Preterm Birth

Over the past decade, data have suggested that antiretroviral therapy (ART) may be associated with an increased risk for adverse pregnancy outcomes, namely, preterm birth (PTB). But a combination of methodologic challenges, demographic gaps, and spotty clinical data has left the question unresolved, especially for pregnant women with HIV who reside in developed countries.

“Given that a lot of the emerging data has come out of resource-limited settings where patient and clinical characteristics are different from developed world settings like the United States, we felt that this was an important question to address,” Kartik Venkatesh, MD, PhD, a high-risk obstetrician and perinatal epidemiologist at the Ohio State Wexner Medical Center, Columbus, told this news organization.

In a prospective cohort study of U.S. women with or at risk for HIV, Dr. Venkatesh and his colleagues found that ART exposure (including highly active antiretroviral therapy [HAART]) was associated with as much as an 80% decline in the likelihood of PTB (defined as birth less than 34 weeks). The study was published in HIV Medicine.
 

24 years of data analyzed

Dr. Venkatesh and his team analyzed self-reported birth data of women with singleton live-born pregnancies enrolled in the ongoing, multicenter, prospective observational Women’s Interagency HIV Study (WIHS) from Oct. 1, 1995, to March 31, 2019.

“We first looked at women with HIV versus without HIV, [who were] matched on many clinical and sociodemographic characteristics and at similarly high risk of some of these obstetrical outcomes like PTB,” explained Dr. Venkatesh. “We then looked at the relative impact of antiretroviral therapy amongst women living with HIV compared to no antiretroviral therapy.”

ART regimens were classified as none, monotherapy, dual therapy, or HAART. (HAART was defined as more than three antiretrovirals, including at least one protease inhibitor [PI], nonnucleoside reverse transcriptase inhibitor, integrase inhibitor, or entry inhibitor.) In this cohort, for 63.5% of women receiving ART, therapy was initiated before pregnancy (mean duration of HAART, 6 years), and most were virally suppressed.

Among the 4,944 women assessed in the WIHS trial, 74% (3,646) had HIV. In total, 383 women had 488 singleton deliveries, including 218 women with HIV (272 deliveries) and 165 without HIV (216 deliveries). Sociodemographics in both cohorts were well matched. For most participants, the mean age was 40-41 years at delivery, most were non-Hispanic Black persons, and the mean pregnancy body mass index was greater than or equal to 29 kg/m2. Of the women with HIV, 33% had chronic hypertension; of those without HIV, 42.1% had chronic hypertension; 4.7% and 5.0%, respectively, had pregestational diabetes.

The findings showed that PTB risk less than 34 weeks was similar between women with (10%) and without (8%) HIV (adjusted risk ratio, 1.30; 95% confidence interval, 0.74-2.31). Among deliveries to women with HIV who were receiving ART, PTB risk less than 34 weeks was lower with HAART (7%), compared with not receiving ART (26%) (aRR, 0.19), as well as with monotherapy or dual therapy (3% vs. no ART) (aRR, 0.12). Notably, 67% of deliveries to women receiving HAART included a PI-containing regimen, but these women were not significantly more likely to have a PTB less than 34 weeks, compared with women taking non-PI HAART regimens (aRR, 2.61; 95% CI, 0.65-10.59). Results were similar for secondary outcomes (PTB less than 28 weeks, less than 37 weeks).
 

Filling in the gaps toward the safest regimen

“This study spans 25 years, so it covers a lot of the history of HIV in pregnancy and is reassuring around using ART in pregnancy,” Shahin Lockman, MD, told this news organization. Dr. Lockman is an associate professor of infectious diseases at Brigham and Women’s Hospital and a co-PI of the Botswana Clinical Trials Unit at the Botswana Harvard AIDS Institute Partnership. She was not involved in the study. “One of the worst things for a mother and for pregnancy outcomes, for the fetus and baby’s health and development, is uncontrolled maternal HIV,’’ she said.

Dr. Lockman also noted potential confounders that drive poor birth outcomes in Southern African women, compared with U.S. women, making comparisons between this and other observational studies difficult. Still, she said that the question is not whether women should be receiving treatment but whether or not there are differences between antiretroviral regimens.

“One of the areas that we did not go deeper into was the subtype of antiretroviral therapy, given the relatively small study numbers [did not] allow us to do a robust analysis,” Dr. Venkatesh said.

Rather, he emphasized that the findings might lend more weight to speculation that immunologic characteristics associated with HIV status and immunotherapy – such as low CD4 cell counts prior to delivery, or duration of HIV infection – may be important drivers of adverse birth outcomes among women with HIV taking ART.

And at least in this cohort, many of these characteristics were similar between the treatment groups.

Both researchers agree that the findings – while reassuring – highlight the importance of collecting robust obstetric and safety data as part of prospective databases of individuals living with HIV, not only in resource-limited settings but also among the domestic U.S. population.

“We’ve learned a lot over the last 10 years,” Dr. Lockman said. “Some regimens (like lopinavir/ritonavir or nevirapine) are associated with significantly worse birth outcomes, whereas efavirenz doesn’t seem to be, or less so, and dolutegravir seems to be associated with even better outcomes. So, I think that where we are moving is to regimens that are the safest.”

Moving forward, Dr. Venkatesh explained, not only should researchers focus on exploring which antiretrovirals are safest in this context but also if the use of preexposure prophylaxis during conception periods affects birth outcomes.

Dr. Venkatesh and Dr. Lockman report no relevant financial relationships.

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

Over the past decade, data have suggested that antiretroviral therapy (ART) may be associated with an increased risk for adverse pregnancy outcomes, namely, preterm birth (PTB). But a combination of methodologic challenges, demographic gaps, and spotty clinical data has left the question unresolved, especially for pregnant women with HIV who reside in developed countries.

“Given that a lot of the emerging data has come out of resource-limited settings where patient and clinical characteristics are different from developed world settings like the United States, we felt that this was an important question to address,” Kartik Venkatesh, MD, PhD, a high-risk obstetrician and perinatal epidemiologist at the Ohio State Wexner Medical Center, Columbus, told this news organization.

In a prospective cohort study of U.S. women with or at risk for HIV, Dr. Venkatesh and his colleagues found that ART exposure (including highly active antiretroviral therapy [HAART]) was associated with as much as an 80% decline in the likelihood of PTB (defined as birth less than 34 weeks). The study was published in HIV Medicine.
 

24 years of data analyzed

Dr. Venkatesh and his team analyzed self-reported birth data of women with singleton live-born pregnancies enrolled in the ongoing, multicenter, prospective observational Women’s Interagency HIV Study (WIHS) from Oct. 1, 1995, to March 31, 2019.

“We first looked at women with HIV versus without HIV, [who were] matched on many clinical and sociodemographic characteristics and at similarly high risk of some of these obstetrical outcomes like PTB,” explained Dr. Venkatesh. “We then looked at the relative impact of antiretroviral therapy amongst women living with HIV compared to no antiretroviral therapy.”

ART regimens were classified as none, monotherapy, dual therapy, or HAART. (HAART was defined as more than three antiretrovirals, including at least one protease inhibitor [PI], nonnucleoside reverse transcriptase inhibitor, integrase inhibitor, or entry inhibitor.) In this cohort, for 63.5% of women receiving ART, therapy was initiated before pregnancy (mean duration of HAART, 6 years), and most were virally suppressed.

Among the 4,944 women assessed in the WIHS trial, 74% (3,646) had HIV. In total, 383 women had 488 singleton deliveries, including 218 women with HIV (272 deliveries) and 165 without HIV (216 deliveries). Sociodemographics in both cohorts were well matched. For most participants, the mean age was 40-41 years at delivery, most were non-Hispanic Black persons, and the mean pregnancy body mass index was greater than or equal to 29 kg/m2. Of the women with HIV, 33% had chronic hypertension; of those without HIV, 42.1% had chronic hypertension; 4.7% and 5.0%, respectively, had pregestational diabetes.

The findings showed that PTB risk less than 34 weeks was similar between women with (10%) and without (8%) HIV (adjusted risk ratio, 1.30; 95% confidence interval, 0.74-2.31). Among deliveries to women with HIV who were receiving ART, PTB risk less than 34 weeks was lower with HAART (7%), compared with not receiving ART (26%) (aRR, 0.19), as well as with monotherapy or dual therapy (3% vs. no ART) (aRR, 0.12). Notably, 67% of deliveries to women receiving HAART included a PI-containing regimen, but these women were not significantly more likely to have a PTB less than 34 weeks, compared with women taking non-PI HAART regimens (aRR, 2.61; 95% CI, 0.65-10.59). Results were similar for secondary outcomes (PTB less than 28 weeks, less than 37 weeks).
 

Filling in the gaps toward the safest regimen

“This study spans 25 years, so it covers a lot of the history of HIV in pregnancy and is reassuring around using ART in pregnancy,” Shahin Lockman, MD, told this news organization. Dr. Lockman is an associate professor of infectious diseases at Brigham and Women’s Hospital and a co-PI of the Botswana Clinical Trials Unit at the Botswana Harvard AIDS Institute Partnership. She was not involved in the study. “One of the worst things for a mother and for pregnancy outcomes, for the fetus and baby’s health and development, is uncontrolled maternal HIV,’’ she said.

Dr. Lockman also noted potential confounders that drive poor birth outcomes in Southern African women, compared with U.S. women, making comparisons between this and other observational studies difficult. Still, she said that the question is not whether women should be receiving treatment but whether or not there are differences between antiretroviral regimens.

“One of the areas that we did not go deeper into was the subtype of antiretroviral therapy, given the relatively small study numbers [did not] allow us to do a robust analysis,” Dr. Venkatesh said.

Rather, he emphasized that the findings might lend more weight to speculation that immunologic characteristics associated with HIV status and immunotherapy – such as low CD4 cell counts prior to delivery, or duration of HIV infection – may be important drivers of adverse birth outcomes among women with HIV taking ART.

And at least in this cohort, many of these characteristics were similar between the treatment groups.

Both researchers agree that the findings – while reassuring – highlight the importance of collecting robust obstetric and safety data as part of prospective databases of individuals living with HIV, not only in resource-limited settings but also among the domestic U.S. population.

“We’ve learned a lot over the last 10 years,” Dr. Lockman said. “Some regimens (like lopinavir/ritonavir or nevirapine) are associated with significantly worse birth outcomes, whereas efavirenz doesn’t seem to be, or less so, and dolutegravir seems to be associated with even better outcomes. So, I think that where we are moving is to regimens that are the safest.”

Moving forward, Dr. Venkatesh explained, not only should researchers focus on exploring which antiretrovirals are safest in this context but also if the use of preexposure prophylaxis during conception periods affects birth outcomes.

Dr. Venkatesh and Dr. Lockman report no relevant financial relationships.

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

Over the past decade, data have suggested that antiretroviral therapy (ART) may be associated with an increased risk for adverse pregnancy outcomes, namely, preterm birth (PTB). But a combination of methodologic challenges, demographic gaps, and spotty clinical data has left the question unresolved, especially for pregnant women with HIV who reside in developed countries.

“Given that a lot of the emerging data has come out of resource-limited settings where patient and clinical characteristics are different from developed world settings like the United States, we felt that this was an important question to address,” Kartik Venkatesh, MD, PhD, a high-risk obstetrician and perinatal epidemiologist at the Ohio State Wexner Medical Center, Columbus, told this news organization.

In a prospective cohort study of U.S. women with or at risk for HIV, Dr. Venkatesh and his colleagues found that ART exposure (including highly active antiretroviral therapy [HAART]) was associated with as much as an 80% decline in the likelihood of PTB (defined as birth less than 34 weeks). The study was published in HIV Medicine.
 

24 years of data analyzed

Dr. Venkatesh and his team analyzed self-reported birth data of women with singleton live-born pregnancies enrolled in the ongoing, multicenter, prospective observational Women’s Interagency HIV Study (WIHS) from Oct. 1, 1995, to March 31, 2019.

“We first looked at women with HIV versus without HIV, [who were] matched on many clinical and sociodemographic characteristics and at similarly high risk of some of these obstetrical outcomes like PTB,” explained Dr. Venkatesh. “We then looked at the relative impact of antiretroviral therapy amongst women living with HIV compared to no antiretroviral therapy.”

ART regimens were classified as none, monotherapy, dual therapy, or HAART. (HAART was defined as more than three antiretrovirals, including at least one protease inhibitor [PI], nonnucleoside reverse transcriptase inhibitor, integrase inhibitor, or entry inhibitor.) In this cohort, for 63.5% of women receiving ART, therapy was initiated before pregnancy (mean duration of HAART, 6 years), and most were virally suppressed.

Among the 4,944 women assessed in the WIHS trial, 74% (3,646) had HIV. In total, 383 women had 488 singleton deliveries, including 218 women with HIV (272 deliveries) and 165 without HIV (216 deliveries). Sociodemographics in both cohorts were well matched. For most participants, the mean age was 40-41 years at delivery, most were non-Hispanic Black persons, and the mean pregnancy body mass index was greater than or equal to 29 kg/m2. Of the women with HIV, 33% had chronic hypertension; of those without HIV, 42.1% had chronic hypertension; 4.7% and 5.0%, respectively, had pregestational diabetes.

The findings showed that PTB risk less than 34 weeks was similar between women with (10%) and without (8%) HIV (adjusted risk ratio, 1.30; 95% confidence interval, 0.74-2.31). Among deliveries to women with HIV who were receiving ART, PTB risk less than 34 weeks was lower with HAART (7%), compared with not receiving ART (26%) (aRR, 0.19), as well as with monotherapy or dual therapy (3% vs. no ART) (aRR, 0.12). Notably, 67% of deliveries to women receiving HAART included a PI-containing regimen, but these women were not significantly more likely to have a PTB less than 34 weeks, compared with women taking non-PI HAART regimens (aRR, 2.61; 95% CI, 0.65-10.59). Results were similar for secondary outcomes (PTB less than 28 weeks, less than 37 weeks).
 

Filling in the gaps toward the safest regimen

“This study spans 25 years, so it covers a lot of the history of HIV in pregnancy and is reassuring around using ART in pregnancy,” Shahin Lockman, MD, told this news organization. Dr. Lockman is an associate professor of infectious diseases at Brigham and Women’s Hospital and a co-PI of the Botswana Clinical Trials Unit at the Botswana Harvard AIDS Institute Partnership. She was not involved in the study. “One of the worst things for a mother and for pregnancy outcomes, for the fetus and baby’s health and development, is uncontrolled maternal HIV,’’ she said.

Dr. Lockman also noted potential confounders that drive poor birth outcomes in Southern African women, compared with U.S. women, making comparisons between this and other observational studies difficult. Still, she said that the question is not whether women should be receiving treatment but whether or not there are differences between antiretroviral regimens.

“One of the areas that we did not go deeper into was the subtype of antiretroviral therapy, given the relatively small study numbers [did not] allow us to do a robust analysis,” Dr. Venkatesh said.

Rather, he emphasized that the findings might lend more weight to speculation that immunologic characteristics associated with HIV status and immunotherapy – such as low CD4 cell counts prior to delivery, or duration of HIV infection – may be important drivers of adverse birth outcomes among women with HIV taking ART.

And at least in this cohort, many of these characteristics were similar between the treatment groups.

Both researchers agree that the findings – while reassuring – highlight the importance of collecting robust obstetric and safety data as part of prospective databases of individuals living with HIV, not only in resource-limited settings but also among the domestic U.S. population.

“We’ve learned a lot over the last 10 years,” Dr. Lockman said. “Some regimens (like lopinavir/ritonavir or nevirapine) are associated with significantly worse birth outcomes, whereas efavirenz doesn’t seem to be, or less so, and dolutegravir seems to be associated with even better outcomes. So, I think that where we are moving is to regimens that are the safest.”

Moving forward, Dr. Venkatesh explained, not only should researchers focus on exploring which antiretrovirals are safest in this context but also if the use of preexposure prophylaxis during conception periods affects birth outcomes.

Dr. Venkatesh and Dr. Lockman report no relevant financial relationships.

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

Group prenatal care did not reduce preterm birth among low-income patients compared to patients receiving individual prenatal care, but the different care models did shrink racial disparities in low-birth-weight and preterm births, according to a study presented Feb. 3 at the annual meeting sponsored by the Society for Maternal-Fetal Medicine. Patients who attended more group prenatal care visits also had better outcomes, reported Amy Crockett, MD, professor of ob.gyn. and director of the Maternal-Fetal Medicine Fellowship Program at the University of South Carolina in Greenville.

Though the results did not show group prenatal care to be the “silver bullet” they might have hoped for in reducing preterm birth and low birth weight among Black women, the study did show group prenatal care to have some clinical effect, Dr. Crockett suggested.

Ilina Pluym, MD, assistant professor of maternal-fetal medicine at the University of California Los Angeles, said that preterm birth and low birth weight are complex problems that cannot be solved by a single fix.

“In terms of the racial disparities, it is difficult to prove that 9 months of good access to prenatal care will undo the years of limited health care and life stressors that, as a whole, possibly contribute more to the overall risk profile of the patient,” Dr. Pluym said. “But as providers, we want to intervene and help in the portion that we can, and optimizing prenatal care is one tangible thing we can try.”

