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Objective: To estimate the prevalence and trend of congenital eye anomalies (CEAs) and the rate of prenatal diagnosis over a 10‐year period. Design: Retrospective population‐based registry study. Setting: All maternity units in Paris, France, from 2010 to 2020. Population: A cohort of 115 cases of CEA detected among all live births or stillbirths, after 22 weeks of gestation, and terminations of pregnancy. Methods: The total prevalence of CEAs and prevalence of each specific CEA were calculated using 95% Poisson exact confidence intervals. Main outcome measures: The total prevalence of CEAs and the proportion of prenatal diagnosis of CEAs, and their evolution. Results: The prevalence of CEAs was 4.1 (95% CI 3.4–5.0) cases, ranging between 3.1 and 5.7 cases, per 10 000 births. CEAs were prenatally diagnosed in 23.5% of cases. CEAs were bilateral in 51 cases (44.3%), unilateral in 43 cases (37.4%) and missing or unknown in 21 cases (18.3%). Of those with CEAs, 20.9% had genetic anomalies and 53.0% had at least one other extraocular anomaly. When detected prenatally, CEAs were bilateral in 15 cases (55.6%), unilateral in eight cases (29.6%) and missing in the four remaining cases. The prenatal diagnosis rate of CEAs associated with genetic anomalies, CEA cases with at least one other malformation and isolated CEA cases were 29.2%, 26.2% and 13.3%, respectively. Conclusions: In total, 115 cases of CEAs were observed during the study period, representing a total prevalence of 4.1 cases per 10 000 births. The overall prenatal detection rate of CEAs in our population was 23.5%, which dropped to 13.3% for isolated cases of CEAs. [ABSTRACT FROM AUTHOR]

LEGAL ASPECTS RELATING TO PRENATAL DIAGNOSIS The guidance also clarifies legal aspects in relation to termination of pregnancy for a germline cancer susceptibility gene variant. Prenatal and pre-implantation genetic testing for monogenic disorders for germline cancer susceptibility gene variants: UK joint consensus guidance Although it is anticipated that there would be fewer requests for prenatal diagnosis or PGT-M for moderate penetrance genes and sex-specific variable penetrance genes, sensitive reproductive counselling by an appropriately trained genetic/genomic healthcare professional and case discussion in multidisciplinary forums is recommended. Testing for germline pathogenic variants in cancer susceptibility genes is now commonplace and routine practice, in order to guide management of individuals with cancer and to determine surveillance and risk-reduction options for those at increased genetic risk. [Extracted from the article]

Background Objectives Search strategy Selection criteria Data collection and analysis Main results Conclusions Brain anomalies (BAs) have been the focus of research, as they have a high impact on fetal health but therapeutic and diagnostic approaches are limited.In this study, the application and efficiency of exome sequencing (ES) in detecting different cases of BAs in fetuses were evaluated and compared with chromosomal microarray analysis (CMA).To conduct this study, three databases including PubMed, Web of Science and Embase were utilised with the keywords ‘prenatal’, ‘diagnoses’, ‘brain anomalies’ and ‘exome sequencing’.Studies were included based on the STARD checklist, for which the ES and CMA diagnostic yields were calculated.Meta‐analysis was performed on the included studies using a random‐effects model and subgroup analysis to define the risk difference between them.We included 11 studies representing 779 fetuses that implemented ES along with imaging techniques. The pooled ES diagnostic yield in fetuses with BAs detected through magnetic resonance imaging (MRI) and ultrasonography was 26.53%, compared with 3.46% for CMA. The risk difference between ES and CMA for complex BAs was 0.36 [95% confidence interval (CI) 0.24–0.47], which was higher than for single BAs (0.22; 95% CI 0.18–0.25].ES is a useful method with a significantly higher diagnostic yield than CMA for genetic assessment of fetuses with complex BAs detected by imaging techniques. Moreover, ES could be applied to suspected fetuses with related family histories to predict congenital diseases with high efficiency. [ABSTRACT FROM AUTHOR]

After NHS introduction of NIPT, majority opted for further screening with NIPT (86%), with remaining choosing invasive diagnostic testing (9%) or further ultrasound scan only (5%), with no one declining further testing. We aimed to investigate the impact of NHS implementation of NIPT on women's preference for non-invasive screening in place of invasive diagnostic testing. Before NHS implementation, women with a higher-chance result were offered further screening with ultrasound or diagnostic chorionic villus sampling (CVS) and/or amniocentesis. [Extracted from the article]

