Scientists study how maternal SARS-CoV-2 infection during pregnancy affects child brain development

Scientists led by the Lieber Institute for Brain Development are studying how a mother’s SARS-CoV-2 infection during pregnancy affects the biology of the placenta and the corresponding trajectory of brain development in the child, including the risk neurodevelopmental disorders such as schizophrenia and autism. The work is made possible by a five-year, $3 million grant from the Eunice Kennedy Shriver National Institute of Child Health & Human Development, part of the National Institutes of Health.

The project announced today stems from a collaboration between the Lieber Institute for Brain Development at the Johns Hopkins Medical Campus in Baltimore, the Children’s National Hospital in Washington, DC, and the Women’s Health Integrated Research Center at Inova Health System in Virginia. .

The group aims to get a clearer picture of how a mother’s SARS-CoV-2 infection during pregnancy affects neurodevelopment in utero, the effects of which can manifest early in a child’s life. child. Researchers hope to understand how infection interacts with other factors relevant to brain development, including genomic risk for neurodevelopmental disorders, maternal stress, and social determinants of health. The team will investigate whether the relationship between maternal SARS-CoV-2 infection and offspring brain development is mediated by changes in placental biology and maternal immune system activation. They will also assess any differences in the effects of SARS-CoV-2 between girls and boys and in the offspring of vaccinated and unvaccinated mothers.

We know that what happens in the womb is crucial for the early stages of development, especially of the brain, and we also know that viral infections contracted by pregnant women can put offspring at higher risk for developmental disorders. brain development. We suspect that exposure to SARS-CoV-2 in utero may also affect the developing brain, with potential outcomes manifesting later in life in a portion of those born during the pandemic.

Gianluca Ursini, MD, Ph.D., project principal investigator and researcher at the Lieber Institute for Brain Development

Researchers hope to turn their findings into clinical interventions as quickly as possible, Dr. Ursini said.

“We hope that this study, made possible by generous and visionary funding from the NIH, will benefit this vulnerable population in a timely manner, informing preventive and therapeutic interventions and guidelines for women exposed to SARS-CoV-2 and their infants. , ” explained Dr. Ursini. “The results of this study may help us understand the mechanism by which other infectious and non-infectious exposures during pregnancy pose a threat to brain development.”

Preliminary data show that pregnant women with symptomatic SARS-CoV-2 infections are more likely to have preterm delivery, placental abnormalities, and prenatal and perinatal complications such as preeclampsia and fetal growth restriction . All of these complications increase the risk of neurodevelopmental disorders in children later in life.

The study will involve 500 pairs of mothers and babies from Northern Virginia, half of whom had symptomatic SARS-CoV-2 infections and the other half were asymptomatic, along with 400 healthy controls. Dr. Larry Maxwell, President of Inova’s Women’s Services Line, and Thomas Conrads, Director of Women’s Health Research for Inova’s Women’s Services Line, will coordinate the assembly and analysis of biological samples from patients before the pandemic as well as at different intervals during the pandemic.

Additionally, the Inova team will use laser microdissection technology to collect specific cells from the placenta for protein analysis, as well as Lieber Institute for Brain Development researchers for genomic testing and sequencing of the RNA. Genetic and proteomic data will be combined to assess the effects of SARS-CoV-2 infection on the placenta in infected mothers compared to uninfected pregnant women serving as controls.

Sarah Mulkey, MD, prenatal-neonatal neurologist at Children’s National Hospital, will lead neurodevelopmental assessments of infants born to mothers infected with SARS-CoV-2 during pregnancy to understand any long-term neurological effects in offspring of mothers cared for at Inova. The researchers will assess the neurological development of the children at 24 and 36 months of age. This work builds on Dr. Mulkey’s longitudinal neurodevelopmental assessments of children exposed to Zika virus in utero.

“What we’ve learned is that even when babies don’t have Zika virus-related birth defects, we still see differences in early childhood development compared to children who haven’t been exposed. Zika virus,” Dr Mulkey said. “With SARS-CoV-2, there is still so much we don’t know. But by better understanding the long-term impact of exposure to COVID during pregnancy, we can ultimately find ways to prevent adverse effects.”

The scientists aim to assess factors that might mediate or moderate the relationship between a mother’s infection and her child’s neurodevelopmental outcomes. These factors include components of the mother’s immune system, changes in the placenta, changes in genes and proteins, and the sex of the fetus. They will also examine the impact of the social determinants of health, including the conditions in the places where people live, learn, work and play that contribute to health risks and outcomes.

Notably, the Inova Health System study group is racially and ethnically diverse and reflects vulnerable populations heavily impacted by the pandemic and health disparities. By identifying the mechanisms at work in the neurodevelopmental complications of maternal SARS-CoV-2 infection, scientists hope to discover how to limit or mitigate the harmful effects.

Dr. Ursini, the project’s principal investigator at the Lieber Institute for Brain Development, focused his research on investigating the role of the early childhood environment in the pathophysiology of neurodevelopmental disorders. His research examined placental biology, its relationship to genomic risk for schizophrenia, and how early complications might interact with the genome to increase this risk.

“The placenta is a critical organ for early childhood development research, although it is most often discarded after birth without investigation,” said Dr. Daniel Weinberger, MD, director and CEO of the Lieber Institute for Brain Development and researcher on this grant. .

“The placenta is an organ of the fetus, not the mother,” noted Dr. Weinberger. “It is a rich source of information about a person’s genome and fetal environment at the time of birth, with direct implications for the growth and health of the newborn. Throughout development, interactions with the environment alter the machinery that regulates the function of a person’s genome.These interactions are thought to underlie many developmental disorders such as schizophrenia.

NIH Program Director Dr. Sai Majji supports this award which will address specific factors or mechanisms responsible for brain development after SARS-CoV-2 infection during pregnancy, leading to the identification of biomarkers that may provide a prognosis for maternal health and well-being. being offspring.