Search

To standardize the measurement of shear wave elastography for assessment of cervical stiffness and its relationship with gestational age and cervical length.A prospective cross-sectional study was conducted from September 2017 to March 2019. Data from 125 unselected women (at 11-13 + 6, 18-22 and 24-28 weeks' gestation) and 55 high-risk women were analyzed for the study. Six regions of interest were evaluated for cervical elastography in the mid-sagittal position by transvaginal ultrasound. Statistical analyses were performed using R statistical language in R-studio. Delivery outcomes were recorded for each patient.The shear wave elastography was feasible with good intraoperator and interoperator reproducibility. The endocervical canal and anterior lip internal position had the highest reproducibility (ICC-0.82, 0.75). Shear wave speed was significantly higher in all internal os regions than the external os. There was a statistically significant negative linear relationship of shear wave speed with the gestational age. There was a weak positive relationship between shear wave speed and cervical length. There was no difference between pregnancies with and without spontaneous preterm delivery in shear wave speed measurements and cervical length, although numbers were small for statistical analysis. The internal os of the large loop excision of the transformation zone group was stiffer than the normal population.Cervical elastography is feasible and effectively evaluates the tensile properties of the cervix during pregnancy. The most reproducible measurements were obtained at the anterior lip of the internal cervical os. Combining evaluation of cervical elasticity and length might further improve the identification of women at risk of preterm delivery. Currently, technical issues hinder the practical application of shear wave elastography in the clinical setting and require further research and development of the imaging modality.

Background Maternal nutrition is associated with epigenetic and cardiometabolic risk factors in offspring. Research in humans has primarily focused on assessing the impact of individual nutrients. Objective We sought to assess the collective impact of maternal dietary monounsaturated (MUFA), polyunsaturated (PUFA), and saturated fat (SFA) on epigenetic aging and cardiometabolic risk markers in healthy newborn infants using a geometric framework approach. Design Body fatness (n = 162), aortic intima-media thickness (n = 131), heart rate variability (n = 118), and epigenetic age acceleration (n = 124) were assessed in newborn infants. Maternal dietary intake was cross-sectionally assessed in the immediate postpartum period via a validated 80-item self-administered food-frequency questionnaire. Generalized additive models were used to explore interactive associations of nutrient intake, with results visualized as response surfaces. Results After adjustment for total energy intake, maternal age, gestational age, and sex there was a 3-way interactive association of MUFA, PUFA, and SFA (P = 0.001) with newborn epigenetic aging. This suggests that the nature of each fat class association depends upon one another. Response surfaces revealed MUFA was positively associated with newborn epigenetic age acceleration only at proportionately lower intakes of SFA or PUFA. We also demonstrate a potential beneficial association of omega-3 PUFA with newborn epigenetic age acceleration (P = 0.008). There was no significant association of fat class with newborn aortic intima-media thickness, heart rate variability, or body fatness. Conclusions In this study, we demonstrate an association between maternal dietary fat class composition and epigenetic aging in newborns. Future research should consider other characteristics such as the source of maternal dietary fatty acids.

Introduction: Preterm prelabour rupture of membranes (PPRoM) is a significant cause of maternal and perinatal morbidity and mortality. The aim of this project was to identify interventions that reduce the prevalence of PPRoM. Methods: Search strategy included a systematic literature search of MEDLINE, EMBASE, PubMed, and Cochrane Library. The selection criteria included randomized control studies that compared a therapy to standard care (no therapy or placebo) in pregnancy and included PPRoM as an outcome. Risk of bias was assessed according to the Cochrane risk-of-bias tool for randomized trials. Odds ratios with 95% confidence intervals were calculated using random-effects models. Quality of evidence was assessed using the GRADE methodology. Results: Twenty-nine studies examining 10 interventions met the inclusion criteria. Therapies included docosahexaenoic acid (DHA), aspirin, rofecoxib, vitamin C alone and with vitamin E, folic acid (alone, with iron, with iron and zinc, within a multiple micronutrient supplement), zinc, calcium, copper, and treatment of bacterial vaginosis. There was no significant difference in the prevalence of PPRoM in the treatment groups compared to placebo, except for rofecoxib which showed an increased risk of PPRoM (RR 2.46, 95% CI 1.28–4.73; p = 0.007, 1 trial, 98 women; very low quality of evidence) and a multiple micronutrient supplement which showed a reduction in PPRoM (RR 0.40, 95% CI 0.19–0.84; p = 0.01, 1 trial, 1,671 women; very low quality of evidence). Conclusions: No interventions have been convincingly shown to reduce the prevalence of PPRoM. Given this is a common problem leading to significant morbidity and mortality, further research is required.

