Ob.Gyn. News

It’s a story of promise at a time of urgent need.

Scientists are optimistic about new evidence into what is causing long COVID, a panel of research experts brought together by the New York State Department of Health said.

They proposed many theories on what might be driving long COVID. A role for a virus “cryptic reservoir” that could reactivate at any time, “viral remnants” that trigger chronic inflammation, and action by “autoimmune antibodies” that cause ongoing symptoms are possibilities.

In fact, it’s likely that research will show long COVID is a condition with more than one cause, the experts said during a recent webinar.

People might experience post-infection problems, including organ damage that takes time to heal after initial COVID-19 illness. Or they may be living with post-immune factors, including ongoing immune system responses triggered by autoantibodies.

Determining the cause or causes of long COVID is essential for treatment. For example, if one person’s symptoms persist because of an overactive immune system, “we need to provide immunosuppressant therapies,” Akiko Iwasaki, PhD, said. “But we don’t want to give that to someone who has a persistent virus reservoir,” meaning remnants of the virus remain in their bodies.

Interestingly, a study preprint, which has not been peer reviewed, found dogs were accurate more than half the time in sniffing out long COVID, said Dr. Iwasaki, professor of immunobiology and developmental biology at Yale University, New Haven, Conn.

The dogs were tasked with identifying 45 people with long COVID versus 188 people without it. The findings suggest the presence of a unique chemical in the sweat of people with long COVID that could someday lead to a diagnostic test.
 

Viral persistence possible

If one of the main theories holds, it could be that the coronavirus somehow remains in the body in some form for some people after COVID-19.

Mady Hornig, MD, agreed this is a possibility that needs to be investigated further.

“A weakened immune response to an infection may mean that you have cryptic reservoirs of virus that are continuing to cause symptoms,” she said during the briefing. Dr. Hornig is a doctor-scientist specializing in epidemiology at Columbia University, New York.

“That may explain why some patients with long COVID feel better after vaccination,” because the vaccine creates a strong antibody response to fight COVID-19, Dr. Iwasaki said.

Researchers are unearthing additional potential factors contributing to long COVID.

Viral persistence could also reactivate other dormant viruses in the body, such as Epstein-Barr virus (EBV), said Lawrence Purpura, MD, MPH, an infectious disease specialist at New York Presbyterian/Columbia University. Reactivation of Epstein-Barr is one of four identifying signs of long COVID revealed in a Jan. 25 study published in the journal Cell.
 

Immune overactivation also possible?

For other people with long COVID, it’s not the virus sticking around but the body’s reaction that’s the issue.

Investigators suggest autoimmunity plays a role, and they point to the presence of autoantibodies, for example.

When these autoantibodies persist, they can cause tissue and organ damage over time.

Other investigators are proposing “immune exhaustion” in long COVID because of similarities to chronic fatigue syndrome, Dr. Hornig said.

“It should be ‘all hands on deck’ for research into long COVID,” she said. “The number of disabled individuals who will likely qualify for a diagnosis of [chronic fatigue syndrome] is growing by the second.”
 

Forging ahead on future research

It’s clear there is more work to do. There are investigators working on banking tissue samples from people with long COVID to learn more, for example.

Also, finding a biomarker unique to long COVID could vastly improve the precision of diagnosing long COVID, especially if the dog sniffing option does not pan out.

Of the thousands of biomarker possibilities, Dr. Hornig said, “maybe that’s one or two that ultimately make a real impact on patient care. So it’s going to be critical to find those quickly, translate them, and make them available.”

In the meantime, some answers might come from a large study sponsored by the National Institutes of Health. The NIH is funding the “Researching COVID to Enhance Recovery” project using $470 million from the American Rescue Plan. Investigators at NYU Langone Health are leading the effort and plan to share the wealth by funding more than 100 researchers at more than 30 institutions to create a “metacohort” to study long COVID. More information is available at recovercovid.org.

“Fortunately, through the global research effort, we are now really starting to expand our understanding of how long COVID manifests, how common it is, and what the underlying mechanisms may be,” Dr. Purpura said.

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

It’s a story of promise at a time of urgent need.

Scientists are optimistic about new evidence into what is causing long COVID, a panel of research experts brought together by the New York State Department of Health said.

They proposed many theories on what might be driving long COVID. A role for a virus “cryptic reservoir” that could reactivate at any time, “viral remnants” that trigger chronic inflammation, and action by “autoimmune antibodies” that cause ongoing symptoms are possibilities.

In fact, it’s likely that research will show long COVID is a condition with more than one cause, the experts said during a recent webinar.

People might experience post-infection problems, including organ damage that takes time to heal after initial COVID-19 illness. Or they may be living with post-immune factors, including ongoing immune system responses triggered by autoantibodies.

Determining the cause or causes of long COVID is essential for treatment. For example, if one person’s symptoms persist because of an overactive immune system, “we need to provide immunosuppressant therapies,” Akiko Iwasaki, PhD, said. “But we don’t want to give that to someone who has a persistent virus reservoir,” meaning remnants of the virus remain in their bodies.

Interestingly, a study preprint, which has not been peer reviewed, found dogs were accurate more than half the time in sniffing out long COVID, said Dr. Iwasaki, professor of immunobiology and developmental biology at Yale University, New Haven, Conn.

The dogs were tasked with identifying 45 people with long COVID versus 188 people without it. The findings suggest the presence of a unique chemical in the sweat of people with long COVID that could someday lead to a diagnostic test.
 

Viral persistence possible

If one of the main theories holds, it could be that the coronavirus somehow remains in the body in some form for some people after COVID-19.

Mady Hornig, MD, agreed this is a possibility that needs to be investigated further.

“A weakened immune response to an infection may mean that you have cryptic reservoirs of virus that are continuing to cause symptoms,” she said during the briefing. Dr. Hornig is a doctor-scientist specializing in epidemiology at Columbia University, New York.

“That may explain why some patients with long COVID feel better after vaccination,” because the vaccine creates a strong antibody response to fight COVID-19, Dr. Iwasaki said.

Researchers are unearthing additional potential factors contributing to long COVID.

Viral persistence could also reactivate other dormant viruses in the body, such as Epstein-Barr virus (EBV), said Lawrence Purpura, MD, MPH, an infectious disease specialist at New York Presbyterian/Columbia University. Reactivation of Epstein-Barr is one of four identifying signs of long COVID revealed in a Jan. 25 study published in the journal Cell.
 

Immune overactivation also possible?

For other people with long COVID, it’s not the virus sticking around but the body’s reaction that’s the issue.

Investigators suggest autoimmunity plays a role, and they point to the presence of autoantibodies, for example.

When these autoantibodies persist, they can cause tissue and organ damage over time.

Other investigators are proposing “immune exhaustion” in long COVID because of similarities to chronic fatigue syndrome, Dr. Hornig said.

“It should be ‘all hands on deck’ for research into long COVID,” she said. “The number of disabled individuals who will likely qualify for a diagnosis of [chronic fatigue syndrome] is growing by the second.”
 

Forging ahead on future research

It’s clear there is more work to do. There are investigators working on banking tissue samples from people with long COVID to learn more, for example.

Also, finding a biomarker unique to long COVID could vastly improve the precision of diagnosing long COVID, especially if the dog sniffing option does not pan out.

Of the thousands of biomarker possibilities, Dr. Hornig said, “maybe that’s one or two that ultimately make a real impact on patient care. So it’s going to be critical to find those quickly, translate them, and make them available.”

In the meantime, some answers might come from a large study sponsored by the National Institutes of Health. The NIH is funding the “Researching COVID to Enhance Recovery” project using $470 million from the American Rescue Plan. Investigators at NYU Langone Health are leading the effort and plan to share the wealth by funding more than 100 researchers at more than 30 institutions to create a “metacohort” to study long COVID. More information is available at recovercovid.org.

“Fortunately, through the global research effort, we are now really starting to expand our understanding of how long COVID manifests, how common it is, and what the underlying mechanisms may be,” Dr. Purpura said.

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

It’s a story of promise at a time of urgent need.

Scientists are optimistic about new evidence into what is causing long COVID, a panel of research experts brought together by the New York State Department of Health said.

They proposed many theories on what might be driving long COVID. A role for a virus “cryptic reservoir” that could reactivate at any time, “viral remnants” that trigger chronic inflammation, and action by “autoimmune antibodies” that cause ongoing symptoms are possibilities.

In fact, it’s likely that research will show long COVID is a condition with more than one cause, the experts said during a recent webinar.

People might experience post-infection problems, including organ damage that takes time to heal after initial COVID-19 illness. Or they may be living with post-immune factors, including ongoing immune system responses triggered by autoantibodies.

Determining the cause or causes of long COVID is essential for treatment. For example, if one person’s symptoms persist because of an overactive immune system, “we need to provide immunosuppressant therapies,” Akiko Iwasaki, PhD, said. “But we don’t want to give that to someone who has a persistent virus reservoir,” meaning remnants of the virus remain in their bodies.

Interestingly, a study preprint, which has not been peer reviewed, found dogs were accurate more than half the time in sniffing out long COVID, said Dr. Iwasaki, professor of immunobiology and developmental biology at Yale University, New Haven, Conn.

The dogs were tasked with identifying 45 people with long COVID versus 188 people without it. The findings suggest the presence of a unique chemical in the sweat of people with long COVID that could someday lead to a diagnostic test.
 

Viral persistence possible

If one of the main theories holds, it could be that the coronavirus somehow remains in the body in some form for some people after COVID-19.

Mady Hornig, MD, agreed this is a possibility that needs to be investigated further.

“A weakened immune response to an infection may mean that you have cryptic reservoirs of virus that are continuing to cause symptoms,” she said during the briefing. Dr. Hornig is a doctor-scientist specializing in epidemiology at Columbia University, New York.

“That may explain why some patients with long COVID feel better after vaccination,” because the vaccine creates a strong antibody response to fight COVID-19, Dr. Iwasaki said.

Researchers are unearthing additional potential factors contributing to long COVID.

Viral persistence could also reactivate other dormant viruses in the body, such as Epstein-Barr virus (EBV), said Lawrence Purpura, MD, MPH, an infectious disease specialist at New York Presbyterian/Columbia University. Reactivation of Epstein-Barr is one of four identifying signs of long COVID revealed in a Jan. 25 study published in the journal Cell.
 

Immune overactivation also possible?

For other people with long COVID, it’s not the virus sticking around but the body’s reaction that’s the issue.

Investigators suggest autoimmunity plays a role, and they point to the presence of autoantibodies, for example.

When these autoantibodies persist, they can cause tissue and organ damage over time.

Other investigators are proposing “immune exhaustion” in long COVID because of similarities to chronic fatigue syndrome, Dr. Hornig said.

“It should be ‘all hands on deck’ for research into long COVID,” she said. “The number of disabled individuals who will likely qualify for a diagnosis of [chronic fatigue syndrome] is growing by the second.”
 

Forging ahead on future research

It’s clear there is more work to do. There are investigators working on banking tissue samples from people with long COVID to learn more, for example.

Also, finding a biomarker unique to long COVID could vastly improve the precision of diagnosing long COVID, especially if the dog sniffing option does not pan out.

Of the thousands of biomarker possibilities, Dr. Hornig said, “maybe that’s one or two that ultimately make a real impact on patient care. So it’s going to be critical to find those quickly, translate them, and make them available.”

In the meantime, some answers might come from a large study sponsored by the National Institutes of Health. The NIH is funding the “Researching COVID to Enhance Recovery” project using $470 million from the American Rescue Plan. Investigators at NYU Langone Health are leading the effort and plan to share the wealth by funding more than 100 researchers at more than 30 institutions to create a “metacohort” to study long COVID. More information is available at recovercovid.org.

“Fortunately, through the global research effort, we are now really starting to expand our understanding of how long COVID manifests, how common it is, and what the underlying mechanisms may be,” Dr. Purpura said.

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

Methylergonovine is often used to control severe bleeding immediately after cesarean deliveries. But a new study suggests that the ergot alkaloid agent could benefit these women if administered before delivery, researchers from the University of Iowa Hospitals, Iowa City, reported in the January edition of the American Journal of Obstetrics and Gynecology. The data were presented Feb. 4 at the 2022 virtual Pregnancy Meeting of the Society of Maternal-Fetal Medicine.

The findings have prompted the institution to begin administering prophylactic methylergonovine in addition to oxytocin at the time of cesarean deliveries, according to the researchers.

“The addition of prophylactic methylergonovine improved uterine tone, decreased the requirement of additional uterotonic agents, decreased the risk of postpartum hemorrhage, and decreased the need for blood transfusions,” lead author Nicole Masse, MD, assistant professor of maternal-fetal medicine at the University of Iowa, said in an interview.

Abnormal uterine tone is the leading cause of postpartum hemorrhage, Dr. Masse said. “Satisfactory uterine tone following delivery is essential. This study found a decreased need for blood transfusions in patients who received prophylactic methylergonovine. Given the risks of blood transfusions, which can include disease transmission and allergic reactions, transfusions should be avoided whenever possible.”

Conducted between June 2019 and February 2021, the single-center, randomized controlled trial of 160 women undergoing an intrapartum cesarean birth is the largest of its kind to date, Dr. Masse said. Women received either intravenous oxytocin at a dose of 300 mU per minute plus 1 mL of intramuscular normal saline (n = 80) or intravenous oxytocin at a dose of 300 mU per minute plus 0.2 mg (1 mL) of intramuscular methylergonovine (n = 80).

Women who received prophylactic methylergonovine required significantly less additional uterotonic agents than those who received oxytocin alone (20% vs. 55%; relative risk, 0.36; 95% confidence interval 0.22-0.59), according to the researchers. Those receiving methylergonovine were more likely to experience improved uterine tone (80% vs. 41.2%; RR, 1.94; 95% CI, 1.46-2.56), a lower incidence of postpartum hemorrhage (35% vs. 58.8%; RR, 0.6; 95% CI, 0.42-0.85), decreased need for a blood transfusion (5% vs. 22.5%; RR, 0.22; 95% CI, 0.08-0.63), and lower mean quantitative blood loss (996 mL vs. 1,315 mL; P = .004), they reported.      

“As the majority of postpartum hemorrhages are preventable, this study is clinically relevant and can serve to decrease the morbidity associated with postpartum hemorrhage,” Dr. Masse said.

Jennifer Choi, DO, clinical assistant professor of maternal-fetal medicine at Stony Brook University Hospital, New York, said the Iowa team’s results are contrary to prior studies showing no benefit with simultaneous use of oxytocin and ergot alkaloids.    

“It would be interesting to see long-term benefits across a diverse population,” she said. “But as methylergonovine is a known contraindication to hypertensive and cardiovascular disorders, including pre-eclampsia, patients would have to be carefully screened.”

Kecia Gaither, MD, MPH, associate professor of clinical obstetrics and gynecology at Weill Cornell Medicine, New York, called the study “a novel idea, but more research and higher numbers are needed for a substantive conclusion.”

Additional studies should look at variables such as the number of prior cesarean deliveries, body mass index, presence of uterine myomas, presence of abnormal placentation (placenta accreta, increta, percreta), and presence of multiple gestation, said Dr. Gaither, who also is director of perinatal services at NYC Health + Hospitals/Lincoln.

“Methergine [methylergonovine] use is contraindicated in women with hypertension/pre-eclampsia spectrum, mitral valve prolapse, history of coronary artery disease, and liver pathology,” she noted.

The researchers reported no relevant financial conflicts of interest.

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

Methylergonovine is often used to control severe bleeding immediately after cesarean deliveries. But a new study suggests that the ergot alkaloid agent could benefit these women if administered before delivery, researchers from the University of Iowa Hospitals, Iowa City, reported in the January edition of the American Journal of Obstetrics and Gynecology. The data were presented Feb. 4 at the 2022 virtual Pregnancy Meeting of the Society of Maternal-Fetal Medicine.

The findings have prompted the institution to begin administering prophylactic methylergonovine in addition to oxytocin at the time of cesarean deliveries, according to the researchers.

“The addition of prophylactic methylergonovine improved uterine tone, decreased the requirement of additional uterotonic agents, decreased the risk of postpartum hemorrhage, and decreased the need for blood transfusions,” lead author Nicole Masse, MD, assistant professor of maternal-fetal medicine at the University of Iowa, said in an interview.

Abnormal uterine tone is the leading cause of postpartum hemorrhage, Dr. Masse said. “Satisfactory uterine tone following delivery is essential. This study found a decreased need for blood transfusions in patients who received prophylactic methylergonovine. Given the risks of blood transfusions, which can include disease transmission and allergic reactions, transfusions should be avoided whenever possible.”

Conducted between June 2019 and February 2021, the single-center, randomized controlled trial of 160 women undergoing an intrapartum cesarean birth is the largest of its kind to date, Dr. Masse said. Women received either intravenous oxytocin at a dose of 300 mU per minute plus 1 mL of intramuscular normal saline (n = 80) or intravenous oxytocin at a dose of 300 mU per minute plus 0.2 mg (1 mL) of intramuscular methylergonovine (n = 80).

Women who received prophylactic methylergonovine required significantly less additional uterotonic agents than those who received oxytocin alone (20% vs. 55%; relative risk, 0.36; 95% confidence interval 0.22-0.59), according to the researchers. Those receiving methylergonovine were more likely to experience improved uterine tone (80% vs. 41.2%; RR, 1.94; 95% CI, 1.46-2.56), a lower incidence of postpartum hemorrhage (35% vs. 58.8%; RR, 0.6; 95% CI, 0.42-0.85), decreased need for a blood transfusion (5% vs. 22.5%; RR, 0.22; 95% CI, 0.08-0.63), and lower mean quantitative blood loss (996 mL vs. 1,315 mL; P = .004), they reported.      

