Search

Background: Although intrauterine devices provide effective contraceptive protection, unintentional pregnancy can occur. Previous studies have shown that a retained intrauterine device during pregnancy is associated with adverse pregnancy outcomes but there is a paucity of nationwide data and analysis., Objective: This study aimed to describe characteristics and outcomes of pregnancies with a retained intrauterine device., Study Design: This serial cross-sectional study used data from the Healthcare Cost and Utilization Project's National Inpatient Sample. The study population comprised 18,067,310 hospital deliveries for national estimates from January 2016 to December 2020. The exposure was retained intrauterine device status, identified by the World Health Organization's International Classification of Diseases, Tenth Revision, code O26.3. The co-primary outcome measures were incidence rate, clinical and pregnancy characteristics, and delivery outcome of patients with a retained intrauterine device. To assess the pregnancy characteristics and delivery outcomes, an inverse probability of treatment weighting cohort was created to mitigate the prepregnant confounders for a retain intrauterine device., Results: A retained intrauterine device was reported in 1 in 8307 hospital deliveries (12.0 per 100,000). In a multivariable analysis, Hispanic individuals, grand multiparity, obesity, alcohol use, and a previous uterine scar were patient characteristics associated with a retained intrauterine device (all P<.05). Current pregnancy characteristics associated with a retained intrauterine device included preterm premature rupture of membrane (9.2% vs 2.7%; adjusted odds ratio, 3.15; 95% confidence interval, 2.41-4.12), fetal malpresentation (10.9% vs 7.2%; adjusted odds ratio, 1.47; 95% confidence interval, 1.15-1.88), fetal anomaly (2.2% vs 1.1%; adjusted odds ratio, 1.71; 95% confidence interval, 1.03-2.85), intrauterine fetal demise (2.6% vs 0.8%; adjusted odds ratio, 2.21; 95% confidence interval, 1.37-3.57), placenta malformation (1.8% vs 0.8%; adjusted odds ratio, 2.12; 95% confidence interval, 1.20-3.76), placenta abruption (4.7% vs 1.1%; adjusted odds ratio, 3.24; 95% confidence interval, 2.25-4.66), and placenta accreta spectrum (0.7% vs 0.1%; adjusted odds ratio, 4.82; 95% confidence interval, 1.99-11.65). Delivery characteristics associated with a retained intrauterine device included previable loss at <22 weeks' gestation (3.4% vs 0.3%; adjusted odds ratio, 5.49; 95% confidence interval, 3.30-9.15) and periviable delivery at 22 to 25 weeks' gestation (3.1% vs 0.5%; adjusted odds ratio, 2.81; 95% confidence interval, 1.63-4.86). Patients in the retained intrauterine device group were more likely to have a diagnosis of retained placenta at delivery (2.5% vs 0.4%; adjusted odds ratio, 4.45; 95% confidence interval, 2.70-7.36) and to undergo manual placental removal (3.2% vs 0.6%; adjusted odds ratio, 4.81; 95% confidence interval, 3.11-7.44)., Conclusion: This nationwide analysis confirmed that pregnancy with a retained intrauterine device is uncommon, but these pregnancies may be associated with high-risk pregnancy characteristics and outcomes., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background and Objectives: Early detection is critical to achieving optimal outcomes in children with congenital cataract. We hypothesized that detection of congenital cataract in preterm infants would be delayed compared with term/post-term peers due to delayed delivery of whole population child health interventions., Methods: Secondary analysis of data using a nested case-control study approach in a prospective population-based cohort study. Inclusion criteria comprised children diagnosed with congenital cataract requiring surgical intervention during the first two years of life in UK and Ireland in 2009 and 2010. Association between late detection (after eight weeks post-natal age, ie outside the neonatal and infant eye national screening programme) of cataract and preterm birth (gestational age less than 37 weeks) was assessed using multivariable logistic regression., Results: Of 186 children with congenital cataract, 17 children were born preterm (9%, gestational age range 24-37weeks). Neonatal detection occurred in 64/186 (34%), and late detection in 64 children (34%). Late detection was independently associated with premature birth, specifically moderate/late preterm birth (adjusted odds ratio 3.0, 95%CI 1.1 to 8.5)., Conclusions: Our findings suggest that, despite enhanced eye surveillance being recommended for those born moderate/late preterm (32+ weeks gestational age, ie not eligible for retinopathy of prematurity screening), congenital cataract is not being effectively detected through the routine screening programme for this vulnerable group. It is necessary to improve the effectiveness of the screening programme, and care must be taken to ensure that competing health care needs of preterm children do not prevent universal child health interventions., Competing Interests: The authors have declared that no competing interests exist, (Copyright: © 2023 Solebo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Preterm birth (PTB) is the leading cause of infant deaths globally. Current clinical measures often fail to identify women who may deliver preterm. Therefore, accurate screening tools are imperative for early prediction of PTB. Here, we show that Raman spectroscopy is a promising tool for studying biological interfaces, and we examine differences in the maternal metabolome of the first trimester plasma of PTB patients and those that delivered at term (healthy). We identified fifteen statistically significant metabolites that are predictive of the onset of PTB. Mass spectrometry metabolomics validates the Raman findings identifying key metabolic pathways that are enriched in PTB. We also show that patient clinical information alone and protein quantification of standard inflammatory cytokines both fail to identify PTB patients. We show for the first time that synergistic integration of Raman and clinical data guided with machine learning results in an unprecedented 85.1% accuracy of risk stratification of PTB in the first trimester that is currently not possible clinically. Correlations between metabolites and clinical features highlight the body mass index and maternal age as contributors of metabolic rewiring. Our findings show that Raman spectral screening may complement current prenatal care for early prediction of PTB, and our approach can be translated to other patient-specific biological interfaces.

Background: Some data suggest an association between abnormal fetal fraction on noninvasive prenatal screening and adverse pregnancy outcomes, including low birthweight, preeclampsia, and preterm birth in the absence of aneuploidy. These findings suggest that abnormal fetal fraction may be associated with placental pathologic processes in early gestation., Objective: This study aimed to determine the independent association of fetal fraction on genetic noninvasive prenatal screening with histologic placental types., Study Design: This was a retrospective cohort study at a single institution in the period between January 2017 and March 2021, including live births at ≥24 weeks for which noninvasive prenatal screening was performed and placental pathology results were available. Results were stratified by trimester of noninvasive prenatal screening. Clinical characteristics were compared by quartile of fetal fraction using chi-square tests. Linear regression was used to model continuous fetal fraction as a function of 3 histologic types representing chronic placental injury-chronic inflammation, maternal vascular malperfusion, and fetal vascular malperfusion. Inverse probability weighting was used to account for selection bias in characteristics of patients with placental pathology examination., Results: A total of 1374 patients had noninvasive prenatal screening in the first trimester and 262 in the second trimester. Preterm birth and hypertensive disorders of pregnancy were most common in the lowest quartile of fetal fraction. Chronic inflammation was associated with a 0.56 percentage point reduction in fetal fraction (95% confidence interval, -0.95 to -0.16), and maternal vascular malperfusion was associated with a 0.48 percentage point reduction in fetal fraction (95% confidence interval, -0.91 to -0.04) in adjusted models. The association with maternal vascular malperfusion was no longer statistically significant after accounting for selection bias in placentas sent for pathologic examination. Second-trimester fetal fraction was not associated with placental pathology., Conclusion: Chronic inflammation is associated with lower first-trimester fetal fraction even after accounting for selection bias. Higher fetal fraction in the second trimester was associated with fetal vascular pathology, although this association was no longer statistically significant after inverse probability weighting to account for selection bias. First-trimester fetal fraction may be a biomarker of adverse outcomes associated with chronic inflammation., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Hypertensive disorders of pregnancy are the leading cause of indicated preterm birth; however, the optimal delivery approach for pregnancies complicated by preterm hypertensive disorders of pregnancy remains uncertain., Objective: This study aimed to compare maternal and neonatal morbidity in patients with hypertensive disorders of pregnancy who either went induction of labor or prelabor cesarean delivery at <33 weeks' gestation. In addition, we aimed to quantify the length of induction of labor and rate of vaginal delivery in those who underwent induction of labor., Study Design: This is a secondary analysis of an observational study which included 115,502 patients in 25 hospitals in the United States from 2008 to 2011. Patients were included in the secondary analysis if they were delivered for pregnancy associated hypertension (gestational hypertension or preeclampsia) between 23 0 and <33 0 weeks' gestation; and were excluded for known fetal anomalies, multiple gestation, fetal malpresentation or demise, or a contraindication to labor. Maternal and neonatal adverse composite outcomes were evaluated by intended mode of delivery. Secondary outcomes were duration of labor induction and rate of cesarean delivery in those who underwent labor induction., Results: A total of 471 patients met inclusion criteria, of whom 271 (58%) underwent induction of labor and 200 (42%) underwent prelabor cesarean delivery. Composite maternal morbidity was 10.2% in the induction group and 21.1% in the cesarean delivery group (unadjusted odds ratio, 0.42 [0.25-0.72]; adjusted odds ratio, 0.44 [0.26-0.76]). Neonatal morbidity in the induction group vs the cesarean delivery was 51.9% and 63.8 %, respectively (unadjusted odds ratio, 0.61 [0.42-0.89]; adjusted odds ratio, 0.71 [0.48-1.06]). The frequency of vaginal delivery in the induction group was 53% (95% confidence interval, 46.8-58.7) and the median duration of labor was 13.9 hours (interquartile range, 8.7-22.2). The frequency of vaginal birth was higher in patients at or beyond 29 weeks (39.9% at 24 0 -28 6 weeks, 56.3% at 29 0 -<33 0 weeks; P=.01)., Conclusion: Among patients delivered for hypertensive disorders of pregnancy <33 0 weeks, labor induction compared with prelabor cesarean delivery is associated with significantly lower odds of maternal but not neonatal morbidity. More than half of patients induced delivered vaginally, with a median duration of labor induction of 13.9 hours., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Microenvironmental factors, including microbe-induced inflammation and immune-checkpoint proteins that modulate immune cells have been associated with both cervical insufficiency and preterm delivery. These factors are incompletely understood. This study aimed to explore and compare interactions among microbiome and inflammatory factors, such as cytokines and immune-checkpoint proteins, in patients with cervical insufficiency and preterm birth. In particular, factors related to predicting preterm birth were identified and the performance of the combination of these factors was evaluated., Methods: A total of 220 swab samples from 110 pregnant women, prospectively recruited at the High-Risk Maternal Neonatal Intensive Care Center, were collected between February 2020 and March 2021. This study included 63 patients with cervical insufficiency receiving cerclage and 47 control participants. Endo- and exocervical swabs and fluids were collected simultaneously. Shotgun metagenomic sequencing for the microbiome and the measurement of 34 immune-checkpoint proteins and inflammatory cytokines were performed., Results: First, we demonstrated that immune-checkpoint proteins, the key immune-regulatory molecules, could be measured in endocervical and exocervical samples. Secondly, we identified significantly different microenvironments in cervical insufficiency and preterm birth, with precise cervical locations, to provide information about practically useful cervical locations in clinical settings. Finally, the presence of Moraxella osloensis (odds ratio = 14.785; P = 0.037) and chemokine CC motif ligand 2 levels higher than 73 pg/mL (odds ratio = 40.049; P = 0.005) in endocervical samples were associated with preterm birth. Combining M. osloensis and chemokine CC motif ligand 2 yielded excellent performance for predicting preterm birth (area under the receiver operating characteristic curve = 0.846, 95% confidence interval = 0.733-0.925)., Conclusion: Multiple relationships between microbiomes, immune-checkpoint proteins, and inflammatory cytokines in the cervical microenvironment were identified. We focus on these factors to aid in the comprehensive understanding and therapeutic modulation of local microbial and immunologic compositions for the management of cervical insufficiency and preterm birth., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Jeong, Cho, Jo, Choi, Lee, Jeon, Park, Song and Lee.)

