Women's Health

Violence against women remains a global dilemma in need of attention. Physical violence in particular, is the most prevalent type of violence across all genders, races, and nationalities.

The Centers for Disease Control and Prevention says more than 43 million women and 38 million men report experiencing psychological aggression by an intimate partner in their lifetime. Meanwhile, 11 million women and 5 million men report enduring sexual or physical violence and intimate partner violence (IPV), and/or stalking by an intimate partner during their lifetimes, according to the CDC.1

COVID pandemic’s influence

Isolation tied to the COVID-19 pandemic has been linked to increased IPV. A study conducted by researchers at the University of California, Davis, suggested that extra stress experienced during the COVID-19 pandemic caused by income loss, and the inability to pay for housing and food exacerbated the prevalence of IPV early during the pandemic.⁶

That study, where researchers collected in surveys of nearly 400 adults in the beginning in April 2020 for 10 weeks, showed that more services and communication are needed so that frontline health care and food bank workers, for example, in addition to social workers, doctors, and therapists, can spot the signs and ask clients questions about potential IPV. They could then link survivors to pertinent assistance and resources.

Furthermore, multiple factors probably have played a pivotal role in increasing the prevalence of IPV during the COVID-19 pandemic. For instance, disruption to usual health and social services as well as diminished access to support systems, such as shelters, and charity helplines negatively affected the reporting of domestic violence.

Long before the pandemic, over the past decade, international and national bodies have played a crucial role in terms of improving the awareness and response to domestic violence.^7,8 In addition, several policies have been introduced in countries around the globe emphasizing the need to inquire routinely about domestic violence. Nevertheless, mental health services often fail to adequately address domestic violence in clinical encounters. A systematic review of domestic violence assessment screening performed in a variety of health care settings found that evidence was insufficient to conclude that routine inquiry improved morbidity and mortality among victims of IPV.⁹ So the question becomes: How can we get our patients to tell us about these experiences so we can intervene?
 

Gender differences in perpetuating IPV

Several studies have found that abuse can result in various mental illnesses, such as depression, PTSD, anxiety, and suicidal ideation. Again, men have a disproportionately higher rate of perpetrating IPV, compared with women. This theory has been a source of debate in the academic community for years, but recent research has confirmed that women do perpetuate violence against their partners to some extent.^10,11

Some members of the LGBTQ+ community also report experiencing violence from partners, so as clinicians, we also need to raise our awareness about the existence of violence among same-sex couples. In fact, a team of Italian researchers report more than 50% of gay men and almost 75% of lesbian women reported that they had been psychologically abused by a partner.¹² More research into this area is needed.
 

Our role as health care professionals

The U.S. Preventive Services Task Force advises that all clinic visits include regular IPV screening.¹³ But these screenings are all too rare. In fact, a meta-analysis of 19 trials of more than 1,600 participants showed only 9%-40% of doctors routinely test for IPV.¹⁴ That research clearly shows how important it is for all clinicians to execute IPV screening. However, numerous challenges toward screening exist, including personal discomfort, limited time during appointments, insufficient resources, and inadequate training.

One ongoing debate revolves around which clinician should screen for IPV. Should the psychiatrist carry out this role – or perhaps the primary care physician, nurse, or social worker? These issues become even more fraught when clinicians worry about offending the patient – especially if the clinician is a male.¹⁵

The bottom line is that physicians should inquire about intimate partner violence, because research indicates that women are more likely to reveal abuse when prompted. In addition, during physician appointments, they can use the physician-patient therapeutic connection to conduct a domestic violence evaluation, give resources to victims, and provide ongoing care. Patients who exhibit treatment resistance, persistent pain, depression, sleeplessness, and headaches should prompt psychiatrists to conduct additional investigations into the likelihood of intimate partner violence and domestic abuse.

W also should be attentive when counseling patients about domestic violence when suggesting life-changing events such as pregnancy, employment loss, separation, or divorce. Similar to the recommendations of the USPSTF that all women and men should be screened for IPV, it is suggested that physicians be conscious of facilitating a conversation and not being overtly judgmental while observing body cues. Using the statements such as “we have been hearing a lot of violence in our community lately” could be a segue to introduce the subject.

Asking the question of whether you are being hit rather than being abused has allowed more women to open up more about domestic violence. While physicians are aware that most victims might recant and often go back to their abusers, victims need to be counseled that the abuse might intensify and lead to death.

For women who perpetuate IPV and survivors of IPV, safety is the priority. Physicians should provide safety options and be the facilitators. Studies have shown that fewer victims get the referral to the supporting agencies when IPV is indicated, which puts their safety at risk. In women who commit IPV, clinicians should assess the role of the individual in an IPV disclosure. There are various treatment modalities, whether the violence is performed through self-defense, bidirectionally, or because of aggression.

With the advancement of technology, web-based training on how to ask for IPV, documentation, acknowledgment, and structured referral increase physicians’ confidence when faced with an IPV disclosure than none.¹⁶ Treatment modalities should include medication reconciliation and cognitive-behavioral therapy – focusing on emotion regulation.

Using instruments such as the danger assessment tool can help physicians intervene early, reducing the risk of domestic violence and IPV recurrence instead of using clinical assessment alone.¹⁷ Physicians should convey empathy, validate victims, and help, especially when abuse is reported.

Also, it is important to evaluate survivors’ safety. Counseling can help people rebuild their self-esteem. Structured referrals for psychiatric help and support services are needed to help survivors on the long road to recovery.

Training all physicians, regardless of specialty, is essential to improve prompt IPV identification and bring awareness to resources available to survivors when IPV is disclosed. Although we described an association between IPV victims becoming possible perpetrators of IPV, more long-term studies are required to show the various processes that influence IPV perpetration rates, especially by survivors.

We would also like international and national regulatory bodies to increase the awareness of IPV and adequately address IPV with special emphasis on how mental health services should assess, identify, and respond to services for people who are survivors and perpetrators of IPV.

Dr. Kumari, Dr. Otite, Dr. Afzal, Dr. Alcera, and Dr. Doumas are affiliated with Hackensack Meridian Health at Ocean Medical Center, Brick, N.J. They have no conflicts of interest.

References

1. Centers for Disease Control and Prevention. Preventing intimate partner violence. 2020 Oct 9.

2. Yu R et al. PLOS Med. 16(12):e1002995. doi: 10.1371/journal.pmed.1002995.

3. Oram S et al. Epidemiol Psychiatr Sci. 2014 Dec;23(4):361-76.

4. Munro OE and Sellbom M. Pers Ment Health. 2020 Mar 11. doi: 10.1002/pmh.1480.

5. Sahraian A et al. Asian J Psychiatry. 2020 Jun. doi: 10.1016/j.ajp.2020.102062.

6. Nikos-Rose K. “COVID-19 Isolation Linked to Increased Domestic Violence, Researchers Suggest.” 2021 Feb 24. University of California, Davis.

7. World Health Organization. “Responding to intimate partner violence and sexual violence against women.” WHO clinical policy guidelines. 2013.

8. National Institute for Health and Care Excellence. “Domestic violence and abuse: Multi-agency working.” PH50. 2014 Feb 26.

9. Feder GS et al. Arch Intern Med. 2006;166(1):22-37.

10. Gondolf EW. Violence Against Women. 2014 Dec;20(12)1539-46.

11. Hamberger LK and Larsen SE. J Fam Violence. 2015;30(6):699-717.

12. Rollè L et al. Front Psychol. 21 Aug 2018. doi: 10.3389/fpsyg.2018.01506.

13. Paterno MT and Draughon JE. J Midwif Women Health. 2016;61(31):370-5.

14. Kalra N et al. Cochrane Database Syst Rev. 2021 May 31;5(5)CD012423.

15. Larsen SE and Hamberger LK. J Fam Viol. 2015;30:1007-30.

16. Kalra N et al. Cochrane Database Syst Rev. 2017 Feb;2017(2):CD012423.

17. Campbell JC et al. J Interpers Violence. 2009;24(4):653-74.

Violence against women remains a global dilemma in need of attention. Physical violence in particular, is the most prevalent type of violence across all genders, races, and nationalities.

The Centers for Disease Control and Prevention says more than 43 million women and 38 million men report experiencing psychological aggression by an intimate partner in their lifetime. Meanwhile, 11 million women and 5 million men report enduring sexual or physical violence and intimate partner violence (IPV), and/or stalking by an intimate partner during their lifetimes, according to the CDC.1

COVID pandemic’s influence

Isolation tied to the COVID-19 pandemic has been linked to increased IPV. A study conducted by researchers at the University of California, Davis, suggested that extra stress experienced during the COVID-19 pandemic caused by income loss, and the inability to pay for housing and food exacerbated the prevalence of IPV early during the pandemic.⁶

That study, where researchers collected in surveys of nearly 400 adults in the beginning in April 2020 for 10 weeks, showed that more services and communication are needed so that frontline health care and food bank workers, for example, in addition to social workers, doctors, and therapists, can spot the signs and ask clients questions about potential IPV. They could then link survivors to pertinent assistance and resources.

Furthermore, multiple factors probably have played a pivotal role in increasing the prevalence of IPV during the COVID-19 pandemic. For instance, disruption to usual health and social services as well as diminished access to support systems, such as shelters, and charity helplines negatively affected the reporting of domestic violence.

Long before the pandemic, over the past decade, international and national bodies have played a crucial role in terms of improving the awareness and response to domestic violence.^7,8 In addition, several policies have been introduced in countries around the globe emphasizing the need to inquire routinely about domestic violence. Nevertheless, mental health services often fail to adequately address domestic violence in clinical encounters. A systematic review of domestic violence assessment screening performed in a variety of health care settings found that evidence was insufficient to conclude that routine inquiry improved morbidity and mortality among victims of IPV.⁹ So the question becomes: How can we get our patients to tell us about these experiences so we can intervene?
 

Gender differences in perpetuating IPV

Several studies have found that abuse can result in various mental illnesses, such as depression, PTSD, anxiety, and suicidal ideation. Again, men have a disproportionately higher rate of perpetrating IPV, compared with women. This theory has been a source of debate in the academic community for years, but recent research has confirmed that women do perpetuate violence against their partners to some extent.^10,11

Some members of the LGBTQ+ community also report experiencing violence from partners, so as clinicians, we also need to raise our awareness about the existence of violence among same-sex couples. In fact, a team of Italian researchers report more than 50% of gay men and almost 75% of lesbian women reported that they had been psychologically abused by a partner.¹² More research into this area is needed.
 

Our role as health care professionals

The U.S. Preventive Services Task Force advises that all clinic visits include regular IPV screening.¹³ But these screenings are all too rare. In fact, a meta-analysis of 19 trials of more than 1,600 participants showed only 9%-40% of doctors routinely test for IPV.¹⁴ That research clearly shows how important it is for all clinicians to execute IPV screening. However, numerous challenges toward screening exist, including personal discomfort, limited time during appointments, insufficient resources, and inadequate training.

One ongoing debate revolves around which clinician should screen for IPV. Should the psychiatrist carry out this role – or perhaps the primary care physician, nurse, or social worker? These issues become even more fraught when clinicians worry about offending the patient – especially if the clinician is a male.¹⁵

The bottom line is that physicians should inquire about intimate partner violence, because research indicates that women are more likely to reveal abuse when prompted. In addition, during physician appointments, they can use the physician-patient therapeutic connection to conduct a domestic violence evaluation, give resources to victims, and provide ongoing care. Patients who exhibit treatment resistance, persistent pain, depression, sleeplessness, and headaches should prompt psychiatrists to conduct additional investigations into the likelihood of intimate partner violence and domestic abuse.

W also should be attentive when counseling patients about domestic violence when suggesting life-changing events such as pregnancy, employment loss, separation, or divorce. Similar to the recommendations of the USPSTF that all women and men should be screened for IPV, it is suggested that physicians be conscious of facilitating a conversation and not being overtly judgmental while observing body cues. Using the statements such as “we have been hearing a lot of violence in our community lately” could be a segue to introduce the subject.

Asking the question of whether you are being hit rather than being abused has allowed more women to open up more about domestic violence. While physicians are aware that most victims might recant and often go back to their abusers, victims need to be counseled that the abuse might intensify and lead to death.

For women who perpetuate IPV and survivors of IPV, safety is the priority. Physicians should provide safety options and be the facilitators. Studies have shown that fewer victims get the referral to the supporting agencies when IPV is indicated, which puts their safety at risk. In women who commit IPV, clinicians should assess the role of the individual in an IPV disclosure. There are various treatment modalities, whether the violence is performed through self-defense, bidirectionally, or because of aggression.

With the advancement of technology, web-based training on how to ask for IPV, documentation, acknowledgment, and structured referral increase physicians’ confidence when faced with an IPV disclosure than none.¹⁶ Treatment modalities should include medication reconciliation and cognitive-behavioral therapy – focusing on emotion regulation.

Using instruments such as the danger assessment tool can help physicians intervene early, reducing the risk of domestic violence and IPV recurrence instead of using clinical assessment alone.¹⁷ Physicians should convey empathy, validate victims, and help, especially when abuse is reported.

Also, it is important to evaluate survivors’ safety. Counseling can help people rebuild their self-esteem. Structured referrals for psychiatric help and support services are needed to help survivors on the long road to recovery.

Training all physicians, regardless of specialty, is essential to improve prompt IPV identification and bring awareness to resources available to survivors when IPV is disclosed. Although we described an association between IPV victims becoming possible perpetrators of IPV, more long-term studies are required to show the various processes that influence IPV perpetration rates, especially by survivors.

We would also like international and national regulatory bodies to increase the awareness of IPV and adequately address IPV with special emphasis on how mental health services should assess, identify, and respond to services for people who are survivors and perpetrators of IPV.

Dr. Kumari, Dr. Otite, Dr. Afzal, Dr. Alcera, and Dr. Doumas are affiliated with Hackensack Meridian Health at Ocean Medical Center, Brick, N.J. They have no conflicts of interest.

References

1. Centers for Disease Control and Prevention. Preventing intimate partner violence. 2020 Oct 9.

2. Yu R et al. PLOS Med. 16(12):e1002995. doi: 10.1371/journal.pmed.1002995.

3. Oram S et al. Epidemiol Psychiatr Sci. 2014 Dec;23(4):361-76.

4. Munro OE and Sellbom M. Pers Ment Health. 2020 Mar 11. doi: 10.1002/pmh.1480.

5. Sahraian A et al. Asian J Psychiatry. 2020 Jun. doi: 10.1016/j.ajp.2020.102062.

6. Nikos-Rose K. “COVID-19 Isolation Linked to Increased Domestic Violence, Researchers Suggest.” 2021 Feb 24. University of California, Davis.

7. World Health Organization. “Responding to intimate partner violence and sexual violence against women.” WHO clinical policy guidelines. 2013.

8. National Institute for Health and Care Excellence. “Domestic violence and abuse: Multi-agency working.” PH50. 2014 Feb 26.

9. Feder GS et al. Arch Intern Med. 2006;166(1):22-37.

10. Gondolf EW. Violence Against Women. 2014 Dec;20(12)1539-46.

11. Hamberger LK and Larsen SE. J Fam Violence. 2015;30(6):699-717.

12. Rollè L et al. Front Psychol. 21 Aug 2018. doi: 10.3389/fpsyg.2018.01506.

13. Paterno MT and Draughon JE. J Midwif Women Health. 2016;61(31):370-5.

14. Kalra N et al. Cochrane Database Syst Rev. 2021 May 31;5(5)CD012423.

15. Larsen SE and Hamberger LK. J Fam Viol. 2015;30:1007-30.

16. Kalra N et al. Cochrane Database Syst Rev. 2017 Feb;2017(2):CD012423.

17. Campbell JC et al. J Interpers Violence. 2009;24(4):653-74.

Violence against women remains a global dilemma in need of attention. Physical violence in particular, is the most prevalent type of violence across all genders, races, and nationalities.

The Centers for Disease Control and Prevention says more than 43 million women and 38 million men report experiencing psychological aggression by an intimate partner in their lifetime. Meanwhile, 11 million women and 5 million men report enduring sexual or physical violence and intimate partner violence (IPV), and/or stalking by an intimate partner during their lifetimes, according to the CDC.1

COVID pandemic’s influence

Isolation tied to the COVID-19 pandemic has been linked to increased IPV. A study conducted by researchers at the University of California, Davis, suggested that extra stress experienced during the COVID-19 pandemic caused by income loss, and the inability to pay for housing and food exacerbated the prevalence of IPV early during the pandemic.⁶

That study, where researchers collected in surveys of nearly 400 adults in the beginning in April 2020 for 10 weeks, showed that more services and communication are needed so that frontline health care and food bank workers, for example, in addition to social workers, doctors, and therapists, can spot the signs and ask clients questions about potential IPV. They could then link survivors to pertinent assistance and resources.

Furthermore, multiple factors probably have played a pivotal role in increasing the prevalence of IPV during the COVID-19 pandemic. For instance, disruption to usual health and social services as well as diminished access to support systems, such as shelters, and charity helplines negatively affected the reporting of domestic violence.

Long before the pandemic, over the past decade, international and national bodies have played a crucial role in terms of improving the awareness and response to domestic violence.^7,8 In addition, several policies have been introduced in countries around the globe emphasizing the need to inquire routinely about domestic violence. Nevertheless, mental health services often fail to adequately address domestic violence in clinical encounters. A systematic review of domestic violence assessment screening performed in a variety of health care settings found that evidence was insufficient to conclude that routine inquiry improved morbidity and mortality among victims of IPV.⁹ So the question becomes: How can we get our patients to tell us about these experiences so we can intervene?
 

Gender differences in perpetuating IPV

Several studies have found that abuse can result in various mental illnesses, such as depression, PTSD, anxiety, and suicidal ideation. Again, men have a disproportionately higher rate of perpetrating IPV, compared with women. This theory has been a source of debate in the academic community for years, but recent research has confirmed that women do perpetuate violence against their partners to some extent.^10,11

Some members of the LGBTQ+ community also report experiencing violence from partners, so as clinicians, we also need to raise our awareness about the existence of violence among same-sex couples. In fact, a team of Italian researchers report more than 50% of gay men and almost 75% of lesbian women reported that they had been psychologically abused by a partner.¹² More research into this area is needed.
 

Our role as health care professionals

The U.S. Preventive Services Task Force advises that all clinic visits include regular IPV screening.¹³ But these screenings are all too rare. In fact, a meta-analysis of 19 trials of more than 1,600 participants showed only 9%-40% of doctors routinely test for IPV.¹⁴ That research clearly shows how important it is for all clinicians to execute IPV screening. However, numerous challenges toward screening exist, including personal discomfort, limited time during appointments, insufficient resources, and inadequate training.

One ongoing debate revolves around which clinician should screen for IPV. Should the psychiatrist carry out this role – or perhaps the primary care physician, nurse, or social worker? These issues become even more fraught when clinicians worry about offending the patient – especially if the clinician is a male.¹⁵

The bottom line is that physicians should inquire about intimate partner violence, because research indicates that women are more likely to reveal abuse when prompted. In addition, during physician appointments, they can use the physician-patient therapeutic connection to conduct a domestic violence evaluation, give resources to victims, and provide ongoing care. Patients who exhibit treatment resistance, persistent pain, depression, sleeplessness, and headaches should prompt psychiatrists to conduct additional investigations into the likelihood of intimate partner violence and domestic abuse.

W also should be attentive when counseling patients about domestic violence when suggesting life-changing events such as pregnancy, employment loss, separation, or divorce. Similar to the recommendations of the USPSTF that all women and men should be screened for IPV, it is suggested that physicians be conscious of facilitating a conversation and not being overtly judgmental while observing body cues. Using the statements such as “we have been hearing a lot of violence in our community lately” could be a segue to introduce the subject.

Asking the question of whether you are being hit rather than being abused has allowed more women to open up more about domestic violence. While physicians are aware that most victims might recant and often go back to their abusers, victims need to be counseled that the abuse might intensify and lead to death.

For women who perpetuate IPV and survivors of IPV, safety is the priority. Physicians should provide safety options and be the facilitators. Studies have shown that fewer victims get the referral to the supporting agencies when IPV is indicated, which puts their safety at risk. In women who commit IPV, clinicians should assess the role of the individual in an IPV disclosure. There are various treatment modalities, whether the violence is performed through self-defense, bidirectionally, or because of aggression.

With the advancement of technology, web-based training on how to ask for IPV, documentation, acknowledgment, and structured referral increase physicians’ confidence when faced with an IPV disclosure than none.¹⁶ Treatment modalities should include medication reconciliation and cognitive-behavioral therapy – focusing on emotion regulation.

Using instruments such as the danger assessment tool can help physicians intervene early, reducing the risk of domestic violence and IPV recurrence instead of using clinical assessment alone.¹⁷ Physicians should convey empathy, validate victims, and help, especially when abuse is reported.

Also, it is important to evaluate survivors’ safety. Counseling can help people rebuild their self-esteem. Structured referrals for psychiatric help and support services are needed to help survivors on the long road to recovery.

Training all physicians, regardless of specialty, is essential to improve prompt IPV identification and bring awareness to resources available to survivors when IPV is disclosed. Although we described an association between IPV victims becoming possible perpetrators of IPV, more long-term studies are required to show the various processes that influence IPV perpetration rates, especially by survivors.

We would also like international and national regulatory bodies to increase the awareness of IPV and adequately address IPV with special emphasis on how mental health services should assess, identify, and respond to services for people who are survivors and perpetrators of IPV.

Dr. Kumari, Dr. Otite, Dr. Afzal, Dr. Alcera, and Dr. Doumas are affiliated with Hackensack Meridian Health at Ocean Medical Center, Brick, N.J. They have no conflicts of interest.

