Pregnant and lactating women should not be excluded from Covid-19 drug, vaccine trials

Citizens of the world are holding their collective breath while awaiting vaccines and therapies to effectively battle the Covid-19 pandemic. Among them are pregnant or lactating women who, in the United States and elsewhere, are being excluded from trials testing new vaccines or treatments.

Reluctance to rigorously study the effectiveness and safety of vaccines and treatments for Covid-19 during pregnancy is misguided and will end up harming pregnant women now and in the future.

To date, more than 140 drug treatments and numerous vaccines are being evaluated to treat and prevent Covid-19 infection. Vaccines for pregnant women are one of the most important public health measures undertaken globally to reduce disease. Yet the pregnant population is currently barred from participating in Covid-19 vaccine and treatment trials during the pandemic, which means that the health of pregnant women and their fetuses will be an afterthought.

This issue was highlighted in the draft plan on equitable allocation of the Covid-19 vaccine released in early September by the National Academies of Sciences, Engineering, and Medicine. During previous pandemics, like H1N1, pregnant and lactating women were a high-priority group for vaccination, but they are noticeably absent from the Covid-19 vaccine allocation plan.

High-risk/high-exposure workers in health care facilities or first responders, along with those who are at greatest risk of severe illness and death, were among the first groups to be named. Pregnant and lactating women who also fit these criteria, then, will need to be vaccinated alongside their non-pregnant peers, and they should not be excluded from prioritization.

Although initial data from the United States and China did not demonstrate increased risk of severe illness from Covid-19 among pregnant women, there are now ample reports of pregnant women — particularly those with comorbid conditions such as diabetes, obesity, and high blood pressure — becoming critically ill and requiring intensive care, supplemental oxygen, and even mechanical ventilation to survive. Some died.

When pregnant women are excluded from Phase 3 vaccine trials, we aren’t able to collect the safety and immunogenicity data that will inform recommendations on vaccinating and protecting pregnant women. We will not know whether a different dose of the vaccine may be needed in pregnancy to achieve antibody levels high enough to benefit mother and child. This is important information, given that pregnancy has dramatic effects on how almost all drugs are metabolized and excreted.

Nine biopharmaceutical companies recently made a public pledge not to seek approval from the Food and Drug Administration for Covid-19 vaccines without rigorously demonstrating safety and effectiveness data in Phase 3 trials. This unprecedented move was meant to instill public confidence in the scientific and regulatory process. But the process glaringly overlooks a population that deserves to have the benefit of that reassurance: pregnant women.

As obstetricians, we are often left wondering about the safety of medications, the appropriate doses to be used, and the ideal candidates for them, because the practice of excluding pregnant women from clinical trials is commonplace. This exclusion ends up leaving us, as clinicians, to do this experimentation outside of official controlled clinical trial settings.

Pregnant women are excluded from clinical trials of therapies and vaccines largely as a result of undue fear about the safety of the fetus. This fear exists despite the fact that many such drugs are eventually and commonly used out of clinical necessity. They are typically deemed as safe in pregnancy, but only years after the opportunity to investigate them carefully has passed.

With regard to anti-Covid-19 therapies, the excitement over remdesivir and its ability to treat the devastating effects of Covid-19 infection is palpable. Yet once again, pregnant women have been summarily excluded from the clinical trials of this and other drugs currently under investigation. That means pregnant women are forced to obtain remdesivir through a “compassionate use” protocol, which means their physicians must apply to the company that makes it to obtain the medication. This is cumbersome and unnecessary, making it difficult for pregnant patients to get the needed medication and leaving physicians without safety and effectiveness data from this important population.

In addition, it is not uncommon for lack of knowledge about drugs in pregnancy to lead well-meaning physicians to withhold or delay lifesaving medications from pregnant women out of misplaced fear. This trend was noted during the 2009 H1N1 influenza pandemic with the guarded use of oseltamivir (Tamiflu), and undoubtedly had an adverse impact given that earlier use of this antiviral is linked with improved clinical outcomes.

Pregnant women deserve better.

Since 2015, government health experts have officially recognized the need for including pregnant and lactating women in drug treatment and vaccine trials, while acknowledging concerns about fetal safety. Strategies exist to help safely study the effects of both medications and vaccines in pregnancy. Examples include the use of pregnant animal models, systematic review of inadvertent pregnancies experienced by women in Phase 3 trials, studies of pregnancy-specific drug metabolism, industry-supported pregnancy registries for new therapeutics and vaccines, and investigation of additional uses for antiviral therapies that have been used during pregnancy to treat other diseases.

Clinicians and patients must be better informed from the onset about the effectiveness and safety of potentially lifesaving medications and vaccines. There is no more prescient population that both realistically and symbolically represents our future than pregnant women, and they must be included in clinical trials now and going forward.

Laura E. Riley is the obstetrician and gynecologist-in-chief at NewYork-Presbyterian/Weill Cornell Medical Center and chair of obstetrics and gynecology at Weill Cornell Medicine. Brenna L. Hughes is chief of the Division of Maternal Fetal Medicine, associate professor of obstetrics and gynecology, and vice chair of obstetrics and quality at Duke University Medical Center. Both are members of the American College of Obstetricians and Gynecologists’ Covid-19 Expert Work Group.