“As the majority of postpartum hemorrhages are preventable, this study is clinically relevant and can serve to decrease the morbidity associated with postpartum hemorrhage,” Dr. Masse said.

Jennifer Choi, DO, clinical assistant professor of maternal-fetal medicine at Stony Brook University Hospital, New York, said the Iowa team’s results are contrary to prior studies showing no benefit with simultaneous use of oxytocin and ergot alkaloids.    

“It would be interesting to see long-term benefits across a diverse population,” she said. “But as methylergonovine is a known contraindication to hypertensive and cardiovascular disorders, including pre-eclampsia, patients would have to be carefully screened.”

Kecia Gaither, MD, MPH, associate professor of clinical obstetrics and gynecology at Weill Cornell Medicine, New York, called the study “a novel idea, but more research and higher numbers are needed for a substantive conclusion.”

Additional studies should look at variables such as the number of prior cesarean deliveries, body mass index, presence of uterine myomas, presence of abnormal placentation (placenta accreta, increta, percreta), and presence of multiple gestation, said Dr. Gaither, who also is director of perinatal services at NYC Health + Hospitals/Lincoln.

“Methergine [methylergonovine] use is contraindicated in women with hypertension/pre-eclampsia spectrum, mitral valve prolapse, history of coronary artery disease, and liver pathology,” she noted.

The researchers reported no relevant financial conflicts of interest.

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

Methylergonovine is often used to control severe bleeding immediately after cesarean deliveries. But a new study suggests that the ergot alkaloid agent could benefit these women if administered before delivery, researchers from the University of Iowa Hospitals, Iowa City, reported in the January edition of the American Journal of Obstetrics and Gynecology. The data were presented Feb. 4 at the 2022 virtual Pregnancy Meeting of the Society of Maternal-Fetal Medicine.

The findings have prompted the institution to begin administering prophylactic methylergonovine in addition to oxytocin at the time of cesarean deliveries, according to the researchers.

“The addition of prophylactic methylergonovine improved uterine tone, decreased the requirement of additional uterotonic agents, decreased the risk of postpartum hemorrhage, and decreased the need for blood transfusions,” lead author Nicole Masse, MD, assistant professor of maternal-fetal medicine at the University of Iowa, said in an interview.

Abnormal uterine tone is the leading cause of postpartum hemorrhage, Dr. Masse said. “Satisfactory uterine tone following delivery is essential. This study found a decreased need for blood transfusions in patients who received prophylactic methylergonovine. Given the risks of blood transfusions, which can include disease transmission and allergic reactions, transfusions should be avoided whenever possible.”

Conducted between June 2019 and February 2021, the single-center, randomized controlled trial of 160 women undergoing an intrapartum cesarean birth is the largest of its kind to date, Dr. Masse said. Women received either intravenous oxytocin at a dose of 300 mU per minute plus 1 mL of intramuscular normal saline (n = 80) or intravenous oxytocin at a dose of 300 mU per minute plus 0.2 mg (1 mL) of intramuscular methylergonovine (n = 80).

Women who received prophylactic methylergonovine required significantly less additional uterotonic agents than those who received oxytocin alone (20% vs. 55%; relative risk, 0.36; 95% confidence interval 0.22-0.59), according to the researchers. Those receiving methylergonovine were more likely to experience improved uterine tone (80% vs. 41.2%; RR, 1.94; 95% CI, 1.46-2.56), a lower incidence of postpartum hemorrhage (35% vs. 58.8%; RR, 0.6; 95% CI, 0.42-0.85), decreased need for a blood transfusion (5% vs. 22.5%; RR, 0.22; 95% CI, 0.08-0.63), and lower mean quantitative blood loss (996 mL vs. 1,315 mL; P = .004), they reported.      

“As the majority of postpartum hemorrhages are preventable, this study is clinically relevant and can serve to decrease the morbidity associated with postpartum hemorrhage,” Dr. Masse said.

Jennifer Choi, DO, clinical assistant professor of maternal-fetal medicine at Stony Brook University Hospital, New York, said the Iowa team’s results are contrary to prior studies showing no benefit with simultaneous use of oxytocin and ergot alkaloids.    

“It would be interesting to see long-term benefits across a diverse population,” she said. “But as methylergonovine is a known contraindication to hypertensive and cardiovascular disorders, including pre-eclampsia, patients would have to be carefully screened.”

Kecia Gaither, MD, MPH, associate professor of clinical obstetrics and gynecology at Weill Cornell Medicine, New York, called the study “a novel idea, but more research and higher numbers are needed for a substantive conclusion.”

Additional studies should look at variables such as the number of prior cesarean deliveries, body mass index, presence of uterine myomas, presence of abnormal placentation (placenta accreta, increta, percreta), and presence of multiple gestation, said Dr. Gaither, who also is director of perinatal services at NYC Health + Hospitals/Lincoln.

“Methergine [methylergonovine] use is contraindicated in women with hypertension/pre-eclampsia spectrum, mitral valve prolapse, history of coronary artery disease, and liver pathology,” she noted.

The researchers reported no relevant financial conflicts of interest.

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

A new study finding that samples from maternal urine and the meconium of their newborn babies frequently produce different results is raising more questions about drug testing of pregnant women.

The study found concerningly high rates of disagreement (or “discordance”) in biochemical testing between maternal urine in women with a documented history of or active drug use and the meconium in their newborns. In some cases, such discordance might be triggering the inappropriate intervention of childcare protective services, including the separation of infants from their mothers, according to the researchers, who presented their findings Feb. 4 at the meeting sponsored by the Society for Maternal-Fetal Medicine.

“There’s a very big debate right now in the obstetrics and perinatology communities about the utility of biochemical testing and the identification of high-risk women,” lead author Cassandra Heiselman, DO, MPH, clinical assistant professor in the department of obstetrics, gynecology and reproductive medicine at Stony Brook (N.Y.) University, said in an interview. “We know that each biochemical test has limitations, which can include basically the inability to detect all substances, especially synthetic opioids like fentanyl, [and] the possibility for false results.”

Inaccuracies in testing can potentially result in inappropriate separation of mother and baby. “Careful scrutiny of results is needed,” Dr. Heiselman said.

The Stony Brook team conducted a retrospective cohort study that identified women presenting for delivery from January 2017 to March 2021 with indications for drug testing, including a known history of or current substance use disorder/misuse, and late or no prenatal care. A standardized panel was used for testing maternal urine and newborn meconium.

Urine tests of 327 women resulted in 187 (57%) positive and 98 (30%) negative results, along with 42 (13%) samples with incomplete data, the researchers reported. In contrast, drug testing of newborn meconium was positive in 273 (83%) cases, negative in 42 (13%), and was not performed in 12 (4%) – for a rate of concordance of 41%.

Concordance of urine/meconium occurred more frequently in male newborns (65%), compared with females (35%). “It is unclear biologically why there is such a difference based on the sex of the infants’ test and is an area that needs further investigation,” Dr. Heiselman said.

Comparing urine and meconium tests for 11 substances resulted in 195/483 (40%) concordance, the researchers said; 18% were discordant with positive maternal urine, and 41% were discordant with newborn positive meconium.

Oxycodone and fentanyl were significantly discordant with positive maternal urine. Cannabis use was the most common factor associated with a positive test of meconium, according to the researchers.

“Some studies have shown cannabis use in the second trimester can show up in meconium testing even if the mother has stopped that behavior,” Dr. Heiselman said. “Then there is also cross-reactivity with other substances that can lead to higher false positive results, especially in the urine toxicology.”

The reasons for the discordant results are not clear and vary by substance, Dr. Heiselman said.

“Cannabis and methadone were the significant factors leading to discordance with positive newborn meconium, which may reflect prior use earlier in pregnancy without recent use before delivery,” she said in an interview. “Urine and meconium reflect potentially different timing in perinatal exposure and the potential differences in windows of detection for different substances. Therefore, we would expect some discordance in our comparisons, just not the extent that we saw.”

Some test results might also have been false positives. Many commonly used medications, from cough syrups to proton pump inhibitors, have the potential to generate positive results for illicit drugs, Dr. Heiselman said.

“The issue of discordance is a complex one, where there are limitations of the tests being performed, possible cross-reactivity with false positives, and the difference in what test reflects as far as timing of prenatal exposure. Furthermore, a negative test does not rule out sporadic use, nor does a positive result diagnose substance use disorder or its severity,” she said.
 

Lack of standards

Dr. Heiselman said states and the federal government lack standards to biochemically evaluate women at risk for drug abuse and their newborns.

“My institution uses a risk-based protocol. Basically, we test cases where we have a known history of substance use disorder or active use, a history in the last 3 years of any kind of substance use, initiation of late prenatal care after 20 weeks, or no prenatal care at all,” she said. “And then the pediatricians on the other side will test neonates if the mother has any of that history or if the neonates themselves have unexplained complications or drug withdrawal symptoms.”

High rates of discordance can result in the inappropriate intervention by childcare protective service agencies when the mother may not have a substance use disorder, she noted.

Perinatologist Kecia Gaither, MD, MPH, associate professor of clinical obstetrics and gynecology at Weill Cornell Medicine, New York, called the findings “no surprise,” but added that negative findings in neonates “do not exclude the possibility of substance abuse by the mother. It is important to recognize the limitations inherent with screening tests for illicit substances in neonates from substance-abusing mothers.”

Dr. Heiselman added that understanding what maternal and infant drug tests truly reflect “can help us as clinicians in deciding when we test, whether it’s medically necessary, instead of just thinking biochemical tests are the best screening tool, because we know that we are screening. We must engage these women in empathetic and nonjudgmental discussions, which often will elucidate a substance use disorder history more so than just biochemical testing, negative or positive.”

The researchers disclosed no relevant financial relationships.

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

A new study finding that samples from maternal urine and the meconium of their newborn babies frequently produce different results is raising more questions about drug testing of pregnant women.

The study found concerningly high rates of disagreement (or “discordance”) in biochemical testing between maternal urine in women with a documented history of or active drug use and the meconium in their newborns. In some cases, such discordance might be triggering the inappropriate intervention of childcare protective services, including the separation of infants from their mothers, according to the researchers, who presented their findings Feb. 4 at the meeting sponsored by the Society for Maternal-Fetal Medicine.

“There’s a very big debate right now in the obstetrics and perinatology communities about the utility of biochemical testing and the identification of high-risk women,” lead author Cassandra Heiselman, DO, MPH, clinical assistant professor in the department of obstetrics, gynecology and reproductive medicine at Stony Brook (N.Y.) University, said in an interview. “We know that each biochemical test has limitations, which can include basically the inability to detect all substances, especially synthetic opioids like fentanyl, [and] the possibility for false results.”

Inaccuracies in testing can potentially result in inappropriate separation of mother and baby. “Careful scrutiny of results is needed,” Dr. Heiselman said.

The Stony Brook team conducted a retrospective cohort study that identified women presenting for delivery from January 2017 to March 2021 with indications for drug testing, including a known history of or current substance use disorder/misuse, and late or no prenatal care. A standardized panel was used for testing maternal urine and newborn meconium.

Urine tests of 327 women resulted in 187 (57%) positive and 98 (30%) negative results, along with 42 (13%) samples with incomplete data, the researchers reported. In contrast, drug testing of newborn meconium was positive in 273 (83%) cases, negative in 42 (13%), and was not performed in 12 (4%) – for a rate of concordance of 41%.

Concordance of urine/meconium occurred more frequently in male newborns (65%), compared with females (35%). “It is unclear biologically why there is such a difference based on the sex of the infants’ test and is an area that needs further investigation,” Dr. Heiselman said.

Comparing urine and meconium tests for 11 substances resulted in 195/483 (40%) concordance, the researchers said; 18% were discordant with positive maternal urine, and 41% were discordant with newborn positive meconium.

Oxycodone and fentanyl were significantly discordant with positive maternal urine. Cannabis use was the most common factor associated with a positive test of meconium, according to the researchers.

“Some studies have shown cannabis use in the second trimester can show up in meconium testing even if the mother has stopped that behavior,” Dr. Heiselman said. “Then there is also cross-reactivity with other substances that can lead to higher false positive results, especially in the urine toxicology.”

The reasons for the discordant results are not clear and vary by substance, Dr. Heiselman said.

“Cannabis and methadone were the significant factors leading to discordance with positive newborn meconium, which may reflect prior use earlier in pregnancy without recent use before delivery,” she said in an interview. “Urine and meconium reflect potentially different timing in perinatal exposure and the potential differences in windows of detection for different substances. Therefore, we would expect some discordance in our comparisons, just not the extent that we saw.”

Some test results might also have been false positives. Many commonly used medications, from cough syrups to proton pump inhibitors, have the potential to generate positive results for illicit drugs, Dr. Heiselman said.

“The issue of discordance is a complex one, where there are limitations of the tests being performed, possible cross-reactivity with false positives, and the difference in what test reflects as far as timing of prenatal exposure. Furthermore, a negative test does not rule out sporadic use, nor does a positive result diagnose substance use disorder or its severity,” she said.
 

Lack of standards

Dr. Heiselman said states and the federal government lack standards to biochemically evaluate women at risk for drug abuse and their newborns.

“My institution uses a risk-based protocol. Basically, we test cases where we have a known history of substance use disorder or active use, a history in the last 3 years of any kind of substance use, initiation of late prenatal care after 20 weeks, or no prenatal care at all,” she said. “And then the pediatricians on the other side will test neonates if the mother has any of that history or if the neonates themselves have unexplained complications or drug withdrawal symptoms.”

High rates of discordance can result in the inappropriate intervention by childcare protective service agencies when the mother may not have a substance use disorder, she noted.

Perinatologist Kecia Gaither, MD, MPH, associate professor of clinical obstetrics and gynecology at Weill Cornell Medicine, New York, called the findings “no surprise,” but added that negative findings in neonates “do not exclude the possibility of substance abuse by the mother. It is important to recognize the limitations inherent with screening tests for illicit substances in neonates from substance-abusing mothers.”

Dr. Heiselman added that understanding what maternal and infant drug tests truly reflect “can help us as clinicians in deciding when we test, whether it’s medically necessary, instead of just thinking biochemical tests are the best screening tool, because we know that we are screening. We must engage these women in empathetic and nonjudgmental discussions, which often will elucidate a substance use disorder history more so than just biochemical testing, negative or positive.”

The researchers disclosed no relevant financial relationships.

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

A new study finding that samples from maternal urine and the meconium of their newborn babies frequently produce different results is raising more questions about drug testing of pregnant women.

The study found concerningly high rates of disagreement (or “discordance”) in biochemical testing between maternal urine in women with a documented history of or active drug use and the meconium in their newborns. In some cases, such discordance might be triggering the inappropriate intervention of childcare protective services, including the separation of infants from their mothers, according to the researchers, who presented their findings Feb. 4 at the meeting sponsored by the Society for Maternal-Fetal Medicine.

“There’s a very big debate right now in the obstetrics and perinatology communities about the utility of biochemical testing and the identification of high-risk women,” lead author Cassandra Heiselman, DO, MPH, clinical assistant professor in the department of obstetrics, gynecology and reproductive medicine at Stony Brook (N.Y.) University, said in an interview. “We know that each biochemical test has limitations, which can include basically the inability to detect all substances, especially synthetic opioids like fentanyl, [and] the possibility for false results.”

Inaccuracies in testing can potentially result in inappropriate separation of mother and baby. “Careful scrutiny of results is needed,” Dr. Heiselman said.

The Stony Brook team conducted a retrospective cohort study that identified women presenting for delivery from January 2017 to March 2021 with indications for drug testing, including a known history of or current substance use disorder/misuse, and late or no prenatal care. A standardized panel was used for testing maternal urine and newborn meconium.

Urine tests of 327 women resulted in 187 (57%) positive and 98 (30%) negative results, along with 42 (13%) samples with incomplete data, the researchers reported. In contrast, drug testing of newborn meconium was positive in 273 (83%) cases, negative in 42 (13%), and was not performed in 12 (4%) – for a rate of concordance of 41%.

Concordance of urine/meconium occurred more frequently in male newborns (65%), compared with females (35%). “It is unclear biologically why there is such a difference based on the sex of the infants’ test and is an area that needs further investigation,” Dr. Heiselman said.

Comparing urine and meconium tests for 11 substances resulted in 195/483 (40%) concordance, the researchers said; 18% were discordant with positive maternal urine, and 41% were discordant with newborn positive meconium.

Oxycodone and fentanyl were significantly discordant with positive maternal urine. Cannabis use was the most common factor associated with a positive test of meconium, according to the researchers.

“Some studies have shown cannabis use in the second trimester can show up in meconium testing even if the mother has stopped that behavior,” Dr. Heiselman said. “Then there is also cross-reactivity with other substances that can lead to higher false positive results, especially in the urine toxicology.”

The reasons for the discordant results are not clear and vary by substance, Dr. Heiselman said.

“Cannabis and methadone were the significant factors leading to discordance with positive newborn meconium, which may reflect prior use earlier in pregnancy without recent use before delivery,” she said in an interview. “Urine and meconium reflect potentially different timing in perinatal exposure and the potential differences in windows of detection for different substances. Therefore, we would expect some discordance in our comparisons, just not the extent that we saw.”

Some test results might also have been false positives. Many commonly used medications, from cough syrups to proton pump inhibitors, have the potential to generate positive results for illicit drugs, Dr. Heiselman said.

