20 SCIENCE NEWS | April 23, 2022C. CHANG C. CHANGFEATURE | THE PREGNANT PAUSE
whether it crosses the placenta. The main way to
gauge whether a drug may harm a fetus is through
animal studies called developmental and repro-
ductive toxicology, or DART, studies. But drug
companies often don’t begin these studies until
they’ve already gotten clinical trials rolling.
This creates a catch-22, because clinical trials
can’t include pregnant people until DART studies
suggest it’s safe to do so. That’s why Lyerly and
others pushing for change say that pharmaceutical
companies should start doing these studies earlier,
before clinical trials begin.
In 2018, the FDA issued draft guidance to help the
pharmaceutical industry decide how and when to
include pregnant people in clinical trials (SN Online:
5/30/18). That guidance is an encouraging first
step, Lyerly says, but it didn’t change any of the
stringent rules for when pregnant people could be
included in research.
Plus, it’s all completely voluntary, says Leyla
Sahin, acting deputy director for safety in FDA’s
Division of Pediatric and Maternal Health. “We
advise industry.... We tell them we recommend that
you include pregnant women in your clinical trials,”
Sahin says. “But there’s no requirement.”
In fact, the FDA doesn’t even have the legal
authority to create a requirement. In that sense,
Sahin says, “we’re where pediatrics was 20 years
ago.” Until Congress passed the Pediatric Research
Equity Act of 2003, children were routinely
excluded from clinical trials just as pregnant
women are now. The pediatric law required drug
companies to gather data on the safety and effec-
tiveness of medications in children and to provide
FDA an appropriate plan for pediatric studies.
Congress could pass a similar law for pregnancy.
And in 2020, a government task force recom-
mended exactly that to the Department of Health
and Human Services, which oversees FDA. But “it’salmost like it’s gone into this black hole,” Sahin says.
“We haven’t heard from HHS. We haven’t heard
from Congress.”Stocking the medicine cabinet
Until clinical trials during pregnancy become
more routine, pregnant people face an untenable
choice — take a drug without knowing its safety, or
leave their medical conditions untreated.
Case in point: A group of 91 doctors and scien-
tists published a consensus statement in September
2021 in Nature Reviews Endocrinology warning that
acetaminophen, the most commonly used drug
during pregnancy, may harm fetal development.
Research suggests the drug disrupts hormones, with
effects ranging from undescended testicles in male
infants to an increased risk of ADHD and autism
spectrum disorder in boys and girls.
But as is often the case with drugs and preg-
nancy, there’s not exactly a consensus among
doctors about what pregnant people should do. In
response to the new paper, the American College of
Obstetricians and Gynecologists issued a statement
saying the evidence wasn’t strong enough to sug-
gest doctors should change their standard practice,
which is to recommend acetaminophen be taken as
needed and in moderation.
Acetaminophen is an active ingredient in more
than 600 medications, including Tylenol, and is
estimated to be used by up to 65 percent of preg-
nant people in the United States. It has long been the
preferred pain medication and fever reducer during
pregnancy because the FDA recommends against the
anti-inflammatory drugs known as NSAIDs — such as
ibuprofen and aspirin — in the second half of preg-
nancy. Those drugs have been linked to rare fetal
kidney problems and low amniotic fluid levels.
While at the University of Copenhagen, clinical
pharmacologist David Kristensen began study-
ing acetaminophen’s effects on fetal development
after noticing that the drug is structurally similar
to chemicals that disrupt hormones. In 2011, he
and colleagues published animal and human stud-
ies linking acetaminophen use during pregnancy
with concerning effects in infants, including unde-
scended testicles.
“My ears perked up when I heard that,” says
Swan, the Mount Sinai reproductive epidemiologist
and coauthor of the 2021 acetaminophen review.
She had seen similar effects with maternal expo-
sure to phthalates, chemicals used in plastics that
are known to alter the activity of hormones needed
to regulate fetal development.
She and colleagues surveyed 25 years ofToo few drugs have pregnancy safety data
Efforts to protect pregnant people and fetuses have resulted in
very little safety information available for them and their doctors.80
percent
Proportion of U.S. pregnant
people who take at least
one medication during
pregnancy98
percent
Proportion of drugs
approved by the FDA from
2000–2010 without data
on fetal safetypregnancy-trials.indd 20pregnancy-trials.indd 20 4/6/22 9:14 AM4/6/22 9:14 AM