Heidi Splete

Maternal mortality in the United States has been rising for several decades, but actions taken at the community level, as well as larger public health initiatives, have the potential to slow this trend, according to experts at a webinar sponsored by the National Institute for Health Care Management.

Maternal mortality in the United States increased by 14% from 2018 to 2020, according to data from the Centers for Disease Control and Prevention’s National Center for Health Statistics.

However, more than 80% of pregnancy-related deaths are preventable, according to 2017-2019 data from the Maternal Mortality Review Committees published online by the CDC. MMRCs include representatives of diverse clinical and nonclinical backgrounds who review the circumstances of pregnancy-related deaths.

In a webinar presented on Sept. 20, the NIHCM enlisted a panel of experts to discuss maternal mortality, the effect of changes to reproductive rights, and potential strategies to improve maternal health outcomes.

Maternal mortality is defined as “death while pregnant or within 42 days of the end of pregnancy, irrespective of the duration and site of pregnancy, from any cause related to pregnancy or its management,” according to the CDC.

Importantly, mortality rates in the United States are approximately three times higher in Black women compared with White women, said Ndidiamaka Amutah-Onukagha, PhD, MPH, of the Tufts University Center for Black Maternal Health & Reproductive Justice. Dr. Amutah-Onukagha addressed some of the potential issues that appear to drive the disparity in care.

The lack of diversity in the health care workforce has a significant effect on patient outcomes, Dr. Amutah-Onukagha said. Overall, Black newborns are more than twice as likely as White newborns to die during their first year of life, but this number is cut in half when Black infants are cared for by Black physicians, she emphasized.

Other factors that may affect disparities in maternal health care include limited access to prenatal care, discriminatory hospital protocols, and mistreatment by health care professionals, said Dr. Amutah-Onukagha. She cited data showing that maternal mortality rates were higher in rural compared with urban areas. “According to the American Hospital Association, half of rural hospitals have no obstetric care, leaving mothers in maternity care deserts; this exacerbates existing disparities,” she said.

In the webinar, Sindhu Srinivas, MD, a maternal-fetal medicine specialist at the University of Pennsylvania, explained how patient, community, and system factors play a role in the disparities in maternal care.

Overall, Black women have to travel further to receive care, which has implications for high-risk pregnancies, and patients on Medicaid have to wait longer for care, and are less likely to be referred, she added. Black women also have higher rates of preexisting conditions compared with other populations that put them in the high-risk category, such as high blood pressure, diabetes, obesity, or being HIV positive, she said.

Other factors contributing to persistent disparities in maternal care include sociodemographics, patient beliefs and knowledge, and psychological issues including stress, said Dr. Srinivas. Community factors, such as social networks, safety, and poverty, also play a role, as do clinician factors of implicit bias and communication skills, she said.

Strategies to reduce disparity

Dr. Srinivas presented several strategies to reduce disparities at various levels. At the policy level, interventions such as establishing a Maternal Mortality Review Committee, establishing a perinatal quality collaborative, and extending Medicaid for a full year postpartum could help improve outcomes, she said. Dr. Srinivas also encouraged clinicians to report maternal mortality data stratified by race and ethnicity, and to participate in the Alliance for Innovation on Maternal Health program (AIM), an initiative in partnership with the American College of Obstetrics and Gynecology.

Dr. Srinivas also proposed maternal health policies to develop payment models “to sustain and scale innovative solutions, and “preserve access to contraception and abortion care.”

For clinicians looking to have an immediate impact, the panelists agreed that working with community health centers can make a significant difference by improving access to maternal care. Consider opportunities for partnership between hospitals and health care delivery centers in the community, said Dr. Srinivas.

Also, don’t underestimate the value of doulas in the birthing process, Dr. Amutah-Onukagha said. She urged clinicians to advocate for doula reimbursement and to take advantage of opportunities for doulas to work with pregnant individuals at the community levels. Data suggest that doulas are associated with increased maternal care visits and with breastfeeding, she noted.

Adam Myers, MD, of the Blue Cross Blue Shield Association, also contributed to the webinar discussion with a key point: Having financial means and commercial coverage is not a buffer against adverse maternal outcomes for racial minorities.

Dr. Myers cited the latest Health of America Report, which included data up to April 2021 with surveys of Medicaid members and their experiences. According to the report, rates of severe maternal mortality (SMM) increased by 9% for commercially and Medicaid-insured women between 2018 and 2020.

Among commercially insured women, SMM was 53% higher among Black women than White women; among Medicaid-insured women, Black women had a 73% higher rate of SMM, compared with White women.

In addition, the report showed that significantly more mothers of color were not able to complete the recommended series of prenatal visits, mainly for reasons of scheduling and transportation, which were greater barriers than COVID-19, Dr. Myers said.

Based on the data, one specific risk profile rose to the top: “We believe women of color aged 35 or higher with comorbid conditions should be treated as very high risk for SMM,” Dr. Myers emphasized. He stressed the need to focus on transportation and scheduling barriers and expressed support for partnerships and health care delivery centers in the community to mitigate these issues.

Finally, Dr. Srinivas encouraged clinicians to have confidence in their expertise and make themselves heard to help their patients and improve maternal health for all. “Use your voice,” said Dr. Srinivas, “As physicians we don’t think of that as an important aspect of our work, or that we can’t articulate, but remember that we are experts, and sharing stories of patients who are impacted is incredibly powerful,” she said.

The presenters had no relevant financial conflicts to disclose.

Maternal mortality in the United States has been rising for several decades, but actions taken at the community level, as well as larger public health initiatives, have the potential to slow this trend, according to experts at a webinar sponsored by the National Institute for Health Care Management.

Maternal mortality in the United States increased by 14% from 2018 to 2020, according to data from the Centers for Disease Control and Prevention’s National Center for Health Statistics.

However, more than 80% of pregnancy-related deaths are preventable, according to 2017-2019 data from the Maternal Mortality Review Committees published online by the CDC. MMRCs include representatives of diverse clinical and nonclinical backgrounds who review the circumstances of pregnancy-related deaths.

In a webinar presented on Sept. 20, the NIHCM enlisted a panel of experts to discuss maternal mortality, the effect of changes to reproductive rights, and potential strategies to improve maternal health outcomes.

Maternal mortality is defined as “death while pregnant or within 42 days of the end of pregnancy, irrespective of the duration and site of pregnancy, from any cause related to pregnancy or its management,” according to the CDC.

Importantly, mortality rates in the United States are approximately three times higher in Black women compared with White women, said Ndidiamaka Amutah-Onukagha, PhD, MPH, of the Tufts University Center for Black Maternal Health & Reproductive Justice. Dr. Amutah-Onukagha addressed some of the potential issues that appear to drive the disparity in care.

The lack of diversity in the health care workforce has a significant effect on patient outcomes, Dr. Amutah-Onukagha said. Overall, Black newborns are more than twice as likely as White newborns to die during their first year of life, but this number is cut in half when Black infants are cared for by Black physicians, she emphasized.

Other factors that may affect disparities in maternal health care include limited access to prenatal care, discriminatory hospital protocols, and mistreatment by health care professionals, said Dr. Amutah-Onukagha. She cited data showing that maternal mortality rates were higher in rural compared with urban areas. “According to the American Hospital Association, half of rural hospitals have no obstetric care, leaving mothers in maternity care deserts; this exacerbates existing disparities,” she said.

In the webinar, Sindhu Srinivas, MD, a maternal-fetal medicine specialist at the University of Pennsylvania, explained how patient, community, and system factors play a role in the disparities in maternal care.

Overall, Black women have to travel further to receive care, which has implications for high-risk pregnancies, and patients on Medicaid have to wait longer for care, and are less likely to be referred, she added. Black women also have higher rates of preexisting conditions compared with other populations that put them in the high-risk category, such as high blood pressure, diabetes, obesity, or being HIV positive, she said.

Other factors contributing to persistent disparities in maternal care include sociodemographics, patient beliefs and knowledge, and psychological issues including stress, said Dr. Srinivas. Community factors, such as social networks, safety, and poverty, also play a role, as do clinician factors of implicit bias and communication skills, she said.

Strategies to reduce disparity

Dr. Srinivas presented several strategies to reduce disparities at various levels. At the policy level, interventions such as establishing a Maternal Mortality Review Committee, establishing a perinatal quality collaborative, and extending Medicaid for a full year postpartum could help improve outcomes, she said. Dr. Srinivas also encouraged clinicians to report maternal mortality data stratified by race and ethnicity, and to participate in the Alliance for Innovation on Maternal Health program (AIM), an initiative in partnership with the American College of Obstetrics and Gynecology.

Dr. Srinivas also proposed maternal health policies to develop payment models “to sustain and scale innovative solutions, and “preserve access to contraception and abortion care.”

For clinicians looking to have an immediate impact, the panelists agreed that working with community health centers can make a significant difference by improving access to maternal care. Consider opportunities for partnership between hospitals and health care delivery centers in the community, said Dr. Srinivas.

Also, don’t underestimate the value of doulas in the birthing process, Dr. Amutah-Onukagha said. She urged clinicians to advocate for doula reimbursement and to take advantage of opportunities for doulas to work with pregnant individuals at the community levels. Data suggest that doulas are associated with increased maternal care visits and with breastfeeding, she noted.

Adam Myers, MD, of the Blue Cross Blue Shield Association, also contributed to the webinar discussion with a key point: Having financial means and commercial coverage is not a buffer against adverse maternal outcomes for racial minorities.

Dr. Myers cited the latest Health of America Report, which included data up to April 2021 with surveys of Medicaid members and their experiences. According to the report, rates of severe maternal mortality (SMM) increased by 9% for commercially and Medicaid-insured women between 2018 and 2020.

Among commercially insured women, SMM was 53% higher among Black women than White women; among Medicaid-insured women, Black women had a 73% higher rate of SMM, compared with White women.

In addition, the report showed that significantly more mothers of color were not able to complete the recommended series of prenatal visits, mainly for reasons of scheduling and transportation, which were greater barriers than COVID-19, Dr. Myers said.

Based on the data, one specific risk profile rose to the top: “We believe women of color aged 35 or higher with comorbid conditions should be treated as very high risk for SMM,” Dr. Myers emphasized. He stressed the need to focus on transportation and scheduling barriers and expressed support for partnerships and health care delivery centers in the community to mitigate these issues.

Finally, Dr. Srinivas encouraged clinicians to have confidence in their expertise and make themselves heard to help their patients and improve maternal health for all. “Use your voice,” said Dr. Srinivas, “As physicians we don’t think of that as an important aspect of our work, or that we can’t articulate, but remember that we are experts, and sharing stories of patients who are impacted is incredibly powerful,” she said.

The presenters had no relevant financial conflicts to disclose.

Maternal mortality in the United States has been rising for several decades, but actions taken at the community level, as well as larger public health initiatives, have the potential to slow this trend, according to experts at a webinar sponsored by the National Institute for Health Care Management.

Maternal mortality in the United States increased by 14% from 2018 to 2020, according to data from the Centers for Disease Control and Prevention’s National Center for Health Statistics.

However, more than 80% of pregnancy-related deaths are preventable, according to 2017-2019 data from the Maternal Mortality Review Committees published online by the CDC. MMRCs include representatives of diverse clinical and nonclinical backgrounds who review the circumstances of pregnancy-related deaths.

In a webinar presented on Sept. 20, the NIHCM enlisted a panel of experts to discuss maternal mortality, the effect of changes to reproductive rights, and potential strategies to improve maternal health outcomes.

Maternal mortality is defined as “death while pregnant or within 42 days of the end of pregnancy, irrespective of the duration and site of pregnancy, from any cause related to pregnancy or its management,” according to the CDC.

Importantly, mortality rates in the United States are approximately three times higher in Black women compared with White women, said Ndidiamaka Amutah-Onukagha, PhD, MPH, of the Tufts University Center for Black Maternal Health & Reproductive Justice. Dr. Amutah-Onukagha addressed some of the potential issues that appear to drive the disparity in care.

The lack of diversity in the health care workforce has a significant effect on patient outcomes, Dr. Amutah-Onukagha said. Overall, Black newborns are more than twice as likely as White newborns to die during their first year of life, but this number is cut in half when Black infants are cared for by Black physicians, she emphasized.

Other factors that may affect disparities in maternal health care include limited access to prenatal care, discriminatory hospital protocols, and mistreatment by health care professionals, said Dr. Amutah-Onukagha. She cited data showing that maternal mortality rates were higher in rural compared with urban areas. “According to the American Hospital Association, half of rural hospitals have no obstetric care, leaving mothers in maternity care deserts; this exacerbates existing disparities,” she said.

In the webinar, Sindhu Srinivas, MD, a maternal-fetal medicine specialist at the University of Pennsylvania, explained how patient, community, and system factors play a role in the disparities in maternal care.

Overall, Black women have to travel further to receive care, which has implications for high-risk pregnancies, and patients on Medicaid have to wait longer for care, and are less likely to be referred, she added. Black women also have higher rates of preexisting conditions compared with other populations that put them in the high-risk category, such as high blood pressure, diabetes, obesity, or being HIV positive, she said.

Other factors contributing to persistent disparities in maternal care include sociodemographics, patient beliefs and knowledge, and psychological issues including stress, said Dr. Srinivas. Community factors, such as social networks, safety, and poverty, also play a role, as do clinician factors of implicit bias and communication skills, she said.

Strategies to reduce disparity

Dr. Srinivas presented several strategies to reduce disparities at various levels. At the policy level, interventions such as establishing a Maternal Mortality Review Committee, establishing a perinatal quality collaborative, and extending Medicaid for a full year postpartum could help improve outcomes, she said. Dr. Srinivas also encouraged clinicians to report maternal mortality data stratified by race and ethnicity, and to participate in the Alliance for Innovation on Maternal Health program (AIM), an initiative in partnership with the American College of Obstetrics and Gynecology.

Dr. Srinivas also proposed maternal health policies to develop payment models “to sustain and scale innovative solutions, and “preserve access to contraception and abortion care.”

For clinicians looking to have an immediate impact, the panelists agreed that working with community health centers can make a significant difference by improving access to maternal care. Consider opportunities for partnership between hospitals and health care delivery centers in the community, said Dr. Srinivas.

Also, don’t underestimate the value of doulas in the birthing process, Dr. Amutah-Onukagha said. She urged clinicians to advocate for doula reimbursement and to take advantage of opportunities for doulas to work with pregnant individuals at the community levels. Data suggest that doulas are associated with increased maternal care visits and with breastfeeding, she noted.

Adam Myers, MD, of the Blue Cross Blue Shield Association, also contributed to the webinar discussion with a key point: Having financial means and commercial coverage is not a buffer against adverse maternal outcomes for racial minorities.

Dr. Myers cited the latest Health of America Report, which included data up to April 2021 with surveys of Medicaid members and their experiences. According to the report, rates of severe maternal mortality (SMM) increased by 9% for commercially and Medicaid-insured women between 2018 and 2020.

Among commercially insured women, SMM was 53% higher among Black women than White women; among Medicaid-insured women, Black women had a 73% higher rate of SMM, compared with White women.

In addition, the report showed that significantly more mothers of color were not able to complete the recommended series of prenatal visits, mainly for reasons of scheduling and transportation, which were greater barriers than COVID-19, Dr. Myers said.

Based on the data, one specific risk profile rose to the top: “We believe women of color aged 35 or higher with comorbid conditions should be treated as very high risk for SMM,” Dr. Myers emphasized. He stressed the need to focus on transportation and scheduling barriers and expressed support for partnerships and health care delivery centers in the community to mitigate these issues.

Finally, Dr. Srinivas encouraged clinicians to have confidence in their expertise and make themselves heard to help their patients and improve maternal health for all. “Use your voice,” said Dr. Srinivas, “As physicians we don’t think of that as an important aspect of our work, or that we can’t articulate, but remember that we are experts, and sharing stories of patients who are impacted is incredibly powerful,” she said.

The presenters had no relevant financial conflicts to disclose.

Tralokinumab has received a positive opinion from the European Medicine Agency’s Committee for Medicinal Products for Human Use to extend use to adolescents aged 12 years and older with moderate-to-severe atopic dermatitis (AD) who are candidates for systemic therapy, according to a statement from the manufacturer.

The positive CHMP opinion, issued on Sept. 15, recommends extending the use of tralokinumab (Adtralza), an interleukin-13 antagonist, to adolescents aged 12-17 years in the EU. The positive opinion recommends an initial dose of 600 mg administered subcutaneously followed by 300 mg every other week, the dosing recommended for adults.

In December 2021, tralokinumab was approved for adults with moderate to severe AD in the United States, where it is marketed as Adbry. It is also approved for adults in the EU, Great Britain, Canada, the United Arab Emirates, and Switzerland. It is not currently approved for treatment of adolescents in any country, according to the LEO Pharma statement.

