Influence of maternal and placental factors on newborn body composition.

AIM: The objective of this study was to assess whether maternal characteristics, placental size or histological chorioamnionitis was associated with newborn body composition. Furthermore, we sought to determine whether placental weight may mediate the association between maternal pre-pregnancy weight and age with newborn body composition. METHODS: A cross-sectional study was conducted at Royal Prince Alfred Hospital, Sydney, Australia. This study included 136 healthy, singleton, term-born newborns. Recruitment was stratified by newborn body fat percentiles (gender and gestational adjusted). Body fat was assessed by air displacement plethysmography. Placental examination was conducted by an anatomical pathologist. Maternal (chorioamnionitis) and fetal (chorionic and umbilical vasculitis, funisitis) inflammatory responses were classified according to Redline criteria. RESULTS: Maternal pre-pregnancy weight, parity, labour, placental weight and surface area were associated with newborn fat mass and fat-free mass. Gestational diabetes and maternal age were associated with newborn fat mass but not fat-free mass. There was no association between histological chorioamnionitis and newborn body composition; however, spontaneous onset of labour was strongly associated with the presence of histological chorioamnionitis. Only 25-31% of the association of maternal weight and age with newborn fat mass was mediated via the placenta. CONCLUSIONS: Maternal factors associated with newborn fat mass and fat-free mass differed, indicating that different mechanisms control fat mass and fat-free mass. Our mediation analysis suggests that placental weight partly mediates the association of maternal factors with newborn body composition. Histological chorioamnionitis was not associated with newborn body composition.

First Trimester Protein Biomarkers for Risk of Spontaneous Preterm Birth: Identifying a Critical Need for More Rigorous Approaches to Biomarker Identification and Validation.

BACKGROUND: Spontaneous preterm birth is the leading cause of perinatal morbidity and mortality worldwide and continues to present a major clinical dilemma. We previously reported that a number of protein species were dysregulated in maternal serum collected at 11-13+6 weeks' gestation from pregnancies that continued to labour spontaneously and deliver preterm. OBJECTIVES AND METHODS: In this study, we aimed to validate changes seen in 4 candidate protein species: alpha-1-antitrypsin, vitamin D-binding protein (VDBP), alpha-1beta-glycoprotein and apolipoprotein A-1 in a larger cohort of women using a western blot approach. RESULTS: Serum levels of all 4 proteins were reduced in women who laboured spontaneously and delivered preterm. This reduction was significant for VDBP (p = 0.04), which has been shown to be involved in a plethora of essential biological functions, including actin scavenging, fatty acid transport, macrophage activation and chemotaxis. CONCLUSIONS: The decrease in select proteoforms of VDBP may result in an imbalance in the optimal intrauterine environment for the developing foetus as well as to a successful uncomplicated pregnancy. Thus, certain (phosphorylated) species of VDBP may be of value in developing a targeted approach to the early prediction of spontaneous preterm labour. Importantly, this study raises the importance of a focus on proteoforms and the need for any biomarker validation process to most effectively take these into account rather than the more widespread practice of simply focussing on the primary amino acid sequence of a protein.

A Novel Early Pregnancy Risk Prediction Model for Gestational Diabetes Mellitus.

INTRODUCTION: Accurate early risk prediction for gestational diabetes mellitus (GDM) would target intervention and prevention in women at the highest risk. We evaluated novel biomarker predictors to develop a first-trimester risk prediction model in a large multiethnic cohort. METHODS: Maternal clinical, aneuploidy and pre-eclampsia screening markers (PAPP-A, free hCGß, mean arterial pressure, uterine artery pulsatility index) were measured prospectively at 11-13+6 weeks' gestation in 980 women (248 with GDM; 732 controls). Nonfasting glucose, lipids, adiponectin, leptin, lipocalin-2, and plasminogen activator inhibitor-2 were measured on banked serum. The relationship between marker multiples-of-the-median and GDM was examined with multivariate regression. Model predictive performance for early (< 24 weeks' gestation) and overall GDM diagnosis was evaluated by receiver operating characteristic curves. RESULTS: Glucose, triglycerides, leptin, and lipocalin-2 were higher, while adiponectin was lower, in GDM (p < 0.05). Lipocalin-2 performed best in Caucasians, and triglycerides in South Asians with GDM. Family history of diabetes, previous GDM, South/East Asian ethnicity, parity, BMI, PAPP-A, triglycerides, and lipocalin-2 were significant independent GDM predictors (all p < 0.01), achieving an area under the curve of 0.91 (95% confidence interval [CI] 0.89-0.94) overall, and 0.93 (95% CI 0.89-0.96) for early GDM, in a combined multivariate prediction model. CONCLUSIONS: A first-trimester risk prediction model, which incorporates novel maternal lipid markers, accurately identifies women at high risk of GDM, including early GDM.