Objective: To assess the impact of the Fetal Medicine Foundation (FMF) first trimester screening algorithm for pre‐eclampsia on health disparities in perinatal death among minority ethnic groups. Design A retrospective cohort study from July 2016 to December 2020. Setting: A large London teaching hospital. Patients and methods: All women who underwent first trimester pre‐eclampsia risk assessment using either the NICE screening checklist or the FMF multimodal approach. Women considered at high‐risk in the FMF cohort were offered 150 mg aspirin before 16 weeks' gestation, serial growth scans and elective birth at 40 weeks. Main outcome measures: Stillbirth, neonatal death and perinatal death rates stratified by screening method and maternal ethnicity. Results: In the NICE cohort, the perinatal death rate was significantly higher in non‐white than white women (7.95 versus 2.63/1000 births, OR 3.035, 95% CI 1.551–5.941). Following the introduction of FMF screening, the perinatal death rate in non‐white women fell from 7.95 to 3.22/1000 births (OR 0.403, 95% CI 0.206–0.789), such that it was no longer significantly different from the perinatal mortality rate in white women (3.22 versus 2.55/1000 births, OR 1.261, 95% CI 0.641–2.483). Conclusions: First trimester combined screening for placental dysfunction is associated with a significant reduction in perinatal death in minority ethnic women. Health disparities in perinatal death among ethnic minority women demand urgent attention from both clinicians and health policy makers. The data of this study suggest that this ethnic health inequality may be avoidable. Multimodal early pregnancy placental dysfunction screening can lead to a significant reduction in perinatal deaths in non‐white women. Multimodal early pregnancy placental dysfunction screening can lead to a significant reduction in perinatal deaths in non‐white women. This article includes Author Insights, a video abstract available at https://vimeo.com/bjogabstracts/authorinsights17109. [ABSTRACT FROM AUTHOR]

Objective: To describe prenatal decision‐making processes and birth plans in pregnancies amenable to planning perinatal palliative care. Design: Multicentre prospective observational study. Setting: Nine Multidisciplinary Centres for Prenatal Diagnosis of the Paris‐Ile‐de‐France region. Population: All cases of major and incurable fetal anomaly eligible for TOP where limitation of life‐sustaining treatments for the neonate was discussed in the prenatal period between 2015 and 2016. Methods: Cases of congenital defects amenable to perinatal palliative care were prospectively included in each centre. Prenatal diagnosis, decision‐making process, type of birth plan, birth characteristics, pregnancy and neonatal outcome were collected prospectively and anonymously. Main outcome measure: Final decision reached following discussions in the antenatal period. Results: We identified 736 continuing pregnancies with a diagnosis of a severe fetal condition eligible for TOP. Perinatal palliative care was considered in 102/736 (13.9%) pregnancies (106 infants); discussions were multidisciplinary in 99/106 (93.4%) cases. Prenatal birth plans involved life‐sustaining treatment limitation and comfort care in 73/736 (9.9%) of the pregnancies. The main reason for planning palliative care at birth was short‐term inevitable death in 39 cases (53.4%). In all, 76/106 (71.7%) infants were born alive, and 18/106 (17%) infants were alive at last follow‐up, including four with a perinatal palliative care birth plan. Conclusions: Only a small proportion of severe and incurable fetal disorders were potentially amenable to limitation of life‐sustaining interventions. Perinatal palliative care may not be considered a universal alternative to termination of pregnancy. Perinatal palliative care is planned in 10% of continuing pregnancies with a major and incurable fetal condition eligible for TOP. Perinatal palliative care is planned in 10% of continuing pregnancies with a major and incurable fetal condition eligible for TOP. [ABSTRACT FROM AUTHOR]

Objective: To assess the cost‐effectiveness of prenatal detection of congenital cytomegalovirus (cCMV) following maternal primary infection in the first trimester within standard pregnancy follow‐up or involving population‐based screening (serological testing at 7 and 12 weeks of gestation), with or without secondary prevention (valaciclovir) in maternal CMV primary infection. Design: Cost‐effectiveness study from the perspective of the French national health insurance system. Setting: Cost‐effectiveness based on previously published probability estimates and associated plausible ranges hypothetical population of 1,000,000 pregnant women. Population: Hypothetical population of 1,000,000 pregnant women. Methods: Cost‐effectiveness of detecting fetal cCMV in terms of the total direct medical costs involved and associated expected outcomes. Main outcome measures: Detection rates and clinical outcomes at birth. Results: Moving to a population‐based approach for targeting fetal CMV infections would generate high monetary and organizational costs while increasing detection rates from 15% to 94%. This resource allocation would help implementing horizontal equity according to which individuals with similar medical needs should be treated equally. Secondary prevention with valaciclovir had a significant effect on maternal‐fetal CMV transmission and clinical outcomes in newborns, with a 58% decrease of severely infected newborns for a 3.5% additional total costs. Accounting for women decision‐making (amniocentesis uptake and termination of pregnancy in severe cases) did not impact the cost‐effectiveness results. Conclusions: These findings could fuel thinking on the opportunity of developing clinical guidelines to rule identification of cCMV infection and administration of in‐utero treatment. These findings could fuel the development of clinical guidelines on the identification of congenital CMV infection and the administration of treatment in utero. CMV serological screening followed by valaciclovir prevention may prevent 58% to 71% of severe cCMV cases for 38 € per pregnancy. CMV serological screening followed by valaciclovir prevention may prevent 58% to 71% of severe cCMV cases for 38 € per pregnancy. [ABSTRACT FROM AUTHOR]

