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Published in: BMC Medicine 1/2023

Open Access 01-12-2023 | Research article

Risk factors for preterm birth: an umbrella review of meta-analyses of observational studies

Authors: Ioannis Mitrogiannis, Evangelos Evangelou, Athina Efthymiou, Theofilos Kanavos, Effrosyni Birbas, George Makrydimas, Stefania Papatheodorou

Published in: BMC Medicine | Issue 1/2023

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Abstract

Background

Preterm birth defined as delivery before 37 gestational weeks is a leading cause of neonatal and infant morbidity and mortality. The aim of this study is to summarize the evidence from meta-analyses of observational studies on risk factors associated with PTB, evaluate whether there are indications of biases in this literature, and identify which of the previously reported associations are supported by robust evidence.

Methods

We searched PubMed and Scopus until February 2021, in order to identify meta-analyses examining associations between risk factors and PTB. For each meta-analysis, we estimated the summary effect size, the 95% confidence interval, the 95% prediction interval, the between-study heterogeneity, evidence of small-study effects, and evidence of excess-significance bias. Evidence was graded as robust, highly suggestive, suggestive, and weak.

Results

Eighty-five eligible meta-analyses were identified, which included 1480 primary studies providing data on 166 associations, covering a wide range of comorbid diseases, obstetric and medical history, drugs, exposure to environmental agents, infections, and vaccines. Ninety-nine (59.3%) associations were significant at P < 0.05, while 41 (24.7%) were significant at P < 10−6. Ninety-one (54.8%) associations had large or very large heterogeneity. Evidence for small-study effects and excess significance bias was found in 37 (22.3%) and 12 (7.2%) associations, respectively. We evaluated all associations according to prespecified criteria. Seven risk factors provided robust evidence: amphetamine exposure, isolated single umbilical artery, maternal personality disorder, sleep-disordered breathing (SDB), prior induced termination of pregnancy with vacuum aspiration (I-TOP with VA), low gestational weight gain (GWG), and interpregnancy interval (IPI) following miscarriage < 6 months.

Conclusions

The results from the synthesis of observational studies suggest that seven risk factors for PTB are supported by robust evidence. Routine screening for sleep quality and mental health is currently lacking from prenatal visits and should be introduced. This assessment can promote the development and training of prediction models using robust risk factors that could improve risk stratification and guide cost-effective preventive strategies.

Trial registration

PROSPERO 2021 CRD42021227296.
Appendix
Available only for authorised users
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Metadata
Title
Risk factors for preterm birth: an umbrella review of meta-analyses of observational studies
Authors
Ioannis Mitrogiannis
Evangelos Evangelou
Athina Efthymiou
Theofilos Kanavos
Effrosyni Birbas
George Makrydimas
Stefania Papatheodorou
Publication date
01-12-2023
Publisher
BioMed Central
Published in
BMC Medicine / Issue 1/2023
Electronic ISSN: 1741-7015
DOI
https://doi.org/10.1186/s12916-023-03171-4

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