sPTB Rate Research Articles

Investigation of factors associated with spontaneous preterm birth in pregnant women living with HIV.

To investigate factors contributing to preterm birth (PTB), including cART use and clinical and social determinants of health, in women living with HIV (WLWH) from British Columbia, Canada. Retrospective observational cohort. We investigated the effect of cART use and other clinical and demographic factors on spontaneous PTB (sPTB) rates (<37 weeks gestational age) among 631 singleton pregnancies between 1997 and 2018. Exposure to cART was modelled in comparison to no exposure, exposure in the first trimester, and between regimens. Differences in sPTB risk were estimated using time-dependent Cox's proportional hazards models. Overall, the sPTB rate was 16%. Cumulative cART use was associated with lower risk of PTB (Wald test P = 0.02; hazard ratio = 0.98, 95% CI = 0.96-0.99) and specific cART regimens were not associated with increased risk of sPTB. Exposure in the first trimester was not associated with sPTB and for each week of cART exposure, the risk of sPTB decreased by 2%. In a multivariable model, HIV viral load and substance use remained associated with risk of sPTB, but not cART exposure. The sPTB rate among pregnant WLWH was more than three times higher than in the general population. However, sPTB was not related specifically to use of cART; in fact, cART appeared to reduce the risk of sPTB. Uncontrolled HIV replication and substance use were associated with increased risk of sPTB among pregnant WLWH. This emphasizes the important role of prenatal care, access to cART, and smoking cessation and harm reduction to reduce the risk of sPTB in WLWH.

The Impact of Previous Obstetric History on the Risk of Spontaneous Preterm Birth in Women with a Sonographic Short Cervix

The natural history of women with a short cervix and a low-risk obstetric history remains poorly defined. In our study, we sought to better characterize the impact of previous obstetric history on the delivery outcomes in women diagnosed with a mid-trimester sonographic short cervix. We performed a retrospective cohort study of women with singleton gestations who underwent transvaginal cervical length screening between 16 and 24 weeks at two urban hospitals in Philadelphia between January 2013 and March 2018 and were found to have a short cervix (defined as ≤2 cm). Women were excluded from the cohort if there were major fetal anomalies noted or if delivery outcome information was not available. The cohort was then divided into three groups based on obstetric history: nulliparous, history of full-term birth only, or history of spontaneous preterm birth (sPTB). The primary outcome was sPTB <37 weeks, while the secondary outcome was sPTB <34 weeks. Our cohort included a total of 384 singleton pregnancies that were diagnosed with a sonographic short cervix: 165 women were nulliparous, 119 women had a history of full-term birth, and 100 women with a history of sPTB. We found that women with a short sonographic cervix had a sPTB rate of 39.6% with no differences found between the three groups. Only two-thirds of nulliparous women and women with a history of full-term birth received the recommended preventative treatment, compared with almost 100% of women with a history of sPTB. Women with and without a history of sPTB are at comparable risk of sPTB in the presence of a sonographically short cervix. Preventative therapies should be recommended to both nulliparous women and women with a history of full-term birth since uptake in this population are not as high.

Development and validation of predictive models for QUiPP App v.2: tool for predicting preterm birth in asymptomatic high-risk women.

Accurate mid-pregnancy prediction of spontaneous preterm birth (sPTB) is essential to ensure appropriate surveillance of high-risk women. Advancing the QUiPP App prototype, QUiPP App v.2 aimed to provide individualized risk of delivery based on cervical length (CL), quantitative fetal fibronectin (qfFN) or both tests combined, taking into account further risk factors, such as multiple pregnancy. Here we report development of the QUiPP App v.2 predictive models for use in asymptomatic high-risk women, and validation using a distinct dataset in order to confirm the accuracy and transportability of the QUiPP App, overall and within specific clinically relevant time frames. This was a prospective secondary analysis of data of asymptomatic women at high risk of sPTB recruited in 13 UK preterm birth clinics. Women were offered longitudinal qfFN testing every 2-4 weeks and/or transvaginal ultrasound CL measurement between 18 + 0 and 36 + 6 weeks' gestation. A total of 1803 women (3878 visits) were included in the training set and 904 women (1400 visits) in the validation set. Prediction models were created based on the training set for use in three groups: patients with risk factors for sPTB and CL measurement alone, with risk factors for sPTB and qfFN measurement alone, and those with risk factors for sPTB and both CL and qfFN measurements. Survival analysis was used to identify the significant predictors of sPTB, and parametric structures for survival models were compared and the best selected. The estimated overall probability of delivery before six clinically important time points (< 30, < 34 and < 37 weeks' gestation and within 1, 2 and 4 weeks after testing) was calculated for each woman and analyzed as a predictive test for the actual occurrence of each event. This allowed receiver-operating-characteristics curves to be plotted, and areas under the curve (AUC) to be calculated. Calibration was performed to measure the agreement between expected and observed outcomes. All three algorithms demonstrated high accuracy for the prediction of sPTB at < 30, < 34 and < 37 weeks' gestation and within 1, 2 and 4 weeks of testing, with AUCs between 0.75 and 0.90 for the use of qfFN and CL combined, between 0.68 and 0.90 for qfFN alone, and between 0.71 and 0.87 for CL alone. The differences between the three algorithms were not statistically significant. Calibration confirmed no significant differences between expected and observed rates of sPTB within 4 weeks and a slight overestimation of risk with the use of CL measurement between 22 + 0 and 25 + 6 weeks' gestation. The QUiPP App v.2 is a highly accurate prediction tool for sPTB that is based on a unique combination of biomarkers, symptoms and statistical algorithms. It can be used reliably in the context of communicating to patients the risk of sPTB. Whilst further work is required to determine its role in identifying women requiring prophylactic interventions, it is a reliable and convenient screening tool for planning follow-up or hospitalization for high-risk women. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

