Women's Health

This transcript has been edited for clarity.

Hello. This is Dr. JoAnn Manson, professor of medicine at Harvard Medical School and Brigham and Women’s Hospital. I’d like to talk with you about a recent report in JAMA Cardiology on atrial fibrillation (AF), sex differences, and modifiable risk factors.

We looked at these questions in our vitamin D and omega-3 trial VITAL in an ancillary study called VITAL Rhythm, led by Dr. Christine Albert at Cedars-Sinai. And this particular project was led by Dr. Hasan Siddiqi at Vanderbilt.

As you know, AF is the most common arrhythmia in the world, and it’s burgeoning in numbers, primarily because of the aging of the population. It’s also a major cause of stroke, heart failure, and cardiovascular mortality. Although women are known to have lower rates of AF than men, they’re also known to have a higher risk for cardiovascular complications and sequelae, such as higher risk for stroke and CVD mortality. Therefore, we thought that understanding sex differences in risk and modifiable risk factors for AF that could reduce the burden of disease would be important.

It’s known that greater height is a risk factor for AF, but the extent to which it explains the differences in AF risk between men and women isn’t really known. So we looked at these questions in the VITAL cohort. VITAL has more than 25,000 participants. It’s a large, diverse, nationwide cohort. About 51% are women, and all are aged 50 years or older, with a mean age of 67. All were free of known clinical cardiovascular disease at the start of the study.

AF reports were confirmed by medical records and also supplemented by Medicare CMS linkage for fuller ascertainment of outcomes. We had 900 incident cases of AF in the study, and we did see that women were less likely to be diagnosed with AF. They had a 32% lower risk – strongly statistically significant compared with men, with a P < .001. Women were also more likely to be symptomatic: About 77% of women vs. 63% of men had symptoms prior to or at diagnosis.

It was very interesting that adjustment for height eliminated the lower risk for AF in women compared with men. After accounting for height, there was not only no reduction in risk for AF among the women, there was actually a reversal of the association so that there was a slightly higher risk for AF in the women. Other risk factors for AF in the cohort included older age, higher body mass index, hypertension, and higher consumption of alcohol. We did not see an association between diabetes and higher risk for AF. We also saw no clear association with physical activity, although very strenuous physical activity has been linked to AF in some other studies.

We looked at the interventions of vitamin D (2,000 IU/day) and omega-3 fatty acids (460 mg/day of EPA and 380 mg/day of DHA) and found no association with AF, although some other studies have seen increased risk for AF with higher doses of the marine omega-3s > 1 g/day and certainly at doses of 4 g/day. So overall, the findings highlight the fact that many of the risk factors for AF do seem to be modifiable, and it is really important to identify and try to reduce these risk factors in order to reduce the burden of AF. This may be particularly important in women because women are more likely to have stroke and cardiovascular mortality in these adverse cardiovascular outcomes.

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

This transcript has been edited for clarity.

Hello. This is Dr. JoAnn Manson, professor of medicine at Harvard Medical School and Brigham and Women’s Hospital. I’d like to talk with you about a recent report in JAMA Cardiology on atrial fibrillation (AF), sex differences, and modifiable risk factors.

We looked at these questions in our vitamin D and omega-3 trial VITAL in an ancillary study called VITAL Rhythm, led by Dr. Christine Albert at Cedars-Sinai. And this particular project was led by Dr. Hasan Siddiqi at Vanderbilt.

As you know, AF is the most common arrhythmia in the world, and it’s burgeoning in numbers, primarily because of the aging of the population. It’s also a major cause of stroke, heart failure, and cardiovascular mortality. Although women are known to have lower rates of AF than men, they’re also known to have a higher risk for cardiovascular complications and sequelae, such as higher risk for stroke and CVD mortality. Therefore, we thought that understanding sex differences in risk and modifiable risk factors for AF that could reduce the burden of disease would be important.

It’s known that greater height is a risk factor for AF, but the extent to which it explains the differences in AF risk between men and women isn’t really known. So we looked at these questions in the VITAL cohort. VITAL has more than 25,000 participants. It’s a large, diverse, nationwide cohort. About 51% are women, and all are aged 50 years or older, with a mean age of 67. All were free of known clinical cardiovascular disease at the start of the study.

AF reports were confirmed by medical records and also supplemented by Medicare CMS linkage for fuller ascertainment of outcomes. We had 900 incident cases of AF in the study, and we did see that women were less likely to be diagnosed with AF. They had a 32% lower risk – strongly statistically significant compared with men, with a P < .001. Women were also more likely to be symptomatic: About 77% of women vs. 63% of men had symptoms prior to or at diagnosis.

It was very interesting that adjustment for height eliminated the lower risk for AF in women compared with men. After accounting for height, there was not only no reduction in risk for AF among the women, there was actually a reversal of the association so that there was a slightly higher risk for AF in the women. Other risk factors for AF in the cohort included older age, higher body mass index, hypertension, and higher consumption of alcohol. We did not see an association between diabetes and higher risk for AF. We also saw no clear association with physical activity, although very strenuous physical activity has been linked to AF in some other studies.

We looked at the interventions of vitamin D (2,000 IU/day) and omega-3 fatty acids (460 mg/day of EPA and 380 mg/day of DHA) and found no association with AF, although some other studies have seen increased risk for AF with higher doses of the marine omega-3s > 1 g/day and certainly at doses of 4 g/day. So overall, the findings highlight the fact that many of the risk factors for AF do seem to be modifiable, and it is really important to identify and try to reduce these risk factors in order to reduce the burden of AF. This may be particularly important in women because women are more likely to have stroke and cardiovascular mortality in these adverse cardiovascular outcomes.

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

This transcript has been edited for clarity.

Hello. This is Dr. JoAnn Manson, professor of medicine at Harvard Medical School and Brigham and Women’s Hospital. I’d like to talk with you about a recent report in JAMA Cardiology on atrial fibrillation (AF), sex differences, and modifiable risk factors.

We looked at these questions in our vitamin D and omega-3 trial VITAL in an ancillary study called VITAL Rhythm, led by Dr. Christine Albert at Cedars-Sinai. And this particular project was led by Dr. Hasan Siddiqi at Vanderbilt.

As you know, AF is the most common arrhythmia in the world, and it’s burgeoning in numbers, primarily because of the aging of the population. It’s also a major cause of stroke, heart failure, and cardiovascular mortality. Although women are known to have lower rates of AF than men, they’re also known to have a higher risk for cardiovascular complications and sequelae, such as higher risk for stroke and CVD mortality. Therefore, we thought that understanding sex differences in risk and modifiable risk factors for AF that could reduce the burden of disease would be important.

It’s known that greater height is a risk factor for AF, but the extent to which it explains the differences in AF risk between men and women isn’t really known. So we looked at these questions in the VITAL cohort. VITAL has more than 25,000 participants. It’s a large, diverse, nationwide cohort. About 51% are women, and all are aged 50 years or older, with a mean age of 67. All were free of known clinical cardiovascular disease at the start of the study.

AF reports were confirmed by medical records and also supplemented by Medicare CMS linkage for fuller ascertainment of outcomes. We had 900 incident cases of AF in the study, and we did see that women were less likely to be diagnosed with AF. They had a 32% lower risk – strongly statistically significant compared with men, with a P < .001. Women were also more likely to be symptomatic: About 77% of women vs. 63% of men had symptoms prior to or at diagnosis.

It was very interesting that adjustment for height eliminated the lower risk for AF in women compared with men. After accounting for height, there was not only no reduction in risk for AF among the women, there was actually a reversal of the association so that there was a slightly higher risk for AF in the women. Other risk factors for AF in the cohort included older age, higher body mass index, hypertension, and higher consumption of alcohol. We did not see an association between diabetes and higher risk for AF. We also saw no clear association with physical activity, although very strenuous physical activity has been linked to AF in some other studies.

We looked at the interventions of vitamin D (2,000 IU/day) and omega-3 fatty acids (460 mg/day of EPA and 380 mg/day of DHA) and found no association with AF, although some other studies have seen increased risk for AF with higher doses of the marine omega-3s > 1 g/day and certainly at doses of 4 g/day. So overall, the findings highlight the fact that many of the risk factors for AF do seem to be modifiable, and it is really important to identify and try to reduce these risk factors in order to reduce the burden of AF. This may be particularly important in women because women are more likely to have stroke and cardiovascular mortality in these adverse cardiovascular outcomes.

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

The standard nonsurgical treatment for pelvic organ prolapse does not appear to work as well as surgery to correct the problem, Dutch researchers have found. 

Pelvic organ prolapse is an uncomfortable condition, causing a troublesome vaginal bulge, often accompanied by urinary, bowel, or sexual dysfunction. Between 3% and 6% of women develop symptomatic prolapse, with the highest incidence in women aged 60-69 years – a fast-growing demographic.

Although many women choose surgical treatment, the American College of Obstetricians and Gynecologists recommends that women be offered a vaginal pessary as a noninvasive alternative, despite inconsistent data from observational studies on their effectiveness.

Lisa van der Vaart, MD, a doctoral student in ob.gyn. at the University of Amsterdam and the lead author of the new study, published in JAMA, said that differences in outcome measures, small sample size, and lack of long-term follow-up have bedeviled previous comparisons of the two techniques.

“We thought it was very important to perform a randomized control trial on this subject to improve counseling to women who suffer from symptomatic pelvic organ prolapse,” Dr. van der Vaart said.

She and her colleagues conducted a noninferiority randomized clinical trial that recruited 1,605 women with stage II or higher prolapse who were referred to specialty care at 21 hospitals in the Netherlands between 2015 and 2019. Of the 440 women who agreed to participate in the trial, 218 received a pessary, a device inserted into the vagina that provides support to tissues displaced by prolapse, and 222 underwent surgery.

The primary outcome was subjective improvement using a standardized questionnaire at 24 months; women were asked to rank their symptoms on a seven-point scale, and subjective improvement was defined as a response of much better or very much better.

“We saw a substantial amount of improvement in both groups,” Dr. van der Vaart said in an interview.

After 24 months of follow-up, outcome data were available for 173 women in the pessary group and 162 in the surgery group. For this intention-to treat population, 76.3% in the pessary group and 81.5% in the surgery group reported improvement.

Results were similar for the smaller group of participants who completed the study per protocol, without crossing over to a treatment to which they had not been allocated.

However, neither the intention-to-treat nor per-protocol analysis met the prespecified criteria for noninferiority, suggesting that use of a vaginal pessary is not equivalent to surgery.

The study also found differences in adverse events. Among women randomly assigned to surgery, 9% suffered a postoperative urinary tract infection, and 5.4% underwent additional therapy, such as pessary or repeat operation.

But use of a pessary also had downsides. The most common adverse event was discomfort (42.7%), and by 24 months, 60% of the participants in the pessary group had discontinued use.

Dr. van der Vaart said that she was surprised by the high number of women assigned to the pessary group who later elected to undergo surgery. “Women should be told that their chance of crossing over to a surgical intervention is quite high – more than 50% do eventually end up having surgery.”

Cheryl Iglesia, MD, director of the National Center for Advanced Pelvic Surgery at MedStar Health and professor of obstetrics and gynecology and urology at Georgetown University, both in Washington, was also struck by the high crossover rate. “We’ve had the same pessaries probably for the last 100 years,” she said. “We need to get better.”

Dr. Iglesia welcomed new approaches to making vaginal pessaries that are custom designed for each woman’s unique anatomy using 3D printing and pointed to promising initial clinical trials of disposable pessaries. With the aging of the population and demand for treatment of prolapse increasing, she cited a need for better nonsurgical alternatives: “We have a work-force issue and may not have enough adequately trained urogynecologists to meet the demand for prolapse repairs as our population ages.”

The study was funded by a grant from ZonMW, a Dutch governmental health care organization. Dr. van der Vaart reported grants from ZonMW during the conduct of the study.

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

The standard nonsurgical treatment for pelvic organ prolapse does not appear to work as well as surgery to correct the problem, Dutch researchers have found. 

Pelvic organ prolapse is an uncomfortable condition, causing a troublesome vaginal bulge, often accompanied by urinary, bowel, or sexual dysfunction. Between 3% and 6% of women develop symptomatic prolapse, with the highest incidence in women aged 60-69 years – a fast-growing demographic.

Although many women choose surgical treatment, the American College of Obstetricians and Gynecologists recommends that women be offered a vaginal pessary as a noninvasive alternative, despite inconsistent data from observational studies on their effectiveness.

Lisa van der Vaart, MD, a doctoral student in ob.gyn. at the University of Amsterdam and the lead author of the new study, published in JAMA, said that differences in outcome measures, small sample size, and lack of long-term follow-up have bedeviled previous comparisons of the two techniques.

“We thought it was very important to perform a randomized control trial on this subject to improve counseling to women who suffer from symptomatic pelvic organ prolapse,” Dr. van der Vaart said.

She and her colleagues conducted a noninferiority randomized clinical trial that recruited 1,605 women with stage II or higher prolapse who were referred to specialty care at 21 hospitals in the Netherlands between 2015 and 2019. Of the 440 women who agreed to participate in the trial, 218 received a pessary, a device inserted into the vagina that provides support to tissues displaced by prolapse, and 222 underwent surgery.

The primary outcome was subjective improvement using a standardized questionnaire at 24 months; women were asked to rank their symptoms on a seven-point scale, and subjective improvement was defined as a response of much better or very much better.

“We saw a substantial amount of improvement in both groups,” Dr. van der Vaart said in an interview.

After 24 months of follow-up, outcome data were available for 173 women in the pessary group and 162 in the surgery group. For this intention-to treat population, 76.3% in the pessary group and 81.5% in the surgery group reported improvement.

Results were similar for the smaller group of participants who completed the study per protocol, without crossing over to a treatment to which they had not been allocated.

However, neither the intention-to-treat nor per-protocol analysis met the prespecified criteria for noninferiority, suggesting that use of a vaginal pessary is not equivalent to surgery.

The study also found differences in adverse events. Among women randomly assigned to surgery, 9% suffered a postoperative urinary tract infection, and 5.4% underwent additional therapy, such as pessary or repeat operation.

But use of a pessary also had downsides. The most common adverse event was discomfort (42.7%), and by 24 months, 60% of the participants in the pessary group had discontinued use.

Dr. van der Vaart said that she was surprised by the high number of women assigned to the pessary group who later elected to undergo surgery. “Women should be told that their chance of crossing over to a surgical intervention is quite high – more than 50% do eventually end up having surgery.”

Cheryl Iglesia, MD, director of the National Center for Advanced Pelvic Surgery at MedStar Health and professor of obstetrics and gynecology and urology at Georgetown University, both in Washington, was also struck by the high crossover rate. “We’ve had the same pessaries probably for the last 100 years,” she said. “We need to get better.”

Dr. Iglesia welcomed new approaches to making vaginal pessaries that are custom designed for each woman’s unique anatomy using 3D printing and pointed to promising initial clinical trials of disposable pessaries. With the aging of the population and demand for treatment of prolapse increasing, she cited a need for better nonsurgical alternatives: “We have a work-force issue and may not have enough adequately trained urogynecologists to meet the demand for prolapse repairs as our population ages.”

The study was funded by a grant from ZonMW, a Dutch governmental health care organization. Dr. van der Vaart reported grants from ZonMW during the conduct of the study.

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

The standard nonsurgical treatment for pelvic organ prolapse does not appear to work as well as surgery to correct the problem, Dutch researchers have found. 

Pelvic organ prolapse is an uncomfortable condition, causing a troublesome vaginal bulge, often accompanied by urinary, bowel, or sexual dysfunction. Between 3% and 6% of women develop symptomatic prolapse, with the highest incidence in women aged 60-69 years – a fast-growing demographic.

Although many women choose surgical treatment, the American College of Obstetricians and Gynecologists recommends that women be offered a vaginal pessary as a noninvasive alternative, despite inconsistent data from observational studies on their effectiveness.

Lisa van der Vaart, MD, a doctoral student in ob.gyn. at the University of Amsterdam and the lead author of the new study, published in JAMA, said that differences in outcome measures, small sample size, and lack of long-term follow-up have bedeviled previous comparisons of the two techniques.

“We thought it was very important to perform a randomized control trial on this subject to improve counseling to women who suffer from symptomatic pelvic organ prolapse,” Dr. van der Vaart said.

She and her colleagues conducted a noninferiority randomized clinical trial that recruited 1,605 women with stage II or higher prolapse who were referred to specialty care at 21 hospitals in the Netherlands between 2015 and 2019. Of the 440 women who agreed to participate in the trial, 218 received a pessary, a device inserted into the vagina that provides support to tissues displaced by prolapse, and 222 underwent surgery.

The primary outcome was subjective improvement using a standardized questionnaire at 24 months; women were asked to rank their symptoms on a seven-point scale, and subjective improvement was defined as a response of much better or very much better.

“We saw a substantial amount of improvement in both groups,” Dr. van der Vaart said in an interview.

After 24 months of follow-up, outcome data were available for 173 women in the pessary group and 162 in the surgery group. For this intention-to treat population, 76.3% in the pessary group and 81.5% in the surgery group reported improvement.

Results were similar for the smaller group of participants who completed the study per protocol, without crossing over to a treatment to which they had not been allocated.

However, neither the intention-to-treat nor per-protocol analysis met the prespecified criteria for noninferiority, suggesting that use of a vaginal pessary is not equivalent to surgery.

The study also found differences in adverse events. Among women randomly assigned to surgery, 9% suffered a postoperative urinary tract infection, and 5.4% underwent additional therapy, such as pessary or repeat operation.

But use of a pessary also had downsides. The most common adverse event was discomfort (42.7%), and by 24 months, 60% of the participants in the pessary group had discontinued use.

Dr. van der Vaart said that she was surprised by the high number of women assigned to the pessary group who later elected to undergo surgery. “Women should be told that their chance of crossing over to a surgical intervention is quite high – more than 50% do eventually end up having surgery.”

Cheryl Iglesia, MD, director of the National Center for Advanced Pelvic Surgery at MedStar Health and professor of obstetrics and gynecology and urology at Georgetown University, both in Washington, was also struck by the high crossover rate. “We’ve had the same pessaries probably for the last 100 years,” she said. “We need to get better.”

Dr. Iglesia welcomed new approaches to making vaginal pessaries that are custom designed for each woman’s unique anatomy using 3D printing and pointed to promising initial clinical trials of disposable pessaries. With the aging of the population and demand for treatment of prolapse increasing, she cited a need for better nonsurgical alternatives: “We have a work-force issue and may not have enough adequately trained urogynecologists to meet the demand for prolapse repairs as our population ages.”

The study was funded by a grant from ZonMW, a Dutch governmental health care organization. Dr. van der Vaart reported grants from ZonMW during the conduct of the study.

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

States that have moderate state abortion laws had lower rates of maternal, fetal, and infant mortality, but not lower all-cause mortality, in reproductive-aged females compared with states that have restrictive laws, new research using 2000-2019 data indicates.

