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Molecular Autism
Published in: Molecular Autism 1/2021

Open Access 01-12-2021 | Autism Spectrum Disorder | Research

Fever during pregnancy as a risk factor for neurodevelopmental disorders: results from a systematic review and meta-analysis

Authors: Stephanie Antoun, Pierre Ellul, Hugo Peyre, Michelle Rosenzwajg, Pierre Gressens, David Klatzmann, Richard Delorme

Published in: Molecular Autism | Issue 1/2021

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Abstract

Background

Fever during pregnancy is a relatively common and most often trivial event. However, under specific conditions, it could affect significantly fetal brain development. Few studies, with inconsistent results, investigated whether fever, regardless the pathogen, could represent a risk factor for neurodevelopmental disorders (NDD) in the offspring. We aimed to explore further this question by performing a systematic review and meta-analysis.

Methods

Peer-reviewed studies exploring the occurrence of NDD in offspring after a fetal exposure to maternal fever were included. We specifically considered the impact of fever severity and duration, taking into consideration some confounding variables such as the use of antipyretic during pregnancy, the trimester in which the fever arose, the maternal age or smoking at time of gestation. MEDLINE, EMBASE, PsycINFO, Cochrane and Web of Science were searched without language restriction. PRISMA recommendations were followed. Odds ratio (OR) were pooled using random-effects meta-analysis. Heterogeneity in effect size across studies was studied using random-effects meta-regression analysis. (PROSPERO CRD42020182801).

Results

We finally considered ten studies gathering a total of 10,304 children with NDD. Among them, 1394 were exposed to fever during pregnancy. The selected studies were divided into 5 case–control studies and 5 cohort studies. Maternal exposure to fever during pregnancy increased the risk of NDD in offspring with an OR of 1.24 [95% CI: 1.12–1.38]. Secondary analysis revealed an increased risk for NDD when fever occurred during the first trimester of gestation [OR 1.13–95% CI: 1.02–1.26].

Limitations

We excluded studies that considered infections with no evidence of fever. Another potential limitation may be the possible heterogeneity between study designs (cohorts and case–control).

Conclusion

Additional evidence supported the association between fever during pregnancy and increased risk for NDD in offspring. Careful monitoring should be considered for children born from mothers with a febrile episode during pregnancy (specifically during the first trimester).
Appendix
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Metadata
Title
Fever during pregnancy as a risk factor for neurodevelopmental disorders: results from a systematic review and meta-analysis
Authors
Stephanie Antoun
Pierre Ellul
Hugo Peyre
Michelle Rosenzwajg
Pierre Gressens
David Klatzmann
Richard Delorme
Publication date
01-12-2021
Publisher
BioMed Central
Published in
Molecular Autism / Issue 1/2021
Electronic ISSN: 2040-2392
DOI
https://doi.org/10.1186/s13229-021-00464-4

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