NICHD report underscores gaps in research on therapies used by pregnant/nursing women

October 9, 2018

Every year, nearly all of the 6 million women who get pregnant in the US will take medication while they are pregnant or breastfeeding, but this population often is excluded from clinical research. PLUS: Do contemporary hormonal contraceptives reduce ovarian cancer risk? ALSO: Are breastfeeding intentions associated with infant health?

Every year, nearly all of the 6 million women who get pregnant in the US will take medication while they are pregnant or breastfeeding. But this population often is excluded from clinical research, one of the gaps highlighted in a new 

 from a task force organized by the National Institute of Child Health and Human Development (NICHD). 

Closing that research gap is one of 15 recommendations from the Task Force on Research Specific to Pregnant Women and Lactating Women (PRGLAC). Established by the 21stCentury Cures Act in late 2016, the panel was charged with advising the Secretary of Health and Human Services (HHS) on identifying and addressing gaps in knowledge and research on safe and effective therapies for pregnant and lactating women. The Secretary of HHS has until December 2018 to decide whether action on the PRGLC recommendations is warranted.

PRGLAC representatives came from across the National Institutes of Health as well as the Centers for Disease Control and Prevention, the HHS Office on Women’s Health, the National Vaccine Program Office, the Agency for Healthcare Research and Quality, and the Health Resources and Services Administration. Also on the panel were the Commissioner of the Food and Drug Administration, the Secretaries of the Department of Veterans Affairs and the Department of Defense and representatives from medical societies, nonprofit organizations, and companies that focus on the health of pregnant women, nursing mothers, or children.

“There is limited scientific knowledge about the effectiveness and optimal dosing of drugs commonly prescribed for pregnant and lactating women,” said NICHD Director Diana W. Bianchi, MD, in a press release. “This needs to change. The theme that resonates clearly throughout the task force recommendations is that we need to emphasize the importance of protecting these populations through research instead of from research.”

Among the other key recommendations from the PRGLAC, an outgrowth of information taken from four open meetings and a public comment period, are the need to:

  • Include and integrate pregnant women and lactating women in the clinical research agenda
  • Expand the workforce of clinicians and research investigators with expertise in obstetric and lactation pharmacology and therapeutics
  • Remove regulatory barriers to research in pregnant women
  • Optimize registries for pregnancy and lactation.

The PRGLAC called for a universal consent for pregnancy lactation studies and a change to the requirement for both maternal and paternal consent before a pregnant woman can participate in a study that benefits only the fetus. The report also emphasizes the need for distinct, separate prioritization processes for products for pregnant women and lactating women. Regarding research, the panel said that investigators and sponsors should be required to justify excluding pregnant women and lactating women from study designs and develop studies to capture physiologic changes that occur over time in these populations.

The charter of the PRGLAC expires in March 2019. However, given the work that still needs to be done on researching therapeutic products used by pregnant women and lactating women, the panel has asked the HHS Secretary to consider exercising his authority to extend the panel’s charter. 

Do contemporary hormonal contraceptives reduce ovarian cancer risk?

Previous research has shown reduced risk of ovarian cancer in women who use combined oral contraceptives. A new study, published inBMJ, sheds light on how new formulations and dosages affect that risk.

The authors used data from the Danish Sex Hormone Register Study on a national cohort of Danish women aged 15 to 49 years from January 1, 1995 to December 31 2014. The study population comprised nearly 2 million women, who were followed up to the first diagnosis of ovarian cancer (based on ICD-10 code 56), death, emigration, age 50, or the end of the study. 

Information about the participants’ use of hormonal contraception was gleaned from their redeemed prescription information. They were categorized as never-users, current or recent users (up to 1 year after stopping use) or former users (more than 1 year after stopping use) of different hormonal contraceptives. Using the age distribution of the cohort as a standard, the researchers calculated age-standardized incidence rates for ovarian cancer per 100,000 person-years. 