References

1. Centers for Disease Control and Prevention. Preventing intimate partner violence. 2020 Oct 9.

2. Yu R et al. PLOS Med. 16(12):e1002995. doi: 10.1371/journal.pmed.1002995.

3. Oram S et al. Epidemiol Psychiatr Sci. 2014 Dec;23(4):361-76.

4. Munro OE and Sellbom M. Pers Ment Health. 2020 Mar 11. doi: 10.1002/pmh.1480.

5. Sahraian A et al. Asian J Psychiatry. 2020 Jun. doi: 10.1016/j.ajp.2020.102062.

6. Nikos-Rose K. “COVID-19 Isolation Linked to Increased Domestic Violence, Researchers Suggest.” 2021 Feb 24. University of California, Davis.

7. World Health Organization. “Responding to intimate partner violence and sexual violence against women.” WHO clinical policy guidelines. 2013.

8. National Institute for Health and Care Excellence. “Domestic violence and abuse: Multi-agency working.” PH50. 2014 Feb 26.

9. Feder GS et al. Arch Intern Med. 2006;166(1):22-37.

10. Gondolf EW. Violence Against Women. 2014 Dec;20(12)1539-46.

11. Hamberger LK and Larsen SE. J Fam Violence. 2015;30(6):699-717.

12. Rollè L et al. Front Psychol. 21 Aug 2018. doi: 10.3389/fpsyg.2018.01506.

13. Paterno MT and Draughon JE. J Midwif Women Health. 2016;61(31):370-5.

14. Kalra N et al. Cochrane Database Syst Rev. 2021 May 31;5(5)CD012423.

15. Larsen SE and Hamberger LK. J Fam Viol. 2015;30:1007-30.

16. Kalra N et al. Cochrane Database Syst Rev. 2017 Feb;2017(2):CD012423.

17. Campbell JC et al. J Interpers Violence. 2009;24(4):653-74.

Tosha Rogers, MD, is a one-woman HIV prevention evangelist. For nearly a decade now, the Atlanta-based ob/gyn has been on a mission to increase her gynecological colleagues’ awareness and prescribing of the oral HIV prevention pill. At the same time, she’s been tracking the development of a flexible vaginal ring loaded with a month’s worth of the HIV prevention medication dapivirine. That, she thought, would fit easily into women’s lives and into the toolbox of methods women already use to prevent pregnancy.

But now she’s not sure when – or if – the ring will find its way to her patients. In December, the ring’s maker, the International Partnership for Microbicides (IPM), pulled its application for FDA approval for the pre-exposure prophylaxis (PrEP) ring. Now, one year after the World Health Organization recommended the ring for member nations, there appears to be no path forward in the United States for either the dapivirine-only ring or an approach Dr. Rogers said would change the game: a vaginal ring that supplies both contraception and HIV prevention.

“It would take things to a whole other level,” she said. “It sucks that this happened, and I do think it was not anything medical. I think it was everything political.”

That leaves cisgender women – especially the Black and Latinx women who make up the vast majority of women who acquire HIV every year – with two HIV prevention options. One is the daily pill, first approved in 2012. It’s now generic but previously sold as Truvada by Gilead Sciences. The other is monthly injectable cabotegravir long-acting (Apretude). Another HIV prevention pill, tenofovir alafenamide/emtricitabine (Descovy), is approved for gay men and transgender women but not cisgender women.
 

Vagina-specific protection from HIV

The WHO recommendation for the vaginal ring was followed last July by a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) for women in low- and middle-income countries outside the European Union.

The flexible silicone ring, similar to the hormonal NuvaRing contraceptive, works by slowly releasing the antiretroviral dapivirine directly into the vaginal canal, thereby protecting women who might be exposed to the virus through vaginal sex only. Because the medicine stays where it’s delivered and doesn’t circulate through the body, it has been found to be extremely safe with few adverse events.

However, in initial studies, the ring was found to be just 27% effective overall. Later studies, where scientists divided women by how much drug was missing from the ring – a proxy for use – found that higher use was associated with higher protection (as much as 54%). By comparison, Truvada has been found to be up to 99% effective when used daily, though it can take up to 21 days to be available in the vagina in high enough concentrations to protect women from vaginal exposure. And the HIV prevention shot was found to be 90% more effective than that in a recent trial of the two methods conducted by the HIV Prevention Trials Network.

This, and an orientation away from topical HIV prevention drugs and toward systemic options, led the National Institute of Allergy and Infectious Diseases (NIAID) to discontinue funding for such projects under its Microbicide Trials Network.

“Clearly you want to counsel women to use the highest efficacy method, and that is part of our label,” Zeda Rosenberg, ScD, IPM’s founder and chief executive officer, told this news organization. “Women should not choose the ring if they can and will use oral PrEP, and I would argue it should be the same thing for [cabotegravir shots]. But if they can’t or don’t want to – and we know that especially many young women don’t want to use systemic methods – then the dapivirine ring is a great option.”

Still, Dr. Rosenberg said that the gap in efficacy, the relatively small number of women affected by HIV in the U.S. compared with gay and bisexual men, and the emergence of products like the HIV prevention shot cabotegravir, made it “very unlikely” that FDA regulators would approve the ring. And rather than be “distracted” by the FDA process, Dr. Rosenberg said IPM chose to concentrate on the countries where the ring has already been approved or where women make up the vast majority of people affected by HIV.

Zimbabwe publicly announced it has approved the ring, and three other countries may have approved it, according to Dr. Rosenberg. She declined to name them, saying they had requested silence while they formulate their new HIV prevention guidelines. Aside from Zimbabwe, the other countries where women participated in the ring clinical trials were South Africa, Malawi, and Uganda.

“The U.S. population ... has widespread access to oral PrEP, which is unlike countries in Africa, and which would have widespread access to injectable cabotegravir,” she said. “The U.S. FDA may not see choice in the same way that African women and African activists and advocates see the need for choice.”

But women’s rates of accessing HIV prevention medications in the U.S. continues to be frustratingly low. At the end of 2018, just 7% of women who could benefit from HIV prevention drugs were taking them, according to Centers for Disease Control and Prevention data.

New CDC guidelines recommend clinicians talk to every sexually active adult and adolescent about HIV prevention medications at least once and prescribe it to anyone who asks for it, whether or not they understand their patients’ HIV risks. However, research continues to show that clinicians struggle with willingness to prescribe PrEP to Black women, and the American College of Obstetrics and Gynecology’s committee opinion on managing women using HIV prevention drugs has not been updated to reflect the new guidelines. And while the HIV prevention shot is approved for women and its maker ViiV Healthcare is already initiating postmarket studies of the ring in key populations including women, there are lots of things that need to line up in order for clinicians to be willing to stock it and prescribe it to women.

From where Dázon Dixon Diallo, executive director of the nonprofit SisterLove, sits, the decision to withdraw the ring from FDA consideration and the FDA’s seeming argument that the epidemiology in the U.S. doesn’t warrant the ring’s approval is a slap in the face to the Black women who have led the movement to end HIV in the U.S. for decades.

“No matter how you slice it, we’re talking about Black women, and then we’re talking about brown women,” said Ms. Diallo. “The value [they place on us] from a government standpoint, from a political standpoint, from a public health standpoint is just woeful. It’s woeful and it’s disrespectful and it’s insulting and I’m sick of it.”
 

‘America sneezes and Africa catches a cold’

When she first heard the decision to pull the ring from FDA consideration, Yvette Raphael, the South Africa-based executive director of Advocates for the Prevention of HIV in Africa, started asking, “What can we do to help our sisters in America get this ring?” And then she started worrying about other women in her own country and those nearby.

“The FDA plays a big role,” she said. “You know, America sneezes and Africa catches a cold.”

She worries that IPM’s decision to withdraw the ring from FDA consideration will signal to regulators in other countries either (a) that they should not approve it or (b) in countries where it’s already been approved but guidelines have not been issued, that they won’t invest money in rolling it out to women in those countries – especially now with the U.S. approval of the prevention shot. In much of Africa, ministries of health prefer to provide injectable contraception, often giving women few or no other options. But women, she said, think about more than administration of the drug. They look at if it’s an easier option for them to manage.

“This is a long journey, an emotional one too, for women in South Africa, because the idea of a microbicide is one of the ideas that came directly from women in South Africa,” she said. “[The jab] can be seen as a solution to all. We can just give jabs to all the women. And after all, we know that women don’t adhere, so we can just grab them.”

Dr. Rosenberg pointed to the positive opinion from the EMA as another “rigorous review” process that she said ought to equally influence ministries of health in countries where women tested the ring. And she pointed to the WHO statement released last month, the same day as IPM’s announcement that it was withdrawing the ring from FDA considerations, recommitting the ring as a good option in sub-Saharan Africa: “The U.S. FDA decision is not based on any new or additional data on efficacy and safety,” it stated. “WHO will continue to support countries as they consider whether to include the [dapivirine vaginal ring]. WHO recognizes that country decisionmaking will vary based on their context and that women’s voices remain central to discussions about their prevention choices.”
 

Dual action ring on the horizon, but not in U.S.

What this means, though, is that the next step in the ring’s development – the combination dapivirine ring with contraceptive levonorgestrel (used in the Mirena intrauterine device) – may not come to the U.S., at least for a long while.

“It’s not out of the question,” Dr. Rosenberg said of conducting HIV/pregnancy prevention ring trials in the U.S. “But without the approval of the dapivirine-only ring by FDA, I imagine they would want to see new efficacy data on dapivirine. That is a very difficult hill to climb. There would have to be an active control group [using oral PrEP or injectable cabotegravir], and it would be very difficult for the dapivirine ring to be able to go head-to-head for either noninferiority and certainly for superiority.”

The study would need to be quite large to get enough results to prove anything, and IPM is a research organization, not a large pharmaceutical company with deep enough pockets to fund that, she said. Raising those funds “would be difficult.”

In addition to NIAID discontinuing its funding for the Microbicides Trials Network, a new 5-year, $85 million research collaboration through USAID hasn’t slated any money to fund trials of the combination HIV prevention and contraceptive ring, according to Dr. Rosenberg.

But that doesn’t mean avenues for its development are closed. NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) is currently funding a phase 1/2 trial of the combination ring, and IPM continues to receive funding from research agencies in Germany, the Netherlands, Denmark, and Ireland. And this means, she said, that the E.U. – not the U.S. – is where they would seek approval for a combination ring first.

That leaves Ms. Rafael and Ms. Diallo debating how to work together to push the FDA – and maybe IPM – to reconsider the ring. For instance, Ms. Diallo suggested that instead of seeking an indication for all women, the FDA might consider the ring for women with very high risk of HIV, such as sex workers or women with HIV positive partners not on treatment. And she said that this has to be bigger than HIV prevention. It has to be about the ways in which women’s health issues in general lag at the FDA. For instance, she pointed to the movement to get contraceptive pills available over the counter, fights against FDA rulings on hormone replacement therapy, and fights for emergency contraception.

In the meantime, ob/gyn Dr. Rogers is expecting access to the ring to follow a similar path as the copper IUD, which migrated to the U.S. from Europe, where it has been among the most popular contraceptive methods for women.

“Contrary to what we may think, we are not innovators, especially for something like this,” she said. “Once we see it is working and doing a good job – that women in Europe love it – then someone here is going to pick it up and make it as if it’s the greatest thing. But for now, I think we’re going to have to take a back seat to Europe.”

Ms. Diallo reports receiving fees from Johnson & Johnson, ViiV Healthcare, and Gilead Sciences. Dr. Rosenberg and Dr. Rogers have disclosed no relevant financial relationships.

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

Tosha Rogers, MD, is a one-woman HIV prevention evangelist. For nearly a decade now, the Atlanta-based ob/gyn has been on a mission to increase her gynecological colleagues’ awareness and prescribing of the oral HIV prevention pill. At the same time, she’s been tracking the development of a flexible vaginal ring loaded with a month’s worth of the HIV prevention medication dapivirine. That, she thought, would fit easily into women’s lives and into the toolbox of methods women already use to prevent pregnancy.

But now she’s not sure when – or if – the ring will find its way to her patients. In December, the ring’s maker, the International Partnership for Microbicides (IPM), pulled its application for FDA approval for the pre-exposure prophylaxis (PrEP) ring. Now, one year after the World Health Organization recommended the ring for member nations, there appears to be no path forward in the United States for either the dapivirine-only ring or an approach Dr. Rogers said would change the game: a vaginal ring that supplies both contraception and HIV prevention.

“It would take things to a whole other level,” she said. “It sucks that this happened, and I do think it was not anything medical. I think it was everything political.”

That leaves cisgender women – especially the Black and Latinx women who make up the vast majority of women who acquire HIV every year – with two HIV prevention options. One is the daily pill, first approved in 2012. It’s now generic but previously sold as Truvada by Gilead Sciences. The other is monthly injectable cabotegravir long-acting (Apretude). Another HIV prevention pill, tenofovir alafenamide/emtricitabine (Descovy), is approved for gay men and transgender women but not cisgender women.
 

Vagina-specific protection from HIV

The WHO recommendation for the vaginal ring was followed last July by a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) for women in low- and middle-income countries outside the European Union.

The flexible silicone ring, similar to the hormonal NuvaRing contraceptive, works by slowly releasing the antiretroviral dapivirine directly into the vaginal canal, thereby protecting women who might be exposed to the virus through vaginal sex only. Because the medicine stays where it’s delivered and doesn’t circulate through the body, it has been found to be extremely safe with few adverse events.

However, in initial studies, the ring was found to be just 27% effective overall. Later studies, where scientists divided women by how much drug was missing from the ring – a proxy for use – found that higher use was associated with higher protection (as much as 54%). By comparison, Truvada has been found to be up to 99% effective when used daily, though it can take up to 21 days to be available in the vagina in high enough concentrations to protect women from vaginal exposure. And the HIV prevention shot was found to be 90% more effective than that in a recent trial of the two methods conducted by the HIV Prevention Trials Network.

This, and an orientation away from topical HIV prevention drugs and toward systemic options, led the National Institute of Allergy and Infectious Diseases (NIAID) to discontinue funding for such projects under its Microbicide Trials Network.

“Clearly you want to counsel women to use the highest efficacy method, and that is part of our label,” Zeda Rosenberg, ScD, IPM’s founder and chief executive officer, told this news organization. “Women should not choose the ring if they can and will use oral PrEP, and I would argue it should be the same thing for [cabotegravir shots]. But if they can’t or don’t want to – and we know that especially many young women don’t want to use systemic methods – then the dapivirine ring is a great option.”

Still, Dr. Rosenberg said that the gap in efficacy, the relatively small number of women affected by HIV in the U.S. compared with gay and bisexual men, and the emergence of products like the HIV prevention shot cabotegravir, made it “very unlikely” that FDA regulators would approve the ring. And rather than be “distracted” by the FDA process, Dr. Rosenberg said IPM chose to concentrate on the countries where the ring has already been approved or where women make up the vast majority of people affected by HIV.

Zimbabwe publicly announced it has approved the ring, and three other countries may have approved it, according to Dr. Rosenberg. She declined to name them, saying they had requested silence while they formulate their new HIV prevention guidelines. Aside from Zimbabwe, the other countries where women participated in the ring clinical trials were South Africa, Malawi, and Uganda.

“The U.S. population ... has widespread access to oral PrEP, which is unlike countries in Africa, and which would have widespread access to injectable cabotegravir,” she said. “The U.S. FDA may not see choice in the same way that African women and African activists and advocates see the need for choice.”

But women’s rates of accessing HIV prevention medications in the U.S. continues to be frustratingly low. At the end of 2018, just 7% of women who could benefit from HIV prevention drugs were taking them, according to Centers for Disease Control and Prevention data.

New CDC guidelines recommend clinicians talk to every sexually active adult and adolescent about HIV prevention medications at least once and prescribe it to anyone who asks for it, whether or not they understand their patients’ HIV risks. However, research continues to show that clinicians struggle with willingness to prescribe PrEP to Black women, and the American College of Obstetrics and Gynecology’s committee opinion on managing women using HIV prevention drugs has not been updated to reflect the new guidelines. And while the HIV prevention shot is approved for women and its maker ViiV Healthcare is already initiating postmarket studies of the ring in key populations including women, there are lots of things that need to line up in order for clinicians to be willing to stock it and prescribe it to women.

From where Dázon Dixon Diallo, executive director of the nonprofit SisterLove, sits, the decision to withdraw the ring from FDA consideration and the FDA’s seeming argument that the epidemiology in the U.S. doesn’t warrant the ring’s approval is a slap in the face to the Black women who have led the movement to end HIV in the U.S. for decades.

“No matter how you slice it, we’re talking about Black women, and then we’re talking about brown women,” said Ms. Diallo. “The value [they place on us] from a government standpoint, from a political standpoint, from a public health standpoint is just woeful. It’s woeful and it’s disrespectful and it’s insulting and I’m sick of it.”
 

‘America sneezes and Africa catches a cold’

When she first heard the decision to pull the ring from FDA consideration, Yvette Raphael, the South Africa-based executive director of Advocates for the Prevention of HIV in Africa, started asking, “What can we do to help our sisters in America get this ring?” And then she started worrying about other women in her own country and those nearby.

“The FDA plays a big role,” she said. “You know, America sneezes and Africa catches a cold.”

She worries that IPM’s decision to withdraw the ring from FDA consideration will signal to regulators in other countries either (a) that they should not approve it or (b) in countries where it’s already been approved but guidelines have not been issued, that they won’t invest money in rolling it out to women in those countries – especially now with the U.S. approval of the prevention shot. In much of Africa, ministries of health prefer to provide injectable contraception, often giving women few or no other options. But women, she said, think about more than administration of the drug. They look at if it’s an easier option for them to manage.

“This is a long journey, an emotional one too, for women in South Africa, because the idea of a microbicide is one of the ideas that came directly from women in South Africa,” she said. “[The jab] can be seen as a solution to all. We can just give jabs to all the women. And after all, we know that women don’t adhere, so we can just grab them.”

Dr. Rosenberg pointed to the positive opinion from the EMA as another “rigorous review” process that she said ought to equally influence ministries of health in countries where women tested the ring. And she pointed to the WHO statement released last month, the same day as IPM’s announcement that it was withdrawing the ring from FDA considerations, recommitting the ring as a good option in sub-Saharan Africa: “The U.S. FDA decision is not based on any new or additional data on efficacy and safety,” it stated. “WHO will continue to support countries as they consider whether to include the [dapivirine vaginal ring]. WHO recognizes that country decisionmaking will vary based on their context and that women’s voices remain central to discussions about their prevention choices.”
 

Dual action ring on the horizon, but not in U.S.

What this means, though, is that the next step in the ring’s development – the combination dapivirine ring with contraceptive levonorgestrel (used in the Mirena intrauterine device) – may not come to the U.S., at least for a long while.

“It’s not out of the question,” Dr. Rosenberg said of conducting HIV/pregnancy prevention ring trials in the U.S. “But without the approval of the dapivirine-only ring by FDA, I imagine they would want to see new efficacy data on dapivirine. That is a very difficult hill to climb. There would have to be an active control group [using oral PrEP or injectable cabotegravir], and it would be very difficult for the dapivirine ring to be able to go head-to-head for either noninferiority and certainly for superiority.”

The study would need to be quite large to get enough results to prove anything, and IPM is a research organization, not a large pharmaceutical company with deep enough pockets to fund that, she said. Raising those funds “would be difficult.”

In addition to NIAID discontinuing its funding for the Microbicides Trials Network, a new 5-year, $85 million research collaboration through USAID hasn’t slated any money to fund trials of the combination HIV prevention and contraceptive ring, according to Dr. Rosenberg.

But that doesn’t mean avenues for its development are closed. NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) is currently funding a phase 1/2 trial of the combination ring, and IPM continues to receive funding from research agencies in Germany, the Netherlands, Denmark, and Ireland. And this means, she said, that the E.U. – not the U.S. – is where they would seek approval for a combination ring first.

That leaves Ms. Rafael and Ms. Diallo debating how to work together to push the FDA – and maybe IPM – to reconsider the ring. For instance, Ms. Diallo suggested that instead of seeking an indication for all women, the FDA might consider the ring for women with very high risk of HIV, such as sex workers or women with HIV positive partners not on treatment. And she said that this has to be bigger than HIV prevention. It has to be about the ways in which women’s health issues in general lag at the FDA. For instance, she pointed to the movement to get contraceptive pills available over the counter, fights against FDA rulings on hormone replacement therapy, and fights for emergency contraception.

In the meantime, ob/gyn Dr. Rogers is expecting access to the ring to follow a similar path as the copper IUD, which migrated to the U.S. from Europe, where it has been among the most popular contraceptive methods for women.

“Contrary to what we may think, we are not innovators, especially for something like this,” she said. “Once we see it is working and doing a good job – that women in Europe love it – then someone here is going to pick it up and make it as if it’s the greatest thing. But for now, I think we’re going to have to take a back seat to Europe.”

Ms. Diallo reports receiving fees from Johnson & Johnson, ViiV Healthcare, and Gilead Sciences. Dr. Rosenberg and Dr. Rogers have disclosed no relevant financial relationships.

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

Tosha Rogers, MD, is a one-woman HIV prevention evangelist. For nearly a decade now, the Atlanta-based ob/gyn has been on a mission to increase her gynecological colleagues’ awareness and prescribing of the oral HIV prevention pill. At the same time, she’s been tracking the development of a flexible vaginal ring loaded with a month’s worth of the HIV prevention medication dapivirine. That, she thought, would fit easily into women’s lives and into the toolbox of methods women already use to prevent pregnancy.