The racial disparities that exist in preterm birth, low birth weight, and infant and maternal mortality are not caused by biologic or genetic factors, Dr. Crockett told attendees.

”Rather, they are the result of long-standing systemic racism and discrimination deeply embedded in the culture of the United States,” she said. “To achieve racial equity, we need reform at the societal level.” But she noted that it might be possible for individual practices to play a role as well, which led her to design a study comparing outcomes from group versus individual prenatal care.

The group care model used for the study is called Centering Pregnancy, in which 8-10 pregnant patients who are due in the same month attend 10 two-hour prenatal care sessions together. Dr. Crockett noted that other research has identified potential reductions in preterm birth with group care models, but some are underpowered while others are observational and limited by confounding, selection bias, or small sample sizes.

The researchers aimed to recruit 3,160 patients to ensure an adequately powered study after estimated losses to follow-up, but they were able to recruit only 2,350 patients, resulting in potentially underpowered results. All the patients were receiving care at a single obstetric practice for a medically low-risk singleton pregnancy of 20 or fewer weeks gestation. A total of 1,176 patients were randomly assigned to attend group prenatal care appointments, and 1,174 patients were assigned to individual prenatal care.

The patients in both groups were an average age of 25 with a prepregnancy body mass index of 29. A similar proportion in both the group and individual care were married (24%) patients and had a government payer (96%-97%). Approximately 41%were Black patients, 37% were White patients, and 21% were Hispanic patients in both groups. Rates of chronic hypertension, smoking, vaginal infection in pregnancy, parity, cervix length, and use of cerclage were similar in both groups.

Gestational age outcomes were available for 1,099 group care patients (94%) and 1,120 individual care patients (95%), and birth weight outcomes were available for 1,028 group care patients (87%) and 1,044 individual care patients (89%).

In the individual care group, 8.7% of the patients had a preterm birth, compared to 10.4% who attended group prenatal care, but the findings did not reach significance (odds ratio [OR], 1.22; 95% confidence interval [CI]: 0.92-1.63). The difference between the 9.6% of group care patients and 8.9% of individual care patients who had babies with low birth weights were not significantly different.

While no significant difference in preterm birth occurred between the groups, the secondary outcome looking at racial disparities yielded one statistically significant result. Black women receiving individual prenatal care were twice as likely as were White women to have an infant with a low birth weight (OR, 2.1; 95% CI: 1.29-3.5). Among those receiving group care, however, the 12.5% of Black women and 8.9% of White women whose infants had a low birth weight were not significantly different.

There was a trend toward narrower disparities in preterm birth in the group versus individual care groups. Among those receiving group care, 11.4% of Black women and 10.8% of White women had a preterm birth, compared to 10.2% of Black women and 7.7% of White women in the individual care group.

Then the researchers compared the groups with regard to compliance while adjusting for baseline differences. “We saw decreasing rates of preterm birth for Black patients relative to White patients, particularly after attending five or more sessions in the group care arm with the rates of preterm birth narrowing and the disparity becoming nonsignificant with more exposure to group care,” Dr. Crockett said. “In individual care, the rate of preterm birth remained the highest for Black women regardless of the number of visits attended.”

The idea of trying group prenatal care is appealing, Dr. Pluym said in an interview, though both models have their advantages.

”The strength of individual care is the focus on the patient exam and individual patient questions,” Dr. Pluym said. “The strengths of group prenatal care are the consolidation of the patient education aspect of prenatal care that is uniform for all patients, the sense of community patients feel, and the opportunity to hear other patients questions that you may not have thought of. It sounds like, anecdotally, patients and providers really found the group sessions valuable and they helped dampen implicit bias and build relationships.”

One potential limitation of this randomized controlled trial is that the providers were the same for both group and individual care, potentially causing some confounding, Dr. Pluym noted. But the study does have one clear clinical message, she said.

“My take away is more prenatal care is better – individual or group,” Dr. Pluym said. “Every clinic should evaluate their own structure and see if group care would be feasible for their patient population. There may be a benefit globally, but is it is not the ‘silver bullet,’ as they said, for lowering preterm birth or growth restriction.”

The research was funded by the Institute of Child Health and Development. The study researchers and Dr. Pluym reported no disclosures.

Group prenatal care did not reduce preterm birth among low-income patients compared to patients receiving individual prenatal care, but the different care models did shrink racial disparities in low-birth-weight and preterm births, according to a study presented Feb. 3 at the annual meeting sponsored by the Society for Maternal-Fetal Medicine. Patients who attended more group prenatal care visits also had better outcomes, reported Amy Crockett, MD, professor of ob.gyn. and director of the Maternal-Fetal Medicine Fellowship Program at the University of South Carolina in Greenville.

Though the results did not show group prenatal care to be the “silver bullet” they might have hoped for in reducing preterm birth and low birth weight among Black women, the study did show group prenatal care to have some clinical effect, Dr. Crockett suggested.

Ilina Pluym, MD, assistant professor of maternal-fetal medicine at the University of California Los Angeles, said that preterm birth and low birth weight are complex problems that cannot be solved by a single fix.

“In terms of the racial disparities, it is difficult to prove that 9 months of good access to prenatal care will undo the years of limited health care and life stressors that, as a whole, possibly contribute more to the overall risk profile of the patient,” Dr. Pluym said. “But as providers, we want to intervene and help in the portion that we can, and optimizing prenatal care is one tangible thing we can try.”

The racial disparities that exist in preterm birth, low birth weight, and infant and maternal mortality are not caused by biologic or genetic factors, Dr. Crockett told attendees.

”Rather, they are the result of long-standing systemic racism and discrimination deeply embedded in the culture of the United States,” she said. “To achieve racial equity, we need reform at the societal level.” But she noted that it might be possible for individual practices to play a role as well, which led her to design a study comparing outcomes from group versus individual prenatal care.

The group care model used for the study is called Centering Pregnancy, in which 8-10 pregnant patients who are due in the same month attend 10 two-hour prenatal care sessions together. Dr. Crockett noted that other research has identified potential reductions in preterm birth with group care models, but some are underpowered while others are observational and limited by confounding, selection bias, or small sample sizes.

The researchers aimed to recruit 3,160 patients to ensure an adequately powered study after estimated losses to follow-up, but they were able to recruit only 2,350 patients, resulting in potentially underpowered results. All the patients were receiving care at a single obstetric practice for a medically low-risk singleton pregnancy of 20 or fewer weeks gestation. A total of 1,176 patients were randomly assigned to attend group prenatal care appointments, and 1,174 patients were assigned to individual prenatal care.

The patients in both groups were an average age of 25 with a prepregnancy body mass index of 29. A similar proportion in both the group and individual care were married (24%) patients and had a government payer (96%-97%). Approximately 41%were Black patients, 37% were White patients, and 21% were Hispanic patients in both groups. Rates of chronic hypertension, smoking, vaginal infection in pregnancy, parity, cervix length, and use of cerclage were similar in both groups.

Gestational age outcomes were available for 1,099 group care patients (94%) and 1,120 individual care patients (95%), and birth weight outcomes were available for 1,028 group care patients (87%) and 1,044 individual care patients (89%).

In the individual care group, 8.7% of the patients had a preterm birth, compared to 10.4% who attended group prenatal care, but the findings did not reach significance (odds ratio [OR], 1.22; 95% confidence interval [CI]: 0.92-1.63). The difference between the 9.6% of group care patients and 8.9% of individual care patients who had babies with low birth weights were not significantly different.

While no significant difference in preterm birth occurred between the groups, the secondary outcome looking at racial disparities yielded one statistically significant result. Black women receiving individual prenatal care were twice as likely as were White women to have an infant with a low birth weight (OR, 2.1; 95% CI: 1.29-3.5). Among those receiving group care, however, the 12.5% of Black women and 8.9% of White women whose infants had a low birth weight were not significantly different.

There was a trend toward narrower disparities in preterm birth in the group versus individual care groups. Among those receiving group care, 11.4% of Black women and 10.8% of White women had a preterm birth, compared to 10.2% of Black women and 7.7% of White women in the individual care group.

Then the researchers compared the groups with regard to compliance while adjusting for baseline differences. “We saw decreasing rates of preterm birth for Black patients relative to White patients, particularly after attending five or more sessions in the group care arm with the rates of preterm birth narrowing and the disparity becoming nonsignificant with more exposure to group care,” Dr. Crockett said. “In individual care, the rate of preterm birth remained the highest for Black women regardless of the number of visits attended.”

The idea of trying group prenatal care is appealing, Dr. Pluym said in an interview, though both models have their advantages.

”The strength of individual care is the focus on the patient exam and individual patient questions,” Dr. Pluym said. “The strengths of group prenatal care are the consolidation of the patient education aspect of prenatal care that is uniform for all patients, the sense of community patients feel, and the opportunity to hear other patients questions that you may not have thought of. It sounds like, anecdotally, patients and providers really found the group sessions valuable and they helped dampen implicit bias and build relationships.”

One potential limitation of this randomized controlled trial is that the providers were the same for both group and individual care, potentially causing some confounding, Dr. Pluym noted. But the study does have one clear clinical message, she said.

“My take away is more prenatal care is better – individual or group,” Dr. Pluym said. “Every clinic should evaluate their own structure and see if group care would be feasible for their patient population. There may be a benefit globally, but is it is not the ‘silver bullet,’ as they said, for lowering preterm birth or growth restriction.”

The research was funded by the Institute of Child Health and Development. The study researchers and Dr. Pluym reported no disclosures.

Group prenatal care did not reduce preterm birth among low-income patients compared to patients receiving individual prenatal care, but the different care models did shrink racial disparities in low-birth-weight and preterm births, according to a study presented Feb. 3 at the annual meeting sponsored by the Society for Maternal-Fetal Medicine. Patients who attended more group prenatal care visits also had better outcomes, reported Amy Crockett, MD, professor of ob.gyn. and director of the Maternal-Fetal Medicine Fellowship Program at the University of South Carolina in Greenville.

Though the results did not show group prenatal care to be the “silver bullet” they might have hoped for in reducing preterm birth and low birth weight among Black women, the study did show group prenatal care to have some clinical effect, Dr. Crockett suggested.

Ilina Pluym, MD, assistant professor of maternal-fetal medicine at the University of California Los Angeles, said that preterm birth and low birth weight are complex problems that cannot be solved by a single fix.

“In terms of the racial disparities, it is difficult to prove that 9 months of good access to prenatal care will undo the years of limited health care and life stressors that, as a whole, possibly contribute more to the overall risk profile of the patient,” Dr. Pluym said. “But as providers, we want to intervene and help in the portion that we can, and optimizing prenatal care is one tangible thing we can try.”

The racial disparities that exist in preterm birth, low birth weight, and infant and maternal mortality are not caused by biologic or genetic factors, Dr. Crockett told attendees.

”Rather, they are the result of long-standing systemic racism and discrimination deeply embedded in the culture of the United States,” she said. “To achieve racial equity, we need reform at the societal level.” But she noted that it might be possible for individual practices to play a role as well, which led her to design a study comparing outcomes from group versus individual prenatal care.

The group care model used for the study is called Centering Pregnancy, in which 8-10 pregnant patients who are due in the same month attend 10 two-hour prenatal care sessions together. Dr. Crockett noted that other research has identified potential reductions in preterm birth with group care models, but some are underpowered while others are observational and limited by confounding, selection bias, or small sample sizes.

The researchers aimed to recruit 3,160 patients to ensure an adequately powered study after estimated losses to follow-up, but they were able to recruit only 2,350 patients, resulting in potentially underpowered results. All the patients were receiving care at a single obstetric practice for a medically low-risk singleton pregnancy of 20 or fewer weeks gestation. A total of 1,176 patients were randomly assigned to attend group prenatal care appointments, and 1,174 patients were assigned to individual prenatal care.

The patients in both groups were an average age of 25 with a prepregnancy body mass index of 29. A similar proportion in both the group and individual care were married (24%) patients and had a government payer (96%-97%). Approximately 41%were Black patients, 37% were White patients, and 21% were Hispanic patients in both groups. Rates of chronic hypertension, smoking, vaginal infection in pregnancy, parity, cervix length, and use of cerclage were similar in both groups.

Gestational age outcomes were available for 1,099 group care patients (94%) and 1,120 individual care patients (95%), and birth weight outcomes were available for 1,028 group care patients (87%) and 1,044 individual care patients (89%).

In the individual care group, 8.7% of the patients had a preterm birth, compared to 10.4% who attended group prenatal care, but the findings did not reach significance (odds ratio [OR], 1.22; 95% confidence interval [CI]: 0.92-1.63). The difference between the 9.6% of group care patients and 8.9% of individual care patients who had babies with low birth weights were not significantly different.

While no significant difference in preterm birth occurred between the groups, the secondary outcome looking at racial disparities yielded one statistically significant result. Black women receiving individual prenatal care were twice as likely as were White women to have an infant with a low birth weight (OR, 2.1; 95% CI: 1.29-3.5). Among those receiving group care, however, the 12.5% of Black women and 8.9% of White women whose infants had a low birth weight were not significantly different.

There was a trend toward narrower disparities in preterm birth in the group versus individual care groups. Among those receiving group care, 11.4% of Black women and 10.8% of White women had a preterm birth, compared to 10.2% of Black women and 7.7% of White women in the individual care group.

Then the researchers compared the groups with regard to compliance while adjusting for baseline differences. “We saw decreasing rates of preterm birth for Black patients relative to White patients, particularly after attending five or more sessions in the group care arm with the rates of preterm birth narrowing and the disparity becoming nonsignificant with more exposure to group care,” Dr. Crockett said. “In individual care, the rate of preterm birth remained the highest for Black women regardless of the number of visits attended.”

The idea of trying group prenatal care is appealing, Dr. Pluym said in an interview, though both models have their advantages.

”The strength of individual care is the focus on the patient exam and individual patient questions,” Dr. Pluym said. “The strengths of group prenatal care are the consolidation of the patient education aspect of prenatal care that is uniform for all patients, the sense of community patients feel, and the opportunity to hear other patients questions that you may not have thought of. It sounds like, anecdotally, patients and providers really found the group sessions valuable and they helped dampen implicit bias and build relationships.”

One potential limitation of this randomized controlled trial is that the providers were the same for both group and individual care, potentially causing some confounding, Dr. Pluym noted. But the study does have one clear clinical message, she said.

“My take away is more prenatal care is better – individual or group,” Dr. Pluym said. “Every clinic should evaluate their own structure and see if group care would be feasible for their patient population. There may be a benefit globally, but is it is not the ‘silver bullet,’ as they said, for lowering preterm birth or growth restriction.”

The research was funded by the Institute of Child Health and Development. The study researchers and Dr. Pluym reported no disclosures.

Researchers evaluating whether endometriosis is linked with preterm birth found no such association in a multicenter cohort study of more than 1300 women.

These new findings, which were published online in JAMA Network Open, suggest that changing monitoring strategies to prevent preterm birth for women with the disease may not be necessary.

The research team, led by Louis Marcellin, MD, PhD, with the department of obstetrics and gynecology at Université de Paris, also found that disease phenotype or whether the preterm birth was induced or spontaneous did not appear to alter the result.

Those results differ from previous research. Data on the phenotypes and their link with preterm birth have been scarce, but previous studies have shown the risk for preterm birth is more pronounced in women who have deep endometriosis than in women with ovarian endometriosis.

Dr. Marcellin said in an interview that “little is known about the impact of endometriosis on obstetric outcomes. In contrast to previous studies, we reported no differences in the risk for preterm delivery between women with endometriosis (34 of 470 [7.2%]) and those without endometriosis (53 of 881 [6.0%]), even when adjusted for multiple factors.”

The authors accounted for mother’s age, body mass index before pregnancy, birth country, number of times the woman had given birth, previous cesarean delivery, and history of preterm birth. After adjusting for potential confounders, endometriosis was not associated with preterm birth (adjusted odds ratio, 1.07; 95% confidence interval, 0.64-1.77).

The researchers found no differences among preterm births based on a mother’s endometriosis phenotype. Those phenotypes include Isolated superficial peritoneal endometriosis, ovarian endometrioma, and deep endometriosis.

“Monitoring pregnancy beyond the normal protocols or changing management strategies may not be warranted in cases of endometriosis,” Dr. Marcellin said.

More research on endometriosis’ potential link to birth outcomes is needed.

An expert not involved with the study said the new paper highlights important new avenues of research but should not be seen as the final word on the connection between endometriosis and preterm birth.

Of the 1,351 study participants (mean age, 32.9 years) who had a singleton delivery after 22 weeks’ gestation, 470 were assigned to the endometriosis group, and 881 were assigned to the control group.

The authors concluded that “pregnant women with endometriosis should not be considered to have an exceptionally high risk for preterm birth. However, further studies are needed to examine the potential for other adverse perinatal outcomes or specific but rare complications.”

Daniela Carusi, MD, said the difficulty with the study’s design is that “premature birth is not one problem or one disease.”