To assess pregnancy outcomes following first trimester combined screening for preterm preeclampsia in Australia.We compared pregnancy outcomes of women with singleton pregnancies who underwent first trimester combined preeclampsia screening with the Fetal Medicine Foundation algorithm between 2014 and 2017 in Melbourne and Sydney, Australia, with those from women who received standard care. The primary outcomes were preterm preeclampsia and screening performance. Effect estimates were presented as risk ratios with 95% confidence intervals.A total of 29 618 women underwent combined screening and 301 566 women received standard care. Women who had combined screening were less likely to have preeclampsia, preterm birth, small neonates, and low Apgar scores than the general population. Women with high-risk results (≥1 in 100) were more likely to develop preterm preeclampsia (2.1% vs. 0.7%, risk ratio [RR] 3.04, 95% CI 2.46-3.77), while low-risk women (risk1 in 100) had lower rates of preterm preeclampsia (0.2% vs. 0.7%, RR 0.26, 95% CI 0.19-0.35) and other pregnancy complications. Screening detected 65.2% (95% CI 56.4-73.2%) of all preterm preeclampsia cases, with improved performance after adjustment for treatment effect.First trimester screening for preeclampsia in clinical practice identified a population at high risk of adverse pregnancy outcomes and low-risk women who may be suitable for less intensive antenatal care.

Introduction: We aim to evaluate the supplementary predictive value of soft tissue markers, including fetal limb volumes, for fetal birth weight and fat tissue weight. Methods: This is a prospective study of 60 patients undergoing term induction of labor. Ultrasound was performed 48 h before birth, and 2D sonographic measurements, subcutaneous tissue thickness, and 3D fetal limb volumes were taken. Birth weight and neonatal fat weight were assessed by plethysmography. Clinical data were collected. The relation between ultrasound and neonatal outcomes was assessed by univariate and multivariate predictive models. The estimated and actual birth weights were compared applying different published formulas, and systematic and random error were collected and compared. Results: 3D fetal limb volumes showed a strong relation to birth weight, absolute weight, and relative fat weight. The Lee 6 formula performed better than either Hadlock 3 or Lee 3 with the lowest random error. Fractional limb volumes involve a highly reproducible technique, with excellent correlation (intra-class coefficient >0.90) for both inter- and intra-observer reliability. The prevalence of estimated EFW measures within 10% error from the actual birth weight was 71.7% with the Hadlock 3 model and 95.0% with the Lee 6 model (p = 0.09). Conclusion: Late assessment of 3D fetal limb volume in upper and lower extremities is not only useful for accurately predicting birth weight but is a useful marker for prediction of birth fat tissue weight.

Introduction: The aim of this study was to obtain expert consensus on the content of a curriculum for learning chorionic villus sampling (CVS) and amniocentesis (AC) and the items of an assessment tool to evaluate CVS and AC competence. Methods: We used a 3-round iterative Delphi process. A steering committee supervised all processes. Seven international collaborators were identified to expand the breadth of the study internationally. The collaborators invited fetal medicine experts to participate as panelists. In the first round, the panelists suggested content for a CVS/AC curriculum and an assessment tool. The steering committee organized and condensed the suggested items and presented them to the panelists in round 2. In the second round, the panelists rated and commented on the suggested items. The results were processed by the steering committee and presented to the panelists in the third round, where final consensus was obtained. Consensus was defined as support by more than 80% of the panelists for an item. Results: Eighty-six experts agreed to participate in the study. The panelists represented 16 countries across 4 continents. The final list of curricular content included 12 theoretical and practical items. The final assessment tool included 11 items, systematically divided into 5 categories: pre-procedure, procedure, post-procedure, nontechnical skills, and overall performance. These items were provided with behavioral scale anchors to rate performance, and an entrustment scale was used for the final overall assessment. Conclusion: We established consensus among international fetal medicine experts on content to be included in a CVS/AC curriculum and on an assessment tool to evaluate CVS/AC skills. These results are important to help transition current training and assessment methods from a time- and volume-based approach to a competency-based approach which is a key step in improving patient safety and outcomes for the 2 most common invasive procedures in fetal medicine.