But now she’s not sure when – or if – the ring will find its way to her patients. In December, the ring’s maker, the International Partnership for Microbicides (IPM), pulled its application for FDA approval for the pre-exposure prophylaxis (PrEP) ring. Now, one year after the World Health Organization recommended the ring for member nations, there appears to be no path forward in the United States for either the dapivirine-only ring or an approach Dr. Rogers said would change the game: a vaginal ring that supplies both contraception and HIV prevention.

“It would take things to a whole other level,” she said. “It sucks that this happened, and I do think it was not anything medical. I think it was everything political.”

That leaves cisgender women – especially the Black and Latinx women who make up the vast majority of women who acquire HIV every year – with two HIV prevention options. One is the daily pill, first approved in 2012. It’s now generic but previously sold as Truvada by Gilead Sciences. The other is monthly injectable cabotegravir long-acting (Apretude). Another HIV prevention pill, tenofovir alafenamide/emtricitabine (Descovy), is approved for gay men and transgender women but not cisgender women.
 

Vagina-specific protection from HIV

The WHO recommendation for the vaginal ring was followed last July by a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) for women in low- and middle-income countries outside the European Union.

The flexible silicone ring, similar to the hormonal NuvaRing contraceptive, works by slowly releasing the antiretroviral dapivirine directly into the vaginal canal, thereby protecting women who might be exposed to the virus through vaginal sex only. Because the medicine stays where it’s delivered and doesn’t circulate through the body, it has been found to be extremely safe with few adverse events.

However, in initial studies, the ring was found to be just 27% effective overall. Later studies, where scientists divided women by how much drug was missing from the ring – a proxy for use – found that higher use was associated with higher protection (as much as 54%). By comparison, Truvada has been found to be up to 99% effective when used daily, though it can take up to 21 days to be available in the vagina in high enough concentrations to protect women from vaginal exposure. And the HIV prevention shot was found to be 90% more effective than that in a recent trial of the two methods conducted by the HIV Prevention Trials Network.

This, and an orientation away from topical HIV prevention drugs and toward systemic options, led the National Institute of Allergy and Infectious Diseases (NIAID) to discontinue funding for such projects under its Microbicide Trials Network.

“Clearly you want to counsel women to use the highest efficacy method, and that is part of our label,” Zeda Rosenberg, ScD, IPM’s founder and chief executive officer, told this news organization. “Women should not choose the ring if they can and will use oral PrEP, and I would argue it should be the same thing for [cabotegravir shots]. But if they can’t or don’t want to – and we know that especially many young women don’t want to use systemic methods – then the dapivirine ring is a great option.”

Still, Dr. Rosenberg said that the gap in efficacy, the relatively small number of women affected by HIV in the U.S. compared with gay and bisexual men, and the emergence of products like the HIV prevention shot cabotegravir, made it “very unlikely” that FDA regulators would approve the ring. And rather than be “distracted” by the FDA process, Dr. Rosenberg said IPM chose to concentrate on the countries where the ring has already been approved or where women make up the vast majority of people affected by HIV.

Zimbabwe publicly announced it has approved the ring, and three other countries may have approved it, according to Dr. Rosenberg. She declined to name them, saying they had requested silence while they formulate their new HIV prevention guidelines. Aside from Zimbabwe, the other countries where women participated in the ring clinical trials were South Africa, Malawi, and Uganda.

“The U.S. population ... has widespread access to oral PrEP, which is unlike countries in Africa, and which would have widespread access to injectable cabotegravir,” she said. “The U.S. FDA may not see choice in the same way that African women and African activists and advocates see the need for choice.”

But women’s rates of accessing HIV prevention medications in the U.S. continues to be frustratingly low. At the end of 2018, just 7% of women who could benefit from HIV prevention drugs were taking them, according to Centers for Disease Control and Prevention data.

New CDC guidelines recommend clinicians talk to every sexually active adult and adolescent about HIV prevention medications at least once and prescribe it to anyone who asks for it, whether or not they understand their patients’ HIV risks. However, research continues to show that clinicians struggle with willingness to prescribe PrEP to Black women, and the American College of Obstetrics and Gynecology’s committee opinion on managing women using HIV prevention drugs has not been updated to reflect the new guidelines. And while the HIV prevention shot is approved for women and its maker ViiV Healthcare is already initiating postmarket studies of the ring in key populations including women, there are lots of things that need to line up in order for clinicians to be willing to stock it and prescribe it to women.

From where Dázon Dixon Diallo, executive director of the nonprofit SisterLove, sits, the decision to withdraw the ring from FDA consideration and the FDA’s seeming argument that the epidemiology in the U.S. doesn’t warrant the ring’s approval is a slap in the face to the Black women who have led the movement to end HIV in the U.S. for decades.

“No matter how you slice it, we’re talking about Black women, and then we’re talking about brown women,” said Ms. Diallo. “The value [they place on us] from a government standpoint, from a political standpoint, from a public health standpoint is just woeful. It’s woeful and it’s disrespectful and it’s insulting and I’m sick of it.”
 

‘America sneezes and Africa catches a cold’

When she first heard the decision to pull the ring from FDA consideration, Yvette Raphael, the South Africa-based executive director of Advocates for the Prevention of HIV in Africa, started asking, “What can we do to help our sisters in America get this ring?” And then she started worrying about other women in her own country and those nearby.

“The FDA plays a big role,” she said. “You know, America sneezes and Africa catches a cold.”

She worries that IPM’s decision to withdraw the ring from FDA consideration will signal to regulators in other countries either (a) that they should not approve it or (b) in countries where it’s already been approved but guidelines have not been issued, that they won’t invest money in rolling it out to women in those countries – especially now with the U.S. approval of the prevention shot. In much of Africa, ministries of health prefer to provide injectable contraception, often giving women few or no other options. But women, she said, think about more than administration of the drug. They look at if it’s an easier option for them to manage.

“This is a long journey, an emotional one too, for women in South Africa, because the idea of a microbicide is one of the ideas that came directly from women in South Africa,” she said. “[The jab] can be seen as a solution to all. We can just give jabs to all the women. And after all, we know that women don’t adhere, so we can just grab them.”

Dr. Rosenberg pointed to the positive opinion from the EMA as another “rigorous review” process that she said ought to equally influence ministries of health in countries where women tested the ring. And she pointed to the WHO statement released last month, the same day as IPM’s announcement that it was withdrawing the ring from FDA considerations, recommitting the ring as a good option in sub-Saharan Africa: “The U.S. FDA decision is not based on any new or additional data on efficacy and safety,” it stated. “WHO will continue to support countries as they consider whether to include the [dapivirine vaginal ring]. WHO recognizes that country decisionmaking will vary based on their context and that women’s voices remain central to discussions about their prevention choices.”
 

Dual action ring on the horizon, but not in U.S.

What this means, though, is that the next step in the ring’s development – the combination dapivirine ring with contraceptive levonorgestrel (used in the Mirena intrauterine device) – may not come to the U.S., at least for a long while.

“It’s not out of the question,” Dr. Rosenberg said of conducting HIV/pregnancy prevention ring trials in the U.S. “But without the approval of the dapivirine-only ring by FDA, I imagine they would want to see new efficacy data on dapivirine. That is a very difficult hill to climb. There would have to be an active control group [using oral PrEP or injectable cabotegravir], and it would be very difficult for the dapivirine ring to be able to go head-to-head for either noninferiority and certainly for superiority.”

The study would need to be quite large to get enough results to prove anything, and IPM is a research organization, not a large pharmaceutical company with deep enough pockets to fund that, she said. Raising those funds “would be difficult.”

In addition to NIAID discontinuing its funding for the Microbicides Trials Network, a new 5-year, $85 million research collaboration through USAID hasn’t slated any money to fund trials of the combination HIV prevention and contraceptive ring, according to Dr. Rosenberg.

But that doesn’t mean avenues for its development are closed. NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) is currently funding a phase 1/2 trial of the combination ring, and IPM continues to receive funding from research agencies in Germany, the Netherlands, Denmark, and Ireland. And this means, she said, that the E.U. – not the U.S. – is where they would seek approval for a combination ring first.

That leaves Ms. Rafael and Ms. Diallo debating how to work together to push the FDA – and maybe IPM – to reconsider the ring. For instance, Ms. Diallo suggested that instead of seeking an indication for all women, the FDA might consider the ring for women with very high risk of HIV, such as sex workers or women with HIV positive partners not on treatment. And she said that this has to be bigger than HIV prevention. It has to be about the ways in which women’s health issues in general lag at the FDA. For instance, she pointed to the movement to get contraceptive pills available over the counter, fights against FDA rulings on hormone replacement therapy, and fights for emergency contraception.

In the meantime, ob/gyn Dr. Rogers is expecting access to the ring to follow a similar path as the copper IUD, which migrated to the U.S. from Europe, where it has been among the most popular contraceptive methods for women.

“Contrary to what we may think, we are not innovators, especially for something like this,” she said. “Once we see it is working and doing a good job – that women in Europe love it – then someone here is going to pick it up and make it as if it’s the greatest thing. But for now, I think we’re going to have to take a back seat to Europe.”

Ms. Diallo reports receiving fees from Johnson & Johnson, ViiV Healthcare, and Gilead Sciences. Dr. Rosenberg and Dr. Rogers have disclosed no relevant financial relationships.

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

A digital algorithm using 24 patient characteristics identifies far more women who are likely to develop a postpartum hemorrhage than currently used tools to predict the risk for bleeding after delivery, according to a study published in the Journal of the American Medical Informatics Association.

About 1 in 10 of the roughly 700 pregnancy-related deaths in the United States are caused by postpartum hemorrhage, according to the U.S. Centers for Disease Control and Prevention. These deaths disproportionately occur among Black women, for whom studies show the risk of dying from a postpartum hemorrhage is fivefold greater than that of White women.

“Postpartum hemorrhage is a preventable medical emergency but remains the leading cause of maternal mortality globally,” the study’s senior author Li Li, MD, senior vice president of clinical informatics at Sema4, a company that uses artificial intelligence and machine learning to develop data-based clinical tools, told this news organization. “Early intervention is critical for reducing postpartum hemorrhage morbidity and mortality.”
 

Porous predictors

Existing tools for risk prediction are not particularly effective, Dr. Li said. For example, the American College of Obstetricians and Gynecologists’ (ACOG) Safe Motherhood Initiative offers checklists of clinical characteristics to classify women as low, medium, or high risk. However, 40% of the women classified as low risk based on this type of tool experience a hemorrhage.

ACOG also recommends quantifying blood loss during delivery or immediately after to identify women who are hemorrhaging, because imprecise estimates from clinicians may delay urgently needed care. Yet many hospitals have not implemented methods for measuring bleeding, said Dr. Li, who also is an assistant professor of genetics and genomic sciences at the Icahn School of Medicine at Mount Sinai, New York.

To develop a more precise way of identifying women at risk, Dr. Li and colleagues turned to artificial intelligence technology to create a “digital phenotype” based on approximately 72,000 births in the Mount Sinai Health System.

The digital tool retrospectively identified about 6,600 cases of postpartum hemorrhage, about 3.8 times the roughly 1,700 cases that would have been predicted based on methods that estimate blood loss. A blinded physician review of a subset of 45 patient charts – including 26 patients who experienced a hemorrhage, 11 who didn’t, and 6 with unclear outcomes – found that the digital approach was 89% percent accurate at identifying cases, whereas blood loss–based methods were accurate 67% of the time.

Several of the 24 characteristics included in the model appear in other risk predictors, including whether a woman has had a previous cesarean delivery or prior postdelivery bleeding and whether she has anemia or related blood disorders. Among the rest were risk factors that have been identified in the literature, including maternal blood pressure, time from admission to delivery, and average pulse during hospitalization. Five more features were new: red blood cell count and distribution width, mean corpuscular hemoglobin, absolute neutrophil count, and white blood cell count.

“These [new] values are easily obtainable from standard blood draws in the hospital but are not currently used in clinical practice to estimate postpartum hemorrhage risk,” Dr. Li said.

In a related retrospective study, Dr. Li and her colleagues used the new tool to classify women into high, low, or medium risk categories. They found that 28% of the women the algorithm classified as high risk experienced a postpartum hemorrhage compared with 15% to 19% of the women classified as high risk by standard predictive tools. They also identified potential “inflection points” where changes in vital signs may suggest a substantial increase in risk. For example, women whose median blood pressure during labor and delivery was above 132 mm Hg had an 11% average increase in their risk for bleeding. 

By more precisely identifying women at risk, the new method “could be used to pre-emptively allocate resources that can ultimately reduce postpartum hemorrhage morbidity and mortality,” Dr. Li said. Sema4 is launching a prospective clinical trial to further assess the algorithm, she added.  
 

Finding the continuum of risk

Holly Ende, MD, an obstetric anesthesiologist at Vanderbilt University Medical Center, Nashville, Tenn., said approaches that leverage electronic health records to identify women at risk for hemorrhage have many advantages over currently used tools.

“Machine learning models or statistical models are able to take into account many more risk factors and weigh each of those risk factors based on how much they contribute to risk,” Dr. Ende, who was not involved in the new studies, told this news organization. “We can stratify women more on a continuum.”

But digital approaches have potential downsides.

“Machine learning algorithms can be developed in such a way that perpetuates racial bias, and it’s important to be aware of potential biases in coded algorithms,” Dr. Li said. To help reduce such bias, they used a database that included a racially and ethnically diverse patient population, but she acknowledged that additional research is needed.

Dr. Ende, the coauthor of a commentary in Obstetrics & Gynecology on risk assessment for postpartum hemorrhage, said algorithm developers must be sensitive to pre-existing disparities in health care that may affect the data they use to build the software.

She pointed to uterine atony – a known risk factor for hemorrhage – as an example. In her own research, she and her colleagues identified women with atony by searching their medical records for medications used to treat the condition. But when they ran their model, Black women were less likely to develop uterine atony, which the team knew wasn’t true in the real world. They traced the problem to an existing disparity in obstetric care: Black women with uterine atony were less likely than women of other races to receive medications for the condition.

“People need to be cognizant as they are developing these types of prediction models and be extremely careful to avoid perpetuating any disparities in care,” Dr. Ende cautioned. On the other hand, if carefully developed, these tools might also help reduce disparities in health care by standardizing risk stratification and clinical practices, she said.

In addition to independent validation of data-based risk prediction tools, Dr. Ende said ensuring that clinicians are properly trained to use these tools is crucial.

“Implementation may be the biggest limitation,” she said.

Dr. Ende and Dr. Li have disclosed no relevant financial relationships.

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

A digital algorithm using 24 patient characteristics identifies far more women who are likely to develop a postpartum hemorrhage than currently used tools to predict the risk for bleeding after delivery, according to a study published in the Journal of the American Medical Informatics Association.

About 1 in 10 of the roughly 700 pregnancy-related deaths in the United States are caused by postpartum hemorrhage, according to the U.S. Centers for Disease Control and Prevention. These deaths disproportionately occur among Black women, for whom studies show the risk of dying from a postpartum hemorrhage is fivefold greater than that of White women.

“Postpartum hemorrhage is a preventable medical emergency but remains the leading cause of maternal mortality globally,” the study’s senior author Li Li, MD, senior vice president of clinical informatics at Sema4, a company that uses artificial intelligence and machine learning to develop data-based clinical tools, told this news organization. “Early intervention is critical for reducing postpartum hemorrhage morbidity and mortality.”
 

Porous predictors

Existing tools for risk prediction are not particularly effective, Dr. Li said. For example, the American College of Obstetricians and Gynecologists’ (ACOG) Safe Motherhood Initiative offers checklists of clinical characteristics to classify women as low, medium, or high risk. However, 40% of the women classified as low risk based on this type of tool experience a hemorrhage.

ACOG also recommends quantifying blood loss during delivery or immediately after to identify women who are hemorrhaging, because imprecise estimates from clinicians may delay urgently needed care. Yet many hospitals have not implemented methods for measuring bleeding, said Dr. Li, who also is an assistant professor of genetics and genomic sciences at the Icahn School of Medicine at Mount Sinai, New York.

To develop a more precise way of identifying women at risk, Dr. Li and colleagues turned to artificial intelligence technology to create a “digital phenotype” based on approximately 72,000 births in the Mount Sinai Health System.

The digital tool retrospectively identified about 6,600 cases of postpartum hemorrhage, about 3.8 times the roughly 1,700 cases that would have been predicted based on methods that estimate blood loss. A blinded physician review of a subset of 45 patient charts – including 26 patients who experienced a hemorrhage, 11 who didn’t, and 6 with unclear outcomes – found that the digital approach was 89% percent accurate at identifying cases, whereas blood loss–based methods were accurate 67% of the time.

Several of the 24 characteristics included in the model appear in other risk predictors, including whether a woman has had a previous cesarean delivery or prior postdelivery bleeding and whether she has anemia or related blood disorders. Among the rest were risk factors that have been identified in the literature, including maternal blood pressure, time from admission to delivery, and average pulse during hospitalization. Five more features were new: red blood cell count and distribution width, mean corpuscular hemoglobin, absolute neutrophil count, and white blood cell count.

“These [new] values are easily obtainable from standard blood draws in the hospital but are not currently used in clinical practice to estimate postpartum hemorrhage risk,” Dr. Li said.

In a related retrospective study, Dr. Li and her colleagues used the new tool to classify women into high, low, or medium risk categories. They found that 28% of the women the algorithm classified as high risk experienced a postpartum hemorrhage compared with 15% to 19% of the women classified as high risk by standard predictive tools. They also identified potential “inflection points” where changes in vital signs may suggest a substantial increase in risk. For example, women whose median blood pressure during labor and delivery was above 132 mm Hg had an 11% average increase in their risk for bleeding. 

By more precisely identifying women at risk, the new method “could be used to pre-emptively allocate resources that can ultimately reduce postpartum hemorrhage morbidity and mortality,” Dr. Li said. Sema4 is launching a prospective clinical trial to further assess the algorithm, she added.  
 

Finding the continuum of risk

Holly Ende, MD, an obstetric anesthesiologist at Vanderbilt University Medical Center, Nashville, Tenn., said approaches that leverage electronic health records to identify women at risk for hemorrhage have many advantages over currently used tools.

“Machine learning models or statistical models are able to take into account many more risk factors and weigh each of those risk factors based on how much they contribute to risk,” Dr. Ende, who was not involved in the new studies, told this news organization. “We can stratify women more on a continuum.”

But digital approaches have potential downsides.

“Machine learning algorithms can be developed in such a way that perpetuates racial bias, and it’s important to be aware of potential biases in coded algorithms,” Dr. Li said. To help reduce such bias, they used a database that included a racially and ethnically diverse patient population, but she acknowledged that additional research is needed.

Dr. Ende, the coauthor of a commentary in Obstetrics & Gynecology on risk assessment for postpartum hemorrhage, said algorithm developers must be sensitive to pre-existing disparities in health care that may affect the data they use to build the software.

She pointed to uterine atony – a known risk factor for hemorrhage – as an example. In her own research, she and her colleagues identified women with atony by searching their medical records for medications used to treat the condition. But when they ran their model, Black women were less likely to develop uterine atony, which the team knew wasn’t true in the real world. They traced the problem to an existing disparity in obstetric care: Black women with uterine atony were less likely than women of other races to receive medications for the condition.

“People need to be cognizant as they are developing these types of prediction models and be extremely careful to avoid perpetuating any disparities in care,” Dr. Ende cautioned. On the other hand, if carefully developed, these tools might also help reduce disparities in health care by standardizing risk stratification and clinical practices, she said.

In addition to independent validation of data-based risk prediction tools, Dr. Ende said ensuring that clinicians are properly trained to use these tools is crucial.

“Implementation may be the biggest limitation,” she said.

Dr. Ende and Dr. Li have disclosed no relevant financial relationships.

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

A digital algorithm using 24 patient characteristics identifies far more women who are likely to develop a postpartum hemorrhage than currently used tools to predict the risk for bleeding after delivery, according to a study published in the Journal of the American Medical Informatics Association.

About 1 in 10 of the roughly 700 pregnancy-related deaths in the United States are caused by postpartum hemorrhage, according to the U.S. Centers for Disease Control and Prevention. These deaths disproportionately occur among Black women, for whom studies show the risk of dying from a postpartum hemorrhage is fivefold greater than that of White women.

“Postpartum hemorrhage is a preventable medical emergency but remains the leading cause of maternal mortality globally,” the study’s senior author Li Li, MD, senior vice president of clinical informatics at Sema4, a company that uses artificial intelligence and machine learning to develop data-based clinical tools, told this news organization. “Early intervention is critical for reducing postpartum hemorrhage morbidity and mortality.”
 

Porous predictors

Existing tools for risk prediction are not particularly effective, Dr. Li said. For example, the American College of Obstetricians and Gynecologists’ (ACOG) Safe Motherhood Initiative offers checklists of clinical characteristics to classify women as low, medium, or high risk. However, 40% of the women classified as low risk based on this type of tool experience a hemorrhage.

ACOG also recommends quantifying blood loss during delivery or immediately after to identify women who are hemorrhaging, because imprecise estimates from clinicians may delay urgently needed care. Yet many hospitals have not implemented methods for measuring bleeding, said Dr. Li, who also is an assistant professor of genetics and genomic sciences at the Icahn School of Medicine at Mount Sinai, New York.

To develop a more precise way of identifying women at risk, Dr. Li and colleagues turned to artificial intelligence technology to create a “digital phenotype” based on approximately 72,000 births in the Mount Sinai Health System.

