are being put to work, she said.

The hospital said it needs a large reserve because its unique operating model relies on donations to fund annual operating costs. “[W]e are highly donor-dependent and subject to the economic driven vagaries of charitable giving,” the hospital said in a written response to ProPublica questions.

But the hospital’s reserve is already more than large enough to buffer against recessions and potential drops in donations, said Ge Bai, a professor of accounting and health policy at Johns Hopkins University. “They should be spending the money as aggressively as they raise it, but they seem to be hoarding,” Bai said.

The hospital said it is also raising billions to fund the construction of new housing and research space, although its plans do not currently include spending any of the reserve on new facilities.

St. Jude’s reserves have ballooned at a time when researchers, oncologists, advocates, and families complain about a dearth of funding for pediatric cancer studies nationally.

Dozens of other children’s hospitals across the country have research divisions devoted to pediatric cancer and enroll their patients in clinical trials for new drugs and procedures. They pay for research staff and studies in part with donations from their local communities, often competing directly against St. Jude. ALSAC has regional offices in several U.S. cities with elite pediatric cancer centers of their own, including Atlanta, Chicago, Denver, and Seattle.

Coury Shadyac, an ALSAC vice president and daughter of the organization’s CEO, Richard Shadyac Jr., oversees a team of 45 fundraisers along the West Coast “raising $300 million annually” for St. Jude, according to her LinkedIn profile. That’s $100 million more in donations than either Children’s Hospital Los Angeles or Seattle Children’s Hospital, two of the nation’s leading pediatric cancer institutions, received in fiscal year 2019, IRS disclosures show. But it’s only a small part of St. Jude’s fundraising haul.

ALSAC’s ubiquitous fundraising has led to concerns that it undercuts other hospitals’ campaigns. Some doctors interviewed by ProPublica said they have encouraged donors to give their money to hospitals closer to home.

David Clark, a pediatrician and former longtime chairperson of pediatrics at Albany Medical Center in New York, said St. Jude raises tens of thousands of dollars in his region that does little to benefit the children with cancer in his area since almost all are treated locally. ALSAC has a fundraising office located a few miles from Albany Medical.

“They think of every way they can to make money and the least amount of ways to spend it,” Clark said. “They deceive people into supporting something that is totally dishonest.”

Nearly all St. Jude solicitations feature the hospital’s patients – the children usually smiling and bald from treatment – along with the familiar promise that it never sends families a bill.

It’s a message that ALSAC has tested and researched to maximize donations. Donors appreciate the promise to never bill families, said Mary Kate Tolan, an ALSAC executive, in a podcast last year. She added that no parent should have to take out a second mortgage or lose their job because their child is being treated at St. Jude.

Alternative messaging to the no-bills promise did not “perform as well,” said Tolan, who develops emerging technologies for ALSAC. Tolan did not return requests for comment.
 

“Borrowing and begging”

Catherine Rainey thought she would be free of financial worry when her 2-year-old daughter Harlee was admitted to St. Jude last year.

“The first thing my dad said was: ‘Catherine, you have nothing to worry about. They raise billions of dollars. Anytime you have a problem, you tell them and they will take care of it,’ ” she said.

But like many families, the Raineys discovered that St. Jude’s charity came with limits on payments for expenses such as travel that could be bewildering.

Harlee ended up at St. Jude after first going to nearby Niswonger Children’s Hospital in Johnson City, Tenn., in October 2020. The doctors there discovered a cancerous mass attached to her right kidney. The hospital is a St. Jude affiliate, and the doctors recommended the toddler be treated in Memphis.

Rainey, a single mother of two young girls, had to leave her job as a nurse for months to be with Harlee at St. Jude. The loss of income quickly created problems. “My family, we don’t come from money,” she said. “We are not doctors and billionaires. We make it. That is it.”

St. Jude did provide food and housing on campus. But the hospital said it couldn’t help with the items that were causing Rainey to worry, including car payments, insurance, and cellphone bills.

