Long overlooked by science, pregnancy is finally getting attention it

Stephanie Hinze holds her son Harrison, 2, at home in Gainesville, Ga.
Hinze, who lives with spina bifida, is five months pregnant with her third
child. (Elijah Nouvelage for The Washington Post)

By Carolyn Y. Johnson
March 6

For two years, a group of world-class scientists pitched their idea for a
hot new biotech company to investors: a start-up focused on a promising
therapy for preeclampsia
a serious pregnancy complication that can become life-threatening. It was
cutting-edge science, backed by a Nobel laureate, a Harvard kidney
specialist, a leading chemist, and a biologist with both expertise and
personal experience.

Eventually, they gave up — not on the science, and not on preeclampsia —
but on the investors.

“We talked to so many different venture capitalists and other companies.
The scientists and doctors would get excited,” said Melissa Moore, a
University of Massachusetts Medical School scientist who began working on
preeclampsia after she suffered from it in 2003 and was put on bed rest for
more than a month, only to give birth seven weeks early to a baby girl who
weighed less than four pounds. “But as soon as their lawyers heard ‘sick,
pregnant women,’ nothing happened,” Moore said. “There’s such a sense of

Moore and her colleagues’ experience highlights a persistent problem in
medical research. About 10 percent of reproductive-age women become
pregnant each year in the United States, but far less research is done into
pregnancy than into much less common conditions. The effect of medicines on
pregnant women and their fetuses is rarely studied. Basic understanding of
pregnancy itself is full of gaping scientific holes, mysteries that include
how the placenta forms and what, exactly, controls the timing of birth.
Some pregnancy experts call the placenta, an organ that is necessary for
all human reproduction, the Rodney Dangerfield
of the human body because it gets “no respect.”

The default assumption has long been — and, to a large extent, still is —
that it’s essential to protect pregnant women from research, rather than
ensure they benefit from its rapid progress. But concerted pressure from
scientists and advocates is slowly beginning to change policy and research

In January, an updated federal policy that governs protections for human
research subjects went into effect, officially removing pregnant women from
being listed
as “vulnerable to coercion or undue influence,” alongside children and
“mentally disabled” people.

“We all joke about pregnancy brain, but I was still able to make decisions
for myself and my fetus,” said Sonja Rasmussen, a pediatrician and clinical
geneticist at the University of Florida.

Separately, a federal task force
last year recommended that pregnant women’s participation in drug trials
that offered benefit to the fetus no longer require the approval of the
father of the child as well.

“Once the child is born, only consent of one parent is needed,” said
Catherine Spong, chief of ­maternal-fetal medicine at the University of
Texas Southwestern Medical Center, who chaired the task force. “Given the
autonomy of pregnant women and the evolution of family structure, we really
should align that with parental consent for pediatrics.”

Activists successfully pushed for more women to be included in medical
research in the 1990s <>, but pregnant and
lactating women have largely been left behind. Now, another round of
activism <> that began
a decade ago is pushing new thinking on pregnancy. High maternal mortality
in the United States have intensified the focus, and there is a growing
awareness that conditions during pregnancy
<> can affect a baby’s
risk of developing chronic conditions late in life.

Some researchers note that pregnant women are increasingly being studied in
their own right — and not just as the environment in which a fetus
develops. Recent evidence suggests that pregnancy complications may predict
women’s susceptibility to dementia
<> or heart disease
decades later.

“Probably most people think pregnancy is a time-limited experience, and
therefore, because it lasts only nine months, we don’t need to invest that
many resources in it — because it’ll be over soon,” said Diana Bianchi,
director of the Eunice Kennedy Shriver National Institute of Child Health
and Human Development. “But that’s really a fallacious idea. Pregnancy is a
stress test for a woman, and there are these dual opportunities, to both
understand what lies ahead for the pregnant woman, but also by doing
research that ensures a healthy pregnancy, we’re contributing to the
long-term health of the nation.”
*Left out of drug trials*

The medical attitude toward pregnancy was shaped more than half a century
ago by the thalidomide
crisis, when women who took the medication for morning sickness had babies
with birth defects. The incident helped launch the modern era of U.S. drug
regulation <>,
with requirements to prove the effectiveness and safety of drugs before
they could be approved for sale. Pregnant women, however, are typically
left out of such research.

One study <> found that the
risks to human pregnancy were “undetermined” in 98 percent of prescription
drugs approved between 2000 and 2010. An analysis of historical data
reaching back to 1980 showed it took nearly three decades on average to get
more-precise risk information. That’s despite the fact that of the
6 million women in the United States who are pregnant each year, 90 percent
take at least one medication.

Anne Drapkin Lyerly, a bioethicist and obstetrician at the University of
North Carolina at Chapel Hill, said that there is a deep-seated norm to
leave pregnant women out of clinical trials, reinforced by policies that
have classified them as “vulnerable” and institutional rules that have made
it easier to avoid considering the ­potential risks and benefits altogether.

*[Listen: Why scientists still know so little about pregnancy

“If you want to exclude a pregnant woman from research, all you’ve got to
do is check the box; she’s excluded, no explanation needed,” Lyerly said.
“If you want to include her, there’s a whole slew of paperwork and
decisions, and you have to justify your decision.”

Taking women out of the vulnerable category is a long way from changing
their access to drug trials or changing the incentives drug companies have
to include them, but advocates say it’s a long-overdue start. Last year,
the U.S. Food and Drug Administration also released draft guidance
on when to include women in clinical trials, laying out the case that there
is a “critical public health need” for more information on how to use drugs
safely in pregnant women.

“If you don’t do these studies, then you don’t have the data to base your
decision, but you’re still making decisions,” Spong said. “You’re providing
care in the absence of data.”