“The issue of discordance is a complex one, where there are limitations of the tests being performed, possible cross-reactivity with false positives, and the difference in what test reflects as far as timing of prenatal exposure. Furthermore, a negative test does not rule out sporadic use, nor does a positive result diagnose substance use disorder or its severity,” she said.
 

Lack of standards

Dr. Heiselman said states and the federal government lack standards to biochemically evaluate women at risk for drug abuse and their newborns.

“My institution uses a risk-based protocol. Basically, we test cases where we have a known history of substance use disorder or active use, a history in the last 3 years of any kind of substance use, initiation of late prenatal care after 20 weeks, or no prenatal care at all,” she said. “And then the pediatricians on the other side will test neonates if the mother has any of that history or if the neonates themselves have unexplained complications or drug withdrawal symptoms.”

High rates of discordance can result in the inappropriate intervention by childcare protective service agencies when the mother may not have a substance use disorder, she noted.

Perinatologist Kecia Gaither, MD, MPH, associate professor of clinical obstetrics and gynecology at Weill Cornell Medicine, New York, called the findings “no surprise,” but added that negative findings in neonates “do not exclude the possibility of substance abuse by the mother. It is important to recognize the limitations inherent with screening tests for illicit substances in neonates from substance-abusing mothers.”

Dr. Heiselman added that understanding what maternal and infant drug tests truly reflect “can help us as clinicians in deciding when we test, whether it’s medically necessary, instead of just thinking biochemical tests are the best screening tool, because we know that we are screening. We must engage these women in empathetic and nonjudgmental discussions, which often will elucidate a substance use disorder history more so than just biochemical testing, negative or positive.”

The researchers disclosed no relevant financial relationships.

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

Updated guidelines for the management and treatment of endometriosis reflect changes in clinical practice to guide clinician and patient decision-making, according to a statement from the European Society of Human Reproduction and Embryology, which issued the guidelines in February 2022.

Although the exact prevalence of endometriosis remains unclear, estimates suggest that approximately 190 million women and adolescent girls are affected by endometriosis during their reproductive years, and women continue to suffer beyond menopause, according to the authors. Endometriosis has a significant impact on society through both direct and indirect health care costs comparable to those of type 2 diabetes, rheumatoid arthritis, and Crohn’s disease, they noted.

The guidelines are the first update on the topic of endometriosis since 2014, and include more than 100 recommendations, according to the European Society of Human Reproduction and Embryology (ESHRE). The target audience, according to the authors, is secondary and tertiary health care providers who treat women with endometriosis. The recommendations were based on research papers published up to Dec. 1, 2020.

Although most of the recent studies confirm previous ESHRE recommendations, several topics reflect significant changes in clinical practice.

Notably, laparoscopy is no longer recommended as the diagnostic gold standard, and should be used only in patients with negative imaging for whom empirical treatment was unsuccessful.

For pain management, studies support the use of GnRH antagonists as a second-line treatment, while laparoscopic uterosacral nerve ablation and presacral neurectomy are no longer included in the recommendations.

The guidelines include new information on pregnancy and fertility preservation for women with endometriosis. The Endometriosis Fertility Index (EFI) was added to support joint decision-making for women seeking pregnancy after surgery. However, the extended use of GnRH antagonist prior to assisted reproductive technology treatments to improve live birth rate is not recommended.

Endometriosis in adolescent patients is included in the guidelines for the first time, and strong recommendations include taking a careful history and using ultrasound if appropriate, but the use of serum biomarkers is not recommended for diagnosis. Strong recommendations for treatment strategies for adolescents include hormonal contraceptives or progestins as a first-line therapy.

Recommendations for managing endometriosis in menopause are more extensive than in previous guidelines and the strongest update is against the use of estrogen-only treatment in these patients. However, the guidelines continue to recommend treating women with a history of endometriosis after surgical menopause with combined estrogen-progestogen therapy “at least up to the age of natural menopause.”

Expanded recommendations related to endometriosis and cancer begin with a strong recommendation for clinicians to advise women that endometriosis is not associated with a significantly higher risk of cancer overall. “Although endometriosis is associated with a higher risk of ovarian, breast, and thyroid cancers in particular, the increase in absolute risk compared with women in the general population is low,” the authors wrote. Other strong recommendations include reassuring women with endometriosis of the low risk of malignancy associated with hormonal contraceptive use, and performing cancer screening according to the existing population-based guidelines without additional screening. Epidemiologic data show that complete excision of visible endometriosis may reduce the risk of ovarian cancer, but the potential benefits must be weighed against the risks of surgery, including morbidity, pain, and ovarian reserve, the authors said.

The guidelines include recommendations related to asymptomatic endometriosis, extrapelvic endometriosis, and primary prevention of endometriosis, but without major changes to the 2014 guidelines.
 

Guidelines expand strategies, but research gaps remain

In 2021, an international working group of the American Association of Gynecologic Laparoscopists, the European Society for Gynecologic Endoscopy, ESHRE, and the World Endometriosis Society defined endometriosis as “a disease characterized by the presence of endometrium-like epithelium and/or stroma outside the endometrium and myometrium, usually with an associated inflammatory process,” Mark P. Trolice, MD, director of The IVF Center, Orlando, Fla., and professor of obstetrics and gynecology at the University of Central Florida, said in an interview.

Although the current guidelines represent the second update since 2005, many unanswered questions remain, Dr. Trolice said. “There is a large diagnostic void between the onset of symptoms and the time to a reliable diagnosis averaging between 8 and 12 years,” he emphasized.

Dr. Trolice noted the change of the addition of an oral GnRH antagonist, “now FDA approved for the treatment of pain associated with endometriosis,” he said. However, “Extended GnRH agonist prior to ART is not recommended due to the lack of any clear benefit,” he noted.

Dr. Trolice noted the inclusion of the Endometriosis Fertility Index (EFI), published in 2010, “as a useful scoring system to predict postoperative non-IVF pregnancy rates (both by natural means and IUI [intrauterine insemination]) based on patient characteristics, revised ASRM staging, and ‘least function score of the adnexa.’ ” He agreed with the need for expanded information on the topics of endometriosis and adolescence and endometriosis and cancer.

The most important changes for clinical practice include reducing unnecessary laparoscopy and procedures without benefit, such as laparoscopic uterosacral nerve ablation and presacral neurectomy, and GnRH suppression using an oral antagonist, said Dr. Trolice. Other especially practical guidance includes the recommendation to discontinue advising patients that pregnancy will reduce symptoms of endometriosis, and to avoid prescribing estrogen-only treatment in menopause given the risk of malignant transformation of endometriosis, he said.

Another clinically useful recommendation, though not a significant update, is the need to identify extrapelvic endometriosis symptoms, such as cyclical shoulder pain, cyclical spontaneous pneumothorax, cyclical cough, or nodules that enlarge during menses, Dr. Trolice added.

Barriers to implementing the updated guidelines include lack of education of clinicians, including primary care providers, and the lack of definitive evidence for many areas, he noted.

As for additional research, more data are needed to explore the genetic, mutational, and epigenetic profile of endometriosis, and to identify biomarkers to noninvasively detect and provide a prognosis for endometriosis, and optimal methods for prevention and management, said Dr. Trolice. Other research gaps include “definitive medical and surgical treatment of endometriosis for improvement of fertility, quality of life, and reduction of pain,” he noted. From a fertility standpoint, more studies are needed on “the use of ovarian tissue or oocytes cryopreservation in adolescents and adults who undergo ovarian surgery for endometriomas, and the role of the EFI as a presurgical triage tool and to predict IUI outcomes,” said Dr. Trolice.

Overall, society recommendations such as these from ESHRE “serve as guides for physicians by providing evidence-based medicine and dispelling prior unproven practices so patients may receive the most effective care of endometriosis, throughout a woman’s life,” Dr. Trolice emphasized.

The current guideline will be considered for revision in 2025, and the full version is available on the ESHRE website.

Members of the ESHRE guideline development group received no payment for participating in the development process, although they were reimbursed for travel expenses related to guideline meetings.

Dr. Trolice had no financial conflicts to disclose and serves on the editorial advisory board of Ob.Gyn News.

Updated guidelines for the management and treatment of endometriosis reflect changes in clinical practice to guide clinician and patient decision-making, according to a statement from the European Society of Human Reproduction and Embryology, which issued the guidelines in February 2022.

Although the exact prevalence of endometriosis remains unclear, estimates suggest that approximately 190 million women and adolescent girls are affected by endometriosis during their reproductive years, and women continue to suffer beyond menopause, according to the authors. Endometriosis has a significant impact on society through both direct and indirect health care costs comparable to those of type 2 diabetes, rheumatoid arthritis, and Crohn’s disease, they noted.

The guidelines are the first update on the topic of endometriosis since 2014, and include more than 100 recommendations, according to the European Society of Human Reproduction and Embryology (ESHRE). The target audience, according to the authors, is secondary and tertiary health care providers who treat women with endometriosis. The recommendations were based on research papers published up to Dec. 1, 2020.

Although most of the recent studies confirm previous ESHRE recommendations, several topics reflect significant changes in clinical practice.

Notably, laparoscopy is no longer recommended as the diagnostic gold standard, and should be used only in patients with negative imaging for whom empirical treatment was unsuccessful.

For pain management, studies support the use of GnRH antagonists as a second-line treatment, while laparoscopic uterosacral nerve ablation and presacral neurectomy are no longer included in the recommendations.

The guidelines include new information on pregnancy and fertility preservation for women with endometriosis. The Endometriosis Fertility Index (EFI) was added to support joint decision-making for women seeking pregnancy after surgery. However, the extended use of GnRH antagonist prior to assisted reproductive technology treatments to improve live birth rate is not recommended.

Endometriosis in adolescent patients is included in the guidelines for the first time, and strong recommendations include taking a careful history and using ultrasound if appropriate, but the use of serum biomarkers is not recommended for diagnosis. Strong recommendations for treatment strategies for adolescents include hormonal contraceptives or progestins as a first-line therapy.

Recommendations for managing endometriosis in menopause are more extensive than in previous guidelines and the strongest update is against the use of estrogen-only treatment in these patients. However, the guidelines continue to recommend treating women with a history of endometriosis after surgical menopause with combined estrogen-progestogen therapy “at least up to the age of natural menopause.”

Expanded recommendations related to endometriosis and cancer begin with a strong recommendation for clinicians to advise women that endometriosis is not associated with a significantly higher risk of cancer overall. “Although endometriosis is associated with a higher risk of ovarian, breast, and thyroid cancers in particular, the increase in absolute risk compared with women in the general population is low,” the authors wrote. Other strong recommendations include reassuring women with endometriosis of the low risk of malignancy associated with hormonal contraceptive use, and performing cancer screening according to the existing population-based guidelines without additional screening. Epidemiologic data show that complete excision of visible endometriosis may reduce the risk of ovarian cancer, but the potential benefits must be weighed against the risks of surgery, including morbidity, pain, and ovarian reserve, the authors said.

The guidelines include recommendations related to asymptomatic endometriosis, extrapelvic endometriosis, and primary prevention of endometriosis, but without major changes to the 2014 guidelines.
 

Guidelines expand strategies, but research gaps remain

In 2021, an international working group of the American Association of Gynecologic Laparoscopists, the European Society for Gynecologic Endoscopy, ESHRE, and the World Endometriosis Society defined endometriosis as “a disease characterized by the presence of endometrium-like epithelium and/or stroma outside the endometrium and myometrium, usually with an associated inflammatory process,” Mark P. Trolice, MD, director of The IVF Center, Orlando, Fla., and professor of obstetrics and gynecology at the University of Central Florida, said in an interview.

Although the current guidelines represent the second update since 2005, many unanswered questions remain, Dr. Trolice said. “There is a large diagnostic void between the onset of symptoms and the time to a reliable diagnosis averaging between 8 and 12 years,” he emphasized.

Dr. Trolice noted the change of the addition of an oral GnRH antagonist, “now FDA approved for the treatment of pain associated with endometriosis,” he said. However, “Extended GnRH agonist prior to ART is not recommended due to the lack of any clear benefit,” he noted.

Dr. Trolice noted the inclusion of the Endometriosis Fertility Index (EFI), published in 2010, “as a useful scoring system to predict postoperative non-IVF pregnancy rates (both by natural means and IUI [intrauterine insemination]) based on patient characteristics, revised ASRM staging, and ‘least function score of the adnexa.’ ” He agreed with the need for expanded information on the topics of endometriosis and adolescence and endometriosis and cancer.

The most important changes for clinical practice include reducing unnecessary laparoscopy and procedures without benefit, such as laparoscopic uterosacral nerve ablation and presacral neurectomy, and GnRH suppression using an oral antagonist, said Dr. Trolice. Other especially practical guidance includes the recommendation to discontinue advising patients that pregnancy will reduce symptoms of endometriosis, and to avoid prescribing estrogen-only treatment in menopause given the risk of malignant transformation of endometriosis, he said.

Another clinically useful recommendation, though not a significant update, is the need to identify extrapelvic endometriosis symptoms, such as cyclical shoulder pain, cyclical spontaneous pneumothorax, cyclical cough, or nodules that enlarge during menses, Dr. Trolice added.

Barriers to implementing the updated guidelines include lack of education of clinicians, including primary care providers, and the lack of definitive evidence for many areas, he noted.

As for additional research, more data are needed to explore the genetic, mutational, and epigenetic profile of endometriosis, and to identify biomarkers to noninvasively detect and provide a prognosis for endometriosis, and optimal methods for prevention and management, said Dr. Trolice. Other research gaps include “definitive medical and surgical treatment of endometriosis for improvement of fertility, quality of life, and reduction of pain,” he noted. From a fertility standpoint, more studies are needed on “the use of ovarian tissue or oocytes cryopreservation in adolescents and adults who undergo ovarian surgery for endometriomas, and the role of the EFI as a presurgical triage tool and to predict IUI outcomes,” said Dr. Trolice.

Overall, society recommendations such as these from ESHRE “serve as guides for physicians by providing evidence-based medicine and dispelling prior unproven practices so patients may receive the most effective care of endometriosis, throughout a woman’s life,” Dr. Trolice emphasized.

The current guideline will be considered for revision in 2025, and the full version is available on the ESHRE website.

Members of the ESHRE guideline development group received no payment for participating in the development process, although they were reimbursed for travel expenses related to guideline meetings.

Dr. Trolice had no financial conflicts to disclose and serves on the editorial advisory board of Ob.Gyn News.

Updated guidelines for the management and treatment of endometriosis reflect changes in clinical practice to guide clinician and patient decision-making, according to a statement from the European Society of Human Reproduction and Embryology, which issued the guidelines in February 2022.

Although the exact prevalence of endometriosis remains unclear, estimates suggest that approximately 190 million women and adolescent girls are affected by endometriosis during their reproductive years, and women continue to suffer beyond menopause, according to the authors. Endometriosis has a significant impact on society through both direct and indirect health care costs comparable to those of type 2 diabetes, rheumatoid arthritis, and Crohn’s disease, they noted.

The guidelines are the first update on the topic of endometriosis since 2014, and include more than 100 recommendations, according to the European Society of Human Reproduction and Embryology (ESHRE). The target audience, according to the authors, is secondary and tertiary health care providers who treat women with endometriosis. The recommendations were based on research papers published up to Dec. 1, 2020.

Although most of the recent studies confirm previous ESHRE recommendations, several topics reflect significant changes in clinical practice.

Notably, laparoscopy is no longer recommended as the diagnostic gold standard, and should be used only in patients with negative imaging for whom empirical treatment was unsuccessful.

For pain management, studies support the use of GnRH antagonists as a second-line treatment, while laparoscopic uterosacral nerve ablation and presacral neurectomy are no longer included in the recommendations.

The guidelines include new information on pregnancy and fertility preservation for women with endometriosis. The Endometriosis Fertility Index (EFI) was added to support joint decision-making for women seeking pregnancy after surgery. However, the extended use of GnRH antagonist prior to assisted reproductive technology treatments to improve live birth rate is not recommended.

Endometriosis in adolescent patients is included in the guidelines for the first time, and strong recommendations include taking a careful history and using ultrasound if appropriate, but the use of serum biomarkers is not recommended for diagnosis. Strong recommendations for treatment strategies for adolescents include hormonal contraceptives or progestins as a first-line therapy.

Recommendations for managing endometriosis in menopause are more extensive than in previous guidelines and the strongest update is against the use of estrogen-only treatment in these patients. However, the guidelines continue to recommend treating women with a history of endometriosis after surgical menopause with combined estrogen-progestogen therapy “at least up to the age of natural menopause.”

Expanded recommendations related to endometriosis and cancer begin with a strong recommendation for clinicians to advise women that endometriosis is not associated with a significantly higher risk of cancer overall. “Although endometriosis is associated with a higher risk of ovarian, breast, and thyroid cancers in particular, the increase in absolute risk compared with women in the general population is low,” the authors wrote. Other strong recommendations include reassuring women with endometriosis of the low risk of malignancy associated with hormonal contraceptive use, and performing cancer screening according to the existing population-based guidelines without additional screening. Epidemiologic data show that complete excision of visible endometriosis may reduce the risk of ovarian cancer, but the potential benefits must be weighed against the risks of surgery, including morbidity, pain, and ovarian reserve, the authors said.

The guidelines include recommendations related to asymptomatic endometriosis, extrapelvic endometriosis, and primary prevention of endometriosis, but without major changes to the 2014 guidelines.
 