Objective: The study aimed to investigate the association between placental growth factor (PlGF) and adverse obstetric outcomes in a mixed-risk cohort of pregnant women screened for preeclampsia (PE) in the first trimester. Methods: We included women with singleton pregnancies screened for PE between April 2014 and September 2016. Outcome data were retrieved from the New South Wales Perinatal Data Collection (NSW PDC) by linkage to the prenatal cohort. Adverse outcomes were defined as spontaneous preterm birth (sPTB) before 37-week gestation, birth weight (BW) below the 3rd centile, PE, gestational hypertension (GH), stillbirth, and neonatal death. Results: The cohort consisted of 11,758 women. PlGF multiple of the median (MoM) was significantly associated with maternal sociodemographic characteristics (particularly smoking status and parity) and all biomarkers used in the PE first trimester screening model (notably pregnancy-associated plasma protein A MoM and uterine artery pulsatility index [PI] MoM). Low levels of PlGF (Conclusions: Low PlGF MoM levels are independently associated with PE and a range of other adverse pregnancy outcomes. Inclusion of PlGF should be considered in future models screening for adverse pregnancy outcomes in the first trimester.

Background: Aspirin has been shown to reduce prevalence of both early‐onset pre‐eclampsia (ePET) and fetal growth restriction (FGR). Aims: To determine whether aspirin prescribed for risk of ePET reduces the prevalence of small for gestational age (SGA) neonates. Material and Methods: Two prospective cohorts were consecutively recruited in a large university hospital in Sydney. The Observational cohort (April 2010 to March 2012) validated an algorithm for ePET screening, where risk for ePET was modelled on history, mean arterial pressure, uterine artery pulsatility index and pregnancy‐associated plasma protein A. The Interventional cohort (April 2012 to December 2017) were screened and allocated women at high risk of developing ePET to aspirin 150 mg. The prevalence of preterm and term SGA was compared using regression analysis. Result: There were 3013 and 8424 women screened in the Observational and Interventional cohorts respectively. Women who screened high risk for ePET were three to four times more likely to give birth to a neonate classified as SGA in the Observational (6.8% vs 1.9%) and Interventional cohorts (6.0% vs 1.8%). In women who screened high risk, there were no statistically significant differences in the prevalence of SGA neonates (6.6% vs 6.0%; adjusted odds ratio 0.84 (0.50–1.42)) in women who received aspirin compared to women who did not. Conclusions: Women who screen high risk for ePET have an increased chance of delivering an SGA infant. A reduction in the prevalence of SGA neonates when aspirin was prescribed to women who screened high risk for ePET did not reach clinical significance in our cohort.

Objectives Women who had hypertensive disorders of pregnancy (HDP) are twice as likely to experience maternal cardiovascular disease later in life. The primary aim of this study (BP2) is to compare outcomes of 3 different management strategies, including lifestyle behaviour change (LBC), in the first 12 months postpartum in women who had HDP in their preceding pregnancy. Secondary aims include assessing the effects on other cardiometabolic parameters. Study design Three-arm multicentre randomised trial in metropolitan Australian hospitals, (registration: ACTRN12618002004246) target sample size 480. Participants are randomised to one of three groups: 1) Optimised usual care: information package and family doctor follow-up 6 months postpartum 2) Brief intervention: information package as per group 1, plus assessment and brief LBC counselling at a specialised clinic with an obstetric physician and dietitian 6 months postpartum 3) Extended intervention: as per group 2 plus enrolment into a 6 month telephone-based LBC program from 6 to 12 months postpartum. All women have an outcome assessment at 12 months. Main outcome measures Primary outcomes: (a) BP change or (b) weight change and/or waist circumference change. Secondary outcomes: maternal health-related quality of life, engagement and retention in LBC program, biochemical markers, vascular function testing, infant weight trajectory, incremental cost-effectiveness ratios. The study is powered to detect a 4 mmHg difference in systolic BP between groups, or a 4 kg weight loss difference/2cm waist circumference change. Conclusions BP2 will provide evidence regarding the feasibility and effectiveness of postpartum LBC interventions and structured clinical follow-up in improving cardiovascular health markers after HDP.