Many very different problems can all end with premature birth. Sometimes it’s an infection or inflammation or bleeding in the uterus or hypertension in the mother, for example, and all those things can lead to a preterm birth, she explained.

“This study inherently lumps all those things together,” said Dr. Carusi, who is director of surgical obstetrics and placental abnormalities in the department of obstetrics and gynecology at Brigham and Women’s Hospital, Boston. “It’s quite possible endometriosis can have a big impact in one of those areas and no impact in the other areas, but the study design wouldn’t be able to pick that up.”
 

Editorialists: Results challenge findings of previous studies

In an accompanying commentary, Liisu Saavalainen, MD, PhD, and Oskari Heikinheimo, MD, PhD, both with the department of obstetrics and gynecology, Helsinki University Hospital, wrote that several previous studies have suggested that women with endometriosis have a slightly higher risk for preterm birth.

Those studies were mostly retrospective and differed in the way they classified endometriosis and the way they selected patients, the editorialists write. Also, most women in these studies typically had subfertility, they added.

The study by Dr. Marcellin and colleagues differs from previous related research in that was prospective and assessed the risk for preterm delivery in women both with endometriosis and those without endometriosis from several maternity centers in France. The women with endometriosis were classified according to the severity of their disease.

The editorialists wrote: “The novel results by Marcellin et al. challenge the findings of most previous studies on this topic. These results are valuable and comforting. However, they are also likely to trigger new studies on the pregnancy risks associated with different types of endometriosis. That is good news.”

Dr. Carusi said the study was well done and included a notably large size. Further complimenting the research, she said it’s important to talk about this little-discussed pregnancy complication. There’s been much more focus for women with endometriosis and their physicians on getting pregnant and on talking about the length of their term.

The study leaves some things unanswered.

The study was funded by research grants from the French Ministry of Health and was sponsored by the Département de la Recherche Clinique et du Développement de l’Assistance Publique–Hôpitaux de Paris. Dr. Carusi reported no relevant financial relationships. One study coauthor reported receiving personal fees from Bioserinity and Ferring outside the submitted work. No other disclosures were reported.

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

Researchers evaluating whether endometriosis is linked with preterm birth found no such association in a multicenter cohort study of more than 1300 women.

These new findings, which were published online in JAMA Network Open, suggest that changing monitoring strategies to prevent preterm birth for women with the disease may not be necessary.

The research team, led by Louis Marcellin, MD, PhD, with the department of obstetrics and gynecology at Université de Paris, also found that disease phenotype or whether the preterm birth was induced or spontaneous did not appear to alter the result.

Those results differ from previous research. Data on the phenotypes and their link with preterm birth have been scarce, but previous studies have shown the risk for preterm birth is more pronounced in women who have deep endometriosis than in women with ovarian endometriosis.

Dr. Marcellin said in an interview that “little is known about the impact of endometriosis on obstetric outcomes. In contrast to previous studies, we reported no differences in the risk for preterm delivery between women with endometriosis (34 of 470 [7.2%]) and those without endometriosis (53 of 881 [6.0%]), even when adjusted for multiple factors.”

The authors accounted for mother’s age, body mass index before pregnancy, birth country, number of times the woman had given birth, previous cesarean delivery, and history of preterm birth. After adjusting for potential confounders, endometriosis was not associated with preterm birth (adjusted odds ratio, 1.07; 95% confidence interval, 0.64-1.77).

The researchers found no differences among preterm births based on a mother’s endometriosis phenotype. Those phenotypes include Isolated superficial peritoneal endometriosis, ovarian endometrioma, and deep endometriosis.

“Monitoring pregnancy beyond the normal protocols or changing management strategies may not be warranted in cases of endometriosis,” Dr. Marcellin said.

More research on endometriosis’ potential link to birth outcomes is needed.

An expert not involved with the study said the new paper highlights important new avenues of research but should not be seen as the final word on the connection between endometriosis and preterm birth.

Of the 1,351 study participants (mean age, 32.9 years) who had a singleton delivery after 22 weeks’ gestation, 470 were assigned to the endometriosis group, and 881 were assigned to the control group.

The authors concluded that “pregnant women with endometriosis should not be considered to have an exceptionally high risk for preterm birth. However, further studies are needed to examine the potential for other adverse perinatal outcomes or specific but rare complications.”

Daniela Carusi, MD, said the difficulty with the study’s design is that “premature birth is not one problem or one disease.”

Many very different problems can all end with premature birth. Sometimes it’s an infection or inflammation or bleeding in the uterus or hypertension in the mother, for example, and all those things can lead to a preterm birth, she explained.

“This study inherently lumps all those things together,” said Dr. Carusi, who is director of surgical obstetrics and placental abnormalities in the department of obstetrics and gynecology at Brigham and Women’s Hospital, Boston. “It’s quite possible endometriosis can have a big impact in one of those areas and no impact in the other areas, but the study design wouldn’t be able to pick that up.”
 

Editorialists: Results challenge findings of previous studies

In an accompanying commentary, Liisu Saavalainen, MD, PhD, and Oskari Heikinheimo, MD, PhD, both with the department of obstetrics and gynecology, Helsinki University Hospital, wrote that several previous studies have suggested that women with endometriosis have a slightly higher risk for preterm birth.

Those studies were mostly retrospective and differed in the way they classified endometriosis and the way they selected patients, the editorialists write. Also, most women in these studies typically had subfertility, they added.

The study by Dr. Marcellin and colleagues differs from previous related research in that was prospective and assessed the risk for preterm delivery in women both with endometriosis and those without endometriosis from several maternity centers in France. The women with endometriosis were classified according to the severity of their disease.

The editorialists wrote: “The novel results by Marcellin et al. challenge the findings of most previous studies on this topic. These results are valuable and comforting. However, they are also likely to trigger new studies on the pregnancy risks associated with different types of endometriosis. That is good news.”

Dr. Carusi said the study was well done and included a notably large size. Further complimenting the research, she said it’s important to talk about this little-discussed pregnancy complication. There’s been much more focus for women with endometriosis and their physicians on getting pregnant and on talking about the length of their term.

The study leaves some things unanswered.

The study was funded by research grants from the French Ministry of Health and was sponsored by the Département de la Recherche Clinique et du Développement de l’Assistance Publique–Hôpitaux de Paris. Dr. Carusi reported no relevant financial relationships. One study coauthor reported receiving personal fees from Bioserinity and Ferring outside the submitted work. No other disclosures were reported.

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

Researchers evaluating whether endometriosis is linked with preterm birth found no such association in a multicenter cohort study of more than 1300 women.

These new findings, which were published online in JAMA Network Open, suggest that changing monitoring strategies to prevent preterm birth for women with the disease may not be necessary.

The research team, led by Louis Marcellin, MD, PhD, with the department of obstetrics and gynecology at Université de Paris, also found that disease phenotype or whether the preterm birth was induced or spontaneous did not appear to alter the result.

Those results differ from previous research. Data on the phenotypes and their link with preterm birth have been scarce, but previous studies have shown the risk for preterm birth is more pronounced in women who have deep endometriosis than in women with ovarian endometriosis.

Dr. Marcellin said in an interview that “little is known about the impact of endometriosis on obstetric outcomes. In contrast to previous studies, we reported no differences in the risk for preterm delivery between women with endometriosis (34 of 470 [7.2%]) and those without endometriosis (53 of 881 [6.0%]), even when adjusted for multiple factors.”

The authors accounted for mother’s age, body mass index before pregnancy, birth country, number of times the woman had given birth, previous cesarean delivery, and history of preterm birth. After adjusting for potential confounders, endometriosis was not associated with preterm birth (adjusted odds ratio, 1.07; 95% confidence interval, 0.64-1.77).

The researchers found no differences among preterm births based on a mother’s endometriosis phenotype. Those phenotypes include Isolated superficial peritoneal endometriosis, ovarian endometrioma, and deep endometriosis.

“Monitoring pregnancy beyond the normal protocols or changing management strategies may not be warranted in cases of endometriosis,” Dr. Marcellin said.

More research on endometriosis’ potential link to birth outcomes is needed.

An expert not involved with the study said the new paper highlights important new avenues of research but should not be seen as the final word on the connection between endometriosis and preterm birth.

Of the 1,351 study participants (mean age, 32.9 years) who had a singleton delivery after 22 weeks’ gestation, 470 were assigned to the endometriosis group, and 881 were assigned to the control group.

The authors concluded that “pregnant women with endometriosis should not be considered to have an exceptionally high risk for preterm birth. However, further studies are needed to examine the potential for other adverse perinatal outcomes or specific but rare complications.”

Daniela Carusi, MD, said the difficulty with the study’s design is that “premature birth is not one problem or one disease.”

Many very different problems can all end with premature birth. Sometimes it’s an infection or inflammation or bleeding in the uterus or hypertension in the mother, for example, and all those things can lead to a preterm birth, she explained.

“This study inherently lumps all those things together,” said Dr. Carusi, who is director of surgical obstetrics and placental abnormalities in the department of obstetrics and gynecology at Brigham and Women’s Hospital, Boston. “It’s quite possible endometriosis can have a big impact in one of those areas and no impact in the other areas, but the study design wouldn’t be able to pick that up.”
 

Editorialists: Results challenge findings of previous studies

In an accompanying commentary, Liisu Saavalainen, MD, PhD, and Oskari Heikinheimo, MD, PhD, both with the department of obstetrics and gynecology, Helsinki University Hospital, wrote that several previous studies have suggested that women with endometriosis have a slightly higher risk for preterm birth.

Those studies were mostly retrospective and differed in the way they classified endometriosis and the way they selected patients, the editorialists write. Also, most women in these studies typically had subfertility, they added.

The study by Dr. Marcellin and colleagues differs from previous related research in that was prospective and assessed the risk for preterm delivery in women both with endometriosis and those without endometriosis from several maternity centers in France. The women with endometriosis were classified according to the severity of their disease.

The editorialists wrote: “The novel results by Marcellin et al. challenge the findings of most previous studies on this topic. These results are valuable and comforting. However, they are also likely to trigger new studies on the pregnancy risks associated with different types of endometriosis. That is good news.”

Dr. Carusi said the study was well done and included a notably large size. Further complimenting the research, she said it’s important to talk about this little-discussed pregnancy complication. There’s been much more focus for women with endometriosis and their physicians on getting pregnant and on talking about the length of their term.

The study leaves some things unanswered.

The study was funded by research grants from the French Ministry of Health and was sponsored by the Département de la Recherche Clinique et du Développement de l’Assistance Publique–Hôpitaux de Paris. Dr. Carusi reported no relevant financial relationships. One study coauthor reported receiving personal fees from Bioserinity and Ferring outside the submitted work. No other disclosures were reported.

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

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

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

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

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

Vaginal progesterone for first trimester bleeding

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

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

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

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

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

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

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

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

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

Vaginal progesterone vs. 17-OHPC

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

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

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

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

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

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

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

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

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

This story was updated on 2/8/2022.

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

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

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

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

Vaginal progesterone for first trimester bleeding

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

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

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

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

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

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

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

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

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

Vaginal progesterone vs. 17-OHPC

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

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

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

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

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

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

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

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

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

This story was updated on 2/8/2022.

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

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

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

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

Vaginal progesterone for first trimester bleeding

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

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

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

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

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

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

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

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

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

Vaginal progesterone vs. 17-OHPC

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

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

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

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

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

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

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

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

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

This story was updated on 2/8/2022.

In the country with one of the highest rates of preterm birth in the world, these early deliveries dropped by 24% with a simple intervention: chewing gum with xylitol during pregnancy. The decrease in preterm births was linked to improvement in oral health, according to research presented at the meeting sponsored by the Society for Maternal-Fetal Medicine.

Although the findings, from a randomized controlled trial of women in Malawi, barely reached statistical significance, the researchers also documented a reduction in periodontitis (gum disease) that appears to correlate with the reduction in early deliveries, according to Kjersti Aagaard, MD, PhD, of Baylor College of Medicine and Texas Children’s Hospital, both in Houston.

“For a while, we have known about the association with poor oral health and preterm birth but I am not aware of a study of this magnitude suggesting a simple and effective treatment option,” said Ilina Pluym, MD, an assistant professor in maternal fetal medicine at the University of California, Los Angeles, who attended the presentation. Dr. Pluym called the new data “compelling” and said the study “adds to our possible strategies to treat a condition that causes a significant burden of disease worldwide.” The findings must be replicated, ideally in countries with lower rates of preterm birth and periodontal disease to see if the effect is similar, before broadly implementing this cheap and simple intervention.

Preterm birth is a leading cause of infant mortality and a major underlying cause of health problems in children under 5 worldwide. As many as 42% of children born preterm have a health condition related to their prematurity or do not survive childhood.

About one in five babies in Malawi are born between 26 and 37 weeks, about double the U.S. rate of 10.8% preterm births, which in this country is considered births that occur between 23 and 37 weeks’ gestation. Researchers also chose Malawi for the trial because residents there see preterm birth as a widespread problem that must be addressed, Dr. Aagaard said.

Multiple previous studies have found a link between periodontal disease and deliveries that are preterm or low birth weight, Dr. Aagaard told attendees. However, 11 randomized controlled trials that involved treating periodontal disease did not reduce preterm birth despite improving periodontitis and oral health.

Dr. Aagaard’s team decided to test the effectiveness of xylitol – a natural prebiotic found in fruits, vegetables, and bran – because harmful oral bacteria cannot metabolize the substance, and regular use of xylitol reduces the number of harmful mouth bacteria while increasing the number of good microbes in the mouth. In addition, a study in 2006 found that children up to 4 years old had fewer cavities and ear infections when their mothers chewed gum containing xylitol and other compounds. Dr. Aagaard noted that gums without xylitol do not appear to produce the same improvements in oral health.

Before beginning the trial, Dr. Aagaard’s group spent 3 years doing a “run-in” study to ensure a larger, longer-term trial in Malawi was feasible. That initial study found a reduction in tooth decay and periodontal inflammation with use of xylitol. The researchers also learned that participants preferred gum over lozenges or lollipops. Nearly all the participants (92%) chewed the gum twice daily.

Among 10,069 women who enrolled in the trial, 96% remained in it until the end. Of the initial total, 4,029 participants underwent an oral health assessment at the start of the study, and 920 had a follow-up oral health assessment.

Of the 4,349 women who chewed xylitol gum, 12.6% gave birth before 37 weeks, compared with 16.5% preterm births among the 5,321 women in the control group – a 24% reduction (P = .045). The 16.5% rate among women not chewing gum was still lower than the national rate of 19.6%, possibly related to the education the participants received, according to the researchers.

No statistically significant reduction occurred for births at less than 34 weeks, but the reduction in late preterm births – babies born between 34 and 37 weeks – was also borderline in statistical significance (P = .049). Only 9.9% of women chewing xylitol gum had a late preterm birth compared to 13.5% of women who only received health education.

The researchers estimated it would take 26 pregnant women chewing xylitol gum to prevent one preterm birth. At a cost of $24-$29 per pregnancy for the gum, preventing each preterm birth in a community would cost $623-$754.

The researchers also observed a 30% reduction in newborns weighing less than 2,500 g (5.5 pounds), with 8.9% of low-birth-weight babies born to moms chewing gum and 12.9% of low-birth-weight babies born to those not provided gum (P = .046). They attributed this reduction in low birth weight to the lower proportion of late preterm births. The groups showed no significant differences in stillbirths or newborn deaths.

The researchers did, however, find a significant reduction in periodontitis among the women who chewed xylitol gum who came for follow-up dental visits. The prevalence of periodontal disease dropped from 31% to 27% in those not chewing gum but from 31% to 21% in gum chewers (P = .04).

“This cannot be attributed to overall oral health, as dental caries composite scores did not significantly differ while periodontitis measures did,” Dr. Aagaard said.

One limitation of the trial is that it was randomized by health centers instead by individual women, although the researchers tried to account for differences that might exist between the populations going to different facilities. Nor did the researchers assess how frequently the participants chewed gum – although the fact that the gum-chewing group had better oral health suggests they appear to have done so regularly.

Whether recommending xylitol chewing gum to pregnant women in other countries would affect rates of preterm birth is unclear. The ideal population for an intervention like this is one where the population has a high rate of periodontal disease or other preterm birth risk factors, Dr. Pluym said.

”Preterm birth is multifactorial,” she said. “There are often multiple risk factors and causes to the complex pathophysiological process and a quick fix is not the solution for everyone.”

The study was funded by the Thrasher Research Fund. Dr. Aagaard and Dr. Pluym reported no disclosures.

This story was updated on Feb. 4, 2022.

In the country with one of the highest rates of preterm birth in the world, these early deliveries dropped by 24% with a simple intervention: chewing gum with xylitol during pregnancy. The decrease in preterm births was linked to improvement in oral health, according to research presented at the meeting sponsored by the Society for Maternal-Fetal Medicine.

Although the findings, from a randomized controlled trial of women in Malawi, barely reached statistical significance, the researchers also documented a reduction in periodontitis (gum disease) that appears to correlate with the reduction in early deliveries, according to Kjersti Aagaard, MD, PhD, of Baylor College of Medicine and Texas Children’s Hospital, both in Houston.