Additionally, having a higher number of laws that restrict abortion in a state was linked with higher maternal and infant mortality in the state, the study states.
 

Mortality increases with number of laws

“Each additional abortion regulation was associated with an increase in maternal mortality (1.09/100,000 live births; 95% confidence interval, 0.36-1.82) and infant mortality (0.20/1,000 live births; 95% CI, 0.12-0.26),” the authors write.

Lorie M. Harper, MD, MSCI, with the department of women’s health, University of Texas at Austin, led a team that simultaneously studied four categories of mortality: all-cause mortality in females ages 15-49 years; maternal mortality; infant mortality; and fetal mortality.

Her team did a retrospective cohort study using the Centers for Disease Control and Prevention’s WONDER (Wide-ranging ONline Data for Epidemiologic Research) database. WONDER collects publicly available data with information on mortality by state.

Data were available from 2000 to 2019 for all-cause, maternal, and infant mortality. Fetal mortality data were available from 2005 to 2019.

Findings were published ahead of print in February’s Obstetrics & Gynecology.

Though the study was done before the Supreme Court decision overturning Roe v. Wade in June 2022, its findings may shed light on potential trends depending on states’ decisions.

In the wake of the Dobbs v. Jackson Women’s Health Organization, an estimated 33 million U.S. women will live in states without available abortion services, the authors note.
 

State abortion laws changed dramatically in the study period

The authors chose the 2-decade time frame because data could be accessed for both maternal and infant mortality for all the years and because state level abortion laws changed dramatically in that time.

The Guttmacher Institute has analyzed each state’s abortion policy landscape and scored states as restrictive, moderate, or supportive. Certain types of abortion laws were associated with higher rates of all-cause mortality in reproductive-age females.

Those laws included trigger laws (the laws that automatically outlaw abortion in a state when federal law is overturned), laws that limit access to medication abortion, and parental consent laws, according to the paper.

Additionally, states that restrict access to abortion have higher rates of maternal and infant death, even after accounting for the general health of the population.
 

Trigger-law states have strong mortality association

Blair G. Darney, PhD, MPH, with the department of obstetrics and gynecology, Oregon Health & Science University and the OHSU-PSU School of Public Health in Portland, and two OHSU coauthors note in an accompanying editorial that having a trigger law in place was associated with elevations in all four mortality measures. However, trigger laws had not yet been enacted during the study.

The existence of trigger laws is likely a proxy for other factors, they write.

“[T]he relationship between trigger laws and increased mortality may more likely be explained by other factors that were not considered in the analysis than by laws that were not enacted at the time of the study,” the editorialists write.

Those factors may include lack of Medicaid expansion, socioeconomic inequities, and other policies.

The editorialists also caution that just because some types of abortion restrictions don’t appear to increase mortality, it doesn’t mean they aren’t harmful.

“For example, laws prohibiting private or Medicaid insurance coverage for abortions were not associated with maternal mortality, but these laws may simply shift the burden of payment to the individual seeking an abortion or be mitigated by funds that support an individual’s out-of-pocket cost for care. The lack of an association may therefore reflect women’s resilience and their ability to obtain needed health care in the face of financial challenges,” they write.

They point out that, conversely, Targeted Regulation of Abortion Providers (TRAP) laws, which supporters say protect women, have been associated instead with increases in maternal mortality.

Dr. Harper and study coauthors, noting that the relationship between abortion laws and mortality is complex, urge states with restrictive abortion laws to consider proven countermeasures to offset the rates, including Medicaid expansion.

One coauthor served on a medical advisory board, was a site primary investigator for several clinical trials, and received royalties from UpToDate for two topics related to trial of labor after cesarean. The other authors did not report any potential conflicts of interest. Dr. Darney’s institution receives research funding from Organon and the Office of Population Affairs on which she is the primary investigator, and she is a member of the board of directors of the Society of Family Planning and a deputy editor at Contraception. She has received an honorarium from ACOG for committee work. The other editorialists did not report any potential conflicts of interest.
 

States that have moderate state abortion laws had lower rates of maternal, fetal, and infant mortality, but not lower all-cause mortality, in reproductive-aged females compared with states that have restrictive laws, new research using 2000-2019 data indicates.

Additionally, having a higher number of laws that restrict abortion in a state was linked with higher maternal and infant mortality in the state, the study states.
 

Mortality increases with number of laws

“Each additional abortion regulation was associated with an increase in maternal mortality (1.09/100,000 live births; 95% confidence interval, 0.36-1.82) and infant mortality (0.20/1,000 live births; 95% CI, 0.12-0.26),” the authors write.

Lorie M. Harper, MD, MSCI, with the department of women’s health, University of Texas at Austin, led a team that simultaneously studied four categories of mortality: all-cause mortality in females ages 15-49 years; maternal mortality; infant mortality; and fetal mortality.

Her team did a retrospective cohort study using the Centers for Disease Control and Prevention’s WONDER (Wide-ranging ONline Data for Epidemiologic Research) database. WONDER collects publicly available data with information on mortality by state.

Data were available from 2000 to 2019 for all-cause, maternal, and infant mortality. Fetal mortality data were available from 2005 to 2019.

Findings were published ahead of print in February’s Obstetrics & Gynecology.

Though the study was done before the Supreme Court decision overturning Roe v. Wade in June 2022, its findings may shed light on potential trends depending on states’ decisions.

In the wake of the Dobbs v. Jackson Women’s Health Organization, an estimated 33 million U.S. women will live in states without available abortion services, the authors note.
 

State abortion laws changed dramatically in the study period

The authors chose the 2-decade time frame because data could be accessed for both maternal and infant mortality for all the years and because state level abortion laws changed dramatically in that time.

The Guttmacher Institute has analyzed each state’s abortion policy landscape and scored states as restrictive, moderate, or supportive. Certain types of abortion laws were associated with higher rates of all-cause mortality in reproductive-age females.

Those laws included trigger laws (the laws that automatically outlaw abortion in a state when federal law is overturned), laws that limit access to medication abortion, and parental consent laws, according to the paper.

Additionally, states that restrict access to abortion have higher rates of maternal and infant death, even after accounting for the general health of the population.
 

Trigger-law states have strong mortality association

Blair G. Darney, PhD, MPH, with the department of obstetrics and gynecology, Oregon Health & Science University and the OHSU-PSU School of Public Health in Portland, and two OHSU coauthors note in an accompanying editorial that having a trigger law in place was associated with elevations in all four mortality measures. However, trigger laws had not yet been enacted during the study.

The existence of trigger laws is likely a proxy for other factors, they write.

“[T]he relationship between trigger laws and increased mortality may more likely be explained by other factors that were not considered in the analysis than by laws that were not enacted at the time of the study,” the editorialists write.

Those factors may include lack of Medicaid expansion, socioeconomic inequities, and other policies.

The editorialists also caution that just because some types of abortion restrictions don’t appear to increase mortality, it doesn’t mean they aren’t harmful.

“For example, laws prohibiting private or Medicaid insurance coverage for abortions were not associated with maternal mortality, but these laws may simply shift the burden of payment to the individual seeking an abortion or be mitigated by funds that support an individual’s out-of-pocket cost for care. The lack of an association may therefore reflect women’s resilience and their ability to obtain needed health care in the face of financial challenges,” they write.

They point out that, conversely, Targeted Regulation of Abortion Providers (TRAP) laws, which supporters say protect women, have been associated instead with increases in maternal mortality.

Dr. Harper and study coauthors, noting that the relationship between abortion laws and mortality is complex, urge states with restrictive abortion laws to consider proven countermeasures to offset the rates, including Medicaid expansion.

One coauthor served on a medical advisory board, was a site primary investigator for several clinical trials, and received royalties from UpToDate for two topics related to trial of labor after cesarean. The other authors did not report any potential conflicts of interest. Dr. Darney’s institution receives research funding from Organon and the Office of Population Affairs on which she is the primary investigator, and she is a member of the board of directors of the Society of Family Planning and a deputy editor at Contraception. She has received an honorarium from ACOG for committee work. The other editorialists did not report any potential conflicts of interest.
 

States that have moderate state abortion laws had lower rates of maternal, fetal, and infant mortality, but not lower all-cause mortality, in reproductive-aged females compared with states that have restrictive laws, new research using 2000-2019 data indicates.

Additionally, having a higher number of laws that restrict abortion in a state was linked with higher maternal and infant mortality in the state, the study states.
 

Mortality increases with number of laws

“Each additional abortion regulation was associated with an increase in maternal mortality (1.09/100,000 live births; 95% confidence interval, 0.36-1.82) and infant mortality (0.20/1,000 live births; 95% CI, 0.12-0.26),” the authors write.

Lorie M. Harper, MD, MSCI, with the department of women’s health, University of Texas at Austin, led a team that simultaneously studied four categories of mortality: all-cause mortality in females ages 15-49 years; maternal mortality; infant mortality; and fetal mortality.

Her team did a retrospective cohort study using the Centers for Disease Control and Prevention’s WONDER (Wide-ranging ONline Data for Epidemiologic Research) database. WONDER collects publicly available data with information on mortality by state.

Data were available from 2000 to 2019 for all-cause, maternal, and infant mortality. Fetal mortality data were available from 2005 to 2019.

Findings were published ahead of print in February’s Obstetrics & Gynecology.

Though the study was done before the Supreme Court decision overturning Roe v. Wade in June 2022, its findings may shed light on potential trends depending on states’ decisions.

In the wake of the Dobbs v. Jackson Women’s Health Organization, an estimated 33 million U.S. women will live in states without available abortion services, the authors note.
 

State abortion laws changed dramatically in the study period

The authors chose the 2-decade time frame because data could be accessed for both maternal and infant mortality for all the years and because state level abortion laws changed dramatically in that time.

The Guttmacher Institute has analyzed each state’s abortion policy landscape and scored states as restrictive, moderate, or supportive. Certain types of abortion laws were associated with higher rates of all-cause mortality in reproductive-age females.

Those laws included trigger laws (the laws that automatically outlaw abortion in a state when federal law is overturned), laws that limit access to medication abortion, and parental consent laws, according to the paper.

Additionally, states that restrict access to abortion have higher rates of maternal and infant death, even after accounting for the general health of the population.
 

Trigger-law states have strong mortality association

Blair G. Darney, PhD, MPH, with the department of obstetrics and gynecology, Oregon Health & Science University and the OHSU-PSU School of Public Health in Portland, and two OHSU coauthors note in an accompanying editorial that having a trigger law in place was associated with elevations in all four mortality measures. However, trigger laws had not yet been enacted during the study.

The existence of trigger laws is likely a proxy for other factors, they write.

“[T]he relationship between trigger laws and increased mortality may more likely be explained by other factors that were not considered in the analysis than by laws that were not enacted at the time of the study,” the editorialists write.

Those factors may include lack of Medicaid expansion, socioeconomic inequities, and other policies.

The editorialists also caution that just because some types of abortion restrictions don’t appear to increase mortality, it doesn’t mean they aren’t harmful.

“For example, laws prohibiting private or Medicaid insurance coverage for abortions were not associated with maternal mortality, but these laws may simply shift the burden of payment to the individual seeking an abortion or be mitigated by funds that support an individual’s out-of-pocket cost for care. The lack of an association may therefore reflect women’s resilience and their ability to obtain needed health care in the face of financial challenges,” they write.

They point out that, conversely, Targeted Regulation of Abortion Providers (TRAP) laws, which supporters say protect women, have been associated instead with increases in maternal mortality.

Dr. Harper and study coauthors, noting that the relationship between abortion laws and mortality is complex, urge states with restrictive abortion laws to consider proven countermeasures to offset the rates, including Medicaid expansion.

One coauthor served on a medical advisory board, was a site primary investigator for several clinical trials, and received royalties from UpToDate for two topics related to trial of labor after cesarean. The other authors did not report any potential conflicts of interest. Dr. Darney’s institution receives research funding from Organon and the Office of Population Affairs on which she is the primary investigator, and she is a member of the board of directors of the Society of Family Planning and a deputy editor at Contraception. She has received an honorarium from ACOG for committee work. The other editorialists did not report any potential conflicts of interest.
 

The American College of Physicians has updated their guideline for pharmacotherapy to reduce fracture risk in adults with primary osteoporosis or osteopenia (low bone mass) based on a systematic review of the evidence.

This is the first update for 5 years since the previous guidance was published in 2017.

It strongly recommends initial therapy with bisphosphonates for postmenopausal women with osteoporosis, as well as men with osteoporosis, among other recommendations.

However, the author of an accompanying editorial, Susan M. Ott, MD, says: “The decision to start a bisphosphonate is actually not that easy.”

She also queries some of the other recommendations in the guidance.

Her editorial, along with the guideline by Amir Qaseem, MD, PhD, MPH, and colleagues, and systematic review by Chelsea Ayers, MPH, and colleagues, were published in the Annals of Internal Medicine.

Ryan D. Mire, MD, MACP, president of the ACP, gave a brief overview of the new guidance in a video.
 

Systematic review

The ACP commissioned a review of the evidence because it says new data have emerged on the efficacy of newer medications for osteoporosis and low bone mass, as well as treatment comparisons, and treatment in men.

The review authors identified 34 randomized controlled trials (in 100 publications) and 36 observational studies, which evaluated the following pharmacologic interventions:

• Antiresorptive drugs: four bisphosphonates (alendronate, ibandronate, risedronate, zoledronate) and a RANK ligand inhibitor (denosumab).
• Anabolic drugs: an analog of human parathyroid hormone (PTH)–related protein (abaloparatide), recombinant human PTH (teriparatide), and a sclerostin inhibitor (romosozumab).
• Estrogen agonists: selective estrogen receptor modulators (bazedoxifene, raloxifene).

The authors focused on effectiveness and harms of active drugs compared with placebo or bisphosphonates.
 

Major changes from 2017 guidelines, some questions

“Though there are many nuanced changes in this [2023 guideline] version, perhaps the major change is the explicit hierarchy of pharmacologic recommendations: bisphosphonates first, then denosumab,” Thomas G. Cooney, MD, senior author of the clinical guideline, explained in an interview.

“Bisphosphonates had the most favorable balance among benefits, harms, patient values and preferences, and cost among the examined drugs in postmenopausal females with primary osteoporosis,” Dr. Cooney, professor of medicine, Oregon Health & Science University, Portland, noted, as is stated in the guideline.

“Denosumab also had a favorable long-term net benefit, but bisphosphonates are much cheaper than other pharmacologic treatments and available in generic formulations,” the document states.

The new guideline suggests use of denosumab as second-line pharmacotherapy in adults who have contraindications to or experience adverse effects with bisphosphonates.

The choice among bisphosphonates (alendronate, risedronate, zoledronic acid) would be based on a patient-centered discussion between physician and patient, addressing costs (often related to insurance), delivery-mode preferences (oral versus intravenous), and “values,” which includes the patient’s priorities, concerns, and expectations regarding their health care, Dr. Cooney explained.

Another update in the new guideline is, “We also clarify the specific, albeit more limited, role of sclerostin inhibitors and recombinant PTH ‘to reduce the risk of fractures only in females with primary osteoporosis with very high-risk of fracture’,” Dr. Cooney noted.

In addition, the guideline now states, “treatment to reduce the risk of fractures in males rather than limiting it to ‘vertebral fracture’ in men,” as in the 2017 guideline.

It also explicitly includes denosumab as second-line therapy for men, Dr. Cooney noted, but as in 2017, the strength of evidence in men remains low.

“Finally, we also clarified that in females over the age of 65 with low bone mass or osteopenia that an individualized approach be taken to treatment (similar to last guideline), but if treatment is initiated, that a bisphosphonate be used (new content),” he said.

The use of estrogen, treatment duration, drug discontinuation, and serial bone mineral density monitoring were not addressed in this guideline, but will likely be evaluated within 2 to 3 years.
 

‘Osteoporosis treatment: Not easy’ – editorial

In her editorial, Dr. Ott writes: “The data about bisphosphonates may seem overwhelmingly positive, leading to strong recommendations for their use to treat osteoporosis, but the decision to start a bisphosphonate is actually not that easy.”

“A strong recommendation should be given only when future studies are unlikely to change it,” continues Dr. Ott, professor of medicine, University of Washington, Seattle.

“Yet, data already suggest that, in patients with serious osteoporosis, treatment should start with anabolic medications because previous treatment with either bisphosphonates or denosumab will prevent the anabolic response of newer medications.”

“Starting with bisphosphonate will change the bone so it will not respond to the newer medicines, and then a patient will lose the chance for getting the best improvement,” Dr. Ott clarified in an email to this news organization.

But, in fact, the new guidance does suggest that, to reduce the risk of fractures in females with primary osteoporosis at very high risk of fracture, one should consider use of the sclerostin inhibitor romosozumab (moderate-certainty evidence) or recombinant human parathyroid hormone (teriparatide) (low-certainty evidence) followed by a bisphosphonate (conditional recommendation).

Dr. Ott said: “If the [fracture] risk is high, then we should start with an anabolic medication for 1-2 years. If the risk is medium, then use a bisphosphonate for up to 5 years, and then stop and monitor the patient for signs that the medicine is wearing off,” based on blood and urine tests.
 

‘We need medicines that will stop bone aging’

Osteopenia is defined by an arbitrary bone density measurement, Dr. Ott explained. “About half of women over 65 will have osteopenia, and by age 85 there are hardly any ‘normal’ women left.”

“We need medicines that will stop bone aging, which might sound impossible, but we should still try,” she continued.

“In the meantime, while waiting on new discoveries,” Dr. Ott said, “I would not use bisphosphonates in patients who did not already have a fracture or whose bone density T-score was better than –2.5 because, in the major study, alendronate did not prevent fractures in this group.”

Many people are worried about bisphosphonates because of problems with the jaw or femur. These are real, but they are very rare during the first 5 years of treatment, Dr. Ott noted. Then the risk starts to rise, up to more than 1 in 1,000 after 8 years. So people can get the benefits of these drugs with very low risk for 5 years.

“An immediate [guideline] update is necessary to address the severity of bone loss and the high risk for vertebral fractures after discontinuation of denosumab,” Dr. Ott urged.

“I don’t agree with using denosumab for osteoporosis as a second-line treatment,” she said. “I would use it only in patients who have cancer or unusually high bone resorption. You have to get a dose strictly every 6 months, and if you need to stop, it is recommended to treat with bisphosphonates. Denosumab is a poor choice for somebody who does not want to take a bisphosphonate. Many patients and even too many doctors do not realize how serious it can be to skip a dose.”

“I also think that men could be treated with anabolic medications,” Dr. Ott said. “Clinical trials show they respond the same as women. Many men have osteoporosis as a consequence of low testosterone, and then they can usually be treated with testosterone. Osteoporosis in men is a serious problem that is too often ignored – almost reverse discrimination.”

It is also unfortunate that the review and recommendations do not address estrogen, one of the most effective medications to prevent osteoporotic fractures, according to Dr. Ott.
 

