Women's Health

If COVID-19 has caused millions of deaths, it may also have prevented or at least led to a postponement of many births.

In an assessment of the pandemic’s early effects, Arnstein Aassve, PhD, and colleagues found a significant COVID-19–related decline in crude birth rates (CBRs) in 7 of 22 high-income countries, particularly in Southwestern Europe.

Dr. Aassve, an economist at the Carlo F. Dondena Center for Research on Social Dynamics and Public Policy at the Università Commerciale Luigi Bocconi, Milan, and colleagues report the results in an article published online August 30 in the Proceedings of the National Academy of Sciences.

Defining the start of the COVID-19 pandemic as February 2020, the study identifies strong declines in Italy (-9.1%), Hungary (-8.5%), Spain (-8.4%), and Portugal (-6.6%) beyond those predicted by past trends. In the United States, CBRs fell by 7.1% relative to 2019 for births occurring in Nov. and Dec. 2020 following conceptions in February and March of that year.

Significant declines in CBR also occurred in Belgium, Austria, and Singapore.

A year-to-year comparison of the mean for monthly CBRs per 1,000 population before and during the pandemic suggests a negative difference for all countries studied except for Denmark, Finland, Germany, and the Netherlands, Dr. Aassve and colleagues write. These findings may have policy implications for childcare, housing, and the labor market.

The Milan researchers compared monthly vital statistics data on live births from the international Human Fertility Database for the period of Jan. 2016 to March 2021. These figures reflect conceptions carried to term between April 2015 and June 2020. The 22 countries in the analysis represent 37% of the total reported COVID-19 cases and 34% of deaths worldwide.

The study findings align with surveys on “fertility intentions” collected early in the first COVID-19 wave in Germany, France, Spain, and the United Kingdom. These surveys indicated that 73% of people who were planning pregnancies in 2020 either decided to delay the pregnancy or they abandoned their plans.

“The popular media speculated that the lockdown would lead to a baby boom, as couples spent more time together,” Dr. Aassve told this news organization. “There’s very little evidence of this when you look to previous disasters and shocks, and the first data suggest more of an immediate collapse than a boom. But as you also see from the paper, the collapse is not seen everywhere.” Other current studies suggest the fertility drop is immediate but temporary, says Dr. Aassve, who is also a professor of demography.

Interestingly, Dr. Aassve and colleagues found that CBRs were relatively stable in Northern Europe. The authors point to supportive social and family policies in that region that might have reduced the effect of the pandemic on births. “These factors are likely to affect CBRs in the subsequent pandemic waves,” they write. They call for future studies to assess the full population implications of the pandemic, the moderating impact of policy interventions, and the nexus between short- and long-run effects in relation to the various waves of the COVID-19 pandemic.
 

Rebounds

Some regions have already reported a rebound from the COVID-19 fertility trough. Molly J. Stout, MD, director of maternal fetal medicine at the University of Michigan, Ann Arbor, and colleagues used electronic medical records to predict a surge in births after the initial decline.

“The surge we’ve seen at the end of this summer is exceeding the usual annual birth rate, as predicted,” she said in an interview. “But I think there’ll be a return to normal after this transient escalation. I don’t think birth rates will stay elevated above the normal because the birth surge is a temporary response to an event, although there will likely be regional differences.”

Looking ahead, Dr. Stout, who was not involved in Dr. Aassve’s analysis, is not certain how a fourth pandemic wave might ultimately modify a couple’s overall family size. But the toll the health crisis has taken on working women who have been forced to withdraw from the economy because of a lack of childcare points to a societal need that should be addressed.

According to Philip N. Cohen, PhD, a professor of sociology at the University of Maryland, College Park, who’s been tracking fertility trends since the onset of the COVID-19 emergency, the pandemic has combined a health crisis with an economic crisis, along with “the additional factor of social distancing and isolation, which all contributed to the decline in birth rates. Some people changed their plans to hold off on having children, while others didn’t get pregnant because they weren’t socializing and meeting people as much.”

Dr. Cohen, who was not involved in the study by Dr. Aassve and associates, said his provisional data show that although in many places, birth rates have rebounded more or less to prepandemic levels after a nadir around Jan. 2021, some areas of the United States still show substantially lower rates, including California, Hawaii, and Oregon.

As to the duration of the pandemic effect, Dr. Aassve cautions that his group’s estimates refer to the first wave only. “We then have the second, third, and currently the fourth wave. We can’t be sure about the impact of these waves on fertility since the data are not there yet, but I’d be surprised if they didn’t continue to have an impact on fertility rates,” he said.

Dr. Cohen agreed: “Some people who delayed childbearing will make up the delay. However, whenever there’s a delay, there’s inevitably some portion of the decline that’s not recouped.”

As for the wider effect across the world, Dr. Aassve said his team’s figures derive from high-income countries where data are readily available. For middle- and low-income countries, fewer data exist, and the quality of those data is not as good.

The lessons from this and other upheavals teach us that unforeseen shocks almost always have a negative impact on fertility, says Dr. Aassve. “[B]ut these effects may be separate from existing declining trends. The issue here is that those overall declining trends may be driven by other factors. In contrast, the shock of the pandemic is short-lived, and we may return to normal rather quickly. But if the pandemic also impacts other societal structures, such as the occupational and industrial sectors, then the pandemic might exacerbate the negative trend.”

The study was supported by funding from the European Research Council for funding under the European Union’s Horizon 2020 Research and Innovation Programme. The study authors, Dr. Stout, and Dr. Cohen have disclosed no relevant financial relationships.

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

If COVID-19 has caused millions of deaths, it may also have prevented or at least led to a postponement of many births.

In an assessment of the pandemic’s early effects, Arnstein Aassve, PhD, and colleagues found a significant COVID-19–related decline in crude birth rates (CBRs) in 7 of 22 high-income countries, particularly in Southwestern Europe.

Dr. Aassve, an economist at the Carlo F. Dondena Center for Research on Social Dynamics and Public Policy at the Università Commerciale Luigi Bocconi, Milan, and colleagues report the results in an article published online August 30 in the Proceedings of the National Academy of Sciences.

Defining the start of the COVID-19 pandemic as February 2020, the study identifies strong declines in Italy (-9.1%), Hungary (-8.5%), Spain (-8.4%), and Portugal (-6.6%) beyond those predicted by past trends. In the United States, CBRs fell by 7.1% relative to 2019 for births occurring in Nov. and Dec. 2020 following conceptions in February and March of that year.

Significant declines in CBR also occurred in Belgium, Austria, and Singapore.

A year-to-year comparison of the mean for monthly CBRs per 1,000 population before and during the pandemic suggests a negative difference for all countries studied except for Denmark, Finland, Germany, and the Netherlands, Dr. Aassve and colleagues write. These findings may have policy implications for childcare, housing, and the labor market.

The Milan researchers compared monthly vital statistics data on live births from the international Human Fertility Database for the period of Jan. 2016 to March 2021. These figures reflect conceptions carried to term between April 2015 and June 2020. The 22 countries in the analysis represent 37% of the total reported COVID-19 cases and 34% of deaths worldwide.

The study findings align with surveys on “fertility intentions” collected early in the first COVID-19 wave in Germany, France, Spain, and the United Kingdom. These surveys indicated that 73% of people who were planning pregnancies in 2020 either decided to delay the pregnancy or they abandoned their plans.

“The popular media speculated that the lockdown would lead to a baby boom, as couples spent more time together,” Dr. Aassve told this news organization. “There’s very little evidence of this when you look to previous disasters and shocks, and the first data suggest more of an immediate collapse than a boom. But as you also see from the paper, the collapse is not seen everywhere.” Other current studies suggest the fertility drop is immediate but temporary, says Dr. Aassve, who is also a professor of demography.

Interestingly, Dr. Aassve and colleagues found that CBRs were relatively stable in Northern Europe. The authors point to supportive social and family policies in that region that might have reduced the effect of the pandemic on births. “These factors are likely to affect CBRs in the subsequent pandemic waves,” they write. They call for future studies to assess the full population implications of the pandemic, the moderating impact of policy interventions, and the nexus between short- and long-run effects in relation to the various waves of the COVID-19 pandemic.
 

Rebounds

Some regions have already reported a rebound from the COVID-19 fertility trough. Molly J. Stout, MD, director of maternal fetal medicine at the University of Michigan, Ann Arbor, and colleagues used electronic medical records to predict a surge in births after the initial decline.

“The surge we’ve seen at the end of this summer is exceeding the usual annual birth rate, as predicted,” she said in an interview. “But I think there’ll be a return to normal after this transient escalation. I don’t think birth rates will stay elevated above the normal because the birth surge is a temporary response to an event, although there will likely be regional differences.”

Looking ahead, Dr. Stout, who was not involved in Dr. Aassve’s analysis, is not certain how a fourth pandemic wave might ultimately modify a couple’s overall family size. But the toll the health crisis has taken on working women who have been forced to withdraw from the economy because of a lack of childcare points to a societal need that should be addressed.

According to Philip N. Cohen, PhD, a professor of sociology at the University of Maryland, College Park, who’s been tracking fertility trends since the onset of the COVID-19 emergency, the pandemic has combined a health crisis with an economic crisis, along with “the additional factor of social distancing and isolation, which all contributed to the decline in birth rates. Some people changed their plans to hold off on having children, while others didn’t get pregnant because they weren’t socializing and meeting people as much.”

Dr. Cohen, who was not involved in the study by Dr. Aassve and associates, said his provisional data show that although in many places, birth rates have rebounded more or less to prepandemic levels after a nadir around Jan. 2021, some areas of the United States still show substantially lower rates, including California, Hawaii, and Oregon.

As to the duration of the pandemic effect, Dr. Aassve cautions that his group’s estimates refer to the first wave only. “We then have the second, third, and currently the fourth wave. We can’t be sure about the impact of these waves on fertility since the data are not there yet, but I’d be surprised if they didn’t continue to have an impact on fertility rates,” he said.

Dr. Cohen agreed: “Some people who delayed childbearing will make up the delay. However, whenever there’s a delay, there’s inevitably some portion of the decline that’s not recouped.”

As for the wider effect across the world, Dr. Aassve said his team’s figures derive from high-income countries where data are readily available. For middle- and low-income countries, fewer data exist, and the quality of those data is not as good.

The lessons from this and other upheavals teach us that unforeseen shocks almost always have a negative impact on fertility, says Dr. Aassve. “[B]ut these effects may be separate from existing declining trends. The issue here is that those overall declining trends may be driven by other factors. In contrast, the shock of the pandemic is short-lived, and we may return to normal rather quickly. But if the pandemic also impacts other societal structures, such as the occupational and industrial sectors, then the pandemic might exacerbate the negative trend.”

The study was supported by funding from the European Research Council for funding under the European Union’s Horizon 2020 Research and Innovation Programme. The study authors, Dr. Stout, and Dr. Cohen have disclosed no relevant financial relationships.

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

If COVID-19 has caused millions of deaths, it may also have prevented or at least led to a postponement of many births.

In an assessment of the pandemic’s early effects, Arnstein Aassve, PhD, and colleagues found a significant COVID-19–related decline in crude birth rates (CBRs) in 7 of 22 high-income countries, particularly in Southwestern Europe.

Dr. Aassve, an economist at the Carlo F. Dondena Center for Research on Social Dynamics and Public Policy at the Università Commerciale Luigi Bocconi, Milan, and colleagues report the results in an article published online August 30 in the Proceedings of the National Academy of Sciences.

Defining the start of the COVID-19 pandemic as February 2020, the study identifies strong declines in Italy (-9.1%), Hungary (-8.5%), Spain (-8.4%), and Portugal (-6.6%) beyond those predicted by past trends. In the United States, CBRs fell by 7.1% relative to 2019 for births occurring in Nov. and Dec. 2020 following conceptions in February and March of that year.

Significant declines in CBR also occurred in Belgium, Austria, and Singapore.

A year-to-year comparison of the mean for monthly CBRs per 1,000 population before and during the pandemic suggests a negative difference for all countries studied except for Denmark, Finland, Germany, and the Netherlands, Dr. Aassve and colleagues write. These findings may have policy implications for childcare, housing, and the labor market.

The Milan researchers compared monthly vital statistics data on live births from the international Human Fertility Database for the period of Jan. 2016 to March 2021. These figures reflect conceptions carried to term between April 2015 and June 2020. The 22 countries in the analysis represent 37% of the total reported COVID-19 cases and 34% of deaths worldwide.

The study findings align with surveys on “fertility intentions” collected early in the first COVID-19 wave in Germany, France, Spain, and the United Kingdom. These surveys indicated that 73% of people who were planning pregnancies in 2020 either decided to delay the pregnancy or they abandoned their plans.

“The popular media speculated that the lockdown would lead to a baby boom, as couples spent more time together,” Dr. Aassve told this news organization. “There’s very little evidence of this when you look to previous disasters and shocks, and the first data suggest more of an immediate collapse than a boom. But as you also see from the paper, the collapse is not seen everywhere.” Other current studies suggest the fertility drop is immediate but temporary, says Dr. Aassve, who is also a professor of demography.

Interestingly, Dr. Aassve and colleagues found that CBRs were relatively stable in Northern Europe. The authors point to supportive social and family policies in that region that might have reduced the effect of the pandemic on births. “These factors are likely to affect CBRs in the subsequent pandemic waves,” they write. They call for future studies to assess the full population implications of the pandemic, the moderating impact of policy interventions, and the nexus between short- and long-run effects in relation to the various waves of the COVID-19 pandemic.
 

Rebounds

Some regions have already reported a rebound from the COVID-19 fertility trough. Molly J. Stout, MD, director of maternal fetal medicine at the University of Michigan, Ann Arbor, and colleagues used electronic medical records to predict a surge in births after the initial decline.

“The surge we’ve seen at the end of this summer is exceeding the usual annual birth rate, as predicted,” she said in an interview. “But I think there’ll be a return to normal after this transient escalation. I don’t think birth rates will stay elevated above the normal because the birth surge is a temporary response to an event, although there will likely be regional differences.”

Looking ahead, Dr. Stout, who was not involved in Dr. Aassve’s analysis, is not certain how a fourth pandemic wave might ultimately modify a couple’s overall family size. But the toll the health crisis has taken on working women who have been forced to withdraw from the economy because of a lack of childcare points to a societal need that should be addressed.

According to Philip N. Cohen, PhD, a professor of sociology at the University of Maryland, College Park, who’s been tracking fertility trends since the onset of the COVID-19 emergency, the pandemic has combined a health crisis with an economic crisis, along with “the additional factor of social distancing and isolation, which all contributed to the decline in birth rates. Some people changed their plans to hold off on having children, while others didn’t get pregnant because they weren’t socializing and meeting people as much.”

Dr. Cohen, who was not involved in the study by Dr. Aassve and associates, said his provisional data show that although in many places, birth rates have rebounded more or less to prepandemic levels after a nadir around Jan. 2021, some areas of the United States still show substantially lower rates, including California, Hawaii, and Oregon.

As to the duration of the pandemic effect, Dr. Aassve cautions that his group’s estimates refer to the first wave only. “We then have the second, third, and currently the fourth wave. We can’t be sure about the impact of these waves on fertility since the data are not there yet, but I’d be surprised if they didn’t continue to have an impact on fertility rates,” he said.

Dr. Cohen agreed: “Some people who delayed childbearing will make up the delay. However, whenever there’s a delay, there’s inevitably some portion of the decline that’s not recouped.”

As for the wider effect across the world, Dr. Aassve said his team’s figures derive from high-income countries where data are readily available. For middle- and low-income countries, fewer data exist, and the quality of those data is not as good.

The lessons from this and other upheavals teach us that unforeseen shocks almost always have a negative impact on fertility, says Dr. Aassve. “[B]ut these effects may be separate from existing declining trends. The issue here is that those overall declining trends may be driven by other factors. In contrast, the shock of the pandemic is short-lived, and we may return to normal rather quickly. But if the pandemic also impacts other societal structures, such as the occupational and industrial sectors, then the pandemic might exacerbate the negative trend.”

The study was supported by funding from the European Research Council for funding under the European Union’s Horizon 2020 Research and Innovation Programme. The study authors, Dr. Stout, and Dr. Cohen have disclosed no relevant financial relationships.

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

Breast cancer screening rates at community health centers (CHCs) in the United States declined during the pandemic, particularly among Black and uninsured individuals, based on a retrospective look at 32 sites.

Still, drops in screening were less dramatic than national declines previously reported, possibly because of the American Cancer Society–directed CHANGE program, which was simultaneously underway at the CHCs involved, reported lead author Stacey A. Fedewa, PhD, senior principal scientist at the ACS in Atlanta, and colleagues.

“This is one of the first studies to examine breast cancer screening rates during the pandemic specifically among clinics providing care to communities of color and lower income populations, a group with lower utilization of and greater barriers to [breast cancer] screening,” the investigators wrote in Cancer. “This is important because these populations have longstanding barriers to accessing care, lower breast screening rates, higher breast cancer mortality rates, and are especially vulnerable to health care disruptions.”

According to a previous analysis of electronic health records by Mast and Munoz del Rio, breast cancer screening rates in the United States dropped 94% in March/April 2020, when the COVID-19 pandemic was declared a national emergency. Although a recent follow-up report showed a rebound in breast cancer screening, the estimated rate remains 13% below average.

The present study evaluated data from 32 out of 1,385 CHCs in the United States. All centers were involved in the ACS-run CHANGE grant program, which funded the clinics for 2 years, during which time they implemented at least three evidence-based provider and client interventions, such as patient navigation or electronic medical record enhancements. The clinics reported breast cancer screening rates on a routine basis throughout the 2-year period, beginning August 2018.

Breast cancer screening rate was defined as the percentage of women aged 50-74 years who had a screening mammogram within the past 27 months, out of a total pool of women who had a medical visit within the past year. For 2018, 2019, and 2020, respectively, 142,207; 142,003; and 150,630 women had a medical visit. Screening rates were compared across years in either June or July. Findings were further characterized by demographic characteristics, urban/rural status, and clinic region.

From 2018 to 2019 breast cancer screening rates rose 18%, from 45.8% to 53.9%. This increase was followed by an 8% decline during the 2019-2020 period, from 53.9% to 49.6%.

The investigators estimated the number of missed mammograms and breast cancer diagnoses for two comparative, hypothetical scenarios: first, if the rising trend from 2018 to 2019 had continued through 2020, and second, if the rate had plateaued at 53.9%.

The rising trend model suggested that 47,517 fewer mammograms than normal were conducted during 2019-2020, resulting in 242 missed breast cancer diagnoses, of which 166 were invasive and 76 were ductal carcinoma in situ. The plateau model suggested that 6,477 fewer mammograms were conducted, leading to 33 missed diagnoses.

Compared with the 8% decline in screening overall, the rate among Black patients dropped 12%, while rates at clinics with a lower proportion of uninsured patients dropped an average of 15%. In contrast, clinics in the South did not have a significant reduction in screening, “possibly reflecting lower baseline rates or impact of stay-at-home orders,” the investigators wrote.

Dr. Fedewa and colleagues also noted that their findings were less dramatic than those reported by Mast and Munoz del Rio. They suggested that the CHANGE program may have softened the blow dealt by the pandemic.