Importance: Cervical cancer screening is associated with reduced cervical cancer mortality; however, clinical trials have also shown an association between excisional procedures for cervical neoplasia and an increased risk of preterm delivery (PTD). National screening guidelines must weigh adverse effects on birth outcomes against benefits of cancer prevention., Objective: To ascertain the population-level association between the number of guideline-recommended cervical cancer screenings and downstream PTD risk among females aged 18 to 24 years., Design, Setting, and Participants: This cross-sectional study used a difference-in-differences approach based on variation in the recommended number of cervical cancer screenings (over time and across individuals giving birth at different ages) to estimate the association between the cumulative recommended number of screenings (by the time of childbirth) and PTD risk. National Vital Statistics System data from females aged 18 to 24 years who had a singleton, nulliparous birth in the US between 1996 and 2018 were used. Regression models were adjusted for maternal educational level, race and ethnicity, comorbidities, marital status, and prenatal care visits. Data were analyzed between June 2020 and March 2023., Exposure: A constructed variable capturing the cumulative number of guideline-recommended cervical cancer screenings for an individual based on their age and year of childbirth., Main Outcomes and Measures: Binary indicators for PTD and very preterm delivery (VPTD), defined as delivery before 37 and 34 weeks' gestational age, respectively, and gestational age was measured in weeks from the first day of the last menstrual period., Results: Among 11 333 151 females aged 18 to 24 years who gave birth between 1996 and 2018, 2 069 713 were Black (18.3%), 2 601 225 were Hispanic (23.0%), 6 068 498 were White (53.5%) individuals, and 593 715 (5.2%) were individuals of other race or ethnicity (Alaska Native; American Indian; Asian; Pacific Islander; multiracial; or unknown or missing race or ethnicity). Mean (SD) age was 20.9 (1.9) years, and 766 001 individuals (6.8%) had hypertension or diabetes. The mean (SD) number of guideline-recommended screenings by time of childbirth was 2.4 (2.2). Overall, PTD and VPTD occurred in 1 140 490 individuals (10.1%) and 333 040 (2.9%) of births, respectively. One additional recommended screening was associated with a 0.073 (95% CI, 0.026-0.120) percentage-point increase in PTD risk but no statistically significant change in VPTD risk. Females with hypertension or diabetes had a higher increase in PTD risk than those without these comorbidities (0.26 [95% CI, 0.11-0.4] vs 0.06 [95% CI, 0.01-0.10] percentage points; Wald test P < .001)., Conclusions and Relevance: Findings of this cross-sectional study suggest that additional recommended cervical cancer screenings before birth were associated with an increased risk of PTD. These results can be used in future simulation models integrating oncological trade-offs to help ascertain optimal screening strategies.

Objective: To evaluate whether the fetal fraction of cell-free DNA at the first and second trimesters is associated with spontaneous preterm birth., Methods: This was a retrospective cohort study with singleton pregnancies who underwent noninvasive prenatal testing. According to pregnancy outcome, eligible patients were divided into a delivery group ≥37 weeks of pregnancy (term group) and <37 weeks of pregnancy (spontaneous preterm group). Stepwise linear regression was used to identify maternal characteristics associated with the fetal fraction of cell-free DNA. Logistic regression analysis was performed to evaluate the association between the fetal fraction of cell-free DNA and spontaneous preterm birth, adjusted for confounding factors., Results: 14,020 cases were included in the study, 13292 cases (94.81%) in the term group and 728 cases (5.19%) in the spontaneous preterm group. The cell-free fraction of fetal DNA was inversely correlated with maternal age and body mass index. Positively correlated with gestational age, fertility, and assisted reproductive technology. After adjusting for the covariates, logistic regression analysis revealed no statistically significant association between the fetal fraction of cell-free DNA and spontaneous preterm birth., Conclusion: In our original study, we found no association between the fetal fraction on NIPT and subsequent spontaneous preterm birth.

Background: Recent literature indicates that adverse childhood experiences have been associated with poor obstetrical outcomes, including pregnancy loss, preterm birth, and low birthweight. Several studies have been conducted in primarily self-identified White individuals who report middle to high income levels. Less is known about the impact of adverse childhood experiences on obstetrical outcomes in minority-identifying and low-income populations, who are known to experience a greater number of adverse childhood experiences and are at higher risk of maternal morbidity., Objective: This study aimed to examine associations between adverse childhood experiences and a broad range of obstetrical outcomes among predominantly Black-identifying pregnant persons who have low income and live in an urban area., Study Design: This is a single-center retrospective cohort study of pregnant persons referred to a mental healthcare manager because of elevated psychosocial risks identified by screening tools or provider concerns during the study period from April 2018 to May 2021. Pregnant persons aged <18 years and those who did not speak English were excluded. Patients completed validated mental and behavioral health screening tools including the Adverse Childhood Experiences Questionnaire. Medical charts were reviewed for obstetrical outcomes, including preterm birth, low birthweight, hypertensive disorders of pregnancy, gestational diabetes mellitus, chorioamnionitis, sexually transmitted infection, maternal group B streptococcus carrier status, type of delivery, and attendance of a postpartum visit. Associations between high (≥4) and very high (≥6) of 10 adverse childhood experience score and obstetrical outcomes were analyzed using bivariate analysis and multivariate logistic regression, adjusting for confounding factors (significant at P<.05 in bivariate analysis)., Results: Our cohort included 192 pregnant persons, of whom 176 (91.7%) self-identified as Black or African American and 181 (94.8%) had public insurance (used as a proxy for low income). Adverse childhood experience score ≥4 was reported by 91 (47.4%) individuals and score ≥6 by 50 (26%). On univariate analysis, adverse childhood experience score ≥4 was associated with preterm birth (odds ratio, 2.17; 95% confidence interval, 1.02-4.61). Adverse childhood experience score ≥6 was associated with hypertensive disorders of pregnancy (odds ratio, 2.09; 95% confidence interval, 1.05-4.15) and preterm birth (odds ratio, 2.29; 95% confidence interval, 1.05-4.96). After accounting for chronic hypertension, associations between adverse childhood experience score and obstetrical outcomes were no longer significant., Conclusion: Approximately half of the pregnant persons referred to a mental healthcare manager had a high adverse childhood experience score, underscoring the high burden of childhood trauma on populations facing long-standing systemic racism and barriers to healthcare access. High and very high adverse childhood experience score may be associated with chronic health conditions that predate pregnancy and can alter obstetrical outcomes. Obstetrical care providers have a unique opportunity to mitigate risk of associated poor health outcomes during preconception and prenatal care by screening for adverse childhood experiences., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Cervical cerclage has been shown to reduce the risk of recurrent spontaneous preterm birth in a high-risk patient population; however, the mechanism is not well understood. Transabdominal cerclage is superior to low and high vaginal cerclage in reducing early spontaneous preterm birth and fetal loss in women with previous failed vaginal cerclage. Cervical length measurements are commonly used to monitor high-risk women and may explain the mechanism of success., Objective: This study aimed to evaluate the rate of change in longitudinal cervical length after randomized placement of low transvaginal, high transvaginal, or transabdominal cerclage in women with a previous failed vaginal cerclage., Study Design: This was a planned analysis of longitudinal transvaginal ultrasound cervical length measurements from patients enrolled in the Vaginal Randomised Intervention of Cerclage trial, a randomized controlled trial comparing transabdominal cerclage or high transvaginal cerclage with low transvaginal cerclage. Cervical length measurements at specific gestational ages were compared over time and between groups, using generalized estimating equations fitted using the maximum-likelihood random-effects estimator. In addition, cervical length measurements were compared in women with transabdominal cerclage placed before and during pregnancy. The diagnostic accuracy of cervical length as a predictor of spontaneous preterm birth at <32 weeks of gestation was explored., Results: This study included 78 women who underwent longitudinal cervical length assessment (70% of the analyzed cohort) with a history of failed cerclage, of whom 25 (32%) were randomized to low transvaginal cerclage, 26 (33%) to high transvaginal cerclage, and 27 (35%) to transabdominal cerclage. Abdominal cerclage was superior to low (P=.008) and high (P=.001) vaginal cerclage at maintaining cervical length over the surveillance period (14 to 26 weeks of gestation) (+0.08 mm/week, 95% confidence interval, -0.40 to 0.22; P=.580). On average, the cervical length was 1.8 mm longer by the end of the 12-week surveillance period in women with transabdominal cerclage (+1.8 mm; 95% confidence interval, -7.89 to 4.30; P=.564). High vaginal cerclage was no better than low cervical cerclage in the prevention of cervical shortening; the cervix shortened by 13.2 mm over 12 weeks in those with low vaginal cerclage (95% confidence interval, -21.7 to -4.7; P=.002) and by 20 mm over 12 weeks in those with high vaginal cerclage (95% confidence interval, -33.1 to -7.4; P=.002). Preconception transabdominal cerclage resulted in a longer cervix than those performed during pregnancy; this difference was significant after 22 weeks of gestation (48.5 mm vs 39.6 mm; P=.039). Overall, cervical length was an excellent predictor of spontaneous preterm birth at <32 weeks of gestation (receiver operating characteristic curve, 0.92; 95% confidence interval, 0.82-1.00)., Conclusion: In women with a previous failed cervical cerclage, in the next pregnancy, the cervical length in women treated with vaginal cerclage funneled and shortened over time, whereas there was preservation of cervical length in women who receive transabdominal cerclage. Cervical length remained longer in transabdominal procedures performed before pregnancy than in transabdominal procedures performed during pregnancy. Overall, cervical length was an excellent predictor of spontaneous preterm birth in our cohort. Our findings may explain the mechanism of benefit for transabdominal cerclage, with its high placement better maintaining the structural integrity of the cervix at the level of the internal os., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Recent observational studies reported a high rate of suboptimal use of antenatal corticosteroids (too anticipated or retrospectively not indicated) for women at risk of preterm delivery despite a recommended use within 7 days before delivery., Objective: This study aimed to elaborate a nomogram aiming at optimizing the timing of administration of antenatal corticosteroids in case of threatened preterm labor, asymptomatic short cervix, or uterine contractions., Study Design: This was an observational retrospective study conducted in a tertiary hospital. All women between 24 and 34 weeks of gestation who received corticosteroids during hospitalization for threatened preterm delivery, asymptomatic short cervix, or uterine contractions requiring tocolysis between 2015 and 2019 were included. Clinical, biological, and sonographic data of women were used to construct logistic regression models for predicting delivery within 7 days. The model was validated on an independent series of women hospitalized in 2020., Results: Among the 1343 women included in this study, the risk factors independently associated with a delivery within 7 days in multivariate analysis were vaginal bleeding (odds ratio, 14.47; 95% confidence interval, 7.81-26.81; P<.001); need for a second-line tocolysis, such as atosiban (odds ratio, 5.66; 95% confidence interval, 3.39-9.45; P<.001); C-reactive protein level (per 1 mg/L increase; odds ratio, 1.03; 95% confidence interval, 1.02-1.04; P<.001); cervical length (per 1 mm increase; odds ratio, 0.84; 95% confidence interval, 0.82-0.87; P<.001); uterine scar (odds ratio, 2.98; 95% confidence interval, 1.33-6.65; P=.008), and gestational age at admission (per week of amenorrhea increase; odds ratio, 1.10; 95% confidence interval, 1.00-1.20; P=.041). Based on these results, a nomogram was developed that, in retrospect, would have allowed physicians to avoid or delay antenatal corticosteroids in 57% of cases in our population. The discrimination of the predictive model was good when applied to the validation set of 232 women hospitalized in 2020. It would have enabled physicians to avoid or delay antenatal corticosteroids in 52% of cases., Conclusion: This study developed a simple use, accurate prognostic score to identify women at risk of delivery within 7 days in cases of threatened preterm delivery, asymptomatic short cervix, or uterine contractions and thereby optimized the use of antenatal corticosteroids., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Preterm birth is a leading cause of infant morbidity and mortality; its multifactorial causes are an obstacle to understanding etiology and pathogenesis. The importance of cytokines and inflammation in its etiology and association with the short cervix is nowadays well-proven. To date, there are no reliable biological or biochemical markers to predict preterm birth; even though the length of the cervix has high specificity, its sensitivity with the cervix below 2.5 cm is low., Objective: We study the association of plasma cytokine levels and cervical length in search of predictors of preterm birth., Study Design: We evaluated a total of 1400 pregnant women carrying a single fetus between 20 and 25 weeks of gestation, and 1370 of them after childbirth in a nested case-control study of a prenatal cohort. Eligible pregnant women were interviewed and submitted to obstetric morphological and transvaginal ultrasound with cervical length measurement, gynecological examination, and blood collection. Preterm birth occurred in 133 women, 129 included in the study, and a control group randomly selected at a 2:1 ratio. A total of 41 cytokines with a higher probability of being associated with preterm birth or being of significance during labor were determined., Results: Cytokine and cervical length analysis by multivariate analysis of the conditional interference tree revealed that growth-related oncogene values of less than 2293 pg/mL were significantly associated with a cervical length of less than 2.5 cm., Conclusions: As well as a cervical length shorter than 2.5 cm, growth-related oncogene levels of less than 2293 pg/ml may be associated with an increased risk of PB. Analysis based on the association of biomarkers and of the interaction between cytokines is a promising pathway in search of a predictor of preterm birth., (© 2023. The Author(s).)