Clinical considerations in addition to drug types

The new guideline also advises:

• Clinicians treating adults with osteoporosis should encourage adherence to recommended treatments and healthy lifestyle habits, including exercise, and counseling to evaluate and prevent falls.
• All adults with osteopenia or osteoporosis should have adequate calcium and vitamin D intake, as part of fracture prevention.
• Clinicians should assess baseline fracture risk based on bone density, fracture history, fracture risk factors, and response to prior osteoporosis treatments.
• Current evidence suggests that more than 3-5 years of bisphosphonate therapy reduces risk for new vertebral but not other fractures; however, it also increases risk for long-term harms. Therefore, clinicians should consider stopping bisphosphonate treatment after 5 years unless the patient has a strong indication for treatment continuation.
• The decision for a bisphosphonate holiday (temporary discontinuation) and its duration should be based on baseline fracture risk, medication half-life in bone, and benefits and harms.
• Women treated with an anabolic agent who discontinue it should be offered an antiresorptive agent to preserve gains and because of serious risk for rebound and multiple vertebral fractures.
• Adults older than 65 years with osteoporosis may be at increased risk for falls or other adverse events because of drug interactions.
• Transgender persons have variable risk for low bone mass.

The review and guideline were funded by the ACP. Dr. Ott has reported no relevant disclosures. Relevant financial disclosures for other authors are listed with the guideline and review.

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

The American College of Physicians has updated their guideline for pharmacotherapy to reduce fracture risk in adults with primary osteoporosis or osteopenia (low bone mass) based on a systematic review of the evidence.

This is the first update for 5 years since the previous guidance was published in 2017.

It strongly recommends initial therapy with bisphosphonates for postmenopausal women with osteoporosis, as well as men with osteoporosis, among other recommendations.

However, the author of an accompanying editorial, Susan M. Ott, MD, says: “The decision to start a bisphosphonate is actually not that easy.”

She also queries some of the other recommendations in the guidance.

Her editorial, along with the guideline by Amir Qaseem, MD, PhD, MPH, and colleagues, and systematic review by Chelsea Ayers, MPH, and colleagues, were published in the Annals of Internal Medicine.

Ryan D. Mire, MD, MACP, president of the ACP, gave a brief overview of the new guidance in a video.
 

Systematic review

The ACP commissioned a review of the evidence because it says new data have emerged on the efficacy of newer medications for osteoporosis and low bone mass, as well as treatment comparisons, and treatment in men.

The review authors identified 34 randomized controlled trials (in 100 publications) and 36 observational studies, which evaluated the following pharmacologic interventions:

• Antiresorptive drugs: four bisphosphonates (alendronate, ibandronate, risedronate, zoledronate) and a RANK ligand inhibitor (denosumab).
• Anabolic drugs: an analog of human parathyroid hormone (PTH)–related protein (abaloparatide), recombinant human PTH (teriparatide), and a sclerostin inhibitor (romosozumab).
• Estrogen agonists: selective estrogen receptor modulators (bazedoxifene, raloxifene).

The authors focused on effectiveness and harms of active drugs compared with placebo or bisphosphonates.
 

Major changes from 2017 guidelines, some questions

“Though there are many nuanced changes in this [2023 guideline] version, perhaps the major change is the explicit hierarchy of pharmacologic recommendations: bisphosphonates first, then denosumab,” Thomas G. Cooney, MD, senior author of the clinical guideline, explained in an interview.

“Bisphosphonates had the most favorable balance among benefits, harms, patient values and preferences, and cost among the examined drugs in postmenopausal females with primary osteoporosis,” Dr. Cooney, professor of medicine, Oregon Health & Science University, Portland, noted, as is stated in the guideline.

“Denosumab also had a favorable long-term net benefit, but bisphosphonates are much cheaper than other pharmacologic treatments and available in generic formulations,” the document states.

The new guideline suggests use of denosumab as second-line pharmacotherapy in adults who have contraindications to or experience adverse effects with bisphosphonates.

The choice among bisphosphonates (alendronate, risedronate, zoledronic acid) would be based on a patient-centered discussion between physician and patient, addressing costs (often related to insurance), delivery-mode preferences (oral versus intravenous), and “values,” which includes the patient’s priorities, concerns, and expectations regarding their health care, Dr. Cooney explained.

Another update in the new guideline is, “We also clarify the specific, albeit more limited, role of sclerostin inhibitors and recombinant PTH ‘to reduce the risk of fractures only in females with primary osteoporosis with very high-risk of fracture’,” Dr. Cooney noted.

In addition, the guideline now states, “treatment to reduce the risk of fractures in males rather than limiting it to ‘vertebral fracture’ in men,” as in the 2017 guideline.

It also explicitly includes denosumab as second-line therapy for men, Dr. Cooney noted, but as in 2017, the strength of evidence in men remains low.

“Finally, we also clarified that in females over the age of 65 with low bone mass or osteopenia that an individualized approach be taken to treatment (similar to last guideline), but if treatment is initiated, that a bisphosphonate be used (new content),” he said.

The use of estrogen, treatment duration, drug discontinuation, and serial bone mineral density monitoring were not addressed in this guideline, but will likely be evaluated within 2 to 3 years.
 

‘Osteoporosis treatment: Not easy’ – editorial

In her editorial, Dr. Ott writes: “The data about bisphosphonates may seem overwhelmingly positive, leading to strong recommendations for their use to treat osteoporosis, but the decision to start a bisphosphonate is actually not that easy.”

“A strong recommendation should be given only when future studies are unlikely to change it,” continues Dr. Ott, professor of medicine, University of Washington, Seattle.

“Yet, data already suggest that, in patients with serious osteoporosis, treatment should start with anabolic medications because previous treatment with either bisphosphonates or denosumab will prevent the anabolic response of newer medications.”

“Starting with bisphosphonate will change the bone so it will not respond to the newer medicines, and then a patient will lose the chance for getting the best improvement,” Dr. Ott clarified in an email to this news organization.

But, in fact, the new guidance does suggest that, to reduce the risk of fractures in females with primary osteoporosis at very high risk of fracture, one should consider use of the sclerostin inhibitor romosozumab (moderate-certainty evidence) or recombinant human parathyroid hormone (teriparatide) (low-certainty evidence) followed by a bisphosphonate (conditional recommendation).

Dr. Ott said: “If the [fracture] risk is high, then we should start with an anabolic medication for 1-2 years. If the risk is medium, then use a bisphosphonate for up to 5 years, and then stop and monitor the patient for signs that the medicine is wearing off,” based on blood and urine tests.
 

‘We need medicines that will stop bone aging’

Osteopenia is defined by an arbitrary bone density measurement, Dr. Ott explained. “About half of women over 65 will have osteopenia, and by age 85 there are hardly any ‘normal’ women left.”

“We need medicines that will stop bone aging, which might sound impossible, but we should still try,” she continued.

“In the meantime, while waiting on new discoveries,” Dr. Ott said, “I would not use bisphosphonates in patients who did not already have a fracture or whose bone density T-score was better than –2.5 because, in the major study, alendronate did not prevent fractures in this group.”

Many people are worried about bisphosphonates because of problems with the jaw or femur. These are real, but they are very rare during the first 5 years of treatment, Dr. Ott noted. Then the risk starts to rise, up to more than 1 in 1,000 after 8 years. So people can get the benefits of these drugs with very low risk for 5 years.

“An immediate [guideline] update is necessary to address the severity of bone loss and the high risk for vertebral fractures after discontinuation of denosumab,” Dr. Ott urged.

“I don’t agree with using denosumab for osteoporosis as a second-line treatment,” she said. “I would use it only in patients who have cancer or unusually high bone resorption. You have to get a dose strictly every 6 months, and if you need to stop, it is recommended to treat with bisphosphonates. Denosumab is a poor choice for somebody who does not want to take a bisphosphonate. Many patients and even too many doctors do not realize how serious it can be to skip a dose.”

“I also think that men could be treated with anabolic medications,” Dr. Ott said. “Clinical trials show they respond the same as women. Many men have osteoporosis as a consequence of low testosterone, and then they can usually be treated with testosterone. Osteoporosis in men is a serious problem that is too often ignored – almost reverse discrimination.”

It is also unfortunate that the review and recommendations do not address estrogen, one of the most effective medications to prevent osteoporotic fractures, according to Dr. Ott.
 

Clinical considerations in addition to drug types

The new guideline also advises:

• Clinicians treating adults with osteoporosis should encourage adherence to recommended treatments and healthy lifestyle habits, including exercise, and counseling to evaluate and prevent falls.
• All adults with osteopenia or osteoporosis should have adequate calcium and vitamin D intake, as part of fracture prevention.
• Clinicians should assess baseline fracture risk based on bone density, fracture history, fracture risk factors, and response to prior osteoporosis treatments.
• Current evidence suggests that more than 3-5 years of bisphosphonate therapy reduces risk for new vertebral but not other fractures; however, it also increases risk for long-term harms. Therefore, clinicians should consider stopping bisphosphonate treatment after 5 years unless the patient has a strong indication for treatment continuation.
• The decision for a bisphosphonate holiday (temporary discontinuation) and its duration should be based on baseline fracture risk, medication half-life in bone, and benefits and harms.
• Women treated with an anabolic agent who discontinue it should be offered an antiresorptive agent to preserve gains and because of serious risk for rebound and multiple vertebral fractures.
• Adults older than 65 years with osteoporosis may be at increased risk for falls or other adverse events because of drug interactions.
• Transgender persons have variable risk for low bone mass.

The review and guideline were funded by the ACP. Dr. Ott has reported no relevant disclosures. Relevant financial disclosures for other authors are listed with the guideline and review.

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

The American College of Physicians has updated their guideline for pharmacotherapy to reduce fracture risk in adults with primary osteoporosis or osteopenia (low bone mass) based on a systematic review of the evidence.

This is the first update for 5 years since the previous guidance was published in 2017.

It strongly recommends initial therapy with bisphosphonates for postmenopausal women with osteoporosis, as well as men with osteoporosis, among other recommendations.

However, the author of an accompanying editorial, Susan M. Ott, MD, says: “The decision to start a bisphosphonate is actually not that easy.”

She also queries some of the other recommendations in the guidance.

Her editorial, along with the guideline by Amir Qaseem, MD, PhD, MPH, and colleagues, and systematic review by Chelsea Ayers, MPH, and colleagues, were published in the Annals of Internal Medicine.

Ryan D. Mire, MD, MACP, president of the ACP, gave a brief overview of the new guidance in a video.
 

Systematic review

The ACP commissioned a review of the evidence because it says new data have emerged on the efficacy of newer medications for osteoporosis and low bone mass, as well as treatment comparisons, and treatment in men.

The review authors identified 34 randomized controlled trials (in 100 publications) and 36 observational studies, which evaluated the following pharmacologic interventions:

• Antiresorptive drugs: four bisphosphonates (alendronate, ibandronate, risedronate, zoledronate) and a RANK ligand inhibitor (denosumab).
• Anabolic drugs: an analog of human parathyroid hormone (PTH)–related protein (abaloparatide), recombinant human PTH (teriparatide), and a sclerostin inhibitor (romosozumab).
• Estrogen agonists: selective estrogen receptor modulators (bazedoxifene, raloxifene).

The authors focused on effectiveness and harms of active drugs compared with placebo or bisphosphonates.
 

Major changes from 2017 guidelines, some questions

“Though there are many nuanced changes in this [2023 guideline] version, perhaps the major change is the explicit hierarchy of pharmacologic recommendations: bisphosphonates first, then denosumab,” Thomas G. Cooney, MD, senior author of the clinical guideline, explained in an interview.

“Bisphosphonates had the most favorable balance among benefits, harms, patient values and preferences, and cost among the examined drugs in postmenopausal females with primary osteoporosis,” Dr. Cooney, professor of medicine, Oregon Health & Science University, Portland, noted, as is stated in the guideline.

“Denosumab also had a favorable long-term net benefit, but bisphosphonates are much cheaper than other pharmacologic treatments and available in generic formulations,” the document states.

The new guideline suggests use of denosumab as second-line pharmacotherapy in adults who have contraindications to or experience adverse effects with bisphosphonates.

The choice among bisphosphonates (alendronate, risedronate, zoledronic acid) would be based on a patient-centered discussion between physician and patient, addressing costs (often related to insurance), delivery-mode preferences (oral versus intravenous), and “values,” which includes the patient’s priorities, concerns, and expectations regarding their health care, Dr. Cooney explained.

Another update in the new guideline is, “We also clarify the specific, albeit more limited, role of sclerostin inhibitors and recombinant PTH ‘to reduce the risk of fractures only in females with primary osteoporosis with very high-risk of fracture’,” Dr. Cooney noted.

In addition, the guideline now states, “treatment to reduce the risk of fractures in males rather than limiting it to ‘vertebral fracture’ in men,” as in the 2017 guideline.

It also explicitly includes denosumab as second-line therapy for men, Dr. Cooney noted, but as in 2017, the strength of evidence in men remains low.

“Finally, we also clarified that in females over the age of 65 with low bone mass or osteopenia that an individualized approach be taken to treatment (similar to last guideline), but if treatment is initiated, that a bisphosphonate be used (new content),” he said.

The use of estrogen, treatment duration, drug discontinuation, and serial bone mineral density monitoring were not addressed in this guideline, but will likely be evaluated within 2 to 3 years.
 

‘Osteoporosis treatment: Not easy’ – editorial

In her editorial, Dr. Ott writes: “The data about bisphosphonates may seem overwhelmingly positive, leading to strong recommendations for their use to treat osteoporosis, but the decision to start a bisphosphonate is actually not that easy.”

“A strong recommendation should be given only when future studies are unlikely to change it,” continues Dr. Ott, professor of medicine, University of Washington, Seattle.

“Yet, data already suggest that, in patients with serious osteoporosis, treatment should start with anabolic medications because previous treatment with either bisphosphonates or denosumab will prevent the anabolic response of newer medications.”

“Starting with bisphosphonate will change the bone so it will not respond to the newer medicines, and then a patient will lose the chance for getting the best improvement,” Dr. Ott clarified in an email to this news organization.

But, in fact, the new guidance does suggest that, to reduce the risk of fractures in females with primary osteoporosis at very high risk of fracture, one should consider use of the sclerostin inhibitor romosozumab (moderate-certainty evidence) or recombinant human parathyroid hormone (teriparatide) (low-certainty evidence) followed by a bisphosphonate (conditional recommendation).

Dr. Ott said: “If the [fracture] risk is high, then we should start with an anabolic medication for 1-2 years. If the risk is medium, then use a bisphosphonate for up to 5 years, and then stop and monitor the patient for signs that the medicine is wearing off,” based on blood and urine tests.
 

‘We need medicines that will stop bone aging’

Osteopenia is defined by an arbitrary bone density measurement, Dr. Ott explained. “About half of women over 65 will have osteopenia, and by age 85 there are hardly any ‘normal’ women left.”

“We need medicines that will stop bone aging, which might sound impossible, but we should still try,” she continued.

“In the meantime, while waiting on new discoveries,” Dr. Ott said, “I would not use bisphosphonates in patients who did not already have a fracture or whose bone density T-score was better than –2.5 because, in the major study, alendronate did not prevent fractures in this group.”

Many people are worried about bisphosphonates because of problems with the jaw or femur. These are real, but they are very rare during the first 5 years of treatment, Dr. Ott noted. Then the risk starts to rise, up to more than 1 in 1,000 after 8 years. So people can get the benefits of these drugs with very low risk for 5 years.

“An immediate [guideline] update is necessary to address the severity of bone loss and the high risk for vertebral fractures after discontinuation of denosumab,” Dr. Ott urged.

“I don’t agree with using denosumab for osteoporosis as a second-line treatment,” she said. “I would use it only in patients who have cancer or unusually high bone resorption. You have to get a dose strictly every 6 months, and if you need to stop, it is recommended to treat with bisphosphonates. Denosumab is a poor choice for somebody who does not want to take a bisphosphonate. Many patients and even too many doctors do not realize how serious it can be to skip a dose.”

“I also think that men could be treated with anabolic medications,” Dr. Ott said. “Clinical trials show they respond the same as women. Many men have osteoporosis as a consequence of low testosterone, and then they can usually be treated with testosterone. Osteoporosis in men is a serious problem that is too often ignored – almost reverse discrimination.”

It is also unfortunate that the review and recommendations do not address estrogen, one of the most effective medications to prevent osteoporotic fractures, according to Dr. Ott.
 

Clinical considerations in addition to drug types

The new guideline also advises:

• Clinicians treating adults with osteoporosis should encourage adherence to recommended treatments and healthy lifestyle habits, including exercise, and counseling to evaluate and prevent falls.
• All adults with osteopenia or osteoporosis should have adequate calcium and vitamin D intake, as part of fracture prevention.
• Clinicians should assess baseline fracture risk based on bone density, fracture history, fracture risk factors, and response to prior osteoporosis treatments.
• Current evidence suggests that more than 3-5 years of bisphosphonate therapy reduces risk for new vertebral but not other fractures; however, it also increases risk for long-term harms. Therefore, clinicians should consider stopping bisphosphonate treatment after 5 years unless the patient has a strong indication for treatment continuation.
• The decision for a bisphosphonate holiday (temporary discontinuation) and its duration should be based on baseline fracture risk, medication half-life in bone, and benefits and harms.
• Women treated with an anabolic agent who discontinue it should be offered an antiresorptive agent to preserve gains and because of serious risk for rebound and multiple vertebral fractures.
• Adults older than 65 years with osteoporosis may be at increased risk for falls or other adverse events because of drug interactions.
• Transgender persons have variable risk for low bone mass.

The review and guideline were funded by the ACP. Dr. Ott has reported no relevant disclosures. Relevant financial disclosures for other authors are listed with the guideline and review.

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

Cervical cancer appears to be rising more rapidly in White women than in Black women in the United States, according to two independent studies. Researchers puzzling over this counterintuitive finding say that, if true, the findings may be a “canary in the coal mine,” signaling problems with U.S. health care that go way beyond women’s health.

Cervical cancer incidence in the United States has plateaued since 2010 and now stands at 7.5 per 100,000 people. Well-known disparities exist: Compared with White women, Black women are more likely to have distant-stage disease at diagnosis and more commonly die of their cancer.

However, two unconnected studies published in the past 5 months suggest that White women are catching up fast.

Cervical cancer rates in White women aged 30-34 are rising 2.8% a year, but holding steady for Black women, according to a recent study led by Ashish A. Deshmukh, PhD, of the Medical University of South Carolina, Charleston. His team analyzed the 2001-2019 National Program of Cancer Registries (NPCR) and Surveillance, Epidemiology, and End Results (SEER) dataset, which covers 98% of the U.S. population and 227,062 cervical cancer cases.

These findings were echoed by an analysis of the same database for 2001-2018 by the University of California, Los Angeles (UCLA), suggesting that distant-stage cervical cancer (defined as disease that has spread to the bladder and/or rectum at diagnosis) is climbing 1.69% a year in White people versus 0.67% in Black individuals.