The mechanical characteristics of tissue can reflect its biochemical content and, therefore, be a powerful tool in the diagnosis of diseases. Many different methods have been developed for testing the mechanical properties of tissue, such as aspiration, indentation and shear wave elastography. Soft tissues are, however, more complex in behaviour than current commercial tissue-mimicking materials and the models used in measurement methods. Complex behaviours of the tissue include anisotropy and heterogeneous elasticity. The oversimplified models assumed in different measuring methods often neglect the effects of these behaviours, resulting in inaccuracies. The aim of this study was to develop a tissue-mimicking material able to capture the complexity of tissue mechanical behaviour. It will be used to improve mechanical property measuring methods by quantitatively determining how complexities in tissue behaviour affect the measurements made and evaluating the effectiveness of methods designed to overcome it, and will be used to train users for consistency in measurement. The tissue-mimicking material designed in this study focuses on the mechanical properties of the cervix as measured by shear wave elastography. The characteristic behaviours of cervical tissues highlighted are anisotropy, a wide range of elasticity that changes with gestational age and an elasticity gradient across the tissue. Magnetorheological gels were used as their elastic properties can be tuned with the application of magnetic fields. The sample was simulated with the finite-element software COMSOL before being tested by shear wave elastography and the INSTRON universal material testing machine. It had an elasticity range of 6.75–11.06 kPa, which is similar to that of cervical tissue. It was determined that a change in the orientation of the probe with respect to the orientation of anisotropy can cause up to a 30 % increase in measured elasticity. There was a 16% decrease in elasticity across the sample.

The fetus that fails to meet its ideal growth trajectory has increased risks of poor health outcomes throughout life. "Gold standard" methods of anthropometric assessment such as measurement of percentage body fat can be difficult to apply across populations and other biomarkers such as serum concentration of umbilical cord blood leptin may be more effective for screening. This study reports cord blood leptin levels in a large prospective consecutive birth cohort and assesses the relationship between leptin and neonatal and maternal factors.Venous umbilical cord blood samples were collected from a prospective consecutive cohort of pregnancies at the time of delivery. Maternal and neonatal characteristics and details of delivery were collated. Serum leptin levels were measured, associations with demographic features were identified, and a normal range was established. The association between cord leptin level and neonatal outcome was tested.Umbilical cord leptin and maternal and neonatal characteristics were collected at 1275 births. The median leptin value was 10.8 ng/ml (IQR: 6.4, 17.8 ng/ml). LogNeonatal cord leptin levels are influenced by a number of maternal and fetal characteristics. Absolute levels can be adjusted to account for normal population variation. Infants requiring admission to NICU have lower mean leptin MoM levels. Further studies are needed to see whether the identification of fetuses with polarized leptin levels (5th or95th centile) will benefit from further surveillance or intervention in infancy.

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.

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 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.

Background Epigenetic aging is associated with higher risk of cardiovascular disease, cancer, and all-cause mortality and may be a mechanistic link between early-life exposures, such as maternal dietary characteristics during pregnancy, and risk of adult disease. Objectives We sought to determine the early-life risk factors for newborn epigenetic aging, specifically maternal dietary macronutrient intake, and whether epigenetic aging is associated with cardiovascular health markers in the newborn. Methods Epigenetic age acceleration of 169 newborns was measured from saliva using the Horvath age calculator. Maternal diet during pregnancy was assessed using food-frequency questionnaires. Results Newborns with positive age acceleration were more likely to be female and have greater body fatness. Maternal intakes of saturated fat [6.2 wk epigenetic age acceleration (95% CI: 1.0, 11.3) per 5% of energy; P = 0.02] and monounsaturated fat [12.4 wk (95% CI: 4.2, 20.5) per 5% of energy; P = 0.003] were associated with higher epigenetic age acceleration in the newborn. The strongest association of individual fatty acids were for palmitoleic acid (25.3 wk; 95% CI: 11.4, 39.2; P = 0.0004), oleic acid (2.2 wk; 95% CI: 0.8, 3.6; P = 0.002), and palmitic acid (2.9 wk; 95% CI: 1.0, 4.9; P = 0.004) per 1% of energy intake. Vitamin D supplementation was associated with lower epigenetic age acceleration (-8.1 wk; 95% CI: -14.5, -1.7; P = 0.01). Epigenetic age acceleration was associated with aortic intima-media thickness in preterm infants [1.0 µm (95% CI: 0.2, 1.8) per week of epigenetic age acceleration; P = 0.01], but not among those born at term (P = 0.78). Epigenetic age acceleration was not associated with heart rate variability in either preterm or term born infants (both P > 0.2). Conclusions This study provides evidence of maternal dietary characteristics that are associated with epigenetic aging in the offspring. Prospective intervention studies are required to determine whether such associations are causal.