Objective: This study aimed to determine whether cervical cerclage for a transvaginal ultrasound-detected short cervical length after 24 weeks of gestation in singleton pregnancies reduces the risk for preterm birth., Data Sources: Ovid MEDLINE, Scopus, and the Cochrane Central Register of Controlled Trials were searched using the following terms: "cerclage, cervical," "uterine cervical incompetence," "obstetrical surgical procedures," "cervix uteri," "randomized controlled trial," and "controlled clinical trial.", Study Eligibility Criteria: All randomized controlled trials comparing cerclage placement with no cerclage in singleton gestations with a transvaginal ultrasound-detected short cervical length ≤25 mm between 24+0/7 and 29+6/7 weeks of gestation were eligible for inclusion., Methods: Individual patient-level data from each trial were collected. If an eligible trial included patients with both multiple and singleton gestations with a short cervical length detected either before or after 24+0/7 weeks of gestation, only singletons who presented at or after 24+0/7 weeks were included. The primary outcome was preterm birth <37 weeks' gestation. Secondary outcomes included preterm birth <34, <32, and <28 weeks' gestation, gestational age at delivery, latency, preterm prelabor rupture of membranes, chorioamnionitis, and adverse neonatal outcomes. Individual patient-level data from each trial were analyzed using a 2-stage approach. Pooled relative risks or mean differences with 95% confidence intervals were calculated as appropriate., Results: Data from the 4 eligible randomized controlled trials were included. A total of 131 singletons presented at 24+0/7 to 26+6/7 weeks of gestation and were further analyzed; there were no data on patients with a cerclage at 27+0/7 weeks' gestation or later. Of those included, 66 (50.4%) were in the cerclage group and 65 (49.6%) were in the no cerclage group. The rate of preterm birth <37 weeks' gestation was similar between patients who were randomized to the cerclage group and those who were randomized to the no cerclage group (27.3% vs 38.5%; relative risk, 0.78; 95% confidence interval, 0.37-1.28). Secondary outcomes including preterm birth <34, <32, and <28 weeks' gestation, gestational age at delivery, time interval from randomization to delivery, preterm prelabor rupture of membranes, and adverse neonatal outcomes such as low birthweight, very low birthweight, and perinatal death were similar between the 2 groups. Planned subgroup analyses revealed no statistically significant differences in the rate of preterm birth <37 weeks' gestation between the 2 groups when compared based on cervical length measurement (≤15 mm or ≤10 mm), gestational age at randomization (24+0/7 to 24+6/7 weeks or 25+0/7 to 26+6/7 weeks), or history of preterm birth., Conclusion: Cervical cerclage did not reduce or increase the rate of preterm birth among singleton pregnancies with a short cervical length detected after 24 weeks of gestation. Because there was a 22% nonsignificant decrease in preterm birth associated with cerclage, which is a similar amount of risk reduction often associated with ultrasound-indicated cerclage before 24 weeks' gestation, further randomized controlled trials in this patient population are warranted., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Given the important roles of immune tolerance and inflammation in both preterm and term labor, some inflammation-related genes could be related to the initiation of labor, even preterm labor. Inspection of cell-free RNA (cfRNA) engaged in inflammation in maternal blood may represent the varied gestational age and may have significant implications for the development of noninvasive diagnostics for preterm birth., Methods: To identify potential biomarkers of preterm birth, we investigated the cfRNA and exosomal miRNA in the peripheral blood of pregnant women at different gestational ages that undergo term labor or preterm labor. 17 inflammatory initiation-related cfRNAs were screened by overlapping with the targets of decreasing miRNAs during gestation and highly expressed cfRNAs at late gestation in maternal blood. To reveal the origins and mechanisms of these screened cfRNAs, the datasets of single-cell RNA sequencing from peripheral blood mononuclear cells of pregnant women, the fetal lung, and the placenta across different gestational ages were analyzed., Results: During late gestation, TNFSF4 expression increased exclusively in pro-inflammatory macrophages of maternal blood, whereas its receptor, TNFRSF4, increased expression in T cells from the decidua, which suggested the potential cell-cell communication of maternally-originated pro-inflammatory macrophages with the decidual T cells and contributed to the initiation of labor. Additionally, the cfRNA of TNFSF4 was also increased in preterm labor compared to term labor in the validation cohorts. The EIF2AK2 and TLR4 transcripts were increased in pro-inflammatory macrophages from both fetal lung and placenta but not in those from maternal mononuclear cells at late gestation, suggesting these cfRNAs are possibly derived from fetal tissues exclusively. Moreover, EIF2AK2 and TLR4 transcripts were found highly expressed in the pro-inflammatory macrophages from decidua as well, which suggested these specific fetal-origin macrophages may function at the maternal-fetal interface to stimulate uterine contractions, which have been implicated as the trigger of parturition and preterm labor., Discussion: Taken together, our findings not only revealed the potential of peripheral TNFSF4 as a novel cfRNA biomarker for noninvasive testing of preterm labor but further illustrated how maternal and fetal signals coordinately modulate the inflammatory process at the maternal-fetal interface, causing the initiation of term or preterm labor., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wang, Ou and Gao.)

Preterm birth (PTB) is defined as delivery occurring before 37 weeks of gestation. In this paper, Artificial Intelligence (AI)-based predictive models are adapted to accurately estimate the probability of PTB. In doing so, pregnant women' objective results and variables extracted from the screening procedure in combination with demographics, medical history, social history, and other medical data are used. A dataset consisting of 375 pregnant women is used and a number of alternative Machine Learning (ML) algorithms are applied to predict PTB. The ensemble voting model produced the best results across all performance metrics with an area under the curve (ROC-AUC) of approximately 0.84 and a precision-recall curve (PR-AUC) of approximately 0.73. An attempt to provide clinicians with an explanation of the prediction is performed to increase trustworthiness.

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Preterm premature rupture of membranes, leading to preterm birth, is associated with neonatal and maternal morbidity and mortality. The study aimed to review the existing data on the best predictive value of pregnancy latency for known biomarkers in pregnancies after preterm premature rupture of membranes. The following databases were screened for the purposes of this systematic review: Pubmed/MEDLINE, Web of Science, EMBASE, Scopus, and the Cochrane Library. The study was conducted according to the PRISMA guidelines for systematic reviews. Only a few studies assessed biomarkers predicting pregnancy duration after PPROM. IL-6, IL-8, CRP, IL1RA, s-endoglin, βhCG, AFP, PCT, urea, creatinine, oxygen radical absorbance capacity, MDA, lipocalin-2, endotoxin activity, MMP-8, MMP-9 and S100 A8/A9 were found to have a positive predictive value for delivery timing prediction. Proinflammatory biomarkers, such as IL-6 or CRP, proved to be best correlated with delivery timing, independent of the occurrence of intrauterine infection.

Background: Spontaneous preterm birth (PTB) affects 6.5% of deliveries in Hong Kong. Quantitative fetal fibronectin (fFN) is under-utilised as a test for PTB prediction in Hong Kong. Our objective was to evaluate the effectiveness of quantitative fFN in predicting spontaneous PTB in women with symptoms of threatened preterm labour (TPTL) in our population., Methods: A prospective, double-blinded cohort study of women with a singleton gestation and TPTL symptoms presenting to a tertiary hospital in Hong Kong between 24 + 0 to 33 + 6 weeks was performed from 1st October 2020 and 31st October 2021. Women with vaginal bleeding, ruptured membranes, and cervical dilation > 3 cm were excluded. The primary outcome was to test the characteristics of quantitative fFN in predicting spontaneous PTB < 37 weeks. Secondary outcome was to investigate the relationship between fFN value and time to PTB. Test characteristics of quantitative fFN at different thresholds were evaluated., Results: 48 women with TPTL were recruited. All had fFN testing at admission with the results being concealed from the obstetrician managing the patient. 10 mothers had PTB (< 37 weeks' gestation). 7/48 (15%) had a subsequent PTB within 14 days from testing and 5 (10%) delivered within 48 h. The negative predictive value (NPV) of predicting delivery within 14 days was 97.3% and 100% when using a cut-off of < 50ng/ml and < 10ng/ml respectively. Using > 200 ng/ml as cut-off can also reliably predict delivery within 48 h - 7 days with positive predictive value PPV of 100%; as well as PTB before 37 weeks., Conclusions: Quantitative fFN has predictive value for spontaneous PTB prediction in symptomatic women in a Hong Kong population. fFN concentration could help clinicians rule out PTB and avoid unnecessary interventions and hospitalisation., (© 2023. The Author(s).)