A regulatory filing with the U.S. Food and Drug Administration is in progress, the company said, and an additional study of tralokinumab for individuals aged 12 years and older is underway, according to the manufacturer.

The CHMP opinion was supported by data from a phase 3 study (ECZTRA 6) that assessed safety and efficacy of 150-mg or 300-mg doses of tralokinumab, compared with placebo in adolescents with moderate-to-severe AD, the company statement said. The primary outcomes were an Investigator Global Assessment score of clear or almost clear skin (IGA 0/1) and an improvement of at least a 75% on the Eczema Area and Severity Index score (EASI-75). In the study, presented as a poster at a meeting in October 2021, a total of 195 adolescents aged 12-17 with moderate to severe AD who were candidates for systemic therapy were randomly assigned to tralokinumab and 94 to placebo.

At 16 weeks, 21.4% and 17.5% of patients who received 150 mg and 300 mg, respectively, of tralokinumab had IGA scores of 0 or 1, compared with 4.3% of those on placebo (P < .001, P = .002, respectively vs. placebo). In addition, 28.6% and 27.8% of the 150-mg and 300-mg tralokinumab groups, respectively, achieved EASI-75, compared with 6.4% of placebo patients (P < .001, P = .001, respectively, compared with placebo).

Adverse events were similar between the groups, and most were mild or moderate; overall safety profiles were similar to those seen in adult patients.

The European Commission will review the positive opinion and make a final decision.

The research was supported by LEO Pharma.

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

Tralokinumab has received a positive opinion from the European Medicine Agency’s Committee for Medicinal Products for Human Use to extend use to adolescents aged 12 years and older with moderate-to-severe atopic dermatitis (AD) who are candidates for systemic therapy, according to a statement from the manufacturer.

The positive CHMP opinion, issued on Sept. 15, recommends extending the use of tralokinumab (Adtralza), an interleukin-13 antagonist, to adolescents aged 12-17 years in the EU. The positive opinion recommends an initial dose of 600 mg administered subcutaneously followed by 300 mg every other week, the dosing recommended for adults.

In December 2021, tralokinumab was approved for adults with moderate to severe AD in the United States, where it is marketed as Adbry. It is also approved for adults in the EU, Great Britain, Canada, the United Arab Emirates, and Switzerland. It is not currently approved for treatment of adolescents in any country, according to the LEO Pharma statement.

A regulatory filing with the U.S. Food and Drug Administration is in progress, the company said, and an additional study of tralokinumab for individuals aged 12 years and older is underway, according to the manufacturer.

The CHMP opinion was supported by data from a phase 3 study (ECZTRA 6) that assessed safety and efficacy of 150-mg or 300-mg doses of tralokinumab, compared with placebo in adolescents with moderate-to-severe AD, the company statement said. The primary outcomes were an Investigator Global Assessment score of clear or almost clear skin (IGA 0/1) and an improvement of at least a 75% on the Eczema Area and Severity Index score (EASI-75). In the study, presented as a poster at a meeting in October 2021, a total of 195 adolescents aged 12-17 with moderate to severe AD who were candidates for systemic therapy were randomly assigned to tralokinumab and 94 to placebo.

At 16 weeks, 21.4% and 17.5% of patients who received 150 mg and 300 mg, respectively, of tralokinumab had IGA scores of 0 or 1, compared with 4.3% of those on placebo (P < .001, P = .002, respectively vs. placebo). In addition, 28.6% and 27.8% of the 150-mg and 300-mg tralokinumab groups, respectively, achieved EASI-75, compared with 6.4% of placebo patients (P < .001, P = .001, respectively, compared with placebo).

Adverse events were similar between the groups, and most were mild or moderate; overall safety profiles were similar to those seen in adult patients.

The European Commission will review the positive opinion and make a final decision.

The research was supported by LEO Pharma.

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

Tralokinumab has received a positive opinion from the European Medicine Agency’s Committee for Medicinal Products for Human Use to extend use to adolescents aged 12 years and older with moderate-to-severe atopic dermatitis (AD) who are candidates for systemic therapy, according to a statement from the manufacturer.

The positive CHMP opinion, issued on Sept. 15, recommends extending the use of tralokinumab (Adtralza), an interleukin-13 antagonist, to adolescents aged 12-17 years in the EU. The positive opinion recommends an initial dose of 600 mg administered subcutaneously followed by 300 mg every other week, the dosing recommended for adults.

In December 2021, tralokinumab was approved for adults with moderate to severe AD in the United States, where it is marketed as Adbry. It is also approved for adults in the EU, Great Britain, Canada, the United Arab Emirates, and Switzerland. It is not currently approved for treatment of adolescents in any country, according to the LEO Pharma statement.

A regulatory filing with the U.S. Food and Drug Administration is in progress, the company said, and an additional study of tralokinumab for individuals aged 12 years and older is underway, according to the manufacturer.

The CHMP opinion was supported by data from a phase 3 study (ECZTRA 6) that assessed safety and efficacy of 150-mg or 300-mg doses of tralokinumab, compared with placebo in adolescents with moderate-to-severe AD, the company statement said. The primary outcomes were an Investigator Global Assessment score of clear or almost clear skin (IGA 0/1) and an improvement of at least a 75% on the Eczema Area and Severity Index score (EASI-75). In the study, presented as a poster at a meeting in October 2021, a total of 195 adolescents aged 12-17 with moderate to severe AD who were candidates for systemic therapy were randomly assigned to tralokinumab and 94 to placebo.

At 16 weeks, 21.4% and 17.5% of patients who received 150 mg and 300 mg, respectively, of tralokinumab had IGA scores of 0 or 1, compared with 4.3% of those on placebo (P < .001, P = .002, respectively vs. placebo). In addition, 28.6% and 27.8% of the 150-mg and 300-mg tralokinumab groups, respectively, achieved EASI-75, compared with 6.4% of placebo patients (P < .001, P = .001, respectively, compared with placebo).

Adverse events were similar between the groups, and most were mild or moderate; overall safety profiles were similar to those seen in adult patients.

The European Commission will review the positive opinion and make a final decision.

The research was supported by LEO Pharma.

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

Individuals with esophageal dysmotility had significantly higher scores on measures of airway reflux symptoms, based on data from 441 patients.

Many patients with chronic respiratory diseases experience persistent symptoms despite optimal treatment, and the reason is often unclear and frustrating for clinicians and patients, Dominic L. Sykes, MD, of Hull (England) University Teaching Hospitals NHS Trust, and colleagues wrote.

Although more studies in recent years have explored the association between gastroesophageal reflux and respiratory diseases such as asthma and chronic obstructive pulmonary disease, data on a potential link between esophageal motility and respiratory disease in adults are limited, they noted.

In a study published in Respiratory Medicine, the researchers reviewed data from 441 adults with refractory respiratory symptoms who were treated at a single center between Jan. 1, 2011, and Dec. 1, 2021. Symptoms included persistent cough and breathlessness despite optimal medication. The participants underwent examination with high-resolution esophageal manometry (HROM). Airway reflux was measured using the Hull Airways Reflux Questionnaire (HARQ). The mean age of the patients was 56.5 years, and 64% were women.

Overall, the most common diagnoses were chronic cough (77%), asthma (10%), and interstitial lung disease (7%). The prevalence of esophageal dysmotility was 66%. Patients with esophageal dysmotility had significantly higher HARQ scores than those with normal motility (40.6 vs. 35.3; P < .001). Approximately one-third of the patients had normal motility (34.5%) on HROM, 54% had ineffective esophageal motility, 7.3% had absent contractility, 3.2% had esophageal-gastric junction outflow obstruction, 0.5% had distal esophageal spasm, 0.5% has achalasia, and one patient had hypercontractile esophagus.

No significant differences in manometric diagnoses appeared between men and women. In addition, HARQ scores showed a significant inverse correlation with esophageal contractility as measured by distal contractile integral (DCI).

“The proportion of patients with esophageal dysmotility is consistently high over a range of respiratory diseases, including interstitial lung disease (72%), airways disease (57%), and chronic cough (68%),” and the findings suggest that esophageal disease may play a role in patients with persistent respiratory symptoms, they noted.

The study authors proposed that “impaired peristaltic activity of the esophagus, leading to aspiration of gaseous nonacidic refluxate into the airways, may be a contributor in the development and progression of respiratory disease.” They added that the HARQ offers clinicians a useful screening tool for assessing the need for esophageal study in patients with persistent respiratory symptoms that should be used before considering antireflux surgery.

The study findings were limited by several factors including the lack of lung function data for patients with airway disease and ILD and the inability to show causality between esophageal dysmotility and refractory respiratory symptoms, the researchers noted. Other limitations include the retrospective design, and the lack of data on symptom severity and the subsequent impact on outcomes.

However, the results support the need for additional research into the relationship between esophageal dysmotility, lung function, and symptom burden in chronic respiratory disease, and may inform investigations of therapeutic targets, they concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose.

Individuals with esophageal dysmotility had significantly higher scores on measures of airway reflux symptoms, based on data from 441 patients.

Many patients with chronic respiratory diseases experience persistent symptoms despite optimal treatment, and the reason is often unclear and frustrating for clinicians and patients, Dominic L. Sykes, MD, of Hull (England) University Teaching Hospitals NHS Trust, and colleagues wrote.

Although more studies in recent years have explored the association between gastroesophageal reflux and respiratory diseases such as asthma and chronic obstructive pulmonary disease, data on a potential link between esophageal motility and respiratory disease in adults are limited, they noted.

In a study published in Respiratory Medicine, the researchers reviewed data from 441 adults with refractory respiratory symptoms who were treated at a single center between Jan. 1, 2011, and Dec. 1, 2021. Symptoms included persistent cough and breathlessness despite optimal medication. The participants underwent examination with high-resolution esophageal manometry (HROM). Airway reflux was measured using the Hull Airways Reflux Questionnaire (HARQ). The mean age of the patients was 56.5 years, and 64% were women.

Overall, the most common diagnoses were chronic cough (77%), asthma (10%), and interstitial lung disease (7%). The prevalence of esophageal dysmotility was 66%. Patients with esophageal dysmotility had significantly higher HARQ scores than those with normal motility (40.6 vs. 35.3; P < .001). Approximately one-third of the patients had normal motility (34.5%) on HROM, 54% had ineffective esophageal motility, 7.3% had absent contractility, 3.2% had esophageal-gastric junction outflow obstruction, 0.5% had distal esophageal spasm, 0.5% has achalasia, and one patient had hypercontractile esophagus.

No significant differences in manometric diagnoses appeared between men and women. In addition, HARQ scores showed a significant inverse correlation with esophageal contractility as measured by distal contractile integral (DCI).

“The proportion of patients with esophageal dysmotility is consistently high over a range of respiratory diseases, including interstitial lung disease (72%), airways disease (57%), and chronic cough (68%),” and the findings suggest that esophageal disease may play a role in patients with persistent respiratory symptoms, they noted.

The study authors proposed that “impaired peristaltic activity of the esophagus, leading to aspiration of gaseous nonacidic refluxate into the airways, may be a contributor in the development and progression of respiratory disease.” They added that the HARQ offers clinicians a useful screening tool for assessing the need for esophageal study in patients with persistent respiratory symptoms that should be used before considering antireflux surgery.

The study findings were limited by several factors including the lack of lung function data for patients with airway disease and ILD and the inability to show causality between esophageal dysmotility and refractory respiratory symptoms, the researchers noted. Other limitations include the retrospective design, and the lack of data on symptom severity and the subsequent impact on outcomes.

However, the results support the need for additional research into the relationship between esophageal dysmotility, lung function, and symptom burden in chronic respiratory disease, and may inform investigations of therapeutic targets, they concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose.

Individuals with esophageal dysmotility had significantly higher scores on measures of airway reflux symptoms, based on data from 441 patients.

Many patients with chronic respiratory diseases experience persistent symptoms despite optimal treatment, and the reason is often unclear and frustrating for clinicians and patients, Dominic L. Sykes, MD, of Hull (England) University Teaching Hospitals NHS Trust, and colleagues wrote.

Although more studies in recent years have explored the association between gastroesophageal reflux and respiratory diseases such as asthma and chronic obstructive pulmonary disease, data on a potential link between esophageal motility and respiratory disease in adults are limited, they noted.

In a study published in Respiratory Medicine, the researchers reviewed data from 441 adults with refractory respiratory symptoms who were treated at a single center between Jan. 1, 2011, and Dec. 1, 2021. Symptoms included persistent cough and breathlessness despite optimal medication. The participants underwent examination with high-resolution esophageal manometry (HROM). Airway reflux was measured using the Hull Airways Reflux Questionnaire (HARQ). The mean age of the patients was 56.5 years, and 64% were women.

Overall, the most common diagnoses were chronic cough (77%), asthma (10%), and interstitial lung disease (7%). The prevalence of esophageal dysmotility was 66%. Patients with esophageal dysmotility had significantly higher HARQ scores than those with normal motility (40.6 vs. 35.3; P < .001). Approximately one-third of the patients had normal motility (34.5%) on HROM, 54% had ineffective esophageal motility, 7.3% had absent contractility, 3.2% had esophageal-gastric junction outflow obstruction, 0.5% had distal esophageal spasm, 0.5% has achalasia, and one patient had hypercontractile esophagus.

No significant differences in manometric diagnoses appeared between men and women. In addition, HARQ scores showed a significant inverse correlation with esophageal contractility as measured by distal contractile integral (DCI).

“The proportion of patients with esophageal dysmotility is consistently high over a range of respiratory diseases, including interstitial lung disease (72%), airways disease (57%), and chronic cough (68%),” and the findings suggest that esophageal disease may play a role in patients with persistent respiratory symptoms, they noted.

The study authors proposed that “impaired peristaltic activity of the esophagus, leading to aspiration of gaseous nonacidic refluxate into the airways, may be a contributor in the development and progression of respiratory disease.” They added that the HARQ offers clinicians a useful screening tool for assessing the need for esophageal study in patients with persistent respiratory symptoms that should be used before considering antireflux surgery.

The study findings were limited by several factors including the lack of lung function data for patients with airway disease and ILD and the inability to show causality between esophageal dysmotility and refractory respiratory symptoms, the researchers noted. Other limitations include the retrospective design, and the lack of data on symptom severity and the subsequent impact on outcomes.

However, the results support the need for additional research into the relationship between esophageal dysmotility, lung function, and symptom burden in chronic respiratory disease, and may inform investigations of therapeutic targets, they concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose.

Inhaled vasodilators with nitric oxide and epoprostenol yielded similar patient outcomes, based on data from more than 11,000 patients.

Mechanically ventilated patients with severe acute respiratory failure may be treated with inhaled vasodilators using nitric oxide or epoprostenol to improve oxygenation, but data on practice patterns and head-to-head comparisons of effectiveness for the two options are limited, wrote Nicholas A. Bosch, MD, of Boston University, and colleagues.

In a study published in the journal Chest, the researchers used the Premier Healthcare Database to emulate a cluster randomized trial. The study population included 11,200 patients aged 18 years and older who were hospitalized at one of 303 hospitals with acute respiratory failure or acute respiratory distress between 2016 and 2020.

The patients received either nitric oxide (iNO) or epoprostenol (iEpo) during a hospital stay. A total of 6,366 patients received iNO first, 4,720 received iEpo first, and 114 received both on the same day. The median age of the patients was 58 years, and 64.6% of patients received neuromuscular blockades on the day they began vasodilator therapy. The primary outcome for effectiveness was successful extubation within 28 days of receiving a vasodilator. The outcomes for evaluating practice patterns included the choice of first inhaled vasodilator, days of invasive mechanical ventilation before starting a vasodilator, duration of use, proportion of patients who switched between iNO and iEpo, and the proportion who received each type of vasodilator.

A total of 104 hospitals (34.3%) used iNO exclusively, and 118 hospitals (38.9%) used iEpo exclusively. No differences in successful extubation rates appeared between these iNO and iEpo groups (37.0% vs. 34.7%; hazard ratio, 0.97). In addition, no differences were observed between the iNO and iEpo hospitals in total hospital costs or patient deaths or discharge to hospice, and the results persisted in a multivariate analysis.

Overall, the results were similar in a subgroup analysis, although patients receiving iNO were more likely to have successful extubation after controlling for organ dysfunction, the researchers noted.

“Our study provides stronger and more robust evidence that there are no differences in patient outcomes based on inhaled vasodilator type,” and suggest that either type may be used for patients whom clinicians think would benefit, the researchers wrote in their discussion. However, neither vasodilator type has been shown to significantly improve mortality, they noted.

