Window Into the Future

The work provides a chance to overcome the dearth of research on pregnant women that has left many important questions unanswered. In 1977, the Food and Drug Administration issued guidelines to exclude “women of childbearing potential” from participating in early-stage clinical trials, partly due to a wave of birth defects in the 1960s caused by the morning sickness drug thalidomide. The agency eventually relaxed the rules to allow research on women who weren’t pregnant, but those who are pregnant are still routinely excluded from most clinical trials and, at times, other forms of research due to their status as part of a “vulnerable population” (a matter under debate in the medical community). As a result, nearly 75 percent of the drugs approved by the FDA since 2000 contain no data about safety or efficacy for pregnant people. This lack of information forces doctors to make educated guesses about whether the benefits of something like a vaccine, mood stabilizer or painkiller outweigh the possible risks to a mother and her developing child.

To begin filling in that knowledge gap, Dr. Osborne and Dr. Martin will analyze de-identified electronic medical record data for mother-infant pairs treated across all of Weill Cornell Medicine’s affiliated hospitals in New York City, including birth and delivery data dating back 10 years. Going forward, and with patients’ permission, the program would enroll women during prenatal care and follow them through the birth, the baby’s hospitalization and, ideally, years into the future if they remain Weill Cornell Medicine patients. Eventually, researchers hope to include biological samples routinely collected from mothers and infants.

This research “is an opportunity to get much more granular and ask many more interesting questions,” says Dr. Laura Riley, chair of the Department of Obstetrics and Gynecology and obstetrician and gynecologist-in-chief at NewYork-Presbyterian/Weill Cornell Medical Center. “Publicly available databases do not generally link mother-baby information, so this is a huge opportunity for Weill Cornell Medicine.”

‘The Numbers Are the Biggest Thing’

More than 7,600 babies were born last year at NewYork-Presbyterian Alexandra Cohen Hospital for Women and Newborns, plus another 8,600 at affiliated hospitals in Brooklyn, Queens and Lower Manhattan. Researchers say the sheer volume of patient data and racial diversity in the region are of immense value to science.

“The numbers are the biggest thing,” says Dr. Martin, who has spent years researching neonatal nutrition, including the biological factors that affect the nutritional content of breast milk. “I’ve done a lot of studies that have involved hundreds of patients — and they are good — but you can’t make big conclusions. There’s so much individual variation among patients that you need big data to answer meaningful questions.”

Doctors already know that maternal conditions like gestational diabetes and preeclampsia can trigger or require preterm birth, increasing the risk of health problems associated with prematurity; however, research into how a mother’s health affects her child remains limited. “If we have a child who’s born with a certain disorder, these data will allow us to look back and see if something that happened during pregnancy could have helped us predict that disorder,” Dr. Osborne says.

This isn’t the first time that Weill Cornell Medicine researchers have used data from mother-infant dyads to answer important questions about health outcomes. In 2020, during the early days of the COVID-19 pandemic, Weill Cornell Medicine scientists began collecting placentas and biological samples from mothers and babies to better understand how the novel coronavirus — and later the COVID vaccine — affected pregnant women and their children.

That repository, which has grown to nearly 5,000 dyads, has yielded more than a dozen studies and sparked numerous research collaborations and findings. For one, scientists from Weill Cornell Medicine used de-identified data to confirm that pregnant women infected with COVID transfer protective antibodies to their babies in the womb. They also discovered that protection from mRNA vaccines is passed from mother to child and identified the ideal time for a pregnant woman to get vaccinated (the sooner, the better).

“We understood that there was a lot of power in having so many datasets that link the mom, the baby and the placenta,” says Dr. Yawei (Jenny) Yang, assistant professor of pathology and laboratory medicine, whose lab spearheaded the creation of the repository and subsequent COVID studies. “Having this repository has already led to so many collaborations — across Weill Cornell Medicine, across universities, across the country and oceans. It’s not only enabled our own research but also the research of many other groups.”

Dr. Martin also has built a repository to find answers about maternal and infant health. In 2009, while working in the neonatal intensive care unit at Beth Israel Deaconess Medical Center in Boston, she began collecting samples of breast milk, baby formula and infants’ urine and stool to better identify — and correct for — nutritional deficits in premature newborns’ diets. Proper feeding is critical for preterm infants because organs like the brain, lungs and eyes are still developing and rely on the right nutrients to fully form outside of the womb.

Over time, that repository led to meaningful discoveries. Dr. Martin and her colleagues found that feeding preterm infants formula or breast milk sooner, rather than later (as often happens), after their birth decreased their risk of intestinal inflammation, which is linked to developmental issues like lung disease and impaired vision. She also identified how deficits in specific lipids and fatty acids found in infant blood affect the health outcomes of preterm newborns — findings that resulted in a five-year, NIH-funded study that she’s currently overseeing at Weill Cornell Medicine and four partner institutions.

“There are a million components in human milk that are yet to be discovered, but it requires the numbers to be able to find consistent patterns,” says Dr. Martin, noting that future research will allow her and fellow researchers to more rapidly identify and provide the nutrients that preterm infants need to reach optimal health.

Dr. Martin, who moved from Boston to work at Weill Cornell Medicine last summer, is eager to validate the smaller studies she conducted while at Beth Israel Deaconess in a larger, more diverse cohort. One of her studies, published last year in the Journal of Pediatrics, found that preterm infants exposed to acetaminophen through breast milk were at greater risk for lung injury. However, because Dr. Martin and her colleagues had only limited information on the mothers’ health, it was impossible to determine whether the drug itself was to blame, versus the condition that led the mothers to consume the painkiller in the first place.