“For a while, we have known about the association with poor oral health and preterm birth but I am not aware of a study of this magnitude suggesting a simple and effective treatment option,” said Ilina Pluym, MD, an assistant professor in maternal fetal medicine at the University of California, Los Angeles, who attended the presentation. Dr. Pluym called the new data “compelling” and said the study “adds to our possible strategies to treat a condition that causes a significant burden of disease worldwide.” The findings must be replicated, ideally in countries with lower rates of preterm birth and periodontal disease to see if the effect is similar, before broadly implementing this cheap and simple intervention.

Preterm birth is a leading cause of infant mortality and a major underlying cause of health problems in children under 5 worldwide. As many as 42% of children born preterm have a health condition related to their prematurity or do not survive childhood.

About one in five babies in Malawi are born between 26 and 37 weeks, about double the U.S. rate of 10.8% preterm births, which in this country is considered births that occur between 23 and 37 weeks’ gestation. Researchers also chose Malawi for the trial because residents there see preterm birth as a widespread problem that must be addressed, Dr. Aagaard said.

Multiple previous studies have found a link between periodontal disease and deliveries that are preterm or low birth weight, Dr. Aagaard told attendees. However, 11 randomized controlled trials that involved treating periodontal disease did not reduce preterm birth despite improving periodontitis and oral health.

Dr. Aagaard’s team decided to test the effectiveness of xylitol – a natural prebiotic found in fruits, vegetables, and bran – because harmful oral bacteria cannot metabolize the substance, and regular use of xylitol reduces the number of harmful mouth bacteria while increasing the number of good microbes in the mouth. In addition, a study in 2006 found that children up to 4 years old had fewer cavities and ear infections when their mothers chewed gum containing xylitol and other compounds. Dr. Aagaard noted that gums without xylitol do not appear to produce the same improvements in oral health.

Before beginning the trial, Dr. Aagaard’s group spent 3 years doing a “run-in” study to ensure a larger, longer-term trial in Malawi was feasible. That initial study found a reduction in tooth decay and periodontal inflammation with use of xylitol. The researchers also learned that participants preferred gum over lozenges or lollipops. Nearly all the participants (92%) chewed the gum twice daily.

Among 10,069 women who enrolled in the trial, 96% remained in it until the end. Of the initial total, 4,029 participants underwent an oral health assessment at the start of the study, and 920 had a follow-up oral health assessment.

Of the 4,349 women who chewed xylitol gum, 12.6% gave birth before 37 weeks, compared with 16.5% preterm births among the 5,321 women in the control group – a 24% reduction (P = .045). The 16.5% rate among women not chewing gum was still lower than the national rate of 19.6%, possibly related to the education the participants received, according to the researchers.

No statistically significant reduction occurred for births at less than 34 weeks, but the reduction in late preterm births – babies born between 34 and 37 weeks – was also borderline in statistical significance (P = .049). Only 9.9% of women chewing xylitol gum had a late preterm birth compared to 13.5% of women who only received health education.

The researchers estimated it would take 26 pregnant women chewing xylitol gum to prevent one preterm birth. At a cost of $24-$29 per pregnancy for the gum, preventing each preterm birth in a community would cost $623-$754.

The researchers also observed a 30% reduction in newborns weighing less than 2,500 g (5.5 pounds), with 8.9% of low-birth-weight babies born to moms chewing gum and 12.9% of low-birth-weight babies born to those not provided gum (P = .046). They attributed this reduction in low birth weight to the lower proportion of late preterm births. The groups showed no significant differences in stillbirths or newborn deaths.

The researchers did, however, find a significant reduction in periodontitis among the women who chewed xylitol gum who came for follow-up dental visits. The prevalence of periodontal disease dropped from 31% to 27% in those not chewing gum but from 31% to 21% in gum chewers (P = .04).

“This cannot be attributed to overall oral health, as dental caries composite scores did not significantly differ while periodontitis measures did,” Dr. Aagaard said.

One limitation of the trial is that it was randomized by health centers instead by individual women, although the researchers tried to account for differences that might exist between the populations going to different facilities. Nor did the researchers assess how frequently the participants chewed gum – although the fact that the gum-chewing group had better oral health suggests they appear to have done so regularly.

Whether recommending xylitol chewing gum to pregnant women in other countries would affect rates of preterm birth is unclear. The ideal population for an intervention like this is one where the population has a high rate of periodontal disease or other preterm birth risk factors, Dr. Pluym said.

”Preterm birth is multifactorial,” she said. “There are often multiple risk factors and causes to the complex pathophysiological process and a quick fix is not the solution for everyone.”

The study was funded by the Thrasher Research Fund. Dr. Aagaard and Dr. Pluym reported no disclosures.

This story was updated on Feb. 4, 2022.

In the country with one of the highest rates of preterm birth in the world, these early deliveries dropped by 24% with a simple intervention: chewing gum with xylitol during pregnancy. The decrease in preterm births was linked to improvement in oral health, according to research presented at the meeting sponsored by the Society for Maternal-Fetal Medicine.

Although the findings, from a randomized controlled trial of women in Malawi, barely reached statistical significance, the researchers also documented a reduction in periodontitis (gum disease) that appears to correlate with the reduction in early deliveries, according to Kjersti Aagaard, MD, PhD, of Baylor College of Medicine and Texas Children’s Hospital, both in Houston.

“For a while, we have known about the association with poor oral health and preterm birth but I am not aware of a study of this magnitude suggesting a simple and effective treatment option,” said Ilina Pluym, MD, an assistant professor in maternal fetal medicine at the University of California, Los Angeles, who attended the presentation. Dr. Pluym called the new data “compelling” and said the study “adds to our possible strategies to treat a condition that causes a significant burden of disease worldwide.” The findings must be replicated, ideally in countries with lower rates of preterm birth and periodontal disease to see if the effect is similar, before broadly implementing this cheap and simple intervention.

Preterm birth is a leading cause of infant mortality and a major underlying cause of health problems in children under 5 worldwide. As many as 42% of children born preterm have a health condition related to their prematurity or do not survive childhood.

About one in five babies in Malawi are born between 26 and 37 weeks, about double the U.S. rate of 10.8% preterm births, which in this country is considered births that occur between 23 and 37 weeks’ gestation. Researchers also chose Malawi for the trial because residents there see preterm birth as a widespread problem that must be addressed, Dr. Aagaard said.

Multiple previous studies have found a link between periodontal disease and deliveries that are preterm or low birth weight, Dr. Aagaard told attendees. However, 11 randomized controlled trials that involved treating periodontal disease did not reduce preterm birth despite improving periodontitis and oral health.

Dr. Aagaard’s team decided to test the effectiveness of xylitol – a natural prebiotic found in fruits, vegetables, and bran – because harmful oral bacteria cannot metabolize the substance, and regular use of xylitol reduces the number of harmful mouth bacteria while increasing the number of good microbes in the mouth. In addition, a study in 2006 found that children up to 4 years old had fewer cavities and ear infections when their mothers chewed gum containing xylitol and other compounds. Dr. Aagaard noted that gums without xylitol do not appear to produce the same improvements in oral health.

Before beginning the trial, Dr. Aagaard’s group spent 3 years doing a “run-in” study to ensure a larger, longer-term trial in Malawi was feasible. That initial study found a reduction in tooth decay and periodontal inflammation with use of xylitol. The researchers also learned that participants preferred gum over lozenges or lollipops. Nearly all the participants (92%) chewed the gum twice daily.

Among 10,069 women who enrolled in the trial, 96% remained in it until the end. Of the initial total, 4,029 participants underwent an oral health assessment at the start of the study, and 920 had a follow-up oral health assessment.

Of the 4,349 women who chewed xylitol gum, 12.6% gave birth before 37 weeks, compared with 16.5% preterm births among the 5,321 women in the control group – a 24% reduction (P = .045). The 16.5% rate among women not chewing gum was still lower than the national rate of 19.6%, possibly related to the education the participants received, according to the researchers.

No statistically significant reduction occurred for births at less than 34 weeks, but the reduction in late preterm births – babies born between 34 and 37 weeks – was also borderline in statistical significance (P = .049). Only 9.9% of women chewing xylitol gum had a late preterm birth compared to 13.5% of women who only received health education.

The researchers estimated it would take 26 pregnant women chewing xylitol gum to prevent one preterm birth. At a cost of $24-$29 per pregnancy for the gum, preventing each preterm birth in a community would cost $623-$754.

The researchers also observed a 30% reduction in newborns weighing less than 2,500 g (5.5 pounds), with 8.9% of low-birth-weight babies born to moms chewing gum and 12.9% of low-birth-weight babies born to those not provided gum (P = .046). They attributed this reduction in low birth weight to the lower proportion of late preterm births. The groups showed no significant differences in stillbirths or newborn deaths.

The researchers did, however, find a significant reduction in periodontitis among the women who chewed xylitol gum who came for follow-up dental visits. The prevalence of periodontal disease dropped from 31% to 27% in those not chewing gum but from 31% to 21% in gum chewers (P = .04).

“This cannot be attributed to overall oral health, as dental caries composite scores did not significantly differ while periodontitis measures did,” Dr. Aagaard said.

One limitation of the trial is that it was randomized by health centers instead by individual women, although the researchers tried to account for differences that might exist between the populations going to different facilities. Nor did the researchers assess how frequently the participants chewed gum – although the fact that the gum-chewing group had better oral health suggests they appear to have done so regularly.

Whether recommending xylitol chewing gum to pregnant women in other countries would affect rates of preterm birth is unclear. The ideal population for an intervention like this is one where the population has a high rate of periodontal disease or other preterm birth risk factors, Dr. Pluym said.

”Preterm birth is multifactorial,” she said. “There are often multiple risk factors and causes to the complex pathophysiological process and a quick fix is not the solution for everyone.”

The study was funded by the Thrasher Research Fund. Dr. Aagaard and Dr. Pluym reported no disclosures.

This story was updated on Feb. 4, 2022.

Policies increasing access to immediate postpartum long-acting reversible contraception (LARC) were associated with reductions in preterm birth and low birth weight, based on data from South Carolina’s Medicaid program.

Preterm birth and low birth weight represent the second-leading cause of infant mortality in the United States, wrote Maria W. Steenland, SD, of Brown University, Providence, R.I., and colleagues. Previous policy interventions to reduce preterm birth and low birth weight have focused on services before and during pregnancy, they said. LARC is a safe and effective postpartum intervention, but cost has been a limiting factor, they noted.

In 2012, the Medicaid program in South Carolina began reimbursing hospitals for immediate postpartum LARC independent of global maternity payments. In a previous study, the researchers found that the implementation of this policy had reduced the number of short-interval births among adolescents.

The goal of the current study, published in JAMA Pediatrics, was to analyze the association between South Carolina’s policy change and rates of preterm birth and low birth weight among individuals with Medicaid coverage during childbirth. The researchers analyzed data from 186,953 Medicaid-paid births between January 2009 and December 2015 in South Carolina. Of these, 46,414 births (24.8%) occurred in hospitals that provided immediate postpartum LARC in response to the policy change. Overall, the implementing hospitals had more annual births paid for by Medicaid compared to nonimplementing hospitals (1,105 vs. 511) and were less likely to be rural (33.3% vs. 46.8%) and had a greater share of preterm births (15.5% vs. 9.5%). Prior to the policy change, the probability of a preterm birth in the next 4 years was 4.4% for patients at implementing hospitals and 3.5% for those in nonimplementing hospitals, and the probability of a low-birth-weight birth was 3.6% and 2.9%, respectively.

The policy change was associated with a decrease of 0.4 percentage points for preterm birth and 0.3 percentage points for subsequent low-birth-weight birth.

When the results were stratified based on race and ethnicity, the policy change was associated with a decrease of 0.5 percentage points in the probability of preterm birth in both non-Hispanic Blacks and non-Hispanic Whites. No significant differences appeared in the association between the policy change and rates of preterm birth or low-birth-weight birth between non-Hispanic Black and non-Hispanic White individuals.

However, the policy was associated with a significant decrease of 0.6 percentage points in the probability of short-interval birth among non-Hispanic Blacks, and a decrease of 1.6 percentage points in the probability of another birth within 4 years overall. The policy change also was associated with a significant increase of 27 days between births among non-Hispanic Blacks, but not with any significant change among non-Hispanic Whites or the study population overall.

“In addition, although our data cannot speak to this, the policy may have affected the intendedness of subsequent pregnancies, leading to healthier behaviors before and during pregnancy, such as early initiation of prenatal care,” the researchers wrote in their discussion of the findings.

The study findings were limited by several factors including the lack of data on pregnancy intention or abortion, and the lack of data on patient-reported outcomes, notably the provision of patient-centered counseling and whether such counseling was biased, the researchers noted. Other limitations included a lack of data on infant mortality and potential confounding from risk profiles of patients in implementing vs. nonimplementing hospitals, they wrote.

Also, the study provides population-level data, which does not guide clinical decision-making about intervals between childbirth and subsequent pregnancy, the researchers emphasized.

Although the data support the value of postpartum contraception in improving birth outcomes, “it is imperative that efforts to expand access focus on assuring comprehensive access to all forms of contraception without coercion,” the researchers concluded. “Additional policy solutions are needed to improve infant health, including those that directly address structural and interpersonal racism to reduce racial disparities in infant health,” they said.

The study is important because, although immediate postpartum LARC policies were first implemented almost a decade ago in the United States, population-level evidence on the effects of these policies remains scarce, Dr. Steenland said in an interview.  

Existing barriers to improving access to immediate postpartum LARC include health professional training and logistics within hospitals, as well as ensuring correct billing and timely reimbursements, Dr. Steenland said. “Simple and clear billing procedures, and advanced reimbursement so that hospitals can have devices stocked would make it easier to provide this service,” she noted.

“This service has gone from being almost completely unavailable, to available in some hospitals, mainly those that are urban, teaching, and high volume,” said Dr. Steenland. “Additional research is needed to determine how health systems can make this service available to all birthing persons,” she said. “Also, critically, additional research is needed to identify strategies to ensure that counseling for immediate postpartum LARC, and family planning more generally, is patient-centered, so that the availability of immediate postpartum LARC increases, rather than restricts, choice,” she added. “Finally, additional research is needed to determine whether postpartum people have affordable and accessible access to LARC removal services,” Dr. Steenland emphasized.
 

Immediate post partum is critical period

The immediate postpartum period is a critical time for access to contraception because many women do not return for postpartum visits after hospital discharge, Tracey A. Wilkinson, MD, and Jeffrey F. Peipert, MD, of Indiana University, Indianapolis, wrote in an accompanying editorial. “The focus on contraception access during the postpartum period prior to hospital discharge is important because of the potential sequelae of a subsequent unintended pregnancy or short interpregnancy intervals,” they noted. These issues may be more acute in marginalized communities, and policies to expand immediate postpartum LARC are in place in a majority of states, the editorialists said.

However, they agreed with the authors’ statements that implementation of LARC must be done in a manner that supports patient choice and avoids coercion. Given the baseline disparities of the infant outcomes studied, increased access to immediate postpartum LARC must be provided in a way that does not exacerbate these disparities, they said. “This ultimately means that plans to increase access to contraception should emphasize availability while avoiding coercion, and if a patient ultimately decides to discontinue a method, enable that to occur easily and seamlessly, including LARC device removal,” they explained.

“Future studies examining patient centeredness of these postpartum LARC implementation efforts would be an important element to augment these data and show the impact in additional spheres beyond infant outcomes,” they added.
 

Overcome trust barriers and offer options

“In a time of restrictive access to abortion and contraception in many states, any additional increase in access can potentially be meaningful,” Sarah W. Prager, MD, of the University of Washington, Seattle, said in an interview. “Additionally, given the significantly higher rates of infant and maternal morbidity and mortality among the non-Hispanic Black population, seeing an intervention that can improve outcomes for both mothers and babies is also potentially very positive,” she said.

Dr. Prager said she was not surprised by the study findings, as immediate LARC is much more common in other countries and has shown similar outcomes. “Additionally, I am reassured by the fact that the increased number of days until the next pregnancy is not higher, as this indirectly indicates that patients were able to get their LARC removed when they desired another pregnancy,” she noted.

Barriers to improving access to immediate postpartum LARC in the Medicaid population may include mistrust for any long-acting contraception, “especially if they perceive that cessation of the method will be difficult to achieve,” Dr. Prager noted. “Certainly, counseling about LARC removal should be an element of counseling prior to any initiation, and lack of access to removal of an IUD or implant can be categorized as a form of reproductive coercion,” she said. Dr. Prager said that such counseling might be more effective if it occurred during prenatal visits, “so if providers are not talking about this during routine OB visits and patients only hear about immediate postpartum LARC when they are in the hospital for delivery, they may be less likely to accept the practice,” she said. “Finally, although Medicaid will cover the cost of immediate postpartum LARC, private insurers do not do so consistently in all states, so some hospitals may find this process too difficult to navigate and therefore not offer immediate postpartum LARC,” Dr. Prager emphasized.

