Maternal stressful life events during the periconceptional period and orofacial clefts: a systematic review and meta-analysis

Christina Tran*, Andrew A Crawford, Alexander J Hamilton, Clare E French, Yvonne E Wren, Jonathan R Sandy, Gemma C Sharp

*Corresponding author for this work

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To assess whether women who experience stressful life events during the periconceptional period are at higher risk of giving birth to a baby with an orofacial cleft (OFC).

Systematic review and meta-analysis of studies reporting the proportion of babies born with OFC to mothers exposed and unexposed to population-level or personal-level stressful life events during the periconceptional period. Six electronic databases were searched from inception to August 2020. Risk of bias was assessed using the Newcastle-Ottawa scale. Odds ratios (ORs) for the odds of OFC in babies of exposed mothers relative to unexposed controls were extracted and/or calculated. Random effects meta-analysis was undertaken, stratified by cleft subtype.

Of 12 eligible studies, 8 examined experience of personal events and 4 examined population-level events. Studies demonstrated low-moderate risk of bias and there was indication of publication bias. There was some evidence that personal stressful life events were associated with greater odds of cleft lip and/or palate (six studies, OR 1.63, 95% confidence interval (CI) 1.16, 2.30, P = 0.001) and cleft palate only (six studies, OR 1.45, 95% CI 1.02, 2.06, P = 0.04). Population-level events were associated with higher odds of OFC in studies that did not specify subtype (three studies, OR 1.64, 95% CI 1.19, 2.25, P = 0.002), but subtype stratified analyses were underpowered. Heterogeneity was high.

Limited evidence indicated a weak positive association between maternal stressful life events during the periconceptional period and risk of OFC in the offspring, but further studies with greater consistency in research design are needed.
Original languageEnglish
Number of pages11
JournalCleft Palate-Craniofacial Journal
Publication statusPublished - 11 Jan 2022

Bibliographical note

Funding Information:
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the University of Bristol (grant number MRC MR/S036520/1, MC_UU_00011/5, MR/S009310/1).

Funding Information:
AH is funded through a National Institute for Health Research (NIHR) Clinical Lectureship

Funding Information:
Christina Tran received funding from the INSPIRE vacation studentship.

Publisher Copyright:
© 2022, American Cleft Palate-Craniofacial Association.


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