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Background: Australian rates of adverse obstetric outcomes have improved little despite guidelines recommending history-based screening and intervention. The first trimester provides a unique opportunity to predict and prevent complications, yet population-based screening has failed to be translated into broad clinical practice., Aims: This study aimed to redesign antenatal care within an Australian public healthcare centre to align with evidence-based maternity care, including population-based first-trimester screening with early initiation of preventative strategies in high-risk pregnancies., Methods: A five-phase action-process model, sharing key elements with implementation science theory, was used to explore barriers to change in antenatal care, co-design a novel service with consumers and establish a population-based antenatal pathway commencing with a multidisciplinary first-trimester screening, assessment and planning visit., Results: The case for change and associated barriers were defined from the perspective of antenatal care stakeholders. Key needs of each group were established, and solutions were created using co-design methodology, allowing the team to create a novel approach to antenatal care which directly addressed identified barriers. Implementation of the service was associated with a fall in the median gestation at first specialist maternity care provider visit from 20 to 13 weeks., Conclusions: This study confirms the feasibility of establishing a comprehensive first-trimester screening program within a public Australian healthcare setting and highlights a co-design process which places individualised assessment at the forefront of antenatal care. This framework may be applicable to most public maternity settings in Australia, with expansion aimed at providing equity of care, including in rural and remote settings., (© 2024 The Authors. Australian and New Zealand Journal of Obstetrics and Gynaecology published by John Wiley & Sons Australia, Ltd on behalf of Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Objectives: To examine the distribution of nuchal translucency thickness (NT), free β-human chorionic gonadotropin (β-hCG) and pregnancy-associated plasma protein-A (PAPP-A) in pregnancies with a fetal 22q11.2 aberration. Furthermore, the performance of combined first-trimester screening (cFTS) and a new risk algorithm targeting 22q11.2 deletions in detecting affected pregnancies was evaluated. Finally, prenatal malformations and pregnancy outcome were assessed., Methods: This was a nationwide registry-based cohort study of all pregnancies that underwent prenatal screening with a due date between January 2008 and December 2018 in Denmark. All cases with a fetal 22q11.2 deletion or duplication (hg19 chr22:18.9mio-25.0mio) diagnosed pre- or postnatally or following pregnancy loss or termination of pregnancy were retrieved from the Danish Cytogenetic Central Register and linked with pregnancy data from the Danish Fetal Medicine Database. Fetal and maternal characteristics, including cFTS results and pregnancy outcome, of pregnancies with any 22q11.2 deletion or duplication (LCR22-A to -H) and pregnancies with a classic deletion or duplication (LCR22-A to -D) diagnosed by chromosomal microarray were compared with those of a chromosomally normal reference group. A risk algorithm was developed for assessing patient-specific risks for classic 22q11.2 deletions based on NT, PAPP-A and β-hCG. Detection rates and false-positive rates at different risk cut-offs were calculated., Results: We included data on 143 pregnancies with a fetal 22q11.2 aberration, of which 97 were deletions (54 classic) and 46 were duplications (32 classic). NT was significantly increased in fetuses with a classic deletion (mean, 1.89 mm), those with any deletion (mean, 1.78 mm) and those with any duplication (mean, 1.86 mm) compared to the reference group (mean, 1.65 mm). β-hCG multiples of the median (MoM) was decreased in all 22q11.2 subgroups compared with the reference group (mean, 1.02) and reached significance in pregnancies with a classic deletion and those with any deletion (mean, 0.77 and 0.71, respectively). PAPP-A MoM was significantly decreased in pregnancies with a classic duplication and those with any duplication (mean, 0.57 and 0.63, respectively), and was significantly increased in pregnancies with a classic deletion and those with any deletion (mean, 1.34 and 1.16, respectively), compared to reference pregnancies (mean, 1.01). The screen-positive rate by cFTS was significantly increased in pregnancies with a classic deletion (13.7%), any deletion (12.5%), a classic duplication (46.9%) or any duplication (37.8%) compared to the reference group (4.5%). A risk algorithm targeting classic 22q11.2 deletions more than doubled the prenatal detection rate of classic 22q11.2 deletions, but with a substantial increase in the false-positive rate. Structural malformations were detected in 41%, 35%, 17% and 25% of the pregnancies with a classic deletion, any deletion, classic duplication or any duplication, respectively. Pregnancy loss occurred in 40% of pregnancies with a classic deletion and 5% of those with a classic duplication diagnosed prenatally or following pregnancy loss., Conclusions: The distribution of cFTS markers in pregnancies with a classic 22q11.2 duplication resembles that of the common trisomies, with decreased levels of PAPP-A. However, classic 22q11.2 deletions are associated with increased levels of PAPP-A, which likely limits early prenatal detection using the current cFTS risk algorithm. The scope for improving early detection of classic 22q11.2 deletions using targeted risk algorithms based on NT, PAPP-A and β-hCG is limited. This demonstrates the capability, but also the limitations, of cFTS markers in detecting atypical chromosomal anomalies, which is important knowledge when designing new prenatal screening programs. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology., (© 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.)

Objective: One goal of prenatal genetic screening is to optimize perinatal care and improve infant outcomes. We sought to determine whether high-risk cfDNA screening for 22q11.2 deletion syndrome (22q11.2DS) affected prenatal or neonatal management., Methods: This was a secondary analysis from the SMART study. Patients with high-risk cfDNA results for 22q11.2DS were compared with the low-risk cohort for pregnancy characteristics and obstetrical management. To assess differences in neonatal care, we compared high-risk neonates without prenatal genetic confirmation with a 1:1 matched low-risk cohort., Results: Of 18,020 eligible participants enrolled between 2015 and 2019, 38 (0.21%) were high-risk and 17,982 (99.79%) were low-risk for 22q11.2DS by cfDNA screening. High-risk participants had more prenatal diagnostic testing (55.3%; 21/38 vs. 2.0%; 352/17,982, p < 0.001) and fetal echocardiography (76.9%; 10/13 vs. 19.6%; 10/51, p < 0.001). High-risk newborns without prenatal diagnostic testing had higher rates of neonatal genetic testing (46.2%; 6/13 vs. 0%; 0/51, P < 0.001), echocardiography (30.8%; 4/13 vs. 4.0%; 2/50, p = 0.013), evaluation of calcium levels (46.2%; 6/13 vs. 4.1%; 2/49, P < 0.001) and lymphocyte count (53.8%; 7/13 vs. 15.7%; 8/51, p = 0.008)., Conclusions: High-risk screening results for 22q11.2DS were associated with higher rates of prenatal and neonatal diagnostic genetic testing and other 22q11.2DS-specific evaluations. However, these interventions were not universally performed, and >50% of high-risk infants were discharged without genetic testing, representing possible missed opportunities to improve outcomes for affected individuals., (© 2023 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd.)