“The CHANGE program–funded interventions – that were established before and continued through 2020 – may have mitigated the pandemic’s effects on breast cancer screening services among the 32 CHCs that were studied,” they wrote. “Further investigation of breast cancer screening rates among additional CHCs will further inform where targeted interventions (e.g., client reminders, education on return to screening) are most needed.”

According to Madeline Sutton, MD, assistant professor of obstetrics and gynecology at Morehouse School of Medicine, Atlanta, “Progress seen with the CHANGE program should be duplicated in other clinical venues based on improvements seen in numbers of mammograms and breast cancers detected.”

Still, Dr. Sutton noted that the racial/ethnic disparities remain cause for concern.

“This study has implications for persons served at CHCs, especially if breast cancer racial/ethnic disparities are unintentionally widened during this pandemic,” Dr. Sutton said in a written comment. “Policy-level changes that decrease BCSR [breast cancer screen rate] gaps for women are warranted.”

Ana Velázquez Mañana, MD, a medical oncology fellow at the University of California, San Francisco, suggested that the effects of the pandemic may have been even more pronounced among medically underserved patients in whom interventions to increase screening were not being conducted, as they were through the CHANGE program.

“One must wonder to what degree these interventions reduced the decline in screening mammography rates observed during the pandemic and to what degree could disparities in screening be magnified in community health centers with less resources,” Dr. Velázquez said in a written comment. “Therefore, understanding barriers to breast cancer screening among our specific health care systems is key to guide resource allocation and the development of evidence-based multilevel interventions that can address these barriers, and ultimately increase screening rates.”

Dr. Velázquez also noted that the study by Dr. Fedewa and colleagues may have missed drops in screening among vulnerable populations that occurred later in the pandemic and in geographic hotspots. In a recent JAMA Network Open study, Dr. Velázquez reported a 41% drop in breast cancer screening at a safety-net hospital in San Francisco during the first stay-at-home order, which lasted from Feb. 1, 2020 to May 31, 2020.

The Breast Health Equity CHANGE grant was funded by the National Football League in partnership with the American Cancer Society. The investigators reported employment by the American Cancer Society. Dr. Wehling and Dr. Wysocki disclosed grants from Pfizer unrelated to this research. Dr. Sutton and Dr. Velázquez disclosed no conflicts of interest.

Breast cancer screening rates at community health centers (CHCs) in the United States declined during the pandemic, particularly among Black and uninsured individuals, based on a retrospective look at 32 sites.

Still, drops in screening were less dramatic than national declines previously reported, possibly because of the American Cancer Society–directed CHANGE program, which was simultaneously underway at the CHCs involved, reported lead author Stacey A. Fedewa, PhD, senior principal scientist at the ACS in Atlanta, and colleagues.

“This is one of the first studies to examine breast cancer screening rates during the pandemic specifically among clinics providing care to communities of color and lower income populations, a group with lower utilization of and greater barriers to [breast cancer] screening,” the investigators wrote in Cancer. “This is important because these populations have longstanding barriers to accessing care, lower breast screening rates, higher breast cancer mortality rates, and are especially vulnerable to health care disruptions.”

According to a previous analysis of electronic health records by Mast and Munoz del Rio, breast cancer screening rates in the United States dropped 94% in March/April 2020, when the COVID-19 pandemic was declared a national emergency. Although a recent follow-up report showed a rebound in breast cancer screening, the estimated rate remains 13% below average.

The present study evaluated data from 32 out of 1,385 CHCs in the United States. All centers were involved in the ACS-run CHANGE grant program, which funded the clinics for 2 years, during which time they implemented at least three evidence-based provider and client interventions, such as patient navigation or electronic medical record enhancements. The clinics reported breast cancer screening rates on a routine basis throughout the 2-year period, beginning August 2018.

Breast cancer screening rate was defined as the percentage of women aged 50-74 years who had a screening mammogram within the past 27 months, out of a total pool of women who had a medical visit within the past year. For 2018, 2019, and 2020, respectively, 142,207; 142,003; and 150,630 women had a medical visit. Screening rates were compared across years in either June or July. Findings were further characterized by demographic characteristics, urban/rural status, and clinic region.

From 2018 to 2019 breast cancer screening rates rose 18%, from 45.8% to 53.9%. This increase was followed by an 8% decline during the 2019-2020 period, from 53.9% to 49.6%.

The investigators estimated the number of missed mammograms and breast cancer diagnoses for two comparative, hypothetical scenarios: first, if the rising trend from 2018 to 2019 had continued through 2020, and second, if the rate had plateaued at 53.9%.

The rising trend model suggested that 47,517 fewer mammograms than normal were conducted during 2019-2020, resulting in 242 missed breast cancer diagnoses, of which 166 were invasive and 76 were ductal carcinoma in situ. The plateau model suggested that 6,477 fewer mammograms were conducted, leading to 33 missed diagnoses.

Compared with the 8% decline in screening overall, the rate among Black patients dropped 12%, while rates at clinics with a lower proportion of uninsured patients dropped an average of 15%. In contrast, clinics in the South did not have a significant reduction in screening, “possibly reflecting lower baseline rates or impact of stay-at-home orders,” the investigators wrote.

Dr. Fedewa and colleagues also noted that their findings were less dramatic than those reported by Mast and Munoz del Rio. They suggested that the CHANGE program may have softened the blow dealt by the pandemic.

“The CHANGE program–funded interventions – that were established before and continued through 2020 – may have mitigated the pandemic’s effects on breast cancer screening services among the 32 CHCs that were studied,” they wrote. “Further investigation of breast cancer screening rates among additional CHCs will further inform where targeted interventions (e.g., client reminders, education on return to screening) are most needed.”

According to Madeline Sutton, MD, assistant professor of obstetrics and gynecology at Morehouse School of Medicine, Atlanta, “Progress seen with the CHANGE program should be duplicated in other clinical venues based on improvements seen in numbers of mammograms and breast cancers detected.”

Still, Dr. Sutton noted that the racial/ethnic disparities remain cause for concern.

“This study has implications for persons served at CHCs, especially if breast cancer racial/ethnic disparities are unintentionally widened during this pandemic,” Dr. Sutton said in a written comment. “Policy-level changes that decrease BCSR [breast cancer screen rate] gaps for women are warranted.”

Ana Velázquez Mañana, MD, a medical oncology fellow at the University of California, San Francisco, suggested that the effects of the pandemic may have been even more pronounced among medically underserved patients in whom interventions to increase screening were not being conducted, as they were through the CHANGE program.

“One must wonder to what degree these interventions reduced the decline in screening mammography rates observed during the pandemic and to what degree could disparities in screening be magnified in community health centers with less resources,” Dr. Velázquez said in a written comment. “Therefore, understanding barriers to breast cancer screening among our specific health care systems is key to guide resource allocation and the development of evidence-based multilevel interventions that can address these barriers, and ultimately increase screening rates.”

Dr. Velázquez also noted that the study by Dr. Fedewa and colleagues may have missed drops in screening among vulnerable populations that occurred later in the pandemic and in geographic hotspots. In a recent JAMA Network Open study, Dr. Velázquez reported a 41% drop in breast cancer screening at a safety-net hospital in San Francisco during the first stay-at-home order, which lasted from Feb. 1, 2020 to May 31, 2020.

The Breast Health Equity CHANGE grant was funded by the National Football League in partnership with the American Cancer Society. The investigators reported employment by the American Cancer Society. Dr. Wehling and Dr. Wysocki disclosed grants from Pfizer unrelated to this research. Dr. Sutton and Dr. Velázquez disclosed no conflicts of interest.

Breast cancer screening rates at community health centers (CHCs) in the United States declined during the pandemic, particularly among Black and uninsured individuals, based on a retrospective look at 32 sites.

Still, drops in screening were less dramatic than national declines previously reported, possibly because of the American Cancer Society–directed CHANGE program, which was simultaneously underway at the CHCs involved, reported lead author Stacey A. Fedewa, PhD, senior principal scientist at the ACS in Atlanta, and colleagues.

“This is one of the first studies to examine breast cancer screening rates during the pandemic specifically among clinics providing care to communities of color and lower income populations, a group with lower utilization of and greater barriers to [breast cancer] screening,” the investigators wrote in Cancer. “This is important because these populations have longstanding barriers to accessing care, lower breast screening rates, higher breast cancer mortality rates, and are especially vulnerable to health care disruptions.”

According to a previous analysis of electronic health records by Mast and Munoz del Rio, breast cancer screening rates in the United States dropped 94% in March/April 2020, when the COVID-19 pandemic was declared a national emergency. Although a recent follow-up report showed a rebound in breast cancer screening, the estimated rate remains 13% below average.

The present study evaluated data from 32 out of 1,385 CHCs in the United States. All centers were involved in the ACS-run CHANGE grant program, which funded the clinics for 2 years, during which time they implemented at least three evidence-based provider and client interventions, such as patient navigation or electronic medical record enhancements. The clinics reported breast cancer screening rates on a routine basis throughout the 2-year period, beginning August 2018.

Breast cancer screening rate was defined as the percentage of women aged 50-74 years who had a screening mammogram within the past 27 months, out of a total pool of women who had a medical visit within the past year. For 2018, 2019, and 2020, respectively, 142,207; 142,003; and 150,630 women had a medical visit. Screening rates were compared across years in either June or July. Findings were further characterized by demographic characteristics, urban/rural status, and clinic region.

From 2018 to 2019 breast cancer screening rates rose 18%, from 45.8% to 53.9%. This increase was followed by an 8% decline during the 2019-2020 period, from 53.9% to 49.6%.

The investigators estimated the number of missed mammograms and breast cancer diagnoses for two comparative, hypothetical scenarios: first, if the rising trend from 2018 to 2019 had continued through 2020, and second, if the rate had plateaued at 53.9%.

The rising trend model suggested that 47,517 fewer mammograms than normal were conducted during 2019-2020, resulting in 242 missed breast cancer diagnoses, of which 166 were invasive and 76 were ductal carcinoma in situ. The plateau model suggested that 6,477 fewer mammograms were conducted, leading to 33 missed diagnoses.

Compared with the 8% decline in screening overall, the rate among Black patients dropped 12%, while rates at clinics with a lower proportion of uninsured patients dropped an average of 15%. In contrast, clinics in the South did not have a significant reduction in screening, “possibly reflecting lower baseline rates or impact of stay-at-home orders,” the investigators wrote.

Dr. Fedewa and colleagues also noted that their findings were less dramatic than those reported by Mast and Munoz del Rio. They suggested that the CHANGE program may have softened the blow dealt by the pandemic.

“The CHANGE program–funded interventions – that were established before and continued through 2020 – may have mitigated the pandemic’s effects on breast cancer screening services among the 32 CHCs that were studied,” they wrote. “Further investigation of breast cancer screening rates among additional CHCs will further inform where targeted interventions (e.g., client reminders, education on return to screening) are most needed.”

According to Madeline Sutton, MD, assistant professor of obstetrics and gynecology at Morehouse School of Medicine, Atlanta, “Progress seen with the CHANGE program should be duplicated in other clinical venues based on improvements seen in numbers of mammograms and breast cancers detected.”

Still, Dr. Sutton noted that the racial/ethnic disparities remain cause for concern.

“This study has implications for persons served at CHCs, especially if breast cancer racial/ethnic disparities are unintentionally widened during this pandemic,” Dr. Sutton said in a written comment. “Policy-level changes that decrease BCSR [breast cancer screen rate] gaps for women are warranted.”

Ana Velázquez Mañana, MD, a medical oncology fellow at the University of California, San Francisco, suggested that the effects of the pandemic may have been even more pronounced among medically underserved patients in whom interventions to increase screening were not being conducted, as they were through the CHANGE program.

“One must wonder to what degree these interventions reduced the decline in screening mammography rates observed during the pandemic and to what degree could disparities in screening be magnified in community health centers with less resources,” Dr. Velázquez said in a written comment. “Therefore, understanding barriers to breast cancer screening among our specific health care systems is key to guide resource allocation and the development of evidence-based multilevel interventions that can address these barriers, and ultimately increase screening rates.”

Dr. Velázquez also noted that the study by Dr. Fedewa and colleagues may have missed drops in screening among vulnerable populations that occurred later in the pandemic and in geographic hotspots. In a recent JAMA Network Open study, Dr. Velázquez reported a 41% drop in breast cancer screening at a safety-net hospital in San Francisco during the first stay-at-home order, which lasted from Feb. 1, 2020 to May 31, 2020.

The Breast Health Equity CHANGE grant was funded by the National Football League in partnership with the American Cancer Society. The investigators reported employment by the American Cancer Society. Dr. Wehling and Dr. Wysocki disclosed grants from Pfizer unrelated to this research. Dr. Sutton and Dr. Velázquez disclosed no conflicts of interest.

Telehealth abortion may be just as safe and effective as in-person care, according to a small study published online in JAMA Network Open.

Of the 110 women from whom researchers collected remote abortion outcome data, 95% had a complete abortion without additional medical interventions, such as aspiration or surgery, and none experienced adverse events. Researchers said this efficacy rate is similar to in-person visits.

“There was no reason to expect that the medications prescribed [via telemedicine] and delivered through the mail would have different outcomes from when a patient traveled to a clinic,” study author Ushma D. Upadhyay, PhD, MPH, associate professor in the department of obstetrics, gynecology, and reproductive sciences at the University of California, San Francisco, said in an interview.

Medication abortion, which usually involves taking mifepristone (Mifeprex) followed by misoprostol (Cytotec) during the first 10 weeks of pregnancy, has been available in the United States since 2000. The Food and Drug Administration’s Risk Evaluation and Mitigation Strategy requires that mifepristone be dispensed in a medical office, clinic, or hospital, prohibiting dispensing from pharmacies in an effort to reduce potential risk for complications.

In April 2021, the FDA lifted the in-person dispensing requirement for mifepristone for the duration of the COVID-19 pandemic. However, Dr. Upadhyay hopes the findings of her current study will make this suspension permanent.

For the study, Dr. Upadhyay and colleagues examined the safety and efficacy of fully remote, medication abortion care. Eligibility for the medication was assessed using an online form that relies on patient history, or patients recalling their last period, to assess pregnancy duration and screen for ectopic pregnancy risks. Nurse practitioners reviewed the form and referred patients with unknown last menstrual period date or ectopic pregnancy risk factors for ultrasonography. A mail-order pharmacy delivered medications to eligible patients. The protocol involved three follow-up contacts: confirmation of medication administration, a 3-day assessment of symptoms, and a home pregnancy test after 4 weeks. Follow-up interactions were conducted by text, secure messaging, or telephone.

Researchers found that in addition to the 95% of the patients having a complete abortion without intervention, 5% (five) of patients required addition medical care to complete the abortion. Two of those patients were treated in EDs.

Gillian Burkhardt, MD, who was not involved in the study, said Dr. Upadhyay’s study proves what has been known all along, that medication is super safe and that women “can help to determine their own eligibility as well as in conjunction with the provider.”

“I hope that this will be one more study that the FDA can use when thinking about changing the risk evaluation administration strategy so that it’s removing the requirement that a person be in the dispensing medical office,” Dr. Burkhardt, assistant professor of family planning in the department of obstetrics & gynecology at the University of New Mexico Hospital, Albuquerque, said in an interview. “I hope it also makes providers feel more comfortable as well, because I think there’s some hesitancy among providers to provide abortion without doing an ultrasound or without seeing the patient typically in front of them.”

This isn’t the first study to suggest the safety of telemedicine abortion. A 2019 study published in Obstetrics & Gynecology, which analyzed records from nearly 6,000 patients receiving medication abortion either through telemedicine or in person at 26 Planned Parenthood health centers in four states found that ongoing pregnancy and aspiration procedures were less common among telemedicine patients. Another 2017 study published in BMJ found that women who used an online consultation service and self-sourced medical abortion during a 3-year period were able to successfully end their pregnancies with few adverse events.

Dr. Upadhyay said one limitation of the current study is its sample size, so more studies should be conducted to prove telemedicine abortion’s safety.

“I think that we need continued research on this model of care just so we have more multiple studies that contribute to the evidence that can convince providers as well that they don’t need a lot of tests and that they can mail,” Dr. Upadhyay said.

Neither Dr. Upadhyay nor Dr. Burkhardt reported conflicts of interests.

Telehealth abortion may be just as safe and effective as in-person care, according to a small study published online in JAMA Network Open.

Of the 110 women from whom researchers collected remote abortion outcome data, 95% had a complete abortion without additional medical interventions, such as aspiration or surgery, and none experienced adverse events. Researchers said this efficacy rate is similar to in-person visits.

“There was no reason to expect that the medications prescribed [via telemedicine] and delivered through the mail would have different outcomes from when a patient traveled to a clinic,” study author Ushma D. Upadhyay, PhD, MPH, associate professor in the department of obstetrics, gynecology, and reproductive sciences at the University of California, San Francisco, said in an interview.

Medication abortion, which usually involves taking mifepristone (Mifeprex) followed by misoprostol (Cytotec) during the first 10 weeks of pregnancy, has been available in the United States since 2000. The Food and Drug Administration’s Risk Evaluation and Mitigation Strategy requires that mifepristone be dispensed in a medical office, clinic, or hospital, prohibiting dispensing from pharmacies in an effort to reduce potential risk for complications.

In April 2021, the FDA lifted the in-person dispensing requirement for mifepristone for the duration of the COVID-19 pandemic. However, Dr. Upadhyay hopes the findings of her current study will make this suspension permanent.

For the study, Dr. Upadhyay and colleagues examined the safety and efficacy of fully remote, medication abortion care. Eligibility for the medication was assessed using an online form that relies on patient history, or patients recalling their last period, to assess pregnancy duration and screen for ectopic pregnancy risks. Nurse practitioners reviewed the form and referred patients with unknown last menstrual period date or ectopic pregnancy risk factors for ultrasonography. A mail-order pharmacy delivered medications to eligible patients. The protocol involved three follow-up contacts: confirmation of medication administration, a 3-day assessment of symptoms, and a home pregnancy test after 4 weeks. Follow-up interactions were conducted by text, secure messaging, or telephone.

Researchers found that in addition to the 95% of the patients having a complete abortion without intervention, 5% (five) of patients required addition medical care to complete the abortion. Two of those patients were treated in EDs.

Gillian Burkhardt, MD, who was not involved in the study, said Dr. Upadhyay’s study proves what has been known all along, that medication is super safe and that women “can help to determine their own eligibility as well as in conjunction with the provider.”

“I hope that this will be one more study that the FDA can use when thinking about changing the risk evaluation administration strategy so that it’s removing the requirement that a person be in the dispensing medical office,” Dr. Burkhardt, assistant professor of family planning in the department of obstetrics & gynecology at the University of New Mexico Hospital, Albuquerque, said in an interview. “I hope it also makes providers feel more comfortable as well, because I think there’s some hesitancy among providers to provide abortion without doing an ultrasound or without seeing the patient typically in front of them.”

This isn’t the first study to suggest the safety of telemedicine abortion. A 2019 study published in Obstetrics & Gynecology, which analyzed records from nearly 6,000 patients receiving medication abortion either through telemedicine or in person at 26 Planned Parenthood health centers in four states found that ongoing pregnancy and aspiration procedures were less common among telemedicine patients. Another 2017 study published in BMJ found that women who used an online consultation service and self-sourced medical abortion during a 3-year period were able to successfully end their pregnancies with few adverse events.