Small extracellular vesicles (sEVs) released from the extravillous trophoblast (EVT) are known to regulate uterine spiral artery remodeling during early pregnancy. The bioactivity and release of these sEVs differ under differing oxygen tensions and in aberrant pregnancy conditions. Whether the placental cell-derived sEVs released from the hypoxic placenta contribute to the pathophysiology of preeclampsia is not known. We hypothesize that, in response to low oxygen tension, the EVT packages a specific set of proteins in sEVs and that these released sEVs interact with endothelial cells to induce inflammation and increase maternal systemic blood pressure. Using a quantitative MS/MS approach, we identified 507 differentially abundant proteins within sEVs isolated from HTR-8/SVneo cells (a commonly used EVT model) cultured at 1% (hypoxia) compared with 8% (normoxia) oxygen. Among these differentially abundant proteins, 206 were up-regulated and 301 were down-regulated (P < 0.05), and they were mainly implicated in inflammation-related pathways. In vitro incubation of hypoxic sEVs with endothelial cells, significantly increased (P < 0.05) the release of GM-CSF, IL-6, IL-8, and VEGF, when compared with control (i.e. cells without sEVs) and normoxic sEVs. In vivo injection of hypoxic sEVs into pregnant rats significantly increased (P < 0.05) mean arterial pressure with increases in systolic and diastolic blood pressures. We propose that oxygen tension regulates the release and bioactivity of sEVs from EVT and that these sEVs regulate inflammation and maternal systemic blood pressure. This novel oxygen-responsive, sEVs signaling pathway, therefore, may contribute to the physiopathology of preeclampsia.

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.

Objective: Monochorionic diamniotic (MCDA) twins are at increased risk of adverse outcome due to unequal placental sharing and placental vascular communications between the fetal circulations. Most centres perform ultrasound examination every 2–3 weeks to identify these complications. Identifying a high-risk cohort of MCDA twins in the first trimester would allow more efficient surveillance. We have attempted to validate first-trimester ultrasound characteristics as predictive tools for twin-twin transfusion syndrome (TTTS) and selective intrauterine growth restriction (sIUGR) in MCDA twins. Material and Methods: This is a prospective cohort study including MCDA twins enrolled at the time of first-trimester combined screening. Differences in crown-rump length (CRL), nuchal translucency (NT) thickness, ductus venosus pulsatility index for veins (DV PIV), presence or absence of tricuspid regurgitation and right ventricular E/A ratio were assessed. Receiver operating characteristic (ROC) curves were used to assess the potential value of these measures as predictive tools for identifying a cohort of MCDA pregnancies at high risk of adverse pregnancy outcome. Results: Sixty-five MCDA pregnancies were included in the analysis. Nine (14%) developed TTTS, 17 (26%) developed sIUGR. The best predictive marker for TTTS was NT discordance of ≥20% (ROC AUC = 0.79; 95% CI 0.59–0.99). Combining measures did not improve performance (AUC = 0.80; 95% CI 0.62–0.99). Conclusion: NT discordance was the most effective characteristic at predicting TTTS but still had a relatively poor positive predictive value (36%). Intertwin differences in CRL, DV PIV and E/A ratio were not predictive of subsequent pregnancy complications. None of these characteristics have sufficient efficacy to be used to triage MCDA twin pregnancies ongoing obstetric surveillance.

