To our knowledge, there has not been a review article summarizing the current evidence with regard to perinatal risk factors, and our aim is to perform a systematic review and meta-analysis of the evidence of perinatal risk factors in single suture craniosynostosis to inform our practice and identify any need for further research in this area. Our target population was pediatric single-suture craniosynostosis patients, and the intervention was perinatal risk factors. The comparison group was an age and sex-matched control group without craniosynostosis and the outcome we investigated was presence of single suture craniosynostosis. The literature search was done using OVID MEDLINE, Pubmed, and Embase databases from 1946 to 2023. A PRISMA flowchart was created, and statistical analysis was performed using RevMan pooled odds ratios, and 95% CIs were used to combine results from individual studies. Our initial search identified 625 abstracts and these were narrowed down to 16 articles, which were included in the final selection for the review. Out of these, 13 were used for the quantitative meta-analysis. Our meta-analysis showed a possible association between craniosynostosis and the following perinatal risk factors; presence of maternal thyroid disease, maternal age greater than 29, paternal age greater than 29, maternal smoking, gestational age above 37 weeks, and maternal underweight (BMI<18.5). Further prospective studies are warranted to investigate definite associations. The next step is to set up a multicenter prospective study among a craniofacial unit network.

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