Guidelines expand strategies, but research gaps remain

In 2021, an international working group of the American Association of Gynecologic Laparoscopists, the European Society for Gynecologic Endoscopy, ESHRE, and the World Endometriosis Society defined endometriosis as “a disease characterized by the presence of endometrium-like epithelium and/or stroma outside the endometrium and myometrium, usually with an associated inflammatory process,” Mark P. Trolice, MD, director of The IVF Center, Orlando, Fla., and professor of obstetrics and gynecology at the University of Central Florida, said in an interview.

Although the current guidelines represent the second update since 2005, many unanswered questions remain, Dr. Trolice said. “There is a large diagnostic void between the onset of symptoms and the time to a reliable diagnosis averaging between 8 and 12 years,” he emphasized.

Dr. Trolice noted the change of the addition of an oral GnRH antagonist, “now FDA approved for the treatment of pain associated with endometriosis,” he said. However, “Extended GnRH agonist prior to ART is not recommended due to the lack of any clear benefit,” he noted.

Dr. Trolice noted the inclusion of the Endometriosis Fertility Index (EFI), published in 2010, “as a useful scoring system to predict postoperative non-IVF pregnancy rates (both by natural means and IUI [intrauterine insemination]) based on patient characteristics, revised ASRM staging, and ‘least function score of the adnexa.’ ” He agreed with the need for expanded information on the topics of endometriosis and adolescence and endometriosis and cancer.

The most important changes for clinical practice include reducing unnecessary laparoscopy and procedures without benefit, such as laparoscopic uterosacral nerve ablation and presacral neurectomy, and GnRH suppression using an oral antagonist, said Dr. Trolice. Other especially practical guidance includes the recommendation to discontinue advising patients that pregnancy will reduce symptoms of endometriosis, and to avoid prescribing estrogen-only treatment in menopause given the risk of malignant transformation of endometriosis, he said.

Another clinically useful recommendation, though not a significant update, is the need to identify extrapelvic endometriosis symptoms, such as cyclical shoulder pain, cyclical spontaneous pneumothorax, cyclical cough, or nodules that enlarge during menses, Dr. Trolice added.

Barriers to implementing the updated guidelines include lack of education of clinicians, including primary care providers, and the lack of definitive evidence for many areas, he noted.

As for additional research, more data are needed to explore the genetic, mutational, and epigenetic profile of endometriosis, and to identify biomarkers to noninvasively detect and provide a prognosis for endometriosis, and optimal methods for prevention and management, said Dr. Trolice. Other research gaps include “definitive medical and surgical treatment of endometriosis for improvement of fertility, quality of life, and reduction of pain,” he noted. From a fertility standpoint, more studies are needed on “the use of ovarian tissue or oocytes cryopreservation in adolescents and adults who undergo ovarian surgery for endometriomas, and the role of the EFI as a presurgical triage tool and to predict IUI outcomes,” said Dr. Trolice.

Overall, society recommendations such as these from ESHRE “serve as guides for physicians by providing evidence-based medicine and dispelling prior unproven practices so patients may receive the most effective care of endometriosis, throughout a woman’s life,” Dr. Trolice emphasized.

The current guideline will be considered for revision in 2025, and the full version is available on the ESHRE website.

Members of the ESHRE guideline development group received no payment for participating in the development process, although they were reimbursed for travel expenses related to guideline meetings.

Dr. Trolice had no financial conflicts to disclose and serves on the editorial advisory board of Ob.Gyn News.

Members of the LGBTQ community who give birth appear to have a greater risk of hypertensive disorders of pregnancy and postpartum hemorrhage, according to new research presented at the annual meeting sponsored by the Society for Maternal-Fetal Medicine.

“Our study found that birthing patients in likely sexual and gender minority partnerships experienced disparities in clinical outcomes,” Stephanie Leonard, PhD, an epidemiology and biostatistics instructor at the Stanford (Calif.) University division of maternal-fetal medicine and obstetrics, told attendees at the meeting. The disparities are likely because of various social determinants and possibly higher use of assisted reproductive technology (ART). The findings establish “how these are significant disparities that have been largely overlooked and set the groundwork for doing further research on maybe ways that we can improve the inclusivity of obstetric care.”

Jenny Mei, MD, a maternal-fetal medicine fellow at the University of California, Los Angeles, who attended the presentation but was not involved in the research, said the findings were “overall unfortunate but not surprising given the existing studies looking at LGBTQ patients and their poorer health outcomes, largely due to lack of access to health care and discrimination in the health care setting.”

Dr. Leonard described the societal, interpersonal, and individual factors that can contribute to health disparities among gender and sexual minority patients.

“At the societal level, there are expectations of what it means to be pregnant, to give birth, and to be a parent. At the community level, there’s the clinical care environment, and at the interpersonal level, there’s an obstetrician’s relationship with the patient,” Dr. Leonard said. “At the individual level, most notably is minority stress, the biological effects of the chronic experience of discrimination.”

It has historically been difficult to collect data on this patient population, but a change in the design of the California birth certificate made it possible to gather more data than previously possible. The updated California birth certificate, issued in 2016, allows the parent not giving birth to check off whether they are the child’s mother, father, parent, or “not specified” instead of defaulting to “father.” In addition, the parent giving birth can select mother, father, parent or not specified instead of being “mother” by default.

The researchers classified sexual and gender minority (SGM) partnerships as those in which the parent giving birth was identified as the father and those where both parents were identified as mothers. Non-SGM minority partnerships were those in which the birthing parent was identified as the mother and the nonbirthing parent was identified as the father.

The population-based cohort study included data from all live birth hospitalizations from 2016-2019 in California, whose annual births represent one in eight babies born each year in the United States. The population of SGM patients different significantly from the non-SGM population in nearly every demographic and clinical factor except rates of pre-existing diabetes. For example, 42% of the SGM birthing patients were age 35 or older, compared with 23% of the non-SGM patients.

SGM patients were more likely to be born in the United States, were more likely to be White, and were less likely to be Asian or Hispanic. SGM patients had higher education levels and were more likely to have private insurance. They were also more likely to be nulliparous and have chronic hypertension. Average body mass index for SGM patients was 33 kg/m², compared with 30 for non-SGM patients. SGM patients were also much more likely to have multifetal gestation: 7.1% of SGM patients versus 1.5% of non-SGM patients.

In terms of clinical outcomes, 14% of SGM patients had hypertensive disorders of pregnancy, compared with 8% of non-SGM patients. Before adjustment for potential confounders, SGM patients were also twice as likely to have postpartum hemorrhage (8% vs. 4% in non-SGM patients) and postterm birth at 42-44 weeks (0.6% vs 0.3% in non-SGM patients).

“Having increased postterm birth is a matter of declining induction of labor, as it is recommended to have an induction by 41 weeks of gestation in general,” Dr. Mei said in an interview. “It is also possible this patient cohort faces more barriers in access to care and possible discrimination as sexual/gender minority patients.”

Rates of severe preeclampsia, induction of labor, cesarean delivery, preterm birth, low birth weight, and a low Apgar score were also higher among SGM patients, but these associations were no longer significant after adjustment for age, education, payment method, parity, prepregnancy weight, comorbidities, and multifetal gestation. The difference in hypertensive disorders of pregnancy, postpartum hemorrhage, and postterm birth remained statistically significant after adjustment.

Past research has shown that only about a third of cisgender female same-sex marriages used ART, so the disparities cannot be completely explained by ART use, Dr. Leonard said.

“I think the main drivers are structural disparities,” Dr. Leonard said. “Every obstetric clinic is focused in a way that’s about mother-father, and many people who don’t feel like they fit into that paradigm feel excluded and disengage with health care.”

Elliott Main, MD, a clinical professor of obstetrics and gynecology at Stanford University and coauthor of the study noted that discrimination and stigma likely play a substantial role in the disparities.

“Sexual and/or gender minority people face this discrimination at structural and interpersonal levels on a regular basis, which can lead to chronic stress and its harmful physical effects as well as lower-quality health care,” Dr. Main said in an interview.

Another coauthor, Juno Obedin-Maliver, MD, an assistant professor of obstetrics and gynecology at Stanford, emphasized how much room for improvement exists in care for SGM obstetric patients.

“We hope that this study brings needed attention to the disparities in perinatal health experienced by sexual and/or gender minority people,” Dr. Obedin-Maliver said. “There is much we can do to better understand the family building goals of sexual and/or gender minority people and help those to be achieved with healthy outcomes for parents and their children.”

One limitation of the study is that it’s possible to misclassify individuals using the birth certificate data, and not everyone may be comfortable selecting the box that accurately represents their identity, particularly if they aren’t “out” or fear discrimination or stigma, so the population may underrepresent the actual numbers of sexual and gender minority individuals giving birth. Dr. Mei added that it would be helpful to see data on neonatal ICU admissions and use of ART.

It’s difficult to say how generalizable the findings are, Dr. Mei said. “It is possible the findings would be more exaggerated in the rest of the country outside of California, if we assume there is potentially lower health access and more stigma.” The fact that California offers different gender options for the birthing and nonbirthing parent is, by itself, an indication of a potentially more accepting social environment than might be found in other states.

”The take-home message is that this patient population is higher risk, likely partially due to baseline increased risk factors, such as older maternal age and likely use of ART, and partially due to possible lack of health access and stigma,” Dr. Mei said. “Health care providers should be notably cognizant of these increased risks, particularly in the psychosocial context and make efforts to reduce those burdens as much as possible.”

The research was funded by the Stanford Maternal and Child Health Research Institute. Dr. Obedin-Maliver has consulted for Sage Therapeutics, Ibis Reproductive Health, and Hims. Dr. Mei and the other authors had no disclosures.

Members of the LGBTQ community who give birth appear to have a greater risk of hypertensive disorders of pregnancy and postpartum hemorrhage, according to new research presented at the annual meeting sponsored by the Society for Maternal-Fetal Medicine.

“Our study found that birthing patients in likely sexual and gender minority partnerships experienced disparities in clinical outcomes,” Stephanie Leonard, PhD, an epidemiology and biostatistics instructor at the Stanford (Calif.) University division of maternal-fetal medicine and obstetrics, told attendees at the meeting. The disparities are likely because of various social determinants and possibly higher use of assisted reproductive technology (ART). The findings establish “how these are significant disparities that have been largely overlooked and set the groundwork for doing further research on maybe ways that we can improve the inclusivity of obstetric care.”

Jenny Mei, MD, a maternal-fetal medicine fellow at the University of California, Los Angeles, who attended the presentation but was not involved in the research, said the findings were “overall unfortunate but not surprising given the existing studies looking at LGBTQ patients and their poorer health outcomes, largely due to lack of access to health care and discrimination in the health care setting.”

Dr. Leonard described the societal, interpersonal, and individual factors that can contribute to health disparities among gender and sexual minority patients.

“At the societal level, there are expectations of what it means to be pregnant, to give birth, and to be a parent. At the community level, there’s the clinical care environment, and at the interpersonal level, there’s an obstetrician’s relationship with the patient,” Dr. Leonard said. “At the individual level, most notably is minority stress, the biological effects of the chronic experience of discrimination.”

It has historically been difficult to collect data on this patient population, but a change in the design of the California birth certificate made it possible to gather more data than previously possible. The updated California birth certificate, issued in 2016, allows the parent not giving birth to check off whether they are the child’s mother, father, parent, or “not specified” instead of defaulting to “father.” In addition, the parent giving birth can select mother, father, parent or not specified instead of being “mother” by default.

The researchers classified sexual and gender minority (SGM) partnerships as those in which the parent giving birth was identified as the father and those where both parents were identified as mothers. Non-SGM minority partnerships were those in which the birthing parent was identified as the mother and the nonbirthing parent was identified as the father.

The population-based cohort study included data from all live birth hospitalizations from 2016-2019 in California, whose annual births represent one in eight babies born each year in the United States. The population of SGM patients different significantly from the non-SGM population in nearly every demographic and clinical factor except rates of pre-existing diabetes. For example, 42% of the SGM birthing patients were age 35 or older, compared with 23% of the non-SGM patients.

SGM patients were more likely to be born in the United States, were more likely to be White, and were less likely to be Asian or Hispanic. SGM patients had higher education levels and were more likely to have private insurance. They were also more likely to be nulliparous and have chronic hypertension. Average body mass index for SGM patients was 33 kg/m², compared with 30 for non-SGM patients. SGM patients were also much more likely to have multifetal gestation: 7.1% of SGM patients versus 1.5% of non-SGM patients.

In terms of clinical outcomes, 14% of SGM patients had hypertensive disorders of pregnancy, compared with 8% of non-SGM patients. Before adjustment for potential confounders, SGM patients were also twice as likely to have postpartum hemorrhage (8% vs. 4% in non-SGM patients) and postterm birth at 42-44 weeks (0.6% vs 0.3% in non-SGM patients).

“Having increased postterm birth is a matter of declining induction of labor, as it is recommended to have an induction by 41 weeks of gestation in general,” Dr. Mei said in an interview. “It is also possible this patient cohort faces more barriers in access to care and possible discrimination as sexual/gender minority patients.”

Rates of severe preeclampsia, induction of labor, cesarean delivery, preterm birth, low birth weight, and a low Apgar score were also higher among SGM patients, but these associations were no longer significant after adjustment for age, education, payment method, parity, prepregnancy weight, comorbidities, and multifetal gestation. The difference in hypertensive disorders of pregnancy, postpartum hemorrhage, and postterm birth remained statistically significant after adjustment.

Past research has shown that only about a third of cisgender female same-sex marriages used ART, so the disparities cannot be completely explained by ART use, Dr. Leonard said.

“I think the main drivers are structural disparities,” Dr. Leonard said. “Every obstetric clinic is focused in a way that’s about mother-father, and many people who don’t feel like they fit into that paradigm feel excluded and disengage with health care.”

Elliott Main, MD, a clinical professor of obstetrics and gynecology at Stanford University and coauthor of the study noted that discrimination and stigma likely play a substantial role in the disparities.

“Sexual and/or gender minority people face this discrimination at structural and interpersonal levels on a regular basis, which can lead to chronic stress and its harmful physical effects as well as lower-quality health care,” Dr. Main said in an interview.

Another coauthor, Juno Obedin-Maliver, MD, an assistant professor of obstetrics and gynecology at Stanford, emphasized how much room for improvement exists in care for SGM obstetric patients.

“We hope that this study brings needed attention to the disparities in perinatal health experienced by sexual and/or gender minority people,” Dr. Obedin-Maliver said. “There is much we can do to better understand the family building goals of sexual and/or gender minority people and help those to be achieved with healthy outcomes for parents and their children.”

One limitation of the study is that it’s possible to misclassify individuals using the birth certificate data, and not everyone may be comfortable selecting the box that accurately represents their identity, particularly if they aren’t “out” or fear discrimination or stigma, so the population may underrepresent the actual numbers of sexual and gender minority individuals giving birth. Dr. Mei added that it would be helpful to see data on neonatal ICU admissions and use of ART.

It’s difficult to say how generalizable the findings are, Dr. Mei said. “It is possible the findings would be more exaggerated in the rest of the country outside of California, if we assume there is potentially lower health access and more stigma.” The fact that California offers different gender options for the birthing and nonbirthing parent is, by itself, an indication of a potentially more accepting social environment than might be found in other states.

”The take-home message is that this patient population is higher risk, likely partially due to baseline increased risk factors, such as older maternal age and likely use of ART, and partially due to possible lack of health access and stigma,” Dr. Mei said. “Health care providers should be notably cognizant of these increased risks, particularly in the psychosocial context and make efforts to reduce those burdens as much as possible.”

The research was funded by the Stanford Maternal and Child Health Research Institute. Dr. Obedin-Maliver has consulted for Sage Therapeutics, Ibis Reproductive Health, and Hims. Dr. Mei and the other authors had no disclosures.

Members of the LGBTQ community who give birth appear to have a greater risk of hypertensive disorders of pregnancy and postpartum hemorrhage, according to new research presented at the annual meeting sponsored by the Society for Maternal-Fetal Medicine.

“Our study found that birthing patients in likely sexual and gender minority partnerships experienced disparities in clinical outcomes,” Stephanie Leonard, PhD, an epidemiology and biostatistics instructor at the Stanford (Calif.) University division of maternal-fetal medicine and obstetrics, told attendees at the meeting. The disparities are likely because of various social determinants and possibly higher use of assisted reproductive technology (ART). The findings establish “how these are significant disparities that have been largely overlooked and set the groundwork for doing further research on maybe ways that we can improve the inclusivity of obstetric care.”

Jenny Mei, MD, a maternal-fetal medicine fellow at the University of California, Los Angeles, who attended the presentation but was not involved in the research, said the findings were “overall unfortunate but not surprising given the existing studies looking at LGBTQ patients and their poorer health outcomes, largely due to lack of access to health care and discrimination in the health care setting.”

Dr. Leonard described the societal, interpersonal, and individual factors that can contribute to health disparities among gender and sexual minority patients.

“At the societal level, there are expectations of what it means to be pregnant, to give birth, and to be a parent. At the community level, there’s the clinical care environment, and at the interpersonal level, there’s an obstetrician’s relationship with the patient,” Dr. Leonard said. “At the individual level, most notably is minority stress, the biological effects of the chronic experience of discrimination.”

It has historically been difficult to collect data on this patient population, but a change in the design of the California birth certificate made it possible to gather more data than previously possible. The updated California birth certificate, issued in 2016, allows the parent not giving birth to check off whether they are the child’s mother, father, parent, or “not specified” instead of defaulting to “father.” In addition, the parent giving birth can select mother, father, parent or not specified instead of being “mother” by default.