Dr. Upadhyay said one limitation of the current study is its sample size, so more studies should be conducted to prove telemedicine abortion’s safety.

“I think that we need continued research on this model of care just so we have more multiple studies that contribute to the evidence that can convince providers as well that they don’t need a lot of tests and that they can mail,” Dr. Upadhyay said.

Neither Dr. Upadhyay nor Dr. Burkhardt reported conflicts of interests.

Telehealth abortion may be just as safe and effective as in-person care, according to a small study published online in JAMA Network Open.

Of the 110 women from whom researchers collected remote abortion outcome data, 95% had a complete abortion without additional medical interventions, such as aspiration or surgery, and none experienced adverse events. Researchers said this efficacy rate is similar to in-person visits.

“There was no reason to expect that the medications prescribed [via telemedicine] and delivered through the mail would have different outcomes from when a patient traveled to a clinic,” study author Ushma D. Upadhyay, PhD, MPH, associate professor in the department of obstetrics, gynecology, and reproductive sciences at the University of California, San Francisco, said in an interview.

Medication abortion, which usually involves taking mifepristone (Mifeprex) followed by misoprostol (Cytotec) during the first 10 weeks of pregnancy, has been available in the United States since 2000. The Food and Drug Administration’s Risk Evaluation and Mitigation Strategy requires that mifepristone be dispensed in a medical office, clinic, or hospital, prohibiting dispensing from pharmacies in an effort to reduce potential risk for complications.

In April 2021, the FDA lifted the in-person dispensing requirement for mifepristone for the duration of the COVID-19 pandemic. However, Dr. Upadhyay hopes the findings of her current study will make this suspension permanent.

For the study, Dr. Upadhyay and colleagues examined the safety and efficacy of fully remote, medication abortion care. Eligibility for the medication was assessed using an online form that relies on patient history, or patients recalling their last period, to assess pregnancy duration and screen for ectopic pregnancy risks. Nurse practitioners reviewed the form and referred patients with unknown last menstrual period date or ectopic pregnancy risk factors for ultrasonography. A mail-order pharmacy delivered medications to eligible patients. The protocol involved three follow-up contacts: confirmation of medication administration, a 3-day assessment of symptoms, and a home pregnancy test after 4 weeks. Follow-up interactions were conducted by text, secure messaging, or telephone.

Researchers found that in addition to the 95% of the patients having a complete abortion without intervention, 5% (five) of patients required addition medical care to complete the abortion. Two of those patients were treated in EDs.

Gillian Burkhardt, MD, who was not involved in the study, said Dr. Upadhyay’s study proves what has been known all along, that medication is super safe and that women “can help to determine their own eligibility as well as in conjunction with the provider.”

“I hope that this will be one more study that the FDA can use when thinking about changing the risk evaluation administration strategy so that it’s removing the requirement that a person be in the dispensing medical office,” Dr. Burkhardt, assistant professor of family planning in the department of obstetrics & gynecology at the University of New Mexico Hospital, Albuquerque, said in an interview. “I hope it also makes providers feel more comfortable as well, because I think there’s some hesitancy among providers to provide abortion without doing an ultrasound or without seeing the patient typically in front of them.”

This isn’t the first study to suggest the safety of telemedicine abortion. A 2019 study published in Obstetrics & Gynecology, which analyzed records from nearly 6,000 patients receiving medication abortion either through telemedicine or in person at 26 Planned Parenthood health centers in four states found that ongoing pregnancy and aspiration procedures were less common among telemedicine patients. Another 2017 study published in BMJ found that women who used an online consultation service and self-sourced medical abortion during a 3-year period were able to successfully end their pregnancies with few adverse events.

Dr. Upadhyay said one limitation of the current study is its sample size, so more studies should be conducted to prove telemedicine abortion’s safety.

“I think that we need continued research on this model of care just so we have more multiple studies that contribute to the evidence that can convince providers as well that they don’t need a lot of tests and that they can mail,” Dr. Upadhyay said.

Neither Dr. Upadhyay nor Dr. Burkhardt reported conflicts of interests.

In medical school, I remember thinking that telling a patient “you have cancer” would be the most professionally challenging phrase I would ever utter. And don’t get me wrong – it certainly isn’t easy; but, compared with telling someone “you are infertile,” it’s a cakewalk.

Maybe it’s because people “have” cancer and cancer is something you “fight.” Or maybe because, unlike infertility, cancer has become a part of public life (think lapel pins and support groups) and is now easier to accept. On the other hand, someone “is” infertile. The condition is a source of embarrassment for the couple and is often hidden from society.

Here’s another concerning point of contrast: While the overall rate of cancer death has declined since the early 1990s, infertility is increasing. Reports now show that one in six couples have problems conceiving and the use of assisted reproductive technologies is increasing by 5%-10% per year. Many theories exist to explain these trends, chief among them the rise in average maternal age and the increasing incidence of obesity, as well as various other male- and female-specific factors.

But interestingly, recent data suggest that the most male of all male-specific factors – total sperm count – may be specifically to blame.

According to a recent meta-analysis, the average total sperm count in men declined by 59.3% between 1973 and 2011. While these data certainly have limitations – including the exclusion of non-English publications, the reliance on total sperm count and not sperm motility, and the potential bias of those patients willing to give a semen sample – the overall trend nevertheless seems to be clearly downward. What’s more concerning, if you believe the data presented, is that there does not appear to be a leveling off of the downward curve in total sperm count.

Think about that last statement. At the current rate of decline, the average sperm count will be zero in 2045. One of the lead authors on the meta-analysis, Hagai Levine, MD, MPH, goes so far as to state, “We should hope for the best and prepare for the worst.”

As a matter of personal philosophy, I’m not a huge fan of end-of-the-world predictions because they tend not to come true (think Montanism back in the 2nd century; the 2012 Mayan calendar scare; or my personal favorite, the Prophet Hen of Leeds). On the other hand, the overall trend of decreased total sperm count in the English-speaking world seems to be true and it raises the interesting question of why.

According to the Mayo Clinic, causes of decreased sperm count include everything from anatomical factors (like varicoceles and ejaculatory issues) and lifestyle issues (such as recreational drugs, weight gain, and emotional stress) to environmental exposures (heavy metal or radiation). The senior author of the aforementioned meta-analysis, Shanna Swan, PhD, has championed another theory: the widespread exposure to endocrine-disrupting chemicals in everyday plastics.

It turns out that at least two chemicals used in the plastics industry, bisphenol A and phthalates, can mimic the effect of estrogen when ingested into the body. Even low levels of these chemicals in our bodies can lead to health problems.

Consider for a moment the presence of plastics in your life: the plastic wrappings on your food, plastic containers for shampoos and beauty products, and even the coatings of our oral supplements. A study by the Centers for Disease Control and Prevention looked at the urine of people participating in the National Health and Nutrition Examination Survey and found detectable concentrations of both of these chemicals in nearly all participants.

In 2045, I intend to be retired. But in the meantime, I think we all need to be aware of the potential impact that various endocrine-disrupting chemicals could be having on humanity. We need more research. If indeed the connection between endocrine disruptors and decreased sperm count is borne out, changes in our environmental exposure to these chemicals need to be made.

Henry Rosevear, MD, is a private-practice urologist based in Colorado Springs. He comes from a long line of doctors, but before entering medicine he served in the U.S. Navy as an officer aboard the USS Pittsburgh, a fast-attack submarine based out of New London, Conn. During his time in the Navy, he served in two deployments to the Persian Gulf, including combat experience as part of Operation Iraqi Freedom. Dr. Rosevear disclosed no relevant financial relationships. A version of this article first appeared on Medscape.com.

In medical school, I remember thinking that telling a patient “you have cancer” would be the most professionally challenging phrase I would ever utter. And don’t get me wrong – it certainly isn’t easy; but, compared with telling someone “you are infertile,” it’s a cakewalk.

Maybe it’s because people “have” cancer and cancer is something you “fight.” Or maybe because, unlike infertility, cancer has become a part of public life (think lapel pins and support groups) and is now easier to accept. On the other hand, someone “is” infertile. The condition is a source of embarrassment for the couple and is often hidden from society.

Here’s another concerning point of contrast: While the overall rate of cancer death has declined since the early 1990s, infertility is increasing. Reports now show that one in six couples have problems conceiving and the use of assisted reproductive technologies is increasing by 5%-10% per year. Many theories exist to explain these trends, chief among them the rise in average maternal age and the increasing incidence of obesity, as well as various other male- and female-specific factors.

But interestingly, recent data suggest that the most male of all male-specific factors – total sperm count – may be specifically to blame.

According to a recent meta-analysis, the average total sperm count in men declined by 59.3% between 1973 and 2011. While these data certainly have limitations – including the exclusion of non-English publications, the reliance on total sperm count and not sperm motility, and the potential bias of those patients willing to give a semen sample – the overall trend nevertheless seems to be clearly downward. What’s more concerning, if you believe the data presented, is that there does not appear to be a leveling off of the downward curve in total sperm count.

Think about that last statement. At the current rate of decline, the average sperm count will be zero in 2045. One of the lead authors on the meta-analysis, Hagai Levine, MD, MPH, goes so far as to state, “We should hope for the best and prepare for the worst.”

As a matter of personal philosophy, I’m not a huge fan of end-of-the-world predictions because they tend not to come true (think Montanism back in the 2nd century; the 2012 Mayan calendar scare; or my personal favorite, the Prophet Hen of Leeds). On the other hand, the overall trend of decreased total sperm count in the English-speaking world seems to be true and it raises the interesting question of why.

According to the Mayo Clinic, causes of decreased sperm count include everything from anatomical factors (like varicoceles and ejaculatory issues) and lifestyle issues (such as recreational drugs, weight gain, and emotional stress) to environmental exposures (heavy metal or radiation). The senior author of the aforementioned meta-analysis, Shanna Swan, PhD, has championed another theory: the widespread exposure to endocrine-disrupting chemicals in everyday plastics.

It turns out that at least two chemicals used in the plastics industry, bisphenol A and phthalates, can mimic the effect of estrogen when ingested into the body. Even low levels of these chemicals in our bodies can lead to health problems.

Consider for a moment the presence of plastics in your life: the plastic wrappings on your food, plastic containers for shampoos and beauty products, and even the coatings of our oral supplements. A study by the Centers for Disease Control and Prevention looked at the urine of people participating in the National Health and Nutrition Examination Survey and found detectable concentrations of both of these chemicals in nearly all participants.

In 2045, I intend to be retired. But in the meantime, I think we all need to be aware of the potential impact that various endocrine-disrupting chemicals could be having on humanity. We need more research. If indeed the connection between endocrine disruptors and decreased sperm count is borne out, changes in our environmental exposure to these chemicals need to be made.

Henry Rosevear, MD, is a private-practice urologist based in Colorado Springs. He comes from a long line of doctors, but before entering medicine he served in the U.S. Navy as an officer aboard the USS Pittsburgh, a fast-attack submarine based out of New London, Conn. During his time in the Navy, he served in two deployments to the Persian Gulf, including combat experience as part of Operation Iraqi Freedom. Dr. Rosevear disclosed no relevant financial relationships. A version of this article first appeared on Medscape.com.

In medical school, I remember thinking that telling a patient “you have cancer” would be the most professionally challenging phrase I would ever utter. And don’t get me wrong – it certainly isn’t easy; but, compared with telling someone “you are infertile,” it’s a cakewalk.

Maybe it’s because people “have” cancer and cancer is something you “fight.” Or maybe because, unlike infertility, cancer has become a part of public life (think lapel pins and support groups) and is now easier to accept. On the other hand, someone “is” infertile. The condition is a source of embarrassment for the couple and is often hidden from society.

Here’s another concerning point of contrast: While the overall rate of cancer death has declined since the early 1990s, infertility is increasing. Reports now show that one in six couples have problems conceiving and the use of assisted reproductive technologies is increasing by 5%-10% per year. Many theories exist to explain these trends, chief among them the rise in average maternal age and the increasing incidence of obesity, as well as various other male- and female-specific factors.

But interestingly, recent data suggest that the most male of all male-specific factors – total sperm count – may be specifically to blame.

According to a recent meta-analysis, the average total sperm count in men declined by 59.3% between 1973 and 2011. While these data certainly have limitations – including the exclusion of non-English publications, the reliance on total sperm count and not sperm motility, and the potential bias of those patients willing to give a semen sample – the overall trend nevertheless seems to be clearly downward. What’s more concerning, if you believe the data presented, is that there does not appear to be a leveling off of the downward curve in total sperm count.

Think about that last statement. At the current rate of decline, the average sperm count will be zero in 2045. One of the lead authors on the meta-analysis, Hagai Levine, MD, MPH, goes so far as to state, “We should hope for the best and prepare for the worst.”

As a matter of personal philosophy, I’m not a huge fan of end-of-the-world predictions because they tend not to come true (think Montanism back in the 2nd century; the 2012 Mayan calendar scare; or my personal favorite, the Prophet Hen of Leeds). On the other hand, the overall trend of decreased total sperm count in the English-speaking world seems to be true and it raises the interesting question of why.

According to the Mayo Clinic, causes of decreased sperm count include everything from anatomical factors (like varicoceles and ejaculatory issues) and lifestyle issues (such as recreational drugs, weight gain, and emotional stress) to environmental exposures (heavy metal or radiation). The senior author of the aforementioned meta-analysis, Shanna Swan, PhD, has championed another theory: the widespread exposure to endocrine-disrupting chemicals in everyday plastics.

It turns out that at least two chemicals used in the plastics industry, bisphenol A and phthalates, can mimic the effect of estrogen when ingested into the body. Even low levels of these chemicals in our bodies can lead to health problems.

Consider for a moment the presence of plastics in your life: the plastic wrappings on your food, plastic containers for shampoos and beauty products, and even the coatings of our oral supplements. A study by the Centers for Disease Control and Prevention looked at the urine of people participating in the National Health and Nutrition Examination Survey and found detectable concentrations of both of these chemicals in nearly all participants.

In 2045, I intend to be retired. But in the meantime, I think we all need to be aware of the potential impact that various endocrine-disrupting chemicals could be having on humanity. We need more research. If indeed the connection between endocrine disruptors and decreased sperm count is borne out, changes in our environmental exposure to these chemicals need to be made.

Henry Rosevear, MD, is a private-practice urologist based in Colorado Springs. He comes from a long line of doctors, but before entering medicine he served in the U.S. Navy as an officer aboard the USS Pittsburgh, a fast-attack submarine based out of New London, Conn. During his time in the Navy, he served in two deployments to the Persian Gulf, including combat experience as part of Operation Iraqi Freedom. Dr. Rosevear disclosed no relevant financial relationships. A version of this article first appeared on Medscape.com.

Young women who received the quadrivalent human papillomavirus (HPV) vaccine had fewer and fewer infections with high-risk HPV strains covered by the vaccine year after year, but the incidence of high-risk strains that were not covered by the vaccine increased over the same 12-year period, researchers report in a study published August 23 in JAMA Open Network.

“One of the unique contributions that this study provides is the evaluation of a real-world example of the HPV infection rates following immunization in a population of adolescent girls and young adult women at a single health center in a large U.S. city, reflecting strong evidence of vaccine effectiveness,” write Nicolas F. Schlecht, PhD, a professor of oncology at Roswell Park Comprehensive Cancer Center, Buffalo, and his colleagues. “Previous surveillance studies from the U.S. have involved older women and populations with relatively low vaccine coverage.”

In addition to supporting the value of continuing to vaccinate teens against HPV, the findings underscore the importance of continuing to screen women for cervical cancer, Dr. Schlecht said in an interview.

“HPV has not and is not going away,” he said. “We need to keep on our toes with screening and other measures to continue to prevent the development of cervix cancer,” including monitoring different high-risk HPV types and keeping a close eye on cervical precancer rates, particularly CIN3 and cervix cancer, he said. “The vaccines are definitely a good thing. Just getting rid of HPV16 is an amazing accomplishment.”

Kevin Ault, MD, a professor of ob/gyn and academic specialist director of clinical and translational research at the University of Kansas, Kansas City, told this news organization that other studies have had similar findings, but this one is larger with longer follow-up.

“The take-home message is that vaccines work, and this is especially true for the HPV vaccine,” said Dr. Ault, who was not involved in the research. “The vaccine prevents HPV infections and the consequences of these infections, such as cervical cancer. The results are consistent with other studies in different settings, so they are likely generalizable.”

The researchers collected data from October 2007, shortly after the vaccine was approved, through September 2019 on sexually active adolescent and young women aged 13 to 21 years who had received the HPV vaccine and had agreed to follow-up assessments every 6 months until they turned 26. Each follow-up included the collecting of samples of cervical and anal cells for polymerase chain reaction testing for the presence of HPV types.

More than half of the 1,453 participants were Hispanic (58.8%), and half were Black (50.4%), including 15% Hispanic and Black patients. The average age of the participants was 18 years. They were tracked for a median 2.4 years. Nearly half the participants (48%) received the HPV vaccine prior to sexual debut.

For the longitudinal study, the researchers adjusted for participants’ age, the year they received the vaccine, and the years since they were vaccinated. They also tracked breakthrough infections for the four types of HPV covered by the vaccine in participants who received the vaccine before sexual debut.

“We evaluated whether infection rates for HPV have changed since the administration of the vaccine by assessing longitudinally the probability of HPV detection over time among vaccinated participants while adjusting for changes in cohort characteristics over time,” the researchers write. In their statistical analysis, they made adjustments for the number of vaccine doses participants received before their first study visit, age at sexual debut, age at first vaccine dose, number of sexual partners in the preceding 6 months, consistency of condom use during sex, history of a positive chlamydia test, and, for anal HPV analyses, whether the participants had had anal sex in the previous 6 months.

The average age at first intercourse remained steady at 15 years throughout the study, but the average age of vaccination dropped from 18 years in 2008 to 12 years in 2019 (P < .001). More than half the participants (64%) had had at least three lifetime sexual partners at baseline.

After adjustment for age, the researchers found that the incidence of the four HPV types covered by the vaccine – HPV-6, HPV-11, HPV-16, and HPV-18 – dropped more each year, shifting from 9.1% from 2008-2010 to 4.7% from 2017-2019. The effect was even greater among those vaccinated prior to sexual debut; for those patients, the incidence of the four vaccine types dropped from 8.8% to 1.7% over the course of the study. Declines over time also occurred for anal types HPV-31 (adjusted odds ratio [aOR] = 0.76) and HPV-45 (aOR = 0.77). Those vaccinated prior to any sexual intercourse had 19% lower odds of infection per year with a vaccine-covered HPV type.

“We were really excited to see that the types targeted by the vaccines were considerably lower over time in our population,” Dr. Schlecht told this news organization. “This is an important observation, since most of these types are the most worrisome for cervical cancer.”

They were surprised, however, to see overall HPV prevalence increase over time, particularly with the high-risk HPV types that were not covered by the quadrivalent vaccine.

Prevalence of cervical high-risk types not in the vaccine increased from 25.1% from 2008-2010 to 30.5% from 2017-2019. Odds of detection of high-risk HPV types not covered by the vaccine increased 8% each year, particularly for HPV-56 and HPV-68; anal HPV types increased 11% each year. Neither age nor recent number of sexual partners affected the findings.

