Racial disparities in cervical length for prediction of preterm birth in a low risk population

Purpose: Racial minorities experience higher rates of spontaneous preterm birth (sPTB). Our objective was to evaluate whether there are racial discrepancies in the incidence of second trimester short cervical length (≤25?mm).

Materials and methods: Retrospective cohort of women with singleton gestations without prior sPTB undergoing universal second trimester transvaginal ultrasound cervical length (CL) screening between January 2012 and December 2013. Black women were compared to non-Hispanic white women. Our primary outcome was the incidence of CL ≤25?mm. Secondary outcomes were incidence of PTB ≤37 weeks, delivery mode, birth weight and neonatal intensive care unit (NICU) admission.

Results: Black women (n?=?1092) differed from non-Hispanic white women (n?=?659) with respect to maternal age (26.0 versus 30.7 years), gravidity (3.1 versus 2.1), prepregnancy BMI (29.6 versus 25.0?kg/m²), and smoking status (9.8% versus 16%), respectively (p?Conclusions: Black women had a 2.8-fold increased risk of CL ≤25?mm compared non-Hispanic white women in a low-risk population.     

Cervical length,risk factors,and delivery outcomes among women with spontaneous preterm birth

Objectives: To evaluate differences in risk factors and delivery outcomes among women with spontaneous preterm birth (sPTB) with short (≤25?mm) versus normal (>25?mm) cervical length (CL).

Methods: Secondary analysis of a prospective cohort study of singleton gestations between 18 0/7 and 23 6/7 weeks, without prior sPTB, undergoing universal transvaginal CL screening between 1 January 2012 and 31 December 2013. Only women with sPTB (<37 0/7 weeks) were included. Demographic characteristics, risk factors for sPTB, delivery outcomes and presentation of PTB were collected. The primary outcome was mean number of risk factors.

Results: The cohort included 2071 women, of which 145 (7%) had PTB and 84 (4%) had sPTB. Sixty-nine (82%) women with sPTB had a CL >25?mm and 15 (18%) had a CL≤25?mm. Women with a short CL did not differ from women with normal CL with respect to demographic variables or mean number of risk factors (4.20?±?2.11 versus 3.52?±?1.97, p?=?0.23), but they did deliver at a significantly earlier gestational age (25.0?±?1.1 versus 34.6?±?3.1 weeks, p?<?0.01). The distribution of the presentation of sPTB was different in women with a short versus normal CL (p?<?0.01).

Conclusions: Among women with sPTB, women with a short CL had similar number of risk factors, but were more likely to deliver at a significantly earlier gestational age. A short CL identifies women at risk for very early sPTB.     

Salivary progesterone and cervical length measurement as predictors of spontaneous preterm birth

Objective: To evaluate the efficacy of salivary progesterone, cervical length measurement in predicting preterm birth (PTB).

Methods: Prospective observational study included 240 pregnant women with gestational age (GA) 26–34 weeks classified into two equal groups; group one are high risk for PTB (those with symptoms of uterine contractions or history of one or more spontaneous preterm delivery or second trimester abortion) and group 2 are controls.

Results: There was a highly significant difference between the two study groups regarding GA at delivery (31.3?±?3.75 in high risk versus 38.5?±?1.3 in control), cervical length measured by transvaginal ultrasound (24.7?±?8.6 in high risk versus 40.1?±?4.67 in control) and salivary progesterone level (728.9?±?222.3 in high risk versus 1099.9?±?189.4 in control; p?p value 0.035) but not in low risk group (p value 0.492). CL measurement showed a sensitivity of 71.5% with 100% specificity, 100% PPV, 69.97% NPV and accuracy of 83%, while salivary progesterone showed a sensitivity of 84% with 90% specificity, 89.8% PPV, 85.9% NPV and accuracy of 92.2%.

Conclusion: The measurement of both salivary progesterone and cervical length are good predictors for development of PTB.     