Objective: Despite its high prevalence and the possible link with perinatal complications, marginal cord insertion is surrounded by considerable controversy regarding management. This meta-analysis aimed to study its association with several perinatal outcomes in a manner that provides trustworthy and exact effect measures, enabling us eventually to evaluate its overall risk for pregnancy., Data Sources: A systematic search was performed in Medline, Scopus, and the Cochrane Library on July 30, 2022, to identify eligible studies., Study Eligibility Criteria: Observational studies, including singleton pregnancies and comparing MCI with central cord insertion or eccentric cord insertion, either prenatally or postnatally identified, were considered eligible., Methods: The Newcastle-Ottawa Scale was used to assess study quality, and the Quality in Prognosis Studies tool was used to assess bias risk. The main outcome was small-for-gestational-age neonates. A Q test and an I 2 score were used to assess study heterogeneity. The analyses were performed using a random-effects model, and the results were expressed as relative risk or mean difference with a 95% confidence interval., Results: Overall, 15 studies (13 cohort studies and 2 case-control studies) contributed data to the analysis. There was a prenatal diagnosis in 7 studies and a postnatal diagnosis in 8 studies. The overall prevalence of marginal cord insertion was 6.15% (range, 1.13%-11.3%). Pregnancies with marginal cord insertion compared with pregnancies with central cord insertion were found to be at higher risk of small-for-gestational-age neonates (relative risk, 1.25; 95% confidence interval, 1.21-1.29), preeclampsia (relative risk, 1.61; 95% confidence interval, 1.54-1.67), placental abruption (relative risk, 1.53; 95% confidence interval, 1.34-1.75), stillbirth (relative risk, 1.97; 95% confidence interval, 1.02-3.78), preterm delivery (relative risk, 1.47; 95% confidence interval, 1.24-1.75), lower mean gestational age at birth (mean difference, -0.20; 95% confidence interval, -0.38 to -0.01), emergency cesarean delivery (relative risk, 1.39; 95% confidence interval, 1.35-1.44), lower mean birthweight (mean difference, -139.19; 95% confidence interval, -185.78 to -92.61), 5-minute Apgar score of <7 (relative risk, 1.48; 95% confidence interval, 1.00-2.19), and neonatal intensive care unit admission (relative risk, 1.57; 95% confidence interval, 1.20-2.06). When only pregnancies with prenatally diagnosed MCI were considered, the risk remained high regarding small for gestational age (relative risk, 1.34; 95% confidence interval, 1.21-1.48), preeclampsia (relative risk, 1.42; 95% confidence interval, 1.01-1.99), stillbirth (relative risk, 2.99; 95% confidence interval, 1.03-8.70), preterm delivery (relative risk, 1.41; 95% confidence interval, 1.19-1.68), lower mean gestational age at birth (mean difference, -0.22; 95% confidence interval, -0.33 to -0.11), and lower mean birthweight (mean difference, -122.41; 95% confidence interval, -166.10 to -78.73)., Conclusion: Here, the higher risk that marginal cord insertion poses for pregnancy, regarding several adverse outcomes, became evident. Many of these associations persisted among the prenatally diagnosed pregnancies. The underlining pathophysiology should be investigated, and further research is needed on the effect of increased surveillance in improving perinatal outcomes., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: This study aimed to identify trends in pregnancy outcomes, especially delivery mode, among pregnant patients older than 45 years., Data Sources: A literature search was performed using PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials for studies published between January 1, 2010, and June 30, 2022., Study Eligibility Criteria: The primary outcomes were cesarean delivery and assisted delivery. The secondary outcomes were preeclampsia, gestational diabetes mellitus, placenta previa, placental abruption, postpartum hemorrhage, and preterm birth. The inclusion criteria were studies examining the relationship between older age pregnancy and pregnancy outcomes, studies that compared pregnancy outcomes at maternal age ≥45 years and <45 years, and at least one of the primary and secondary pregnancy outcomes were included., Methods: Study screening was performed after duplicates were identified and removed. The quality of each study and publication bias were assessed. Forest plots and I 2 statistics were calculated for each study outcome for each group. The main analysis was a random-effects analysis. The inverse variance method was used to integrate the results if studies had an adjusted analysis., Results: Among 4209 studies initially retrieved, 24 were included in this review. All studies were retrospective, observational studies. Pregnant patients aged ≥45 years had a significantly higher cesarean delivery rate (odds ratio, 2.87; 95% confidence interval, 2.50-3.30; I 2 =97%) than those aged <45 years. However, the emergency cesarean delivery rate was lower in older pregnant patients (odds ratio, 0.61; 95% confidence interval, 0.47-0.79; I 2 =79%). Pregnancy in older individuals was associated with a lower assisted delivery rate than pregnancy in younger individuals (odds ratio, 0.85; 95% confidence interval, 0.75-0.97; I 2 =48%). Preeclampsia, gestational diabetes mellitus, placenta previa, placental abruption, postpartum hemorrhage, and preterm birth were more likely to occur in pregnant patients aged ≥45 years than in those aged <45 years. Adjusted pooled analyses showed trends similar to those in the unadjusted pooled analyses., Conclusion: Adverse pregnancy outcomes, typically cesarean delivery, were more likely to occur in older (≥45 years) pregnant patients than in younger pregnant patients. However, the assisted delivery rate was lower in older pregnant patients., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Cervical cerclage is an effective intervention to prevent preterm birth among individuals with a history of cervical insufficiency, individuals with a short cervix and history of preterm birth, or individuals with second-trimester painless dilation. Although cerclage reduces the mechanical stress on the cervix by reinforcing it with sutures, cerclage could also cause scarring of the cervix, which may affect the progress of labor., Objective: This study aimed to compare the labor curves between individuals who underwent cerclage and those who did not undergo cerclage., Study Design: This was a retrospective cohort study of individuals with singleton term pregnancy, vertex presentation, and vaginal delivery, using the data from the Consortium on Safe Labor. We excluded individuals with fetal anomalies, stillbirth, or abnormal perinatal outcomes, including 5-minute Apgar score of <7, birth injury, and neonatal intensive care unit admission. We modeled the course of cervical dilation using repeated-measures analysis with a polynomial function and generated smoothed labor curves. An interval-censored regression analysis was performed to estimate traverse times (the elapsed time between 2 cervical dilation measures). The traverse times were compared between individuals who underwent cerclage and those who did not undergo cerclage, controlling for induction of labor and parity., Results: There were 245 individuals who underwent cerclage and 110,080 individuals who did not undergo cerclage. Individuals who underwent cerclage compared with those who did not undergo cerclage had a similar traverse time from 1 to 6 cm (median, 9.1 vs 10.3 hours; adjusted P=.37) and from 6 to 10 cm (median, 1.5 vs 1.5 hours; adjusted P=.23). Individuals who underwent cerclage compared with those who did not undergo cerclage had a longer traverse time from rupture of membranes to delivery (median, 4.0 vs 3.0 hours; adjusted P<.01)., Conclusion: Cervical cerclage did not affect the overall progress of labor., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: An abnormally soft cervix could contribute to the pathophysiology of cervical shortening and cervical insufficiency. Multiple techniques to measure cervical softness have been developed but none are used routinely in clinical practice. A clinically acceptable technique to measure cervical softness could improve identification of patients at risk for cervix-related preterm birth., Objective: This study aimed to measure cervical softness in patients with cervical insufficiency and in normal controls using a novel, aspiration-based device. We hypothesized that the cervix is softer in patients with cervical insufficiency., Study Design: This was a cross-sectional study of patients presenting for cerclage at a single academic medical center. Cervical softness was measured using a noninvasive, aspiration-based device placed on the anterior lip of the cervix during a speculum examination. The device measured the aspiration pressure required to displace cervical tissue to a predefined deformation level. Stiff tissue required increased aspiration pressure, whereas soft tissue required lower pressure values. Cerclage patients were subdivided into 3 groups, namely history-indicated, ultrasound-indicated, and examination-indicated cerclage. Controls were healthy volunteers between 12+0 weeks and 23+6 weeks of gestation without a history of cervical insufficiency and were matched by gestational age to the patients in the cerclage groups. Women with a cerclage in place, multiple gestations, active genital infection, or previous cervical excision procedures were excluded. Delivery information was subsequently recorded as well., Results: Data from 133 women were analyzed; of those, 54 patients were in the cerclage group (23 history-indicated, 12 ultrasound-indicated, and 19 examination-indicated participants) and 79 were controls (40 in the first trimester and 39 in the second trimester groups). Patients who presented for ultrasound-indicated cerclage had significantly softer cervices (median; interquartile range) than second trimester controls (62 mbar; 50.5-114 vs 81 mbar; 75-101; P=.042). The difference in cervical softness was not significantly different between the history-indicated and examination-indicated cerclage groups and their respective control groups., Conclusion: Patients presenting for ultrasound-indicated cerclage had significantly softer cervices than normal controls as measured by an aspiration-based device. Quantitative measurement of cervical softness with the aspiration-based device is a promising technique for objective measurement of cervical softness during pregnancy., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Short cervical length measured during the second trimester of pregnancy is an important risk factor for spontaneous preterm birth (sPTB). The aim of this study is to identify the association between mid-pregnancy cervical length (CL) and gestational age at birth in asymptomatic singleton pregnant women., Methods: This is a prospective cohort study involving singleton pregnant women who participated in the screening phase of a Brazilian multicenter randomized controlled trial (P5 trial) between July 2015 and March 2019. Transvaginal ultrasound to measure CL was performed from 18 to 22 + 6 weeks. Women with CL ≤ 30 mm received vaginal progesterone (200 mg/day) until 36 weeks' gestation. For this analysis we considered all women with CL ≤ 30 mm receiving progesterone and a random selection of women with CL > 30 mm, keeping the populational distribution of CL. We obtained prognostic effectiveness data (area under receive operating characteristic curve (AUC), sensitivity and specificity and estimated Kaplan-Meier curves for preterm birth using different CL cutoff points., Results: We report on 3139 women and identified a negative association between cervical length and sPTB. CL ≤ 25 mm was associated with sPTB < 28, sPTB < 34 and sPTB < 37 weeks, whereas a CL 25-30 mm was directly associated with late sPTB. CL by transvaginal ultrasound presented an AUC of 0.82 to predict sPTB < 28 weeks and 0.67 for sPTB < 34 weeks. Almost half of the sPTB occurred in nulliparous women and CL ≤ 30 mm was associated with sPTB at < 37 weeks (OR = 7.84; 95%CI = 5.5-11.1). The number needed to screen to detect one sPTB < 34 weeks in women with CL ≤ 25 mm is 121 and we estimated that 248 screening tests are necessary to prevent one sPTB < 34 weeks using progesterone prophylaxis., Conclusions: CL measured by transvaginal ultrasound should be used to predict sPTB < 34 weeks. Women with CL ≤ 30 mm are at increased risk for late sPTB., (© 2023. The Author(s).)

A cervical length (CL) assessment may predict preterm birth (PTB). This study aimed to analyze and compare the recommendations of guidelines on the role of CL in the prediction of PTB. There is no consensus regarding universal screening of asymptomatic women without a history of prior spontaneous PTB (sPTB), using CL. On the other hand, CL assessment is recommended in cases with a history of sPTB due to the high recurrence rate. Finally, there is discrepancy regarding CL assessment in asymptomatic women with multiple pregnancy. Although far from perfect, CL measurement remains the best available method to predict PTB., (© 2022 Wiley Periodicals LLC.)

