JAMA Netw Open. 2026 May 1;9(5):e2611440. doi: 10.1001/jamanetworkopen.2026.11440.
ABSTRACT
IMPORTANCE: There is conflicting evidence for associations between maternal SARS-CoV-2 infection and neonatal congenital anomalies. Population-based studies evaluating confirmed maternal infection during pregnancy and at specific gestational time periods are needed.
OBJECTIVE: To evaluate associations between laboratory-confirmed maternal SARS-CoV-2 infection in pregnancy and neonatal congenital anomalies, overall during pregnancy and by specific trimester of exposure.
DESIGN, SETTING, AND PARTICIPANTS: This population-based, matched cohort study of live births with maternal SARS-CoV-2 infection in pregnancy matched 1:4 to live births without maternal infection in Ontario, Canada, was conducted from December 14, 2020, to December 31, 2021. Matching was performed on maternal age, delivery date, gestational age at birth, neonatal sex, and prepregnancy diabetes. Analyses were conducted from May to August 2025.
EXPOSURE: Maternal SARS-CoV-2 infection in pregnancy confirmed by positive real-time polymerase chain reaction (RT-PCR) test. Pregnancies with no positive RT-PCR test were considered SARS-CoV-2 negative.
MAIN OUTCOMES AND MEASURES: The primary outcome was any neonatal congenital anomaly. The secondary outcome was any neonatal cardiac anomaly. Crude incidence rates of congenital anomalies per 1000 live births by maternal SARS-CoV-2 infection status with 95% CI were determined with a Poisson distribution for the study sample overall, and by each trimester of exposure.
RESULTS: A total of 5049 live births with corresponding maternal SARS-CoV-2 infection in pregnancy (mean [SD] maternal age, 31.0 [4.9] years) were matched 1:4 to 20 196 live births without maternal infection (mean [SD] maternal age, 31.1 [4.7] years). Compared with patients without infection, those with infection were more likely to be immigrants and to have high levels of material deprivation and were less likely to receive COVID-19 vaccination and live in rural areas. The crude incidence rate of any congenital anomaly was 32.5 anomalies per 1000 live births (95% CI, 27.9-37.9 anomalies per 1000 live births) with maternal SARS-CoV-2 infection and 31.1 anomalies per 1000 live births (95% CI, 28.8-33.6 anomalies per 1000 live births) without maternal SARS-CoV-2 infection (unadjusted rate ratio, 1.04; 95% CI, 0.87-1.24; P = .65). Multivariable logistic regression adjusting for maternal socioeconomic variables and prepregnancy COVID-19 vaccination did not alter these findings. Infection separately by trimester was not statistically significantly associated with the outcome. There were no statistically significant associations between maternal SARS-CoV-2 infection and cardiac anomalies in pregnancy overall or by trimester.
CONCLUSIONS AND RELEVANCE: In this Ontario population-based study of 5049 live births with maternal SARS-CoV-2 infection matched to 20 196 live births without maternal infection, there was no association between laboratory-confirmed maternal SARS-CoV-2 infection and neonatal congenital anomalies in pregnancy overall, or by trimester of infection. These findings may provide reassurance to pregnant patients and their health care professionals, although further studies evaluating first trimester infection and risks of specific anomalies are warranted.
PMID:42096200 | DOI:10.1001/jamanetworkopen.2026.11440
