Subsequent risk for preterm birth following second trimester medical termination of pregnancy.

BACKGROUND Medical termination of pregnancy (using mifepristone and misoprostol) is a commonly performed health intervention. High quality cohort studies are warranted to investigate the association of second-trimester medical termination of pregnancy and subsequent pregnancy outcomes. OBJECTIVE This study aims to assess the risk of subsequent spontaneous preterm birth following second trimester medical termination of pregnancy. STUDY DESIGN We performed a cohort study in the Amsterdam University Medical Centre, location AMC. We included all individuals who underwent a second trimester medical termination of pregnancy between 2008-2023 using mifepristone and/or misoprostol and had a known subsequent pregnancy up to 2024. Exclusion criteria were other methods of termination (e.g. cesarean section, hysterectomy, curettage or foley catheter) and indication for mTOP due to intra-uterine fetal demise or previable prelabor rupture of membranes. The primary outcome was spontaneous preterm birth < 37 weeks in the subsequent pregnancy. Secondary outcomes included subsequent miscarriage < 16 weeks, repeated termination, and rates of total, spontaneous and iatrogenic preterm birth < 37, < 32 and < 28 week. Subgroup analyses were performed on the interpregnancy interval, gestational age at medical termination of pregnancy and postpartum surgical interventions using logistic regression estimating odds ratios (OR) and 95% confidence intervals, with adjustment for confounders. Subsequent singleton and multiple pregnancies were assessed separately. RESULTS Out of the 1,438 eligible cases, 1,033 were known to have a subsequent pregnancy of which 986 outcomes were available (singletons n=962, multiples n=24). In subsequent singleton pregnancies exceeding 16 weeks, spontaneous preterm birth < 37 weeks occurred in 39/831 cases (4.7%). In multiples, spontaneous preterm birth < 37 weeks occurred in 4/24 cases (16.7%). In subsequent singletons, rates of spontaneous preterm birth < 37 weeks were higher following an IPI < 3 months compared to 12-24 months (6.8% vs 3.2% aOR 2.2 95% CI 0.69-7.4, p-value 0.2), and higher for a GA >20 weeks at mTOP compared to < 12+0 - 15+6 weeks (5.9% vs 2.6% aOR 2.2 95% CI 0.92 - 5.4, p-value 0.07), though both not statistically significant. However, when gestational age at mTOP was included as a continues variable (in weeks) in a linear regression model, a significant positive association with subsequent spontaneous preterm birth was found (B=0.56, R2=0.31, p=0.04). CONCLUSION Second-trimester medical termination of pregnancy can be considered safe with regards to subsequent spontaneous preterm birth risk. As recommended following preterm and term birth, patient counseling should include the importance of allowing time for cervical remodeling to mitigate preterm birth risks, especially for those with a medical termination of pregnancy at higher gestational ages.