Search

Objective: To assess the performance of the Fetal Medicine Foundation (FMF) first-trimester competing-risks screening model for small-for-gestational-age (SGA) fetuses requiring delivery at < 37 weeks' gestation, in a large cohort of women receiving maternity care in Australia., Methods: This was a retrospective analysis of prospectively collected data from a cohort of women attending one of two private multicenter fetal medicine practices for first-trimester screening for preterm pre-eclampsia (PE), defined as PE requiring delivery before 37 weeks' gestation. Risk for preterm SGA, defined as SGA requiring delivery before 37 weeks, was calculated but was not disclosed to the patient or referring physician. Screening data were matched to obstetric outcomes. The primary outcome was the efficacy of the FMF screening model in assessing the risk of preterm SGA. The potential effect on identifying other adverse pregnancy outcomes was also assessed., Results: During the study period, 22 841 women with a singleton pregnancy underwent combined first-trimester screening for preterm PE. These data were compared with those of 301 721 women in the state of Victoria with a singleton pregnancy who did not undergo screening during the study period. Calculation of the risk for preterm SGA identified 3030 (13.3%) pregnancies as high risk. The sensitivity of the model was 48.6% (95% CI, 41.0-56.2%), specificity was 87.0% (95% CI, 86.6-87.5%) and positive and negative predictive values were 2.9% (95% CI, 2.7-3.1%) and 99.5% (95% CI, 99.4-99.6%) respectively. Pregnancies at high risk for preterm SGA were also more likely to have preterm PE (risk ratio (RR), 2.28 (95% CI, 1.72-3.03)) and preterm birth (RR, 1.46 (95% CI, 1.32-1.63)), compared with unscreened pregnancies. Pregnancies at low risk for preterm SGA were less likely to result in a stillbirth (RR, 0.64 (95% CI, 0.47-0.86)) compared with unscreened pregnancies., Conclusion: Combined first-trimester screening for preterm SGA shows moderate screening efficacy and therefore could help to inform pregnancy management and improve antenatal resource allocation. © 2025 International Society of Ultrasound in Obstetrics and Gynecology., (© 2025 International Society of Ultrasound in Obstetrics and Gynecology.)

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., (© 2024 The Authors. International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.)

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.)

Background: Cesarean delivery rates continue to rise globally, the reasons for which are incompletely understood., Objective: We aimed to characterize the attributable factors for the increasing cesarean delivery rates over a 30-year period within our health network., Study Design: This was a planned observational cohort study across 2 hospitals (a large tertiary referral hospital and a metropolitan hospital) in Sydney, Australia using data from a previously published study. The following 2 time periods were compared: 1989-99 and 2009-16, between which the cesarean delivery rate increased from 19% to 30%. The participants were all women who had a cesarean delivery after 24 weeks' gestational age. The data were analyzed using multiple imputation and robust Poisson regression to calculate the differences in the adjusted and unadjusted relative risk of cesarean delivery and estimate the changes in the cesarean delivery rate attributable to maternal and clinical factors. The primary outcome was cesarean delivery., Results: After 576 exclusions, 102,589 births were included in the analysis. Fifty-six percent of the increase in the rate of cesarean delivery was attributed to changes in the distribution of the maternal age, body mass index, and parity and to a history of previous cesarean delivery. An additional 10% of the increase was attributed to changes in the obstetrical management of the following high-risk pregnancies: multiple gestation, malpresentation (mainly breech), and preterm singleton birth. When prelabor cesarean deliveries for maternal choice, suspected fetal compromise, previous pregnancy issues, and suspected large fetus were excluded, 78% of the increase was attributed to either maternal factors or changes in the obstetrical management of these high-risk pregnancies., Conclusion: Most of the steep rise in the cesarean delivery rate from 19% to 30% was attributed to changes in the maternal demographic and clinical factors. This observation is relevant to developing preventative strategies that account for nulliparity, age, body mass index, and management of high-risk pregnancies., (Crown Copyright © 2021. Published by Elsevier Inc. All rights reserved.)

