Neurodevelopmental Outcomes at 1 Year in Infants of Mothers Who Tested Positive for SARS-CoV-2 During Pregnancy

IMPORTANCE Epidemiologic studies suggest maternal immune activation during pregnancy may be associated with neurodevelopmental effects in offspring. OBJECTIVE To evaluate whether in utero exposure to SARS-CoV-2 is associated with risk for neurodevelopmental disorders in the first 12 months after birth. DESIGN, SETTING, AND PARTICIPANTS This retrospective cohort study examined live offspring of all mothers who delivered between March and September 2020 at any of 6 Massachusetts hospitals across 2 health systems. Statistical analysis was performed from October to December 2021. EXPOSURES Maternal SARS-CoV-2 infection confirmed by a polymerase chain reaction test during pregnancy. MAIN OUTCOMES AND MEASURES Neurodevelopmental disorders determined from International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) diagnostic codes over the first 12 months of life; sociodemographic and clinical features of mothers and offspring; all drawn from the electronic health record. RESULTS The cohort included 7772 live births (7466 pregnancies, 96% singleton, 222 births to SARS-CoV-2 positive mothers), with mean (SD) maternal age of 32.9 (5.0) years; offspring were 9.9% Asian (772), 8.4% Black (656), and 69.0% White (5363); 15.1% (1134) were of Hispanic ethnicity. Preterm delivery was more likely among exposed mothers: 14.4% (32) vs 8.7% (654) (P = .003). Maternal SARS-CoV-2 positivity during pregnancy was associated with greater rate of neurodevelopmental diagnoses in unadjusted models (odds ratio [OR], 2.17 [95% CI, 1.24-3.79]; P = .006) as well as those adjusted for race, ethnicity, insurance status, offspring sex, maternal age, and preterm status (adjusted OR, 1.86 [95% CI, 1.03.3.36]; P = .04). Third-trimester infection was associated with effects of larger magnitude (adjusted OR, 2.34 [95% CI, 123-4.44]; P = .01). CONCLUSIONS AND RELEVANCE This cohort study of SARS-CoV-2 exposure in utero found preliminary evidence that maternal SARS-CoV-2 may be associated with neurodevelopmental sequelae in some offspring. Prospective studies with longer follow-up duration will be required to exclude confounding and confirm these associations.

Automated summary

This study found preliminary evidence that in utero exposure to SARS-CoV-2 may be associated with neurodevelopmental disorders in the first 12 months after birth.