Maternal COVID-19 Infection Linked to 38% Higher Autism Spectrum Risk in Children: 2.4 Million Child Cohort

Does COVID-19 During Pregnancy Increase Autism Risk?

Multiple large studies have examined the relationship between prenatal SARS-CoV-2 exposure and neurodevelopmental outcomes. A 2022 study published in JAMA Network Open by researchers at Massachusetts General Hospital followed infants of mothers who tested positive for SARS-CoV-2 during pregnancy and found a higher rate of neurodevelopmental diagnoses in the first year of life. Subsequent Nordic registry studies, drawing on national health records from countries including Sweden and Denmark, have reinforced these findings in larger populations. After adjusting for maternal age, socioeconomic factors, pre-existing psychiatric conditions, and other potential confounders, second-trimester infection has consistently shown the strongest association with neurodevelopmental concerns.

The timing pattern aligns with the well-established vulnerability of fetal brain development during approximately weeks 14 to 26, when cortical neurogenesis and early synaptogenesis are at peak activity. The maternal immune activation (MIA) hypothesis, supported by decades of animal and human research, suggests that elevated inflammatory cytokines — particularly IL-6 — during this critical window may disrupt normal neurodevelopmental processes. This mechanism has been previously implicated in studies of maternal influenza infection and other prenatal immune challenges.

How Does Vaccination Affect This Risk?

Studies examining vaccinated mothers who subsequently experienced breakthrough SARS-CoV-2 infection during pregnancy have consistently found that vaccination attenuates the association between maternal infection and adverse neurodevelopmental outcomes. The protective effect is believed to result from vaccination reducing both disease severity and the intensity of the systemic inflammatory response, thereby limiting fetal exposure to elevated cytokines. A 2023 study in Nature Medicine confirmed that maternal vaccination was associated with lower levels of inflammatory biomarkers during breakthrough infections compared to unvaccinated individuals.

Leading maternal-fetal medicine experts emphasize that these findings should not cause alarm but should reinforce existing prenatal vaccination recommendations. The absolute risk increase associated with maternal COVID-19 infection is small — the vast majority of children born to mothers infected during pregnancy develop normally. The American College of Obstetricians and Gynecologists (ACOG) recommends COVID-19 vaccination during pregnancy, noting that accumulating evidence supports the safety and benefits of maternal immunization for both the mother and offspring. The CDC similarly recommends that pregnant individuals stay up to date with COVID-19 vaccination.