As for additional research, Dr. Prager said she would like to see more studies in an overall United States population of pregnant people, both Medicaid patients and others, on whether the immediate postpartum timing of LARC is desired.

“I would like to couple that with patients’ impressions or experiences of their ability to access contraception outside of the immediate postpartum time period, and also their impressions or experience with ability to have LARC removed, since they are the only contraceptives not necessarily within personal control for initiation or cessation,” Dr. Prager said.

The study was supported by the National Institute for Child Health and Development, and lead author Dr. Steenland received support from other National Institutes of Health grants. The researchers had no financial conflicts to disclose. The editorial was supported in part by the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Dr. Peipert disclosed serving on advisory boards for Bayer and CooperSurgical, and receiving research support from Merck, Bayer, and CooperSurgical/Teva. Dr. Wilkinson had no financial conflicts to disclose. Dr. Prager had no financial conflicts to disclose and serves on the editorial advisory board of Ob.Gyn. News.

Policies increasing access to immediate postpartum long-acting reversible contraception (LARC) were associated with reductions in preterm birth and low birth weight, based on data from South Carolina’s Medicaid program.

Preterm birth and low birth weight represent the second-leading cause of infant mortality in the United States, wrote Maria W. Steenland, SD, of Brown University, Providence, R.I., and colleagues. Previous policy interventions to reduce preterm birth and low birth weight have focused on services before and during pregnancy, they said. LARC is a safe and effective postpartum intervention, but cost has been a limiting factor, they noted.

In 2012, the Medicaid program in South Carolina began reimbursing hospitals for immediate postpartum LARC independent of global maternity payments. In a previous study, the researchers found that the implementation of this policy had reduced the number of short-interval births among adolescents.

The goal of the current study, published in JAMA Pediatrics, was to analyze the association between South Carolina’s policy change and rates of preterm birth and low birth weight among individuals with Medicaid coverage during childbirth. The researchers analyzed data from 186,953 Medicaid-paid births between January 2009 and December 2015 in South Carolina. Of these, 46,414 births (24.8%) occurred in hospitals that provided immediate postpartum LARC in response to the policy change. Overall, the implementing hospitals had more annual births paid for by Medicaid compared to nonimplementing hospitals (1,105 vs. 511) and were less likely to be rural (33.3% vs. 46.8%) and had a greater share of preterm births (15.5% vs. 9.5%). Prior to the policy change, the probability of a preterm birth in the next 4 years was 4.4% for patients at implementing hospitals and 3.5% for those in nonimplementing hospitals, and the probability of a low-birth-weight birth was 3.6% and 2.9%, respectively.

The policy change was associated with a decrease of 0.4 percentage points for preterm birth and 0.3 percentage points for subsequent low-birth-weight birth.

When the results were stratified based on race and ethnicity, the policy change was associated with a decrease of 0.5 percentage points in the probability of preterm birth in both non-Hispanic Blacks and non-Hispanic Whites. No significant differences appeared in the association between the policy change and rates of preterm birth or low-birth-weight birth between non-Hispanic Black and non-Hispanic White individuals.

However, the policy was associated with a significant decrease of 0.6 percentage points in the probability of short-interval birth among non-Hispanic Blacks, and a decrease of 1.6 percentage points in the probability of another birth within 4 years overall. The policy change also was associated with a significant increase of 27 days between births among non-Hispanic Blacks, but not with any significant change among non-Hispanic Whites or the study population overall.

“In addition, although our data cannot speak to this, the policy may have affected the intendedness of subsequent pregnancies, leading to healthier behaviors before and during pregnancy, such as early initiation of prenatal care,” the researchers wrote in their discussion of the findings.

The study findings were limited by several factors including the lack of data on pregnancy intention or abortion, and the lack of data on patient-reported outcomes, notably the provision of patient-centered counseling and whether such counseling was biased, the researchers noted. Other limitations included a lack of data on infant mortality and potential confounding from risk profiles of patients in implementing vs. nonimplementing hospitals, they wrote.

Also, the study provides population-level data, which does not guide clinical decision-making about intervals between childbirth and subsequent pregnancy, the researchers emphasized.

Although the data support the value of postpartum contraception in improving birth outcomes, “it is imperative that efforts to expand access focus on assuring comprehensive access to all forms of contraception without coercion,” the researchers concluded. “Additional policy solutions are needed to improve infant health, including those that directly address structural and interpersonal racism to reduce racial disparities in infant health,” they said.

The study is important because, although immediate postpartum LARC policies were first implemented almost a decade ago in the United States, population-level evidence on the effects of these policies remains scarce, Dr. Steenland said in an interview.  

Existing barriers to improving access to immediate postpartum LARC include health professional training and logistics within hospitals, as well as ensuring correct billing and timely reimbursements, Dr. Steenland said. “Simple and clear billing procedures, and advanced reimbursement so that hospitals can have devices stocked would make it easier to provide this service,” she noted.

“This service has gone from being almost completely unavailable, to available in some hospitals, mainly those that are urban, teaching, and high volume,” said Dr. Steenland. “Additional research is needed to determine how health systems can make this service available to all birthing persons,” she said. “Also, critically, additional research is needed to identify strategies to ensure that counseling for immediate postpartum LARC, and family planning more generally, is patient-centered, so that the availability of immediate postpartum LARC increases, rather than restricts, choice,” she added. “Finally, additional research is needed to determine whether postpartum people have affordable and accessible access to LARC removal services,” Dr. Steenland emphasized.
 

Immediate post partum is critical period

The immediate postpartum period is a critical time for access to contraception because many women do not return for postpartum visits after hospital discharge, Tracey A. Wilkinson, MD, and Jeffrey F. Peipert, MD, of Indiana University, Indianapolis, wrote in an accompanying editorial. “The focus on contraception access during the postpartum period prior to hospital discharge is important because of the potential sequelae of a subsequent unintended pregnancy or short interpregnancy intervals,” they noted. These issues may be more acute in marginalized communities, and policies to expand immediate postpartum LARC are in place in a majority of states, the editorialists said.

However, they agreed with the authors’ statements that implementation of LARC must be done in a manner that supports patient choice and avoids coercion. Given the baseline disparities of the infant outcomes studied, increased access to immediate postpartum LARC must be provided in a way that does not exacerbate these disparities, they said. “This ultimately means that plans to increase access to contraception should emphasize availability while avoiding coercion, and if a patient ultimately decides to discontinue a method, enable that to occur easily and seamlessly, including LARC device removal,” they explained.

“Future studies examining patient centeredness of these postpartum LARC implementation efforts would be an important element to augment these data and show the impact in additional spheres beyond infant outcomes,” they added.
 

Overcome trust barriers and offer options

“In a time of restrictive access to abortion and contraception in many states, any additional increase in access can potentially be meaningful,” Sarah W. Prager, MD, of the University of Washington, Seattle, said in an interview. “Additionally, given the significantly higher rates of infant and maternal morbidity and mortality among the non-Hispanic Black population, seeing an intervention that can improve outcomes for both mothers and babies is also potentially very positive,” she said.

Dr. Prager said she was not surprised by the study findings, as immediate LARC is much more common in other countries and has shown similar outcomes. “Additionally, I am reassured by the fact that the increased number of days until the next pregnancy is not higher, as this indirectly indicates that patients were able to get their LARC removed when they desired another pregnancy,” she noted.

Barriers to improving access to immediate postpartum LARC in the Medicaid population may include mistrust for any long-acting contraception, “especially if they perceive that cessation of the method will be difficult to achieve,” Dr. Prager noted. “Certainly, counseling about LARC removal should be an element of counseling prior to any initiation, and lack of access to removal of an IUD or implant can be categorized as a form of reproductive coercion,” she said. Dr. Prager said that such counseling might be more effective if it occurred during prenatal visits, “so if providers are not talking about this during routine OB visits and patients only hear about immediate postpartum LARC when they are in the hospital for delivery, they may be less likely to accept the practice,” she said. “Finally, although Medicaid will cover the cost of immediate postpartum LARC, private insurers do not do so consistently in all states, so some hospitals may find this process too difficult to navigate and therefore not offer immediate postpartum LARC,” Dr. Prager emphasized.

As for additional research, Dr. Prager said she would like to see more studies in an overall United States population of pregnant people, both Medicaid patients and others, on whether the immediate postpartum timing of LARC is desired.

“I would like to couple that with patients’ impressions or experiences of their ability to access contraception outside of the immediate postpartum time period, and also their impressions or experience with ability to have LARC removed, since they are the only contraceptives not necessarily within personal control for initiation or cessation,” Dr. Prager said.

The study was supported by the National Institute for Child Health and Development, and lead author Dr. Steenland received support from other National Institutes of Health grants. The researchers had no financial conflicts to disclose. The editorial was supported in part by the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Dr. Peipert disclosed serving on advisory boards for Bayer and CooperSurgical, and receiving research support from Merck, Bayer, and CooperSurgical/Teva. Dr. Wilkinson had no financial conflicts to disclose. Dr. Prager had no financial conflicts to disclose and serves on the editorial advisory board of Ob.Gyn. News.

Policies increasing access to immediate postpartum long-acting reversible contraception (LARC) were associated with reductions in preterm birth and low birth weight, based on data from South Carolina’s Medicaid program.

Preterm birth and low birth weight represent the second-leading cause of infant mortality in the United States, wrote Maria W. Steenland, SD, of Brown University, Providence, R.I., and colleagues. Previous policy interventions to reduce preterm birth and low birth weight have focused on services before and during pregnancy, they said. LARC is a safe and effective postpartum intervention, but cost has been a limiting factor, they noted.

In 2012, the Medicaid program in South Carolina began reimbursing hospitals for immediate postpartum LARC independent of global maternity payments. In a previous study, the researchers found that the implementation of this policy had reduced the number of short-interval births among adolescents.

The goal of the current study, published in JAMA Pediatrics, was to analyze the association between South Carolina’s policy change and rates of preterm birth and low birth weight among individuals with Medicaid coverage during childbirth. The researchers analyzed data from 186,953 Medicaid-paid births between January 2009 and December 2015 in South Carolina. Of these, 46,414 births (24.8%) occurred in hospitals that provided immediate postpartum LARC in response to the policy change. Overall, the implementing hospitals had more annual births paid for by Medicaid compared to nonimplementing hospitals (1,105 vs. 511) and were less likely to be rural (33.3% vs. 46.8%) and had a greater share of preterm births (15.5% vs. 9.5%). Prior to the policy change, the probability of a preterm birth in the next 4 years was 4.4% for patients at implementing hospitals and 3.5% for those in nonimplementing hospitals, and the probability of a low-birth-weight birth was 3.6% and 2.9%, respectively.

The policy change was associated with a decrease of 0.4 percentage points for preterm birth and 0.3 percentage points for subsequent low-birth-weight birth.

When the results were stratified based on race and ethnicity, the policy change was associated with a decrease of 0.5 percentage points in the probability of preterm birth in both non-Hispanic Blacks and non-Hispanic Whites. No significant differences appeared in the association between the policy change and rates of preterm birth or low-birth-weight birth between non-Hispanic Black and non-Hispanic White individuals.

However, the policy was associated with a significant decrease of 0.6 percentage points in the probability of short-interval birth among non-Hispanic Blacks, and a decrease of 1.6 percentage points in the probability of another birth within 4 years overall. The policy change also was associated with a significant increase of 27 days between births among non-Hispanic Blacks, but not with any significant change among non-Hispanic Whites or the study population overall.

“In addition, although our data cannot speak to this, the policy may have affected the intendedness of subsequent pregnancies, leading to healthier behaviors before and during pregnancy, such as early initiation of prenatal care,” the researchers wrote in their discussion of the findings.

The study findings were limited by several factors including the lack of data on pregnancy intention or abortion, and the lack of data on patient-reported outcomes, notably the provision of patient-centered counseling and whether such counseling was biased, the researchers noted. Other limitations included a lack of data on infant mortality and potential confounding from risk profiles of patients in implementing vs. nonimplementing hospitals, they wrote.

Also, the study provides population-level data, which does not guide clinical decision-making about intervals between childbirth and subsequent pregnancy, the researchers emphasized.

Although the data support the value of postpartum contraception in improving birth outcomes, “it is imperative that efforts to expand access focus on assuring comprehensive access to all forms of contraception without coercion,” the researchers concluded. “Additional policy solutions are needed to improve infant health, including those that directly address structural and interpersonal racism to reduce racial disparities in infant health,” they said.

The study is important because, although immediate postpartum LARC policies were first implemented almost a decade ago in the United States, population-level evidence on the effects of these policies remains scarce, Dr. Steenland said in an interview.  

Existing barriers to improving access to immediate postpartum LARC include health professional training and logistics within hospitals, as well as ensuring correct billing and timely reimbursements, Dr. Steenland said. “Simple and clear billing procedures, and advanced reimbursement so that hospitals can have devices stocked would make it easier to provide this service,” she noted.

“This service has gone from being almost completely unavailable, to available in some hospitals, mainly those that are urban, teaching, and high volume,” said Dr. Steenland. “Additional research is needed to determine how health systems can make this service available to all birthing persons,” she said. “Also, critically, additional research is needed to identify strategies to ensure that counseling for immediate postpartum LARC, and family planning more generally, is patient-centered, so that the availability of immediate postpartum LARC increases, rather than restricts, choice,” she added. “Finally, additional research is needed to determine whether postpartum people have affordable and accessible access to LARC removal services,” Dr. Steenland emphasized.
 

Immediate post partum is critical period

The immediate postpartum period is a critical time for access to contraception because many women do not return for postpartum visits after hospital discharge, Tracey A. Wilkinson, MD, and Jeffrey F. Peipert, MD, of Indiana University, Indianapolis, wrote in an accompanying editorial. “The focus on contraception access during the postpartum period prior to hospital discharge is important because of the potential sequelae of a subsequent unintended pregnancy or short interpregnancy intervals,” they noted. These issues may be more acute in marginalized communities, and policies to expand immediate postpartum LARC are in place in a majority of states, the editorialists said.

However, they agreed with the authors’ statements that implementation of LARC must be done in a manner that supports patient choice and avoids coercion. Given the baseline disparities of the infant outcomes studied, increased access to immediate postpartum LARC must be provided in a way that does not exacerbate these disparities, they said. “This ultimately means that plans to increase access to contraception should emphasize availability while avoiding coercion, and if a patient ultimately decides to discontinue a method, enable that to occur easily and seamlessly, including LARC device removal,” they explained.

“Future studies examining patient centeredness of these postpartum LARC implementation efforts would be an important element to augment these data and show the impact in additional spheres beyond infant outcomes,” they added.
 

Overcome trust barriers and offer options

“In a time of restrictive access to abortion and contraception in many states, any additional increase in access can potentially be meaningful,” Sarah W. Prager, MD, of the University of Washington, Seattle, said in an interview. “Additionally, given the significantly higher rates of infant and maternal morbidity and mortality among the non-Hispanic Black population, seeing an intervention that can improve outcomes for both mothers and babies is also potentially very positive,” she said.

Dr. Prager said she was not surprised by the study findings, as immediate LARC is much more common in other countries and has shown similar outcomes. “Additionally, I am reassured by the fact that the increased number of days until the next pregnancy is not higher, as this indirectly indicates that patients were able to get their LARC removed when they desired another pregnancy,” she noted.

Barriers to improving access to immediate postpartum LARC in the Medicaid population may include mistrust for any long-acting contraception, “especially if they perceive that cessation of the method will be difficult to achieve,” Dr. Prager noted. “Certainly, counseling about LARC removal should be an element of counseling prior to any initiation, and lack of access to removal of an IUD or implant can be categorized as a form of reproductive coercion,” she said. Dr. Prager said that such counseling might be more effective if it occurred during prenatal visits, “so if providers are not talking about this during routine OB visits and patients only hear about immediate postpartum LARC when they are in the hospital for delivery, they may be less likely to accept the practice,” she said. “Finally, although Medicaid will cover the cost of immediate postpartum LARC, private insurers do not do so consistently in all states, so some hospitals may find this process too difficult to navigate and therefore not offer immediate postpartum LARC,” Dr. Prager emphasized.

As for additional research, Dr. Prager said she would like to see more studies in an overall United States population of pregnant people, both Medicaid patients and others, on whether the immediate postpartum timing of LARC is desired.

“I would like to couple that with patients’ impressions or experiences of their ability to access contraception outside of the immediate postpartum time period, and also their impressions or experience with ability to have LARC removed, since they are the only contraceptives not necessarily within personal control for initiation or cessation,” Dr. Prager said.

The study was supported by the National Institute for Child Health and Development, and lead author Dr. Steenland received support from other National Institutes of Health grants. The researchers had no financial conflicts to disclose. The editorial was supported in part by the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Dr. Peipert disclosed serving on advisory boards for Bayer and CooperSurgical, and receiving research support from Merck, Bayer, and CooperSurgical/Teva. Dr. Wilkinson had no financial conflicts to disclose. Dr. Prager had no financial conflicts to disclose and serves on the editorial advisory board of Ob.Gyn. News.

