Preterm Birth Following Active Surveillance vs Loop Excision for Cervical Intraepithelial Neoplasia Grade 2

Importance: Active surveillance for cervical intraepithelial neoplasia grade 2 (CIN2) is being implemented in many high-income countries due to the association of excisional treatment with preterm birth. However, it is unknown whether active surveillance results in lower risk of preterm birth given that cervical dysplasia itself is associated with higher risk of preterm birth. Objective: To compare the preterm birth risk between women with CIN2 undergoing active surveillance or immediate loop electrosurgical excision procedure (LEEP). Design, Setting, and Participants: This historical population-based cohort study included women with a first-time diagnosis of CIN2 and a subsequent singleton birth from 1998 to 2018 in Denmark. Women with prior CIN grade 3 or greater or LEEP were excluded. Data were collected from 4 Danish health care registries. Analyses were conducted from October 2022 to June 2023. Exposure: Women were categorized into active surveillance (cervical biopsy and/or cytology) or immediate LEEP based on their first cervical sample after CIN2 diagnosis. The active surveillance group was further subdivided based on whether a delayed LEEP was performed within 28 months from CIN2 diagnosis. Main Outcomes and Measures: Risk of preterm birth (<37 + 0 weeks) was assessed and relative risks (RRs) were calculated using modified Poisson regression. Analyses used inverse probability treatment weighting of the propensity scores to adjust for age, parity, calendar year, index cytology, and smoking. Results: A total of 10 537 women with CIN2 and a singleton birth were identified; 4430 (42%) underwent active surveillance and 6107 (58%) were treated with immediate LEEP. For both groups, most were aged 23 to 29 years at CIN2 diagnosis (3125 [70%] and 3907 [64%], respectively). Overall, 869 births (8.2%) were preterm. The risk of preterm birth was comparable between active surveillance and immediate LEEP (RR, 1.03; 95% CI, 0.90-1.18). However, for women undergoing delayed LEEP after active surveillance (1539 of the active surveillance group [35%]), the risk of preterm birth was higher than for women treated with immediate LEEP (RR, 1.29; 95% CI, 1.08-1.55). Conclusions and relevance: In this cohort study of women with CIN2, the risk of preterm birth was comparable between active surveillance and immediate LEEP. However, delayed LEEP was associated with 30% higher risk of preterm birth than immediate LEEP. Thus, risk stratification at CIN2 diagnosis is important to identify women with increased risk of delayed LEEP.