Objective: Velamentous cord insertion may be identified prenatally, but the clinical implications of this diagnosis remain controversial. This meta-analysis aimed to quantitatively summarize current data on the association of velamentous cord insertion and adverse perinatal outcomes., Data Sources: A systematic search was performed in MEDLINE, Scopus, and the Cochrane Library from inception until May 22, 2022 to identify eligible studies., Study Eligibility Criteria: Observational studies including singleton pregnancies with velamentous cord insertion, either prenatally or postnatally identified, and comparing them with those with central/eccentric cord insertion were considered eligible., Methods: The quality of the studies was assessed with the Newcastle-Ottawa scale and the risk of bias with the Quality In Prognosis Studies (QUIPS) tool. The main outcome was small-for-gestational-age neonates. Heterogeneity of the studies was evaluated using a Q test and an I 2 index. Analyses were performed using a random-effects model, with outcome data reported as relative risk or mean difference with 95% confidence interval., Results: In total, 9 cohort and 2 case-control studies, of which 4 had prenatal and 7 had postnatal velamentous cord insertion diagnosis, were included. The overall prevalence of velamentous cord insertion was estimated to be 1.4% among singleton pregnancies. Compared with the central/eccentric cord insertion control group, pregnancies with velamentous cord insertion were at higher risk of several adverse perinatal outcomes, namely small-for-gestational-age neonates (relative risk, 1.93; 95% confidence interval, 1.54-2.41), preeclampsia (relative risk, 1.85; 95% confidence interval, 1.01-3.39), pregnancy-induced hypertension (relative risk, 1.58; 95% confidence interval, 1.46-1.70), stillbirth (relative risk, 4.12; 95% confidence interval, 1.92-8.87), placental abruption (relative risk, 2.94; 95% confidence interval, 1.72-5.03), preterm delivery (relative risk, 2.14; 95% confidence interval, 1.73-2.65), emergency cesarean delivery (relative risk, 2.03; 95% confidence interval, 1.22-3.38), 1-minute Apgar score <7 (relative risk, 1.53; 95% confidence interval, 1.14-2.05), 5-minute Apgar score <7 (relative risk, 1.97; 95% confidence interval, 1.43-2.71), and neonatal intensive care unit admission (relative risk, 1.63; 95% confidence interval, 1.32-2.02). In a subgroup analysis, prenatally diagnosed velamentous cord insertion was associated with small-for-gestational-age neonates (relative risk, 1.66; 95% confidence interval, 1.19-2.32), stillbirth (relative risk, 4.78; 95% confidence interval, 1.42-16.08), and preterm delivery (relative risk, 2.69; 95% confidence interval, 2.01-3.60). In a sensitivity analysis of studies excluding cases with vasa previa, velamentous cord insertion was associated with an increased risk of small-for-gestational-age neonates (relative risk, 2.69; 95% confidence interval, 1.73-4.17), pregnancy-induced hypertension (relative risk, 1.94; 95% confidence interval, 1.24-3.01), and stillbirth (relative risk, 9.42; 95% confidence interval, 3.19-27.76), but not preterm delivery (relative risk, 1.92; 95% confidence interval, 0.82-4.54)., Conclusion: Velamentous cord insertion is associated with several adverse perinatal outcomes, including stillbirth, and these associations persist when only prenatally diagnosed cases are considered and when vasa previa cases are excluded. According to these findings, the exact pathophysiology should be further investigated and an effective prenatal monitoring plan should be developed., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Cervical length is a commonly used clinical indicator for evaluating preterm birth. However, some studies have shown that cervical length does not change in patients with cervical insufficiency., Objective: This study aimed to use the transvaginal ultrasound E-Cervix to quantitatively evaluate the cervical stiffness in women with singleton and twin pregnancies to provide a reference for the clinical prediction of preterm birth., Study Design: We collected the cervical length, cervical hardness ratio, mean internal os strain, and mean external os strain using transvaginal ultrasonographic E-Cervix assessments in pregnant women undergoing routine examinations in the obstetrics department of our hospital from January 2020 to December 2020. We summarized the range of cervical elasticity parameters at different gestational ages and compared the cervical elasticity parameters between singleton and twin pregnancies and between preterm births and full-term births., Results: A total of 988 pregnant women were enrolled in this study, and after exclusion, 770 pregnant women were enlisted; the interrater and internal consistency for various elasticity parameters were favorable; and cervical elasticity changes in women at full term showed some particular patterns. The declines in cervical length and hardness ratio were commensurate with gestational age, whereas the internal os strain and external os strain rose with increasing gestational age. The cervical hardness ratio in women with twin pregnancies was lower than in women with singleton pregnancies at the same gestational age, although the internal os strain in women with twin pregnancies was higher than in women with singleton pregnancies at the same gestational age (P<.05). The cervical length of women with twin pregnancies was shorter than that of women with singleton pregnancies at the same gestational age when the gestational age was ≥28 weeks of gestation (all P<.05), and the hardness ratio was linearly correlated with gestational age (r=0.68 and r=0.71). The regression model for the cervical hardness ratio in women with singleton pregnancies was hardness ratio = -0.8764×gestational age+100.99, whereas the regression model for the cervical hardness ratio in women with twin pregnancies was hardness ratio = -1.3037×gestational age+103.03. When we compared cervical elasticity parameters between preterm and full-term births, we noted that the cervical hardness ratio in pregnant women who exhibited preterm births was lower regardless of whether they carried singleton or twin pregnancies (P=.000 and P=.000), although their internal os strain was higher (P=.023 and P=.000). We observed no significant difference when we compared the cervical length and external os strain of pregnant women manifesting preterm births vs women with full-term births (P=.216 and P=.345 vs P=.475 and P=.363)., Conclusion: When used for the quantification of cervical hardness, the E-Cervix cervical elasticity changes in pregnant women at full term showed some particular patterns. Cervical length and hardness ratio diminished as gestational age increased, whereas internal os strain and external os strain rose as gestational age increased; moreover, the degree of these changes was greater in women with twin pregnancies than in women with singleton pregnancies. Pregnant women experiencing preterm births exhibited a reduced cervical hardness ratio and augmented internal os strain relative to women experiencing full-term births., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Despite vast research, premature birth's electrophysiological mechanisms are not fully understood. Prediction of preterm birth contributes to child survival by providing timely and skilled care to both mother and child. Electrohysterography is an affordable, noninvasive technique that has been highly sensitive in diagnosing preterm labor. This study aimed to choose the more appropriate combination of characteristics, such as electrode channel and bandwidth, as well as those linear, time-frequency, and nonlinear features of the electrohysterogram (EHG) for predicting preterm birth using classifiers., Methods: We analyzed two open-access datasets of 30 minutes of EHG obtained in regular checkups of women around 31 weeks of pregnancy who experienced premature labor (P) and term labor (T). The current approach filtered the raw EHGs in three relevant frequency subbands (0.3-1 Hz, 1-2 Hz, and 2-3Hz). The EHG time series were then segmented to create 120-second windows, from which individual characteristics were calculated. The linear, time-frequency, and nonlinear indices of EHG of each combination (channel-filter) were fed to different classifiers using feature selection techniques., Results: The best performance, i.e., 88.52% accuracy, 83.83% sensitivity, and 93.22% specificity, was obtained in the 2-3 Hz bands using Medium Frequency, Continuous Wavelet Transform (CWT), and entropy-based indices. Interestingly, CWT features were significantly different in all filter-channel combinations. The proposed study uses small samples of EHG signals to diagnose preterm birth accurately, showing their potential application in the clinical environment., Discussion: Our results suggest that CWT and novel entropy-based features of EHG could be suitable descriptors for analyzing and understanding the complex nature of preterm labor mechanisms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Romero-Morales, Muñoz-Montes de Oca, Mora-Martínez, Mina-Paz and Reyes-Lagos.)

Objective: The study aimed to estimate the predictive value of midtrimester cervical length (CL) and the optimal cut-off of CL that should be applied with asymptomatic nulliparous women for the prediction of spontaneous preterm birth (sPTB)., Study Design: This is a prospective cohort study of asymptomatic nulliparous women with a singleton gestation. Participants underwent CL measurement by transvaginal ultrasound between 20 and 24 weeks of gestation. The participants and their health care providers remained blinded to the results of CL measurement. The primary outcomes were sPTB before 35 weeks and sPTB before 37 weeks. Receiver operating characteristics (ROC) curve analyses were performed. Analyses were repeated by using multiples of median (MoM) of CL adjusted for gestational age., Results: Of 796 participants, the mean midtrimester CL was 40 ± 6 mm with a 1st, 5th, and 10th percentile of 25, 29, and 32 mm, respectively. ROC curve analyses suggest that a cut-off of 30 mm was the optimal CL to predict sPTB before 35 weeks (area under the ROC curve [AUC]: 0.70, 95% confidence interval [CI]: 0.56-0.85) and before 37 weeks (AUC: 0.70, 95% CI: 0.59-0.80). Midtrimester CL <30 mm could detect 35% of all sPTB before 35 weeks at a false-positive rate of 5% (relative risk: 9.1, 95% CI: 3.5-23.5, p  < 0.001). We observed similar results using a cut-off of CL <0.75 MoM adjusted for gestational age., Conclusion: A midtrimester CL cut-off of 30 mm (instead of 25 mm), or CL less than 0.75 MoM, should be used to identify nulliparous women at high risk of sPTB., Key Points: · The optimal CL cut-off for the prediction of sPTB is 30 mm in nulliparous women.. · In nulliparous women, a midtrimester CL < 30 mm is highly associated with sPTB before 35 and 37 weeks.. · A midtrimester of CL <30 mm (5th percentile) should define a short cervix in asymptomatic nulliparous women.., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Preterm birth remains a major public health issue affecting 10% of all pregnancies and increases risks of neonatal morbidity and mortality. Approximately 50% to 60% of preterm births are spontaneous, resulting from preterm premature rupture of membranes or preterm labor. The pathogenesis of spontaneous preterm birth is incompletely understood, and prediction of preterm birth remains elusive. Accurate prediction of preterm birth would reduce infant morbidity and mortality through targeted patient referral to hospitals equipped to care for preterm infants. Two previous studies have analyzed cervical microRNAs in association with spontaneous preterm birth and the length of gestation, but the extent to which microRNAs serve as predictive biomarkers remains unknown., Objective: This study aimed to examine associations between cervical microRNA expression and spontaneous preterm birth, with the specific goal of identifying a subset of microRNAs that predict spontaneous preterm birth., Study Design: We performed a prospective, nested, case-control study of 25 cases with spontaneous preterm birth and 49 term controls. Controls were matched to cases in a 2:1 ratio on the basis of age, parity, and self-identified race. Cervical swabs were collected at a mean gestational age of 17.1 (4.8) weeks of gestation, and microRNAs were analyzed using a quantitative polymerase chain reaction array. Normalized microRNA expression was compared between cases and controls, and a false discovery rate of 0.2 was applied to account for multiple comparisons. Histopathologic analysis of slides of cervical swab samples was performed to quantify leukocyte burden for adjustment in conditional regression models. We explored the use of Relief-based unsupervised identification of top microRNAs and support vector machines to predict spontaneous preterm birth. We performed microRNA enrichment analysis to explore potential biologic targets and pathways in which up-regulated microRNAs might be involved., Results: Of the 754 microRNAs on the polymerase chain reaction array, 346 were detected in ≥75% of participants' cervical swabs. Average cervical microRNA expression was significantly higher in cases of spontaneous preterm birth than in controls (P=.01). There were 95 significantly up-regulated individual microRNAs (>2-fold change) in cases of subsequent spontaneous preterm birth compared with term controls (P<.05; q<0.2). Notably, miR-143, miR-30e-3p, and miR-199b were all significantly up-regulated, which is consistent with the 1 previous study of cervical microRNA and spontaneous preterm birth. A Relief-based, novel variable (feature) selection machine learning approach had low-to-moderate prediction accuracy, with an area under the receiver operating curve of 0.71. Enrichment analysis revealed that identified microRNAs may modulate inflammatory cell signaling., Conclusion: In this prospective nested case-control study of cervical microRNA expression and spontaneous preterm birth, we identified a global increase in microRNA expression and up-regulation of 95 distinct microRNAs in association with subsequent spontaneous preterm birth. Larger and more diverse studies are required to determine the ability of microRNAs to accurately predict spontaneous preterm birth, and mechanistic work to facilitate development of novel therapeutic interventions to prevent spontaneous preterm birth is warranted., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: In this meta-analysis, we aimedto demonstrate the relationship between uterocervical angle and preterm labor in singleton pregnancies more clearly and reliablywith this meta-analysis., Material and Metods: In this study, we use keywords such as "uterocervical angle," "cervical angle," "angle," "cervix," "cervical," "preterm," and "preterm labour." We searched various databases, including PubMed, MEDLINE, ClinicalKey, Scopus, ScienceDirect, Web of Science, and Google Scholar. The search encompassed the period from January 1, 2010, to December 27, 2020. As a result of the literature review, a total of 585 articles were identified. After the screening and selection process, six studies met the inclusion criteria and were included in the analysis. These six studies were deemed relevant and provided valuable information on the research topic., Results: When the Egger test (p = 0.020) and Begg test (p = 0.188) were performed, no significant publication bias was found in the studies examined. These statistical tests assess publication bias, and the resulting p-values indicate a low probability of bias in the included studies. Cochran's Q test revealed the presence of heterogeneity among the included studies. Heterogeneity indicates variability in the results beyond what would be expected by chance alone. This finding suggests that the studies may differ in methodologies, populations, or other factors, which could impact the overall results and require further investigation. There was a significant difference between the patient and control groups (p < 0.001). This result provides strong evidence to support the importance of the difference between the two groups compared., Conclusions: Based on the findings of this study, a wider uterocervical angle appeared to be significantly associated with an increased risk of preterm delivery in overall effect. It concluded that a wide uterocervical angle may be a potential risk factor for preterm delivery. Moreover, the study revealed a significant association between wider uterocervical angles and an elevated risk of preterm labour in singleton pregnancies. In this study, the definition of preterm birth accepts as birth before 37 weeks of gestation. These results highlight the potential significance of evaluating the uterocervical angle as a meaningful predictor for identifying the propensity of preterm labour in singleton pregnancies.