The digital tool retrospectively identified about 6,600 cases of postpartum hemorrhage, about 3.8 times the roughly 1,700 cases that would have been predicted based on methods that estimate blood loss. A blinded physician review of a subset of 45 patient charts – including 26 patients who experienced a hemorrhage, 11 who didn’t, and 6 with unclear outcomes – found that the digital approach was 89% percent accurate at identifying cases, whereas blood loss–based methods were accurate 67% of the time.

Several of the 24 characteristics included in the model appear in other risk predictors, including whether a woman has had a previous cesarean delivery or prior postdelivery bleeding and whether she has anemia or related blood disorders. Among the rest were risk factors that have been identified in the literature, including maternal blood pressure, time from admission to delivery, and average pulse during hospitalization. Five more features were new: red blood cell count and distribution width, mean corpuscular hemoglobin, absolute neutrophil count, and white blood cell count.

“These [new] values are easily obtainable from standard blood draws in the hospital but are not currently used in clinical practice to estimate postpartum hemorrhage risk,” Dr. Li said.

In a related retrospective study, Dr. Li and her colleagues used the new tool to classify women into high, low, or medium risk categories. They found that 28% of the women the algorithm classified as high risk experienced a postpartum hemorrhage compared with 15% to 19% of the women classified as high risk by standard predictive tools. They also identified potential “inflection points” where changes in vital signs may suggest a substantial increase in risk. For example, women whose median blood pressure during labor and delivery was above 132 mm Hg had an 11% average increase in their risk for bleeding. 

By more precisely identifying women at risk, the new method “could be used to pre-emptively allocate resources that can ultimately reduce postpartum hemorrhage morbidity and mortality,” Dr. Li said. Sema4 is launching a prospective clinical trial to further assess the algorithm, she added.  
 

Finding the continuum of risk

Holly Ende, MD, an obstetric anesthesiologist at Vanderbilt University Medical Center, Nashville, Tenn., said approaches that leverage electronic health records to identify women at risk for hemorrhage have many advantages over currently used tools.

“Machine learning models or statistical models are able to take into account many more risk factors and weigh each of those risk factors based on how much they contribute to risk,” Dr. Ende, who was not involved in the new studies, told this news organization. “We can stratify women more on a continuum.”

But digital approaches have potential downsides.

“Machine learning algorithms can be developed in such a way that perpetuates racial bias, and it’s important to be aware of potential biases in coded algorithms,” Dr. Li said. To help reduce such bias, they used a database that included a racially and ethnically diverse patient population, but she acknowledged that additional research is needed.

Dr. Ende, the coauthor of a commentary in Obstetrics & Gynecology on risk assessment for postpartum hemorrhage, said algorithm developers must be sensitive to pre-existing disparities in health care that may affect the data they use to build the software.

She pointed to uterine atony – a known risk factor for hemorrhage – as an example. In her own research, she and her colleagues identified women with atony by searching their medical records for medications used to treat the condition. But when they ran their model, Black women were less likely to develop uterine atony, which the team knew wasn’t true in the real world. They traced the problem to an existing disparity in obstetric care: Black women with uterine atony were less likely than women of other races to receive medications for the condition.

“People need to be cognizant as they are developing these types of prediction models and be extremely careful to avoid perpetuating any disparities in care,” Dr. Ende cautioned. On the other hand, if carefully developed, these tools might also help reduce disparities in health care by standardizing risk stratification and clinical practices, she said.

In addition to independent validation of data-based risk prediction tools, Dr. Ende said ensuring that clinicians are properly trained to use these tools is crucial.

“Implementation may be the biggest limitation,” she said.

Dr. Ende and Dr. Li have disclosed no relevant financial relationships.

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

An intensive weight-loss intervention prior to conception had no effect on birth rates in women with obesity and unexplained infertility, compared with a standard weight-maintenance program, based on data from nearly 400 women.

Obese women experiencing infertility are often counseled to lose weight before attempting fertility treatments in order to improve outcomes based on epidemiologic evidence of an association between obesity and infertility, but data to support this advice are limited, wrote Richard S. Legro, MD, of Penn State University, Hershey, and colleagues.

The researchers proposed that a more intensive preconception weight loss intervention followed by infertility treatment would be more likely to yield a healthy live birth, compared with a standard weight maintenance intervention.

In an open-label study published in PLOS Medicine, the researchers randomized 379 women at nine academic centers to a standard lifestyle group that followed a weight-maintenance plan focused on physical activity, but not weight loss; or an intensive intervention of diet and medication with a target weight loss of 7%. Both interventions lasted for 16 weeks between July 2015 and July 2018. After the interventions, patients in both groups underwent standardized empiric fertility treatment with three cycles of ovarian stimulation and intrauterine insemination.

The primary outcome was a live birth at 37 weeks’ gestation or later, with no congenital abnormalities and a birth weight between 2,500 g and 4,000 g. Baseline characteristics including age, education level, race, and body mass index (BMI) were similar between the groups.

The incidence of healthy live births was not significantly different between the standard treatment and intensive treatment groups (15.2% vs. 12.2%; P = 0.40) by the final follow-up time of September 2019. However, women in the intensive group had significantly greater weight loss, compared with the standard group (–6.6% vs. –0.3%; P < .001). Women in the intensive group also showed improvements in metabolic health. Notably, the incidence of metabolic syndrome dropped from 53.6% to 49.4% in the standard group, compared with a decrease from 52.8% to 32.2% in the intensive group over the 16-week study period, the researchers wrote.

Gastrointestinal side effects were significantly more common in the intensive group, but these were consistent with documented side effects of the weight loss medication used (Orlistat).

First-trimester pregnancy loss was higher in the intensive group, compared with the standard group (33.3% vs. 23.7%), but the difference was not significant. Most pregnancy complications, including preterm labor, premature rupture of membranes, preeclampsia, and gestational diabetes had nonsignificant improvements in the intensive group, compared with the standard group. Similarly, nonsignificant improvements were noted in the intervention group for intrauterine growth restriction and admission to the neonatal ICU.

Limitations of the study included the relatively small number of pregnancies, which prevented assessment of rare complications in subgroups, and the challenge of matching control interventions, the researchers noted.

However, the results were strengthened by the focus on women with unexplained infertility, the inclusion of a comparison group, and the collection of data on complications after conception, they wrote.

Avenues for future research include interventions of different duration and intensity prior to conception, which may improve outcomes, the researchers said in their discussion of the findings. “A period of weight stabilization and maintenance after a weight-loss intervention prior to commencing infertility therapy is worth exploring,” they noted, but couples eager to conceive may be reluctant to wait for a weight-loss intervention, they added.

“Our findings directly impact current standards of clinical care, where women who are obese with unexplained infertility are to our knowledge routinely counseled to lose weight prior to initiation of infertility treatment,” they concluded.
 

Data may inform patient discussions

The current study is important because a large amount of previous research has shown an association between obesity and decreased fecundity in women and men, Mark P. Trolice, MD, of the University of Central Florida, Orlando, and director of the IVF Center in Winter Park, Fla., said in an interview.

According to the Centers for Disease Control and Prevention, the prevalence of obesity in the United States remains more than 40%, said Dr. Trolice. “Patients and physicians would benefit from clarity of obesity’s effect, if any, on reproduction,” he noted.

In contrast to the authors’ hypothesis, “the study did not find a difference in the live birth rate following up to three cycles of intrauterine insemination (IUI) between an intensive weight loss group [and] women who exercised without weight loss,” said Dr. Trolice. “Prior to this study, many reports suggested a decline in fertility with elevations in BMI, particularly during fertility treatment,” he added.

The take-home message from the current study is a that an elevated BMI, while possibly increasing the risks of metabolic disorders, did not appear to impact fecundity, he said.

The authors therefore concluded, “There is not strong evidence to recommend weight loss prior to conception in women who are obese with unexplained infertility,” Dr. Trolice said.

Regardless of the potential effect of preconception weight loss on fertility, barriers to starting a weight loss program include a woman’s eagerness to move forward with fertility treatments without waiting for weight loss, Dr. Trolice noted. “By the time a woman reaches an infertility specialist, she has been trying to conceive for at least 1 year,” he said. “At the initial consultation, these patients are anxious to undergo necessary additional diagnostic testing followed by treatment. Consequently, initiation of a weight-loss program is viewed as a delay toward the goal of family building,” he explained.

“More research is needed to demonstrate the safety of intensive weight loss preconception,” said Dr. Trolice. However, he said, “the issue of elevated BMI and increased risk of pregnancy complications remains, but this study provides important information for providers regarding counseling their patients desiring pregnancy.”

The study was supported by multiple grants from the National Institutes of Health through the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Center for Advancing Translational Sciences. Nutrisystem provided discounted coupons for food allotments in the standardized treatment group, and FitBit provided the study organizers with discounted Fitbits for activity monitoring. Lead author Dr. Legro disclosed consulting fees from InSupp, Ferring, Bayer, Abbvie and Fractyl, and research sponsorship from Guerbet and the National Institutes of Health. Dr. Trolice had no financial conflicts to disclose and serves on the Editorial Advisory Board of Ob.Gyn News.

An intensive weight-loss intervention prior to conception had no effect on birth rates in women with obesity and unexplained infertility, compared with a standard weight-maintenance program, based on data from nearly 400 women.

Obese women experiencing infertility are often counseled to lose weight before attempting fertility treatments in order to improve outcomes based on epidemiologic evidence of an association between obesity and infertility, but data to support this advice are limited, wrote Richard S. Legro, MD, of Penn State University, Hershey, and colleagues.

The researchers proposed that a more intensive preconception weight loss intervention followed by infertility treatment would be more likely to yield a healthy live birth, compared with a standard weight maintenance intervention.

In an open-label study published in PLOS Medicine, the researchers randomized 379 women at nine academic centers to a standard lifestyle group that followed a weight-maintenance plan focused on physical activity, but not weight loss; or an intensive intervention of diet and medication with a target weight loss of 7%. Both interventions lasted for 16 weeks between July 2015 and July 2018. After the interventions, patients in both groups underwent standardized empiric fertility treatment with three cycles of ovarian stimulation and intrauterine insemination.

The primary outcome was a live birth at 37 weeks’ gestation or later, with no congenital abnormalities and a birth weight between 2,500 g and 4,000 g. Baseline characteristics including age, education level, race, and body mass index (BMI) were similar between the groups.

The incidence of healthy live births was not significantly different between the standard treatment and intensive treatment groups (15.2% vs. 12.2%; P = 0.40) by the final follow-up time of September 2019. However, women in the intensive group had significantly greater weight loss, compared with the standard group (–6.6% vs. –0.3%; P < .001). Women in the intensive group also showed improvements in metabolic health. Notably, the incidence of metabolic syndrome dropped from 53.6% to 49.4% in the standard group, compared with a decrease from 52.8% to 32.2% in the intensive group over the 16-week study period, the researchers wrote.

Gastrointestinal side effects were significantly more common in the intensive group, but these were consistent with documented side effects of the weight loss medication used (Orlistat).

First-trimester pregnancy loss was higher in the intensive group, compared with the standard group (33.3% vs. 23.7%), but the difference was not significant. Most pregnancy complications, including preterm labor, premature rupture of membranes, preeclampsia, and gestational diabetes had nonsignificant improvements in the intensive group, compared with the standard group. Similarly, nonsignificant improvements were noted in the intervention group for intrauterine growth restriction and admission to the neonatal ICU.

Limitations of the study included the relatively small number of pregnancies, which prevented assessment of rare complications in subgroups, and the challenge of matching control interventions, the researchers noted.

However, the results were strengthened by the focus on women with unexplained infertility, the inclusion of a comparison group, and the collection of data on complications after conception, they wrote.

Avenues for future research include interventions of different duration and intensity prior to conception, which may improve outcomes, the researchers said in their discussion of the findings. “A period of weight stabilization and maintenance after a weight-loss intervention prior to commencing infertility therapy is worth exploring,” they noted, but couples eager to conceive may be reluctant to wait for a weight-loss intervention, they added.

“Our findings directly impact current standards of clinical care, where women who are obese with unexplained infertility are to our knowledge routinely counseled to lose weight prior to initiation of infertility treatment,” they concluded.
 

Data may inform patient discussions

The current study is important because a large amount of previous research has shown an association between obesity and decreased fecundity in women and men, Mark P. Trolice, MD, of the University of Central Florida, Orlando, and director of the IVF Center in Winter Park, Fla., said in an interview.

According to the Centers for Disease Control and Prevention, the prevalence of obesity in the United States remains more than 40%, said Dr. Trolice. “Patients and physicians would benefit from clarity of obesity’s effect, if any, on reproduction,” he noted.

In contrast to the authors’ hypothesis, “the study did not find a difference in the live birth rate following up to three cycles of intrauterine insemination (IUI) between an intensive weight loss group [and] women who exercised without weight loss,” said Dr. Trolice. “Prior to this study, many reports suggested a decline in fertility with elevations in BMI, particularly during fertility treatment,” he added.

The take-home message from the current study is a that an elevated BMI, while possibly increasing the risks of metabolic disorders, did not appear to impact fecundity, he said.

The authors therefore concluded, “There is not strong evidence to recommend weight loss prior to conception in women who are obese with unexplained infertility,” Dr. Trolice said.

Regardless of the potential effect of preconception weight loss on fertility, barriers to starting a weight loss program include a woman’s eagerness to move forward with fertility treatments without waiting for weight loss, Dr. Trolice noted. “By the time a woman reaches an infertility specialist, she has been trying to conceive for at least 1 year,” he said. “At the initial consultation, these patients are anxious to undergo necessary additional diagnostic testing followed by treatment. Consequently, initiation of a weight-loss program is viewed as a delay toward the goal of family building,” he explained.

“More research is needed to demonstrate the safety of intensive weight loss preconception,” said Dr. Trolice. However, he said, “the issue of elevated BMI and increased risk of pregnancy complications remains, but this study provides important information for providers regarding counseling their patients desiring pregnancy.”

The study was supported by multiple grants from the National Institutes of Health through the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Center for Advancing Translational Sciences. Nutrisystem provided discounted coupons for food allotments in the standardized treatment group, and FitBit provided the study organizers with discounted Fitbits for activity monitoring. Lead author Dr. Legro disclosed consulting fees from InSupp, Ferring, Bayer, Abbvie and Fractyl, and research sponsorship from Guerbet and the National Institutes of Health. Dr. Trolice had no financial conflicts to disclose and serves on the Editorial Advisory Board of Ob.Gyn News.

An intensive weight-loss intervention prior to conception had no effect on birth rates in women with obesity and unexplained infertility, compared with a standard weight-maintenance program, based on data from nearly 400 women.

Obese women experiencing infertility are often counseled to lose weight before attempting fertility treatments in order to improve outcomes based on epidemiologic evidence of an association between obesity and infertility, but data to support this advice are limited, wrote Richard S. Legro, MD, of Penn State University, Hershey, and colleagues.

The researchers proposed that a more intensive preconception weight loss intervention followed by infertility treatment would be more likely to yield a healthy live birth, compared with a standard weight maintenance intervention.

In an open-label study published in PLOS Medicine, the researchers randomized 379 women at nine academic centers to a standard lifestyle group that followed a weight-maintenance plan focused on physical activity, but not weight loss; or an intensive intervention of diet and medication with a target weight loss of 7%. Both interventions lasted for 16 weeks between July 2015 and July 2018. After the interventions, patients in both groups underwent standardized empiric fertility treatment with three cycles of ovarian stimulation and intrauterine insemination.

The primary outcome was a live birth at 37 weeks’ gestation or later, with no congenital abnormalities and a birth weight between 2,500 g and 4,000 g. Baseline characteristics including age, education level, race, and body mass index (BMI) were similar between the groups.

The incidence of healthy live births was not significantly different between the standard treatment and intensive treatment groups (15.2% vs. 12.2%; P = 0.40) by the final follow-up time of September 2019. However, women in the intensive group had significantly greater weight loss, compared with the standard group (–6.6% vs. –0.3%; P < .001). Women in the intensive group also showed improvements in metabolic health. Notably, the incidence of metabolic syndrome dropped from 53.6% to 49.4% in the standard group, compared with a decrease from 52.8% to 32.2% in the intensive group over the 16-week study period, the researchers wrote.

Gastrointestinal side effects were significantly more common in the intensive group, but these were consistent with documented side effects of the weight loss medication used (Orlistat).

First-trimester pregnancy loss was higher in the intensive group, compared with the standard group (33.3% vs. 23.7%), but the difference was not significant. Most pregnancy complications, including preterm labor, premature rupture of membranes, preeclampsia, and gestational diabetes had nonsignificant improvements in the intensive group, compared with the standard group. Similarly, nonsignificant improvements were noted in the intervention group for intrauterine growth restriction and admission to the neonatal ICU.

Limitations of the study included the relatively small number of pregnancies, which prevented assessment of rare complications in subgroups, and the challenge of matching control interventions, the researchers noted.

However, the results were strengthened by the focus on women with unexplained infertility, the inclusion of a comparison group, and the collection of data on complications after conception, they wrote.

Avenues for future research include interventions of different duration and intensity prior to conception, which may improve outcomes, the researchers said in their discussion of the findings. “A period of weight stabilization and maintenance after a weight-loss intervention prior to commencing infertility therapy is worth exploring,” they noted, but couples eager to conceive may be reluctant to wait for a weight-loss intervention, they added.

“Our findings directly impact current standards of clinical care, where women who are obese with unexplained infertility are to our knowledge routinely counseled to lose weight prior to initiation of infertility treatment,” they concluded.
 

Data may inform patient discussions

The current study is important because a large amount of previous research has shown an association between obesity and decreased fecundity in women and men, Mark P. Trolice, MD, of the University of Central Florida, Orlando, and director of the IVF Center in Winter Park, Fla., said in an interview.

According to the Centers for Disease Control and Prevention, the prevalence of obesity in the United States remains more than 40%, said Dr. Trolice. “Patients and physicians would benefit from clarity of obesity’s effect, if any, on reproduction,” he noted.

In contrast to the authors’ hypothesis, “the study did not find a difference in the live birth rate following up to three cycles of intrauterine insemination (IUI) between an intensive weight loss group [and] women who exercised without weight loss,” said Dr. Trolice. “Prior to this study, many reports suggested a decline in fertility with elevations in BMI, particularly during fertility treatment,” he added.

The take-home message from the current study is a that an elevated BMI, while possibly increasing the risks of metabolic disorders, did not appear to impact fecundity, he said.

The authors therefore concluded, “There is not strong evidence to recommend weight loss prior to conception in women who are obese with unexplained infertility,” Dr. Trolice said.

Regardless of the potential effect of preconception weight loss on fertility, barriers to starting a weight loss program include a woman’s eagerness to move forward with fertility treatments without waiting for weight loss, Dr. Trolice noted. “By the time a woman reaches an infertility specialist, she has been trying to conceive for at least 1 year,” he said. “At the initial consultation, these patients are anxious to undergo necessary additional diagnostic testing followed by treatment. Consequently, initiation of a weight-loss program is viewed as a delay toward the goal of family building,” he explained.

“More research is needed to demonstrate the safety of intensive weight loss preconception,” said Dr. Trolice. However, he said, “the issue of elevated BMI and increased risk of pregnancy complications remains, but this study provides important information for providers regarding counseling their patients desiring pregnancy.”

The study was supported by multiple grants from the National Institutes of Health through the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Center for Advancing Translational Sciences. Nutrisystem provided discounted coupons for food allotments in the standardized treatment group, and FitBit provided the study organizers with discounted Fitbits for activity monitoring. Lead author Dr. Legro disclosed consulting fees from InSupp, Ferring, Bayer, Abbvie and Fractyl, and research sponsorship from Guerbet and the National Institutes of Health. Dr. Trolice had no financial conflicts to disclose and serves on the Editorial Advisory Board of Ob.Gyn News.

More pregnant Americans indulged – and overindulged – in alcohol from 2018 to 2020 than in previous years, but researchers found no sharp increase associated with the first wave of COVID-19 lockdowns, according to a new report from the Centers for Disease Control and Prevention.

The pandemic notwithstanding, health officials worry about a rising tide of pregnant women using alcohol and binge drinking since the CDC survey began in 2011. In the period ending in 2013, 1 in 10 women reported having had a drink in the previous 30 days; by 2017, that figure was 1 in 9; and in the latest survey, the number had risen to 1 in 7.

That mark is “the highest to date,” said Lucas Gosdin, PhD, MPH, an epidemic intelligence officer at the CDC’s National Center on Birth Defects and Developmental Disabilities, Atlanta, and first author of the report, which was published in Morbidity and Mortality Weekly Report.

“We’re concerned that this number has been slowly increasing,” Amanda Cohn, MD, director of the CDC’s Division of Birth Defects and Infant Disorders, told this news organization. “We need to be doing more outreach, both to pregnant persons as well as health care providers who are caring for them.”

Exposure to alcohol in the womb has been linked to a wide range of neurologic and physical problems in children, ranging from fetal alcohol syndrome to stunted learning abilities. Even if these problems are unlikely, experts insist there’s no known “safe” amount of alcohol a pregnant woman can have.

Dr. Cohn likened alcohol use to that of tobacco. “Lots of people smoke who don’t get lung cancer. Still, everyone is at an increased risk,” she said. “The safest way to not get lung cancer is to not smoke at all. It’s a behavior that can prevent additional harm.”

The report summarizes the results of a phone survey of 6,327 pregnant Americans between the ages of 18 and 49. The survey asked whether women had consumed an alcoholic beverage or had at least four drinks on one occasion – a common definition of binge drinking – in the past 30 days.

According to the report, 13.5% of women reported using alcohol, and 5.2% said they had binged on alcohol. Women who experienced frequent mental distress – describing their mental health as “not good” for 14 or more days in the past month – were twice as likely to drink and three times likelier to binge drink, the researchers found.

