F. da Silva Costa

Clinical implementation of cell‐free DNA‐based aneuploidy screening: perspectives from a national audit

In late 2011, a prenatal screening test for fetal chromosomal abnormalities using cell-free DNA in maternal plasma was introduced commercially in the USA. This next-generation sequencing-based method, commonly referred to as non-invasive prenatal testing (NIPT), represented the most accurate form of screening for trisomy 21 to date1. While the NIPT market expanded rapidly in the USA, its clinical implementation in other developed countries varied considerably due to local factors, such as existing care models, insurance coverage and legal restrictions. In late 2012, NIPT became available clinically in Australia, through overseas laboratories, 1 year after it did in the USA. By the end of 2013, there were five providers in the Australian market offering NIPT on a self-funded basis. Australian subspecialists in maternal–fetal medicine and obstetric ultrasound quickly became the major sources of referral for NIPT due to their well-established role in first-trimester screening and prenatal diagnostic procedures. Despite being ‘early adopters’ of technology, Australian sonologists had concerns about NIPT that were common to many countries. Among these were definition of the appropriate indications for use, and the uncertain test-failure rates and turnaround times associated with offshore laboratory processing outside trial conditions. The lack of government regulation and lack of data collection were also key concerns2. At the time, international reports on clinical implementation were either single-center experiences3,4, or multicenter industry-sponsored studies of a single commercial assay5. In response to these issues, a group of Australian obstetric sonologists formed a collaboration to document the collective national experience of NIPT, across a range of practice types and using a variety of NIPT providers.

First‐trimester maternal ophthalmic artery Doppler analysis for prediction of pre‐eclampsia

To determine the performance of a multiparametric test comprising maternal risk factors, uterine artery Doppler and ophthalmic artery Doppler in the first trimester of pregnancy for the prediction of pre‐eclampsia (PE).

OPHTHALMIC ARTERY DOPPLER ANALYSIS: A WINDOW INTO THE CEREBROVASCULATURE OF WOMEN WITH PRE-ECLAMPSIA

The neurological complications of pre-eclampsia, including eclampsia (seizures) and intracerebral haemorrhage, are responsible for much of the maternal morbidity and mortality associated with this condition. Animal models and neuroimaging in humans suggest that pre-eclampsia is associated with a loss of cerebral autoregulation, which consequent hyperperfusion and vasogenic oedema. Treatments given to pre-eclamptic women are aimed at preventing these cerebral sequelae, and include antihypertensive agents (to prevent intracranial haemorrhage) and magnesium sulphate (for seizure prophylaxis). It is likely that these agents have a direct effect on the maternal cerebrovasculature, although their precise mechanisms of action remain incompletely understood. Doppler analysis of the maternal ophthalmic artery represents a safe, well-tolerated, reproducible, readily accessible, real-time imaging modality by which cerebrovascular haemodynamic changes can be assessed. Existing research has shown pre-eclampsia to be associated with changes in the Doppler parameters of the ophthalmic artery that are consistent with increased perfusion. This sonographic technique could also be used to determine the cerebrovascular effects of anticonvulsant and antihypertensive therapies in pre-eclampsia. In time, it may prove to be a useful point-of-care tool for the individualisation of risk for neurological events in pre-eclampsia, potentially allowing for more appropriately targeted therapy, and ensuring an adequate cerebrovascular response in those deemed high risk. In so doing, ophthalmic artery Doppler studies may play an important role in ameliorating the potentially devastating short- and long-term cerebral complications of pre-eclampsia.

Congenital heart disease and adverse perinatal outcome in fetuses with confirmed isolated single functioning umbilical artery