Objective: This study aimed to investigate the association between early pregnancy with subchorionic hematoma and preterm delivery and other adverse pregnancy outcomes in singleton pregnancies., Data Sources: English studies published from 2000 to July 15, 2022 were retrieved from PubMed, Web of Science, and the Cochrane Library., Study Eligibility Criteria: The inclusion criteria were: singleton pregnancy, subchorionic hematoma, and perinatal outcomes. Studies including multiple pregnancy, basic molecular studies, case reports (series), and conference reviews were excluded., Methods: Data analysis was mainly conducted with Review Manager (RevMan) and Stata, and the results were represented with odds ratios and 95% confidence intervals. The methodological quality of the included studies was evaluated by the Cochrane risk assessment scale., Results: In total, 370 studies were retrieved from the above databases. Our review included 16 studies and divided them into 2 subgroups: natural pregnancy (12 studies) and assisted reproductive pregnancy (4 studies). The relevant characteristics of each study were analyzed in detail. The primary outcome was preterm delivery. The secondary outcomes were miscarriage, fetal growth restriction, cesarean delivery, and preeclampsia. We found that subchorionic hematoma in the first trimester was not significantly associated with preterm delivery (odds ratio, 1.11; 95% confidence interval, 0.82-1.51) or other adverse outcomes in singleton pregnancy. Regression analysis found that the large heterogeneity of the included studies might be related to whether the included study population (early pregnancy with subchorionic hematoma) was complicated with threatened abortion (P<.05). However, no studies caused large heterogeneity according to sensitivity analysis. Finally, 15 studies related to preterm delivery did not have publication bias (Egger test: P=.26). However, subchorionic hematoma in the first trimester was associated with miscarriage in single pregnancies (natural pregnancy: odds ratio, 3.07; 95% confidence interval, 1.98-4.75; assisted reproductive pregnancy: odds ratio, 1.45; 95% confidence interval, 1.1-1.90)., Conclusion: In singleton pregnancy, we found no association between subchorionic hematoma in the first trimester and preterm delivery. Although there was a correlation with miscarriage, the possible gestational age of miscarriage was not stated. More studies are needed to further address the herein posed research questions., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Asymptomatic cervical changes, such as cervical length shortening and dilation, which often occur before spontaneous preterm birth, have been described well in singleton pregnancies with or without history of preterm birth. The current screening strategies available to identify patients at increased risk of spontaneous preterm birth include use of transvaginal ultrasound for cervical length assessment and for detection of a short cervical length (≤25 mm) before 24 weeks of gestation. Whether an additional evaluation of the cervix (ie, via speculum or manual exam) is indicated is often pondered by clinicians and may depend on how short the cervical length is and if there is a history of preterm birth. Based on expert opinion, we developed a novel staging system of asymptomatic cervical changes including the following: cervical length measurement, cervical and membrane appearance on speculum exam, and cervical dilation by manual exam. This staging system, if proven accurate, may aid in standardizing definitions for purposes of patient prognosis, evaluation of intervention efficacy, and clinical management., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Reducing the rate of preterm birth is a cornerstone of global efforts to address child mortality, however existing screening tests offer imperfect prediction. Cervical electrical impedance spectroscopy (EIS) is a novel technique to quantify the ripening changes which precede labour. Mid-trimester EIS measurements have been shown to accurately predict preterm birth in asymptomatic women. This study aimed to comprehensively evaluate the acceptability of cervical EIS to low and high-risk women as part of a package of screening tests performed during a larger prospective trial., Methods: In this parallel convergent mixed methods study, 40 women completed questionnaires before and after screening tests (EIS, cervical length measurement and fetal fibronectin quantification). Quantitative outcomes were anxiety levels before and after screening (Spielberger State Trait Anxiety Inventory, STAI-6), pain (Short Form McGill Pain Questionnaire) and ratings of EIS device appearance and test acceptability (visual analogue scales). Twenty-one women (11 high-risk, 10 low-risk) also attended a semi-structured qualitative interview. Interviews were recorded and transcribed, then thematic analysis was performed. A convergence coding matrix was constructed to enable triangulation of quantitative and qualitative results., Results: High risk women demonstrated a significant reduction in anxiety following screening (mean STAI-6 score 34.5 vs. 29.0, p = 0.002). A similar trend was observed among low-risk participants. Ratings of pain, EIS device appearance and procedural acceptability did not differ between groups. Mean pain ratings were low (visual analogue scale 0.97 and 1.01), comparing favourably to published evaluations of conventional screening tests. Qualitative analysis provided insight into both the physical consequences and emotional experiences of screening. Additional determinants of the screening experience included device design, pre-existing perspectives on intimate examination, attitudes to knowledge in pregnancy and interaction with clinical staff. Finally, a range of practical considerations regarding wider use of EIS were identified, with valuable complementary detail regarding acceptability for use in antenatal care., Conclusions: Cervical EIS is well tolerated and acceptable to both low and high-risk women when performed as part of a multi-modal screening package. These results provide useful insights to inform the design of future study and screening protocols., (© 2022. The Author(s).)

Preterm birth may have a pathological impact on intrauterine development of the fetal brain, resulting in developmental disabilities. In this study, we examine the expression of soluble Fms-like tyrosine kinase 1 (sFLT-1) and placental growth factor (PlGF), which is one of the vascular endothelial growth factors (VEGFs), as these play a key role in angiogenesis; in particular, we examine their effect on the sFLT-1/PlGF ratio in cases of preterm birth as compared to typical pregnancies. Enzyme-linked immunosorbent assay was performed on samples of maternal-derived plasma and extracellular vesicles-exosomes (EVs-EXs) isolated at the third trimester, consisting of 17 samples from cases of preterm birth and 38 control cases. Our results showed that both sFLT-1 (P=0.0014) and PlGF (P=0.0032) were significantly downregulated in cases of preterm birth compared to controls, while the sFLT-1/PIGF ratio was significantly (P=0.0008) increased in EVs-EXs, but not in maternal plasma. Our results suggest that this reduced expression of sFLT-1 and PlGF with an elevated sFLT-1/PlGF ratio in EVs-EXs may represent a potential biomarker for prediction of PTB., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hussein, Ju, Pizzella, Flory, Chu, Wang and Zhong.)

Aim: The aim of this study was to compare the clinical characteristics of singleton and twin pregnancies that resulted in spontaneous preterm births (sPTB) and to evaluate the prognostic value of phosphorylated insulin-like growth factor binding protein-1 (phIGFB-1) and placental alpha macroglobulin-1(PAMG-1) for sPTB prediction in symptomatic women., Patients and Methods: The study included 420 women and included two parts. Firstly, we performed a retrospective cohort study comparing pregnancy and neonatal outcomes in 170 women with singleton pregnancies and spontaneous preterm birth before 37 weeks of gestation with 150 women with twin pregnancies who delivered at the same gestational age. In order to obtain the link between clinical and biochemical predictors of preterm labor we organized the second part of the research. The second part was a prospective observational study in 100 women with singleton and twin pregnancies between 24 and 33 + 6 weeks of gestation and symptoms of threatening preterm labor and intact membranes. We assessed the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for phIGFBP-1 and PAMG-1 in terms of sPTB within 7 days and 14 days after testing., Results: The rate of preterm premature rupture of membranes was higher in singleton pregnancies (67.1 versus 42.8%, p  = 0.034). Cervical shortening in multiples was diagnosed at an earlier mean gestational age than in singleton pregnancies (30.1 ± 4.3 versus 35.9 ± 3.1 weeks, p  = 0.013). In the singleton pregnancies group, the rate of microbial cervical colonization and the rate of bacterial vaginosis were significantly higher than in twin pregnancies (49.4 versus 15.3%, p  < 0.001; 32.9 versus 12.0%, p  = 0.007, respectively). Premature twins had a longer oxygen dependency period, while the singletons were more predisposed to infectious morbidity. The study showed low sensitivity of phIGFBP-1 for sPTB, while the sensitivity of the PAMG-1 test was higher (sensitivity 60% and 90% within 7 days after testing and 50 versus 75% within 14 days after testing). Both tests showed a high NPV for sPTB (93.3% for phIGFBP-1 versus 98.9% for PAMG-1). The NPV for preterm labor in twins was also high for both tests (93% for phIGFBP-1 and 96% for PAMG-1)., Conclusion: Cervical shortening is the main risk factor of sPTB in women with twin pregnancies; sPTB among singletons is associated with ascendent infection, involving fetal membranes. The PAMG-1 test showed high PPV and NPV for sPTB in symptomatic women and could be a reliable prognostic tool in clinical obstetrics. High NPV was observed for phIGFBP-1 and PAMG-1 in twin pregnancies.

Objective: Measure availability and use of fetal fibronectin (fFN) testing and transvaginal ultrasound to measure cervical length (TVCL) for symptomatic preterm labor (PTL) patients. Additionally, assess the presence and impact of PTL triage protocols., Study Design: Cross-sectional online survey among clinicians from 255 unique hospitals regarding prior 12-month practices (pre-COVID-19)., Results: fFN testing was always available in 87% (221) of hospitals, while TVCL was always available in 69% (175) of hospitals. Utilization was lower: fFN specimens were often/always collected in 61% (156) of hospitals and TVCL was often/always performed in 43% (110) of hospitals. fFN testing was significantly more likely than TVCL to be available and used ( p  < .05). Written PTL protocols were available in 47% (121) of hospitals but not consistently followed., Conclusion: The most accurate risk assessment approach for imminent spontaneous preterm birth is the implementation of a universal screening program for symptomatic patients, including fFN testing and TVCL.

Objectives: We aimed to assess the risk of preterm birth in those with real-time dynamic cervical shortening., Methods: A retrospective matched case-control study. The study group comprised all women with dynamic cervical shortening (≥4 mm) noted from 24 to 34 weeks of gestation during 2010-2017 at a university hospital. Two control groups of women were established by matching the minimal and maximal cervical length measured, as well as age, parity, gestational age, history of spontaneous preterm birth, symptoms of preterm labor, and delivery year., Results: Data from 339 women were analyzed, 113 with dynamic cervical shortening comprised the study group, and two groups with 113 women each, matched for the minimal and maximal cervical lengths measured comprised the control groups. Rates of spontaneous preterm birth rate at <37 weeks (32.7% vs. 15.9%; OR [95% CI]: 2.60 (1.36, 4.87), p  = .004) and <35 weeks (15.9% vs. 5.3%; OR [95% CI]: 3.38 (1.29, 8.86), p  = .013) were significantly higher among those with dynamic cervix than among the control group matched for the maximal cervical length, and comparable to the control group matched for the minimal cervical length. The negative predictive values of cervical length for preterm birth occurrence at various cutoff values were lower in those with dynamic cervix., Conclusions: The minimal cervical length measured should be used to guide patient management when dynamic cervix is noted. In the setting of dynamic cervical change, the value of cervical length as a negative predictor of preterm birth is limited.

Objective: Preterm birth is the leading cause of morbidity and mortality involving over 10% of infants. Tools for timely diagnosis of preterm birth are lacking and the underlying physiological mechanisms are unclear. The aim of the present study is to improve early assessment of pregnancy progression by combining and optimizing a large number of electrohysterography (EHG) features with a dedicated machine learning framework., Methods: A set of reported EHG features are extracted. In addition, novel cross and multichannel entropy and mutual information are employed. The optimal feature set is selected using a wrapper method according to the accuracy of the leave-one-out cross validation. An annotated database of 74 EHG recordings in women with preterm contractions was employed to test the ability of the proposed method to recognize the onset of labor and the risk of preterm birth. Difference between using the contractile segments only and the whole EHG signal was compared., Results: The proposed method produces an accuracy of 96.4% and 90.5% for labor and preterm prediction, respectively, much higher than that reported in previous studies. The best labor prediction was observed with the contraction segments and the best preterm prediction achieved with the whole EHG signal. Entropy features, particularly the newly-employed cross entropy contribute significantly to the optimal feature set for both labor and preterm prediction., Significance: Our results suggest that changes in the EHG, particularly the regularity, might manifest early in pregnancy. Single-channel and cross entropy may therefore provide relevant prognostic opportunities for pregnancy monitoring.