The increase within the 3-year period was roughly the same as in previous surveys.

“There was no evidence of increased alcohol consumption by pregnant adults in 2020 relative to 2019, despite possible increased alcohol sales and consumption among the general population during the first months of the COVID-19 pandemic,” the report states.

“That is one finding that was unexpected but that we were pleased to see,” Dr. Gosdin said.

Experts stressed that the survey covered only the first 9 months of the COVID-19 pandemic. “We’re still in the depths of it,” Samuel T. Bauer, MD, associate professor of obstetrics and gynecology at Duke University Medical Center, Durham, N.C., told this news organization. “People with alcohol use disorders certainly have been challenged during COVID. I think this is a preliminary answer.”

Dr. Gosdin said the effects of the pandemic on drinking habits bear watching. “We are concerned about the impacts of COVID-19,” he said. “We know it’s affected how people access regular care.”

Although virtual care has “exploded during COVID,” Dr. Bauer said, insurers have “turned off reimbursing” for doctor-patient visits via telephone, but not for visits by Internet-based video platforms like Zoom.

That split creates equity issues in many parts of the country, including his home state of North Carolina, where broadband is scarce, and patients may live 100 miles or more away from caregivers.

The “full-blown birth defect” of fetal alcohol syndrome is just the most visible hazard of drinking. Other medical and developmental issues include speech delays, slower learning and reading skills, attention-deficit and hyperactivity disorders, and problems with the heart and kidneys.

So, when Dr. Bauer encounters patients who believe that a few drinks will not harm their baby, he says he tells them: “’Why is this going to be where you put your flag?’ That leads to a different form of conversation.”

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

More pregnant Americans indulged – and overindulged – in alcohol from 2018 to 2020 than in previous years, but researchers found no sharp increase associated with the first wave of COVID-19 lockdowns, according to a new report from the Centers for Disease Control and Prevention.

The pandemic notwithstanding, health officials worry about a rising tide of pregnant women using alcohol and binge drinking since the CDC survey began in 2011. In the period ending in 2013, 1 in 10 women reported having had a drink in the previous 30 days; by 2017, that figure was 1 in 9; and in the latest survey, the number had risen to 1 in 7.

That mark is “the highest to date,” said Lucas Gosdin, PhD, MPH, an epidemic intelligence officer at the CDC’s National Center on Birth Defects and Developmental Disabilities, Atlanta, and first author of the report, which was published in Morbidity and Mortality Weekly Report.

“We’re concerned that this number has been slowly increasing,” Amanda Cohn, MD, director of the CDC’s Division of Birth Defects and Infant Disorders, told this news organization. “We need to be doing more outreach, both to pregnant persons as well as health care providers who are caring for them.”

Exposure to alcohol in the womb has been linked to a wide range of neurologic and physical problems in children, ranging from fetal alcohol syndrome to stunted learning abilities. Even if these problems are unlikely, experts insist there’s no known “safe” amount of alcohol a pregnant woman can have.

Dr. Cohn likened alcohol use to that of tobacco. “Lots of people smoke who don’t get lung cancer. Still, everyone is at an increased risk,” she said. “The safest way to not get lung cancer is to not smoke at all. It’s a behavior that can prevent additional harm.”

The report summarizes the results of a phone survey of 6,327 pregnant Americans between the ages of 18 and 49. The survey asked whether women had consumed an alcoholic beverage or had at least four drinks on one occasion – a common definition of binge drinking – in the past 30 days.

According to the report, 13.5% of women reported using alcohol, and 5.2% said they had binged on alcohol. Women who experienced frequent mental distress – describing their mental health as “not good” for 14 or more days in the past month – were twice as likely to drink and three times likelier to binge drink, the researchers found.

The increase within the 3-year period was roughly the same as in previous surveys.

“There was no evidence of increased alcohol consumption by pregnant adults in 2020 relative to 2019, despite possible increased alcohol sales and consumption among the general population during the first months of the COVID-19 pandemic,” the report states.

“That is one finding that was unexpected but that we were pleased to see,” Dr. Gosdin said.

Experts stressed that the survey covered only the first 9 months of the COVID-19 pandemic. “We’re still in the depths of it,” Samuel T. Bauer, MD, associate professor of obstetrics and gynecology at Duke University Medical Center, Durham, N.C., told this news organization. “People with alcohol use disorders certainly have been challenged during COVID. I think this is a preliminary answer.”

Dr. Gosdin said the effects of the pandemic on drinking habits bear watching. “We are concerned about the impacts of COVID-19,” he said. “We know it’s affected how people access regular care.”

Although virtual care has “exploded during COVID,” Dr. Bauer said, insurers have “turned off reimbursing” for doctor-patient visits via telephone, but not for visits by Internet-based video platforms like Zoom.

That split creates equity issues in many parts of the country, including his home state of North Carolina, where broadband is scarce, and patients may live 100 miles or more away from caregivers.

The “full-blown birth defect” of fetal alcohol syndrome is just the most visible hazard of drinking. Other medical and developmental issues include speech delays, slower learning and reading skills, attention-deficit and hyperactivity disorders, and problems with the heart and kidneys.

So, when Dr. Bauer encounters patients who believe that a few drinks will not harm their baby, he says he tells them: “’Why is this going to be where you put your flag?’ That leads to a different form of conversation.”

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

More pregnant Americans indulged – and overindulged – in alcohol from 2018 to 2020 than in previous years, but researchers found no sharp increase associated with the first wave of COVID-19 lockdowns, according to a new report from the Centers for Disease Control and Prevention.

The pandemic notwithstanding, health officials worry about a rising tide of pregnant women using alcohol and binge drinking since the CDC survey began in 2011. In the period ending in 2013, 1 in 10 women reported having had a drink in the previous 30 days; by 2017, that figure was 1 in 9; and in the latest survey, the number had risen to 1 in 7.

That mark is “the highest to date,” said Lucas Gosdin, PhD, MPH, an epidemic intelligence officer at the CDC’s National Center on Birth Defects and Developmental Disabilities, Atlanta, and first author of the report, which was published in Morbidity and Mortality Weekly Report.

“We’re concerned that this number has been slowly increasing,” Amanda Cohn, MD, director of the CDC’s Division of Birth Defects and Infant Disorders, told this news organization. “We need to be doing more outreach, both to pregnant persons as well as health care providers who are caring for them.”

Exposure to alcohol in the womb has been linked to a wide range of neurologic and physical problems in children, ranging from fetal alcohol syndrome to stunted learning abilities. Even if these problems are unlikely, experts insist there’s no known “safe” amount of alcohol a pregnant woman can have.

Dr. Cohn likened alcohol use to that of tobacco. “Lots of people smoke who don’t get lung cancer. Still, everyone is at an increased risk,” she said. “The safest way to not get lung cancer is to not smoke at all. It’s a behavior that can prevent additional harm.”

The report summarizes the results of a phone survey of 6,327 pregnant Americans between the ages of 18 and 49. The survey asked whether women had consumed an alcoholic beverage or had at least four drinks on one occasion – a common definition of binge drinking – in the past 30 days.

According to the report, 13.5% of women reported using alcohol, and 5.2% said they had binged on alcohol. Women who experienced frequent mental distress – describing their mental health as “not good” for 14 or more days in the past month – were twice as likely to drink and three times likelier to binge drink, the researchers found.

The increase within the 3-year period was roughly the same as in previous surveys.

“There was no evidence of increased alcohol consumption by pregnant adults in 2020 relative to 2019, despite possible increased alcohol sales and consumption among the general population during the first months of the COVID-19 pandemic,” the report states.

“That is one finding that was unexpected but that we were pleased to see,” Dr. Gosdin said.

Experts stressed that the survey covered only the first 9 months of the COVID-19 pandemic. “We’re still in the depths of it,” Samuel T. Bauer, MD, associate professor of obstetrics and gynecology at Duke University Medical Center, Durham, N.C., told this news organization. “People with alcohol use disorders certainly have been challenged during COVID. I think this is a preliminary answer.”

Dr. Gosdin said the effects of the pandemic on drinking habits bear watching. “We are concerned about the impacts of COVID-19,” he said. “We know it’s affected how people access regular care.”

Although virtual care has “exploded during COVID,” Dr. Bauer said, insurers have “turned off reimbursing” for doctor-patient visits via telephone, but not for visits by Internet-based video platforms like Zoom.

That split creates equity issues in many parts of the country, including his home state of North Carolina, where broadband is scarce, and patients may live 100 miles or more away from caregivers.

The “full-blown birth defect” of fetal alcohol syndrome is just the most visible hazard of drinking. Other medical and developmental issues include speech delays, slower learning and reading skills, attention-deficit and hyperactivity disorders, and problems with the heart and kidneys.

So, when Dr. Bauer encounters patients who believe that a few drinks will not harm their baby, he says he tells them: “’Why is this going to be where you put your flag?’ That leads to a different form of conversation.”

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

Evidence summary

Early evidence suggested benefit from IM progesterone

A 2003 RCT compared weekly IM progesterone (n = 310) and placebo (n = 153) injections in women with a history of spontaneous preterm delivery. Participants were at 15w0d to 20w3d of a singleton pregnancy with no fetal abnormality. The 17-OHP group, compared to the placebo group, had significantly fewer deliveries at < 37 weeks (36.3% vs 54.9%; relative risk [RR] = 0.66; 95% CI, 0.54 to 0.81; number needed to treat [NNT] = 6), at < 35 weeks (20.6% vs 30.7%; RR = 0.67; 95% CI, 0.48 to 0.93; NNT = 10), and at < 32 weeks (11.4% vs 19.6%; RR = 0.58; 95% CI, 0.37 to 0.91; NNT = 13).¹ There were significantly lower rates of necrotizing enterocolitis, intraventricular hemorrhage, and need for supplemental oxygen in infants of women in the treatment group.¹ The study was underpowered to detect neonatal morbidity.

A 2013 Cochrane Review (5 studies including the 2003 RCT; 602 women) found that 17-OHP led to a decreased risk of birth at < 34 weeks (RR = 0.31; 95% CI, 0.14-0.69). It also led to a significant reduction in perinatal and neonatal mortality, birth at < 37 weeks, birthweight < 2500 g, use of assisted ventilation, incidence of necrotizing enterocolitis, and admission to the neonatal ICU.²

In a large follow-up study, progesterone did not demonstrate benefit

The PROLONG study was a double-blind, placebo-controlled international RCT of women with a previous singleton spontaneous preterm birth. The study involved 93 clinical centers in 9 countries: 41 in the United States and 52 outside the United States. The ­PROLONG study was much larger than the 2003 study: 1139 active treatment (vs 310) and 578 placebo (vs 153) participants. Women were randomized 2:1 to receive either 250 mg 17-OHP or inert oil placebo weekly from 16w0d-20w6d until 36 weeks. The outcome measures were: (1) delivery at < 35 weeks and (2) a neonatal morbidity composite index. This composite index included any of the following: neonatal death, grade 3 or 4 intraventricular hemorrhage, respiratory distress syndrome, bronchopulmonary dysplasia, necrotizing enterocolitis, and proven sepsis.³

Our best evidence does not support routine IM progesterone use to prevent preterm delivery.

Progesterone did not improve any of the studied outcomes: there were no significant differences in the frequency of birth at < 35 weeks (17-OHP 11% vs placebo 11.5%; RR = 0.95; 95% CI, 0.71-1.26), in neonatal morbidity index (17-OHP 5.6% vs placebo 5%; RR = 1.12; 95% CI, 0.68-1.61), and in frequency of fetal/early infant death (17-OHP 1.7% vs placebo 1.9%; RR = 0.87; 95% CI, 0.4-1.81).³ In the United States subgroup (n = 391; 23% of all patients), there was no significant difference in rate of birth at < 35 weeks (17-OHP 15.6% vs placebo 17.6%; RR = 0.88; 95% CI, 0.55-1.40).³

However, PROLONG had some limitations. Importantly, the 2003 RCT included 183 (59%) non-Hispanic Black women in the experimental group and 90 (58.5%) in the control group, whereas the 2020 PROLONG study had only 6.6% non-Hispanic Black participants. The neonatal outcome data for the PROLONG study only included 6 Black women in the experimental arm and 3 in the control arm.^3,4 Black women have prematurity rates that are 2 to 3 times higher than those in White women.⁵

Additionally, the PROLONG study had fewer smokers and more women who were married/living with a partner. Compared with prior studies, the PROLONG study had a lower proportion of women with > 1 spontaneous preterm birth and fewer with a shortened cervix (< 2%).³ As a result of having lower risk participants, PROLONG may have been underpowered to detect improvements in outcome.³

A subsequent meta-analysis suggests some benefit for high-risk women

The 2021 Evaluating Progestogens for Preventing Preterm birth International Collaborative (EPPPIC) meta-analysis of individual data from 31 RCTs—involving 11,644 women and 16,185 babies—found that, compared with placebo, 17-OHP for women with a history of preterm delivery or short cervix did not significantly decrease the number of babies born before 34 weeks (5 trials [including the 2003 RCT and PROLONG studies]; 3053 women; RR = 0.83; 95% CI, 0.68–1.01).⁶ However, it found that vaginal progesterone significantly decreased birth prior to 34 weeks (9 trials; 3769 women; RR = 0.78, 95% CI, 0.68-0.90).⁶ The authors concluded that both IM and vaginal progesterone decreased preterm delivery in high-risk women. The effect was stronger for women with a short cervix than for women with a history of preterm delivery.⁶

Continue to: Recommendations from others

 

 

Recommendations from others

In 2008, a joint ACOG/SMFM statement said, “Progesterone supplementation for the prevention of recurrent preterm birth should be offered to women with a singleton pregnancy and prior spontaneous preterm birth.”⁷ A 2012 ACOG Practice Bulletin stated that, “A woman with a singleton gestation and a prior spontaneous preterm singleton birth should be offered progesterone supplementation starting at 16 to 24 weeks of gestation, regardless of transvaginal ultrasound cervical length, to reduce the risk of recurrent spontaneous preterm birth.”⁸

In 2011, Makena (hydroxyprogesterone caproate injection) received accelerated approval from the FDA. In October 2020, the FDA Advisory Committee recommended that Makena be withdrawn from the market (9 to 7 vote).⁹ On October 5, 2020, the FDA’s Center for Drug Evaluation and Research (CDER) proposed that Makena be withdrawn from the market “because the required postmarket study failed to verify clinical benefit and we have concluded that the available evidence does not show Makena is effective for its approved use.”¹⁰ A subgroup analysis by CDER did not find benefit for any subgroup, including high-risk women.¹⁰ However, Makena will remain on the market unless its manufacturer withdraws it or the FDA Commissioner mandates its removal.

In response to the FDA’s proposal, both ACOG and SMFM recommended that “obstetric health care professionals discuss Makena’s benefits, risks, and uncertainties with their patients”¹¹ as part of “a shared ­decision-making approach, taking into account the lack of short-term safety concerns but uncertainty regarding benefit.”¹² Both organizations reiterated their position on shared decision-making after the EPPPIC meta-analysis was published.¹³

Studies comparing the 2 routes of administration (vaginal and IM) are underway.¹³

Editor’s takeaway

Our best evidence does not support routine IM progesterone use to prevent preterm delivery. However, therapeutic inertia, uncertainty, and defensive medicine may slow down adoption of this newer evidence. Shared decision-making can assist treatment decisions, but it is not a substitute for following the best evidence.

Evidence summary

Early evidence suggested benefit from IM progesterone

A 2003 RCT compared weekly IM progesterone (n = 310) and placebo (n = 153) injections in women with a history of spontaneous preterm delivery. Participants were at 15w0d to 20w3d of a singleton pregnancy with no fetal abnormality. The 17-OHP group, compared to the placebo group, had significantly fewer deliveries at < 37 weeks (36.3% vs 54.9%; relative risk [RR] = 0.66; 95% CI, 0.54 to 0.81; number needed to treat [NNT] = 6), at < 35 weeks (20.6% vs 30.7%; RR = 0.67; 95% CI, 0.48 to 0.93; NNT = 10), and at < 32 weeks (11.4% vs 19.6%; RR = 0.58; 95% CI, 0.37 to 0.91; NNT = 13).¹ There were significantly lower rates of necrotizing enterocolitis, intraventricular hemorrhage, and need for supplemental oxygen in infants of women in the treatment group.¹ The study was underpowered to detect neonatal morbidity.

A 2013 Cochrane Review (5 studies including the 2003 RCT; 602 women) found that 17-OHP led to a decreased risk of birth at < 34 weeks (RR = 0.31; 95% CI, 0.14-0.69). It also led to a significant reduction in perinatal and neonatal mortality, birth at < 37 weeks, birthweight < 2500 g, use of assisted ventilation, incidence of necrotizing enterocolitis, and admission to the neonatal ICU.²

In a large follow-up study, progesterone did not demonstrate benefit

The PROLONG study was a double-blind, placebo-controlled international RCT of women with a previous singleton spontaneous preterm birth. The study involved 93 clinical centers in 9 countries: 41 in the United States and 52 outside the United States. The ­PROLONG study was much larger than the 2003 study: 1139 active treatment (vs 310) and 578 placebo (vs 153) participants. Women were randomized 2:1 to receive either 250 mg 17-OHP or inert oil placebo weekly from 16w0d-20w6d until 36 weeks. The outcome measures were: (1) delivery at < 35 weeks and (2) a neonatal morbidity composite index. This composite index included any of the following: neonatal death, grade 3 or 4 intraventricular hemorrhage, respiratory distress syndrome, bronchopulmonary dysplasia, necrotizing enterocolitis, and proven sepsis.³

Our best evidence does not support routine IM progesterone use to prevent preterm delivery.

Progesterone did not improve any of the studied outcomes: there were no significant differences in the frequency of birth at < 35 weeks (17-OHP 11% vs placebo 11.5%; RR = 0.95; 95% CI, 0.71-1.26), in neonatal morbidity index (17-OHP 5.6% vs placebo 5%; RR = 1.12; 95% CI, 0.68-1.61), and in frequency of fetal/early infant death (17-OHP 1.7% vs placebo 1.9%; RR = 0.87; 95% CI, 0.4-1.81).³ In the United States subgroup (n = 391; 23% of all patients), there was no significant difference in rate of birth at < 35 weeks (17-OHP 15.6% vs placebo 17.6%; RR = 0.88; 95% CI, 0.55-1.40).³

However, PROLONG had some limitations. Importantly, the 2003 RCT included 183 (59%) non-Hispanic Black women in the experimental group and 90 (58.5%) in the control group, whereas the 2020 PROLONG study had only 6.6% non-Hispanic Black participants. The neonatal outcome data for the PROLONG study only included 6 Black women in the experimental arm and 3 in the control arm.^3,4 Black women have prematurity rates that are 2 to 3 times higher than those in White women.⁵

Additionally, the PROLONG study had fewer smokers and more women who were married/living with a partner. Compared with prior studies, the PROLONG study had a lower proportion of women with > 1 spontaneous preterm birth and fewer with a shortened cervix (< 2%).³ As a result of having lower risk participants, PROLONG may have been underpowered to detect improvements in outcome.³

A subsequent meta-analysis suggests some benefit for high-risk women

The 2021 Evaluating Progestogens for Preventing Preterm birth International Collaborative (EPPPIC) meta-analysis of individual data from 31 RCTs—involving 11,644 women and 16,185 babies—found that, compared with placebo, 17-OHP for women with a history of preterm delivery or short cervix did not significantly decrease the number of babies born before 34 weeks (5 trials [including the 2003 RCT and PROLONG studies]; 3053 women; RR = 0.83; 95% CI, 0.68–1.01).⁶ However, it found that vaginal progesterone significantly decreased birth prior to 34 weeks (9 trials; 3769 women; RR = 0.78, 95% CI, 0.68-0.90).⁶ The authors concluded that both IM and vaginal progesterone decreased preterm delivery in high-risk women. The effect was stronger for women with a short cervix than for women with a history of preterm delivery.⁶

Continue to: Recommendations from others

 

 

Recommendations from others

In 2008, a joint ACOG/SMFM statement said, “Progesterone supplementation for the prevention of recurrent preterm birth should be offered to women with a singleton pregnancy and prior spontaneous preterm birth.”⁷ A 2012 ACOG Practice Bulletin stated that, “A woman with a singleton gestation and a prior spontaneous preterm singleton birth should be offered progesterone supplementation starting at 16 to 24 weeks of gestation, regardless of transvaginal ultrasound cervical length, to reduce the risk of recurrent spontaneous preterm birth.”⁸

In 2011, Makena (hydroxyprogesterone caproate injection) received accelerated approval from the FDA. In October 2020, the FDA Advisory Committee recommended that Makena be withdrawn from the market (9 to 7 vote).⁹ On October 5, 2020, the FDA’s Center for Drug Evaluation and Research (CDER) proposed that Makena be withdrawn from the market “because the required postmarket study failed to verify clinical benefit and we have concluded that the available evidence does not show Makena is effective for its approved use.”¹⁰ A subgroup analysis by CDER did not find benefit for any subgroup, including high-risk women.¹⁰ However, Makena will remain on the market unless its manufacturer withdraws it or the FDA Commissioner mandates its removal.

In response to the FDA’s proposal, both ACOG and SMFM recommended that “obstetric health care professionals discuss Makena’s benefits, risks, and uncertainties with their patients”¹¹ as part of “a shared ­decision-making approach, taking into account the lack of short-term safety concerns but uncertainty regarding benefit.”¹² Both organizations reiterated their position on shared decision-making after the EPPPIC meta-analysis was published.¹³

Studies comparing the 2 routes of administration (vaginal and IM) are underway.¹³

Editor’s takeaway

Our best evidence does not support routine IM progesterone use to prevent preterm delivery. However, therapeutic inertia, uncertainty, and defensive medicine may slow down adoption of this newer evidence. Shared decision-making can assist treatment decisions, but it is not a substitute for following the best evidence.