Individualised counselling of the merits of CVS versus amniocentesis should be provided for women considering CVS during this time period; a video demonstrating the recommended technique for transabdominal CVS is available online at www.rcog.org.uk/gtg8. [Grade C] Aim The aim of this guideline is to provide a concise set of evidence-based standards for provision and performance of amniocentesis and chorionic villus sampling (CVS) used for prenatal diagnosis. Background Pregnant women are offered amniocentesis or CVS for prenatal diagnosis for a variety of reasons including a higher chance aneuploidy screening result, fetal structural anomaly, or a known risk of inherited genetic disease. Agarwal et al.32 meta-analysed data from four observational studies of CVS in twin pregnancies (632 procedures) and reported an overall pregnancy loss rate of 3.8% (95% CI 2.5-5.5) following CVS. [Extracted from the article]

Background: Phaeochromocytoma and paraganglioma (PPGL) in pregnancy, if not diagnosed antepartum, pose a high risk for mother and child. Objective: To examine the clinical clues of antepartum and postpartum/postmortem diagnosis of PPGL. Search strategy: Case reports on PPGL in pregnancy published between 1 January 1988 and 30 June 2019 in English, German, Dutch or French. Selection criteria: Case reports containing a predefined minimum of clinical data on PPGL and pregnancy. Data collection and analysis: Two authors independently performed data extraction and assessed data quality. We calculated odds ratios (OR) (with 95% confidence intervals) and used uni‐ and multivariable logistic regression analysis. Main results: Maternal and fetal/neonatal mortalities were 9.0% (18/200) and 14.2% (29/204), respectively. Maternal mortality was 42‐fold higher with PPGL diagnosed postpartum/postmortem (17/58; 29.3%) than antepartum (1/142; 0.7%) (adjusted OR 45.9, 95% CI 5.67–370, P = 0.0003). Offspring mortality was 2.6‐fold higher with PPGL diagnosed postpartum/postmortem than antepartum (OR 3.1, 95% CI 1.38–6.91, P = 0.0044). Hypertension at admission (OR 2.29, 95% CI 1.12–4.68, P = 0.022), sweating (OR 3.14, 95% CI 1.29–7.63, P = 0.014) and a history of PPGL, a known PPGL‐associated gene mutation or adrenal mass (OR 8.87, 95% CI 1.89–41.64, P = 0.0056) were independent factors of antepartum diagnosis. Acute onset of symptoms (OR 8.49, 95% CI 3.52–20.5, P < 0.0001), initial diagnosis of pre‐eclampsia (OR 6.34, 95% CI 2.60–15.5, P < 0.0001), admission for obstetric care (OR 10.71, 95% CI 2.70–42.45, P = 0.0007) and maternal tachycardia (OR 2.72, 95% CI 1.26–5.85, P = 0.011) were independent factors of postpartum diagnosis. Conclusion: Several clinical clues can assist clinicians in considering an antenatal diagnosis of PPGL in pregnancy, thus potentially improving outcome. Systematic review of 204 pregnant patients with phaeochromocytoma identified clinical clues for a timely antepartum diagnosis. Systematic review of 204 pregnant patients with phaeochromocytoma identified clinical clues for a timely antepartum diagnosis. [ABSTRACT FROM AUTHOR]