The findings were limited by several factors including the observational design, lack of data on medication dose, and the use of nonrandom samples of hospitalizations and patients with laboratory and vital signs data, the researchers noted. The study also did not identify the specific indication for inhaled vasodilator therapy, and did not adjust for other therapies such as prone positioning or adherence to lung protective ventilation, they said.

However, the results were strengthened by the large sample size and more precise estimates of effectiveness than previous smaller studies, and suggest similar outcomes for patients and costs for hospitals, they concluded.

The study was funded by the National Institutes of Health National Center for Advancing Translational Sciences. Lead author Dr. Bosch also was supported by NIH/NCATS, the National Heart, Lung, and Blood Institute, and the Department of Defense. The researchers had no financial conflicts to disclose.

Inhaled vasodilators with nitric oxide and epoprostenol yielded similar patient outcomes, based on data from more than 11,000 patients.

Mechanically ventilated patients with severe acute respiratory failure may be treated with inhaled vasodilators using nitric oxide or epoprostenol to improve oxygenation, but data on practice patterns and head-to-head comparisons of effectiveness for the two options are limited, wrote Nicholas A. Bosch, MD, of Boston University, and colleagues.

In a study published in the journal Chest, the researchers used the Premier Healthcare Database to emulate a cluster randomized trial. The study population included 11,200 patients aged 18 years and older who were hospitalized at one of 303 hospitals with acute respiratory failure or acute respiratory distress between 2016 and 2020.

The patients received either nitric oxide (iNO) or epoprostenol (iEpo) during a hospital stay. A total of 6,366 patients received iNO first, 4,720 received iEpo first, and 114 received both on the same day. The median age of the patients was 58 years, and 64.6% of patients received neuromuscular blockades on the day they began vasodilator therapy. The primary outcome for effectiveness was successful extubation within 28 days of receiving a vasodilator. The outcomes for evaluating practice patterns included the choice of first inhaled vasodilator, days of invasive mechanical ventilation before starting a vasodilator, duration of use, proportion of patients who switched between iNO and iEpo, and the proportion who received each type of vasodilator.

A total of 104 hospitals (34.3%) used iNO exclusively, and 118 hospitals (38.9%) used iEpo exclusively. No differences in successful extubation rates appeared between these iNO and iEpo groups (37.0% vs. 34.7%; hazard ratio, 0.97). In addition, no differences were observed between the iNO and iEpo hospitals in total hospital costs or patient deaths or discharge to hospice, and the results persisted in a multivariate analysis.

Overall, the results were similar in a subgroup analysis, although patients receiving iNO were more likely to have successful extubation after controlling for organ dysfunction, the researchers noted.

“Our study provides stronger and more robust evidence that there are no differences in patient outcomes based on inhaled vasodilator type,” and suggest that either type may be used for patients whom clinicians think would benefit, the researchers wrote in their discussion. However, neither vasodilator type has been shown to significantly improve mortality, they noted.

The findings were limited by several factors including the observational design, lack of data on medication dose, and the use of nonrandom samples of hospitalizations and patients with laboratory and vital signs data, the researchers noted. The study also did not identify the specific indication for inhaled vasodilator therapy, and did not adjust for other therapies such as prone positioning or adherence to lung protective ventilation, they said.

However, the results were strengthened by the large sample size and more precise estimates of effectiveness than previous smaller studies, and suggest similar outcomes for patients and costs for hospitals, they concluded.

The study was funded by the National Institutes of Health National Center for Advancing Translational Sciences. Lead author Dr. Bosch also was supported by NIH/NCATS, the National Heart, Lung, and Blood Institute, and the Department of Defense. The researchers had no financial conflicts to disclose.

Inhaled vasodilators with nitric oxide and epoprostenol yielded similar patient outcomes, based on data from more than 11,000 patients.

Mechanically ventilated patients with severe acute respiratory failure may be treated with inhaled vasodilators using nitric oxide or epoprostenol to improve oxygenation, but data on practice patterns and head-to-head comparisons of effectiveness for the two options are limited, wrote Nicholas A. Bosch, MD, of Boston University, and colleagues.

In a study published in the journal Chest, the researchers used the Premier Healthcare Database to emulate a cluster randomized trial. The study population included 11,200 patients aged 18 years and older who were hospitalized at one of 303 hospitals with acute respiratory failure or acute respiratory distress between 2016 and 2020.

The patients received either nitric oxide (iNO) or epoprostenol (iEpo) during a hospital stay. A total of 6,366 patients received iNO first, 4,720 received iEpo first, and 114 received both on the same day. The median age of the patients was 58 years, and 64.6% of patients received neuromuscular blockades on the day they began vasodilator therapy. The primary outcome for effectiveness was successful extubation within 28 days of receiving a vasodilator. The outcomes for evaluating practice patterns included the choice of first inhaled vasodilator, days of invasive mechanical ventilation before starting a vasodilator, duration of use, proportion of patients who switched between iNO and iEpo, and the proportion who received each type of vasodilator.

A total of 104 hospitals (34.3%) used iNO exclusively, and 118 hospitals (38.9%) used iEpo exclusively. No differences in successful extubation rates appeared between these iNO and iEpo groups (37.0% vs. 34.7%; hazard ratio, 0.97). In addition, no differences were observed between the iNO and iEpo hospitals in total hospital costs or patient deaths or discharge to hospice, and the results persisted in a multivariate analysis.

Overall, the results were similar in a subgroup analysis, although patients receiving iNO were more likely to have successful extubation after controlling for organ dysfunction, the researchers noted.

“Our study provides stronger and more robust evidence that there are no differences in patient outcomes based on inhaled vasodilator type,” and suggest that either type may be used for patients whom clinicians think would benefit, the researchers wrote in their discussion. However, neither vasodilator type has been shown to significantly improve mortality, they noted.

The findings were limited by several factors including the observational design, lack of data on medication dose, and the use of nonrandom samples of hospitalizations and patients with laboratory and vital signs data, the researchers noted. The study also did not identify the specific indication for inhaled vasodilator therapy, and did not adjust for other therapies such as prone positioning or adherence to lung protective ventilation, they said.

However, the results were strengthened by the large sample size and more precise estimates of effectiveness than previous smaller studies, and suggest similar outcomes for patients and costs for hospitals, they concluded.

The study was funded by the National Institutes of Health National Center for Advancing Translational Sciences. Lead author Dr. Bosch also was supported by NIH/NCATS, the National Heart, Lung, and Blood Institute, and the Department of Defense. The researchers had no financial conflicts to disclose.

Congenital cytomegalovirus cases declined significantly during the COVID-19 pandemic, compared with a period before the pandemic, based on data from nearly 20,000 newborns.

A study originated to explore racial and ethnic differences in congenital cytomegalovirus (cCMV) began in 2016, but was halted in April 2020 because of the COVID-19 pandemic, wrote Mark R. Schleiss, MD, of the University of Minnesota, Minneapolis, and colleagues. The study resumed for a period from August 2020 to December 2021, and the researchers compared data on cCMV before and during the pandemic. The prepandemic period included data from April 2016 to March 2020.

“We have been screening for congenital CMV infection in Minnesota for 6 years as a part of a multicenter collaborative study that I lead as the primary investigator,” Dr. Schleiss said in an interview. “Our efforts have contributed to the decision, vetted through the Minnesota Legislature and signed into law in 2021 (the “Vivian Act”), to begin universal screening for all newborns in Minnesota in 2023. In the context of this ongoing screening/surveillance study, it was important and scientifically very interesting to examine the impact of the COVID-19 pandemic on the risk of congenital CMV infection,” he explained.

The findings were published in a research letter in JAMA Network Open. A total of 15,697 newborns were screened before the pandemic and 4,222 were screened during the pandemic period at six hospitals. The majority of the mothers participating during the prepandemic and pandemic periods were non-Hispanic White (71% and 60%, respectively).

Overall, the percentage screened prevalence for cCMV was 79% in the prepandemic period and 21% during the pandemic, with rates of 4.5 per 1,000 and 1.4 per 1,000, respectively.

Although the highest percentage of cCMV cases occurred in newborns of mothers aged 25 years and older (86%), the prevalence was highest among newborns of mothers aged 24 years and younger (6.0 per 1,000). The prevalence of cCMV overall was higher in infants of non-Hispanic Black mothers vs. non-Hispanic White mothers, but not significantly different (5.1 per 1,000 vs. 4.6 per 1,000) and among second newborns vs. first newborns (6.0 vs. 3.2 per 1,000, respectively).

Factors related to COVID-19, including reduced day care attendance, behavioral changes, and mitigation measures at childcare facilities such as smaller classes and increased hand hygiene and disinfection may have contributed to this decrease in cCMV in the pandemic period, the researchers wrote in their discussion.

The comparable prevalence in newborns of non-Hispanic Black and White mothers contrasts with previous studies showing a higher prevalence in children of non-Hispanic Black mothers, the researchers noted in their discussion.

The study was limited by several factors, including the variation in time points for enrollment at different sites and the exclusion of families in the newborn nursery with positive COVID-19 results during the pandemic, they wrote. More research is needed on the potential effects of behavioral interventions to reduce CMV risk during pregnancy, as well as future CMV vaccination for childbearing-aged women and young children, they concluded.

However, the researchers were surprised by the impact of COVID-19 on the prevalence of cCMV, Dr. Schleiss said in an interview. “We have had the knowledge for many years that CMV infections in young women are commonly acquired through interactions with their toddlers. These interactions – sharing food, wiping drool and nasal discharge from the toddler’s nose, changing diapers, kissing the child on the mouth – can transmit CMV,” he said. In addition, toddlers may acquire CMV from group day care; the child then sheds CMV and transmits the virus to their pregnant mother, who then transmits the virus across the placenta, leading to cCMV infection in the newborn, Dr. Schleiss explained.

Although the researchers expected a decrease in CMV in the wake of closures of group day care, increased home schooling, decreased interactions among children, hygienic precautions, and social isolation, the decrease exceeded their expectations, said Dr. Schleiss. “Our previous work showed that in the 5-year period leading up to the pandemic, about one baby in every 200 births was born with CMV. Between August 2020 and December 2021, the number decreased to one baby in every 1,000 births,” a difference he and his team found striking.

The message from the study is that CMV can be prevented, said Dr. Schleiss. “Hygienic precautions during pregnancy had a big impact. Since congenital CMV infection is the most common congenital infection in the United States, and probably globally, that causes disabilities in children, the implications are highly significant,” he said. “The hygienic precautions we all have engaged in during the pandemic, such as masking, handwashing, and infection prevention behaviors, were almost certainly responsible for the reduction in CMV transmission, which in turn protected mothers and newborns from the potentially devastating effects of the CMV virus,” he noted.

Looking ahead, “Vaccines are moving forward in clinical trials that aim to confer immunity on young women of childbearing age to protect future pregnancies against transmission of CMV to the newborn infant; it would be very important to examine in future studies whether hygienic precautions would have the same impact as a potential vaccine,” Dr. Schleiss said. More research is needed to examine the effect of education of women about CMV transmission, he added. “We think it is very important to share this knowledge from our study with the pediatric community, since pediatricians can be important in counseling women about future pregnancies and the risks of CMV acquisition and transmission,” he noted.

Implications for other viruses

Although CMV poses minimal risk for healthy populations, irreversible complications for infants born with congenital CMV, especially hearing loss, are very concerning, said Catherine Haut, DNP, CPNP-AC/PC, a pediatric nurse practitioner in Rehoboth Beach, Del., in an interview.

“The study of viral transmission during a time of isolation, masking, and other mitigation procedures for COVID-19 assists in awareness that other viruses may also be limited with the use of these measures,” she said.

Dr. Haut was not surprised by the findings, given that CMV is transmitted primarily through direct contact with body fluids and that more than 50% of American adults have been infected by age 40, according to the Centers for Disease Control and Prevention, she said.

The take-home message for pediatricians, Dr. Haut said, is measures to prevent transmission of viral infection can yield significant positive health outcomes for the pediatric population; however, the effect of isolation, which has been associated with a higher rate of mental health problems, should not be ignored.

“Despite appropriate statistical analyses and presentation of findings in this study, the population sampled during the pandemic was less than 30% of the pre-COVID sampling, representing a study limitation,” and conducting research in a single state limits generalizability, Dr. Haut noted. “I agree with the authors that additional study is necessary to better understand prevention measures and apply these methods to reduce CMV transmission. Pursuit of CMV immunization opportunities is also needed,” she said.

The study was supported by the Centers for Disease Control and Prevention, the National Vaccine Program Office, the Minnesota Department of Health Newborn Screening Program, and the University of South Carolina Disability Research and Dissemination Center. Lead author Dr. Schleiss disclosed grants from the CDC, the National Institutes of Health, and the DRDC during the conduct of the study; he also disclosed receiving personal fees from Moderna, Sanofi, GlaxoSmithKline, and Merck unrelated to the study. Dr. Haut had no financial conflicts to disclose and serves on the Editorial Advisory Board of Pediatric News.

Congenital cytomegalovirus cases declined significantly during the COVID-19 pandemic, compared with a period before the pandemic, based on data from nearly 20,000 newborns.

A study originated to explore racial and ethnic differences in congenital cytomegalovirus (cCMV) began in 2016, but was halted in April 2020 because of the COVID-19 pandemic, wrote Mark R. Schleiss, MD, of the University of Minnesota, Minneapolis, and colleagues. The study resumed for a period from August 2020 to December 2021, and the researchers compared data on cCMV before and during the pandemic. The prepandemic period included data from April 2016 to March 2020.

“We have been screening for congenital CMV infection in Minnesota for 6 years as a part of a multicenter collaborative study that I lead as the primary investigator,” Dr. Schleiss said in an interview. “Our efforts have contributed to the decision, vetted through the Minnesota Legislature and signed into law in 2021 (the “Vivian Act”), to begin universal screening for all newborns in Minnesota in 2023. In the context of this ongoing screening/surveillance study, it was important and scientifically very interesting to examine the impact of the COVID-19 pandemic on the risk of congenital CMV infection,” he explained.

The findings were published in a research letter in JAMA Network Open. A total of 15,697 newborns were screened before the pandemic and 4,222 were screened during the pandemic period at six hospitals. The majority of the mothers participating during the prepandemic and pandemic periods were non-Hispanic White (71% and 60%, respectively).

Overall, the percentage screened prevalence for cCMV was 79% in the prepandemic period and 21% during the pandemic, with rates of 4.5 per 1,000 and 1.4 per 1,000, respectively.

Although the highest percentage of cCMV cases occurred in newborns of mothers aged 25 years and older (86%), the prevalence was highest among newborns of mothers aged 24 years and younger (6.0 per 1,000). The prevalence of cCMV overall was higher in infants of non-Hispanic Black mothers vs. non-Hispanic White mothers, but not significantly different (5.1 per 1,000 vs. 4.6 per 1,000) and among second newborns vs. first newborns (6.0 vs. 3.2 per 1,000, respectively).

Factors related to COVID-19, including reduced day care attendance, behavioral changes, and mitigation measures at childcare facilities such as smaller classes and increased hand hygiene and disinfection may have contributed to this decrease in cCMV in the pandemic period, the researchers wrote in their discussion.

The comparable prevalence in newborns of non-Hispanic Black and White mothers contrasts with previous studies showing a higher prevalence in children of non-Hispanic Black mothers, the researchers noted in their discussion.

The study was limited by several factors, including the variation in time points for enrollment at different sites and the exclusion of families in the newborn nursery with positive COVID-19 results during the pandemic, they wrote. More research is needed on the potential effects of behavioral interventions to reduce CMV risk during pregnancy, as well as future CMV vaccination for childbearing-aged women and young children, they concluded.

However, the researchers were surprised by the impact of COVID-19 on the prevalence of cCMV, Dr. Schleiss said in an interview. “We have had the knowledge for many years that CMV infections in young women are commonly acquired through interactions with their toddlers. These interactions – sharing food, wiping drool and nasal discharge from the toddler’s nose, changing diapers, kissing the child on the mouth – can transmit CMV,” he said. In addition, toddlers may acquire CMV from group day care; the child then sheds CMV and transmits the virus to their pregnant mother, who then transmits the virus across the placenta, leading to cCMV infection in the newborn, Dr. Schleiss explained.

Although the researchers expected a decrease in CMV in the wake of closures of group day care, increased home schooling, decreased interactions among children, hygienic precautions, and social isolation, the decrease exceeded their expectations, said Dr. Schleiss. “Our previous work showed that in the 5-year period leading up to the pandemic, about one baby in every 200 births was born with CMV. Between August 2020 and December 2021, the number decreased to one baby in every 1,000 births,” a difference he and his team found striking.