1065: Are rates of spontaneous preterm birth stable across a range of normal cervical lengths?

Cervical length (CL) screening is an effective adjunct to reduce recurrent spontaneous preterm birth (sPTB) in high-risk women. While the efficacy of universal screening in women with no prior sPTB is debated, studies have shown benefit to identifying low-risk women with shortened CL ≤20 mm. In high-risk women a range of normal CLs (≥25 mm) has been associated with a stable risk of recurrent sPTB; however, it is unclear how rates of sPTB vary over a range of measured-normal CLs in low-risk women. Retrospective cohort of women with singletons and no prior sPTB who had universal mid-trimester transvaginal CL screening 1/2016-8/2018 and a measured (Normal) CL ≥25mm. We excluded fetal anomalies or an unmeasurable CL due to a poorly-developed lower uterine segment. The primary outcome was sPTB < 37 wk. We considered CL in interval groups: 25-29 mm, 30-34 mm, 35-39 mm, 30-44 mm, and ≥45 mm (χ2 test of trend) and as a continuum (logistic regression and ROC curve). A secondary outcome was the number of hospital evaluations for suspected preterm labor (PTL). 990 low-risk women were included. The incidence of sPTB < 37 wk was 3.6%; mean CL was 39.2±6.0 mm (interdecile range=31.6, 47.0), measured at 19.4±1.1 wk. The median number of PTL evaluations was 0 (range 0-4) and mean birth gestational age was 38±2.4 wk. There was a significant decreasing trend in rates of sPTB across increasing CL groups (p=0.001; Table). Increasing CL as a continuous variable was also associated with a significantly lower odds of sPTB (OR=0.92, 95% CI 0.87, 0.98). However, the number of evaluations for suspected PTL was not associated with CL (p=0.55). The ROC (Figure) AUC for sPTB was only 0.64, suggesting that a range of normal CLs in low-risk women was a poor predictor of sPTB. Among low-risk women with a normal CL observed during mid-trimester screening, there was only a modest effect of a range of measured-normal CLs on sPTB < 37 wk and no significant association with the number of hospital evaluations for PTL.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

931: Mid-trimester cervical length screening: effect of poorly-developed lower uterine segment on pregnancy outcome

Poorly developed lower segment (PDLUS) is characterized by a long “cervix” (> ∼5 cm), S-shaped canal, different echogenicties in the “cervix”, increased bladder-to-amniotic cavity distance, and “internal os” cephalad to the inferior edge of the bladder reflection (Figure). PDLUS precludes accurate CL measurement as the location of the true internal os is obscured. PDLUS is protective against sPTB in women with a prior sPTB < 34 weeks. Whether PDLUS affects gestational length in low-risk women is unknown. Retrospective cohort study of women with singletons and no prior sPTB who had mid-trimester transvaginal CL screening, 1/2016-8/2018; fetal anomalies were excluded. We compared birth gestational age (GA) between women with a measured (Normal) CL ≥ 25mm versus PDLUS. A sample of 1135 with a Normal:PDLUS ratio of 4:1 had 80% power to detect a 1/2-wk difference in birth GA (ɑ=.05, GA SD=2.4 wks). Secondary outcomes included sPTB < 37 wks, preterm labor (PTL) evaluations, and a Cox survival model that examined time from CL scan to delivery. Indicated PTBs were censored at birth, and to account for elective inductions ≥39 wks, we censored the time at 39.0 wks. 990 (79%) women with Normal CL and 265 (21%) with PDLUS were included. Characteristics were comparable (Table) but multiparity was more common in PDLUS; age and BMI were different but not clinically significant. Birth GA was 38.7±2.4 wks with Normal vs 38.9 ± 2.0 wks with PDLUS (p=0.10); 19% with Normal CL had ≥ 1 PTL evaluation vs. 17% with PDLUS (p=0.54), and at a similar GA for the initial visit (31±4.8 wks vs 30±5.4 wks, p=0.36). In the Cox model, PDLUS was found to have a significantly lower hazard ratio (HR) of 0.67 (95% CI 0.46, 0.98; p=0.04) for earlier birth. After controlling for parity, the HR fell to 0.64 (p=0.02). The incidence of sPTB < 37 wk was 3.6% for Normal CL and 1.1% for PDLUS (p=0.04). PDLUS observed at mid-trimester CL screening in low-risk women was associated with a significantly lower rate of sPTB < 37 wk and a lower HR for earlier birth.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Modifiable risk factors for spontaneous preterm birth in nulliparous women: a prospective study.

