Purpose: 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.
Methods: 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.
Results: 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)).
Conclusions: Only 45 non-genetic factors had statistically significant associations without bias and heterogeneity, but were classified in the associations supported by suggestive evidence group because the PI (95%) included the null value.
Keywords: Early pregnancy loss; Miscarriage; Non-genetic factors; Risk factors; Spontaneous abortion; Umbrella review.
© 2025. The Author(s).