“The underlying mechanisms for the observed increased detection of specific non-vaccine HPV types over time are not yet clear.”

“We hope this doesn’t translate into some increase in cervical neoplasia that is unanticipated,” Dr. Schlecht said. He noted that the attributable risks for cancer associated with nonvaccine high-risk HPV types remain low. “Theoretical concerns are one thing; actual data is what drives the show,” he said.

The research was funded by the National Institutes of Health and the Icahn School of Medicine at Mount Sinai, New York. Dr. Schlecht has served on advisory boards for Merck, GlaxoSmithKline (GSK), and PDS Biotechnology. One author previously served on a GSK advisory board, and another worked with Merck on an early vaccine trial. Dr. Ault has disclosed no relevant financial relationships.

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

Young women who received the quadrivalent human papillomavirus (HPV) vaccine had fewer and fewer infections with high-risk HPV strains covered by the vaccine year after year, but the incidence of high-risk strains that were not covered by the vaccine increased over the same 12-year period, researchers report in a study published August 23 in JAMA Open Network.

“One of the unique contributions that this study provides is the evaluation of a real-world example of the HPV infection rates following immunization in a population of adolescent girls and young adult women at a single health center in a large U.S. city, reflecting strong evidence of vaccine effectiveness,” write Nicolas F. Schlecht, PhD, a professor of oncology at Roswell Park Comprehensive Cancer Center, Buffalo, and his colleagues. “Previous surveillance studies from the U.S. have involved older women and populations with relatively low vaccine coverage.”

In addition to supporting the value of continuing to vaccinate teens against HPV, the findings underscore the importance of continuing to screen women for cervical cancer, Dr. Schlecht said in an interview.

“HPV has not and is not going away,” he said. “We need to keep on our toes with screening and other measures to continue to prevent the development of cervix cancer,” including monitoring different high-risk HPV types and keeping a close eye on cervical precancer rates, particularly CIN3 and cervix cancer, he said. “The vaccines are definitely a good thing. Just getting rid of HPV16 is an amazing accomplishment.”

Kevin Ault, MD, a professor of ob/gyn and academic specialist director of clinical and translational research at the University of Kansas, Kansas City, told this news organization that other studies have had similar findings, but this one is larger with longer follow-up.

“The take-home message is that vaccines work, and this is especially true for the HPV vaccine,” said Dr. Ault, who was not involved in the research. “The vaccine prevents HPV infections and the consequences of these infections, such as cervical cancer. The results are consistent with other studies in different settings, so they are likely generalizable.”

The researchers collected data from October 2007, shortly after the vaccine was approved, through September 2019 on sexually active adolescent and young women aged 13 to 21 years who had received the HPV vaccine and had agreed to follow-up assessments every 6 months until they turned 26. Each follow-up included the collecting of samples of cervical and anal cells for polymerase chain reaction testing for the presence of HPV types.

More than half of the 1,453 participants were Hispanic (58.8%), and half were Black (50.4%), including 15% Hispanic and Black patients. The average age of the participants was 18 years. They were tracked for a median 2.4 years. Nearly half the participants (48%) received the HPV vaccine prior to sexual debut.

For the longitudinal study, the researchers adjusted for participants’ age, the year they received the vaccine, and the years since they were vaccinated. They also tracked breakthrough infections for the four types of HPV covered by the vaccine in participants who received the vaccine before sexual debut.

“We evaluated whether infection rates for HPV have changed since the administration of the vaccine by assessing longitudinally the probability of HPV detection over time among vaccinated participants while adjusting for changes in cohort characteristics over time,” the researchers write. In their statistical analysis, they made adjustments for the number of vaccine doses participants received before their first study visit, age at sexual debut, age at first vaccine dose, number of sexual partners in the preceding 6 months, consistency of condom use during sex, history of a positive chlamydia test, and, for anal HPV analyses, whether the participants had had anal sex in the previous 6 months.

The average age at first intercourse remained steady at 15 years throughout the study, but the average age of vaccination dropped from 18 years in 2008 to 12 years in 2019 (P < .001). More than half the participants (64%) had had at least three lifetime sexual partners at baseline.

After adjustment for age, the researchers found that the incidence of the four HPV types covered by the vaccine – HPV-6, HPV-11, HPV-16, and HPV-18 – dropped more each year, shifting from 9.1% from 2008-2010 to 4.7% from 2017-2019. The effect was even greater among those vaccinated prior to sexual debut; for those patients, the incidence of the four vaccine types dropped from 8.8% to 1.7% over the course of the study. Declines over time also occurred for anal types HPV-31 (adjusted odds ratio [aOR] = 0.76) and HPV-45 (aOR = 0.77). Those vaccinated prior to any sexual intercourse had 19% lower odds of infection per year with a vaccine-covered HPV type.

“We were really excited to see that the types targeted by the vaccines were considerably lower over time in our population,” Dr. Schlecht told this news organization. “This is an important observation, since most of these types are the most worrisome for cervical cancer.”

They were surprised, however, to see overall HPV prevalence increase over time, particularly with the high-risk HPV types that were not covered by the quadrivalent vaccine.

Prevalence of cervical high-risk types not in the vaccine increased from 25.1% from 2008-2010 to 30.5% from 2017-2019. Odds of detection of high-risk HPV types not covered by the vaccine increased 8% each year, particularly for HPV-56 and HPV-68; anal HPV types increased 11% each year. Neither age nor recent number of sexual partners affected the findings.

“The underlying mechanisms for the observed increased detection of specific non-vaccine HPV types over time are not yet clear.”

“We hope this doesn’t translate into some increase in cervical neoplasia that is unanticipated,” Dr. Schlecht said. He noted that the attributable risks for cancer associated with nonvaccine high-risk HPV types remain low. “Theoretical concerns are one thing; actual data is what drives the show,” he said.

The research was funded by the National Institutes of Health and the Icahn School of Medicine at Mount Sinai, New York. Dr. Schlecht has served on advisory boards for Merck, GlaxoSmithKline (GSK), and PDS Biotechnology. One author previously served on a GSK advisory board, and another worked with Merck on an early vaccine trial. Dr. Ault has disclosed no relevant financial relationships.

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

Young women who received the quadrivalent human papillomavirus (HPV) vaccine had fewer and fewer infections with high-risk HPV strains covered by the vaccine year after year, but the incidence of high-risk strains that were not covered by the vaccine increased over the same 12-year period, researchers report in a study published August 23 in JAMA Open Network.

“One of the unique contributions that this study provides is the evaluation of a real-world example of the HPV infection rates following immunization in a population of adolescent girls and young adult women at a single health center in a large U.S. city, reflecting strong evidence of vaccine effectiveness,” write Nicolas F. Schlecht, PhD, a professor of oncology at Roswell Park Comprehensive Cancer Center, Buffalo, and his colleagues. “Previous surveillance studies from the U.S. have involved older women and populations with relatively low vaccine coverage.”

In addition to supporting the value of continuing to vaccinate teens against HPV, the findings underscore the importance of continuing to screen women for cervical cancer, Dr. Schlecht said in an interview.

“HPV has not and is not going away,” he said. “We need to keep on our toes with screening and other measures to continue to prevent the development of cervix cancer,” including monitoring different high-risk HPV types and keeping a close eye on cervical precancer rates, particularly CIN3 and cervix cancer, he said. “The vaccines are definitely a good thing. Just getting rid of HPV16 is an amazing accomplishment.”

Kevin Ault, MD, a professor of ob/gyn and academic specialist director of clinical and translational research at the University of Kansas, Kansas City, told this news organization that other studies have had similar findings, but this one is larger with longer follow-up.

“The take-home message is that vaccines work, and this is especially true for the HPV vaccine,” said Dr. Ault, who was not involved in the research. “The vaccine prevents HPV infections and the consequences of these infections, such as cervical cancer. The results are consistent with other studies in different settings, so they are likely generalizable.”

The researchers collected data from October 2007, shortly after the vaccine was approved, through September 2019 on sexually active adolescent and young women aged 13 to 21 years who had received the HPV vaccine and had agreed to follow-up assessments every 6 months until they turned 26. Each follow-up included the collecting of samples of cervical and anal cells for polymerase chain reaction testing for the presence of HPV types.

More than half of the 1,453 participants were Hispanic (58.8%), and half were Black (50.4%), including 15% Hispanic and Black patients. The average age of the participants was 18 years. They were tracked for a median 2.4 years. Nearly half the participants (48%) received the HPV vaccine prior to sexual debut.

For the longitudinal study, the researchers adjusted for participants’ age, the year they received the vaccine, and the years since they were vaccinated. They also tracked breakthrough infections for the four types of HPV covered by the vaccine in participants who received the vaccine before sexual debut.

“We evaluated whether infection rates for HPV have changed since the administration of the vaccine by assessing longitudinally the probability of HPV detection over time among vaccinated participants while adjusting for changes in cohort characteristics over time,” the researchers write. In their statistical analysis, they made adjustments for the number of vaccine doses participants received before their first study visit, age at sexual debut, age at first vaccine dose, number of sexual partners in the preceding 6 months, consistency of condom use during sex, history of a positive chlamydia test, and, for anal HPV analyses, whether the participants had had anal sex in the previous 6 months.

The average age at first intercourse remained steady at 15 years throughout the study, but the average age of vaccination dropped from 18 years in 2008 to 12 years in 2019 (P < .001). More than half the participants (64%) had had at least three lifetime sexual partners at baseline.

After adjustment for age, the researchers found that the incidence of the four HPV types covered by the vaccine – HPV-6, HPV-11, HPV-16, and HPV-18 – dropped more each year, shifting from 9.1% from 2008-2010 to 4.7% from 2017-2019. The effect was even greater among those vaccinated prior to sexual debut; for those patients, the incidence of the four vaccine types dropped from 8.8% to 1.7% over the course of the study. Declines over time also occurred for anal types HPV-31 (adjusted odds ratio [aOR] = 0.76) and HPV-45 (aOR = 0.77). Those vaccinated prior to any sexual intercourse had 19% lower odds of infection per year with a vaccine-covered HPV type.

“We were really excited to see that the types targeted by the vaccines were considerably lower over time in our population,” Dr. Schlecht told this news organization. “This is an important observation, since most of these types are the most worrisome for cervical cancer.”

They were surprised, however, to see overall HPV prevalence increase over time, particularly with the high-risk HPV types that were not covered by the quadrivalent vaccine.

Prevalence of cervical high-risk types not in the vaccine increased from 25.1% from 2008-2010 to 30.5% from 2017-2019. Odds of detection of high-risk HPV types not covered by the vaccine increased 8% each year, particularly for HPV-56 and HPV-68; anal HPV types increased 11% each year. Neither age nor recent number of sexual partners affected the findings.

“The underlying mechanisms for the observed increased detection of specific non-vaccine HPV types over time are not yet clear.”

“We hope this doesn’t translate into some increase in cervical neoplasia that is unanticipated,” Dr. Schlecht said. He noted that the attributable risks for cancer associated with nonvaccine high-risk HPV types remain low. “Theoretical concerns are one thing; actual data is what drives the show,” he said.

The research was funded by the National Institutes of Health and the Icahn School of Medicine at Mount Sinai, New York. Dr. Schlecht has served on advisory boards for Merck, GlaxoSmithKline (GSK), and PDS Biotechnology. One author previously served on a GSK advisory board, and another worked with Merck on an early vaccine trial. Dr. Ault has disclosed no relevant financial relationships.

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

The potential of polygenic risk scores (PRSs) to become key components in the assessment of individual risk for disease in the clinical setting is inching closer to fruition; however, the technology is plagued by one glaring omission of most existing PRSs – the lack of applicability to those of non-European ancestry.

Polygenic risk scores predict an individual’s risk of disease based on common genetic variants identified in large genomewide association studies (GWASs). They have gained ground in research, as well as in the unregulated realm of the direct-to-consumer market where they are sold as add-ons to DNA ancestry kits such as 23andMe and MyHeritage.com.

While the risk scores show strong validation in estimating risk among people of European descent, their striking caveat is the lack of applicability to other ancestries, particularly African, and their use in practice outside of clinical trials is discouraged in National Comprehensive Cancer Network guidelines.

Study underscores need for ethnically diverse datasets

In a recent study published in JAMA Network Open, researchers evaluated the use of polygenic risk scores’ models in a clinical setting. Researchers tested 7 PRSs models for breast cancer risk against the medical records data of 39,591 women of European, African, and Latinx ancestry.

The PRSs models – all used only for research purposes – included three models involving European ancestry cohorts, two from Latinx cohorts, and two from women African descent.

After adjusting for factors including age, breast cancer family history, and ancestry, the PRSs from women with European ancestry highly corresponded to breast cancer risk, with a mean odds ratio of 1.46 per standard deviation increase in the score.

PRSs were also generalized relatively well among women of Latinx ancestry with a mean OR of 1.31. The authors noted that association is likely caused by Latinx individuals in the United States having a greater proportion of European ancestry than individuals with African ancestry. Importantly, however, the effect size was lower for women of African ancestry with a highest OR of 1.19 per standard deviation.

In the highest percentiles of breast cancer risk, women of European descent had odds ratio as high as 2.19-2.48, suggesting a statistically significant association with overall breast cancer risk. No statistically significant associations were found among women of Latinx and African-ancestry.

The PRSs models were smaller for women of non-European ancestry and included fewer genetic variants for women of non-European ancestry were notably smaller and hence reflected fewer genetic variants. Of the two risk scores involving African ancestry, the Women’s Health Initiative for Women with African ancestry risk score had just 75 variants, while the African diaspora study (ROOT) had 34 variants, compared with 3,820 and 5,218 in the two largest European ancestry PRSs, the Breast Cancer Association Consortium and the UK Biobank, respectively.

“These results highlight the need to improve representation of diverse population groups, particularly women with African ancestry, in genomic research cohorts,” the authors wrote.

First author, Cong Liu, PhD, of Columbia University Irving Medical Center, New York, said that efforts are underway to improve the inclusivity in the Electronic Medical Records and Genomics network data set used in this study.

“Until well-developed and validated PRSs for women with non-European ancestry become available, the current PRSs based on cohorts with European ancestry could be adapted for Latinx women, but not women with African ancestry until additional data sets become available in this important and high-risk group,” Dr. Liu and colleagues wrote.

In a commentary published with the study, Payal D. Shah, MD, of the Basser Center for BRCA at the University of Pennsylvania, Philadelphia, said that PRSs are “disproportionately applicable to patients with European ancestry and are insufficiently vetted and developed in other populations. If an instrument exists that has clinical utility in informing effective cancer risk mitigation strategies, then we must strive to ensure that it is available and applicable to all.”

Higher morality among African American women

While American Cancer Society data shows women with African ancestry generally have incidence rates of breast cancer similar to White women, they have significantly higher mortality from the disease in part because of later-stage diagnosis and health care barriers.

Anne Marie McCarthy, PhD, of the University of Pennsylvania, and Katrina Armstrong, MD, of Harvard Medical School, Boston, wrote in the Journal of the National Cancer Institute that African American women “have 42% higher breast cancer mortality than white women, despite having lower disease incidence, and are more likely to be diagnosed with triple-negative breast cancer, which has poorer prognosis than other molecular subtypes.”

Dr. McCarthy and Dr. Armstrong wrote that African American women are chronically underrepresented in breast cancer studies. And as such, it is impossible to know the extent of the prevalence of mutations and risk.

Failing to address the lack of diversity in genomic studies may worsen health disparities for women with African ancestry, Dr. Liu and colleagues wrote. The higher mortality “underscores the urgent need to increase diversity in genomic studies so that future clinical applications of the PRS do not exacerbate existing health disparities. These results highlight the need to improve representation of diverse population groups, particularly women with African ancestry, in genomic research cohorts.”
 

Potential PRS benefits underscore need to eliminate bias

The potentially important benefits of PRSs as risk prediction tools used in combination with family history, reproductive history and other factors, should provide strong incentive to push for improvement, Dr. Shah wrote.

For instance, if an individual is estrogen receptor positive and shows elevations in breast cancer risk on a reliable PRS, “this may inform antiestrogen chemoprevention strategies,” she wrote.

A risk score could furthermore influence the age at which breast cancer screening should begin or factor into whether a patient should also receive surveillance breast MRI.

Importantly, PRSs could also add to other risk factors to provide more precise risk estimates and inform management of women with a pathogenic variant in a breast cancer risk predisposition gene, Dr. Shah wrote.

Confluence project

Among the most promising developments in research is the National Cancer Institute’s Confluence Project, a large research resource aiming to include approximately 300,000 breast cancer cases and 300,000 controls of different races/ethnicities, utilizing the confluence of existing GWAS and new genomewide genotyping data.

Having started enrollment in 2018, the project is approaching implementation, said Montserrat García-Closas, MD, MPH, DrPH, deputy director of cancer epidemiology and genetics with the National Cancer Institute.

“We expect genotyping to be completed by the end of 2022 and for the data to be made available to the research community soon after that,” she said.

Among the project’s key objectives are the development of PRSs to be integrated with known risk factors to provide a personalized risk assessment for breast cancer, overall and by ancestral subtype.

“We plan to apply novel methods to derive multiancestry PRS that will account for differences and similarities in genetic architecture across ethnic/racial groups to develop breast cancer PRSs that can be applied in multiethnic/racial populations,” she said.

NCI is working with investigators in Africa, Central and South America, and Asia, and reaching out to non-European organizations such as AORTIC for studies of African populations.

Direct-to-consumer global PRS

In the commercial PRS market, efforts to address diversity shortcomings are also gaining momentum, with Myriad Genetics touting a first-of-its kind “global PRS.”

The PRS, a recalibrated version the company’s riskScore PRS, sold as part of its Myriad myRisk Hereditary Cancer test, will reportedly apply to all ethnicities in estimating an individual’s 5-year and lifetime risk of breast cancer.

A study presented in June at the American Society of Clinical Oncology meeting, describes the development of the model with the use of three large ancestry-specific PRSs based on African American, Asian, and European cohorts, with the system including a total of 149 single-nucleotide polymorphisms, including 93 well established for breast cancer and 56 that are ancestry specific.

In validation of the data in an independent cohort of 62,707 individuals, the global PRS was strongly associated with breast cancer in the full combined validation cohort as well as in all three of the ancestry subcohorts.

However, the effect size among women with African ancestry was still the lowest of all of the groups, with a mean OR of 1.24 per standard deviation, versus the highest rate of mixed ancestry (OR, 1.59).

According to senior author Holly Pederson, MD, director of medical breast services at the Cleveland Clinic, the applicability of the PRS to women with African ancestry is expected to further improve as additional data become available.

“The discriminatory power in women of African descent was significantly improved but still suboptimal,” she said. “The need for more data, particularly in Black women, is challenging not only because there is likely more diversity in the genomic landscape of women of African descent, but also because the barriers created by historical, cultural, institutional and interpersonal dynamics result in the paucity of this data.”

“We must be committed to ending bias resulting in health care disparities,” Dr. Pederson said. She noted that the global PRS is nevertheless “still clinically useful in Black women,” and recommended that clinicians be up front with patients on the status of the research challenges.