Rainey’s boss set up a GoFundMe account to help make up some of her lost income. A small local charity, Kari’s Heart Foundation, also helped out by paying about $3,000 worth of phone bills and car payments, staving off repossession.

“It was just a bunch of borrowing and begging,” Rainey said of her experience while her daughter was treated in Memphis. “They acted like it was coming out of their own pocket.”

Harlee has checkups at St. Jude every three months that last about four days. The costs of travel to and from St. Jude put an additional strain on Rainey and Harlee. St. Jude is an eight-hour ride, without stops, from Rainey’s home in Appalachia, Va., a town of 1,432 people near the Kentucky border.

Rainey said her daughter generally can make it about two-thirds of the way, with frequent stops, before she has had enough. “When she is done, she is really done,” Rainey said. “She will scream, cry, and kick.”

In July, in advance of an August trip to Memphis, Rainey called the patient services department at St. Jude to see whether they could help pay for a hotel to break up the travel day — an expense Rainey said she could not afford.

To qualify for a hotel reimbursement, Rainey said, St. Jude told her she had to live more than 500 miles from Memphis. The ride from her home to the hospital is 530 miles (a measurement ProPublica confirmed with mapping tools). However, Rainey said, St. Jude told her it measured the trip from city limit to city limit and came up with a distance of 491 miles. Even using that metric, the distance is still more than 500 miles, ProPublica found.

When she challenged the hospital’s stance, Rainey said she was berated by a patient services representative.

“I was feeling pissed off, and I was crying,” Rainey said of the interaction. “You give up your whole life for your child, and they tell you don’t worry about anything, we will cover this and then they tell you to just push through the drive.”

Rainey did what she could to make the trip go smoothly: She configured a small table to extend across her daughter’s car seat, so Harlee could play with the coloring books, markers, and Play-Doh bought for the ride. She packed snacks and a cooler full of drinks. Since Harlee was still potty training, she brought extra towels and clothes for accidents. The final step was handing Harlee her Baby Yoda doll once she settled into her car seat. Rainey had sewed a port in the doll’s chest to mirror the one Harlee has in hers.

About three hours from Memphis, Harlee was crying inconsolably. Rainey pulled off the interstate and stopped at the first hotel she could find. She later learned it had been described in online reviews as “awful,” a “nightmare,” “disgusting,” and “horrible.”

“I didn’t know the area,” she said. “The hotel was garbage. It just made it worse.”

The drive home also required a hotel stop, but this time Rainey was able to find one that was cleaner. A $100 donation from a local charity helped to offset the cost.

Among the changes St. Jude is making is to reimburse families like Rainey’s, who live more than 400 miles from the hospital, for an overnight stay at a hotel when making the trip to Memphis.

Rainey said she was called by a St. Jude representative after ProPublica asked about her situation and was told the hospital would pay for her past hotel stays when traveling back and forth to St. Jude. The representative, Rainey said, also told her the hospital discovered the way it had been measuring mileage was inaccurate.

“I am not the only one,” Rainey said. “There are others. They should reimburse all the families.”

The anxiety of unpaid bills piling up, combined with caring for a child undergoing chemotherapy or radiation, takes a severe toll on parents and guardians, said Christopher Hope, a UPS driver who started a Memphis-based foundation after meeting St. Jude parents who were in financial crisis.

Hope’s small charity spent $12,000 last year to help families. Parents in St. Jude social media groups often refer families in need to it. The charity has helped families cover mortgage and car payments.

“I never knew anything about this until hearing about it from families,” Hope said. “All we hear is about kids and treatment, not the other side of it.”
 

“It’s not free”

In addition to charities like Hope’s, St. Jude families have repeatedly turned to fundraising sites and networks of their relatives, friends, and neighbors to help cover basic expenses while unable to work during their children’s treatment. Parents’ requests on fundraising sites are sometimes desperate pleas.