Pregnant women who are at risk of preeclampsia can now be identified early before symptoms develop, finds new research from Kings College London and Guy’s and St Thomas’ NHS Foundation Trust, published in Nature.

The study, supported by the National Institute for Health Research and in partnership with the Mirvie RNA platform, analyzed the genetic material from over 2,500 blood samples of pregnant women from eight independent cohorts with multiple demographics, including socioeconomic background, geographic location, ethnicity, and nationality, collected 14.5 weeks before delivery.

“Because the study drew upon samples for a diverse group of women, including participants recruited across King’s Health Partners, the molecular signature is very reliable and has potential to outperform currently available tests,” said Rachel Tribe, PhD, department of women and children’s health, King’s College London.

Researchers used plasma cell-free RNA (cfRNA) transcripts to examine the standard molecular mechanism between the fetus, maternal, and placental tissues in order to determine fetal development and healthy pregnancy progression. Deviation from the standard cfRNA expression was also observed to establish the molecular pathway for those at risk of preeclampsia before clinical presentation.

A cfRNA signal from a single blood sample showed a 32.3% positive-predictive value and 75% sensitivity, which exceeds current positive-predictive values from recent clinical state-of-the-art models.

In addition, 73% of participants with a positive-predictive value were identified “as destined to have a medically indicated preterm birth over 3 months in advance of the preeclampsia symptoms,” said the authors.

With up to 1 in 12 pregnancies affected by preeclampsia, and the diagnosis most often only being made in the third trimester, these results provide a promising outlook for pregnant women “so that they can be more closely monitored and treated by the clinicians involved,” commented Dr. Tribe.

“We are now focused on ongoing clinical research to further validate these results and improve the understanding of other pregnancy complications,” she said. “As a scientist, it was also extremely interesting to see that the molecular signature tells us something about mechanisms associated with health in pregnancy and complications including preeclampsia; such knowledge will aid development of treatment strategies in the future.”

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

Pregnant women who are at risk of preeclampsia can now be identified early before symptoms develop, finds new research from Kings College London and Guy’s and St Thomas’ NHS Foundation Trust, published in Nature.

The study, supported by the National Institute for Health Research and in partnership with the Mirvie RNA platform, analyzed the genetic material from over 2,500 blood samples of pregnant women from eight independent cohorts with multiple demographics, including socioeconomic background, geographic location, ethnicity, and nationality, collected 14.5 weeks before delivery.

“Because the study drew upon samples for a diverse group of women, including participants recruited across King’s Health Partners, the molecular signature is very reliable and has potential to outperform currently available tests,” said Rachel Tribe, PhD, department of women and children’s health, King’s College London.

Researchers used plasma cell-free RNA (cfRNA) transcripts to examine the standard molecular mechanism between the fetus, maternal, and placental tissues in order to determine fetal development and healthy pregnancy progression. Deviation from the standard cfRNA expression was also observed to establish the molecular pathway for those at risk of preeclampsia before clinical presentation.

A cfRNA signal from a single blood sample showed a 32.3% positive-predictive value and 75% sensitivity, which exceeds current positive-predictive values from recent clinical state-of-the-art models.

In addition, 73% of participants with a positive-predictive value were identified “as destined to have a medically indicated preterm birth over 3 months in advance of the preeclampsia symptoms,” said the authors.

With up to 1 in 12 pregnancies affected by preeclampsia, and the diagnosis most often only being made in the third trimester, these results provide a promising outlook for pregnant women “so that they can be more closely monitored and treated by the clinicians involved,” commented Dr. Tribe.

“We are now focused on ongoing clinical research to further validate these results and improve the understanding of other pregnancy complications,” she said. “As a scientist, it was also extremely interesting to see that the molecular signature tells us something about mechanisms associated with health in pregnancy and complications including preeclampsia; such knowledge will aid development of treatment strategies in the future.”

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

Pregnant women who are at risk of preeclampsia can now be identified early before symptoms develop, finds new research from Kings College London and Guy’s and St Thomas’ NHS Foundation Trust, published in Nature.

The study, supported by the National Institute for Health Research and in partnership with the Mirvie RNA platform, analyzed the genetic material from over 2,500 blood samples of pregnant women from eight independent cohorts with multiple demographics, including socioeconomic background, geographic location, ethnicity, and nationality, collected 14.5 weeks before delivery.

“Because the study drew upon samples for a diverse group of women, including participants recruited across King’s Health Partners, the molecular signature is very reliable and has potential to outperform currently available tests,” said Rachel Tribe, PhD, department of women and children’s health, King’s College London.

Researchers used plasma cell-free RNA (cfRNA) transcripts to examine the standard molecular mechanism between the fetus, maternal, and placental tissues in order to determine fetal development and healthy pregnancy progression. Deviation from the standard cfRNA expression was also observed to establish the molecular pathway for those at risk of preeclampsia before clinical presentation.

A cfRNA signal from a single blood sample showed a 32.3% positive-predictive value and 75% sensitivity, which exceeds current positive-predictive values from recent clinical state-of-the-art models.

In addition, 73% of participants with a positive-predictive value were identified “as destined to have a medically indicated preterm birth over 3 months in advance of the preeclampsia symptoms,” said the authors.

With up to 1 in 12 pregnancies affected by preeclampsia, and the diagnosis most often only being made in the third trimester, these results provide a promising outlook for pregnant women “so that they can be more closely monitored and treated by the clinicians involved,” commented Dr. Tribe.

“We are now focused on ongoing clinical research to further validate these results and improve the understanding of other pregnancy complications,” she said. “As a scientist, it was also extremely interesting to see that the molecular signature tells us something about mechanisms associated with health in pregnancy and complications including preeclampsia; such knowledge will aid development of treatment strategies in the future.”

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

Delayed umbilical cord clamping for at least 60 seconds after birth significantly reduced death or disability in infants of less than 30 weeks’ gestation, according to data from nearly 1,500 infants.

The burden of disability and mortality for babies born before 30 weeks’ gestation remains high, especially in low- and middle-income countries, wrote Kristy P. Robledo, PhD, of the University of Sydney, Australia, and colleagues. Delayed clamping of the umbilical cord is a simple procedure that may improve mortality in this population, but more research is needed; recommended times to delayed clamping range from 30 seconds to 3 minutes, they noted.

In a study published in The Lancet Child & Adolescent Health, the researchers randomized 767 very preterm infants to delayed clamping at least 60 seconds after birth and 764 to immediate clamping. Of these, 384 were multiple births (who were individually randomized), 862 were male, and 505 were born before 27 weeks’ gestation. The primary outcome was death or disability at 2 years of age. Major disability was defined as cerebral palsy, severe visual loss, deafness requiring a hearing aid or cochlear implants, major language or speech problems, or cognitive delay at 2 years corrected age. The median time to clamping was 60 seconds in the delayed group and 5 seconds in the immediate group.

Primary outcome data were available for 1,419 infants. Death or major disability occurred in 29% of infants assigned to delayed clamping compared to 34% of those assigned to immediate clamping (relative risk 0.83, P = .010). The infants were part of the APTS Childhood Follow-Up Study, an open-label superiority trial conducted in Australia and New Zealand.

By age 2 years, 8% of infants in the delayed group and 11% of those in the immediate group had died; 23% and 26%, respectively, met criteria for major disability. The impact of delayed clamping translates to a 30% reduction in relative risk of mortality at 2 years of age, but no significant impact on major disability, the researchers wrote.

The findings were limited by several factors including the unblinded study design, lack of data on heart rate or time to first breath, and the clamping prior to 60 seconds in 26% of infants in the delayed group based on clinical concerns for these specific infants, the researchers noted.

However, the results were strengthened by the large size, low risk of bias, and specific primary outcome, they said. The data support findings from recent systematic reviews and highlight the need for further trials to evaluate delayed clamping at different time points, with larger populations, inclusion of time to first breath and heart rate, and improved measures of disability, the researchers added.

In clinical practice, “Given that aiming to delay cord clamping for 60 seconds or more improved 2-year outcomes and short-term hematological measures with no evidence of significant harm, it seems reasonable to conclude that delayed clamping is appropriate as standard care in very preterm infants,” they concluded.
 

Accepting simple intervention could have great impact

This study is important in light of the overwhelming burden of preterm birth on the health care system and society as a whole, Lisette D. Tanner, MD, of Emory University, Atlanta, said in an interview.

“Preterm birth is associated with billions in health care costs each year, and a large portion of that money is directed to the complications associated with preterm birth, such as early intervention services, educational support, and ongoing medical care,” Dr. Tanner said. “This study is particularly timely, as we are quickly approaching 2030, the deadline for achieving the United Nations Sustainable Development Goal of ending preventable deaths of newborns and children under 5 years of age,” she said. The goal involves “all countries aiming to reduce neonatal mortality to at least as low as 12 per 1,000 live births and under-5 mortality to at least as low as 25 per 1,000 live births. Effective treatments to reduce infant and child mortality would make strong inroads toward this goal,” she explained.

Dr. Tanner said she was not surprised by the findings because previous studies have shown similar results. “However, the large, multicenter nature of this study provides additional weight to recommendations to delay cord clamping as standard practice,” she said.

“The findings of this study support the recommendations of a number of large organizations,” said Dr. Tanner. “The World Health Organization recommends that the umbilical cord not be clamped earlier than 1 minute after birth in term or preterm infants who do not require positive pressure ventilation. The American College of Obstetricians and Gynecologists and the American Academy of Pediatrics now recommend a delay in umbilical cord clamping in vigorous term and preterm infants for at least 30–60 seconds after birth,” she said. “The Royal College of Obstetricians and Gynaecologists also recommends deferring umbilical cord clamping for healthy term and preterm infants for at least 2 minutes after birth,” she added.  

However, “the delay in adoption of this guidelines in practice appears to be related to some concerns regarding universal adoption of this approach,” Dr. Tanner noted. “Some clinicians have suggested that delayed cord clamping could delay vital neonatal resuscitative efforts, leading to worse neonatal outcomes, but this concern has not been borne out in the data, as all guidelines specifically state that this intervention is for vigorous newborns,” she said. “In fact, in preterm infants, delayed cord clamping is associated with improved transitional circulation, decreased need for blood transfusion, and lower incidence of necrotizing enterocolitis and intraventricular hemorrhage,” Dr. Tanner emphasized. “Additionally, concerns persist that delayed cord clamping could lead to excessive transfusion with resultant polycythemia. Again, no data have supported this claim to date,” she said.

“Finally, some clinicians are concerned that delayed clamping could lead to delay in addressing maternal complications of birth such as hemorrhage, but studies have shown the opposite; delayed umbilical cord clamping has not been associated with an increased risk of postpartum hemorrhage or increased blood loss at delivery, nor has it been with a difference in the need for blood transfusion,” said Dr. Tanner.

Ideally, practitioners will become more comfortable in delaying cord clamping as a routine practice as more data demonstrating the safety and benefit of this easy intervention are disseminated, she said.

Additional research delineating which gestational ages benefit most from delayed cord clamping would help direct education efforts to implement this intervention, Dr. Tanner noted.

The study was funded by the Australian National Health and Medical Research Council. The researchers and Dr. Tanner had no financial conflicts to disclose.

Delayed umbilical cord clamping for at least 60 seconds after birth significantly reduced death or disability in infants of less than 30 weeks’ gestation, according to data from nearly 1,500 infants.

The burden of disability and mortality for babies born before 30 weeks’ gestation remains high, especially in low- and middle-income countries, wrote Kristy P. Robledo, PhD, of the University of Sydney, Australia, and colleagues. Delayed clamping of the umbilical cord is a simple procedure that may improve mortality in this population, but more research is needed; recommended times to delayed clamping range from 30 seconds to 3 minutes, they noted.

In a study published in The Lancet Child & Adolescent Health, the researchers randomized 767 very preterm infants to delayed clamping at least 60 seconds after birth and 764 to immediate clamping. Of these, 384 were multiple births (who were individually randomized), 862 were male, and 505 were born before 27 weeks’ gestation. The primary outcome was death or disability at 2 years of age. Major disability was defined as cerebral palsy, severe visual loss, deafness requiring a hearing aid or cochlear implants, major language or speech problems, or cognitive delay at 2 years corrected age. The median time to clamping was 60 seconds in the delayed group and 5 seconds in the immediate group.

Primary outcome data were available for 1,419 infants. Death or major disability occurred in 29% of infants assigned to delayed clamping compared to 34% of those assigned to immediate clamping (relative risk 0.83, P = .010). The infants were part of the APTS Childhood Follow-Up Study, an open-label superiority trial conducted in Australia and New Zealand.

By age 2 years, 8% of infants in the delayed group and 11% of those in the immediate group had died; 23% and 26%, respectively, met criteria for major disability. The impact of delayed clamping translates to a 30% reduction in relative risk of mortality at 2 years of age, but no significant impact on major disability, the researchers wrote.

The findings were limited by several factors including the unblinded study design, lack of data on heart rate or time to first breath, and the clamping prior to 60 seconds in 26% of infants in the delayed group based on clinical concerns for these specific infants, the researchers noted.

However, the results were strengthened by the large size, low risk of bias, and specific primary outcome, they said. The data support findings from recent systematic reviews and highlight the need for further trials to evaluate delayed clamping at different time points, with larger populations, inclusion of time to first breath and heart rate, and improved measures of disability, the researchers added.

In clinical practice, “Given that aiming to delay cord clamping for 60 seconds or more improved 2-year outcomes and short-term hematological measures with no evidence of significant harm, it seems reasonable to conclude that delayed clamping is appropriate as standard care in very preterm infants,” they concluded.
 

Accepting simple intervention could have great impact

This study is important in light of the overwhelming burden of preterm birth on the health care system and society as a whole, Lisette D. Tanner, MD, of Emory University, Atlanta, said in an interview.

“Preterm birth is associated with billions in health care costs each year, and a large portion of that money is directed to the complications associated with preterm birth, such as early intervention services, educational support, and ongoing medical care,” Dr. Tanner said. “This study is particularly timely, as we are quickly approaching 2030, the deadline for achieving the United Nations Sustainable Development Goal of ending preventable deaths of newborns and children under 5 years of age,” she said. The goal involves “all countries aiming to reduce neonatal mortality to at least as low as 12 per 1,000 live births and under-5 mortality to at least as low as 25 per 1,000 live births. Effective treatments to reduce infant and child mortality would make strong inroads toward this goal,” she explained.

Dr. Tanner said she was not surprised by the findings because previous studies have shown similar results. “However, the large, multicenter nature of this study provides additional weight to recommendations to delay cord clamping as standard practice,” she said.

“The findings of this study support the recommendations of a number of large organizations,” said Dr. Tanner. “The World Health Organization recommends that the umbilical cord not be clamped earlier than 1 minute after birth in term or preterm infants who do not require positive pressure ventilation. The American College of Obstetricians and Gynecologists and the American Academy of Pediatrics now recommend a delay in umbilical cord clamping in vigorous term and preterm infants for at least 30–60 seconds after birth,” she said. “The Royal College of Obstetricians and Gynaecologists also recommends deferring umbilical cord clamping for healthy term and preterm infants for at least 2 minutes after birth,” she added.  

However, “the delay in adoption of this guidelines in practice appears to be related to some concerns regarding universal adoption of this approach,” Dr. Tanner noted. “Some clinicians have suggested that delayed cord clamping could delay vital neonatal resuscitative efforts, leading to worse neonatal outcomes, but this concern has not been borne out in the data, as all guidelines specifically state that this intervention is for vigorous newborns,” she said. “In fact, in preterm infants, delayed cord clamping is associated with improved transitional circulation, decreased need for blood transfusion, and lower incidence of necrotizing enterocolitis and intraventricular hemorrhage,” Dr. Tanner emphasized. “Additionally, concerns persist that delayed cord clamping could lead to excessive transfusion with resultant polycythemia. Again, no data have supported this claim to date,” she said.

“Finally, some clinicians are concerned that delayed clamping could lead to delay in addressing maternal complications of birth such as hemorrhage, but studies have shown the opposite; delayed umbilical cord clamping has not been associated with an increased risk of postpartum hemorrhage or increased blood loss at delivery, nor has it been with a difference in the need for blood transfusion,” said Dr. Tanner.

Ideally, practitioners will become more comfortable in delaying cord clamping as a routine practice as more data demonstrating the safety and benefit of this easy intervention are disseminated, she said.

Additional research delineating which gestational ages benefit most from delayed cord clamping would help direct education efforts to implement this intervention, Dr. Tanner noted.

The study was funded by the Australian National Health and Medical Research Council. The researchers and Dr. Tanner had no financial conflicts to disclose.

Delayed umbilical cord clamping for at least 60 seconds after birth significantly reduced death or disability in infants of less than 30 weeks’ gestation, according to data from nearly 1,500 infants.

The burden of disability and mortality for babies born before 30 weeks’ gestation remains high, especially in low- and middle-income countries, wrote Kristy P. Robledo, PhD, of the University of Sydney, Australia, and colleagues. Delayed clamping of the umbilical cord is a simple procedure that may improve mortality in this population, but more research is needed; recommended times to delayed clamping range from 30 seconds to 3 minutes, they noted.

