Women's Health

Women treated with oral bisphosphonate drugs for osteoporosis for 5 years get no additional benefit – in terms of hip fracture risk – if the treatment is extended for another 5 years, new research shows.

Raycat/Getty Images

“We found that hip fracture risk in women did not differ if women stopped bisphosphonate use after 5 years or stayed on the medication for 10 years,” coauthor Joan C. Lo, MD, Kaiser Permanente Northern California, Oakland, said in an interview.

The new study, published Dec. 7 in JAMA Network Open, did show a small benefit in continuing the treatment through 7 years vs. 5 years, but it wasn’t clear if this was significant.

“Whether there is a benefit to staying on the drug for 7 years needs to be further studied in randomized trials,” Dr. Lo stressed.

It is well established that oral bisphosphonates are effective in reducing the risk for fracture within the first 3-5 years of treatment; however, evidence on the effects of treatment beyond 5 years is lacking.

The most recent guidance from the American Society of Bone and Mineral Research (ASBMR) on the issue, which were released in 2015, recommends continuation of bisphosphonates beyond 5 years for high-risk patients, but it recommends a “drug holiday” for low-risk patients.
 

Study adds important new evidence

However, that guidance acknowledges that data are limited regarding long-term use. This large new study adds important new evidence to the discussion, Robert A. Adler, MD, who was a member of the ASBMR Task Force for the recent guidance, said in an interview.

“[With the lack of recent research,] this new study from Kaiser Permanente is of great interest,” said Dr. Adler, chief of endocrinology and metabolism at Central Virginia Veterans Affairs Health Care System and professor of internal medicine and of epidemiology at Virginia Commonwealth University, Richmond.

“It is new data and suggests we might temper our enthusiasm for long-term treatment with bisphosphonates,” he said.

“Importantly, it is the first large observational trial and is closer to a real-world setting than a randomized controlled trial,” he said.

But, Dr. Adler emphasized: “The take-home message is that while this suggests that patients can probably be given a drug holiday for a couple of years ... they should be retested, and if they appear to be at an increased risk of fracture, they probably should restart again.

“Osteoporosis is a chronic disorder,” he emphasized. “It isn’t cured by any of our treatments, and as people get older, they are at a higher fracture risk.

“So we really need to follow our patients for a lifetime and reassess their fracture risk every couple of years – whether they are still on therapy or on a drug holiday.”
 

Possible that 7 years is better than 5 but remains to be proven

The new study involved data from Kaiser Permanente Northern and Southern California on 29,685 women who had completed 5 years of treatment with oral bisphosphonates, including alendronate, risedronate, or ibandronate, between 2002 and 2014.

Among the women, 11,105 (37%) continued taking the drugs beyond 5 years to 7 years, and 2,725 (9.2%) completed a total of 10 years of treatment.

Their median age was 71. Among those for whom bone mineral density data were available, 37% had osteoporosis after the first 5 years of treatment.

During these 5 years of treatment, 507 hip fractures occurred.

The cumulative incidence of hip fracture among for those who discontinued study therapy at entry, i.e., those who underwent treatment for 5 years, was 23.0 per 1,000 individuals.

After 7 years of treatment, the rate was 20.8 per 1000. For those who continued therapy for 10 years, the rate was 26.8 per 1000 individuals.

The rate in the 7-year treatment group was based on patients taking a 6-month drug holiday after the initial 5 years, but the results are hard to interpret, Dr. Lo said.

“It’s possible that 7 years is better than 5, but this is not a randomized trial, and some of the data analyses done in the study suggest more research should be done to look at a benefit after 7 years.

“At the end of the day, doctors and women need to decide at 5 years what an individual woman’s risk fracture risk is and determine if she should stay on the drug longer,” Dr. Lo emphasized.
 

Limitations: Subgroups not identified, adherence hard to assess

The uncertainty of any benefit of treatment with bisphosphonates beyond 5 years is further reflected in U.S. recommendations – the Food and Drug Administration has concluded on the basis of pooled data from the extension phase of major clinical trials that any advantages of treatment beyond 3-5 years are unclear.

Key limitations of the current study include the fact that the incidence of hip fracture was not evaluated in low-risk vs. high-risk subgroups; therefore, “these findings may not be applicable to older women at higher risk of osteoporotic fracture,” the authors wrote.

Furthermore, the study did not assess outcomes of fractures other than hip fractures, such as vertebral fractures, they noted.

Dr. Adler pointed out that another limitation is that adherence in the trial was defined as taking 60% of prescribed pills.

“I think this is the biggest weakness with the study,” he said. “Particularly with medications like oral bisphosphonates that don’t really make patients feel any different, it’s a real challenge to make sure patients continue to take these drugs properly.”

The findings should give some reassurance for patients who take a break from the drugs after 5 years. However, reassessment of their risk is critical, Dr. Adler reiterated.

The study was supported by a grant from the National Institute on Aging and the National Institute of Arthritis, Musculoskeletal, and Skin Diseases of the National Institutes of Health. The authors and Adler have disclosed no relevant financial relationships.

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

Women treated with oral bisphosphonate drugs for osteoporosis for 5 years get no additional benefit – in terms of hip fracture risk – if the treatment is extended for another 5 years, new research shows.

Raycat/Getty Images

“We found that hip fracture risk in women did not differ if women stopped bisphosphonate use after 5 years or stayed on the medication for 10 years,” coauthor Joan C. Lo, MD, Kaiser Permanente Northern California, Oakland, said in an interview.

The new study, published Dec. 7 in JAMA Network Open, did show a small benefit in continuing the treatment through 7 years vs. 5 years, but it wasn’t clear if this was significant.

“Whether there is a benefit to staying on the drug for 7 years needs to be further studied in randomized trials,” Dr. Lo stressed.

It is well established that oral bisphosphonates are effective in reducing the risk for fracture within the first 3-5 years of treatment; however, evidence on the effects of treatment beyond 5 years is lacking.

The most recent guidance from the American Society of Bone and Mineral Research (ASBMR) on the issue, which were released in 2015, recommends continuation of bisphosphonates beyond 5 years for high-risk patients, but it recommends a “drug holiday” for low-risk patients.
 

Study adds important new evidence

However, that guidance acknowledges that data are limited regarding long-term use. This large new study adds important new evidence to the discussion, Robert A. Adler, MD, who was a member of the ASBMR Task Force for the recent guidance, said in an interview.

“[With the lack of recent research,] this new study from Kaiser Permanente is of great interest,” said Dr. Adler, chief of endocrinology and metabolism at Central Virginia Veterans Affairs Health Care System and professor of internal medicine and of epidemiology at Virginia Commonwealth University, Richmond.

“It is new data and suggests we might temper our enthusiasm for long-term treatment with bisphosphonates,” he said.

“Importantly, it is the first large observational trial and is closer to a real-world setting than a randomized controlled trial,” he said.

But, Dr. Adler emphasized: “The take-home message is that while this suggests that patients can probably be given a drug holiday for a couple of years ... they should be retested, and if they appear to be at an increased risk of fracture, they probably should restart again.

“Osteoporosis is a chronic disorder,” he emphasized. “It isn’t cured by any of our treatments, and as people get older, they are at a higher fracture risk.

“So we really need to follow our patients for a lifetime and reassess their fracture risk every couple of years – whether they are still on therapy or on a drug holiday.”
 

Possible that 7 years is better than 5 but remains to be proven

The new study involved data from Kaiser Permanente Northern and Southern California on 29,685 women who had completed 5 years of treatment with oral bisphosphonates, including alendronate, risedronate, or ibandronate, between 2002 and 2014.

Among the women, 11,105 (37%) continued taking the drugs beyond 5 years to 7 years, and 2,725 (9.2%) completed a total of 10 years of treatment.

Their median age was 71. Among those for whom bone mineral density data were available, 37% had osteoporosis after the first 5 years of treatment.

During these 5 years of treatment, 507 hip fractures occurred.

The cumulative incidence of hip fracture among for those who discontinued study therapy at entry, i.e., those who underwent treatment for 5 years, was 23.0 per 1,000 individuals.

After 7 years of treatment, the rate was 20.8 per 1000. For those who continued therapy for 10 years, the rate was 26.8 per 1000 individuals.

The rate in the 7-year treatment group was based on patients taking a 6-month drug holiday after the initial 5 years, but the results are hard to interpret, Dr. Lo said.

“It’s possible that 7 years is better than 5, but this is not a randomized trial, and some of the data analyses done in the study suggest more research should be done to look at a benefit after 7 years.

“At the end of the day, doctors and women need to decide at 5 years what an individual woman’s risk fracture risk is and determine if she should stay on the drug longer,” Dr. Lo emphasized.
 

Limitations: Subgroups not identified, adherence hard to assess

The uncertainty of any benefit of treatment with bisphosphonates beyond 5 years is further reflected in U.S. recommendations – the Food and Drug Administration has concluded on the basis of pooled data from the extension phase of major clinical trials that any advantages of treatment beyond 3-5 years are unclear.

Key limitations of the current study include the fact that the incidence of hip fracture was not evaluated in low-risk vs. high-risk subgroups; therefore, “these findings may not be applicable to older women at higher risk of osteoporotic fracture,” the authors wrote.

Furthermore, the study did not assess outcomes of fractures other than hip fractures, such as vertebral fractures, they noted.

Dr. Adler pointed out that another limitation is that adherence in the trial was defined as taking 60% of prescribed pills.

“I think this is the biggest weakness with the study,” he said. “Particularly with medications like oral bisphosphonates that don’t really make patients feel any different, it’s a real challenge to make sure patients continue to take these drugs properly.”

The findings should give some reassurance for patients who take a break from the drugs after 5 years. However, reassessment of their risk is critical, Dr. Adler reiterated.

The study was supported by a grant from the National Institute on Aging and the National Institute of Arthritis, Musculoskeletal, and Skin Diseases of the National Institutes of Health. The authors and Adler have disclosed no relevant financial relationships.

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

Women treated with oral bisphosphonate drugs for osteoporosis for 5 years get no additional benefit – in terms of hip fracture risk – if the treatment is extended for another 5 years, new research shows.

Raycat/Getty Images

“We found that hip fracture risk in women did not differ if women stopped bisphosphonate use after 5 years or stayed on the medication for 10 years,” coauthor Joan C. Lo, MD, Kaiser Permanente Northern California, Oakland, said in an interview.

The new study, published Dec. 7 in JAMA Network Open, did show a small benefit in continuing the treatment through 7 years vs. 5 years, but it wasn’t clear if this was significant.

“Whether there is a benefit to staying on the drug for 7 years needs to be further studied in randomized trials,” Dr. Lo stressed.

It is well established that oral bisphosphonates are effective in reducing the risk for fracture within the first 3-5 years of treatment; however, evidence on the effects of treatment beyond 5 years is lacking.

The most recent guidance from the American Society of Bone and Mineral Research (ASBMR) on the issue, which were released in 2015, recommends continuation of bisphosphonates beyond 5 years for high-risk patients, but it recommends a “drug holiday” for low-risk patients.
 

Study adds important new evidence

However, that guidance acknowledges that data are limited regarding long-term use. This large new study adds important new evidence to the discussion, Robert A. Adler, MD, who was a member of the ASBMR Task Force for the recent guidance, said in an interview.

“[With the lack of recent research,] this new study from Kaiser Permanente is of great interest,” said Dr. Adler, chief of endocrinology and metabolism at Central Virginia Veterans Affairs Health Care System and professor of internal medicine and of epidemiology at Virginia Commonwealth University, Richmond.

“It is new data and suggests we might temper our enthusiasm for long-term treatment with bisphosphonates,” he said.

“Importantly, it is the first large observational trial and is closer to a real-world setting than a randomized controlled trial,” he said.

But, Dr. Adler emphasized: “The take-home message is that while this suggests that patients can probably be given a drug holiday for a couple of years ... they should be retested, and if they appear to be at an increased risk of fracture, they probably should restart again.

“Osteoporosis is a chronic disorder,” he emphasized. “It isn’t cured by any of our treatments, and as people get older, they are at a higher fracture risk.

“So we really need to follow our patients for a lifetime and reassess their fracture risk every couple of years – whether they are still on therapy or on a drug holiday.”
 

Possible that 7 years is better than 5 but remains to be proven

The new study involved data from Kaiser Permanente Northern and Southern California on 29,685 women who had completed 5 years of treatment with oral bisphosphonates, including alendronate, risedronate, or ibandronate, between 2002 and 2014.

Among the women, 11,105 (37%) continued taking the drugs beyond 5 years to 7 years, and 2,725 (9.2%) completed a total of 10 years of treatment.

Their median age was 71. Among those for whom bone mineral density data were available, 37% had osteoporosis after the first 5 years of treatment.

During these 5 years of treatment, 507 hip fractures occurred.

The cumulative incidence of hip fracture among for those who discontinued study therapy at entry, i.e., those who underwent treatment for 5 years, was 23.0 per 1,000 individuals.

After 7 years of treatment, the rate was 20.8 per 1000. For those who continued therapy for 10 years, the rate was 26.8 per 1000 individuals.

The rate in the 7-year treatment group was based on patients taking a 6-month drug holiday after the initial 5 years, but the results are hard to interpret, Dr. Lo said.

“It’s possible that 7 years is better than 5, but this is not a randomized trial, and some of the data analyses done in the study suggest more research should be done to look at a benefit after 7 years.

“At the end of the day, doctors and women need to decide at 5 years what an individual woman’s risk fracture risk is and determine if she should stay on the drug longer,” Dr. Lo emphasized.
 

Limitations: Subgroups not identified, adherence hard to assess

The uncertainty of any benefit of treatment with bisphosphonates beyond 5 years is further reflected in U.S. recommendations – the Food and Drug Administration has concluded on the basis of pooled data from the extension phase of major clinical trials that any advantages of treatment beyond 3-5 years are unclear.

Key limitations of the current study include the fact that the incidence of hip fracture was not evaluated in low-risk vs. high-risk subgroups; therefore, “these findings may not be applicable to older women at higher risk of osteoporotic fracture,” the authors wrote.

Furthermore, the study did not assess outcomes of fractures other than hip fractures, such as vertebral fractures, they noted.

Dr. Adler pointed out that another limitation is that adherence in the trial was defined as taking 60% of prescribed pills.

“I think this is the biggest weakness with the study,” he said. “Particularly with medications like oral bisphosphonates that don’t really make patients feel any different, it’s a real challenge to make sure patients continue to take these drugs properly.”

The findings should give some reassurance for patients who take a break from the drugs after 5 years. However, reassessment of their risk is critical, Dr. Adler reiterated.

The study was supported by a grant from the National Institute on Aging and the National Institute of Arthritis, Musculoskeletal, and Skin Diseases of the National Institutes of Health. The authors and Adler have disclosed no relevant financial relationships.

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

Women who use substances during pregnancy need support and education, not judgment, to promote the best outcomes, according to a panel of experts speaking at the 2020 virtual meeting of the American College of Obstetricians and Gynecologists. The panelists highlighted several key issues for addressing alcohol, opioids, and cannabis use by pregnant women.

No amount of alcohol is safe

Highwaystarz-Photography/Thinkstock

Many women believe that a limited amount of alcohol is safe during pregnancy, in part because of mixed messages in the media suggesting that light drinking is okay, according to Erin Tracy Bradley, MD, MPH, of Massachusetts General Hospital, Boston.

“We need to do a better job teaching our patients about the potential dangers of alcohol,” Dr. Bradley said in her presentation.

In fact, data suggest that women more at risk for an alcohol-exposed pregnancy are older and better educated. Dr. Bradley described the pattern of malformation for fetal alcohol syndrome (FAS) that includes small eyes, a thin upper lip, and smooth skin between the upper lip and nose.

“The only cause we know of [for FAS] is alcohol exposure intrauterine for the fetus,” so it is preventable with counseling and care, and thought to be the leading preventable cause of birth defects during pregnancies, she said.

The bottom line is that there is no safe amount of alcohol,” said Dr. Bradley. However, providers are inconsistent in discussing alcohol with their pregnant patients. In addition, universal screening is important because it is difficult to predict which women will be drinking during pregnancy.

Screening allows providers to quickly assess the severity of substance use, offer a brief intervention to raise patient awareness, and refer if necessary. “There should be ‘absolutely no judgment, no shame, no stigma,’ ” Dr. Bradley emphasized. “We are the patient’s partners, and we are trying to help them have a healthy pregnancy. “

Opioid use in pregnancy spiked in recent decades

“Women have always been overrepresented when opioids are involved,” said Tricia E. Wright, MD, of the University of California, San Francisco.

Long-term studies have shown that, overall, women are more likely to be given opioids and given higher doses, compared with men, often for conditions in which opioids are not effective, she noted.

Women use substances differently than men; “they use them to cope with everyday life,” and a history of interpersonal violence and sexual assault are coming among women with opioid use disorders, said Dr. Wright.

The majority of women with opioid use disorders are of childbearing age, which has led to an increase in neonatal abstinence syndrome (NAS) said Dr. Wright.

She cited 2014 data from the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report showing an increase in NAS from 1.2 per 1,000 hospital births in 2000 to 5.8 per 1,000 hospital births in 2012. This increase has led to “misguided” efforts to prevent NAS through opioid detoxification, Dr. Wright said. She and colleagues conducted a systematic review in 2018 and found that, in fact, the evidence does not support detoxification as a recommended treatment intervention during pregnancy.

Opioid agonist therapy has multiple benefits for both the mother and fetus, Dr. Wright said. Maternal benefits include reduction in overdose-related deaths; decrease in the risk of HIV, hepatitis B, and hepatitis C; and increased engagement in prenatal care and recovery treatment. Fetal benefits include reduced fetal stress with the reduced fluctuations in maternal opioid levels, as well as decreases in intrauterine fetal death, intrauterine growth restriction, and preterm delivery.

“We know that relapse kills” because patients lose their tolerance, Dr. Wright said. “What we have seen is that overdose deaths are a leading cause of death in the postpartum period.”

When it comes to treatment, both methadone and buprenorphine are safe and effective options in pregnancy, she said. Treatment decisions should be made based on available options, patient preference, and a patient’s previous treatment experiences, as well as disease severity, social support, and the intensity of treatment needed.

“Whatever medicine you choose, it takes a village to coordinate the care,” Dr. Wright said. Maternal dose has no effect on neonatal withdrawal, so women should be encouraged to report any concerns. Either medication is compatible with breastfeeding. In fact, breastfeeding has many benefits in preventing neonatal withdrawal syndrome. Smoking cessation should be encouraged because it improves neonatal withdrawal.

Minimizing stigma is paramount, said Dr. Wright. “Substance use disorders are among the most stigmatized medical conditions, and pregnant women with substance use disorders are even more stigmatized.”

Clinicians can support patients by focusing on appropriate language, patients aren’t “addicts,” they are people with an opioid use disorder, she said.

Compassionate care for cannabis users

Cannabis use has a long history of association with women’s health, said Mishka Terplan, MD, MPH, of Friends Research Institute, Baltimore. Although cannabis use overall has increased steadily in recent years, data indicate that people who are pregnant are less likely to use cannabis than those who aren’t. The exception is that individuals who report using cannabis for medical purposes only remain consistent cannabis users during pregnancy.

“The concern is cannabis and birth outcomes, as well as developmental outcomes,” Dr. Terplan said. Multiple studies on this topic support several systematic reviews, and “depending on which decade you read, the results differ slightly.”

Reviews from the 1990s showed little to no effect on birth weight, but more recent studies, such as a meta-analysis published in BMJ Open in 2015, showed increased risk of neonatal outcomes such as low birth weight, anemia, and odds of admission to the neonatal ICU.

