ABSTRACT: In the United States, ∼12% of all neonates are born preterm. Prior excisional procedures to diagnose and treat cervical dysplasia are a risk factor of preterm delivery. Studies on the risk for preterm birth in women after cold knife conization, laser cone, or loop electrosurgical excision procedure (LEEP) have provided conflicting results. One consideration is whether the increased risk for preterm birth is attributable to the cervical excision procedure itself or secondary to risk factors associated with cervical dysplasia. This review was performed to assess whether LEEP increases the risk for preterm birth before 37 weeks’ gestation and to clarify whether the increased risk for preterm birth is attributable to the procedure or to risk factors associated with cervical dysplasia.
The review and meta-analysis were based on a predesigned protocol; PubMed, EMBASE, SCOPUS, CENTRAL, and ClinicalTrials.gov databases were searched. The review included cohort and case-control studies that compared rates of preterm birth in women with prior LEEP and women with no history of cervical excision. The primary outcome was preterm birth at less than 37 weeks. Secondary outcomes were preterm birth at less than 34 weeks, spontaneous preterm birth, preterm premature rupture of membranes, and perinatal mortality. The exposure was a history of LEEP for treatment of cervical dysplasia. Two unexposed categories included women with no or unknown history of cervical dysplasia and women with a history of cervical dysplasia but no excisional procedure. Data were analyzed using Stata 12.0 with METAN software.
From 559 publications, 47 studies were examined; the final analysis included 16 retrospective cohort and 2 prospective cohort studies and 1 case-control study. These reports comprised 6589 patients with a history of LEEP (exposed) and 1,415,015 without a history of LEEP (unexposed). All studies reported preterm birth at less than 37 weeks’ gestation as an outcome. Loop electrosurgical excision procedure was associated with a higher risk for preterm birth at less than 37 weeks (8.8% vs 5.1%; pooled relative risk (RR) 1.61; 95% confidence interval [CI], 1.35–1.92; P = 0.001). No statistically significant difference was found in the risk for preterm birth when the prior LEEP group was compared with women with a history of cervical dysplasia but no excision procedure (4 studies: 10.0% vs 7.2%; pooled RR, 1.08; 95% CI, 0.88–1.33; P = 0.654). The association between LEEP and preterm birth persisted when the comparison group was women with either no history or unknown history of dysplasia (15 studies: 8.6% vs 4.6%; pooled RR, 1.86; 95% CI, 1.58–2.21; P = 0.69). In 8 studies, spontaneous preterm birth at less than 37 weeks could specifically be assessed. Although a similar magnitude of increase in risk was found, it was not statistically significant (8 studies: 6.8% vs 3.4%; pooled RR, 1.60; 95% CI, 0.99–2.55). The risk for preterm premature rupture of membranes was increased greater than 2-fold in women with a history of LEEP (6 studies: 5.1% vs 2.5%; pooled RR, 2.37; 95% CI, 1.64–3.44), as was the risk for preterm birth at less than 34 weeks (5 studies: 2.9% vs 2.3%; pooled RR, 2.21; 95% CI, 1.33–3.67). The perinatal mortality risk was elevated in women with a prior LEEP but was not statistically significant (1.0% vs0.8%; pooled RR, 1.63; 95% CI, 0.95–2.80; P = 0.911).
Women with a prior LEEP are at increased risk for preterm birth before 37 weeks, but the risk was not significantly different when compared with women with prior dysplasia but no cervical excision. Risk factors of dysplasia and preterm birth are shared, and LEEP itself may not be an independent risk factor of preterm birth. If LEEP is not an independent risk factor of preterm birth, the risk and benefits of LEEP or expectant management might be altered, thus ensuring optimal therapy without fear of increasing the risk for preterm birth.
Departments of Obstetrics and Gynecology and Surgery, Washington University in St. Louis, St. Louis, MO