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This article discusses the identification of partial hydatidiform mole (PHM) using non-invasive single-cell sequencing of fetal circulating extravillous trophoblasts (cEVTs) isolated from maternal blood. PHM is a condition that is typically triploid and associated with risks such as pre-eclampsia and gestational trophoblastic disease. The article presents a case study where a novel cell-based non-invasive prenatal testing (CB-NIPT) platform was used to accurately diagnose PHM. The study found that the number of cEVTs recovered from maternal blood was significantly higher in the PHM case compared to healthy controls, suggesting the potential for cEVTs as an early marker for associated hypertensive disorders and pre-eclampsia. Early diagnosis of PHM is crucial for optimal management and this study demonstrates the potential of CB-NIPT technology for early blood-based detection of PHM. [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 [ABSTRACT FROM AUTHOR]

Objective: To evaluate three birth-weight (BW) standards (Australian population-based, Fenton and INTERGROWTH-21st ) and three estimated-fetal-weight (EFW) standards (Hadlock, INTERGROWTH-21st 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-21st BW and EFW standards classified half the number of SGA (< 10th centile) babies (3-4% vs 7-11%) and twice the number of LGA (> 90th 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 (< 3rd centile) babies, the RR of perinatal death using the two INTERGROWTH-21st standards was up to 1.5-fold higher than those of the other standards (including the WHO-EFW and Hadlock-EFW), while the INTERGROWTH-21st -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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The current model was developed in a mixed population of 35 948 women with singleton pregnancy attending a routine visit at one of two UK hospitals, and a combination of maternal factors, uterine artery PI, MAP and PlGF can predict 90% of cases of early-onset pre-eclampsia, 75% of preterm pre-eclampsia and 41% of term pre-eclampsia, at a screen-positive rate of 10%[[31], [35]]. The PROGNOSIS study[19], a prospective observational study conducted in 14 countries, was designed to investigate the value of using the sFlt-1/PlGF ratio to predict the absence of pre-eclampsia within 1 week and to predict the presence of pre-eclampsia within 4 weeks in women with clinical suspicion of pre-eclampsia. PlGF-based testing to help diagnose suspected pre-eclampsia (Triage PlGF test, Elecsys immunoassay sFlt-1/PlGF ratio, DELFIA Xpress PlGF 1-2-3 test, and BRAHMS sFlt-1 Kryptor/BRAHMS PlGF plus Kryptor PE ratio). [Extracted from the article]

Objective: To assess the effect of maternal sildenafil therapy on fetal growth in pregnancies with early-onset fetal growth restriction.Design: A randomised placebo-controlled trial.Setting: Thirteen maternal-fetal medicine units across New Zealand and Australia.Population: Women with singleton pregnancies affected by fetal growth restriction at 22+0 to 29+6 weeks.Methods: Women were randomised to oral administration of 25 mg sildenafil citrate or visually matching placebo three times daily until 32+0 weeks, birth or fetal death (whichever occurred first).Main Outcome Measures: The primary outcome was the proportion of pregnancies with an increase in fetal growth velocity. Secondary outcomes included live birth, survival to hospital discharge free of major neonatal morbidity and pre-eclampsia.Results: Sildenafil did not affect the proportion of pregnancies with an increase in fetal growth velocity; 32/61 (52.5%) sildenafil-treated, 39/57 (68.4%) placebo-treated [adjusted odds ratio (OR) 0.49, 95% CI 0.23-1.05] and had no effect on abdominal circumference Z-scores (P = 0.61). Sildenafil use was associated with a lower mean uterine artery pulsatility index after 48 hours of treatment (1.56 versus 1.81; P = 0.02). The live birth rate was 56/63 (88.9%) for sildenafil-treated and 47/59 (79.7%) for placebo-treated (adjusted OR 2.50, 95% CI 0.80-7.79); survival to hospital discharge free of major neonatal morbidity was 42/63 (66.7%) for sildenafil-treated and 33/59 (55.9%) for placebo-treated (adjusted OR 1.93, 95% CI 0.84-4.45); and new-onset pre-eclampsia was 9/51 (17.7%) for sildenafil-treated and 14/55 (25.5%) for placebo-treated (OR 0.67, 95% CI 0.26-1.75).Conclusions: Maternal sildenafil use had no effect on fetal growth velocity. Prospectively planned meta-analyses will determine whether sildenafil exerts other effects on maternal and fetal/neonatal wellbeing.Tweetable Abstract: Maternal sildenafil use has no beneficial effect on growth in early-onset FGR, but also no evidence of harm. [ABSTRACT FROM AUTHOR]

