Maternal Infection with SARS-Cov-2 Virus During Pregnancy: Male Children More Likely to Have Neurodevelopmental Disorder at One Year of Age

A new research study published in JAMA Network Open found that male, but not female, children born to mothers infected with SARS‐CoV‐2 during pregnancy were more likely to be diagnosed with a neurodevelopmental diagnosis during the first year of life compared to children born to uninfected mothers.  

Numerous epidemiologic studies have demonstrated that maternal infection with certain viruses during pregnancy (for example, influenza) is associated with an increased risk for neuropsychiatric or neurodevelopmental disorders in exposed offspring.  In a retrospective cohort study, researchers from the Center for Quantitative Health at MGH, including Victor Castro, MS and Roy Perlis, MD, have teamed up with Department of Obstetrics and Gynecology at Mass General to examine whether exposure to the novel SARS-CoV-2 coronavirus during pregnancy is associated with risk for neurodevelopmental disorders in exposed children.

The researchers examined the electronic health records from 8 Massachusetts hospitals, identifying 18,355 children born during the COVID-19 pandemic (51.2% boys), including 883 (4.8%) children born to mothers testing positive for SARS‐CoV‐2 infection during pregnancy.  Neurodevelopmental disorders in children were identified using ICD-10 diagnostic codes.

Of the 883 SARS‐CoV‐2–exposed children, 26 (3.0%) received a diagnosis of a neurodevelopmental disorder during the first 12 months of life, compared to 317 (1.8%) in the SARS‐CoV‐2–unexposed offspring.  

After accounting for potential confounding variables, including race, ethnicity, insurance status, hospital type (academic center or community), maternal age, and preterm status, the researchers observed that maternal SARS-CoV-2 infection during pregnancy was associated with an increased risk for neurodevelopmental disorder at 12 months among male children (adjusted OR, 1.94; 95% CI 1.12-3.17).  This association was not observed in female offspring (adjusted OR, 0.89; 95% CI, 0.39-1.76). At 18 months, more modest effects were observed in male offspring (adjusted OR, 1.42; 95% CI, 0.92-2.11).

Further Study, Longer Follow-Up is Needed 

Although we do not fully understand the mechanism by which maternal infection with COVID increases the risk of neurodevelopmental disorders, studies of mothers infected with other viruses have observed that activation of the immune system during pregnancy appears to play an important role.  Furthermore, these studies have shown that males may be more vulnerable than females to the deleterious effects of viral infection and immune activation.

It is important to note that the findings of this study were based on ICD-10 diagnoses in the electronic health record rather than direct evaluation by blinded raters.  It is reasonable to consider the possibility that providers caring for SARS-CoV-2- exposed infants may be more vigilant, looking for potential sequelae of infection, and thus may be more likely to overdiagnose problems in this population.  In addition, this study followed children only up to one year of age.  Future studies with longer follow-up and assessment of neurodevelopmental problems using blinded raters will help us to develop a better understanding of the impact of the SARS-CoV-2 infection on pregnancy and the developing fetus.

While the results are preliminary, this study highlights the importance of infection prevention and vaccination.  In addition to our concerns about the effects of SARS-CoV-2 infection on the developing fetus, it must be emphasized that during pregnancy, women are more likely to develop more severe illness and are more likely to be hospitalized after infection with the SARS‐CoV‐2 virus.  

In Utero SARS‐CoV‐2 Exposure Linked to Higher Risk of Neurodevelopmental Disorders (Harvard Medical School)