Epidemic of large babies highlighted by use of INTERGROWTH21st international standard.

OBJECTIVE: To compare birth weights in central Sydney to the INTERGROWTH21st international standard to describe current trends in relation to optimal growth and to define areas that may benefit from improved obstetric surveillance and intervention. METHODS: Retrospective analysis of prospectively collected cohort. DESIGN: hospital-based cohort study. SETTING: Sydney Local Health District, Australia. POPULATION OR SAMPLE: women with singleton pregnancies who had first trimester screening for aneuploidy between 16 April, 2010 and 9 March, 2012. Analysis of 2966 births. MAIN OUTCOME MEASURES: Large for gestational age (LGA) >4000 g, >4500 g, >5000 g, >90th, >95th, >97th centiles and small for gestational age (SGA) <1500 g, <2500 g,

Is ultrasound measured fetal biometry predictive of intrapartum caesarean section for failure to progress?

BACKGROUND: There are global concerns regarding excessive caesarean rates, which could be reduced by identification of risk factors leading to preventative measures such as induction of labour. AIMS: This study aims to describe the association between antenatal ultrasound and emergency caesarean section for: (i) failure to progress; (ii) other indications; and (iii) any indication. MATERIALS AND METHODS: Women who had an ultrasound in pregnancy between 36(+0/7) to 38(+6/7) weeks at Royal Prince Alfred Hospital from January 2005 to June 2009 were included. Ultrasound parameters were linked to clinical parameters from the maternity database. Missing clinical data were imputed and multiple logistic regression performed. RESULTS: Fetal biometry data were available for 2006 pregnancies. After adjusting for maternal age, height, body mass index, parity, previous caesarean section and diabetes, caesarean section for failure to progress was associated with estimated fetal weight (odds ratio (OR) 2.24 (95% CI: 1.76-2.84) per 500 g increase); or biparietal diameter (OR 1.51 (1.16-1.97) per 5 mm increase) and abdominal circumference (OR for the 4th quartile (>75th centile) compared with the 10-25th centile group was 2.09 (1.13-3.85)).* There were also non-linear associations between components of fetal biometry and caesarean section for fetal distress and for any indication. CONCLUSIONS: Components of fetal biometry in the third trimester are associated with intrapartum caesarean section for failure to progress. These parameters could be incorporated into models to predict emergency caesarean section which could lead to implementation of preventative strategies. *[Corrections added on 29 January 2018, after first online publication, '(OR for the 4th quartile (>7th centile)' has been changed to '(OR for the 4th quartile (>75th centile)'.].

A New Approach to Developing Birth Weight Reference Charts: A Retrospective Observational Study.

INTRODUCTION: Birth weight reference charts based on historical infant birth weights have significant bias at preterm gestations because many preterm births are associated with abnormal growth. This study aims to determine whether more accurate birth weight charts can be constructed using data only from births that follow spontaneous onset of labour. MATERIALS AND METHODS: This study was a single-centre retrospective observational study of 115,712 singleton live births. Births were classified as spontaneous or iatrogenic. Quantile regression was used to model the relationship between gestational age, sex, labour onset, and birth weight. Comparison was made of birth weights in the spontaneous and iatrogenic cohorts by gestation, and to existing ultrasound-based charts. RESULTS: Birth weights of spontaneous and iatrogenic births were significantly different for gestational age at the median and 10th centiles. Iatrogenic preterm infants weighed less than their spontaneous preterm counterparts. Median and 10th centile birth weights derived from the spontaneous birth cohort closely approximate previous ultrasound-based curves. DISCUSSION: Iatrogenic births are more likely to be associated with pre-existing growth disturbance. Inclusion of these data has significant impact on centile charts. Birth weight charts derived from only spontaneous births may offer a more accurate reference for clinicians.