Objective: There is a lack of consensus about the management of twins with significant cervical length (CL) shortening, especially if CL is above 25 mm. Therefore, it is important to define "abnormal" CL change over time, and to compare the performance of different strategies. The aim of this study was twofold, to describe the performance of the cervical shortening and that of an integrated strategy that includes both the cervical shortening and a fixed CL cutoff <25 mm in any measurement as predictor of spontaneous PTB (sPTB) < 34 weeks in uncomplicated twin pregnancies., Material and Methods: Retrospective cohort study of twins followed in our Twins Clinic at Hospital Italiano de Buenos Aires from 2013 to 2017. Inclusion criteria were dichorionic or monochorionic diamniotic twins with CL measurement between 18 and 33 + 6 weeks with available data of the delivery. Exclusion criteria included any of the following complications: iatrogenic preterm delivery <34 weeks, cerclage, fetal growth restriction, fetal death, structural anomalies, polyhydramnios, twin-twin transfusion syndrome, selective fetal growth restriction, twin anemia-polycythemia sequence, and twin reversed arterial perfusion sequence. Spontaneous preterm birth was defined as spontaneous delivery <34 weeks. Cervical shortening was analyzed in the following periods: 20-24 weeks, 20-28 weeks, 24-28 weeks, 24-32 weeks and 28-32 weeks. Cervical changes were analyzed as velocity of shortening over time (mm/week) and as the ratio of shortening over time (%/week). ROC curves for each period were constructed and two different cutoffs were used to classify changes of the CL as positive or negative screening: a) the shortening of CL associated to the highest value of the Youden Index and b) fixing a 10% false positive rate (FPR). For the second objective, we analyzed an integrated strategy considering a fixed cutoff of 25 mm at any GA and/or a significant shortening. The screening was considered positive if any CL measurement was <25 mm at any GA or there was a shortening of the CL ≥ the cutoff obtained for each period. We report sensitivity, specificity, positive and negative predictive value, positive and negative likelihood ratio and area under the ROC curve., Results: We included 378 patients and 1417 measurements, 284 (75%) dichorionic and 94 (25%) monochorionic. Between 20 and 28 weeks, with a change in CL cutoff = 1.6 mm/week or 4.1%/week the detection rate was 54.2% (32.8-74.4%) and the specificity 80.5% (75.1-85.1%) and 83.5% (78.5-87.8%) respectively. In the integrated strategy, the detection rate was 65.7% (47.8-80.9%) and the specificity 69 (63.7-74). All the ROC curves of the periods studied showed an AUC < 0.7. In the group of patients that delivered preterm the initial mean CL was shorter than in the term group, 39 (±12) mm vs. 43 (± 7.7) mm ( p  = .02) and the most important change in CL was at 20-24 weeks both in the velocity and in the ratio of shortening over time. Conversely, patients that delivered at term showed a higher change in CL in the third trimester., Conclusion: The performance of all the strategies analyzed as a predictor of sPTB <34 weeks was moderate. The period 20-28 weeks detected half of the patients at risk with a FPR around 10-20% and the integrated strategy increased the sensitivity up to a detection of two thirds of the patients at risk but with a FPR of ∼30%. Future analyses need to explore other strategies to improve the performance and to really identify the patients at higher risk.

Objectives: To address the disproportionate burden of preterm birth (PTB) in low- and middle-income countries, this study aimed to (1) verify the performance of the United States-validated spontaneous PTB (sPTB) predictor, comprised of the IBP4/SHBG protein ratio, in subjects from Bangladesh, Pakistan and Tanzania enrolled in the Alliance for Maternal and Newborn Health Improvement (AMANHI) biorepository study, and (2) discover biomarkers that improve performance of IBP4/SHBG in the AMANHI cohort., Study Design: The performance of the IBP4/SHBG biomarker was first evaluated in a nested case control validation study, then utilized in a follow-on discovery study performed on the same samples. Levels of serum proteins were measured by targeted mass spectrometry. Differences between the AMANHI and U.S. cohorts were adjusted using body mass index (BMI) and gestational age (GA) at blood draw as covariates. Prediction of sPTB < 37 weeks and < 34 weeks was assessed by area under the receiver operator curve (AUC). In the discovery phase, an artificial intelligence method selected additional protein biomarkers complementary to IBP4/SHBG in the AMANHI cohort., Results: The IBP4/SHBG biomarker significantly predicted sPTB < 37 weeks ( n  = 88 vs. 171 terms ≥ 37 weeks) after adjusting for BMI and GA at blood draw (AUC= 0.64, 95% CI: 0.57-0.71, p  < .001). Performance was similar for sPTB < 34 weeks ( n  = 17 vs. 184 ≥ 34 weeks): AUC = 0.66, 95% CI: 0.51-0.82, p  = .012. The discovery phase of the study showed that the addition of endoglin, prolactin, and tetranectin to the above model resulted in the prediction of sPTB < 37 with an AUC= 0.72 (95% CI: 0.66-0.79, p -value < .001) and prediction of sPTB < 34 with an AUC of 0.78 (95% CI: 0.67-0.90, p  < .001)., Conclusion: A protein biomarker pair developed in the U.S. may have broader application in diverse non-U.S. populations.

Objective: Pregnancy after conization is associated with a high risk of preterm delivery. However, because risk factors for preterm delivery after conization remain unknown, we conducted a multicenter observational study to investigate risk factors associated with preterm delivery., Methods: We selected patients who had previously undergone conization and reviewed medical records from 18 hospitals in cooperation with Keio University School of Medicine between January 2013 and December 2019. Women were classified as nulliparous and primiparous, and a multiple logistic regression analysis was performed to evaluate the relative contributions of the various maternal risk factors for preterm delivery (i.e. delivery before 37 gestational weeks)., Results: Among 409 pregnant women after conization, 68 women delivered preterm (17%). The incidence of nulliparity ( p  = .014) was higher and a history of preterm delivery ( p  = .0010) was more common in the preterm delivery group than in the term delivery group. Furthermore, the proportion of women diagnosed with adenocarcinoma in situ (AIS) and cervical cancer in the preterm delivery group was higher than that in the term delivery group ( p  = .0099 and .0004, respectively). In multiple regression models in nulliparous women, cervical cancer or AIS (Odds ratio [OR]: 4.16, 95% CI: 1.26-13.68, p  = .019) and a short cervix in the second trimester (OR: 13.41, 95% CI: 3.88-46.42, p  < .0001) increased the risk of preterm delivery. Furthermore, a history of preterm delivery (OR: 7.35, 95% CI: 1.55-34.86, p  = .012), cervical cancer or AIS (OR: 5.07, 95% CI: 1.24-20.73, p  = .024), and a short cervix in the second trimester (OR: 4.29, 95% CI: 1.11-16.62, p  = .035) increased the risk of preterm delivery in the multiple regression models in primiparous women., Conclusion: Pregnant women who previously underwent conization are at risk for preterm delivery. The histological type of AIS and cervical cancer was evaluated as a risk factor for preterm delivery. KEY MESSAGESPrior preterm delivery, presence of a short cervix, and cervical cancer or AIS were predictors of preterm delivery after conization.The depth of conization in cervical cancer or AIS group was significantly larger than that in the CIN group.

Background: Identifying pregnancies at risk for preterm birth, one of the leading causes of worldwide infant mortality, has the potential to improve prenatal care. However, we lack broadly applicable methods to accurately predict preterm birth risk. The dense longitudinal information present in electronic health records (EHRs) is enabling scalable and cost-efficient risk modeling of many diseases, but EHR resources have been largely untapped in the study of pregnancy., Methods: Here, we apply machine learning to diverse data from EHRs with 35,282 deliveries to predict singleton preterm birth., Results: We find that machine learning models based on billing codes alone can predict preterm birth risk at various gestational ages (e.g., ROC-AUC = 0.75, PR-AUC = 0.40 at 28 weeks of gestation) and outperform comparable models trained using known risk factors (e.g., ROC-AUC = 0.65, PR-AUC = 0.25 at 28 weeks). Examining the patterns learned by the model reveals it stratifies deliveries into interpretable groups, including high-risk preterm birth subtypes enriched for distinct comorbidities. Our machine learning approach also predicts preterm birth subtypes (spontaneous vs. indicated), mode of delivery, and recurrent preterm birth. Finally, we demonstrate the portability of our approach by showing that the prediction models maintain their accuracy on a large, independent cohort (5978 deliveries) from a different healthcare system., Conclusions: By leveraging rich phenotypic and genetic features derived from EHRs, we suggest that machine learning algorithms have great potential to improve medical care during pregnancy. However, further work is needed before these models can be applied in clinical settings., (© 2022. The Author(s).)

Objectives: To evaluate different cut-off values of first trimester pregnancy associated plasma protein-A (PAPP-A) in screening for adverse pregnancy outcomes in a retrospective cohort study., Methods: During the study period of 1.1.2014-31.12.2018, total of 23,482 women with singleton pregnancies participated in first trimester combined screening for chromosomal abnormalities. Maternal serum PAPP-A multiple of medians (MoM) levels were measured, and study population was divided into three study groups of PAPP-A ≤0.40 (n=1,030), ≤0.35 (n=630) and ≤0.30 (n=363) MoM., Results: Small for gestational age (SGA), preterm birth (PTB) and composite outcome (SGA, hypertensive disorder of pregnancy (HDP) and/or PTB) were more frequent in all three PAPP-A MoM study groups and pre-eclampsia in ≤0.40 and ≤0.35 study groups than in their control groups (p < 0.05). The odds ratio (OR) for SGA varied from 3.7 to 5.4 and sensitivity and specificity from 6.9 to 13.8% and from 95.9 to 98.6%, between study groups. Using PAPP-A ≤0.30 MoM as a screening cut-off instead of PAPP-A ≤0.40 MoM, resulted in approximately 50% reduction in screening detection of SGA and PTB., Conclusions: PAPP-A ≤0.40 MoM should be considered as a primary screening cut-off for adverse pregnancy outcomes as approximately 23% will develop either SGA, HDP or PTB. It seems to be the best cut-off to screen for SGA., (© 2022 Walter de Gruyter GmbH, Berlin/Boston.)

Background: Fetal fibronectin is a useful biomarker in the diagnosis and management of preterm labour., Objectives: To evaluate the relationship between cervical fetal fibronectin and preterm delivery and the association between cervical fetal fibronectin level and gestational age at delivery., Materials and Methods: A prospective cohort study was performed in a tertiary hospital in Nigeria, involving equal number of pregnant women with (96) and without (96) preterm labour. Fetal fibronectin assay was done using solid-phase immunogold assay. The data were analysed using IBM SPSS version 24. Descriptive and inferential statistical analyses were done. The level of significance was p -value <0.05., Results: Less than half (47.9%) of the women in the study group had preterm delivery while 13.09% of the women in the control group delivered preterm. Fetal fibronectin test had a sensitivity, specificity, positive predictive value and negative predictive value of 78%, 86.5%, 71.9%, and 89.0%, respectively, a positive likelihood ratio and negative likelihood ratio of 5.76(95% CI, 3.67 - 9.64) and 0.26(95% CI, 0.16 - 0.41), respectively., Conclusion: The findings in our study value of fetal fibronectin in predicting preterm delivery. Its use will support less intervention for patients with negative results., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2022 Cyril C. Ikeoha et al.)

