Researcher Spotlight: Protecting Pregnant People Through Novel Health Outcomes Research

About 70% of women take at least one prescription medicine during pregnancy. However, because pregnant people are excluded from most biomedical research due to ethical concerns about fetal safety, little evidence exists about the safety and efficacy of medication use during pregnancy.

Mollie E. Wood, PhD, MPH, an assistant professor in the Department of Epidemiology at the University of North Carolina at Chapel Hill, stumbled onto this research gap during her doctoral work. She was interested in the fetal origins of mental illness and sought to conduct a systematic review of studies examining use of antidepressants during pregnancy. She was surprised by how few studies there were, and how rarely they were able to convincingly disentangle the effects of the medications from the effects of maternal depression.

Discovering this knowledge gap led Wood to focus her career on researching the safety of medication use during pregnancy. “It’s infuriating how little we know about optimal medication use during pregnancy, given how this touches the lives of every human being,” said Wood, a recipient of a 2022 PhRMA Foundation Research Starter Grant in Health Outcomes Research.

Specifically, Wood studies the use during pregnancy of medications that treat chronic conditions such as depression, migraine, and diabetes. “There are a lot of really important and difficult methodological issues when you are thinking about both safety and efficacy for both the pregnant person and the developing fetus,” she said. “I love complicated methods problems. It’s like research catnip.”

As a growing number of reproductive-age women have chronic conditions, there is an urgent need for research in this area. Some women who become pregnant may already take medicine to treat a chronic condition, while other women may be diagnosed with a chronic condition during pregnancy. These women and their health care providers are faced with decisions about whether to continue, discontinue, or initiate treatment. But they have limited information to guide their choices.

Without adequate evidence, some women and providers may overestimate the risks of medication use and choose to avoid all drugs, which can also pose risks, Wood said. This cautious attitude is hardly surprising given the thalidomide tragedy in the late 1950s and early 1960s that resulted in birth defects in thousands of children. In the wake of this tragedy, the organization that would ultimately become the PhRMA Foundation was created to fund research aimed at preventing adverse events in the future, thus establishing the field of toxicology, which plays a critical role in ensuring medication safety today.

“We have to avoid another thalidomide disaster, but we also need to recognize that most drugs are not thalidomide,” Wood said. “It’s easy to say you should avoid all risk, but that’s not realistic.”

This year, Wood received a PhRMA Foundation Research Starter Grant for a project examining methods for evaluating treatment of chronic hypertension (high blood pressure) during pregnancy. Chronic hypertension affects about 1% of pregnant women and can cause maternal and fetal morbidity and mortality.

While clinical guidelines recommend treating pregnant women with severe hypertension with medication, little is evidence available to guide treatment decisions for pregnant women with mild or moderate high blood pressure. “Whenever you find that kind of gap in the research, it’s very clear anything you can do to improve the quality of evidence could have a big impact on health,” Wood said.

Fortunately, the New England Journal of Medicine just published results in April from a rare randomized clinical trial, called the Chronic Hypertension and Pregnancy (CHAP) Project. The study found that treating pregnant women with mild chronic hypertension was associated with better pregnancy outcomes than reserving treatment only for severe hypertension.

Wood’s research seeks to build on the CHAP Project by using real-world data from electronic medical records to study the treatment of pre-existing chronic hypertension during pregnancy and its effects on maternal and fetal outcomes. “Our goal is to contribute additional information to support the findings from the randomized clinical trial on antihypertensives in pregnancy,” she said.

She also noted that the CHAP Project’s trial population was limited, with only 1 in 12 women eligible to participate out of those screened. For instance, the study excluded women with history of severe high blood pressure, high-risk comorbidities (e.g., cardiac disorders, chronic kidney disease), and multifetal pregnancies (e.g., twins, triplets).

Because Wood’s study looks at real-world data, it will help to expand the research population and elucidate which baseline risk factors, such as pregestational diabetes or history of pregnancy loss, might influence treatment outcomes. The results from Wood’s project will provide support for clinicians and pregnant people who need to make decisions about taking medications during pregnancy.

There is a growing recognition that more and more pregnant people will need pharmacotherapy, Wood said, and the culture is slowly shifting to recognize that we should protect women through research, not from research. “This is a fundamental public health concern, and we don’t spend enough time talking about it,” she said.