“The difference in these two eras is thought to be caused by the change in the definition of what cannabis is, and the potency has increased, and possibly therefore, as a consequence, we see outcomes we hadn’t seen before,” Dr. Terplan explained.

There is a concern with increased use and increased legalization that, there could be adverse effects on neonatal health, but recent studies in Colorado do not show a significant difference in neonatal outcomes before and after legalization, he said.

Data from pregnant women suggest that with regard to cannabis, they are concerned about their health, but they tend to seek information about cannabis use in pregnancy from family, friends, and the Internet rather than their health providers, said Dr. Terplan.

However, studies also show that providers tend to fall short and do a poor job of talking to pregnant patients about cannabis. When providers do discuss cannabis, they tend to focus on the legal aspects. “We are failing our patients when it comes to cannabis,” Dr. Terplan said. “We don’t provide the information and support they need and desire.” Instead, many providers “deploy urine drug testing, which we misinterpret.”

Dr. Terplan explained that point-of-care cannabis testing that shows “THC” is not measuring tetrahydrocannabinol, the psychoactive compound; rather it captures the nonpsychoactive metabolite of THC, one that sticks around for a long time in the biological compartment.

Dr. Terplan urged clinicians not to use urine tests as a default indicator of cannabis use, but instead, “we need to sit, listen, and work with our patients from a place of empathy.”
 

Questions answered

During a question-and-answer session following the panel, Dr. Bradley was asked about preconception counseling related to alcohol consumption.

“Preconception time is a perfect time to do screening, or offer contraception if a patient is a place where she doesn’t want to become pregnant or if she wants to take advantage of any therapeutic options to get well prior to pregnancy,” she said.

Dr. Wright responded to a question about the impact of punitive actions such as drug testing and incarceration. “These things decrease the chance that patients will get adequate prenatal care,” she said. “We need to advocate for our patients and advocate for changing drug laws.”

Dr. Terplan responded to a question about the impact of substance use on parenting. Parents use nicotine, alcohol, and also cannabis, he said. Data showing an association between substance use and cases of child abuse and neglect, “are of poor quality and do not support this association.”

Overall, “we need to have consistent messaging that we are not there to judge patients,” Dr. Bradley added. “The last thing we want is for patients not to be honest with us.”

Dr. Wright disclosed consulting fees from McKesson and royalties as the coauthor of a book, “Opioid-Use Disorders in Pregnancy.” Dr. Bradley had no financial conflicts to disclose. Dr. Terplan had no financial conflicts to disclose.

Women who use substances during pregnancy need support and education, not judgment, to promote the best outcomes, according to a panel of experts speaking at the 2020 virtual meeting of the American College of Obstetricians and Gynecologists. The panelists highlighted several key issues for addressing alcohol, opioids, and cannabis use by pregnant women.

No amount of alcohol is safe

Highwaystarz-Photography/Thinkstock

Many women believe that a limited amount of alcohol is safe during pregnancy, in part because of mixed messages in the media suggesting that light drinking is okay, according to Erin Tracy Bradley, MD, MPH, of Massachusetts General Hospital, Boston.

“We need to do a better job teaching our patients about the potential dangers of alcohol,” Dr. Bradley said in her presentation.

In fact, data suggest that women more at risk for an alcohol-exposed pregnancy are older and better educated. Dr. Bradley described the pattern of malformation for fetal alcohol syndrome (FAS) that includes small eyes, a thin upper lip, and smooth skin between the upper lip and nose.

“The only cause we know of [for FAS] is alcohol exposure intrauterine for the fetus,” so it is preventable with counseling and care, and thought to be the leading preventable cause of birth defects during pregnancies, she said.

The bottom line is that there is no safe amount of alcohol,” said Dr. Bradley. However, providers are inconsistent in discussing alcohol with their pregnant patients. In addition, universal screening is important because it is difficult to predict which women will be drinking during pregnancy.

Screening allows providers to quickly assess the severity of substance use, offer a brief intervention to raise patient awareness, and refer if necessary. “There should be ‘absolutely no judgment, no shame, no stigma,’ ” Dr. Bradley emphasized. “We are the patient’s partners, and we are trying to help them have a healthy pregnancy. “

Opioid use in pregnancy spiked in recent decades

“Women have always been overrepresented when opioids are involved,” said Tricia E. Wright, MD, of the University of California, San Francisco.

Long-term studies have shown that, overall, women are more likely to be given opioids and given higher doses, compared with men, often for conditions in which opioids are not effective, she noted.

Women use substances differently than men; “they use them to cope with everyday life,” and a history of interpersonal violence and sexual assault are coming among women with opioid use disorders, said Dr. Wright.

The majority of women with opioid use disorders are of childbearing age, which has led to an increase in neonatal abstinence syndrome (NAS) said Dr. Wright.

She cited 2014 data from the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report showing an increase in NAS from 1.2 per 1,000 hospital births in 2000 to 5.8 per 1,000 hospital births in 2012. This increase has led to “misguided” efforts to prevent NAS through opioid detoxification, Dr. Wright said. She and colleagues conducted a systematic review in 2018 and found that, in fact, the evidence does not support detoxification as a recommended treatment intervention during pregnancy.

Opioid agonist therapy has multiple benefits for both the mother and fetus, Dr. Wright said. Maternal benefits include reduction in overdose-related deaths; decrease in the risk of HIV, hepatitis B, and hepatitis C; and increased engagement in prenatal care and recovery treatment. Fetal benefits include reduced fetal stress with the reduced fluctuations in maternal opioid levels, as well as decreases in intrauterine fetal death, intrauterine growth restriction, and preterm delivery.

“We know that relapse kills” because patients lose their tolerance, Dr. Wright said. “What we have seen is that overdose deaths are a leading cause of death in the postpartum period.”

When it comes to treatment, both methadone and buprenorphine are safe and effective options in pregnancy, she said. Treatment decisions should be made based on available options, patient preference, and a patient’s previous treatment experiences, as well as disease severity, social support, and the intensity of treatment needed.

“Whatever medicine you choose, it takes a village to coordinate the care,” Dr. Wright said. Maternal dose has no effect on neonatal withdrawal, so women should be encouraged to report any concerns. Either medication is compatible with breastfeeding. In fact, breastfeeding has many benefits in preventing neonatal withdrawal syndrome. Smoking cessation should be encouraged because it improves neonatal withdrawal.

Minimizing stigma is paramount, said Dr. Wright. “Substance use disorders are among the most stigmatized medical conditions, and pregnant women with substance use disorders are even more stigmatized.”

Clinicians can support patients by focusing on appropriate language, patients aren’t “addicts,” they are people with an opioid use disorder, she said.

Compassionate care for cannabis users

Cannabis use has a long history of association with women’s health, said Mishka Terplan, MD, MPH, of Friends Research Institute, Baltimore. Although cannabis use overall has increased steadily in recent years, data indicate that people who are pregnant are less likely to use cannabis than those who aren’t. The exception is that individuals who report using cannabis for medical purposes only remain consistent cannabis users during pregnancy.

“The concern is cannabis and birth outcomes, as well as developmental outcomes,” Dr. Terplan said. Multiple studies on this topic support several systematic reviews, and “depending on which decade you read, the results differ slightly.”

Reviews from the 1990s showed little to no effect on birth weight, but more recent studies, such as a meta-analysis published in BMJ Open in 2015, showed increased risk of neonatal outcomes such as low birth weight, anemia, and odds of admission to the neonatal ICU.

“The difference in these two eras is thought to be caused by the change in the definition of what cannabis is, and the potency has increased, and possibly therefore, as a consequence, we see outcomes we hadn’t seen before,” Dr. Terplan explained.

There is a concern with increased use and increased legalization that, there could be adverse effects on neonatal health, but recent studies in Colorado do not show a significant difference in neonatal outcomes before and after legalization, he said.

Data from pregnant women suggest that with regard to cannabis, they are concerned about their health, but they tend to seek information about cannabis use in pregnancy from family, friends, and the Internet rather than their health providers, said Dr. Terplan.

However, studies also show that providers tend to fall short and do a poor job of talking to pregnant patients about cannabis. When providers do discuss cannabis, they tend to focus on the legal aspects. “We are failing our patients when it comes to cannabis,” Dr. Terplan said. “We don’t provide the information and support they need and desire.” Instead, many providers “deploy urine drug testing, which we misinterpret.”

Dr. Terplan explained that point-of-care cannabis testing that shows “THC” is not measuring tetrahydrocannabinol, the psychoactive compound; rather it captures the nonpsychoactive metabolite of THC, one that sticks around for a long time in the biological compartment.

Dr. Terplan urged clinicians not to use urine tests as a default indicator of cannabis use, but instead, “we need to sit, listen, and work with our patients from a place of empathy.”
 

Questions answered

During a question-and-answer session following the panel, Dr. Bradley was asked about preconception counseling related to alcohol consumption.

“Preconception time is a perfect time to do screening, or offer contraception if a patient is a place where she doesn’t want to become pregnant or if she wants to take advantage of any therapeutic options to get well prior to pregnancy,” she said.

Dr. Wright responded to a question about the impact of punitive actions such as drug testing and incarceration. “These things decrease the chance that patients will get adequate prenatal care,” she said. “We need to advocate for our patients and advocate for changing drug laws.”

Dr. Terplan responded to a question about the impact of substance use on parenting. Parents use nicotine, alcohol, and also cannabis, he said. Data showing an association between substance use and cases of child abuse and neglect, “are of poor quality and do not support this association.”

Overall, “we need to have consistent messaging that we are not there to judge patients,” Dr. Bradley added. “The last thing we want is for patients not to be honest with us.”

Dr. Wright disclosed consulting fees from McKesson and royalties as the coauthor of a book, “Opioid-Use Disorders in Pregnancy.” Dr. Bradley had no financial conflicts to disclose. Dr. Terplan had no financial conflicts to disclose.

Women who use substances during pregnancy need support and education, not judgment, to promote the best outcomes, according to a panel of experts speaking at the 2020 virtual meeting of the American College of Obstetricians and Gynecologists. The panelists highlighted several key issues for addressing alcohol, opioids, and cannabis use by pregnant women.

No amount of alcohol is safe

Highwaystarz-Photography/Thinkstock

Many women believe that a limited amount of alcohol is safe during pregnancy, in part because of mixed messages in the media suggesting that light drinking is okay, according to Erin Tracy Bradley, MD, MPH, of Massachusetts General Hospital, Boston.

“We need to do a better job teaching our patients about the potential dangers of alcohol,” Dr. Bradley said in her presentation.

In fact, data suggest that women more at risk for an alcohol-exposed pregnancy are older and better educated. Dr. Bradley described the pattern of malformation for fetal alcohol syndrome (FAS) that includes small eyes, a thin upper lip, and smooth skin between the upper lip and nose.

“The only cause we know of [for FAS] is alcohol exposure intrauterine for the fetus,” so it is preventable with counseling and care, and thought to be the leading preventable cause of birth defects during pregnancies, she said.

The bottom line is that there is no safe amount of alcohol,” said Dr. Bradley. However, providers are inconsistent in discussing alcohol with their pregnant patients. In addition, universal screening is important because it is difficult to predict which women will be drinking during pregnancy.

Screening allows providers to quickly assess the severity of substance use, offer a brief intervention to raise patient awareness, and refer if necessary. “There should be ‘absolutely no judgment, no shame, no stigma,’ ” Dr. Bradley emphasized. “We are the patient’s partners, and we are trying to help them have a healthy pregnancy. “

Opioid use in pregnancy spiked in recent decades

“Women have always been overrepresented when opioids are involved,” said Tricia E. Wright, MD, of the University of California, San Francisco.

Long-term studies have shown that, overall, women are more likely to be given opioids and given higher doses, compared with men, often for conditions in which opioids are not effective, she noted.

Women use substances differently than men; “they use them to cope with everyday life,” and a history of interpersonal violence and sexual assault are coming among women with opioid use disorders, said Dr. Wright.

The majority of women with opioid use disorders are of childbearing age, which has led to an increase in neonatal abstinence syndrome (NAS) said Dr. Wright.

She cited 2014 data from the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report showing an increase in NAS from 1.2 per 1,000 hospital births in 2000 to 5.8 per 1,000 hospital births in 2012. This increase has led to “misguided” efforts to prevent NAS through opioid detoxification, Dr. Wright said. She and colleagues conducted a systematic review in 2018 and found that, in fact, the evidence does not support detoxification as a recommended treatment intervention during pregnancy.

Opioid agonist therapy has multiple benefits for both the mother and fetus, Dr. Wright said. Maternal benefits include reduction in overdose-related deaths; decrease in the risk of HIV, hepatitis B, and hepatitis C; and increased engagement in prenatal care and recovery treatment. Fetal benefits include reduced fetal stress with the reduced fluctuations in maternal opioid levels, as well as decreases in intrauterine fetal death, intrauterine growth restriction, and preterm delivery.

“We know that relapse kills” because patients lose their tolerance, Dr. Wright said. “What we have seen is that overdose deaths are a leading cause of death in the postpartum period.”

When it comes to treatment, both methadone and buprenorphine are safe and effective options in pregnancy, she said. Treatment decisions should be made based on available options, patient preference, and a patient’s previous treatment experiences, as well as disease severity, social support, and the intensity of treatment needed.

“Whatever medicine you choose, it takes a village to coordinate the care,” Dr. Wright said. Maternal dose has no effect on neonatal withdrawal, so women should be encouraged to report any concerns. Either medication is compatible with breastfeeding. In fact, breastfeeding has many benefits in preventing neonatal withdrawal syndrome. Smoking cessation should be encouraged because it improves neonatal withdrawal.

Minimizing stigma is paramount, said Dr. Wright. “Substance use disorders are among the most stigmatized medical conditions, and pregnant women with substance use disorders are even more stigmatized.”

Clinicians can support patients by focusing on appropriate language, patients aren’t “addicts,” they are people with an opioid use disorder, she said.

Compassionate care for cannabis users

Cannabis use has a long history of association with women’s health, said Mishka Terplan, MD, MPH, of Friends Research Institute, Baltimore. Although cannabis use overall has increased steadily in recent years, data indicate that people who are pregnant are less likely to use cannabis than those who aren’t. The exception is that individuals who report using cannabis for medical purposes only remain consistent cannabis users during pregnancy.

“The concern is cannabis and birth outcomes, as well as developmental outcomes,” Dr. Terplan said. Multiple studies on this topic support several systematic reviews, and “depending on which decade you read, the results differ slightly.”

Reviews from the 1990s showed little to no effect on birth weight, but more recent studies, such as a meta-analysis published in BMJ Open in 2015, showed increased risk of neonatal outcomes such as low birth weight, anemia, and odds of admission to the neonatal ICU.

“The difference in these two eras is thought to be caused by the change in the definition of what cannabis is, and the potency has increased, and possibly therefore, as a consequence, we see outcomes we hadn’t seen before,” Dr. Terplan explained.

There is a concern with increased use and increased legalization that, there could be adverse effects on neonatal health, but recent studies in Colorado do not show a significant difference in neonatal outcomes before and after legalization, he said.

Data from pregnant women suggest that with regard to cannabis, they are concerned about their health, but they tend to seek information about cannabis use in pregnancy from family, friends, and the Internet rather than their health providers, said Dr. Terplan.

However, studies also show that providers tend to fall short and do a poor job of talking to pregnant patients about cannabis. When providers do discuss cannabis, they tend to focus on the legal aspects. “We are failing our patients when it comes to cannabis,” Dr. Terplan said. “We don’t provide the information and support they need and desire.” Instead, many providers “deploy urine drug testing, which we misinterpret.”

Dr. Terplan explained that point-of-care cannabis testing that shows “THC” is not measuring tetrahydrocannabinol, the psychoactive compound; rather it captures the nonpsychoactive metabolite of THC, one that sticks around for a long time in the biological compartment.

Dr. Terplan urged clinicians not to use urine tests as a default indicator of cannabis use, but instead, “we need to sit, listen, and work with our patients from a place of empathy.”
 

Questions answered

During a question-and-answer session following the panel, Dr. Bradley was asked about preconception counseling related to alcohol consumption.

“Preconception time is a perfect time to do screening, or offer contraception if a patient is a place where she doesn’t want to become pregnant or if she wants to take advantage of any therapeutic options to get well prior to pregnancy,” she said.

Dr. Wright responded to a question about the impact of punitive actions such as drug testing and incarceration. “These things decrease the chance that patients will get adequate prenatal care,” she said. “We need to advocate for our patients and advocate for changing drug laws.”

Dr. Terplan responded to a question about the impact of substance use on parenting. Parents use nicotine, alcohol, and also cannabis, he said. Data showing an association between substance use and cases of child abuse and neglect, “are of poor quality and do not support this association.”

Overall, “we need to have consistent messaging that we are not there to judge patients,” Dr. Bradley added. “The last thing we want is for patients not to be honest with us.”

Dr. Wright disclosed consulting fees from McKesson and royalties as the coauthor of a book, “Opioid-Use Disorders in Pregnancy.” Dr. Bradley had no financial conflicts to disclose. Dr. Terplan had no financial conflicts to disclose.

About 20% of gestational carriers at one institution did not meet recommended criteria developed by the American Society for Reproductive Medicine, according to a retrospective study of 194 patients.

The University of California, San Francisco, offers additional, stricter recommendations, including that gestational carriers have a body mass index less than 35. Under these stricter criteria, about 30% of the gestational carriers did not meet recommendations, Brett Stark, MD, MPH, reported at the American Society for Reproductive Medicine’s 2020 annual meeting, held virtually this year.

Deviating from BMI or age recommendations may be associated with increased likelihood of spontaneous abortion, the analysis suggested. In addition, elements of a gestational carrier’s obstetric history not described in current guidelines, such as prior preterm birth, may influence gestational surrogacy outcomes.

The study was limited by incomplete information for some patients, the retrospective design, and the reliance on a relatively small cohort at a single center. Nevertheless, the findings potentially could inform discussions with patients, said Dr. Stark, a 3rd-year obstetrics and gynecology resident at the university.

Investigators aim to enroll patients in a longitudinal cohort study to further examine these questions, he said.

Protecting intended parents and carriers

“Gestational surrogacy has become an increasingly common form of third-party reproduction,” Dr. Stark said at the virtual meeting. The number of cases of in vitro fertilization (IVF) with gestational carriers increased from approximately 700 in 1999 to more than 5,500 in 2016, according to data from the Society for Assisted Reproductive Technology. “Despite the increasing prevalence of gestational carrier utilization, there remains limited guidance with regard to optimizing outcomes for both the intended parents and gestational carriers.”

ASRM and UCSF recommendations are based on expert opinion and include surprisingly little discussion about the prior pregnancy outcomes of potential gestational carriers, Dr. Stark said.

“It is important for all parties involved that we generate research and data that can help drive the development of the guidelines,” he said. Such evidence may help intended parents understand characteristics of gestational carriers that may lead to live births. “For the gestational carriers, it is important that we have information on safety so that they know they are making appropriate decisions for their family and their life.”

Gestational carrier characteristics in the present study that deviated from 2017 ASRM recommendations included age less than 21 years or greater than 45 years, mental health conditions, and having more than five prior deliveries.

“ASRM guidelines focused on criteria for gestational carriers are meant to protect infertile couples, the carrier, as well as the supporting agency,” Alan Penzias, MD, chair of ASRM’s Practice Committee who is in private practice in Boston, said in a society news release that highlighted Dr. Stark’s study. “It is important that gestational carriers have a complete medical history and examination, in addition to a psychological session with a mental health professional to ensure there are no reasons for the carrier to not move forward with pregnancy.”