The UCLA researchers, headed by Alex Francoeur, MD, a resident in the department of obstetrics and gynecology, found that disparities were most stark in adenocarcinoma, with an annual increase of 3.40% a year among White women and 1.71% in Black women.

Such findings have equity researchers scratching their heads. In cancer, it’s rare to see evidence that Black patients are doing better than their White counterparts.

One theoretical explanation is that the data are flawed, Ahmedin Jemal, DVM, PhD, senior vice president of surveillance and health equity science at the American Cancer Society, told this news organization. For example, the UCLA analysis may have been fogged by changes in staging definitions over time, Dr. Jemal said, although this would not explain the racial disparities per se.

Dr. Deshmukh stands by his data and said that, for him, the message is clear: “If rising incidence is not for localized-stage disease, but for advanced stages, that means it’s attributable to lack of screening,” he told this news organization.  

However, this ‘simple’ explanation generates even more questions, Dr. Deshmukh said: “Screening is not a one-time procedure [but] a spectrum of timely cervical precancer treatment if [required]. We don’t know when exactly non-Hispanic White women are falling behind on that spectrum.”

The UCLA study supports Dr. Deshmukh’s conclusions. Using data from the Behavioral Risk Factor Surveillance System to calculate trends in “nonguideline screening,” the researchers found that White women were almost twice as likely to report that they were not following screening guidelines compared with Black women over the period of 2001-2016 (26.6% vs. 13.8%; P < .001).

“It’s not an artifact, it’s real,” said Timothy Rebbeck, PhD, the Vincent L. Gregory Jr. Professor of Cancer Prevention at Harvard TH Chan School of Public Health, Boston, who was not an author of either study and was approached for comment.

“The data are correct but there are so many things going on that might explain these patterns,” he told this news organization.

“This is a great example of complex changes in our social system, political system, health care system that are having really clear, measurable effects,” Dr. Rebbeck said. “Cervical cancer is almost a canary in the coal mine for some of this because it’s so preventable.”

(The saying “canary in a coal mine” is a warning of danger or trouble ahead. It comes from the time when coal miners would carry a caged canary down into the tunnels to warn them of noxious gases, which would kill the bird but give men time to escape.)

For example, Dr. Rebbeck said, recent turmoil in U.S. health care has left many people distrustful of the system. Although he acknowledged this was “high speculation,” he suggested that some women may have become less willing to participate in any mass health care intervention because of their political beliefs.

The UCLA study found that distant cervical cancer was rising fastest in middle-aged White women in the U.S. South, at a rate of 4.5% per year (P < .001).

Dr. Rebbeck also suggested that Medicaid expansion – the broadening of health insurance coverage in some states since the Affordable Care Act in 2014 – could be implicated. Of the 11 states that have not yet expanded Medicaid, eight are in the South.

“White populations who are in states that didn’t expand Medicaid are not getting a lot of the standard treatment and care that you would expect ...” Dr. Rebbeck said. “You could very well imagine that Medicaid nonexpanding states would have all kinds of patterns that would lead to more aggressive disease.”

In fact, there is already evidence that Medicaid expansion has affected racial disparities, disproportionately benefiting Black and Hispanic families, as for example, from an analysis of 65 studies by the Kaiser Family Foundation in 2020.

Commenting on these data, Dr. Rebbeck said, “Does that mean that the patterns of advanced cervical cancer had a smaller effect on Black women in this period because there was a greater shift in access to care? This is again a speculation, but it does fit with the ‘canary in a coal mine’ concept that advanced cervical cancer may be more rapidly influenced by health care access than other health conditions.” 

The authors of the UCLA study suggested another explanation for their results: Differing enthusiasm for human papillomavirus (HPV) vaccination among White and Black families. The team also analyzed data on HPV vaccination, which offers protection against cervical cancer. The researchers found that vaccination rates were lowest, at 66.1%, among White teenagers aged 13-17 years, compared with Hispanics at 75.3%, Black teenagers at 74.6%, and Asians at 68.1%.

However, this theory was dismissed by both Dr. Jemal and Dr. Rebbeck due to timing. HPV vaccines have been around for approximately 15 years, so women who benefited (or didn’t benefit) from vaccination would be only in their late 20s today, they pointed out.

“Ninety-five percent of the cervical cancer cases we see now are in women who have not been vaccinated,” said Dr. Jemal, “So that’s out of the equation.”

Dr. Rebbeck agreed: “HPV may or may not be a thing here because it’s [got] such a latency.”

HPV vaccination may be out of the picture, but what about the epidemiology of HPV itself? Could the virus directly or indirectly be boosting advanced cervical cancer in White women?

Dr. Deshmukh thinks that it might be doing so.

He published an analysis of 2000-2018 SEER data showing that U.S. counties with the highest incidences of HPV-associated cancers also had the highest levels of smoking.

Other recent data suggest that middle-aged White women in the United States are more likely to reach for a smoke than are Black women.

Dr. Deshmukh acknowledges that the link is speculative but reasonable: “We don’t know exactly what the impact of smoking would be in terms of ... the ability to clear HPV infection. It may inhibit apoptosis, promoting tumor growth. There’s no causal association. It’s a cofactor risk.”

Dr. Rebbeck is also suspicious that smoking patterns might be a factor, pointing out that “smoking is certainly associated with both health behaviors and advanced cervical cancer.”

Both Dr. Rebbeck and Dr. Deshmukh concluded that, at this point, we can only speculate on what’s driving the puzzling acceleration of cervical cancer in White women in the United States.

However, whether it’s political aversion to screening, smoking-boosted HPV infection, Medicaid expansion or lack of it, or something else, they all agree that this canary in the coal mine clearly needs urgent medical attention.

Dr. Rebbeck and Dr. Jemal have declared no conflicts of interest. Dr. Deshmukh has declared consultant or advisory roles for Merck and Value Analytics Labs. None of the authors of the UCLA study have declared competing interests.

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

Cervical cancer appears to be rising more rapidly in White women than in Black women in the United States, according to two independent studies. Researchers puzzling over this counterintuitive finding say that, if true, the findings may be a “canary in the coal mine,” signaling problems with U.S. health care that go way beyond women’s health.

Cervical cancer incidence in the United States has plateaued since 2010 and now stands at 7.5 per 100,000 people. Well-known disparities exist: Compared with White women, Black women are more likely to have distant-stage disease at diagnosis and more commonly die of their cancer.

However, two unconnected studies published in the past 5 months suggest that White women are catching up fast.

Cervical cancer rates in White women aged 30-34 are rising 2.8% a year, but holding steady for Black women, according to a recent study led by Ashish A. Deshmukh, PhD, of the Medical University of South Carolina, Charleston. His team analyzed the 2001-2019 National Program of Cancer Registries (NPCR) and Surveillance, Epidemiology, and End Results (SEER) dataset, which covers 98% of the U.S. population and 227,062 cervical cancer cases.

These findings were echoed by an analysis of the same database for 2001-2018 by the University of California, Los Angeles (UCLA), suggesting that distant-stage cervical cancer (defined as disease that has spread to the bladder and/or rectum at diagnosis) is climbing 1.69% a year in White people versus 0.67% in Black individuals.

The UCLA researchers, headed by Alex Francoeur, MD, a resident in the department of obstetrics and gynecology, found that disparities were most stark in adenocarcinoma, with an annual increase of 3.40% a year among White women and 1.71% in Black women.

Such findings have equity researchers scratching their heads. In cancer, it’s rare to see evidence that Black patients are doing better than their White counterparts.

One theoretical explanation is that the data are flawed, Ahmedin Jemal, DVM, PhD, senior vice president of surveillance and health equity science at the American Cancer Society, told this news organization. For example, the UCLA analysis may have been fogged by changes in staging definitions over time, Dr. Jemal said, although this would not explain the racial disparities per se.

Dr. Deshmukh stands by his data and said that, for him, the message is clear: “If rising incidence is not for localized-stage disease, but for advanced stages, that means it’s attributable to lack of screening,” he told this news organization.  

However, this ‘simple’ explanation generates even more questions, Dr. Deshmukh said: “Screening is not a one-time procedure [but] a spectrum of timely cervical precancer treatment if [required]. We don’t know when exactly non-Hispanic White women are falling behind on that spectrum.”

The UCLA study supports Dr. Deshmukh’s conclusions. Using data from the Behavioral Risk Factor Surveillance System to calculate trends in “nonguideline screening,” the researchers found that White women were almost twice as likely to report that they were not following screening guidelines compared with Black women over the period of 2001-2016 (26.6% vs. 13.8%; P < .001).

“It’s not an artifact, it’s real,” said Timothy Rebbeck, PhD, the Vincent L. Gregory Jr. Professor of Cancer Prevention at Harvard TH Chan School of Public Health, Boston, who was not an author of either study and was approached for comment.

“The data are correct but there are so many things going on that might explain these patterns,” he told this news organization.

“This is a great example of complex changes in our social system, political system, health care system that are having really clear, measurable effects,” Dr. Rebbeck said. “Cervical cancer is almost a canary in the coal mine for some of this because it’s so preventable.”

(The saying “canary in a coal mine” is a warning of danger or trouble ahead. It comes from the time when coal miners would carry a caged canary down into the tunnels to warn them of noxious gases, which would kill the bird but give men time to escape.)

For example, Dr. Rebbeck said, recent turmoil in U.S. health care has left many people distrustful of the system. Although he acknowledged this was “high speculation,” he suggested that some women may have become less willing to participate in any mass health care intervention because of their political beliefs.

The UCLA study found that distant cervical cancer was rising fastest in middle-aged White women in the U.S. South, at a rate of 4.5% per year (P < .001).

Dr. Rebbeck also suggested that Medicaid expansion – the broadening of health insurance coverage in some states since the Affordable Care Act in 2014 – could be implicated. Of the 11 states that have not yet expanded Medicaid, eight are in the South.

“White populations who are in states that didn’t expand Medicaid are not getting a lot of the standard treatment and care that you would expect ...” Dr. Rebbeck said. “You could very well imagine that Medicaid nonexpanding states would have all kinds of patterns that would lead to more aggressive disease.”

In fact, there is already evidence that Medicaid expansion has affected racial disparities, disproportionately benefiting Black and Hispanic families, as for example, from an analysis of 65 studies by the Kaiser Family Foundation in 2020.

Commenting on these data, Dr. Rebbeck said, “Does that mean that the patterns of advanced cervical cancer had a smaller effect on Black women in this period because there was a greater shift in access to care? This is again a speculation, but it does fit with the ‘canary in a coal mine’ concept that advanced cervical cancer may be more rapidly influenced by health care access than other health conditions.” 

The authors of the UCLA study suggested another explanation for their results: Differing enthusiasm for human papillomavirus (HPV) vaccination among White and Black families. The team also analyzed data on HPV vaccination, which offers protection against cervical cancer. The researchers found that vaccination rates were lowest, at 66.1%, among White teenagers aged 13-17 years, compared with Hispanics at 75.3%, Black teenagers at 74.6%, and Asians at 68.1%.

However, this theory was dismissed by both Dr. Jemal and Dr. Rebbeck due to timing. HPV vaccines have been around for approximately 15 years, so women who benefited (or didn’t benefit) from vaccination would be only in their late 20s today, they pointed out.

“Ninety-five percent of the cervical cancer cases we see now are in women who have not been vaccinated,” said Dr. Jemal, “So that’s out of the equation.”

Dr. Rebbeck agreed: “HPV may or may not be a thing here because it’s [got] such a latency.”

HPV vaccination may be out of the picture, but what about the epidemiology of HPV itself? Could the virus directly or indirectly be boosting advanced cervical cancer in White women?

Dr. Deshmukh thinks that it might be doing so.

He published an analysis of 2000-2018 SEER data showing that U.S. counties with the highest incidences of HPV-associated cancers also had the highest levels of smoking.

Other recent data suggest that middle-aged White women in the United States are more likely to reach for a smoke than are Black women.

Dr. Deshmukh acknowledges that the link is speculative but reasonable: “We don’t know exactly what the impact of smoking would be in terms of ... the ability to clear HPV infection. It may inhibit apoptosis, promoting tumor growth. There’s no causal association. It’s a cofactor risk.”

Dr. Rebbeck is also suspicious that smoking patterns might be a factor, pointing out that “smoking is certainly associated with both health behaviors and advanced cervical cancer.”

Both Dr. Rebbeck and Dr. Deshmukh concluded that, at this point, we can only speculate on what’s driving the puzzling acceleration of cervical cancer in White women in the United States.

However, whether it’s political aversion to screening, smoking-boosted HPV infection, Medicaid expansion or lack of it, or something else, they all agree that this canary in the coal mine clearly needs urgent medical attention.

Dr. Rebbeck and Dr. Jemal have declared no conflicts of interest. Dr. Deshmukh has declared consultant or advisory roles for Merck and Value Analytics Labs. None of the authors of the UCLA study have declared competing interests.

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

Cervical cancer appears to be rising more rapidly in White women than in Black women in the United States, according to two independent studies. Researchers puzzling over this counterintuitive finding say that, if true, the findings may be a “canary in the coal mine,” signaling problems with U.S. health care that go way beyond women’s health.

Cervical cancer incidence in the United States has plateaued since 2010 and now stands at 7.5 per 100,000 people. Well-known disparities exist: Compared with White women, Black women are more likely to have distant-stage disease at diagnosis and more commonly die of their cancer.

However, two unconnected studies published in the past 5 months suggest that White women are catching up fast.

Cervical cancer rates in White women aged 30-34 are rising 2.8% a year, but holding steady for Black women, according to a recent study led by Ashish A. Deshmukh, PhD, of the Medical University of South Carolina, Charleston. His team analyzed the 2001-2019 National Program of Cancer Registries (NPCR) and Surveillance, Epidemiology, and End Results (SEER) dataset, which covers 98% of the U.S. population and 227,062 cervical cancer cases.

These findings were echoed by an analysis of the same database for 2001-2018 by the University of California, Los Angeles (UCLA), suggesting that distant-stage cervical cancer (defined as disease that has spread to the bladder and/or rectum at diagnosis) is climbing 1.69% a year in White people versus 0.67% in Black individuals.

The UCLA researchers, headed by Alex Francoeur, MD, a resident in the department of obstetrics and gynecology, found that disparities were most stark in adenocarcinoma, with an annual increase of 3.40% a year among White women and 1.71% in Black women.

Such findings have equity researchers scratching their heads. In cancer, it’s rare to see evidence that Black patients are doing better than their White counterparts.

One theoretical explanation is that the data are flawed, Ahmedin Jemal, DVM, PhD, senior vice president of surveillance and health equity science at the American Cancer Society, told this news organization. For example, the UCLA analysis may have been fogged by changes in staging definitions over time, Dr. Jemal said, although this would not explain the racial disparities per se.

Dr. Deshmukh stands by his data and said that, for him, the message is clear: “If rising incidence is not for localized-stage disease, but for advanced stages, that means it’s attributable to lack of screening,” he told this news organization.  

However, this ‘simple’ explanation generates even more questions, Dr. Deshmukh said: “Screening is not a one-time procedure [but] a spectrum of timely cervical precancer treatment if [required]. We don’t know when exactly non-Hispanic White women are falling behind on that spectrum.”

The UCLA study supports Dr. Deshmukh’s conclusions. Using data from the Behavioral Risk Factor Surveillance System to calculate trends in “nonguideline screening,” the researchers found that White women were almost twice as likely to report that they were not following screening guidelines compared with Black women over the period of 2001-2016 (26.6% vs. 13.8%; P < .001).

“It’s not an artifact, it’s real,” said Timothy Rebbeck, PhD, the Vincent L. Gregory Jr. Professor of Cancer Prevention at Harvard TH Chan School of Public Health, Boston, who was not an author of either study and was approached for comment.

“The data are correct but there are so many things going on that might explain these patterns,” he told this news organization.

“This is a great example of complex changes in our social system, political system, health care system that are having really clear, measurable effects,” Dr. Rebbeck said. “Cervical cancer is almost a canary in the coal mine for some of this because it’s so preventable.”

(The saying “canary in a coal mine” is a warning of danger or trouble ahead. It comes from the time when coal miners would carry a caged canary down into the tunnels to warn them of noxious gases, which would kill the bird but give men time to escape.)

For example, Dr. Rebbeck said, recent turmoil in U.S. health care has left many people distrustful of the system. Although he acknowledged this was “high speculation,” he suggested that some women may have become less willing to participate in any mass health care intervention because of their political beliefs.

The UCLA study found that distant cervical cancer was rising fastest in middle-aged White women in the U.S. South, at a rate of 4.5% per year (P < .001).

Dr. Rebbeck also suggested that Medicaid expansion – the broadening of health insurance coverage in some states since the Affordable Care Act in 2014 – could be implicated. Of the 11 states that have not yet expanded Medicaid, eight are in the South.

“White populations who are in states that didn’t expand Medicaid are not getting a lot of the standard treatment and care that you would expect ...” Dr. Rebbeck said. “You could very well imagine that Medicaid nonexpanding states would have all kinds of patterns that would lead to more aggressive disease.”

In fact, there is already evidence that Medicaid expansion has affected racial disparities, disproportionately benefiting Black and Hispanic families, as for example, from an analysis of 65 studies by the Kaiser Family Foundation in 2020.

Commenting on these data, Dr. Rebbeck said, “Does that mean that the patterns of advanced cervical cancer had a smaller effect on Black women in this period because there was a greater shift in access to care? This is again a speculation, but it does fit with the ‘canary in a coal mine’ concept that advanced cervical cancer may be more rapidly influenced by health care access than other health conditions.” 

The authors of the UCLA study suggested another explanation for their results: Differing enthusiasm for human papillomavirus (HPV) vaccination among White and Black families. The team also analyzed data on HPV vaccination, which offers protection against cervical cancer. The researchers found that vaccination rates were lowest, at 66.1%, among White teenagers aged 13-17 years, compared with Hispanics at 75.3%, Black teenagers at 74.6%, and Asians at 68.1%.

However, this theory was dismissed by both Dr. Jemal and Dr. Rebbeck due to timing. HPV vaccines have been around for approximately 15 years, so women who benefited (or didn’t benefit) from vaccination would be only in their late 20s today, they pointed out.

“Ninety-five percent of the cervical cancer cases we see now are in women who have not been vaccinated,” said Dr. Jemal, “So that’s out of the equation.”

Dr. Rebbeck agreed: “HPV may or may not be a thing here because it’s [got] such a latency.”

HPV vaccination may be out of the picture, but what about the epidemiology of HPV itself? Could the virus directly or indirectly be boosting advanced cervical cancer in White women?

Dr. Deshmukh thinks that it might be doing so.

He published an analysis of 2000-2018 SEER data showing that U.S. counties with the highest incidences of HPV-associated cancers also had the highest levels of smoking.

Other recent data suggest that middle-aged White women in the United States are more likely to reach for a smoke than are Black women.

Dr. Deshmukh acknowledges that the link is speculative but reasonable: “We don’t know exactly what the impact of smoking would be in terms of ... the ability to clear HPV infection. It may inhibit apoptosis, promoting tumor growth. There’s no causal association. It’s a cofactor risk.”

