Cynthia Gyamfi-Bannerman, an obstetrician in New York City, was treating patients when the COVID-19 pandemic struck. Hospitals began to fill up. Among the sick were some of her pregnant patients.
It was a frightening period. Doctors had to make difficult decisions because nothing was known about the SARS-CoV-2 virus, let alone how it would damage a pregnancy. Gyamfi-Bannerman recalls doctors obtaining exemptions to provide the antiviral medicine remdesivir to pregnant COVID-19 patients, despite the fact that the treatment had not been tested during pregnancy.
“Our goal is to help the mom,” she says. “If we had something that might save her life — or she might die — we were 100 percent using all of those medications.”
Even before the pandemic, obstetricians were faced with life-or-death decisions. Pregnant women have long been barred from participating in most drug tests in order to protect the fetus. As a result, there is minimal evidence that many drugs are safe to consume while pregnant. This involves difficult decisions for the roughly 80% of pregnant women who will take at least one drug. Some have major illnesses that, if unchecked, can be harmful to both the mother and the fetus, such as high blood pressure or diabetes.
“Pregnant women are much the same as everyone else,” Gyamfi-Bannerman explains. They have the same underlying problems and require the same medications. Antibiotics, asthma and allergy medications, metformin for diabetes, and antidepressants were among the top 20 prescriptions filled during the first trimester, according to a 2013 survey. Even for common medicines, the only recommendation is to “speak to your doctor” if you’re pregnant. Doctors too lack answers in the absence of data.
Many doctors and researchers are frustrated because this lack of knowledge is intentional. Even at the final stages of most clinical studies, which assess a new drug’s safety and efficacy in humans, pregnant women are specifically excluded to avoid damage to the fetus. But in the wake of a pandemic that disproportionately harmed the pregnant population, researchers are questioning more than ever whether this is the best approach.
Typically, researchers have to justify excluding certain groups, such as older adults, from clinical trials in which they might benefit. “You never have to justify why you’re excluding pregnant people,” says Gyamfi-Bannerman, who now heads the obstetrics, gynecology and reproductive science department at the University of California, San Diego. “You can just go ahead and exclude them.
Pregnant women are much the same as everyone else. They have the same underlying problems and require the same medications. Antibiotics, asthma and allergy medications, metformin for diabetes, and antidepressants were among the top 20 prescriptions filled during the first trimester, according to a 2013 survey.Gyamfi-Bannerman
Pregnant in a crisis
Teresa Mathews was 43 years old when she discovered she was pregnant in June 2020, just as the pandemic ravaged the United States. “I was very concerned,” she admits. In addition to her age, Mathews has sickle cell trait, which means she has one defective gene copy, making her prone to anemia and shortness of breath. COVID-19 also causes shortness of breath, so Mathews was concerned that if she had the virus, her unborn kid might go without oxygen.
Furthermore, the child would be her first. “I don’t want to seem dramatic, but that was my final chance to have a baby, right?” So I didn’t want to take any chances.” She went into full lockdown for the rest of her pregnancy.
With good reason. During the first year of the epidemic in England, researchers discovered that pregnant women infected with the virus were roughly twice as likely to have a stillbirth or premature birth. In addition, the Centers for Disease Control and Prevention revealed in November 2020 that pregnant women are almost three times more likely than other women to be admitted to intensive care with COVID-19, and 70 percent more likely to die from the illness.
As the race to develop a vaccine began, many doctors and policymakers thought that vaccinations would be tested in pregnant women and found to be safe. There were encouraging signs: the Food and Drug Administration of the United States encouraged vaccine developers to include pregnant women in their studies. A large body of previous research suggested that risks would be low for vaccines like those for COVID-19, which do not contain live viruses.
However, the three vaccinations approved for use in the United States by the FDA, from Pfizer/BioNTech, Moderna, and Johnson & Johnson, excluded pregnant women from their original clinical trials. Pfizer began recruiting pregnant women for a clinical trial after its vaccine was approved for emergency use in December 2020, but it was canceled when government regulators urged that all pregnant women be immunized. The business cited difficulties in enrolling enough women for the experiment, as well as ethical concerns about providing pregnant women a placebo after the vaccine was recommended.
Doctors recognized it would be difficult to convince pregnant women to take a vaccination that hadn’t been studied during pregnancy when pregnant persons were excluded from vaccine trials.
Mathews says she would have gotten vaccinated while pregnant if there had been facts to back up her decision. But the decision had already been made for her. Eulalia, her baby, was born healthily in February 2021, just before the immunizations were made available to all adults in Mathews’ city of Knoxville, Tenn. There was still no clear recommendation at the time on whether to get vaccinated while pregnant or nursing.
Meanwhile, conspiracy theories and horror stories about vaccines causing infertility or miscarriages filled the space on social media and pregnancy websites. The American College of Obstetricians and Gynecologists expressed concern last October, stating that “the spread of misinformation and mistrust in doctors and science is contributing to staggeringly low vaccination rates among pregnant people.”
Indeed, the CDC had issued an urgent health recommendation the previous month, warning that just 31% of pregnant women were completely vaccinated, compared to roughly 56% of the overall population. (The CDC and many experts prefer the term “pregnant people” as a catch-all.) Science News uses the terminology provided by sources and refers to pregnant women when a study population is defined as such.)
Following the vaccines’ emergency use authorisation, the CDC examined the outcomes of nearly 2,500 vaccinated pregnant individuals and discovered no pregnancy-related safety concerns. Anyone who is pregnant, lactating, or thinking about getting pregnant should get vaccinated, according to the FDA. However, that suggestion came more than six months after the first vaccine was made accessible.
Since then, the vaccines have also proved to be highly effective in pregnancy. More than 98 percent of COVID-19 critical care admissions in a group of more than 130,000 pregnant women in Scotland were unvaccinated, researchers reported in January in Nature Medicine. And all of the infants who died had unvaccinated moms.
Scientists are increasingly challenging what Gyamfi-Bannerman refers to as a “knee-jerk” propensity to reject pregnant women from clinical studies. Lyerly and colleagues founded the Second Wave Initiative in 2009 to promote ethical methods of including pregnant women in research. More researchers, mostly women, have hosted conferences and spearheaded research as their views have expanded. Collectively, they are challenging the prevalent mentality that “pregnant women need to be shielded from research rather than protected through research,” according to Bianchi.
“We came here with good intentions,” says Brookie Best, a UC San Diego clinical pharmacologist who investigates medication use in pregnant women. “There have been some terrible, terrible tragedies with pregnant women taking a medicine and having negative effects.”
Thalidomid was the most well-known of them. The medicine was administered for morning sickness beginning in the late 1950s, but it had never been evaluated in pregnant women. It was evident by the early 1960s that it produced birth abnormalities such as missing or deformed limbs. Following that, pharmaceutical corporations were hesitant to take on the risk, or legal liability, of potential birth abnormalities. While the FDA implemented additional safety standards in reaction to the thalidomide disaster, the agency did not require pre-market testing during pregnancy.