Is neonatal head circumference related to caesarean section for failure to progress?

BACKGROUND: There is global concern about rising caesarean section rates. Identification of risk factors could lead to preventative measures. AIMS: To describe the association between neonatal head circumference and (i) caesarean section for failure to progress, (ii) intrapartum caesarean section overall. MATERIALS AND METHODS: This was a retrospective cohort study of 11 687 singleton live births with cephalic presentation, attempted vaginal birth and at least 37 completed weeks gestation from January 2005 to June 2009. Neonatal head circumference was grouped into quartiles and multiple logistic regressions performed. RESULTS: The rates of caesarean section for failure to progress were 4.1, 6.4, 8.8 and 14.3% in successive head circumference quartiles. Rates of intrapartum caesarean section overall were 8.7, 12.1, 15.8 and 21.5%. The odds ratios for caesarean section for failure to progress were: 1.00, 1.33 (95% CI 1.02- 1.73), 1.54 (1.18-2.02) and 1.93 (1.44-2.57) for successive head circumference quartiles after adjusting for multiple demographic and clinical factors. The adjusted odds ratios for intrapartum caesarean section for any indication were: 1.00, 1.52 (95% CI 1.24-1.87), 1.99 (1.62-2.46) and 2.38 (1.89-3.00), respectively. CONCLUSIONS: There is a strong positive relationship between head circumference quartile and both caesarean section for failure to progress and caesarean for any indication. If this finding is confirmed using ultrasound measurements, there is potential for head circumference to be incorporated into predictive models for intrapartum caesarean section with a view to offering interventions to reduce the risk of caesarean section.

Influence of sampling site on uterine artery Doppler indices at 11-13⁺6 weeks gestation.

INTRODUCTION: Uterine artery pulsatility index (PI) is a key variable in the first trimester screening for pre-eclampsia. The aims of the study were to examine the effect of sampling the uterine arteries at a site distal to the level of the internal os, and to determine a lower limit of peak systolic velocity (PSV) to establish an auditable standard. MATERIAL AND METHODS: PI and PSV measurements were performed at 11-13(+6) weeks' gestation at two sites: at the level of the internal os and 3 cm distal to the internal os. Comparative analyses utilised the Student's paired t-test. A 90% reference interval of transformed PSV measurements at the internal os was generated by polynomial regression. RESULTS: There was a significant reduction in both the PI (14.9%) and the PSV (17.4%) when measured at the distal site compared to the level of the internal os (both p < 0.001). The best estimated 5th centile for uterine artery PSV at 11-13(+6) weeks was 60.9 cm/s. CONCLUSION: PI measurements performed distal to the internal os are significantly lower and will result in inaccurate pre-eclampsia risk assessment. PSV measurements below 60 cm/s are likely to indicate an incorrect sampling site. Development of auditable measurement standards is important to ensure accuracy of prospective pre-eclampsia screening.

Treatment of Primary Fetal Hydrothorax with OK-432 (Picibanil): Outcome in 14 Fetuses and a Review of the Literature.

BACKGROUND: Primary fetal hydrothorax (PFHT) is an uncommon condition with an estimated prevalence of 1 in 10,000/15,000 pregnancies. Therapeutic interventions include thoracocentesis, thoraco-amniotic shunting (TAS), and pleurodesis using OK-432. METHODS: A review of the literature was performed to identify all cases of PFHT treated with TAS and OK-432. All cases of PFHT referred to the Fetal Maternal Unit at Royal Prince Alfred Hospital between 2002 and 2012 were retrospectively reviewed. In the cohort of fetuses treated with OK-432, the main perinatal outcomes evaluated were termination of pregnancy, live birth, neonatal death, and fetal death in utero. Secondary outcomes included gestational age (GA) at diagnosis, GA at treatment, GA at resolution, birth weight, and GA at birth. The development of the children was screened using the Ages and Stages Questionnaires, Version 3 (ASQ-3, 2009). RESULTS: Primary hydrothorax was diagnosed in 31 fetuses, of which 14 had treatment with OK-432. One pregnancy terminated after treatment with OK-432. Survival was 85% (11/13): 100% in fetuses treated with OK-432 without hydrops, and 78% in those treated with hydrops. This compares well to the cases of TAS in the literature with an average survival of 63%: 85% in fetuses without hydrops and 55% with hydrops. The mean GA at birth was 36(+4) weeks and mean birth weight 3,007 g. Eight of the 9 children screened with ASQ-3 scored well within the normal range. CONCLUSION: OK-432 appears to be a valid treatment option in fetuses with PFHT, particularly in those diagnosed at early GAs.

