Each year about 700 women die from pregnancy or birth complications in the U.S., the worst maternal mortality rate out of all industrialized countries. The need to improve U.S. rates of maternal mortality, as well as bolster research on the safety of prescription drugs for the health of pregnant and lactating women, were both raised during last week’s House Appropriations Committee hearing about the National Institutes of Health (NIH) future research and funding priorities.
The maternal mortality crisis
The rate of maternal deaths has been rising in the U.S. since 2000, taking a serious toll on families from all different backgrounds. Maternal mortality is defined as any deaths during a pregnancy or within 42 days of the end of the pregnancy from “any cause related to or aggravated by the pregnancy or its management.” More than half of maternal deaths occur after the day of birth, and one third occur during the pregnancy. The most common causes of death are cardiomyopathy (weakened heart muscles), blood clots, hypertension (high blood pressure), stroke, infection, and hemorrhage (heavy bleeding). This crisis is also exacerbated by disparities experienced by people of color: Black women are 2.5 times more likely to die than White women and three times more likely to die than Hispanic women.
Reducing maternal deaths, particularly among communities of color, is a top priority for Diana Bianchi, the director of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). Just last year, the NIH established the Implementing a Maternal health and PRegnancy Outcomes Vision for Everyone (IMPROVE) Initiative. It aims to “mitigate preventable maternal mortality… and promote health equity” by using “an integrated approach to understand biological, behavioral, sociocultural, and structural factors.” The IMPROVE initiative has already awarded over $7 million in grants to address disparities in maternal mortality.
The lack of knowledge about safe drugs for pregnant and lactating women
While there are several active efforts to address maternal mortality, one aspect of women’s health that has not received as much attention: there is a significant lack of knowledge as to which drugs are safe for pregnant and lactating women to use. While this problem has existed for a long time, it is brought into clear focus when examining the recent clinical trials for COVID-19 treatments. Out of 927 clinical trials worldwide, only 16, less than 2%, evaluated the effectiveness of a treatment on pregnant women and their fetuses. More than half of the clinical trials excluded pregnant women specifically. Both Representatives John Moolenaar (R-MI) and Lois Frankel (D-FL) raised the knowledge gap in safe treatments for pregnant and lactating women during the hearing.
The exclusion of pregnant women from clinical trials largely stems from the thalidomide and diethylstilbestrol (DES) tragedies in the mid-1900s. DES entered the market in 1938 and was promoted as a way to prevent miscarriages and premature births, but almost 40 years later, researchers found the drug actually caused rare cancers in the daughters born to mothers who took it, as well as structural changes to the reproductive tract, and infertility. It also elevated risks of breast cancer in the mothers. Thalidomide was used during the late 1950s and early 1960s to treat morning sickness. Researchers found, however, that the drug caused devastating birth defects in babies. After these tragedies, the Food and Drug Administration (FDA) published guidelines in 1977 that prevented pregnant women from participating in phase I and phase II clinical trials.
Though it is now possible for pregnant women to enroll in clinical trials due to the passage of the NIH Revitalization Act of 1993, the researchers may only recruit them if the clinical trials adhere to strict regulations. Current regulations require conducting preclinical studies with pregnant animals and clinical studies with nonpregnant women prior to enrolling pregnant women. The clinical trials must also ensure the “least possible” risk to achieve objectives of the research, among other obligations. Because these requirements add time and cost to clinical trials, as well as necessitate the recruitment of sufficient numbers of pregnant women, many researchers opt not to include them. The Centers for Disease Control and Prevention estimate that 70% of pregnant women take at least one prescription drug. Nevertheless, the fact that researchers rarely include pregnant women in clinical trials results in these women not having clear information about what drugs are safe for them and their babies. One study found that 90% of drugs approved by the FDA between 1980 and 2000 had no data about the drugs’ potential effects on pregnant women and their fetuses. Drug manufacturers now choose to track possible side effects after a drug’s release via self-reported registries. However, the requirement for pregnant women to report their own symptoms can skew the data toward only severe reactions, and omit any milder, but still clinically important, symptoms.
As part of the 21st Century Cures Act, NIH established the Task Force on Research Specific to Pregnant Women and Lactating Women (PRGLAC) to provide recommendations and an implementation plan on how to integrate pregnant and lactating women into drug safety research. The task force has already had a positive effect on the work at NIH, and helped launch the Maternal and Pediatric Precision in Therapeutics (MPRINT) Hub. The goal of the hub is to establish a center of knowledge that explains what drugs pregnant and lactating women can take safely, and the effects of medicines on babies.
More to be done
The initiatives NIH has launched so far are vital to reduce maternal mortality and support the health of pregnant and lactating women. These topics will likely continue to be priorities of the Biden Administration and Congress. If you have ideas on how the federal government can support further research in maternal health, we encourage you to serve as a resource for Members of Congress and their staff.