Dr. Rebbeck is also suspicious that smoking patterns might be a factor, pointing out that “smoking is certainly associated with both health behaviors and advanced cervical cancer.”

Both Dr. Rebbeck and Dr. Deshmukh concluded that, at this point, we can only speculate on what’s driving the puzzling acceleration of cervical cancer in White women in the United States.

However, whether it’s political aversion to screening, smoking-boosted HPV infection, Medicaid expansion or lack of it, or something else, they all agree that this canary in the coal mine clearly needs urgent medical attention.

Dr. Rebbeck and Dr. Jemal have declared no conflicts of interest. Dr. Deshmukh has declared consultant or advisory roles for Merck and Value Analytics Labs. None of the authors of the UCLA study have declared competing interests.

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

Women in the United States who followed a Mediterranean-style diet – heavy on fresh foods, fish, and olive oil – around the time of conception had lower risk of developing a pregnancy complication, results of a large new study suggest.

The study included 7,798 women who had not given birth before. The group was geographically, racially, and ethnically diverse.

Researchers led by Nour Makarem, PhD, MS, with the department of epidemiology, Columbia University, New York, published their results in JAMA Network Open.

“Generally, higher intakes of vegetables, fruits, legumes, fish, and whole grains and lower intakes of red and processed meat were associated with lower risk of APOs [adverse pregnancy outcomes],” the authors wrote.
 

21% lower risk of complications

The investigators found that women in the study – who were part of the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be, which enrolled 10,038 women between Oct. 1, 2010, and Sept. 30, 2013, and scored high on adherence to a Mediterranean diet – had a 21% lower risk of developing any adverse pregnancy outcome (APO) than those who had low adherence. And the better the adherence, the lower the risk of adverse outcomes, especially preeclampsia or eclampsia and gestational diabetes, the researchers wrote.

The research team also studied how following the diet correlated with gestational high blood pressure, preterm birth, delivery of a small-for-gestational-age infant, and stillbirth.

Women were scored on consumption of nine components: vegetables (excluding potatoes), fruits, nuts, whole grains, legumes, fish, monounsaturated to saturated fat ratio, red and processed meats, and alcohol.
 

No differences by race, ethnicity, or BMI

There were no differences in adverse pregnancy outcomes by race, ethnicity, or the woman’s body mass index before pregnancy, but associations were stronger in the women who were 35 years or older, according to the paper.

The authors pointed out that the women in the study had access to prenatal care at a large academic medical center during their first 3 months of pregnancy so the study may actually underestimate the importance of the diet in the pregnancy outcomes.

Christina Han, MD, division director of maternal-fetal medicine at University of California, Los Angeles, who was not part of the study, said that the results make sense as the researchers looked at the time of conception, which is a time that reflects the way a person chooses to live their life.

“We know that your health state as you enter pregnancy can significantly affect your outcomes for that pregnancy,” she said. “We’ve known for decades now that a Mediterranean diet is good for just about everybody.”
 

Unequal access to foods on diet

Dr. Han said that, while it’s great the researchers were able to confirm the benefit of the Mediterranean diet, it highlights inequity as lower income people are not as likely to be able to afford fresh fruits and vegetables and fish.

“This is a call to arms for our food distribution system to even out the big divide in what patients have access to,” Dr. Han said.

She noted that most of the women in this study were married, non-Hispanic White, and had higher levels of education which may make it hard to generalize these results to the general population.

A limitation of the study is that the women were asked to report what they ate themselves, which can be less accurate than when researchers record what is eaten in a controlled setting.

The researchers suggested a next step: “Long-term intervention studies are needed to assess whether promoting a Mediterranean-style diet around the time of conception and throughout pregnancy can prevent APOs.”

Dr. Makarem reported receiving grants from the National Institutes of Health and the American Heart Association outside the submitted work. One coauthor reported receiving grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development during the study. One coauthor reported receiving personal fees for serving on the board of directors for iRhythm and from fees paid through Cedars-Sinai Medical Center from Abbott Diagnostics and Sanofi outside the submitted work, and one coauthor reported serving as a clinical end point committee member for GlaxoSmithKline outside the submitted work. No other disclosures were reported. Dr. Han reported no relevant financial relationships.

Women in the United States who followed a Mediterranean-style diet – heavy on fresh foods, fish, and olive oil – around the time of conception had lower risk of developing a pregnancy complication, results of a large new study suggest.

The study included 7,798 women who had not given birth before. The group was geographically, racially, and ethnically diverse.

Researchers led by Nour Makarem, PhD, MS, with the department of epidemiology, Columbia University, New York, published their results in JAMA Network Open.

“Generally, higher intakes of vegetables, fruits, legumes, fish, and whole grains and lower intakes of red and processed meat were associated with lower risk of APOs [adverse pregnancy outcomes],” the authors wrote.
 

21% lower risk of complications

The investigators found that women in the study – who were part of the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be, which enrolled 10,038 women between Oct. 1, 2010, and Sept. 30, 2013, and scored high on adherence to a Mediterranean diet – had a 21% lower risk of developing any adverse pregnancy outcome (APO) than those who had low adherence. And the better the adherence, the lower the risk of adverse outcomes, especially preeclampsia or eclampsia and gestational diabetes, the researchers wrote.

The research team also studied how following the diet correlated with gestational high blood pressure, preterm birth, delivery of a small-for-gestational-age infant, and stillbirth.

Women were scored on consumption of nine components: vegetables (excluding potatoes), fruits, nuts, whole grains, legumes, fish, monounsaturated to saturated fat ratio, red and processed meats, and alcohol.
 

No differences by race, ethnicity, or BMI

There were no differences in adverse pregnancy outcomes by race, ethnicity, or the woman’s body mass index before pregnancy, but associations were stronger in the women who were 35 years or older, according to the paper.

The authors pointed out that the women in the study had access to prenatal care at a large academic medical center during their first 3 months of pregnancy so the study may actually underestimate the importance of the diet in the pregnancy outcomes.

Christina Han, MD, division director of maternal-fetal medicine at University of California, Los Angeles, who was not part of the study, said that the results make sense as the researchers looked at the time of conception, which is a time that reflects the way a person chooses to live their life.

“We know that your health state as you enter pregnancy can significantly affect your outcomes for that pregnancy,” she said. “We’ve known for decades now that a Mediterranean diet is good for just about everybody.”
 

Unequal access to foods on diet

Dr. Han said that, while it’s great the researchers were able to confirm the benefit of the Mediterranean diet, it highlights inequity as lower income people are not as likely to be able to afford fresh fruits and vegetables and fish.

“This is a call to arms for our food distribution system to even out the big divide in what patients have access to,” Dr. Han said.

She noted that most of the women in this study were married, non-Hispanic White, and had higher levels of education which may make it hard to generalize these results to the general population.

A limitation of the study is that the women were asked to report what they ate themselves, which can be less accurate than when researchers record what is eaten in a controlled setting.

The researchers suggested a next step: “Long-term intervention studies are needed to assess whether promoting a Mediterranean-style diet around the time of conception and throughout pregnancy can prevent APOs.”

Dr. Makarem reported receiving grants from the National Institutes of Health and the American Heart Association outside the submitted work. One coauthor reported receiving grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development during the study. One coauthor reported receiving personal fees for serving on the board of directors for iRhythm and from fees paid through Cedars-Sinai Medical Center from Abbott Diagnostics and Sanofi outside the submitted work, and one coauthor reported serving as a clinical end point committee member for GlaxoSmithKline outside the submitted work. No other disclosures were reported. Dr. Han reported no relevant financial relationships.

Women in the United States who followed a Mediterranean-style diet – heavy on fresh foods, fish, and olive oil – around the time of conception had lower risk of developing a pregnancy complication, results of a large new study suggest.

The study included 7,798 women who had not given birth before. The group was geographically, racially, and ethnically diverse.

Researchers led by Nour Makarem, PhD, MS, with the department of epidemiology, Columbia University, New York, published their results in JAMA Network Open.

“Generally, higher intakes of vegetables, fruits, legumes, fish, and whole grains and lower intakes of red and processed meat were associated with lower risk of APOs [adverse pregnancy outcomes],” the authors wrote.
 

21% lower risk of complications

The investigators found that women in the study – who were part of the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be, which enrolled 10,038 women between Oct. 1, 2010, and Sept. 30, 2013, and scored high on adherence to a Mediterranean diet – had a 21% lower risk of developing any adverse pregnancy outcome (APO) than those who had low adherence. And the better the adherence, the lower the risk of adverse outcomes, especially preeclampsia or eclampsia and gestational diabetes, the researchers wrote.

The research team also studied how following the diet correlated with gestational high blood pressure, preterm birth, delivery of a small-for-gestational-age infant, and stillbirth.

Women were scored on consumption of nine components: vegetables (excluding potatoes), fruits, nuts, whole grains, legumes, fish, monounsaturated to saturated fat ratio, red and processed meats, and alcohol.
 

No differences by race, ethnicity, or BMI

There were no differences in adverse pregnancy outcomes by race, ethnicity, or the woman’s body mass index before pregnancy, but associations were stronger in the women who were 35 years or older, according to the paper.

The authors pointed out that the women in the study had access to prenatal care at a large academic medical center during their first 3 months of pregnancy so the study may actually underestimate the importance of the diet in the pregnancy outcomes.

Christina Han, MD, division director of maternal-fetal medicine at University of California, Los Angeles, who was not part of the study, said that the results make sense as the researchers looked at the time of conception, which is a time that reflects the way a person chooses to live their life.

“We know that your health state as you enter pregnancy can significantly affect your outcomes for that pregnancy,” she said. “We’ve known for decades now that a Mediterranean diet is good for just about everybody.”
 

Unequal access to foods on diet

Dr. Han said that, while it’s great the researchers were able to confirm the benefit of the Mediterranean diet, it highlights inequity as lower income people are not as likely to be able to afford fresh fruits and vegetables and fish.

“This is a call to arms for our food distribution system to even out the big divide in what patients have access to,” Dr. Han said.

She noted that most of the women in this study were married, non-Hispanic White, and had higher levels of education which may make it hard to generalize these results to the general population.

A limitation of the study is that the women were asked to report what they ate themselves, which can be less accurate than when researchers record what is eaten in a controlled setting.

The researchers suggested a next step: “Long-term intervention studies are needed to assess whether promoting a Mediterranean-style diet around the time of conception and throughout pregnancy can prevent APOs.”

Dr. Makarem reported receiving grants from the National Institutes of Health and the American Heart Association outside the submitted work. One coauthor reported receiving grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development during the study. One coauthor reported receiving personal fees for serving on the board of directors for iRhythm and from fees paid through Cedars-Sinai Medical Center from Abbott Diagnostics and Sanofi outside the submitted work, and one coauthor reported serving as a clinical end point committee member for GlaxoSmithKline outside the submitted work. No other disclosures were reported. Dr. Han reported no relevant financial relationships.

Irregular and especially long menstrual cycles, particularly in early and mid adulthood, are associated with an increased risk for cardiovascular disease. This finding is demonstrated in a new analysis of the Nurses’ Health Study II.

“To date, several studies have reported increased risks of cardiovascular risk factors or cardiovascular disease in connection with cycle disorders,” Yi-Xin Wang, MD, PhD, a research fellow in nutrition, and associates from the Harvard School of Public Health, Boston, wrote in an article published in JAMA Network Open.

Ute Seeland, MD, speaker of the Gender Medicine in Cardiology Working Group of the German Cardiology Society, said in an interview“We know that women who have indicated in their medical history that they have irregular menstrual cycles, invariably in connection with polycystic ovary syndrome (PCOS), more commonly develop diabetes and other metabolic disorders, as well as cardiovascular diseases.”
 

Cycle disorders’ role

However, the role that irregular or especially long cycles play at different points of a woman’s reproductive life span was unclear. Therefore, the research group investigated the associations in the Nurses’ Health Study II between cycle irregularity and cycle length in women of different age groups who later experienced cardiovascular events.

At the end of this study in 1989, the participants also provided information regarding the length and irregularity of their menstrual cycle from ages 14 to 17 years and again from ages 18 to 22 years. The information was updated in 1993 when the participants were aged 29-46 years. The data from 2019 to 2022 were analyzed.

“This kind of long-term cohort study is extremely rare and therefore something special,” said Dr. Seeland, who conducts research at the Institute for Social Medicine, Epidemiology, and Health Economics at the Charité – University Hospital Berlin.

The investigators used the following cycle classifications: very regular (no more than 3 or 4 days before or after the expected date), regular (within 5-7 days), usually irregular, always irregular, or no periods.

The cycle lengths were divided into the following categories: less than 21 days, 21-25 days, 26-31 days, 32-39 days, 40-50 days, more than 50 days, and too irregular to estimate the length.

The onset of cardiovascular diseases was determined using information from the participants and was confirmed by reviewing the medical files. Relevant to the study were lethal and nonlethal coronary heart diseases (such as myocardial infarction or coronary artery revascularization), as well as strokes.
 

Significant in adulthood

The data from 80,630 study participants were included in the analysis. At study inclusion, the average age of the participants was 37.7 years, and the average body mass index (BMI) was 25.1. “Since it was predominantly White nurses who took part in the study, the data are not transferable to other, more diverse populations,” said Dr. Seeland.

Over 24 years, 1,816 women (2.4%) had a cardiovascular event. “We observed an increased rate of cardiovascular events in women with an irregular cycle and longer cycle, both in early an in mid-adulthood,” wrote Dr. Wang and associates. “Similar trends were also observed for cycle disorders when younger, but this association was weaker than in adulthood.”

Compared with women with very regular cycles, women with irregular cycles or without periods who were aged 14-17 years, 18-22 years, or 29-49 years exhibited a 15%, 36%, and 40% higher risk of a cardiovascular event, respectively.

Similarly, women aged 18-22 years or 29-46 years with long cycles of 40 days or more had a 44% or 30% higher risk of cardiovascular disease, respectively, compared with women with cycle lengths of 26-31 days.

“The coronary heart diseases were decisive for the increase, and less so, the strokes,” wrote the researchers.
 

Classic risk factors?

Dr. Seeland praised the fact that the study authors tried to determine the role that classic cardiovascular risk factors played. “Compared with women with a regular cycle, women with an irregular cycle had a higher BMI, more frequently increased cholesterol levels, and an elevated blood pressure,” she said. Women with a long cycle displayed a similar pattern.

It can be assumed from this that over a woman’s life span, BMI affects the risk of cardiovascular disease. Therefore, Dr. Wang and coauthors adjusted the results on the basis of BMI, which varies over time.

Regarding other classic risk factors that may have played a role, “hypercholesterolemia, chronic high blood pressure, and type 2 diabetes were only responsible in 5.4%-13.5% of the associations,” wrote the researchers.

“Our results suggest that certain characteristics of the menstrual cycle across a woman’s reproductive lifespan may constitute additional risk markers for cardiovascular disease,” according to the authors.

The highest rates of cardiovascular disease were among women with permanently irregular or long cycles in early to mid adulthood, as well as women who had regular cycles when younger but had irregular cycles in mid adulthood. “This indicates that the change from one cycle phenotype to another could be a surrogate marker for metabolic changes, which in turn contribute to the formation of cardiovascular diseases,” wrote the authors.

The study was observational and so conclusions cannot be drawn regarding causal relationships. But Dr. Wang and associates indicate that the most common cause of an irregular menstrual cycle may be PCOS. “Roughly 90% of women with cycle disorders or oligomenorrhea have signs of PCOS. And it was shown that women with PCOS have an increased risk of cardiovascular disease.”

They concluded that “the associations observed between irregular and long cycles in early to mid-adulthood and cardiovascular diseases are likely attributable to underlying PCOS.”

For Dr. Seeland, however, this conclusion is “too monocausal. At no point in time did there seem to be any direct information regarding the frequency of PCOS during the data collection by the respondents.”

For now, we can only speculate about the mechanisms. “The association between a very irregular and long cycle and the increased risk of cardiovascular diseases has now only been described. More research should be done on the causes,” said Dr. Seeland.

This article was translated from the Medscape German edition. A version of this article first appeared on Medscape.com.

Irregular and especially long menstrual cycles, particularly in early and mid adulthood, are associated with an increased risk for cardiovascular disease. This finding is demonstrated in a new analysis of the Nurses’ Health Study II.

“To date, several studies have reported increased risks of cardiovascular risk factors or cardiovascular disease in connection with cycle disorders,” Yi-Xin Wang, MD, PhD, a research fellow in nutrition, and associates from the Harvard School of Public Health, Boston, wrote in an article published in JAMA Network Open.

Ute Seeland, MD, speaker of the Gender Medicine in Cardiology Working Group of the German Cardiology Society, said in an interview“We know that women who have indicated in their medical history that they have irregular menstrual cycles, invariably in connection with polycystic ovary syndrome (PCOS), more commonly develop diabetes and other metabolic disorders, as well as cardiovascular diseases.”
 

Cycle disorders’ role

However, the role that irregular or especially long cycles play at different points of a woman’s reproductive life span was unclear. Therefore, the research group investigated the associations in the Nurses’ Health Study II between cycle irregularity and cycle length in women of different age groups who later experienced cardiovascular events.

At the end of this study in 1989, the participants also provided information regarding the length and irregularity of their menstrual cycle from ages 14 to 17 years and again from ages 18 to 22 years. The information was updated in 1993 when the participants were aged 29-46 years. The data from 2019 to 2022 were analyzed.

“This kind of long-term cohort study is extremely rare and therefore something special,” said Dr. Seeland, who conducts research at the Institute for Social Medicine, Epidemiology, and Health Economics at the Charité – University Hospital Berlin.

The investigators used the following cycle classifications: very regular (no more than 3 or 4 days before or after the expected date), regular (within 5-7 days), usually irregular, always irregular, or no periods.

The cycle lengths were divided into the following categories: less than 21 days, 21-25 days, 26-31 days, 32-39 days, 40-50 days, more than 50 days, and too irregular to estimate the length.

The onset of cardiovascular diseases was determined using information from the participants and was confirmed by reviewing the medical files. Relevant to the study were lethal and nonlethal coronary heart diseases (such as myocardial infarction or coronary artery revascularization), as well as strokes.
 

Significant in adulthood

The data from 80,630 study participants were included in the analysis. At study inclusion, the average age of the participants was 37.7 years, and the average body mass index (BMI) was 25.1. “Since it was predominantly White nurses who took part in the study, the data are not transferable to other, more diverse populations,” said Dr. Seeland.

Over 24 years, 1,816 women (2.4%) had a cardiovascular event. “We observed an increased rate of cardiovascular events in women with an irregular cycle and longer cycle, both in early an in mid-adulthood,” wrote Dr. Wang and associates. “Similar trends were also observed for cycle disorders when younger, but this association was weaker than in adulthood.”

Compared with women with very regular cycles, women with irregular cycles or without periods who were aged 14-17 years, 18-22 years, or 29-49 years exhibited a 15%, 36%, and 40% higher risk of a cardiovascular event, respectively.

