Whether SARS-CoV-2 infection during pregnancy affects a child’s risk for neurodevelopmental disorders?

Study will examine molecular risk factors found in the placenta.

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Previous studies have shown that SARS-CoV-2 infection during pregnancy is more likely to cause preterm delivery, abnormalities in the placenta, and prenatal and perinatal complications. All these complications increase a child’s risk of neurodevelopmental disorders later in life.

A new study led by the Lieber Institute for Brain Development sought to determine the impact of a mother’s SARS-CoV-2 infection during pregnancy on a child’s neurodevelopment in utero. Scientists want to understand how the infection interacts with other factors relevant to brain development, including genomic risk for neurodevelopmental disorders, maternal stress, and social determinants of health.

For this, scientists are studying how a mother’s SARS-CoV-2 infection during pregnancy affects the biology of the placenta and the corresponding trajectory of the child’s brain development. They will also gauge any differences in the effects of SARS-CoV-2 between female and male children and in the offspring of vaccinated and unvaccinated mothers.

Gianluca Ursini, M.D., Ph.D., the principal investigator of the project and an investigator at the Lieber Institute for Brain Development, said, “We know that what happens in the womb is crucial to the early stages of development, particularly of the brain, and we also know that viral infections contracted by pregnant women can place offspring at higher risk for disorders of brain development. We suspect that exposure to SARS-CoV-2 in utero may affect the developing brain too, with potential outcomes manifesting later in life in a portion of those born over the course of the pandemic.”

“We hope to turn their findings into clinical interventions as quickly as possible.”

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

The trial will include 400 healthy controls and 500 pairs of mothers and infants from northern Virginia, of which half had symptomatic SARS-CoV-2 infections and half were asymptomatic. The assembly and analysis of the biological samples taken from the patients before the pandemic and at different intervals during the pandemic will be coordinated.

The team will also use laser microdissection technology to collect specific cells from the placenta for protein analysis, as well as for use by investigators at the Lieber Institute for Brain Development for genomic testing and RNA sequencing. The impact of SARS-CoV-2 infection on the placenta in infected moms relative to uninfected pregnant women serving as controls will be evaluated by combining the genomic and proteomic data.

To understand any potential long-term neurological effects in children of mothers treated at Inova, Sarah Mulkey, M.D., a prenatal-neonatal neurologist at Children’s National Hospital, will oversee the neurodevelopmental assessments of the infants born to mothers who contracted SARS-CoV-2 during pregnancy. The children’s neurodevelopment will be assessed at 24 and 36 months old. This research expands upon Dr. Mulkey’s longitudinal assessments of the neurodevelopmental status of fetuses exposed to the Zika virus.

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

Scientists want to evaluate the factors that could mediate or modify the association between a mother’s infection and the neurodevelopmental outcomes of a child. These factors include the mother’s immune system, placental modifications, gene and protein alterations, and fetal sex. They will also consider how social determinants of health, such as the surroundings in which individuals reside, learn, work, and play, affect health risks and results.

Interestingly, the study group from Inova Health System reflects the vulnerable communities severely affected by the pandemic and health inequities and is racially and ethnically diverse. Scientists want to learn how to prevent or treat any illness by understanding the mechanisms causing neurodevelopmental issues brought on by maternal SARS-CoV-2 infection.

Dr. Daniel Weinberger, M.D., Director and CEO of the Lieber Institute for Brain Development, said, “The placenta is a critical organ for research about early child development, though it is most often discarded after birth without investigation.”

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

The work is made possible by a $3 million, five-year grant from the Eunice Kennedy Shriver National Institute of Child Health & Human Development, part of the National Institutes of Health.

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