The researchers classified sexual and gender minority (SGM) partnerships as those in which the parent giving birth was identified as the father and those where both parents were identified as mothers. Non-SGM minority partnerships were those in which the birthing parent was identified as the mother and the nonbirthing parent was identified as the father.

The population-based cohort study included data from all live birth hospitalizations from 2016-2019 in California, whose annual births represent one in eight babies born each year in the United States. The population of SGM patients different significantly from the non-SGM population in nearly every demographic and clinical factor except rates of pre-existing diabetes. For example, 42% of the SGM birthing patients were age 35 or older, compared with 23% of the non-SGM patients.

SGM patients were more likely to be born in the United States, were more likely to be White, and were less likely to be Asian or Hispanic. SGM patients had higher education levels and were more likely to have private insurance. They were also more likely to be nulliparous and have chronic hypertension. Average body mass index for SGM patients was 33 kg/m², compared with 30 for non-SGM patients. SGM patients were also much more likely to have multifetal gestation: 7.1% of SGM patients versus 1.5% of non-SGM patients.

In terms of clinical outcomes, 14% of SGM patients had hypertensive disorders of pregnancy, compared with 8% of non-SGM patients. Before adjustment for potential confounders, SGM patients were also twice as likely to have postpartum hemorrhage (8% vs. 4% in non-SGM patients) and postterm birth at 42-44 weeks (0.6% vs 0.3% in non-SGM patients).

“Having increased postterm birth is a matter of declining induction of labor, as it is recommended to have an induction by 41 weeks of gestation in general,” Dr. Mei said in an interview. “It is also possible this patient cohort faces more barriers in access to care and possible discrimination as sexual/gender minority patients.”

Rates of severe preeclampsia, induction of labor, cesarean delivery, preterm birth, low birth weight, and a low Apgar score were also higher among SGM patients, but these associations were no longer significant after adjustment for age, education, payment method, parity, prepregnancy weight, comorbidities, and multifetal gestation. The difference in hypertensive disorders of pregnancy, postpartum hemorrhage, and postterm birth remained statistically significant after adjustment.

Past research has shown that only about a third of cisgender female same-sex marriages used ART, so the disparities cannot be completely explained by ART use, Dr. Leonard said.

“I think the main drivers are structural disparities,” Dr. Leonard said. “Every obstetric clinic is focused in a way that’s about mother-father, and many people who don’t feel like they fit into that paradigm feel excluded and disengage with health care.”

Elliott Main, MD, a clinical professor of obstetrics and gynecology at Stanford University and coauthor of the study noted that discrimination and stigma likely play a substantial role in the disparities.

“Sexual and/or gender minority people face this discrimination at structural and interpersonal levels on a regular basis, which can lead to chronic stress and its harmful physical effects as well as lower-quality health care,” Dr. Main said in an interview.

Another coauthor, Juno Obedin-Maliver, MD, an assistant professor of obstetrics and gynecology at Stanford, emphasized how much room for improvement exists in care for SGM obstetric patients.

“We hope that this study brings needed attention to the disparities in perinatal health experienced by sexual and/or gender minority people,” Dr. Obedin-Maliver said. “There is much we can do to better understand the family building goals of sexual and/or gender minority people and help those to be achieved with healthy outcomes for parents and their children.”

One limitation of the study is that it’s possible to misclassify individuals using the birth certificate data, and not everyone may be comfortable selecting the box that accurately represents their identity, particularly if they aren’t “out” or fear discrimination or stigma, so the population may underrepresent the actual numbers of sexual and gender minority individuals giving birth. Dr. Mei added that it would be helpful to see data on neonatal ICU admissions and use of ART.

It’s difficult to say how generalizable the findings are, Dr. Mei said. “It is possible the findings would be more exaggerated in the rest of the country outside of California, if we assume there is potentially lower health access and more stigma.” The fact that California offers different gender options for the birthing and nonbirthing parent is, by itself, an indication of a potentially more accepting social environment than might be found in other states.

”The take-home message is that this patient population is higher risk, likely partially due to baseline increased risk factors, such as older maternal age and likely use of ART, and partially due to possible lack of health access and stigma,” Dr. Mei said. “Health care providers should be notably cognizant of these increased risks, particularly in the psychosocial context and make efforts to reduce those burdens as much as possible.”

The research was funded by the Stanford Maternal and Child Health Research Institute. Dr. Obedin-Maliver has consulted for Sage Therapeutics, Ibis Reproductive Health, and Hims. Dr. Mei and the other authors had no disclosures.

Exposure to opioid analgesics during the first trimester of pregnancy appears to increase the risk of congenital anomalies diagnosed in the first year of life, researchers report.

While the absolute risk of congenital anomalies was low, these findings add to an increasing body of evidence suggesting that prenatal exposure to opioids may confer harm to infants post partum.

“We undertook a population-based cohort study to estimate associations between opioid analgesic exposure during the first trimester and congenital anomalies using health administrative data capturing all narcotic prescriptions during pregnancy,” lead author Alexa C. Bowie, MPH, of Queen’s University in Kingston, Ont., and colleagues reported in CMAJ.

The researchers retrospectively reviewed administrative health data in a single-payer health care system from 2013 to 2018. They identified parent-infant pair records for all live births and stillbirths that occurred at more than 20 weeks’ gestation.

The exposure of interest was a prescription for any opioid analgesic with a fill date between the estimated date of conception and less than 14 weeks’ gestation. The referent group included any infant not exposed to an opioid analgesic during the index pregnancy period.
 

Results

The study cohort included a total of 599,579 gestational parent-infant pairs. Of these, 11,903 (2.0%) were exposed to opioid analgesics, and most were exposed during the first trimester only (75.8%).

Overall, 2.0% of these infants developed a congenital anomaly during the first year of life; the prevalence of congenital anomalies was 2.0% in unexposed infants and 2.8% in exposed infants.

Relative to unexposed infants, the researchers observed greater risks among infants who were exposed for some anomaly groups, including many specific anomalies, such as ankyloglossia (any opioid: adjusted risk ratio, 1.88; 95% confidence interval, 1.30-2.72; codeine: aRR, 2.14; 95% CI, 1.35-3.40), as well as gastrointestinal anomalies (any opioid: aRR, 1.46; 95% CI, 1.15-1.85; codeine: aRR, 1.53; 95% CI, 1.12-2.09; tramadol: aRR, 2.69; 95% CI 1.34-5.38).

After sensitivity analyses, which included exposure 4 weeks before conception or excluded individuals with exposure to opioid analgesics before pregnancy, the findings remained unchanged.

“Although the overall risk was low, we observed an increased risk of any congenital anomaly with tramadol, and a previously unreported risk with morphine,” the researchers wrote.

“Previous studies reported elevated risks of heart anomalies with first-trimester exposure to any opioid analgesic, codeine, and tramadol, but others reported no association with any opioid analgesic or codeine,” they explained.
 

Interpreting the results

Study author Susan Brogly, PhD, of Queen’s University said “Our population-based study confirms evidence of a small increased risk of birth defects from opioid analgesic exposure in the first trimester that was observed in a recent study of private insurance and Medicaid beneficiaries in the U.S. We further show that this small increased risk is not due to other risk factors for fetal harm in women who may take these medications.”

“An opioid prescription dispensed in the first trimester would imply that there was an acute injury or chronic condition also present in the first trimester, which may also be associated with congenital abnormalities,” commented Elisabeth Poorman, MD, MPH, a clinical instructor and primary care physician at the University of Washington in Seattle.

“Opioid use disorder is often diagnosed incorrectly; since the researchers used diagnostic billing codes to exclude individuals with opioid use disorder, some women may have been missed,” Dr. Poorman explained.

Ms. Bowie and colleagues acknowledged that a key limitation of the study was the identification of cases using diagnostic billing codes. As a result, exposure-dependent recording bias could be present and limit the applicability of the findings.

“The diagnosis and documentation of minor anomalies and those with subtle medical significance could be vulnerable to exposure-dependent recording bias,” Ms. Bowie wrote.

Dr. Poorman recommended that these results should be interpreted with caution given these and other limitations. “Overall, results from this study may imply that there is limited evidence to suspect opioids are related to congenital abnormalities due to a very small difference observed in relatively unequal groups,” she concluded.

This study received funding from the Eunice Kennedy Shriver National Institutes of Child Health and Human Development and was also supported by the Institute for Clinical Evaluative Sciences, which is funded by an annual grant from the Ontario Ministry of Health. One author reported receiving honoraria from the National Institutes of Health and a grant from the Canadian Institute of Health Research, outside the submitted work. No other competing interests were declared.

Exposure to opioid analgesics during the first trimester of pregnancy appears to increase the risk of congenital anomalies diagnosed in the first year of life, researchers report.

While the absolute risk of congenital anomalies was low, these findings add to an increasing body of evidence suggesting that prenatal exposure to opioids may confer harm to infants post partum.

“We undertook a population-based cohort study to estimate associations between opioid analgesic exposure during the first trimester and congenital anomalies using health administrative data capturing all narcotic prescriptions during pregnancy,” lead author Alexa C. Bowie, MPH, of Queen’s University in Kingston, Ont., and colleagues reported in CMAJ.

The researchers retrospectively reviewed administrative health data in a single-payer health care system from 2013 to 2018. They identified parent-infant pair records for all live births and stillbirths that occurred at more than 20 weeks’ gestation.

The exposure of interest was a prescription for any opioid analgesic with a fill date between the estimated date of conception and less than 14 weeks’ gestation. The referent group included any infant not exposed to an opioid analgesic during the index pregnancy period.
 

Results

The study cohort included a total of 599,579 gestational parent-infant pairs. Of these, 11,903 (2.0%) were exposed to opioid analgesics, and most were exposed during the first trimester only (75.8%).

Overall, 2.0% of these infants developed a congenital anomaly during the first year of life; the prevalence of congenital anomalies was 2.0% in unexposed infants and 2.8% in exposed infants.

Relative to unexposed infants, the researchers observed greater risks among infants who were exposed for some anomaly groups, including many specific anomalies, such as ankyloglossia (any opioid: adjusted risk ratio, 1.88; 95% confidence interval, 1.30-2.72; codeine: aRR, 2.14; 95% CI, 1.35-3.40), as well as gastrointestinal anomalies (any opioid: aRR, 1.46; 95% CI, 1.15-1.85; codeine: aRR, 1.53; 95% CI, 1.12-2.09; tramadol: aRR, 2.69; 95% CI 1.34-5.38).

After sensitivity analyses, which included exposure 4 weeks before conception or excluded individuals with exposure to opioid analgesics before pregnancy, the findings remained unchanged.

“Although the overall risk was low, we observed an increased risk of any congenital anomaly with tramadol, and a previously unreported risk with morphine,” the researchers wrote.

“Previous studies reported elevated risks of heart anomalies with first-trimester exposure to any opioid analgesic, codeine, and tramadol, but others reported no association with any opioid analgesic or codeine,” they explained.
 

Interpreting the results

Study author Susan Brogly, PhD, of Queen’s University said “Our population-based study confirms evidence of a small increased risk of birth defects from opioid analgesic exposure in the first trimester that was observed in a recent study of private insurance and Medicaid beneficiaries in the U.S. We further show that this small increased risk is not due to other risk factors for fetal harm in women who may take these medications.”

“An opioid prescription dispensed in the first trimester would imply that there was an acute injury or chronic condition also present in the first trimester, which may also be associated with congenital abnormalities,” commented Elisabeth Poorman, MD, MPH, a clinical instructor and primary care physician at the University of Washington in Seattle.

“Opioid use disorder is often diagnosed incorrectly; since the researchers used diagnostic billing codes to exclude individuals with opioid use disorder, some women may have been missed,” Dr. Poorman explained.

Ms. Bowie and colleagues acknowledged that a key limitation of the study was the identification of cases using diagnostic billing codes. As a result, exposure-dependent recording bias could be present and limit the applicability of the findings.

“The diagnosis and documentation of minor anomalies and those with subtle medical significance could be vulnerable to exposure-dependent recording bias,” Ms. Bowie wrote.

Dr. Poorman recommended that these results should be interpreted with caution given these and other limitations. “Overall, results from this study may imply that there is limited evidence to suspect opioids are related to congenital abnormalities due to a very small difference observed in relatively unequal groups,” she concluded.

This study received funding from the Eunice Kennedy Shriver National Institutes of Child Health and Human Development and was also supported by the Institute for Clinical Evaluative Sciences, which is funded by an annual grant from the Ontario Ministry of Health. One author reported receiving honoraria from the National Institutes of Health and a grant from the Canadian Institute of Health Research, outside the submitted work. No other competing interests were declared.

Exposure to opioid analgesics during the first trimester of pregnancy appears to increase the risk of congenital anomalies diagnosed in the first year of life, researchers report.

While the absolute risk of congenital anomalies was low, these findings add to an increasing body of evidence suggesting that prenatal exposure to opioids may confer harm to infants post partum.

“We undertook a population-based cohort study to estimate associations between opioid analgesic exposure during the first trimester and congenital anomalies using health administrative data capturing all narcotic prescriptions during pregnancy,” lead author Alexa C. Bowie, MPH, of Queen’s University in Kingston, Ont., and colleagues reported in CMAJ.

The researchers retrospectively reviewed administrative health data in a single-payer health care system from 2013 to 2018. They identified parent-infant pair records for all live births and stillbirths that occurred at more than 20 weeks’ gestation.

The exposure of interest was a prescription for any opioid analgesic with a fill date between the estimated date of conception and less than 14 weeks’ gestation. The referent group included any infant not exposed to an opioid analgesic during the index pregnancy period.
 

Results

The study cohort included a total of 599,579 gestational parent-infant pairs. Of these, 11,903 (2.0%) were exposed to opioid analgesics, and most were exposed during the first trimester only (75.8%).

Overall, 2.0% of these infants developed a congenital anomaly during the first year of life; the prevalence of congenital anomalies was 2.0% in unexposed infants and 2.8% in exposed infants.

Relative to unexposed infants, the researchers observed greater risks among infants who were exposed for some anomaly groups, including many specific anomalies, such as ankyloglossia (any opioid: adjusted risk ratio, 1.88; 95% confidence interval, 1.30-2.72; codeine: aRR, 2.14; 95% CI, 1.35-3.40), as well as gastrointestinal anomalies (any opioid: aRR, 1.46; 95% CI, 1.15-1.85; codeine: aRR, 1.53; 95% CI, 1.12-2.09; tramadol: aRR, 2.69; 95% CI 1.34-5.38).

After sensitivity analyses, which included exposure 4 weeks before conception or excluded individuals with exposure to opioid analgesics before pregnancy, the findings remained unchanged.

“Although the overall risk was low, we observed an increased risk of any congenital anomaly with tramadol, and a previously unreported risk with morphine,” the researchers wrote.

“Previous studies reported elevated risks of heart anomalies with first-trimester exposure to any opioid analgesic, codeine, and tramadol, but others reported no association with any opioid analgesic or codeine,” they explained.
 

Interpreting the results

Study author Susan Brogly, PhD, of Queen’s University said “Our population-based study confirms evidence of a small increased risk of birth defects from opioid analgesic exposure in the first trimester that was observed in a recent study of private insurance and Medicaid beneficiaries in the U.S. We further show that this small increased risk is not due to other risk factors for fetal harm in women who may take these medications.”

“An opioid prescription dispensed in the first trimester would imply that there was an acute injury or chronic condition also present in the first trimester, which may also be associated with congenital abnormalities,” commented Elisabeth Poorman, MD, MPH, a clinical instructor and primary care physician at the University of Washington in Seattle.

“Opioid use disorder is often diagnosed incorrectly; since the researchers used diagnostic billing codes to exclude individuals with opioid use disorder, some women may have been missed,” Dr. Poorman explained.

Ms. Bowie and colleagues acknowledged that a key limitation of the study was the identification of cases using diagnostic billing codes. As a result, exposure-dependent recording bias could be present and limit the applicability of the findings.

“The diagnosis and documentation of minor anomalies and those with subtle medical significance could be vulnerable to exposure-dependent recording bias,” Ms. Bowie wrote.

Dr. Poorman recommended that these results should be interpreted with caution given these and other limitations. “Overall, results from this study may imply that there is limited evidence to suspect opioids are related to congenital abnormalities due to a very small difference observed in relatively unequal groups,” she concluded.

This study received funding from the Eunice Kennedy Shriver National Institutes of Child Health and Human Development and was also supported by the Institute for Clinical Evaluative Sciences, which is funded by an annual grant from the Ontario Ministry of Health. One author reported receiving honoraria from the National Institutes of Health and a grant from the Canadian Institute of Health Research, outside the submitted work. No other competing interests were declared.

Long COVID continues to be a moving target – continuously evolving and still surprising doctors and patients who have sometimes incapacitating long-term symptoms.

Little about the disorder seems predictable at this point. People can have long COVID after asymptomatic, mild, or severe COVID-19, for example. And when a person gets long COVID – also known as long-haul COVID – symptoms can vary widely.

To address all the uncertainty, the New York State Department of Health gathered experts in primary care, pediatrics, physical medicine, rehabilitation, and pulmonology to answer some pressing questions.

New York in 2020 was the first epicenter of the pandemic in the United States, making it also the center of the long COVID epidemic, says Emily Lutterloh, MD, director of the Division of Epidemiology at the New York State Department of Health.
 

What do you do when you’re seeing a patient with long COVID for the first time?

The first exam varies because there are so many different ways long COVID presents itself, says Benjamin Abramoff, MD, a physical medicine and rehabilitation specialist at Penn Medicine in Philadelphia.