Background Spontaneous preterm birth (sPTB) has a detrimental impact on perinatal outcome, as well as on the resources of health systems in high-income countries. Thus, the objective of the current study was to determine the incidence of modifiable risk factors in pregnancy and their impact on the rate of sPTB. Methods All nulliparous pregnant women, in singleton pregnancies, with free medical and obstetric history, were eligible to participate in this study. The primary outcome of interest was the incidence of specific modifiable risk factors for sPTB. The correlations between these risk factors and sPTB were also investigated. Results Overall, 2027 women were eligible for the study and agreed to participate. The incidence of sPTB was 4.9%; 25.5% (n = 518) of the participants were in extreme maternal age (<20 or >35 years), 34.5% (n = 701) had an abnormal body mass index (BMI) (<18.5 or ≥25 kg/m2), 4.4% (n = 89) reported use of assisted reproductive technology (ART) and 10.9% (n = 220) reported themselves as smokers in pregnancy. In the multivariate analysis, sPTB was significantly correlated with ART conception [odds ratio (OR): 2.494, 95% confidence interval (CI): 1.196-5.199]. Conclusion Approximately one in 20 primiparous pregnant women in the study had a sPTB. The study population included a high percentage of women of advanced maternal age, with abnormal BMI and smokers, but these characteristics did not affect the incidence of sPTB. On the other hand, conception following ART increased two-fold the risk of sPTB.

Microbial supernatants from Mobiluncus mulieris, a bacteria strongly associated with spontaneous preterm birth, disrupts the cervical epithelial barrier through inflammatory and miRNA mediated mechanisms

Recent human clinical studies have identified Mobiluncus mulieris, a fastidious strict anaerobic bacterium present in the cervicovaginal (CV) space, as being strongly associated with spontaneous preterm birth (sPTB). However, the molecular mechanisms that underlie this association remain unknown. As disruption of the cervical epithelial barrier has been shown to contribute to the premature cervical remodeling that precedes sPTB, we hypothesize that M. mulieris, a microbe strongly associated with sPTB in humans, has the ability to alter cervical epithelial function. We investigated if bacteria-free supernatants of M. mulieris were able to disrupt the cervical epithelial barrier through immunological and epigenetic based mechanisms in an in vitro model system. Ectocervical cells were treated with supernatant from cultured M. mulieris and epithelial cell permeability, immune cytokines and microRNAs (miRNAs) were investigated. M. mulieris supernatant significantly increased cell permeability and the expression of two inflammatory mediators associated with cervical epithelial breakdown, IL-6 and IL-8. Moreover, treatment of the ectocervical cells with the M. mulieris supernatant also increased the expression of miRNAs that have been associated with either sPTB or a shorter gestational length in humans. Collectively, these results suggest that M. mulieris induces molecular and functional changes in the cervical epithelial barrier thought to contribute to the pathogenesis of sPTB, which allows us to hypothesize that targeting CV bacteria such as M. mulieris could provide a therapeutic opportunity to reduce sPTB rates.

Predictive Value of Midtrimester Universal Cervical Length Screening Based on Parity.