In January 2017, one father in North Carolina said he’d had to abandon a business venture to take time for his son to receive care at St. Jude. His income had plummeted. He asked friends to give as little as $10 to “at least make it possible to survive.”

This year, a mother in Memphis whose 1-year-old son receives care at St. Jude for sickle cell disorder ran out of medical leave and couldn’t work her shifts at a clothing distribution center. After the child had a flare-up in July requiring several days of treatment at the hospital, she said she returned home to find her power shut off. Sitting in a dark apartment, unable to pay her utility bills, she set up a GoFundMe campaign. She received less than $20 through the site; her relatives eventually pooled $350 to get her electricity restored.

Even parents with stable jobs and private health insurance often take on debt and need outside help.

When Taylr and Treg Murphy’s 17-year-old son Peyton was diagnosed with cancer and needed monthslong treatment at St. Jude in 2017, the entire family – mom, dad, sister, and brother – went with him, traveling from their home in Lafayette, La., to Memphis. Treg took a leave from his job at an oil mining company and Taylr, who works at her mother’s bakery, did the same.

“We knew that it was going to be a collective team effort,” Treg said. “Without even a discussion, we figured that if Peyton’s got to go for the surgery, we’re all going.”

Peyton had an enormous tumor that had grown out of his right femur and was crowding his knee. Rounds of chemotherapy appeared to have killed osteosarcoma cells elsewhere in his body. But he needed to undergo a procedure called limb-sparing surgery that would require weeks of recovery time at the hospital.

The hospital agreed to allow all five family members to stay for free at St. Jude if they bunked together in a single room. It assigned them a spot in Tri Delta Place, its hotel-like short-term patient residence on the campus. Tri Delta is set up for visits of up to seven days, according to the hospital’s guide for volunteers, but the Murphys were there for almost 50.

Taylr said the unit at Tri Delta had no oven or stove and St. Jude provided no grocery money, instead allotting them a $50-per-day credit at the hospital cafeteria, Kay Kafe – not enough to feed the family of five. As the weeks wore on, the Murphys split grilled cheese sandwiches and paid for food out of pocket.

After ProPublica asked about the hospital’s food allowances, St. Jude said it would increase them as part of the changes scheduled to go into effect this month. The hospital switched from a $50-a-day cap per family to providing $25 a day to each family member. For a family of four, that would double the food benefit. A weekly stipend given to families in long-term housing was increased to $150 from $125.

For the Murphys, it was the loss of their work income, more than out-of-pocket expenses, that put them into a financial hole as Peyton’s treatment went on. Treg’s employer couldn’t pay him during his long absences.

Fearful of being evicted or having their car repossessed, Taylr said she asked a St. Jude social worker for assistance. The social worker helped her apply for grants from other charities. Taylr said the B+ Foundation paid their rent one month, which ensured they’d have a home to return to.

In the years since his initial treatment, Peyton has gone back to St. Jude repeatedly for exams and surgeries to remove malignant growths in his lungs. Taylr and Treg have missed more work to bring Peyton to Memphis, costing them thousands of dollars more in income.

By the start of this year, Taylr and Treg said they were about $20,000 in debt and panicking. Dustin Poirier, a former UFC champion from their hometown, heard from a friend about Peyton and the family’s financial trouble. He donated $10,000 to them from his personal charity and in May hosted a local fundraiser that collected enough to pay off their credit cards.

St. Jude families sometimes commiserate about money problems with each other, Taylr said, but few are aware of the extent of the hospital’s unspent resources. The Murphys said they didn’t know St. Jude has more than $5 billion in reserve or that it continues to raise hundreds of millions of dollars in surplus donations each year.

“That’s just insane,” Taylr said. “That just blows my mind. When we first started getting treated, people would be like, ‘Oh, St. Jude covers everything, that’s awesome.’ That’s not how it works. People don’t understand that. I truly didn’t understand before I got into St. Jude.”