The retrospective study for effectiveness of cervical cerclage in preventing recurrent preterm birth

ObjectiveThis study aimed to clarify the effectiveness of cervical cerclage in preventing recurrent preterm births.Materials and methodsA retrospective study was conducted using the perinatal registration database of the Japan Society of Obstetrics and Gynecology for the Perinatal Center from 2014 to 2016. The efficacies of history-indicated, ultrasound-indicated, and physical examination-indicated cerclage as preventive treatments for women with a history of preterm birth were evaluated by comparing cerclage and non-cerclage cases. Fisher's exact test was performed to evaluate any significant differences in patient backgrounds. Prior to the evaluation, propensity score matching was performed for history-indicated and ultrasound-indicated cerclage patients.ResultsFor this study, 6060 multiparous women with a history of preterm birth were reviewed. After excluding 17 patients with unknown indications for cervical cerclage, 6043 patients were included in the study. History-indicated and ultrasound-indicated cerclage did not reduce the risk of preterm birth in subsequent pregnancies for any of the pregnancy periods (p = 0.413, p = 1.000). In contrast, physical examination-indicated cerclage significantly reduced the risk of subsequent preterm births for all pregnancy periods (p < 0.001).ConclusionSubsequent preterm births were effectively prevented only in physical examination-indicated cerclage cases. For history- or ultrasound-indicated cerclage, statistically significant differences in subsequent preterm births were not evident.     

Prediction of spontaneous preterm birth: salivary progesterone assay and transvaginal cervical length assessment after 24 weeks of gestation,another critical window of opportunity

Objectives: Measurement of salivary progesterone (SP4) levels and cervical length (CL) after 24 weeks to assess their potential predictive value among asymptomatic women at high risk of spontaneous preterm birth (PTB).

Methods: This prospective observational (noninterventional) study consecutively recruited asymptomatic women at high risk of spontaneous PTB. SP4 and CL were measured at recruitment (24–28 weeks of gestation) then repeated after 3–4 weeks. All recruited women were followed up regularly till delivery. The primary outcome measure was the occurrence of spontaneous PTB.

Results: One hundred and thirty four women completed the study, 22 (16.4%) and 32 (23.9%) women had early (<34 weeks) and late (≥34 weeks) PTB, respectively. Initially, the mean CL was 3.2?±?0.6?cm and the mean SP4 was 4062.8?±?814.6?pg/ml; with follow up, the mean CL became 3.0?±?0.6?cm and the mean SP4 became 3871.6?±?1136.9. Women with early PTB had significantly lower initial and follow up CL and SP4 measures when compared to women with late PTB and those who had birth at term. The rate of drop in SP4 and CL measurements between the two visits was also significantly higher among women with early PTB than those with late PTB and term birth. Receiver-operating characteristic (ROC) curves showed that, CL was a good predictor but SP4 was a better predictor of PTB as the area under the curve (AUC) for CL was less than that for SP4 at both visits (i.e. 0.858 and 0.868 versus 0.986 and 0.990 at the initial and follow up visits, respectively). There was a statistically significant correlation between CL and SP4 measurements. Multivariable binary logistic regression analysis revealed that follow up SP4 measurement was the only independent predictor of spontaneous PTB, and neither BMI, maternal age, SP4 nor CL were independent predictors of early spontaneous PTB.

Conclusions: After 24 gestational weeks, SP4 assessment is a simple and reliable promising tool to predict spontaneous PTB among asymptomatic high-risk women, with a little superior performance than CL measurement.     

High interleukin-16 concentrations in the early second trimester amniotic fluid: an independent predictive marker for preterm birth

Objective: Infection is believed to be one of frequent and important causes of preterm labor. We attempted to evaluate whether the level of inflammatory markers, e.g. interleukin-16 (IL-16), interleukin-18 (IL-18), and ferritin, in amniotic fluid at early second trimester can predict preterm birth. Methods: Amniotic fluid (AF) samples were collected from 350 pregnant women who had trans-abdominal amniocentesis for genetic indications at 16 to 20 weeks of gestation. AF levels of IL-16, IL-18 and ferritin levels were measured by immunoassay and were correlated with pregnancy outcomes. Results: Among the 350 pregnant women, 58 (16.6%) had preterm birth (<37 weeks gestation). AF levels of IL-16, IL-18, and ferritin were significantly higher in pregnant women with subsequent preterm birth. Multivariate analyses showed that a quartile higher of AF IL-16 level was significantly associated with preterm birth (OR: 3.09, 95% CI 1.52–6.27, p = 0.002). A receiver operating characteristic analysis revealed that an IL-16 cutoff value of 105 pg/ml was a reliable predictor of preterm birth (sensitivity, 90.2%; specificity, 52.7%; negative predictive value, 84.3%). Conclusion: It is feasible to predict preterm birth by measuring the AF levels of IL-16 especially for the pregnant women requiring genetic amniocentesis during early second trimester.     