Objective: To assess the quality of mean uterine artery (UtA) pulsatility index (PI) measurement in a first-trimester pre-eclampsia screening program.Methods: Consecutive women with a singleton pregnancy attending first-trimester screening for fetal chromosomal abnormalities also had combined screening for pre-eclampsia based on the Fetal Medicine Foundation (FMF) algorithm, at a large practice in Sydney, Australia, from May 2014 to February 2017. Distributions of mean UtA-PI multiples of the median (MoM) on a logarithmic scale were plotted in relation to the normal median with 95% CI for each operator and for each month. Central tendency and dispersion and cumulative sum charts were produced. Mean UtA-PI MoM values between 0.95 and 1.05 were considered ideal and those between 0.90 and 1.10 were considered acceptable. The screen-positive rates for preterm pre-eclampsia in different groups of sonographers according to their mean log10 UtA-PI MoM were calculated and compared using the chi-square test.Results: A total of 21 010 women attended for first-trimester ultrasound and had screening for pre-eclampsia. The overall median UtA-PI MoM was 1.042 (interquartile range (IQR), 0.85-1.26). Of 46 sonographers, 42 (91.3%) performed more than 50 examinations and, of those, 41 (97.6%) measured UtA-PI within the acceptable range. Sonographers measuring UtA-PI MoM on average below 0.95 and those measuring it above 1.05 had, respectively, lower and higher screen-positive rates when compared with those with measurements within the 0.95-1.05 UtA-PI MoM interval (7.2% and 13.2% vs 11.2%, respectively, P < 0.001).Conclusion: UtA Doppler is measured well among trained operators when following an established protocol. While slight variations are expected, systematic error in this measurement impacts on the screen-positive rate. Therefore, a quality control process should be in place and retraining of staff may be required. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: Pre-eclampsia (PE) remains a leading cause of maternal and fetal morbidity and mortality. A first-trimester screening algorithm predicting the risk of early-onset PE has been developed and validated. Early prediction coupled with initiation of aspirin at 11-13 weeks in women identified as high risk is effective at reducing the prevalence of early-onset PE. The aim of this study was to evaluate the cost-effectiveness of this first-trimester screening program coupled with early use of low-dose aspirin in women at high risk of developing early-onset PE, in comparison to current practice in Canada.Methods: A decision analysis was performed based on a theoretical population of 387 516 live births in Canada in 1 year. The clinical and financial impact of early preventative screening using the Fetal Medicine Foundation algorithm for prediction of early-onset PE coupled with early (< 16 weeks) use of low-dose aspirin in those at high risk was simulated and compared with current practice using decision-tree analysis. The probabilities at each decision point and associated costs of utilized resources were calculated based on published literature and public databases.Results: Of the theoretical 387 516 births per year, the estimated prevalence of early PE based on first-trimester screening and aspirin use was 705 vs 1801 cases based on the current practice. This was associated with an estimated total cost of C$9.52 million with the first-trimester screening program compared with C$23.91 million with current practice for the diagnosis and management of women with early-onset PE. This equals an annual cost saving to the Canadian healthcare system of approximately C$14.39 million.Conclusions: The implementation of a first-trimester screening program for PE and early intervention with aspirin in women identified as high risk for early PE has the potential to prevent a significant number of early-onset PE cases with a substantial associated cost saving to the healthcare system in Canada. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

