Evidence map›Paper›PMID 34537069›Full record

SynthesisMolecular autism2021

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

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

Open access · goldAbstract readMeta-AnalysisSystematic Review
In one paragraph

Synthesis in Molecular autism, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed, 4 pooled it
9.7field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

38 citing papers in PubMed, 4 syntheses or guidelines pooled it, 48 citations in OpenAlex.

  1. Pooled it
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  5. Article
  6. CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne · 2026
    Article
  7. Genes · 2026
    Article
  8. Article
  9. Article
  10. Acetaminophen in pregnancy.CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne · 2026
    Article
  11. Emerging Discussions on Folinic Acid and Acetaminophen in Autism.Journal of autism and developmental disorders · 2026
    Article
  12. Article
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  14. Paracetamol in Pregnancy: Reassurance Amidst Uncertainty.BJOG : an international journal of obstetrics and gynaecology · 2026
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 4 institutions in 2 countries.

Stephanie Antoun *Child and Adolescent Psychiatry Department, Robert Debré Hospital, APHP, Paris University, Paris, France. stephanie.antoun@aphp.fr.ORCID 0000-0002-2911-1607
Pierre Ellul *Child and Adolescent Psychiatry Department, Robert Debré Hospital, APHP, Paris University, Paris, France.
Hugo PeyreChild and Adolescent Psychiatry Department, Robert Debré Hospital, APHP, Paris University, Paris, France.
Michelle RosenzwajgImmunology-Immunopathology-Immunotherapy (i3), INSERM U959, Sorbonne University, Paris, France.
Pierre GressensUniversité de Paris, Inserm UMR, 1141 NeuroDiderot, Paris, France.
David KlatzmannImmunology-Immunopathology-Immunotherapy (i3), INSERM U959, Sorbonne University, Paris, France.
Richard DelormeChild and Adolescent Psychiatry Department, Robert Debré Hospital, APHP, Paris University, Paris, France.
Inserm · FRAssistance Publique – Hôpitaux de Paris · FRInstitut Pasteur · FRSt Thomas' Hospital · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundFever 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.

methodsPeer-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).

resultsWe 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).

conclusionAdditional 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).

Indexed as

Neurodevelopmental DisordersPregnancy ComplicationsChildFemaleHumansMothersPregnancyPregnancy Trimester, FirstRisk FactorsAutismChildrenImmunologyMaternal immune activation

Identifiers

PMID34537069
PMCPMC8449704
OpenAlexW3201321086

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.