During the flu pandemic of 2009, Rasmussen recalled deliberating with other
experts on whether the Centers for Disease Control and Prevention should
recommend that pregnant women be given Tamiflu
<> *
<>— *which it did.

“It’s one of the things I’m proudest of in my career, is we looked at that
and weighed the risk and benefits instead of the knee-jerk ‘We can’t let
pregnant women have that because the data are limited,’ ” Rasmussen said.

Another teaching moment for the medical community came last year, when an
HIV drug called dolutegravir
was flagged as potentially causing birth defects through a study that
surveilled the use of the drug in Botswana.

“The dolutegravir finding was something that oriented the whole HIV
research community toward research in pregnancy, even people who don’t work
with pregnant women. It raised questions about how to think about women,”
Lyerly said.
*Women with disabilities*

For people who are pregnant or hope to conceive, the unknowns extend far
beyond what drugs women can safely take. The National Institutes of Health,
which tracks its research funding on nearly 300 health categories
<>, ranging from rare
Batten disease to ubiquitous allergies, began breaking out its spending on
pregnancy, maternal health and breast-feeding in only 2017.
[image: image.png]
Stephanie Hinze at home with her sons Ethan, 3, and Harrison, 2. (Elijah
Nouvelage for The Washington Post)

Stephanie Hinze, 37, of suburban Atlanta, lives with spina bifida and has
used a wheelchair since she was 8 years old. When she and her husband
decided to conceive, there was little information for her to rely on —
except for an informal network of other women with disabilities who had
already had children. Concerns included whether it was safe to carry a
child at all; fertility questions; whether she was gaining weight at the
right rate, given that doctor’s offices weren’t equipped with accessible
scales; and what to do when she couldn’t feel the baby moving because of a
decreased lack of sensation in her abdomen.

Hinze, who has two sons, one of whom is adopted, is now pregnant for the
second time. She says she was lucky — her first pregnancy went smoothly and
her medical team was supportive, contrasting with anecdotes she has heard
from others. But at each step, they were solving new puzzles.

“My doctor, while he was great and very receptive, didn’t know everything
to expect. As things happened during the pregnancy, he’d say, ‘Let’s deal
with this issue and let’s figure this out.’ ” Hinze said. “You don’t want
to go in and your doctor’s not entirely sure what the solution will be for
what’s going on.”

NIH last year partnered with the CDC to survey how disabled women
experience pregnancy <>.
The questions they hope to answer include: Are they more likely to develop
complications? Does disability affect women’s ability to breast-feed? What
is their basic experience of pregnancy like?

“We don’t know,” said Alison Cernich, director of the National Center for
Medical Rehabilitation Research, describing the evidence gap around
disability and pregnancy that she attributes to a “quadfecta” of barriers
for women: Women’s health is often overlooked, many disabled women belong
to ethnic groups that do not receive optimal care because of bias, many
disabled people experience poverty, and disabilities are often stigmatized.

The basic science of pregnancy, too, is getting a closer look, as NIH has
so far funded $76 million in research projects to study the human placenta,
the temporary organ that provides oxygen and nutrients to the fetus. The
recent discovery that it is possible to grow a miniature version of the
placenta in a laboratory setting may help scientists understand fundamental
questions about how it develops, in part in response to secretions from the

“Even in the 21st century, we don’t know what’s in the secretions, we don’t
know the composition of them, which the whole of the future of the human
species depends on,” said Graham Burton, a professor of the physiology of
reproduction at the University of Cambridge.

The placenta is necessary for a successful pregnancy, but it also affects
the health of the pregnant woman. Preeclampsia, which causes maternal high
blood pressure, is caused in part by proteins released from the placenta
that affect the function of blood vessels in the mother. There is no
treatment for preeclampsia, which ends only when the woman delivers the
baby — and the placenta.

Surendra Sharma, a professor of pediatrics at Brown University, has been
trying to tease out the science behind an alarming observation made by
other researchers: Women with preeclampsia appear to be at increased risk
for dementia <>
decades later. Intriguingly, he has found that there are misfolded proteins
in placentas from women with preeclampsia, similar to those found in the
brains of patients with Alzheimer’s. Women with preeclampsia are also at
increased risk for heart disease and stroke

The idea that treating preeclampsia could help both mothers and babies adds
urgency to the quest of Moore and colleagues, who have been disappointed
but not deterred by the lack of investor enthusiasm.

“It was an eye-opener, really, to see how worried drug developers seemed to
be about the pregnancy indication, but on the other hand, I don’t think
it’s an insurmountable thing,” said Craig Mello, a Nobel laureate and
co-founder of the fizzled start-up.

Late last year, Moore and colleagues demonstrated a therapy’s promise in
treating a baboon version of preeclampsia
They hope to develop the drug through an unconventional nonprofit model.

Moore’s expertise is rooted in basic biology, a deep understanding of a
molecule called RNA that performs a slew of basic functions in cells,
including turning instructions written in the genetic code into proteins
and regulating the genome. When Moore was pregnant and suffering from
preeclampsia, she first met S. Ananth Karumanchi, a Harvard physician who
had discovered a protein that was overabundant in women with preeclampsia —
and they began talking about using RNA to reduce the level of protein.
Translating that insight into an effective drug now depends critically on a
UMass Medical School chemist, Anastasia Khvorova.

As relative newcomers to the field of pregnancy, the team is undeterred by

“One of the reasons we’ve not had a lot of drugs for pregnant women is the
risk is viewed as too high — and that’s really unfortunate,” said
Karumanchi, who recently moved to Cedars-Sinai Medical Center in Los
Angeles. “I think not doing anything for these pregnant women is not an

Stephanie Hinze makes chocolate chip cookies with her son Ethan. (Elijah
Nouvelage for The Washington Post)