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Objective: To evaluate the performance of high-resolution chromosomal microarray (CMA) as the standard diagnostic approach for genomic imbalances in pregnancies with increased risk based on combined first-trimester screening (cFTS).Methods: This was a retrospective study of genomic findings in a cohort of 575 consecutive pregnancies undergoing invasive testing because of a cFTS risk ≥ 1:300 on a publicly funded population-based screening program in the Central and Northern Regions of Denmark, between September 2015 and September 2016. Women with fetal nuchal translucency thickness ≥ 3.5 mm or opting for non-invasive prenatal testing (NIPT) were excluded. Comparative genomic hybridization was performed using a 180-K oligonucleotide array on DNA extracted directly from chorionic villus/amniocentesis samples. Genomic outcomes were reported in relation to cFTS findings.Results: Of the 575 pregnancies that underwent invasive testing, CMA detected 22 (3.8% (95% CI, 2.5-5.7%)) cases of trisomies 21, 18 and 13, 14 (2.4% (95% CI, 1.4-4.0%)) cases of other types of aneuploidy and 15 (2.6% (95% CI, 1.5-4.3%)) cases with a pathogenic or probably pathogenic copy number variant (CNV). Of the 15 CNVs, three were > 10 Mb and would probably have been detected by chromosomal analysis, but the other 12 would most probably not have been detected using conventional cytogenetic techniques; therefore, the overall detection rate of CMA (8.9% (95% CI, 6.8-11.5%)) was significantly higher than that estimated for conventional cytogenetic analysis (6.8% (95% CI, 5.0-9.1%)) (P = 0.0049). Reducing the cFTS risk threshold for invasive diagnostic testing to 1 in 100 or 1 in 50 would have led, respectively, to 60% or 100% of the pathogenic CNVs being missed.Conclusions: CMA is a valuable diagnostic technique that can identify an increased number of genomic aberrations in pregnancies at increased risk on cFTS. Limiting diagnostic testing to pregnancies with a risk above 1 in 100 or 1 in 50, as proposed in contingent NIPT/invasive testing models, would lead to a significant proportion of pathogenic CNVs being missed at first-trimester screening. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

An editorial is presented of the important aspects on the clinical implementation of early screening for and prevention of pre-eclampsia (PE). It explores the impact of PE on perinatal and maternal health and the early-onset of PE leading to preterm delivery. The evidence on the effectiveness of aspirin in reducing the risk of preterm PE by more than 60% and the risk of early-onset PE by more than 80% when given to high-risk women is explored.