To evaluate the effect of parity on performance characteristics of midtrimester cervical length (CL) in predicting spontaneous preterm birth (sPTB) before 37 weeks. This was a retrospective cohort study of 13,508 women with no history of sPTB undergoing universal transvaginal CL screening at 17 to 23 weeks' gestation from 2011 to 2016. Patients who declined screening or with unknown delivery outcomes were excluded. Areas under the receiver operator characteristic curves were used to assess and compare the predictive ability of CL screening for sPTB. The sensitivity, specificity, and positive and negative predictive values were estimated for specific CL cutoffs for prediction of sPTB. There were 20,100 patients, of whom 2087 (10%) declined screening and 4505 (22%) did not meet inclusion criteria. Of the remaining 13,508 patients, 43% were nulliparous. The incidence rates of sPTB were 6.5% in nulliparas and 4.9% in multiparas (P < .001). The mean CLs were 39.9 mm in nulliparas and 41.8 mm in multiparas (P < .001), and those of the first percentiles were 19.0 mm in nulliparas and 24.0 mm in multiparas. Cervical length was significantly more predictive of sPTB in nulliparas (area under the curve, 0.67; 95% confidence interval, 0.63-0.70; versus 0.61, 95% confidence interval, 0.57-0.63; P = .008). At CL cutoffs of 10, 15, 20, and 25 mm or less, the sensitivity was lower in multiparas, and the specificity was comparable between the groups. Midtrimester CL is less predictive of sPTB in multiparas compared to nulliparas. The poor predictive ability, especially in multiparas, calls into question the value of universal CL screening in this population.

Evaluation of the efficacy of cervical pessary combined with vaginal progesterone in women with a short cervix and additional risk factors for preterm delivery

Objective The aim of this study was to examine the efficacy of a combined management with cervical pessary and vaginal progesterone of women with a singleton pregnancy and a short cervix in both low and high risk-cases based on their previous obstetrical history and maternal factors. Study design This was a prospective cohort study of women with a singleton pregnancy and a sonographically detected mid-trimester cervical length ≤ 25 mm. The high-risk group consisted of women with a history of a previous spontaneous preterm birth (PB), or a second-trimester miscarriage, or a loop electrosurgical excision procedure of the cervix (LEEP) while the low-risk group of women without such a history. All women were managed with cervical pessary and daily vaginal administration of 200 mg of progesterone. The primary outcome measure was spontaneous delivery before 34 weeks (238 days) of gestation. Results One hundred ninety-six cases with a CL ≤ 25 mm were detected during the study period. Fifty-two women declined to participate in the study. The remaining 144 women were divided into two groups based on the presence (n = 44) or absence (n = 100) of specific risk factors for PB. The rate of PTB < 34 weeks was similar in both low and high-risk pregnancies while a significantly higher rate of sPTB < 37 weeks was found in women with high-risk pregnancies (p = .005). Conclusion The combined treatment of cervical pessary and vaginal progesterone has a similar influence on preterm delivery rate < 34 weeks, in both low and high-risk women, with a mid-trimester short cervix.

Barriers to Vaginal Progesterone in the Treatment of Incidental Short Cervix [27H

INTRODUCTION: Barriers in obtaining vaginal progesterone (VP) may adversely affect perinatal outcomes in women with short cervix. Aim of this study is to evaluate if delay in obtaining VP was associated with increased rate of sPTB. METHODS: Retrospective cohort study of singleton pregnancy with incidental short cervix (ISC) ≤20mm, prescribed VP and delivered at University of Illinois at Chicago, between June 2016 and June 2018. Rates of sPTB <37 weeks in women with delay in treatment were compared to women without delay. IRB approval was obtained. RESULTS: A total of 74 women with ISC were prescribed VP: 69(93%) received insurance approval. Of those 69, 8 (12%) received initial claim rejection, but subsequently received approval only for oral Prometrium to use vaginally. 15/74 (22%) women did not receive VP due to barriers or other causes. 29/47 (62%) who received VP timely, delivered preterm. 12 (20%) women encountered an insurance delay in obtaining VP ≥14 days, and 4 of those experienced sPTB. There was no significant difference in sPTD rate in women who began VP <14 days versus those ≥14 days, p=0.07. Those who experienced a delay compared to those with no VP at all, still had lower rate of sPTB 4/12 (33%) versus 11/15 (73%), respectively (p=0.038). CONCLUSION: Despite barriers, 93% of patients had access to VP treatment. Delay ≥14 days did not impact the rate of PTBs <37 weeks. Patients who received VP, despite delay, had a lower rate of PTBs than those who did not receive it at all.