The message from the study is that CMV can be prevented, said Dr. Schleiss. “Hygienic precautions during pregnancy had a big impact. Since congenital CMV infection is the most common congenital infection in the United States, and probably globally, that causes disabilities in children, the implications are highly significant,” he said. “The hygienic precautions we all have engaged in during the pandemic, such as masking, handwashing, and infection prevention behaviors, were almost certainly responsible for the reduction in CMV transmission, which in turn protected mothers and newborns from the potentially devastating effects of the CMV virus,” he noted.

Looking ahead, “Vaccines are moving forward in clinical trials that aim to confer immunity on young women of childbearing age to protect future pregnancies against transmission of CMV to the newborn infant; it would be very important to examine in future studies whether hygienic precautions would have the same impact as a potential vaccine,” Dr. Schleiss said. More research is needed to examine the effect of education of women about CMV transmission, he added. “We think it is very important to share this knowledge from our study with the pediatric community, since pediatricians can be important in counseling women about future pregnancies and the risks of CMV acquisition and transmission,” he noted.

Implications for other viruses

Although CMV poses minimal risk for healthy populations, irreversible complications for infants born with congenital CMV, especially hearing loss, are very concerning, said Catherine Haut, DNP, CPNP-AC/PC, a pediatric nurse practitioner in Rehoboth Beach, Del., in an interview.

“The study of viral transmission during a time of isolation, masking, and other mitigation procedures for COVID-19 assists in awareness that other viruses may also be limited with the use of these measures,” she said.

Dr. Haut was not surprised by the findings, given that CMV is transmitted primarily through direct contact with body fluids and that more than 50% of American adults have been infected by age 40, according to the Centers for Disease Control and Prevention, she said.

The take-home message for pediatricians, Dr. Haut said, is measures to prevent transmission of viral infection can yield significant positive health outcomes for the pediatric population; however, the effect of isolation, which has been associated with a higher rate of mental health problems, should not be ignored.

“Despite appropriate statistical analyses and presentation of findings in this study, the population sampled during the pandemic was less than 30% of the pre-COVID sampling, representing a study limitation,” and conducting research in a single state limits generalizability, Dr. Haut noted. “I agree with the authors that additional study is necessary to better understand prevention measures and apply these methods to reduce CMV transmission. Pursuit of CMV immunization opportunities is also needed,” she said.

The study was supported by the Centers for Disease Control and Prevention, the National Vaccine Program Office, the Minnesota Department of Health Newborn Screening Program, and the University of South Carolina Disability Research and Dissemination Center. Lead author Dr. Schleiss disclosed grants from the CDC, the National Institutes of Health, and the DRDC during the conduct of the study; he also disclosed receiving personal fees from Moderna, Sanofi, GlaxoSmithKline, and Merck unrelated to the study. Dr. Haut had no financial conflicts to disclose and serves on the Editorial Advisory Board of Pediatric News.

Congenital cytomegalovirus cases declined significantly during the COVID-19 pandemic, compared with a period before the pandemic, based on data from nearly 20,000 newborns.

A study originated to explore racial and ethnic differences in congenital cytomegalovirus (cCMV) began in 2016, but was halted in April 2020 because of the COVID-19 pandemic, wrote Mark R. Schleiss, MD, of the University of Minnesota, Minneapolis, and colleagues. The study resumed for a period from August 2020 to December 2021, and the researchers compared data on cCMV before and during the pandemic. The prepandemic period included data from April 2016 to March 2020.

“We have been screening for congenital CMV infection in Minnesota for 6 years as a part of a multicenter collaborative study that I lead as the primary investigator,” Dr. Schleiss said in an interview. “Our efforts have contributed to the decision, vetted through the Minnesota Legislature and signed into law in 2021 (the “Vivian Act”), to begin universal screening for all newborns in Minnesota in 2023. In the context of this ongoing screening/surveillance study, it was important and scientifically very interesting to examine the impact of the COVID-19 pandemic on the risk of congenital CMV infection,” he explained.

The findings were published in a research letter in JAMA Network Open. A total of 15,697 newborns were screened before the pandemic and 4,222 were screened during the pandemic period at six hospitals. The majority of the mothers participating during the prepandemic and pandemic periods were non-Hispanic White (71% and 60%, respectively).

Overall, the percentage screened prevalence for cCMV was 79% in the prepandemic period and 21% during the pandemic, with rates of 4.5 per 1,000 and 1.4 per 1,000, respectively.

Although the highest percentage of cCMV cases occurred in newborns of mothers aged 25 years and older (86%), the prevalence was highest among newborns of mothers aged 24 years and younger (6.0 per 1,000). The prevalence of cCMV overall was higher in infants of non-Hispanic Black mothers vs. non-Hispanic White mothers, but not significantly different (5.1 per 1,000 vs. 4.6 per 1,000) and among second newborns vs. first newborns (6.0 vs. 3.2 per 1,000, respectively).

Factors related to COVID-19, including reduced day care attendance, behavioral changes, and mitigation measures at childcare facilities such as smaller classes and increased hand hygiene and disinfection may have contributed to this decrease in cCMV in the pandemic period, the researchers wrote in their discussion.

The comparable prevalence in newborns of non-Hispanic Black and White mothers contrasts with previous studies showing a higher prevalence in children of non-Hispanic Black mothers, the researchers noted in their discussion.

The study was limited by several factors, including the variation in time points for enrollment at different sites and the exclusion of families in the newborn nursery with positive COVID-19 results during the pandemic, they wrote. More research is needed on the potential effects of behavioral interventions to reduce CMV risk during pregnancy, as well as future CMV vaccination for childbearing-aged women and young children, they concluded.

However, the researchers were surprised by the impact of COVID-19 on the prevalence of cCMV, Dr. Schleiss said in an interview. “We have had the knowledge for many years that CMV infections in young women are commonly acquired through interactions with their toddlers. These interactions – sharing food, wiping drool and nasal discharge from the toddler’s nose, changing diapers, kissing the child on the mouth – can transmit CMV,” he said. In addition, toddlers may acquire CMV from group day care; the child then sheds CMV and transmits the virus to their pregnant mother, who then transmits the virus across the placenta, leading to cCMV infection in the newborn, Dr. Schleiss explained.

Although the researchers expected a decrease in CMV in the wake of closures of group day care, increased home schooling, decreased interactions among children, hygienic precautions, and social isolation, the decrease exceeded their expectations, said Dr. Schleiss. “Our previous work showed that in the 5-year period leading up to the pandemic, about one baby in every 200 births was born with CMV. Between August 2020 and December 2021, the number decreased to one baby in every 1,000 births,” a difference he and his team found striking.

The message from the study is that CMV can be prevented, said Dr. Schleiss. “Hygienic precautions during pregnancy had a big impact. Since congenital CMV infection is the most common congenital infection in the United States, and probably globally, that causes disabilities in children, the implications are highly significant,” he said. “The hygienic precautions we all have engaged in during the pandemic, such as masking, handwashing, and infection prevention behaviors, were almost certainly responsible for the reduction in CMV transmission, which in turn protected mothers and newborns from the potentially devastating effects of the CMV virus,” he noted.

Looking ahead, “Vaccines are moving forward in clinical trials that aim to confer immunity on young women of childbearing age to protect future pregnancies against transmission of CMV to the newborn infant; it would be very important to examine in future studies whether hygienic precautions would have the same impact as a potential vaccine,” Dr. Schleiss said. More research is needed to examine the effect of education of women about CMV transmission, he added. “We think it is very important to share this knowledge from our study with the pediatric community, since pediatricians can be important in counseling women about future pregnancies and the risks of CMV acquisition and transmission,” he noted.

Implications for other viruses

Although CMV poses minimal risk for healthy populations, irreversible complications for infants born with congenital CMV, especially hearing loss, are very concerning, said Catherine Haut, DNP, CPNP-AC/PC, a pediatric nurse practitioner in Rehoboth Beach, Del., in an interview.

“The study of viral transmission during a time of isolation, masking, and other mitigation procedures for COVID-19 assists in awareness that other viruses may also be limited with the use of these measures,” she said.

Dr. Haut was not surprised by the findings, given that CMV is transmitted primarily through direct contact with body fluids and that more than 50% of American adults have been infected by age 40, according to the Centers for Disease Control and Prevention, she said.

The take-home message for pediatricians, Dr. Haut said, is measures to prevent transmission of viral infection can yield significant positive health outcomes for the pediatric population; however, the effect of isolation, which has been associated with a higher rate of mental health problems, should not be ignored.

“Despite appropriate statistical analyses and presentation of findings in this study, the population sampled during the pandemic was less than 30% of the pre-COVID sampling, representing a study limitation,” and conducting research in a single state limits generalizability, Dr. Haut noted. “I agree with the authors that additional study is necessary to better understand prevention measures and apply these methods to reduce CMV transmission. Pursuit of CMV immunization opportunities is also needed,” she said.

The study was supported by the Centers for Disease Control and Prevention, the National Vaccine Program Office, the Minnesota Department of Health Newborn Screening Program, and the University of South Carolina Disability Research and Dissemination Center. Lead author Dr. Schleiss disclosed grants from the CDC, the National Institutes of Health, and the DRDC during the conduct of the study; he also disclosed receiving personal fees from Moderna, Sanofi, GlaxoSmithKline, and Merck unrelated to the study. Dr. Haut had no financial conflicts to disclose and serves on the Editorial Advisory Board of Pediatric News.

Deucravacitinib, an oral, selective tyrosine kinase 2 (TYK2) inhibitor, has been approved by the Food and Drug Administration for treating adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy, the manufacturer announced on Sept. 9.

Deucravacitinib targets TYK2, which inhibits signaling of interleukin-23, interleukin-12, and type 1 interferons, key cytokines involved in the pathogenesis of multiple immune-mediated diseases, according to Bristol Myers Squibb (BMS). This is the first approval for deucravacitinib, which will be marketed as Sotyktu, and the first drug in this class to be approved.

It is also currently under review for the same indication in Europe and Japan, and elsewhere, and for treating pustular psoriasis and erythrodermic psoriasis in Japan.

FDA approval was based on the results of POETYK PSO-1 and POETYK PSO-2, phase 3 trials of almost 1,700 adults with moderate to severe plaque psoriasis. In these studies, treatment with once-daily deucravacitinib showed significant and clinically meaningful improvements in skin clearance and symptoms, compared with placebo and with apremilast (Otezla), according to the company.

In the two studies, patients were randomly assigned to receive 6 mg daily of deucravacitinib, placebo, or a 30-mg twice-daily dose of apremilast, the oral phosphodiesterase 4 inhibitor approved for psoriasis. The primary endpoints were the percentage of patients who achieved a Psoriasis Area and Severity Index (PASI) 75 response and a static Physician’s Global Assessment (sPGA) score of 0 or 1 (clear or almost clear) at 16 weeks.

At 16 weeks, 58% and 53% of patients receiving deucravacitinib in the POETYK PSO-1 and POETYK PSO-2 studies, respectively, achieved PASI 75 response, compared with 13% and 9% of those receiving placebo (P < .0001 for both) and 35% and 40% receiving apremilast (P < .0001, P = .0004, respectively), according to the company’s announcement of the approval. PASI 75 responses were maintained through 52 weeks among the patients who remained on treatment, in both studies, according to BMS.

In the POETYK PSO-1 and PSO-2 studies, respectively, 54% and 50% of those on deucravacitinib achieved an sPGA of 0/1 at 16 weeks, compared with 7% and 9% of those receiving placebo (P < .0001 for both) and 32% and 34% of those receiving apremilast (P < .0001 for both).

Across the two studies, at 16 weeks, the most common adverse events that affected at least 1% of patients on deucravacitinib and that occurred at higher rates than in the placebo group were upper respiratory infections (19.2%), increases in serum creatine phosphokinase (2.7%), herpes simplex (2%), mouth ulcers (1.9%), folliculitis (1.7%), and acne (1.4%). Adverse events resulting in discontinuation of treatment were reported in 2.4% of persons receiving deucravacitinib and 5.2% of those receiving apremilast, compared with 3.8% of those receiving placebo.

Up to 16 weeks, according to the BMS statement, 28% of persons receiving deucravacitinib had infections, most of which were mild to moderate and not serious and did not result in stopping treatment, compared with 22% of those receiving placebo. In addition, five patients treated with deucravacitinib and five patients receiving placebo had serious infections, and three patients receiving deucravacitinib had cancer (not including nonmelanoma skin cancer).

Deucravacitinib is also being evaluated in clinical trials for psoriatic arthritis, lupus, and inflammatory bowel disease. It is not recommended for use in combination with other potent immunosuppressants, according to BMS.

The prescribing information and patient medication guide are available online.

The POETYK PSO-1 and POETYK PSO-2 studies were funded by Bristol Myers Squibb.

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

Deucravacitinib, an oral, selective tyrosine kinase 2 (TYK2) inhibitor, has been approved by the Food and Drug Administration for treating adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy, the manufacturer announced on Sept. 9.

Deucravacitinib targets TYK2, which inhibits signaling of interleukin-23, interleukin-12, and type 1 interferons, key cytokines involved in the pathogenesis of multiple immune-mediated diseases, according to Bristol Myers Squibb (BMS). This is the first approval for deucravacitinib, which will be marketed as Sotyktu, and the first drug in this class to be approved.

It is also currently under review for the same indication in Europe and Japan, and elsewhere, and for treating pustular psoriasis and erythrodermic psoriasis in Japan.

FDA approval was based on the results of POETYK PSO-1 and POETYK PSO-2, phase 3 trials of almost 1,700 adults with moderate to severe plaque psoriasis. In these studies, treatment with once-daily deucravacitinib showed significant and clinically meaningful improvements in skin clearance and symptoms, compared with placebo and with apremilast (Otezla), according to the company.

In the two studies, patients were randomly assigned to receive 6 mg daily of deucravacitinib, placebo, or a 30-mg twice-daily dose of apremilast, the oral phosphodiesterase 4 inhibitor approved for psoriasis. The primary endpoints were the percentage of patients who achieved a Psoriasis Area and Severity Index (PASI) 75 response and a static Physician’s Global Assessment (sPGA) score of 0 or 1 (clear or almost clear) at 16 weeks.

At 16 weeks, 58% and 53% of patients receiving deucravacitinib in the POETYK PSO-1 and POETYK PSO-2 studies, respectively, achieved PASI 75 response, compared with 13% and 9% of those receiving placebo (P < .0001 for both) and 35% and 40% receiving apremilast (P < .0001, P = .0004, respectively), according to the company’s announcement of the approval. PASI 75 responses were maintained through 52 weeks among the patients who remained on treatment, in both studies, according to BMS.

In the POETYK PSO-1 and PSO-2 studies, respectively, 54% and 50% of those on deucravacitinib achieved an sPGA of 0/1 at 16 weeks, compared with 7% and 9% of those receiving placebo (P < .0001 for both) and 32% and 34% of those receiving apremilast (P < .0001 for both).

Across the two studies, at 16 weeks, the most common adverse events that affected at least 1% of patients on deucravacitinib and that occurred at higher rates than in the placebo group were upper respiratory infections (19.2%), increases in serum creatine phosphokinase (2.7%), herpes simplex (2%), mouth ulcers (1.9%), folliculitis (1.7%), and acne (1.4%). Adverse events resulting in discontinuation of treatment were reported in 2.4% of persons receiving deucravacitinib and 5.2% of those receiving apremilast, compared with 3.8% of those receiving placebo.

Up to 16 weeks, according to the BMS statement, 28% of persons receiving deucravacitinib had infections, most of which were mild to moderate and not serious and did not result in stopping treatment, compared with 22% of those receiving placebo. In addition, five patients treated with deucravacitinib and five patients receiving placebo had serious infections, and three patients receiving deucravacitinib had cancer (not including nonmelanoma skin cancer).

Deucravacitinib is also being evaluated in clinical trials for psoriatic arthritis, lupus, and inflammatory bowel disease. It is not recommended for use in combination with other potent immunosuppressants, according to BMS.

The prescribing information and patient medication guide are available online.

The POETYK PSO-1 and POETYK PSO-2 studies were funded by Bristol Myers Squibb.

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

Deucravacitinib, an oral, selective tyrosine kinase 2 (TYK2) inhibitor, has been approved by the Food and Drug Administration for treating adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy, the manufacturer announced on Sept. 9.

Deucravacitinib targets TYK2, which inhibits signaling of interleukin-23, interleukin-12, and type 1 interferons, key cytokines involved in the pathogenesis of multiple immune-mediated diseases, according to Bristol Myers Squibb (BMS). This is the first approval for deucravacitinib, which will be marketed as Sotyktu, and the first drug in this class to be approved.