In a study published in The Lancet Child & Adolescent Health, the researchers randomized 767 very preterm infants to delayed clamping at least 60 seconds after birth and 764 to immediate clamping. Of these, 384 were multiple births (who were individually randomized), 862 were male, and 505 were born before 27 weeks’ gestation. The primary outcome was death or disability at 2 years of age. Major disability was defined as cerebral palsy, severe visual loss, deafness requiring a hearing aid or cochlear implants, major language or speech problems, or cognitive delay at 2 years corrected age. The median time to clamping was 60 seconds in the delayed group and 5 seconds in the immediate group.

Primary outcome data were available for 1,419 infants. Death or major disability occurred in 29% of infants assigned to delayed clamping compared to 34% of those assigned to immediate clamping (relative risk 0.83, P = .010). The infants were part of the APTS Childhood Follow-Up Study, an open-label superiority trial conducted in Australia and New Zealand.

By age 2 years, 8% of infants in the delayed group and 11% of those in the immediate group had died; 23% and 26%, respectively, met criteria for major disability. The impact of delayed clamping translates to a 30% reduction in relative risk of mortality at 2 years of age, but no significant impact on major disability, the researchers wrote.

The findings were limited by several factors including the unblinded study design, lack of data on heart rate or time to first breath, and the clamping prior to 60 seconds in 26% of infants in the delayed group based on clinical concerns for these specific infants, the researchers noted.

However, the results were strengthened by the large size, low risk of bias, and specific primary outcome, they said. The data support findings from recent systematic reviews and highlight the need for further trials to evaluate delayed clamping at different time points, with larger populations, inclusion of time to first breath and heart rate, and improved measures of disability, the researchers added.

In clinical practice, “Given that aiming to delay cord clamping for 60 seconds or more improved 2-year outcomes and short-term hematological measures with no evidence of significant harm, it seems reasonable to conclude that delayed clamping is appropriate as standard care in very preterm infants,” they concluded.
 

Accepting simple intervention could have great impact

This study is important in light of the overwhelming burden of preterm birth on the health care system and society as a whole, Lisette D. Tanner, MD, of Emory University, Atlanta, said in an interview.

“Preterm birth is associated with billions in health care costs each year, and a large portion of that money is directed to the complications associated with preterm birth, such as early intervention services, educational support, and ongoing medical care,” Dr. Tanner said. “This study is particularly timely, as we are quickly approaching 2030, the deadline for achieving the United Nations Sustainable Development Goal of ending preventable deaths of newborns and children under 5 years of age,” she said. The goal involves “all countries aiming to reduce neonatal mortality to at least as low as 12 per 1,000 live births and under-5 mortality to at least as low as 25 per 1,000 live births. Effective treatments to reduce infant and child mortality would make strong inroads toward this goal,” she explained.

Dr. Tanner said she was not surprised by the findings because previous studies have shown similar results. “However, the large, multicenter nature of this study provides additional weight to recommendations to delay cord clamping as standard practice,” she said.

“The findings of this study support the recommendations of a number of large organizations,” said Dr. Tanner. “The World Health Organization recommends that the umbilical cord not be clamped earlier than 1 minute after birth in term or preterm infants who do not require positive pressure ventilation. The American College of Obstetricians and Gynecologists and the American Academy of Pediatrics now recommend a delay in umbilical cord clamping in vigorous term and preterm infants for at least 30–60 seconds after birth,” she said. “The Royal College of Obstetricians and Gynaecologists also recommends deferring umbilical cord clamping for healthy term and preterm infants for at least 2 minutes after birth,” she added.  

However, “the delay in adoption of this guidelines in practice appears to be related to some concerns regarding universal adoption of this approach,” Dr. Tanner noted. “Some clinicians have suggested that delayed cord clamping could delay vital neonatal resuscitative efforts, leading to worse neonatal outcomes, but this concern has not been borne out in the data, as all guidelines specifically state that this intervention is for vigorous newborns,” she said. “In fact, in preterm infants, delayed cord clamping is associated with improved transitional circulation, decreased need for blood transfusion, and lower incidence of necrotizing enterocolitis and intraventricular hemorrhage,” Dr. Tanner emphasized. “Additionally, concerns persist that delayed cord clamping could lead to excessive transfusion with resultant polycythemia. Again, no data have supported this claim to date,” she said.

“Finally, some clinicians are concerned that delayed clamping could lead to delay in addressing maternal complications of birth such as hemorrhage, but studies have shown the opposite; delayed umbilical cord clamping has not been associated with an increased risk of postpartum hemorrhage or increased blood loss at delivery, nor has it been with a difference in the need for blood transfusion,” said Dr. Tanner.

Ideally, practitioners will become more comfortable in delaying cord clamping as a routine practice as more data demonstrating the safety and benefit of this easy intervention are disseminated, she said.

Additional research delineating which gestational ages benefit most from delayed cord clamping would help direct education efforts to implement this intervention, Dr. Tanner noted.

The study was funded by the Australian National Health and Medical Research Council. The researchers and Dr. Tanner had no financial conflicts to disclose.

In recent weeks, the Centers for Disease Control and Prevention has greatly expanded recommendations for boosters for vaccinations against COVID-19.

These recommendations have been widened because of the continued emergence of new variants of the virus and the wane of protection over time for both vaccinations and previous disease.

The new recommendations take away some of the questions surrounding eligibility for booster vaccinations while potentially leaving some additional questions. All in all, they provide flexibility for individuals to help protect themselves against the COVID-19 virus, as many are considering celebrating the holidays with friends and family.

The first item that has become clear is that all individuals over 18 are now not only eligible for a booster vaccination a certain time after they have completed their series, but have a recommendation for one.¹

But what about a fourth dose?  There is a possibility that some patients should be receiving one.  For those who require a three-dose series due to a condition that makes them immunocompromised, they should receive their booster vaccination six months after completion of the three-dose series.  This distinction  may cause confusion for some, but is important for those immunocompromised.

Boosters in women who are pregnant

The recommendations also include specific comments about individuals who are pregnant. Although initial studies did not include pregnant individuals, there has been increasing real world data that vaccination against COVID, including booster vaccinations, is safe and recommended. As pregnancy increases the risk of severe disease if infected by COVID-19, both the CDC and the American College of Obstetricians and Gynecologists,² along with other specialty organizations, such as the Royal College of Obstetricians and Gynaecologists, recommend vaccinations for pregnant individuals.

The CDC goes on to describe that there is no evidence of vaccination increasing the risk of infertility. The vaccine protects the pregnant individual and also provides protection to the baby once born. The same is true of breastfeeding individuals.³

I hope that this information allows physicians to feel comfortable recommending vaccinations and boosters to those who are pregnant and breast feeding.
 

Expanded recommendations for those aged 16-17 years

Recently, the CDC also expanded booster recommendations to include those aged 16-17 years, 6 months after completing their vaccine series.

Those under 18 are currently only able to receive the Pfizer-BioNtech vaccine. This new guidance has left some parents wondering if there will also be approval for booster vaccinations soon for those aged 12-16 who are approaching or have reached six months past the initial vaccine.¹

Booster brand for those over 18 years?

Although the recommendation has been simplified for all over age 18 years, there is still a decision to be made about which vaccine to use as the booster.

The recommendations allow individuals to decide which brand of vaccine they would like to have as a booster. They may choose to be vaccinated with the same vaccine they originally received or with a different vaccine. This vaccine flexibility may cause confusion, but ultimately is a good thing as it allows individuals to receive whatever vaccine is available and most convenient. This also allows individuals who have been vaccinated outside of the United States by a different brand of vaccine to also receive a booster vaccination with one of the options available here.
 

Take home message

Overall, the expansion of booster recommendations will help everyone avoid severe disease from COVID-19 infections. Physicians now have more clarity on who should be receiving these vaccines. Along with testing, masking, and appropriate distancing, these recommendations should help prevent severe disease and death from COVID-19.

Dr. Wheat is a family physician at Erie Family Health Center in Chicago. She is program director of Northwestern’s McGaw Family Medicine residency program, also in Chicago. Dr. Wheat serves on the editorial advisory board of Family Practice News. You can contact her at fpnews@mdedge.com.

References

1. COVID-19 Vaccine Booster Shots. Centers for Disease Control and Prevention. 2021 Dec 9.

2. COVID-19 Vaccines and Pregnancy: Conversation Guide. American College of Obstetricians and Gynecologists. 2021 November.

3. COVID-19 Vaccines While Pregnant or Breastfeeding. Centers for Disease Control and Prevention. 2021 Dec 6.

In recent weeks, the Centers for Disease Control and Prevention has greatly expanded recommendations for boosters for vaccinations against COVID-19.

These recommendations have been widened because of the continued emergence of new variants of the virus and the wane of protection over time for both vaccinations and previous disease.

The new recommendations take away some of the questions surrounding eligibility for booster vaccinations while potentially leaving some additional questions. All in all, they provide flexibility for individuals to help protect themselves against the COVID-19 virus, as many are considering celebrating the holidays with friends and family.

The first item that has become clear is that all individuals over 18 are now not only eligible for a booster vaccination a certain time after they have completed their series, but have a recommendation for one.¹

But what about a fourth dose?  There is a possibility that some patients should be receiving one.  For those who require a three-dose series due to a condition that makes them immunocompromised, they should receive their booster vaccination six months after completion of the three-dose series.  This distinction  may cause confusion for some, but is important for those immunocompromised.

Boosters in women who are pregnant

The recommendations also include specific comments about individuals who are pregnant. Although initial studies did not include pregnant individuals, there has been increasing real world data that vaccination against COVID, including booster vaccinations, is safe and recommended. As pregnancy increases the risk of severe disease if infected by COVID-19, both the CDC and the American College of Obstetricians and Gynecologists,² along with other specialty organizations, such as the Royal College of Obstetricians and Gynaecologists, recommend vaccinations for pregnant individuals.

The CDC goes on to describe that there is no evidence of vaccination increasing the risk of infertility. The vaccine protects the pregnant individual and also provides protection to the baby once born. The same is true of breastfeeding individuals.³

I hope that this information allows physicians to feel comfortable recommending vaccinations and boosters to those who are pregnant and breast feeding.
 

Expanded recommendations for those aged 16-17 years

Recently, the CDC also expanded booster recommendations to include those aged 16-17 years, 6 months after completing their vaccine series.

Those under 18 are currently only able to receive the Pfizer-BioNtech vaccine. This new guidance has left some parents wondering if there will also be approval for booster vaccinations soon for those aged 12-16 who are approaching or have reached six months past the initial vaccine.¹

Booster brand for those over 18 years?

Although the recommendation has been simplified for all over age 18 years, there is still a decision to be made about which vaccine to use as the booster.

The recommendations allow individuals to decide which brand of vaccine they would like to have as a booster. They may choose to be vaccinated with the same vaccine they originally received or with a different vaccine. This vaccine flexibility may cause confusion, but ultimately is a good thing as it allows individuals to receive whatever vaccine is available and most convenient. This also allows individuals who have been vaccinated outside of the United States by a different brand of vaccine to also receive a booster vaccination with one of the options available here.
 

Take home message

Overall, the expansion of booster recommendations will help everyone avoid severe disease from COVID-19 infections. Physicians now have more clarity on who should be receiving these vaccines. Along with testing, masking, and appropriate distancing, these recommendations should help prevent severe disease and death from COVID-19.

Dr. Wheat is a family physician at Erie Family Health Center in Chicago. She is program director of Northwestern’s McGaw Family Medicine residency program, also in Chicago. Dr. Wheat serves on the editorial advisory board of Family Practice News. You can contact her at fpnews@mdedge.com.

References

1. COVID-19 Vaccine Booster Shots. Centers for Disease Control and Prevention. 2021 Dec 9.

2. COVID-19 Vaccines and Pregnancy: Conversation Guide. American College of Obstetricians and Gynecologists. 2021 November.

3. COVID-19 Vaccines While Pregnant or Breastfeeding. Centers for Disease Control and Prevention. 2021 Dec 6.

In recent weeks, the Centers for Disease Control and Prevention has greatly expanded recommendations for boosters for vaccinations against COVID-19.

These recommendations have been widened because of the continued emergence of new variants of the virus and the wane of protection over time for both vaccinations and previous disease.

The new recommendations take away some of the questions surrounding eligibility for booster vaccinations while potentially leaving some additional questions. All in all, they provide flexibility for individuals to help protect themselves against the COVID-19 virus, as many are considering celebrating the holidays with friends and family.

The first item that has become clear is that all individuals over 18 are now not only eligible for a booster vaccination a certain time after they have completed their series, but have a recommendation for one.¹

But what about a fourth dose?  There is a possibility that some patients should be receiving one.  For those who require a three-dose series due to a condition that makes them immunocompromised, they should receive their booster vaccination six months after completion of the three-dose series.  This distinction  may cause confusion for some, but is important for those immunocompromised.

Boosters in women who are pregnant

The recommendations also include specific comments about individuals who are pregnant. Although initial studies did not include pregnant individuals, there has been increasing real world data that vaccination against COVID, including booster vaccinations, is safe and recommended. As pregnancy increases the risk of severe disease if infected by COVID-19, both the CDC and the American College of Obstetricians and Gynecologists,² along with other specialty organizations, such as the Royal College of Obstetricians and Gynaecologists, recommend vaccinations for pregnant individuals.

The CDC goes on to describe that there is no evidence of vaccination increasing the risk of infertility. The vaccine protects the pregnant individual and also provides protection to the baby once born. The same is true of breastfeeding individuals.³

I hope that this information allows physicians to feel comfortable recommending vaccinations and boosters to those who are pregnant and breast feeding.
 

Expanded recommendations for those aged 16-17 years

Recently, the CDC also expanded booster recommendations to include those aged 16-17 years, 6 months after completing their vaccine series.

Those under 18 are currently only able to receive the Pfizer-BioNtech vaccine. This new guidance has left some parents wondering if there will also be approval for booster vaccinations soon for those aged 12-16 who are approaching or have reached six months past the initial vaccine.¹

Booster brand for those over 18 years?

Although the recommendation has been simplified for all over age 18 years, there is still a decision to be made about which vaccine to use as the booster.

The recommendations allow individuals to decide which brand of vaccine they would like to have as a booster. They may choose to be vaccinated with the same vaccine they originally received or with a different vaccine. This vaccine flexibility may cause confusion, but ultimately is a good thing as it allows individuals to receive whatever vaccine is available and most convenient. This also allows individuals who have been vaccinated outside of the United States by a different brand of vaccine to also receive a booster vaccination with one of the options available here.
 

Take home message

Overall, the expansion of booster recommendations will help everyone avoid severe disease from COVID-19 infections. Physicians now have more clarity on who should be receiving these vaccines. Along with testing, masking, and appropriate distancing, these recommendations should help prevent severe disease and death from COVID-19.

Dr. Wheat is a family physician at Erie Family Health Center in Chicago. She is program director of Northwestern’s McGaw Family Medicine residency program, also in Chicago. Dr. Wheat serves on the editorial advisory board of Family Practice News. You can contact her at fpnews@mdedge.com.

References

1. COVID-19 Vaccine Booster Shots. Centers for Disease Control and Prevention. 2021 Dec 9.

2. COVID-19 Vaccines and Pregnancy: Conversation Guide. American College of Obstetricians and Gynecologists. 2021 November.

3. COVID-19 Vaccines While Pregnant or Breastfeeding. Centers for Disease Control and Prevention. 2021 Dec 6.

Women who had a preterm delivery were at least 1.6 times as likely to develop hypertension over the next decade as those who had full-term deliveries, based on data from a national cohort study of more than 2 million women.

Pregnancy complications such as preeclampsia and other hypertensive disorders of pregnancy have been associated with chronic hypertension as well as with preterm delivery, but the independent role of preterm delivery in chronic hypertension risk remains unclear, Casey Crump, MD, of the Icahn School of Medicine at Mount Sinai, New York, and colleagues wrote. “A better understanding of the long-term hypertension risks associated with preterm delivery is needed to improve risk stratification, clinical monitoring, and CVD [cardiovascular disease] prevention in women.”

In a study published in JAMA Cardiology, the researchers reviewed data from 2,195,989 women with 4,308,286 singleton deliveries in Sweden from Jan. 1, 1973, to Dec. 31, 2015. Women with preexisting hypertension before their first pregnancy were excluded. Pregnancy duration was based on maternal reports of the last menstrual period for patients in the 1970s, and based on ultrasound estimates in the 1980s and beyond. Pregnancy duration was divided into six groups in terms of completed weeks of gestation: extremely preterm (22-27 weeks), moderately preterm (28-33 weeks), late preterm (34-36 weeks), early term (37-38 weeks), full term (39-41 weeks), and post term (≥42 weeks). Full-term delivery was used as the reference, and the three preterm groups were combined for summaries of preterm delivery (less than 37 weeks).