Objective: Inclusion of the three vessels and trachea view in the routine assessment of the fetal heart at the 18-20-week morphology scan improves recognition of a right-sided aortic arch (RAA). We report our experience of RAA diagnosed in an unselected population of pregnant women attending for a routine morphology scan.Methods: The obstetric imaging databases of two ultrasound centers were reviewed retrospectively to identify all routine fetal morphology scans performed at 18-22 weeks' gestation between January 2011 and December 2014. A review of postnatal charts was conducted to ascertain findings at birth, neonatal complications and the anatomical findings at any neonatal echocardiographic or surgical procedure. Parents of older infants were contacted by phone to assess their wellbeing and identify any respiratory or feeding difficulties.Results: In the 48-month study period, 43 083 routine anomaly scans were performed. Twenty-three cases of isolated RAA were identified, a prevalence of 0.05%. Nineteen (83%) cases of isolated RAA had a left-sided arterial duct and four (17%) had a right-sided duct. Postnatal follow-up data were obtained in all cases. The prevalence of a symptomatic vascular ring due to a double aortic arch was 13% (3/23). One (4%) case was diagnosed with DiGeorge syndrome.Conclusions: RAA can be identified easily on a routine fetal anomaly scan, however the prevalence of RAA is low in an unselected population. Antenatally diagnosed cases should be referred for detailed fetal echocardiography and the patient should be made aware of the association with DiGeorge syndrome and the symptoms associated with a vascular ring. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: To determine the acute effects of corticosteroids on the cardiovascular system in growth-restricted fetuses.Methods: This was a prospective cohort study conducted at a tertiary hospital between January 2011 and October 2013. Fetal cardiovascular function in fetuses with intrauterine growth restriction (IUGR) was assessed immediately before and 24 h after the first dose of betamethasone, administered in routine management of IUGR. Fetal arterial and venous Dopplers were assessed. Fetal cardiac function was evaluated by tissue Doppler echocardiography, with the assessment of both left and right ventricular function by calculating myocardial performance index (MPI') and E':A' ratios. Values were compared before and after exposure.Results: Seventeen patients were included at a mean gestational age of 34 + 1 (range, 29 + 1 to 37 + 4) weeks. Fifteen fetuses were below the 5(th) percentile and two were below the 10(th) percentile for estimated fetal weight and abdominal circumference and all had no interval growth during a 2-week period. There was a decrease in right MPI' (from 0.56 to 0.47; P = 0.007) after corticosteroid exposure but no change in left MPI' (from 0.49 to 0.48). Right MPI' was higher than left MPI' before exposure (0.56 vs 0.49, respectively; P = 0.001), but not after exposure (P = 0.55). There was no change in left or right ventricular E':A' ratios and no difference was detected in umbilical artery, middle cerebral artery or ductus venosus pulsatility index following administration of corticosteroids.Conclusions: Corticosteroids altered right-sided, but not left-sided, tissue Doppler MPI' in IUGR fetuses, with no detectable change in arterial or venous Doppler pulsatility indices. Before exposure, the mean right MPI' was higher than the left. However, after exposure, there was no difference, suggesting that corticosteroids may reverse the negative effect of IUGR on fetal heart function. Large prospective studies with a larger sample size are needed to confirm this finding. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: To examine the effect of a combination of screening and treatment with low-dose aspirin on the prevalence of early-onset pre-eclampsia (PE).Methods: This was a retrospective analysis of two consecutive cohorts of women screened for early PE. The first cohort was observed to determine whether algorithms developed to screen for PE at 11 to 13 + 6 weeks' gestation could be applied to our population. High-risk women in the second cohort were advised on their risk and offered aspirin (150 mg at night), with treatment starting immediately after screening. The prevalence of early PE and the proportion of women with PE delivering at 34-37 weeks' gestation were compared between the cohorts.Results: In the observational and interventional cohorts, 3066 and 2717 women, respectively, were screened. There were 12 (0.4%) cases of early PE in the observational cohort and one (0.04%) in the interventional cohort (P < 0.01). Among all women with PE delivering before 37 weeks, 25 (0.83%) were in the observational cohort and 10 (0.37%) in the interventional cohort (P = 0.03).Conclusions: A strategy of first-trimester screening for early PE coupled with prescription of aspirin to the high-risk group appears to be effective in reducing the prevalence of early PE. [ABSTRACT FROM AUTHOR]

To assess the performance of first trimester combined screening for preterm pre-eclampsia (PE) in Australia. Conclusions First trimester combined PE screening performed well in a large Australian population, and future studies should account for the effect of treatment. VP37.10: Performance of routine first trimester combined screening for preterm pre-eclampsia after multicentre clinical implementation in Australia. [Extracted from the article]

To assess pregnancy outcomes following first trimester combined screening for preterm pre-eclampsia (PE). OC07.06: Pregnancy outcomes following multicentre clinical implementation of routine first trimester screening for preterm pre-eclampsia in Australia Conclusions First trimester screening for PE identified a group at high risk of adverse outcomes who could benefit from aspirin prophylaxis and low-risk women who may be suitable for less intensive antenatal care. [Extracted from the article]

Concordance between reported fetal-sex with cfDNA and genetic testing results were determined in participants who received low-risk cfDNA results. To describe the performance of cfDNA screening for the sex chromosomes in an unselected obstetrical population. [Extracted from the article]

SMART participants were excluded from this analysis if pregnancy outcome was unknown, fetal aneuploidy or major anomaly was identified, or the pregnancy was interrupted. OP09.05: Prediction of pre-eclampsia using machine learning The main aim was to develop a method to predict pre-eclampsia using novel machine learning tools. [Extracted from the article]

An abstract of the article "Comparison of microbial contamination of transabdominal versus transvaginal transducers" by S. C. Westerway is presented.