Background: The fetal occiput transverse position in the second stage of labor is associated with adverse maternal and perinatal outcomes. Prophylactic manual rotation in the second stage of labor is considered a safe and easy to perform procedure that has been used to prevent operative deliveries., Objective: This study aimed to determine the efficacy of prophylactic manual rotation in the management of the occiput transverse position for preventing operative delivery. We hypothesized that among women who are at ≥37 weeks' gestation with a baby in the occiput transverse position early in the second stage of labor, manual rotation compared with a "sham" rotation will reduce the rate of operative delivery., Study Design: A double-blinded, parallel, superiority, multicenter, randomized controlled clinical trial in 3 tertiary hospitals was conducted in Australia. The primary outcome was operative (cesarean, forceps, or vacuum) delivery. Secondary outcomes were cesarean delivery, serious maternal morbidity and mortality, and serious perinatal morbidity and mortality. Outcomes were analyzed by intention to treat. Proportions were compared using χ 2 tests adjusted for stratification variables using the Mantel-Haenszel method or Fisher exact test. Planned subgroup analyses by operator experience and technique of manual rotation (digital or whole hand rotation) were performed. The planned sample size was 416 participants (trial registration: ACTRN12613000005752)., Results: Here, 160 women with a term pregnancy and a baby in the occiput transverse position in the second stage of labor, confirmed by ultrasound, were randomly assigned to receive either a prophylactic manual rotation (n=80) or a sham procedure (n=80), which was less than our original intended sample size. Operative delivery occurred in 41 of 80 women (51%) assigned to prophylactic manual rotation and 40 of 80 women (50%) assigned to a sham rotation (common risk difference, -4.2% [favors sham rotation]; 95% confidence interval, -21 to 13; P=.63). Among more experienced proceduralists, operative delivery occurred in 24 of 47 women (51%) assigned to manual rotation and 29 of 46 women (63%) assigned to a sham rotation (common risk difference, 11%; 95% confidence interval, -11 to 33; P=.33). Cesarean delivery occurred in 6 of 80 women (7.5%) in the manual rotation group and 7 of 80 women (8.7%) in the sham group. Instrumental (forceps or vacuum) delivery occurred in 35 of 80 women (44%) in the manual rotation group and 33 of 80 women (41%) in the sham group. There was no significant difference in the combined maternal and perinatal outcomes. The trial was terminated early because of limited resources., Conclusion: Planned prophylactic manual rotation did not result in fewer operative deliveries. More research is needed in the use of manual rotation from the occiput transverse position for preventing operative deliveries., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: To evaluate three birth-weight (BW) standards (Australian population-based, Fenton and INTERGROWTH-21 st ) and three estimated-fetal-weight (EFW) standards (Hadlock, INTERGROWTH-21 st and WHO) for classifying small-for-gestational age (SGA) and large-for-gestational age (LGA) and predicting adverse perinatal outcomes in preterm and term babies., Methods: This was a nationwide population-based study conducted on a total of 2.4 million singleton births that occurred from 24 + 0 to 40 + 6 weeks' gestation between 2004 and 2013 in Australia. The performance of the growth charts was evaluated according to SGA and LGA classification, and relative risk (RR) and diagnostic accuracy based on the areas under the receiver-operating-characteristics curves (AUCs) for stillbirth, neonatal death, perinatal death, composite morbidity and a composite of perinatal death and morbidity outcomes. The analysis was stratified according to gestational age at delivery (< 37 + 0 vs ≥ 37 + 0 weeks)., Results: Following exclusions, 2 392 782 singleton births were analyzed. There were significant differences in the SGA and LGA classification and risk of adverse outcomes between the six BW and EFW standards evaluated. For the term group, compared with the other standards, the INTERGROWTH-21 st BW and EFW standards classified half the number of SGA (< 10 th centile) babies (3-4% vs 7-11%) and twice the number of LGA (> 90 th centile) babies (24-25% vs 8-15%), resulting in a smaller cohort of term SGA at higher risk of adverse outcome and a larger LGA cohort at lower risk of adverse outcome. For term SGA (< 3 rd centile) babies, the RR of perinatal death using the two INTERGROWTH-21 st standards was up to 1.5-fold higher than those of the other standards (including the WHO-EFW and Hadlock-EFW), while the INTERGROWTH-21 st -EFW standard indicated a 12-26% reduced risk of perinatal death for LGA cases across centile thresholds. Conversely, for the preterm group, the WHO-EFW and Hadlock-EFW standards identified a higher SGA classification rate than did the other standards (18-19% vs 10-11%) and a 20-65% increased risk of perinatal death in term LGA babies. All BW and EFW charts had similarly poor performance in predicting adverse outcomes, including the composite outcome (AUC range, 0.49-0.62) for both preterm (AUC range, 0.58-0.62) and term (AUC range, 0.49-0.50) cases and across centiles. Furthermore, specific centile thresholds for identifying adverse outcomes varied markedly by chart between BW and EFW standards., Conclusions: This study addresses the recurrent problem of identifying fetuses at risk of morbidity and perinatal mortality associated with growth disorders and provides new insights into the applicability of international growth standards. Our findings of marked variation in classification and the similarly poor performance of prescriptive international standards and the other commonly used standards raise questions about whether the prescriptive international standards that were constructed for universal adoption are indeed applicable to a multiethnic population such as that of Australia. Thus, caution is needed when adopting universal standards for clinical and epidemiological use. © 2020 International Society of Ultrasound in Obstetrics and Gynecology., (© 2020 International Society of Ultrasound in Obstetrics and Gynecology.)

Background: Persistent occiput posterior position in labor is associated with adverse maternal and perinatal outcomes. Prophylactic manual rotation from the occiput posterior position to the occiput anterior position in the second stage of labor is considered a safe and easy to perform procedure that in observational studies has shown promise as a method for preventing operative deliveries., Objective: This study aimed to determine the efficacy of prophylactic manual rotation in the management of occiput posterior position for preventing operative delivery. The hypothesis was that among women who are at least 37 weeks pregnant and whose baby is in the occiput posterior position early in the second stage of labor, manual rotation will reduce the rate of operative delivery compared with the "sham" rotation., Study Design: A double-blinded, parallel, superiority, multicenter, randomized controlled clinical trial in 4 tertiary hospitals was conducted in Australia. A total of 254 nulliparous and parous women with a term pregnancy and a baby in the occiput posterior position in the second stage of labor were randomly assigned to receive either a prophylactic manual rotation (n=127) or a sham rotation (n=127). The primary outcome was operative delivery (cesarean, forceps, or vacuum delivery). Secondary outcomes were cesarean delivery, combined maternal mortality and serious morbidity, and combined perinatal mortality and serious morbidity. Analysis was by intention to treat. Proportions were compared using chi-square tests adjusted for stratification variables using the Mantel-Haenszel method or the Fisher exact test. Planned subgroup analyses by operator experience and by manual rotation technique (digital or whole-hand rotation) were performed., Results: Operative delivery occurred in 79 of 127 women (62%) assigned to prophylactic manual rotation and 90 of 127 women (71%) assigned to sham rotation (common risk difference, 12; 95% confidence interval, -1.7 to 26; P=.09). Among more experienced operators or investigators, operative delivery occurred in 46 of 74 women (62%) assigned to manual rotation and 52 of 71 women (73%) assigned to a sham rotation (common risk difference, 18; 95% confidence interval, -0.5 to 36; P=.07). Cesarean delivery occurred in 22 of 127 women (17%) in both groups. Instrumental delivery (forceps or vacuum) occurred in 57 of 127 women (45%) assigned to prophylactic manual rotation and 68 of 127 women (54%) assigned to sham rotation (common risk difference, 10; 95% confidence interval, -3.1 to 22; P=.14). There was no significant difference in the combined maternal and perinatal outcomes., Conclusion: Prophylactic manual rotation did not result in a reduction in the rate of operative delivery. Given manual rotation was associated with a nonsignificant reduction in operative delivery, more randomized trials are needed, as our trial might have been underpowered. In addition, further research is required to further explore the potential impact of operator or investigator experience., (Crown Copyright © 2021. Published by Elsevier Inc. All rights reserved.)

