The risk of preterm birth of treated versus untreated cervical intraepithelial neoplasia (CIN): a systematic review and meta-analysis

Cervical surgery is associated with preterm birth (PTB) and neonatal morbidity. However, it is unknown whether this increased risk is due to the surgery itself or to the cervical intraepithelial neoplasia (CIN) underlying the surgery. Our objective was to assess the risk for PTB in women with treated and untreated CIN. We performed an electronic literature search in MEDLINE, Embase and CENTRAL for studies that reported on pregnancy outcome after treated and untreated CIN. The methodological quality was scored using the STROBE combined checklist for observational studies. We extracted data on PTB <37 weeks, very PTB <32 weeks, spontaneous PTB <37 weeks, (preterm) premature rupture of membranes ((P)PROM), perinatal mortality and section caesarean each before and after treatment for CIN. We used the Mantel-Haenszel method to estimate summarizing odds ratios. Our search identified 620 studies, of which 20 were reporting on pregnancy outcome for a total of 12,159,293 women. There were 20,832 women who gave birth after treatment for CIN before pregnancy, 52 women who gave birth after treatment for CIN during pregnancy, 64,237 women with CIN who gave birth before treatment, and 8,902,865 women who gave birth without CIN. Compared to women with untreated CIN, women treated for CIN before or during pregnancy, had a significantly higher risk of PTB <37 weeks (OR 1.7, 95% CI 1.0-2.7). When comparing women treated for CIN before pregnancy (n=20,832) to women with untreated CIN (n=64,162), we found an OR of 1.4 with a 95% confidence interval of 0.85-2.3. Women treated during pregnancy had a clearly increased risk for PTB (OR 6.5, 95% CI 1.1-37), and (P)PROM (OR 1.8, 95% CI 1.4-2.2). In women with cervical surgery, the risks for spontaneous PTB <37 weeks (OR 0.87, 95% CI 0.54-1.4), caesarean section (OR 1.0, 95% CI 0.71-1.5) and perinatal mortality (OR 1.0, 95% CI 0.38-2.8) were not increased. The increased risk of PTB in women who underwent cervical surgery for CIN is especially increased when performed during pregnancy. When performed before pregnancy the risk of PTB is increased, although insignificant