I’ve now been seriously ill with #LongCovid for 11 months. I was never hospitalized. I didn’t even have a “mild” covid case. Instead, I developed Long Covid from an asymptomatic infection.

I’m far from unique. Up to 1/5 of asymptomatic patients go on to have long-term symptoms.

— Ravi Veriah Jacques (@RaviHVJ) February 3, 2022

Assessing their previous and current care also helps to direct their ongoing management, says Zijian Chen, MD, medical director of the Center for Post-COVID Care at Mount Sinai Health System in New York.
 

Can vaccination help people with long COVID?

Anything that we can do to help prevent people from being critically ill or being hospitalized with COVID-19 is helpful to prevent long COVID, says Dr. Abramoff, who is also director of the long COVID clinic at the University of Pennsylvania, Philadelphia.

“So that’s something I always discuss with patients. In some research, sometimes patients do feel better after the vaccine,” he says.
 

What kind of therapies do you find helpful for your patients?

Rehabilitation is a key part of recovery from long COVID, Dr. Abramoff says. “It is very important to make this very patient-specific.”

“We have patients that are working. They’re already going to the gym in some cases but don’t feel like they have the same endurance,” he says. “And then we have patients who are so crippled by their fatigue that they can’t get out of bed.”
 

1/ What is #LongCOVID?!

A disabling malady from ongoing inflammation, autoimmunity, & potential viral reservoirs (GI, brain?)

NEW DATA: The Lungs “light up” on special MRI Scans 3 to 9 months later in patients never hospitalized for COVID.https://t.co/I2kyZ4cK5F pic.twitter.com/dL1P67L2DK

— WesElyMD (@WesElyMD) February 2, 2022

An exercise program can help people who have long COVID.

“There’s a big role for therapy services in the recovery of these patients,” says John Baratta, MD, of the department of physical medicine and rehabilitation at the University of North Carolina at Chapel Hill.

But the limited number of long COVID clinics can mean some people are unable to get to therapists trained on the needs of patients with lingering COVID symptoms. Educating community physical and occupational therapists is one solution.
 

How long does it take for people with long COVID to recover and get back to 100% if they can?

Specific numbers aren’t really available, Dr. Baratta says.

“But I can tell you the general trend that I see is that a lot of patients have a gradual improvement of symptoms. The slow but steady improvement with time may be the body’s natural healing process, a result of medical interventions, or both.”

It can help to reassure people with long COVID that they will not be discharged from care until they feel they’ve maximized their health, says Sharagim Kemp, DO, medical director of the COVID Recovery Program for Nuvance Health, a health system in New York and Connecticut.

It’s essential to set realistic recovery expectations and tell patients that not everyone will return to 100% of their pre-COVID functioning, she says.

“Once we are able to help them reset their expectations, there’s almost an accelerated recovery because they are not putting that pressure on themselves anymore,” Dr. Kemp says.
 

What are the most common symptoms you’re seeing in long COVID?

It’s helpful to think of long COVID as a very broad umbrella term, Dr. Abramoff says.

Echoing what many others have observed, fatigue, cognitive dysfunction or “brain fog,“ and shortness of breath or troubled breathing appear to be the most common symptoms, he says.

Some reported vague symptoms, Dr. Kemp says.

People may go to the doctor “not even realizing that they had COVID. That’s one of the important points here – to have a high index of suspicion for patients who come in with multiple symptoms,” she says.

For this reason, patients can report symptoms that don’t necessarily fit into any specialty, says Sarah J. Ryan, MD, an internal medicine doctor at Columbia University Irving Medical Center in New York. People say they are “just not themselves” or they are tired after their COVID-19 recovery.
 

Is there a connection between severe COVID cases and severe long COVID?

“It’s not like that at all. I would say that more than 80% of the patients that we see had mild to moderate illness and they were not hospitalized,” Dr. Baratta says.

Long COVID is a bit different in children and teenagers, says Ixsy Ramirez, MD, a pediatric pulmonologist at University of Michigan Health, Ann Arbor. Most patients in the long COVID clinic at the University of Michigan were previously healthy, and not children with asthma or other lung conditions as one might expect. In fact, many are student athletes, or were before they had long COVID.

In this population, shortness of breath is most common, followed by chest pain and fatigue. Unfortunately, the symptoms are so serious for many kids that their performance is limited, even if they can return to competitive play.
 

Are there defined criteria you use to diagnose long COVID? How do you give someone a diagnosis?

That’s an ever-evolving question, Dr. Kemp says. The generally accepted definition centers on persistent or new symptoms 4 weeks or more after the original COVID-19 illness, but there are exceptions.

Researchers are working on lab tests to help confirm the diagnosis. But without a definitive blood biomarker, getting to the diagnosis requires “some thorough detective work,” Dr. Ryan says.
 

Do you bring in mental health providers to help with treatment?

“We focus on mental health quite a bit actually,” says, Dr. Chen, cofounder of his institution’s COVID recovery clinic. Mount Sinai offers one-on-one and group mental health services, for example.

“Personally, I’ve seen patients that I did not expect to have such severe mental health changes” with long COVID.
 

One of the most powerful accounts and testimonies I have seen on what most #LongCovid patients experience when interacting with their doctors.

“I did not fit in a box, so they chose not to see me, even worse they made me feel like it was my fault for not fitting in their box” pic.twitter.com/7GQLBucuO5

— charlos (@loscharlos) February 3, 2022

Examples include severe depression, cases of acute psychosis, hallucinations, and other problems “that are really unexpected after a viral illness.”

Stony Brook University Hospital in New York has a long COVID clinic staffed by multiple primary care doctors who do exams and refer patients to services. A bonus of offering psychological services to all post-COVID patients is doctors get a more complete picture of each person and a better understanding of what they are going through, says Abigail Chua, MD, a pulmonologist at Stony Brook.

Some empathy is essential, Dr. Baratta says. “It’s important to recognize that a lot of these patients present with a sense of grief or loss for their prior life.”
 

What does the future hold?

A simple test to diagnose long COVID, combined with an effective treatment that helps people feel better within a week, would be ideal, Dr. Abramoff says.

“That would be lovely. But you know, we’re just not at that point.”

And it would be helpful to start identifying subtypes of long COVID so diagnosis and treatment can be more targeted, Dr. Abramoff says. Otherwise, “It’s going to be a very challenging approach to try to treat all of our patients with long COVID symptoms the same way.”

Good clinical trials likewise are needed to address all the subtleties of long COVID.

A number of long COVID centers are collaborating on research to find out more, Dr. Chen says. Actions include setting up a bank of tissue samples from people with long COVID so researchers can continue to figure out the condition.

One goal, Dr. Chen says, would be the ability to treat long COVID rather than just its symptoms.

Long COVID emphasizes the need to prevent people from getting COVID in the first place, Dr. Ramirez says. This will continue to be important, particularly when some people dismiss the seriousness of COVID, comparing it to a cold if they get it. That attitude discounts the large number of people who unfortunately go on to develop long-term, often debilitating, symptoms.

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

Long COVID continues to be a moving target – continuously evolving and still surprising doctors and patients who have sometimes incapacitating long-term symptoms.

Little about the disorder seems predictable at this point. People can have long COVID after asymptomatic, mild, or severe COVID-19, for example. And when a person gets long COVID – also known as long-haul COVID – symptoms can vary widely.

To address all the uncertainty, the New York State Department of Health gathered experts in primary care, pediatrics, physical medicine, rehabilitation, and pulmonology to answer some pressing questions.

New York in 2020 was the first epicenter of the pandemic in the United States, making it also the center of the long COVID epidemic, says Emily Lutterloh, MD, director of the Division of Epidemiology at the New York State Department of Health.
 

What do you do when you’re seeing a patient with long COVID for the first time?

The first exam varies because there are so many different ways long COVID presents itself, says Benjamin Abramoff, MD, a physical medicine and rehabilitation specialist at Penn Medicine in Philadelphia.

I’ve now been seriously ill with #LongCovid for 11 months. I was never hospitalized. I didn’t even have a “mild” covid case. Instead, I developed Long Covid from an asymptomatic infection.

I’m far from unique. Up to 1/5 of asymptomatic patients go on to have long-term symptoms.

— Ravi Veriah Jacques (@RaviHVJ) February 3, 2022

Assessing their previous and current care also helps to direct their ongoing management, says Zijian Chen, MD, medical director of the Center for Post-COVID Care at Mount Sinai Health System in New York.
 

Can vaccination help people with long COVID?

Anything that we can do to help prevent people from being critically ill or being hospitalized with COVID-19 is helpful to prevent long COVID, says Dr. Abramoff, who is also director of the long COVID clinic at the University of Pennsylvania, Philadelphia.

“So that’s something I always discuss with patients. In some research, sometimes patients do feel better after the vaccine,” he says.
 

What kind of therapies do you find helpful for your patients?

Rehabilitation is a key part of recovery from long COVID, Dr. Abramoff says. “It is very important to make this very patient-specific.”

“We have patients that are working. They’re already going to the gym in some cases but don’t feel like they have the same endurance,” he says. “And then we have patients who are so crippled by their fatigue that they can’t get out of bed.”
 

1/ What is #LongCOVID?!

A disabling malady from ongoing inflammation, autoimmunity, & potential viral reservoirs (GI, brain?)

NEW DATA: The Lungs “light up” on special MRI Scans 3 to 9 months later in patients never hospitalized for COVID.https://t.co/I2kyZ4cK5F pic.twitter.com/dL1P67L2DK

— WesElyMD (@WesElyMD) February 2, 2022

An exercise program can help people who have long COVID.

“There’s a big role for therapy services in the recovery of these patients,” says John Baratta, MD, of the department of physical medicine and rehabilitation at the University of North Carolina at Chapel Hill.

But the limited number of long COVID clinics can mean some people are unable to get to therapists trained on the needs of patients with lingering COVID symptoms. Educating community physical and occupational therapists is one solution.
 

How long does it take for people with long COVID to recover and get back to 100% if they can?

Specific numbers aren’t really available, Dr. Baratta says.

“But I can tell you the general trend that I see is that a lot of patients have a gradual improvement of symptoms. The slow but steady improvement with time may be the body’s natural healing process, a result of medical interventions, or both.”

It can help to reassure people with long COVID that they will not be discharged from care until they feel they’ve maximized their health, says Sharagim Kemp, DO, medical director of the COVID Recovery Program for Nuvance Health, a health system in New York and Connecticut.

It’s essential to set realistic recovery expectations and tell patients that not everyone will return to 100% of their pre-COVID functioning, she says.

“Once we are able to help them reset their expectations, there’s almost an accelerated recovery because they are not putting that pressure on themselves anymore,” Dr. Kemp says.
 

What are the most common symptoms you’re seeing in long COVID?

It’s helpful to think of long COVID as a very broad umbrella term, Dr. Abramoff says.

Echoing what many others have observed, fatigue, cognitive dysfunction or “brain fog,“ and shortness of breath or troubled breathing appear to be the most common symptoms, he says.

Some reported vague symptoms, Dr. Kemp says.

People may go to the doctor “not even realizing that they had COVID. That’s one of the important points here – to have a high index of suspicion for patients who come in with multiple symptoms,” she says.

For this reason, patients can report symptoms that don’t necessarily fit into any specialty, says Sarah J. Ryan, MD, an internal medicine doctor at Columbia University Irving Medical Center in New York. People say they are “just not themselves” or they are tired after their COVID-19 recovery.
 

Is there a connection between severe COVID cases and severe long COVID?

“It’s not like that at all. I would say that more than 80% of the patients that we see had mild to moderate illness and they were not hospitalized,” Dr. Baratta says.

Long COVID is a bit different in children and teenagers, says Ixsy Ramirez, MD, a pediatric pulmonologist at University of Michigan Health, Ann Arbor. Most patients in the long COVID clinic at the University of Michigan were previously healthy, and not children with asthma or other lung conditions as one might expect. In fact, many are student athletes, or were before they had long COVID.

In this population, shortness of breath is most common, followed by chest pain and fatigue. Unfortunately, the symptoms are so serious for many kids that their performance is limited, even if they can return to competitive play.
 

Are there defined criteria you use to diagnose long COVID? How do you give someone a diagnosis?

That’s an ever-evolving question, Dr. Kemp says. The generally accepted definition centers on persistent or new symptoms 4 weeks or more after the original COVID-19 illness, but there are exceptions.

Researchers are working on lab tests to help confirm the diagnosis. But without a definitive blood biomarker, getting to the diagnosis requires “some thorough detective work,” Dr. Ryan says.
 

Do you bring in mental health providers to help with treatment?

“We focus on mental health quite a bit actually,” says, Dr. Chen, cofounder of his institution’s COVID recovery clinic. Mount Sinai offers one-on-one and group mental health services, for example.

“Personally, I’ve seen patients that I did not expect to have such severe mental health changes” with long COVID.
 

One of the most powerful accounts and testimonies I have seen on what most #LongCovid patients experience when interacting with their doctors.

“I did not fit in a box, so they chose not to see me, even worse they made me feel like it was my fault for not fitting in their box” pic.twitter.com/7GQLBucuO5

— charlos (@loscharlos) February 3, 2022

Examples include severe depression, cases of acute psychosis, hallucinations, and other problems “that are really unexpected after a viral illness.”

Stony Brook University Hospital in New York has a long COVID clinic staffed by multiple primary care doctors who do exams and refer patients to services. A bonus of offering psychological services to all post-COVID patients is doctors get a more complete picture of each person and a better understanding of what they are going through, says Abigail Chua, MD, a pulmonologist at Stony Brook.

Some empathy is essential, Dr. Baratta says. “It’s important to recognize that a lot of these patients present with a sense of grief or loss for their prior life.”
 

What does the future hold?

A simple test to diagnose long COVID, combined with an effective treatment that helps people feel better within a week, would be ideal, Dr. Abramoff says.

“That would be lovely. But you know, we’re just not at that point.”

And it would be helpful to start identifying subtypes of long COVID so diagnosis and treatment can be more targeted, Dr. Abramoff says. Otherwise, “It’s going to be a very challenging approach to try to treat all of our patients with long COVID symptoms the same way.”

Good clinical trials likewise are needed to address all the subtleties of long COVID.

A number of long COVID centers are collaborating on research to find out more, Dr. Chen says. Actions include setting up a bank of tissue samples from people with long COVID so researchers can continue to figure out the condition.

One goal, Dr. Chen says, would be the ability to treat long COVID rather than just its symptoms.

Long COVID emphasizes the need to prevent people from getting COVID in the first place, Dr. Ramirez says. This will continue to be important, particularly when some people dismiss the seriousness of COVID, comparing it to a cold if they get it. That attitude discounts the large number of people who unfortunately go on to develop long-term, often debilitating, symptoms.

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

Long COVID continues to be a moving target – continuously evolving and still surprising doctors and patients who have sometimes incapacitating long-term symptoms.

Little about the disorder seems predictable at this point. People can have long COVID after asymptomatic, mild, or severe COVID-19, for example. And when a person gets long COVID – also known as long-haul COVID – symptoms can vary widely.

To address all the uncertainty, the New York State Department of Health gathered experts in primary care, pediatrics, physical medicine, rehabilitation, and pulmonology to answer some pressing questions.

New York in 2020 was the first epicenter of the pandemic in the United States, making it also the center of the long COVID epidemic, says Emily Lutterloh, MD, director of the Division of Epidemiology at the New York State Department of Health.
 

What do you do when you’re seeing a patient with long COVID for the first time?

The first exam varies because there are so many different ways long COVID presents itself, says Benjamin Abramoff, MD, a physical medicine and rehabilitation specialist at Penn Medicine in Philadelphia.

I’ve now been seriously ill with #LongCovid for 11 months. I was never hospitalized. I didn’t even have a “mild” covid case. Instead, I developed Long Covid from an asymptomatic infection.

I’m far from unique. Up to 1/5 of asymptomatic patients go on to have long-term symptoms.

— Ravi Veriah Jacques (@RaviHVJ) February 3, 2022

Assessing their previous and current care also helps to direct their ongoing management, says Zijian Chen, MD, medical director of the Center for Post-COVID Care at Mount Sinai Health System in New York.
 

Can vaccination help people with long COVID?

Anything that we can do to help prevent people from being critically ill or being hospitalized with COVID-19 is helpful to prevent long COVID, says Dr. Abramoff, who is also director of the long COVID clinic at the University of Pennsylvania, Philadelphia.

“So that’s something I always discuss with patients. In some research, sometimes patients do feel better after the vaccine,” he says.
 

What kind of therapies do you find helpful for your patients?

Rehabilitation is a key part of recovery from long COVID, Dr. Abramoff says. “It is very important to make this very patient-specific.”

“We have patients that are working. They’re already going to the gym in some cases but don’t feel like they have the same endurance,” he says. “And then we have patients who are so crippled by their fatigue that they can’t get out of bed.”
 

1/ What is #LongCOVID?!

A disabling malady from ongoing inflammation, autoimmunity, & potential viral reservoirs (GI, brain?)

NEW DATA: The Lungs “light up” on special MRI Scans 3 to 9 months later in patients never hospitalized for COVID.https://t.co/I2kyZ4cK5F pic.twitter.com/dL1P67L2DK

— WesElyMD (@WesElyMD) February 2, 2022

An exercise program can help people who have long COVID.

“There’s a big role for therapy services in the recovery of these patients,” says John Baratta, MD, of the department of physical medicine and rehabilitation at the University of North Carolina at Chapel Hill.

But the limited number of long COVID clinics can mean some people are unable to get to therapists trained on the needs of patients with lingering COVID symptoms. Educating community physical and occupational therapists is one solution.
 