Background: Birthweight is the most commonly used proxy marker but does not adequately define true nutritional status. Modalities like DXA (dual energy x-ray absorptiometry) and TOtal Body Electric Conductivity (TOBEC) have been validated to assess body composition but their accuracy in neonates has not been established. The PEAPOD (COSMED, Rome Italy) has been validated as an accurate tool for measuring percentage body fat (%BF) in newborns. The study aim was to determine the gender-specific %BF percentiles at different gestations (35-41 weeks) for a healthy population of newborn infants. A secondary aim was to determine whether there is any relationship between %BF and neonatal condition at birth (cord gas measurement)., Methods: %BF was measured using air displacement plethysmography (PEAPOD) within 6 h of birth., Results: There is an increase in the mean %BF with increasing gestation for female and males from 36 weeks' gestation in the 7667 infants who underwent assessment. Females have a higher %BF than their male equivalents. There was no correlation between %BF and cord pH., Conclusion: Gender and gestation are both important in determining the quantiles and mean %BF at birth. There was no correlation between low cord pH and %BF., Impact: Measuring the percentage body fat (PEAPOD) at birth is a useful marker of an infant's nutritional status. This is the largest hospital-based cohort of gestational age and gender-specific %BF in healthy newborns. The normative graphs from this study will help to accurately determine high-risk infants with low %BF so they can be monitored appropriately.

Objectives: Placental related adverse pregnancy outcomes such as fetal growth restriction have significant short- and long-term implications for both mother and fetus. This study aimed to determine if conventional and novel early first trimester ultrasound measures are associated with small for gestational age (SGA) neonates. In addition, we aimed to assess whether a combination of ultrasound measures, maternal characteristics and biochemistry improved the prediction of this adverse pregnancy outcome., Methods: This was a prospective cohort study including ultrasound measurements: trophoblast thickness (TT), trophoblast volume (TV), mean uterine artery pulsatility index, crown-rump length, fetal heart rate, mean sac diameter (MSD) and yolk sac diameter. Biochemical markers considered in the analysis were placental growth factor (PIGF), pregnancy - associated plasma protein A (PAPP-A), beta human chorionic gonadotropin and alpha fetoprotein. Regression models were fitted for ultrasound parameters using multiples of the median (MoM). All measures were compared with normal birthweight (BW) ≥10 th centile and SGA (BW < 10 th centile). Logistic regression analysis was used to create a clinical prediction model for SGA based on maternal characteristics, ultrasound measurements at <11 weeks gestational age and maternal biochemistry collected at 10-14 weeks., Results: As compared to pregnancies delivered of babies with normal BW (n = 1068), MoM values for TT, TV, MSD, PAPP-A and PIGF were significantly reduced (P < 0.05) in pregnancies delivered of SGA babies (n = 73). The proposed logistic regression model includes maternal height, TV and PIGF resulting in an area under the receiver operator curve 0.70 (95% CI 0.63-0.76) for the prediction of SGA., Conclusion: A significantly decreased TV, measured <11 weeks gestation, is predictive of BW < 10 th centile. With addition of maternal height and PIGF, this three-marker algorithm provided a reasonable predictive value for the development of SGA later in pregnancy., Competing Interests: No known conflicts of interest., (© 2020 Australasian Society for Ultrasound in Medicine.)

Introduction: The cesarean delivery rate has been increasing globally in recent decades. The reasons for this are complex and subject to ongoing debate. Investigation of the indications for cesarean delivery and how these have changed over an extended period of time could provide insight into the reasons for changing obstetric practice. Our objective was to explore contributing factors to the increasing rate of cesarean delivery by examining the incidence of and indications for cesarean delivery over the past three decades at our institutions., Material and Methods: We conducted a retrospective observational study of all cesarean deliveries, from 24 weeks' gestational age onwards, within an inner-city hospital network in Sydney, Australia, between August 1989 and December 2016. The primary outcome measures were the rates of and indications for emergency and planned cesarean delivery. We also examined our data within the Robson 10-Group Classification system., Results: There were 147 722 births over the study period, with 37 309 cesarean deliveries for an overall rate of 25.3%. The rate of cesarean delivery increased from 18.7% in 1989-1994 (8.7% emergency, 10% planned) to 30.4% in 2010-2016 (11.4% emergency, 19% planned). Emergency cesarean delivery for slow progress increased from 3.4% to 5.5% of all births (a relative increase of 62%) and other emergency cesareans mainly performed for suspected intrapartum fetal compromise increased from 5.2% to 5.6% (a relative increase of 8%). Previous uterine surgery (predominantly cesarean section) was the largest contributor to the increase in planned procedures from 3.8% to 9.0% of all births, and 29% of all cesarean deliveries. Primary cesarean delivery for planned antenatal fetal indications, previous pregnancy problems, multiple gestation and maternal choice all increased substantially in combined rate from 0.7% to 4.9%. Cesarean rates in Robson groups 6, 7 and 8 (term breech and multiple gestations) increased most over time., Conclusions: The increased rate of cesarean delivery is mainly attributable to a greater number of procedures performed for slow progress in labor, breech presentation or repeat cesarean section., (© 2020 Nordic Federation of Societies of Obstetrics and Gynecology.)

Objectives: To prepare more accurate population-based Australian birthweight centile charts by using the most recent population data available and by excluding pre-term deliveries by obstetric intervention of small for gestational age babies., Design: Population-based retrospective observational study., Setting: Australian Institute of Health and Welfare National Perinatal Data Collection., Participants: All singleton births in Australia of 23-42 completed weeks' gestation and with spontaneous onset of labour, 2004-2013. Births initiated by obstetric intervention were excluded to minimise the influence of decisions to deliver small for gestational age babies before term., Main Outcome Measures: Birthweight centile curves, by gestational age and sex., Results: Gestational age, birthweight, sex, and labour onset data were available for 2 807 051 singleton live births; onset of labour was spontaneous for 1 582 137 births (56.4%). At pre-term gestational ages, the 10th centile was higher than the corresponding centile in previous Australian birthweight charts based upon all births., Conclusion: Current birthweight centile charts probably underestimate the incidence of intra-uterine growth restriction because obstetric interventions for delivering pre-term small for gestational age babies depress the curves at earlier gestational ages. Our curves circumvent this problem by excluding intervention-initiated births; they also incorporate more recent population data. These updated centile curves could facilitate more accurate diagnosis of small for gestational age babies in Australia., (© 2020 AMPCo Pty Ltd.)