Similarly, women aged 18-22 years or 29-46 years with long cycles of 40 days or more had a 44% or 30% higher risk of cardiovascular disease, respectively, compared with women with cycle lengths of 26-31 days.

“The coronary heart diseases were decisive for the increase, and less so, the strokes,” wrote the researchers.
 

Classic risk factors?

Dr. Seeland praised the fact that the study authors tried to determine the role that classic cardiovascular risk factors played. “Compared with women with a regular cycle, women with an irregular cycle had a higher BMI, more frequently increased cholesterol levels, and an elevated blood pressure,” she said. Women with a long cycle displayed a similar pattern.

It can be assumed from this that over a woman’s life span, BMI affects the risk of cardiovascular disease. Therefore, Dr. Wang and coauthors adjusted the results on the basis of BMI, which varies over time.

Regarding other classic risk factors that may have played a role, “hypercholesterolemia, chronic high blood pressure, and type 2 diabetes were only responsible in 5.4%-13.5% of the associations,” wrote the researchers.

“Our results suggest that certain characteristics of the menstrual cycle across a woman’s reproductive lifespan may constitute additional risk markers for cardiovascular disease,” according to the authors.

The highest rates of cardiovascular disease were among women with permanently irregular or long cycles in early to mid adulthood, as well as women who had regular cycles when younger but had irregular cycles in mid adulthood. “This indicates that the change from one cycle phenotype to another could be a surrogate marker for metabolic changes, which in turn contribute to the formation of cardiovascular diseases,” wrote the authors.

The study was observational and so conclusions cannot be drawn regarding causal relationships. But Dr. Wang and associates indicate that the most common cause of an irregular menstrual cycle may be PCOS. “Roughly 90% of women with cycle disorders or oligomenorrhea have signs of PCOS. And it was shown that women with PCOS have an increased risk of cardiovascular disease.”

They concluded that “the associations observed between irregular and long cycles in early to mid-adulthood and cardiovascular diseases are likely attributable to underlying PCOS.”

For Dr. Seeland, however, this conclusion is “too monocausal. At no point in time did there seem to be any direct information regarding the frequency of PCOS during the data collection by the respondents.”

For now, we can only speculate about the mechanisms. “The association between a very irregular and long cycle and the increased risk of cardiovascular diseases has now only been described. More research should be done on the causes,” said Dr. Seeland.

This article was translated from the Medscape German edition. A version of this article first appeared on Medscape.com.

Irregular and especially long menstrual cycles, particularly in early and mid adulthood, are associated with an increased risk for cardiovascular disease. This finding is demonstrated in a new analysis of the Nurses’ Health Study II.

“To date, several studies have reported increased risks of cardiovascular risk factors or cardiovascular disease in connection with cycle disorders,” Yi-Xin Wang, MD, PhD, a research fellow in nutrition, and associates from the Harvard School of Public Health, Boston, wrote in an article published in JAMA Network Open.

Ute Seeland, MD, speaker of the Gender Medicine in Cardiology Working Group of the German Cardiology Society, said in an interview“We know that women who have indicated in their medical history that they have irregular menstrual cycles, invariably in connection with polycystic ovary syndrome (PCOS), more commonly develop diabetes and other metabolic disorders, as well as cardiovascular diseases.”
 

Cycle disorders’ role

However, the role that irregular or especially long cycles play at different points of a woman’s reproductive life span was unclear. Therefore, the research group investigated the associations in the Nurses’ Health Study II between cycle irregularity and cycle length in women of different age groups who later experienced cardiovascular events.

At the end of this study in 1989, the participants also provided information regarding the length and irregularity of their menstrual cycle from ages 14 to 17 years and again from ages 18 to 22 years. The information was updated in 1993 when the participants were aged 29-46 years. The data from 2019 to 2022 were analyzed.

“This kind of long-term cohort study is extremely rare and therefore something special,” said Dr. Seeland, who conducts research at the Institute for Social Medicine, Epidemiology, and Health Economics at the Charité – University Hospital Berlin.

The investigators used the following cycle classifications: very regular (no more than 3 or 4 days before or after the expected date), regular (within 5-7 days), usually irregular, always irregular, or no periods.

The cycle lengths were divided into the following categories: less than 21 days, 21-25 days, 26-31 days, 32-39 days, 40-50 days, more than 50 days, and too irregular to estimate the length.

The onset of cardiovascular diseases was determined using information from the participants and was confirmed by reviewing the medical files. Relevant to the study were lethal and nonlethal coronary heart diseases (such as myocardial infarction or coronary artery revascularization), as well as strokes.
 

Significant in adulthood

The data from 80,630 study participants were included in the analysis. At study inclusion, the average age of the participants was 37.7 years, and the average body mass index (BMI) was 25.1. “Since it was predominantly White nurses who took part in the study, the data are not transferable to other, more diverse populations,” said Dr. Seeland.

Over 24 years, 1,816 women (2.4%) had a cardiovascular event. “We observed an increased rate of cardiovascular events in women with an irregular cycle and longer cycle, both in early an in mid-adulthood,” wrote Dr. Wang and associates. “Similar trends were also observed for cycle disorders when younger, but this association was weaker than in adulthood.”

Compared with women with very regular cycles, women with irregular cycles or without periods who were aged 14-17 years, 18-22 years, or 29-49 years exhibited a 15%, 36%, and 40% higher risk of a cardiovascular event, respectively.

Similarly, women aged 18-22 years or 29-46 years with long cycles of 40 days or more had a 44% or 30% higher risk of cardiovascular disease, respectively, compared with women with cycle lengths of 26-31 days.

“The coronary heart diseases were decisive for the increase, and less so, the strokes,” wrote the researchers.
 

Classic risk factors?

Dr. Seeland praised the fact that the study authors tried to determine the role that classic cardiovascular risk factors played. “Compared with women with a regular cycle, women with an irregular cycle had a higher BMI, more frequently increased cholesterol levels, and an elevated blood pressure,” she said. Women with a long cycle displayed a similar pattern.

It can be assumed from this that over a woman’s life span, BMI affects the risk of cardiovascular disease. Therefore, Dr. Wang and coauthors adjusted the results on the basis of BMI, which varies over time.

Regarding other classic risk factors that may have played a role, “hypercholesterolemia, chronic high blood pressure, and type 2 diabetes were only responsible in 5.4%-13.5% of the associations,” wrote the researchers.

“Our results suggest that certain characteristics of the menstrual cycle across a woman’s reproductive lifespan may constitute additional risk markers for cardiovascular disease,” according to the authors.

The highest rates of cardiovascular disease were among women with permanently irregular or long cycles in early to mid adulthood, as well as women who had regular cycles when younger but had irregular cycles in mid adulthood. “This indicates that the change from one cycle phenotype to another could be a surrogate marker for metabolic changes, which in turn contribute to the formation of cardiovascular diseases,” wrote the authors.

The study was observational and so conclusions cannot be drawn regarding causal relationships. But Dr. Wang and associates indicate that the most common cause of an irregular menstrual cycle may be PCOS. “Roughly 90% of women with cycle disorders or oligomenorrhea have signs of PCOS. And it was shown that women with PCOS have an increased risk of cardiovascular disease.”

They concluded that “the associations observed between irregular and long cycles in early to mid-adulthood and cardiovascular diseases are likely attributable to underlying PCOS.”

For Dr. Seeland, however, this conclusion is “too monocausal. At no point in time did there seem to be any direct information regarding the frequency of PCOS during the data collection by the respondents.”

For now, we can only speculate about the mechanisms. “The association between a very irregular and long cycle and the increased risk of cardiovascular diseases has now only been described. More research should be done on the causes,” said Dr. Seeland.

This article was translated from the Medscape German edition. A version of this article first appeared on Medscape.com.

An investigational vaccine against respiratory syncytial virus (RSV) in pregnant women has been shown to help protect infants against severe disease, according to the vaccine’s manufacturer.

Pfizer recently announced that in the course of a randomized, double-blind, placebo-controlled phase 3 study, the vaccine RSVpreF had an almost 82% efficacy against severe RSV infection in infants from birth through the first 90 days of life, according to a company press release.

The vaccine also had a 69% efficacy against severe disease through the first 6 months of life. A total of 7,400 women had received a single dose of 120 mcg RSVpreF in the late second or third trimester of their pregnancy. There were no signs of safety issues for the mothers or infants.

Due to the good results, the enrollment in the study was halted on the recommendation of the study’s Data Monitoring Committee after achieving a primary endpoint. The company plans to apply for marketing authorization to the U.S. Food and Drug Administration by the end of 2022 and to other regulatory agencies in 2023.

“The directness of the strategy, to vaccinate expectant mothers during pregnancy so that their newborn is then later protected, is new and a very interesting approach,” commented Prof. Ortwin Adams, MD, head of virologic diagnostics at the Institute for Virology of the University Hospital of Düsseldorf (Germany) to the Science Media Centre (SMC).

In terms of the RSV vaccination strategy presented, “the unborn child has taken center stage from the outset.” Because the vaccination route is the placental transfer of antibodies from mother to child (“passive immunity”), “... the medical points of contact for this vaccination will be the gynecologists, not the pediatricians,” Dr. Adams said.

“This concept imitates the natural process, since the mother normally passes immune defenses she acquired through infections to the child via the umbilical cord and her breast milk before and after birth. This procedure is long-proven and practiced worldwide, especially in nonindustrialized countries, for a variety of diseases, including tetanus, whooping cough (pertussis), and viral flu (influenza),” explained Markus Rose, MD, PhD, head of Pediatric Pulmonology at the Olgahospital, Stuttgart, Germany.

The development of an RSV vaccine had ground to a halt for many decades: A tragedy in the 1960s set the whole field of research back. Using the model of the first polio vaccine, scientists had manufactured an experimental vaccine with inactivated viruses. However, tests showed that the vaccine did not protect the children vaccinated, but it actually infected them with RSV, they then fell ill, and two children died. Today, potential RSV vaccines are first tested on adults and not on children.
 

Few treatment options

RSV causes seasonal epidemics, can lead to bronchiolitis and pneumonia in infants, and is one of the main causes of hospital stays in young children. Monoclonal antibodies are currently the only preventive option, since there is still no vaccine. Usually, 60%-70% of infants and nearly all children younger than 2 years are infected with RSV, but the virus can also trigger pneumonia in adults.

“RSV infections constitute a major public health challenge: It is the most dangerous respiratory virus for young infants, it is also a threat to the chronically ill and immunocompromised of all ages, and [it] is the second most common cause of death worldwide (after malaria) in young children,” stated Dr. Rose.

Recently, pandemic-related measures (face masks, more intense disinfection) meant that the “normal” RSV infections in healthy adults, which usually progress like a mild cold, were prevented, and mothers were unable to pass on as much RSV immune defense to their children. “This was presumably responsible in part for the massive wave of RSV infections in fall and winter of 2021/22,” explained Dr. Rose.

Thomas Mertens, MD, PhD, chair of the Standing Committee on Vaccination at the Robert Koch Institute (STIKO) and former director of the Institute for Virology at Ulm University Hospital, Germany, also noted: “It would be an important and potentially achievable goal to significantly reduce the incidence rate of hospitalizations. In this respect, RSV poses a significant problem for young children, their parents, and the burden on pediatric clinics.”
 

Final evaluation pending

“I am definitely finding the data interesting, but the original data are needed,” Dr. Mertens said. Once the data are published at a conference or published in a peer-reviewed journal, physicians will be able to better judge the data for themselves, he said.

Dr. Rose characterized the new vaccine as “novel,” including in terms of its composition. Earlier RSV vaccines used the so-called postfusion F protein as their starting point. But it has become known in the meantime that the key to immunogenicity is the continued prefusion state of the apical epitope: Prefusion F-specific memory B cells in adults naturally infected with RSV produce potent neutralizing antibodies.

The new vaccine is bivalent and protects against both RSV A and RSV B.

To date, RSV vaccination directly in young infants have had only had a weak efficacy and were sometimes poorly tolerated. The vaccine presented here is expected to be tested in young adults first, then in school children, then young children.

Through successful vaccination of the entire population, the transfer of RS viruses to young children could be prevented. “To what extent this, or any other RSV vaccine still to be developed on the same basis, will also be effective and well tolerated in young infants is still difficult to assess,” said Dr. Rose.

Dr. Mertens emphasized that all of the study data now needs to be seen as quickly as possible: “This is also a general requirement for transparency from the pharmaceutical companies, which is also rightly criticized.”

This article was originally published in Medscape’s German edition and a version appeared on Medscape.com.

An investigational vaccine against respiratory syncytial virus (RSV) in pregnant women has been shown to help protect infants against severe disease, according to the vaccine’s manufacturer.

Pfizer recently announced that in the course of a randomized, double-blind, placebo-controlled phase 3 study, the vaccine RSVpreF had an almost 82% efficacy against severe RSV infection in infants from birth through the first 90 days of life, according to a company press release.

The vaccine also had a 69% efficacy against severe disease through the first 6 months of life. A total of 7,400 women had received a single dose of 120 mcg RSVpreF in the late second or third trimester of their pregnancy. There were no signs of safety issues for the mothers or infants.

Due to the good results, the enrollment in the study was halted on the recommendation of the study’s Data Monitoring Committee after achieving a primary endpoint. The company plans to apply for marketing authorization to the U.S. Food and Drug Administration by the end of 2022 and to other regulatory agencies in 2023.

“The directness of the strategy, to vaccinate expectant mothers during pregnancy so that their newborn is then later protected, is new and a very interesting approach,” commented Prof. Ortwin Adams, MD, head of virologic diagnostics at the Institute for Virology of the University Hospital of Düsseldorf (Germany) to the Science Media Centre (SMC).

In terms of the RSV vaccination strategy presented, “the unborn child has taken center stage from the outset.” Because the vaccination route is the placental transfer of antibodies from mother to child (“passive immunity”), “... the medical points of contact for this vaccination will be the gynecologists, not the pediatricians,” Dr. Adams said.

“This concept imitates the natural process, since the mother normally passes immune defenses she acquired through infections to the child via the umbilical cord and her breast milk before and after birth. This procedure is long-proven and practiced worldwide, especially in nonindustrialized countries, for a variety of diseases, including tetanus, whooping cough (pertussis), and viral flu (influenza),” explained Markus Rose, MD, PhD, head of Pediatric Pulmonology at the Olgahospital, Stuttgart, Germany.

The development of an RSV vaccine had ground to a halt for many decades: A tragedy in the 1960s set the whole field of research back. Using the model of the first polio vaccine, scientists had manufactured an experimental vaccine with inactivated viruses. However, tests showed that the vaccine did not protect the children vaccinated, but it actually infected them with RSV, they then fell ill, and two children died. Today, potential RSV vaccines are first tested on adults and not on children.
 

Few treatment options

RSV causes seasonal epidemics, can lead to bronchiolitis and pneumonia in infants, and is one of the main causes of hospital stays in young children. Monoclonal antibodies are currently the only preventive option, since there is still no vaccine. Usually, 60%-70% of infants and nearly all children younger than 2 years are infected with RSV, but the virus can also trigger pneumonia in adults.

“RSV infections constitute a major public health challenge: It is the most dangerous respiratory virus for young infants, it is also a threat to the chronically ill and immunocompromised of all ages, and [it] is the second most common cause of death worldwide (after malaria) in young children,” stated Dr. Rose.

Recently, pandemic-related measures (face masks, more intense disinfection) meant that the “normal” RSV infections in healthy adults, which usually progress like a mild cold, were prevented, and mothers were unable to pass on as much RSV immune defense to their children. “This was presumably responsible in part for the massive wave of RSV infections in fall and winter of 2021/22,” explained Dr. Rose.

Thomas Mertens, MD, PhD, chair of the Standing Committee on Vaccination at the Robert Koch Institute (STIKO) and former director of the Institute for Virology at Ulm University Hospital, Germany, also noted: “It would be an important and potentially achievable goal to significantly reduce the incidence rate of hospitalizations. In this respect, RSV poses a significant problem for young children, their parents, and the burden on pediatric clinics.”
 

Final evaluation pending

“I am definitely finding the data interesting, but the original data are needed,” Dr. Mertens said. Once the data are published at a conference or published in a peer-reviewed journal, physicians will be able to better judge the data for themselves, he said.

Dr. Rose characterized the new vaccine as “novel,” including in terms of its composition. Earlier RSV vaccines used the so-called postfusion F protein as their starting point. But it has become known in the meantime that the key to immunogenicity is the continued prefusion state of the apical epitope: Prefusion F-specific memory B cells in adults naturally infected with RSV produce potent neutralizing antibodies.

The new vaccine is bivalent and protects against both RSV A and RSV B.

To date, RSV vaccination directly in young infants have had only had a weak efficacy and were sometimes poorly tolerated. The vaccine presented here is expected to be tested in young adults first, then in school children, then young children.

Through successful vaccination of the entire population, the transfer of RS viruses to young children could be prevented. “To what extent this, or any other RSV vaccine still to be developed on the same basis, will also be effective and well tolerated in young infants is still difficult to assess,” said Dr. Rose.

Dr. Mertens emphasized that all of the study data now needs to be seen as quickly as possible: “This is also a general requirement for transparency from the pharmaceutical companies, which is also rightly criticized.”

This article was originally published in Medscape’s German edition and a version appeared on Medscape.com.

An investigational vaccine against respiratory syncytial virus (RSV) in pregnant women has been shown to help protect infants against severe disease, according to the vaccine’s manufacturer.

Pfizer recently announced that in the course of a randomized, double-blind, placebo-controlled phase 3 study, the vaccine RSVpreF had an almost 82% efficacy against severe RSV infection in infants from birth through the first 90 days of life, according to a company press release.

The vaccine also had a 69% efficacy against severe disease through the first 6 months of life. A total of 7,400 women had received a single dose of 120 mcg RSVpreF in the late second or third trimester of their pregnancy. There were no signs of safety issues for the mothers or infants.

Due to the good results, the enrollment in the study was halted on the recommendation of the study’s Data Monitoring Committee after achieving a primary endpoint. The company plans to apply for marketing authorization to the U.S. Food and Drug Administration by the end of 2022 and to other regulatory agencies in 2023.

“The directness of the strategy, to vaccinate expectant mothers during pregnancy so that their newborn is then later protected, is new and a very interesting approach,” commented Prof. Ortwin Adams, MD, head of virologic diagnostics at the Institute for Virology of the University Hospital of Düsseldorf (Germany) to the Science Media Centre (SMC).

In terms of the RSV vaccination strategy presented, “the unborn child has taken center stage from the outset.” Because the vaccination route is the placental transfer of antibodies from mother to child (“passive immunity”), “... the medical points of contact for this vaccination will be the gynecologists, not the pediatricians,” Dr. Adams said.