OBJECTIVE: To develop reference ranges for the ductus venosus (DV) and tricuspid valve (TV) waveforms at 11–14 weeks and define auditable standards to assess operator measurement performance. MATERIALS AND METHODS: A single operator prospectively obtained quantitative measurements of a number of DV and TV Doppler indices to develop medians and 90% reference intervals (RIs). Measurement agreement studies between two experienced operators were also performed. The measurement bias of three additional operators was subsequently assessed using the newly defined auditable standards. RESULTS: Doppler measurements were obtained in 292 patients (DV) and 321 patients (TV). Reference ranges were constructed for DV pulsatility index for veins (PIV) which did not change over gestation (mean 1.06; 90% RI 0.86–1.23) and for the TV E–A ratio reference range which was positively correlated with gestation. Measurement agreement studies on 30 additional patients showed the within‐operator agreement was almost perfect for DV PIV (ICC, intraclass correlation 0.82–0.86) and strong for TV E–A ratio (ICC 0.68–0.78) while the between‐operator agreement was good for both DV PIV and TV E–A ratio measurements (ICC 0.46 for both). DISCUSSION: Development of local reference ranges enabled the definition of quantitative auditable standards that can be utilised in assessment of operator training and ongoing Doppler measurement quality assurance. Measurements of DV PIV and TV E–A ratio by experienced operators were found to be reproducible.

BACKGROUND: Historically, prenatal screening has focused primarily on the detection of fetal aneuploidies. Cell-free DNA now enables noninvasive screening for subchromosomal copy number variants, including 22q11.2 deletion syndrome (or DiGeorge syndrome), which is the most common microdeletion and a leading cause of congenital heart defects and neurodevelopmental delay. Although smaller studies have demonstrated the feasibility of screening for 22q11.2 deletion syndrome, large cohort studies with confirmatory postnatal testing to assess test performance have not been reported. OBJECTIVE: This study aimed to assess the performance of single-nucleotide polymorphism-based, prenatal cell-free DNA screening for detection of 22q11.2 deletion syndrome. STUDY DESIGN: Patients who underwent single-nucleotide polymorphism-based prenatal cell-free DNA screening for 22q11.2 deletion syndrome were prospectively enrolled at 21 centers in 6 countries. Prenatal or newborn DNA samples were requested in all cases for genetic confirmation using chromosomal microarrays. The primary outcome was sensitivity, specificity, positive predictive value, and negative predictive value of cell-free DNA screening for the detection of all deletions, including the classical deletion and nested deletions that are ≥500 kb, in the 22q11.2 low-copy repeat A-D region. Secondary outcomes included the prevalence of 22q11.2 deletion syndrome and performance of an updated cell-free DNA algorithm that was evaluated with blinding to the pregnancy outcome. RESULTS: Of the 20,887 women enrolled, a genetic outcome was available for 18,289 (87.6%). A total of 12 22q11.2 deletion syndrome cases were confirmed in the cohort, including 5 (41.7%) nested deletions, yielding a prevalence of 1 in 1524. In the total cohort, cell-free DNA screening identified 17,976 (98.3%) cases as low risk for 22q11.2 deletion syndrome and 38 (0.2%) cases as high risk; 275 (1.5%) cases were nonreportable. Overall, 9 of 12 cases of 22q11.2 were detected, yielding a sensitivity of 75.0% (95% confidence interval, 42.8-94.5); specificity of 99.84% (95% confidence interval, 99.77-99.89); positive predictive value of 23.7% (95% confidence interval, 11.44-40.24), and negative predictive value of 99.98% (95% confidence interval, 99.95-100). None of the cases with a nonreportable result was diagnosed with 22q11.2 deletion syndrome. The updated algorithm detected 10 of 12 cases (83.3%; 95% confidence interval, 51.6-97.9) with a lower false positive rate (0.05% vs 0.16%; P

Background Abnormal fetal growth is a risk factor for perinatal mortality and morbidity. There is considerable debate about the choice and performance of growth charts to classify newborns as small or large for gestational age (SGA and LGA) as a proxy for the at-risk infants. Several international charts have been proposed to be adopted worldwide. We aim to evaluate the performance of commonly-used growth charts (including international INTERGROWTH-21st-standards) for predicting adverse outcomes among SGA and LGA babies. Methods A population cohort of 2.4 million singleton births (24+0–40+6 weeks) delivered in Australia, 2004–2013. Performance was evaluated by prevalence, relative risk and diagnostic accuracy for adverse outcome based on AUC. Results There was wide variation in SGA and LGA classification across charts. For example, compared to other charts, the INTERGROWTH-21st-standards classified half of the number of term-SGA babies (prevalence: 3-4% vs. 7-10%) (90th-centile), resulting in a smaller cohort of term-SGA at higher-risk of adverse outcome, and a larger LGA cohort with lower-risk of adverse outcome. All charts performed poorly for detecting adverse outcomes (AUC range for a composite outcome: 0.49-0.68) and across birthweight centiles. Conclusions Significant differences in the classification of newborns and the chart performance raises concerns about whether the INTERGROWTH-21st-standards are applicable to a multi-ethnic population such as Australia. Key messages Significant differences in the classification of newborns and the relatively poor predictive ability of growth charts means that over reliance on infant size alone may misclassify, and thus miss at-risk infants.