Objectives: (1) To compare brain findings between large and non-large neural tube defect (NTD); (2) to evaluate the impact of large lesion on the surgical parameters; (3) to study any associations between the size of the lesions and brain findings 6 weeks postoperatively and neurological short-term outcomes.Design: Retrospective cohort study.Setting: Texas Children's Hospital, between 2011 and 2018.Population: Patients who underwent prenatal NTD repair.Methods: Large lesion was defined when the lesion's surface was >75th centile of our cohorts' lesions.Main Outcome Measures: Time of referral: ventriculomegaly and anatomical level of the lesion; surgery: duration and need for relaxing incisions. 6 weeks postoperative: hindbrain herniation (HBH) and ventriculomegaly. After delivery: dehiscence, need for hydrocephalus treatment and motor function.Results: A total of 99 patients were included, 25 of whom presented with large lesions. Type of lesion and ventriculomegaly were comparable between individuals with large and non-large lesions. Individuals with large lesions were associated with increased need for relaxing incisions by 5.4 times (95% CI 1.3-23.2, P = 0.02). Six weeks postoperatively, having a large lesion decreased by ten times the likelihood of having a postoperative reversal of HBH (odds ratio = 0.1, 95% CI 0.1-0.4, P < 0.01). At birth, larger lesions increased the risk for repair dehiscence by 6.1 times (95% CI 1.6-22.5, P < 0.01) and the risk of dehiscence or leakage of cerebrospinal fluid at birth by 5.5 times (95% CI 1.6-18.9, P < 0.01).Conclusion: Prenatal repair of patients with large NTD presents a lower proportion of HBH reversal 6 weeks after the surgery, a higher risk of dehiscence and a higher need for postnatal repair.Tweetable Abstract: Evaluation of the size of fetal NTD can predict adverse neurological outcomes after prenatal NTD repair. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effectiveness of secondary screening using non‐invasive prenatal testing (NIPT) in a routine NHS setting including test performance, turn‐around times (TATs) and no‐call (failure to obtain result) rates. To examine the influence of maternal and fetal characteristics on test performance. Design: Retrospective cohort. Setting: London teaching hospital. Sample: A total of 8651 pregnancies undergoing screening for fetal trisomy using NIPT provided by an NHS cell‐free DNA screening laboratory – the SAFE laboratory. Methods: Screening test evaluation and TATs. Univariate and multivariate logistic regression analysis to identify significant predictors of no‐call results and reported by low fetal fraction (<2%), very high fetal fraction (>40%) and processing failure. Main outcome measures: Test performance, TATs and no‐call rates, factors affecting no‐call results. Results: Average TAT was 4.0 days (95% CI 4.0–4.2 days). Test sensitivities for trisomies 21 and 13/18 were 98.9% (95% CI 95.9–99.9%) and 90.4% (95% CI 80.0–96.8%), respectively. The overall no‐call rate was 32/8651 (0.37%, 95% CI 0.26–0.52%). The overall risk of a no‐call result was influenced by gestational age, dichorionic twin pregnancy, history of malignancy and pregnancies affected by trisomy 13/18, but not by maternal weight or use of low‐molecular‐weight heparin. Conclusions: High‐throughput NIPT can be effectively embedded into a public health NHS setting. TATs of 4 days and no‐calls of <0.5% were well within clinically desirable tolerances. Gestational age, maternal weight, assisted reproductive techniques, use of low‐molecular‐weight heparin and past history of malignancy did not have major impacts on test no‐call rates and should not constitute reasons for withholding the option of NIPT from women. Turn‐around times of 4 days, no‐call (test failure) rates of 0.37% and highly accurate NIPT can be successfully embedded in the NHS. Turn‐around times of 4 days, no‐call (test failure) rates of 0.37% and highly accurate NIPT can be successfully embedded in the NHS. [ABSTRACT FROM AUTHOR]

Objective: We hypothesised that a multi-compartment magnetic resonance imaging (MRI) technique that is sensitive to fetal blood oxygenation would identify changes in placental blood volume and fetal blood oxygenation in pregnancies complicated by early-onset fetal growth restriction (FGR).Design: Case-control study.Setting: London, UK.Population: Women with uncomplicated pregnancies (estimated fetal weight [EFW] >10th centile for gestational age [GA] and normal maternal and fetal Doppler ultrasound, n = 12) or early-onset FGR (EFW <3rd centile with or without abnormal Doppler ultrasound <32 weeks GA, n = 12) were studied.Methods: All women underwent MRI examination. Using a multi-compartment MRI technique, we quantified fetal and maternal blood volume and feto-placental blood oxygenation.Main Outcome Measures: Disease severity was stratified according to Doppler pulsatility index and the relationship to the MRI parameters was investigated, including the influence of GA at scan.Results: The FGR group (mean GA 27+5  weeks, range 24+2 to 33+6  weeks) had a significantly lower EFW compared with the control group (mean GA 29+1  weeks; -705 g, 95% CI -353 to -1057 g). MRI-derived feto-placental oxygen saturation was higher in controls compared with FGR (75 ± 9.6% versus 56 ± 16.2%, P = 0.02, 95% CI 7.8-30.3%). Feto-placental oxygen saturation estimation correlated strongly with GA at scan in controls (r = -0.83).Conclusion: Using a novel multimodal MRI protocol we demonstrated reduced feto-placental blood oxygen saturation in pregnancies complicated by early-onset FGR. The degree of abnormality correlated with disease severity defined by ultrasound Doppler findings. Gestational age-dependent changes in oxygen saturation were also present in normal pregnancies.Tweetable Abstract: MRI reveals differences in feto-placental oxygen saturation between normal and FGR pregnancy that is associated with disease severity. [ABSTRACT FROM AUTHOR]