“As with any clinical shared decision-making conversation between a patient and her provider, it is important for Black women to know that data is limited in the African American population, particularly given the vast genomic diversity of the African continent,” she said. “This model, as models that have gone before it, will improve with additional data, particularly in this population.”

Commercial PRSs may benefit research

While the commercial marketing of PRSs in a direct-to-consumer fashion have raised some concerns, such as how individuals respond to their risk scores, there could be important benefits as well, commented Megan C. Roberts, PhD.

“There may be an opportunity to learn from these companies about how to engage diverse communities in genomic testing,” said Dr. Roberts, an assistant professor and director of implementation science in precision health and society at the University of North Carolina at Chapel Hill. “Moreover, the data they collect from their customers often can be used for research purposes as well.”

In a recent perspective, Dr. Roberts and colleagues addressed the role of health disparities in PRSs. She’ll be joining international precision public health researchers in October in hosting a free virtual conference at UNC on the topic.

“There is a huge need to improve racial and ethnic diversity in our genomic datasets,” Dr. Roberts said. “Without this, we will not be able to return on the promise of precision medicine and prevention for improving the health of our whole population.”

Dr. Pederson disclosed that she is a consultant for Myriad Genetics.

The potential of polygenic risk scores (PRSs) to become key components in the assessment of individual risk for disease in the clinical setting is inching closer to fruition; however, the technology is plagued by one glaring omission of most existing PRSs – the lack of applicability to those of non-European ancestry.

Polygenic risk scores predict an individual’s risk of disease based on common genetic variants identified in large genomewide association studies (GWASs). They have gained ground in research, as well as in the unregulated realm of the direct-to-consumer market where they are sold as add-ons to DNA ancestry kits such as 23andMe and MyHeritage.com.

While the risk scores show strong validation in estimating risk among people of European descent, their striking caveat is the lack of applicability to other ancestries, particularly African, and their use in practice outside of clinical trials is discouraged in National Comprehensive Cancer Network guidelines.

Study underscores need for ethnically diverse datasets

In a recent study published in JAMA Network Open, researchers evaluated the use of polygenic risk scores’ models in a clinical setting. Researchers tested 7 PRSs models for breast cancer risk against the medical records data of 39,591 women of European, African, and Latinx ancestry.

The PRSs models – all used only for research purposes – included three models involving European ancestry cohorts, two from Latinx cohorts, and two from women African descent.

After adjusting for factors including age, breast cancer family history, and ancestry, the PRSs from women with European ancestry highly corresponded to breast cancer risk, with a mean odds ratio of 1.46 per standard deviation increase in the score.

PRSs were also generalized relatively well among women of Latinx ancestry with a mean OR of 1.31. The authors noted that association is likely caused by Latinx individuals in the United States having a greater proportion of European ancestry than individuals with African ancestry. Importantly, however, the effect size was lower for women of African ancestry with a highest OR of 1.19 per standard deviation.

In the highest percentiles of breast cancer risk, women of European descent had odds ratio as high as 2.19-2.48, suggesting a statistically significant association with overall breast cancer risk. No statistically significant associations were found among women of Latinx and African-ancestry.

The PRSs models were smaller for women of non-European ancestry and included fewer genetic variants for women of non-European ancestry were notably smaller and hence reflected fewer genetic variants. Of the two risk scores involving African ancestry, the Women’s Health Initiative for Women with African ancestry risk score had just 75 variants, while the African diaspora study (ROOT) had 34 variants, compared with 3,820 and 5,218 in the two largest European ancestry PRSs, the Breast Cancer Association Consortium and the UK Biobank, respectively.

“These results highlight the need to improve representation of diverse population groups, particularly women with African ancestry, in genomic research cohorts,” the authors wrote.

First author, Cong Liu, PhD, of Columbia University Irving Medical Center, New York, said that efforts are underway to improve the inclusivity in the Electronic Medical Records and Genomics network data set used in this study.

“Until well-developed and validated PRSs for women with non-European ancestry become available, the current PRSs based on cohorts with European ancestry could be adapted for Latinx women, but not women with African ancestry until additional data sets become available in this important and high-risk group,” Dr. Liu and colleagues wrote.

In a commentary published with the study, Payal D. Shah, MD, of the Basser Center for BRCA at the University of Pennsylvania, Philadelphia, said that PRSs are “disproportionately applicable to patients with European ancestry and are insufficiently vetted and developed in other populations. If an instrument exists that has clinical utility in informing effective cancer risk mitigation strategies, then we must strive to ensure that it is available and applicable to all.”

Higher morality among African American women

While American Cancer Society data shows women with African ancestry generally have incidence rates of breast cancer similar to White women, they have significantly higher mortality from the disease in part because of later-stage diagnosis and health care barriers.

Anne Marie McCarthy, PhD, of the University of Pennsylvania, and Katrina Armstrong, MD, of Harvard Medical School, Boston, wrote in the Journal of the National Cancer Institute that African American women “have 42% higher breast cancer mortality than white women, despite having lower disease incidence, and are more likely to be diagnosed with triple-negative breast cancer, which has poorer prognosis than other molecular subtypes.”

Dr. McCarthy and Dr. Armstrong wrote that African American women are chronically underrepresented in breast cancer studies. And as such, it is impossible to know the extent of the prevalence of mutations and risk.

Failing to address the lack of diversity in genomic studies may worsen health disparities for women with African ancestry, Dr. Liu and colleagues wrote. The higher mortality “underscores the urgent need to increase diversity in genomic studies so that future clinical applications of the PRS do not exacerbate existing health disparities. These results highlight the need to improve representation of diverse population groups, particularly women with African ancestry, in genomic research cohorts.”
 

Potential PRS benefits underscore need to eliminate bias

The potentially important benefits of PRSs as risk prediction tools used in combination with family history, reproductive history and other factors, should provide strong incentive to push for improvement, Dr. Shah wrote.

For instance, if an individual is estrogen receptor positive and shows elevations in breast cancer risk on a reliable PRS, “this may inform antiestrogen chemoprevention strategies,” she wrote.

A risk score could furthermore influence the age at which breast cancer screening should begin or factor into whether a patient should also receive surveillance breast MRI.

Importantly, PRSs could also add to other risk factors to provide more precise risk estimates and inform management of women with a pathogenic variant in a breast cancer risk predisposition gene, Dr. Shah wrote.

Confluence project

Among the most promising developments in research is the National Cancer Institute’s Confluence Project, a large research resource aiming to include approximately 300,000 breast cancer cases and 300,000 controls of different races/ethnicities, utilizing the confluence of existing GWAS and new genomewide genotyping data.

Having started enrollment in 2018, the project is approaching implementation, said Montserrat García-Closas, MD, MPH, DrPH, deputy director of cancer epidemiology and genetics with the National Cancer Institute.

“We expect genotyping to be completed by the end of 2022 and for the data to be made available to the research community soon after that,” she said.

Among the project’s key objectives are the development of PRSs to be integrated with known risk factors to provide a personalized risk assessment for breast cancer, overall and by ancestral subtype.

“We plan to apply novel methods to derive multiancestry PRS that will account for differences and similarities in genetic architecture across ethnic/racial groups to develop breast cancer PRSs that can be applied in multiethnic/racial populations,” she said.

NCI is working with investigators in Africa, Central and South America, and Asia, and reaching out to non-European organizations such as AORTIC for studies of African populations.

Direct-to-consumer global PRS

In the commercial PRS market, efforts to address diversity shortcomings are also gaining momentum, with Myriad Genetics touting a first-of-its kind “global PRS.”

The PRS, a recalibrated version the company’s riskScore PRS, sold as part of its Myriad myRisk Hereditary Cancer test, will reportedly apply to all ethnicities in estimating an individual’s 5-year and lifetime risk of breast cancer.

A study presented in June at the American Society of Clinical Oncology meeting, describes the development of the model with the use of three large ancestry-specific PRSs based on African American, Asian, and European cohorts, with the system including a total of 149 single-nucleotide polymorphisms, including 93 well established for breast cancer and 56 that are ancestry specific.

In validation of the data in an independent cohort of 62,707 individuals, the global PRS was strongly associated with breast cancer in the full combined validation cohort as well as in all three of the ancestry subcohorts.

However, the effect size among women with African ancestry was still the lowest of all of the groups, with a mean OR of 1.24 per standard deviation, versus the highest rate of mixed ancestry (OR, 1.59).

According to senior author Holly Pederson, MD, director of medical breast services at the Cleveland Clinic, the applicability of the PRS to women with African ancestry is expected to further improve as additional data become available.

“The discriminatory power in women of African descent was significantly improved but still suboptimal,” she said. “The need for more data, particularly in Black women, is challenging not only because there is likely more diversity in the genomic landscape of women of African descent, but also because the barriers created by historical, cultural, institutional and interpersonal dynamics result in the paucity of this data.”

“We must be committed to ending bias resulting in health care disparities,” Dr. Pederson said. She noted that the global PRS is nevertheless “still clinically useful in Black women,” and recommended that clinicians be up front with patients on the status of the research challenges.

“As with any clinical shared decision-making conversation between a patient and her provider, it is important for Black women to know that data is limited in the African American population, particularly given the vast genomic diversity of the African continent,” she said. “This model, as models that have gone before it, will improve with additional data, particularly in this population.”

Commercial PRSs may benefit research

While the commercial marketing of PRSs in a direct-to-consumer fashion have raised some concerns, such as how individuals respond to their risk scores, there could be important benefits as well, commented Megan C. Roberts, PhD.

“There may be an opportunity to learn from these companies about how to engage diverse communities in genomic testing,” said Dr. Roberts, an assistant professor and director of implementation science in precision health and society at the University of North Carolina at Chapel Hill. “Moreover, the data they collect from their customers often can be used for research purposes as well.”

In a recent perspective, Dr. Roberts and colleagues addressed the role of health disparities in PRSs. She’ll be joining international precision public health researchers in October in hosting a free virtual conference at UNC on the topic.

“There is a huge need to improve racial and ethnic diversity in our genomic datasets,” Dr. Roberts said. “Without this, we will not be able to return on the promise of precision medicine and prevention for improving the health of our whole population.”

Dr. Pederson disclosed that she is a consultant for Myriad Genetics.

The potential of polygenic risk scores (PRSs) to become key components in the assessment of individual risk for disease in the clinical setting is inching closer to fruition; however, the technology is plagued by one glaring omission of most existing PRSs – the lack of applicability to those of non-European ancestry.

Polygenic risk scores predict an individual’s risk of disease based on common genetic variants identified in large genomewide association studies (GWASs). They have gained ground in research, as well as in the unregulated realm of the direct-to-consumer market where they are sold as add-ons to DNA ancestry kits such as 23andMe and MyHeritage.com.

While the risk scores show strong validation in estimating risk among people of European descent, their striking caveat is the lack of applicability to other ancestries, particularly African, and their use in practice outside of clinical trials is discouraged in National Comprehensive Cancer Network guidelines.

Study underscores need for ethnically diverse datasets

In a recent study published in JAMA Network Open, researchers evaluated the use of polygenic risk scores’ models in a clinical setting. Researchers tested 7 PRSs models for breast cancer risk against the medical records data of 39,591 women of European, African, and Latinx ancestry.

The PRSs models – all used only for research purposes – included three models involving European ancestry cohorts, two from Latinx cohorts, and two from women African descent.

After adjusting for factors including age, breast cancer family history, and ancestry, the PRSs from women with European ancestry highly corresponded to breast cancer risk, with a mean odds ratio of 1.46 per standard deviation increase in the score.

PRSs were also generalized relatively well among women of Latinx ancestry with a mean OR of 1.31. The authors noted that association is likely caused by Latinx individuals in the United States having a greater proportion of European ancestry than individuals with African ancestry. Importantly, however, the effect size was lower for women of African ancestry with a highest OR of 1.19 per standard deviation.

In the highest percentiles of breast cancer risk, women of European descent had odds ratio as high as 2.19-2.48, suggesting a statistically significant association with overall breast cancer risk. No statistically significant associations were found among women of Latinx and African-ancestry.

The PRSs models were smaller for women of non-European ancestry and included fewer genetic variants for women of non-European ancestry were notably smaller and hence reflected fewer genetic variants. Of the two risk scores involving African ancestry, the Women’s Health Initiative for Women with African ancestry risk score had just 75 variants, while the African diaspora study (ROOT) had 34 variants, compared with 3,820 and 5,218 in the two largest European ancestry PRSs, the Breast Cancer Association Consortium and the UK Biobank, respectively.

“These results highlight the need to improve representation of diverse population groups, particularly women with African ancestry, in genomic research cohorts,” the authors wrote.

First author, Cong Liu, PhD, of Columbia University Irving Medical Center, New York, said that efforts are underway to improve the inclusivity in the Electronic Medical Records and Genomics network data set used in this study.

“Until well-developed and validated PRSs for women with non-European ancestry become available, the current PRSs based on cohorts with European ancestry could be adapted for Latinx women, but not women with African ancestry until additional data sets become available in this important and high-risk group,” Dr. Liu and colleagues wrote.

In a commentary published with the study, Payal D. Shah, MD, of the Basser Center for BRCA at the University of Pennsylvania, Philadelphia, said that PRSs are “disproportionately applicable to patients with European ancestry and are insufficiently vetted and developed in other populations. If an instrument exists that has clinical utility in informing effective cancer risk mitigation strategies, then we must strive to ensure that it is available and applicable to all.”

Higher morality among African American women

While American Cancer Society data shows women with African ancestry generally have incidence rates of breast cancer similar to White women, they have significantly higher mortality from the disease in part because of later-stage diagnosis and health care barriers.

Anne Marie McCarthy, PhD, of the University of Pennsylvania, and Katrina Armstrong, MD, of Harvard Medical School, Boston, wrote in the Journal of the National Cancer Institute that African American women “have 42% higher breast cancer mortality than white women, despite having lower disease incidence, and are more likely to be diagnosed with triple-negative breast cancer, which has poorer prognosis than other molecular subtypes.”

Dr. McCarthy and Dr. Armstrong wrote that African American women are chronically underrepresented in breast cancer studies. And as such, it is impossible to know the extent of the prevalence of mutations and risk.

Failing to address the lack of diversity in genomic studies may worsen health disparities for women with African ancestry, Dr. Liu and colleagues wrote. The higher mortality “underscores the urgent need to increase diversity in genomic studies so that future clinical applications of the PRS do not exacerbate existing health disparities. These results highlight the need to improve representation of diverse population groups, particularly women with African ancestry, in genomic research cohorts.”
 

Potential PRS benefits underscore need to eliminate bias

The potentially important benefits of PRSs as risk prediction tools used in combination with family history, reproductive history and other factors, should provide strong incentive to push for improvement, Dr. Shah wrote.

For instance, if an individual is estrogen receptor positive and shows elevations in breast cancer risk on a reliable PRS, “this may inform antiestrogen chemoprevention strategies,” she wrote.

A risk score could furthermore influence the age at which breast cancer screening should begin or factor into whether a patient should also receive surveillance breast MRI.

Importantly, PRSs could also add to other risk factors to provide more precise risk estimates and inform management of women with a pathogenic variant in a breast cancer risk predisposition gene, Dr. Shah wrote.

Confluence project

Among the most promising developments in research is the National Cancer Institute’s Confluence Project, a large research resource aiming to include approximately 300,000 breast cancer cases and 300,000 controls of different races/ethnicities, utilizing the confluence of existing GWAS and new genomewide genotyping data.

Having started enrollment in 2018, the project is approaching implementation, said Montserrat García-Closas, MD, MPH, DrPH, deputy director of cancer epidemiology and genetics with the National Cancer Institute.

“We expect genotyping to be completed by the end of 2022 and for the data to be made available to the research community soon after that,” she said.

Among the project’s key objectives are the development of PRSs to be integrated with known risk factors to provide a personalized risk assessment for breast cancer, overall and by ancestral subtype.

“We plan to apply novel methods to derive multiancestry PRS that will account for differences and similarities in genetic architecture across ethnic/racial groups to develop breast cancer PRSs that can be applied in multiethnic/racial populations,” she said.

NCI is working with investigators in Africa, Central and South America, and Asia, and reaching out to non-European organizations such as AORTIC for studies of African populations.

Direct-to-consumer global PRS

In the commercial PRS market, efforts to address diversity shortcomings are also gaining momentum, with Myriad Genetics touting a first-of-its kind “global PRS.”

The PRS, a recalibrated version the company’s riskScore PRS, sold as part of its Myriad myRisk Hereditary Cancer test, will reportedly apply to all ethnicities in estimating an individual’s 5-year and lifetime risk of breast cancer.

A study presented in June at the American Society of Clinical Oncology meeting, describes the development of the model with the use of three large ancestry-specific PRSs based on African American, Asian, and European cohorts, with the system including a total of 149 single-nucleotide polymorphisms, including 93 well established for breast cancer and 56 that are ancestry specific.

In validation of the data in an independent cohort of 62,707 individuals, the global PRS was strongly associated with breast cancer in the full combined validation cohort as well as in all three of the ancestry subcohorts.

However, the effect size among women with African ancestry was still the lowest of all of the groups, with a mean OR of 1.24 per standard deviation, versus the highest rate of mixed ancestry (OR, 1.59).

According to senior author Holly Pederson, MD, director of medical breast services at the Cleveland Clinic, the applicability of the PRS to women with African ancestry is expected to further improve as additional data become available.

“The discriminatory power in women of African descent was significantly improved but still suboptimal,” she said. “The need for more data, particularly in Black women, is challenging not only because there is likely more diversity in the genomic landscape of women of African descent, but also because the barriers created by historical, cultural, institutional and interpersonal dynamics result in the paucity of this data.”

“We must be committed to ending bias resulting in health care disparities,” Dr. Pederson said. She noted that the global PRS is nevertheless “still clinically useful in Black women,” and recommended that clinicians be up front with patients on the status of the research challenges.

“As with any clinical shared decision-making conversation between a patient and her provider, it is important for Black women to know that data is limited in the African American population, particularly given the vast genomic diversity of the African continent,” she said. “This model, as models that have gone before it, will improve with additional data, particularly in this population.”

Commercial PRSs may benefit research

While the commercial marketing of PRSs in a direct-to-consumer fashion have raised some concerns, such as how individuals respond to their risk scores, there could be important benefits as well, commented Megan C. Roberts, PhD.

“There may be an opportunity to learn from these companies about how to engage diverse communities in genomic testing,” said Dr. Roberts, an assistant professor and director of implementation science in precision health and society at the University of North Carolina at Chapel Hill. “Moreover, the data they collect from their customers often can be used for research purposes as well.”

In a recent perspective, Dr. Roberts and colleagues addressed the role of health disparities in PRSs. She’ll be joining international precision public health researchers in October in hosting a free virtual conference at UNC on the topic.

“There is a huge need to improve racial and ethnic diversity in our genomic datasets,” Dr. Roberts said. “Without this, we will not be able to return on the promise of precision medicine and prevention for improving the health of our whole population.”

Dr. Pederson disclosed that she is a consultant for Myriad Genetics.

Since evidence shows that medication abortion is extremely safe, why is mifepristone so restricted? And should it be? Mifepristone, used with misoprostol for medication abortion for pregnancies up to 10 weeks’ gestation, is highly regulated in the United States. Going back to 2000, when the Food and Drug Administration approved Mifeprex (brand name of mifepristone), its access was restricted under the FDA Risk Evaluation and Mitigation Strategy (REMS).