An abstract of the article "Does low dose aspirin effect mean uterine artery Doppler pulsatility index in women deemed high risk for early pre-eclampsia?" by F. Leduc and colleagues is presented.

Objectives To assess the effect of audit and feedback on the performance of first-trimester uterine artery pulsatility index ( UtA-PI) measurement, to determine whether operator experience affects performance and whether an operator's measurement profile affects the screen-positive rate for early-onset pre-eclampsia ( PE). Methods This was a prospective cohort study in which UtA-PI measurements were collected between 11 to 13 + 6 weeks' gestation by 12 operators and were entered into individualized calculators to convert them to multiples of a locally-derived median ( MoM). Individual sonographer cumulative sum ( CUSUM) and target charts were generated to assess central tendency and dispersion to identify systematic measurement errors and deviation from expected measurement performance. Six of the operators received regular feedback whilst the remaining six received no feedback. Each group consisted of four experienced operators and two relatively inexperienced operators. The average MoM for each operator was compared with their respective screen-positive rates for early-onset PE. Results The group that received feedback performed better than that which received none, with results more closely matching the expected measurement distribution. UtA-PI measurements were comparable between the experienced and inexperienced sonographers (mean log10 lowest PI MoM, -0.0089 vs 0.0124, respectively); however the inexperienced sonographers had a higher overall screen-positive rate for early-onset PE (10.0% vs 2.7%, respectively). There was a significant positive correlation between the mean MoM for each operator and the screen-positive rate ( r = 0.63). Conclusions CUSUM and target graphs are an effective method of audit for first-trimester UtA-PI measurement. Feedback to operators resulted in improved measurement performance, which will ultimately result in improved screening accuracy for PE. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

ABSTRACT Objectives Targeted non-invasive prenatal testing ( NIPT) tests for trisomies 21, 18 and 13 and sex chromosome aneuploidies and could be an alternative to traditional karyotyping. The aim of this study was to determine the risk of missing other abnormal karyotypes of probable phenotypic significance by NIPT. Methods This was a retrospective population-based analysis of all singleton pregnancies booked for combined first-trimester screening ( cFTS) in Denmark over a 4-year period. Data concerning maternal demographics, cFTS and prenatal or postnatal karyotypes were collected from the Danish Fetal Medicine database. Karyotypes were classified according to whether the chromosomal anomaly would have been detected by NIPT and whether it was likely to affect phenotype. Results cFTS was completed in 193 638 pregnancies. 10 205 (5.3%) had cytogenetic or molecular analysis performed. Of these, 1122 (11.0%) had an abnormal karyotype, of which 262 (23.4%) would have been missed by NIPT, but would probably have been clinically significant. The prevalence of such 'atypical abnormal karyotypes' was increased in women above 45 years of age, in pregnancies with increased nuchal translucency ( NT) thickness (≥ 3.5 mm), with abnormal levels of free β-human chorionic gonadotropin (< 0.2 or ≥ 5.0 multiples of the median ( MoM)) or pregnancy-associated plasma protein-A < 0.2 MoM. One or more of these factors was present in 3% of women, and the prevalence of atypical abnormal karyotypes in this high-risk cohort was 1.6%. Conclusions A significant proportion of karyotypic abnormalities will be missed by targeted NIPT. Women of advanced maternal age, or with increased fetal NT or abnormal biochemistry, have a higher risk of having a fetus affected by an atypical abnormal karyotype and need to be counseled accordingly when considering NIPT. Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd [ABSTRACT FROM AUTHOR]