Prolonged Second Stage in the First Pregnancy and Risk of Subsequent Spontaneous Preterm Birth [30R

INTRODUCTION: Preterm birth (PTB) is the leading cause of neonatal morbidity/mortality. Although some risk factors for spontaneous PTB (sPTB) are known, sPTB often occurs without identifiable risk factors. A prolonged second stage may increase sPTB risk via mechanical trauma that disrupts cervical integrity. This study examines the association between second stage length and subsequent sPTB. METHODS: This retrospective study included women with two consecutive singleton deliveries at one institution from 07/2012-06/2018, with the first delivery occurring at term. Prolonged second stage (PSS) was defined as 4 hours or more, based on this cohort's 75th percentile and on national recommendations. Very prolonged second stage (VPSS) was defined as 7 hours or more, based on this cohort's 95th percentile. The primary outcome was subsequent sPTB before 37 weeks. Fisher exact test, Kruskal-Wallis test, and logistic regression were used for statistical analysis. RESULTS: Among 1,032 included women, the overall subsequent sPTB rate was 3.1%. Identified in 24.4%, PSS was not associated with increased rate of sPTB (4.4% with PSS vs 2.7% without PSS, p=0.21). Identified in 4.3%, VPSS was associated with a higher rate of sPTB (9.1% with VPSS vs 2.8% without VPSS, p=0.04, OR 3.4, 95% CI 1.1-10.2). CONCLUSION: When dichotomized using the nationally-accepted cutoff of 4 hours, prior second stage length was not associated with subsequent sPTB. However, there was an association between increased risk of sPTB and second stage length when using a higher cutoff of 7 hours. Because that population's sample size was small, larger studies are required to confirm this association.

The efficacy of quantitative fetal fibronectin in predicting spontaneous preterm birth in symptomatic women: A retrospective cohort study.

Recent data suggest that quantitative measurements of fetal fibronectin can be used accurately to predict increased risk of preterm birth. The purpose of this study was to demonstrate that the quantification of fetal fibronectin improves diagnostic accuracy in women who present with symptoms suggestive of threatened preterm labour (TPL) using a quantitative fetal fibronectin (qfFN) bedside analyser. This was a retrospective cohort study of pregnant women who presented between 22+6 and 32+6 weeks gestation with symptoms of TPL who had qfFN measured using the Rapid fFN Q10 system. The ability to predict spontaneous preterm birth (sPTB) within 48h, 14days and <34weeks gestation at qfFN thresholds of 10, 50 and 200ng/mL was assessed. The overall rate of sPTB <34weeks was 4.1% (n=373). For deliveries within 48h, within 14days and <34weeks, a qfFN threshold of 200ng/mL had positive predictive values of 26.7%, 42.9% and 46.7%, respectively, when compared to patients with qfFN values of 0-9ng/mL. The corresponding relative risks were 68.5, 53.8 and 38.0, respectively CONCLUSION: Quantitative fetal fibronectin testing with thresholds of 10, 50 and 200ng/mL allows for more accurate prediction of preterm birth in symptomatic women. This higher degree of discrimination allows for more directed interventions for high-risk patients and reduces the cost and burden of unnecessary treatment for low-risk patients.

Second trimester uterocervical angle and spontaneous preterm birth in twins

Objective: To determine if there is an association between uterocervical angle (UCA) and spontaneous preterm birth (sPTB) < 37 weeks for women with twins. Materials and methods: Retrospective cohort study from 2014 to 2017 of twin pregnancies with cervical length (CL) screening between 15 0/7 and 24 6/7 weeks. Monochorionic-monoamniotic twins were excluded. Post-hoc UCA measurements were analyzed as a continuous variable and a wide UCA was also defined as an angle >95° and >110°. The primary outcome was sPTB < 37 weeks. Secondary outcomes were sPTB <34 weeks, <32 weeks, CL, and performance metrics for UCA. Binary logistic regression controlled for age, tobacco use, prior sPTB, CL, and gestational age at CL measurement. Results: A total of 114 women were studied. The rate of sPTB <37 weeks was 35.0%, <34 weeks was 21.4%, and <32 weeks was 17.1%. As a continuous variable, mean UCA was 117.9° (SD 27.1°) for delivery ≥37 weeks and 133.1° (SD 23.1°) <37 weeks (p = .002). A wider mean UCA was also associated with sPTB <34 weeks (sPTB ≥34 weeks: 120.9° [SD 26.5°] vs. <34 weeks: 133.0° [SD 22.8°], p = .025) and sPTB <32 weeks (sPTB ≥32 weeks: 121.2° [SD 25.9°] vs. <32 weeks: 135.0° [SD 24.0°], p = .018). However, after controlling for age, prior sPTB, tobacco use, CL measurement, and gestational age at CL measurement, UCA was not associated with sPTB <37 weeks, <34 weeks, or <32 weeks. UCA >110° was associated with sPTB <37 weeks after controlling for confounders (aOR 3.6 [95% CI 1.2–10.5], p = 0.02). There was no association between UCA >110° and sPTB <34 or <32 weeks. Furthermore, a UCA >95° was not associated with sPTB <37, <34, or <32 weeks. As a screening tool for sPTB <37 weeks, a UCA of >110° had a sensitivity of 85.7%, specificity of 43.1%, positive predictive value of 53.2%, negative predictive value of 80.0%, positive likelihood ratio of 1.5, and negative likelihood ratio of 0.3. Conclusions: In a cohort of dichorionic-diamniotic and monochroionic-diamniotic twins, UCA >110° was associated with sPTB <37 weeks. However, second trimester UCA had a low positive likelihood ratio and was not a robust marker for the prediction of sPTB in twins.