A retrospective study by Kate Swanson, MD, and associates found that nonadherence to ASRM guidelines was associated with increased rates of cesarean delivery, neonatal morbidity, and preterm birth.

To examine how adherence to ASRM and UCSF recommendations relates to pregnancy outcomes and maternal and neonatal morbidity and death, Dr. Stark and colleagues assessed births from gestational carrier pregnancies at UCSF between 2008 and 2019.

Of 194 gestational carriers included in the analysis, 98.9% had a prior term pregnancy, 11.9% had a prior preterm pregnancy, and 17.5% had a prior spontaneous abortion.

Indications for use of gestational surrogates included serious medical condition of intended parent (25%), uterine factor infertility (23%), recurrent pregnancy loss (10%), and same-sex male couples (8%).

When the researchers compared pregnancy outcomes for gestational carriers who met ASRM guidelines with outcomes for 38 gestational carriers who did not meet ASRM guidelines, there were no statistically significant differences. Antepartum, intrapartum, and postpartum complication rates and cesarean delivery rates did not significantly differ based on ASRM guideline adherence.

Nonadherence to the stricter UCSF guidelines, however, was associated with increased likelihood of spontaneous abortion. In all, 23.7% of the 59 gestational carriers who were nonadherent to UCSF guidelines had a pregnancy end in a spontaneous abortion, compared with 6.7% of gestational carriers who were adherent to the UCSF recommendations (odds ratio, 4.35).

An analysis of individual criteria and poor pregnancy outcomes found that BMI greater than 35 was associated with increased likelihood of spontaneous abortion (OR, 4.29), as was age less than 21 years or greater than 45 years (OR, 3.37).

Prior spontaneous abortion was associated with increased likelihood of a biochemical pregnancy (OR, 3.2), and prior preterm birth was associated with increased likelihood of spontaneous abortion (OR, 3.19), previable delivery (OR, 25.2), cesarean delivery (OR, 2.59), and antepartum complications (OR, 3.56).
 

The role of agencies

About 76% of the gestational carriers had pregnancies mediated through a gestational surrogacy agency. Surrogates from agencies were about three times more likely than surrogates who were family, friends, or from private surrogacy arrangements to adhere to ASRM and UCSF guidelines.

Even after hearing about gestational carrier recommendations, patients may prefer to work with someone they know. “We want to provide our patients with evidence-based information if possible, but ultimately it is their decision to make,” Dr. Stark said. “And we just need to make sure that they are making an informed decision.”

Dr. Stark had no relevant disclosures. Dr. Penzias helped develop the ASRM committee opinion. He had no relevant conflicts of interest.

jremaly@mdedge.com

SOURCE: Stark B et al. ASRM 2020, Abstract O-251.

About 20% of gestational carriers at one institution did not meet recommended criteria developed by the American Society for Reproductive Medicine, according to a retrospective study of 194 patients.

The University of California, San Francisco, offers additional, stricter recommendations, including that gestational carriers have a body mass index less than 35. Under these stricter criteria, about 30% of the gestational carriers did not meet recommendations, Brett Stark, MD, MPH, reported at the American Society for Reproductive Medicine’s 2020 annual meeting, held virtually this year.

Deviating from BMI or age recommendations may be associated with increased likelihood of spontaneous abortion, the analysis suggested. In addition, elements of a gestational carrier’s obstetric history not described in current guidelines, such as prior preterm birth, may influence gestational surrogacy outcomes.

The study was limited by incomplete information for some patients, the retrospective design, and the reliance on a relatively small cohort at a single center. Nevertheless, the findings potentially could inform discussions with patients, said Dr. Stark, a 3rd-year obstetrics and gynecology resident at the university.

Investigators aim to enroll patients in a longitudinal cohort study to further examine these questions, he said.

Protecting intended parents and carriers

“Gestational surrogacy has become an increasingly common form of third-party reproduction,” Dr. Stark said at the virtual meeting. The number of cases of in vitro fertilization (IVF) with gestational carriers increased from approximately 700 in 1999 to more than 5,500 in 2016, according to data from the Society for Assisted Reproductive Technology. “Despite the increasing prevalence of gestational carrier utilization, there remains limited guidance with regard to optimizing outcomes for both the intended parents and gestational carriers.”

ASRM and UCSF recommendations are based on expert opinion and include surprisingly little discussion about the prior pregnancy outcomes of potential gestational carriers, Dr. Stark said.

“It is important for all parties involved that we generate research and data that can help drive the development of the guidelines,” he said. Such evidence may help intended parents understand characteristics of gestational carriers that may lead to live births. “For the gestational carriers, it is important that we have information on safety so that they know they are making appropriate decisions for their family and their life.”

Gestational carrier characteristics in the present study that deviated from 2017 ASRM recommendations included age less than 21 years or greater than 45 years, mental health conditions, and having more than five prior deliveries.

“ASRM guidelines focused on criteria for gestational carriers are meant to protect infertile couples, the carrier, as well as the supporting agency,” Alan Penzias, MD, chair of ASRM’s Practice Committee who is in private practice in Boston, said in a society news release that highlighted Dr. Stark’s study. “It is important that gestational carriers have a complete medical history and examination, in addition to a psychological session with a mental health professional to ensure there are no reasons for the carrier to not move forward with pregnancy.”

A retrospective study by Kate Swanson, MD, and associates found that nonadherence to ASRM guidelines was associated with increased rates of cesarean delivery, neonatal morbidity, and preterm birth.

To examine how adherence to ASRM and UCSF recommendations relates to pregnancy outcomes and maternal and neonatal morbidity and death, Dr. Stark and colleagues assessed births from gestational carrier pregnancies at UCSF between 2008 and 2019.

Of 194 gestational carriers included in the analysis, 98.9% had a prior term pregnancy, 11.9% had a prior preterm pregnancy, and 17.5% had a prior spontaneous abortion.

Indications for use of gestational surrogates included serious medical condition of intended parent (25%), uterine factor infertility (23%), recurrent pregnancy loss (10%), and same-sex male couples (8%).

When the researchers compared pregnancy outcomes for gestational carriers who met ASRM guidelines with outcomes for 38 gestational carriers who did not meet ASRM guidelines, there were no statistically significant differences. Antepartum, intrapartum, and postpartum complication rates and cesarean delivery rates did not significantly differ based on ASRM guideline adherence.

Nonadherence to the stricter UCSF guidelines, however, was associated with increased likelihood of spontaneous abortion. In all, 23.7% of the 59 gestational carriers who were nonadherent to UCSF guidelines had a pregnancy end in a spontaneous abortion, compared with 6.7% of gestational carriers who were adherent to the UCSF recommendations (odds ratio, 4.35).

An analysis of individual criteria and poor pregnancy outcomes found that BMI greater than 35 was associated with increased likelihood of spontaneous abortion (OR, 4.29), as was age less than 21 years or greater than 45 years (OR, 3.37).

Prior spontaneous abortion was associated with increased likelihood of a biochemical pregnancy (OR, 3.2), and prior preterm birth was associated with increased likelihood of spontaneous abortion (OR, 3.19), previable delivery (OR, 25.2), cesarean delivery (OR, 2.59), and antepartum complications (OR, 3.56).
 

The role of agencies

About 76% of the gestational carriers had pregnancies mediated through a gestational surrogacy agency. Surrogates from agencies were about three times more likely than surrogates who were family, friends, or from private surrogacy arrangements to adhere to ASRM and UCSF guidelines.

Even after hearing about gestational carrier recommendations, patients may prefer to work with someone they know. “We want to provide our patients with evidence-based information if possible, but ultimately it is their decision to make,” Dr. Stark said. “And we just need to make sure that they are making an informed decision.”

Dr. Stark had no relevant disclosures. Dr. Penzias helped develop the ASRM committee opinion. He had no relevant conflicts of interest.

jremaly@mdedge.com

SOURCE: Stark B et al. ASRM 2020, Abstract O-251.

About 20% of gestational carriers at one institution did not meet recommended criteria developed by the American Society for Reproductive Medicine, according to a retrospective study of 194 patients.

The University of California, San Francisco, offers additional, stricter recommendations, including that gestational carriers have a body mass index less than 35. Under these stricter criteria, about 30% of the gestational carriers did not meet recommendations, Brett Stark, MD, MPH, reported at the American Society for Reproductive Medicine’s 2020 annual meeting, held virtually this year.

Deviating from BMI or age recommendations may be associated with increased likelihood of spontaneous abortion, the analysis suggested. In addition, elements of a gestational carrier’s obstetric history not described in current guidelines, such as prior preterm birth, may influence gestational surrogacy outcomes.

The study was limited by incomplete information for some patients, the retrospective design, and the reliance on a relatively small cohort at a single center. Nevertheless, the findings potentially could inform discussions with patients, said Dr. Stark, a 3rd-year obstetrics and gynecology resident at the university.

Investigators aim to enroll patients in a longitudinal cohort study to further examine these questions, he said.

Protecting intended parents and carriers

“Gestational surrogacy has become an increasingly common form of third-party reproduction,” Dr. Stark said at the virtual meeting. The number of cases of in vitro fertilization (IVF) with gestational carriers increased from approximately 700 in 1999 to more than 5,500 in 2016, according to data from the Society for Assisted Reproductive Technology. “Despite the increasing prevalence of gestational carrier utilization, there remains limited guidance with regard to optimizing outcomes for both the intended parents and gestational carriers.”

ASRM and UCSF recommendations are based on expert opinion and include surprisingly little discussion about the prior pregnancy outcomes of potential gestational carriers, Dr. Stark said.

“It is important for all parties involved that we generate research and data that can help drive the development of the guidelines,” he said. Such evidence may help intended parents understand characteristics of gestational carriers that may lead to live births. “For the gestational carriers, it is important that we have information on safety so that they know they are making appropriate decisions for their family and their life.”

Gestational carrier characteristics in the present study that deviated from 2017 ASRM recommendations included age less than 21 years or greater than 45 years, mental health conditions, and having more than five prior deliveries.

“ASRM guidelines focused on criteria for gestational carriers are meant to protect infertile couples, the carrier, as well as the supporting agency,” Alan Penzias, MD, chair of ASRM’s Practice Committee who is in private practice in Boston, said in a society news release that highlighted Dr. Stark’s study. “It is important that gestational carriers have a complete medical history and examination, in addition to a psychological session with a mental health professional to ensure there are no reasons for the carrier to not move forward with pregnancy.”

A retrospective study by Kate Swanson, MD, and associates found that nonadherence to ASRM guidelines was associated with increased rates of cesarean delivery, neonatal morbidity, and preterm birth.

To examine how adherence to ASRM and UCSF recommendations relates to pregnancy outcomes and maternal and neonatal morbidity and death, Dr. Stark and colleagues assessed births from gestational carrier pregnancies at UCSF between 2008 and 2019.

Of 194 gestational carriers included in the analysis, 98.9% had a prior term pregnancy, 11.9% had a prior preterm pregnancy, and 17.5% had a prior spontaneous abortion.

Indications for use of gestational surrogates included serious medical condition of intended parent (25%), uterine factor infertility (23%), recurrent pregnancy loss (10%), and same-sex male couples (8%).

When the researchers compared pregnancy outcomes for gestational carriers who met ASRM guidelines with outcomes for 38 gestational carriers who did not meet ASRM guidelines, there were no statistically significant differences. Antepartum, intrapartum, and postpartum complication rates and cesarean delivery rates did not significantly differ based on ASRM guideline adherence.

Nonadherence to the stricter UCSF guidelines, however, was associated with increased likelihood of spontaneous abortion. In all, 23.7% of the 59 gestational carriers who were nonadherent to UCSF guidelines had a pregnancy end in a spontaneous abortion, compared with 6.7% of gestational carriers who were adherent to the UCSF recommendations (odds ratio, 4.35).

An analysis of individual criteria and poor pregnancy outcomes found that BMI greater than 35 was associated with increased likelihood of spontaneous abortion (OR, 4.29), as was age less than 21 years or greater than 45 years (OR, 3.37).

Prior spontaneous abortion was associated with increased likelihood of a biochemical pregnancy (OR, 3.2), and prior preterm birth was associated with increased likelihood of spontaneous abortion (OR, 3.19), previable delivery (OR, 25.2), cesarean delivery (OR, 2.59), and antepartum complications (OR, 3.56).
 

The role of agencies

About 76% of the gestational carriers had pregnancies mediated through a gestational surrogacy agency. Surrogates from agencies were about three times more likely than surrogates who were family, friends, or from private surrogacy arrangements to adhere to ASRM and UCSF guidelines.

Even after hearing about gestational carrier recommendations, patients may prefer to work with someone they know. “We want to provide our patients with evidence-based information if possible, but ultimately it is their decision to make,” Dr. Stark said. “And we just need to make sure that they are making an informed decision.”

Dr. Stark had no relevant disclosures. Dr. Penzias helped develop the ASRM committee opinion. He had no relevant conflicts of interest.

jremaly@mdedge.com

SOURCE: Stark B et al. ASRM 2020, Abstract O-251.

COVID-19 vaccines should not be withheld from people who are pregnant or lactating and want to be vaccinated, despite a lack of safety data in these populations, according to guidance from the Centers for Disease Control and Prevention, the American College of Obstetricians and Gynecologists, and the Society for Maternal-Fetal Medicine.

Thye Aun Ngo/Fotolia.com

Pregnant women who opt not to receive the vaccine should be supported in that decision as well, a practice advisory from ACOG recommends.

“Pregnant women who experience fever following vaccination should be counseled to take acetaminophen,” the advisory notes.

In addition, women do not need to avoid pregnancy after receiving the Pfizer-BioNTech COVID-19 vaccine, according to the CDC’s interim clinical considerations for its use. The U.S. Food and Drug Administration issued an emergency use authorization for the vaccine on Dec. 11.

Although investigators excluded pregnant women from clinical trials, experts believe that mRNA vaccines, which are not live vaccines, “are unlikely to pose a risk for people who are pregnant” and “are not thought to be a risk to the breastfeeding infant,” the CDC notes.

Meanwhile, women who are pregnant may be at greater risk of severe COVID-19, even though the absolute risk of severe illness is low. COVID-19 also may increase the risk of adverse pregnancy outcomes, such as preterm birth, although the data have been mixed with some studies finding an association and others not.

“If pregnant people are part of a group that is recommended to receive a COVID-19 vaccine (e.g., health care personnel), they may choose to be vaccinated,” the CDC advises. “A conversation between the patient and their clinical team may assist with decisions regarding the use of vaccines approved under EUA for the prevention of COVID-19. While a conversation with a health care provider may be helpful, it is not required prior to vaccination.”
 

Acknowledging side effects and uncertainty

ACOG’s advisory reiterates that approach. The group notes that, based on the mRNA vaccine’s mechanism of action and its safety and efficacy in clinical trials, “it is expected that the safety and efficacy profile of the vaccine for pregnant individuals would be similar to that observed in nonpregnant individuals ... That said, there are no safety data specific to mRNA vaccine use in pregnant or lactating individuals and the potential risks to a pregnant individual and the fetus are unknown.” 

In clinical trials, most participants experienced mild influenza-like symptoms following vaccination, including injection site reactions, fatigue, chills, muscle and joint pain, and headache. Among participants aged 18-55 years, fever greater than 38°C occurred in 3.7% of participants after the first dose and in 15.8% after the second dose. Most symptoms resolved within a few days. 

Women who are pregnant should treat fever with acetaminophen because “fever has been associated with adverse pregnancy outcomes,” according to the ACOG guidance. “Acetaminophen has been proven to be safe for use in pregnancy and does not appear to impact antibody response to COVID-19 vaccines.” Patients may treat other vaccine side effects, such as injection-site soreness with acetaminophen as well.

When counseling patients, clinicians should explain that side effects are a normal part of developing antibodies to protect against COVID-19. “Regardless of their decision,” the group says, “these conversations provide an opportunity to remind patients about the importance of other prevention measures such as hand washing, physical distancing, and wearing a mask.”
 

More data expected

Data from developmental and reproductive toxicity studies in animals are expected soon, the CDC said. In addition, the manufacturer is following clinical trial participants who became pregnant during the study. 

Women who are pregnant and their physicians should weigh factors such as the extent of COVID-19 transmission in the community, the patient’s risk of contracting COVID-19, risks of COVID-19 to the patient and fetus, vaccine efficacy and side effects, and the lack of data about COVID-19 vaccination during pregnancy.

The Society for Maternal-Fetal Medicine recommends that pregnant and lactating women have access to COVID-19 vaccines in general and has advocated for the inclusion of women who are pregnant or lactating in vaccine trials. The society has suggested that health care professionals “counsel their patients that the theoretical risk of fetal harm from mRNA vaccines is very low.” It published resources this week for physicians and patients focused on COVID-19 vaccination and pregnancy.

In a review published online Dec. 10 in the American Journal of Obstetrics & Gynecology MFM, Amanda M. Craig, MD, of Duke University Health System in Durham, N.C., and coauthors note that there “is a theoretical risk for fetal harm from any untested medical intervention and this is no different for COVID-19 vaccines.”

“Pregnant individuals should be given the opportunity, along with their obstetric provider, to weigh the potential risk of severe maternal disease against the unknown risk of fetal exposure, and make an autonomous decision about whether or not to accept vaccine until pregnancy safety data are available,” they write.

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

COVID-19 vaccines should not be withheld from people who are pregnant or lactating and want to be vaccinated, despite a lack of safety data in these populations, according to guidance from the Centers for Disease Control and Prevention, the American College of Obstetricians and Gynecologists, and the Society for Maternal-Fetal Medicine.

Thye Aun Ngo/Fotolia.com

Pregnant women who opt not to receive the vaccine should be supported in that decision as well, a practice advisory from ACOG recommends.

“Pregnant women who experience fever following vaccination should be counseled to take acetaminophen,” the advisory notes.

In addition, women do not need to avoid pregnancy after receiving the Pfizer-BioNTech COVID-19 vaccine, according to the CDC’s interim clinical considerations for its use. The U.S. Food and Drug Administration issued an emergency use authorization for the vaccine on Dec. 11.

Although investigators excluded pregnant women from clinical trials, experts believe that mRNA vaccines, which are not live vaccines, “are unlikely to pose a risk for people who are pregnant” and “are not thought to be a risk to the breastfeeding infant,” the CDC notes.

Meanwhile, women who are pregnant may be at greater risk of severe COVID-19, even though the absolute risk of severe illness is low. COVID-19 also may increase the risk of adverse pregnancy outcomes, such as preterm birth, although the data have been mixed with some studies finding an association and others not.

“If pregnant people are part of a group that is recommended to receive a COVID-19 vaccine (e.g., health care personnel), they may choose to be vaccinated,” the CDC advises. “A conversation between the patient and their clinical team may assist with decisions regarding the use of vaccines approved under EUA for the prevention of COVID-19. While a conversation with a health care provider may be helpful, it is not required prior to vaccination.”
 

Acknowledging side effects and uncertainty

ACOG’s advisory reiterates that approach. The group notes that, based on the mRNA vaccine’s mechanism of action and its safety and efficacy in clinical trials, “it is expected that the safety and efficacy profile of the vaccine for pregnant individuals would be similar to that observed in nonpregnant individuals ... That said, there are no safety data specific to mRNA vaccine use in pregnant or lactating individuals and the potential risks to a pregnant individual and the fetus are unknown.” 