Objectives: Maternal hypertensive disorders (MHD), including pregnancy-induced hypertension and pre-eclampsia, are estimated to occur in 7-10% of pregnancies worldwide and have significant short- and long-term implications for both mother and fetus. This study aimed to determine the association of conventional and novel early first-trimester ultrasound measures with MHD and whether these ultrasound measures, combined with maternal characteristics and biochemistry, improve the prediction of MHD., Methods: This was a prospective cohort study of consecutive women with a singleton pregnancy, attending for an early (5 + 1 to 11 + 0 weeks' gestation) ultrasound examination at a private obstetric ultrasound practice between February 2016 and August 2018. Recorded ultrasound measurements included mean sac diameter, yolk sac diameter, crown-rump length, fetal heart rate (FHR), trophoblast thickness, trophoblast volume (TV) and mean uterine artery pulsatility index. Maternal biochemistry was assessed at 10-14 weeks and included beta-human chorionic gonadotropin, pregnancy-associated plasma protein-A (PAPP-A), placental growth factor (PlGF) and maternal serum alpha-fetoprotein. Regression models were fitted for each ultrasound parameter and multiples of the median (MoM) were calculated. All measures were compared between women who had a normotensive outcome and those who subsequently developed MHD. Logistic regression analysis was used to create a prediction model for MHD based on maternal characteristics, ultrasound measurements at 5 + 1 to 11 + 0 weeks' gestation and maternal biochemistry at 10-14 weeks., Results: In total, 1141 women were included in the analysis, of whom 1086 (95.2%) were normotensive at delivery and 55 (4.8%) developed MHD. Women who developed MHD weighed significantly more than did normotensive women (P < 0.0001). Mean MoM values for TV (P = 0.006), PAPP-A (P = 0.031) and PlGF (P = 0.044) were decreased significantly in pregnancies that subsequently developed MHD. The proposed logistic regression model includes maternal weight and height and MoM values for TV, FHR and PlGF, resulting in an area under the receiver-operating-characteristics curve of 0.80 (95% CI, 0.75-0.86)., Conclusion: The combination of maternal weight and height, TV and FHR, measured prior to 11 weeks' gestation, and first-trimester PlGF appears to have good predictive value for development of MHD later in pregnancy. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.)

Background: Ultrasound probe covers should be used for any ultrasound procedure where there is contact with body fluids or mucous membranes. The type and quality of probe covers used in clinical practice differ widely and studies in the early 1990s showed that condoms were more superior for use with transvaginal examinations than commercial probe covers. Since then, although products have changed, there have been no further studies to assess the breakage rate of different probe covers. The objectives of this study were to assess the integrity of the most commonly used probe covers for transvaginal ultrasound examinations under clinical conditions and report the breakage rate., Methods: The study was conducted in public and private hospitals and private practices. A total of 500 covers for each of 10 brands of commercial covers and condoms (latex and latex free) were distributed to ultrasound practitioners. The transvaginal ultrasound examination practice was unchanged except that all covers were placed in a container for assessment instead of discarding post ultrasound examination. All covers were collected and subjected to a water leak test. Covers that broke upon deployment onto the ultrasound probe prior to the ultrasound examination were recorded. All covers that were broken or had microtears or leaks were recorded as well as photographed. Statistical analysis was performed along with Chi-squared analysis of the data and significance considered at P < 0.05., Results: None of the commercial covers broke upon deployment onto the ultrasound probe prior to ultrasound examination. A total of 5000 probe covers were examined post-transvaginal ultrasound examinations. The breakage rate for condoms ranged from 0.4% to 13% and for commercial covers 0-5%. Statistical analysis of the data by comparison of p-values revealed that the best performing group were the commercial non-latex probe covers and worst performing group were the non-latex condoms., Conclusion: The breakage rates for commercial covers were not as high as previously reported and do not break upon deployment onto the ultrasound probe. This is the first comprehensive study that thoroughly evaluated the integrity of commercial covers and condoms used for transvaginal ultrasound examination in a clinical setting, with regards to brand, numbers and types of covers assessed., (Copyright © 2019 Australasian College for Infection Prevention and Control. Published by Elsevier B.V. All rights reserved.)

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., (© 2019 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

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., (© 2020 S. Karger AG, Basel.)

Objective: Mean uterine artery pulsatility index (meanUAPI) is commonly measured at 11-13+6 weeks to predict adverse pregnancy outcomes including hypertensive disorders and small-for-gestational age. The aims of this study were to establish a population-specific reference range for meanUAPI at <11 weeks, to determine if an abnormal meanUAPI at <11 weeks was associated with adverse pregnancy outcome, and to assess changes in meanUAPI between <11 weeks and 11-13+6 weeks., Methods: A prospective cohort was examined at <11 weeks and at 11-13+6 weeks to develop reference ranges for meanUAPI. Based on these regression models, meanUAPI Z-scores were compared between outcome groups using a two-sample t test. Longitudinal changes in the meanUAPI between <11 and 11-13+6 weeks were assessed by two-way mixed ANOVA., Results: Prior to 11 weeks, there was no significant difference in meanUAPI between normal (n = 622) and adverse (n = 80) outcomes (mean [95% CI]: 2.62 [2.57-2.67] and 2.67 [2.50-2.84], respectively; p = 0.807). At 11-13+6 weeks, meanUAPI was significantly higher in the adverse (n = 66) compared with the normal (n = 535) outcome group (mean [95% CI]: 1.87 [1.70-2.03] and 1.67 [1.63-1.72], respectively; p = 0.040). There was a statistically significant decrease (p < 0.0001) in meanUAPI between the two time points., Conclusion: MeanUAPI measured at <11 weeks' gestation does not appear to be a useful marker for the prediction of placental-related adverse pregnancy outcomes, supporting an argument for the prediction of risk at 11-13+6 weeks' gestation., (© 2019 S. Karger AG, Basel.)