Background: Mounting evidence shows the risk of COVID-19 on perinatal outcomes, as well as the safety and efficacy of vaccination during pregnancy. However, little is known about vaccine uptake among pregnant women in Australia, including women who are culturally and linguistically diverse (CALD), and about sources of information pregnant women use when making decisions about vaccines. We aimed to determine the proportion of pregnant women who had been vaccinated and to identify factors associated with vaccine uptake or decline during pregnancy., Method: A cross-sectional, anonymous, online survey was conducted from October 2021 to January 2022 in two metropolitan hospitals in New South Wales, Australia., Results: Of 914 pregnant women, 406 (44%) did not speak English at home. Overall, 101 (11%) received a vaccine prepregnancy and 699 (76%) during pregnancy. In the nonvaccinated cohort, 87 (76%) declined vaccination during pregnancy. The uptake was more than 87% among women during pregnancy who received information from government or health professional websites but 37% when received from personal blogs. The main reasons for vaccine uptake were (1) hearing that COVID-19 affects pregnant women, (2) being concerned about the COVID-19 outbreak, and (3) receiving vaccine recommendation from a general practitioner. In a multivariable logistic regression, three main factors associated with declining or feeling unsure about vaccination were (1) concerns about the safety of the COVID-19 vaccine, (2) lack of trust and being unsatisfied with the information received about COVID-19 vaccination during pregnancy, and (3) doubting the importance of COVID-19 vaccine., Conclusion: Clinicians play a critical role in counseling women to alleviate vaccine fear, support vaccine acceptance, and direct women to use reliable information sources, such as government and professional healthcare organizations, for information about vaccines., (© 2023 Wiley Periodicals LLC.)

Background: The clinical implications of nonreportable cell-free DNA screening results are uncertain, but such results may indicate poor placental implantation in some cases and be associated with adverse obstetrical and perinatal outcomes., Objective: This study aimed to assess the outcomes of pregnancies with nonreportable cell-free DNA screening in a cohort of patients with complete genetic and obstetrical outcomes., Study Design: This was a prespecified secondary analysis of a multicenter prospective observational study of prenatal cell-free DNA screening for fetal aneuploidy and 22q11.2 deletion syndrome. Participants who underwent cell-free DNA screening from April 2015 through January 2019 were offered participation. Obstetrical outcomes and neonatal genetic testing results were collected from 21 primary-care and referral centers in the United States, Europe, and Australia. The primary outcome was risk for adverse obstetrical and perinatal outcomes (aneuploidy, preterm birth at <28, <34, and <37 weeks' gestation, preeclampsia, small for gestational age or birthweight <10th percentile for gestational week, and a composite outcome that included preterm birth at <37 weeks, preeclampsia, small for gestational age, and stillbirth at >20 weeks) after nonreportable cell-free DNA screening because of low fetal fraction or other causes. Multivariable analyses were performed, adjusting for variables known to be associated with obstetrical and perinatal outcomes, nonreportable results, or fetal fraction., Results: In total, 25,199 pregnant individuals were screened, and 20,194 were enrolled. Genetic confirmation was missing in 1165 (5.8%), 1085 (5.4%) were lost to follow-up, and 93 (0.5%) withdrew; the final study cohort included 17,851 (88.4%) participants who had cell-free DNA, fetal or newborn genetic confirmatory testing, and obstetrical and perinatal outcomes collected. Results were nonreportable in 602 (3.4%) participants. A sample was redrawn and testing attempted again in 427; in 112 (26.2%) participants, results were again nonreportable. Nonreportable results were associated with higher body mass index, chronic hypertension, later gestational age, lower fetal fraction, and Black race. Trisomy 13, 18, or 21 was confirmed in 1.6% with nonreportable tests vs 0.7% with reported results (P=.013). Rates of preterm birth at <28, 34, and 37 weeks, preeclampsia, and the composite outcome were higher among participants with nonreportable results, and further increased among those with a second nonreportable test, whereas the rate of small for gestational age infants was not increased. After adjustment for confounders, the adjusted odds ratios were 2.2 (95% confidence interval, 1.1-4.4) and 2.6 (95% confidence interval, 0.6-10.8) for aneuploidy, and 1.5 (95% confidence interval, 1.2-1.8) and 2.1 (95% confidence interval, 1.4-3.2) for the composite outcome after a first and second nonreportable test, respectively. Of the patients with nonreportable tests, 94.9% had a live birth, as opposed to 98.8% of those with reported test results (adjusted odds ratio for livebirth, 0.20 [95% confidence interval, 0.13-0.30])., Conclusion: Patients with nonreportable cell-free DNA results are at increased risk for a number of adverse outcomes, including aneuploidy, preeclampsia, and preterm birth. They should be offered diagnostic genetic testing, and clinicians should be aware of the increased risk of pregnancy complications., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: The aim of this study was to assess the performance of cell-free DNA (cfDNA) screening to detect sex chromosome aneuploidies (SCAs) in an unselected obstetrical population with genetic confirmation., Methods: This was a planned secondary analysis of the multicenter, prospective SNP-based Microdeletion and Aneuploidy RegisTry (SMART) study. Patients receiving cfDNA results for autosomal aneuploidies and who had confirmatory genetic results for the relevant sex chromosomal aneuploidies were included. Screening performance for SCAs, including monosomy X (MX) and the sex chromosome trisomies (SCT: 47,XXX; 47,XXY; 47,XYY) was determined. Fetal sex concordance between cfDNA and genetic screening was also evaluated in euploid pregnancies., Results: A total of 17,538 cases met inclusion criteria. Performance of cfDNA for MX, SCTs, and fetal sex was determined in 17,297, 10,333, and 14,486 pregnancies, respectively. Sensitivity, specificity, and positive predictive value (PPV) of cfDNA were 83.3%, 99.9%, and 22.7% for MX and 70.4%, 99.9%, and 82.6%, respectively, for the combined SCTs. The accuracy of fetal sex prediction by cfDNA was 100%., Conclusion: Screening performance of cfDNA for SCAs is comparable to that reported in other studies. The PPV for the SCTs was similar to the autosomal trisomies, whereas the PPV for MX was substantially lower. No discordance in fetal sex was observed between cfDNA and postnatal genetic screening in euploid pregnancies. These data will assist interpretation and counseling for cfDNA results for sex chromosomes., Competing Interests: Conflict of Interest All site principal investigators (Pe’er Dar, Bo Jacobsson, Fergal Malone, Ronald J. Wapner, Ashley S. Roman, Asma Khalil, Revital Faro, Rajeevi Madankumar, Sina Haeri, Robert M. Silver, Nidhi Vohra, Jon Hyett, Cora MacPherson, and Mary E. Norton) received institutional research support from the funding sponsor (Natera). Melissa Egbert, Zachary Demko, and Matt Rabinowitz are employed by the study’s funding sponsor (Natera) and hold stock or options to hold stock. Kimberly Martin is a consultant to the funding sponsor (Natera) and holds stock and options to hold stock. Jon Hyett has an ongoing research collaboration that includes financial support for biochemical analytes from Perkin Elmer; has earned honoraria and/or given talks that were not compensated from Natera, Roche, and Canon; and has participated in Asian/Australasian expert consultancies for Natera and Roche. Bo Jacobsson collaborated in the Improving Maternal Pregnancy And Child ouTcomes (IMPACT) study where Roche, Perkin Elmer, and Thermo Fisher provide reagents to Placental Growth Factor (PLGF) analyses. Ronald J. Wapner receives research funding from National Institute of Child Health and Human Development and support from Illumina for research reagents. Mary E. Norton is a consultant to Luna Genetics. All other authors declare no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Traditional obstetric practice relies upon history-based assessment to screen for preeclampsia and guide preventative therapies but is hampered by low sensitivity, high false-positive rates and low treatment rates. First-trimester screening algorithms represent the most efficacious approach for risk prediction and could target early initiation of aspirin to well-defined high-risk populations. A large randomised controlled trial has demonstrated the clinical benefits of this approach, but widespread practice implementation has remained elusive., Methods: We performed a systematic review and meta-analysis summarising studies linking first-trimester preeclampsia screening algorithms with the initiation of preventative therapy and examined their effect on pre-term preeclampsia rates compared with standard maternity care. Odds ratios were calculated together with 95% confidence intervals., Results: 7 studies with a total of 377,790 participants were included. Within singleton populations, early initiation of aspirin in response to a high-risk screening algorithm result reduced the prevalence of pre-term preeclampsia by 39% compared with routine antenatal care (odds ratio 0.61; 95% CI: 0.52-0.70). There were significant reductions in the prevalence of preeclampsia at <32-34 weeks, preeclampsia at any gestation and stillbirth., Conclusion: First-trimester screening algorithms for preeclampsia aligned with early initiation of preventative therapy with aspirin reduce the prevalence of pre-term preeclampsia., (© 2023 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd.)