In clinical trials, most participants experienced mild influenza-like symptoms following vaccination, including injection site reactions, fatigue, chills, muscle and joint pain, and headache. Among participants aged 18-55 years, fever greater than 38°C occurred in 3.7% of participants after the first dose and in 15.8% after the second dose. Most symptoms resolved within a few days. 

Women who are pregnant should treat fever with acetaminophen because “fever has been associated with adverse pregnancy outcomes,” according to the ACOG guidance. “Acetaminophen has been proven to be safe for use in pregnancy and does not appear to impact antibody response to COVID-19 vaccines.” Patients may treat other vaccine side effects, such as injection-site soreness with acetaminophen as well.

When counseling patients, clinicians should explain that side effects are a normal part of developing antibodies to protect against COVID-19. “Regardless of their decision,” the group says, “these conversations provide an opportunity to remind patients about the importance of other prevention measures such as hand washing, physical distancing, and wearing a mask.”
 

More data expected

Data from developmental and reproductive toxicity studies in animals are expected soon, the CDC said. In addition, the manufacturer is following clinical trial participants who became pregnant during the study. 

Women who are pregnant and their physicians should weigh factors such as the extent of COVID-19 transmission in the community, the patient’s risk of contracting COVID-19, risks of COVID-19 to the patient and fetus, vaccine efficacy and side effects, and the lack of data about COVID-19 vaccination during pregnancy.

The Society for Maternal-Fetal Medicine recommends that pregnant and lactating women have access to COVID-19 vaccines in general and has advocated for the inclusion of women who are pregnant or lactating in vaccine trials. The society has suggested that health care professionals “counsel their patients that the theoretical risk of fetal harm from mRNA vaccines is very low.” It published resources this week for physicians and patients focused on COVID-19 vaccination and pregnancy.

In a review published online Dec. 10 in the American Journal of Obstetrics & Gynecology MFM, Amanda M. Craig, MD, of Duke University Health System in Durham, N.C., and coauthors note that there “is a theoretical risk for fetal harm from any untested medical intervention and this is no different for COVID-19 vaccines.”

“Pregnant individuals should be given the opportunity, along with their obstetric provider, to weigh the potential risk of severe maternal disease against the unknown risk of fetal exposure, and make an autonomous decision about whether or not to accept vaccine until pregnancy safety data are available,” they write.

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

COVID-19 vaccines should not be withheld from people who are pregnant or lactating and want to be vaccinated, despite a lack of safety data in these populations, according to guidance from the Centers for Disease Control and Prevention, the American College of Obstetricians and Gynecologists, and the Society for Maternal-Fetal Medicine.

Thye Aun Ngo/Fotolia.com

Pregnant women who opt not to receive the vaccine should be supported in that decision as well, a practice advisory from ACOG recommends.

“Pregnant women who experience fever following vaccination should be counseled to take acetaminophen,” the advisory notes.

In addition, women do not need to avoid pregnancy after receiving the Pfizer-BioNTech COVID-19 vaccine, according to the CDC’s interim clinical considerations for its use. The U.S. Food and Drug Administration issued an emergency use authorization for the vaccine on Dec. 11.

Although investigators excluded pregnant women from clinical trials, experts believe that mRNA vaccines, which are not live vaccines, “are unlikely to pose a risk for people who are pregnant” and “are not thought to be a risk to the breastfeeding infant,” the CDC notes.

Meanwhile, women who are pregnant may be at greater risk of severe COVID-19, even though the absolute risk of severe illness is low. COVID-19 also may increase the risk of adverse pregnancy outcomes, such as preterm birth, although the data have been mixed with some studies finding an association and others not.

“If pregnant people are part of a group that is recommended to receive a COVID-19 vaccine (e.g., health care personnel), they may choose to be vaccinated,” the CDC advises. “A conversation between the patient and their clinical team may assist with decisions regarding the use of vaccines approved under EUA for the prevention of COVID-19. While a conversation with a health care provider may be helpful, it is not required prior to vaccination.”
 

Acknowledging side effects and uncertainty

ACOG’s advisory reiterates that approach. The group notes that, based on the mRNA vaccine’s mechanism of action and its safety and efficacy in clinical trials, “it is expected that the safety and efficacy profile of the vaccine for pregnant individuals would be similar to that observed in nonpregnant individuals ... That said, there are no safety data specific to mRNA vaccine use in pregnant or lactating individuals and the potential risks to a pregnant individual and the fetus are unknown.” 

In clinical trials, most participants experienced mild influenza-like symptoms following vaccination, including injection site reactions, fatigue, chills, muscle and joint pain, and headache. Among participants aged 18-55 years, fever greater than 38°C occurred in 3.7% of participants after the first dose and in 15.8% after the second dose. Most symptoms resolved within a few days. 

Women who are pregnant should treat fever with acetaminophen because “fever has been associated with adverse pregnancy outcomes,” according to the ACOG guidance. “Acetaminophen has been proven to be safe for use in pregnancy and does not appear to impact antibody response to COVID-19 vaccines.” Patients may treat other vaccine side effects, such as injection-site soreness with acetaminophen as well.

When counseling patients, clinicians should explain that side effects are a normal part of developing antibodies to protect against COVID-19. “Regardless of their decision,” the group says, “these conversations provide an opportunity to remind patients about the importance of other prevention measures such as hand washing, physical distancing, and wearing a mask.”
 

More data expected

Data from developmental and reproductive toxicity studies in animals are expected soon, the CDC said. In addition, the manufacturer is following clinical trial participants who became pregnant during the study. 

Women who are pregnant and their physicians should weigh factors such as the extent of COVID-19 transmission in the community, the patient’s risk of contracting COVID-19, risks of COVID-19 to the patient and fetus, vaccine efficacy and side effects, and the lack of data about COVID-19 vaccination during pregnancy.

The Society for Maternal-Fetal Medicine recommends that pregnant and lactating women have access to COVID-19 vaccines in general and has advocated for the inclusion of women who are pregnant or lactating in vaccine trials. The society has suggested that health care professionals “counsel their patients that the theoretical risk of fetal harm from mRNA vaccines is very low.” It published resources this week for physicians and patients focused on COVID-19 vaccination and pregnancy.

In a review published online Dec. 10 in the American Journal of Obstetrics & Gynecology MFM, Amanda M. Craig, MD, of Duke University Health System in Durham, N.C., and coauthors note that there “is a theoretical risk for fetal harm from any untested medical intervention and this is no different for COVID-19 vaccines.”

“Pregnant individuals should be given the opportunity, along with their obstetric provider, to weigh the potential risk of severe maternal disease against the unknown risk of fetal exposure, and make an autonomous decision about whether or not to accept vaccine until pregnancy safety data are available,” they write.

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

What is more stressful in the mind of a patient – a diagnosis of cancer or infertility? An infertile woman’s anxiety and depression scores are equivalent to one with cancer (J Psychosom Obstet Gynecol. 1993;14 Suppl:45-52). These two diseases intersect in the burgeoning field of oncofertility, the collaboration of oncology with reproductive endocrinology to offer patients the option of fertility preservation. The term oncofertility was first coined by Teresa Woodruff, PhD, in 2005 during her invited lecture at the University of Calgary symposium called “Pushing the Boundaries – Advances that Will Change the World in 20 Years.” Her prediction has reached its fruition. This article will review fertility preservation options for female oncology patients.

The ability for oncofertility to exist is the result of improved cancer survival rates and advances in reproductive medicine. Improvements in the treatment of cancer enable many young women to survive and focus on the potential of having a family. Malignancies striking young people, particularly breast, lymphoma, and melanoma, have encouraging 5-year survival rates. If invasive cancer is located only in the breast (affecting 62% of women diagnosed), the 5-year survival rate is 99%. For all with Hodgkin lymphoma, the 5-year survival is 87%, increasing to 92% if the cancer is found in its earliest stages. Among all people with melanoma of the skin, from the time of initial diagnosis, the 5-year survival is 92%.

Long-term survival is expected for 80% of children and adolescents diagnosed with cancer (Obstet Gynecol. 2010;116: 1171-83).
 

Iatrogenic effects

The reproductive risk of cancer treatment is gonadotoxicity and the subsequent iatrogenic primary ovarian insufficiency (POI, prior termed premature ovarian failure) or infertility.

Chemotherapy with alkylating agents, such as cyclophosphamide, is associated with the greatest chance of amenorrhea (Breast Cancer Res Treat. 2014;145:113-28). Chemotherapy with cyclophosphamide, methotrexate, and 5 fluorouracil (CMF – commonly used for the treatment of breast cancer) will usually result in loss of ovarian function in 33% of women under age 30, 50% of women aged 30-35, 75% of women aged 35-40, and 95% of women over age 40 (J Clin Oncol. 2006;24:5769-79).

The dose at which 50% of oocytes are lost due to radiation is under 2 Gy (Hum Reprod. 2003;18:117-21). Unfortunately, the minimum dose decreases with advancing age of the woman, contributed by natural diminishing reserve and an increase in radiosensitivity of oocytes. Age, proximity of the radiation field to the ovaries, and total dose are important factors determining risk of POI. For brain tumors, cranial irradiation may result in hypothalamic amenorrhea.
 

Protection

The use of GnRH agonist for 6 months during chemotherapy has been controversial with mixed results in avoiding ovarian failure. A recent study suggests a GnRH agonist does reduce the prevalence of POI (J Clin Oncol. 2018;36:1981-90) in women treated for breast cancer but the subsequent ovarian reserve is low (Ann Oncol. 2017;28:1811-6). There are not enough data now to consider this the sole viable option for all patients to preserve fertility.

Patients requiring local pelvic radiation treatment may benefit from transposition of the ovaries to sites away from maximal radiation exposure.
 

Oocyte cryopreservation (OC) and ovarian tissue cryopreservation (OTC)

Since 2012, the American Society for Reproductive Medicine lifted the experimental designation on OC and, last year, the society removed the same label for OTC, providing an additional fertility preservation option.

Ovarian stimulation and egg retrieval for OC can now occur literally within 2 weeks because of a random start protocol whereby women are stimulated any day in their cycle, pre- and post ovulation. Studies have shown equivalent yield of oocytes.

OC followed by thawing for subsequent fertilization and embryo transfer is employed as a routine matter with egg donation cycles. While there remains debate over whether live birth rates using frozen eggs are inferior to fresh eggs, a learning curve with the new technology may be the important factor (Obstet Gynecol. 2020;135:709-16).

When urgent cancer treatment precludes ovarian stimulation for OC, then OTC is a viable option. Another population that could benefit from OTC are prepubertal girls facing gonadotoxic therapy. More research is required to determine the quality of eggs obtained through ovarian stimulation in adolescent and young adult patients. While leukemic patients are eligible for OTC, there is concern about reseeding malignant cells with future autologous transplantation of tissue.

OTC involves obtaining ovarian cortical tissue, dissecting the tissue into small fragments, and cryopreserving it using either a slow-cool technique or vitrification. Orthotopic transplantation has been the most successful method for using ovarian tissue in humans. To date, live birth rates are modest (Fertil Steril. 2015;104:1097-8).

Recent research has combined the freezing of both mature and immature eggs, the latter undergoing IVM (in-vitro maturation) to maximize the potential for fertilizable eggs. Women with polycystic ovary syndrome and certain cancers or medical conditions that warrant avoiding supraphysiologic levels of estradiol from ovarian stimulation, may benefit from the retrieval of immature eggs from unstimulated ovaries.

Pregnancy outcomes using embryos created from ovaries recently exposed to chemotherapy in humans are not known but animal studies suggest there may be higher rates of miscarriage and birth defects.
 

Breast cancer – a special scenario

With every breast cancer patient, I review the theoretical concern over increasing estradiol levels during an IVF stimulation cycle with the potential impact on her cancer prognosis. Fortunately, the literature has not demonstrated an increased risk of breast cancer or recurrence after undergoing an IVF cycle. Currently, the use of aromatase inhibitors with gonadotropins along with a GnRH-antagonist is the protocol to maintain a lower estradiol level during stimulation, which may be of benefit for breast cancer prognosis. The use of aromatase inhibitors is an off-label indication for fertility with no definitive evidence of teratogenicity. Preimplantation genetic testing of embryos is available and approved by the American Society for Reproductive Medicine for BRCA gene mutation patients.

Oncofertility is an exciting field to allow cancer survivors the option for a biological child. We recommend all our cancer patients meet with our reproductive psychologist to assist in coping with the overwhelming information presented in a short time frame.
 

Dr. Trolice is director of Fertility CARE – The IVF Center in Winter Park, Fla., and associate professor of obstetrics and gynecology at the University of Central Florida, Orlando.

What is more stressful in the mind of a patient – a diagnosis of cancer or infertility? An infertile woman’s anxiety and depression scores are equivalent to one with cancer (J Psychosom Obstet Gynecol. 1993;14 Suppl:45-52). These two diseases intersect in the burgeoning field of oncofertility, the collaboration of oncology with reproductive endocrinology to offer patients the option of fertility preservation. The term oncofertility was first coined by Teresa Woodruff, PhD, in 2005 during her invited lecture at the University of Calgary symposium called “Pushing the Boundaries – Advances that Will Change the World in 20 Years.” Her prediction has reached its fruition. This article will review fertility preservation options for female oncology patients.

The ability for oncofertility to exist is the result of improved cancer survival rates and advances in reproductive medicine. Improvements in the treatment of cancer enable many young women to survive and focus on the potential of having a family. Malignancies striking young people, particularly breast, lymphoma, and melanoma, have encouraging 5-year survival rates. If invasive cancer is located only in the breast (affecting 62% of women diagnosed), the 5-year survival rate is 99%. For all with Hodgkin lymphoma, the 5-year survival is 87%, increasing to 92% if the cancer is found in its earliest stages. Among all people with melanoma of the skin, from the time of initial diagnosis, the 5-year survival is 92%.

Long-term survival is expected for 80% of children and adolescents diagnosed with cancer (Obstet Gynecol. 2010;116: 1171-83).
 

Iatrogenic effects

The reproductive risk of cancer treatment is gonadotoxicity and the subsequent iatrogenic primary ovarian insufficiency (POI, prior termed premature ovarian failure) or infertility.

Chemotherapy with alkylating agents, such as cyclophosphamide, is associated with the greatest chance of amenorrhea (Breast Cancer Res Treat. 2014;145:113-28). Chemotherapy with cyclophosphamide, methotrexate, and 5 fluorouracil (CMF – commonly used for the treatment of breast cancer) will usually result in loss of ovarian function in 33% of women under age 30, 50% of women aged 30-35, 75% of women aged 35-40, and 95% of women over age 40 (J Clin Oncol. 2006;24:5769-79).

The dose at which 50% of oocytes are lost due to radiation is under 2 Gy (Hum Reprod. 2003;18:117-21). Unfortunately, the minimum dose decreases with advancing age of the woman, contributed by natural diminishing reserve and an increase in radiosensitivity of oocytes. Age, proximity of the radiation field to the ovaries, and total dose are important factors determining risk of POI. For brain tumors, cranial irradiation may result in hypothalamic amenorrhea.
 

Protection

The use of GnRH agonist for 6 months during chemotherapy has been controversial with mixed results in avoiding ovarian failure. A recent study suggests a GnRH agonist does reduce the prevalence of POI (J Clin Oncol. 2018;36:1981-90) in women treated for breast cancer but the subsequent ovarian reserve is low (Ann Oncol. 2017;28:1811-6). There are not enough data now to consider this the sole viable option for all patients to preserve fertility.

Patients requiring local pelvic radiation treatment may benefit from transposition of the ovaries to sites away from maximal radiation exposure.
 

Oocyte cryopreservation (OC) and ovarian tissue cryopreservation (OTC)

Since 2012, the American Society for Reproductive Medicine lifted the experimental designation on OC and, last year, the society removed the same label for OTC, providing an additional fertility preservation option.

Ovarian stimulation and egg retrieval for OC can now occur literally within 2 weeks because of a random start protocol whereby women are stimulated any day in their cycle, pre- and post ovulation. Studies have shown equivalent yield of oocytes.

OC followed by thawing for subsequent fertilization and embryo transfer is employed as a routine matter with egg donation cycles. While there remains debate over whether live birth rates using frozen eggs are inferior to fresh eggs, a learning curve with the new technology may be the important factor (Obstet Gynecol. 2020;135:709-16).

When urgent cancer treatment precludes ovarian stimulation for OC, then OTC is a viable option. Another population that could benefit from OTC are prepubertal girls facing gonadotoxic therapy. More research is required to determine the quality of eggs obtained through ovarian stimulation in adolescent and young adult patients. While leukemic patients are eligible for OTC, there is concern about reseeding malignant cells with future autologous transplantation of tissue.

OTC involves obtaining ovarian cortical tissue, dissecting the tissue into small fragments, and cryopreserving it using either a slow-cool technique or vitrification. Orthotopic transplantation has been the most successful method for using ovarian tissue in humans. To date, live birth rates are modest (Fertil Steril. 2015;104:1097-8).

Recent research has combined the freezing of both mature and immature eggs, the latter undergoing IVM (in-vitro maturation) to maximize the potential for fertilizable eggs. Women with polycystic ovary syndrome and certain cancers or medical conditions that warrant avoiding supraphysiologic levels of estradiol from ovarian stimulation, may benefit from the retrieval of immature eggs from unstimulated ovaries.

Pregnancy outcomes using embryos created from ovaries recently exposed to chemotherapy in humans are not known but animal studies suggest there may be higher rates of miscarriage and birth defects.
 

Breast cancer – a special scenario

With every breast cancer patient, I review the theoretical concern over increasing estradiol levels during an IVF stimulation cycle with the potential impact on her cancer prognosis. Fortunately, the literature has not demonstrated an increased risk of breast cancer or recurrence after undergoing an IVF cycle. Currently, the use of aromatase inhibitors with gonadotropins along with a GnRH-antagonist is the protocol to maintain a lower estradiol level during stimulation, which may be of benefit for breast cancer prognosis. The use of aromatase inhibitors is an off-label indication for fertility with no definitive evidence of teratogenicity. Preimplantation genetic testing of embryos is available and approved by the American Society for Reproductive Medicine for BRCA gene mutation patients.

Oncofertility is an exciting field to allow cancer survivors the option for a biological child. We recommend all our cancer patients meet with our reproductive psychologist to assist in coping with the overwhelming information presented in a short time frame.
 

Dr. Trolice is director of Fertility CARE – The IVF Center in Winter Park, Fla., and associate professor of obstetrics and gynecology at the University of Central Florida, Orlando.

What is more stressful in the mind of a patient – a diagnosis of cancer or infertility? An infertile woman’s anxiety and depression scores are equivalent to one with cancer (J Psychosom Obstet Gynecol. 1993;14 Suppl:45-52). These two diseases intersect in the burgeoning field of oncofertility, the collaboration of oncology with reproductive endocrinology to offer patients the option of fertility preservation. The term oncofertility was first coined by Teresa Woodruff, PhD, in 2005 during her invited lecture at the University of Calgary symposium called “Pushing the Boundaries – Advances that Will Change the World in 20 Years.” Her prediction has reached its fruition. This article will review fertility preservation options for female oncology patients.

The ability for oncofertility to exist is the result of improved cancer survival rates and advances in reproductive medicine. Improvements in the treatment of cancer enable many young women to survive and focus on the potential of having a family. Malignancies striking young people, particularly breast, lymphoma, and melanoma, have encouraging 5-year survival rates. If invasive cancer is located only in the breast (affecting 62% of women diagnosed), the 5-year survival rate is 99%. For all with Hodgkin lymphoma, the 5-year survival is 87%, increasing to 92% if the cancer is found in its earliest stages. Among all people with melanoma of the skin, from the time of initial diagnosis, the 5-year survival is 92%.