It is also currently under review for the same indication in Europe and Japan, and elsewhere, and for treating pustular psoriasis and erythrodermic psoriasis in Japan.

FDA approval was based on the results of POETYK PSO-1 and POETYK PSO-2, phase 3 trials of almost 1,700 adults with moderate to severe plaque psoriasis. In these studies, treatment with once-daily deucravacitinib showed significant and clinically meaningful improvements in skin clearance and symptoms, compared with placebo and with apremilast (Otezla), according to the company.

In the two studies, patients were randomly assigned to receive 6 mg daily of deucravacitinib, placebo, or a 30-mg twice-daily dose of apremilast, the oral phosphodiesterase 4 inhibitor approved for psoriasis. The primary endpoints were the percentage of patients who achieved a Psoriasis Area and Severity Index (PASI) 75 response and a static Physician’s Global Assessment (sPGA) score of 0 or 1 (clear or almost clear) at 16 weeks.

At 16 weeks, 58% and 53% of patients receiving deucravacitinib in the POETYK PSO-1 and POETYK PSO-2 studies, respectively, achieved PASI 75 response, compared with 13% and 9% of those receiving placebo (P < .0001 for both) and 35% and 40% receiving apremilast (P < .0001, P = .0004, respectively), according to the company’s announcement of the approval. PASI 75 responses were maintained through 52 weeks among the patients who remained on treatment, in both studies, according to BMS.

In the POETYK PSO-1 and PSO-2 studies, respectively, 54% and 50% of those on deucravacitinib achieved an sPGA of 0/1 at 16 weeks, compared with 7% and 9% of those receiving placebo (P < .0001 for both) and 32% and 34% of those receiving apremilast (P < .0001 for both).

Across the two studies, at 16 weeks, the most common adverse events that affected at least 1% of patients on deucravacitinib and that occurred at higher rates than in the placebo group were upper respiratory infections (19.2%), increases in serum creatine phosphokinase (2.7%), herpes simplex (2%), mouth ulcers (1.9%), folliculitis (1.7%), and acne (1.4%). Adverse events resulting in discontinuation of treatment were reported in 2.4% of persons receiving deucravacitinib and 5.2% of those receiving apremilast, compared with 3.8% of those receiving placebo.

Up to 16 weeks, according to the BMS statement, 28% of persons receiving deucravacitinib had infections, most of which were mild to moderate and not serious and did not result in stopping treatment, compared with 22% of those receiving placebo. In addition, five patients treated with deucravacitinib and five patients receiving placebo had serious infections, and three patients receiving deucravacitinib had cancer (not including nonmelanoma skin cancer).

Deucravacitinib is also being evaluated in clinical trials for psoriatic arthritis, lupus, and inflammatory bowel disease. It is not recommended for use in combination with other potent immunosuppressants, according to BMS.

The prescribing information and patient medication guide are available online.

The POETYK PSO-1 and POETYK PSO-2 studies were funded by Bristol Myers Squibb.

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

Baseline dyskinesia and neurological soft signs (NSS) predicted the disease process of schizophrenia over a 21-year follow-up period, based on data from 243 adult patients.

Neuromotor abnormalities in psychotic disorders have long been ignored as side effects of antipsychotic drugs, but they are gaining new attention as a component of the disease process, with implications for outcomes and management, wrote Victor Peralta, MD, PhD, of Servicio Navarro de Salud, Pamplona, Spain, and colleagues.

Previous research has suggested links between increased levels of parkinsonism, dyskinesia, and NSS and poor symptomatic and functional outcomes, but “the impact of primary neuromotor dysfunction on the long-term course and outcome of psychotic disorders remains largely unknown,” they said.

In a study published in Schizophrenia Research , the investigators identified 243 consecutive schizophrenia patients admitted to a psychiatric ward at a single center.

Patients were assessed at baseline for variables including parkinsonism, dyskinesia, NSS, and catatonia, and were reassessed 21 years later for the same variables, along with psychopathology, functioning, personal recovery, cognitive performance, and comorbidity.

Overall, baseline dyskinesia and NSS measures were stable over time, with Intraclass Correlation Coefficients (ICC) of 0.92 and 0.86, respectively, while rating stability was low for parkinsonism and catatonia (ICC = 0.42 and 0.31, respectively).

Baseline dyskinesia and NSS each were independent predictors of more positive and negative symptoms, poor functioning, and less personal recovery at 21 years. In a multivariate model, neuromotor dysfunction at follow-up was significantly associated with family history of schizophrenia, obstetric complications, neurodevelopmental delay, and premorbid IQ, as well as baseline dyskinesia and NSS; “these variables explained 51% of the variance in the neuromotor outcome, 35% of which corresponded to baseline dyskinesia and NSS,” the researchers said. As for other outcomes, baseline neuromotor ratings predicted a range from 4% for medical comorbidity to 15% for cognitive impairment.

“The distinction between primary and drug-induced neuromotor dysfunction is a very complex issue, mainly because antipsychotic drugs may cause de novo motor dysfunction, such as improve or worsen the disease-based motor dysfunction,” the researchers explained in their discussion.

Baseline parkinsonism, dyskinesia, and NSS were significantly related to increased risk of antipsychotic exposure over the illness course, possibly because primary neuromotor dysfunction was predictive of greater severity of illness in general, which confounds differentiation between primary and drug-induced motor symptoms, they noted.

The study findings were limited by several factors including potential selection bias because of the selection of first-admission psychosis, which may limit generalizability, the researchers noted. Other limitations include the use of standard clinical rating scales rather than instrumental procedures to measuring neuromotor abnormalities.

However, “our findings confirm the significance of baseline and follow-up neuromotor abnormalities as a core dimension of psychosis,” and future studies “should complement clinical rating scales with instrumental assessment to capture neuromotor dysfunction more comprehensively,” they said.

The results highlight the clinical relevance of examining neuromotor abnormalities as a routine part of practice prior to starting antipsychotics because of their potential as predictors of long-term outcomes “and to disentangle the primary versus drug-induced character of neuromotor impairment in treated patients,” they concluded.

The study was supported by the Spanish Ministry of Economy, Industry, and Competitiveness, and the Regional Government of Navarra. The researchers had no financial conflicts to disclose.

Baseline dyskinesia and neurological soft signs (NSS) predicted the disease process of schizophrenia over a 21-year follow-up period, based on data from 243 adult patients.

Neuromotor abnormalities in psychotic disorders have long been ignored as side effects of antipsychotic drugs, but they are gaining new attention as a component of the disease process, with implications for outcomes and management, wrote Victor Peralta, MD, PhD, of Servicio Navarro de Salud, Pamplona, Spain, and colleagues.

Previous research has suggested links between increased levels of parkinsonism, dyskinesia, and NSS and poor symptomatic and functional outcomes, but “the impact of primary neuromotor dysfunction on the long-term course and outcome of psychotic disorders remains largely unknown,” they said.

In a study published in Schizophrenia Research , the investigators identified 243 consecutive schizophrenia patients admitted to a psychiatric ward at a single center.

Patients were assessed at baseline for variables including parkinsonism, dyskinesia, NSS, and catatonia, and were reassessed 21 years later for the same variables, along with psychopathology, functioning, personal recovery, cognitive performance, and comorbidity.

Overall, baseline dyskinesia and NSS measures were stable over time, with Intraclass Correlation Coefficients (ICC) of 0.92 and 0.86, respectively, while rating stability was low for parkinsonism and catatonia (ICC = 0.42 and 0.31, respectively).

Baseline dyskinesia and NSS each were independent predictors of more positive and negative symptoms, poor functioning, and less personal recovery at 21 years. In a multivariate model, neuromotor dysfunction at follow-up was significantly associated with family history of schizophrenia, obstetric complications, neurodevelopmental delay, and premorbid IQ, as well as baseline dyskinesia and NSS; “these variables explained 51% of the variance in the neuromotor outcome, 35% of which corresponded to baseline dyskinesia and NSS,” the researchers said. As for other outcomes, baseline neuromotor ratings predicted a range from 4% for medical comorbidity to 15% for cognitive impairment.

“The distinction between primary and drug-induced neuromotor dysfunction is a very complex issue, mainly because antipsychotic drugs may cause de novo motor dysfunction, such as improve or worsen the disease-based motor dysfunction,” the researchers explained in their discussion.

Baseline parkinsonism, dyskinesia, and NSS were significantly related to increased risk of antipsychotic exposure over the illness course, possibly because primary neuromotor dysfunction was predictive of greater severity of illness in general, which confounds differentiation between primary and drug-induced motor symptoms, they noted.

The study findings were limited by several factors including potential selection bias because of the selection of first-admission psychosis, which may limit generalizability, the researchers noted. Other limitations include the use of standard clinical rating scales rather than instrumental procedures to measuring neuromotor abnormalities.

However, “our findings confirm the significance of baseline and follow-up neuromotor abnormalities as a core dimension of psychosis,” and future studies “should complement clinical rating scales with instrumental assessment to capture neuromotor dysfunction more comprehensively,” they said.

The results highlight the clinical relevance of examining neuromotor abnormalities as a routine part of practice prior to starting antipsychotics because of their potential as predictors of long-term outcomes “and to disentangle the primary versus drug-induced character of neuromotor impairment in treated patients,” they concluded.

The study was supported by the Spanish Ministry of Economy, Industry, and Competitiveness, and the Regional Government of Navarra. The researchers had no financial conflicts to disclose.

Baseline dyskinesia and neurological soft signs (NSS) predicted the disease process of schizophrenia over a 21-year follow-up period, based on data from 243 adult patients.

Neuromotor abnormalities in psychotic disorders have long been ignored as side effects of antipsychotic drugs, but they are gaining new attention as a component of the disease process, with implications for outcomes and management, wrote Victor Peralta, MD, PhD, of Servicio Navarro de Salud, Pamplona, Spain, and colleagues.

Previous research has suggested links between increased levels of parkinsonism, dyskinesia, and NSS and poor symptomatic and functional outcomes, but “the impact of primary neuromotor dysfunction on the long-term course and outcome of psychotic disorders remains largely unknown,” they said.

In a study published in Schizophrenia Research , the investigators identified 243 consecutive schizophrenia patients admitted to a psychiatric ward at a single center.

Patients were assessed at baseline for variables including parkinsonism, dyskinesia, NSS, and catatonia, and were reassessed 21 years later for the same variables, along with psychopathology, functioning, personal recovery, cognitive performance, and comorbidity.

Overall, baseline dyskinesia and NSS measures were stable over time, with Intraclass Correlation Coefficients (ICC) of 0.92 and 0.86, respectively, while rating stability was low for parkinsonism and catatonia (ICC = 0.42 and 0.31, respectively).

Baseline dyskinesia and NSS each were independent predictors of more positive and negative symptoms, poor functioning, and less personal recovery at 21 years. In a multivariate model, neuromotor dysfunction at follow-up was significantly associated with family history of schizophrenia, obstetric complications, neurodevelopmental delay, and premorbid IQ, as well as baseline dyskinesia and NSS; “these variables explained 51% of the variance in the neuromotor outcome, 35% of which corresponded to baseline dyskinesia and NSS,” the researchers said. As for other outcomes, baseline neuromotor ratings predicted a range from 4% for medical comorbidity to 15% for cognitive impairment.

“The distinction between primary and drug-induced neuromotor dysfunction is a very complex issue, mainly because antipsychotic drugs may cause de novo motor dysfunction, such as improve or worsen the disease-based motor dysfunction,” the researchers explained in their discussion.

Baseline parkinsonism, dyskinesia, and NSS were significantly related to increased risk of antipsychotic exposure over the illness course, possibly because primary neuromotor dysfunction was predictive of greater severity of illness in general, which confounds differentiation between primary and drug-induced motor symptoms, they noted.

The study findings were limited by several factors including potential selection bias because of the selection of first-admission psychosis, which may limit generalizability, the researchers noted. Other limitations include the use of standard clinical rating scales rather than instrumental procedures to measuring neuromotor abnormalities.

However, “our findings confirm the significance of baseline and follow-up neuromotor abnormalities as a core dimension of psychosis,” and future studies “should complement clinical rating scales with instrumental assessment to capture neuromotor dysfunction more comprehensively,” they said.

The results highlight the clinical relevance of examining neuromotor abnormalities as a routine part of practice prior to starting antipsychotics because of their potential as predictors of long-term outcomes “and to disentangle the primary versus drug-induced character of neuromotor impairment in treated patients,” they concluded.

The study was supported by the Spanish Ministry of Economy, Industry, and Competitiveness, and the Regional Government of Navarra. The researchers had no financial conflicts to disclose.

Only one-third of pediatric dermatologists who prescribed isotretinoin for acne reported feeling confident in their understanding of emergency contraception (EC), in a survey of 57 clinicians.

Pregnancies among patients on isotretinoin have declined since the iPLEDGE risk management program was introduced in 2005, but from 2011 to 2017, 210 to 310 pregnancies were reported to the Food and Drug Administration every year, wrote Catherine E. Smiley of Penn State University, Hershey, Pa., and coauthors Melissa Butt, DrPH, and Andrea L. Zaenglein, MD, of Penn State.

For patients on isotretinoin, EC “becomes critical when abstinence fails or contraception is not used properly,” but EC merits only a brief mention in iPLEDGE materials for patients and providers, they noted.

Patients on isotretinoin who choose abstinence as their form of birth control are the group at greatest risk for pregnancy, Dr. Zaenglein, professor of dermatology and pediatric dermatology, Penn State University, said in an interview. “However, the iPLEDGE program fails to educate patients adequately on emergency contraception,” she explained.

To assess pediatric dermatologists’ understanding of EC and their contraception counseling practices for isotretinoin patients, the researchers surveyed 57 pediatric dermatologists who prescribed isotretinoin as part of their practices. The findings were published in Pediatric Dermatology.Respondents included 53 practicing dermatologists, 2 residents, and 2 fellows. Approximately one-third (31.6%) had been in practice for 6-10 years, almost 23% had been in practice for 3-5 years, and almost 20% had been in practice for 21 or more years. Almost two-thirds practiced pediatric dermatology only.

Overall, 58% of the respondents strongly agreed that they provided contraception counseling to patients at their initial visit for isotretinoin, but only 7% and 3.5% reported providing EC counseling at initial and follow-up visits, respectively. More than half (58%) said they did not counsel patients on the side effects of EC.

As for provider education, 7.1% of respondents said they had received formal education on EC counseling, 25% reported receiving informal education on EC counseling, and 68% said they received no education on EC counseling.

A total of 32% of respondents said they were at least somewhat confident in how to obtain EC in their state.

EC is an effective form of contraception if used after unprotected intercourse, and discounts can reduce the price to as low as $9.69, the researchers wrote in their discussion. “Given that most providers in this study did not receive formal education on EC, and most do not provide EC counseling to their patients of reproductive potential on isotretinoin, EC education should be a core competency in dermatology residency education on isotretinoin prescribing,” the researchers noted. In addition, EC counseling in the iPLEDGE program should be improved by including more information in education materials and reminding patients that EC is an option, they said.

The study findings were limited by several factors including the small sample size and the multiple-choice format that prevented respondents to share rationales for their responses, the researchers noted.

However, the results highlight the need to improve EC education among pediatric dermatologists to better inform patients considering isotretinoin, especially those choosing abstinence as a method of birth control, they emphasized.

“This study is very important at this specific time for two reasons,” Dr. Zaenglein said in an interview. “The first is that with the recent disastrous rollout of the new iPLEDGE changes, there have been many calls to reform the REMS program. For the first time in the 22-year history of the program, the isotretinoin manufacturers, who manage the iPLEDGE program as an unidentified group (the IPMG), have been forced by the FDA to meet with the AAD iPLEDGE Task Force,” said Dr. Zaenglein, a member of the task force.

“The task force is currently advocating for common sense changes to iPLEDGE and I think enhancing education on emergency contraception is vital to the goal of the program, stated as ‘to manage the risk of isotretinoin’s teratogenicity and to minimize fetal exposure,’ ” she added. For many patients who previously became pregnant on isotretinoin, Plan B, an over-the-counter, FDA-approved form of contraception, might have prevented that pregnancy if the patients received adequate education on EC, she said.

The current study is especially relevant now, said Dr. Zaenglein. “With the reversal of Roe v. Wade, access to abortion is restricted or completely banned in many states, which makes educating our patients on how to prevent pregnancy even more important.”

Dr. Zaenglein said she was “somewhat surprised” by how many respondents were not educating their isotretinoin patients on EC. “However, these results follow a known trend among dermatologists. Only 50% of dermatologists prescribe oral contraceptives for acne, despite its being an FDA-approved treatment for the most common dermatologic condition we see in adolescents and young adults,” she noted.