Objective Fetal nuchal translucency (NT) is assessed by ultrasonography as a screening tool for aneuploidy at 11 to 13 + 6 weeks' gestation. Fetuses with increased NT but apparently normal karyotype are still at higher risk of structural abnormality and a range of genetic syndromes, which may be related to major and submicroscopic chromosomal abnormalities. The aim of this study was to report the prevalence of submicroscopic chromosomal abnormalities in a cohort of apparently euploid fetuses that presented with increased NT. Methods DNA was extracted from stored chorionic villus samples from fetuses found to have increased NT (> 3.5 mm) during first-trimester screening. These samples were examined by microarray-based comparative genomic hybridization (aCGH) using a 44K oligonucleotide array specifically constructed for prenatal screening. Variations in copy number (CNVs) were reported after excluding known non-pathogenic variants and after validation with multiplex ligation-dependent probe amplification (MLPA) or real-time quantitative polymerase chain reaction (qPCR). The prevalence of pathogenic CNVs is reported and the association with NT and other ultrasound findings described. Results CNVs were reported in 6/48 (12.5%) cases by aCGH and the microdeletions or microduplications ranged from 1.1 to 7.9 Mb. Five of these were validated by MLPA/real-time qPCR and four (8.3%) were considered to be pathogenic and clinically significant. The incidence of pathogenic CNVs was 20.0% (2/10) among those cases with other sonographic anomalies and 5.3% (2/38) among those without. Conclusion aCGH allows detection of submicroscopic chromosomal abnormalities, the prevalence of which may be increased in fetuses with NT > 3.5 mm and an apparently normal karyotype. Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Introduction: Standardization of first-trimester nuchal translucency (NT) image acquisition is crucial to the success of screening for Down syndrome. Rigorous audit of operator performance and constructive feedback from assessors maintain standards. This process relies on good inter-rater agreement on image assessment. We describe the Australian approach to NT image assessment and evaluate the impact of a targeted intervention on inter-rater agreement. Methods: Between 2002 and 2008 a group of experienced practitioners met nine times to compare their assessment of a series of NT images. Each assessor had previously scored the images according to a system described in 2002. Inter-rater agreement was evaluated before and after an intervention where the assessors were required to refer to a detailed resource manual designed to reduce the subjectivity inherent in image assessment. Results: There was a statistical improvement in inter-rater agreement for all elements of image assessment (original scores and individual component scores) after the intervention, apart from horizontal fetal position. However, even after the intervention, inter-rater agreement levels generally remained moderate (kappa range: 0.14-0.58). Conclusions: This study has shown that provision of detailed resource documentation to experienced assessors can significantly improve inter-rater agreement in all facets of NT image assessment. It also highlights areas of image assessment that require critical review. It is recommended that all audit bodies regularly review their inter-rater agreement to ensure consistent feedback to operators who submit images for expert peer review. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The article presents a study on the development of image scoring methodology for reliable evaluation of practitioners on nasal bone imaging. It discloses that 20 images of nasal bone for quality assurance audit were submitted by 20 sonographers and that its criteria were statistically compared by three raters from The Fetal Medicine Foundation. It reveals that clear definition of assessment criteria and qualitative scoring method enhance the reliability of peer review for nasal bone imaging.