Background: Induction of labour is associated with a reduction in caesarean delivery, but the mechanism of action and which groups of women might benefit remain unknown., Aims: To assess the association between induction of labour at 38-39 weeks pregnancy, and caesarean delivery: (i) overall; (ii) for slow progress in labour; and (iii) for suspected fetal compromise., Material and Methods: Retrospective observational study in two Sydney hospitals from 2009 to 2016, among nulliparous women with induction of labour at 38 or 39 completed weeks pregnancy and a singleton, cephalic presenting fetus. The comparator was all planned vaginal births beyond 39 (+1/7) weeks, whether or not labour was induced. Binary and multinomial multiple logistic regressions adjusting for multiple confounders were performed., Results: There were 2388 and 15 259 women in the study and comparison groups respectively. Induction of labour was associated with caesarean delivery overall only for women <25 years of age (adjusted odds ratio 1.63; 95% CI 1.17-2.27) and was not associated with caesarean delivery for slow progress. Induction of labour was positively associated with increased caesarean delivery for suspected fetal compromise among young women (<30 years), with the association weakening as maternal age increased. The association between induction of labour and caesarean delivery was different for slow progress compared with suspected compromise (P = 0.005)., Conclusions: Induction of labour has different effects on the likelihood of caesarean delivery for slow progress and for suspected fetal compromise. Women <30 years of age are at higher risk of caesarean delivery for suspected fetal compromise, potentially due to uterine hyperstimulation., (© 2019 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Background: First-trimester miscarriage is common, with women increasingly offered an ultrasound scan early in the first trimester to assess the status of their pregnancy. Ultrasound is uniquely situated to significantly impact the clinical management of these women., Aims: This study aims to determine whether there were any differences in the early ultrasound appearances of pregnancies that continued to be viable or resulted in miscarriage before 12 weeks gestation., Materials and Methods: This was a prospective cohort study including ultrasound measurements: mean sac diameter (MSD), yolk sac diameter (YSD), crown-rump length (CRL), fetal heart rate (FHR), trophoblast thickness, trophoblast volume (TTV) and mean uterine artery pulsatility index (meanUAPI). Regression models were fitted for each parameter and Z-scores compared between cohorts that progressed or miscarried after the scan but before 12 weeks gestation. Logistic regression analysis was used to create a prediction model for miscarriage prior to 12 weeks gestation based on the standardised ultrasound measurements recorded during the early first-trimester scan., Results: Comparison of Z-Scores for meanUAPI, TTV, FHR and MSD demonstrated significant variation between the two groups. The proposed logistic regression model resulted in an area under the receiver operator curve of 0.81. At a false-positive rate of 30%, the model resulted in a sensitivity of 76% (95% CI 64-89%)., Conclusion: The combination of FHR, meanUAPI, TTV in a prediction model for miscarriage may prove to be of value for ongoing pregnancy management in the first trimester., (© 2019 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Background: Knowledge of the outcomes of induction of labour for different indications is sparse., Aims: To describe the mode of birth and other outcomes for nulliparous women induced at 38-39 weeks gestational age by indication for induction of labour., Material and Methods: This was a retrospective observational study in a tertiary referral hospital, and a metropolitan teaching hospital in Sydney. The study population was nulliparous women with induction of labour at 38 or 39 completed weeks of pregnancy and a singleton, cephalic presenting baby planning a vaginal birth, from 2009 to 2016. The indication for induction of labour was classified into 12 groups. Mode of birth and other maternal and perinatal outcomes were described in each group, for women who spontaneously laboured at 38 or 39 weeks, and for women who gave birth from 40 completed weeks onward. The main outcome measure was mode of birth., Results: There were 3330 women with induction of labour at 38 or 39 weeks gestation. Rates of vaginal birth varied widely, ranging from 54% when the indication for induction was suspected large fetus, to 82% when the indication was suspected fetal compromise, and was 74% overall. Indications for caesarean delivery also varied by indication for induction. Among women giving birth ≥40 weeks gestational age, 75% had a vaginal birth., Conclusions: In nulliparous women, rates of vaginal birth following induction of labour at 38 or 39 weeks gestation vary widely according to the indication for induction. These data are useful for antenatal counselling., (© 2018 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Pre‐eclampsia (PE) is a multisystem disorder that typically affects 2%–5% of pregnant women and is one of the leading causes of maternal and perinatal morbidity and mortality, especially when the condition is of early onset. Globally, 76 000 women and 500 000 babies die each year from this disorder. Furthermore, women in low‐resource countries are at a higher risk of developing PE compared with those in high‐resource countries. Although a complete understanding of the pathogenesis of PE remains unclear, the current theory suggests a two‐stage process. The first stage is caused by shallow invasion of the trophoblast, resulting in inadequate remodeling of the spiral arteries. This is presumed to lead to the second stage, which involves the maternal response to endothelial dysfunction and imbalance between angiogenic and antiangiogenic factors, resulting in the clinical features of the disorder. Accurate prediction and uniform prevention continue to elude us. The quest to effectively predict PE in the first trimester of pregnancy is fueled by the desire to identify women who are at high risk of developing PE, so that necessary measures can be initiated early enough to improve placentation and thus prevent or at least reduce the frequency of its occurrence. Furthermore, identification of an “at risk” group will allow tailored prenatal surveillance to anticipate and recognize the onset of the clinical syndrome and manage it promptly. PE has been previously defined as the onset of hypertension accompanied by significant proteinuria after 20 weeks of gestation. Recently, the definition of PE has been broadened. Now the internationally agreed definition of PE is the one proposed by the International Society for the Study of Hypertension in Pregnancy (ISSHP). According to the ISSHP, PE is defined as systolic blood pressure at ≥140 mm Hg and/or diastolic blood pressure at ≥90 mm Hg on at least two occasions measured 4 hours apart in previously normotensive women and is accompanied by one or more of the following new‐onset conditions at or after 20 weeks of gestation: 1.Proteinuria (i.e. ≥30 mg/mol protein:creatinine ratio; ≥300 mg/24 hour; or ≥2 + dipstick); 2.Evidence of other maternal organ dysfunction, including: acute kidney injury (creatinine ≥90 μmol/L; 1 mg/dL); liver involvement (elevated transaminases, e.g. alanine aminotransferase or aspartate aminotransferase >40 IU/L) with or without right upper quadrant or epigastric abdominal pain; neurological complications (e.g. eclampsia, altered mental status, blindness, stroke, clonus, severe headaches, and persistent visual scotomata); or hematological complications (thrombocytopenia–platelet count <150 000/μL, disseminated intravascular coagulation, hemolysis); or 3.Uteroplacental dysfunction (such as fetal growth restriction, abnormal umbilical artery Doppler waveform analysis, or stillbirth). It is well established that a number of maternal risk factors are associated with the development of PE: advanced maternal age; nulliparity; previous history of PE; short and long interpregnancy interval; use of assisted reproductive technologies; family history of PE; obesity; Afro‐Caribbean and South Asian racial origin; co‐morbid medical conditions including hyperglycemia in pregnancy; pre‐existing chronic hypertension; renal disease; and autoimmune diseases, such as systemic lupus erythematosus and antiphospholipid syndrome. These risk factors have been described by various professional organizations for the identification of women at risk of PE; however, this approach to screening is inadequate for effective prediction of PE. PE can be subclassified into: 1.Early‐onset PE (with delivery at <34+0 weeks of gestation); 2.Preterm PE (with delivery at <37+0 weeks of gestation); 3.Late‐onset PE (with delivery at ≥34+0 weeks of gestation); 4.Term PE (with delivery at ≥37+0 weeks of gestation). These subclassifications are not mutually exclusive. Early‐onset PE is associated with a much higher risk of short‐ and long‐term maternal and perinatal morbidity and mortality. Obstetricians managing women with preterm PE are faced with the challenge of balancing the need to achieve fetal maturation in utero with the risks to the mother and fetus of continuing the pregnancy longer. These risks include progression to eclampsia, development of placental abruption and HELLP (hemolysis, elevated liver enzyme, low platelet) syndrome. On the other hand, preterm delivery is associated with higher infant mortality rates and increased morbidity resulting from small for gestational age (SGA), thrombocytopenia, bronchopulmonary dysplasia, cerebral palsy, and an increased risk of various chronic diseases in adult life, particularly type 2 diabetes, cardiovascular disease, and obesity. Women who have experienced PE may also face additional health problems in later life, as the condition is associated with an increased risk of death from future cardiovascular disease, hypertension, stroke, renal impairment, metabolic syndrome, and diabetes. The life expectancy of women who developed preterm PE is reduced on average by 10 years. There is also significant impact on the infants in the long term, such as increased risks of insulin resistance, diabetes mellitus, coronary artery disease, and hypertension in infants born to pre‐eclamptic women. The International Federation of Gynecology and Obstetrics (FIGO) brought together international experts to discuss and evaluate current knowledge on PE and develop a document to frame the issues and suggest key actions to address the health burden posed by PE. FIGO's objectives, as outlined in this document, are: (1) To raise awareness of the links between PE and poor maternal and perinatal outcomes, as well as to the future health risks to mother and offspring, and demand a clearly defined global health agenda to tackle this issue; and (2) To create a consensus document that provides guidance for the first‐trimester screening and prevention of preterm PE, and to disseminate and encourage its use. Based on high‐quality evidence, the document outlines current global standards for the first‐trimester screening and prevention of preterm PE, which is in line with FIGO good clinical practice advice on first trimester screening and prevention of pre‐eclampsia in singleton pregnancy.1 It provides both the best and the most pragmatic recommendations according to the level of acceptability, feasibility, and ease of implementation that have the potential to produce the most significant impact in different resource settings. Suggestions are provided for a variety of different regional and resource settings based on their financial, human, and infrastructure resources, as well as for research priorities to bridge the current knowledge and evidence gap. To deal with the issue of PE, FIGO recommends the following: Public health focus: There should be greater international attention given to PE and to the links between maternal health and noncommunicable diseases (NCDs) on the Sustainable Developmental Goals agenda. Public health measures to increase awareness, access, affordability, and acceptance of preconception counselling, and prenatal and postnatal services for women of reproductive age should be prioritized. Greater efforts are required to raise awareness of the benefits of early prenatal visits targeted at reproductive‐aged women, particularly in low‐resource countries. Universal screening: All pregnant women should be screened for preterm PE during early pregnancy by the first‐trimester combined test with maternal risk factors and biomarkers as a one‐step procedure. The risk calculator is available free of charge at https://fetalmedicine.org/research/assess/preeclampsia. FIGO encourages all countries and its member associations to adopt and promote strategies to ensure this. The best combined test is one that includes maternal risk factors, measurements of mean arterial pressure (MAP), serum placental growth factor (PLGF), and uterine artery pulsatility index (UTPI). Where it is not possible to measure PLGF and/or UTPI, the baseline screening test should be a combination of maternal risk factors with MAP, and not maternal risk factors alone. If maternal serum pregnancy‐associated plasma protein A (PAPP‐A) is measured for routine first‐trimester screening for fetal aneuploidies, the result can be included for PE risk assessment. Variations to the full combined test would lead to a reduction in the performance screening. A woman is considered high risk when the risk is 1 in 100 or more based on the first‐trimester combined test with maternal risk factors, MAP, PLGF, and UTPI. Contingent screening: Where resources are limited, routine screening for preterm PE by maternal factors and MAP in all pregnancies and reserving measurements of PLGF and UTPI for a subgroup of the population (selected on the basis of the risk derived from screening by maternal factors and MAP) can be considered. Prophylactic measures: Following first‐trimester screening for preterm PE, women identified at high risk should receive aspirin prophylaxis commencing at 11–14+6 weeks of gestation at a dose of ~150 mg to be taken every night until 36 weeks of gestation, when delivery occurs, or when PE is diagnosed. Low‐dose aspirin should not be prescribed to all pregnant women. In women with low calcium intake (<800 mg/d), either calcium replacement (≤1 g elemental calcium/d) or calcium supplementation (1.5–2 g elemental calcium/d) may reduce the burden of both early‐ and late‐onset PE.