REMS is an FDA drug safety program, where certain medications with serious safety concerns are subject to restrictions intended to ensure that the benefits of the medication outweigh its risks. For example, the drug vigabatrin, with a side effect of permanent vision loss, is used to treat epilepsy. The REMS for vigabatrin requires counseling on the risk of vision loss and periodic vision monitoring.

The FDA claims that rare side effects of mifepristone – heavy vaginal bleeding, severe infection, and incomplete abortion – are risks that warrant the REMS, despite the known safety of medication abortion, with less than 1% of patients requiring emergency intervention for heavy vaginal bleeding or infection. The mifepristone REMS requires that the drug is dispensed in a hospital, clinic or medical office by a certified health care provider and not in a pharmacy as is the case with most prescribed medications, and that patients must read and sign the patient agreement form in the physical presence of the dispensing physician and may not receive counseling via telemedicine, for example.

Since FDA approval over 20 years ago, much evidence shows that the REMS is unnecessary and creates a major obstacle to access. Many clinicians cannot meet the REMS requirements. Many women must travel great distances to obtain mifepristone or delay their abortion past the acceptable gestational age for medication abortion.

In spring 2020, at the onset of the COVID-19 pandemic, the Centers for Disease Control and Prevention issued general guidance recommending use of telemedicine to limit in-person medical visits to reduce risk of exposure to the SARS-CoV-2 virus, and to ensure access to medication abortion, the ACLU filed a federal lawsuit against the FDA to suspend the requirement for in-person mifepristone dispensing. In July 2020, a Maryland District Judge granted a preliminary injunction, preventing the FDA from enforcing the in-person dispensing requirement for the duration of the declared public health emergency, allowing telemedicine medication abortion using mail or delivery service for administration of mifepristone. All other REMS requirements remained in effect.

In January 2021, the FDA appealed, seeking to reinstate the REMS. The U.S. Supreme Court, with its conservative majority, ruled to reimpose the REMS. Following this decision, a large coalition of reproductive rights groups petitioned the Biden administration to suspend the mifepristone in-person requirement during the public health emergency of the pandemic. In April 2021, the FDA announced it would use discretion and cease to enforce the in-person dispensing requirement throughout the remainder of the public health emergency.

We applaud the FDA for doing the right thing, taking the advice of numerous scientific and advocacy groups to expand access to mifepristone by at least temporarily nullifying unnecessary and burdensome restrictions that disproportionately affect people of color; young people; and people who live in rural areas, have lower incomes, and/or who are undocumented. We join the voices of numerous colleagues and organizations, including the American College of Obstetricians and Gynecologists, our premier women’s health organization, in calling for a permanent end to the mifepristone REMS.

Dr. Dale is an obstetrics and gynecology specialist in Albuquerque, N.M.; Dr. Black is an obstetrics and gynecology specialist in Albuquerque, N.M., who currently practices at the University of New Mexico Children’s Psychiatric Center, Albuquerque; and Dr. Espey is professor and chair of the department of ob.gyn. and family planning, and fellowship director at the University of New Mexico, Albuquerque.

This article was updated 8/24/21.

Since evidence shows that medication abortion is extremely safe, why is mifepristone so restricted? And should it be? Mifepristone, used with misoprostol for medication abortion for pregnancies up to 10 weeks’ gestation, is highly regulated in the United States. Going back to 2000, when the Food and Drug Administration approved Mifeprex (brand name of mifepristone), its access was restricted under the FDA Risk Evaluation and Mitigation Strategy (REMS).

REMS is an FDA drug safety program, where certain medications with serious safety concerns are subject to restrictions intended to ensure that the benefits of the medication outweigh its risks. For example, the drug vigabatrin, with a side effect of permanent vision loss, is used to treat epilepsy. The REMS for vigabatrin requires counseling on the risk of vision loss and periodic vision monitoring.

The FDA claims that rare side effects of mifepristone – heavy vaginal bleeding, severe infection, and incomplete abortion – are risks that warrant the REMS, despite the known safety of medication abortion, with less than 1% of patients requiring emergency intervention for heavy vaginal bleeding or infection. The mifepristone REMS requires that the drug is dispensed in a hospital, clinic or medical office by a certified health care provider and not in a pharmacy as is the case with most prescribed medications, and that patients must read and sign the patient agreement form in the physical presence of the dispensing physician and may not receive counseling via telemedicine, for example.

Since FDA approval over 20 years ago, much evidence shows that the REMS is unnecessary and creates a major obstacle to access. Many clinicians cannot meet the REMS requirements. Many women must travel great distances to obtain mifepristone or delay their abortion past the acceptable gestational age for medication abortion.

In spring 2020, at the onset of the COVID-19 pandemic, the Centers for Disease Control and Prevention issued general guidance recommending use of telemedicine to limit in-person medical visits to reduce risk of exposure to the SARS-CoV-2 virus, and to ensure access to medication abortion, the ACLU filed a federal lawsuit against the FDA to suspend the requirement for in-person mifepristone dispensing. In July 2020, a Maryland District Judge granted a preliminary injunction, preventing the FDA from enforcing the in-person dispensing requirement for the duration of the declared public health emergency, allowing telemedicine medication abortion using mail or delivery service for administration of mifepristone. All other REMS requirements remained in effect.

In January 2021, the FDA appealed, seeking to reinstate the REMS. The U.S. Supreme Court, with its conservative majority, ruled to reimpose the REMS. Following this decision, a large coalition of reproductive rights groups petitioned the Biden administration to suspend the mifepristone in-person requirement during the public health emergency of the pandemic. In April 2021, the FDA announced it would use discretion and cease to enforce the in-person dispensing requirement throughout the remainder of the public health emergency.

We applaud the FDA for doing the right thing, taking the advice of numerous scientific and advocacy groups to expand access to mifepristone by at least temporarily nullifying unnecessary and burdensome restrictions that disproportionately affect people of color; young people; and people who live in rural areas, have lower incomes, and/or who are undocumented. We join the voices of numerous colleagues and organizations, including the American College of Obstetricians and Gynecologists, our premier women’s health organization, in calling for a permanent end to the mifepristone REMS.

Dr. Dale is an obstetrics and gynecology specialist in Albuquerque, N.M.; Dr. Black is an obstetrics and gynecology specialist in Albuquerque, N.M., who currently practices at the University of New Mexico Children’s Psychiatric Center, Albuquerque; and Dr. Espey is professor and chair of the department of ob.gyn. and family planning, and fellowship director at the University of New Mexico, Albuquerque.

This article was updated 8/24/21.

Since evidence shows that medication abortion is extremely safe, why is mifepristone so restricted? And should it be? Mifepristone, used with misoprostol for medication abortion for pregnancies up to 10 weeks’ gestation, is highly regulated in the United States. Going back to 2000, when the Food and Drug Administration approved Mifeprex (brand name of mifepristone), its access was restricted under the FDA Risk Evaluation and Mitigation Strategy (REMS).

REMS is an FDA drug safety program, where certain medications with serious safety concerns are subject to restrictions intended to ensure that the benefits of the medication outweigh its risks. For example, the drug vigabatrin, with a side effect of permanent vision loss, is used to treat epilepsy. The REMS for vigabatrin requires counseling on the risk of vision loss and periodic vision monitoring.

The FDA claims that rare side effects of mifepristone – heavy vaginal bleeding, severe infection, and incomplete abortion – are risks that warrant the REMS, despite the known safety of medication abortion, with less than 1% of patients requiring emergency intervention for heavy vaginal bleeding or infection. The mifepristone REMS requires that the drug is dispensed in a hospital, clinic or medical office by a certified health care provider and not in a pharmacy as is the case with most prescribed medications, and that patients must read and sign the patient agreement form in the physical presence of the dispensing physician and may not receive counseling via telemedicine, for example.

Since FDA approval over 20 years ago, much evidence shows that the REMS is unnecessary and creates a major obstacle to access. Many clinicians cannot meet the REMS requirements. Many women must travel great distances to obtain mifepristone or delay their abortion past the acceptable gestational age for medication abortion.

In spring 2020, at the onset of the COVID-19 pandemic, the Centers for Disease Control and Prevention issued general guidance recommending use of telemedicine to limit in-person medical visits to reduce risk of exposure to the SARS-CoV-2 virus, and to ensure access to medication abortion, the ACLU filed a federal lawsuit against the FDA to suspend the requirement for in-person mifepristone dispensing. In July 2020, a Maryland District Judge granted a preliminary injunction, preventing the FDA from enforcing the in-person dispensing requirement for the duration of the declared public health emergency, allowing telemedicine medication abortion using mail or delivery service for administration of mifepristone. All other REMS requirements remained in effect.

In January 2021, the FDA appealed, seeking to reinstate the REMS. The U.S. Supreme Court, with its conservative majority, ruled to reimpose the REMS. Following this decision, a large coalition of reproductive rights groups petitioned the Biden administration to suspend the mifepristone in-person requirement during the public health emergency of the pandemic. In April 2021, the FDA announced it would use discretion and cease to enforce the in-person dispensing requirement throughout the remainder of the public health emergency.

We applaud the FDA for doing the right thing, taking the advice of numerous scientific and advocacy groups to expand access to mifepristone by at least temporarily nullifying unnecessary and burdensome restrictions that disproportionately affect people of color; young people; and people who live in rural areas, have lower incomes, and/or who are undocumented. We join the voices of numerous colleagues and organizations, including the American College of Obstetricians and Gynecologists, our premier women’s health organization, in calling for a permanent end to the mifepristone REMS.

Dr. Dale is an obstetrics and gynecology specialist in Albuquerque, N.M.; Dr. Black is an obstetrics and gynecology specialist in Albuquerque, N.M., who currently practices at the University of New Mexico Children’s Psychiatric Center, Albuquerque; and Dr. Espey is professor and chair of the department of ob.gyn. and family planning, and fellowship director at the University of New Mexico, Albuquerque.

This article was updated 8/24/21.

Postpartum depression, in many respects, has become a household term. Over the last decade, there has been increasing awareness of the importance of screening for postpartum depression, with increased systematic screening across clinical settings where care is delivered to women during pregnancy and the postpartum period. There have also been greater efforts to identify women who are suffering postpartum depression and to support them with appropriate clinical interventions, whether through psychotherapy and/or pharmacologic therapy. Clinical interventions are supplemented by the increasing awareness of the value of community-based support groups for women who are suffering from postpartum mood and anxiety disorders.

Despite the growing, appropriate focus on recognition and acute treatment of postpartum depression as well as assessing clinical outcomes for those who suffer from postpartum mood and anxiety disorders, less attention has been given to postpartum psychosis, the most severe form of postpartum depression. It is indeed, the least common postpartum psychiatric syndrome (1 in 1,000 births) and comes to public attention when there has been a tragedy during the acute postpartum period such as maternal suicide or infanticide. In this sense, postpartum psychosis is ironically an underappreciated clinical entity across America given its severity, the effect it has on longer-term psychiatric morbidity, and its effect on children and families.

Our group at the Center for Women’s Mental Health has been interested in postpartum psychosis for years and started the Postpartum Psychosis Project in an effort to better understand the phenomenology, course, treatment, outcome, and genomic underpinnings of postpartum psychosis. Risk factors that are well established for postpartum psychosis have been described and overwhelmingly include patients with bipolar disorder. The risk for recurrent postpartum psychosis in women who have had a previous episode is as great as 75%-90% in the absence of prophylactic intervention. With that said, we are extremely interested in understanding the etiology of postpartum psychosis. Various studies over the last 5 years have looked at a whole host of psychosocial as well as neurobiologic variables that may contribute to risk for postpartum psychosis, including dysregulation of the stress axis, heightened inflammation as well as a history of child adversity and heightened experience of stress during the perinatal period.

There have also been anecdotal reports during Virtual Rounds at the Center for Women’s Mental Health of higher recent rates of postpartum psychosis manifesting during the postpartum period. This is a clinical observation and has not been systematically studied. However, one can wonder whether the experience of the pandemic has constituted a stressor for at-risk women, tipping the scales toward women becoming ill, or whether clinicians are seeing this finding more because of our ability to observe it more within the context of the pandemic.

Precise quantification of risk for postpartum psychosis is complicated; as noted, women with bipolar disorder have a predictably high risk for getting ill during the postpartum period and many go on to have clinical courses consistent with recurrent bipolar disorder. However, there are other women who have circumscribed episodes of psychotic illness in the postpartum period who recover and are totally well without any evidence of psychiatric disorder until they have another child, at which time the risk for recurrence of postpartum psychosis is very high. Interest in developing a model of risk that could reliably predict an illness as serious as postpartum psychosis is on the minds of researchers around the world.

One recent study that highlights the multiple factors involved in risk of postpartum psychosis involved a prospective longitudinal study of a group of women who were followed across the peripartum period from the third trimester until 4 weeks postpartum. In this group, 51 women were at increased risk for postpartum psychosis based on their diagnosis of bipolar disorder, schizoaffective disorder, or a previous episode of postpartum psychosis. These women were matched with a control group with no past or current diagnosis of psychiatric disorder or family history of postpartum psychosis. The findings suggested that women at risk for postpartum psychosis who experienced a psychiatric relapse during the first 4 weeks postpartum relative to women at risk who remained well had histories of severe childhood adversity as well as biomarkers consistent with a dysregulated stress axis (a statistically higher daily cortisol level). This is consistent with other data that have implicated the complex role between psychosocial variables as well as neurobiologic variables, such as a dysregulation in the hypothalamic pituitary adrenal axis and other studies that suggest that dysregulated inflammatory status may also drive risk for postpartum psychosis (Hazelgrove K et al. Psychoneuroendocrinology. 2021 Jun. doi: 10.1016/j.psyneuen.2021.105218).

At the end of the day, postpartum psychosis is a psychiatric and obstetrical emergency. In our center, it is rare for women not to be hospitalized with this condition to ensure the safety of the mother as well as her newborn, and to also get her recompensated and functioning as quickly and as significantly as possible. However, an interesting extrapolation of the findings noted by Hazelgrove and colleagues is that it raises the question of what effective treatments might be used to mitigate risk for those at greatest risk for postpartum psychosis. For example, are there other treatments over and above the few effective ones that have been studied as prophylactic pharmacologic interventions that might mitigate risk for recurrence of an illness as serious as postpartum psychosis?

The data suggesting dysregulation of the stress axis as a predictor variable for risk in women vulnerable to postpartum psychosis opens an array of opportunities that are nonpharmacologic, such as mindfulness-based cognitive therapy or other interventions that help to modulate the stress axis. This is a terrific opportunity to have pharmacologic intervention meet nonpharmacologic intervention to potentially mitigate risk for postpartum psychosis with its attendant serious sequelae.

In our own work, where we are evaluating genomic data in an extremely well-characterized group of women with known histories of postpartum psychosis, we are interested to see if we can enhance understanding of the model of risk for postpartum psychosis by factoring in genomic underpinning, history of diagnosis, and psychosocial variables to optimally craft interventions for this population of at-risk women. This brings us one step closer to the future in women’s mental health, to the practice of “precision reproductive psychiatry,” matching interventions to specific presentations across perinatal populations.
 

Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications. Email Dr. Cohen at [email protected].

Postpartum depression, in many respects, has become a household term. Over the last decade, there has been increasing awareness of the importance of screening for postpartum depression, with increased systematic screening across clinical settings where care is delivered to women during pregnancy and the postpartum period. There have also been greater efforts to identify women who are suffering postpartum depression and to support them with appropriate clinical interventions, whether through psychotherapy and/or pharmacologic therapy. Clinical interventions are supplemented by the increasing awareness of the value of community-based support groups for women who are suffering from postpartum mood and anxiety disorders.

Despite the growing, appropriate focus on recognition and acute treatment of postpartum depression as well as assessing clinical outcomes for those who suffer from postpartum mood and anxiety disorders, less attention has been given to postpartum psychosis, the most severe form of postpartum depression. It is indeed, the least common postpartum psychiatric syndrome (1 in 1,000 births) and comes to public attention when there has been a tragedy during the acute postpartum period such as maternal suicide or infanticide. In this sense, postpartum psychosis is ironically an underappreciated clinical entity across America given its severity, the effect it has on longer-term psychiatric morbidity, and its effect on children and families.

Our group at the Center for Women’s Mental Health has been interested in postpartum psychosis for years and started the Postpartum Psychosis Project in an effort to better understand the phenomenology, course, treatment, outcome, and genomic underpinnings of postpartum psychosis. Risk factors that are well established for postpartum psychosis have been described and overwhelmingly include patients with bipolar disorder. The risk for recurrent postpartum psychosis in women who have had a previous episode is as great as 75%-90% in the absence of prophylactic intervention. With that said, we are extremely interested in understanding the etiology of postpartum psychosis. Various studies over the last 5 years have looked at a whole host of psychosocial as well as neurobiologic variables that may contribute to risk for postpartum psychosis, including dysregulation of the stress axis, heightened inflammation as well as a history of child adversity and heightened experience of stress during the perinatal period.

There have also been anecdotal reports during Virtual Rounds at the Center for Women’s Mental Health of higher recent rates of postpartum psychosis manifesting during the postpartum period. This is a clinical observation and has not been systematically studied. However, one can wonder whether the experience of the pandemic has constituted a stressor for at-risk women, tipping the scales toward women becoming ill, or whether clinicians are seeing this finding more because of our ability to observe it more within the context of the pandemic.

Precise quantification of risk for postpartum psychosis is complicated; as noted, women with bipolar disorder have a predictably high risk for getting ill during the postpartum period and many go on to have clinical courses consistent with recurrent bipolar disorder. However, there are other women who have circumscribed episodes of psychotic illness in the postpartum period who recover and are totally well without any evidence of psychiatric disorder until they have another child, at which time the risk for recurrence of postpartum psychosis is very high. Interest in developing a model of risk that could reliably predict an illness as serious as postpartum psychosis is on the minds of researchers around the world.

One recent study that highlights the multiple factors involved in risk of postpartum psychosis involved a prospective longitudinal study of a group of women who were followed across the peripartum period from the third trimester until 4 weeks postpartum. In this group, 51 women were at increased risk for postpartum psychosis based on their diagnosis of bipolar disorder, schizoaffective disorder, or a previous episode of postpartum psychosis. These women were matched with a control group with no past or current diagnosis of psychiatric disorder or family history of postpartum psychosis. The findings suggested that women at risk for postpartum psychosis who experienced a psychiatric relapse during the first 4 weeks postpartum relative to women at risk who remained well had histories of severe childhood adversity as well as biomarkers consistent with a dysregulated stress axis (a statistically higher daily cortisol level). This is consistent with other data that have implicated the complex role between psychosocial variables as well as neurobiologic variables, such as a dysregulation in the hypothalamic pituitary adrenal axis and other studies that suggest that dysregulated inflammatory status may also drive risk for postpartum psychosis (Hazelgrove K et al. Psychoneuroendocrinology. 2021 Jun. doi: 10.1016/j.psyneuen.2021.105218).