Long-term survival is expected for 80% of children and adolescents diagnosed with cancer (Obstet Gynecol. 2010;116: 1171-83).
 

Iatrogenic effects

The reproductive risk of cancer treatment is gonadotoxicity and the subsequent iatrogenic primary ovarian insufficiency (POI, prior termed premature ovarian failure) or infertility.

Chemotherapy with alkylating agents, such as cyclophosphamide, is associated with the greatest chance of amenorrhea (Breast Cancer Res Treat. 2014;145:113-28). Chemotherapy with cyclophosphamide, methotrexate, and 5 fluorouracil (CMF – commonly used for the treatment of breast cancer) will usually result in loss of ovarian function in 33% of women under age 30, 50% of women aged 30-35, 75% of women aged 35-40, and 95% of women over age 40 (J Clin Oncol. 2006;24:5769-79).

The dose at which 50% of oocytes are lost due to radiation is under 2 Gy (Hum Reprod. 2003;18:117-21). Unfortunately, the minimum dose decreases with advancing age of the woman, contributed by natural diminishing reserve and an increase in radiosensitivity of oocytes. Age, proximity of the radiation field to the ovaries, and total dose are important factors determining risk of POI. For brain tumors, cranial irradiation may result in hypothalamic amenorrhea.
 

Protection

The use of GnRH agonist for 6 months during chemotherapy has been controversial with mixed results in avoiding ovarian failure. A recent study suggests a GnRH agonist does reduce the prevalence of POI (J Clin Oncol. 2018;36:1981-90) in women treated for breast cancer but the subsequent ovarian reserve is low (Ann Oncol. 2017;28:1811-6). There are not enough data now to consider this the sole viable option for all patients to preserve fertility.

Patients requiring local pelvic radiation treatment may benefit from transposition of the ovaries to sites away from maximal radiation exposure.
 

Oocyte cryopreservation (OC) and ovarian tissue cryopreservation (OTC)

Since 2012, the American Society for Reproductive Medicine lifted the experimental designation on OC and, last year, the society removed the same label for OTC, providing an additional fertility preservation option.

Ovarian stimulation and egg retrieval for OC can now occur literally within 2 weeks because of a random start protocol whereby women are stimulated any day in their cycle, pre- and post ovulation. Studies have shown equivalent yield of oocytes.

OC followed by thawing for subsequent fertilization and embryo transfer is employed as a routine matter with egg donation cycles. While there remains debate over whether live birth rates using frozen eggs are inferior to fresh eggs, a learning curve with the new technology may be the important factor (Obstet Gynecol. 2020;135:709-16).

When urgent cancer treatment precludes ovarian stimulation for OC, then OTC is a viable option. Another population that could benefit from OTC are prepubertal girls facing gonadotoxic therapy. More research is required to determine the quality of eggs obtained through ovarian stimulation in adolescent and young adult patients. While leukemic patients are eligible for OTC, there is concern about reseeding malignant cells with future autologous transplantation of tissue.

OTC involves obtaining ovarian cortical tissue, dissecting the tissue into small fragments, and cryopreserving it using either a slow-cool technique or vitrification. Orthotopic transplantation has been the most successful method for using ovarian tissue in humans. To date, live birth rates are modest (Fertil Steril. 2015;104:1097-8).

Recent research has combined the freezing of both mature and immature eggs, the latter undergoing IVM (in-vitro maturation) to maximize the potential for fertilizable eggs. Women with polycystic ovary syndrome and certain cancers or medical conditions that warrant avoiding supraphysiologic levels of estradiol from ovarian stimulation, may benefit from the retrieval of immature eggs from unstimulated ovaries.

Pregnancy outcomes using embryos created from ovaries recently exposed to chemotherapy in humans are not known but animal studies suggest there may be higher rates of miscarriage and birth defects.
 

Breast cancer – a special scenario

With every breast cancer patient, I review the theoretical concern over increasing estradiol levels during an IVF stimulation cycle with the potential impact on her cancer prognosis. Fortunately, the literature has not demonstrated an increased risk of breast cancer or recurrence after undergoing an IVF cycle. Currently, the use of aromatase inhibitors with gonadotropins along with a GnRH-antagonist is the protocol to maintain a lower estradiol level during stimulation, which may be of benefit for breast cancer prognosis. The use of aromatase inhibitors is an off-label indication for fertility with no definitive evidence of teratogenicity. Preimplantation genetic testing of embryos is available and approved by the American Society for Reproductive Medicine for BRCA gene mutation patients.

Oncofertility is an exciting field to allow cancer survivors the option for a biological child. We recommend all our cancer patients meet with our reproductive psychologist to assist in coping with the overwhelming information presented in a short time frame.
 

Dr. Trolice is director of Fertility CARE – The IVF Center in Winter Park, Fla., and associate professor of obstetrics and gynecology at the University of Central Florida, Orlando.

With increasing whooping cough numbers, developing an effective new vaccine against Bordetella pertussis is a priority. Results from the multifactorial PERISCOPE Project will help scientists and clinicians move forward.

MarianVejcik/Getty Images

Dominic Kelly, PhD, talked about vaccine-induced immunity and provided an overview of ongoing clinical trials in the PERISCOPE (Pertussis Correlates of Protection Europe) project in a key research session at the start of the annual meeting of the European Society for Paediatric Infectious Diseases, held virtually this year. Dr. Kelly, a pediatrician at the Children’s Hospital in Oxford and a member of the Oxford Vaccines Group, leads one of the studies in the project looking at infant vaccination.

Dr. Kelly began his presentation by showing a figure depicting where vaccine-induced immunity fits into the larger suite of clinical studies. These studies involve mouse models, human challenge models, and infection patients. A key theme is the use of a core group of immunoassays across all studies, with the hope that they will allow effective cross comparisons.

Dr. Kelly stated, “If we find a correlate of protection in the challenge model, we can then interpret the vaccine studies in the light of that because we are using standardized constant immunoassays.”

The assays being used depend in part on the specific study and the volume of blood available. They will generally include Bordetella-specific antibody and functional antibody assays, as well as interesting studies collecting mucosal samples from infants and adults to look at serological responses. Also under examination are a range of enzyme-linked immune absorbent spot, flow cytometry, and culture techniques looking at Memory B cells, T cells, and gene expression.

Complementing these assay studies, PERISCOPE includes a series of clinical investigations designed to throw light on three areas of interest, described below:

First, researchers hope to gain a better understanding regarding the effects of the original whole cell vaccine versus the current acellular variety. The former uses an inactivated version of the whole organism. Epidemiological studies, animal data, and experience in the field demonstrate that whole-cell vaccination results in a broad, long-lasting, and effective immune response.

By comparison, the acellular pertussis vaccine consists of between three and five protein components, which are purified from cultured Bordetella pertussis. While it is an effective vaccine, its effects are less durable; routine use in some countries is associated with cyclical outbreaks of increasing severity.

A second issue for researchers involved in the PERISCOPE project concerns the effects of maternal immunization. In the United Kingdom in 2012, for example, an increasing number of cases were noted 6-7 years after adoption of an acellular vaccine for routine vaccination in the 2nd-3rd trimester of pregnancy. Vaccination appears to effectively control neonatal disease, but whether this influences infant immune responses and long-term control of pertussis for a population is unknown.

Finally, the group is interested in the effects of an acellular booster across all age groups. While the effects may be short-lived, the booster is a potential strategy for controlling a population by repeated boosting of immunity. This is another area where using novel immunoassays may aid better understanding.

To find answers, the consortium has established four studies: the Gambia Pertussis study (GaPs) in Gambia and AWARE, the sister study to GaPs in the United Kingdom, addressing the acellular pertussis versus cellular pertussis question; the Pertussis Maternal Immunization Study in Finland (MIFI) addressing maternal immunization; and the Booster against Pertussis (BERT) study across three countries (U.K., the Netherlands, and Finland) looking at acellular booster across age groups.
 

Gambia pertussis study

GaPs is the largest single study in the project and is being run at the Medical Research Council–funded London School of Tropical Medicine center in Gambia. Beate Kampmann, MD, PhD, of Imperial College London, England, is the project lead. It is due to complete in 2022. GaPs seeks to enroll 600 mother/infant pairs and randomize the mothers to either an acellular pertussis booster in pregnancy or a tetanus toxoid control vaccine. Infants are subsequently randomized to an acellular or whole-cell pertussis schedule of primary immunization. The vaccine doses are being given at 2, 3, and 4 months. The primary endpoint is a serological finding being measured at 9 months of age, when the infant would usually receive yellow fever, measles, and rubella vaccination.

GaPs has a number of pathways. Within each of the four arms generated by the two randomizations, the maternal randomization and the infant randomization, there are five subgroups. They are designed to study time points in subgroups A and B after the first dose in more detail, looking at the innate immune responses using gene expression. It will enable researchers to study adaptive immune responses to T cells and B cells after the second dose of vaccine. By employing a range of subgroups, the team can explore the immune profile using the assays referred to above. Such information should provide new insights into the differences between acellular and whole-cell vaccines.
 

The AWARE study

AWARE is the sister study to GaPs and looks at the acellular/whole pertussis issue. Because many developed countries, such as the United Kingdom, have established maternal immunization programs, it is not possible to randomize mothers. Consequently, researchers have opted to recruit infants of mothers who have received an acellular vaccine in pregnancy and randomize them to either an acellular schedule of primary immunization or a whole-cell schedule.

The selected vaccine is ComVac5 from Bharat Biotech. This whole-cell vaccine differs from that used in Gambia. An early obstacle for AWARE has been seeking permission to import a non-conventional vaccine into Europe. It has delayed the anticipated end date to 2023. Participating infants will receive a two-dose schedule at 2 and 4 months of age per their randomization; then, both groups will go on to receive an acellular pertussis booster at 12 months. At all time points, the team will sample blood for cells and serum, as well as mucosal fluid from the nose. Because the mucosal surface is where the action is, this approach will likely generate new data around antibody responses.
 

The MIFI

The Pertussis Maternal Immunization Study in Finland is being run by Jussi Mertsola, of the University of Turku, Finland, and Qiushui He, of the National Public Health Institute, Turku. It is due to complete in late 2021. Where, in the United Kingdom, researchers are unable to randomize mothers because of the current guidelines, researchers in Finland do not have a maternal immunization program to consider. MIFI will randomize 80 mothers, 40 to immunization with acellular pertussis and 40 to a control group. Dr. Kelly stated that whole cell vaccines are not available for use in Finland. Participants will receive a two-dose schedule at 3 and 5 months. Blood samples will then be taken to compare the serological and cellular responses, which will help researchers understand the effects of maternal immunization. In addition, there will be sampling of mucosal fluid using a device that collects a standardized aliquot of fluid.
 

The BERT study

The final clinical element of PERISCOPE presented by Dr. Kelly was the Booster against Pertussis study. This study is near completion. It seeks to examine the use of an acellular booster across different age groups and three countries: the United Kingdom, the Netherlands, and Finland. The study is being coordinated by Guy Berbers, PhD, at the National Institute for Public Health and the Environment in the Netherlands.

BERT comprises four cohorts (A, B, C, D) of different ages: 7-10 years (36 participants), 11-15 years (36 participants), mid-adult (25 participants), and older age (25 participants). After receiving an acellular booster, participants will undergo intense sampling. Sampling will take place immediately after immunization at day 7 and look at adaptive effects, then again at day 28 and day 365.

Because some participants will have already received whole cell or acellular vaccination, this approach will allow researchers to look at the effects of priming (i.e., how long the B cell/T cell antibody responses last).

Involving different countries across Europe ensures wide applicability of results, but also allows researchers to compare the effects of very different immunization histories.

At the end of this ESPID session, Dimitri Diavatopoulos, PhD, assistant professor at the Radboud University Medical Centre Nijmegen, the Netherlands, commented that a future problem in studying pertussis vaccines and their potential clinical application is that most vaccination schedules now involve combination products. Obtaining a stand-alone vaccination may prove difficult, and there may be resistance if it complicates current vaccination programs.

Dr. Kelly acknowledged funding for the PERISCOPE project from GlaxoSmithKline and Pasteur Sanofi.

With increasing whooping cough numbers, developing an effective new vaccine against Bordetella pertussis is a priority. Results from the multifactorial PERISCOPE Project will help scientists and clinicians move forward.

MarianVejcik/Getty Images

Dominic Kelly, PhD, talked about vaccine-induced immunity and provided an overview of ongoing clinical trials in the PERISCOPE (Pertussis Correlates of Protection Europe) project in a key research session at the start of the annual meeting of the European Society for Paediatric Infectious Diseases, held virtually this year. Dr. Kelly, a pediatrician at the Children’s Hospital in Oxford and a member of the Oxford Vaccines Group, leads one of the studies in the project looking at infant vaccination.

Dr. Kelly began his presentation by showing a figure depicting where vaccine-induced immunity fits into the larger suite of clinical studies. These studies involve mouse models, human challenge models, and infection patients. A key theme is the use of a core group of immunoassays across all studies, with the hope that they will allow effective cross comparisons.

Dr. Kelly stated, “If we find a correlate of protection in the challenge model, we can then interpret the vaccine studies in the light of that because we are using standardized constant immunoassays.”

The assays being used depend in part on the specific study and the volume of blood available. They will generally include Bordetella-specific antibody and functional antibody assays, as well as interesting studies collecting mucosal samples from infants and adults to look at serological responses. Also under examination are a range of enzyme-linked immune absorbent spot, flow cytometry, and culture techniques looking at Memory B cells, T cells, and gene expression.

Complementing these assay studies, PERISCOPE includes a series of clinical investigations designed to throw light on three areas of interest, described below:

First, researchers hope to gain a better understanding regarding the effects of the original whole cell vaccine versus the current acellular variety. The former uses an inactivated version of the whole organism. Epidemiological studies, animal data, and experience in the field demonstrate that whole-cell vaccination results in a broad, long-lasting, and effective immune response.

By comparison, the acellular pertussis vaccine consists of between three and five protein components, which are purified from cultured Bordetella pertussis. While it is an effective vaccine, its effects are less durable; routine use in some countries is associated with cyclical outbreaks of increasing severity.

A second issue for researchers involved in the PERISCOPE project concerns the effects of maternal immunization. In the United Kingdom in 2012, for example, an increasing number of cases were noted 6-7 years after adoption of an acellular vaccine for routine vaccination in the 2nd-3rd trimester of pregnancy. Vaccination appears to effectively control neonatal disease, but whether this influences infant immune responses and long-term control of pertussis for a population is unknown.

Finally, the group is interested in the effects of an acellular booster across all age groups. While the effects may be short-lived, the booster is a potential strategy for controlling a population by repeated boosting of immunity. This is another area where using novel immunoassays may aid better understanding.

To find answers, the consortium has established four studies: the Gambia Pertussis study (GaPs) in Gambia and AWARE, the sister study to GaPs in the United Kingdom, addressing the acellular pertussis versus cellular pertussis question; the Pertussis Maternal Immunization Study in Finland (MIFI) addressing maternal immunization; and the Booster against Pertussis (BERT) study across three countries (U.K., the Netherlands, and Finland) looking at acellular booster across age groups.
 

Gambia pertussis study

GaPs is the largest single study in the project and is being run at the Medical Research Council–funded London School of Tropical Medicine center in Gambia. Beate Kampmann, MD, PhD, of Imperial College London, England, is the project lead. It is due to complete in 2022. GaPs seeks to enroll 600 mother/infant pairs and randomize the mothers to either an acellular pertussis booster in pregnancy or a tetanus toxoid control vaccine. Infants are subsequently randomized to an acellular or whole-cell pertussis schedule of primary immunization. The vaccine doses are being given at 2, 3, and 4 months. The primary endpoint is a serological finding being measured at 9 months of age, when the infant would usually receive yellow fever, measles, and rubella vaccination.

GaPs has a number of pathways. Within each of the four arms generated by the two randomizations, the maternal randomization and the infant randomization, there are five subgroups. They are designed to study time points in subgroups A and B after the first dose in more detail, looking at the innate immune responses using gene expression. It will enable researchers to study adaptive immune responses to T cells and B cells after the second dose of vaccine. By employing a range of subgroups, the team can explore the immune profile using the assays referred to above. Such information should provide new insights into the differences between acellular and whole-cell vaccines.
 

The AWARE study

AWARE is the sister study to GaPs and looks at the acellular/whole pertussis issue. Because many developed countries, such as the United Kingdom, have established maternal immunization programs, it is not possible to randomize mothers. Consequently, researchers have opted to recruit infants of mothers who have received an acellular vaccine in pregnancy and randomize them to either an acellular schedule of primary immunization or a whole-cell schedule.

The selected vaccine is ComVac5 from Bharat Biotech. This whole-cell vaccine differs from that used in Gambia. An early obstacle for AWARE has been seeking permission to import a non-conventional vaccine into Europe. It has delayed the anticipated end date to 2023. Participating infants will receive a two-dose schedule at 2 and 4 months of age per their randomization; then, both groups will go on to receive an acellular pertussis booster at 12 months. At all time points, the team will sample blood for cells and serum, as well as mucosal fluid from the nose. Because the mucosal surface is where the action is, this approach will likely generate new data around antibody responses.
 

The MIFI

The Pertussis Maternal Immunization Study in Finland is being run by Jussi Mertsola, of the University of Turku, Finland, and Qiushui He, of the National Public Health Institute, Turku. It is due to complete in late 2021. Where, in the United Kingdom, researchers are unable to randomize mothers because of the current guidelines, researchers in Finland do not have a maternal immunization program to consider. MIFI will randomize 80 mothers, 40 to immunization with acellular pertussis and 40 to a control group. Dr. Kelly stated that whole cell vaccines are not available for use in Finland. Participants will receive a two-dose schedule at 3 and 5 months. Blood samples will then be taken to compare the serological and cellular responses, which will help researchers understand the effects of maternal immunization. In addition, there will be sampling of mucosal fluid using a device that collects a standardized aliquot of fluid.
 

The BERT study

The final clinical element of PERISCOPE presented by Dr. Kelly was the Booster against Pertussis study. This study is near completion. It seeks to examine the use of an acellular booster across different age groups and three countries: the United Kingdom, the Netherlands, and Finland. The study is being coordinated by Guy Berbers, PhD, at the National Institute for Public Health and the Environment in the Netherlands.

BERT comprises four cohorts (A, B, C, D) of different ages: 7-10 years (36 participants), 11-15 years (36 participants), mid-adult (25 participants), and older age (25 participants). After receiving an acellular booster, participants will undergo intense sampling. Sampling will take place immediately after immunization at day 7 and look at adaptive effects, then again at day 28 and day 365.

Because some participants will have already received whole cell or acellular vaccination, this approach will allow researchers to look at the effects of priming (i.e., how long the B cell/T cell antibody responses last).

Involving different countries across Europe ensures wide applicability of results, but also allows researchers to compare the effects of very different immunization histories.

At the end of this ESPID session, Dimitri Diavatopoulos, PhD, assistant professor at the Radboud University Medical Centre Nijmegen, the Netherlands, commented that a future problem in studying pertussis vaccines and their potential clinical application is that most vaccination schedules now involve combination products. Obtaining a stand-alone vaccination may prove difficult, and there may be resistance if it complicates current vaccination programs.

Dr. Kelly acknowledged funding for the PERISCOPE project from GlaxoSmithKline and Pasteur Sanofi.

With increasing whooping cough numbers, developing an effective new vaccine against Bordetella pertussis is a priority. Results from the multifactorial PERISCOPE Project will help scientists and clinicians move forward.

