A host of studies have revealed that pregnant women whose immune systems are activated due to transmissible infections, both during and outside of pandemics, have an increased risk of giving birth to children who experience neurodevelopmental disorders. Building on that knowledge, a recent study examined the effects of maternal SARS-CoV-2 infection during pregnancy on offspring and found an elevated risk in male babies in particular.
A team of scientists at Massachusetts General Hospital in Boston conducted a retrospective cohort study comparing outcomes for babies born in 2018 and part of 2019 with those born between March 1, 2020 and May 31, 2021, during the early part of the COVID-19 pandemic. The team looked at electronic health records (EHR) for babies born in 8 hospitals in various Massachusetts locations during that time. A total of 18,355 births were analyzed, including 883 in which the mother had received a positive COVID-19 test during pregnancy. Relying on the presence of certain ICD-10 billing codes, the scientists were able to determine which children had been diagnosed with a neurodevelopmental disorder within 12 months of their birth, as well as within 18 months of their birth in a secondary analysis.
The results indicated higher rates of neurodevelopmental abnormalities in areas such as motor function and speech and language during the first year among babies born to women who had experienced a COVID-19 infection during pregnancy–2.9% vs. 1.8% of babies born to women without a diagnosed COVID-19 infection. However, when parsing the differences between male and female babies, the researchers saw a statistically significant difference in risk. The male babies born to women with diagnosed infection had an adjusted odds ratio of 1.94 [95% confidence interval, 1.12-3.17] of having neurodevelopmental disorders, while the female babies had an adjusted odds ratio of 0.89 [95% confidence interval, 0.39-1.76].
Male fetuses’ greater vulnerability in the womb is not a new discovery. “We know that male children and male adolescents are more likely to be diagnosed with neurodevelopmental disorders,” Andrea Edlow, MD, a maternal-fetal medicine specialist at Massachusetts General Hospital and an author of the study, told Contagion. “Males can be more sensitive to inflammatory and immune-mediated exposures in utero.”
COVID-19, it seems, is no exception: A 2021 study in Science Translational Medicine found reduced placental antibody transfer to male fetuses during maternal COVID-19 infection. If male fetuses have less protection from the harmful effects of their mothers’ COVID-19 infections, it stands to reason that they may experience a higher rate of developmental abnormalities.
Rather than use her study’s findings to scare parents, Edlow urges practitioners to approach each child holistically. When evaluating pediatric patients, clinicians can make it a practice to ask the mother about her COVID-19 status. Pregnant women should be advised to get vaccinated against COVID-19 and get at least 1 booster, which not only protects them against severe disease, hospitalization, and death but also provides protection for babies. Edlow cautions, however, that it’s not possible right now to extrapolate from the data how maternal vaccination might affect the risk of neurodevelopmental disorders.
Because COVID-19 is so endemic, with most Americans having been infected, Edlow is hoping to raise awareness without making parents feel guilty. “I don’t think pregnant people should feel that they’ve failed if they get COVID-19,” she said, recommending that parents pay attention to their babies’ development and bring any concerns to their pediatrician. “Knowledge is power.”
Edlow’s team will continue to study gender differences in neurodevelopmental outcomes of babies and toddlers born to women who had COVID-19 during pregnancy. She said she and her colleagues plan to add subjects to their study and follow them on an ongoing basis through EHR, while acknowledging that a very large cohort will be needed in order to parse future results, especially when it comes to diagnoses such as autism. Most important, she stressed, is that study authors report outcomes in children of both genders, separating them out so there is no dilution of results. “Consider sex and gender in different types of health analyses,” she urged.