During more than 21.4 million person-years of observation (approximately 11.4 years per woman), 1,249 women had incident ovarian cancer. During more than 13 million person-years of follow-up, 478 ovarian cancers were found among ever-users of any hormonal contraception. Ovarian cancer was found among 771 never-users in more than 8 million person-years of follow-up. 

The authors found that participants who currently use (relative risk [RR] 0.58, 95% CI 0.49-0.68) or formerly used (RR 0.77, 95% CI 0.66-0.91) any hormonal contraception had reduced risk of ovarian cancer compared with never-users. They also noticed that ovarian cancer risk among current or ever-users decreased with increasing duration (from RR 0.82, 95% CI 0.59-1.12 with ≤ 1 year of use to RR 0.26, 95% CI 0.16-0.43 with ≥ 10 years of use;< 0.001). The authors found that use of progestogen-only products was not associated with ovarian cancer risk. 

Identified strengths of the study included the large nationwide population, the age range of the cohort, which limited exposure to hormone replacement therapy, and the study design, which allowed the researchers to adjust for several confounding variables. Limitations include lack of information about hormonal contraceptives prescribed before study entry and inability to examine the association between duration of use and time since last current use among women who switched type of hormonal contraception.

The authors believe that while more research is necessary, their initial findings suggest that contemporary combined hormonal contraceptives are associated with a reduced risk of ovarian cancer in women and the risk continues to be reduced even after women stop using the drugs. 

Are breastfeeding intentions associated with infant health?

Breastfeeding’s benefits are well known but it’s not yet clear if they are associative or causal. In a study published in Social Science & Medicine: Population Health, researchers looked systematically at the role of an expectant mother’s breastfeeding intentions and its ultimate impact on her offspring’s health outcomes.

The authors included 1008 mothers from the Infant Feeding Practices Study (IFPS) II. The mothers were contacted during their third trimester and asked what method they planned to use to feed their new baby in the first few weeks. The response options were breastfeed only, formula feed only, both breast and formula feed, or don’t know yet. The women’s actual breastfeeding behavior was captured from follow-up responses about what their infants consumed through the first 2 months of life. 

Based on their responses, the participants were classified into three groups: those who intended to breastfeed and did (n=409), those who intended to breastfeed and did not (n=357), and those who did not intend to breastfeed and did not (n=242). To measure the infants’ health outcomes, the authors looked at rates of ear infections, respiratory syncytial virus (RSV), and antibiotic usage in the offspring’s first year. 

The authors found that exclusively breastfed infants had 27% fewer ear infections, over 56% fewer episodes of RSV, and 23% fewer incidents of use of prescribed antibiotics. When accounting for prenatal intentions, the intentions coefficient was negatively associated with all health outcomes and statistically significant. The researchers believe this suggests that breastfeeding intentions are an important consideration in estimating the relationship between breastfeeding and infant health. 

Infants who were born to mothers who intended to and did breastfeed had approximately 35% fewer ear infections, were approximately 83% less likely to have an episode of RSV and had 38% fewer incidents of antibiotic usage than infants born to mothers who did not intend to breastfeed. Infants who were born to mothers who intended to breastfeed but did not had approximately 29% fewer ear infections and had 40% fewer incidents of antibiotic usage compared to mothers who did not intend to breastfeed. 

Rates of RSV in infants of mothers who intended to breastfeed but did not were not statistically significantly different than those for all mothers in the study, but the authors said that RSV was a relatively rare outcome in the sample. They found that mothers who intended to breastfeed had more information about nutrition and diet and consulted their physicians more frequently than the mothers who did not intend to breastfeed.

The authors noted some limitations to their study. Based on the reported demographics, respondents to the study were more advantaged and more likely to breastfeed than the national average. The researchers also were unable to quantify how much impact a mother’s behavior during the pregnancy impacted the health of her child or if the women who were unable to breastfeed compensated in other ways to ensure good health for their babies.