MarianVejcik/Getty Images

Dominic Kelly, PhD, talked about vaccine-induced immunity and provided an overview of ongoing clinical trials in the PERISCOPE (Pertussis Correlates of Protection Europe) project in a key research session at the start of the annual meeting of the European Society for Paediatric Infectious Diseases, held virtually this year. Dr. Kelly, a pediatrician at the Children’s Hospital in Oxford and a member of the Oxford Vaccines Group, leads one of the studies in the project looking at infant vaccination.

Dr. Kelly began his presentation by showing a figure depicting where vaccine-induced immunity fits into the larger suite of clinical studies. These studies involve mouse models, human challenge models, and infection patients. A key theme is the use of a core group of immunoassays across all studies, with the hope that they will allow effective cross comparisons.

Dr. Kelly stated, “If we find a correlate of protection in the challenge model, we can then interpret the vaccine studies in the light of that because we are using standardized constant immunoassays.”

The assays being used depend in part on the specific study and the volume of blood available. They will generally include Bordetella-specific antibody and functional antibody assays, as well as interesting studies collecting mucosal samples from infants and adults to look at serological responses. Also under examination are a range of enzyme-linked immune absorbent spot, flow cytometry, and culture techniques looking at Memory B cells, T cells, and gene expression.

Complementing these assay studies, PERISCOPE includes a series of clinical investigations designed to throw light on three areas of interest, described below:

First, researchers hope to gain a better understanding regarding the effects of the original whole cell vaccine versus the current acellular variety. The former uses an inactivated version of the whole organism. Epidemiological studies, animal data, and experience in the field demonstrate that whole-cell vaccination results in a broad, long-lasting, and effective immune response.

By comparison, the acellular pertussis vaccine consists of between three and five protein components, which are purified from cultured Bordetella pertussis. While it is an effective vaccine, its effects are less durable; routine use in some countries is associated with cyclical outbreaks of increasing severity.

A second issue for researchers involved in the PERISCOPE project concerns the effects of maternal immunization. In the United Kingdom in 2012, for example, an increasing number of cases were noted 6-7 years after adoption of an acellular vaccine for routine vaccination in the 2nd-3rd trimester of pregnancy. Vaccination appears to effectively control neonatal disease, but whether this influences infant immune responses and long-term control of pertussis for a population is unknown.

Finally, the group is interested in the effects of an acellular booster across all age groups. While the effects may be short-lived, the booster is a potential strategy for controlling a population by repeated boosting of immunity. This is another area where using novel immunoassays may aid better understanding.

To find answers, the consortium has established four studies: the Gambia Pertussis study (GaPs) in Gambia and AWARE, the sister study to GaPs in the United Kingdom, addressing the acellular pertussis versus cellular pertussis question; the Pertussis Maternal Immunization Study in Finland (MIFI) addressing maternal immunization; and the Booster against Pertussis (BERT) study across three countries (U.K., the Netherlands, and Finland) looking at acellular booster across age groups.
 

Gambia pertussis study

GaPs is the largest single study in the project and is being run at the Medical Research Council–funded London School of Tropical Medicine center in Gambia. Beate Kampmann, MD, PhD, of Imperial College London, England, is the project lead. It is due to complete in 2022. GaPs seeks to enroll 600 mother/infant pairs and randomize the mothers to either an acellular pertussis booster in pregnancy or a tetanus toxoid control vaccine. Infants are subsequently randomized to an acellular or whole-cell pertussis schedule of primary immunization. The vaccine doses are being given at 2, 3, and 4 months. The primary endpoint is a serological finding being measured at 9 months of age, when the infant would usually receive yellow fever, measles, and rubella vaccination.

GaPs has a number of pathways. Within each of the four arms generated by the two randomizations, the maternal randomization and the infant randomization, there are five subgroups. They are designed to study time points in subgroups A and B after the first dose in more detail, looking at the innate immune responses using gene expression. It will enable researchers to study adaptive immune responses to T cells and B cells after the second dose of vaccine. By employing a range of subgroups, the team can explore the immune profile using the assays referred to above. Such information should provide new insights into the differences between acellular and whole-cell vaccines.
 

The AWARE study

AWARE is the sister study to GaPs and looks at the acellular/whole pertussis issue. Because many developed countries, such as the United Kingdom, have established maternal immunization programs, it is not possible to randomize mothers. Consequently, researchers have opted to recruit infants of mothers who have received an acellular vaccine in pregnancy and randomize them to either an acellular schedule of primary immunization or a whole-cell schedule.

The selected vaccine is ComVac5 from Bharat Biotech. This whole-cell vaccine differs from that used in Gambia. An early obstacle for AWARE has been seeking permission to import a non-conventional vaccine into Europe. It has delayed the anticipated end date to 2023. Participating infants will receive a two-dose schedule at 2 and 4 months of age per their randomization; then, both groups will go on to receive an acellular pertussis booster at 12 months. At all time points, the team will sample blood for cells and serum, as well as mucosal fluid from the nose. Because the mucosal surface is where the action is, this approach will likely generate new data around antibody responses.
 

The MIFI

The Pertussis Maternal Immunization Study in Finland is being run by Jussi Mertsola, of the University of Turku, Finland, and Qiushui He, of the National Public Health Institute, Turku. It is due to complete in late 2021. Where, in the United Kingdom, researchers are unable to randomize mothers because of the current guidelines, researchers in Finland do not have a maternal immunization program to consider. MIFI will randomize 80 mothers, 40 to immunization with acellular pertussis and 40 to a control group. Dr. Kelly stated that whole cell vaccines are not available for use in Finland. Participants will receive a two-dose schedule at 3 and 5 months. Blood samples will then be taken to compare the serological and cellular responses, which will help researchers understand the effects of maternal immunization. In addition, there will be sampling of mucosal fluid using a device that collects a standardized aliquot of fluid.
 

The BERT study

The final clinical element of PERISCOPE presented by Dr. Kelly was the Booster against Pertussis study. This study is near completion. It seeks to examine the use of an acellular booster across different age groups and three countries: the United Kingdom, the Netherlands, and Finland. The study is being coordinated by Guy Berbers, PhD, at the National Institute for Public Health and the Environment in the Netherlands.

BERT comprises four cohorts (A, B, C, D) of different ages: 7-10 years (36 participants), 11-15 years (36 participants), mid-adult (25 participants), and older age (25 participants). After receiving an acellular booster, participants will undergo intense sampling. Sampling will take place immediately after immunization at day 7 and look at adaptive effects, then again at day 28 and day 365.

Because some participants will have already received whole cell or acellular vaccination, this approach will allow researchers to look at the effects of priming (i.e., how long the B cell/T cell antibody responses last).

Involving different countries across Europe ensures wide applicability of results, but also allows researchers to compare the effects of very different immunization histories.

At the end of this ESPID session, Dimitri Diavatopoulos, PhD, assistant professor at the Radboud University Medical Centre Nijmegen, the Netherlands, commented that a future problem in studying pertussis vaccines and their potential clinical application is that most vaccination schedules now involve combination products. Obtaining a stand-alone vaccination may prove difficult, and there may be resistance if it complicates current vaccination programs.

Dr. Kelly acknowledged funding for the PERISCOPE project from GlaxoSmithKline and Pasteur Sanofi.

Among women with type 2 endometrial cancer, diagnostic hysteroscopy may not be associated with increased odds of positive peritoneal cytology at the time of surgical staging or with decreased survival, according to a retrospective study of 127 patients.

Compared with another diagnostic method, dilation and curettage, hysteroscopy “might present equal safety” in this patient population, a researcher said at the meeting sponsored by AAGL, held virtually this year.
 

Possible associations between cytology and procedures

Prior research has found that positive peritoneal cytology may correlate with greater likelihood of death among patients with endometrial cancer, and researchers have wondered whether pressure on the uterine cavity during hysteroscopy increases the presence of positive peritoneal cytology. “According to some systematic reviews ... it seems that it does,” said study author Luiz Brito, MD, PhD, associate professor of obstetrics and gynecology at the University of Campinas in Brazil.

Nevertheless, research suggests that “most of the time hysteroscopy does not have a powerful impact on the prognosis of these patients,” he said.

Studies have tended to focus on patients with type 1 endometrial cancer, however. Type 2 endometrial cancer, which is more aggressive, “is scarcely studied,” Dr. Brito said. One retrospective study that focused on type 2 endometrial cancer included 140 patients. Among patients who underwent hysteroscopy, 30% had positive cytology. In comparison, 12% of patients in the curettage group had positive cytology. But the difference in disease-specific survival between groups was not statistically significant, and about 33% of the patients in each group developed a recurrence.

To examine associations between diagnostic methods and outcomes in another group of patients with type 2 endometrial cancer, Dr. Brito and colleagues analyzed data from a hospital registry in Brazil.

The database included 1,183 patients with endometrial cancer between 2002 and 2017, including 235 patients with type 2 endometrial cancer. After excluding patients with synchronous tumor and those who did not undergo surgery or did not have peritoneal cytology performed, 127 patients remained for the analysis. The study included follow-up to December 2019.

The researchers compared the prevalence of positive peritoneal cytology among 43 patients who underwent hysteroscopy with that among 84 patients who underwent curettage. The groups had similar baseline characteristics.

Positive peritoneal cytology was more common in the curettage group than in the hysteroscopy group (10.7% vs. 4.6%), although the difference was not statistically significant. Lymphovascular invasion and advanced surgical staging were more common in the curettage group.

In a multivariate analysis, older age and advanced cancer staging were the only factors associated with decreased disease-free survival. Age, advanced cancer staging, and vascular invasion were associated with decreased disease-specific survival.

The researchers also had considered factors such as peritoneal cytology, diagnostic method, age of menarche, menopause time, parity, comorbidities, smoking status, body mass index, abnormal uterine bleeding, histological type, and adjuvant treatment.

A limitation of the study is that it relied on data from a public health system that often has long wait times for diagnosis and treatment, Dr. Brito noted.
 

Some doctors may forgo cytology

The available research raises questions about the role and relevance of peritoneal cytology in caring for patients with endometrial cancer, René Pareja, MD, a gynecologic oncologist at Instituto Nacional de Cancerología, Bogotá, Colombia, said in a discussion following the presentation.

Peritoneal cytology has not been part of endometrial cancer staging since 2009, Dr. Pareja said. Still, guidelines recommend that surgeons collect cytology during surgical staging, with the idea that the results could inform adjuvant treatment decisions.

“Peritoneal cytology is recommended in the guidelines, but there are no recommendations on how to proceed if it is positive,” Dr. Pareja said. “While some gynecologic oncologists continue to take cytology during endometrial cancer staging, some have stopped doing so. And in Colombia, most of us are not performing pelvic cytology.”

Although some studies indicate that hysteroscopy may increase the rate of positive cytology, positive cytology may not be associated with worse oncological outcomes independent of other risk factors for recurrence, said Dr. Pareja.

So far, studies have been retrospective. Furthermore, the sensitivity and specificity of pelvic cytology tests are not 100%. “Should we continue performing pelvic cytology given the results of this and other studies?” Dr. Pareja asked.

Despite limited knowledge about this variable, physicians may want to be aware if a patient has positive cytology, Dr. Brito suggested. “At least it will give us some red flags so we can be attentive to these patients.”

If researchers were to design a prospective study that incorporates hysteroscopic variables, it could provide more complete answers about the relationship between hysteroscopy and peritoneal cytology and clarify the importance of positive cytology, Dr. Brito said.

Dr. Brito had no relevant disclosures. Dr. Pareja disclosed consulting for Johnson & Johnson.

jremaly@mdedge.com

SOURCE: Oliveira Brito LG et al. J Minim Invasive Gynecol. 2020 Nov. doi: 10.1016/j.jmig.2020.08.356.

Among women with type 2 endometrial cancer, diagnostic hysteroscopy may not be associated with increased odds of positive peritoneal cytology at the time of surgical staging or with decreased survival, according to a retrospective study of 127 patients.

Compared with another diagnostic method, dilation and curettage, hysteroscopy “might present equal safety” in this patient population, a researcher said at the meeting sponsored by AAGL, held virtually this year.
 

Possible associations between cytology and procedures

Prior research has found that positive peritoneal cytology may correlate with greater likelihood of death among patients with endometrial cancer, and researchers have wondered whether pressure on the uterine cavity during hysteroscopy increases the presence of positive peritoneal cytology. “According to some systematic reviews ... it seems that it does,” said study author Luiz Brito, MD, PhD, associate professor of obstetrics and gynecology at the University of Campinas in Brazil.

Nevertheless, research suggests that “most of the time hysteroscopy does not have a powerful impact on the prognosis of these patients,” he said.

Studies have tended to focus on patients with type 1 endometrial cancer, however. Type 2 endometrial cancer, which is more aggressive, “is scarcely studied,” Dr. Brito said. One retrospective study that focused on type 2 endometrial cancer included 140 patients. Among patients who underwent hysteroscopy, 30% had positive cytology. In comparison, 12% of patients in the curettage group had positive cytology. But the difference in disease-specific survival between groups was not statistically significant, and about 33% of the patients in each group developed a recurrence.

To examine associations between diagnostic methods and outcomes in another group of patients with type 2 endometrial cancer, Dr. Brito and colleagues analyzed data from a hospital registry in Brazil.

The database included 1,183 patients with endometrial cancer between 2002 and 2017, including 235 patients with type 2 endometrial cancer. After excluding patients with synchronous tumor and those who did not undergo surgery or did not have peritoneal cytology performed, 127 patients remained for the analysis. The study included follow-up to December 2019.

The researchers compared the prevalence of positive peritoneal cytology among 43 patients who underwent hysteroscopy with that among 84 patients who underwent curettage. The groups had similar baseline characteristics.

Positive peritoneal cytology was more common in the curettage group than in the hysteroscopy group (10.7% vs. 4.6%), although the difference was not statistically significant. Lymphovascular invasion and advanced surgical staging were more common in the curettage group.

In a multivariate analysis, older age and advanced cancer staging were the only factors associated with decreased disease-free survival. Age, advanced cancer staging, and vascular invasion were associated with decreased disease-specific survival.

The researchers also had considered factors such as peritoneal cytology, diagnostic method, age of menarche, menopause time, parity, comorbidities, smoking status, body mass index, abnormal uterine bleeding, histological type, and adjuvant treatment.

A limitation of the study is that it relied on data from a public health system that often has long wait times for diagnosis and treatment, Dr. Brito noted.
 

Some doctors may forgo cytology

The available research raises questions about the role and relevance of peritoneal cytology in caring for patients with endometrial cancer, René Pareja, MD, a gynecologic oncologist at Instituto Nacional de Cancerología, Bogotá, Colombia, said in a discussion following the presentation.

Peritoneal cytology has not been part of endometrial cancer staging since 2009, Dr. Pareja said. Still, guidelines recommend that surgeons collect cytology during surgical staging, with the idea that the results could inform adjuvant treatment decisions.

“Peritoneal cytology is recommended in the guidelines, but there are no recommendations on how to proceed if it is positive,” Dr. Pareja said. “While some gynecologic oncologists continue to take cytology during endometrial cancer staging, some have stopped doing so. And in Colombia, most of us are not performing pelvic cytology.”

Although some studies indicate that hysteroscopy may increase the rate of positive cytology, positive cytology may not be associated with worse oncological outcomes independent of other risk factors for recurrence, said Dr. Pareja.

So far, studies have been retrospective. Furthermore, the sensitivity and specificity of pelvic cytology tests are not 100%. “Should we continue performing pelvic cytology given the results of this and other studies?” Dr. Pareja asked.

Despite limited knowledge about this variable, physicians may want to be aware if a patient has positive cytology, Dr. Brito suggested. “At least it will give us some red flags so we can be attentive to these patients.”

If researchers were to design a prospective study that incorporates hysteroscopic variables, it could provide more complete answers about the relationship between hysteroscopy and peritoneal cytology and clarify the importance of positive cytology, Dr. Brito said.

Dr. Brito had no relevant disclosures. Dr. Pareja disclosed consulting for Johnson & Johnson.

jremaly@mdedge.com

SOURCE: Oliveira Brito LG et al. J Minim Invasive Gynecol. 2020 Nov. doi: 10.1016/j.jmig.2020.08.356.

Among women with type 2 endometrial cancer, diagnostic hysteroscopy may not be associated with increased odds of positive peritoneal cytology at the time of surgical staging or with decreased survival, according to a retrospective study of 127 patients.

Compared with another diagnostic method, dilation and curettage, hysteroscopy “might present equal safety” in this patient population, a researcher said at the meeting sponsored by AAGL, held virtually this year.
 

Possible associations between cytology and procedures

Prior research has found that positive peritoneal cytology may correlate with greater likelihood of death among patients with endometrial cancer, and researchers have wondered whether pressure on the uterine cavity during hysteroscopy increases the presence of positive peritoneal cytology. “According to some systematic reviews ... it seems that it does,” said study author Luiz Brito, MD, PhD, associate professor of obstetrics and gynecology at the University of Campinas in Brazil.

Nevertheless, research suggests that “most of the time hysteroscopy does not have a powerful impact on the prognosis of these patients,” he said.

Studies have tended to focus on patients with type 1 endometrial cancer, however. Type 2 endometrial cancer, which is more aggressive, “is scarcely studied,” Dr. Brito said. One retrospective study that focused on type 2 endometrial cancer included 140 patients. Among patients who underwent hysteroscopy, 30% had positive cytology. In comparison, 12% of patients in the curettage group had positive cytology. But the difference in disease-specific survival between groups was not statistically significant, and about 33% of the patients in each group developed a recurrence.

To examine associations between diagnostic methods and outcomes in another group of patients with type 2 endometrial cancer, Dr. Brito and colleagues analyzed data from a hospital registry in Brazil.

The database included 1,183 patients with endometrial cancer between 2002 and 2017, including 235 patients with type 2 endometrial cancer. After excluding patients with synchronous tumor and those who did not undergo surgery or did not have peritoneal cytology performed, 127 patients remained for the analysis. The study included follow-up to December 2019.

The researchers compared the prevalence of positive peritoneal cytology among 43 patients who underwent hysteroscopy with that among 84 patients who underwent curettage. The groups had similar baseline characteristics.

Positive peritoneal cytology was more common in the curettage group than in the hysteroscopy group (10.7% vs. 4.6%), although the difference was not statistically significant. Lymphovascular invasion and advanced surgical staging were more common in the curettage group.

In a multivariate analysis, older age and advanced cancer staging were the only factors associated with decreased disease-free survival. Age, advanced cancer staging, and vascular invasion were associated with decreased disease-specific survival.

The researchers also had considered factors such as peritoneal cytology, diagnostic method, age of menarche, menopause time, parity, comorbidities, smoking status, body mass index, abnormal uterine bleeding, histological type, and adjuvant treatment.

A limitation of the study is that it relied on data from a public health system that often has long wait times for diagnosis and treatment, Dr. Brito noted.
 

Some doctors may forgo cytology

The available research raises questions about the role and relevance of peritoneal cytology in caring for patients with endometrial cancer, René Pareja, MD, a gynecologic oncologist at Instituto Nacional de Cancerología, Bogotá, Colombia, said in a discussion following the presentation.

Peritoneal cytology has not been part of endometrial cancer staging since 2009, Dr. Pareja said. Still, guidelines recommend that surgeons collect cytology during surgical staging, with the idea that the results could inform adjuvant treatment decisions.

“Peritoneal cytology is recommended in the guidelines, but there are no recommendations on how to proceed if it is positive,” Dr. Pareja said. “While some gynecologic oncologists continue to take cytology during endometrial cancer staging, some have stopped doing so. And in Colombia, most of us are not performing pelvic cytology.”