Factors Associated with Utilization of 17-Hydroxyprogesterone Caproate for the Prevention of Recurrent Preterm Birth.

Weekly 17-hydroxyprogesterone caproate (17OHP-C) from 16 to 36 weeks' gestation reduces the risk of recurrent spontaneous preterm birth (sPTB). Limited data suggest poor adherence to published guidelines. This study aimed to identify factors associated with 17OHP-C utilization. This retrospective cohort study included women with a singleton pregnancy who delivered within one academic health system between January 2014 and December 2015. Eligible women had a history of ≥1 singleton sPTB. Primary outcomes were counseling about, receipt of, and adherence to 17OHP-C therapy. Demographic and clinical predictors of the primary outcomes were determined using stepwise logistic regression. Of 410 eligible subjects, 69% (N = 284) were counseled about and 36% (N = 148) received 17OHP-C. Hispanic ethnicity, delay in prenatal care initiation, and a history of prior term births were associated with lower odds of 17OHP-C counseling. Each week delay in prenatal care initiation, Hispanic ethnicity, and each additional week's gestation of the earliest prior sPTB decreased the odds of receiving 17OHP-C. Maternal age and prior term births were associated with adherence. Utilization of evidence-based 17OHP-C therapy remains suboptimal: cultural and access-to-care barriers for eligible women may impede efforts to decrease recurrent sPTB rates.

10: Stress, local immune responses, and spontaneous preterm birth risk in a majority African American cohort

The role of host immunity and maternal psychosocial stress in the pathogenesis of spontaneous preterm birth (sPTB) remains unclear. Antimicrobial proteins in the cervicovaginal CV) space, such as beta-defensins (βD), modulate immune responses to bacteria. While stress is known to induce immunological changes, no study has examined the interplay between stress and the CV immune response in association with sPTB. From the Motherhood & Microbiome cohort (n=2000), we performed a nested case-control study of 519 pregnant women (110 sPTB and 409 term). Stress and CV-βD were measured at 16-20 weeks’ gestation. Stress was dichotomized at 30 on Cohen’s Perceived Stress Scale (PSS-14). We measured CV-βD with ELISA and dichotomized at the median. We compared sPTB rates with Chi-Square tests and modeled adjusted associations of stress and CV-βD with odds of sPTB with logistic regression. In the dataset, 73% were African American, 64% were overweight or obese, 31% were married, 51% had Medicaid insurance, and 20% had a PSS-14 score >30. Median CV-βD levels were 17,098 pg/mL, IQR: 64,559. The cohort sPTB rate was 6%, but 21% in the analytic dataset. sPTB rates were 28% and 19% with high and low stress, respectively, and 24% and 18% with low and high CV-βD levels, respectively. Women with both low stress and high βD had the lowest sPTB rate (17%) and women with both high stress and low βD had the highest rate of sPTB (38%) (Fig 1). In adjusted models, high stress and low βD were each associated with increased odds of sPTB (aOR 1.8 (1.1- 3.0) and 1.6 (1.001-2.5), respectively), (interaction P=0.4). Women with both high stress and low CV-βD had much higher odds of sPTB compared with all other women (aOR 2.7 (1.3-5.5)). Restricting to African American women, the results were stronger (aOR 3.2 (1.4-7.0)). High stress and low CV-βD levels are associated with increased odds of sPTB. The presence of both result in high odds of sPTB in a majority African American cohort. Understanding whether stress induces changes in the CV immune response or whether these are independent risk factors for sPTB in African American women will help guide therapeutic strategies to reduce sPTB. (R01NR014784; ME)

146: Clinical presentation of preterm birth and gestational latency after cerclage