At the end of the day, postpartum psychosis is a psychiatric and obstetrical emergency. In our center, it is rare for women not to be hospitalized with this condition to ensure the safety of the mother as well as her newborn, and to also get her recompensated and functioning as quickly and as significantly as possible. However, an interesting extrapolation of the findings noted by Hazelgrove and colleagues is that it raises the question of what effective treatments might be used to mitigate risk for those at greatest risk for postpartum psychosis. For example, are there other treatments over and above the few effective ones that have been studied as prophylactic pharmacologic interventions that might mitigate risk for recurrence of an illness as serious as postpartum psychosis?

The data suggesting dysregulation of the stress axis as a predictor variable for risk in women vulnerable to postpartum psychosis opens an array of opportunities that are nonpharmacologic, such as mindfulness-based cognitive therapy or other interventions that help to modulate the stress axis. This is a terrific opportunity to have pharmacologic intervention meet nonpharmacologic intervention to potentially mitigate risk for postpartum psychosis with its attendant serious sequelae.

In our own work, where we are evaluating genomic data in an extremely well-characterized group of women with known histories of postpartum psychosis, we are interested to see if we can enhance understanding of the model of risk for postpartum psychosis by factoring in genomic underpinning, history of diagnosis, and psychosocial variables to optimally craft interventions for this population of at-risk women. This brings us one step closer to the future in women’s mental health, to the practice of “precision reproductive psychiatry,” matching interventions to specific presentations across perinatal populations.
 

Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications. Email Dr. Cohen at [email protected].

Postpartum depression, in many respects, has become a household term. Over the last decade, there has been increasing awareness of the importance of screening for postpartum depression, with increased systematic screening across clinical settings where care is delivered to women during pregnancy and the postpartum period. There have also been greater efforts to identify women who are suffering postpartum depression and to support them with appropriate clinical interventions, whether through psychotherapy and/or pharmacologic therapy. Clinical interventions are supplemented by the increasing awareness of the value of community-based support groups for women who are suffering from postpartum mood and anxiety disorders.

Despite the growing, appropriate focus on recognition and acute treatment of postpartum depression as well as assessing clinical outcomes for those who suffer from postpartum mood and anxiety disorders, less attention has been given to postpartum psychosis, the most severe form of postpartum depression. It is indeed, the least common postpartum psychiatric syndrome (1 in 1,000 births) and comes to public attention when there has been a tragedy during the acute postpartum period such as maternal suicide or infanticide. In this sense, postpartum psychosis is ironically an underappreciated clinical entity across America given its severity, the effect it has on longer-term psychiatric morbidity, and its effect on children and families.

Our group at the Center for Women’s Mental Health has been interested in postpartum psychosis for years and started the Postpartum Psychosis Project in an effort to better understand the phenomenology, course, treatment, outcome, and genomic underpinnings of postpartum psychosis. Risk factors that are well established for postpartum psychosis have been described and overwhelmingly include patients with bipolar disorder. The risk for recurrent postpartum psychosis in women who have had a previous episode is as great as 75%-90% in the absence of prophylactic intervention. With that said, we are extremely interested in understanding the etiology of postpartum psychosis. Various studies over the last 5 years have looked at a whole host of psychosocial as well as neurobiologic variables that may contribute to risk for postpartum psychosis, including dysregulation of the stress axis, heightened inflammation as well as a history of child adversity and heightened experience of stress during the perinatal period.

There have also been anecdotal reports during Virtual Rounds at the Center for Women’s Mental Health of higher recent rates of postpartum psychosis manifesting during the postpartum period. This is a clinical observation and has not been systematically studied. However, one can wonder whether the experience of the pandemic has constituted a stressor for at-risk women, tipping the scales toward women becoming ill, or whether clinicians are seeing this finding more because of our ability to observe it more within the context of the pandemic.

Precise quantification of risk for postpartum psychosis is complicated; as noted, women with bipolar disorder have a predictably high risk for getting ill during the postpartum period and many go on to have clinical courses consistent with recurrent bipolar disorder. However, there are other women who have circumscribed episodes of psychotic illness in the postpartum period who recover and are totally well without any evidence of psychiatric disorder until they have another child, at which time the risk for recurrence of postpartum psychosis is very high. Interest in developing a model of risk that could reliably predict an illness as serious as postpartum psychosis is on the minds of researchers around the world.

One recent study that highlights the multiple factors involved in risk of postpartum psychosis involved a prospective longitudinal study of a group of women who were followed across the peripartum period from the third trimester until 4 weeks postpartum. In this group, 51 women were at increased risk for postpartum psychosis based on their diagnosis of bipolar disorder, schizoaffective disorder, or a previous episode of postpartum psychosis. These women were matched with a control group with no past or current diagnosis of psychiatric disorder or family history of postpartum psychosis. The findings suggested that women at risk for postpartum psychosis who experienced a psychiatric relapse during the first 4 weeks postpartum relative to women at risk who remained well had histories of severe childhood adversity as well as biomarkers consistent with a dysregulated stress axis (a statistically higher daily cortisol level). This is consistent with other data that have implicated the complex role between psychosocial variables as well as neurobiologic variables, such as a dysregulation in the hypothalamic pituitary adrenal axis and other studies that suggest that dysregulated inflammatory status may also drive risk for postpartum psychosis (Hazelgrove K et al. Psychoneuroendocrinology. 2021 Jun. doi: 10.1016/j.psyneuen.2021.105218).

At the end of the day, postpartum psychosis is a psychiatric and obstetrical emergency. In our center, it is rare for women not to be hospitalized with this condition to ensure the safety of the mother as well as her newborn, and to also get her recompensated and functioning as quickly and as significantly as possible. However, an interesting extrapolation of the findings noted by Hazelgrove and colleagues is that it raises the question of what effective treatments might be used to mitigate risk for those at greatest risk for postpartum psychosis. For example, are there other treatments over and above the few effective ones that have been studied as prophylactic pharmacologic interventions that might mitigate risk for recurrence of an illness as serious as postpartum psychosis?

The data suggesting dysregulation of the stress axis as a predictor variable for risk in women vulnerable to postpartum psychosis opens an array of opportunities that are nonpharmacologic, such as mindfulness-based cognitive therapy or other interventions that help to modulate the stress axis. This is a terrific opportunity to have pharmacologic intervention meet nonpharmacologic intervention to potentially mitigate risk for postpartum psychosis with its attendant serious sequelae.

In our own work, where we are evaluating genomic data in an extremely well-characterized group of women with known histories of postpartum psychosis, we are interested to see if we can enhance understanding of the model of risk for postpartum psychosis by factoring in genomic underpinning, history of diagnosis, and psychosocial variables to optimally craft interventions for this population of at-risk women. This brings us one step closer to the future in women’s mental health, to the practice of “precision reproductive psychiatry,” matching interventions to specific presentations across perinatal populations.
 

Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications. Email Dr. Cohen at [email protected].

Preterm and early birth is associated with an increased risk of autism independent of genetic or environmental factors, according to new research published in Pediatrics.

Although previous studies have linked preterm births to an increased risk of autism – one 2017 study published in Cerebral Cortex found that 27.4% of the children born extremely preterm were diagnosed with autism – Casey Crump, MD, PhD, said potential causality, sex-specific differences, and association with early-term births were still unclear.

“Preterm birth had previously been linked with higher risk of autism; however, several important questions remained unanswered,” said Dr. Crump, professor and vice chair for research at the department of family medicine and community health and professor of epidemiology in the department of population health science and policy at Icahn School of Medicine at Mount Sinai New York. “To our knowledge, [our study] is the largest to date of gestational age at birth in relation to autism, and one of the first to investigate sex-specific differences, early term birth, or the influence of shared familial factors.”

Dr. Crump and colleagues examined data from more than 4 million infants born in Sweden between 1973 and 2013 who were followed-up for autism spectrum disorder identified from nationwide outpatient and inpatient diagnoses through December 2015. Children born between 22 and 27 weeks were considered extremely preterm, those born between 28 and 33 week were characterized as very to moderate preterm, and those born between 34 and 36 weeks were considered late preterm. Early-term births are characterized as infants born between 37 and 38 weeks and children born between 39 and 41 weeks were considered term births.

They found that 6.1% of those born extremely preterm were diagnosed with autism. Meanwhile, autism spectrum disorder prevalences were 2.6% for very to moderate preterm, 1.9% for late preterm, 2.1% for all preterm, and 1.6% for early term, compared with 1.4% for term birth.

The researchers’ analysis showed that preterm and early birth were associated with a significantly increased risk of autism in males and females. Children who were born extremely preterm had an approximately fourfold increased risk of autism. Researchers also found that each additional week of gestation was associated with a 5% lower prevalence of autism spectrum disorder (ASD) on average.

“The elevated risk even in [late preterm] infants is not completely surprising because a number of investigators have shown higher incidences of early cognitive, language motor and impairment, and school problems ... and psychiatric disorders, some of which may extend to adulthood,” Elisabeth McGowan, MD, who was not involved in the study, said in a solicited editorial commentary about the study.

Dr. Crump believes the association between preterm birth and autism may be because of increased inflammatory marker levels. A 2009 study published in Reproductive Sciences found that increased proinflammatory cytokine levels have been associated with the timing and initiation of preterm birth, and also have been detected in the brain and cerebrospinal fluid of individuals with autism “and may play a key role in its pathogenesis,” Dr. Crump said.

“Inflammatory-driven alteration of neuronal connections during critical periods of brain development may be central to the development of autism,” Dr. Crump explained.

However, Dr. Crump said that, although the relative risks of autism were higher in those born preterm, the absolute risk of the condition is low.

“The report by Crump is in many ways a definitive accounting of the elevated rates of ASD in preterm infants,” said Dr. McGowan, associate professor of pediatrics at the Women and Infants Hospital, Providence, R.I. “And although the impact of prematurity on brain development may be part of the causal chain resulting in ASD (or other neurodevelopmental outcomes), these factors are operating in a complex biological landscape, with pathways to ASD outcomes that can be expected to be heterogeneous.”

ASD is a developmental condition that affects about 1 in 54 children, according to the Centers for Disease Control and Prevention. Many children are not diagnosed with ASD until later in childhood, which in some cases delays treatment and early intervention. ASD may be detected as early as 18 months, but the average age of diagnosis for ASD is 4.3 years, according to the CDC.

“Children born prematurely need early evaluation and long-term follow-up to facilitate timely detection and treatment of autism, especially those born at the earliest gestational ages,” Dr. Crump said in an interview. “In patients of all ages, gestational age at birth should be routinely included in history-taking and medical records to help identify in clinical practice those born preterm or early term. Such information can provide additional valuable context for understanding patients’ health and may facilitate earlier evaluation for autism and other neurodevelopmental conditions in those born prematurely.”

Dr. Crump and colleagues said more research is needed to understand the biologic mechanisms linking preterm birth with higher risks of autism, which “may reveal new targets for intervention at critical windows of neurodevelopment to improve the disease trajectory.”

Experts interviewed did not disclose any relevant financial relationships.

Preterm and early birth is associated with an increased risk of autism independent of genetic or environmental factors, according to new research published in Pediatrics.

Although previous studies have linked preterm births to an increased risk of autism – one 2017 study published in Cerebral Cortex found that 27.4% of the children born extremely preterm were diagnosed with autism – Casey Crump, MD, PhD, said potential causality, sex-specific differences, and association with early-term births were still unclear.

“Preterm birth had previously been linked with higher risk of autism; however, several important questions remained unanswered,” said Dr. Crump, professor and vice chair for research at the department of family medicine and community health and professor of epidemiology in the department of population health science and policy at Icahn School of Medicine at Mount Sinai New York. “To our knowledge, [our study] is the largest to date of gestational age at birth in relation to autism, and one of the first to investigate sex-specific differences, early term birth, or the influence of shared familial factors.”

Dr. Crump and colleagues examined data from more than 4 million infants born in Sweden between 1973 and 2013 who were followed-up for autism spectrum disorder identified from nationwide outpatient and inpatient diagnoses through December 2015. Children born between 22 and 27 weeks were considered extremely preterm, those born between 28 and 33 week were characterized as very to moderate preterm, and those born between 34 and 36 weeks were considered late preterm. Early-term births are characterized as infants born between 37 and 38 weeks and children born between 39 and 41 weeks were considered term births.

They found that 6.1% of those born extremely preterm were diagnosed with autism. Meanwhile, autism spectrum disorder prevalences were 2.6% for very to moderate preterm, 1.9% for late preterm, 2.1% for all preterm, and 1.6% for early term, compared with 1.4% for term birth.

The researchers’ analysis showed that preterm and early birth were associated with a significantly increased risk of autism in males and females. Children who were born extremely preterm had an approximately fourfold increased risk of autism. Researchers also found that each additional week of gestation was associated with a 5% lower prevalence of autism spectrum disorder (ASD) on average.

“The elevated risk even in [late preterm] infants is not completely surprising because a number of investigators have shown higher incidences of early cognitive, language motor and impairment, and school problems ... and psychiatric disorders, some of which may extend to adulthood,” Elisabeth McGowan, MD, who was not involved in the study, said in a solicited editorial commentary about the study.

Dr. Crump believes the association between preterm birth and autism may be because of increased inflammatory marker levels. A 2009 study published in Reproductive Sciences found that increased proinflammatory cytokine levels have been associated with the timing and initiation of preterm birth, and also have been detected in the brain and cerebrospinal fluid of individuals with autism “and may play a key role in its pathogenesis,” Dr. Crump said.

“Inflammatory-driven alteration of neuronal connections during critical periods of brain development may be central to the development of autism,” Dr. Crump explained.

However, Dr. Crump said that, although the relative risks of autism were higher in those born preterm, the absolute risk of the condition is low.

“The report by Crump is in many ways a definitive accounting of the elevated rates of ASD in preterm infants,” said Dr. McGowan, associate professor of pediatrics at the Women and Infants Hospital, Providence, R.I. “And although the impact of prematurity on brain development may be part of the causal chain resulting in ASD (or other neurodevelopmental outcomes), these factors are operating in a complex biological landscape, with pathways to ASD outcomes that can be expected to be heterogeneous.”

ASD is a developmental condition that affects about 1 in 54 children, according to the Centers for Disease Control and Prevention. Many children are not diagnosed with ASD until later in childhood, which in some cases delays treatment and early intervention. ASD may be detected as early as 18 months, but the average age of diagnosis for ASD is 4.3 years, according to the CDC.

“Children born prematurely need early evaluation and long-term follow-up to facilitate timely detection and treatment of autism, especially those born at the earliest gestational ages,” Dr. Crump said in an interview. “In patients of all ages, gestational age at birth should be routinely included in history-taking and medical records to help identify in clinical practice those born preterm or early term. Such information can provide additional valuable context for understanding patients’ health and may facilitate earlier evaluation for autism and other neurodevelopmental conditions in those born prematurely.”

Dr. Crump and colleagues said more research is needed to understand the biologic mechanisms linking preterm birth with higher risks of autism, which “may reveal new targets for intervention at critical windows of neurodevelopment to improve the disease trajectory.”

Experts interviewed did not disclose any relevant financial relationships.

Preterm and early birth is associated with an increased risk of autism independent of genetic or environmental factors, according to new research published in Pediatrics.

Although previous studies have linked preterm births to an increased risk of autism – one 2017 study published in Cerebral Cortex found that 27.4% of the children born extremely preterm were diagnosed with autism – Casey Crump, MD, PhD, said potential causality, sex-specific differences, and association with early-term births were still unclear.

“Preterm birth had previously been linked with higher risk of autism; however, several important questions remained unanswered,” said Dr. Crump, professor and vice chair for research at the department of family medicine and community health and professor of epidemiology in the department of population health science and policy at Icahn School of Medicine at Mount Sinai New York. “To our knowledge, [our study] is the largest to date of gestational age at birth in relation to autism, and one of the first to investigate sex-specific differences, early term birth, or the influence of shared familial factors.”

Dr. Crump and colleagues examined data from more than 4 million infants born in Sweden between 1973 and 2013 who were followed-up for autism spectrum disorder identified from nationwide outpatient and inpatient diagnoses through December 2015. Children born between 22 and 27 weeks were considered extremely preterm, those born between 28 and 33 week were characterized as very to moderate preterm, and those born between 34 and 36 weeks were considered late preterm. Early-term births are characterized as infants born between 37 and 38 weeks and children born between 39 and 41 weeks were considered term births.

They found that 6.1% of those born extremely preterm were diagnosed with autism. Meanwhile, autism spectrum disorder prevalences were 2.6% for very to moderate preterm, 1.9% for late preterm, 2.1% for all preterm, and 1.6% for early term, compared with 1.4% for term birth.

The researchers’ analysis showed that preterm and early birth were associated with a significantly increased risk of autism in males and females. Children who were born extremely preterm had an approximately fourfold increased risk of autism. Researchers also found that each additional week of gestation was associated with a 5% lower prevalence of autism spectrum disorder (ASD) on average.

“The elevated risk even in [late preterm] infants is not completely surprising because a number of investigators have shown higher incidences of early cognitive, language motor and impairment, and school problems ... and psychiatric disorders, some of which may extend to adulthood,” Elisabeth McGowan, MD, who was not involved in the study, said in a solicited editorial commentary about the study.

Dr. Crump believes the association between preterm birth and autism may be because of increased inflammatory marker levels. A 2009 study published in Reproductive Sciences found that increased proinflammatory cytokine levels have been associated with the timing and initiation of preterm birth, and also have been detected in the brain and cerebrospinal fluid of individuals with autism “and may play a key role in its pathogenesis,” Dr. Crump said.

“Inflammatory-driven alteration of neuronal connections during critical periods of brain development may be central to the development of autism,” Dr. Crump explained.

However, Dr. Crump said that, although the relative risks of autism were higher in those born preterm, the absolute risk of the condition is low.

“The report by Crump is in many ways a definitive accounting of the elevated rates of ASD in preterm infants,” said Dr. McGowan, associate professor of pediatrics at the Women and Infants Hospital, Providence, R.I. “And although the impact of prematurity on brain development may be part of the causal chain resulting in ASD (or other neurodevelopmental outcomes), these factors are operating in a complex biological landscape, with pathways to ASD outcomes that can be expected to be heterogeneous.”

ASD is a developmental condition that affects about 1 in 54 children, according to the Centers for Disease Control and Prevention. Many children are not diagnosed with ASD until later in childhood, which in some cases delays treatment and early intervention. ASD may be detected as early as 18 months, but the average age of diagnosis for ASD is 4.3 years, according to the CDC.

“Children born prematurely need early evaluation and long-term follow-up to facilitate timely detection and treatment of autism, especially those born at the earliest gestational ages,” Dr. Crump said in an interview. “In patients of all ages, gestational age at birth should be routinely included in history-taking and medical records to help identify in clinical practice those born preterm or early term. Such information can provide additional valuable context for understanding patients’ health and may facilitate earlier evaluation for autism and other neurodevelopmental conditions in those born prematurely.”

Dr. Crump and colleagues said more research is needed to understand the biologic mechanisms linking preterm birth with higher risks of autism, which “may reveal new targets for intervention at critical windows of neurodevelopment to improve the disease trajectory.”

Experts interviewed did not disclose any relevant financial relationships.