Fetal growth restriction is a leading cause of stillbirth that often remains undetected during pregnancy. Identifying novel biomarkers may improve detection of pregnancies at risk. This study aimed to assess syndecan-1 as a biomarker for small for gestational age (SGA) or fetal growth restricted (FGR) pregnancies and determine its molecular regulation. Circulating maternal syndecan-1 was measured in several cohorts; a large prospective cohort collected around 36 weeks’ gestation (n = 1206), a case control study from the Manchester Antenatal Vascular service (285 women sampled at 24–34 weeks’ gestation); two prospective cohorts collected on the day of delivery (36 + 3–41 + 3 weeks’ gestation, n = 562 and n = 405 respectively) and a cohort who delivered for preterm FGR (

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.

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

Background Preterm birth is the leading cause of death in children under the age of five years. Transvaginal cervical length (TVCL) assessment can be used to predict preterm delivery risk at the mid-trimester scan. To optimise the screening tool, developing and maintaining quality standards is important. Aims To develop an Australian reference range for TVCL at 18.0-21.0 weeks' gestation, quality standards for measurement and audit mechanisms for ultrasound operators. Materials and methods A retrospective audit was performed of consecutive patients scanned at 18.0-21.0 weeks' gestation. Each TVCL measurement ultrasound image was reviewed, and exclusions were made based on a defined set of quality criteria. Fractional polynomial Bayesian methodology was used to establish a reference range. Central tendency, dispersion plots and cumulative sum charts for operators in the original reference range cohort were created. These plots were then applied to a second validation cohort of operators to establish the efficacy of this quality assurance audit tool. Results Median TVCL from 1031 participants was 36.0 mm (interquartile range 32.7-40.0 mm), which was independent of gestational age. The quality audit tool was applied to 15 operators from the reference cohort with a mean cervix length multiple of the median of 1.01 and a mean SD log10 cervix length multiple of the median of 0.06. Of the 22 operators in the validation cohort, 20 (90.9%) demonstrated ideal or acceptable central tendency results, and 19 (86.4%) remained in the appropriate cumulative sum zone. Conclusion An Australian cervix length measurement reference range at 18.0-21.0 weeks' gestation has been developed along with a validated quality assurance audit tool for ultrasound operators.

Background: Placental dysfunction, inflammation and degradation of fetal membranes has been hypothesized as a cause of preterm prelabor of rupture of membranes.Objective: To examine the effect of a...

OBJECTIVE Pre-eclampsia (PE) remains a leading cause of maternal and fetal morbidity and mortality. A first-trimester screening algorithm predicting the risk of early-onset PE has been developed and validated. Early prediction coupled with initiation of aspirin at 11-13 weeks in women identified as high risk is effective at reducing the prevalence of early-onset PE. The aim of this study was to evaluate the cost-effectiveness of this first-trimester screening program coupled with early use of low-dose aspirin in women at high risk of developing early-onset PE, in comparison to current practice in Canada. METHODS A decision analysis was performed based on a theoretical population of 387 516 live births in Canada in 1 year. The clinical and financial impact of early preventative screening using the Fetal Medicine Foundation algorithm for prediction of early-onset PE coupled with early (

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.

Pre-eclampsia (PE) is a severe disorder that affects up to 8% of all pregnancies and represents an important cause of maternal and perinatal morbidity and mortality. The screening of the disease is a subject of studies, but the complexity and uncertainties regarding its etiology make this objective a difficult task. In addition, the costs related to screening protocols, the heterogeneity of the most affected populations and the lack of highly effective prevention methods reduce the potential of current available algorithms for screening. Thus, the National Specialized Commission of Hypertension in Pregnancy of the Brazilian Association of Gynecology and Obstetrics Federation (Febrasgo, in the Portuguese acronym) (NSC Hypertension in Pregnancy of the Febrasgo) considers that there are no screening algorithms to be implemented in the country to date and advocates that Aspirin and calcium should be widely used.