“In general, dermatologists, and subsequently dermatology residents, are poorly educated on issues of reproductive health and how they are relevant to dermatologic care,” she added.

Dr. Zaenglein’s take home message: “Dermatologists should educate all patients of childbearing potential taking isotretinoin on how to acquire and use emergency contraception at every visit.” As for additional research, she said that since the study was conducted with pediatric dermatologists, “it would be very interesting to see if general dermatologists had the same lack of comfort in educating patients on emergency contraception and what their standard counseling practices are.”

The study received no outside funding. Dr. Zaenglein is a member of the AAD’s iPLEDGE Work Group and serves as an editor-in-chief of Pediatric Dermatology.

Only one-third of pediatric dermatologists who prescribed isotretinoin for acne reported feeling confident in their understanding of emergency contraception (EC), in a survey of 57 clinicians.

Pregnancies among patients on isotretinoin have declined since the iPLEDGE risk management program was introduced in 2005, but from 2011 to 2017, 210 to 310 pregnancies were reported to the Food and Drug Administration every year, wrote Catherine E. Smiley of Penn State University, Hershey, Pa., and coauthors Melissa Butt, DrPH, and Andrea L. Zaenglein, MD, of Penn State.

For patients on isotretinoin, EC “becomes critical when abstinence fails or contraception is not used properly,” but EC merits only a brief mention in iPLEDGE materials for patients and providers, they noted.

Patients on isotretinoin who choose abstinence as their form of birth control are the group at greatest risk for pregnancy, Dr. Zaenglein, professor of dermatology and pediatric dermatology, Penn State University, said in an interview. “However, the iPLEDGE program fails to educate patients adequately on emergency contraception,” she explained.

To assess pediatric dermatologists’ understanding of EC and their contraception counseling practices for isotretinoin patients, the researchers surveyed 57 pediatric dermatologists who prescribed isotretinoin as part of their practices. The findings were published in Pediatric Dermatology.Respondents included 53 practicing dermatologists, 2 residents, and 2 fellows. Approximately one-third (31.6%) had been in practice for 6-10 years, almost 23% had been in practice for 3-5 years, and almost 20% had been in practice for 21 or more years. Almost two-thirds practiced pediatric dermatology only.

Overall, 58% of the respondents strongly agreed that they provided contraception counseling to patients at their initial visit for isotretinoin, but only 7% and 3.5% reported providing EC counseling at initial and follow-up visits, respectively. More than half (58%) said they did not counsel patients on the side effects of EC.

As for provider education, 7.1% of respondents said they had received formal education on EC counseling, 25% reported receiving informal education on EC counseling, and 68% said they received no education on EC counseling.

A total of 32% of respondents said they were at least somewhat confident in how to obtain EC in their state.

EC is an effective form of contraception if used after unprotected intercourse, and discounts can reduce the price to as low as $9.69, the researchers wrote in their discussion. “Given that most providers in this study did not receive formal education on EC, and most do not provide EC counseling to their patients of reproductive potential on isotretinoin, EC education should be a core competency in dermatology residency education on isotretinoin prescribing,” the researchers noted. In addition, EC counseling in the iPLEDGE program should be improved by including more information in education materials and reminding patients that EC is an option, they said.

The study findings were limited by several factors including the small sample size and the multiple-choice format that prevented respondents to share rationales for their responses, the researchers noted.

However, the results highlight the need to improve EC education among pediatric dermatologists to better inform patients considering isotretinoin, especially those choosing abstinence as a method of birth control, they emphasized.

“This study is very important at this specific time for two reasons,” Dr. Zaenglein said in an interview. “The first is that with the recent disastrous rollout of the new iPLEDGE changes, there have been many calls to reform the REMS program. For the first time in the 22-year history of the program, the isotretinoin manufacturers, who manage the iPLEDGE program as an unidentified group (the IPMG), have been forced by the FDA to meet with the AAD iPLEDGE Task Force,” said Dr. Zaenglein, a member of the task force.

“The task force is currently advocating for common sense changes to iPLEDGE and I think enhancing education on emergency contraception is vital to the goal of the program, stated as ‘to manage the risk of isotretinoin’s teratogenicity and to minimize fetal exposure,’ ” she added. For many patients who previously became pregnant on isotretinoin, Plan B, an over-the-counter, FDA-approved form of contraception, might have prevented that pregnancy if the patients received adequate education on EC, she said.

The current study is especially relevant now, said Dr. Zaenglein. “With the reversal of Roe v. Wade, access to abortion is restricted or completely banned in many states, which makes educating our patients on how to prevent pregnancy even more important.”

Dr. Zaenglein said she was “somewhat surprised” by how many respondents were not educating their isotretinoin patients on EC. “However, these results follow a known trend among dermatologists. Only 50% of dermatologists prescribe oral contraceptives for acne, despite its being an FDA-approved treatment for the most common dermatologic condition we see in adolescents and young adults,” she noted.

“In general, dermatologists, and subsequently dermatology residents, are poorly educated on issues of reproductive health and how they are relevant to dermatologic care,” she added.

Dr. Zaenglein’s take home message: “Dermatologists should educate all patients of childbearing potential taking isotretinoin on how to acquire and use emergency contraception at every visit.” As for additional research, she said that since the study was conducted with pediatric dermatologists, “it would be very interesting to see if general dermatologists had the same lack of comfort in educating patients on emergency contraception and what their standard counseling practices are.”

The study received no outside funding. Dr. Zaenglein is a member of the AAD’s iPLEDGE Work Group and serves as an editor-in-chief of Pediatric Dermatology.

Only one-third of pediatric dermatologists who prescribed isotretinoin for acne reported feeling confident in their understanding of emergency contraception (EC), in a survey of 57 clinicians.

Pregnancies among patients on isotretinoin have declined since the iPLEDGE risk management program was introduced in 2005, but from 2011 to 2017, 210 to 310 pregnancies were reported to the Food and Drug Administration every year, wrote Catherine E. Smiley of Penn State University, Hershey, Pa., and coauthors Melissa Butt, DrPH, and Andrea L. Zaenglein, MD, of Penn State.

For patients on isotretinoin, EC “becomes critical when abstinence fails or contraception is not used properly,” but EC merits only a brief mention in iPLEDGE materials for patients and providers, they noted.

Patients on isotretinoin who choose abstinence as their form of birth control are the group at greatest risk for pregnancy, Dr. Zaenglein, professor of dermatology and pediatric dermatology, Penn State University, said in an interview. “However, the iPLEDGE program fails to educate patients adequately on emergency contraception,” she explained.

To assess pediatric dermatologists’ understanding of EC and their contraception counseling practices for isotretinoin patients, the researchers surveyed 57 pediatric dermatologists who prescribed isotretinoin as part of their practices. The findings were published in Pediatric Dermatology.Respondents included 53 practicing dermatologists, 2 residents, and 2 fellows. Approximately one-third (31.6%) had been in practice for 6-10 years, almost 23% had been in practice for 3-5 years, and almost 20% had been in practice for 21 or more years. Almost two-thirds practiced pediatric dermatology only.

Overall, 58% of the respondents strongly agreed that they provided contraception counseling to patients at their initial visit for isotretinoin, but only 7% and 3.5% reported providing EC counseling at initial and follow-up visits, respectively. More than half (58%) said they did not counsel patients on the side effects of EC.

As for provider education, 7.1% of respondents said they had received formal education on EC counseling, 25% reported receiving informal education on EC counseling, and 68% said they received no education on EC counseling.

A total of 32% of respondents said they were at least somewhat confident in how to obtain EC in their state.

EC is an effective form of contraception if used after unprotected intercourse, and discounts can reduce the price to as low as $9.69, the researchers wrote in their discussion. “Given that most providers in this study did not receive formal education on EC, and most do not provide EC counseling to their patients of reproductive potential on isotretinoin, EC education should be a core competency in dermatology residency education on isotretinoin prescribing,” the researchers noted. In addition, EC counseling in the iPLEDGE program should be improved by including more information in education materials and reminding patients that EC is an option, they said.

The study findings were limited by several factors including the small sample size and the multiple-choice format that prevented respondents to share rationales for their responses, the researchers noted.

However, the results highlight the need to improve EC education among pediatric dermatologists to better inform patients considering isotretinoin, especially those choosing abstinence as a method of birth control, they emphasized.

“This study is very important at this specific time for two reasons,” Dr. Zaenglein said in an interview. “The first is that with the recent disastrous rollout of the new iPLEDGE changes, there have been many calls to reform the REMS program. For the first time in the 22-year history of the program, the isotretinoin manufacturers, who manage the iPLEDGE program as an unidentified group (the IPMG), have been forced by the FDA to meet with the AAD iPLEDGE Task Force,” said Dr. Zaenglein, a member of the task force.

“The task force is currently advocating for common sense changes to iPLEDGE and I think enhancing education on emergency contraception is vital to the goal of the program, stated as ‘to manage the risk of isotretinoin’s teratogenicity and to minimize fetal exposure,’ ” she added. For many patients who previously became pregnant on isotretinoin, Plan B, an over-the-counter, FDA-approved form of contraception, might have prevented that pregnancy if the patients received adequate education on EC, she said.

The current study is especially relevant now, said Dr. Zaenglein. “With the reversal of Roe v. Wade, access to abortion is restricted or completely banned in many states, which makes educating our patients on how to prevent pregnancy even more important.”

Dr. Zaenglein said she was “somewhat surprised” by how many respondents were not educating their isotretinoin patients on EC. “However, these results follow a known trend among dermatologists. Only 50% of dermatologists prescribe oral contraceptives for acne, despite its being an FDA-approved treatment for the most common dermatologic condition we see in adolescents and young adults,” she noted.

“In general, dermatologists, and subsequently dermatology residents, are poorly educated on issues of reproductive health and how they are relevant to dermatologic care,” she added.

Dr. Zaenglein’s take home message: “Dermatologists should educate all patients of childbearing potential taking isotretinoin on how to acquire and use emergency contraception at every visit.” As for additional research, she said that since the study was conducted with pediatric dermatologists, “it would be very interesting to see if general dermatologists had the same lack of comfort in educating patients on emergency contraception and what their standard counseling practices are.”

The study received no outside funding. Dr. Zaenglein is a member of the AAD’s iPLEDGE Work Group and serves as an editor-in-chief of Pediatric Dermatology.

Women who are pregnant or breastfeeding showed no long-term adverse reactions after a third or booster dose of COVID-19 vaccine, according to a study of more than 17,000 individuals.

Doctors and health professionals continue to recommend COVID-19 vaccine boosters or third doses for adolescents and adults more than 5 months after their initial vaccinations with the Pfizer-BioNTech BNT162b2 or Moderna mRNA-1273 primary vaccine series or more than 2 months after receiving the Janssen JNJ-78436735 vaccine, Alisa Kachikis, MD, of the University of Washington, Seattle, and colleagues wrote in JAMA Network Open.

Although multiple studies have shown that the COVID-19 primary series is safe and well tolerated in pregnant and lactating women, information on the safety and tolerability of boosters are lacking, the researchers noted.

“COVID-19 will be with us for a while, and it is important to continue to provide data on COVID-19 vaccines in these groups, particularly because there still are many questions about the vaccine, and because pregnant individuals have been, understandably, more hesitant to receive COVID-19 vaccines,” Dr. Kachikis said in an interview. “The findings of this study that COVID-19 booster doses are well tolerated among pregnant and lactating individuals are especially pertinent with the new COVID-19 boosters available this fall.”

In the new study, the researchers reviewed data from 17,014 participants who were part of an ongoing online prospective study of COVID-19 vaccines in pregnant and lactating individuals. Data were collected between October 2021 and April 2022 through an online survey.

The study population included 2,009 participants (11.8%) who were pregnant at the time of their booster or third dose, 10,279 (60.4%) who were lactating, and 4,726 (27.8%) who were neither pregnant nor lactating. The mean age of the participants was 33.3 years; 92.1% self-identified as White, 94.5% self-identified as non-Hispanic, and 99.7% self-identified as female.

The receipt of a booster was similar across trimesters; 26.4%, 36.5%, and 37.1% of participants received boosters or third doses in the first, second, and third trimester, respectively. The primary outcome was self-reported vaccine reactions within 24 hours of the dose.

Overall, 82.8% of the respondents reported a reaction at the site of the injection, such as redness, pain, or swelling, and 67.9% reported at least one systemic symptom, such as aches and pains, headache, chills, or fever. The most frequently reported symptoms across all groups were injection-site pain (82.2%) and fatigue (54.4%).

The pregnant women were significantly more likely than nonpregnant or nonlactating individuals to report any local reaction at the injection site (adjusted odds ratio, 1.2; P = .01), but less likely to report any systemic reaction (aOR, 0.7; P < .001).

The majority (97.6%) of the pregnant respondents and 96.0% of those lactating reported no obstetric or lactation concerns after vaccination.

Overall, a majority of the respondents reported that recommendations from public health authorities were helpful in their decision to receive a COVID-19 booster or third dose (90.0% of pregnant respondents, 89.9% of lactating respondents, and 88.1% of those neither pregnant nor lactating).

Although vaccine uptake in the current study population was high (91.1% overall and 95.0% of those pregnant), “the importance of the health care professional’s recommendation is pertinent given the ongoing increased vaccine hesitancy among pregnant individuals in the context of the COVID-19 vaccine,” the researchers emphasized.

The study findings were limited by several factors including the reliance on self-reports and a convenience sample composed mainly of health care workers because of their vaccine eligibility at the time the study started, which limits generalizability, the researchers noted. Analyses on the pregnancy outcomes of those who were pregnant when vaccinated are in progress.

The results were strengthened by the large study population that included participants from all 50 states and several territories, and ability to compare results between pregnant and lactating individuals with those who were neither pregnant nor lactating, but were of childbearing age, they said.

The results support the safety of COVID-19 boosters for pregnant and breastfeeding individuals, and these data are important to inform discussions between patients and clinicians to boost vaccine uptake and acceptance in this population, they concluded.

“Our earlier data analysis showed that pregnant and lactating individuals did very well with the initial COVID-19 vaccine series, so it was not very surprising that they also did well with COVID-19 booster or third doses,” Dr. Kachikis said in an interview.

There are two takeaway messages for clinicians, she said: “First, pregnant and lactating individuals tolerated the COVID-19 booster well. The second is that clinicians are very important when it comes to vaccine acceptance.”

“In our study, we found that, while pregnant participants were more likely to report that they were hesitant to receive the booster, they also were more likely to have discussed the COVID-19 booster with their health care provider, and to have received a recommendation to receive the booster. So, spending a little bit of extra time with patients discussing COVID-19 boosters and recommending them can make a significant difference,” she said.

The message of the study is highly reassuring for pregnant and lactating individuals, Dr. Kachikis added. “Most of the participants reported that they had fewer symptoms with the COVID-19 booster compared to the primary vaccine series, which is good news, especially since a new COVID-19 booster is being recommended for the fall.”
 

Reassuring findings for doctors and patients

The current study is especially timely, as updated COVID-19 boosters have now been recommended for most individuals by the Centers for Disease Control and Prevention, Martina L. Badell, MD, a maternal-fetal medicine specialist at Emory University, Atlanta, said in an interview.

The findings support previous studies on the tolerability of COVID-19 vaccinations in pregnant and lactating persons, said Dr. Badell, who was not involved in the study.

The reassuring message for clinicians is that COVID-19 booster vaccinations are similarly well tolerated in pregnancy and lactation as they are in nonpregnant individuals, said Dr. Badell. “Given the risks of COVID infections in pregnancy and neonates, reassuring data on the tolerability and safety of vaccination in this population is very important.” Also, the researchers found that all three cohorts reported that recommendations from public or medical health authorities helped them make a decision about vaccination; “thus the more data to support these recommendations, the better,” she emphasized.

If you are pregnant or breastfeeding, the message from the study is that COVID-19 booster vaccinations are similarly well tolerated by those who are pregnant or breastfeeding and those who are not, said Dr. Badell.

“This study provides additional support for the strong recommendation to encourage not only COVID-19 vaccination in pregnancy and lactation, but booster vaccinations specifically,” and pregnant and breastfeeding individuals should not be excluded from the new CDC recommendations for COVID-19 boosters, she said.
 

Future research suggestions

Next steps for research include evaluating the obstetrical and neonatal outcomes in pregnancy and lactation following COVID- 19 boosters, Dr. Badell added.

Dr. Kachikis suggested studies try to answer the remaining questions about COVID-19 vaccines and the immunity of pregnant and lactating persons, particularly since they were excluded from the early clinical trials in 2020.