Seven cases of 45,X were confirmed in the cohort including 4 with mosaicism, for a prevalence of 1:2614. cfDNA identified 6/7 cases (sensitivity=85.7%). cfDNA results reported high risk for 45,X in 24 cases; 6 of these were confirmed (PPV=25.0%). CfDNA screening for 45,X can be complicated by mosaicism and the diagnosis may be delayed due to variable and late onset of manifestations. We aimed to define the prevalence and screening performance for 45,X using single nucleotide polymorphism (SNP) - based cfDNA screening for aneuploidy and 22q11.2DS, in a large prospective registry study with genetic confirmation (SMART registry study). [Extracted from the article]

Because diagnostic test results are expected to affect perinatal management, HR22q pregnancies were stratified by use of invasive testing. The goal of the study was to determine whether results of SNP-based cfDNA screening for 22q11.2DS affects prenatal or neonatal management. HR22q pregnancies with normal prenatal diagnosis results had significantly fewer Caesarean sections and had fewer postnatal evaluations. [Extracted from the article]

Objectives The aims of this study were to investigate if (i) urinary concentrations of activin A and inhibin A are altered in pre-eclampsia (PE) and (ii) to study the relationship between uterine vein and peripheral vein concentrations of these hormones in PE patients. Design and method In a retrospective study, maternal peripheral vein and uterine vein serum and maternal urine samples collected at the time of delivery were analysed. There were three groups of patients; (i) group 1: term normal pregnancies ( n = 19) (ii) group 2: patients who developed PE ≤ 37 weeks ( n = 17) and (iii) group 3: patients who developed PE 37–40 weeks ( n = 8). Serum and urinary activin A, follistatin, inhibin A and pro alpha C and urinary creatinine levels were measured using enzyme immunoassays in the laboratory. Results Normal pregnant urine samples had very low levels of activin A and inhibin A. Both groups 2 and 3 PE patients had significantly higher levels of inhibin A ( P < 0·001) and activin A ( P < 0·001) compared to the controls. Pro-alpha C was not altered and follistatin was below the detection limit of the assay in the urine. Maternal peripheral serum activin A and inhibin A were significantly higher in groups 2 ( P < 0·001) and 3 ( P < 0·05) patients compared to the controls. Pro-alpha C-containing inhibins were higher in group 2 patients ( P < 0·05) compared to the controls in the peripheral circulation. Uterine vein serum activin A and inhibin A levels were also significantly higher in groups 2 ( P < 0·001) and 3 ( P < 0·05) patients compared to the controls. There was a highly significant positive correlation between peripheral and uterine vein serum concentrations of activin A, follistatin, inhibin A and pro alpha C, suggesting the same source for these proteins in PE. Conclusion Urinary activin A and inhibin A are raised in groups 2 and 3 PE patients. The magnitude of rise (> 25-fold) suggests these proteins may rise in patients before the onset of the clinical symptoms of PE. Uterine vein levels of these proteins are also raised in PE. [ABSTRACT FROM AUTHOR]

Ten carriers of haemophilia referred for prenatal diagnosis were offered first trimester non-invasive fetal gender determination by ultrasound and analysis of free fetal DNA (ffDNA) in maternal plasma in an attempt to reduce the need for an invasive diagnostic procedure in female pregnancies. Although repeat testing was required in three cases, fetal gender was determined correctly in all cases (four females, six males) at a median gestation of 12+3 (11+2 to 14+1) using both methods. In all cases of a female fetus, the mothers opted not to have invasive testing. Both methods provide a reliable option of avoiding invasive testing in female pregnancies. [ABSTRACT FROM AUTHOR]