Evidence summary

Early evidence suggested benefit from IM progesterone

A 2003 RCT compared weekly IM progesterone (n = 310) and placebo (n = 153) injections in women with a history of spontaneous preterm delivery. Participants were at 15w0d to 20w3d of a singleton pregnancy with no fetal abnormality. The 17-OHP group, compared to the placebo group, had significantly fewer deliveries at < 37 weeks (36.3% vs 54.9%; relative risk [RR] = 0.66; 95% CI, 0.54 to 0.81; number needed to treat [NNT] = 6), at < 35 weeks (20.6% vs 30.7%; RR = 0.67; 95% CI, 0.48 to 0.93; NNT = 10), and at < 32 weeks (11.4% vs 19.6%; RR = 0.58; 95% CI, 0.37 to 0.91; NNT = 13).¹ There were significantly lower rates of necrotizing enterocolitis, intraventricular hemorrhage, and need for supplemental oxygen in infants of women in the treatment group.¹ The study was underpowered to detect neonatal morbidity.

A 2013 Cochrane Review (5 studies including the 2003 RCT; 602 women) found that 17-OHP led to a decreased risk of birth at < 34 weeks (RR = 0.31; 95% CI, 0.14-0.69). It also led to a significant reduction in perinatal and neonatal mortality, birth at < 37 weeks, birthweight < 2500 g, use of assisted ventilation, incidence of necrotizing enterocolitis, and admission to the neonatal ICU.²

In a large follow-up study, progesterone did not demonstrate benefit

The PROLONG study was a double-blind, placebo-controlled international RCT of women with a previous singleton spontaneous preterm birth. The study involved 93 clinical centers in 9 countries: 41 in the United States and 52 outside the United States. The ­PROLONG study was much larger than the 2003 study: 1139 active treatment (vs 310) and 578 placebo (vs 153) participants. Women were randomized 2:1 to receive either 250 mg 17-OHP or inert oil placebo weekly from 16w0d-20w6d until 36 weeks. The outcome measures were: (1) delivery at < 35 weeks and (2) a neonatal morbidity composite index. This composite index included any of the following: neonatal death, grade 3 or 4 intraventricular hemorrhage, respiratory distress syndrome, bronchopulmonary dysplasia, necrotizing enterocolitis, and proven sepsis.³

Our best evidence does not support routine IM progesterone use to prevent preterm delivery.

Progesterone did not improve any of the studied outcomes: there were no significant differences in the frequency of birth at < 35 weeks (17-OHP 11% vs placebo 11.5%; RR = 0.95; 95% CI, 0.71-1.26), in neonatal morbidity index (17-OHP 5.6% vs placebo 5%; RR = 1.12; 95% CI, 0.68-1.61), and in frequency of fetal/early infant death (17-OHP 1.7% vs placebo 1.9%; RR = 0.87; 95% CI, 0.4-1.81).³ In the United States subgroup (n = 391; 23% of all patients), there was no significant difference in rate of birth at < 35 weeks (17-OHP 15.6% vs placebo 17.6%; RR = 0.88; 95% CI, 0.55-1.40).³

However, PROLONG had some limitations. Importantly, the 2003 RCT included 183 (59%) non-Hispanic Black women in the experimental group and 90 (58.5%) in the control group, whereas the 2020 PROLONG study had only 6.6% non-Hispanic Black participants. The neonatal outcome data for the PROLONG study only included 6 Black women in the experimental arm and 3 in the control arm.^3,4 Black women have prematurity rates that are 2 to 3 times higher than those in White women.⁵

Additionally, the PROLONG study had fewer smokers and more women who were married/living with a partner. Compared with prior studies, the PROLONG study had a lower proportion of women with > 1 spontaneous preterm birth and fewer with a shortened cervix (< 2%).³ As a result of having lower risk participants, PROLONG may have been underpowered to detect improvements in outcome.³

A subsequent meta-analysis suggests some benefit for high-risk women

The 2021 Evaluating Progestogens for Preventing Preterm birth International Collaborative (EPPPIC) meta-analysis of individual data from 31 RCTs—involving 11,644 women and 16,185 babies—found that, compared with placebo, 17-OHP for women with a history of preterm delivery or short cervix did not significantly decrease the number of babies born before 34 weeks (5 trials [including the 2003 RCT and PROLONG studies]; 3053 women; RR = 0.83; 95% CI, 0.68–1.01).⁶ However, it found that vaginal progesterone significantly decreased birth prior to 34 weeks (9 trials; 3769 women; RR = 0.78, 95% CI, 0.68-0.90).⁶ The authors concluded that both IM and vaginal progesterone decreased preterm delivery in high-risk women. The effect was stronger for women with a short cervix than for women with a history of preterm delivery.⁶

Continue to: Recommendations from others

 

 

Recommendations from others

In 2008, a joint ACOG/SMFM statement said, “Progesterone supplementation for the prevention of recurrent preterm birth should be offered to women with a singleton pregnancy and prior spontaneous preterm birth.”⁷ A 2012 ACOG Practice Bulletin stated that, “A woman with a singleton gestation and a prior spontaneous preterm singleton birth should be offered progesterone supplementation starting at 16 to 24 weeks of gestation, regardless of transvaginal ultrasound cervical length, to reduce the risk of recurrent spontaneous preterm birth.”⁸

In 2011, Makena (hydroxyprogesterone caproate injection) received accelerated approval from the FDA. In October 2020, the FDA Advisory Committee recommended that Makena be withdrawn from the market (9 to 7 vote).⁹ On October 5, 2020, the FDA’s Center for Drug Evaluation and Research (CDER) proposed that Makena be withdrawn from the market “because the required postmarket study failed to verify clinical benefit and we have concluded that the available evidence does not show Makena is effective for its approved use.”¹⁰ A subgroup analysis by CDER did not find benefit for any subgroup, including high-risk women.¹⁰ However, Makena will remain on the market unless its manufacturer withdraws it or the FDA Commissioner mandates its removal.

In response to the FDA’s proposal, both ACOG and SMFM recommended that “obstetric health care professionals discuss Makena’s benefits, risks, and uncertainties with their patients”¹¹ as part of “a shared ­decision-making approach, taking into account the lack of short-term safety concerns but uncertainty regarding benefit.”¹² Both organizations reiterated their position on shared decision-making after the EPPPIC meta-analysis was published.¹³

Studies comparing the 2 routes of administration (vaginal and IM) are underway.¹³

Editor’s takeaway

Our best evidence does not support routine IM progesterone use to prevent preterm delivery. However, therapeutic inertia, uncertainty, and defensive medicine may slow down adoption of this newer evidence. Shared decision-making can assist treatment decisions, but it is not a substitute for following the best evidence.

Two new studies show how COVID-19 threatens the health of pregnant people and their newborn infants.

A study conducted in Scotland showed that unvaccinated pregnant people who got COVID were much more likely to have a stillborn infant or one that dies in the first 28 days. The study also found that pregnant women infected with COVID died or needed hospitalization at a much higher rate than vaccinated women who got pregnant.

The University of Edinburgh and Public Health Scotland studied national data in 88,000 pregnancies between Dec. 2020 and Oct. 2021, according to the study published in Nature Medicine.

Overall, 77.4% of infections, 90.9% of COVID-related hospitalizations, and 98% of critical care cases occurred in the unvaccinated people, as did all newborn deaths.

The study said 2,364 babies were born to women infected with COVID, with 2,353 live births. Eleven babies were stillborn and eight live-born babies died within 28 days. Of the live births, 241 were premature.

The problems were more likely if the infection occurred 28 days or less before the delivery date, the researchers said.

The authors said the low vaccination rate among pregnant people was a problem. Only 32% of people giving birth in Oct. 2021 were fully vaccinated, while 77% of the Scottish female population aged 18-44 was fully vaccinated.

“Vaccine hesitancy in pregnancy thus requires addressing, especially in light of new recommendations for booster vaccination administration 3 months after the initial vaccination course to help protect against new variants such as Omicron,” the authors wrote. “Addressing low vaccine uptake rates in pregnant women is imperative to protect the health of women and babies in the ongoing pandemic.”

Vaccinated women who were pregnant had complication rates that were about the same for all pregnant women, the study shows.

The second study, published in The Lancet, found that women who got COVID while pregnant in five Western U.S. states were more likely to have premature births, low birth weights, and stillbirths, even when the COVID cases are mild.

The Institute for Systems Biology researchers in Seattle studied data for women who gave birth in Alaska, California, Montana, Oregon, or Washington from March 5, 2020, to July 4, 2021. About 18,000 of them were tested for COVID, with 882 testing positive. Of the positive tests, 85 came in the first trimester, 226 in the second trimester, and 571 in the third semester. None of the pregnant women had been vaccinated at the time they were infected.

Most of the birth problems occurred with first and second trimester infections, the study noted, and problems occurred even if the pregnant person didn’t have respiratory complications, a major COVID symptom.

“Pregnant people are at an increased risk of adverse outcomes following SARS-CoV-2 infection, even when maternal COVID-19 is less severe, and they may benefit from increased monitoring following infection,” Jennifer Hadlock, MD, an author of the paper, said in a news release.

The study also pointed out continuing inequities in health care, with most of the positive cases occurring among young, non-White people with Medicaid and high body mass index.

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

Two new studies show how COVID-19 threatens the health of pregnant people and their newborn infants.

A study conducted in Scotland showed that unvaccinated pregnant people who got COVID were much more likely to have a stillborn infant or one that dies in the first 28 days. The study also found that pregnant women infected with COVID died or needed hospitalization at a much higher rate than vaccinated women who got pregnant.

The University of Edinburgh and Public Health Scotland studied national data in 88,000 pregnancies between Dec. 2020 and Oct. 2021, according to the study published in Nature Medicine.

Overall, 77.4% of infections, 90.9% of COVID-related hospitalizations, and 98% of critical care cases occurred in the unvaccinated people, as did all newborn deaths.

The study said 2,364 babies were born to women infected with COVID, with 2,353 live births. Eleven babies were stillborn and eight live-born babies died within 28 days. Of the live births, 241 were premature.

The problems were more likely if the infection occurred 28 days or less before the delivery date, the researchers said.

The authors said the low vaccination rate among pregnant people was a problem. Only 32% of people giving birth in Oct. 2021 were fully vaccinated, while 77% of the Scottish female population aged 18-44 was fully vaccinated.

“Vaccine hesitancy in pregnancy thus requires addressing, especially in light of new recommendations for booster vaccination administration 3 months after the initial vaccination course to help protect against new variants such as Omicron,” the authors wrote. “Addressing low vaccine uptake rates in pregnant women is imperative to protect the health of women and babies in the ongoing pandemic.”

Vaccinated women who were pregnant had complication rates that were about the same for all pregnant women, the study shows.

The second study, published in The Lancet, found that women who got COVID while pregnant in five Western U.S. states were more likely to have premature births, low birth weights, and stillbirths, even when the COVID cases are mild.

The Institute for Systems Biology researchers in Seattle studied data for women who gave birth in Alaska, California, Montana, Oregon, or Washington from March 5, 2020, to July 4, 2021. About 18,000 of them were tested for COVID, with 882 testing positive. Of the positive tests, 85 came in the first trimester, 226 in the second trimester, and 571 in the third semester. None of the pregnant women had been vaccinated at the time they were infected.

Most of the birth problems occurred with first and second trimester infections, the study noted, and problems occurred even if the pregnant person didn’t have respiratory complications, a major COVID symptom.

“Pregnant people are at an increased risk of adverse outcomes following SARS-CoV-2 infection, even when maternal COVID-19 is less severe, and they may benefit from increased monitoring following infection,” Jennifer Hadlock, MD, an author of the paper, said in a news release.

The study also pointed out continuing inequities in health care, with most of the positive cases occurring among young, non-White people with Medicaid and high body mass index.

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

Two new studies show how COVID-19 threatens the health of pregnant people and their newborn infants.

A study conducted in Scotland showed that unvaccinated pregnant people who got COVID were much more likely to have a stillborn infant or one that dies in the first 28 days. The study also found that pregnant women infected with COVID died or needed hospitalization at a much higher rate than vaccinated women who got pregnant.

The University of Edinburgh and Public Health Scotland studied national data in 88,000 pregnancies between Dec. 2020 and Oct. 2021, according to the study published in Nature Medicine.

Overall, 77.4% of infections, 90.9% of COVID-related hospitalizations, and 98% of critical care cases occurred in the unvaccinated people, as did all newborn deaths.

The study said 2,364 babies were born to women infected with COVID, with 2,353 live births. Eleven babies were stillborn and eight live-born babies died within 28 days. Of the live births, 241 were premature.

The problems were more likely if the infection occurred 28 days or less before the delivery date, the researchers said.

The authors said the low vaccination rate among pregnant people was a problem. Only 32% of people giving birth in Oct. 2021 were fully vaccinated, while 77% of the Scottish female population aged 18-44 was fully vaccinated.

“Vaccine hesitancy in pregnancy thus requires addressing, especially in light of new recommendations for booster vaccination administration 3 months after the initial vaccination course to help protect against new variants such as Omicron,” the authors wrote. “Addressing low vaccine uptake rates in pregnant women is imperative to protect the health of women and babies in the ongoing pandemic.”

Vaccinated women who were pregnant had complication rates that were about the same for all pregnant women, the study shows.

The second study, published in The Lancet, found that women who got COVID while pregnant in five Western U.S. states were more likely to have premature births, low birth weights, and stillbirths, even when the COVID cases are mild.

The Institute for Systems Biology researchers in Seattle studied data for women who gave birth in Alaska, California, Montana, Oregon, or Washington from March 5, 2020, to July 4, 2021. About 18,000 of them were tested for COVID, with 882 testing positive. Of the positive tests, 85 came in the first trimester, 226 in the second trimester, and 571 in the third semester. None of the pregnant women had been vaccinated at the time they were infected.

Most of the birth problems occurred with first and second trimester infections, the study noted, and problems occurred even if the pregnant person didn’t have respiratory complications, a major COVID symptom.

“Pregnant people are at an increased risk of adverse outcomes following SARS-CoV-2 infection, even when maternal COVID-19 is less severe, and they may benefit from increased monitoring following infection,” Jennifer Hadlock, MD, an author of the paper, said in a news release.

The study also pointed out continuing inequities in health care, with most of the positive cases occurring among young, non-White people with Medicaid and high body mass index.

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

In a meta-analysis of more than 1 million mothers, those who breastfed their children had an 11% to 17% lower risk of developing cardiovascular disease (CVD), coronary heart disease (CHD), or stroke, and of dying from CVD, in later life than mothers who did not.

On average, the women had two children and had breastfed for 15.9 months in total. Longer breastfeeding was associated with greater CV health benefit.

This meta-analysis of eight studies from different countries was published online Jan. 11 in an issue of the Journal of the American Heart Association devoted to the impact of pregnancy on CV health in the mother and child.

Breastfeeding is known to be associated with a lower risk for death from infectious disease and with fewer respiratory infections in babies, the researchers write, but what is less well known is that it is also associated with a reduced risk for breast and ovarian cancer and type 2 diabetes in mothers.

The current study showed a clear association between breastfeeding and reduced risk for CVD in later life, lead author Lena Tschiderer, Dipl.-Ing., PhD, and senior author Peter Willeit, MD, MPhil, PhD, summarized in a joint email to this news organization.

Specifically, mothers who had breastfed their children at any time had an 11% lower risk for CVD, a 14% lower risk for CHD, a 12% lower risk for stroke, and a 17% lower risk of dying from CVD in later life, compared with other mothers.

On the basis of existing evidence, the researchers write, the World Health Organization recommends exclusive breastfeeding until a baby is 6 months old, followed by breastfeeding plus complementary feeding until the baby is 2 years or older.

“We believe that [breastfeeding] benefits for the mother are communicated poorly,” said Dr. Tschiderer and Dr. Willeit, from the University of Innsbruck, Austria.

“Positive effects of breastfeeding on mothers need to be communicated effectively, awareness for breastfeeding recommendations needs to be raised, and interventions to promote and facilitate breastfeeding need to be implemented and reinforced,” the researchers conclude.
 

‘Should not be ignored’

Two cardiologists invited to comment, who were not involved with the research, noted that this study provides insight into an important topic.

“This is yet another body of evidence [and the largest population to date] to show that breastfeeding is protective for women and may show important beneficial effects in terms of CV risk,” Roxana Mehran, MD, said in an email.

“The risk reductions were 11% for CVD events and 14% for CHD events; these are impressive numbers,” said Dr. Mehran, from Icahn School of Medicine at Mount Sinai, New York.

“The caveat,” she said, “is that these are data from several trials, but nonetheless, this is a very important observation that should not be ignored.”

The study did not address the definitive amount of time of breastfeeding and its correlation to the improvement of CVD risk, but it did show that for the lifetime duration, the longer the better.

“The beneficial effects,” she noted, “can be linked to hormones during breastfeeding, as well as weight loss associated with breastfeeding, and resetting the maternal metabolism, as the authors suggest.”

Clinicians and employers “must provide ways to educate women about breastfeeding and make it easy for women who are in the workplace to pump, and to provide them with resources” where possible, Dr. Mehran said.

Michelle O’Donoghue, MD, MPH, noted that over the past several years, there has been intense interest in the possible health benefits of breastfeeding for both mother and child.

There is biologic plausibility for some of the possible maternal benefits because the favorable CV effects of both prolactin and oxytocin are only now being better understood, said Dr. O’Donoghue, from Brigham and Women’s Hospital and Harvard Medical School, Boston.

“The current meta-analysis provides a large dataset that helps support the concept that breastfeeding may offer some cardiovascular benefit for the mother,” she agreed.

“However, ultimately more research will be necessary since this method of combining data across trials relies upon the robustness of the statistical method in each study,” Dr. O’Donoghue said. “I applaud the authors for shining a spotlight on this important topic.”

Although the benefits of breastfeeding appear to continue over time, “it is incredibly difficult for women to continue breastfeeding once they return to work,” she added. “Women in some countries outside the U.S. have an advantage due to longer durations of maternity leave.

“If we want to encourage breastfeeding,” Dr. O’Donoghue stressed, “we need to make sure that we put the right supports in place. Women need protected places to breastfeed in the workplace and places to store their milk. Most importantly, women need to be allowed dedicated time to make it happen.”
 

First large study of CVD in mothers

Emerging individual studies suggest that mothers who breastfeed may have a lower risk for CVD in later life, but studies have been inconsistent, and it is not clear if longer breastfeeding would strengthen this benefit, the authors note.

To examine this, they pooled data from the following eight studies (with study acronym, country, and baseline enrolment dates in brackets): 45&Up (Australia, 2006-2009), China Kadoorie Biobank (CKB, China, 2004-2008), European Prospective Investigation into Cancer and Nutrition (EPIC, multinational, 1992-2000), Gallagher et al. (China, 1989-1991), Nord-Trøndelag Health Survey 2 (HUNT2, Norway, 1995-1997), Japan Public Health Center-based Prospective Study (JPHC, Japan, 1990-1994), Nurses’ Health Study (NHS, U.S., 1986), and the Woman’s Health Initiative (WHI, U.S., 1993-1998).

On average, the women were 51.3 years old (range, 40-65 years) when they enrolled in the study, and they were followed for a median of 10.3 years (range, 7.9-20.9 years, in the individual studies).

On average, they had their first child at age 25 and had two to three children (mean, 2.3); 82% had breastfed at some point (ranging from 58% of women in the two U.S. studies to 97% in CKB and HUNT2).

The women had breastfed for a mean of 7.4 to 18.9 months during their lifetimes (except women in the CKB study, who had breastfed for a median of 24 months).

Among the 1,192,700 women, there were 54,226 incident CVD events, 26,913 incident CHD events, 30,843 incident strokes, and 10,766 deaths from CVD during follow-up.

The researchers acknowledge that study limitations include the fact that there could have been publication bias, since fewer than 10 studies were available for pooling. There was significant between-study heterogeneity for CVD, CHD, and stroke outcomes.

Participant-level data were also lacking, and breastfeeding was self-reported. There may have been unaccounted residual confounding, and the benefits of lifetime breastfeeding that is longer than 2 years are not clear, because few women in this population breastfed that long.

The research was funded by the Austrian Science Fund. The researchers and Dr. Mehran and Dr. O’Donoghue have no relevant financial disclosures.

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

In a meta-analysis of more than 1 million mothers, those who breastfed their children had an 11% to 17% lower risk of developing cardiovascular disease (CVD), coronary heart disease (CHD), or stroke, and of dying from CVD, in later life than mothers who did not.

On average, the women had two children and had breastfed for 15.9 months in total. Longer breastfeeding was associated with greater CV health benefit.

This meta-analysis of eight studies from different countries was published online Jan. 11 in an issue of the Journal of the American Heart Association devoted to the impact of pregnancy on CV health in the mother and child.

Breastfeeding is known to be associated with a lower risk for death from infectious disease and with fewer respiratory infections in babies, the researchers write, but what is less well known is that it is also associated with a reduced risk for breast and ovarian cancer and type 2 diabetes in mothers.

The current study showed a clear association between breastfeeding and reduced risk for CVD in later life, lead author Lena Tschiderer, Dipl.-Ing., PhD, and senior author Peter Willeit, MD, MPhil, PhD, summarized in a joint email to this news organization.