Is there an association between sonographically determined occipito-transverse position in the second stage of labor and operative delivery?

OBJECTIVE: To evaluate if ultrasound-determined occipito-transverse position early in the second stage of labor is associated with operative delivery. DESIGN: Retrospective review of two prospective cohort studies. SETTING: An Australian tertiary referral hospital. POPULATION: Women with term, cephalic singleton pregnancies. METHODS: Retrospective analysis of data from two prospective studies. Logistic regression was undertaken to assess the independent contribution of the occipito-transverse position to operative delivery. MAIN OUTCOME MEASURE: Operative delivery (cesarean section, forceps or vacuum extraction). RESULTS: Among 422 women included, the occipito-transverse position was present in 80, occipito-anterior in 303 and the occipito-posterior in 39. Compared with occipito-anterior, the adjusted odds ratio for operative delivery was 2.1 (95% confidence interval 1.2-3.8, p = 0.02) for the occipito-transverse position, and 7.4 (95% confidence interval 3.2-17) for the occipito-posterior position. Factors that independently predicted operative delivery were nulliparity, abnormal second stage cardiotocography, maternal place of birth and epidural analgesia. The length of second stage of labor was longer for the occipito-transverse group than for the occipito-anterior group (median 2 h 7 min vs. 1 h 36 min, p = 0.003). CONCLUSION: The occipito-transverse position early in the second stage of labor was associated with an increased operative delivery rate.

Ultrasound assessment of cervical length at 18-21 weeks' gestation in an Australian obstetric population: comparison of transabdominal and transvaginal approaches.

BACKGROUND: Using a fixed cut-off of ≤25 mm, ultrasound assessment of cervical length during the 18-23 week anomaly scan has been shown to identify approximately 50% of pregnancies that would deliver prior to 34 weeks. AIM: To determine whether a policy of reverting to transvaginal cervical assessment only if the cervix appears short (≤25 mm) on transabdominal assessment affects the efficiency of screening. METHODS: Women with a singleton pregnancy that presented for a routine anomaly scan had their cervical length assessed transabdominally, initially with the maternal bladder full (TABF) and then empty (TABE). Cervical length was then assessed transvaginally (TV). RESULTS: One hundred and ninety-eight women agreed to participate in the study. Identification of the internal and external cervical os was possible during TABF, TABE and TV sonography in 97.0, 82.8 and 100%, respectively. Compared with TV sonography, TABF overestimates cervical length (6.1 mm difference in median values; P < 0.01). There was no significant difference between TV and TABE. However, TABE assessment was not possible in one in six women. If TABF sonography was to be used as a screening tool and using ≤25 mm as the critical cut-off, the sensitivity and specificity was 15.4 and 93.2%, respectively. CONCLUSION: This study has shown that assessment of cervical length using a TA approach is only routinely possible when the bladder is full. However, measurements are significantly overestimated. Therefore, we feel that TV assessment of cervical length is the preferred method of reliable cervical assessment. As such, all women should be offered a TV assessment of cervical length at the time of the fetal anomaly ultrasound as a screening test for preterm birth.

Persistent occiput posterior: OUTcomes following digital rotation: a pilot randomised controlled trial.

