April 2020 was a confusing and uncertain time. Just weeks after the emergence of the first U.S. cases of COVID-19, guidance on the new virus was changing daily. “Only grocery stores were open. People were wiping everything down. All the playgrounds were shut,” says Penn psychologist Rebecca Waller. “It was quite scary for everyone, but we imagined, particularly for pregnant individuals.”
Waller and colleagues from the Perelman School of Medicine and the Children’s Hospital of Philadelphia (CHOP) had recently begun working together on an interdisciplinary initiative. They called it the Intergenerational Exposome Project—IGNITE for short—and their aim was to unite traditionally siloed research areas to better understand risk factors for preterm birth and poor pregnancy outcomes.
“Plenty of data from animal and human studies show that the intrauterine environment matters, and that a stressful life can have long-term effects on the development of the fetus,” says Raquel Gur, a Penn Medicine psychiatrist who runs the Lifespan Brain Institute (LiBI). “Genes are important, but they are expressed in the context of an environment.”
Though IGNITE had to pivot online in those early pandemic days, the researchers had already put in place the infrastructure necessary to conduct the project they envisioned. About 1,000 individuals and their children are now part of this study, which includes data from most stages of pregnancy and the postpartum period, plus 12 and 24 months following delivery.
So far, the work has revealed a great deal about the pandemic’s effect on pregnancy in the United States. The team’s first paper, published in Psychiatry Research in November 2020, confirmed that, like many facets of COVID-19, the pandemic has placed a disproportionate burden on Black pregnant individuals. The researchers’ latest, published in August in the Archives of Women’s Mental Health, showed that people who reported traumatic birth experiences had an increased risk of developing postpartum depression.
There’s still much more to learn, Waller says. “We’ve now seen some of these children for the second time. The future of this research is really exciting.”
Weaving disparate threads
Though IGNITE itself is nascent, the threads the collaboration weaves together have been around for years. LiBI, for one, began about six years ago, created by Gur to better understand risk factors that affect the developing brain. Several National Institutes of Health (NIH) grants awarded to Penn Medicine’s Michal Elovitz have allowed her to study cohorts of pregnant individuals to learn about preterm birth and poor pregnancy outcomes, which affect Black populations at significantly higher rates. For her part, Waller has 12 years under her belt studying parenting and risk for aggressive and antisocial behavior in children.
Project IGNITE includes others partners from a range of disciplines, like Wanjikũ Njoroge, an infant-preschool psychiatrist at CHOP, who is medical director of the Young Child Clinic; Lauren White, a LiBI psychologist; Ran Barzilay, a psychiatrist at CHOP and Penn who studies risk factors for youth suicide; Sara Kornfield, a licensed clinical psychologist and director of Penn Medicine’s Maternal Wellness Initiative; Barbara Chaiyachati, a CHOP physician with Safe Place: The Center for Child Protection and Health who studies early-life adversity; and neonatologist Heather Burris.
Though many of the individuals knew each other from previous partnerships or overlapping research interests, no prior project matched the intended scope of IGNITE, which aimed to merge research on maternal-fetal medicine, obstetrics and gynecology, psychiatry, psychology, neonatology, and pediatrics.
“One of the big challenges at Penn and CHOP is that they are these massive institutions with so much great research happening on both campuses, but it can be hard to connect,” says Njoroge. Elovitz, for example, focuses on pregnant individuals, and their research participation typically finishes once the baby is born. Njoroge studies the next developmental phase, working with infants and young children, and Waller’s research centers on young elementary-age children.
The team hypothesized that getting a fuller picture of these families, starting at pregnancy and extending through the first few years of a child’s life, could offer greater insight into how early-childhood exposures might affect development. “We cannot understand much about these children without learning about their families, their parents,” Njoroge says. “We formed this collaboration to better understand the environment in which these children will live and grow.”
Pivoting during a pandemic
IGNITE was just getting off the ground when COVID-19 arrived in the U.S. Rather than put the plans on hold or cancel the project altogether, the researchers decided to change course slightly. Innately, they understood that the stress from a global pandemic would affect pregnant individuals and their children in a big way—but they wanted to figure out precisely how.
“People who were pregnant already or who got pregnant during the pandemic, they were isolated, they couldn’t have visitors,” Gur says. “It was a terrible time.”
Through her prior research, Elovitz already had a group of individuals—pregnant or who had recently given birth—who had agreed to take part in research studies. Beyond that, several of the IGNITE researchers who are also clinicians were still treating patients. “We were actively seeing families struggle and we started thinking, ‘We should see how women are doing. It looks like they’re not doing well,’” explains Njoroge.
The IGNITE team received institutional approval to proceed with a new research protocol, then created a standardized questionnaire to dig into some of the prevalent issues. “We wanted to evaluate depression, anxiety, health disparities, worries related to COVID,” Gur says. More than 1,000 people filled out that survey.
Analysis of those data soon led to the Psychiatry Research paper. It revealed that in many ways, Black pregnant individuals felt a greater burden from COVID-19 than their white counterparts: They reported more concerns about economic hardships and negative employment consequences, plus more worry at every stage of the birthing experience—from prenatal care to postnatal needs. They were also more likely to meet criteria for clinical depression.