Objective To investigate the procedure-related complications of rapid amniodrainage in the treatment of polyhydramnios. Methods We followed prospectively all patients with polyhydramnios treated with rapid amniodrainage under continuous ultrasound guidance using a vacuum wound- drainage system from 1995 to 2002 in the fetal medicine unit of a university teaching hospital. We recorded: maternal age, type of pregnancy (singleton/twin), cause of polyhydramnios, gestational age at amniocentesis, volume of amniotic fluid drained, duration of the procedure, other intrauterine procedures in addition to the amniodrainage, and procedure-related complications including placental abruption, premature rupture of membranes (PROM), chorioamnionitis, fetal bradycardia and preterm delivery within 48 h of amniodrainage. Results Seventy-four consecutive women had 134 rapid amniodrainage procedures during the study period. Four procedures were excluded because the women were already in labor at the time of amniodrainage and they delivered within 48 h of the procedure. The final database therefore consisted of 70 patients with 130 procedures. Sixty-two percent (80/130) of the procedures were performed for the treatment of twin-twin transfusion syndrome (TTTS). There were altogether four procedure- related complications (3.1%; 95% CI, 1.0-8.0%). Three of them occurred in the TTTS group (3/80 procedures, 3.8%; 95% CI, 1.0-11.0%): one case each of placental abruption, PROM and fetal bradycardia. One PROM occurred in the non-TYTS group (1/50 procedures, 2.0%; 95% CI, 0-11.0%). In both cases of PROM the women presented in labor. Conclusions Rapid amniodrainage using a vacuum wound-drainage system is safe and efficient to treat severe polyhydramnios, with a 3.1% complication rate. [ABSTRACT FROM AUTHOR]

Abstract Objective To assess differences in adipose deposition in fetuses from normal pregnancies and women with diabetes. Research design and methods The study group consisted of 15 well controlled insulin-dependent women with diabetes and 16 controls with a normal glucose. Ultrasound measurements were taken of subcuticular tissue thickness at the abdominal and suprascapular level at 31 and 37 weeks gestation. Triceps and subscapular skinfold thickness were also measured at birth. Results Gestational age at delivery and birthweights were not significantly different. At 31 weeks, fasting glucose levels were 5.0 ± 1 mmol/l for diabetic vs. 3.3 ± 0.3 mmol/l for controls (P < 0.01), post-prandial 5.6 ± 0.4 vs. 5.1 ± 0.3 mmol/l (P < 0.01). At 37 weeks, they were 4.6 ± 0.2 mmol/l vs. 3.8 ± 1.1 mmol/l (P < 0.01) and 6.0 ± 0.6 mmol/l vs. 5.3 ± 0.3 mmol/l (P < 0.01). Abdominal and suprascapular subcuticular thickness were 4.4 ± 0.1 mm vs. 3.7 ± 0.1 mm (P < 0.05) and 4.3 ± 0.2 mm vs. 3.5 ± 0.2 mm (P < 0.05) at 31; 5.6 ± 0.2 mm vs. 4.8 ± 0.1 mm (P < 0.05) and 5.4 ± 0.2 mm vs. 4.4 ± 0.1 mm (P < 0.05) at 37 weeks. At birth, triceps and suprascapular skinfolds were 4.7 ± 0.1 mm vs. 4.1 ± 0.1 mm (P < 0.05) and 4.7 ± 0.2 mm vs. 3.8 ± 0.1 mm (P < 0.01). Conclusion Adipose tissue disposition is increased in fetuses of women with well-controlled diabetes. This may be a reflection of higher maternal glucose levels in these women and may explain why even well-controlled diabetic pregnancies are at risk of macrosomia. [ABSTRACT FROM AUTHOR]

Fetal heart rate, umbilical artery pulsatility index, end-diastolicflow, nuchal translucency thickness and placental thickness were recorded in 250 women with a viable singleton pregnancy undergoing chorionic villous sampling for fetal karyotyping at 11–14 weeks of gestation. The fetal karyotype was normal in 210 cases and abnormal in 40, including 21 with trisomy 21, 13 with trisomy 18, three with triploidy, two with monosomy X and one with trisomy 13. A total of 52 fetuses with a normal karyotype had a nuchal translucency ≥3 mm and were considered separately. There was a stable and significant increase in the mean fetal heart rate in trisomy 21 pregnancies compared to controls. No significant difference was found for the other variables between the groups. In chromosomally normal fetuses with an increased nuchal thickness, the development of fetal heart rate and compliance of the umbilico-placental circulation were within the normal ranges. Some fetuses with trisomy 18 or triploidy had an increased resistance to blood flow in the umbilical artery, which was probably due to abnormal placental development. [ABSTRACT FROM PUBLISHER]