AIM: To determine the feasibility of a multicentre randomised controlled trial (RCT) to investigate whether digital rotation of the fetal head from occiput posterior (OP) position in the second stage of labour reduces the risk of operative delivery (defined as caesarean section (CS) or instrumental delivery). METHODS: We conducted the study between December 2010 and December 2011 in a tertiary referral hospital in Australia. A transabdominal ultrasound was performed early in the second stage of labour on women with cephalic, singleton pregnancies to determine the fetal position. Those women with a fetus in the OP position were randomised to either a digital rotation or a sham procedure. In all other ways, participants received their usual intrapartum care. Data regarding demographics, mode of delivery, labour, post natal period and neonatal outcomes were collected. RESULTS: One thousand and four women were consented, 834 achieved full dilatation, and 30 were randomised. An additional portable ultrasound scan and a blinded 'sham' digital rotation were acceptable to women and staff. Operative delivery rates were 13/15 in the digital rotation (four CS and nine instrumental) and 12/15 in the sham (three CS and nine instrumental) groups, respectively. CONCLUSION: A large double-blinded multicentre RCT would be feasible and acceptable to women and staff. Strategies to improve recruitment such as consenting women with an effective epidural in active labour should be considered. This would be the first RCT to answer a clinically important question which could significantly affect the operative delivery rate in Australia and internationally.

Uterine artery pulsatility index assessment at 11-13 weeks' gestation.

INTRODUCTION: First-trimester uterine artery pulsatility index (PI) measurements form part of an algorithm used to assess the risk of developing pre-eclampsia. The objective of this study was to construct a population-specific reference range for both the lower and mean maternal uterine artery PI at 11-13(+6) weeks' gestation and to assess measurement agreement. MATERIALS AND METHODS: Reference ranges for mean and lower PI measurements were developed using polynomial regression models following prospective collection of maternal uterine artery PI measurements at 11-13(+6) weeks' gestation. Measurement agreement studies were performed by two experienced operators. RESULTS: Measurements from 298 women were included in the primary study. Polynomial regression indicated no change over gestational age for the lower PI (mean 1.44). There was an inverse relationship between the average PI and gestational age (mean [0.8960 + (2.9771 × CRL(-1/2))]2). PI measurement agreement was good-strong (intraclass correlation (ICC) 0.50-0.79) between operators, and within-operator agreement was almost perfect (ICC 0.88-0.93). CONCLUSIONS: Reference ranges for both the average and lowest PI of the maternal uterine arteries were derived at 11-13(+6) weeks' gestation. This will provide a basis for development of auditable standards for first-trimester uterine artery Doppler measurements. The PI measurements are reproducible and reliable.

Prediction and prevention of preterm birth: Quality assessment and systematic review of clinical practice guidelines using the AGREE II framework.

BACKGROUND: Prediction of pregnancies at risk of preterm birth (PTB) may allow targeted prevention strategies. OBJECTIVES: To assess quality of clinical practice guidelines (CPGs) and identify areas of agreement and contention in prediction and prevention of spontaneous PTB. SEARCH STRATEGY: We searched for CPGs regarding PTB prediction and prevention in asymptomatic singleton pregnancies without language restriction in January 2024. SELECTION CRITERIA: CPGs included were published between July 2017 and December 2023 and contained statements intended to direct clinical practice. DATA COLLECTION AND ANALYSIS: CPG quality was assessed using the AGREE-II tool. Recommendations were extracted and grouped under domains of prediction and prevention, in general populations and high-risk groups. MAIN RESULTS: We included 37 CPGs from 20 organizations; all were of moderate or high quality overall. There was consensus in prediction of PTB by identification of risk factors and cervical length screening in high-risk pregnancies and prevention of PTB by universal screening and treatment for asymptomatic bacteriuria, screening and treatment for BV in high-risk pregnancies, and use of preventative progesterone and cerclage. Areas of contention or limited consensus were the role of PTB clinics, universal cervical length measurement, biomarkers and cervical pessaries. CONCLUSIONS: This review identified strengths and limitations of current PTB CPGs, and areas for future research.

A cross-sectional study of maternal perception of fetal movements and antenatal advice in a general pregnant population, using a qualitative framework.