“This concept imitates the natural process, since the mother normally passes immune defenses she acquired through infections to the child via the umbilical cord and her breast milk before and after birth. This procedure is long-proven and practiced worldwide, especially in nonindustrialized countries, for a variety of diseases, including tetanus, whooping cough (pertussis), and viral flu (influenza),” explained Markus Rose, MD, PhD, head of Pediatric Pulmonology at the Olgahospital, Stuttgart, Germany.

The development of an RSV vaccine had ground to a halt for many decades: A tragedy in the 1960s set the whole field of research back. Using the model of the first polio vaccine, scientists had manufactured an experimental vaccine with inactivated viruses. However, tests showed that the vaccine did not protect the children vaccinated, but it actually infected them with RSV, they then fell ill, and two children died. Today, potential RSV vaccines are first tested on adults and not on children.
 

Few treatment options

RSV causes seasonal epidemics, can lead to bronchiolitis and pneumonia in infants, and is one of the main causes of hospital stays in young children. Monoclonal antibodies are currently the only preventive option, since there is still no vaccine. Usually, 60%-70% of infants and nearly all children younger than 2 years are infected with RSV, but the virus can also trigger pneumonia in adults.

“RSV infections constitute a major public health challenge: It is the most dangerous respiratory virus for young infants, it is also a threat to the chronically ill and immunocompromised of all ages, and [it] is the second most common cause of death worldwide (after malaria) in young children,” stated Dr. Rose.

Recently, pandemic-related measures (face masks, more intense disinfection) meant that the “normal” RSV infections in healthy adults, which usually progress like a mild cold, were prevented, and mothers were unable to pass on as much RSV immune defense to their children. “This was presumably responsible in part for the massive wave of RSV infections in fall and winter of 2021/22,” explained Dr. Rose.

Thomas Mertens, MD, PhD, chair of the Standing Committee on Vaccination at the Robert Koch Institute (STIKO) and former director of the Institute for Virology at Ulm University Hospital, Germany, also noted: “It would be an important and potentially achievable goal to significantly reduce the incidence rate of hospitalizations. In this respect, RSV poses a significant problem for young children, their parents, and the burden on pediatric clinics.”
 

Final evaluation pending

“I am definitely finding the data interesting, but the original data are needed,” Dr. Mertens said. Once the data are published at a conference or published in a peer-reviewed journal, physicians will be able to better judge the data for themselves, he said.

Dr. Rose characterized the new vaccine as “novel,” including in terms of its composition. Earlier RSV vaccines used the so-called postfusion F protein as their starting point. But it has become known in the meantime that the key to immunogenicity is the continued prefusion state of the apical epitope: Prefusion F-specific memory B cells in adults naturally infected with RSV produce potent neutralizing antibodies.

The new vaccine is bivalent and protects against both RSV A and RSV B.

To date, RSV vaccination directly in young infants have had only had a weak efficacy and were sometimes poorly tolerated. The vaccine presented here is expected to be tested in young adults first, then in school children, then young children.

Through successful vaccination of the entire population, the transfer of RS viruses to young children could be prevented. “To what extent this, or any other RSV vaccine still to be developed on the same basis, will also be effective and well tolerated in young infants is still difficult to assess,” said Dr. Rose.

Dr. Mertens emphasized that all of the study data now needs to be seen as quickly as possible: “This is also a general requirement for transparency from the pharmaceutical companies, which is also rightly criticized.”

This article was originally published in Medscape’s German edition and a version appeared on Medscape.com.

Women with preexisting ischemic heart disease without another cardiac diagnosis have a higher risk of severe maternal morbidity and mortality than women with no cardiac disease, a new study suggests.

However, after adjustment for other comorbidities, the risk associated with isolated preexisting ischemic heart disease without additional evidence of cardiomyopathy was relatively similar to that of other low-risk cardiac diseases.

“These are reassuring findings,” lead author of the study, Anna E. Denoble, MD, Yale University, New Haven, Conn., told this news organization. “The risk is not zero. Women with preexisting ischemic heart disease are at a small increased risk compared to women without preexisting cardiac disease. But with good control of cardiovascular risk factors, these women have a good chance of a positive outcome.”

The study was published online in JACC: Advances.

“To our knowledge, this study provides the largest analysis to date examining the risk of severe morbidity and mortality among pregnant people with pre-existing ischemic heart disease,” the authors noted.

Dr. Denoble, a maternal and fetal medicine specialist, explained that in recent years, there has been an increase in the number of patients with preexisting ischemic heart disease who are considering pregnancy or who are pregnant when they present, but there is little information on outcomes for these patients.

The diagnosis of ischemic heart disease is not included in the main classification used for heart disease in pregnancy – the modified World Health Organization classification, Dr. Denoble noted. “This classification includes information on pregnancy outcomes in women with many cardiac conditions, including arrhythmias, congenital heart disease, heart failure, and aortic aneurysm, but ischemic heart disease is missing.”

She suggested this is probably because ischemic heart disease is regarded as a condition that occurs mainly in older people. “But we are seeing more and more women with ischemic heart disease who are pregnant or considering pregnancy. This could be because women are now often older when considering pregnancy, and also risk factors for ischemic heart disease, such as obesity and diabetes, are becoming more frequent in younger women.”

The researchers conducted the current study to investigate pregnancy outcomes for these women.

The retrospective cohort study analyzed data from the Nationwide Readmissions Database on women who had experienced a delivery hospitalization from Oct. 1, 2015, to Dec. 31, 2018. They compared outcomes for women with isolated preexisting ischemic heart disease with those of women who had no apparent cardiac condition and to those with mild or more severe cardiac conditions included in the mWHO classification after controlling for other comorbidities.

The primary outcome was severe maternal morbidity or death. Dr. Denoble explained that severe maternal morbidity includes mechanical ventilation, blood transfusion, and hysterectomy – the more severe maternal adverse outcomes of pregnancy.

Results showed that, of 11,556,136 delivery hospitalizations, 65,331 patients had another cardiac diagnosis, and 3,009 had ischemic heart disease alone. Patients with ischemic heart disease were older, and rates of diabetes and hypertension were higher.

In unadjusted analyses, adverse outcomes were more common among patients with ischemic heart disease alone than among patients with no cardiac disease and mild cardiac conditions (mWHO class I-II cardiac disease).

Of those with preexisting ischemic heart disease, 6.6% experienced severe maternal morbidity or death, compared with 1.5% of those without a cardiac disease (unadjusted relative risk vs. no cardiac disease, 4.3; 95% confidence interval, 3.5-5.2).

In comparison, 4.2% of women with mWHO I-II cardiac diseases and 23.1% of those with more severe mWHO II/III-IV cardiac diseases experienced severe maternal morbidity or death.

Similar differences were noted for nontransfusion severe maternal morbidity and mortality, as well as cardiac severe maternal morbidity and mortality.

After adjustment, ischemic heart disease alone was associated with a higher risk of severe maternal morbidity or death compared to no cardiac disease (adjusted RR, 1.51; 95% CI, 1.19-1.92).

In comparison, the aRR was 1.90 for WHO class I-II diseases and 5.87 (95% CI, 5.49-6.27) for more severe cardiac conditions defined as WHO II/III-IV diseases.

Risk for nontransfusion severe maternal morbidity or death (aRR, 1.60) and cardiac severe maternal morbidity or death (aRR, 2.98) were also higher for those with ischemic heart disease than for women without any cardiac disease.

There were no significant differences in preterm birth for those with preexisting ischemic heart disease compared to those with no cardiac disease after adjustment.

The risk of severe maternal morbidity and mortality, nontransfusion severe maternal morbidity and mortality, and cardiac severe maternal morbidity and mortality for ischemic heart disease alone most closely approximated that of mWHO class I or II cardiac diseases, the researchers said.

“We found that individuals with preexisting ischemic heart disease had a rate of severe maternal morbidity/mortality in the same range as those with other cardiac diagnoses in the mild cardiac disease classification (class I or II),” Dr. Denoble commented.

“This prognosis suggests it is very reasonable for these women to consider pregnancy. The risk of adverse outcomes is not so high that pregnancy is contraindicated,” she added.

Dr. Denoble said this information will be very helpful when counseling women with preexisting ischemic heart disease who are considering pregnancy. “These patients may need some extra monitoring, but in general, they have a high chance of a good outcome,” she noted.

“I would still advise these women to register with a high-risk obstetrics provider to have a baseline cardiovascular pregnancy evaluation. As long as that is reassuring, then further frequent intensive supervision may not be necessary,” she said.

However, the authors pointed out, “it is important to communicate to patients that while pregnancy may be considered low risk in the setting of pre-existing ischemic heart disease, 6.6% of patients with pre-existing ischemic heart disease alone did experience severe maternal morbidity or death during the delivery hospitalization.”

They added that other medical comorbidities should be factored into discussions regarding the risks of pregnancy.

The researchers also noted that the study was limited to evaluation of maternal outcomes occurring during the delivery hospitalization and that additional research that assesses rates of maternal adverse cardiac events and maternal morbidity occurring prior to or after the delivery hospitalization would be beneficial.

Future studies examining the potential gradation in risk associated with additional cardiac comorbidities in individuals with preexisting ischemic heart disease would also be worthwhile, they added.

The study was supported by funding from the National Institutes of Health and the Foundation for Women and Girls with Blood Disorders. The authors disclosed no relevant financial relationships.

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

Women with preexisting ischemic heart disease without another cardiac diagnosis have a higher risk of severe maternal morbidity and mortality than women with no cardiac disease, a new study suggests.

However, after adjustment for other comorbidities, the risk associated with isolated preexisting ischemic heart disease without additional evidence of cardiomyopathy was relatively similar to that of other low-risk cardiac diseases.

“These are reassuring findings,” lead author of the study, Anna E. Denoble, MD, Yale University, New Haven, Conn., told this news organization. “The risk is not zero. Women with preexisting ischemic heart disease are at a small increased risk compared to women without preexisting cardiac disease. But with good control of cardiovascular risk factors, these women have a good chance of a positive outcome.”

The study was published online in JACC: Advances.

“To our knowledge, this study provides the largest analysis to date examining the risk of severe morbidity and mortality among pregnant people with pre-existing ischemic heart disease,” the authors noted.

Dr. Denoble, a maternal and fetal medicine specialist, explained that in recent years, there has been an increase in the number of patients with preexisting ischemic heart disease who are considering pregnancy or who are pregnant when they present, but there is little information on outcomes for these patients.

The diagnosis of ischemic heart disease is not included in the main classification used for heart disease in pregnancy – the modified World Health Organization classification, Dr. Denoble noted. “This classification includes information on pregnancy outcomes in women with many cardiac conditions, including arrhythmias, congenital heart disease, heart failure, and aortic aneurysm, but ischemic heart disease is missing.”

She suggested this is probably because ischemic heart disease is regarded as a condition that occurs mainly in older people. “But we are seeing more and more women with ischemic heart disease who are pregnant or considering pregnancy. This could be because women are now often older when considering pregnancy, and also risk factors for ischemic heart disease, such as obesity and diabetes, are becoming more frequent in younger women.”

The researchers conducted the current study to investigate pregnancy outcomes for these women.

The retrospective cohort study analyzed data from the Nationwide Readmissions Database on women who had experienced a delivery hospitalization from Oct. 1, 2015, to Dec. 31, 2018. They compared outcomes for women with isolated preexisting ischemic heart disease with those of women who had no apparent cardiac condition and to those with mild or more severe cardiac conditions included in the mWHO classification after controlling for other comorbidities.

The primary outcome was severe maternal morbidity or death. Dr. Denoble explained that severe maternal morbidity includes mechanical ventilation, blood transfusion, and hysterectomy – the more severe maternal adverse outcomes of pregnancy.

Results showed that, of 11,556,136 delivery hospitalizations, 65,331 patients had another cardiac diagnosis, and 3,009 had ischemic heart disease alone. Patients with ischemic heart disease were older, and rates of diabetes and hypertension were higher.

In unadjusted analyses, adverse outcomes were more common among patients with ischemic heart disease alone than among patients with no cardiac disease and mild cardiac conditions (mWHO class I-II cardiac disease).

Of those with preexisting ischemic heart disease, 6.6% experienced severe maternal morbidity or death, compared with 1.5% of those without a cardiac disease (unadjusted relative risk vs. no cardiac disease, 4.3; 95% confidence interval, 3.5-5.2).

In comparison, 4.2% of women with mWHO I-II cardiac diseases and 23.1% of those with more severe mWHO II/III-IV cardiac diseases experienced severe maternal morbidity or death.

Similar differences were noted for nontransfusion severe maternal morbidity and mortality, as well as cardiac severe maternal morbidity and mortality.

After adjustment, ischemic heart disease alone was associated with a higher risk of severe maternal morbidity or death compared to no cardiac disease (adjusted RR, 1.51; 95% CI, 1.19-1.92).

In comparison, the aRR was 1.90 for WHO class I-II diseases and 5.87 (95% CI, 5.49-6.27) for more severe cardiac conditions defined as WHO II/III-IV diseases.

Risk for nontransfusion severe maternal morbidity or death (aRR, 1.60) and cardiac severe maternal morbidity or death (aRR, 2.98) were also higher for those with ischemic heart disease than for women without any cardiac disease.

There were no significant differences in preterm birth for those with preexisting ischemic heart disease compared to those with no cardiac disease after adjustment.

The risk of severe maternal morbidity and mortality, nontransfusion severe maternal morbidity and mortality, and cardiac severe maternal morbidity and mortality for ischemic heart disease alone most closely approximated that of mWHO class I or II cardiac diseases, the researchers said.

“We found that individuals with preexisting ischemic heart disease had a rate of severe maternal morbidity/mortality in the same range as those with other cardiac diagnoses in the mild cardiac disease classification (class I or II),” Dr. Denoble commented.

“This prognosis suggests it is very reasonable for these women to consider pregnancy. The risk of adverse outcomes is not so high that pregnancy is contraindicated,” she added.

Dr. Denoble said this information will be very helpful when counseling women with preexisting ischemic heart disease who are considering pregnancy. “These patients may need some extra monitoring, but in general, they have a high chance of a good outcome,” she noted.

“I would still advise these women to register with a high-risk obstetrics provider to have a baseline cardiovascular pregnancy evaluation. As long as that is reassuring, then further frequent intensive supervision may not be necessary,” she said.

However, the authors pointed out, “it is important to communicate to patients that while pregnancy may be considered low risk in the setting of pre-existing ischemic heart disease, 6.6% of patients with pre-existing ischemic heart disease alone did experience severe maternal morbidity or death during the delivery hospitalization.”

They added that other medical comorbidities should be factored into discussions regarding the risks of pregnancy.

The researchers also noted that the study was limited to evaluation of maternal outcomes occurring during the delivery hospitalization and that additional research that assesses rates of maternal adverse cardiac events and maternal morbidity occurring prior to or after the delivery hospitalization would be beneficial.

Future studies examining the potential gradation in risk associated with additional cardiac comorbidities in individuals with preexisting ischemic heart disease would also be worthwhile, they added.

The study was supported by funding from the National Institutes of Health and the Foundation for Women and Girls with Blood Disorders. The authors disclosed no relevant financial relationships.

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

Women with preexisting ischemic heart disease without another cardiac diagnosis have a higher risk of severe maternal morbidity and mortality than women with no cardiac disease, a new study suggests.

However, after adjustment for other comorbidities, the risk associated with isolated preexisting ischemic heart disease without additional evidence of cardiomyopathy was relatively similar to that of other low-risk cardiac diseases.

“These are reassuring findings,” lead author of the study, Anna E. Denoble, MD, Yale University, New Haven, Conn., told this news organization. “The risk is not zero. Women with preexisting ischemic heart disease are at a small increased risk compared to women without preexisting cardiac disease. But with good control of cardiovascular risk factors, these women have a good chance of a positive outcome.”

The study was published online in JACC: Advances.

“To our knowledge, this study provides the largest analysis to date examining the risk of severe morbidity and mortality among pregnant people with pre-existing ischemic heart disease,” the authors noted.

Dr. Denoble, a maternal and fetal medicine specialist, explained that in recent years, there has been an increase in the number of patients with preexisting ischemic heart disease who are considering pregnancy or who are pregnant when they present, but there is little information on outcomes for these patients.

The diagnosis of ischemic heart disease is not included in the main classification used for heart disease in pregnancy – the modified World Health Organization classification, Dr. Denoble noted. “This classification includes information on pregnancy outcomes in women with many cardiac conditions, including arrhythmias, congenital heart disease, heart failure, and aortic aneurysm, but ischemic heart disease is missing.”

She suggested this is probably because ischemic heart disease is regarded as a condition that occurs mainly in older people. “But we are seeing more and more women with ischemic heart disease who are pregnant or considering pregnancy. This could be because women are now often older when considering pregnancy, and also risk factors for ischemic heart disease, such as obesity and diabetes, are becoming more frequent in younger women.”

The researchers conducted the current study to investigate pregnancy outcomes for these women.

The retrospective cohort study analyzed data from the Nationwide Readmissions Database on women who had experienced a delivery hospitalization from Oct. 1, 2015, to Dec. 31, 2018. They compared outcomes for women with isolated preexisting ischemic heart disease with those of women who had no apparent cardiac condition and to those with mild or more severe cardiac conditions included in the mWHO classification after controlling for other comorbidities.

The primary outcome was severe maternal morbidity or death. Dr. Denoble explained that severe maternal morbidity includes mechanical ventilation, blood transfusion, and hysterectomy – the more severe maternal adverse outcomes of pregnancy.

Results showed that, of 11,556,136 delivery hospitalizations, 65,331 patients had another cardiac diagnosis, and 3,009 had ischemic heart disease alone. Patients with ischemic heart disease were older, and rates of diabetes and hypertension were higher.

In unadjusted analyses, adverse outcomes were more common among patients with ischemic heart disease alone than among patients with no cardiac disease and mild cardiac conditions (mWHO class I-II cardiac disease).

Of those with preexisting ischemic heart disease, 6.6% experienced severe maternal morbidity or death, compared with 1.5% of those without a cardiac disease (unadjusted relative risk vs. no cardiac disease, 4.3; 95% confidence interval, 3.5-5.2).

In comparison, 4.2% of women with mWHO I-II cardiac diseases and 23.1% of those with more severe mWHO II/III-IV cardiac diseases experienced severe maternal morbidity or death.

Similar differences were noted for nontransfusion severe maternal morbidity and mortality, as well as cardiac severe maternal morbidity and mortality.

After adjustment, ischemic heart disease alone was associated with a higher risk of severe maternal morbidity or death compared to no cardiac disease (adjusted RR, 1.51; 95% CI, 1.19-1.92).

In comparison, the aRR was 1.90 for WHO class I-II diseases and 5.87 (95% CI, 5.49-6.27) for more severe cardiac conditions defined as WHO II/III-IV diseases.

Risk for nontransfusion severe maternal morbidity or death (aRR, 1.60) and cardiac severe maternal morbidity or death (aRR, 2.98) were also higher for those with ischemic heart disease than for women without any cardiac disease.

There were no significant differences in preterm birth for those with preexisting ischemic heart disease compared to those with no cardiac disease after adjustment.

