In-Utero COVID-19 Exposure Tied to Neurodevelopmental Changes at Year 1

Neurodevelopmental diagnoses are more common among offspring of mothers who were infected with SARS-CoV-2, especially during the third trimester, according to study findings published in JAMA Network Open.

Initial research regarding immune activation in COVID-19 infection has indicated maternal and placental inflammation may impact the developing fetal brain and cytokine expression. Furthermore, COVID-19 infection may be associated with birth complications. Other research has shown that maternal infection in pregnancy is associated with adverse neurodevelopmental outcomes in their offspring, which may not manifest until adolescence or adulthood. Some COVID-19 patients showed neuropsychiatric symptoms that persisted up to a year later.

In the current study, researchers sought to estimate the risk for neurodevelopmental impact among mothers with SARS-CoV-2 infection.

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The researchers conducted statistical analysis of electronic health records (EHR) of 2 academic medical centers and 6 community hospitals of 7772 live births (96% singleton; maternal age 32.9±5.0 years; 9.9% Asian, 8.4% Black, 15.1% Hispanic) between March and September 2020.

There were a total of 222 cases of SARS-CoV-2 positivity in pregnancy. Mothers exposed to SARS-CoV-2 were more likely to be Hispanic, not White or Asian. They were also more likely to have public, not private, insurance.

Preterm delivery was associated with SARS-CoV-2 exposure (P =.003).

Fourteen of the 222 exposed infants (6.3%) and 227 of the 7550 unexposed infants (3.0%) were diagnosed with a neurodevelopmental disorder within 1 year (crude odds ratio [OR], 2.17; P=.006).

The most common disorders were specific developmental disorder of motor function (F82), expressive language disorder (F80.1), and unspecified developmental disorder of speech and language (F80.9).

Time to diagnosis tended to be earlier among exposed individuals (median 214 days vs 275 days).

Adjusting for nonsingleton deliveries, developmental diagnosis among COVID-exposed offspring was 1.86 compared with unexposed (95% CI, 1.03-3.36; P=.04).

Limiting infection to third trimester infections led to an adjusted OR of 2.34 (P=.01).

The researchers calculated that any confounders they did not detect would need to be 3.12 times more common among exposed individuals and cause 3.12 times the risk to produce the observed effect.

Among 27 diagnostic categories, only any viral infection was more common among exposed offspring (crude OR, 2.59; AOR, 1.81).

Study limitations included short follow-up, possible ascertainment bias, error in test result, and relatively small sample size.

In-utero exposure to SARS-CoV-2 during the third trimester was associated with a greater risk for adverse neurodevelopmental outcomes at year 1 among offspring.

The researchers believe their findings “highlight the urgency of follow-up studies in large and representative cohorts.” “More broadly, our analysis indicates the feasibility of leveraging EHR data for a retrospective cohort study that may enable detection of risk signals before such large-scale, prospective follow-up studies are available. The approach described here, using coded clinical data extracted from the EHR, is amenable to scaling across multiple health systems in the US and internationally,” they concluded.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Edlow AG, Castro VM, Shook LL, et al. Neurodevelopmental outcomes at 1 year in infants of mothers who tested positive for SARS-CoV-2 during pregnancy. JAMA Network Open. Published online June 9, 2022. doi: 10.1001/jamanetworkopen.2022.15787

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