Pre-eclampsia is a life-threatening disease of pregnancy unique to humans and a leading cause of maternal and neonatal morbidity and mortality. Women who survive pre-eclampsia have reduced life expectancy, with increased risks of stroke, cardiovascular disease and diabetes, while babies from a pre-eclamptic pregnancy have increased risks of preterm birth, perinatal death and neurodevelopmental disability and cardiovascular and metabolic disease later in life. Pre-eclampsia is a complex multisystem disease, diagnosed by sudden-onset hypertension (>20 weeks of gestation) and at least one other associated complication, including proteinuria, maternal organ dysfunction or uteroplacental dysfunction. Pre-eclampsia is found only when a placenta is or was recently present and is classified as preterm (delivery <37 weeks of gestation), term (delivery ≥37 weeks of gestation) and postpartum pre-eclampsia. The maternal syndrome of pre-eclampsia is driven by a dysfunctional placenta, which releases factors into maternal blood causing systemic inflammation and widespread maternal endothelial dysfunction. Available treatments target maternal hypertension and seizures, but the only 'cure' for pre-eclampsia is delivery of the dysfunctional placenta and baby, often prematurely. Despite decades of research, the aetiology of pre-eclampsia, particularly of term and postpartum pre-eclampsia, remains poorly defined. Significant advances have been made in the prediction and prevention of preterm pre-eclampsia, which is predicted in early pregnancy through combined screening and is prevented with daily low-dose aspirin, starting before 16 weeks of gestation. By contrast, the prediction of term and postpartum pre-eclampsia is limited and there are no preventive treatments. Future research must investigate the pathogenesis of pre-eclampsia, in particular of term and postpartum pre-eclampsia, and evaluate new prognostic tests and treatments in adequately powered clinical trials., (© 2023. Springer Nature Limited.)

Objectives: To standardize the measurement of shear wave elastography for assessment of cervical stiffness and its relationship with gestational age and cervical length., Methods: 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., Results: 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., Conclusion: 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.

Objective: To determine whether vaginal progesterone reduces spontaneous preterm birth (sPTB) before 37 weeks in asymptomatic high-risk women with a singleton pregnancy and normal mid-gestation cervical length. Study design: Databases were searched (from inception to December 2020) with the search terms "progesterone" and "premature birth" or "preterm birth". Studies were screened and included if they assessed vaginal progesterone compared to placebo in women with normal cervical length. Data were pooled and synthesized in a meta-analysis using a random effects model. Data sources : MEDLINE and Embase databases. Study synthesis: Following PRISMA screening guidelines, data from 1127 women across three studies were available for synthesis. All studies had low risk of bias and were of high quality. The primary outcome was sPTB <37 weeks, with secondary outcomes of sPTB <34 weeks. Vaginal progesterone did not significantly reduce sPTB before 37 weeks, or before 34 weeks with a relative risk (RR) of 0.76 (95% CI 0.37-1.55, p  = .45) and 0.51 (95% CI 0.12-2.13, p  = .35), respectively. Conclusions: Vaginal progesterone does not decrease the risk of sPTB in high-risk singleton pregnancies with a normal mid-gestation cervical length.

