Rethinking Vaccine Trials: The Exclusion of Pregnant Individuals

Understanding the Exclusion of Pregnant Individuals from Trials

In September, Molly Cohen, a city policy director in San Francisco, came across a CNN article discussing Covid-19 vaccines and noticed a link to volunteer for a clinical trial. Eager to participate, she clicked the link, stating, “I’m totally pro-vaccine. Go science!” However, upon disclosing her pregnancy, she was disqualified from joining.

Pregnant and breastfeeding individuals have been systematically excluded from all Covid-19 vaccine clinical trials in the U.S., leaving unanswered questions about the implications for this demographic as vaccines become available. Will this exclusion impact their access to vaccines or influence their confidence in the vaccine's safety for them? Furthermore, how thoroughly will their responses to the vaccines be monitored?

The advantages of vaccinating pregnant individuals are significant, as Covid-19 poses risks to both their health and that of their fetuses. Yet, due to the lack of research, it's still uncertain whether a Covid-19 vaccine administered to a pregnant person would provide antibodies to the fetus. Medical and bioethics experts have published numerous articles in esteemed journals like The Lancet and the British Medical Journal, urging the inclusion of pregnant individuals in vaccine trials. “Are they being included enough? Not at all,” asserts Atul Malhotra, a neonatologist at Monash Children’s Hospital in Melbourne, Australia.

Historical Context of Exclusion

The exclusion of pregnant individuals from clinical trials is not a recent phenomenon. It has been the norm for decades, primarily due to concerns for fetal safety, especially after the thalidomide tragedy in the 1950s and 1960s, which resulted in severe birth defects. Experts have long advocated for the inclusion of pregnant individuals in phase 3 vaccine trials, citing various reasons: current testing and regulatory measures are much more stringent than in the past; there is a wealth of information regarding vaccine safety during pregnancy; and clinical trials would gather more detailed data than administering the vaccine later.

According to David Baud, who leads obstetric services at the University of Lausanne in Switzerland, “The maternal and fetal risks of Covid during pregnancy are much higher than any vaccine.” Despite these calls for inclusion, their recommendations have frequently been overlooked. For instance, experts advocated for the inclusion of pregnant individuals in Ebola vaccine trials, yet this did not occur.

The Importance of Phase 3 Trials

Phase 3 trials are crucial for assessing the immune responses of pregnant individuals to vaccines, as these responses cannot be assumed based on data from non-pregnant populations. Paul Heath, director of the Vaccine Institute at St George’s, University of London, and his colleagues have emphasized this in The Lancet. However, with phase 3 trials for Covid-19 vaccines already in progress or completed, the opportunity to include pregnant individuals is dwindling.

Weighing Risks: Vaccination vs. Covid-19

Every medical intervention, including vaccination, involves a balance of risks. While there may be unknown risks of side effects for pregnant individuals or their fetuses, the dangers of contracting Covid-19 are substantial. Data indicates that pregnant individuals are more likely to require intensive care or ventilation compared to their non-pregnant counterparts. For example, about 11 out of every 1,000 pregnant individuals with Covid-19 need ICU care, versus four out of 1,000 non-pregnant individuals.

Conversely, a recent study published in JAMA found that 95% of pregnant individuals who tested positive for Covid-19 experienced no significant adverse outcomes, while 5% faced severe complications. Moreover, pregnant individuals with Covid-19 have an increased risk of premature birth, with the likelihood rising from the usual 10% to approximately 13%. This translates to a potential increase in premature births among the 44,183 documented cases of Covid-19 in pregnant individuals in the U.S., equating to about 1,325 additional premature births.

Ethical Considerations Surrounding Exclusion

Concerns about enrolling pregnant individuals in vaccine trials predominantly center around the possibility of adverse effects or different reactions compared to non-pregnant individuals. However, Baud argues that most vaccines are safe during pregnancy. “You can vaccinate with almost everything except live vaccines,” he explains. The Covid-19 vaccines are not live, and many other vaccines, such as those for flu and TDAP, are routinely given during pregnancy.

Johnson & Johnson’s Covid-19 vaccine, for instance, is built on the same technology as its Ebola vaccine, which has been deemed safe for pregnant individuals. Although pregnant individuals have not been enrolled in trials, some may become pregnant during the study. Bill Gruber, a senior vice president at Pfizer, noted that he anticipated about 1% of women in their phase 2/3 trial would become pregnant, though this data has yet to be published.

The Need for Comprehensive Data

Excluding pregnant individuals from clinical trials raises ethical questions about how quickly a Covid-19 vaccine can be made available to them. Baud emphasizes that vaccinating a pregnant individual also protects the fetus from the heightened risk of premature birth. If pregnant individuals are not included in trials, he argues, alternative protections, such as paid leave, should be offered, though he notes that he is unaware of any country providing such support universally.

Malhotra highlights that excluding pregnant individuals from trials limits the breadth of data gathered on their responses to the vaccine. While the FDA plans to monitor reactions post-vaccine rollout, the data collected in clinical trials would be significantly more comprehensive. In a trial setting, participants undergo regular blood tests and analyses that assess not only visible side effects but also immune responses and antibody production. Thus, by excluding pregnant individuals, the data collected represents only a fraction of the potential insights.

The Perspective of Pregnant Individuals

Hallie Spierings, a financial analyst from Marblehead, Massachusetts, who is due in mid-March, shares her thoughts on the matter. Like Cohen, Spierings supports vaccines but asserts, “Until it’s tested on pregnant folk, I’m not interested” in receiving the vaccine. While she may not need to make this decision herself, as she is likely to give birth before vaccines are available for non-frontline pregnant individuals, she insists on the necessity of testing for fetal development impacts before considering vaccination during pregnancy. “It is sort of a dealbreaker for me.”