Abstract To examine the association between isolated single umbilical artery (SUA) and congenital heart disease/adverse perinatal outcome in an Australian tertiary centre. The study population was comprised of fetuses diagnosed with SUA at the mid-trimester scan between May 2003 and March 2009 during detailed ultrasound examination at The Royal Womens Hospital Melbourne, Australia. Colour Doppler was used to visualise the umbilical arteries adjacent to the fetal bladder and in a section of a free loop of cord. The diagnosis of SUA was confirmed on histopathology examination of the placenta and umbilical cord. Monochorionic twins, fetuses with chromosomal abnormalities or concurrent extracardiac anomalies were excluded from the study. A total of 261 fetuses with SUA were identified in the study period and 146 (59%) cases were isolated; no chromosomal or extracardiac abnormalities were present. Complete data were available in 104/146 pregnancies (71.2%). The mean gestational age at diagnosis was 21 weeks. A cardiac anomaly was detected in 19 of these fetuses (13.0%): six hypoplastic left heart syndromes; three coarctations of the aorta; two tetralogies of Fallot; two hypoplastic right heart syndromes; two pulmonary atresia/stenosis; one absent ductus venosus with cardiomegaly; one left isomerism; one right isomerism and one transposition of the great arteries. Fetal growth restriction was present in 9.8% (10) and preterm delivery before 34 weeks occurred in nine cases (8.7%). Our study has shown that isolated SUA is associated with cardiac anomalies, but is not associated with increased frequency of FGR and preterm delivery before 34 weeks.

Cervical length as a predictor for spontaneous preterm birth in high-risk singleton pregnancy: current knowledge.

†The University of Melbourne, Department of Obstetrics and Gynaecology, The Royal Women’s Hospital, Locked Bag 300, Parkville, Victoria 3052, Australia; ‡Pregnancy Research Centre, Department of Maternal-Fetal Medicine, The Royal Women’s Hospital, Parkville, Victoria, Australia; §Department of Obstetrics, Paulista School of Medicine Federal University of São Paulo, São Paulo, Brazil *Correspondence. (e-mail: Fabricio.Costa@thewomens.org.au)

Implications of failure to achieve a result from prenatal maternal serum cell‐free DNA testing: a historical cohort study

To investigate the pregnancy outcomes in a cohort of women who failed to obtain a result in non‐invasive prenatal testing (NIPT).

OS088. First trimester triple vascular test for pre-eclampsia prediction.

INTRODUCTION Although PE represents a major cause of maternal and fetal morbidity and mortality, the vascular mechanisms underlying this disorder have not been clearly identified. During the past three decades, while numerous clinical, biophysical, and biochemical screening tests have been proposed for the early detection of preeclampsia, maternal circulation changes during early pregnancy have yet to be fully evaluated for their contribution to PE prediction. OBJECTIVES The aim of this study was to examine a combination of maternal risk factors, mean arterial blood pressure, uterine artery Doppler, brachial artery flow-mediated dilatation (FMD), and ophthalmic artery Doppler for pre-eclampsia prediction during the first trimester of pregnancy. METHODS Prospective study with singleton pregnancies examined at 11-14 weeks of gestation, presenting consecutively for antenatal care in a tertiary Brazilian hospital. The base-cohort population constituted of 487 singleton pregnancies, including 9 case subjects who developed pre-eclampsia (PE) requiring delivery before 34 weeks (early PE) and 22 with late PE, 47 with gestational hypertension, and 409 cases subjects (84%) who were unaffected by PE or gestational hypertension. Maternal history (nulliparity, previous and family history of PE), body mass index (BMI), mean arterial pressure (MAP), uterine artery pulsatility index, brachial artery FMD and ophthalmic artery Doppler were recorded in all of the cases. Univariate and logistic regression analysis was used to derive algorithms for the prediction of hypertensive disorders. RESULTS Uterine artery percentile of mean PI was higher in the PE than in the control group (p<0.01). The mean brachial artery FMD was 7.4%±8.2% in the control group and 7.3%±8.2% in the PE group. Logistic regression analysis determined that FDM was not a predictor of PE (OR=0.99, CI 95% 0.94-1.04; p=0.90) and this test was withdrawn from the predictive model. The average of the first diastolic peak velocity in the ophthalmic artery was higher in the PE group compared with controls (24.56cm/s×21.13cm/s; p<0.01).It was estimated that, with the prediction algorithm for PE, a combination of maternal factors + MAP + uterine artery Doppler or ophthalmic artery Doppler can detect 78% of early-onset PE with 10% false-positive rate. CONCLUSION Maternal ophthalmic artery Doppler in the first trimester of pregnancy is a novel predictive parameter for PE (especially early-onset PE), it has the same detection rate contribution in a multi-parameter predictive model as would be the case uterine artery Doppler was used instead.