Although some studies indicate that hysteroscopy may increase the rate of positive cytology, positive cytology may not be associated with worse oncological outcomes independent of other risk factors for recurrence, said Dr. Pareja.

So far, studies have been retrospective. Furthermore, the sensitivity and specificity of pelvic cytology tests are not 100%. “Should we continue performing pelvic cytology given the results of this and other studies?” Dr. Pareja asked.

Despite limited knowledge about this variable, physicians may want to be aware if a patient has positive cytology, Dr. Brito suggested. “At least it will give us some red flags so we can be attentive to these patients.”

If researchers were to design a prospective study that incorporates hysteroscopic variables, it could provide more complete answers about the relationship between hysteroscopy and peritoneal cytology and clarify the importance of positive cytology, Dr. Brito said.

Dr. Brito had no relevant disclosures. Dr. Pareja disclosed consulting for Johnson & Johnson.

jremaly@mdedge.com

SOURCE: Oliveira Brito LG et al. J Minim Invasive Gynecol. 2020 Nov. doi: 10.1016/j.jmig.2020.08.356.

Labor induction at 39 weeks instead of 41 weeks may have a positive impact on neonatal outcomes, Aaron B. Caughey, MD, PhD, said at the 2020 virtual meeting of the American College of Obstetricians and Gynecologists.

For much of the 20th century, term gestation has been defined as 37 weeks and beyond, said Dr. Caughey, of Oregon Health & Science University, Portland. He noted several studies showing a U-shaped distribution in neonatal outcomes during the period from 37 weeks to 41 weeks for some outcomes, including Apgar scores. However, respiratory outcomes in a study from 2008 showed an increase, with meconium stained amniotic fluid increasing from 2.27% at 37 weeks to 10.33% at 41 weeks, and meconium aspiration increasing from 0.07% at 37 weeks to 0.27% at 41 weeks.

Late-term induction may carry more risk

The study “that really got everyone’s attention” in terms of neonatal outcomes was published in 2009 in the New England Journal of Medicine. The cohort study included 24,077 elective cesarean deliveries between 37 and 42 weeks and reviewed a range of neonatal outcomes based on gestational age.

The rate of any adverse outcome decreased from 37 weeks to 39 weeks, “but then started going back up again,” Dr. Caughey said. He reviewed data from another study that factored in stillbirth and the risk of expectant management based on gestational age. A composite risk of perinatal death with expectant management was 15.4 deaths per 10,000 cases at 37 weeks and 39 weeks, but increased to 19.9 at 42 weeks.

“The morbidity appears to have a U-shaped distribution and the mortality seems to favor delivery at 39 weeks,” he said.

When it comes to induction of labor, medically indicated vs. nonmedically indicated does matter, Dr. Caughey said. Factors not considered a medical indication include impending macrosomia, increased risk for developing preeclampsia or intrauterine growth retardation, and a favorable cervix, he noted.

“For indicated induction of labor, the risks and benefits of induction of labor vs. expectant management have been considered and weighed in by the field of experts that care for pregnant women,” he said. With nonmedically indicated induction, experts “either decided that risks and benefits don’t favor induction of labor, or we haven’t come down hard on what the protocol might be.

“It is important to consider the risks and benefits,” said Dr. Caughey. The factors you want to include are neonatal outcomes, maternal preferences, and doctor preferences. However, “we want to be thoughtful about this intervention,” because of the association of higher costs and increased risk of cesarean with induction of labor.

As for timing of induction of labor, certain conditions favoring early-term induction include preeclampsia and gestational hypertension, chronic hypertension, diabetes, intrauterine growth restriction, nonreassuring fetal testing, cholestasis, placenta previa or accreta, and twins.
 

Data support value of 39 weeks

As for late-term induction of labor, “at 41 weeks it is pretty clear that neonatal outcomes would be improved by delivery,” he said. Historically, clinicians have raised concerns about the increased risk of cesarean delivery following induction of labor, but this risk has not been borne out in recent studies. Dr. Caughey said. However, in the findings from the ARRIVE trial, a large study of 6,106 women who were randomized to induction or labor or expectant management at 39 weeks, “they found a reduction in their risk of cesarean delivery compared to expectant management (18.6% vs. 22.2%). Rates of preeclampsia also were lower among induced women, while rate of chorioamnionitis, postpartum hemorrhage, and intensive care were similar between the groups. The researchers did not find significant differences in perinatal outcomes.

Dr. Caughey and colleagues conducted a systematic review of cesarean risk and induction of labor, and found a risk ratio of 0.83, similar to the ARRIVE trial. “The data suggest a consistently reduced risk for cesarean delivery with the induction of labor.”

However, “I would caution us to be thoughtful about research protocols vs. actual practice,” he said. “You must think about the environment.” The latent phase of labor can continue for a long time after induction, and patience is called for, he emphasized.

Dr. Caughey said that despite the ARRIVE trial and other studies, 39 weeks should not necessarily be the new standard for induction of labor. “The proportion of women impacted is dramatically different, if you would be inducing every woman at 39 weeks, that would be 60% to 70%,” which could have a great impact on resources.

Based on current research, early-term induction of labor at 37 weeks “is a bad idea without indication,” said Dr. Caughey. Induction at 41 weeks (sometimes considered post term) is the current ACOG recommendation and is associated with improved outcomes.

Induction of labor at full term (39-40 weeks) depends in part on the environment, and is not a violation of standard of care, he said. “Evidence is evolving, and individual hospitals are trying to figure this out.”

Cesarean data are convincing, at least in some settings, he said. However, “we need more global trials and different medical settings” to determine the optimal time for induction of labor.
 

Consider maternal preferences and characteristics

During a question-and-answer session, Dr. Caughey was asked whether all women should be offered induction of labor at 39 weeks.

“I think it is OK if your entire health system has agreed to offering, to have that shared medical decision making, but you need to have careful conversation to make sure you have the resources,” he noted. Also, he said he believed clinicians should respond to women as they request labor induction at 39 weeks.

In response to a question about induction of labor in obese women, he noted that women with a body mass index greater than 35 kg/m² are not equally successful with induction of labor. “We know they have a higher risk of cesarean delivery,” however, “it has been demonstrated that they have the same potential benefits of reduced risk of cesarean.”

As for factoring in the Bishop score to determine a favorable or unfavorable cervix, Dr. Caughey noted that women with a favorable cervix are more likely to go into labor on their own, while those with an unfavorable cervix may benefit from cervical ripening.

Dr. Caughey had no financial conflicts relevant to this talk, but disclosed serving as a medical adviser to Celmatix and Mindchild, as well as an endowment to his academic department from Bob’s Red Mill, an Oregon-based whole grain foods manufacturer.

Labor induction at 39 weeks instead of 41 weeks may have a positive impact on neonatal outcomes, Aaron B. Caughey, MD, PhD, said at the 2020 virtual meeting of the American College of Obstetricians and Gynecologists.

For much of the 20th century, term gestation has been defined as 37 weeks and beyond, said Dr. Caughey, of Oregon Health & Science University, Portland. He noted several studies showing a U-shaped distribution in neonatal outcomes during the period from 37 weeks to 41 weeks for some outcomes, including Apgar scores. However, respiratory outcomes in a study from 2008 showed an increase, with meconium stained amniotic fluid increasing from 2.27% at 37 weeks to 10.33% at 41 weeks, and meconium aspiration increasing from 0.07% at 37 weeks to 0.27% at 41 weeks.

Late-term induction may carry more risk

The study “that really got everyone’s attention” in terms of neonatal outcomes was published in 2009 in the New England Journal of Medicine. The cohort study included 24,077 elective cesarean deliveries between 37 and 42 weeks and reviewed a range of neonatal outcomes based on gestational age.

The rate of any adverse outcome decreased from 37 weeks to 39 weeks, “but then started going back up again,” Dr. Caughey said. He reviewed data from another study that factored in stillbirth and the risk of expectant management based on gestational age. A composite risk of perinatal death with expectant management was 15.4 deaths per 10,000 cases at 37 weeks and 39 weeks, but increased to 19.9 at 42 weeks.

“The morbidity appears to have a U-shaped distribution and the mortality seems to favor delivery at 39 weeks,” he said.

When it comes to induction of labor, medically indicated vs. nonmedically indicated does matter, Dr. Caughey said. Factors not considered a medical indication include impending macrosomia, increased risk for developing preeclampsia or intrauterine growth retardation, and a favorable cervix, he noted.

“For indicated induction of labor, the risks and benefits of induction of labor vs. expectant management have been considered and weighed in by the field of experts that care for pregnant women,” he said. With nonmedically indicated induction, experts “either decided that risks and benefits don’t favor induction of labor, or we haven’t come down hard on what the protocol might be.

“It is important to consider the risks and benefits,” said Dr. Caughey. The factors you want to include are neonatal outcomes, maternal preferences, and doctor preferences. However, “we want to be thoughtful about this intervention,” because of the association of higher costs and increased risk of cesarean with induction of labor.

As for timing of induction of labor, certain conditions favoring early-term induction include preeclampsia and gestational hypertension, chronic hypertension, diabetes, intrauterine growth restriction, nonreassuring fetal testing, cholestasis, placenta previa or accreta, and twins.
 

Data support value of 39 weeks

As for late-term induction of labor, “at 41 weeks it is pretty clear that neonatal outcomes would be improved by delivery,” he said. Historically, clinicians have raised concerns about the increased risk of cesarean delivery following induction of labor, but this risk has not been borne out in recent studies. Dr. Caughey said. However, in the findings from the ARRIVE trial, a large study of 6,106 women who were randomized to induction or labor or expectant management at 39 weeks, “they found a reduction in their risk of cesarean delivery compared to expectant management (18.6% vs. 22.2%). Rates of preeclampsia also were lower among induced women, while rate of chorioamnionitis, postpartum hemorrhage, and intensive care were similar between the groups. The researchers did not find significant differences in perinatal outcomes.

Dr. Caughey and colleagues conducted a systematic review of cesarean risk and induction of labor, and found a risk ratio of 0.83, similar to the ARRIVE trial. “The data suggest a consistently reduced risk for cesarean delivery with the induction of labor.”

However, “I would caution us to be thoughtful about research protocols vs. actual practice,” he said. “You must think about the environment.” The latent phase of labor can continue for a long time after induction, and patience is called for, he emphasized.

Dr. Caughey said that despite the ARRIVE trial and other studies, 39 weeks should not necessarily be the new standard for induction of labor. “The proportion of women impacted is dramatically different, if you would be inducing every woman at 39 weeks, that would be 60% to 70%,” which could have a great impact on resources.

Based on current research, early-term induction of labor at 37 weeks “is a bad idea without indication,” said Dr. Caughey. Induction at 41 weeks (sometimes considered post term) is the current ACOG recommendation and is associated with improved outcomes.

Induction of labor at full term (39-40 weeks) depends in part on the environment, and is not a violation of standard of care, he said. “Evidence is evolving, and individual hospitals are trying to figure this out.”

Cesarean data are convincing, at least in some settings, he said. However, “we need more global trials and different medical settings” to determine the optimal time for induction of labor.
 

Consider maternal preferences and characteristics

During a question-and-answer session, Dr. Caughey was asked whether all women should be offered induction of labor at 39 weeks.

“I think it is OK if your entire health system has agreed to offering, to have that shared medical decision making, but you need to have careful conversation to make sure you have the resources,” he noted. Also, he said he believed clinicians should respond to women as they request labor induction at 39 weeks.

In response to a question about induction of labor in obese women, he noted that women with a body mass index greater than 35 kg/m² are not equally successful with induction of labor. “We know they have a higher risk of cesarean delivery,” however, “it has been demonstrated that they have the same potential benefits of reduced risk of cesarean.”

As for factoring in the Bishop score to determine a favorable or unfavorable cervix, Dr. Caughey noted that women with a favorable cervix are more likely to go into labor on their own, while those with an unfavorable cervix may benefit from cervical ripening.

Dr. Caughey had no financial conflicts relevant to this talk, but disclosed serving as a medical adviser to Celmatix and Mindchild, as well as an endowment to his academic department from Bob’s Red Mill, an Oregon-based whole grain foods manufacturer.

Labor induction at 39 weeks instead of 41 weeks may have a positive impact on neonatal outcomes, Aaron B. Caughey, MD, PhD, said at the 2020 virtual meeting of the American College of Obstetricians and Gynecologists.

For much of the 20th century, term gestation has been defined as 37 weeks and beyond, said Dr. Caughey, of Oregon Health & Science University, Portland. He noted several studies showing a U-shaped distribution in neonatal outcomes during the period from 37 weeks to 41 weeks for some outcomes, including Apgar scores. However, respiratory outcomes in a study from 2008 showed an increase, with meconium stained amniotic fluid increasing from 2.27% at 37 weeks to 10.33% at 41 weeks, and meconium aspiration increasing from 0.07% at 37 weeks to 0.27% at 41 weeks.

Late-term induction may carry more risk

The study “that really got everyone’s attention” in terms of neonatal outcomes was published in 2009 in the New England Journal of Medicine. The cohort study included 24,077 elective cesarean deliveries between 37 and 42 weeks and reviewed a range of neonatal outcomes based on gestational age.

The rate of any adverse outcome decreased from 37 weeks to 39 weeks, “but then started going back up again,” Dr. Caughey said. He reviewed data from another study that factored in stillbirth and the risk of expectant management based on gestational age. A composite risk of perinatal death with expectant management was 15.4 deaths per 10,000 cases at 37 weeks and 39 weeks, but increased to 19.9 at 42 weeks.

“The morbidity appears to have a U-shaped distribution and the mortality seems to favor delivery at 39 weeks,” he said.

When it comes to induction of labor, medically indicated vs. nonmedically indicated does matter, Dr. Caughey said. Factors not considered a medical indication include impending macrosomia, increased risk for developing preeclampsia or intrauterine growth retardation, and a favorable cervix, he noted.

“For indicated induction of labor, the risks and benefits of induction of labor vs. expectant management have been considered and weighed in by the field of experts that care for pregnant women,” he said. With nonmedically indicated induction, experts “either decided that risks and benefits don’t favor induction of labor, or we haven’t come down hard on what the protocol might be.

“It is important to consider the risks and benefits,” said Dr. Caughey. The factors you want to include are neonatal outcomes, maternal preferences, and doctor preferences. However, “we want to be thoughtful about this intervention,” because of the association of higher costs and increased risk of cesarean with induction of labor.

As for timing of induction of labor, certain conditions favoring early-term induction include preeclampsia and gestational hypertension, chronic hypertension, diabetes, intrauterine growth restriction, nonreassuring fetal testing, cholestasis, placenta previa or accreta, and twins.
 

Data support value of 39 weeks

As for late-term induction of labor, “at 41 weeks it is pretty clear that neonatal outcomes would be improved by delivery,” he said. Historically, clinicians have raised concerns about the increased risk of cesarean delivery following induction of labor, but this risk has not been borne out in recent studies. Dr. Caughey said. However, in the findings from the ARRIVE trial, a large study of 6,106 women who were randomized to induction or labor or expectant management at 39 weeks, “they found a reduction in their risk of cesarean delivery compared to expectant management (18.6% vs. 22.2%). Rates of preeclampsia also were lower among induced women, while rate of chorioamnionitis, postpartum hemorrhage, and intensive care were similar between the groups. The researchers did not find significant differences in perinatal outcomes.

Dr. Caughey and colleagues conducted a systematic review of cesarean risk and induction of labor, and found a risk ratio of 0.83, similar to the ARRIVE trial. “The data suggest a consistently reduced risk for cesarean delivery with the induction of labor.”

However, “I would caution us to be thoughtful about research protocols vs. actual practice,” he said. “You must think about the environment.” The latent phase of labor can continue for a long time after induction, and patience is called for, he emphasized.

Dr. Caughey said that despite the ARRIVE trial and other studies, 39 weeks should not necessarily be the new standard for induction of labor. “The proportion of women impacted is dramatically different, if you would be inducing every woman at 39 weeks, that would be 60% to 70%,” which could have a great impact on resources.

Based on current research, early-term induction of labor at 37 weeks “is a bad idea without indication,” said Dr. Caughey. Induction at 41 weeks (sometimes considered post term) is the current ACOG recommendation and is associated with improved outcomes.

Induction of labor at full term (39-40 weeks) depends in part on the environment, and is not a violation of standard of care, he said. “Evidence is evolving, and individual hospitals are trying to figure this out.”

Cesarean data are convincing, at least in some settings, he said. However, “we need more global trials and different medical settings” to determine the optimal time for induction of labor.
 

Consider maternal preferences and characteristics

During a question-and-answer session, Dr. Caughey was asked whether all women should be offered induction of labor at 39 weeks.

“I think it is OK if your entire health system has agreed to offering, to have that shared medical decision making, but you need to have careful conversation to make sure you have the resources,” he noted. Also, he said he believed clinicians should respond to women as they request labor induction at 39 weeks.

In response to a question about induction of labor in obese women, he noted that women with a body mass index greater than 35 kg/m² are not equally successful with induction of labor. “We know they have a higher risk of cesarean delivery,” however, “it has been demonstrated that they have the same potential benefits of reduced risk of cesarean.”

As for factoring in the Bishop score to determine a favorable or unfavorable cervix, Dr. Caughey noted that women with a favorable cervix are more likely to go into labor on their own, while those with an unfavorable cervix may benefit from cervical ripening.

Dr. Caughey had no financial conflicts relevant to this talk, but disclosed serving as a medical adviser to Celmatix and Mindchild, as well as an endowment to his academic department from Bob’s Red Mill, an Oregon-based whole grain foods manufacturer.

Cannabis is ineffective at alleviating depression in pregnant women undergoing opioid agonist therapy (OAT), new research shows.

RyanKing999/iStock/Getty Images

A study of more than 120 pregnant women undergoing treatment of opioid use disorder (OUD) showed that those who used cannabis to alleviate their depressive symptoms while undergoing OAT continued to have high depression scores at the end of opioid treatment.

In addition, depression scores improved for those who abstained from cannabis use after their first positive screen. Interestingly, cannabis use did not affect patient retention in treatment for OUD, the investigators note.

“To our knowledge, this is the first time looking at the impact of cannabis on the specific population of pregnant women with opioid use disorder, who are very vulnerable to depression,” lead author Abigail Richison, MD, University of Arkansas for Medical Sciences, Little Rock, said in an interview.

The findings were presented at the American Academy of Addiction Psychiatry (AAAP) 31st Annual Meeting, which was held online this year because of the COVID-19 pandemic.
 

A safer alternative?

Data from the National Survey on Drug Use and Health show that perinatal cannabis use increased by 62% between 2002 and 2014. Many women try to ameliorate their depression symptoms by using cannabis in the mistaken belief that it will help their depression, the investigators noted.

In addition, many women consider cannabis safer during pregnancy than prescribed medications for improving mood, said Dr. Richison. She said that cannabis does not alleviate depression and may even worsen it.

Dr. Richison noted that at her center, which has a women’s health program that treats pregnant women with OUDs, she was seeing a lot of patients who reported using cannabis to improve their mood.

“However, it didn’t seem like it was really helping, so I started researching about cannabis and depression,” Dr. Richison said.

“I’ve always been interested in this population because they are very vulnerable to legal implications and can be accused of perinatal substance use. I think it is very important to screen for depression as well as cannabis use in this population,” she added.

To shed some light on the impact of cannabis use by pregnant patients with OUD, the investigators conducted a retrospective chart review of 121 pregnant women with OUD who attended outpatient OAT. All were prescribed buprenorphine.

