Non-genetic risk factors of miscarriage: a comprehensive umbrella review of systematic review and meta-analysis
Abstract
Numerous systematic reviews have examined the non-genetic factors associated with the risk of miscarriage. Therefore, this study aimed to conduct an umbrella review on non-genetic factors associated with the risk of miscarriage. Scopus, PubMed, Embase, and Web of Science were searched until 2025 and the systematic review and meta-analysis articles that were conducted on observational studies were extracted. Quality assessment of the selected review articles was done by AMSTAR. For each selected meta-analysis, the summary effect size with the 95% confidence interval was estimated using the random-effects model and the predictive interval (PI) at 95% was estimated too. The between-study heterogeneity was assessed by the I2 index. In addition, two biases, including small-study effects and excess statistical significance, were investigated. Finally, 147 meta-analyses and 29 systematic review studies remained. None of the factors met all the necessary criteria and showed a definite association. However, 45 factors were classified as associations supported by suggestive evidence. Among these 45 factors, three factors—hypothyroidism, high serum β-human chorionic gonadotropin, and hairdressers—included the most complete information (they had more than 1,000 cases, significant based on the random-effects model, p < 0.001, respectively; (2/01(1/66–2/44), 2/88(1/76–4/68), 1/28(1/11–1/47)). Only 45 non-genetic factors had statistically significant associations without bias and…
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