Equine osteoarthritis is a chronic degenerative disease of the articular joint, characterised by cartilage degradation resulting in pain and reduced mobility and thus is a prominent equine welfare concern. Diagnosis is usually at a late stage through clinical examination and radiographic imaging, whilst treatment is symptomatic not curative. Extracellular vesicles are nanoparticles that are involved in intercellular communication. The objective of this study was to investigate the feasibility of Raman and Optical Photothermal Infrared Spectroscopies to detect osteoarthritis using plasma-derived extracellular vesicles, specifically differentiating extracellular vesicles in diseased and healthy controls within the parameters of the techniques used. Plasma samples were derived from thoroughbred racehorses. A total of 14 samples were selected (control; n = 6 and diseased; n = 8). Extracellular vesicles were isolated using differential ultracentrifugation and characterised using nanoparticle tracking analysis, transmission electron microscopy, and human tetraspanin chips. Samples were then analysed using combined Raman and Optical Photothermal Infrared Spectroscopies. Infrared spectra were collected between 950-1800 cm -1 . Raman spectra had bands between the wavelengths of 900-1800 cm -1 analysed. Spectral data for both Raman and Optical Photothermal Infrared Spectroscopy were used to generate clustering via principal components analysis and classification models were generated using partial least squared discriminant analysis in order to characterize the techniques' ability to distinguish diseased samples. Optical Photothermal Infrared Spectroscopy could differentiate osteoarthritic extracellular vesicles from healthy with good classification (93.4% correct classification rate) whereas Raman displayed poor classification (correct classification rate = -64.3%). Inspection of the infrared spectra indicated that plasma-derived extracellular vesicles from osteoarthritic horses contained increased signal for proteins, lipids and nucleic acids. For the first time we demonstrated the ability to use optical photothermal infrared spectroscopy combined with Raman spectroscopy to interrogate extracellular vesicles and osteoarthritis-related samples. Optical Photothermal Infrared Spectroscopy was superior to Raman in this study, and could distinguish osteoarthritis samples, suggestive of its potential use diagnostically to identify osteoarthritis in equine patients. This study demonstrates the potential of Raman and Optical Photothermal Infrared Spectroscopy to be used as a future diagnostic tool in clinical practice, with the capacity to detect changes in extracellular vesicles from clinically derived samples.

Objective: To assess pregnancy outcomes following first trimester combined screening for preterm preeclampsia in Australia., Methods: 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., Results: 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 (risk <1 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., Conclusions: 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., (© 2021 International Federation of Gynecology and Obstetrics.)

Background: Cell-free DNA noninvasive prenatal screening for trisomies 21, 18, and 13 has been rapidly adopted into clinical practice. However, previous studies are limited by a lack of follow-up genetic testing to confirm the outcomes and accurately assess test performance, particularly in women at a low risk for aneuploidy., Objective: To measure and compare the performance of cell-free DNA screening for trisomies 21, 18, and 13 between women at a low and high risk for aneuploidy in a large, prospective cohort with genetic confirmation of results STUDY DESIGN: This was a multicenter prospective observational study at 21 centers in 6 countries. Women who had single-nucleotide-polymorphism-based cell-free DNA screening for trisomies 21, 18, and 13 were enrolled. Genetic confirmation was obtained from prenatal or newborn DNA samples. The test performance and test failure (no-call) rates were assessed for the cohort, and women with low and high previous risks for aneuploidy were compared. An updated cell-free DNA algorithm blinded to the pregnancy outcome was also assessed., Results: A total of 20,194 women were enrolled at a median gestational age of 12.6 weeks (interquartile range, 11.6-13.9). The genetic outcomes were confirmed in 17,851 cases (88.4%): 13,043 (73.1%) low-risk and 4808 (26.9%) high-risk cases for aneuploidy. Overall, 133 trisomies were diagnosed (100 trisomy 21; 18 trisomy 18; 15 trisomy 13). The cell-free DNA screen positive rate was lower in the low-risk vs the high-risk group (0.27% vs 2.2%; P<.0001). The sensitivity and specificity were similar between the groups. The positive predictive value for the low- and high-risk groups was 85.7% vs 97.5%; P=.058 for trisomy 21; 50.0% vs 81.3%; P=.283 for trisomy 18; and 62.5% vs 83.3; P=.58 for trisomy 13, respectively. Overall, 602 (3.4%) patients had no-call result after the first draw and 287 (1.61%) after including cases with a second draw. The trisomy rate was higher in the 287 cases with no-call results than patients with a result on a first draw (2.8% vs 0.7%; P=.001). The updated algorithm showed similar sensitivity and specificity to the study algorithm with a lower no-call rate., Conclusion: In women at a low risk for aneuploidy, single-nucleotide-polymorphism-based cell-free DNA has high sensitivity and specificity, positive predictive value of 85.7% for trisomy 21 and 74.3% for the 3 common trisomies. Patients who receive a no-call result are at an increased risk of aneuploidy and require additional investigation., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

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<.001) and a positive predictive value of 52.6% (10/19; 95% confidence interval, 28.9-75.6)., Conclusion: Noninvasive cell-free DNA prenatal screening for 22q11.2 deletion syndrome can detect most affected cases, including smaller nested deletions, with a low false positive rate., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: 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., Methods: 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., Results: 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). Log 10 leptin was significantly associated with gestation at delivery, birthweight (BWt), infant sex, plurality, and maternal body mass index (BMI) ( p  < .001). Observed leptin values were expressed as multiples of the median (MoM). The mean leptin MoM was significantly lower in infants admitted to NICU following delivery (0.85; 95% confidence interval [CI]: 0.78-0.91 versus 1.05; 95% CI: 1.03-1.06 (controls), p  < .001). There was no significant association between leptin MoM values and 5-min Apgar scores., Conclusions: Neonatal 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 or >95th centile) will benefit from further surveillance or intervention in infancy.