Counting ovarian antral follicles by ultrasound: a practical guide

This Consensus Opinion summarizes the main aspects of several techniques for performing ovarian antral follicle count (AFC), proposes a standardized report and provides recommendations for future research. AFC should be performed using a transvaginal ultrasound (US) probe with frequency ≥ 7 MHz. For training, we suggest a minimum of 20–40 supervised examinations. The operator should be able to adjust the machine settings in order to achieve the best contrast between follicular fluid and ovarian stroma. AFC may be evaluated using real‐time two‐dimensional (2D) US, stored 2D‐US cine‐loops and stored three‐dimensional (3D) US datasets. Real‐time 2D‐US has the advantage of permitting additional maneuvers to determine whether an anechoic structure is a follicle, but may require a longer scanning time, particularly when there is a large number of follicles, resulting in more discomfort to the patient. 2D‐US cine‐loops have the advantages of reduced scanning time and the possibility for other observers to perform the count. The 3D‐US technique requires US machines with 3D capability and the operators to receive additional training for acquisition/analysis, but has the same advantages as cine‐loop and also allows application of different imaging techniques, such as volume contrast imaging, inversion mode and semi‐automated techniques such as sonography‐based automated volume calculation. In this Consensus Opinion, we make certain recommendations based on the available evidence. However, there is no strong evidence that any one method is better than another; the operator should choose the best method for counting ovarian follicles based on availability of resources and on their own preference and skill. More studies evaluating how to improve the reliability of AFC should be encouraged. Copyright

PP114. First trimester multi-parameter prediction of pre-eclampsia.

INTRODUCTION Pre-eclampsia (PE), which affects about 3-5% of pregnant women, is the most frequent serious medical complication in pregnancy and a major cause of maternal and perinatal morbidity and mortality. During the past three decades, numerous clinical, biophysical, and biochemical screening tests have been proposed for the early detection of PE. Literature shows large variations in the sensitivity and predictive value of these tests. No single screening test used for PE prediction has gained widespread acceptance into clinical practice. Instead, panels of tests, which combine several clinical measurements, seem to be of more value for increasing the predictive value for PE. OBJECTIVES The aim of this study was to examine a combination of maternal risk factors, mean arterial blood pressure, and uterine artery Doppler for pre-eclampsia prediction during the first trimester of pregnancy. METHODS Prospective study with singleton pregnancies examined at 11-14 weeks of gestation, presenting consecutively for antenatal care in a tertiary Brazilian hospital. The base-cohort population was 487 singleton pregnancies, including nine case subjects who developed PE requiring delivery before 34 weeks (early PE) and 22 with late PE, 47 with gestational hypertension, and 409 cases subjects (84%) who were unaffected by PE or gestational hypertension. Maternal history, body mass index (BMI), mean arterial pressure (MAP), and uterine artery pulsatility index were recorded in all of the cases. Univariate and logistic regression analysis was used to derive algorithms for the prediction of hypertensive disorders. RESULTS The maternal characteristics selected by regression analysis to be part of the final predictive model were nulliparity, previous personal and family history of PE. MAP was higher (86 versus 78 mmHg) in patients who developed PE (p<0.01). The uterine artery percentile of mean PI was higher in the PE than in the control group (50.3%±31.7% versus 37.4%±30.0%; p<0.01). It was estimated that, with the algorithm for PE, 78%, 45%, and 26% of early PE, late PE, and gestational hypertension, respectively, could be detected with a 10% false-positive rate. CONCLUSION The traditional approach to screening for PE, which is based on maternal demographic characteristics and medical history, identifies ∼60% of cases destined to develop early PE for a false-positive rate of 10%. This study proposes that a combination of maternal risk factors, mean arterial blood pressure, and uterine artery Doppler, for the same false-positive rate of 10%, could identify 78% of cases of early PE.

Ophthalmic artery Doppler for prediction of pre‐eclampsia: systematic review and meta‐analysis

To determine the accuracy of ophthalmic artery Doppler in pregnancy for the prediction of pre‐eclampsia (PE).