Second-generation antipsychotics (SGAs) taken by pregnant women are linked to a low rate of adverse effects in their children, new research suggests.

monkeybusinessimages/Thinkstock

Data from a large registry study of almost 2,000 women showed that 2.5% of the live births in a group that had been exposed to antipsychotics had confirmed major malformations compared with 2% of the live births in a non-exposed group. This translated into an estimated odds ratio of 1.5 for major malformations.

“The 2.5% absolute risk for major malformations is consistent with the estimates of the Centers for Disease Control and Prevention’s national baseline rate of major malformations in the general population,” lead author Adele Viguera, MD, MPH, director of research for women’s mental health, Cleveland Clinic Neurological Institute, told this news organization.

“Our results are reassuring and suggest that second-generation antipsychotics, as a class, do not substantially increase the risk of major malformations,” Dr. Viguera said.

The findings were published online August 3 in the Journal of Clinical Psychiatry.
 

Safety data scarce

Despite the increasing use of SGAs to treat a “spectrum of psychiatric disorders,” relatively little data are available on the reproductive safety of these agents, Dr. Viguera said.

The National Pregnancy Registry for Atypical Antipsychotics (NPRAA) was established in 2008 to determine risk for major malformation among infants exposed to these medications during the first trimester, relative to a comparison group of unexposed infants of mothers with histories of psychiatric morbidity.

The NPRAA follows pregnant women (aged 18 to 45 years) with psychiatric illness who are exposed or unexposed to SGAs during pregnancy. Participants are recruited through nationwide provider referral, self-referral, and advertisement through the Massachusetts General Hospital Center for Women’s Mental Health website.

The women are interviewed by phone at three timepoints: Enrollment, 7 months, and 3 months postpartum. Specific data collected are shown in the following table.

Demographic differences

Of the 1,906 women who enrolled as of April 2020, 1,311 (mean age, 32.6 years; 81.3% White) completed the study and were eligible for inclusion in the analysis.

Although the groups had a virtually identical mean age, fewer women in the exposure group were married compared with those in the non-exposure group (77% vs. 90%, respectively) and fewer had a college education (71.2% vs. 87.8%). There was also a higher percentage of first-trimester cigarette smokers in the exposure group (18.4% vs. 5.1%).

On the other hand, more women in the non-exposure group used alcohol than in the exposure group (28.6% vs. 21.4%, respectively).

The most frequent psychiatric disorder in the exposure group was bipolar disorder (63.9%), followed by major depression (12.9%), anxiety (5.8%), and schizophrenia (4.5%). Only 11.4% of women in the non-exposure group were diagnosed with bipolar disorder, whereas 34.1% were diagnosed with major depression, 31.3% with anxiety, and none with schizophrenia.

Notably, a large percentage of women in both groups had a history of postpartum depression and/or psychosis (41.4% and 35.5%, respectively).

The most frequently used SGAs in the exposure group were quetiapine (Seroquel), aripiprazole (Abilify), and lurasidone (Latuda).

Participants in the exposure group had a higher age at initial onset of primary psychiatric diagnosis and a lower proportion of lifetime illness compared with those in the non-exposure group.
 

Major clinical implication?

Among 640 live births in the exposure group, which included 17 twin pregnancies and 1 triplet pregnancy, 2.5% reported major malformations. Among 704 live births in the control group, which included 14 twin pregnancies, 1.99% reported major malformations.

The estimated OR for major malformations comparing exposed and unexposed infants was 1.48 (95% confidence interval, 0.625-3.517).

The authors note that their findings were consistent with one of the largest studies to date, which included a nationwide sample of more than 1 million women. Its results showed that, among infants exposed to SGAs versus those who were not exposed, the estimated risk ratio after adjusting for psychiatric conditions was 1.05 (95% CI, 0.96-1.16).

Additionally, “a hallmark of a teratogen is that it tends to cause a specific type or pattern of malformations, and we found no preponderance of one single type of major malformation or specific pattern of malformations among the exposed and unexposed groups,” Dr. Viguera said

“A major clinical implication of these findings is that for women with major mood and/or psychotic disorders, treatment with an atypical antipsychotic during pregnancy may be the most prudent clinical decision, much as continued treatment is recommended for pregnant women with other serious and chronic medical conditions, such as epilepsy,” she added.
 

The concept of ‘satisficing’

Commenting on the study, Vivien Burt, MD, PhD, founder and director/consultant of the Women’s Life Center at the Resnick University of California, Los Angeles (UCLA) Neuropsychiatric Hospital, called the findings “reassuring.”

The results “support the conclusion that in pregnant women with serious psychiatric illnesses, the use of SGAs is often a better option than avoiding these medications and exposing both the women and their offspring to the adverse consequences of maternal mental illness,” she said.

An accompanying editorial co-authored by Dr. Burt and colleague Sonya Rasminsky, MD, introduced the concept of “satisficing” – a term coined by Herbert Simon, a behavioral economist and Nobel Laureate. “Satisficing” is a “decision-making strategy that aims for a satisfactory (‘good enough’) outcome rather than a perfect one.”

The concept applies to decision-making beyond the field of economics “and is critical to how physicians help patients make decisions when they are faced with multiple treatment options,” said Dr. Burt, a professor emeritus of psychiatry at UCLA.

“The goal of ‘satisficing’ is to plan for the most satisfactory outcome, knowing that there are always unknowns, so in an uncertain world, clinicians should carefully help their patients make decisions that will allow them to achieve an outcome they can best live with,” she noted.

The investigators note that their findings may not be generalizable to the larger population of women taking SGAs, given that their participants were “overwhelmingly White, married, and well-educated women.”

They add that enrollment into the NPRAA registry is ongoing and larger sample sizes will “further narrow the confidence interval around the risk estimates and allow for adjustment of likely sources of confounding.”

The NPRAA is supported by Alkermes, Johnson & Johnson/Janssen Pharmaceuticals, Otsuka America Pharmaceutical, Sunovion Pharmaceuticals, SAGE Therapeutics, Teva Pharmaceuticals, and Aurobindo Pharma. Past sponsors of the NPRAA are listed in the original paper. Dr. Viguera receives research support from the NPRAA, Alkermes Biopharmaceuticals, Aurobindo Pharma, Janssen Pharmaceuticals, Otsuka Pharmaceutical, Sunovion Pharmaceuticals, Teva Pharmaceuticals, and SAGE Therapeutics and receives adviser/consulting fees from Up-to-Date. Dr. Burt has been a consultant/speaker for Sage Therapeutics. Dr. Rasminsky has disclosed no relevant financial relationships.

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

Second-generation antipsychotics (SGAs) taken by pregnant women are linked to a low rate of adverse effects in their children, new research suggests.

monkeybusinessimages/Thinkstock

Data from a large registry study of almost 2,000 women showed that 2.5% of the live births in a group that had been exposed to antipsychotics had confirmed major malformations compared with 2% of the live births in a non-exposed group. This translated into an estimated odds ratio of 1.5 for major malformations.

“The 2.5% absolute risk for major malformations is consistent with the estimates of the Centers for Disease Control and Prevention’s national baseline rate of major malformations in the general population,” lead author Adele Viguera, MD, MPH, director of research for women’s mental health, Cleveland Clinic Neurological Institute, told this news organization.

“Our results are reassuring and suggest that second-generation antipsychotics, as a class, do not substantially increase the risk of major malformations,” Dr. Viguera said.

The findings were published online August 3 in the Journal of Clinical Psychiatry.
 

Safety data scarce

Despite the increasing use of SGAs to treat a “spectrum of psychiatric disorders,” relatively little data are available on the reproductive safety of these agents, Dr. Viguera said.

The National Pregnancy Registry for Atypical Antipsychotics (NPRAA) was established in 2008 to determine risk for major malformation among infants exposed to these medications during the first trimester, relative to a comparison group of unexposed infants of mothers with histories of psychiatric morbidity.

The NPRAA follows pregnant women (aged 18 to 45 years) with psychiatric illness who are exposed or unexposed to SGAs during pregnancy. Participants are recruited through nationwide provider referral, self-referral, and advertisement through the Massachusetts General Hospital Center for Women’s Mental Health website.

The women are interviewed by phone at three timepoints: Enrollment, 7 months, and 3 months postpartum. Specific data collected are shown in the following table.

Demographic differences

Of the 1,906 women who enrolled as of April 2020, 1,311 (mean age, 32.6 years; 81.3% White) completed the study and were eligible for inclusion in the analysis.

Although the groups had a virtually identical mean age, fewer women in the exposure group were married compared with those in the non-exposure group (77% vs. 90%, respectively) and fewer had a college education (71.2% vs. 87.8%). There was also a higher percentage of first-trimester cigarette smokers in the exposure group (18.4% vs. 5.1%).

On the other hand, more women in the non-exposure group used alcohol than in the exposure group (28.6% vs. 21.4%, respectively).

The most frequent psychiatric disorder in the exposure group was bipolar disorder (63.9%), followed by major depression (12.9%), anxiety (5.8%), and schizophrenia (4.5%). Only 11.4% of women in the non-exposure group were diagnosed with bipolar disorder, whereas 34.1% were diagnosed with major depression, 31.3% with anxiety, and none with schizophrenia.

Notably, a large percentage of women in both groups had a history of postpartum depression and/or psychosis (41.4% and 35.5%, respectively).

The most frequently used SGAs in the exposure group were quetiapine (Seroquel), aripiprazole (Abilify), and lurasidone (Latuda).

Participants in the exposure group had a higher age at initial onset of primary psychiatric diagnosis and a lower proportion of lifetime illness compared with those in the non-exposure group.
 

Major clinical implication?

Among 640 live births in the exposure group, which included 17 twin pregnancies and 1 triplet pregnancy, 2.5% reported major malformations. Among 704 live births in the control group, which included 14 twin pregnancies, 1.99% reported major malformations.

The estimated OR for major malformations comparing exposed and unexposed infants was 1.48 (95% confidence interval, 0.625-3.517).

The authors note that their findings were consistent with one of the largest studies to date, which included a nationwide sample of more than 1 million women. Its results showed that, among infants exposed to SGAs versus those who were not exposed, the estimated risk ratio after adjusting for psychiatric conditions was 1.05 (95% CI, 0.96-1.16).

Additionally, “a hallmark of a teratogen is that it tends to cause a specific type or pattern of malformations, and we found no preponderance of one single type of major malformation or specific pattern of malformations among the exposed and unexposed groups,” Dr. Viguera said

“A major clinical implication of these findings is that for women with major mood and/or psychotic disorders, treatment with an atypical antipsychotic during pregnancy may be the most prudent clinical decision, much as continued treatment is recommended for pregnant women with other serious and chronic medical conditions, such as epilepsy,” she added.
 

The concept of ‘satisficing’

Commenting on the study, Vivien Burt, MD, PhD, founder and director/consultant of the Women’s Life Center at the Resnick University of California, Los Angeles (UCLA) Neuropsychiatric Hospital, called the findings “reassuring.”

The results “support the conclusion that in pregnant women with serious psychiatric illnesses, the use of SGAs is often a better option than avoiding these medications and exposing both the women and their offspring to the adverse consequences of maternal mental illness,” she said.

An accompanying editorial co-authored by Dr. Burt and colleague Sonya Rasminsky, MD, introduced the concept of “satisficing” – a term coined by Herbert Simon, a behavioral economist and Nobel Laureate. “Satisficing” is a “decision-making strategy that aims for a satisfactory (‘good enough’) outcome rather than a perfect one.”

The concept applies to decision-making beyond the field of economics “and is critical to how physicians help patients make decisions when they are faced with multiple treatment options,” said Dr. Burt, a professor emeritus of psychiatry at UCLA.

“The goal of ‘satisficing’ is to plan for the most satisfactory outcome, knowing that there are always unknowns, so in an uncertain world, clinicians should carefully help their patients make decisions that will allow them to achieve an outcome they can best live with,” she noted.

The investigators note that their findings may not be generalizable to the larger population of women taking SGAs, given that their participants were “overwhelmingly White, married, and well-educated women.”

They add that enrollment into the NPRAA registry is ongoing and larger sample sizes will “further narrow the confidence interval around the risk estimates and allow for adjustment of likely sources of confounding.”

The NPRAA is supported by Alkermes, Johnson & Johnson/Janssen Pharmaceuticals, Otsuka America Pharmaceutical, Sunovion Pharmaceuticals, SAGE Therapeutics, Teva Pharmaceuticals, and Aurobindo Pharma. Past sponsors of the NPRAA are listed in the original paper. Dr. Viguera receives research support from the NPRAA, Alkermes Biopharmaceuticals, Aurobindo Pharma, Janssen Pharmaceuticals, Otsuka Pharmaceutical, Sunovion Pharmaceuticals, Teva Pharmaceuticals, and SAGE Therapeutics and receives adviser/consulting fees from Up-to-Date. Dr. Burt has been a consultant/speaker for Sage Therapeutics. Dr. Rasminsky has disclosed no relevant financial relationships.

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

Second-generation antipsychotics (SGAs) taken by pregnant women are linked to a low rate of adverse effects in their children, new research suggests.

monkeybusinessimages/Thinkstock

Data from a large registry study of almost 2,000 women showed that 2.5% of the live births in a group that had been exposed to antipsychotics had confirmed major malformations compared with 2% of the live births in a non-exposed group. This translated into an estimated odds ratio of 1.5 for major malformations.

“The 2.5% absolute risk for major malformations is consistent with the estimates of the Centers for Disease Control and Prevention’s national baseline rate of major malformations in the general population,” lead author Adele Viguera, MD, MPH, director of research for women’s mental health, Cleveland Clinic Neurological Institute, told this news organization.

“Our results are reassuring and suggest that second-generation antipsychotics, as a class, do not substantially increase the risk of major malformations,” Dr. Viguera said.

The findings were published online August 3 in the Journal of Clinical Psychiatry.
 

Safety data scarce

Despite the increasing use of SGAs to treat a “spectrum of psychiatric disorders,” relatively little data are available on the reproductive safety of these agents, Dr. Viguera said.

The National Pregnancy Registry for Atypical Antipsychotics (NPRAA) was established in 2008 to determine risk for major malformation among infants exposed to these medications during the first trimester, relative to a comparison group of unexposed infants of mothers with histories of psychiatric morbidity.

The NPRAA follows pregnant women (aged 18 to 45 years) with psychiatric illness who are exposed or unexposed to SGAs during pregnancy. Participants are recruited through nationwide provider referral, self-referral, and advertisement through the Massachusetts General Hospital Center for Women’s Mental Health website.

The women are interviewed by phone at three timepoints: Enrollment, 7 months, and 3 months postpartum. Specific data collected are shown in the following table.

Demographic differences

Of the 1,906 women who enrolled as of April 2020, 1,311 (mean age, 32.6 years; 81.3% White) completed the study and were eligible for inclusion in the analysis.

Although the groups had a virtually identical mean age, fewer women in the exposure group were married compared with those in the non-exposure group (77% vs. 90%, respectively) and fewer had a college education (71.2% vs. 87.8%). There was also a higher percentage of first-trimester cigarette smokers in the exposure group (18.4% vs. 5.1%).

On the other hand, more women in the non-exposure group used alcohol than in the exposure group (28.6% vs. 21.4%, respectively).

The most frequent psychiatric disorder in the exposure group was bipolar disorder (63.9%), followed by major depression (12.9%), anxiety (5.8%), and schizophrenia (4.5%). Only 11.4% of women in the non-exposure group were diagnosed with bipolar disorder, whereas 34.1% were diagnosed with major depression, 31.3% with anxiety, and none with schizophrenia.

Notably, a large percentage of women in both groups had a history of postpartum depression and/or psychosis (41.4% and 35.5%, respectively).

The most frequently used SGAs in the exposure group were quetiapine (Seroquel), aripiprazole (Abilify), and lurasidone (Latuda).

Participants in the exposure group had a higher age at initial onset of primary psychiatric diagnosis and a lower proportion of lifetime illness compared with those in the non-exposure group.
 

Major clinical implication?

Among 640 live births in the exposure group, which included 17 twin pregnancies and 1 triplet pregnancy, 2.5% reported major malformations. Among 704 live births in the control group, which included 14 twin pregnancies, 1.99% reported major malformations.

The estimated OR for major malformations comparing exposed and unexposed infants was 1.48 (95% confidence interval, 0.625-3.517).

The authors note that their findings were consistent with one of the largest studies to date, which included a nationwide sample of more than 1 million women. Its results showed that, among infants exposed to SGAs versus those who were not exposed, the estimated risk ratio after adjusting for psychiatric conditions was 1.05 (95% CI, 0.96-1.16).

Additionally, “a hallmark of a teratogen is that it tends to cause a specific type or pattern of malformations, and we found no preponderance of one single type of major malformation or specific pattern of malformations among the exposed and unexposed groups,” Dr. Viguera said

“A major clinical implication of these findings is that for women with major mood and/or psychotic disorders, treatment with an atypical antipsychotic during pregnancy may be the most prudent clinical decision, much as continued treatment is recommended for pregnant women with other serious and chronic medical conditions, such as epilepsy,” she added.
 

The concept of ‘satisficing’

Commenting on the study, Vivien Burt, MD, PhD, founder and director/consultant of the Women’s Life Center at the Resnick University of California, Los Angeles (UCLA) Neuropsychiatric Hospital, called the findings “reassuring.”

The results “support the conclusion that in pregnant women with serious psychiatric illnesses, the use of SGAs is often a better option than avoiding these medications and exposing both the women and their offspring to the adverse consequences of maternal mental illness,” she said.

An accompanying editorial co-authored by Dr. Burt and colleague Sonya Rasminsky, MD, introduced the concept of “satisficing” – a term coined by Herbert Simon, a behavioral economist and Nobel Laureate. “Satisficing” is a “decision-making strategy that aims for a satisfactory (‘good enough’) outcome rather than a perfect one.”

The concept applies to decision-making beyond the field of economics “and is critical to how physicians help patients make decisions when they are faced with multiple treatment options,” said Dr. Burt, a professor emeritus of psychiatry at UCLA.

“The goal of ‘satisficing’ is to plan for the most satisfactory outcome, knowing that there are always unknowns, so in an uncertain world, clinicians should carefully help their patients make decisions that will allow them to achieve an outcome they can best live with,” she noted.

The investigators note that their findings may not be generalizable to the larger population of women taking SGAs, given that their participants were “overwhelmingly White, married, and well-educated women.”

They add that enrollment into the NPRAA registry is ongoing and larger sample sizes will “further narrow the confidence interval around the risk estimates and allow for adjustment of likely sources of confounding.”

The NPRAA is supported by Alkermes, Johnson & Johnson/Janssen Pharmaceuticals, Otsuka America Pharmaceutical, Sunovion Pharmaceuticals, SAGE Therapeutics, Teva Pharmaceuticals, and Aurobindo Pharma. Past sponsors of the NPRAA are listed in the original paper. Dr. Viguera receives research support from the NPRAA, Alkermes Biopharmaceuticals, Aurobindo Pharma, Janssen Pharmaceuticals, Otsuka Pharmaceutical, Sunovion Pharmaceuticals, Teva Pharmaceuticals, and SAGE Therapeutics and receives adviser/consulting fees from Up-to-Date. Dr. Burt has been a consultant/speaker for Sage Therapeutics. Dr. Rasminsky has disclosed no relevant financial relationships.

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