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Background: Preterm labor and the following preterm births, which account for most of the perinatal deaths, are an important issue in public health. The study aims to assess the risk of subsequent preterm labor in pregnant females who have prepregnancy polycystic ovary syndrome (PCOS). Methods: This study has enrolled 1,000,000 randomly sampled females retrieved from the Taiwan National Health Insurance Research Database (NHIRD) during 1998–2012. The study excluded prepregnancy PCOS females who were initially diagnosed at age  45, and those who had inconsistent diagnoses. Moreover, the medical records of blood hormone tests, gynecologic ultrasonography, pelvic examinations, and tocometers were verified to confirm the accuracy of both diagnoses of PCOS and preterm labor. Among the prepregnancy PCOS females who became pregnant (the case group), each was age-matched to four females without prepregnancy PCOS (the control group). Results: Pregnant females in the case group (n = 1959) had a higher incidence of preterm labor than those in the control group (n = 7836) (42.98% vs. 21.99%, p &lt; 0.0001). Analyzed by using logistic regression, the risk of preterm labor was significantly higher in the case group compared with the control group (crude OR: 2.674; 95% CI: 2.410–2.968, p &lt; 0.0001). After adjustment with covariates, further analysis revealed a similar trend (adjusted OR: 2.405; 95% CI: 2.158–2.680, p &lt; 0.0001). Among 1959 PCOS females in the case group, 196 had undergone metformin treatment. Compared with females without metformin treatment (the non-metformin subgroup), the metformin users (metformin subgroup) presented a reduced risk for preterm labor (adjusted OR: 2.238; 95% CI: 1.657–3.023). The risk of subsequent preterm labor was reduced by about 10% for the metformin subgroup compared with the non-metformin subgroup. Conclusions: Prepregnancy PCOS is an independent and significant risk factor of subsequent preterm labor. Among prepregnancy PCOS females, the risk of preterm labor is lowered by about 10% in metformin users compared with non-metformin females.

Prepregnancy Polycystic Ovary Syndrome as a Risk Factor of Subsequent Preterm Labor: A National Population-Based Cohort Study