Background: The efficacy of maintenance tocolytic therapy after successful arrest of preterm labor remains controversial. The purpose of this study was to evaluate the efficacy of 400 mg of daily vaginal progesterone (cyclogest) after successful parenteral tocolysis to increase latency period and improvement of neonatal outcomes in women with threatened preterm labor., Materials and Methods: In this randomized, double-blind, placebo-controlled trial, 85 participants were randomly allocated to either 400 mg daily of vaginal progesterone ( n  = 45) or placebo ( n  = 40) until 34 weeks of gestation. The primary outcomes were the time until delivery (latency period) and cervical length after 1 week of treatment. Secondary outcome were GA on delivery, type of delivery, incidence of low birth weight, perinatal morbidity and mortality., Results: Longer mean latency until delivery (53.6 ± 16.8 versus 34.5 ± 12.9) days p  = .0001; longer mean of gestational age on delivery (37.5 ± 2.2 versus 34.2 ± 2.1) weeks p  = .0001; cervical length after 1 week of treatment (27.5 ± 5.5 versus 20.7 ± 3.1) mm p  = .0001; low birth weight 12 (29.3%) versus 19 (57.6%) p  = .01; and NICU admission 9 (22%) versus 15 (45.5%), were significantly different between the two groups. No significant differences were found between neonatal death 1 (2.4%) versus 2 (6.1%), p  = .43; RDS 5 (12.2%) versus 8 (24.2%), p  = .17; and need to mechanical ventilator 2 (5.4%) versus 6 (18.2%) p  = .136, for the progesterone and placebo groups, respectively., Conclusion: Daily administration of 400 mg vaginal progesterone after successful parenteral tocolysis may increase latency preceding delivery and improves cervical shortening and neonatal outcome in women with preterm labor. Further confirmatory studies are warranted.

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., Objectives: We sought to assess the collective impact of maternal dietary MUFAs, PUFAs, and SFAs on epigenetic aging and cardiometabolic risk markers in healthy newborn infants using a geometric framework approach., Methods: Body fatness (n = 162), aortic intima-media thickness (aIMT; 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 FFQ. 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 MUFAs, PUFAs, and SFAs (P = 0.001) with newborn epigenetic aging. This suggests that the nature of each fat class association depends upon one another. Response surfaces revealed MUFAs were positively associated with newborn epigenetic age acceleration only at proportionately lower intakes of SFAs or PUFAs. We also demonstrate a potential beneficial association of omega-3 (n-3) PUFAs with newborn epigenetic age acceleration (P = 0.008). There was no significant association of fat class with newborn aIMT, heart rate variability, or body fatness., Conclusions: In this study, we demonstrated 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., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

The nonlinear mechanical behaviour of cervical tissue causes unpredictable changes in measured elastograms when pressure is applied. These uncontrolled variables prevent the reliable measurement of tissue elasticity in a clinical setting. Measuring the nonlinear properties of tissue is difficult due to the need for both shear modulus and strain to be taken simultaneously. A simulation-based method is proposed in this paper to resolve this. This study describes the nonlinear behaviour of cervical tissue using the hyperelastic material models of Demiray-Fung and Veronda-Westmann. Elastograms from 33 low-risk patients between 18 and 22 weeks gestation were obtained. The average measured properties of the hyperelastic material models are: Demiray-Fung-A1α = 2.07 (1.65-2.58) kPa, α = 6.74 (4.07-19.55); Veronda-Westmann-C1C2 = 4.12 (3.24-5.04) kPa, C2 = 4.86 (2.86-14.28). The Demiray-Fung and Veronda-Westmann models performed similarly in fitting to the elastograms with an average root mean square deviation of 0.41 and 0.47 ms-1, respectively. The use of hyperelastic material models to calibrate shear-wave speed measurements improved the consistency of measurements. This method could be applied in a large-scale clinical setting but requires updated models and higher data resolution.

Objectives: Pre-eclampsia (PE) causes substantial maternal and neonatal mortality and morbidity. In addition to the personal impact on women, children and their families, PE has a significant economic impact on our society. Recent research suggests that a first-trimester multivariate model is highly predictive of preterm (< 37 weeks' gestation) PE and can be combined successfully with targeted prophylaxis (low-dose aspirin), resulting in an 80% reduction in prevalence of disease. The aim of this study was to examine the potential health outcomes and cost implications following introduction of first-trimester prediction and prevention of preterm PE within a public healthcare setting, compared with usual care, and to conduct a cost-effectiveness analysis to inform health-service decisions regarding implementation of such a program., Methods: A decision-analytic model was used to compare usual care with the proposed first-trimester screening intervention within the obstetric population (n = 6822) attending two public hospitals within a metropolitan district health service in New South Wales, Australia, between January 2015 and December 2016. The model, applied from early pregnancy, included exposure to a variety of healthcare professionals and addressed type of risk assessment (usual care or first-trimester screening) and use of (compliance with) low-dose aspirin prescribed prophylactically for prevention of PE. All pathways culminated in six possible health outcomes, ranging from no PE to maternal death. Results were presented as the number of cases of PE gained/avoided and the incremental increase/decrease in economic costs arising from the intervention compared with usual care. Significant assumptions were tested in sensitivity/uncertainty analyses., Results: The intervention produced, across all gestational ages, 31 fewer cases of PE and reduced aggregate economic health-service costs by 1 431 186 Australian dollars over the 2-year period. None of the tested iterations of uncertainty analyses reported additional cases of PE or higher economic costs. The new intervention based on first-trimester screening dominated usual care., Conclusion: This cost-effectiveness analysis demonstrated a reduction in prevalence of preterm PE and substantial cost savings associated with a population-based program of first-trimester prediction and prevention of PE, and supports implementation of such a policy. © 2020 International Society of Ultrasound in Obstetrics and Gynecology., (© 2020 International Society of Ultrasound in Obstetrics and Gynecology.)