At each visit, Beck Depression Inventory (BDI) scores were obtained and urine drug screens were administered. The primary outcome was BDI score. Other measures included retention, urinary drug screen results, and antidepressant use.

The women were divided into two groups. The first comprised cannabis users, defined as having more than one urine drug screen that was positive for cannabis (n = 35). The other group comprised nonusers, defined as having urine drug screens that were negative for cannabis (n = 86).

Cannabis users were a little younger (mean age, 27 years) than non–cannabis users (mean age, 29.5 years; P = .006). Most of the participants were White (80.2%). Roughly half were on Medicaid, and most of the other participants had private insurance; a small number of women had no insurance.

Results showed that cannabis users had significantly higher BDI scores than non–cannabis users (mean scores, 16 vs. 9.3; P < .001).

Cannabis use continued to be associated with elevated scores for depression when controlling for opioid misuse and antidepressant use. There were no significant differences in retention or lapse to opioid misuse between the two groups.
 

More evidence of risk

Commenting on the findings in an interview, Carla Marienfeld, MD, professor of psychiatry at the University of California, San Diego, said there is a growing body of evidence about risks from cannabis use during pregnancy, “a time where we already know the endocannabinoid system is very active in the developing fetus.”

She noted that the current study’s design makes it hard to know whether marijuana use causes worse depression.

However, “it clearly is not associated with helping to improve mood the way people who are using it believe or hope for,” said Dr. Marienfeld, who was not part of the research.

“The risk for harm in terms of worse mood for the pregnant woman or risks for harm to the developing fetus are being better understood with many new studies,” she added.

Yet as more and more states legalize medical marijuana, cannabis use during pregnancy is only going to rise, experts fear.

Cornel Stanciu, MD, of Dartmouth-Hitchcock Medical Center, Lebanon, N.H., who was asked for comment, noted that public endorsement for potential benefits of the marijuana plant is at an all-time high.

“To date, 33 states and the District of Columbia have responded by legalizing medical marijuana, with 10 states also having legalized recreational use of marijuana. The current practice is said to be ahead of science, as robust research has been hindered by strict regulations – and most epidemiological studies point toward harmful associations,” Dr. Stanciu said in an interview.

“Given the decreased perception of harm by the general public, women are certainly compelled to seek what they perceive as more natural self-management remedies,” he said.
 

A harmful habit

Dr. Stanciu cited a recent study conducted in Colorado in which researchers contacted cannabis dispensaries, identified themselves as being pregnant, and asked for guidance in managing pregnancy-related symptoms.

Almost 70% of dispensaries recommended products to treat symptoms, particularly in the vulnerable first trimester; 36% of them also provided reassurance of the safety profile. Very few encouraged a discussion with the physician.

“Consumption of cannabis during pregnancy results in cannabinoid placental crossing and accumulation in the fetal brain, as well as other organs, where it interferes with neurodevelopment and the endocannabinoid system,” he said.

In addition, retrospective studies have shown an association between prenatal cannabis ingestion and anemia in the mothers, low birth weight, greater risk for preterm and stillbirths, and increased need for neonatal ICU admissions.

“Children born to mothers who used cannabis during pregnancy have higher rates of impulsivity, delinquency, learning and memory impairment, as well as executive function deficits. There is also an increased association with proneness to psychosis during middle childhood,” Dr. Stanciu said.

When used during pregnancy, cannabis has been associated with increased anxiety in mothers, as well as increased risk for depressive disorders, incidence of suicidal ideations and behavior, and symptoms of mania and psychosis among those with bipolar and schizophrenia spectrum conditions. Cannabis has also been linked to coingestion of other substances and with alcohol use.

“So cannabis can pose harm, especially when used by those with affective disorders,” Dr. Stanciu said.

The study was funded by the National Institute on Drug Abuse. Dr. Richison, Dr. Marienfeld, and Dr. Stanciu have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com

Cannabis is ineffective at alleviating depression in pregnant women undergoing opioid agonist therapy (OAT), new research shows.

RyanKing999/iStock/Getty Images

A study of more than 120 pregnant women undergoing treatment of opioid use disorder (OUD) showed that those who used cannabis to alleviate their depressive symptoms while undergoing OAT continued to have high depression scores at the end of opioid treatment.

In addition, depression scores improved for those who abstained from cannabis use after their first positive screen. Interestingly, cannabis use did not affect patient retention in treatment for OUD, the investigators note.

“To our knowledge, this is the first time looking at the impact of cannabis on the specific population of pregnant women with opioid use disorder, who are very vulnerable to depression,” lead author Abigail Richison, MD, University of Arkansas for Medical Sciences, Little Rock, said in an interview.

The findings were presented at the American Academy of Addiction Psychiatry (AAAP) 31st Annual Meeting, which was held online this year because of the COVID-19 pandemic.
 

A safer alternative?

Data from the National Survey on Drug Use and Health show that perinatal cannabis use increased by 62% between 2002 and 2014. Many women try to ameliorate their depression symptoms by using cannabis in the mistaken belief that it will help their depression, the investigators noted.

In addition, many women consider cannabis safer during pregnancy than prescribed medications for improving mood, said Dr. Richison. She said that cannabis does not alleviate depression and may even worsen it.

Dr. Richison noted that at her center, which has a women’s health program that treats pregnant women with OUDs, she was seeing a lot of patients who reported using cannabis to improve their mood.

“However, it didn’t seem like it was really helping, so I started researching about cannabis and depression,” Dr. Richison said.

“I’ve always been interested in this population because they are very vulnerable to legal implications and can be accused of perinatal substance use. I think it is very important to screen for depression as well as cannabis use in this population,” she added.

To shed some light on the impact of cannabis use by pregnant patients with OUD, the investigators conducted a retrospective chart review of 121 pregnant women with OUD who attended outpatient OAT. All were prescribed buprenorphine.

At each visit, Beck Depression Inventory (BDI) scores were obtained and urine drug screens were administered. The primary outcome was BDI score. Other measures included retention, urinary drug screen results, and antidepressant use.

The women were divided into two groups. The first comprised cannabis users, defined as having more than one urine drug screen that was positive for cannabis (n = 35). The other group comprised nonusers, defined as having urine drug screens that were negative for cannabis (n = 86).

Cannabis users were a little younger (mean age, 27 years) than non–cannabis users (mean age, 29.5 years; P = .006). Most of the participants were White (80.2%). Roughly half were on Medicaid, and most of the other participants had private insurance; a small number of women had no insurance.

Results showed that cannabis users had significantly higher BDI scores than non–cannabis users (mean scores, 16 vs. 9.3; P < .001).

Cannabis use continued to be associated with elevated scores for depression when controlling for opioid misuse and antidepressant use. There were no significant differences in retention or lapse to opioid misuse between the two groups.
 

More evidence of risk

Commenting on the findings in an interview, Carla Marienfeld, MD, professor of psychiatry at the University of California, San Diego, said there is a growing body of evidence about risks from cannabis use during pregnancy, “a time where we already know the endocannabinoid system is very active in the developing fetus.”

She noted that the current study’s design makes it hard to know whether marijuana use causes worse depression.

However, “it clearly is not associated with helping to improve mood the way people who are using it believe or hope for,” said Dr. Marienfeld, who was not part of the research.

“The risk for harm in terms of worse mood for the pregnant woman or risks for harm to the developing fetus are being better understood with many new studies,” she added.

Yet as more and more states legalize medical marijuana, cannabis use during pregnancy is only going to rise, experts fear.

Cornel Stanciu, MD, of Dartmouth-Hitchcock Medical Center, Lebanon, N.H., who was asked for comment, noted that public endorsement for potential benefits of the marijuana plant is at an all-time high.

“To date, 33 states and the District of Columbia have responded by legalizing medical marijuana, with 10 states also having legalized recreational use of marijuana. The current practice is said to be ahead of science, as robust research has been hindered by strict regulations – and most epidemiological studies point toward harmful associations,” Dr. Stanciu said in an interview.

“Given the decreased perception of harm by the general public, women are certainly compelled to seek what they perceive as more natural self-management remedies,” he said.
 

A harmful habit

Dr. Stanciu cited a recent study conducted in Colorado in which researchers contacted cannabis dispensaries, identified themselves as being pregnant, and asked for guidance in managing pregnancy-related symptoms.

Almost 70% of dispensaries recommended products to treat symptoms, particularly in the vulnerable first trimester; 36% of them also provided reassurance of the safety profile. Very few encouraged a discussion with the physician.

“Consumption of cannabis during pregnancy results in cannabinoid placental crossing and accumulation in the fetal brain, as well as other organs, where it interferes with neurodevelopment and the endocannabinoid system,” he said.

In addition, retrospective studies have shown an association between prenatal cannabis ingestion and anemia in the mothers, low birth weight, greater risk for preterm and stillbirths, and increased need for neonatal ICU admissions.

“Children born to mothers who used cannabis during pregnancy have higher rates of impulsivity, delinquency, learning and memory impairment, as well as executive function deficits. There is also an increased association with proneness to psychosis during middle childhood,” Dr. Stanciu said.

When used during pregnancy, cannabis has been associated with increased anxiety in mothers, as well as increased risk for depressive disorders, incidence of suicidal ideations and behavior, and symptoms of mania and psychosis among those with bipolar and schizophrenia spectrum conditions. Cannabis has also been linked to coingestion of other substances and with alcohol use.

“So cannabis can pose harm, especially when used by those with affective disorders,” Dr. Stanciu said.

The study was funded by the National Institute on Drug Abuse. Dr. Richison, Dr. Marienfeld, and Dr. Stanciu have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com

Cannabis is ineffective at alleviating depression in pregnant women undergoing opioid agonist therapy (OAT), new research shows.

RyanKing999/iStock/Getty Images

A study of more than 120 pregnant women undergoing treatment of opioid use disorder (OUD) showed that those who used cannabis to alleviate their depressive symptoms while undergoing OAT continued to have high depression scores at the end of opioid treatment.

In addition, depression scores improved for those who abstained from cannabis use after their first positive screen. Interestingly, cannabis use did not affect patient retention in treatment for OUD, the investigators note.

“To our knowledge, this is the first time looking at the impact of cannabis on the specific population of pregnant women with opioid use disorder, who are very vulnerable to depression,” lead author Abigail Richison, MD, University of Arkansas for Medical Sciences, Little Rock, said in an interview.

The findings were presented at the American Academy of Addiction Psychiatry (AAAP) 31st Annual Meeting, which was held online this year because of the COVID-19 pandemic.
 

A safer alternative?

Data from the National Survey on Drug Use and Health show that perinatal cannabis use increased by 62% between 2002 and 2014. Many women try to ameliorate their depression symptoms by using cannabis in the mistaken belief that it will help their depression, the investigators noted.

In addition, many women consider cannabis safer during pregnancy than prescribed medications for improving mood, said Dr. Richison. She said that cannabis does not alleviate depression and may even worsen it.

Dr. Richison noted that at her center, which has a women’s health program that treats pregnant women with OUDs, she was seeing a lot of patients who reported using cannabis to improve their mood.

“However, it didn’t seem like it was really helping, so I started researching about cannabis and depression,” Dr. Richison said.

“I’ve always been interested in this population because they are very vulnerable to legal implications and can be accused of perinatal substance use. I think it is very important to screen for depression as well as cannabis use in this population,” she added.

To shed some light on the impact of cannabis use by pregnant patients with OUD, the investigators conducted a retrospective chart review of 121 pregnant women with OUD who attended outpatient OAT. All were prescribed buprenorphine.

At each visit, Beck Depression Inventory (BDI) scores were obtained and urine drug screens were administered. The primary outcome was BDI score. Other measures included retention, urinary drug screen results, and antidepressant use.

The women were divided into two groups. The first comprised cannabis users, defined as having more than one urine drug screen that was positive for cannabis (n = 35). The other group comprised nonusers, defined as having urine drug screens that were negative for cannabis (n = 86).

Cannabis users were a little younger (mean age, 27 years) than non–cannabis users (mean age, 29.5 years; P = .006). Most of the participants were White (80.2%). Roughly half were on Medicaid, and most of the other participants had private insurance; a small number of women had no insurance.

Results showed that cannabis users had significantly higher BDI scores than non–cannabis users (mean scores, 16 vs. 9.3; P < .001).

Cannabis use continued to be associated with elevated scores for depression when controlling for opioid misuse and antidepressant use. There were no significant differences in retention or lapse to opioid misuse between the two groups.
 

More evidence of risk

Commenting on the findings in an interview, Carla Marienfeld, MD, professor of psychiatry at the University of California, San Diego, said there is a growing body of evidence about risks from cannabis use during pregnancy, “a time where we already know the endocannabinoid system is very active in the developing fetus.”

She noted that the current study’s design makes it hard to know whether marijuana use causes worse depression.

However, “it clearly is not associated with helping to improve mood the way people who are using it believe or hope for,” said Dr. Marienfeld, who was not part of the research.

“The risk for harm in terms of worse mood for the pregnant woman or risks for harm to the developing fetus are being better understood with many new studies,” she added.

Yet as more and more states legalize medical marijuana, cannabis use during pregnancy is only going to rise, experts fear.

Cornel Stanciu, MD, of Dartmouth-Hitchcock Medical Center, Lebanon, N.H., who was asked for comment, noted that public endorsement for potential benefits of the marijuana plant is at an all-time high.

“To date, 33 states and the District of Columbia have responded by legalizing medical marijuana, with 10 states also having legalized recreational use of marijuana. The current practice is said to be ahead of science, as robust research has been hindered by strict regulations – and most epidemiological studies point toward harmful associations,” Dr. Stanciu said in an interview.

“Given the decreased perception of harm by the general public, women are certainly compelled to seek what they perceive as more natural self-management remedies,” he said.
 

A harmful habit

Dr. Stanciu cited a recent study conducted in Colorado in which researchers contacted cannabis dispensaries, identified themselves as being pregnant, and asked for guidance in managing pregnancy-related symptoms.

Almost 70% of dispensaries recommended products to treat symptoms, particularly in the vulnerable first trimester; 36% of them also provided reassurance of the safety profile. Very few encouraged a discussion with the physician.

“Consumption of cannabis during pregnancy results in cannabinoid placental crossing and accumulation in the fetal brain, as well as other organs, where it interferes with neurodevelopment and the endocannabinoid system,” he said.

In addition, retrospective studies have shown an association between prenatal cannabis ingestion and anemia in the mothers, low birth weight, greater risk for preterm and stillbirths, and increased need for neonatal ICU admissions.

“Children born to mothers who used cannabis during pregnancy have higher rates of impulsivity, delinquency, learning and memory impairment, as well as executive function deficits. There is also an increased association with proneness to psychosis during middle childhood,” Dr. Stanciu said.

When used during pregnancy, cannabis has been associated with increased anxiety in mothers, as well as increased risk for depressive disorders, incidence of suicidal ideations and behavior, and symptoms of mania and psychosis among those with bipolar and schizophrenia spectrum conditions. Cannabis has also been linked to coingestion of other substances and with alcohol use.

“So cannabis can pose harm, especially when used by those with affective disorders,” Dr. Stanciu said.

The study was funded by the National Institute on Drug Abuse. Dr. Richison, Dr. Marienfeld, and Dr. Stanciu have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com

In 2017, Global Pediatric Health published a case report series associated with the use of long-acting reversible contraceptives, specifically the etonogestrel implant. The cases highlighted challenging removals of the etonogestrel implants because of migration, fracture, or a bent device, and served as a caution to providers.

In November 2020, the makers of the etonogestrel implant (Merck) recommended a change in practice with the release of a notice to health care providers certified in the training of this product. This mass marketing blast included an updated warning and cautions for prescribers as well as patient information on the potential risks of migration, fracture, and bent devices attributable to trauma or sports. “Broken or Bent Implant (Section 5.16). The addition of the following underlined language: “There have been reports of broken or bent implants, which may be related to external forces (e.g., manipulation of the implant or contact sports) while in the patient’s arm. There have also been reports of migration of a broken implant fragment within the arm.”

Clearly the etonogestrel subdermal hormonal implant is an effective form of contraception and particularly beneficial in nonadherent sexually active teens who struggle to remember oral contraceptives. But it is important to be aware of this alert. Little is known about the type of trauma or rate of external force required to cause migration, fracture, or bend implants. This update requires adequate counseling of potential risks and complications of the etonogestrel implant, including the risk of migration, fracture, or bent devices specifically in the event of contact sports and trauma.
 

Ms. Thew is medical director of the department of adolescent medicine at Children’s Wisconsin in Milwaukee. She is a member of the Pediatric News editorial advisory board. She had no relevant financial disclosures. Email Ms. Thew at pdnews@mdedge.com.

In 2017, Global Pediatric Health published a case report series associated with the use of long-acting reversible contraceptives, specifically the etonogestrel implant. The cases highlighted challenging removals of the etonogestrel implants because of migration, fracture, or a bent device, and served as a caution to providers.

In November 2020, the makers of the etonogestrel implant (Merck) recommended a change in practice with the release of a notice to health care providers certified in the training of this product. This mass marketing blast included an updated warning and cautions for prescribers as well as patient information on the potential risks of migration, fracture, and bent devices attributable to trauma or sports. “Broken or Bent Implant (Section 5.16). The addition of the following underlined language: “There have been reports of broken or bent implants, which may be related to external forces (e.g., manipulation of the implant or contact sports) while in the patient’s arm. There have also been reports of migration of a broken implant fragment within the arm.”

Clearly the etonogestrel subdermal hormonal implant is an effective form of contraception and particularly beneficial in nonadherent sexually active teens who struggle to remember oral contraceptives. But it is important to be aware of this alert. Little is known about the type of trauma or rate of external force required to cause migration, fracture, or bend implants. This update requires adequate counseling of potential risks and complications of the etonogestrel implant, including the risk of migration, fracture, or bent devices specifically in the event of contact sports and trauma.
 

Ms. Thew is medical director of the department of adolescent medicine at Children’s Wisconsin in Milwaukee. She is a member of the Pediatric News editorial advisory board. She had no relevant financial disclosures. Email Ms. Thew at pdnews@mdedge.com.

In 2017, Global Pediatric Health published a case report series associated with the use of long-acting reversible contraceptives, specifically the etonogestrel implant. The cases highlighted challenging removals of the etonogestrel implants because of migration, fracture, or a bent device, and served as a caution to providers.

In November 2020, the makers of the etonogestrel implant (Merck) recommended a change in practice with the release of a notice to health care providers certified in the training of this product. This mass marketing blast included an updated warning and cautions for prescribers as well as patient information on the potential risks of migration, fracture, and bent devices attributable to trauma or sports. “Broken or Bent Implant (Section 5.16). The addition of the following underlined language: “There have been reports of broken or bent implants, which may be related to external forces (e.g., manipulation of the implant or contact sports) while in the patient’s arm. There have also been reports of migration of a broken implant fragment within the arm.”

Clearly the etonogestrel subdermal hormonal implant is an effective form of contraception and particularly beneficial in nonadherent sexually active teens who struggle to remember oral contraceptives. But it is important to be aware of this alert. Little is known about the type of trauma or rate of external force required to cause migration, fracture, or bend implants. This update requires adequate counseling of potential risks and complications of the etonogestrel implant, including the risk of migration, fracture, or bent devices specifically in the event of contact sports and trauma.
 

Ms. Thew is medical director of the department of adolescent medicine at Children’s Wisconsin in Milwaukee. She is a member of the Pediatric News editorial advisory board. She had no relevant financial disclosures. Email Ms. Thew at pdnews@mdedge.com.