Specifically, mothers who had breastfed their children at any time had an 11% lower risk for CVD, a 14% lower risk for CHD, a 12% lower risk for stroke, and a 17% lower risk of dying from CVD in later life, compared with other mothers.

On the basis of existing evidence, the researchers write, the World Health Organization recommends exclusive breastfeeding until a baby is 6 months old, followed by breastfeeding plus complementary feeding until the baby is 2 years or older.

“We believe that [breastfeeding] benefits for the mother are communicated poorly,” said Dr. Tschiderer and Dr. Willeit, from the University of Innsbruck, Austria.

“Positive effects of breastfeeding on mothers need to be communicated effectively, awareness for breastfeeding recommendations needs to be raised, and interventions to promote and facilitate breastfeeding need to be implemented and reinforced,” the researchers conclude.
 

‘Should not be ignored’

Two cardiologists invited to comment, who were not involved with the research, noted that this study provides insight into an important topic.

“This is yet another body of evidence [and the largest population to date] to show that breastfeeding is protective for women and may show important beneficial effects in terms of CV risk,” Roxana Mehran, MD, said in an email.

“The risk reductions were 11% for CVD events and 14% for CHD events; these are impressive numbers,” said Dr. Mehran, from Icahn School of Medicine at Mount Sinai, New York.

“The caveat,” she said, “is that these are data from several trials, but nonetheless, this is a very important observation that should not be ignored.”

The study did not address the definitive amount of time of breastfeeding and its correlation to the improvement of CVD risk, but it did show that for the lifetime duration, the longer the better.

“The beneficial effects,” she noted, “can be linked to hormones during breastfeeding, as well as weight loss associated with breastfeeding, and resetting the maternal metabolism, as the authors suggest.”

Clinicians and employers “must provide ways to educate women about breastfeeding and make it easy for women who are in the workplace to pump, and to provide them with resources” where possible, Dr. Mehran said.

Michelle O’Donoghue, MD, MPH, noted that over the past several years, there has been intense interest in the possible health benefits of breastfeeding for both mother and child.

There is biologic plausibility for some of the possible maternal benefits because the favorable CV effects of both prolactin and oxytocin are only now being better understood, said Dr. O’Donoghue, from Brigham and Women’s Hospital and Harvard Medical School, Boston.

“The current meta-analysis provides a large dataset that helps support the concept that breastfeeding may offer some cardiovascular benefit for the mother,” she agreed.

“However, ultimately more research will be necessary since this method of combining data across trials relies upon the robustness of the statistical method in each study,” Dr. O’Donoghue said. “I applaud the authors for shining a spotlight on this important topic.”

Although the benefits of breastfeeding appear to continue over time, “it is incredibly difficult for women to continue breastfeeding once they return to work,” she added. “Women in some countries outside the U.S. have an advantage due to longer durations of maternity leave.

“If we want to encourage breastfeeding,” Dr. O’Donoghue stressed, “we need to make sure that we put the right supports in place. Women need protected places to breastfeed in the workplace and places to store their milk. Most importantly, women need to be allowed dedicated time to make it happen.”
 

First large study of CVD in mothers

Emerging individual studies suggest that mothers who breastfeed may have a lower risk for CVD in later life, but studies have been inconsistent, and it is not clear if longer breastfeeding would strengthen this benefit, the authors note.

To examine this, they pooled data from the following eight studies (with study acronym, country, and baseline enrolment dates in brackets): 45&Up (Australia, 2006-2009), China Kadoorie Biobank (CKB, China, 2004-2008), European Prospective Investigation into Cancer and Nutrition (EPIC, multinational, 1992-2000), Gallagher et al. (China, 1989-1991), Nord-Trøndelag Health Survey 2 (HUNT2, Norway, 1995-1997), Japan Public Health Center-based Prospective Study (JPHC, Japan, 1990-1994), Nurses’ Health Study (NHS, U.S., 1986), and the Woman’s Health Initiative (WHI, U.S., 1993-1998).

On average, the women were 51.3 years old (range, 40-65 years) when they enrolled in the study, and they were followed for a median of 10.3 years (range, 7.9-20.9 years, in the individual studies).

On average, they had their first child at age 25 and had two to three children (mean, 2.3); 82% had breastfed at some point (ranging from 58% of women in the two U.S. studies to 97% in CKB and HUNT2).

The women had breastfed for a mean of 7.4 to 18.9 months during their lifetimes (except women in the CKB study, who had breastfed for a median of 24 months).

Among the 1,192,700 women, there were 54,226 incident CVD events, 26,913 incident CHD events, 30,843 incident strokes, and 10,766 deaths from CVD during follow-up.

The researchers acknowledge that study limitations include the fact that there could have been publication bias, since fewer than 10 studies were available for pooling. There was significant between-study heterogeneity for CVD, CHD, and stroke outcomes.

Participant-level data were also lacking, and breastfeeding was self-reported. There may have been unaccounted residual confounding, and the benefits of lifetime breastfeeding that is longer than 2 years are not clear, because few women in this population breastfed that long.

The research was funded by the Austrian Science Fund. The researchers and Dr. Mehran and Dr. O’Donoghue have no relevant financial disclosures.

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

In a meta-analysis of more than 1 million mothers, those who breastfed their children had an 11% to 17% lower risk of developing cardiovascular disease (CVD), coronary heart disease (CHD), or stroke, and of dying from CVD, in later life than mothers who did not.

On average, the women had two children and had breastfed for 15.9 months in total. Longer breastfeeding was associated with greater CV health benefit.

This meta-analysis of eight studies from different countries was published online Jan. 11 in an issue of the Journal of the American Heart Association devoted to the impact of pregnancy on CV health in the mother and child.

Breastfeeding is known to be associated with a lower risk for death from infectious disease and with fewer respiratory infections in babies, the researchers write, but what is less well known is that it is also associated with a reduced risk for breast and ovarian cancer and type 2 diabetes in mothers.

The current study showed a clear association between breastfeeding and reduced risk for CVD in later life, lead author Lena Tschiderer, Dipl.-Ing., PhD, and senior author Peter Willeit, MD, MPhil, PhD, summarized in a joint email to this news organization.

Specifically, mothers who had breastfed their children at any time had an 11% lower risk for CVD, a 14% lower risk for CHD, a 12% lower risk for stroke, and a 17% lower risk of dying from CVD in later life, compared with other mothers.

On the basis of existing evidence, the researchers write, the World Health Organization recommends exclusive breastfeeding until a baby is 6 months old, followed by breastfeeding plus complementary feeding until the baby is 2 years or older.

“We believe that [breastfeeding] benefits for the mother are communicated poorly,” said Dr. Tschiderer and Dr. Willeit, from the University of Innsbruck, Austria.

“Positive effects of breastfeeding on mothers need to be communicated effectively, awareness for breastfeeding recommendations needs to be raised, and interventions to promote and facilitate breastfeeding need to be implemented and reinforced,” the researchers conclude.
 

‘Should not be ignored’

Two cardiologists invited to comment, who were not involved with the research, noted that this study provides insight into an important topic.

“This is yet another body of evidence [and the largest population to date] to show that breastfeeding is protective for women and may show important beneficial effects in terms of CV risk,” Roxana Mehran, MD, said in an email.

“The risk reductions were 11% for CVD events and 14% for CHD events; these are impressive numbers,” said Dr. Mehran, from Icahn School of Medicine at Mount Sinai, New York.

“The caveat,” she said, “is that these are data from several trials, but nonetheless, this is a very important observation that should not be ignored.”

The study did not address the definitive amount of time of breastfeeding and its correlation to the improvement of CVD risk, but it did show that for the lifetime duration, the longer the better.

“The beneficial effects,” she noted, “can be linked to hormones during breastfeeding, as well as weight loss associated with breastfeeding, and resetting the maternal metabolism, as the authors suggest.”

Clinicians and employers “must provide ways to educate women about breastfeeding and make it easy for women who are in the workplace to pump, and to provide them with resources” where possible, Dr. Mehran said.

Michelle O’Donoghue, MD, MPH, noted that over the past several years, there has been intense interest in the possible health benefits of breastfeeding for both mother and child.

There is biologic plausibility for some of the possible maternal benefits because the favorable CV effects of both prolactin and oxytocin are only now being better understood, said Dr. O’Donoghue, from Brigham and Women’s Hospital and Harvard Medical School, Boston.

“The current meta-analysis provides a large dataset that helps support the concept that breastfeeding may offer some cardiovascular benefit for the mother,” she agreed.

“However, ultimately more research will be necessary since this method of combining data across trials relies upon the robustness of the statistical method in each study,” Dr. O’Donoghue said. “I applaud the authors for shining a spotlight on this important topic.”

Although the benefits of breastfeeding appear to continue over time, “it is incredibly difficult for women to continue breastfeeding once they return to work,” she added. “Women in some countries outside the U.S. have an advantage due to longer durations of maternity leave.

“If we want to encourage breastfeeding,” Dr. O’Donoghue stressed, “we need to make sure that we put the right supports in place. Women need protected places to breastfeed in the workplace and places to store their milk. Most importantly, women need to be allowed dedicated time to make it happen.”
 

First large study of CVD in mothers

Emerging individual studies suggest that mothers who breastfeed may have a lower risk for CVD in later life, but studies have been inconsistent, and it is not clear if longer breastfeeding would strengthen this benefit, the authors note.

To examine this, they pooled data from the following eight studies (with study acronym, country, and baseline enrolment dates in brackets): 45&Up (Australia, 2006-2009), China Kadoorie Biobank (CKB, China, 2004-2008), European Prospective Investigation into Cancer and Nutrition (EPIC, multinational, 1992-2000), Gallagher et al. (China, 1989-1991), Nord-Trøndelag Health Survey 2 (HUNT2, Norway, 1995-1997), Japan Public Health Center-based Prospective Study (JPHC, Japan, 1990-1994), Nurses’ Health Study (NHS, U.S., 1986), and the Woman’s Health Initiative (WHI, U.S., 1993-1998).

On average, the women were 51.3 years old (range, 40-65 years) when they enrolled in the study, and they were followed for a median of 10.3 years (range, 7.9-20.9 years, in the individual studies).

On average, they had their first child at age 25 and had two to three children (mean, 2.3); 82% had breastfed at some point (ranging from 58% of women in the two U.S. studies to 97% in CKB and HUNT2).

The women had breastfed for a mean of 7.4 to 18.9 months during their lifetimes (except women in the CKB study, who had breastfed for a median of 24 months).

Among the 1,192,700 women, there were 54,226 incident CVD events, 26,913 incident CHD events, 30,843 incident strokes, and 10,766 deaths from CVD during follow-up.

The researchers acknowledge that study limitations include the fact that there could have been publication bias, since fewer than 10 studies were available for pooling. There was significant between-study heterogeneity for CVD, CHD, and stroke outcomes.

Participant-level data were also lacking, and breastfeeding was self-reported. There may have been unaccounted residual confounding, and the benefits of lifetime breastfeeding that is longer than 2 years are not clear, because few women in this population breastfed that long.

The research was funded by the Austrian Science Fund. The researchers and Dr. Mehran and Dr. O’Donoghue have no relevant financial disclosures.

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

A new investigation has found that rates of physical trauma following operative vaginal delivery (OVD) in Canada are higher than previously reported.

The cohort study of more than 1.3 million deliveries in the country found trauma rates were highest with forceps delivery, with more than 1 in 4 pregnancies resulting in maternal trauma and 1 in 105 infants experiencing neonatal trauma. Maternal and neonatal trauma following vacuum deliveries was less common, occurring in 1 in 8 pregnancies and 1 in 104 infants, according to the researchers, who reported their findings in the Canadian Medical Association Journal .

“The rates of trauma following OVD in Canada are higher than previously reported, irrespective of region, level of obstetric care, and volume of instrument use among hospitals,” lead author Giulia Muraca, PhD, MPH, assistant professor of obstetrics and gynecology at McMaster University, Hamilton, Ont., said in an interview. “While OVDs may be associated with low rates of morbidity in carefully selected circumstances, the uniformly high rates of trauma among forceps and vacuum deliveries documented across regions, levels of obstetric care, and hospitals show that such conditions do not apply to routine obstetric practice in Canada.”

The American College of Obstetricians and Gynecologists considers OVD a way to reduce the rate of cesarean deliveries. However, the group has also pointed to a decline in familiarity with the procedures among clinicians new to the field.

Current reports also show that while OVD accounts for up to 15% of deliveries in Canada, Australia, and the United Kingdom, the risks associated with the approach are heavily dependent on the expertise of the provider. Declining use of OVD in favor of cesarean delivery has reduced opportunities for clinicians to acquire proficiency in performing these deliveries, according to the researchers.

Given these various factors, the investigators said the consensus on the safety of OVD is under scrutiny.

“An examination of maternal and neonatal trauma among OVD in contemporary practice is necessary to ensure that health care providers, policy makers, and pregnant individuals are informed regarding the risks of OVD typically experienced in routine obstetric practice, rather than those encountered under ideal conditions,” Dr. Muraca said.
 

Over 1 million deliveries studied

Dr. Muraca and colleagues looked at 1,326,191 deliveries occurring across Canada (except Quebec) between April 2013 and March 2019. The researchers included all singleton, term (≥37 weeks), in-hospital deliveries to women who had not undergone a previous cesarean delivery.

The study’s primary outcome measures were composite maternal trauma and composite neonatal trauma. Maternal trauma included obstetric anal sphincter injury (OASI); cervical or high vaginal laceration; pelvic hematoma; obstetric injury to the pelvic organs, pelvic joints, or ligaments; injury to the bladder or urethra; and other pelvic trauma. Neonatal trauma comprised intracranial hemorrhage and laceration, skull fracture, severe injury to the central or peripheral nervous system, fracture of the long bones, injury to the liver or spleen, seizures, and neonatal death.

The analysis found that 38,500 (2.9%) of the cases involved attempted forceps deliveries while 110,987 (8.4%) were attempted vacuum deliveries. Of the attempted forceps deliveries, 1,606 (4.2%) failed, while 8,791 (7.9%) of attempted vacuum deliveries failed.

Maternal trauma was observed in 25.3% of all forceps deliveries (n = 9,728) and 13.2% of all vacuum deliveries (n = 14,614), the researchers reported. The most common form of maternal trauma was OASI, which was observed in 21.52% of women undergoing forceps delivery and 11.67% of those undergoing vacuum delivery. The rates of all other forms of maternal trauma were higher among patients undergoing attempted forceps delivery than among their counterparts undergoing attempted vacuum delivery.

After adjusting for possible confounders, rates of maternal trauma remained higher with forceps than with vacuum deliveries (adjusted rate ratio, 1.70).

The rate of neonatal trauma was comparable for forceps (9.56/1,000 live births) and vacuum deliveries (9.58/1,000 live births). In these cases, damage to the peripheral nervous system was the most common form of neonatal trauma, occurring in 4.85/1,000 live births with forceps delivery and 3.41/1,000 live births for vacuum delivery, the researchers found.
 

Consider morbidity following OVD against potential alternatives, authors say

According to Dr. Muraca, the rates of maternal trauma in her study – along with accumulating evidence of the severe long-term consequences of these injuries – demonstrates the importance of reporting timely, empirically derived risk measures that accurately reflect those that pregnant individuals may encounter in typical obstetric practice.

“Although there is merit in understanding the estimates of risk that can be achieved when conditions are optimal, the interpretation of these estimates can be misleading, especially given secular shifts in patterns of practice,” she said. “The failure to do so compromises women’s autonomy in making evidence-informed decisions regarding childbirth interventions, such as evaluating the short- and long-term risks of OVD and cesarean delivery.

Her group recommended that morbidity following OVD be weighed against potential alternatives to such procedures, which carry their own risks. “This includes an extended second stage of labor and a spontaneous vaginal delivery, or a second-stage cesarean delivery, both of which are associated with significant morbidity,” Dr. Muraca said. “However, a comprehensive consideration of high population rates of OVD morbidity also prompts questions about choice of instrument, obstetrician training in OVD use, and for recognizing cases that would benefit from a cesarean delivery earlier in labor.”

Alan Peaceman, MD, professor of obstetrics and gynecology at Northwestern University, Chicago, said he was not surprised by the rates of sphincter injury, but that the rate of severe neonatal injury rate was higher than he expected. However, he added, “I don’t think clinicians should change their approach based on a single study. They should continue with the approach that they are most skilled at and is appropriate for the clinical circumstances.”

The study was funded by a grant from the Canadian Institutes of Health Research. Dr. Muraca and Dr. Peaceman have disclosed no relevant financial relationships.

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

A new investigation has found that rates of physical trauma following operative vaginal delivery (OVD) in Canada are higher than previously reported.

The cohort study of more than 1.3 million deliveries in the country found trauma rates were highest with forceps delivery, with more than 1 in 4 pregnancies resulting in maternal trauma and 1 in 105 infants experiencing neonatal trauma. Maternal and neonatal trauma following vacuum deliveries was less common, occurring in 1 in 8 pregnancies and 1 in 104 infants, according to the researchers, who reported their findings in the Canadian Medical Association Journal .

“The rates of trauma following OVD in Canada are higher than previously reported, irrespective of region, level of obstetric care, and volume of instrument use among hospitals,” lead author Giulia Muraca, PhD, MPH, assistant professor of obstetrics and gynecology at McMaster University, Hamilton, Ont., said in an interview. “While OVDs may be associated with low rates of morbidity in carefully selected circumstances, the uniformly high rates of trauma among forceps and vacuum deliveries documented across regions, levels of obstetric care, and hospitals show that such conditions do not apply to routine obstetric practice in Canada.”

The American College of Obstetricians and Gynecologists considers OVD a way to reduce the rate of cesarean deliveries. However, the group has also pointed to a decline in familiarity with the procedures among clinicians new to the field.

Current reports also show that while OVD accounts for up to 15% of deliveries in Canada, Australia, and the United Kingdom, the risks associated with the approach are heavily dependent on the expertise of the provider. Declining use of OVD in favor of cesarean delivery has reduced opportunities for clinicians to acquire proficiency in performing these deliveries, according to the researchers.

Given these various factors, the investigators said the consensus on the safety of OVD is under scrutiny.

“An examination of maternal and neonatal trauma among OVD in contemporary practice is necessary to ensure that health care providers, policy makers, and pregnant individuals are informed regarding the risks of OVD typically experienced in routine obstetric practice, rather than those encountered under ideal conditions,” Dr. Muraca said.
 

Over 1 million deliveries studied

Dr. Muraca and colleagues looked at 1,326,191 deliveries occurring across Canada (except Quebec) between April 2013 and March 2019. The researchers included all singleton, term (≥37 weeks), in-hospital deliveries to women who had not undergone a previous cesarean delivery.

The study’s primary outcome measures were composite maternal trauma and composite neonatal trauma. Maternal trauma included obstetric anal sphincter injury (OASI); cervical or high vaginal laceration; pelvic hematoma; obstetric injury to the pelvic organs, pelvic joints, or ligaments; injury to the bladder or urethra; and other pelvic trauma. Neonatal trauma comprised intracranial hemorrhage and laceration, skull fracture, severe injury to the central or peripheral nervous system, fracture of the long bones, injury to the liver or spleen, seizures, and neonatal death.

The analysis found that 38,500 (2.9%) of the cases involved attempted forceps deliveries while 110,987 (8.4%) were attempted vacuum deliveries. Of the attempted forceps deliveries, 1,606 (4.2%) failed, while 8,791 (7.9%) of attempted vacuum deliveries failed.

Maternal trauma was observed in 25.3% of all forceps deliveries (n = 9,728) and 13.2% of all vacuum deliveries (n = 14,614), the researchers reported. The most common form of maternal trauma was OASI, which was observed in 21.52% of women undergoing forceps delivery and 11.67% of those undergoing vacuum delivery. The rates of all other forms of maternal trauma were higher among patients undergoing attempted forceps delivery than among their counterparts undergoing attempted vacuum delivery.

After adjusting for possible confounders, rates of maternal trauma remained higher with forceps than with vacuum deliveries (adjusted rate ratio, 1.70).

The rate of neonatal trauma was comparable for forceps (9.56/1,000 live births) and vacuum deliveries (9.58/1,000 live births). In these cases, damage to the peripheral nervous system was the most common form of neonatal trauma, occurring in 4.85/1,000 live births with forceps delivery and 3.41/1,000 live births for vacuum delivery, the researchers found.
 

Consider morbidity following OVD against potential alternatives, authors say

According to Dr. Muraca, the rates of maternal trauma in her study – along with accumulating evidence of the severe long-term consequences of these injuries – demonstrates the importance of reporting timely, empirically derived risk measures that accurately reflect those that pregnant individuals may encounter in typical obstetric practice.

“Although there is merit in understanding the estimates of risk that can be achieved when conditions are optimal, the interpretation of these estimates can be misleading, especially given secular shifts in patterns of practice,” she said. “The failure to do so compromises women’s autonomy in making evidence-informed decisions regarding childbirth interventions, such as evaluating the short- and long-term risks of OVD and cesarean delivery.

Her group recommended that morbidity following OVD be weighed against potential alternatives to such procedures, which carry their own risks. “This includes an extended second stage of labor and a spontaneous vaginal delivery, or a second-stage cesarean delivery, both of which are associated with significant morbidity,” Dr. Muraca said. “However, a comprehensive consideration of high population rates of OVD morbidity also prompts questions about choice of instrument, obstetrician training in OVD use, and for recognizing cases that would benefit from a cesarean delivery earlier in labor.”

Alan Peaceman, MD, professor of obstetrics and gynecology at Northwestern University, Chicago, said he was not surprised by the rates of sphincter injury, but that the rate of severe neonatal injury rate was higher than he expected. However, he added, “I don’t think clinicians should change their approach based on a single study. They should continue with the approach that they are most skilled at and is appropriate for the clinical circumstances.”