Objective: To evaluate the discrepancy between historical and more recent descriptions of the first stage of labour by testing whether the statistical techniques used recently (repeated-measures polynomial and interval-censored regression) were appropriate for detection of periods of rapid acceleration of cervical dilatation as might occur at the time of transition from a latent to an active phase of labour., Design and Setting: A simulation study using regression techniques., Sample: We created a simulated data set for 500 000 labours with clearly defined latent and active phases using the parameters described by Friedman. Additionally, we created a data set comprising 500 000 labours with a progressively increasing rate of cervical dilatation., Methods: Repeated-measures polynomial regression was used to create summary labour curves based on simulated cervical examinations. Interval-censored regression was used to create centimetre-by-centimetre estimates of rates of cervical dilatation and their 95th centiles., Main Outcome Measures: Labour summary curves and rates of cervical dilatation., Results: Repeated-measures polynomial regression did not detect the rapid acceleration in cervical dilatation (i.e. acceleration phase) and overestimated lengths of labour, especially at smaller cervical dilatations. There was a two-fold overestimation in the mean rate of cervical dilatation from 4 to 6 cm. Interval-censored regression overestimated median transit times, at 4- to 5-cm cervical dilatation or when cervical examinations occurred less frequently than 0.5- to 1.5-hourly., Conclusion: Repeated-measures polynomial regression and interval-censored regression should not be routinely used to define labour progress because they do not accurately reflect the underlying data., Tweetable Abstract: Repeated-measures polynomial and interval-censored regression techniques are not appropriate to model first stage of labour., (© 2021 John Wiley & Sons Ltd.)

About half of Australian women have a body mass index in the overweight or obese range at the start of pregnancy, with serious consequences including preterm birth, gestational hypertension and diabetes, caesarean section, stillbirth, and childhood obesity. Trials to limit weight gain during pregnancy have had limited success and reducing weight before pregnancy has greater potential to improve outcomes. The PreBabe Pilot study was a randomised controlled pilot trial to assess the feasibility, acceptability and potential weight loss achieved using a commercial online partial meal replacement program, (MR) vs. telephone-based conventional dietary advice, (DA) for pre-conception weight-loss over a 10-week period. Women 18-40 years of age with a BMI ≥ 25 kg/m 2 planning pregnancy within the next 6 to 12 months were included in the study. All participants had three clinic visits with a dietitian and one obstetric consultation. In total, 50 women were enrolled in the study between June 2018 and October 2019-26 in MR and 24 in DA. Study retention at the end of 10 week intervention 81% in the MR arm and 75% in the DA arm. In the-intention-to-treat analysis, women using meal replacements lost on average 5.4 ± 3.1% body weight compared to 2.3 ± 4.2% for women receiving conventional advice ( p = 0.029). Over 80% of women in the MR arm rated the support received as excellent, compared to 39% in the DA arm ( p < 0.001). Women assigned to the MR intervention were more likely to achieve pregnancy within 12 months of the 10 week intervention (57% (12 of 21) women assigned to MR intervention vs. 22% (4 of 18) assigned to the DA group ( p = 0.049) became pregnant). The findings suggest that a weight loss intervention using meal replacements in the preconception period was acceptable and may result in greater weight loss than conventional dietary advice alone.

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., Competing Interests: Debra Paoletti is a member of the ASUM board of directors, the ASUM DMU board of examiners and an associate editor of AJUM., (© 2021 Australasian Society for Ultrasound in Medicine.)

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 (< 34 weeks). Circulating syndecan-1 was consistently reduced in women destined to deliver growth restricted infants and those delivering for preterm disease. Syndecan-1 secretion was reduced by hypoxia, and its loss impaired proliferation. Matrix metalloproteinases and mitochondrial electron transport chain inhibitors significantly reduced syndecan-1 secretion, an effect that was rescued by coadministration of succinate, a mitochondrial electron transport chain activator. In conclusion, circulating syndecan-1 is reduced among cases of term and preterm growth restriction and has potential for inclusion in multi-marker algorithms to improve detection of poorly grown fetuses., (© 2021. The Author(s).)

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: 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., (© 2020 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Competing Interests: The authors have no conflict of interests to declare.

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 aspirin, an anti-inflammatory agent, on the prevalence of preterm prelabor rupture of membranes (PPRoMs). Methods: A retrospective analysis was conducted to examine the effect of aspirin on the prevalence of PPRoM. Aspirin (150 mg, nocte) was prescribed to women who were identified through a screening program at 11-13 +6 weeks' gestation as being at high risk for developing early-onset preeclampsia. Women who were at low risk for developing preeclampsia did not receive aspirin. The prevalence of PPRoM was compared with an observational cohort. Results: In the observational cohort, there were 3027 women, including 32 (1.1%) cases of PPRoM. The prevalence of PPRoM in the high risk group was 3.1% (4/128) and was statistically significantly higher compared to the low risk group (1.0%) (28/2899). The relative risk was 3.02 (95% CI 1.2-7.7; p = .04). In the interventional cohort, there were 7280 women, with 114 (1.6%) cases of PPRoM. The prevalence of PPRoM in the high risk group who were treated with aspirin was 1.8% (14/766) compared to 1.5% (100/6516) in the low risk group ( p = .54). The prevalence of PPRoM in high risk patients in the observational group (who did not receive aspirin) compared with the high risk patients in the interventional group (who were treated with aspirin) was not statistically significant ( p = .31). Conclusions: PPRoM is significantly associated with a description of high risk for ePET; although, this algorithm is not a good screening tool for predicting PPRoM. Aspirin treatment of women deemed high risk for ePET is safe in the context of PPRoM and there may be some reduction in prevalence of PPRoM in treated high risk women; although, this study was not powered to demonstrate a small reduction in the prevalence of PPRoM. The findings merit further investigation through a larger prospective study with adequate sample size.