Combined fetal fibronectin and cervical length and spontaneous preterm birth in asymptomatic triplet pregnancies

Objective: To estimate the association between fetal fibronectin (fFN), cervical length (CL), and spontaneous preterm birth (SPTB) in asymptomatic women with triplet pregnancies. Study design: A cohort of 39 consecutive women with triplet pregnancies managed in one Maternal-Fetal medicine practice from 2005–2011 was analyzed. Combined fFN and CL testing was performed every 2 weeks from 22–32 weeks. A short CL was defined as ≤20 mm. Results: A positive fFN was significantly associated with SPTB <28 weeks, <30 weeks, <32 weeks, and <34 weeks. A short CL was significantly associated with SPTB <32 weeks. On combined testing, having both tests positive was associated with the highest likelihood of SPTB at all gestational ages. As a screening test for SPTB <32 weeks, having both a positive fFN and a short CL had a sensitivity of 62.5%, specificity of 90%, positive predictive value of 62.5%, negative predictive value of 90%, positive likelihood ration of 2.98 and negative likelihood ratio of 0.88. Combined fFN and CL outperformed fFN alone, CL alone, or either test being positive alone. Conclusions: In asymptomatic women with triplet pregnancies, fFN and CL are each significantly associated with SPTB. For the prediction of SPTB, combined fFN and CL testing outperforms either test alone.     

The association between fetal fibronectin and spontaneous preterm birth in twin pregnancies with a shortened cervical length*

Objective: To estimate the association between a positive fetal fibronectin (fFN) and spontaneous preterm birth (SPTB) in twin pregnancies with a shortened cervical length (CL).

Study design: Retrospective cohort study of asymptomatic twin pregnancies managed by a single MFM practice from 2005 to 2016. We included all women with a shortened CL ≤25?mm at 22–28 weeks, and compared outcomes between women with a positive and negative fFN result.

Results: One hundred fifty-five patients were included, 129 (83.2%) of whom had a negative fFN and 26 (16.8%) of whom had a positive fFN. Baseline characteristics were similar between groups, except for the CL at the time of diagnosis of short cervix (15?mm in the positive fFN group versus 20?mm in the negative fFN group, p?=?.002). The risk of SPTB <32 weeks was significantly higher in the positive fFN group (46.2 versus 12.6%, aOR 3.54, 95% CI 1.26, 9.92) and the mean gestational age at delivery was significantly earlier (31.1 versus 35.2 weeks, p?Conclusions: In asymptomatic women with twin pregnancies and a shortened CL, a positive fFN is significantly associated with SPTB and can modify the risk substantially. If performing a screening CL assessment in a twin pregnancy, fFN testing should be done concurrently.     

Preterm birth: the value of sonographic measurement of cervical length

Transvaginal ultrasound scanning of cervical length at approximately 20 weeks of gestation in women attending for routine antenatal care is useful for predicting the likelihood of spontaneous early preterm birth. The risk of early birth increases exponentially with decreasing cervical length in both singleton and multiple pregnancies. In such women, individualisation of risk would lead to rationalisation of antenatal care, including frequency of visits, patient education in recognising and reporting symptoms of spontaneous preterm labour and timely administration of steroids. It is also possible that in women identified as being at high risk, the rate of preterm birth might be reduced by the prophylactic use of progesterone. In women presenting with threatened spontaneous preterm labour, transvaginal measurement of cervical length provides a useful distinction between those who are likely to deliver within the subsequent 7 days and those who are not. Since only 10–20% of such women are in true spontaneous preterm labour, the cervical length measurement in rational care can avoid the current practice of hospitalisation and administration of steroids and tocolytics to all. This article reviews the evidence in support of the clinical introduction of transvaginal sonography for both the prediction and management of spontaneous preterm labour.     

Management of pregnancy at increased risk of preterm birth

The Department of Health's ‘Safer Maternity Care’ report extended the ‘Maternity 4 Safety Ambition’ to include reducing preterm births from 8% to 6%. This new element focuses on three areas of intervention to improve outcomes; prediction and prevention of preterm birth, and better preparation when preterm birth is unavoidable. This article describes how the preterm birth prevention clinic operates at the University Hospitals of Leicester, and uses a variety of clinical scenarios to illustrate this.     