Taylr and Treg said the doctors at St. Jude are “amazing” and they’re grateful for their son’s care. But they bristled at the assumption that it was covered by the hospital’s charity. The family’s insurance paid a substantial part of the bills.

“It’s not free,” Taylr said. “My husband works very hard for the insurance we have – and they are billed.” The Murphys pay $12,000 in health insurance premiums each year.

Their struggle continues. Peyton’s cancer has relapsed, and he’s making regular trips with his mom or dad back to St. Jude for chemotherapy. The family is again applying for help from other charities.
 

Wiped out savings

The costs associated with care at St. Jude caused at least one family to stop going to Memphis altogether.

Last winter, Kelly Edwards was excitedly searching through Tulsa real estate listings after years of diligently saving $10,000 for a down payment on a house. She craved a permanent home for herself and the two young brothers she had taken in five years earlier at the behest of a family friend. She hoped to adopt the boys, now 13 and 9, who call her mom.

In February, the older boy, DJ, was lethargic and uninterested in his schoolwork. After several doctor visits, he was diagnosed with acute lymphoblastic leukemia at a Tulsa hospital. The cancer, referred to as ALL, is the most common type among children, with survival rates that exceed 90%. A day after his diagnosis, DJ and Edwards were driving six hours to Memphis for treatment at St. Jude, which is affiliated with the Oklahoma hospital.

The pair stayed for free at an independently operated Ronald McDonald House near St. Jude, and a weekly stipend from the hospital helped to pay for meals – aid that Edwards said was a blessing. DJ had health insurance through the Oklahoma Medicaid program.

But as with the Murphys, lost income soon put Edwards’ family into financial jeopardy. She works as a supervisor for a company that delivers packages for Amazon. After she used up two weeks of paid time off, she stopped getting paychecks. The bills, however, kept coming: rent, car payments, utilities. To that was added the $250 a week she paid a friend to stay with DJ’s younger brother and her two dogs in Tulsa.

Within four months, her house savings were wiped out. Edwards said she told her St. Jude social worker about her financial woes but got no additional help.

One of Edwards’ adult daughters started a GoFundMe campaign to help, bringing in just over $3,000. Edwards said she appreciated the aid but believes donations were kept low by the widespread perception that St. Jude families don’t have financial problems.

“Everyone hears that everything is taken care of by St. Jude,” she said. “That is not true, but everyone has that mentality.” She said someone she knew asked her “what is that money going for if St. Jude’s is paying for everything?”

DJ was scheduled to go back to St. Jude for three weeks of treatment in August, but Edwards decided she simply couldn’t afford it. “I don’t have the money to go back and forth,” she said. She worked with DJ’s local doctors and found that the hospital near her home in Tulsa could provide the same treatment he was scheduled to get in Tennessee.

The local treatment allowed her to continue working some shifts and to be at home with both of her boys. DJ is also happier when he is home, Edwards said.

Edwards and the boys are now living in a small house her brother owns just outside Tulsa. Late on a recent weekday afternoon, DJ slowly shuffled into the living room, exhausted from a day of chemotherapy treatment.

He is in the midst of a 20-week regimen where he receives the cancer-killing drugs every other day, just one phase of a nearly three-year treatment plan. He wore an orange knit hat, T-shirt, and shorts. He rubbed his eyes before asking a visitor, “How is your day going?” He smiled at the positive response. When he heard the family was eating steak for dinner, he eagerly jumped up to start helping in the kitchen. After they moved in, Edwards hung family portraits on the walls to make it feel homier. She doesn’t expect they will be moving again any time soon.

The dream of buying a home of their own is gone.

Former ProPublica reporter Marshall Allen contributed reporting. Kirsten Berg contributed research.

This story was originally published on ProPublica. ProPublica is a nonprofit newsroom that investigates abuses of power. Sign up to receive their biggest stories as soon as they’re published.