Mothers’ COVID-19 Infections May Harm Children’s Brain Development

Children exposed to COVID-19 in the womb face a higher risk of developmental challenges by age three, according to new research from Mass General Brigham. The study, published in Obstetrics & Gynecology, found that maternal infection with SARS-CoV-2 was associated with a 29 percent increase in the odds of neurodevelopmental diagnoses such as speech delay, autism spectrum disorder, and motor coordination issues.

The findings come from a large retrospective analysis of 18,124 live births between March 2020 and May 2021, during the pandemic’s peak in the northeastern United States. Of those, 861 children were born to mothers who tested positive for COVID-19 during pregnancy. By the time the children reached three years old, 16.3 percent of the exposed group had received a neurodevelopmental diagnosis, compared with 9.7 percent among unexposed children.

When the researchers adjusted for maternal age, race, insurance type, and preterm birth, the statistical link persisted. The team also observed that boys were more vulnerable than girls, and that infection during the third trimester carried the greatest risk.

“These findings highlight that COVID-19, like many other infections in pregnancy, may pose risks not only to the mother, but to fetal brain development,” said senior author Andrea Edlow, MD MSc, a Maternal-Fetal Medicine specialist at Mass General Brigham. “They also support the importance of trying to prevent COVID-19 infection in pregnancy and are particularly relevant when public trust in vaccines—including the COVID-19 vaccine—is being eroded.”

Infection Timing and Sex Differences

Third-trimester exposure appeared to exert the strongest effects, with an adjusted odds ratio of 1.36. Male offspring showed a 43 percent higher adjusted risk compared with unexposed male peers. These patterns align with animal research showing that maternal immune activation during late gestation can disrupt normal neuronal growth and connectivity in the fetal brain.

The researchers emphasize that although the relative increase in risk is statistically significant, the absolute likelihood of developing a disorder remains low. Out of every 100 children exposed to maternal COVID-19, approximately seven additional cases of developmental diagnoses would be expected compared with unexposed peers.

“The overall risk of adverse neurodevelopmental outcomes in exposed children likely remains low,” said co-senior author Roy Perlis, MD MSc, of the Mass General Brigham Department of Psychiatry. “Parental awareness of the potential for adverse child neurodevelopmental outcomes after COVID-19 in pregnancy is key. By understanding the risks, parents can appropriately advocate for their children to have proper evaluation and support.”

Monitoring the Pandemic’s Youngest Generation

Lead author Lydia Shook, MD, also a Maternal-Fetal Medicine specialist, noted that the team will continue tracking the cohort as the children reach school age. Future analyses aim to determine whether these early developmental differences persist, resolve, or evolve into more specific learning or behavioral diagnoses.

While the biological mechanisms remain under investigation, prior studies suggest that inflammation and immune responses triggered by maternal infection can alter fetal brain signaling pathways. The results underscore the importance of vaccination and preventive care during pregnancy, particularly during waves of infectious disease.

As the first large-scale follow-up of children born during the COVID-19 pandemic, the study offers an early glimpse into potential long-term effects. It also highlights the value of health system data in tracing how global health crises may ripple through the next generation.

Obstetrics & Gynecology: 10.1097/AOG.0000000000006112