BACKGROUND: Maternal perception of fetal movements has been used as a measure of fetal well-being. Yet a Cochrane review does not recommend formal fetal movement counting compared to discretional fetal movement counting. There is some evidence that suggests that the quality of fetal movements can precede quantitative changes however there has been almost no assessment of how women describe movements and whether these descriptions may be useful in a clinical setting. Therefore we aimed to examine maternal perception of fetal movements using a qualitative framework. METHODS: Using a cross-sectional design we identified women during routine antenatal care at a tertiary referral hospital, in Sydney, Australia. Eligible women were pregnant ≥ 28 weeks, carrying a single child, > 18 years old, and with sufficient English literacy to self-complete a questionnaire. Post-natally the medical records were reviewed and demographic, pregnancy and fetal outcome data were extracted. Text responses to questions regarding maternal descriptions of fetal movements throughout pregnancy, were analysed using thematic analysis in an explicit process. RESULTS: 156 women participated. There was a general pattern to fetal movement descriptions with increasing gestation, beginning with words such as "gentle", to descriptions of "strong" and "limb" movements, and finally to "whole body" movements. Women perceived and described qualitative changes to fetal movements that changed throughout gestation. The majority (83%) reported that they were asked to assess fetal movements in an implicit qualitative method during their antenatal care. In contrast, only 16% regularly counted fetal movements and many described counting as confusing and reported that the advice they had received on counting differed. CONCLUSIONS: This is the first study to use qualitative analysis to identify that pregnant women perceive fetal movements and can describe them in a relatively homogenous way throughout pregnancy that follow a general pattern of fetal growth and development. These findings suggest that women's perception of fetal wellbeing based on their own assessment of fetal movement is used in an ad hoc method in antenatal care by clinicians.

When should women be recruited to intrapartum research projects? A retrospective review.

OBJECTIVE: To review and describe the impact of varied recruitment processes in two intrapartum studies. DESIGN: Retrospective review of one prospective cohort study and one pilot randomized controlled trial. SETTING: Australian tertiary referral hospital. POPULATION: Women with term, cephalic singleton pregnancies. METHODS: Recruitment processes in one observational and one interventional study examining the management of occipitoposterior position in labor were reviewed. Data concerning recruitment and serial attrition for these studies were collected. The value of allowing consent in early labor in addition to consent in the antenatal period was assessed. MAIN OUTCOME MEASURE: Relative proportions of women participating compared with the numbers approached and recruited. RESULTS: One in 48 women approached about the observational study agreed to participate and then had a fetus in occipitoposterior position. One in 33 women in the intervention study were eventually randomized. Women approached in early labor were more likely to agree to participate (77% vs. 58%; p < 0.0001), more likely to have an ultrasound scan during labor (40% vs. 15%; p < 0.0001) and more likely to be randomized to intervention (4% vs. 1.5%; p = 0.02). CONCLUSION: Intrapartum research is associated with low rates of recruitment and these rates may be improved by asking women to provide informed consent during labor rather than the antenatal period. It is important to consider ways to facilitate randomized controlled trials involving women in labor to advance evidence-based care in this environment. This should include prospective research that seeks to define the best approach to patient recruitment.

Clinical evaluation of a first trimester algorithm predicting the risk of hypertensive disease of pregnancy.

BACKGROUND: The aim of this study is to validate the Fetal Medicine Foundation (FMF) multiple logistic regression algorithm for prediction of risk of pre-eclampsia in an Australian population. This model, which predicts risk using the population rate of pre-eclampsia, a variety of demographic factors, mean maternal arterial blood pressure (MAP), uterine artery PI (UtA PI) and pregnancy-associated plasma protein A (PAPP-A), has been shown to predict early-onset pre-eclampsia (delivery prior to 34 weeks) in 95% of women at a 10% false-positive rate. METHODS: All women who attended first trimester screening at the Royal Prince Alfred Hospital had their body mass index (BMI), MAP and UtA PI assessed in addition to factors traditionally used to assess aneuploidy (including PAPP-A MoM). After delivery, risks of early-onset (delivery prior to 34 weeks) pre-eclampsia, late pre-eclampsia and gestational hypertension were calculated using the FMF risk algorithm. RESULTS: A total of 3099 women were screened and delivered locally. 3066 (98.9%) women had all data to perform pre-eclampsia screening available. This included 3014 (98.3%) women with a live birth, where risks of early pre-eclampsia were calculated. Twelve women were delivered before 34 weeks because of early pre-eclampsia with a prevalence of early pre-eclampsia of 1 in 256 pregnancies. Risks generated through the use of maternal history, MAP, UtA PI and PAPP-A detected 41.7 and 91.7% of early pre-eclampsia at a false-positive rate of 5 and 10%, respectively. CONCLUSIONS: This study shows that the FMF early pre-eclampsia algorithm is effective in an Australian population.

First-trimester prediction of preterm prelabour rupture of membranes incorporating cervical length measurement.

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.