Objective: To assess in women with early-onset severe pre-eclampsia whether longitudinal changes in angiogenic factors improve the prediction of adverse outcome.Design: Prospective cohort study.Setting: Maternity units in two Spanish hospitals.Population: Women with diagnosis of early-onset severe pre-eclampsia.Methods: Levels of placental growth factor (PlGF), soluble fms-like tyrosine kinase (sFlt-) and sFlt-1/PlGF ratio were measured at admission and before delivery, and average daily change calculated. The association of longitudinal changes of angiogenic factors with the time interval to delivery and with complications was evaluated by logistic and Cox regression.Main Outcome Measures: Interval to delivery and composite of adverse outcomes.Results: We included 63 women, of which 26 (41.3%) had a complication. Longitudinal changes of sFlt-1 were more pronounced in complicated pregnancies (median: 1047 versus 342 pg/ml/day; P = 0.04). On the multivariate analysis, the clinical risk score and sFlt-1 at admission explained 6.2% of the uncertainty for complication; the addition of sFlt-1 longitudinal changes improved this to 25.3% (P = 0.002). The median time from admission to delivery was 4 days (95% CI 1.6-6.04) in those in the highest quartile of sFlt-1 longitudinal changes versus 16 days (95% CI 12.4-19.6) in the remaining women (Log-rank test P < 0.001).Conclusions: Longitudinal changes in sFlt-1 maternal levels from admission for confirmed early-onset severe pre-eclampsia add to baseline characteristics in the prediction of adverse outcome and interval to delivery.Tweetable Abstract: In early-onset severe pre-eclampsia, longitudinal changes in sFlt-1 levels improve the prediction of complications and interval to delivery. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the clinical feasibility of noninvasive prenatal diagnosis (NIPD) for β-thalassaemia using circulating single molecule amplification and re-sequencing technology (cSMART).Design: Through carrier screening, 102 pregnant Chinese couples carrying pathogenic HBB gene variants were recruited to the study. Pregnancies were managed using traditional invasive prenatal diagnosis (IPD). Retrospectively, we evaluated the archived pregnancy plasma DNA by NIPD to evaluate the performance of our cSMART assay for fetal genotyping.Setting: Chinese prenatal diagnostic centres specialising in thalassaemia testing.Population: Chinese carrier couples at high genetic risk for β-thalassaemia.Methods: Fetal cell sampling was performed by amniocentesis and HBB genotypes were determined by reverse dot blot. NIPD was performed by a newly designed HBB cSMART assay and fetal genotypes were called by measuring the allelic ratios in the maternal cell-free DNA.Main Outcome Measures: Concordance of HBB fetal genotyping between IPD and NIPD and the sensitivity and specificity of NIPD.Results: Invasive prenatal diagnosis identified 29 affected homozygotes or compound heterozygotes, 54 heterozygotes and 19 normal homozygotes. Compared with IPD results, 99 of 102 fetuses (97%) were correctly genotyped by our NIPD assay. Two of three discordant samples were false positives and the other sample involved an incorrect call of a heterozygote carrier as a homozygote normal. Overall, the sensitivity and specificity of our NIPD assay was 100% (95% CI 88.06-100.00%) and 97.26% (95% CI 90.45-99.67%), respectively.Conclusions: This study demonstrates that our cSMART-based NIPD assay for β-thalassaemia has potential clinical utility as an alternative to IPD for pregnant HBB carrier couples.Tweetable Abstract: A new noninvasive test for pregnancies at risk for β-thalassaemia. [ABSTRACT FROM AUTHOR]

