First-trimester prediction of preterm prelabour rupture of membranes incorporating cervical length measurement

Objectives: To examine early pregnancy risk factors for preterm prelabour rupture of membranes (PPROM) and develop a predictive model. Study design: Retrospective analysis of a cohort of mixed-risk singleton pregnancies screened in the first and second trimesters in three Danish tertiary fetal medicine centres, including a cervical length measurement at 11–14 weeks, at 19–21 weeks and at 23–24 weeks of gestation. Univariable and multivariable logistic regression analyses were employed to identify predictive maternal characteristics, biochemical and sonographic factors. Receiver operating characteristic (ROC) curve analysis was used to determine predictors for the most accurate model. Results: Of 3477 screened women, 77 (2.2%) had PPROM. Maternal factors predictive of PPROM in univariable analysis were nulliparity (OR 2.0 (95% CI 1.2–3.3)), PAPP-A < 0.5 MoM (OR 2.6 (1.1–6.2)), previous preterm birth (OR 4.2 (1.9–8.9)), previous cervical conization (OR 3.6 (2.0–6.4)) and cervical length ≤ 25 mm on transvaginal imaging (first-trimester OR 15.9 (4.3–59.3)). These factors all remained statistically significant in a multivariable adjusted model with an AUC of 0.72 in the most discriminatory first-trimester model. The detection rate using this model would be approximately 30% at a false-positive rate of 10%. Potential predictors such as bleeding in early pregnancy and pre-existing diabetes mellitus affected very few cases and could not be formally assessed. Conclusions: Several maternal characteristics, placental biochemical and sonographic features are predictive of PPROM with moderate discrimination. Larger numbers are required to validate this algorithm and additional biomarkers, not currently used for first-trimester screening, may improve model performance

Does low dose aspirin prescribed for risk of early onset preeclampsia reduce the prevalence of preterm prelabor rupture of membranes?

Background: Placental dysfunction, inflammation and degradation of fetal membranes has been hypothesized as a cause of preterm prelabor of rupture of membranes. Objective: To examine the effect of aspirin, an anti-inflammatory agent, on the prevalence of preterm prelabor rupture of membranes (PPRoMs). Methods: A retrospective analysis was conducted to examine the effect of aspirin on the prevalence of PPRoM. Aspirin (150 mg, nocte) was prescribed to women who were identified through a screening program at 11–13þ6 weeks’ gestation as being at high risk for developing earlyonset preeclampsia. Women who were at low risk for developing preeclampsia did not receive aspirin. The prevalence of PPRoM was compared with an observational cohort. Results: In the observational cohort, there were 3027 women, including 32 (1.1%) cases of PPRoM. The prevalence of PPRoM in the high risk group was 3.1% (4/128) and was statistically significantly higher compared to the low risk group (1.0%) (28/2899). The relative risk was 3.02 (95% CI 1.2–7.7; p¼ .04). In the interventional cohort, there were 7280 women, with 114 (1.6%) cases of PPRoM. The prevalence of PPRoM in the high risk group who were treated with aspirin was 1.8% (14/766) compared to 1.5% (100/6516) in the low risk group (p¼ .54). The prevalence of PPRoM in high risk patients in the observational group (who did not receive aspirin) compared with the high risk patients in the interventional group (who were treated with aspirin) was not statistically significant (p¼ .31). Conclusions: PPRoM is significantly associated with a description of high risk for ePET; although, this algorithm is not a good screening tool for predicting PPRoM. Aspirin treatment of women deemed high risk for ePET is safe in the context of PPRoM and there may be some reduction in prevalence of PPRoM in treated high risk women; although, this study was not powered to demonstrate a small reduction in the prevalence of PPRoM. The findings merit further investigation through a larger prospective study with adequate sample size

First-trimester prediction of preterm prelabour rupture of membranes

Background: Preterm prelabour rupture of membranes (PPRoM) is commonly associated with preterm delivery and affects up to 3% of all pregnancies. It is associated with high rates of morbidity and mortality for the mother and the newborn. Objectives: To identify risk factors for PPRoM and develop a model for first-trimester prediction of risk of PPRoM. Methods: A retrospective analysis of a series of women who had first-trimester (11–13+6 weeks) screening for aneuploidy and pre-eclampsia and delivered in the same institution was performed. Univariate and multivariate logistic regression analyses were used to identify maternal and pregnancy factors and then develop a clinical prediction model for PPRoM. Results: 10,280 women were screened between April 2010 and October 2016. 144 (1.4%) had PPRoM. Maternal factors predictive of PPRoM included nulliparity (parous women, OR 0.53; 95% CI 0.4–0.8), pre-existing diabetes mellitus (DM) (Type 1 DM, OR 6.7; 95% CI 2.3–19.4, Type 2 DM, OR 5.3; 95% CI 1.6–18.3), maternal age group (p = 0.004), and BMI category (p = 0.012). Uterine artery pulsatility index (UAPI) and biochemical parameters (PAPP-A, free βHCG) did not reach statistical significance. The predictive model had moderate efficacy with an area under the ROC curve of 0.67. Conclusions: Several maternal characteristics collected during first-trimester screening predict PPRoM. Biomarkers currently measured during first-trimester screening (PAPP-A, βHCG, and UAPI) do not predict PPRoM. Whilst a predictive model can be generated with information currently collected at 11–13+6 weeks, this has only modest screening performance. First-trimester screening provides a structured framework where other predictors could improve model performance, and future studies should focus on the addition of other risk factors and biomarkers that may improve screening efficacy