Background: Vasa praevia can cause stillbirth or early neonatal death if it is not diagnosed antenatally and managed appropriately. Experiencing undiagnosed vasa praevia during labour is challenging and traumatic for women and their care providers. Little is known about the experiences of midwives who care for these women., Aim: To investigate the experience of Australian midwives caring for women with undiagnosed vasa praevia during labour and birth., Methods: A qualitative descriptive study was conducted with midwives in Australia who had cared for at least one woman with vasa praevia during 2010-2016. Semi-structured in-depth telephone interviews were conducted and analysed using thematic analysis., Findings: Twelve of the 20 midwives interviewed were involved in a neonatal death and/or near-miss due to vasa praevia. There was one over-arching theme, which described the 'devastating and dreadful experience' for the midwives. This had two inter-related categories of feeling the personal impacts and addressing the professional processes. Feeling scared, shocked, and guilty described how the experience took its toll on the midwives personally. The professional processes included working in organised chaos; feeling for the parents; finding communication to be hard; and, doing their best to save the baby., Discussion: Caring for women who experienced ruptured vasa praevia had a profound impact on the emotional and professional well-being of midwives even when the baby survived., Conclusion: Ruptured vasa praevia was recognised as a traumatic experience that warrants serious considerations from maternity care providers, managers and policy makers. Midwives should be supported and adequately prepared to cope with traumatic events., (Copyright © 2018 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.)