Background: Induction of labour (IOL) and caesarean section (CS) rates continue to increase in Australia, New Zealand and globally. There is evidence that CS rates are decreased in the context of medically indicated and elective IOL; therefore, the emerging concept of using IOL as means of preventing CS warrants investigation., Aims: To assess obstetricians' opinions of elective IOL at 39 weeks gestation, its feasibility, generalisability and utility as a means of preventing CS in Australia and New Zealand., Materials and Methods: A de-identified cross-sectional survey was distributed electronically to all Fellows and trainees of The Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG). The survey was voluntary and distributed with the approval of the RANZCOG Continuing Education Committee. The survey addressed opinions relating to rates of and indications for IOL, the perceived validity of those indications and explored the acceptability of using a screening tool to predict women at increased risk of intra-partum CS and tailoring obstetric management to include the option of IOL at 39 weeks gestation., Results: The overall response rate was 34% (492/1423) (including trainees) and the response rate was 53% (394/750) for currently practising obstetricians. The majority (90%) of responders agreed on medical and clinical indications for IOL. There was no consensus on the validity of IOL if a woman were at apparent high risk of intra-partum CS; however, 81% (360/443) of clinicians would be interested in a tool that could predict those women at risk., Conclusions: There is heterogeneity of obstetrician's beliefs on using IOL at 39 weeks as a mechanism to reduce the CS rate., (© 2020 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

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., (© 2021 S. Karger AG, Basel.)

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 (<0.3 MoM and <0.5 MoM) were independently associated with sPTB, low BW, PE, GH, and a composite adverse pregnancy outcome score, with odds ratios between 1.81 and 4.44 on multivariable logistic regression analyses., 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., (© 2021 S. Karger AG, Basel.)

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.

Objective: To evaluate time of diagnosis of 22q11.2 deletion and 22q11.2 duplication as well as trisomies 21, 13, and 18 before and after introduction of a prenatal screening program including combined first-trimester screening (cFTS) for the trisomies in Denmark in 2004., Method: Cross-sectional, population-based register study employing The Danish Cytogenetic Central Register. Proportions of cases diagnosed 1998-2004 and 2005-2017 were compared before 14 +0 and 22 +0 weeks and birth (prenatal cases) or up to 1 or 10 years of age (postnatal cases)., Results: In total, 4562 cases were included. From 1998-2004 to 2005-2017, the proportion of 22q11.2 deletion cases identified prenatally increased from 4.3% (95% CI: 0.9-12.0%) to 27.3% (21.2-34.0%), while for 22q11.2 duplication an increase from 0/6 to 26/87 (prenatal cases/all cases) was observed. Similarly, proportions of trisomies 21, 13, and 18 detected before birth increased. A greater proportion of the studied conditions was identified earlier in pregnancy, but not generally earlier in the postnatal course., Conclusion: Proportions of 22q11.2 deletion and 22q11.2 duplication identified prenatally increased after introduction of a prenatal screening program not aimed specifically to identify these conditions,. A greater proportion of all cases were detected earlier in pregnancy, but not earlier postnatally, following introduction of screening., (© 2020 John Wiley & Sons Ltd.)

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., (© 2021 S. Karger AG, Basel.)

Background and Objective: Hypertensive disorders of pregnancy (HDPs) affect 5%-10% of pregnancies and have been associated with excess maternal cardiovascular disease (CVD) risk. The primary aim of this study was to reliably estimate absolute and relative risks of CVD after HDP., Methods: A retrospective cohort of women who had singleton pregnancies in New South Wales, Australia, between 2002 and 2016 and identified using linked population health administrative databases. The primary exposure was new-onset HDP (pre-eclampsia/eclampsia and gestational hypertension), and the endpoint was hospitalisation or death due to ischaemic or hypertensive heart disease, or stroke. Kaplan-Meier analysis estimated risks among mothers following their first birth, and multivariable time-dependent Cox regression estimated the association between HDP and CVD., Results: Among 528 106 women, 10.3% experienced HDP in their first pregnancy. The 10-year estimated risk of CVD was 2.1 per 1000 if no HDP and 5.5 per 1000 following HDP. Adjusting for demographics, gestational diabetes, small for gestational age and preterm birth, we found that there was an interaction between smoking and HDP, and a larger effect of early-onset (<34 weeks) HDP, compared with late-onset HDP. The HR for women with early-onset HDP who did not smoke was 4.90 (95% CI 3.00 to 7.80) and the HR for those who did smoke was 23.5 (95% CI 13.5 to 40.5), each compared with women without HDP who did not smoke., Conclusion: In this nationally representative Australian cohort, HDP, especially early onset, conferred a clear increase in the risk of CVD, with amplification by smoking. Targeted preventive health, during and after pregnancy, could prevent a substantial burden of CVD among childbearing women., Competing Interests: Competing interests: MW has received consulting fees from Amgen, Inc, and Kyowa Kirin Co, Ltd., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

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 (BP 2 ) 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: BP 2 will provide evidence regarding the feasibility and effectiveness of postpartum LBC interventions and structured clinical follow-up in improving cardiovascular health markers after HDP., (Copyright © 2020 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

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., (Copyright © 2020 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Objective: To report on the findings of a survey of sonographer skill-teaching practices in Australia using the SonoSTePs tool., Method: A cross-sectional survey of all qualified sonographers registered with the Australian Sonographer Accreditation Registry., Results: The 528 responses showed the use of a two-step skill-teaching approach to teach scanning skills and the incorporation of additional instructional practices to support a learner's initial acquisition of scanning skills, which include: providing coaching and guidance as the skill is practised; performing physical guidance; providing immediate error correction; and providing end-task feedback. Based on our findings, sonographer skill-teaching practices fall short of best pedagogical approaches., Conclusion: There is a pressing need to identify the optimal pedagogical approaches to teach complex psychomotor scanning skills. Research is required to ensure that the scanning skills are taught efficiently and that the pedagogical approaches to teach scanning skills foster the learner's long-term retention of the skill. There is also an accompanying need for sonographers involved in teaching scanning skills to have knowledge of the motor-learning theories and principles related to teaching a complex psychomotor skill., Competing Interests: No disclosure., (© 2020 Australasian Society for Ultrasound in Medicine.)