A double blow
“Folks were surprised by the findings from our first study,” Njoroge says. “But I’m a health equity researcher. I wasn’t shocked by the results.” They did, however, spur her to pull back the curtain further; she began examining historical redlining maps of Philly.
“Colleagues at Drexel were taking these same maps and overlaying current maps to show the disproportionate impact of the pandemic on Philadelphians. I started thinking about the cohort we had been working with.” From the original IGNITE participants, 151 Black individuals had completed two additional online surveys, which centered around the double impact of institutionalized racism and the global health crisis of COVID-19 on postpartum mental health.
Njoroge learned that many of the participants live in districts redlined some 80 years ago, areas that still experience less investment and more poverty today. The JAMA Psychiatry paper the team subsequently published spells out the findings plainly: “Associations between interpersonal racism, structural racism, and negative COVID-19 pandemic experiences were associated with greater risk for postpartum depression and anxiety.”
The data bore out the researchers’ suspicions. “Here we are in 2022 and Black individuals are still being affected by the decisions made in the 1930s,” Njoroge says. “It’s a continuation of this story about the impacts of structural racism on the health and wellness of Black people.”
Looking ahead
Beyond studying the pandemic’s effect on pregnancy, the researchers have also figured out a way to continue seeing families beyond the initial postpartum period, checking in with both parent and child after about a year.
“A parent with a 1-year-old who might have other kids during a pandemic—we knew we weren’t going to get those data by bringing people in,” Waller says. Instead, they sent home a packet with games and books. “We asked the parent to sit with their child and read the books, play with a rattle, play a game with a cup and ball,” she explains. The IGNITE team recorded and coded the behaviors during the interactions.
The setting and the number of parent-child exchanges, Waller admits, allow for a more complete picture than people coming into a lab a few times. “In a non-pandemic world, we have this rather sophisticated set-up with cameras in every corner. You can zoom in and pan out,” she says. “But there’s a lot to be said for pulling out a phone or laptop at home. It changes the quality, richness, and amount of behavioral data we can collect.”
Thanks to recently secured NIH funding, the team can now see those families again around when the child turns 2. Recruitment and data collection for that effort, called “Prenatal to Preschool,” is ongoing. In a parallel sub-study funded by LiBI, the team is sending home saliva kits to collect participant DNA and RNA in the hopes of better understanding how stress becomes biologically embedded.
Despite the tough subject matter—or perhaps because of it—there’s excitement about the potential of this collaboration. How it functions as a research unit can become a model for other interdisciplinary work across the University. What the researchers learn can shape policy with data and most importantly, save lives through relatively simple and appropriately timed interventions.
“Yes, IGNITE has shown some bleak data so far, but the flipside is that even though the data don’t look great, they also showcase amazing stories of resilience,” Njoroge says. “Part of our work is to show what families and communities are doing, weaving that together into a tapestry. People have found amazing ways to support each other. That’s what we hope our work does, too.”
Funding for Project IGNITE comes from the National Institutes of Health and the Lifespan Brain Institute.
Collaborators on the Project IGNITE team include: Ran Barzilay, an assistant professor in the Department of Psychiatry at the Perelman School of Medicine at Penn and a psychiatrist with the Youth Suicide Prevention, Intervention, and Research Center at the Children’s Hospital of Philadelphia (CHOP); Heather Burris, a neonatologist at the Hospital of the University of Pennsylvania and CHOP; Barbara Chaiyachati, a CHOP physician with Safe Place: The Center for Child Protection and Health; Andrea Duncan, a neonatologist at CHOP who directs the Neonatal Follow-up Program; Michal Elovitz, the Hilarie L. Morgan and Mitchell L. Morgan President’s Distinguished Professor in Women’s Health in the Department of Obstetrics and Gynecology at Penn Medicine and a member of the Center for Research in Reproduction and Women’s Health; Raquel Gur, professor of psychiatry, neurology, and radiology at the Perelman School of Medicine, where she directs the Neuropsychiatry Section and the Schizophrenia Research Center, is vice chair of research development in the Department of Psychiatry, and runs the Lifespan Brain Institute (LiBI), a joint initiative between Penn and CHOP; Sara Kornfield, director of the Maternal Wellness Initiative and an assistant professor in Penn Medicine’s Department of Psychiatry; Wanjikũ Njoroge, an assistant professor in Penn Medicine’s Department of Psychiatry and medical director of the Young Child Clinic at CHOP, where she is also chair of DEI for the Department of Child and Adolescent Psychiatry and Behavioral Sciences and faculty at the PolicyLab; Julia Parish Morris, a scientist in the Center for Autism Research and faculty in the Department of Biomedical & Health Informatics at CHOP; Jakob Seidlitz, a postdoctoral researcher at Penn and CHOP; Rebecca Waller, an assistant professor in the Department of Psychology in the School of Arts & Sciences at Penn; and Lauren White, a research associate at LiBI.