Objective: To investigate cerebral anomalies other than Chiari type 2 malformation in fetuses with myelomeningocele (MMC).Design: A retrospective cohort study in a single tertiary centre.Setting: A review of associated cerebral anomalies in cases with prenatal diagnosis of myelomeningocele.Population: Seventy cases of fetal myelomeningocele.Methods: Ultrasound and MRI images were blindly reviewed. Postnatal imaging and results of the postmortem results were also reviewed. The association between cerebral anomalies and the following ultrasound findings was measured: level of the defect, ventriculomegaly, microcephaly and fetal talipes.Main Outcome Measures: A microcephaly was observed in 32/70 cases (46%) and a ventriculomegaly was observed in 39/70 cases (56%). Other cerebral anomalies were diagnosed in 47/70 (67%).Results: Other cerebral anomalies were represented by 42/70 cases with abnormal CC (60%), 8/70 cases with perinodular heterotopia (PNH; 11%), 2/70 cases with abnormal gyration (3%). MRI performed only in fetal surgery cases confirmed the ulltrasound findings in all cases and provided additional findings in two cases (PNH). Risk ratios of fetal cerebral anomalies associated with MMC did not reach significance for microcephaly, ventriculomegaly, talipes or the level of the defect There was an overall good correlation between pre- and postnatal findings with a Kappa value of 0.79 [95% CI 0.57-1] and 82% agreement.Conclusion: Fetal brain anomalies other than Chiari type 2 malformation are frequently observed in fetuses with myelomeningocele, predominantly represented by CC anomalies. Whether these associated cerebral anomalies have an impact on selecting cases eligible for fetal surgery needs further evaluation.Tweetable Abstract: Fetal cerebral anomalies other than Chiari type 2 malformation, microcephaly, and ventriculomegaly may be associated with MMC in up to 67% of the cases. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to establish rotational thromboelastometry (ROTEM® ) baseline parameters in labouring women at term gestation. The secondary aim was to compare these reference ranges with those from previous studies on labouring women and from the manufacturer.Design: A prospective, observational study.Setting: Tertiary referral hospital.Participants: Healthy women in labour.Methods: Ethics approval was granted for an opt-out recruitment approach. ROTEM® testing was performed in labouring women at term gestation. Women with any condition affecting coagulation were excluded. ROTEM® Delta reference ranges were derived by calculating the 2.5% and 97.5% centiles for INTEM/EXTEM/FIBTEM parameters including amplitude at 5 minutes (A5), coagulation time (CT) and maximum clot firmness (MCF).Main Outcome Measures: ROTEM® parameters were measured in labouring women before delivery. The following tests were performed: FIBTEM, EXTEM and INTEM.Results: One hundred and twenty-one women met the inclusion criteria, with a mean (± SD) age of 29.6 ± 5.4 years and median (interquartile range) gestation of 39.4 weeks (37.4-40.4 weeks). Seventy-five (62.0%) women were nulliparous and 71 (58.7%) delivered vaginally. The median and interquartile ranges for selected ROTEM® parameters were: FIBTEM A5, 21 mm (IQR 18-23 mm); EXTEM A5, 55 mm (52-58 mm); and EXTEM CT, 52 seconds (48-56 seconds).Conclusions: The FIBTEM/EXTEM/INTEM amplitudes were higher than the manufacturer's reference ranges for non-obstetric patients. The FIBTEM MCF upper and lower limits were higher and the EXTEM/INTEM CT was shorter and narrower in range. This study provides reference ranges for ROTEM® values in healthy labouring women at term gestation with uncomplicated pregnancies.Tweetable Abstract: This is the first study to report on ROTEM® reference ranges with over 120 healthy labouring women of normal weight at term gestation. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the risk of inducing RhD immunisation in pregnancies of RhD-negative mothers with an RhD-positive fetus undergoing chorionic villus samplings (CVS) or amniocenteses (AC).Design, Setting and Population: Registry-based study in a Danish cohort which has not been given rhesus prophylaxis.Methods: Data were retrieved from the Department of Clinical Immunology at Rigshospitalet. All RhD-negative women carrying an RhD-positive fetus with screen test results from weeks 8-12 and weeks 25-29 were linked to data from the Danish Fetal Medicine Database. Data were divided into cases where no invasive prenatal diagnostic procedure was performed, cases that had AC performed, and cases that had CVS performed.Main Outcome Measures: A comparison of the proportion of women who developed RhD immunisation between the two screen tests.Results: The cohort consisted of 10 085 women: 9353 had no invasive procedures performed, 189 had AC and 543 had CVS performed. No women were immunised spontaneously or due to the procedure between the first and second screen test in the group with no procedure performed, or in the AC group. One woman was immunised in the CVS group. When comparing the proportion of women who was immunised in the CVS group with the no invasive test group a non-significant difference was found (P = 0.055).Conclusion: The RhD immunisation rate before gestational weeks 25-29 in RhD-negative women carrying an RhD-positive fetus is very low, even in women undergoing prenatal invasive testing without rhesus prophylaxis.Tweetable Abstract: The RhD immunisation rate during pregnancy is very low even in women undergoing prenatal invasive testing. [ABSTRACT FROM AUTHOR]

Objective: To assess the diagnostic performance of a novel circulating single molecule amplification and re-sequencing technology (cSMART) method for noninvasive prenatal testing (NIPT) of Phenylketonuria (PKU).Design: Blinded NIPT analysis of pregnancies at high risk for PKU.Setting: Shanghai Xinhua Hospital and Hunan Jiahui Genetics Hospital, China.Population: Couples (n = 33) with a child diagnosed with PKU.Methods: Trio testing for pathogenic PAH mutations was performed by Sanger sequencing. In second pregnancies, invasive prenatal diagnosis (IPD) was used to determine fetal genotypes. NIPT was performed using a PAH gene-specific cSMART assay. Based on the plasma DNA mutation ratio relative to the fetal DNA fraction, fetal genotypes were assigned using a maximum-likelihood algorithm.Main Outcome Measures: Concordance of fetal genotyping results between IPD and NIPT, and the sensitivity and specificity of the NIPT assay.Results: Compared with gold standard IPD results, 32 of 33 fetuses (96.97%) were accurately genotyped by NIPT. The sensitivity and specificity of the NIPT assay was 100.00% (95% CI 59.04-100.00%) and 96.15% (95% CI 80.36-99.90%), respectively.Conclusions: The novel cSMART assay demonstrated high accuracy for correctly calling fetal genotypes. We propose that this test has useful clinical utility for the rapid screening of high-risk and low-risk pregnancies with a known history of PKU on one or both sides of the family.Tweetable Abstract: NIPT of couples at high risk for PKU using a full-coverage cSMART PAH gene test. [ABSTRACT FROM AUTHOR]