Objectives: To define current obstetric opinion and clinical practice regarding the prenatal diagnosis of vasa previa in Australia and New Zealand., Methods: A population-based cross-sectional survey of Fellows of the Royal Australian and New Zealand College of Obstetricians and Gynaecologists was conducted from April to May, 2016. Descriptive analysis was used to define factors influencing opinion and practice regarding definition of vasa previa, attributable risk factors, and the value of screening., Results: Overall, 453 respondents were included in the study. Two-thirds (304/453; 67.1%) defined vasa previa as exposed fetal vessel(s) running over or within 2 cm of the internal os. A higher proportion of ultrasound specialists (30/65; 46.2%) preferred a broader definition as compared with generalists (115/388; 29.6%; P<0.001). Overall, Fellows were supportive (342/430; 79.5%) of both reporting ultrasound-based risk factors at the 20-week anomaly scan and targeted screening (298/430; 69.3%). Only 77/453 (17.0%) respondents recognized all five "known" risk factors for vasa previa., Conclusions: There was a lack of consensus regarding the definition and diagnosis process for vasa previa. There was also a knowledge gap in risk factors for vasa previa that would inform a targeted screening policy. Nevertheless, support for targeted screening was strong from obstetricians who responded., (© 2018 International Federation of Gynecology and Obstetrics.)

Objective: To explore the barriers to providing quality maternity care for women with vasa praevia as identified by Australian midwives., Design: A qualitative descriptive study using semi-structured in-depth telephone interviews., Setting: Australian maternity system., Methods: Midwives were recruited from across Australia. Interviews were audio-recorded, transcribed verbatim, and analysed using thematic analysis., Participants: Twenty midwives from five Australian states practising in 15 different public or private hospitals who had cared for at least one woman with vasa praevia during 2010-2016 were interviewed. More than half of the participants held senior positions. Twelve were involved in a neonatal death or 'near-miss' due to vasa praevia., Findings: Two categories and five themes were identified in relation to barriers to the provision of quality care. Practitioner-level barriers included two themes: identifying lack of midwifery education and lack of knowledge. System-level barriers included lack of a local policy to guide practice, limited information for women, and paucity of research about vasa praevia., Conclusion: Midwives experienced a number of barriers in caring for women with vasa praevia. Offering more comprehensive pre-registration and continuing professional education to midwives, developing local protocols, and providing clear written information for women may improve the provision of quality care., Implications for Practice: Midwives have a critical role in caring for and supporting women with vasa praevia. Improving midwives' knowledge with contemporary evidence and clinical guidelines could enable them to deliver safer maternity care and improve a women's journey through this potentially catastrophic condition., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

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 hCGβ, 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., (© 2018 S. Karger AG, Basel.)

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)'.]., (© 2017 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

The International Federation of Gynecology and Obstetrics (FIGO) has identified non communicable maternal diseases (NCDs) as a new focus area. NCDs and exposures as related to pregnancy complications and later impairment of maternal and offspring health will form the basis for action in the forthcoming years. This paper summarizes recent advances, centered on the use of first-trimester testing, as a window of opportunity to predict and prevent many pregnancy complications; and for potential future prevention of NCDs in mother and offspring. Recent results from a large-scale randomized control trial have provided definitive proof that effective screening for preterm preeclampsia (preterm-PE), requiring delivery before 37 weeks' gestation, can be achieved with a combined test of maternal factors and biomarkers at 11-13 weeks and that aspirin, given to high-risk women, is effective in reducing the risk of preterm-PE and the length of stay in neonatal intensive care unit. This is the first successful example to illustrate that pregnancy complications is predictable and preventable in early pregnancy. Similar prediction and prevention strategies are being developed for hyperglycemia in pregnancy and preterm birth, with the intention for longer lasting interventions leading to significant downstream impact in improving long-term health in both mothers and babies., (Copyright © 2018. Published by Elsevier B.V.)

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,

Objective: We examined whether first trimester aneuploidy and pre-eclampsia screening markers predict gestational diabetes mellitus (GDM) in a large multi-ethnic cohort and the influence of local population characteristics on markers., Methods: Clinical and first trimester markers (mean arterial pressure (MAP), uterine artery pulsatility index (UtA PI), pregnancy associated plasma protein A (PAPP-A), free-β human chorionic gonadotropin (free-hCGβ)) were measured in a case-control study of 980 women (248 with GDM, 732 controls) at 11 to 13 + 6 weeks' gestation. Clinical parameters, MAP-, UtA PI-, PAPP-A-, and free-hCGβ-multiples-of-the-median (MoM) were compared between GDM and controls; stratified by ethnicity, parity, and GDM diagnosis <24 versus ≥24 weeks' gestation. GDM model screening performance was evaluated using AUROC., Results: PAPP-A- and UtA PI-MoM were significantly lower in GDM versus controls (median ((IQR) PAPP-A-MoM 0.81 (0.58-1.20) versus 1.00 (0.70-1.46); UtA PI-MoM 1.01 (0.82-1.21) versus 1.05 (0.84-1.29); p < .05). Previous GDM, family history of diabetes, south/east Asian ethnicity, parity, BMI, MAP, UtA PI, and PAPP-A were significant predictors in multivariate analysis (p < .05). The AUC for a model based on clinical parameters was 0.88 (95%CI 0.85-0.92), increasing to 0.90 (95%CI 0.87-0.92) with first trimester markers combined. The combined model best predicted GDM <24 weeks' gestation (AUC 0.96 (95%CI 0.94-0.98))., Conclusions: Addition of aneuploidy and pre-eclampsia markers is cost-effective and enhances early GDM detection, accurately identifying early GDM, a high-risk cohort requiring early detection, and intervention. Ethnicity and parity modified marker association with GDM, suggesting differences in pathophysiology and vascular risk.

