Neurodevelopmental disorders from in utero COVID-19 exposure based on sex

Unlike male offspring, female offspring of mothers with a positive COVID-19 test during pregnancy are not at an increased risk of developing neurodevelopmental disorders, according to a recent study published in JAMA Network Open.

Maternal infection during pregnancy has been associated with an increased risk of neurodevelopmental disorders for offspring. The COVID-19 pandemic has led to an urgent need to fully understand this association and the effects on offspring.

Sex-specific responses to COVID-19 have been found in previous studies of maternal and placental immune response. However, data has remained limited because of sample sizes and a lack of contemporaneous comparator groups.

To determine the sex-specific risks of COVID-19 exposure in utero, investigators conducted a cohort study using electronic health record (EHRs) containing data from 8 hospitals in Eastern Massachusetts.

A pandemic cohort consisted of live births from March 1, 2020, to May 31, 2021, while a comparison cohort consisted of live births from January 1 to December 31, 2018. A third cohort consisting of live births from March 1 to December 31, 2019, was also analyzed for sensitivity analysis.

Offspring sex, medical record number, and date and time of birth were used to link offspring to pregnant parents, with maternal medical history categorized through International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) billing codes. 

COVID-19 vaccination status was gathered from electronic data warehouse documentation. Sociodemographic factors were also determined through EHRs.

A diagnosis of a neurodevelopmental disorder with 12 months of birth was defined as the primary outcomes of the study, with a diagnosis within 18 months of birth evaluated for secondary analysis. The presence of at least one ICD-10 code was needed for diagnosis.

The presence of a positive COVID-19 polymerase chain reaction (PCR) test result during pregnancy was used to determine maternal COVID-19 infection. As universal screening was available in participating hospitals during the study period, asymptomatic patients at minimum would have been tested during hospitalization.

There were 18,355 live births included in the pandemic cohort, 51.2% of which were boys and 48.8% girls. Most of the cohort was White, and 14.3% were Hispanic. The average maternal age was 33 years.

Of the pandemic cohort, 4.8% of offspring were born to mothers with a confirmed positive COVID-19 PCR test, with Black or other race and Hispanic ethnicity more likely among these individuals. This group was also more likely to have public insurance and offspring were more likely to be delivered preterm.

A neurodevelopmental disorder diagnosis was given within the first 12 months of life to 2.8% of offspring born to mothers with COVID-19 during pregnancy, compared to 1.8% of offspring born to mothers without COVID-19 during pregnancy. While male offspring were at a significantly increased risk from COVID-19 exposure in utero, this risk was not seen in female offspring.

Reference

Edlow AG, Castro VM, Shook LL, Haneuse S, Kaimal AJ, Perlis RH. Sex-specific neurodevelopmental outcomes among offspring of mothers with SARS-CoV-2 infection during pregnancy. JAMA Netw Open. 2023;6(3):e234415. doi:10.1001/jamanetworkopen.2023.4415