Is cervical treatment for preinvasive and early invasive disease associated with subsequent adverse obstetric outcomes?
Cervical treatments for dysplasia and early cervical carcinoma are associated with subsequent risk of preterm birth. Excisional treatments carry higher risk than ablative treatments, and multiple treatments carry higher risk than single treatments. The frequency and severity of prematurity-related outcomes increase with increasing cone depth and volume. (Level of Evidence = 2a)
This report is a meta-analysis of observational studies to assess the associations between local treatments for cervical intraepithelial neoplasia or early invasive carcinoma and subsequent obstetric outcomes. The authors included 71 studies (70 cohort, one case-control) with 65,082 treated women and 6,292,563 untreated women. Several types of untreated comparison groups were used, including a small subset in which women with high-grade lesions were not treated. The overall risk of premature birth (before 37 weeks' gestation) was higher among treated women than among untreated women (relative risk [RR] = 1.78; 95% confidence interval [CI], 1.60 to 1.98). It was also higher for severe prematurity (32 to 34 weeks' gestation) and extreme prematurity (28 to 30 weeks' gestation), with RRs of 2.40 (95% CI, 1.92 to 2.99) and 2.54 (95% CI, 1.77 to 3.63), respectively.
The magnitude of effect was higher for excision over ablative treatments (e.g., the RR of prematurity was 2.7 [95% CI, 2.14 to 3.40] with cold knife conization and 1.46 [95% CI, 1.27 to 1.66] for ablation not otherwise specified). Within excisional treatments, the magnitude of effect was greater with greater depth of cone (up to RR of 4.91 for 20 mm or more) and greater volume of excision (up to RR of 13.9 for 6 mL or more). Multiple treatments were associated with progressively greater risk (e.g., the RR for two excisional treatments was 5.48; 95% CI, 2.68 to 11.24). Subgroup analyses were performed on the different types of untreated comparison groups. The increase in risk of prematurity was attenuated when the untreated comparison group was composed of women who also had cervical intraepithelial neoplasia (RR = 1.27; 95% CI, 1.14 to 1.41), which implies an increase in baseline risk of prematurity due to the disease process itself in addition to the effects of cervical treatments. The risks of spontaneous preterm labor and chorioamnionitis were also increased among treated women. Neonatal outcomes were as expected related to prematurity.
Study design: Meta-analysis
Funding source: Foundation
Setting: Various (meta-analysis)
Reference: KyrgiouMAthanasiouAParaskevaidiMet alAdverse obstetric outcomes after local treatment for cervical preinvasive and early invasive disease according to cone depth: systematic review and meta-analysis. BMJ2016;354:i3633.