The study was supported by the National Institute of Allergy and Infectious Diseases, a Women’s Reproductive Health Research Award, and the National Center for Advancing Translational Sciences of the National Institutes of Health. \Dr. Kachikis disclosed serving as a research consultant for Pfizer and GlaxoSmithKline and as an unpaid consultant for GlaxoSmithKline unrelated to the current study, as well as grant support from Merck and Pfizer unrelated to the current study. Dr. Badell had no financial conflicts to disclose.

Women who are pregnant or breastfeeding showed no long-term adverse reactions after a third or booster dose of COVID-19 vaccine, according to a study of more than 17,000 individuals.

Doctors and health professionals continue to recommend COVID-19 vaccine boosters or third doses for adolescents and adults more than 5 months after their initial vaccinations with the Pfizer-BioNTech BNT162b2 or Moderna mRNA-1273 primary vaccine series or more than 2 months after receiving the Janssen JNJ-78436735 vaccine, Alisa Kachikis, MD, of the University of Washington, Seattle, and colleagues wrote in JAMA Network Open.

Although multiple studies have shown that the COVID-19 primary series is safe and well tolerated in pregnant and lactating women, information on the safety and tolerability of boosters are lacking, the researchers noted.

“COVID-19 will be with us for a while, and it is important to continue to provide data on COVID-19 vaccines in these groups, particularly because there still are many questions about the vaccine, and because pregnant individuals have been, understandably, more hesitant to receive COVID-19 vaccines,” Dr. Kachikis said in an interview. “The findings of this study that COVID-19 booster doses are well tolerated among pregnant and lactating individuals are especially pertinent with the new COVID-19 boosters available this fall.”

In the new study, the researchers reviewed data from 17,014 participants who were part of an ongoing online prospective study of COVID-19 vaccines in pregnant and lactating individuals. Data were collected between October 2021 and April 2022 through an online survey.

The study population included 2,009 participants (11.8%) who were pregnant at the time of their booster or third dose, 10,279 (60.4%) who were lactating, and 4,726 (27.8%) who were neither pregnant nor lactating. The mean age of the participants was 33.3 years; 92.1% self-identified as White, 94.5% self-identified as non-Hispanic, and 99.7% self-identified as female.

The receipt of a booster was similar across trimesters; 26.4%, 36.5%, and 37.1% of participants received boosters or third doses in the first, second, and third trimester, respectively. The primary outcome was self-reported vaccine reactions within 24 hours of the dose.

Overall, 82.8% of the respondents reported a reaction at the site of the injection, such as redness, pain, or swelling, and 67.9% reported at least one systemic symptom, such as aches and pains, headache, chills, or fever. The most frequently reported symptoms across all groups were injection-site pain (82.2%) and fatigue (54.4%).

The pregnant women were significantly more likely than nonpregnant or nonlactating individuals to report any local reaction at the injection site (adjusted odds ratio, 1.2; P = .01), but less likely to report any systemic reaction (aOR, 0.7; P < .001).

The majority (97.6%) of the pregnant respondents and 96.0% of those lactating reported no obstetric or lactation concerns after vaccination.

Overall, a majority of the respondents reported that recommendations from public health authorities were helpful in their decision to receive a COVID-19 booster or third dose (90.0% of pregnant respondents, 89.9% of lactating respondents, and 88.1% of those neither pregnant nor lactating).

Although vaccine uptake in the current study population was high (91.1% overall and 95.0% of those pregnant), “the importance of the health care professional’s recommendation is pertinent given the ongoing increased vaccine hesitancy among pregnant individuals in the context of the COVID-19 vaccine,” the researchers emphasized.

The study findings were limited by several factors including the reliance on self-reports and a convenience sample composed mainly of health care workers because of their vaccine eligibility at the time the study started, which limits generalizability, the researchers noted. Analyses on the pregnancy outcomes of those who were pregnant when vaccinated are in progress.

The results were strengthened by the large study population that included participants from all 50 states and several territories, and ability to compare results between pregnant and lactating individuals with those who were neither pregnant nor lactating, but were of childbearing age, they said.

The results support the safety of COVID-19 boosters for pregnant and breastfeeding individuals, and these data are important to inform discussions between patients and clinicians to boost vaccine uptake and acceptance in this population, they concluded.

“Our earlier data analysis showed that pregnant and lactating individuals did very well with the initial COVID-19 vaccine series, so it was not very surprising that they also did well with COVID-19 booster or third doses,” Dr. Kachikis said in an interview.

There are two takeaway messages for clinicians, she said: “First, pregnant and lactating individuals tolerated the COVID-19 booster well. The second is that clinicians are very important when it comes to vaccine acceptance.”

“In our study, we found that, while pregnant participants were more likely to report that they were hesitant to receive the booster, they also were more likely to have discussed the COVID-19 booster with their health care provider, and to have received a recommendation to receive the booster. So, spending a little bit of extra time with patients discussing COVID-19 boosters and recommending them can make a significant difference,” she said.

The message of the study is highly reassuring for pregnant and lactating individuals, Dr. Kachikis added. “Most of the participants reported that they had fewer symptoms with the COVID-19 booster compared to the primary vaccine series, which is good news, especially since a new COVID-19 booster is being recommended for the fall.”
 

Reassuring findings for doctors and patients

The current study is especially timely, as updated COVID-19 boosters have now been recommended for most individuals by the Centers for Disease Control and Prevention, Martina L. Badell, MD, a maternal-fetal medicine specialist at Emory University, Atlanta, said in an interview.

The findings support previous studies on the tolerability of COVID-19 vaccinations in pregnant and lactating persons, said Dr. Badell, who was not involved in the study.

The reassuring message for clinicians is that COVID-19 booster vaccinations are similarly well tolerated in pregnancy and lactation as they are in nonpregnant individuals, said Dr. Badell. “Given the risks of COVID infections in pregnancy and neonates, reassuring data on the tolerability and safety of vaccination in this population is very important.” Also, the researchers found that all three cohorts reported that recommendations from public or medical health authorities helped them make a decision about vaccination; “thus the more data to support these recommendations, the better,” she emphasized.

If you are pregnant or breastfeeding, the message from the study is that COVID-19 booster vaccinations are similarly well tolerated by those who are pregnant or breastfeeding and those who are not, said Dr. Badell.

“This study provides additional support for the strong recommendation to encourage not only COVID-19 vaccination in pregnancy and lactation, but booster vaccinations specifically,” and pregnant and breastfeeding individuals should not be excluded from the new CDC recommendations for COVID-19 boosters, she said.
 

Future research suggestions

Next steps for research include evaluating the obstetrical and neonatal outcomes in pregnancy and lactation following COVID- 19 boosters, Dr. Badell added.

Dr. Kachikis suggested studies try to answer the remaining questions about COVID-19 vaccines and the immunity of pregnant and lactating persons, particularly since they were excluded from the early clinical trials in 2020.

The study was supported by the National Institute of Allergy and Infectious Diseases, a Women’s Reproductive Health Research Award, and the National Center for Advancing Translational Sciences of the National Institutes of Health. \Dr. Kachikis disclosed serving as a research consultant for Pfizer and GlaxoSmithKline and as an unpaid consultant for GlaxoSmithKline unrelated to the current study, as well as grant support from Merck and Pfizer unrelated to the current study. Dr. Badell had no financial conflicts to disclose.

Women who are pregnant or breastfeeding showed no long-term adverse reactions after a third or booster dose of COVID-19 vaccine, according to a study of more than 17,000 individuals.

Doctors and health professionals continue to recommend COVID-19 vaccine boosters or third doses for adolescents and adults more than 5 months after their initial vaccinations with the Pfizer-BioNTech BNT162b2 or Moderna mRNA-1273 primary vaccine series or more than 2 months after receiving the Janssen JNJ-78436735 vaccine, Alisa Kachikis, MD, of the University of Washington, Seattle, and colleagues wrote in JAMA Network Open.

Although multiple studies have shown that the COVID-19 primary series is safe and well tolerated in pregnant and lactating women, information on the safety and tolerability of boosters are lacking, the researchers noted.

“COVID-19 will be with us for a while, and it is important to continue to provide data on COVID-19 vaccines in these groups, particularly because there still are many questions about the vaccine, and because pregnant individuals have been, understandably, more hesitant to receive COVID-19 vaccines,” Dr. Kachikis said in an interview. “The findings of this study that COVID-19 booster doses are well tolerated among pregnant and lactating individuals are especially pertinent with the new COVID-19 boosters available this fall.”

In the new study, the researchers reviewed data from 17,014 participants who were part of an ongoing online prospective study of COVID-19 vaccines in pregnant and lactating individuals. Data were collected between October 2021 and April 2022 through an online survey.

The study population included 2,009 participants (11.8%) who were pregnant at the time of their booster or third dose, 10,279 (60.4%) who were lactating, and 4,726 (27.8%) who were neither pregnant nor lactating. The mean age of the participants was 33.3 years; 92.1% self-identified as White, 94.5% self-identified as non-Hispanic, and 99.7% self-identified as female.

The receipt of a booster was similar across trimesters; 26.4%, 36.5%, and 37.1% of participants received boosters or third doses in the first, second, and third trimester, respectively. The primary outcome was self-reported vaccine reactions within 24 hours of the dose.

Overall, 82.8% of the respondents reported a reaction at the site of the injection, such as redness, pain, or swelling, and 67.9% reported at least one systemic symptom, such as aches and pains, headache, chills, or fever. The most frequently reported symptoms across all groups were injection-site pain (82.2%) and fatigue (54.4%).

The pregnant women were significantly more likely than nonpregnant or nonlactating individuals to report any local reaction at the injection site (adjusted odds ratio, 1.2; P = .01), but less likely to report any systemic reaction (aOR, 0.7; P < .001).

The majority (97.6%) of the pregnant respondents and 96.0% of those lactating reported no obstetric or lactation concerns after vaccination.

Overall, a majority of the respondents reported that recommendations from public health authorities were helpful in their decision to receive a COVID-19 booster or third dose (90.0% of pregnant respondents, 89.9% of lactating respondents, and 88.1% of those neither pregnant nor lactating).

Although vaccine uptake in the current study population was high (91.1% overall and 95.0% of those pregnant), “the importance of the health care professional’s recommendation is pertinent given the ongoing increased vaccine hesitancy among pregnant individuals in the context of the COVID-19 vaccine,” the researchers emphasized.

The study findings were limited by several factors including the reliance on self-reports and a convenience sample composed mainly of health care workers because of their vaccine eligibility at the time the study started, which limits generalizability, the researchers noted. Analyses on the pregnancy outcomes of those who were pregnant when vaccinated are in progress.

The results were strengthened by the large study population that included participants from all 50 states and several territories, and ability to compare results between pregnant and lactating individuals with those who were neither pregnant nor lactating, but were of childbearing age, they said.

The results support the safety of COVID-19 boosters for pregnant and breastfeeding individuals, and these data are important to inform discussions between patients and clinicians to boost vaccine uptake and acceptance in this population, they concluded.

“Our earlier data analysis showed that pregnant and lactating individuals did very well with the initial COVID-19 vaccine series, so it was not very surprising that they also did well with COVID-19 booster or third doses,” Dr. Kachikis said in an interview.

There are two takeaway messages for clinicians, she said: “First, pregnant and lactating individuals tolerated the COVID-19 booster well. The second is that clinicians are very important when it comes to vaccine acceptance.”

“In our study, we found that, while pregnant participants were more likely to report that they were hesitant to receive the booster, they also were more likely to have discussed the COVID-19 booster with their health care provider, and to have received a recommendation to receive the booster. So, spending a little bit of extra time with patients discussing COVID-19 boosters and recommending them can make a significant difference,” she said.

The message of the study is highly reassuring for pregnant and lactating individuals, Dr. Kachikis added. “Most of the participants reported that they had fewer symptoms with the COVID-19 booster compared to the primary vaccine series, which is good news, especially since a new COVID-19 booster is being recommended for the fall.”
 

Reassuring findings for doctors and patients

The current study is especially timely, as updated COVID-19 boosters have now been recommended for most individuals by the Centers for Disease Control and Prevention, Martina L. Badell, MD, a maternal-fetal medicine specialist at Emory University, Atlanta, said in an interview.

The findings support previous studies on the tolerability of COVID-19 vaccinations in pregnant and lactating persons, said Dr. Badell, who was not involved in the study.

The reassuring message for clinicians is that COVID-19 booster vaccinations are similarly well tolerated in pregnancy and lactation as they are in nonpregnant individuals, said Dr. Badell. “Given the risks of COVID infections in pregnancy and neonates, reassuring data on the tolerability and safety of vaccination in this population is very important.” Also, the researchers found that all three cohorts reported that recommendations from public or medical health authorities helped them make a decision about vaccination; “thus the more data to support these recommendations, the better,” she emphasized.

If you are pregnant or breastfeeding, the message from the study is that COVID-19 booster vaccinations are similarly well tolerated by those who are pregnant or breastfeeding and those who are not, said Dr. Badell.

“This study provides additional support for the strong recommendation to encourage not only COVID-19 vaccination in pregnancy and lactation, but booster vaccinations specifically,” and pregnant and breastfeeding individuals should not be excluded from the new CDC recommendations for COVID-19 boosters, she said.
 

Future research suggestions

Next steps for research include evaluating the obstetrical and neonatal outcomes in pregnancy and lactation following COVID- 19 boosters, Dr. Badell added.

Dr. Kachikis suggested studies try to answer the remaining questions about COVID-19 vaccines and the immunity of pregnant and lactating persons, particularly since they were excluded from the early clinical trials in 2020.

The study was supported by the National Institute of Allergy and Infectious Diseases, a Women’s Reproductive Health Research Award, and the National Center for Advancing Translational Sciences of the National Institutes of Health. \Dr. Kachikis disclosed serving as a research consultant for Pfizer and GlaxoSmithKline and as an unpaid consultant for GlaxoSmithKline unrelated to the current study, as well as grant support from Merck and Pfizer unrelated to the current study. Dr. Badell had no financial conflicts to disclose.

A dolutegravir-based treatment regimen holds its own as a first choice of antiretroviral therapy (ART) for pregnant individuals, based on data from more than 1,200 patients.

“Dolutegravir is increasingly used in pregnancy in the United States,” Kunjal Patel, DSc, one of the investigators, said in an interview. “While its effectiveness and safety in pregnancy have been compared to efavirenz in previous studies, including three randomized trials, efavirenz isn’t really used in the United States and Europe for treatment of HIV; it is mainly used in Africa,” she said. Therefore, it was important to compare dolutegravir use in pregnancy to the other antiretroviral regimens that are listed as being preferred for use in pregnancy in the U.S., including atazanavir/ritonavir, darunavir/ritonavir, and raltegravir, and others often used in the U.S. and Europe, she said.

In the study published in the New England Journal of Medicine, Dr. Patel, of Harvard T.H. Chan School of Public Health, Boston, and colleagues analyzed data from kids enrolled in the Surveillance and Monitoring for ART Toxicities Dynamic (SMARTT) cohort. This group is part of an ongoing research project focused on evaluating ART toxicities during pregnancy in children who were exposed to HIV perinatally but not infected. It included pregnancies from 2007 until January 2020 that involved use of the ARTs listed.

The study population of 1,257 pregnancies with observed birth outcomes included 120 individuals with an initial ART of dolutegravir (DTG), 464 started on atazanavir–ritonavir (ATV/r), 185 on darunavir–ritonavir (DRV/r), 243 on oral rilpivirine (RPV), 86 on raltegravir (RAL), and 159 on elvitegravir–cobicistat (EVG/c). In approximately half of the pregnancies (51%), ART was started before conception, and the initial ART was changed in 27%.

The primary outcomes were viral suppression at delivery, and adverse birth outcomes, including preterm and very preterm birth, low and very low birth weight, and neonatal death within 14 days.

The median age of the patients at conception was 29 years, and 66% were non-Hispanic Black, representative of persons with HIV of childbearing age in the United States, the researchers noted. Overall, 96.7% of the patients who received dolutegravir showed viral suppression at delivery, compared to 90.1% for darunavir–ritonavir, 89.8% for elvitegravir–cobicistat, 89.2% for raltegravir, and 84.0% for atazanavir–ritonavir.

“We expected that dolutegravir to be similar with regards to viral suppression at delivery compared to raltegravir so were surprised that we observed less viral suppression with raltegravir compared to dolutegravir,” Dr. Patel said in an interview. “Our results may be due to the higher pill burden and lower barrier to resistance with RAL compared to dolutegravir, but we did not assess adherence or resistance in our study,” she noted.

Across ART regimens, the observed risks of preterm birth ranged from 13.6% to 17.6%, risks of low birth weight ranged from 11.9% to 16.7%, and risks of being small for gestational age ranged from 9.1% to 12.5%. For the composite of any adverse birth outcome and any severe adverse birth outcome, the observed risks ranged from 22.6% to 27.9% and 0% to 4.2%, respectively.

