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Systematic Review and Meta-Analysis: The Associations of Prenatal Exposure to SARS-CoV-2 Infection and COVID-19
Marco Rizzo1, Rushna Tubassum1, Carly A Kaplan1
1Icahn School of Medicine at Mount Sinai, New York City, New York.
Insights
Prenatal exposure to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection was linked to temporary issues in child hearing and motor skills. However, research does not support a causal link between SARS-CoV-2 exposure or COVID-19 vaccination and long-term neurodevelopmental problems.
Area of Science:
- Pediatric Neurodevelopment
- Infectious Disease Epidemiology
- Maternal-Fetal Medicine
Background:
- Prenatal exposure to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and COVID-19 vaccination are global health concerns.
- Understanding the impact on child neurodevelopment is crucial for public health guidance.
Purpose of the Study:
- To systematically review and meta-analyze evidence on the associations between prenatal exposure to SARS-CoV-2 infection or COVID-19 vaccination and child neurodevelopmental outcomes.
- To assess potential risks and inform clinical practice and parental counseling.
Main Methods:
- Comprehensive search of multiple databases (MEDLINE, EMBASE, PsycINFO, Web of Science, Scopus, Cochrane CENTRAL) for relevant studies.
- Inclusion of original research published in any language before November 8, 2024.
- Meta-analyses performed on outcomes reported in ≥3 controlled studies.
Main Results:
- Seventy studies examined neurological, neuroimaging, motor, audiological, and neurodevelopmental assessments in children up to 36 months of follow-up.
- Meta-analyses indicated a higher risk of transient hearing impairment and delays in fine motor and problem-solving skills in infants exposed prenatally to SARS-CoV-2.
- No associations were found with atypical neurological or neuroimaging outcomes, and no adverse effects were reported for prenatal COVID-19 vaccination.
Conclusions:
- Prenatal SARS-CoV-2 exposure is associated with early, but seemingly transient, impairments in hearing and motor skills.
- Current evidence does not support a causal relationship between prenatal SARS-CoV-2 infection or COVID-19 vaccination and adverse neurodevelopmental outcomes.
- Further research with robust methodologies is needed to confirm these findings and address study limitations.
Objective:
To systematically review and meta-analyze evidence on the associations between prenatal exposure to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection or COVID-19 vaccination and child neurodevelopmental outcomes.
Method:
MEDLINE, EMBASE, PsycINFO, Web of Science, Scopus, and Cochrane CENTRAL databases were searched for original research on neurodevelopmental outcomes in children prenatally exposed to SARS-CoV-2 infection and COVID-19 vaccination published in any language before November 8, 2024. Meta-analyses were performed on any outcome reported in ≥3 controlled studies.
Results:
A total of 70 studies were identified on neurological (7), neuroimaging (12), motor (3), audiological (29), and neurodevelopmental (35) assessments and neurodevelopmental disorders (2) with median sample sizes of 117 (interquartile range: 44-340) and follow-up ≤36 months. Meta-analyses of neonatal auditory screenings (10), Ages and Stages Questionnaire, 3rd Edition (9), and Ages and Stages Questionnaire: Social-Emotional (3) data suggested a higher risk of transient hearing impairment (risk ratio 2.01, 95% CI 1.39-2.91) and delays in fine motor (risk ratio 1.55, 95% CI 1.14-2.10) and problem-solving (risk ratio 1.32, 95% CI 1.01-1.74) skills in children prenatally exposed to SARS-CoV-2 compared with unexposed children.
Conclusion:
Prenatal SARS-CoV-2 exposure was associated with early impairments in hearing, fine motor skills, and problem-solving skills, which appear to resolve with time. No associations were identified with atypical neurological or neuroimaging outcomes. No adverse neurodevelopmental effects were reported in 2 studies that examined prenatal COVID-19 vaccination. Study quality was generally moderate, with small sample sizes, inappropriate control groups, and unmeasured confounding. Taken together, the current body of research does not support a causal relation between prenatal exposure to SARS-CoV-2 infection or COVID-19 vaccination and adverse neurodevelopmental outcomes.
Study Registration Information:
The Association of Intrauterine Exposure to SARS-CoV-2 and the COVID-19 Vaccine With Child Neurodevelopment: A Systematic Review; https://www.crd.york.ac.uk/PROSPERO/view/CRD42023451206.