The risk of severe maternal morbidity and mortality, nontransfusion severe maternal morbidity and mortality, and cardiac severe maternal morbidity and mortality for ischemic heart disease alone most closely approximated that of mWHO class I or II cardiac diseases, the researchers said.

“We found that individuals with preexisting ischemic heart disease had a rate of severe maternal morbidity/mortality in the same range as those with other cardiac diagnoses in the mild cardiac disease classification (class I or II),” Dr. Denoble commented.

“This prognosis suggests it is very reasonable for these women to consider pregnancy. The risk of adverse outcomes is not so high that pregnancy is contraindicated,” she added.

Dr. Denoble said this information will be very helpful when counseling women with preexisting ischemic heart disease who are considering pregnancy. “These patients may need some extra monitoring, but in general, they have a high chance of a good outcome,” she noted.

“I would still advise these women to register with a high-risk obstetrics provider to have a baseline cardiovascular pregnancy evaluation. As long as that is reassuring, then further frequent intensive supervision may not be necessary,” she said.

However, the authors pointed out, “it is important to communicate to patients that while pregnancy may be considered low risk in the setting of pre-existing ischemic heart disease, 6.6% of patients with pre-existing ischemic heart disease alone did experience severe maternal morbidity or death during the delivery hospitalization.”

They added that other medical comorbidities should be factored into discussions regarding the risks of pregnancy.

The researchers also noted that the study was limited to evaluation of maternal outcomes occurring during the delivery hospitalization and that additional research that assesses rates of maternal adverse cardiac events and maternal morbidity occurring prior to or after the delivery hospitalization would be beneficial.

Future studies examining the potential gradation in risk associated with additional cardiac comorbidities in individuals with preexisting ischemic heart disease would also be worthwhile, they added.

The study was supported by funding from the National Institutes of Health and the Foundation for Women and Girls with Blood Disorders. The authors disclosed no relevant financial relationships.

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

In a cautiously optimistic report, researchers described pregnancy outcomes in 25 women living with HIV in clinical trials of a new long-acting injectable antiretroviral regimen of cabotegravir and rilpivirine (CAB + RPV).

Among 10 live births, there was one birth defect (congenital ptosis, or droopy eyelid), which was not attributed to the trial drugs. There were no instances of perinatal HIV transmission at delivery or during the 1-year follow-up.

“Long-acting cabotegravir-rilpivirine is the first and only complete injectable regimen potentially available for pregnant women,” first author Parul Patel, PharmD, global medical affairs director for cabotegravir at ViiV Healthcare, said in an interview. The regimen was approved by the U.S. Food and Drug Administration in January 2021 for injections every 4 weeks and in February 2022 for injections every 8 weeks.

“Importantly, it can be dosed monthly or every 2 months,” Patel said. “This could be advantageous for women who are experiencing constant change during pregnancy. This could be a consideration for women who might have problems tolerating oral pills during pregnancy or might have problems with emesis.”

The study was published in HIV Medicine.

“We are really pursuing the development of the long-acting version of cabotegravir in combination with rilpivirine,” Dr. Patel said. “It’s an industry standard during initial development that you start very conservatively and not allow a woman who is pregnant to continue dosing of a drug while still evaluating its overall safety profile. We really want to understand the use of this agent in nonpregnant adults before exposing pregnant women to active treatment.”
 

Pregnancies in trials excluding pregnant women

In the paper, Dr. Patel and her coauthors noted the limited data on pregnant women exposed to CAB + RPV. They analyzed pregnancies in four phase 2b/3/3b clinical trials sponsored by ViiV Healthcare and a compassionate use program. All clinical trial participants first received oral CAB + RPV daily for 4 weeks to assess individual tolerance before the experimental long-acting injection of CAB + RPV every 4 weeks or every 8 weeks.

Women participants were required to use highly effective contraception during the trials and for at least 52 weeks after the last injection. Urine pregnancy tests were given at baseline, before each injection, and when pregnancy was suspected. If a pregnancy was detected, CAB + RPV (oral or long-acting injections) was discontinued and the woman switched to an alternative oral antiretroviral, unless she and her physician decided to continue with injections in the compassionate use program.
 

Pregnancy outcomes

Among 25 reported pregnancies in 22 women during the trial, there were 10 live births. Nine of the mothers who delivered their babies at term had switched to an alternative antiretroviral regimen and maintained virologic suppression throughout pregnancy and post partum, or the last available viral load assessment.

The 10th participant remained on long-acting CAB + RPV during her pregnancy and had a live birth with congenital ptosis that was resolving without treatment at the 4-month ophthalmology consult, the authors wrote. The mother experienced persistent low-level viremia before and throughout her pregnancy.

Two of the pregnancies occurred after the last monthly injection, during the washout period. Other studies have reported that each long-acting drug, CAB and RPV, can be detected more than 1 year after the last injection. In the new report, plasma CAB and RPV washout concentrations during pregnancy were within the range of those in nonpregnant women, the authors wrote.

Among the 14 participants with non–live birth outcomes, 13 switched to an alternative antiretroviral regimen during pregnancy and maintained virologic suppression through pregnancy and post partum, or until their last viral assessment. The remaining participant received long-acting CAB + RPV and continued this treatment for the duration of their pregnancy.

“It’s a very limited data set, so we’re not in a position to be able to make definitive conclusions around long-acting cabotegravir-rilpivirine in pregnancy,” Dr. Patel acknowledged. “But the data that we presented among the 25 women who were exposed to cabotegravir-rilpivirine looks reassuring.”
 

Planned studies during pregnancy

Vani Vannappagari, MBBS, MPH, PhD, global head of epidemiology and real-world evidence at ViiV Healthcare and study coauthor, said in an interview that the initial results are spurring promising new research.

“We are working with an external IMPAACT [International Maternal Pediatric Adolescent AIDS Clinical Trials Network] group on a clinical trial ... to try to determine the appropriate dose of long-acting cabotegravir-rilpivirine during pregnancy,” Dr. Vannappagari said. “The clinical trial will give us the immediate safety, dose information, and viral suppression rates for both the mother and the infant. But long-term safety, especially birth defects and any adverse pregnancy and neonatal outcomes, will come from our antiretroviral pregnancy registry and other noninterventional studies.

“In the very small cohort studied, [in] pregnancies that were continued after exposure to long-acting cabotegravir and rilpivirine in the first trimester, there were no significant adverse fetal outcomes identified,” he said. “That’s reassuring, as is the fact that at the time these patients were switched in early pregnancy, their viral loads were all undetectable at the time that their pregnancies were diagnosed.”

Neil Silverman, MD, professor of clinical obstetrics and gynecology and director of the Infections in Pregnancy Program at the University of California, Los Angeles, Medical Center, who was not associated with the study, provided a comment to this news organization.

“The larger question still remains why pregnant women were so actively excluded from the original study design when this trial was evaluating a newer long-acting preparation of two anti-HIV medications that otherwise would be perfectly fine to use during pregnancy?”

Dr. Silverman continued, “In this case, it’s particularly frustrating since the present study was simply evaluating established medications currently being used to manage HIV infection, but in a newer longer-acting mode of administration by an injection every 2 months. If a patient had already been successfully managed on an oral antiviral regimen containing an integrase inhibitor and a non-nucleoside reverse transcriptase inhibitor, like the two drugs studied here, it would not be considered reasonable to switch that regimen simply because she was found to be pregnant.”

Dr. Patel and Dr. Vannappagari are employees of ViiV Healthcare and stockholders of GlaxoSmithKline.

This analysis was funded by ViiV Healthcare, and all studies were cofunded by ViiV Healthcare and Janssen Research & Development. Dr. Silverman reported no relevant financial relationships.

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

In a cautiously optimistic report, researchers described pregnancy outcomes in 25 women living with HIV in clinical trials of a new long-acting injectable antiretroviral regimen of cabotegravir and rilpivirine (CAB + RPV).

Among 10 live births, there was one birth defect (congenital ptosis, or droopy eyelid), which was not attributed to the trial drugs. There were no instances of perinatal HIV transmission at delivery or during the 1-year follow-up.

“Long-acting cabotegravir-rilpivirine is the first and only complete injectable regimen potentially available for pregnant women,” first author Parul Patel, PharmD, global medical affairs director for cabotegravir at ViiV Healthcare, said in an interview. The regimen was approved by the U.S. Food and Drug Administration in January 2021 for injections every 4 weeks and in February 2022 for injections every 8 weeks.

“Importantly, it can be dosed monthly or every 2 months,” Patel said. “This could be advantageous for women who are experiencing constant change during pregnancy. This could be a consideration for women who might have problems tolerating oral pills during pregnancy or might have problems with emesis.”

The study was published in HIV Medicine.

“We are really pursuing the development of the long-acting version of cabotegravir in combination with rilpivirine,” Dr. Patel said. “It’s an industry standard during initial development that you start very conservatively and not allow a woman who is pregnant to continue dosing of a drug while still evaluating its overall safety profile. We really want to understand the use of this agent in nonpregnant adults before exposing pregnant women to active treatment.”
 

Pregnancies in trials excluding pregnant women

In the paper, Dr. Patel and her coauthors noted the limited data on pregnant women exposed to CAB + RPV. They analyzed pregnancies in four phase 2b/3/3b clinical trials sponsored by ViiV Healthcare and a compassionate use program. All clinical trial participants first received oral CAB + RPV daily for 4 weeks to assess individual tolerance before the experimental long-acting injection of CAB + RPV every 4 weeks or every 8 weeks.

Women participants were required to use highly effective contraception during the trials and for at least 52 weeks after the last injection. Urine pregnancy tests were given at baseline, before each injection, and when pregnancy was suspected. If a pregnancy was detected, CAB + RPV (oral or long-acting injections) was discontinued and the woman switched to an alternative oral antiretroviral, unless she and her physician decided to continue with injections in the compassionate use program.
 

Pregnancy outcomes

Among 25 reported pregnancies in 22 women during the trial, there were 10 live births. Nine of the mothers who delivered their babies at term had switched to an alternative antiretroviral regimen and maintained virologic suppression throughout pregnancy and post partum, or the last available viral load assessment.

The 10th participant remained on long-acting CAB + RPV during her pregnancy and had a live birth with congenital ptosis that was resolving without treatment at the 4-month ophthalmology consult, the authors wrote. The mother experienced persistent low-level viremia before and throughout her pregnancy.

Two of the pregnancies occurred after the last monthly injection, during the washout period. Other studies have reported that each long-acting drug, CAB and RPV, can be detected more than 1 year after the last injection. In the new report, plasma CAB and RPV washout concentrations during pregnancy were within the range of those in nonpregnant women, the authors wrote.

Among the 14 participants with non–live birth outcomes, 13 switched to an alternative antiretroviral regimen during pregnancy and maintained virologic suppression through pregnancy and post partum, or until their last viral assessment. The remaining participant received long-acting CAB + RPV and continued this treatment for the duration of their pregnancy.

“It’s a very limited data set, so we’re not in a position to be able to make definitive conclusions around long-acting cabotegravir-rilpivirine in pregnancy,” Dr. Patel acknowledged. “But the data that we presented among the 25 women who were exposed to cabotegravir-rilpivirine looks reassuring.”
 

Planned studies during pregnancy

Vani Vannappagari, MBBS, MPH, PhD, global head of epidemiology and real-world evidence at ViiV Healthcare and study coauthor, said in an interview that the initial results are spurring promising new research.

“We are working with an external IMPAACT [International Maternal Pediatric Adolescent AIDS Clinical Trials Network] group on a clinical trial ... to try to determine the appropriate dose of long-acting cabotegravir-rilpivirine during pregnancy,” Dr. Vannappagari said. “The clinical trial will give us the immediate safety, dose information, and viral suppression rates for both the mother and the infant. But long-term safety, especially birth defects and any adverse pregnancy and neonatal outcomes, will come from our antiretroviral pregnancy registry and other noninterventional studies.

“In the very small cohort studied, [in] pregnancies that were continued after exposure to long-acting cabotegravir and rilpivirine in the first trimester, there were no significant adverse fetal outcomes identified,” he said. “That’s reassuring, as is the fact that at the time these patients were switched in early pregnancy, their viral loads were all undetectable at the time that their pregnancies were diagnosed.”

Neil Silverman, MD, professor of clinical obstetrics and gynecology and director of the Infections in Pregnancy Program at the University of California, Los Angeles, Medical Center, who was not associated with the study, provided a comment to this news organization.

“The larger question still remains why pregnant women were so actively excluded from the original study design when this trial was evaluating a newer long-acting preparation of two anti-HIV medications that otherwise would be perfectly fine to use during pregnancy?”

Dr. Silverman continued, “In this case, it’s particularly frustrating since the present study was simply evaluating established medications currently being used to manage HIV infection, but in a newer longer-acting mode of administration by an injection every 2 months. If a patient had already been successfully managed on an oral antiviral regimen containing an integrase inhibitor and a non-nucleoside reverse transcriptase inhibitor, like the two drugs studied here, it would not be considered reasonable to switch that regimen simply because she was found to be pregnant.”

Dr. Patel and Dr. Vannappagari are employees of ViiV Healthcare and stockholders of GlaxoSmithKline.

This analysis was funded by ViiV Healthcare, and all studies were cofunded by ViiV Healthcare and Janssen Research & Development. Dr. Silverman reported no relevant financial relationships.

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

In a cautiously optimistic report, researchers described pregnancy outcomes in 25 women living with HIV in clinical trials of a new long-acting injectable antiretroviral regimen of cabotegravir and rilpivirine (CAB + RPV).

Among 10 live births, there was one birth defect (congenital ptosis, or droopy eyelid), which was not attributed to the trial drugs. There were no instances of perinatal HIV transmission at delivery or during the 1-year follow-up.

“Long-acting cabotegravir-rilpivirine is the first and only complete injectable regimen potentially available for pregnant women,” first author Parul Patel, PharmD, global medical affairs director for cabotegravir at ViiV Healthcare, said in an interview. The regimen was approved by the U.S. Food and Drug Administration in January 2021 for injections every 4 weeks and in February 2022 for injections every 8 weeks.

“Importantly, it can be dosed monthly or every 2 months,” Patel said. “This could be advantageous for women who are experiencing constant change during pregnancy. This could be a consideration for women who might have problems tolerating oral pills during pregnancy or might have problems with emesis.”

The study was published in HIV Medicine.

“We are really pursuing the development of the long-acting version of cabotegravir in combination with rilpivirine,” Dr. Patel said. “It’s an industry standard during initial development that you start very conservatively and not allow a woman who is pregnant to continue dosing of a drug while still evaluating its overall safety profile. We really want to understand the use of this agent in nonpregnant adults before exposing pregnant women to active treatment.”
 

Pregnancies in trials excluding pregnant women

In the paper, Dr. Patel and her coauthors noted the limited data on pregnant women exposed to CAB + RPV. They analyzed pregnancies in four phase 2b/3/3b clinical trials sponsored by ViiV Healthcare and a compassionate use program. All clinical trial participants first received oral CAB + RPV daily for 4 weeks to assess individual tolerance before the experimental long-acting injection of CAB + RPV every 4 weeks or every 8 weeks.

Women participants were required to use highly effective contraception during the trials and for at least 52 weeks after the last injection. Urine pregnancy tests were given at baseline, before each injection, and when pregnancy was suspected. If a pregnancy was detected, CAB + RPV (oral or long-acting injections) was discontinued and the woman switched to an alternative oral antiretroviral, unless she and her physician decided to continue with injections in the compassionate use program.
 

Pregnancy outcomes

Among 25 reported pregnancies in 22 women during the trial, there were 10 live births. Nine of the mothers who delivered their babies at term had switched to an alternative antiretroviral regimen and maintained virologic suppression throughout pregnancy and post partum, or the last available viral load assessment.

The 10th participant remained on long-acting CAB + RPV during her pregnancy and had a live birth with congenital ptosis that was resolving without treatment at the 4-month ophthalmology consult, the authors wrote. The mother experienced persistent low-level viremia before and throughout her pregnancy.

Two of the pregnancies occurred after the last monthly injection, during the washout period. Other studies have reported that each long-acting drug, CAB and RPV, can be detected more than 1 year after the last injection. In the new report, plasma CAB and RPV washout concentrations during pregnancy were within the range of those in nonpregnant women, the authors wrote.

Among the 14 participants with non–live birth outcomes, 13 switched to an alternative antiretroviral regimen during pregnancy and maintained virologic suppression through pregnancy and post partum, or until their last viral assessment. The remaining participant received long-acting CAB + RPV and continued this treatment for the duration of their pregnancy.

“It’s a very limited data set, so we’re not in a position to be able to make definitive conclusions around long-acting cabotegravir-rilpivirine in pregnancy,” Dr. Patel acknowledged. “But the data that we presented among the 25 women who were exposed to cabotegravir-rilpivirine looks reassuring.”
 

Planned studies during pregnancy

Vani Vannappagari, MBBS, MPH, PhD, global head of epidemiology and real-world evidence at ViiV Healthcare and study coauthor, said in an interview that the initial results are spurring promising new research.

“We are working with an external IMPAACT [International Maternal Pediatric Adolescent AIDS Clinical Trials Network] group on a clinical trial ... to try to determine the appropriate dose of long-acting cabotegravir-rilpivirine during pregnancy,” Dr. Vannappagari said. “The clinical trial will give us the immediate safety, dose information, and viral suppression rates for both the mother and the infant. But long-term safety, especially birth defects and any adverse pregnancy and neonatal outcomes, will come from our antiretroviral pregnancy registry and other noninterventional studies.

“In the very small cohort studied, [in] pregnancies that were continued after exposure to long-acting cabotegravir and rilpivirine in the first trimester, there were no significant adverse fetal outcomes identified,” he said. “That’s reassuring, as is the fact that at the time these patients were switched in early pregnancy, their viral loads were all undetectable at the time that their pregnancies were diagnosed.”

Neil Silverman, MD, professor of clinical obstetrics and gynecology and director of the Infections in Pregnancy Program at the University of California, Los Angeles, Medical Center, who was not associated with the study, provided a comment to this news organization.

“The larger question still remains why pregnant women were so actively excluded from the original study design when this trial was evaluating a newer long-acting preparation of two anti-HIV medications that otherwise would be perfectly fine to use during pregnancy?”

Dr. Silverman continued, “In this case, it’s particularly frustrating since the present study was simply evaluating established medications currently being used to manage HIV infection, but in a newer longer-acting mode of administration by an injection every 2 months. If a patient had already been successfully managed on an oral antiviral regimen containing an integrase inhibitor and a non-nucleoside reverse transcriptase inhibitor, like the two drugs studied here, it would not be considered reasonable to switch that regimen simply because she was found to be pregnant.”

Dr. Patel and Dr. Vannappagari are employees of ViiV Healthcare and stockholders of GlaxoSmithKline.

This analysis was funded by ViiV Healthcare, and all studies were cofunded by ViiV Healthcare and Janssen Research & Development. Dr. Silverman reported no relevant financial relationships.

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