Objective: To report the qualitative findings of the inaugural survey of sonographer skill-teaching practices in Australia using the SonoSTePs tool., Method: A national cross-sectional survey of all qualified sonographers registered with the Australian Sonographer Accreditation Registry. A mix of quantitative and qualitative data was collected. This paper reports on a content analysis of the qualitative data relating to factors that impact on teaching., Results: A total of 528 respondents provided a range of qualitative data in five extended text questions. Five key themes emerged from the analysis: limited protected teaching time; perceived skill complexity; learner skill level and credentials; avoiding overwhelming the learner; and patient well-being and their willingness to be scanned. Novel teaching interactions between the educator and the student sonographer were identified. Information was provided to learners at four time-points across the continuum of clinical practice performance. The type, quantity and purpose of the information provided by the educator to the learner differed at each of these four time-points and included the following: (i) pre-task clarification, guidance and practice norms; (ii) in-task verbal information and scanning support; (iii) post-task support and information; and (iv) end-task or terminal feedback., Conclusion: This is the first published study which reports the push and pull factors affecting pedagogical approaches to teach and learn complex scanning skills. These results provide a corpus of new knowledge, and the first analysis and review, about the pedagogical findings related to teaching scanning skills for clinical practice. This study provides a basis for further research and practice improvements., Competing Interests: No disclosure., (© 2020 Australasian Society for Ultrasound in Medicine.)

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.)

Cardiovascular disease (CVD) is the leading cause of death and disability in women globally, accounting for 32% of deaths in females. There are several female-specific risk factors for CVD that are under appreciated clinically, insufficiently researched and not given adequate attention in CVD risk prediction. Hypertensive and metabolic disorders of pregnancy are independent risk factors for the development of premature CVD. They confer more than double the risk of CVD in exposed women, but are not included in any current, multivariable CVD risk prediction models. Failure to recognise this risk leads to a lost opportunity to identify at risk women, institute primary preventive strategies, and potentially improve their health trajectory. This also translates into a missed opportunity to educate women and their families about their CVD risks, and to a lack of awareness and prioritisation of CVD within the broader community. Improving CVD outcomes for women globally also requires attention to research methodology and analysis. Researchers should be encouraged to include a thorough pregnancy history in prospective CVD datasets and to power their studies to report on gender disaggregated CVD outcomes. Particular attention should be given to the inclusion of young women of child-bearing age in CVD intervention trials. Ultimately, women should be offered CVD assessment using gender specific risk prediction models that are validated across broad ethic and socioeconomic groups. These prediction models should account for female specific risk factors and their complex interactions with traditional risk factors. This will pave the way for a gender-specific approach to CVD diagnosis, investigation and management., (Copyright © 2019 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Preterm birth, defined as a delivery before 37 weeks' gestation, continues to affect 8-15% of all pregnancies and is associated with significant neonatal morbidity and mortality. Effective prediction of timing of delivery among women identified to be at significant risk for preterm birth would allow proper implementation of prophylactic therapeutic interventions. This paper aims first to develop a model that acts as a decision support system for pregnant women at high risk of delivering prematurely before having cervical cerclage. The model will predict whether the pregnancy will continue beyond 26 weeks' gestation and the potential value of adding the cerclage in prolonging the pregnancy. The second aim is to develop a model that predicts the timing of spontaneous delivery in this high risk cohort after cerclage. The model will help treating physicians to define the chronology of management in relation to the risk of preterm birth, reducing the neonatal complications associated with it. Data from 274 pregnancies managed with cervical cerclage were included. 29 of the procedures involved multiple pregnancies. To build the first model, a data balancing technique called SMOTE was applied to overcome the problem of highly imbalanced class distribution in the dataset. After that, four classification models, namely Decision Tree, Random Forest, K-Nearest Neighbors (K-NN), and Neural Network (NN) were used to build the prediction model. The results showed that Random Forest classifier gave the best results in terms of G-mean and sensitivity with values of 0.96 and 1.00, respectively. These results were achieved at an oversampling ratio of 200%. For the second prediction model, five classification models were used to predict the time of spontaneous delivery; linear regression, Gaussian process, Random Forest, K-star, and LWL classifier. The Random Forest classifier performed best, with 0.752 correlation value. In conclusion, computational models can be developed to predict the need for cerclage and the gestation of delivery after this procedure. These models have moderate/high sensitivity for clinical application., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

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., (© 2020 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)

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., (Copyright © The Author(s) 2020.)

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., (© 2019 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

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., (© 2020 S. Karger AG, Basel.)

Background: Preterm prelabour rupture of membranes (PPRoM) is commonly associated with preterm delivery and affects up to 3% of all pregnancies. It is associated with high rates of morbidity and mortality for the mother and the newborn., Objectives: To identify risk factors for PPRoM and develop a model for first-trimester prediction of risk of PPRoM., Methods: A retrospective analysis of a series of women who had first-trimester (11-13+6 weeks) screening for aneuploidy and pre-eclampsia and delivered in the same institution was performed. Univariate and multivariate logistic regression analyses were used to identify maternal and pregnancy factors and then develop a clinical prediction model for PPRoM., Results: 10,280 women were screened between April 2010 and October 2016. 144 (1.4%) had PPRoM. Maternal factors predictive of PPRoM included nulliparity (parous women, OR 0.53; 95% CI 0.4-0.8), pre-existing diabetes mellitus (DM) (Type 1 DM, OR 6.7; 95% CI 2.3-19.4, Type 2 DM, OR 5.3; 95% CI 1.6-18.3), maternal age group (p = 0.004), and BMI category (p = 0.012). Uterine artery pulsatility index (UAPI) and biochemical parameters (PAPP-A, free βHCG) did not reach statistical significance. The predictive model had moderate efficacy with an area under the ROC curve of 0.67., Conclusions: Several maternal characteristics collected during first-trimester screening predict PPRoM. Biomarkers currently measured during first-trimester screening (PAPP-A, βHCG, and UAPI) do not predict PPRoM. Whilst a predictive model can be generated with information currently collected at 11-13+6 weeks, this has only modest screening performance. First-trimester screening provides a structured framework where other predictors could improve model performance, and future studies should focus on the addition of other risk factors and biomarkers that may improve screening efficacy., (© 2020 S. Karger AG, Basel.)