How long does it take for people with long COVID to recover and get back to 100% if they can?

Specific numbers aren’t really available, Dr. Baratta says.

“But I can tell you the general trend that I see is that a lot of patients have a gradual improvement of symptoms. The slow but steady improvement with time may be the body’s natural healing process, a result of medical interventions, or both.”

It can help to reassure people with long COVID that they will not be discharged from care until they feel they’ve maximized their health, says Sharagim Kemp, DO, medical director of the COVID Recovery Program for Nuvance Health, a health system in New York and Connecticut.

It’s essential to set realistic recovery expectations and tell patients that not everyone will return to 100% of their pre-COVID functioning, she says.

“Once we are able to help them reset their expectations, there’s almost an accelerated recovery because they are not putting that pressure on themselves anymore,” Dr. Kemp says.
 

What are the most common symptoms you’re seeing in long COVID?

It’s helpful to think of long COVID as a very broad umbrella term, Dr. Abramoff says.

Echoing what many others have observed, fatigue, cognitive dysfunction or “brain fog,“ and shortness of breath or troubled breathing appear to be the most common symptoms, he says.

Some reported vague symptoms, Dr. Kemp says.

People may go to the doctor “not even realizing that they had COVID. That’s one of the important points here – to have a high index of suspicion for patients who come in with multiple symptoms,” she says.

For this reason, patients can report symptoms that don’t necessarily fit into any specialty, says Sarah J. Ryan, MD, an internal medicine doctor at Columbia University Irving Medical Center in New York. People say they are “just not themselves” or they are tired after their COVID-19 recovery.
 

Is there a connection between severe COVID cases and severe long COVID?

“It’s not like that at all. I would say that more than 80% of the patients that we see had mild to moderate illness and they were not hospitalized,” Dr. Baratta says.

Long COVID is a bit different in children and teenagers, says Ixsy Ramirez, MD, a pediatric pulmonologist at University of Michigan Health, Ann Arbor. Most patients in the long COVID clinic at the University of Michigan were previously healthy, and not children with asthma or other lung conditions as one might expect. In fact, many are student athletes, or were before they had long COVID.

In this population, shortness of breath is most common, followed by chest pain and fatigue. Unfortunately, the symptoms are so serious for many kids that their performance is limited, even if they can return to competitive play.
 

Are there defined criteria you use to diagnose long COVID? How do you give someone a diagnosis?

That’s an ever-evolving question, Dr. Kemp says. The generally accepted definition centers on persistent or new symptoms 4 weeks or more after the original COVID-19 illness, but there are exceptions.

Researchers are working on lab tests to help confirm the diagnosis. But without a definitive blood biomarker, getting to the diagnosis requires “some thorough detective work,” Dr. Ryan says.
 

Do you bring in mental health providers to help with treatment?

“We focus on mental health quite a bit actually,” says, Dr. Chen, cofounder of his institution’s COVID recovery clinic. Mount Sinai offers one-on-one and group mental health services, for example.

“Personally, I’ve seen patients that I did not expect to have such severe mental health changes” with long COVID.
 

One of the most powerful accounts and testimonies I have seen on what most #LongCovid patients experience when interacting with their doctors.

“I did not fit in a box, so they chose not to see me, even worse they made me feel like it was my fault for not fitting in their box” pic.twitter.com/7GQLBucuO5

— charlos (@loscharlos) February 3, 2022

Examples include severe depression, cases of acute psychosis, hallucinations, and other problems “that are really unexpected after a viral illness.”

Stony Brook University Hospital in New York has a long COVID clinic staffed by multiple primary care doctors who do exams and refer patients to services. A bonus of offering psychological services to all post-COVID patients is doctors get a more complete picture of each person and a better understanding of what they are going through, says Abigail Chua, MD, a pulmonologist at Stony Brook.

Some empathy is essential, Dr. Baratta says. “It’s important to recognize that a lot of these patients present with a sense of grief or loss for their prior life.”
 

What does the future hold?

A simple test to diagnose long COVID, combined with an effective treatment that helps people feel better within a week, would be ideal, Dr. Abramoff says.

“That would be lovely. But you know, we’re just not at that point.”

And it would be helpful to start identifying subtypes of long COVID so diagnosis and treatment can be more targeted, Dr. Abramoff says. Otherwise, “It’s going to be a very challenging approach to try to treat all of our patients with long COVID symptoms the same way.”

Good clinical trials likewise are needed to address all the subtleties of long COVID.

A number of long COVID centers are collaborating on research to find out more, Dr. Chen says. Actions include setting up a bank of tissue samples from people with long COVID so researchers can continue to figure out the condition.

One goal, Dr. Chen says, would be the ability to treat long COVID rather than just its symptoms.

Long COVID emphasizes the need to prevent people from getting COVID in the first place, Dr. Ramirez says. This will continue to be important, particularly when some people dismiss the seriousness of COVID, comparing it to a cold if they get it. That attitude discounts the large number of people who unfortunately go on to develop long-term, often debilitating, symptoms.

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

A breakthrough neuromodulation system rapidly restores motor function in patients with a severe spinal cord injury (SCI), new research shows.

The study demonstrated that an epidural electrical stimulation (EES) system developed specifically for spinal cord injuries enabled three men with complete paralysis to stand, walk, cycle, swim, and move their torso within 1 day.

“Thanks to this technology, we have been able to target individuals with the most serious spinal cord injury, meaning those with clinically complete spinal cord injury, with no sensation and no movement in the legs,” Grégoire Courtine, PhD, professor of neuroscience and neurotechnology at the Swiss Federal Institute of Technology, University Hospital Lausanne (Switzerland), and the University of Lausanne, told reporters attending a press briefing.

The study was published online Feb. 7, 2022, in Nature Medicine.
 

More rapid, precise, effective

SCIs involve severed connections between the brain and extremities. To compensate for these lost connections, researchers have investigated stem cell therapy, brain-machine interfaces, and powered exoskeletons.

However, these approaches aren’t yet ready for prime time.

In the meantime, researchers discovered even patients with a “complete” injury may have low-functioning connections and started investigating epidural stimulators designed to treat chronic pain. Recent studies – including three published in 2018 – showed promise for these pain-related stimulators in patients with incomplete SCI.

But using such “repurposed” technology meant the electrode array was relatively narrow and short, “so we could not target all the regions of the spinal cord involving control of leg and trunk movements,” said Dr. Courtine. With the newer technology “we are much more precise, effective, and more rapid in delivering therapy.”

To develop this new approach, the researchers designed a paddle lead with an arrangement of electrodes that targets sacral, lumbar, and low-thoracic dorsal roots involved in leg and trunk movements. They also established a personalized computational framework that allows for optimal surgical placement of this paddle lead.

In addition, they developed software that renders the configuration of individualized activity–dependent stimulation programs rapid, simple, and predictable.

They tested these neurotechnologies in three men with complete sensorimotor paralysis as part of an ongoing clinical trial. The participants, aged 29, 32, and 41 years, suffered an SCI from a motor bike accident 3, 9, and 1 year before enrollment.

All three patients exhibited complete sensorimotor paralysis. They were unable to take any step, and muscles remained quiescent during these attempts.

A neurosurgeon implanted electrodes along the spinal cord of study subjects. Wires from these electrodes were connected to a neurostimulator implanted under the skin in the abdomen.

The men can select different activity-based programs from a tablet that sends signals to the implanted device.
 

Personalized approach

Within a single day of the surgery, the participants were able to stand, walk, cycle, swim, and control trunk movements.

“It was not perfect at the very beginning, but they could train very early on to have a more fluid gait,” said study investigator neurosurgeon Joceylyne Bloch, MD, associate professor, University of Lausanne and University Hospital Lausanne.

At this stage, not all paralyzed patients are eligible for the procedure. Dr. Bloch explained that at least 6 cm of healthy spinal cord under the lesion is needed to implant the electrodes.

“There’s a huge variability of spinal cord anatomy between individuals. That’s why it’s important to study each person individually and to have individual models in order to be precise.”

Researchers envision having “a library of electrode arrays,” added Dr. Courtine. With preoperative imaging of the individual’s spinal cord, “the neurosurgeon can select the more appropriate electrode array for that specific patient.”

Dr. Courtine noted recovery of sensation with the system differs from one individual to another. One study participant, Michel Roccati, now 30, told the briefing he feels a contraction in his muscle during the stimulation.

Currently, only individuals whose injury is more than a year old are included in the study to ensure patients have “a stable lesion” and reached “a plateau of recovery,” said Dr. Bloch. However, animal models show intervening earlier might boost the benefits.

A patient’s age can influence the outcome, as younger patients are likely in better condition and more motivated than older patients, said Dr. Bloch. However, she noted patients closing in on 50 years have responded well to the therapy.

Such stimulation systems may prove useful in treating conditions typically associated with SCI, such as hypertension and bladder control, and perhaps also in patients with Parkinson’s disease, said Dr. Courtine.

The researchers plan to conduct another study that will include a next-generation pulse generator with features that make the stimulation even more effective and user friendly. A voice recognition system could eventually be connected to the system.

“The next step is a minicomputer that you implant in the body that communicates in real time with an external iPhone,” said Dr. Courtine.

ONWARD Medical, which developed the technology, has received a breakthrough device designation from the Food and Drug Administration. The company is in discussions with the FDA to carry out a clinical trial of the device in the United States.
 

A ‘huge step forward’

Peter J. Grahn, PhD, assistant professor, department of physical medicine and rehabilitation and department of neurologic surgery, Mayo Clinic, Rochester, Minn., an author of one of the 2018 studies, said this technology “is a huge step forward” and “really pushes the field.”

Compared with the device used in his study that’s designed to treat neuropathic pain, this new system “is much more capable of dynamic stimulation,” said Dr. Grahn. “You can tailor the stimulation based on which area of the spinal cord you want to target during a specific function.”

There has been “a lot of hope and hype” recently around stem cells and biological molecules that were supposed to be “magic pills” to cure spinal cord dysfunction, said Dr. Grahn. “I don’t think this is one of those.”

However, he questioned the researchers’ use of the word “walking.”

“They say independent stepping or walking is restored on day 1, but the graphs show day 1 function is having over 60% of their body weight supported when they’re taking these steps,” he said.

In addition, the “big question” is how this technology can “be distilled down” into an approach “applicable across rehabilitation centers,” said Dr. Grahn.

The study was supported by numerous organizations, including ONWARD Medical. Dr. Courtine and Dr. Bloch hold various patents in relation with the present work. Dr. Courtine is a consultant with ONWARD Medical, and he and Dr. Bloch are shareholders of ONWARD Medical, a company with direct relationships with the presented work. Dr. Grahn reported no relevant financial relationships.

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

A breakthrough neuromodulation system rapidly restores motor function in patients with a severe spinal cord injury (SCI), new research shows.

The study demonstrated that an epidural electrical stimulation (EES) system developed specifically for spinal cord injuries enabled three men with complete paralysis to stand, walk, cycle, swim, and move their torso within 1 day.

“Thanks to this technology, we have been able to target individuals with the most serious spinal cord injury, meaning those with clinically complete spinal cord injury, with no sensation and no movement in the legs,” Grégoire Courtine, PhD, professor of neuroscience and neurotechnology at the Swiss Federal Institute of Technology, University Hospital Lausanne (Switzerland), and the University of Lausanne, told reporters attending a press briefing.

The study was published online Feb. 7, 2022, in Nature Medicine.
 

More rapid, precise, effective

SCIs involve severed connections between the brain and extremities. To compensate for these lost connections, researchers have investigated stem cell therapy, brain-machine interfaces, and powered exoskeletons.

However, these approaches aren’t yet ready for prime time.

In the meantime, researchers discovered even patients with a “complete” injury may have low-functioning connections and started investigating epidural stimulators designed to treat chronic pain. Recent studies – including three published in 2018 – showed promise for these pain-related stimulators in patients with incomplete SCI.

But using such “repurposed” technology meant the electrode array was relatively narrow and short, “so we could not target all the regions of the spinal cord involving control of leg and trunk movements,” said Dr. Courtine. With the newer technology “we are much more precise, effective, and more rapid in delivering therapy.”

To develop this new approach, the researchers designed a paddle lead with an arrangement of electrodes that targets sacral, lumbar, and low-thoracic dorsal roots involved in leg and trunk movements. They also established a personalized computational framework that allows for optimal surgical placement of this paddle lead.

In addition, they developed software that renders the configuration of individualized activity–dependent stimulation programs rapid, simple, and predictable.

They tested these neurotechnologies in three men with complete sensorimotor paralysis as part of an ongoing clinical trial. The participants, aged 29, 32, and 41 years, suffered an SCI from a motor bike accident 3, 9, and 1 year before enrollment.

All three patients exhibited complete sensorimotor paralysis. They were unable to take any step, and muscles remained quiescent during these attempts.

A neurosurgeon implanted electrodes along the spinal cord of study subjects. Wires from these electrodes were connected to a neurostimulator implanted under the skin in the abdomen.

The men can select different activity-based programs from a tablet that sends signals to the implanted device.
 

Personalized approach

Within a single day of the surgery, the participants were able to stand, walk, cycle, swim, and control trunk movements.

“It was not perfect at the very beginning, but they could train very early on to have a more fluid gait,” said study investigator neurosurgeon Joceylyne Bloch, MD, associate professor, University of Lausanne and University Hospital Lausanne.

At this stage, not all paralyzed patients are eligible for the procedure. Dr. Bloch explained that at least 6 cm of healthy spinal cord under the lesion is needed to implant the electrodes.

“There’s a huge variability of spinal cord anatomy between individuals. That’s why it’s important to study each person individually and to have individual models in order to be precise.”

Researchers envision having “a library of electrode arrays,” added Dr. Courtine. With preoperative imaging of the individual’s spinal cord, “the neurosurgeon can select the more appropriate electrode array for that specific patient.”

Dr. Courtine noted recovery of sensation with the system differs from one individual to another. One study participant, Michel Roccati, now 30, told the briefing he feels a contraction in his muscle during the stimulation.

Currently, only individuals whose injury is more than a year old are included in the study to ensure patients have “a stable lesion” and reached “a plateau of recovery,” said Dr. Bloch. However, animal models show intervening earlier might boost the benefits.

A patient’s age can influence the outcome, as younger patients are likely in better condition and more motivated than older patients, said Dr. Bloch. However, she noted patients closing in on 50 years have responded well to the therapy.

Such stimulation systems may prove useful in treating conditions typically associated with SCI, such as hypertension and bladder control, and perhaps also in patients with Parkinson’s disease, said Dr. Courtine.

The researchers plan to conduct another study that will include a next-generation pulse generator with features that make the stimulation even more effective and user friendly. A voice recognition system could eventually be connected to the system.

“The next step is a minicomputer that you implant in the body that communicates in real time with an external iPhone,” said Dr. Courtine.

ONWARD Medical, which developed the technology, has received a breakthrough device designation from the Food and Drug Administration. The company is in discussions with the FDA to carry out a clinical trial of the device in the United States.
 

A ‘huge step forward’

Peter J. Grahn, PhD, assistant professor, department of physical medicine and rehabilitation and department of neurologic surgery, Mayo Clinic, Rochester, Minn., an author of one of the 2018 studies, said this technology “is a huge step forward” and “really pushes the field.”

Compared with the device used in his study that’s designed to treat neuropathic pain, this new system “is much more capable of dynamic stimulation,” said Dr. Grahn. “You can tailor the stimulation based on which area of the spinal cord you want to target during a specific function.”

There has been “a lot of hope and hype” recently around stem cells and biological molecules that were supposed to be “magic pills” to cure spinal cord dysfunction, said Dr. Grahn. “I don’t think this is one of those.”

However, he questioned the researchers’ use of the word “walking.”

“They say independent stepping or walking is restored on day 1, but the graphs show day 1 function is having over 60% of their body weight supported when they’re taking these steps,” he said.

In addition, the “big question” is how this technology can “be distilled down” into an approach “applicable across rehabilitation centers,” said Dr. Grahn.

The study was supported by numerous organizations, including ONWARD Medical. Dr. Courtine and Dr. Bloch hold various patents in relation with the present work. Dr. Courtine is a consultant with ONWARD Medical, and he and Dr. Bloch are shareholders of ONWARD Medical, a company with direct relationships with the presented work. Dr. Grahn reported no relevant financial relationships.

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

A breakthrough neuromodulation system rapidly restores motor function in patients with a severe spinal cord injury (SCI), new research shows.

The study demonstrated that an epidural electrical stimulation (EES) system developed specifically for spinal cord injuries enabled three men with complete paralysis to stand, walk, cycle, swim, and move their torso within 1 day.

“Thanks to this technology, we have been able to target individuals with the most serious spinal cord injury, meaning those with clinically complete spinal cord injury, with no sensation and no movement in the legs,” Grégoire Courtine, PhD, professor of neuroscience and neurotechnology at the Swiss Federal Institute of Technology, University Hospital Lausanne (Switzerland), and the University of Lausanne, told reporters attending a press briefing.

The study was published online Feb. 7, 2022, in Nature Medicine.
 

More rapid, precise, effective

SCIs involve severed connections between the brain and extremities. To compensate for these lost connections, researchers have investigated stem cell therapy, brain-machine interfaces, and powered exoskeletons.

However, these approaches aren’t yet ready for prime time.

In the meantime, researchers discovered even patients with a “complete” injury may have low-functioning connections and started investigating epidural stimulators designed to treat chronic pain. Recent studies – including three published in 2018 – showed promise for these pain-related stimulators in patients with incomplete SCI.