Objective: To quantify the effect of different methodological decisions on the identification of potential core outcomes to inform the development of recommendations for future core coutcome set developers.Design: Mixed methods study.Setting: A core outcome set for pre-eclampsia was used as an exemplar.Sample: A long list of potential core outcomes was developed by undertaking a systematic review of pre-eclampsia trials and performing a thematic analysis of in-depth patient interviews.Methods: Specific methods used to generate long lists of potential core outcomes were evaluated.Results: Different methodological decisions had a substantial impact on the identification of potential core outcomes. Extracting outcomes from published pre-eclampsia trials was an effective way of identifying 48 maternal, eight fetal, 25 neonatal outcomes, and eight patient-reported outcomes. Limiting the extraction of outcomes to primary outcomes or outcomes commonly reported in pre-eclampsia trials reduced the number and diversity of potential core outcomes identified. Thematic analysis of in-depth patient interviews ensured an additional five patient reported outcomes and six outcomes related to future child health were identified.Conclusions: Future core outcome set developers should use quantitative and qualitative methods when developing a long list of potential core outcomes. TWEETABLE ABSTRACT: @OfficialNIHR research published in @BJOGtweets informs new recommendations for future @coreoutcomes developers. [ABSTRACT FROM AUTHOR]

Objective: To explore the separate effects of being 'at risk' of gestational diabetes mellitus (GDM) and screening for GDM, and of raised fasting plasma glucose (FPG) and clinical diagnosis of GDM, on the risk of late stillbirth.Design: Prospective case-control study.Setting: Forty-one maternity units in the UK.Population: Women who had a stillbirth ≥28 weeks of gestation (n = 291) and women with an ongoing pregnancy at the time of interview (n = 733).Methods: Causal mediation analysis explored the joint effects of (i) 'at risk' of GDM and screening for GDM and (ii) raised FPG (≥5.6 mmol/l) and clinical diagnosis of GDM on the risks of late stillbirth. Adjusted odds ratios (aOR) were estimated by logistic regression adjusted for confounders identified by directed acyclic graphs.Main Outcome Measures: Screening for GDM and FPG levels RESULTS: Women 'at risk' of GDM, but not screened, experienced 44% greater risk of late stillbirth than those not 'at risk' (aOR 1.44, 95% CI 1.01-2.06). Women 'at risk' of GDM who were screened experienced no such increase (aOR 0.98, 95% CI 0.70-1.36). Women with raised FPG not diagnosed with GDM experienced four-fold greater risk of late stillbirth than women with normal FPG (aOR 4.22, 95% CI 1.04-17.02). Women with raised FPG who were diagnosed with GDM experienced no such increase (aOR 1.10, 95% CI 0.31-3.91).Conclusions: Optimal screening and diagnosis of GDM mitigate the higher risks of late stillbirth in women 'at risk' of GDM and/or with raised FPG. Failure to diagnose GDM leaves women with raised FPG exposed to avoidable risk of late stillbirth.Tweetable Abstract: Risk of #stillbirth in gestational diabetes is mitigated by effective screening and diagnosis. [ABSTRACT FROM AUTHOR]

Heart problems are common in newborn babies, affecting approximately 5-10 in 1000 babies. Some are more serious than others, but most babies born with heart problems do not have other health issues. Of those babies who have a serious heart problem, almost 1 in 4 will have heart surgery in their first year. In the UK, pregnant women are offered a scan at around 20 weeks to try and spot any heart problems. In most cases there is not a clear reason for the problem, but sometimes other issues, such as genetic conditions, are discovered. In recent years the care given to these babies after they are born has improved their chances of surviving. However, it is recognised that babies born with heart problems have a risk of delays in their learning and development. This may be due to their medical condition, or as a result of surgery and complications after birth. In babies with heart problems, there is a need for more research on ultrasound and magnetic resonance imaging (MRI) to understand how the brain develops and why these babies are more likely to have delays in learning and development. This paper discusses the way ultrasound and MRI are used in assessing the baby's brain. Ultrasound is often used to spot any problems, looking at how the baby's brain develops in pregnancy. Advances in ultrasound technologies have made this easier. MRI is well-established and safe in pregnancy, and if problems in the brain have been seen on ultrasound, MRI may be used to look at these problems in more detail. While it is not always clear what unusual MRI findings can mean for the baby in the long term, increased understanding may mean parents can be given more information about possible outcomes for the baby and may help to improve the counselling they are offered before their baby's birth. [ABSTRACT FROM AUTHOR]