“The acetaminophen study was a snapshot from a small cohort of preterm babies. With the work we’re planning, we will be able to see the linkage between moms and babies to understand what’s really going on,” Dr. Martin says. “The possibilities will truly be endless.”

Prediction and Prevention

After learning about Klein’s miscarriages and subsequent symptoms, Dr. Osborne believed that her patient was suffering from postpartum depression and an immune-mediated illness, caused by abnormal activity of the body’s immune cells.

“Later-term miscarriages, or recurrent miscarriages, are often an immune-mediated phenomenon,” Dr. Osborne says. “When a really severe postpartum depression or anxiety arises after that, it may be partially grief at the loss of the pregnancy, but it may also be connected biologically — and we don’t have the answers to what those connections are.”

Klein’s rashes and allergies gradually subsided, and Dr. Osborne was able to treat Klein’s postpartum depression by prescribing different psychotropic medications, eventually landing on a winning combination that eased her symptoms. But until then, Klein suffered extensively — a reality common for many women.

At least one in four women experiences depression or anxiety during pregnancy or following childbirth. When left untreated, these illnesses not only harm mothers but also can lead to impaired cognitive development and higher rates of psychiatric disorders in their children. Even in the case of miscarriage, postpartum depression can take a toll on children who may already be in the home. “My suffering impacted my three children, my husband, my extended family and my friends,” Klein remembers. “Everyone did what they could to help, but no matter who I saw or where I went, I couldn’t get answers.”

By collecting information from thousands of women, Dr. Osborne hopes her and Dr. Martin’s research will provide information that helps doctors predict who is likely to be affected by a mood disorder and, ideally, how to address it before it causes harm. Her research has already revealed physiological processes that could indicate future mental illness.

One such study, published in Molecular Psychiatry last year, found that postpartum depression was more common in women with impaired autophagy, a cellular process that clears waste from cells. But Dr. Osborne is quick to point out that the study’s data — gathered during her time working at Johns Hopkins University School of Medicine — came from a cohort of 14 participants, most of whom were white and highly educated. To verify the findings, she wants to study a larger, more racially diverse cohort of 600 women.

“If we can replicate our initial research, the study could form the basis of a biological test for pregnant women to help predict postpartum depression,” she says. Understanding the biological triggers associated with postpartum depression could help doctors prevent and manage the condition, whether through antidepressants or nonpharmacologic means, like mindfulness therapies or taking certain vitamins.

The repository could likewise help researchers identify the triggers and biomarkers of nonpsychiatric diseases. For example, about one in 25 women develop preeclampsia — a serious condition characterized by high blood pressure and other complications during or immediately following pregnancy — often with no warning signs. Not only is preeclampsia responsible for the deaths of approximately 76,000 women and 500,000 infants globally every year, but women with a history of the illness are also twice as likely to develop cardiovascular disease and are at greater risk for chronic hypertension and Type 2 diabetes, even decades after they’ve delivered.

“Right now, we don’t have great ways of predicting who is going to develop preeclampsia,” Dr. Osborne says. “Instead of studying someone after they get preeclampsia, [our work] will give us an opportunity to look at women’s blood before they get the disease. That might allow us to study the underlying causes and, importantly, to trace the effects of preeclampsia on the body and placenta throughout pregnancy.”

Dr. Osborne’s lab also plans to study immune changes in pregnant women with anxiety. Research has shown that anxious mothers are more likely to have children with asthma and allergies, but no one knows the mechanism that causes it. Her team hopes to identify specific epigenetic markers in the umbilical cord that predict which children will be at increased risk for allergic diseases.

“Being able to connect things that are going on in the child’s life with things that happened while the woman was pregnant, that’s an unusual thing to be able to do on such a large scale,” Dr. Osborne says. “That’s the excitement of this project.”

Where Innovation Happens

Fostering collaborative, interdisciplinary research is an integral part of Dr. Osborne’s and Dr. Martin’s mission. The duo plan to cultivate relationships among diverse researchers, many with overlapping areas of study. Eventually, they hope to start a training program for scholars from multiple disciplines who are interested in dyadic maternal-child research.

Drs. Osborne and Martin, both Weill Cornell Medicine alumna, were hired last year as part of a mission to expand specialized maternal and infant research. Building collaborative research structures between the departments of pediatrics and OBGYN is a key part of that vision, says Dr. Sallie Permar, chair of the Department of Pediatrics and pediatrician-in-chief at NewYork-Presbyterian/Weill Cornell Medical Center and NewYork-Presbyterian Komansky Children’s Hospital, who worked closely with Dr. Riley to recruit the two doctors.

“Either one of these leaders working alone would not be as strong as they are working together,” Dr. Permar says. “Together, they could really transform what we’re able to do in perinatal health.”

When it comes to obstetrics and neonatology, which focus on developmental periods that influence a baby’s lifelong health, speeding up the pace of progress can be a game changer for millions of patients, says Dr. Permar, whose own work focuses on how to prevent maternally transmitted viral infections, such as HIV, Zika and cytomegalovirus — a leading cause of birth defects. “Making gains on major health problems in childhood and in pregnancy will contribute to better overall population health, because the first three years are critical. It’s the highest-yield time in terms of changing the trajectory of health for the rest of a person’s life,” she says.

While the pace of discovery wasn’t fast enough to prevent Klein’s illness, she hopes the work underway at Weill Cornell Medicine will make a difference for her three daughters.

“I dream of the day that a predisposition to postpartum depression is something pregnant women can be tested for,” Klein says. “The greatest obstacle in my journey was not finding a cure — it was the confounding complexity of detecting what was wrong with my body. I want to believe that when my daughters have children, they won’t struggle with all these unknowns.”