But using such “repurposed” technology meant the electrode array was relatively narrow and short, “so we could not target all the regions of the spinal cord involving control of leg and trunk movements,” said Dr. Courtine. With the newer technology “we are much more precise, effective, and more rapid in delivering therapy.”

To develop this new approach, the researchers designed a paddle lead with an arrangement of electrodes that targets sacral, lumbar, and low-thoracic dorsal roots involved in leg and trunk movements. They also established a personalized computational framework that allows for optimal surgical placement of this paddle lead.

In addition, they developed software that renders the configuration of individualized activity–dependent stimulation programs rapid, simple, and predictable.

They tested these neurotechnologies in three men with complete sensorimotor paralysis as part of an ongoing clinical trial. The participants, aged 29, 32, and 41 years, suffered an SCI from a motor bike accident 3, 9, and 1 year before enrollment.

All three patients exhibited complete sensorimotor paralysis. They were unable to take any step, and muscles remained quiescent during these attempts.

A neurosurgeon implanted electrodes along the spinal cord of study subjects. Wires from these electrodes were connected to a neurostimulator implanted under the skin in the abdomen.

The men can select different activity-based programs from a tablet that sends signals to the implanted device.
 

Personalized approach

Within a single day of the surgery, the participants were able to stand, walk, cycle, swim, and control trunk movements.

“It was not perfect at the very beginning, but they could train very early on to have a more fluid gait,” said study investigator neurosurgeon Joceylyne Bloch, MD, associate professor, University of Lausanne and University Hospital Lausanne.

At this stage, not all paralyzed patients are eligible for the procedure. Dr. Bloch explained that at least 6 cm of healthy spinal cord under the lesion is needed to implant the electrodes.

“There’s a huge variability of spinal cord anatomy between individuals. That’s why it’s important to study each person individually and to have individual models in order to be precise.”

Researchers envision having “a library of electrode arrays,” added Dr. Courtine. With preoperative imaging of the individual’s spinal cord, “the neurosurgeon can select the more appropriate electrode array for that specific patient.”

Dr. Courtine noted recovery of sensation with the system differs from one individual to another. One study participant, Michel Roccati, now 30, told the briefing he feels a contraction in his muscle during the stimulation.

Currently, only individuals whose injury is more than a year old are included in the study to ensure patients have “a stable lesion” and reached “a plateau of recovery,” said Dr. Bloch. However, animal models show intervening earlier might boost the benefits.

A patient’s age can influence the outcome, as younger patients are likely in better condition and more motivated than older patients, said Dr. Bloch. However, she noted patients closing in on 50 years have responded well to the therapy.

Such stimulation systems may prove useful in treating conditions typically associated with SCI, such as hypertension and bladder control, and perhaps also in patients with Parkinson’s disease, said Dr. Courtine.

The researchers plan to conduct another study that will include a next-generation pulse generator with features that make the stimulation even more effective and user friendly. A voice recognition system could eventually be connected to the system.

“The next step is a minicomputer that you implant in the body that communicates in real time with an external iPhone,” said Dr. Courtine.

ONWARD Medical, which developed the technology, has received a breakthrough device designation from the Food and Drug Administration. The company is in discussions with the FDA to carry out a clinical trial of the device in the United States.
 

A ‘huge step forward’

Peter J. Grahn, PhD, assistant professor, department of physical medicine and rehabilitation and department of neurologic surgery, Mayo Clinic, Rochester, Minn., an author of one of the 2018 studies, said this technology “is a huge step forward” and “really pushes the field.”

Compared with the device used in his study that’s designed to treat neuropathic pain, this new system “is much more capable of dynamic stimulation,” said Dr. Grahn. “You can tailor the stimulation based on which area of the spinal cord you want to target during a specific function.”

There has been “a lot of hope and hype” recently around stem cells and biological molecules that were supposed to be “magic pills” to cure spinal cord dysfunction, said Dr. Grahn. “I don’t think this is one of those.”

However, he questioned the researchers’ use of the word “walking.”

“They say independent stepping or walking is restored on day 1, but the graphs show day 1 function is having over 60% of their body weight supported when they’re taking these steps,” he said.

In addition, the “big question” is how this technology can “be distilled down” into an approach “applicable across rehabilitation centers,” said Dr. Grahn.

The study was supported by numerous organizations, including ONWARD Medical. Dr. Courtine and Dr. Bloch hold various patents in relation with the present work. Dr. Courtine is a consultant with ONWARD Medical, and he and Dr. Bloch are shareholders of ONWARD Medical, a company with direct relationships with the presented work. Dr. Grahn reported no relevant financial relationships.

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

The potential effectiveness of using vaginal progesterone to prevent preterm birth in two different populations was the focus of a pair of studies with mixed results at the annual meeting sponsored by the Society for Maternal-Fetal Medicine on Feb. 3. One study found no benefit from vaginal progesterone in those with first trimester bleeding, while the other, in a head-to-head comparison with 17-alpha-hydroxyprogesterone caproate (17-OHPC), found vaginal progesterone performs similarly to 17-OHPC in singleton pregnancies with a history of preterm birth.

While the first study does not suggest any changes in clinical practice, the second one suggests that vaginal progesterone is an alternative to 17-OHPC, as the American College of Obstetricians and Gynecologists currently recommends. SMFM currently only includes 17-OHPC in its guidelines.

“In otherwise low-risk pregnancies with first trimester bleeding, progesterone should not be prescribed for the prevention of miscarriage or prematurity,” Haim A. Abenhaim, MD, MPH, of the Jewish General Hospital at McGill University, Montreal, told attendees in his presentation.

”Publishing the negative result is so important because this helps the overall body of literature reduce the amount of publication bias that exists in the literature,” Michael Richley, MD, an ob.gyn. and maternal-fetal medicine fellow at the University of California, Los Angeles, said in an interview. Dr. Richley was not involved in the research but attended the presentation.
 

Vaginal progesterone for first trimester bleeding

Most preterm birth occurs in pregnancies with no identifiable risk factors, but first-trimester bleeding may indicate subchorionic hemorrhage from placental detachment, which can increase the risk of preterm birth. Other risk factors where progesterone has previously shown effectiveness in reducing preterm birth risk include short cervix and a history of prior preterm birth.

The first study (PREEMPT) was a double-blind, randomized controlled trial conducted at six Canadian hospitals with 533 women. The participants all experienced bleeding within the first 14 weeks of pregnancy and a documented subchorionic hemorrhage. The trial excluded those who already required progesterone, had contraindications to progesterone or had an alternate cause of bleeding.

The intervention group included 264 women randomly assigned to use 200 mg of micronized progesterone administered with a vaginal suppository at bedtime, while the placebo group included 269 women who used a vaginal suppository with no medication, both administered until 34 weeks of pregnancy. The groups were not significantly different in age, race, or former pregnancies, live births, and miscarriages. They were also similar in clinical characteristics of bleeding and subchorionic hemorrhage.

The proportion of term births was similar between the progesterone (74.6%) and placebo (70.6%) groups (P =.3), as was the proportion of preterm births (10.2% progesterone vs. 12.3% placebo, P =.46). There were also no significant differences in the secondary outcomes of cramping, hospital admission, bed rest, or preventive measures, including pessary, cerclage, antibiotics, magnesium, and nifedipine. Newborns across both groups were statistically similar in average birth weight and distribution of birth weights and in incidence of neonatal ICU admission or respiratory distress syndrome. Adverse events were similar across both groups.

”The results are not surprising as several studies in the past have shown similar lack of efficacy,” Dr. said. “The pathophysiology of subchorionic hematoma is different from the multifactorial etiologies of spontaneous preterm birth, and given our lack of clear understanding of the actions of progesterone, the lack of efficacy in this subgroup with subchorionic hematoma is not surprising.”

Dr. Richley did note that having a low-risk population to start with may have affected the findings, which might be different in a high-risk population.

“I don’t believe this will change anything within clinical practice. At this time, progesterone is not used in any form in the setting of first trimester threatened abortion by maternal-fetal medicine specialists,” Dr. Richley said. “There may be other subgroups of clinicians who do prescribe progesterone in this setting, and these data should further encourage them to move away from this practice.”

Dr. Abenhaim noted a couple unexpected issues that occurred during the course of the study, such as underreporting of subchorionic hemorrhage with radiologic confirmation that resulted in a smaller population and a change in protocol to include patients with no identifiable secondary source of bleeding. The pandemic also halted enrollment, and the investigators halted the trial when recruitment could have continued since interim analysis showed no likely benefit.

Though first trimester bleeding is associated with a 25%-30% increased risk of miscarriage or preterm birth, the findings showed that progesterone did not prevent miscarriage or prematurity, or increase the live birth rate, in low-risk patients with first trimester bleeding.
 

Vaginal progesterone vs. 17-OHPC

Although a 2017 meta-analysis had found vaginal progesterone to be superior to 17-OHPC in preventing preterm birth, few studies were available, and they had wide confidence intervals. This open-label randomized controlled trial took place at five U.S. sites and included participants who had a singleton pregnancy less than 24 weeks along and a history of singleton preterm birth between 16 and 37 weeks. The trials excluded those with placenta previa or accreta, preterm labor, preterm premature rupture of the membranes, clinical chorioamnionitis, or a major fetal anomaly or chromosomal disorder.

Among 205 women initially randomized, 94 in each group completed the trial, either inserting 200 mg of micronized progesterone daily with a vaginal suppository or receiving 250 mg of weekly intramuscular injections of 17-OHPC from 16 to 36 weeks’ gestation. The only significant difference between the groups in demographics or clinical features was that the vaginal progesterone group had a higher proportion of multiple past preterm births (33%) compared with the 17-OHPC group (17%). Cervical length and use of cerclage were also similar between the groups.

Though 30.9% of the vaginal progesterone group delivered preterm before 37 weeks, compared with 38.3% in the 17-OHPC group, the difference was not significant (P =.28). There was a borderline statistical difference between gestational age at delivery: 37.4 weeks in the vaginal progesterone group versus 36.3 weeks in the 17-OHPC group (P =.047). Neonatal outcomes were clinically similar between the two groups. Therapy initiation did slightly differ between the groups, with an average start 1 gestational week earlier in the vaginal progesterone group (16.9 vs. 17.8, P =.001) and a higher proportion of patients in the 17-OHPC group initiating therapy after 20 weeks (16.5% vs. 2.2%, P =.001). Adherence was otherwise similar between the groups, and the groups reported similar rates and types of side effects.

The trial did not meet the primary endpoint of vaginal progesterone reducing risk of recurrent preterm birth by 50%, compared with 17-OHPC, but it may increase latency to delivery, Rupsa C. Boelig, MD, of Thomas Jefferson University, Philadelphia, told attendees. Though this was the largest trial to compare vaginal progesterone with 17-OHPC for preventing preterm birth, it was underpowered to detect a difference in efficacy, to conduct subgroup analyses, and to assess secondary outcomes, Dr. Boelig noted. “Baseline difference in preterm birth risk may affect apparent relative efficacy of vaginal progesterone.”

Nevertheless, the “totality of evidence appears to be greater for vaginal progesterone,” Dr. Boelig said, making vaginal progesterone an acceptable alternative to 17-OHPC. ACOG recommendations currently include offering either, but SMFM recommendations only mention 17-OHPC.

It’s worth noting, however, that the future of 17-OHPC, a synthetic compound, compared with naturally occurring micronized progesterone, continues to be uncertain following a 2020 study that found no evidence of its efficacy, leading the Food and Drug Administration to withdraw its approval for prevention of preterm birth. ”These findings are important especially in light of the controversy surrounding 17-OHP,” Jenny Mei, MD, a maternal-fetal medicine fellow at UCLA, said in an interview after attending the presentation. “It is also sometimes difficult for patients to commit to weekly 17-OHPC injections, which requires time and many doctors visits, as compared to vaginal progesterone, which patients can administer at home.” Since this study does not have a placebo group, “it does not address the question of the overall efficacy of either medication compared to a control,” Dr. Mei said. ”It is also a somewhat small patient population so the results may change with a larger population. The authors conclude it is worth readdressing the use of vaginal progesterone for these patients.”

Herman L. Hedriana, MD, professor and director of the division of maternal-fetal medicine and the maternal-fetal medicine fellowship program at the University of California, Davis, also pointed out notable differences between the two compounds.

“One has to remember that the formulation and mechanism of action are very different between 17-OHPC and the vaginal application of micronized progesterone. We do not have enough data to say one is superior versus the other,” said Dr. Hedriana, who was not involved in the research. “With 17-OHPC, the mechanism of action appears to be influenced by how the drug is metabolized based on race and ethnicity makeup, and may be influence by epigenetics,” while the mechanism for vaginal progesterone is probably local “given it is applied directly next to the cervix; hence, the results are it is effective in short cervices.” But those differing mechanisms don’t change the clinical significance of the findings. “One can use vaginal progesterone or 17-OHPC based on patient preference and availability,” Dr. Hedriana said.

The researchers of both studies reported no personal financial or industry disclosures, though Dr. Boelig disclosed that she had taken 17-OHPC and had cerclages during both her pregnancies, which resulted in healthy children today. The PREEMPT trial was funded by the Canadian Institutes of Health Research. The head-to-head trial was funded by the National Institute of Child Health and Development, the March of Dimes, the EW Thrasher Foundation, the PhRMA Foundation, and Covis Pharma, who manufactures the 17-OHPC drug Makena.

This story was updated on 2/8/2022.

The potential effectiveness of using vaginal progesterone to prevent preterm birth in two different populations was the focus of a pair of studies with mixed results at the annual meeting sponsored by the Society for Maternal-Fetal Medicine on Feb. 3. One study found no benefit from vaginal progesterone in those with first trimester bleeding, while the other, in a head-to-head comparison with 17-alpha-hydroxyprogesterone caproate (17-OHPC), found vaginal progesterone performs similarly to 17-OHPC in singleton pregnancies with a history of preterm birth.

While the first study does not suggest any changes in clinical practice, the second one suggests that vaginal progesterone is an alternative to 17-OHPC, as the American College of Obstetricians and Gynecologists currently recommends. SMFM currently only includes 17-OHPC in its guidelines.

“In otherwise low-risk pregnancies with first trimester bleeding, progesterone should not be prescribed for the prevention of miscarriage or prematurity,” Haim A. Abenhaim, MD, MPH, of the Jewish General Hospital at McGill University, Montreal, told attendees in his presentation.

”Publishing the negative result is so important because this helps the overall body of literature reduce the amount of publication bias that exists in the literature,” Michael Richley, MD, an ob.gyn. and maternal-fetal medicine fellow at the University of California, Los Angeles, said in an interview. Dr. Richley was not involved in the research but attended the presentation.
 

Vaginal progesterone for first trimester bleeding

Most preterm birth occurs in pregnancies with no identifiable risk factors, but first-trimester bleeding may indicate subchorionic hemorrhage from placental detachment, which can increase the risk of preterm birth. Other risk factors where progesterone has previously shown effectiveness in reducing preterm birth risk include short cervix and a history of prior preterm birth.

The first study (PREEMPT) was a double-blind, randomized controlled trial conducted at six Canadian hospitals with 533 women. The participants all experienced bleeding within the first 14 weeks of pregnancy and a documented subchorionic hemorrhage. The trial excluded those who already required progesterone, had contraindications to progesterone or had an alternate cause of bleeding.

The intervention group included 264 women randomly assigned to use 200 mg of micronized progesterone administered with a vaginal suppository at bedtime, while the placebo group included 269 women who used a vaginal suppository with no medication, both administered until 34 weeks of pregnancy. The groups were not significantly different in age, race, or former pregnancies, live births, and miscarriages. They were also similar in clinical characteristics of bleeding and subchorionic hemorrhage.

The proportion of term births was similar between the progesterone (74.6%) and placebo (70.6%) groups (P =.3), as was the proportion of preterm births (10.2% progesterone vs. 12.3% placebo, P =.46). There were also no significant differences in the secondary outcomes of cramping, hospital admission, bed rest, or preventive measures, including pessary, cerclage, antibiotics, magnesium, and nifedipine. Newborns across both groups were statistically similar in average birth weight and distribution of birth weights and in incidence of neonatal ICU admission or respiratory distress syndrome. Adverse events were similar across both groups.

”The results are not surprising as several studies in the past have shown similar lack of efficacy,” Dr. said. “The pathophysiology of subchorionic hematoma is different from the multifactorial etiologies of spontaneous preterm birth, and given our lack of clear understanding of the actions of progesterone, the lack of efficacy in this subgroup with subchorionic hematoma is not surprising.”

Dr. Richley did note that having a low-risk population to start with may have affected the findings, which might be different in a high-risk population.

“I don’t believe this will change anything within clinical practice. At this time, progesterone is not used in any form in the setting of first trimester threatened abortion by maternal-fetal medicine specialists,” Dr. Richley said. “There may be other subgroups of clinicians who do prescribe progesterone in this setting, and these data should further encourage them to move away from this practice.”

Dr. Abenhaim noted a couple unexpected issues that occurred during the course of the study, such as underreporting of subchorionic hemorrhage with radiologic confirmation that resulted in a smaller population and a change in protocol to include patients with no identifiable secondary source of bleeding. The pandemic also halted enrollment, and the investigators halted the trial when recruitment could have continued since interim analysis showed no likely benefit.

Though first trimester bleeding is associated with a 25%-30% increased risk of miscarriage or preterm birth, the findings showed that progesterone did not prevent miscarriage or prematurity, or increase the live birth rate, in low-risk patients with first trimester bleeding.