Spontaneous preterm birth (sPTB) remains a leading cause of perinatal morbidity. Recent data have demonstrated that the risk of recurrent sPTB differs significantly between patients based upon symptoms at the time of presentation. Our primary objective was to evaluate cervical cerclage efficacy based upon clinical presentation of prior sPTB. This is a retrospective cohort study of women with a history of preterm birth and cervical cerclage placement at a large academic center from 2011-2016. Included were women with a history of singleton sPTB who received progesterone and underwent ultrasound or history-indicated cerclage placement in the current pregnancy. Women with a multifetal gestation and those with a previously placed abdominal cerclage were excluded. Women were divided into groups based upon the presenting symptom that preceded their first sPTB. Those groups included painless dilation, preterm premature rupture of membranes (PPROM), and painful dilation (preterm labor or PTL). The primary outcome was delivery after 34 weeks. Secondary outcomes included delivery after 28 and 37 weeks. Rates of sPTB in the 3 groups were compared using the Chi-square test. Multivariable logistic regression was used to adjust for race and cerclage indication. A total of 121 women were included. Of those, 34 presented with painless dilation, 51 with PPROM, and 36 with PTL in their first preterm delivery. The painless dilation group had the highest proportion of history-indicated cerclages (53%) placed in the index pregnancy whereas the preterm labor group had the highest proportion of ultrasound-indicated cerclages (89%). PTL was significantly associated with earliest sPTB after 32 weeks, as was painless dilation with earliest sPTB before 24 weeks [Table 1]. After adjusting for race and cerclage indication, and using the PTL group as referent, rates of delivery after 28, 34, and 37 weeks were similar among the 3 groups [Table 2]. Though limited by sample size, our study found no significant association between clinical presentation of prior sPTB and gestational latency after cerclage placement. With this data we cannot conclude that the clinical presentation of preterm birth predicts the outcome of subsequent cerclage. Our findings support current recommendations surrounding cerclage candidacy and may aid in the counseling and management of these high -risk patients.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Quantitative fetal fibronectin and cervical length in symptomatic women: results from a prospective blinded cohort study

Objectives: Our objectives were to determine whether quantitative fetal fibronectin (fFN) and cervical length (CL) screening can be used alone or in combination as prognostic tests to identify symptomatic women at the highest or lowest risk for spontaneous preterm birth (sPTB).Methods: A prospective, blinded cohort study of women presenting with a singleton gestation to our triage unit between 22-33w6d with preterm labor symptoms was performed. Women with ruptured membranes, moderate/severe bleeding, and dilation >2 cm were excluded. The primary outcome was sPTB <37 weeks. We evaluated test characteristics of quantitative fFN and CL assessment, both separately and in combination, considering traditionally reported cut-points (fFN ≥50 and CL <25), as well as cut-points above and below these measures. We found interactions between fFN >50 and CL <25 and sPTB by parity and obstetric history (p < .05) and therefore stratified results. Test characteristics are presented with positive predictive value (PPV) and negative predictive value (NPV).Results: Five hundred eighty women were enrolled and 537 women were available for analysis. Overall sPTB rate was 11.1%. Among nulliparous women, increasing levels of fFN were associated with increasing risk of sPTB, with PPV going from 26.5% at ≥20 ng/mL to 44.4% at ≥200 ng/mL. A cut-point of 20 ng/mL had higher sensitivity (69.2%) and higher NPV (96.8%) and therefore identified a “low-risk” group. fFN was not informative for multiparous women regardless of prior obstetrical history or quantitative level chosen. For all women, a shorter CL was associated with an increased sPTB risk. Among nulliparas and multiparas without a prior sPTB, a CL <20 mm optimized test characteristics (PPV 25 and 20%, NPV 95.5, and 92.7%, respectively). For multiparas with a prior sPTB, CL <25 mm was more useful. Using fFN and CL in combination for nulliparas did not improve test characteristics over using the individual fFN (p = .74) and CL (p = .31) components separately.Conclusions: This study identifies the importance of stratifying by parity and obstetrical history when using screening modalities for risk assessment in symptomatic women. For nulliparous women, either quantitative fFN or cervical length assessment can be utilized, depending on resources available, but a lower cut-point of 20 ng/mL should be used for quantitative fFN. For multiparous women, fFN is not useful and cervical length assessment should be the main screening tool utilized when there is clinical uncertainty. Regardless of parity, the PPV of fFN and CL is low and therefore the greatest clinical utility remains in its NPV.

Predictors of Cervical Cerclage Success in the Prevention of Spontaneous Preterm Birth [13L