Predicting preterm birth: Cervical length and fetal fibronectin

Spontaneous preterm birth remains the leading cause of neonatal morbidity and mortality worldwide, and accounts for a significant global health burden. Several obstetric strategies to screen for spontaneous preterm delivery, such as cervical length and fetal fibronectin measurement, have emerged. However, the effectiveness of these strategies relies on their ability to accurately predict those pregnancies at increased risk for spontaneous preterm birth (SPTB). Transvaginal cervical shortening is predictive of preterm birth and when coupled with appropriate preterm birth prevention strategies, has been associated with reductions in SPTB in asymptomatic women with a singleton gestation. The use of qualitative fetal fibronectin may be useful in conjunction with cervical length assessment in women with acute preterm labor symptoms, but data supporting its clinical utility remain limited. As both cervical length and qualitative fetal fibronectin have limited capacity to predict preterm birth, further studies are needed to investigate other potential screening modalities.     

Fetal fibronectin,cervical length,and the risk of preterm birth in patients with an ultrasound or physical exam indicated cervical cerclage

Objective: The objective of this study is to estimate the risk of preterm birth in patients with an ultrasound or physical exam indicated cervical cerclage based on the results of fetal fibronectin (fFN) and cervical length (CL) screening.

Methods: Retrospective cohort of patients with a singleton pregnancy and an ultrasound or physical exam indicated Shirodkar cerclage placed by one maternal–fetal medicine practice from November 2005 to January 2015. Patients routinely underwent serial CL and fFN testing from 22 to 32 weeks. Based on ROC curve analysis, a short CL was defined as?≤15?mm. All fFN and CL results included are from after the cerclage placement.

Results: One hundred and four patients were included. Seventy eight (75%) patients had an ultrasound-indicated cerclage and 26 (25%) patients had a physical exam-indicated cerclage. A positive fFN was associate with preterm birth?<32 weeks (15.6% versus 4.2%, p?=?0.043), <35 weeks (37.5% versus 11.1%, p?=?0.002), <37 weeks (65.6% versus 20.8%, p?<?0.001), and earlier gestational ages at delivery (35.2?±?3.9 versus 37.4?±?2.9, p?=?0.001). A short CL was also associated with preterm birth?<35 weeks (50.0% versus 11.9%, p?<?0.01), preterm birth?<37 weeks (55.0% versus 29.8%, p?=?0.033), and earlier gestational ages at delivery (34.8?±?4.1 versus 37.2?±?3.0, p?=?0.004). The risk of preterm birth?<32, <35, and?<37 weeks increased significantly with the number of abnormal markers.

Conclusion: In patients with an ultrasound or physical exam indicated cerclage, a positive fFN and a short CL are both associated with preterm birth. The risk of preterm birth increases with the number of abnormal biomarkers.     

A comparison of cervical length measurement techniques for the prediction of spontaneous preterm birth

Objective: To evaluate the clinical utility of a novel means of assessing the cervix by measuring the angle of the curvature and to evaluate the performance of this technique as well as two other commonly used techniques of cervical length assessment in predicting spontaneous preterm birth (SPTB).

Methods: This was a retrospective cohort analysis of singleton gestations with a history of SPTB. Transvaginal ultrasound images of cervical length obtained between 20 and 23 6/7 weeks were re-measured using three techniques: (1) straight linear distance between the internal and external os, (2) sum of two contiguous linear segments tracing the internal to the external os, and (3) measurement of the angle of the curve within the cervix using an electronic protractor. A short cervical length was defined as?≤25?mm.

Results: A total of 181 women were included. The relative risk (RR) for SPTB by cervical angle?≤160° was 1.2 (95% CI 0.7–2.0) and the ROC curve revealed an area under the curve of 0.54 (95% CI 0.44–0.63). The RR for SPTB by short cervical length measured by the straight technique was 2.3 (95% CI 1.3–4.0) and by the segmental technique 2.1 (95% CI 1.2–3.8). There was a 99.4% agreement between the two techniques with an intraclass Kappa coefficient of 0.96.

Conclusions: In women with a history of SPTB, cervical angle measurement does not correlate with the risk of SPTB. Cervical length measured via straight and segmental techniques had excellent agreement in identifying short cervix, and both identified a short cervix predictive of SPTB.     

Novel developments on cervical length screening and progesterone for preventing preterm birth

Cervical length (CL) measured by transvaginal ultrasound is an effective screening test for the prevention of preterm birth (PTB). The criteria for an effective screening test are all met by CL. It studies an important condition (PTB); it is safe and acceptable by >99% of women; it recognises an early asymptomatic phase that precedes PTB by many weeks; it has a well-described technique, is reproducible, is predictive of PTB in all populations studies so far; and, perhaps most importantly, it has been shown that 'early' treatment is effective in prevention. These two interventions, effective only in specific populations, are ultrasound-indicated cerclage and vaginal progesterone.