Cervical length and quantitative fetal fibronectin in the prediction of spontaneous preterm birth in asymptomatic women with congenital uterine anomaly

Abstract

Short Title: Preterm birth prediction by cervical length and quantitative fetal 31 fibronectin in congenital uterine anomalies. 32 33 AJOG at a GLANCE: 34 A: Why was the study conducted? 35 • To assess the performance of current predictive markers of sPTB, quantitative 36 fetal fibronectin (qfFN) and transvaginal cervical length (CL) measurement in 37 asymptomatic high-risk women with Congenital Uterine Anomalies (CUA) 38 • To characterise rates of early delivery by type of CUA 39 B: What are the key findings? 40 • CUA, particularly fusion defects, are associated with high rates of late 41 miscarriage and PTB 42• CL and qfFN have utility in prediction of sPTB in women with resorption 43 defects, however were no better than chance in women with fusion defects. 44This is contrary to other high-risk populations." 45 C: What does this study add to what is already known? 46 These findings need to be accounted for when planning antenatal care and have 47 potential implications for the predictive tests used in sPTB surveillance and 48 intervention.49 50 Abstract 58 59 Background: Congenital uterine anomalies (CUA) are associated with late 60 miscarriage and spontaneous preterm birth (sPTB). 61 62 Objectives: Our aim was to 1) determine the rate of sPTB in each type of CUA and 63 2) assess the performance of quantitative fetal fibronectin (qfFN) and transvaginal 64 cervical length (CL) measurement by ultrasound in asymptomatic women with CUA 65 for the prediction of sPTB at <34 and <37 weeks of gestation. 66 67 Study design: This was a retrospective cohort of women with CUA asymptomatic 68 for sPTB, from four UK tertiary referral centres (2001-2016). CUAs were categorised 69 into fusion (unicornuate, didelphic and bicornuate uteri) or resorption defects 70 (septate, with or without resection and arcuate uteri), based on pre-pregnancy 71 diagnosis. 72All women underwent serial transvaginal ultrasound CL assessment in the second 73 trimester (16 to 24 weeks' gestation); a subgroup underwent qfFN testing from 18 74 weeks' gestation. We investigated the relationship between CUA and predictive test 75 performance for sPTB before 34 and 37 weeks' gestation. 76 77 Results: Three hundred and nineteen women were identified as having CUA within 78 our high-risk population. 7% (23/319) delivered spontaneously <34 weeks, and 18% 79 (56/319) <37 weeks' gestation. Rates of sPTB by type were: 26% (7/27) for 80 M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT 5unicornuate, 21% (7/34) for didelphic, 16% (31/189) for bicornuate, 13% (7/56) for 81 septate and 31% (4/13) for arcuate. 82 80% (45/56) of women who had sPTB <37 weeks did not develop a short CL (<25 83 mm) during the surveillance period (16-24 weeks). The diagnostic accuracy of short 84 CL had low sensitivity (20.3) for predicting sPTB <34 weeks. 85Cervical Length had ROC AUC of 0.56 (95% CI 0.48 to 0.64) and 0.59 (95% CI 86 0.55 to 0.64) for prediction of sPTB <34 and 37 weeks' respectively. 87The AUC for CL to predict sPTB <34 weeks was 0.48 for fusion defects (95% CI 0...

Cervical length surveillance for predicting spontaneous preterm birth in women with uterine anomalies: A cohort study

“…The apparently stronger association between short cervix and SPTB in the septate uterus subgroup warrants further analysis, but small numbers precluded this. The larger study by Ridout et al 12 suggests that the association we found is valid, and our study, although smaller, provides independent evidence supporting the other report.…”

“…This increases the possibility of a type II error, in that an association between short cervix and SPTB might truly exist but could not be detected in this small group. However, a larger study 12 drew similar conclusions, adding weight to our findings.…”

“…Crane et al 11 studied 52 women with uterine anomalies and reported that TVUS cervical length measurement <30 mm was predictive of SPTB <35 weeks (odds ratio [OR] 62.1, 95% CI 5.7‐676). Most recently, Ridout et al 12 described outcomes from 319 women with uterine anomalies, in whom a short cervix <25 mm did not predict SPTB <37 or 34 weeks. When subgroup analysis was performed, however, short cervix was shown to predict SPTB in women with resorption defects (area under the curve [AUC] 0.80, 95% CI 0.62‐0.97 for women with septate uterus, AUC 0.83, 95% CI 0.51‐0.98 for women with arcuate uterus), but not fusion defects.…”

Cervical Assessment for Predicting Preterm Birth—Cervical Length and Beyond

“…A recent study [53] described outcomes of 319 women with uterine anomalies, in whom a short cervix <25 mm did not predict sPTB at <37 or <34 weeks. However, in subgroup analysis, a short cervix was shown to predict sPTB in women with resorption defects but not fusion defects.…”

Preterm birth prediction in asymptomatic women at mid-gestation using a panel of novel protein biomarkers: the Prediction of PreTerm Labor (PPeTaL) study

“…It is worth noting that the single patient with spontaneous preterm labor that was incorrectly classified was known to have a uterine anomaly, and that this may explain the false-negative classification, as the mechanism of PTB likely relates to myometrial stretch rather than cervical mechanisms. 9…”