Subsequent risk of preterm birth after 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 between second-trimester medical termination of pregnancy and subsequent pregnancy outcomes. Objective: This study aimed to assess the risk of subsequent spontaneous preterm birth after second-trimester medical termination of pregnancy. Study Design: This was a cohort study performed at the Amsterdam University Medical Center of the University of Amsterdam. All individuals who underwent a second-trimester medical termination of pregnancy between 2008 and 2023 using mifepristone and/or misoprostol and had a known subsequent pregnancy up to 2024 were included. The exclusion criteria were other methods of termination (eg, cesarean delivery, hysterectomy, curettage, or Foley catheter) and indication for medical termination of pregnancy due to intrauterine fetal demise or preterm premature rupture of membranes. The primary outcome was spontaneous preterm birth at <37 weeks of gestation in the subsequent pregnancy. The secondary outcomes included subsequent miscarriage at <16 weeks of gestation, repeated termination, and rates of total, spontaneous, and iatrogenic preterm births at <37, <32, and <28 weeks of gestation. 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 and 95% confidence intervals, with adjustment for confounders. Subsequent singleton and multiple pregnancies were assessed separately. Results: Of 1438 eligible cases, 1033 were known to have a subsequent pregnancy, of which 986 outcomes were available (962 singleton pregnancies and 24 multiple pregnancies). In subsequent singleton pregnancies exceeding 16 weeks of gestation, spontaneous preterm birth at <37 weeks of gestation occurred in 39 of 831 cases (4.7%). In multiple pregnancies, spontaneous preterm birth at <37 weeks of gestation occurred in 4 of 24 cases (16.7%). In subsequent singleton pregnancies, the rates of spontaneous preterm birth at <37 weeks of gestation were higher after an interpregnancy interval of <3 months than an interpregnancy interval of 12 to 24 months (6.8% vs 3.2%, respectively; adjusted odds ratio, 2.2 [95% confidence interval, 0.69–7.40]; P=.2) and higher for a gestational age of >20 0/7 weeks at medical termination of pregnancy than a gestational age of <12 0/7 to 15 6/7 weeks (5.9% vs 2.6%, respectively; adjusted odds ratio, 2.2 [95% confidence interval, 0.92–5.4]; P=.07). However, both results were not statistically significant. However, when gestational age at medical termination of pregnancy was included as a continuous 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=.04). Conclusion: Second-trimester medical termination of pregnancy can be considered safe with regard to subsequent spontaneous preterm birth risk. As recommended after preterm and term births, patient counseling should include the importance of allowing time for cervical remodeling to mitigate preterm birth risks, particularly for those with a medical termination of pregnancy at higher gestational ages.