The study was funded by a grant from the Canadian Institutes of Health Research. Dr. Muraca and Dr. Peaceman have disclosed no relevant financial relationships.

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

A new investigation has found that rates of physical trauma following operative vaginal delivery (OVD) in Canada are higher than previously reported.

The cohort study of more than 1.3 million deliveries in the country found trauma rates were highest with forceps delivery, with more than 1 in 4 pregnancies resulting in maternal trauma and 1 in 105 infants experiencing neonatal trauma. Maternal and neonatal trauma following vacuum deliveries was less common, occurring in 1 in 8 pregnancies and 1 in 104 infants, according to the researchers, who reported their findings in the Canadian Medical Association Journal .

“The rates of trauma following OVD in Canada are higher than previously reported, irrespective of region, level of obstetric care, and volume of instrument use among hospitals,” lead author Giulia Muraca, PhD, MPH, assistant professor of obstetrics and gynecology at McMaster University, Hamilton, Ont., said in an interview. “While OVDs may be associated with low rates of morbidity in carefully selected circumstances, the uniformly high rates of trauma among forceps and vacuum deliveries documented across regions, levels of obstetric care, and hospitals show that such conditions do not apply to routine obstetric practice in Canada.”

The American College of Obstetricians and Gynecologists considers OVD a way to reduce the rate of cesarean deliveries. However, the group has also pointed to a decline in familiarity with the procedures among clinicians new to the field.

Current reports also show that while OVD accounts for up to 15% of deliveries in Canada, Australia, and the United Kingdom, the risks associated with the approach are heavily dependent on the expertise of the provider. Declining use of OVD in favor of cesarean delivery has reduced opportunities for clinicians to acquire proficiency in performing these deliveries, according to the researchers.

Given these various factors, the investigators said the consensus on the safety of OVD is under scrutiny.

“An examination of maternal and neonatal trauma among OVD in contemporary practice is necessary to ensure that health care providers, policy makers, and pregnant individuals are informed regarding the risks of OVD typically experienced in routine obstetric practice, rather than those encountered under ideal conditions,” Dr. Muraca said.
 

Over 1 million deliveries studied

Dr. Muraca and colleagues looked at 1,326,191 deliveries occurring across Canada (except Quebec) between April 2013 and March 2019. The researchers included all singleton, term (≥37 weeks), in-hospital deliveries to women who had not undergone a previous cesarean delivery.

The study’s primary outcome measures were composite maternal trauma and composite neonatal trauma. Maternal trauma included obstetric anal sphincter injury (OASI); cervical or high vaginal laceration; pelvic hematoma; obstetric injury to the pelvic organs, pelvic joints, or ligaments; injury to the bladder or urethra; and other pelvic trauma. Neonatal trauma comprised intracranial hemorrhage and laceration, skull fracture, severe injury to the central or peripheral nervous system, fracture of the long bones, injury to the liver or spleen, seizures, and neonatal death.

The analysis found that 38,500 (2.9%) of the cases involved attempted forceps deliveries while 110,987 (8.4%) were attempted vacuum deliveries. Of the attempted forceps deliveries, 1,606 (4.2%) failed, while 8,791 (7.9%) of attempted vacuum deliveries failed.

Maternal trauma was observed in 25.3% of all forceps deliveries (n = 9,728) and 13.2% of all vacuum deliveries (n = 14,614), the researchers reported. The most common form of maternal trauma was OASI, which was observed in 21.52% of women undergoing forceps delivery and 11.67% of those undergoing vacuum delivery. The rates of all other forms of maternal trauma were higher among patients undergoing attempted forceps delivery than among their counterparts undergoing attempted vacuum delivery.

After adjusting for possible confounders, rates of maternal trauma remained higher with forceps than with vacuum deliveries (adjusted rate ratio, 1.70).

The rate of neonatal trauma was comparable for forceps (9.56/1,000 live births) and vacuum deliveries (9.58/1,000 live births). In these cases, damage to the peripheral nervous system was the most common form of neonatal trauma, occurring in 4.85/1,000 live births with forceps delivery and 3.41/1,000 live births for vacuum delivery, the researchers found.
 

Consider morbidity following OVD against potential alternatives, authors say

According to Dr. Muraca, the rates of maternal trauma in her study – along with accumulating evidence of the severe long-term consequences of these injuries – demonstrates the importance of reporting timely, empirically derived risk measures that accurately reflect those that pregnant individuals may encounter in typical obstetric practice.

“Although there is merit in understanding the estimates of risk that can be achieved when conditions are optimal, the interpretation of these estimates can be misleading, especially given secular shifts in patterns of practice,” she said. “The failure to do so compromises women’s autonomy in making evidence-informed decisions regarding childbirth interventions, such as evaluating the short- and long-term risks of OVD and cesarean delivery.

Her group recommended that morbidity following OVD be weighed against potential alternatives to such procedures, which carry their own risks. “This includes an extended second stage of labor and a spontaneous vaginal delivery, or a second-stage cesarean delivery, both of which are associated with significant morbidity,” Dr. Muraca said. “However, a comprehensive consideration of high population rates of OVD morbidity also prompts questions about choice of instrument, obstetrician training in OVD use, and for recognizing cases that would benefit from a cesarean delivery earlier in labor.”

Alan Peaceman, MD, professor of obstetrics and gynecology at Northwestern University, Chicago, said he was not surprised by the rates of sphincter injury, but that the rate of severe neonatal injury rate was higher than he expected. However, he added, “I don’t think clinicians should change their approach based on a single study. They should continue with the approach that they are most skilled at and is appropriate for the clinical circumstances.”

The study was funded by a grant from the Canadian Institutes of Health Research. Dr. Muraca and Dr. Peaceman have disclosed no relevant financial relationships.

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

Pregnant women’s thyroid hormone trajectories (levels in the first, second, and third trimester) may predict whether their male offspring are aggressive or withdrawn at age 4.

Certain maternal thyroid hormone trajectories were associated with problem behaviors in preschool boys in a study of close to 2,000 mother-child pairs in China.

The researchers identified low, moderate, and high thyroid-stimulating hormone (TSH) and free thyroxine (FT4) trajectories. 

shironosov/Getty Images

‘Study supports monitoring thyroid function in pregnancy’

“Our findings highlight the significance of close monitoring and management of maternal thyroid function during pregnancy,” senior author Kun Huang, PhD, said in a press release from the Endocrine Society.

“This research presents a new perspective in early intervention of children’s emotional and behavioral problems,” added Dr. Huang, from Anhui Medical University, Hefei, China.

The results add to a growing body of literature about a controversial link between maternal thyroid hormones in pregnancy, when the fetal brain is developing, and subsequent behavior in preschool children, Caroline T. Nguyen, MD, who was not involved with this research, commented in an email.

“Some studies show an association between thyroid levels and behavioral outcomes, others not,” added Dr. Nguyen, assistant professor of clinical medicine, Keck School of Medicine, University of Southern California, Los Angeles. And “some studies have found sex-specific associations with maternal thyroid levels and neurocognitive/behavioral outcomes, others have not.”

Women considering pregnancy should be evaluated for possible thyroid disease, she continued. Currently, no universal screening mandates exist for thyroid disease in pregnancy, but the 2017 American Thyroid Association guidelines do recommend screening women at risk for thyroid dysfunction.

“I think screening for thyroid peroxidase antibody (TPOAb) positivity is helpful in women desiring pregnancy,” Dr. Nguyen continued, “because we know that patients with TPOAb positivity are at increased risk for miscarriage and have a blunted response to the increased demands of pregnancy for thyroid hormone production.”

TPOAb positivity is also associated with the increased risk of postpartum and long-term thyroid dysfunction.

This current study, Dr. Nguyen summarized, “adds to a growing body of research of the relationship of thyroid hormone levels and neurocognitive outcomes [in offspring] and supports the monitoring of thyroid disease in pregnancy.”  

“However, we do not have sufficient data to demonstrate the benefits of intervention with levothyroxine treatment,” she noted. 

Nevertheless, the lack of positive data does not suggest there is no theoretical benefit of intervention, she said, as such studies are very challenging to do. 

“Physicians can help reduce stress and anxiety in patients desiring pregnancy by [recommending] preconception counseling, screening patients at risk for thyroid disease, and optimizing thyroid hormone levels before and during pregnancy,” according to Dr. Nguyen.
 

Maternal TSH and FT4 trajectories and preschoolers’ behaviors

Previous studies have reported that during pregnancy, maternal subclinical hypothyroidism (elevated TSH with normal FT4) as well as isolated hypothyroxinemia (decreased FT4 with normal TSH) are associated with adverse maternal and child outcomes, including preterm delivery and low birth weight.

However, most studies have not determined maternal thyroid hormone levels in different trimesters.

Researchers recruited pregnant women going for their first antenatal checkup at the Ma’anshan Maternal and Child Health Hospital in China from May 2013 to September 2014 and identified 1,860 mother-child pairs.

They determined maternal thyroid hormone levels from blood samples taken during the first, second, and third trimester: on average, gestational week 10, 25, and 34, respectively.

The researchers found that TSH levels increased somewhat from trimester 1 to trimester 2 and then decreased slightly in trimester 3. Most women (68%) had a low TSH trajectory, 28% had a moderate TSH trajectory, and 4% had a high TSH trajectory.

FT4 levels dropped sharply from trimester 1 to trimester 2 and then increased somewhat in trimester 3. About half of the women (52%) had a moderate FT4 trajectory, 33% had a low FT4 trajectory, and 15% had a high FT4 trajectory.

Most women (96.5%) had a low and stable TPOAb level, and the rest (3.5%) had high and decreasing TPOAb levels.  

When the children in the study were 4 years old, their main caregiver (parent or grandparent) completed the 100-question Achenbach Child Behavior checklist to identify whether the child often, sometimes, or never displayed three internalizing problem behaviors (emotionally reactive, anxious/depressed, or withdrawn) and/or two externalizing problem behaviors (attention problems or aggressive behavior).
 

Study limitations, more research needed

It is not clear why the associations between maternal hormones and offspring behavior were only seen in boys. Perhaps male fetuses are more sensitive than female fetuses to changing maternal thyroid hormone levels in pregnancy, the researchers speculate.

They acknowledge that study limitations include there were few children with aggressive behavior, so the confidence interval for the association of the moderate TSH trajectory with aggressive behavior was very wide.

In addition, evaluation of children’s behavior by caregivers was subjective. Also, the researchers did not have information about iodine levels, and low iodine levels can impair child brain development.

And there may have been residual confounders that researchers did not account for, such as differences in family upbringing, parental marital status, and the mother’s exposure to endocrine disruptors.

Therefore, further research is needed.

The study was supported by grants from the National Natural Science Foundation of China, the University Synergy Innovation Program of Anhui Province, the Sci-Tech Basic Resources Research Program of China, the National Key Research and Development Program, the Chinese Academy of Medical Sciences, and the Research Fund of Anhui Institute of Translational Medicine. The researchers and Dr. Nguyen have reported no relevant financial relationships.

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

Pregnant women’s thyroid hormone trajectories (levels in the first, second, and third trimester) may predict whether their male offspring are aggressive or withdrawn at age 4.

Certain maternal thyroid hormone trajectories were associated with problem behaviors in preschool boys in a study of close to 2,000 mother-child pairs in China.

The researchers identified low, moderate, and high thyroid-stimulating hormone (TSH) and free thyroxine (FT4) trajectories. 

shironosov/Getty Images

‘Study supports monitoring thyroid function in pregnancy’

“Our findings highlight the significance of close monitoring and management of maternal thyroid function during pregnancy,” senior author Kun Huang, PhD, said in a press release from the Endocrine Society.

“This research presents a new perspective in early intervention of children’s emotional and behavioral problems,” added Dr. Huang, from Anhui Medical University, Hefei, China.

The results add to a growing body of literature about a controversial link between maternal thyroid hormones in pregnancy, when the fetal brain is developing, and subsequent behavior in preschool children, Caroline T. Nguyen, MD, who was not involved with this research, commented in an email.

“Some studies show an association between thyroid levels and behavioral outcomes, others not,” added Dr. Nguyen, assistant professor of clinical medicine, Keck School of Medicine, University of Southern California, Los Angeles. And “some studies have found sex-specific associations with maternal thyroid levels and neurocognitive/behavioral outcomes, others have not.”

Women considering pregnancy should be evaluated for possible thyroid disease, she continued. Currently, no universal screening mandates exist for thyroid disease in pregnancy, but the 2017 American Thyroid Association guidelines do recommend screening women at risk for thyroid dysfunction.

“I think screening for thyroid peroxidase antibody (TPOAb) positivity is helpful in women desiring pregnancy,” Dr. Nguyen continued, “because we know that patients with TPOAb positivity are at increased risk for miscarriage and have a blunted response to the increased demands of pregnancy for thyroid hormone production.”

TPOAb positivity is also associated with the increased risk of postpartum and long-term thyroid dysfunction.

This current study, Dr. Nguyen summarized, “adds to a growing body of research of the relationship of thyroid hormone levels and neurocognitive outcomes [in offspring] and supports the monitoring of thyroid disease in pregnancy.”  

“However, we do not have sufficient data to demonstrate the benefits of intervention with levothyroxine treatment,” she noted. 

Nevertheless, the lack of positive data does not suggest there is no theoretical benefit of intervention, she said, as such studies are very challenging to do. 

“Physicians can help reduce stress and anxiety in patients desiring pregnancy by [recommending] preconception counseling, screening patients at risk for thyroid disease, and optimizing thyroid hormone levels before and during pregnancy,” according to Dr. Nguyen.
 

Maternal TSH and FT4 trajectories and preschoolers’ behaviors

Previous studies have reported that during pregnancy, maternal subclinical hypothyroidism (elevated TSH with normal FT4) as well as isolated hypothyroxinemia (decreased FT4 with normal TSH) are associated with adverse maternal and child outcomes, including preterm delivery and low birth weight.

However, most studies have not determined maternal thyroid hormone levels in different trimesters.

Researchers recruited pregnant women going for their first antenatal checkup at the Ma’anshan Maternal and Child Health Hospital in China from May 2013 to September 2014 and identified 1,860 mother-child pairs.

They determined maternal thyroid hormone levels from blood samples taken during the first, second, and third trimester: on average, gestational week 10, 25, and 34, respectively.

The researchers found that TSH levels increased somewhat from trimester 1 to trimester 2 and then decreased slightly in trimester 3. Most women (68%) had a low TSH trajectory, 28% had a moderate TSH trajectory, and 4% had a high TSH trajectory.

FT4 levels dropped sharply from trimester 1 to trimester 2 and then increased somewhat in trimester 3. About half of the women (52%) had a moderate FT4 trajectory, 33% had a low FT4 trajectory, and 15% had a high FT4 trajectory.

Most women (96.5%) had a low and stable TPOAb level, and the rest (3.5%) had high and decreasing TPOAb levels.  

When the children in the study were 4 years old, their main caregiver (parent or grandparent) completed the 100-question Achenbach Child Behavior checklist to identify whether the child often, sometimes, or never displayed three internalizing problem behaviors (emotionally reactive, anxious/depressed, or withdrawn) and/or two externalizing problem behaviors (attention problems or aggressive behavior).
 

Study limitations, more research needed

It is not clear why the associations between maternal hormones and offspring behavior were only seen in boys. Perhaps male fetuses are more sensitive than female fetuses to changing maternal thyroid hormone levels in pregnancy, the researchers speculate.

They acknowledge that study limitations include there were few children with aggressive behavior, so the confidence interval for the association of the moderate TSH trajectory with aggressive behavior was very wide.

In addition, evaluation of children’s behavior by caregivers was subjective. Also, the researchers did not have information about iodine levels, and low iodine levels can impair child brain development.

And there may have been residual confounders that researchers did not account for, such as differences in family upbringing, parental marital status, and the mother’s exposure to endocrine disruptors.

Therefore, further research is needed.

The study was supported by grants from the National Natural Science Foundation of China, the University Synergy Innovation Program of Anhui Province, the Sci-Tech Basic Resources Research Program of China, the National Key Research and Development Program, the Chinese Academy of Medical Sciences, and the Research Fund of Anhui Institute of Translational Medicine. The researchers and Dr. Nguyen have reported no relevant financial relationships.

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

Pregnant women’s thyroid hormone trajectories (levels in the first, second, and third trimester) may predict whether their male offspring are aggressive or withdrawn at age 4.

Certain maternal thyroid hormone trajectories were associated with problem behaviors in preschool boys in a study of close to 2,000 mother-child pairs in China.

The researchers identified low, moderate, and high thyroid-stimulating hormone (TSH) and free thyroxine (FT4) trajectories. 

shironosov/Getty Images

‘Study supports monitoring thyroid function in pregnancy’

“Our findings highlight the significance of close monitoring and management of maternal thyroid function during pregnancy,” senior author Kun Huang, PhD, said in a press release from the Endocrine Society.

“This research presents a new perspective in early intervention of children’s emotional and behavioral problems,” added Dr. Huang, from Anhui Medical University, Hefei, China.

The results add to a growing body of literature about a controversial link between maternal thyroid hormones in pregnancy, when the fetal brain is developing, and subsequent behavior in preschool children, Caroline T. Nguyen, MD, who was not involved with this research, commented in an email.

“Some studies show an association between thyroid levels and behavioral outcomes, others not,” added Dr. Nguyen, assistant professor of clinical medicine, Keck School of Medicine, University of Southern California, Los Angeles. And “some studies have found sex-specific associations with maternal thyroid levels and neurocognitive/behavioral outcomes, others have not.”

Women considering pregnancy should be evaluated for possible thyroid disease, she continued. Currently, no universal screening mandates exist for thyroid disease in pregnancy, but the 2017 American Thyroid Association guidelines do recommend screening women at risk for thyroid dysfunction.

“I think screening for thyroid peroxidase antibody (TPOAb) positivity is helpful in women desiring pregnancy,” Dr. Nguyen continued, “because we know that patients with TPOAb positivity are at increased risk for miscarriage and have a blunted response to the increased demands of pregnancy for thyroid hormone production.”

TPOAb positivity is also associated with the increased risk of postpartum and long-term thyroid dysfunction.

This current study, Dr. Nguyen summarized, “adds to a growing body of research of the relationship of thyroid hormone levels and neurocognitive outcomes [in offspring] and supports the monitoring of thyroid disease in pregnancy.”  

“However, we do not have sufficient data to demonstrate the benefits of intervention with levothyroxine treatment,” she noted. 

Nevertheless, the lack of positive data does not suggest there is no theoretical benefit of intervention, she said, as such studies are very challenging to do. 

“Physicians can help reduce stress and anxiety in patients desiring pregnancy by [recommending] preconception counseling, screening patients at risk for thyroid disease, and optimizing thyroid hormone levels before and during pregnancy,” according to Dr. Nguyen.
 

Maternal TSH and FT4 trajectories and preschoolers’ behaviors

Previous studies have reported that during pregnancy, maternal subclinical hypothyroidism (elevated TSH with normal FT4) as well as isolated hypothyroxinemia (decreased FT4 with normal TSH) are associated with adverse maternal and child outcomes, including preterm delivery and low birth weight.

However, most studies have not determined maternal thyroid hormone levels in different trimesters.

Researchers recruited pregnant women going for their first antenatal checkup at the Ma’anshan Maternal and Child Health Hospital in China from May 2013 to September 2014 and identified 1,860 mother-child pairs.

They determined maternal thyroid hormone levels from blood samples taken during the first, second, and third trimester: on average, gestational week 10, 25, and 34, respectively.

The researchers found that TSH levels increased somewhat from trimester 1 to trimester 2 and then decreased slightly in trimester 3. Most women (68%) had a low TSH trajectory, 28% had a moderate TSH trajectory, and 4% had a high TSH trajectory.

FT4 levels dropped sharply from trimester 1 to trimester 2 and then increased somewhat in trimester 3. About half of the women (52%) had a moderate FT4 trajectory, 33% had a low FT4 trajectory, and 15% had a high FT4 trajectory.

Most women (96.5%) had a low and stable TPOAb level, and the rest (3.5%) had high and decreasing TPOAb levels.  

When the children in the study were 4 years old, their main caregiver (parent or grandparent) completed the 100-question Achenbach Child Behavior checklist to identify whether the child often, sometimes, or never displayed three internalizing problem behaviors (emotionally reactive, anxious/depressed, or withdrawn) and/or two externalizing problem behaviors (attention problems or aggressive behavior).
 

Study limitations, more research needed

It is not clear why the associations between maternal hormones and offspring behavior were only seen in boys. Perhaps male fetuses are more sensitive than female fetuses to changing maternal thyroid hormone levels in pregnancy, the researchers speculate.

They acknowledge that study limitations include there were few children with aggressive behavior, so the confidence interval for the association of the moderate TSH trajectory with aggressive behavior was very wide.

In addition, evaluation of children’s behavior by caregivers was subjective. Also, the researchers did not have information about iodine levels, and low iodine levels can impair child brain development.

And there may have been residual confounders that researchers did not account for, such as differences in family upbringing, parental marital status, and the mother’s exposure to endocrine disruptors.

Therefore, further research is needed.

The study was supported by grants from the National Natural Science Foundation of China, the University Synergy Innovation Program of Anhui Province, the Sci-Tech Basic Resources Research Program of China, the National Key Research and Development Program, the Chinese Academy of Medical Sciences, and the Research Fund of Anhui Institute of Translational Medicine. The researchers and Dr. Nguyen have reported no relevant financial relationships.

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