Spontaneous preterm birth (sPTB) remains a major clinical dilemma; current diagnostics and interventions have not reduced the rate of this serious healthcare burden. This study characterizes differential protein profiles and post-translational modifications (PTMs) in first trimester maternal serum using a refined top-down approach coupling two-dimensional gel electrophoresis (2DE) and mass spectrometry (MS) to directly compare subsequent term and preterm labour events and identify marked protein differences. 30 proteoforms were found to be significantly increased or decreased in the sPTB group including 9 phosphoproteins and 11 glycoproteins. Changes occurred in proteins associated with immune and defence responses. We identified protein species that are associated with several clinically relevant biological processes, including interrelated biological networks linked to regulation of the complement cascade and coagulation pathways, immune modulation, metabolic processes and cell signalling. The finding of altered proteoforms in maternal serum from pregnancies that delivered preterm suggests these as potential early biomarkers of sPTB and also possible mediators of the disorder., Biological Significance: Identifying changes in protein profiles is critical in the study of cell biology, and disease treatment and prevention. Identifying consistent changes in the maternal serum proteome during early pregnancy, including specific protein PTMs (e.g. phosphorylation, glycosylation), is likely to provide better opportunities for prediction, intervention and prevention of preterm birth. This is the first study to examine first trimester maternal serum using a highly refined top-down proteomic analytical approach based on high resolution 2DE coupled with mass spectrometry to directly compare preterm (<37 weeks) and preterm (≥37 weeks) events and identify select protein differences between these conditions. As such, the data present a promising avenue for translation of biomarker discovery to a clinical setting as well as for future investigation of underlying aetiological processes., (Copyright © 2018 Elsevier B.V. All rights reserved.)

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., (© 2017 S. Karger AG, Basel.)

Objective: To undertake a cost-effectiveness analysis of noninvasive fetal RHD genotyping to target pregnant women for antenatal anti-D prophylaxis therapy., Method: A decision-analytic model was constructed to compare RHD testing and targeted anti-D prophylaxis, with current universal anti-D prophylaxis among pregnant women with RhD negative blood type. Model estimates were derived from national perinatal statistics, published literature, donor program records, and national cost sources. One-way sensitivity analyses addressed the uncertainty of variables on the main findings., Results: The unit cost for RHD genotyping was estimated at AU$45.48 (US$31.84). The "mean cost per healthy baby" was AU$7495 (US$5247) for universal prophylaxis and AU$7471 (US$5230) for targeted prophylaxis. The findings were sensitive to the unit costs of anti-D 625 IU (AU$59-AU$88) (US$41-US$62), the genetic test (AU$36-AU$55) (US$25-US$39), and packaging/transport costs of the samples for testing (AU$15-AU$40, US$11-US$28 per sample). With RHD genotyping, 13 938 women would avoid antenatal anti-D prophylaxis at a total cost savings to the National Blood Authority of AU$2.1 million (US$1.5 million) per year. To the health system, net cost savings of AU$159 701 (US$111 791) per year (0.05%) were predicted for total health care costs., Conclusions: Given the vulnerable supply of donor plasma and other health concerns, RHD genotyping is an economically sound option for Australia., (© 2017 John Wiley & Sons, Ltd.)

Non-invasive fetal RHD genotyping in Australia to reduce anti-D usage will need to accommodate both prolonged sample transport times and a diverse population demographic harbouring a range of RHD blood group gene variants. We compared RHD genotyping accuracy using two blood sample collection tube types for RhD negative women stratified into deleted RHD gene haplotype and RHD gene variant cohorts. Maternal blood samples were collected into EDTA and cell-free (cf)DNA stabilising (BCT) tubes from two sites, one interstate. Automated DNA extraction and polymerase chain reaction (PCR) were used to amplify RHD exons 5 and 10 and CCR5. Automated analysis flagged maternal RHD variants, which were classified by genotyping. Time between sample collection and processing ranged from 2.9 to 187.5 hours. cfDNA levels increased with time for EDTA (range 0.03-138 ng/μL) but not BCT samples (0.01-3.24 ng/μL). For the 'deleted' cohort (n=647) all fetal RHD genotyping outcomes were concordant, excepting for one unexplained false negative EDTA sample. Matched against cord RhD serology, negative predictive values using BCT and EDTA tubes were 100% and 99.6%, respectively. Positive predictive values were 99.7% for both types. Overall 37.2% of subjects carried an RhD negative baby. The 'variant' cohort (n=15) included one novel RHD and eight hybrid or African pseudogene variants. Review for fetal RHD specific signals, based on one exon, showed three EDTA samples discordant to BCT, attributed to high maternal cfDNA levels arising from prolonged transport times. For the deleted haplotype cohort, fetal RHD genotyping accuracy was comparable for samples collected in EDTA and BCT tubes despite higher cfDNA levels in the EDTA tubes. Capacity to predict fetal RHD genotype for maternal carriers of hybrid or pseudogene RHD variants requires stringent control of cfDNA levels. We conclude that fetal RHD genotyping is feasible in the Australian environment to avoid unnecessary anti-D immunoglobulin prophylaxis., (Copyright © 2017. Published by Elsevier B.V.)

Background: Cell-free fetal miRNAs have been identified as potential biomarkers for fetal abnormalities and/or placental function. Factors affecting the stability of cell-free fetal miRNA samples (type of collection tube and time interval between sampling and analysis) have not previously been reported., Methods: Blood from pregnant women (n = 12, 18 ± 4 weeks' gestation) was collected into two types of tube (EDTA and RNA BCT) and was stored at different temperatures for up to 72 h. Expression of seven apparently placental specific miRNAs was then measured to compare the effects of sampling and storage. These miRNAs were also assessed in non-pregnant women (n = 9)., Results: The quantity of miRNA extracted was not affected by time or tube. Three miRNAs (miR-518b, miR-525 and miR-526a*) were measureable only in pregnant women, but miR-518b was not always present. Detailed study of the two pregnancy specific miRNAs showed no effect of tube type at 4 h. However, variability in miRNA level was observed with increased time and was significant for one miRNA in the BCT tube at >48 h (p < 0.005)., Conclusion: Some cffmiRNAs are placental specific, and these samples are stable when analyzed within 48 h of collection in either tube type. © 2017 John Wiley & Sons, Ltd., (© 2017 John Wiley & Sons, Ltd.)