INTRODUCTION: Cerclage is one of the interventions to prevent spontaneous preterm birth (sPTB). This study aimed to identify predictive factors of cerclage success in preventing sPTB. METHODS: Retrospective study of singleton pregnancy at high risk of sPTB in University of Illinois at Chicago between 2013 and 2017. Baseline characteristics, duration of pregnancy, pregnancy outcomes and other predictive factors were analyzed using χ2, student t test, and multiple logistic regression analysis. RESULTS: Of the 310 women identified, 90 (29%) had rescue cerclage, and 65 (21%) had prophylactic cerclage. Most statistically significant predictors of sPTB of rescue cerclage were insertions at 17–20 weeks, aOR 2.26 (95% CI: 1.47–3.50, P&lt;.0001), and at 21–22 weeks, aOR 1.81 (95% CI: 1.15–2.87, P&lt;.0001). Cerclages placed at CL &lt;10 mm was associated with increased likelihood of sPTB, aOR 1.60 (95% CI: 1.10–2.34, P&lt;.0001). Cervical length at 21–25 mm and cerclage at GA &lt;16 weeks were associated with decreased rate of sPTB, aOR 0.40 (95% CI: 0.26–0.61, P&lt;.0001), and aOR 0.26 (95% CI: 0.16–0.40, P&lt;.0001). Except for indomethacin in prophylactic cerclage, cervical dilatation, funneling, presence of sludge, prior sPTB, vaginal infections and use of 17-OHPC, these were not statistically significant in preventing sPTB. CONCLUSION: The success of cerclage in the prevention of sPTB depends on several factors. The most predictive factors were the degree of short cervix and earlier GA at cerclage placement.

Prevention of preterm birth with pessary in singletons (PoPPS): randomized controlled trial.

To determine if pessary use prevents preterm birth (PTB) in women with singleton pregnancy, with short cervical length (CL) measured on transvaginal sonography (TVS) and without prior spontaneous PTB (sPTB). This was an open-label multicenter randomized trial of asymptomatic women presenting at 18 + 0 to 23 + 6 weeks' gestation with a singleton pregnancy, CL ≤ 25 mm on TVS and no prior sPTB. sPTB included those with spontaneous onset of labor and those with rupture of membranes prior to labor. Subjects were randomized to receive either a Bioteque cup pessary or no pessary. Pessaries were inserted by trained maternal-fetal medicine staff. Vaginal progesterone was recommended to women with CL ≤ 20 mm. The primary outcome was PTB < 37 weeks. A sample size of 121 women in each group (n = 242) was needed to detect a reduction in the primary outcome from 30% in the no-pessary group to 15% in the pessary group. The trial was stopped early before complete enrollment. Between 17 March 2014 and 29 July 2016, 17 383 women underwent CL measurement on TVS. Of these, 422 (2.4%) had CL ≤ 25 mm and 391 (92.7%) met the full eligibility criteria, of which 122 (31.2%) agreed to randomization. Sixty-one (50%) women were randomized to the pessary group and 61 (50%) to the no-pessary group. Baseline characteristics were similar between the groups. There were no significant differences between the pessary and no-pessary groups in the rate of PTB < 37 weeks (43% vs 40%; relative risk 1.09; 95% CI, 0.71-1.68) or in secondary outcomes, such as rate of PTB < 34 weeks, rate of PTB < 28 weeks, gestational age at delivery, birth weight and rate of composite adverse neonatal outcome. Cervical pessary use was not associated with prevention of PTB in women with a singleton pregnancy, short CL on TVS and no prior sPTB in this small, underpowered randomized controlled trial. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

424: Uterocervical angle does not predict spontaneous preterm birth in either a low-risk or high-risk group: A prospective study

Retrospective studies have demonstrated an association between wide uterocervical angle (UCA) and increased risk of spontaneous preterm birth (sPTB). We sought to investigate the performance of UCA in predicting sPTB prospectively. We conducted a prospective cohort study from February 2016 to March 2017 of singleton gestations between 16 0/7-23 6/7 weeks undergoing transvaginal cervical imaging. UCA was measured between the lower uterine segment and the cervical canal as previously described. The primary outcome was spontaneous preterm birth < 37 wks. The study included both a low-risk group from the general population and a high-risk group with a history of sPTB. A total of 348 subjects were recruited. The rate of sPTB <37 wks in this cohort was 7.1%. There was no significant association between UCA ≥ 95 degrees and sPTB < 37 weeks in the total cohort (OR 0.91, 95% CI 0.35-2.34), the low-risk group (OR 1.02, 95% CI 0.25-4.19) or the high-risk group (OR 0.31, 95% CI 0.06-1.52). A UCA cutoff of ≥105 was also not associated with sPTB < 37 weeks or < 34 weeks in our population regardless of pregnancy history. In contrast, cervical length ≤ 25 mm significantly predicted spontaneous preterm birth < 37 weeks (p=0.009; sensitivity, 14.3%; negative predictive value, 94%). UCA was positively correlated with maternal age (p=0.002) and there was a significant association with nulliparity (p<0.001), but there was no association with race or body mass index. This prospective study found that UCA did not perform well as a predictor of sPTB either in a low- or high-risk population. Additional prospective studies are needed to further evaluate this screening tool.