Preeclampsia (PE) is associated with long-term morbidity in mothers and lifelong morbidities for their children, ranging from cerebral palsy and cognitive delay in preterm infants, to hypertension, diabetes and obesity in adolescents and young adults. There are several processes that are critical for development of materno-fetal exchange, including establishing adequate perfusion of the placenta by maternal blood, and the formation of the placental villous vascular tree. Recent studies provide persuasive evidence that placenta-derived extracellular vesicles (EVs) represent a significant intercellular communication pathway, and that they may play an important role in placental and endothelial cell (both fetal and maternal) function. These functions are known to be altered in PE. EVs can carry and transport a wide range of bioactive molescules that have potential to be used as biomarkers and therapeutic delivery tools for PE. EV content is often parent cell specific, thus providing an insight or "thumbprint" of the intracellular environment of the originating cell (e.g., human placenta). EV have been identified in plasma under both normal and pathological conditions, including PE. The concentration of EVs and their content in plasma has been reported to increase in association with disease severity and/or progression. Placenta-derived EVs have been identified in maternal plasma during normal pregnancy and PE pregnancies. They contain placenta-specific proteins and miRNAs and, as such, may be differentiated from maternally-derived EVs. The aim of this review, thus, is to describe the potential roles of EVs in preecmpatic pregnancies, focussing on EVs secreted from placental cells. The biogenesis, specificity of placental EVs, and methods used to characterise EVs in the context of PE pregnancies will be also discussed.

INTRODUCTION: Inconsistent reporting practices in third trimester ultrasound, the choice of reference charts in particular, have the potential to misdiagnose abnormal fetal growth. But this may lead to unnecessary anxiety and confusion amongst patients and clinicians and ultimately influence clinical management. Therefore, we sought to determine the extent of variability in choice of fetal biometry and Doppler reference charts and reporting practices in Australia and New Zealand. METHODS: Clinicians performing and/or reporting obstetric ultrasound were invited to answer questions about fetal biometry and Doppler charts in a web‐based survey. RESULTS: At least four population‐based charts are in current use. The majority of respondents (78%) report the percentile for known gestational age (GA) alongside measurements and 63% using a cut‐off of estimated fetal weight (EFW) < 10(th) percentile when reporting small for gestational age (SGA) and/or fetal growth restriction (FGR). The thresholds for the use of fetal and maternal Doppler in third trimester ultrasound varied in terms of the GA, EFW cut‐off, and how measures were reported. The majority of respondents were not sure of which Doppler charts were used in their practice. CONCLUSION: This survey revealed inconsistencies in choice of reference chart and reporting practices. The potential for misdiagnosis of abnormal fetal growth remains a significant issue.

Objective: Caesarean delivery rates continue to rise globally the reasons for which are poorly understood. We aimed to characterize attributable factors for increasing caesarean delivery rates over a 30-year period within our health network. Design: Observational cohort study. Setting: Two hospitals (large tertiary referral hospital and metropolitan hospital) in Sydney, Australia, across two time periods: 1989-1999 and 2009-2016, between which the caesarean delivery rate increased from 19% to 30%. Participants: All women who had a caesarean delivery after 24 weeks gestation Methods: Data were analysed using multiple imputation and robust Poisson regression to estimate the changes in the caesarean delivery rate attributable to maternal and clinical factors. Main outcome measures: Caesarean delivery. Results: Fifty-six percent of the increase in the rate of caesarean delivery was attributed to changes in the distribution of maternal factors including maternal age, body mass index, parity and history of previous caesarean delivery. When changes in the obstetric management of multiple gestation, malpresentation and preterm singleton birth were considered, 66% of the increase in caesarean rate was explained. When pre-labour caesarean deliveries for maternal choice, suspected fetal compromise, previous pregnancy issues and suspected large fetus were excluded, 78% of the increase was explained. Conclusions: Most of the steep rise in the caesarean delivery rate from 19% to 30% is attributable to changes in maternal demographic and clinical factors.