Biden administration health officials and maternal-health experts have redoubled their outreach efforts to pregnant Americans. But some physicians and public-health leaders are also looking to the future, pressing the medical establishment to learn from the Covid-19 experience by including pregnant and breastfeeding people in the earliest studies of new shots and treatments.
“If you needed evidence in your face that the old way of doing things wasn’t working, we now have that,” said Ruth Faden, founder of the Johns Hopkins Berman Institute of Bioethics, whose research has focused on women’s health.
There’s a long history of pharmaceutical companies excluding pregnant people from clinical trials over ethical and legal concerns, a reluctance that traces back to the thalidomide-linked birth defects of the early 1960s. The drug was never approved by the FDA, thanks to the actions of agency reviewer Frances Kelsey, but it was widely used in Europe for several years to treat morning sickness. Thousands of children exposed to the drug in utero were born with birth defects, including flipper-like limbs.
Pregnant people in the U.S., who are routinely counseled to avoid everything from sushi and deli meats to hot tubs, are often wary of doing or taking anything that has not been proven safe for their fetuses. Many were understandably wary of getting Covid-19 shots during the first months of the national rollout, without a clear-cut recommendation from health authorities.
That set the stage for a grim summer, when Covid-19 cases soared as the Delta variant spread, spurring the CDC to revise its endorsement for the vaccine in that population to reflect the urgency. The agency “strongly” recommended in a Sept. 29 health advisory that people who were currently or recently pregnant, or who might become pregnant in the future, get inoculated.
“COVID-19 vaccination is recommended for all people 12 years and older, including people who are pregnant, breastfeeding, trying to get pregnant now, or might become pregnant in the future,” CDC now says on its website, in language that it added on Aug. 11.
But the CDC’s statements on Covid vaccination during pregnancy have evolved since the shots first became available, which experts say hasn’t helped to quell expectant parents’ fears.
“I think it hurt us to be able to not strongly come out of the gate and recommend these vaccines, instead of saying pregnant women may choose to be vaccinated,” said Linda Eckert, ACOG’s liaison to the CDC’s independent advisory panel on immunization.
Maternal-health experts have worked for decades to shift the medical community’s approach to including pregnant people in clinical research. The push gained urgency during the respiratory virus pandemics of the early 2000s, including the H1N1 flu, and the Zika and Ebola outbreaks of the 2010s. Faden’s Hopkins group and a federal task force issued recommendations in 2018 in anticipation of the next pandemic.
They included early initiation of non-clinical research — like developmental and reproductive toxicology, or DART, studies in animals — required for trials in pregnant people before any efficacy trials begin. Another was to allow pregnant people to enroll in vaccine studies during epidemics when the potential benefits outweigh the risks to them and their babies.
“Almost none of them were followed when it actually came to the pandemic,” Faden told POLITICO.
There was a “ridiculous lag” between when the Covid vaccines in development looked promising and when the pharmaceutical companies started to invest in DART studies, Faden said, even though most Covid vaccine makers took federal aid.
“This was the one time where even the financial disincentives to doing DART studies were removed,” she said, and it still wasn’t enough to start them early.
A task force created by 2016’s 21st Century Cures Act issued its own report in 2018 making similar recommendations regarding research on pregnant and lactating people, as well as policy proposals specific to the Department of Health and Human Services.
The group called for FDA to remove pregnant women from the list of “vulnerable populations” outlined in the Common Rule, the country’s ethical code for medical research in humans; HHS did so in a regulatory rewrite that went into effect in 2018. Maternal-health experts have long argued that pregnant people’s inclusion on that list of subjects who warrant special considerations has fed into a “presumption of exclusion” from medical research.
“Our mantra is: We need to protect pregnant women through research instead of from research,” said Diana W. Bianchi, director of NIH’s National Institute of Child Health and Human Development who led the task force, dubbed PRGLAC.
The group also recommended changing the Common Rule to allow maternal consent alone for participation in research, “given the recognized autonomy of a pregnant woman, the evolution of family structure, that for a child only one parental signature is required for research to help benefit the child and to align with parental consent for pediatrics.” Certain types of research currently require consent from both parents.
But not every issue has a clear-cut recommendation. Liability concerns that arise from conducting research on pregnant and lactating people have proven difficult to tackle, the group acknowledged.
“Concerns about liability faced by researchers and clinicians working within the U.S. healthcare and legal systems are more pervasive than the issue of including pregnant women and lactating women in research alone,” the PRGLAC task force said in an August 2020 implementation plan.
It suggested implementing a mitigation strategy akin to the federal government’s Vaccine Injury Compensation Program — which evaluates claims arising from 15 childhood vaccines and seasonal flu shots — or bolstering FDA’s authority to require “clinically relevant data” to inform safety and dosing recommendations for pregnant and lactating people.
Senate HELP Chair Patty Murray (D-Wash.), who spearheaded the task force’s inclusion in the 2016 law, has had “multiple calls with HHS” regarding its implementation of the PRGLAC recommendations, a committee aide told POLITICO.
Pregnant people “deserve to know they have been included in studies and trials, so they can get the information they need to feel confident about their health decisions,” Murray said in a statement. “I’m pushing as hard as I can to make that a reality.”
HHS didn’t respond to a request for comment on its implementation of the recommendations.
FDA is still working on harmonizing its regulations with the updated Common Rule, agency spokesperson Chanapa Tantibanchachai said. The agency has supported expanding a reporting system to identify instances where existing drugs are used in new ways to treat infectious diseases in pregnant people to cover Covid-19, she said.
Agency guidance to Covid drug and vaccine developers encourages them to consider developing early data that could support including pregnant individuals in late-stage clinical trials, Tantibanchachai said.
“The FDA remains committed to increasing enrollment of diverse populations in medical product development and will continue to engage with federal partners, medical product manufacturers, medical professionals, and health advocates to encourage this important goal,” she said.
“The will is there” nationally and globally to generate enough data on medical treatments to be able to officially recommend them for pregnant people, Faden said.
“The pandemic has crystallized — if there was any doubt over what the cost is of failing to change this presumption of exclusion — it’s been very bad for pregnant women globally and for their babies and for the people who love them,” Faden said. “I believe that there is a really good chance that this time, pregnant people will not be left behind but will get a place at the table.”