A total of 20 very preterm births, including 15 infants with very low birth weight, occurred across patients receiving all ART regimens, and no neonatal deaths occurred. The researchers found no apparent patterns of differences in the observed risk of adverse birth outcomes across all groups related to the timing of ART initiation in pregnancy, but the risks were greater among those who began the drugs during pregnancy compared to those who began before conception.

“Our results confirm the recommendation of DTG as “preferred” in U.S. perinatal guidelines, and provide evidence suggesting ATV/r and RAL provides lower HIV viral suppression at delivery compared to DTG, and support DRV/r as a reasonable alternative when DTG use is not feasible,” Dr. Patel said in an interview.

“With regards to next steps, we are interested in comparing the effectiveness and safety of dolutegravir-based regimens that include tenofovir alafenamide (TAF) vs. tenofovir disoproxil fumarate (TDF) in our U.S. setting,” she said.

The study findings were limited by several factors including the lack of data on predictors of preterm birth and low birth weight, such as previous preterm birth and prepregnancy body mass index, the researchers noted.

However, the results indicate that other common ARTs provide less HIV viral suppression at delivery than dolutegravir, with similar adverse birth outcomes; the results also support darunavir–ritonavir as a reasonable alternative when dolutegravir use is not feasible, as it showed the next highest level of viral suppression after dolutegravir, the researchers concluded.
 

Findings fill a key research gap

The current study is important given the limited data on effectiveness and outcomes in pregnancy with the use of contemporary HIV regimens in the United States, Martina L. Badell, MD, a maternal-fetal medicine specialist at Emory University, Atlanta, said in an interview.

“Pregnancy is still among exclusion criteria for most drug studies,” said Dr. Badell, who was not involved in the current study. “Dolutegravir-based ART is first line in the U.S. today because of its effectiveness, lower side effects, and higher barrier to resistance; therefore understanding the benefits and birth outcomes in pregnancy is critical,” she explained.

Dr. Badell said she was not surprised by the study findings. “However it is very reassuring to see in a large observational study comparing the dolutegravir regimens to other contemporary regimens in pregnancy, such a high level of viral suppression and no increased risk of adverse perinatal outcomes,” she said.

The study findings will impact clinical practice by reaffirming patient counseling regarding the use of dolutegravir in pregnancy, said Dr. Badell. “The use of ART in pregnancy is complex given the number of drug choices, whether the patient was on ART prior to pregnancy or initiated during pregnancy, and the various factors other than ART that affect perinatal outcomes, such as preterm birth and congenital anomalies, she explained.

The finding that the risk of adverse outcomes was higher for those who initiated ART during pregnancy vs. those who were already on ARTs when they became pregnant contradicts some previous research, said Dr. Badell. But this is “reassuring, as we highly recommend ART with viral suppression prior to pregnancy or to start as early as possible in pregnancy.”

Adverse birth outcomes can be affected by many variables such as age, substance abuse, prior adverse birth outcome and other factors, and larger studies that control for these variables will allow better evaluation of the effect of the ART drugs, Dr. Badell added.

The study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, along with the Office of the Director, National Institutes of Health; National Institute of Dental and Craniofacial Research; National Institute of Allergy and Infectious Diseases; National Institute of Neurological Disorders and Stroke; National Institute on Deafness and Other Communication Disorders; National Institute of Mental Health; National Institute on Drug Abuse; National Cancer Institute; National Institute on Alcohol Abuse and Alcoholism; and National Heart, Lung, and Blood Institute through cooperative agreements with the Harvard T.H. Chan School of Public Health and the Tulane University School of Medicine.

The researchers and Dr. Badell had no financial conflicts to disclose.

A dolutegravir-based treatment regimen holds its own as a first choice of antiretroviral therapy (ART) for pregnant individuals, based on data from more than 1,200 patients.

“Dolutegravir is increasingly used in pregnancy in the United States,” Kunjal Patel, DSc, one of the investigators, said in an interview. “While its effectiveness and safety in pregnancy have been compared to efavirenz in previous studies, including three randomized trials, efavirenz isn’t really used in the United States and Europe for treatment of HIV; it is mainly used in Africa,” she said. Therefore, it was important to compare dolutegravir use in pregnancy to the other antiretroviral regimens that are listed as being preferred for use in pregnancy in the U.S., including atazanavir/ritonavir, darunavir/ritonavir, and raltegravir, and others often used in the U.S. and Europe, she said.

In the study published in the New England Journal of Medicine, Dr. Patel, of Harvard T.H. Chan School of Public Health, Boston, and colleagues analyzed data from kids enrolled in the Surveillance and Monitoring for ART Toxicities Dynamic (SMARTT) cohort. This group is part of an ongoing research project focused on evaluating ART toxicities during pregnancy in children who were exposed to HIV perinatally but not infected. It included pregnancies from 2007 until January 2020 that involved use of the ARTs listed.

The study population of 1,257 pregnancies with observed birth outcomes included 120 individuals with an initial ART of dolutegravir (DTG), 464 started on atazanavir–ritonavir (ATV/r), 185 on darunavir–ritonavir (DRV/r), 243 on oral rilpivirine (RPV), 86 on raltegravir (RAL), and 159 on elvitegravir–cobicistat (EVG/c). In approximately half of the pregnancies (51%), ART was started before conception, and the initial ART was changed in 27%.

The primary outcomes were viral suppression at delivery, and adverse birth outcomes, including preterm and very preterm birth, low and very low birth weight, and neonatal death within 14 days.

The median age of the patients at conception was 29 years, and 66% were non-Hispanic Black, representative of persons with HIV of childbearing age in the United States, the researchers noted. Overall, 96.7% of the patients who received dolutegravir showed viral suppression at delivery, compared to 90.1% for darunavir–ritonavir, 89.8% for elvitegravir–cobicistat, 89.2% for raltegravir, and 84.0% for atazanavir–ritonavir.

“We expected that dolutegravir to be similar with regards to viral suppression at delivery compared to raltegravir so were surprised that we observed less viral suppression with raltegravir compared to dolutegravir,” Dr. Patel said in an interview. “Our results may be due to the higher pill burden and lower barrier to resistance with RAL compared to dolutegravir, but we did not assess adherence or resistance in our study,” she noted.

Across ART regimens, the observed risks of preterm birth ranged from 13.6% to 17.6%, risks of low birth weight ranged from 11.9% to 16.7%, and risks of being small for gestational age ranged from 9.1% to 12.5%. For the composite of any adverse birth outcome and any severe adverse birth outcome, the observed risks ranged from 22.6% to 27.9% and 0% to 4.2%, respectively.

A total of 20 very preterm births, including 15 infants with very low birth weight, occurred across patients receiving all ART regimens, and no neonatal deaths occurred. The researchers found no apparent patterns of differences in the observed risk of adverse birth outcomes across all groups related to the timing of ART initiation in pregnancy, but the risks were greater among those who began the drugs during pregnancy compared to those who began before conception.

“Our results confirm the recommendation of DTG as “preferred” in U.S. perinatal guidelines, and provide evidence suggesting ATV/r and RAL provides lower HIV viral suppression at delivery compared to DTG, and support DRV/r as a reasonable alternative when DTG use is not feasible,” Dr. Patel said in an interview.

“With regards to next steps, we are interested in comparing the effectiveness and safety of dolutegravir-based regimens that include tenofovir alafenamide (TAF) vs. tenofovir disoproxil fumarate (TDF) in our U.S. setting,” she said.

The study findings were limited by several factors including the lack of data on predictors of preterm birth and low birth weight, such as previous preterm birth and prepregnancy body mass index, the researchers noted.

However, the results indicate that other common ARTs provide less HIV viral suppression at delivery than dolutegravir, with similar adverse birth outcomes; the results also support darunavir–ritonavir as a reasonable alternative when dolutegravir use is not feasible, as it showed the next highest level of viral suppression after dolutegravir, the researchers concluded.
 

Findings fill a key research gap

The current study is important given the limited data on effectiveness and outcomes in pregnancy with the use of contemporary HIV regimens in the United States, Martina L. Badell, MD, a maternal-fetal medicine specialist at Emory University, Atlanta, said in an interview.

“Pregnancy is still among exclusion criteria for most drug studies,” said Dr. Badell, who was not involved in the current study. “Dolutegravir-based ART is first line in the U.S. today because of its effectiveness, lower side effects, and higher barrier to resistance; therefore understanding the benefits and birth outcomes in pregnancy is critical,” she explained.

Dr. Badell said she was not surprised by the study findings. “However it is very reassuring to see in a large observational study comparing the dolutegravir regimens to other contemporary regimens in pregnancy, such a high level of viral suppression and no increased risk of adverse perinatal outcomes,” she said.

The study findings will impact clinical practice by reaffirming patient counseling regarding the use of dolutegravir in pregnancy, said Dr. Badell. “The use of ART in pregnancy is complex given the number of drug choices, whether the patient was on ART prior to pregnancy or initiated during pregnancy, and the various factors other than ART that affect perinatal outcomes, such as preterm birth and congenital anomalies, she explained.

The finding that the risk of adverse outcomes was higher for those who initiated ART during pregnancy vs. those who were already on ARTs when they became pregnant contradicts some previous research, said Dr. Badell. But this is “reassuring, as we highly recommend ART with viral suppression prior to pregnancy or to start as early as possible in pregnancy.”

Adverse birth outcomes can be affected by many variables such as age, substance abuse, prior adverse birth outcome and other factors, and larger studies that control for these variables will allow better evaluation of the effect of the ART drugs, Dr. Badell added.

The study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, along with the Office of the Director, National Institutes of Health; National Institute of Dental and Craniofacial Research; National Institute of Allergy and Infectious Diseases; National Institute of Neurological Disorders and Stroke; National Institute on Deafness and Other Communication Disorders; National Institute of Mental Health; National Institute on Drug Abuse; National Cancer Institute; National Institute on Alcohol Abuse and Alcoholism; and National Heart, Lung, and Blood Institute through cooperative agreements with the Harvard T.H. Chan School of Public Health and the Tulane University School of Medicine.

The researchers and Dr. Badell had no financial conflicts to disclose.

A dolutegravir-based treatment regimen holds its own as a first choice of antiretroviral therapy (ART) for pregnant individuals, based on data from more than 1,200 patients.

“Dolutegravir is increasingly used in pregnancy in the United States,” Kunjal Patel, DSc, one of the investigators, said in an interview. “While its effectiveness and safety in pregnancy have been compared to efavirenz in previous studies, including three randomized trials, efavirenz isn’t really used in the United States and Europe for treatment of HIV; it is mainly used in Africa,” she said. Therefore, it was important to compare dolutegravir use in pregnancy to the other antiretroviral regimens that are listed as being preferred for use in pregnancy in the U.S., including atazanavir/ritonavir, darunavir/ritonavir, and raltegravir, and others often used in the U.S. and Europe, she said.

In the study published in the New England Journal of Medicine, Dr. Patel, of Harvard T.H. Chan School of Public Health, Boston, and colleagues analyzed data from kids enrolled in the Surveillance and Monitoring for ART Toxicities Dynamic (SMARTT) cohort. This group is part of an ongoing research project focused on evaluating ART toxicities during pregnancy in children who were exposed to HIV perinatally but not infected. It included pregnancies from 2007 until January 2020 that involved use of the ARTs listed.

The study population of 1,257 pregnancies with observed birth outcomes included 120 individuals with an initial ART of dolutegravir (DTG), 464 started on atazanavir–ritonavir (ATV/r), 185 on darunavir–ritonavir (DRV/r), 243 on oral rilpivirine (RPV), 86 on raltegravir (RAL), and 159 on elvitegravir–cobicistat (EVG/c). In approximately half of the pregnancies (51%), ART was started before conception, and the initial ART was changed in 27%.

The primary outcomes were viral suppression at delivery, and adverse birth outcomes, including preterm and very preterm birth, low and very low birth weight, and neonatal death within 14 days.

The median age of the patients at conception was 29 years, and 66% were non-Hispanic Black, representative of persons with HIV of childbearing age in the United States, the researchers noted. Overall, 96.7% of the patients who received dolutegravir showed viral suppression at delivery, compared to 90.1% for darunavir–ritonavir, 89.8% for elvitegravir–cobicistat, 89.2% for raltegravir, and 84.0% for atazanavir–ritonavir.

“We expected that dolutegravir to be similar with regards to viral suppression at delivery compared to raltegravir so were surprised that we observed less viral suppression with raltegravir compared to dolutegravir,” Dr. Patel said in an interview. “Our results may be due to the higher pill burden and lower barrier to resistance with RAL compared to dolutegravir, but we did not assess adherence or resistance in our study,” she noted.

Across ART regimens, the observed risks of preterm birth ranged from 13.6% to 17.6%, risks of low birth weight ranged from 11.9% to 16.7%, and risks of being small for gestational age ranged from 9.1% to 12.5%. For the composite of any adverse birth outcome and any severe adverse birth outcome, the observed risks ranged from 22.6% to 27.9% and 0% to 4.2%, respectively.

A total of 20 very preterm births, including 15 infants with very low birth weight, occurred across patients receiving all ART regimens, and no neonatal deaths occurred. The researchers found no apparent patterns of differences in the observed risk of adverse birth outcomes across all groups related to the timing of ART initiation in pregnancy, but the risks were greater among those who began the drugs during pregnancy compared to those who began before conception.

“Our results confirm the recommendation of DTG as “preferred” in U.S. perinatal guidelines, and provide evidence suggesting ATV/r and RAL provides lower HIV viral suppression at delivery compared to DTG, and support DRV/r as a reasonable alternative when DTG use is not feasible,” Dr. Patel said in an interview.

“With regards to next steps, we are interested in comparing the effectiveness and safety of dolutegravir-based regimens that include tenofovir alafenamide (TAF) vs. tenofovir disoproxil fumarate (TDF) in our U.S. setting,” she said.

The study findings were limited by several factors including the lack of data on predictors of preterm birth and low birth weight, such as previous preterm birth and prepregnancy body mass index, the researchers noted.

However, the results indicate that other common ARTs provide less HIV viral suppression at delivery than dolutegravir, with similar adverse birth outcomes; the results also support darunavir–ritonavir as a reasonable alternative when dolutegravir use is not feasible, as it showed the next highest level of viral suppression after dolutegravir, the researchers concluded.
 

Findings fill a key research gap

The current study is important given the limited data on effectiveness and outcomes in pregnancy with the use of contemporary HIV regimens in the United States, Martina L. Badell, MD, a maternal-fetal medicine specialist at Emory University, Atlanta, said in an interview.

“Pregnancy is still among exclusion criteria for most drug studies,” said Dr. Badell, who was not involved in the current study. “Dolutegravir-based ART is first line in the U.S. today because of its effectiveness, lower side effects, and higher barrier to resistance; therefore understanding the benefits and birth outcomes in pregnancy is critical,” she explained.

Dr. Badell said she was not surprised by the study findings. “However it is very reassuring to see in a large observational study comparing the dolutegravir regimens to other contemporary regimens in pregnancy, such a high level of viral suppression and no increased risk of adverse perinatal outcomes,” she said.

The study findings will impact clinical practice by reaffirming patient counseling regarding the use of dolutegravir in pregnancy, said Dr. Badell. “The use of ART in pregnancy is complex given the number of drug choices, whether the patient was on ART prior to pregnancy or initiated during pregnancy, and the various factors other than ART that affect perinatal outcomes, such as preterm birth and congenital anomalies, she explained.

The finding that the risk of adverse outcomes was higher for those who initiated ART during pregnancy vs. those who were already on ARTs when they became pregnant contradicts some previous research, said Dr. Badell. But this is “reassuring, as we highly recommend ART with viral suppression prior to pregnancy or to start as early as possible in pregnancy.”

Adverse birth outcomes can be affected by many variables such as age, substance abuse, prior adverse birth outcome and other factors, and larger studies that control for these variables will allow better evaluation of the effect of the ART drugs, Dr. Badell added.

The study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, along with the Office of the Director, National Institutes of Health; National Institute of Dental and Craniofacial Research; National Institute of Allergy and Infectious Diseases; National Institute of Neurological Disorders and Stroke; National Institute on Deafness and Other Communication Disorders; National Institute of Mental Health; National Institute on Drug Abuse; National Cancer Institute; National Institute on Alcohol Abuse and Alcoholism; and National Heart, Lung, and Blood Institute through cooperative agreements with the Harvard T.H. Chan School of Public Health and the Tulane University School of Medicine.

The researchers and Dr. Badell had no financial conflicts to disclose.