Objective: This study aimed to systematically investigate a wide range of obstetrical and neonatal outcomes as they relate to gestational weight gain less than the current Institute of Medicine and the American College of Obstetricians and Gynecologists guidelines when compared with weight gain within the guideline range and to stratify outcomes by the class of obesity and by the type of study analysis., Data Sources: We systematically searched studies on PubMed, Scopus, Embase, and the Cochrane Library from 2009 to April 30, 2021., Study Eligibility Criteria: Studies reporting on obstetrical and neonatal outcomes of singleton pregnancies related to gestational weight gain less than the current Institute of Medicine and the American College of Obstetricians and Gynecologists guidelines in comparison with weight gain within the guidelines among women with obesity overall (body mass index >30 kg/m 2 ) and/or a specific class of obesity (I: body mass index, 30-34.9 kg/m 2 ; II: body mass index, 35-39.9 kg/m 2 ; and III: body mass index >40 kg/m 2 )., Methods: Among the studies that met the inclusion criteria, multiple obstetrical and neonatal outcomes were tabulated and compared between pregnancies with weight gain less than recommended in the guidelines and those with weight gain within the guidelines, further classified by the class of obesity if applicable. Primary outcomes included small for gestational age neonates, large for gestational age neonates, preeclampsia, and gestational diabetes mellitus. Secondary outcomes included cesarean delivery, preterm birth, postpartum weight retention, and composite neonatal morbidity. A meta-analysis of univariate and adjusted multivariate analysis studies was conducted. The random-effect model was used to pool the mean differences or odds ratios and the corresponding 95% confidence intervals. Heterogeneity was assessed using the I 2 value. The Newcastle-Ottawa Scale was used to assess individual study quality., Results: A total of 54 studies reporting on 30,245,946 pregnancies were included of which 11,515,411 pregnancies were in the univariate analysis and 18,730,535 pregnancies were in the adjusted multivariate analysis. In the meta-analysis of univariate studies, compared with women who gained weight as recommended in the guidelines, those who gained less than the weight recommended in the guidelines had higher odds of having a small for gestational age neonate among those with obesity class I and II (odds ratio, 1.30; 95% confidence interval, 1.17-1.45; I 2 =0%; P<.00001; and odds ratio, 1.56; 95% confidence interval, 1.31-1.85; I 2 =0%; P<.00001, respectively). However, the incidence of small for gestational age neonates was below the expected limits (<10%) and was not associated with increased neonatal morbidity. Furthermore, after adjusting for covariates, that difference was not statistically significant anymore. The difference was not statistically significant for class III obesity. Following adjusted multivariate analysis, no significant differences in small for gestational age rates were noted for any classes of obesity between groups. Significantly lower odds for large for gestational age neonates were seen in the group with gestational weight gain less than the recommended guidelines among those with obesity class I, II, and III (odds ratio, 0.69; 95% confidence interval, 0.64-0.73; I 2 =0%; P<.00001; odds ratio, 0.68; 95% confidence interval, 0.63-0.74; I 2 =0%; P<.00001; and odds ratio, 0.65; 95% confidence interval, 0.57-0.75; I 2 =34%; P<.00001, respectively), and similar findings were seen in the adjusted multivariate analysis. Women with weight gain less than the recommended guidelines had significantly lower odds for preeclampsia among those with obesity class I, II, and III (odds ratio, 0.71; 95% confidence interval, 0.63-0.79; I 2 =0%; P<.00001; odds ratio, 0.82; 95% confidence interval, 0.73-0.91; I 2 =0%; P<.00001; and odds ratio, 0.82; 95% confidence interval, 0.70-0.94; I 2 =0%; P=.006, respectively), and similar findings were seen in the adjusted multivariate analysis. No significant differences were seen in gestational diabetes mellitus between groups. Regarding preterm birth, available univariate analysis studies only reported on overall obesity and mixed iatrogenic and spontaneous preterm birth showing a significant increase in the odds of preterm birth (odds ratio, 1.42; 95% confidence interval, 1.40-1.43; I 2 =0%; P<.00001) among women with low weight gain, whereas the adjusted multivariate studies in overall obesity and in all 3 classes showed no significant differences in preterm birth between groups. Women with low weight gain had significantly lower odds for cesarean delivery in obesity class I, II, and III (odds ratio, 0.76; 95% confidence interval, 0.72-0.81; I 2 =0%; P<.00001; odds ratio, 0.82; 95% confidence interval, 0.77-0.87; I 2 =0%; P<.00001; and odds ratio, 0.87; 95% confidence interval, 0.82-0.91; I 2 =0%; P<.00001, respectively), and similar findings were seen in the adjusted multivariate analysis. There was significantly lower odds for postpartum weight retention (odds ratio, 0.20; 95% confidence interval, 0.05-0.82; I 2 =0%; P=.03) and lower odds for composite neonatal morbidity in the overall obesity group with low gestational weight gain (odds ratio, 0.93; 95% confidence interval, 0.87-0.99; I 2 =19.6%; P=.04)., Conclusion: Contrary to previous reports, the current systematic review and meta-analysis showed no significant increase in small for gestational age rates in pregnancies with weight gain below the current guidelines for all classes of maternal obesity. Furthermore, gaining less weight than recommended in the guidelines was associated with lower large for gestational age, preeclampsia, and cesarean delivery rates. Our study provides the evidence that the current recommended gestational weight gain range is high for all classes of obesity. These results provide pertinent information supporting the notion to revisit the current gestational weight gain recommendations for women with obesity and furthermore to classify them by the class of obesity rather than by an overall obesity category as is done in the current recommendations., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Preterm labor is the leading cause of premature mortality and morbidity. Therefore, to rule-in and rule-out preterm delivery is a very important issue in our clinical practice., Objective: The aim of this study was to investigate the value of placental alpha microglobulin-1 (PAMG-1) molecule positivity in cervicovaginal secretions of women who have a CL <25 mm and presenting with preterm labor symptoms to predict spontaneous preterm birth within seven days., Materials and Methods: This was a prospective cohort study conducted in Ankara University Department of Obstetrics and Gynecology between August 2017 and February 2019 on the patients who had Preterm labor symptoms, <25 mm transvaginal cervical length (CL), clinically intact membranes. The primary outcome of the study was the power of CL and PAMG-1 positivity on the prediction of preterm birth in seven days., Results: Sensitivity and specificity values of PAMG-1 in our study population to predict spontaneous preterm birth in seven days were calculated 52.94% and 98.84%, respectively, negative predictive value (NPV) and positive predictive value (PPV) were calculated 91.4% and 90%, respectively. When we investigated our data according to different CL cutoffs, sensitivity and NPV for 20 mm cutoff were 88.24% and 96.3% that was better than PAMG-1, but specificity and PPV were 60.47% and 30.61%, respectively, that was more ineffective than PAMG-1. If we calculate the values according to 15 mm and 10 mm CL cutoffs sensitivity values were 58.8% and 23.53%, specificity values were 81.4% and 91.86%, NPV were 90.9% and 85.87%, PPV were 38.46% and 36.36%, respectively. Finally, accuracy value of PAMG-1 to predict spontaneous preterm birth in seven days was 91.26% that was better than other CL cutoffs (20 mm, 15 mm, and 10 mm)., Conclusion: PAMG-1 molecule with high NPV and PPV (91.4% and 90%) combination will contribute our clinical decision on the population who had preterm labor symptoms and a CL shorter than 25 mm.

Background: Cerclage is used for the prevention of spontaneous preterm birth; however, many patients at high risk of spontaneous preterm birth who have a cerclage in place eventually deliver before term. Although inflammation, measured by biomarkers (eg, cytokines), is a known risk factor for preterm delivery, evaluation of inflammation to determine pregnancy outcomes among patients with cerclage is poorly understood., Objective: We sought to examine levels of maternal plasma inflammatory cytokines in the midtrimester among asymptomatic patients with a cervical cerclage (placed for any indication, including history, ultrasound, and examination indications) to evaluate the association between cytokine levels and preterm birth., Study Design: This was a prospective cohort study of singleton, nonanomalous pregnancies who had a cerclage placed at <24 weeks of gestation from 2015 to 2018 at a single tertiary institution. Maternal plasma was collected perioperatively whenever possible. A custom magnetic bead Luminex cytokine assay was used to measure plasma inflammatory cytokine levels from these stored samples. The primary outcome was preterm birth at <37 weeks of gestation. A statistical cut point was calculated for each cytokine level to assess its optimal sensitivity and specificity for spontaneous preterm birth prediction. Patients were classified as having a "high" or "low" result for each cytokine based on this cut point. Receiver operating characteristic curve analysis was performed to estimate sensitivity, specificity, and positive and negative predictive values for spontaneous preterm birth prediction. Cox proportional-hazards regression modeled the association between the number of "high" inflammatory cytokines and gestational age at delivery, adjusting for confounders. Additional analyses were performed on the subgroup of patients with history-indicated cerclage and those with an ultrasound- or examination-indicated cerclage., Results: A total of 43 patients participated in this study: 20 (46.5%) had spontaneous preterm birth (median, 30.9 weeks of gestation; interquartile range, 28.4-35.0). Plasma samples were collected at a median of 0 (interquartile range, -2 to 17) days concerning cerclage placement and a median of 18 (interquartile range, 13-21) weeks of gestation. Based on the statistical cut point for each cytokine level, 7% of patients had zero, 20.9% had 1, 18.6% had 2, 20.9% had 3, and 32.6% had ≥4 "high" cytokine results. Each additional "high" cytokine level was associated with earlier delivery (hazard ratio, 1.51; 95% confidence interval, 1.25-1.81) even after controlling for ultrasound- or examination-indication for cerclage (hazard ratio, 1.73; 95% confidence interval, 0.95-3.15). The presence of ≥4 "high" cytokine levels was 70% sensitive and 74% specific for predicting spontaneous preterm birth (area under the curve, 0.846; 95% confidence interval, 0.728-0.964; positive predictive value, 70%; negative predictive value, 73.9%)., Conclusion: Among patients with a cervical cerclage, elevated midtrimester maternal plasma cytokine profiles were associated with subsequent preterm birth and can estimate the probability of preterm birth. Confirmation and refinement of this noninvasive panel may provide insight into improved selection of individuals who may benefit from cerclage placement and investigation of therapeutic strategies to mitigate midpregnancy inflammation., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: Spontaneous preterm birth (SPB) can't be predicted accurately nowadays. We aim to investigate the value of serum amyloid A(SAA) and interleukin-6(IL-6) for forecasting the risk of SPB., Methods: A total of 302 pregnant women who completed delivery in our hospital from January 2019 to December 2021 were included. According to gestational days, they were divided into the case group (28-33 +6 weeks, 41 cases; 34-36 +6 weeks, 96 cases) and the control group (37-42 weeks, 165 cases). The general data of the two groups were analyzed and the values of SAA and IL-6 in speculating the risk of SPB were studied in this study., Results: The levels of SAA and IL-6 in the case group were higher than those in the control group(P < 0.05), and the most practical value of SAA and IL-6 access SPB risk were 17.35 mg/L, 112.41 pg/mL respectively. The area under the ROC curve of diagnosis to predict SPB were 0.8849, 0.8664., Conclusions: The assessment of SPB risk by SAA and IL-6 bearscertain clinical value, which could assist clinicians in recognizing and evaluating the potential dangers of SPB., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objectives: To develop gestational age-based reference ranges for cervical length in triplet pregnancies. The secondary objective was to assess the performance of cervical length measured between 18 and 20 + 6 days for the prediction of preterm delivery before 28 and 32 weeks, respectively., Methods: Observational retrospective study of triplet pregnancies in three Spanish tertiary-care hospitals between 2001 and 2019. Cervical length measurements were consecutively obtained between 15 and 34 weeks of gestation. Pregnancies undergoing multifetal reduction or fetal surgery were excluded., Results: Two hundred and six triplet pregnancies were included in the final analysis. There was a quadratic decrease in cervical length with gestational age. The median and fifth centiles for cervical length at 20 weeks were 35 and 13 mm. In the prediction of preterm birth < 28 weeks, for a false positive rate of 5%, and 10%, the detection rates were 40.9%, and 40.9%, respectively, and the prediction of preterm birth < 32 weeks, 22.0% and 26.0%, respectively., Conclusions: In triplet pregnancies, cervical length decreases with gestational age. The performance of cervical length at 18-20 + 6 in screening for preterm birth before 28 and 32 weeks is poor., (© 2022. The Author(s).)