Precocious cervical ripening as a screening target to predict spontaneous preterm delivery among asymptomatic singleton pregnancies: a systematic review

Abstract

Routine second-trimester transvaginal ultrasonographic (TVU) screening for short cervical length (CL) predicts spontaneous preterm delivery (SPTD), albeit with limited sensitivity (35–40%) and moderate positive likelihood ratio (LR+: 4–6). However, CL describes one of multidimensional changes associated with precocious cervical ripening (PCCR), which also include cervical softening, cervical funneling (CF), and dilation. PCCR, a precursor and a strong predictor for SPTD, was proposed as a potential screening target. We hypothesized that screening for composite measures of PCCR (e.g. CL, CF, cervical consistency, and dilation) using either digital exam (DE) or TVU would improve prediction of SPTD compared to screening for short CL alone. We searched PubMed and EMBASE electronic databases for observational cohort studies to evaluate cervical screening in asymptomatic obstetric populations. Multidimensional composite cervical measures were assessed in 10 datasets (n=22,050 pregnancies) and 12 publications. Appreciable heterogeneity in cervical measurements, data quality, and outcomes across studies prevented quantitative meta-analysis. Only one study reported intra- and inter-observer reliability of cervical measurements. The prevalence of CF ranged from 0.7% to 9.1%. Five studies compared composite measures of PCCR (i.e., CL and CF) to short CL alone, and consistently reported improved screening performance. Among three TVU studies, gains in sensitivity ranged from 5% to 27%, and increases in LR+ ranged from 3 to 16. Our findings suggest composite measures of PCCR might serve as valuable screening targets. High-quality interdisciplinary studies integrating epidemiologic approaches are needed to test this hypothesis and accelerate the translation of advances in cervical pathophysioloy into effective preventive interventions.

Vaginal progesterone decreases preterm birth ≤ 34 weeks of gestation in women with a singleton pregnancy and a short cervix: an updated meta‐analysis including data from the OPPTIMUM study

“…Preterm birth is a syndrome attributable to multiple pathological processes such as infection, vascular disorders, decidual senescence, uterine overdistension, a decline in progesterone action, cervical disease, breakdown of maternal‐fetal tolerance and stress, among others. A short cervix, traditionally defined as a transvaginal sonographic cervical length (CL) ≤ 25 mm in the mid‐trimester of pregnancy, is an important risk factor for preterm birth and has emerged as one of the strongest and most consistent predictors of preterm birth in asymptomatic women with a singleton or twin gestation.…”

Vaginal progesterone to prevent preterm birth in pregnant women with a sonographic short cervix: clinical and public health implications

“…8 Today, a short cervix is a well-accepted risk factor for preterm birth 9–12 and one of the strongest predictors of preterm birth in both singleton 13–18 and twin 17,19–22 gestations. In the absence of any intervention, an estimated 17% of infants born to mothers with a CL ≤25 mm before 25 weeks of gestation will die during the neonatal period or develop major neonatal complications such as respiratory distress syndrome, intraventricular hemorrhage, necrotizing enterocolitis, or neonatal sepsis.…”

17 alpha-hydroxyprogesterone caproate does not prolong pregnancy or reduce the rate of preterm birth in women at high risk for preterm delivery and a short cervix: a randomized controlled trial

“…A second-trimester measurement of cervical length (CL) by transvaginal ultrasound (TVU) can predict the likelihood of PTB. [5][6][7][8][9] Furthermore, recent studies and metaanalyses have provided sound evidence about the benefits of prophylactic progestogen for stopping progression to PTB. [10][11][12][13][14] In 2003, Meis et al 15 published the results of their double-blind, placebocontrolled trial of pregnant women with a documented history of spontaneous PTB: weekly injections of 17 alphahydroxyprogesterone caproate (17OHP-C) substantially reduced the rate of recurrent PTB and therefore the risk of several specific neonatal complications.…”