Overall, women who delivered at less than 37 weeks’ gestation had a 1.6-fold increased risk of hypertension (adjusted hazard ratio, 1.67) within the next 10 years, compared with women who delivered full term after controlling for preeclampsia, other hypertensive disorders of pregnancy, and maternal factors.

When further stratified by pregnancy duration, the aHRs for extremely preterm, moderately preterm, late preterm, and early term, compared with full-term deliveries were 2.23, 1.85, 1.55, and 1.26, respectively, in the first decade after delivery. Each additional week of pregnancy was associated with a mean 7% reduction in hypertension risk (a HR, 0.93).

The increased hypertension risk following preterm delivery (less than 37 weeks) persisted at 10-19 years, 20-29 years, and 30-43 years, with aHRs of 1.40, 1.20, and 1.12, respectively. Early-term delivery at 37-38 weeks also carried an increased risk of long-term hypertension compared with full-term delivery, with aHRs of 1.12 and 1.06 at 20-29 years and 30-43 years, respectively.

“Cosibling analyses suggested that these findings were only partially explained by familial (genetic and/or early-life environmental) factors that are shared determinants of both preterm delivery and hypertension,” the researchers noted. The findings suggest that preterm delivery itself may contribute to or affect the pathophysiology that leads to cardiovascular disease, they added, hypothesizing that endothelial dysfunction caused by preterm delivery may cause functional impairments in the microvasculature.

The study findings were limited by several factors including the lack of detailed records to verify hypertension and the use of data from a single country, the researchers noted. However, the results were strengthened by the large study population, the use of highly complete prenatal and birth records to minimize selection bias, and the long-term follow-up.

The results are consistent with those from previous studies, and support the recognition of preterm delivery as a lifetime risk factor for hypertension, but future studies should focus on racial and ethnic subgroups already at increased risk for both preterm delivery and hypertension, they added.

“Additional follow-up will be needed to examine these associations in older adulthood when hypertension increasingly and disproportionately affects women,” they concluded.

Data highlight the need for patient and provider education

“This study furthers our knowledge regarding long-term complications associated with the frequent pregnancy complication of preterm delivery,” Stephen S. Crane, MD, an ob.gyn. and maternal-fetal medicine specialist in private practice in Orlando, said in an interview. “Cardiovascular disease is the leading cause of death and often goes unrecognized in women. There are shared risk factors among women and men for developing CVD, the most common being hypertension. However, women have the unique risk factor of pregnancy and its attendant complications including preeclampsia, glucose intolerance, and preterm delivery. Hypertensive disorders in pregnancy often lead to indicated premature delivery, and are associated with development of chronic hypertension and subsequent CVD. However, prior data suggest that preterm delivery itself is a risk factor for developing chronic hypertension later in life.

“The current study, which evaluates one of the most complete population data sets with up to 43 years of follow-up, is the first to assess for familial determinants by cosibling analysis, and supports preterm delivery as an independent risk factor for the development of hypertension,” he said. The study results illustrate that this risk is longstanding, and that recurrent preterm birth further increases the risk of developing hypertension.

Dr. Crane said he was not surprised by the study findings, given that inflammatory processes have been linked to the development of hypertension and CVD. “Similarly, inflammatory processes have been implicated in the pathophysiology of preterm labor and inflammatory cytokines may also play a role in normal term labor. Therefore, it is not surprising that preterm delivery would be a marker for the risk of development of hypertension, as both may be responses to underlying inflammatory processes. Identification of these underlying inflammatory processes and methods for prevention will be critical if we are to decrease both the incidence of preterm birth and CVD.

“As prenatal care may be the only medical care women obtain, it is important to take this opportunity to educate patients regarding their long-term risks of developing hypertension and the need for long-term follow up. Interventions that may help reduce the risk for recurrent preterm birth and long-term risks for developing hypertension and CVD include weight loss, increased activity, and smoking cessation; the resources to achieve these goals need to be shared with patients,” he said.

“Knowledge deficits both on the part of the provider and patient may be a significant barrier to intervention that may be overcome with improved education,” said Dr. Crane. “Care providers need education regarding the long-term risks associated with a history of preterm delivery in order to better educate their patients regarding both prevention of recurrent preterm birth and the development of hypertension and CVD.” However, socioeconomic status, education level, and the inability to obtain further health care remain common barriers to intervention for many women.

“Additional research is needed to identify the causes of inflammatory processes leading to preterm delivery and risks for hypertension and CVD,” said Dr. Crane. “Only after the causes are identified can treatments be sought to successfully treat these conditions.”

The study was supported by the National Heart, Lung, and Blood Institute at the National Institutes of Health; the Swedish Research Council; the Swedish Heart-Lung Foundation; and an Avtal om Läkarutbildning och Forskning (Agreement on Medical Training and Research) (ALF) project grant from Region Skåne/Lund University. Neither the researchers nor Dr. Crane had any financial conflicts to disclose.

Women who had a preterm delivery were at least 1.6 times as likely to develop hypertension over the next decade as those who had full-term deliveries, based on data from a national cohort study of more than 2 million women.

Pregnancy complications such as preeclampsia and other hypertensive disorders of pregnancy have been associated with chronic hypertension as well as with preterm delivery, but the independent role of preterm delivery in chronic hypertension risk remains unclear, Casey Crump, MD, of the Icahn School of Medicine at Mount Sinai, New York, and colleagues wrote. “A better understanding of the long-term hypertension risks associated with preterm delivery is needed to improve risk stratification, clinical monitoring, and CVD [cardiovascular disease] prevention in women.”

In a study published in JAMA Cardiology, the researchers reviewed data from 2,195,989 women with 4,308,286 singleton deliveries in Sweden from Jan. 1, 1973, to Dec. 31, 2015. Women with preexisting hypertension before their first pregnancy were excluded. Pregnancy duration was based on maternal reports of the last menstrual period for patients in the 1970s, and based on ultrasound estimates in the 1980s and beyond. Pregnancy duration was divided into six groups in terms of completed weeks of gestation: extremely preterm (22-27 weeks), moderately preterm (28-33 weeks), late preterm (34-36 weeks), early term (37-38 weeks), full term (39-41 weeks), and post term (≥42 weeks). Full-term delivery was used as the reference, and the three preterm groups were combined for summaries of preterm delivery (less than 37 weeks).

Overall, women who delivered at less than 37 weeks’ gestation had a 1.6-fold increased risk of hypertension (adjusted hazard ratio, 1.67) within the next 10 years, compared with women who delivered full term after controlling for preeclampsia, other hypertensive disorders of pregnancy, and maternal factors.

When further stratified by pregnancy duration, the aHRs for extremely preterm, moderately preterm, late preterm, and early term, compared with full-term deliveries were 2.23, 1.85, 1.55, and 1.26, respectively, in the first decade after delivery. Each additional week of pregnancy was associated with a mean 7% reduction in hypertension risk (a HR, 0.93).

The increased hypertension risk following preterm delivery (less than 37 weeks) persisted at 10-19 years, 20-29 years, and 30-43 years, with aHRs of 1.40, 1.20, and 1.12, respectively. Early-term delivery at 37-38 weeks also carried an increased risk of long-term hypertension compared with full-term delivery, with aHRs of 1.12 and 1.06 at 20-29 years and 30-43 years, respectively.

“Cosibling analyses suggested that these findings were only partially explained by familial (genetic and/or early-life environmental) factors that are shared determinants of both preterm delivery and hypertension,” the researchers noted. The findings suggest that preterm delivery itself may contribute to or affect the pathophysiology that leads to cardiovascular disease, they added, hypothesizing that endothelial dysfunction caused by preterm delivery may cause functional impairments in the microvasculature.

The study findings were limited by several factors including the lack of detailed records to verify hypertension and the use of data from a single country, the researchers noted. However, the results were strengthened by the large study population, the use of highly complete prenatal and birth records to minimize selection bias, and the long-term follow-up.

The results are consistent with those from previous studies, and support the recognition of preterm delivery as a lifetime risk factor for hypertension, but future studies should focus on racial and ethnic subgroups already at increased risk for both preterm delivery and hypertension, they added.

“Additional follow-up will be needed to examine these associations in older adulthood when hypertension increasingly and disproportionately affects women,” they concluded.

Data highlight the need for patient and provider education

“This study furthers our knowledge regarding long-term complications associated with the frequent pregnancy complication of preterm delivery,” Stephen S. Crane, MD, an ob.gyn. and maternal-fetal medicine specialist in private practice in Orlando, said in an interview. “Cardiovascular disease is the leading cause of death and often goes unrecognized in women. There are shared risk factors among women and men for developing CVD, the most common being hypertension. However, women have the unique risk factor of pregnancy and its attendant complications including preeclampsia, glucose intolerance, and preterm delivery. Hypertensive disorders in pregnancy often lead to indicated premature delivery, and are associated with development of chronic hypertension and subsequent CVD. However, prior data suggest that preterm delivery itself is a risk factor for developing chronic hypertension later in life.

“The current study, which evaluates one of the most complete population data sets with up to 43 years of follow-up, is the first to assess for familial determinants by cosibling analysis, and supports preterm delivery as an independent risk factor for the development of hypertension,” he said. The study results illustrate that this risk is longstanding, and that recurrent preterm birth further increases the risk of developing hypertension.

Dr. Crane said he was not surprised by the study findings, given that inflammatory processes have been linked to the development of hypertension and CVD. “Similarly, inflammatory processes have been implicated in the pathophysiology of preterm labor and inflammatory cytokines may also play a role in normal term labor. Therefore, it is not surprising that preterm delivery would be a marker for the risk of development of hypertension, as both may be responses to underlying inflammatory processes. Identification of these underlying inflammatory processes and methods for prevention will be critical if we are to decrease both the incidence of preterm birth and CVD.

“As prenatal care may be the only medical care women obtain, it is important to take this opportunity to educate patients regarding their long-term risks of developing hypertension and the need for long-term follow up. Interventions that may help reduce the risk for recurrent preterm birth and long-term risks for developing hypertension and CVD include weight loss, increased activity, and smoking cessation; the resources to achieve these goals need to be shared with patients,” he said.

“Knowledge deficits both on the part of the provider and patient may be a significant barrier to intervention that may be overcome with improved education,” said Dr. Crane. “Care providers need education regarding the long-term risks associated with a history of preterm delivery in order to better educate their patients regarding both prevention of recurrent preterm birth and the development of hypertension and CVD.” However, socioeconomic status, education level, and the inability to obtain further health care remain common barriers to intervention for many women.

“Additional research is needed to identify the causes of inflammatory processes leading to preterm delivery and risks for hypertension and CVD,” said Dr. Crane. “Only after the causes are identified can treatments be sought to successfully treat these conditions.”

The study was supported by the National Heart, Lung, and Blood Institute at the National Institutes of Health; the Swedish Research Council; the Swedish Heart-Lung Foundation; and an Avtal om Läkarutbildning och Forskning (Agreement on Medical Training and Research) (ALF) project grant from Region Skåne/Lund University. Neither the researchers nor Dr. Crane had any financial conflicts to disclose.

Women who had a preterm delivery were at least 1.6 times as likely to develop hypertension over the next decade as those who had full-term deliveries, based on data from a national cohort study of more than 2 million women.

Pregnancy complications such as preeclampsia and other hypertensive disorders of pregnancy have been associated with chronic hypertension as well as with preterm delivery, but the independent role of preterm delivery in chronic hypertension risk remains unclear, Casey Crump, MD, of the Icahn School of Medicine at Mount Sinai, New York, and colleagues wrote. “A better understanding of the long-term hypertension risks associated with preterm delivery is needed to improve risk stratification, clinical monitoring, and CVD [cardiovascular disease] prevention in women.”

In a study published in JAMA Cardiology, the researchers reviewed data from 2,195,989 women with 4,308,286 singleton deliveries in Sweden from Jan. 1, 1973, to Dec. 31, 2015. Women with preexisting hypertension before their first pregnancy were excluded. Pregnancy duration was based on maternal reports of the last menstrual period for patients in the 1970s, and based on ultrasound estimates in the 1980s and beyond. Pregnancy duration was divided into six groups in terms of completed weeks of gestation: extremely preterm (22-27 weeks), moderately preterm (28-33 weeks), late preterm (34-36 weeks), early term (37-38 weeks), full term (39-41 weeks), and post term (≥42 weeks). Full-term delivery was used as the reference, and the three preterm groups were combined for summaries of preterm delivery (less than 37 weeks).

Overall, women who delivered at less than 37 weeks’ gestation had a 1.6-fold increased risk of hypertension (adjusted hazard ratio, 1.67) within the next 10 years, compared with women who delivered full term after controlling for preeclampsia, other hypertensive disorders of pregnancy, and maternal factors.

When further stratified by pregnancy duration, the aHRs for extremely preterm, moderately preterm, late preterm, and early term, compared with full-term deliveries were 2.23, 1.85, 1.55, and 1.26, respectively, in the first decade after delivery. Each additional week of pregnancy was associated with a mean 7% reduction in hypertension risk (a HR, 0.93).

The increased hypertension risk following preterm delivery (less than 37 weeks) persisted at 10-19 years, 20-29 years, and 30-43 years, with aHRs of 1.40, 1.20, and 1.12, respectively. Early-term delivery at 37-38 weeks also carried an increased risk of long-term hypertension compared with full-term delivery, with aHRs of 1.12 and 1.06 at 20-29 years and 30-43 years, respectively.

“Cosibling analyses suggested that these findings were only partially explained by familial (genetic and/or early-life environmental) factors that are shared determinants of both preterm delivery and hypertension,” the researchers noted. The findings suggest that preterm delivery itself may contribute to or affect the pathophysiology that leads to cardiovascular disease, they added, hypothesizing that endothelial dysfunction caused by preterm delivery may cause functional impairments in the microvasculature.

The study findings were limited by several factors including the lack of detailed records to verify hypertension and the use of data from a single country, the researchers noted. However, the results were strengthened by the large study population, the use of highly complete prenatal and birth records to minimize selection bias, and the long-term follow-up.

The results are consistent with those from previous studies, and support the recognition of preterm delivery as a lifetime risk factor for hypertension, but future studies should focus on racial and ethnic subgroups already at increased risk for both preterm delivery and hypertension, they added.

“Additional follow-up will be needed to examine these associations in older adulthood when hypertension increasingly and disproportionately affects women,” they concluded.

Data highlight the need for patient and provider education

“This study furthers our knowledge regarding long-term complications associated with the frequent pregnancy complication of preterm delivery,” Stephen S. Crane, MD, an ob.gyn. and maternal-fetal medicine specialist in private practice in Orlando, said in an interview. “Cardiovascular disease is the leading cause of death and often goes unrecognized in women. There are shared risk factors among women and men for developing CVD, the most common being hypertension. However, women have the unique risk factor of pregnancy and its attendant complications including preeclampsia, glucose intolerance, and preterm delivery. Hypertensive disorders in pregnancy often lead to indicated premature delivery, and are associated with development of chronic hypertension and subsequent CVD. However, prior data suggest that preterm delivery itself is a risk factor for developing chronic hypertension later in life.

“The current study, which evaluates one of the most complete population data sets with up to 43 years of follow-up, is the first to assess for familial determinants by cosibling analysis, and supports preterm delivery as an independent risk factor for the development of hypertension,” he said. The study results illustrate that this risk is longstanding, and that recurrent preterm birth further increases the risk of developing hypertension.

Dr. Crane said he was not surprised by the study findings, given that inflammatory processes have been linked to the development of hypertension and CVD. “Similarly, inflammatory processes have been implicated in the pathophysiology of preterm labor and inflammatory cytokines may also play a role in normal term labor. Therefore, it is not surprising that preterm delivery would be a marker for the risk of development of hypertension, as both may be responses to underlying inflammatory processes. Identification of these underlying inflammatory processes and methods for prevention will be critical if we are to decrease both the incidence of preterm birth and CVD.

“As prenatal care may be the only medical care women obtain, it is important to take this opportunity to educate patients regarding their long-term risks of developing hypertension and the need for long-term follow up. Interventions that may help reduce the risk for recurrent preterm birth and long-term risks for developing hypertension and CVD include weight loss, increased activity, and smoking cessation; the resources to achieve these goals need to be shared with patients,” he said.

“Knowledge deficits both on the part of the provider and patient may be a significant barrier to intervention that may be overcome with improved education,” said Dr. Crane. “Care providers need education regarding the long-term risks associated with a history of preterm delivery in order to better educate their patients regarding both prevention of recurrent preterm birth and the development of hypertension and CVD.” However, socioeconomic status, education level, and the inability to obtain further health care remain common barriers to intervention for many women.

“Additional research is needed to identify the causes of inflammatory processes leading to preterm delivery and risks for hypertension and CVD,” said Dr. Crane. “Only after the causes are identified can treatments be sought to successfully treat these conditions.”

The study was supported by the National Heart, Lung, and Blood Institute at the National Institutes of Health; the Swedish Research Council; the Swedish Heart-Lung Foundation; and an Avtal om Läkarutbildning och Forskning (Agreement on Medical Training and Research) (ALF) project grant from Region Skåne/Lund University. Neither the researchers nor Dr. Crane had any financial conflicts to disclose.