Objective: To evaluate whether a nationwide prenatal anomaly screening programme improves detection rates of univentricular heart (UVH) and transposition of great arteries (TGA), and whether maternal risk factors for severe fetal heart disease affect prenatal detection.Design: Population-based cohort study.Setting: Nationwide data from Finnish registries 2004-14.Population: A total of 642 456 parturients and 3449 terminated pregnancies due to severe fetal anomaly.Methods: Prenatal detection rates were calculated in three time periods (prescreening, transition and screening phase). The effect of maternal risk factors (obesity, in vitro fertilisation, pregestational diabetes and smoking) was evaluated.Main Outcome Measures: Change in detection rates and impact of maternal risk factors on screening programme efficacy.Results: In total, 483 cases of UVH and 184 of TGA were detected. The prenatal detection rate of UVH increased from 50.4% to 82.8% and of TGA from 12.3% to 41.0% (P < 0.0001). Maternal risk factors did not affect prenatal detection rate, but detection rate differed substantially by region.Conclusions: A nationwide screening programme improved overall UVH and TGA detection rates, but regional differences were observed. Obesity or other maternal risk factors did not affect the screening programme efficacy. The establishment of structured guidelines and recommendations is essential when implementing the screening programme. In addition, a prospective screening register is highly recommended to ensure high quality of screening.Tweetable Abstract: Implementation of a nationwide prenatal anomaly screening improved detection rates of UVH and TGA. [ABSTRACT FROM AUTHOR]

The article presents a guideline on the diagnosis and management of vasa praevia. Topics include the management of women with undignosed vasa praevia at delivery, considerations in managing women with vasa praevia, and gestation to perform elective delivery. A review of the evidence-based approach to the clinical management of vasa praevia is offered.

The article offers the authors' insights on various studies including the effects of diabetic control to birth defects, the importance of antenatal detection of cardiac abnormalities, and the importance of oxytocin in the prevention of postpartum haemorrhage (PPH). Topics mentioned include the medical termination of pregnancy (TOP), the effects of Vitamin D to cancer risk, and the effects of cannabis to pregnancy.

Objective: Ultrasound is widely regarded as an important adjunct to antenatal care (ANC) to guide practice and reduce perinatal mortality. We assessed the impact of ANC ultrasound use at health centres in resource-limited countries.Design: Cluster randomised trial.Setting: Clusters within five countries (Democratic Republic of Congo, Guatemala, Kenya, Pakistan, and Zambia) METHODS: Clusters were randomised to standard ANC or standard care plus two ultrasounds and referral for complications. The study trained providers in intervention clusters to perform basic obstetric ultrasounds.Main Outcome Measures: The primary outcome was a composite of maternal mortality, maternal near-miss mortality, stillbirth, and neonatal mortality.Results: During the 24-month trial, 28 intervention and 28 control clusters had 24 263 and 23 160 births, respectively; 78% in the intervention clusters received at least one study ultrasound; 60% received two. The prevalence of conditions noted including twins, placenta previa, and abnormal lie was within expected ranges. 9% were referred for an ultrasound-diagnosed condition, and 71% attended the referral. The ANC (RR 1.0 95% CI 1.00, 1.01) and hospital delivery rates for complicated pregnancies (RR 1.03 95% CI 0.89, 1.20) did not differ between intervention and control clusters nor did the composite outcome (RR 1.09 95% CI 0.97, 1.23) or its individual components.Conclusions: Despite availability of ultrasound at ANC in the intervention clusters, neither ANC nor hospital delivery for complicated pregnancies increased. The composite outcome and the individual components were not reduced.Tweetable Abstract: Antenatal care ultrasound did not improve a composite outcome that included maternal, fetal, and neonatal mortality. [ABSTRACT FROM AUTHOR]

Objective: Intrauterine adhesions (IUAs) are a problematic complication after termination of pregnancy, but their incidence is unknown. Our objective was to assess the incidence of IUAs following induced termination of pregnancy and the risk factors for IUAs.Design: Retrospective cohort study.Setting: A nationwide registry study.Sample: All women undergoing induced termination of pregnancy (n = 80 015) in Finland between 2000 and 2008.Methods: The data were retrieved from the Finnish Abortion Registry and the Hospital Discharge Registry. The diagnosis of IUAs or complications was based on the diagnostic codes (International Statistical Classification of Diseases and Related Health Problems 10th Revision, ICD-10) and operative codes according to the Nordic Medico-Statistical Committee (NOMESCO) Classification of Surgical Procedures (NCSP). IUAs were defined as ICD-10 code N85.6 or operative code LCG02. A subanalysis of IUA cases and five matched controls was performed.Main Outcome Measures: The incidence of and risk factors for IUAs.Results: A total of 12 (1.5 per 10 000) IUA diagnoses were identified from 79 960 eligible induced terminations of pregnancy. The rate of IUAs was 1.5 and 2.0 cases per 10 000 terminations of pregnancy following medically and surgically induced termination of pregnancy, respectively (P = 0.19). In a subgroup analysis of IUA cases and five matched controls, surgical treatment of the remaining products of conception following termination of pregnancy significantly increased the risk of IUAs (odds ratio, OR 5.50; 95% confidence interval, 95% CI 1.46-20.79; P = 0.012).Conclusion: IUAs that require further treatment are rare after an induced termination of pregnancy. Surgical evacuation following medical or surgical termination of pregnancy was a risk factor for the diagnosis of IUAs. These results suggest that trauma to a recently pregnant uterus is an important risk factor for IUAs.Tweetable Abstract: IUA is rare after induced termination of pregnancy (iTOP), but surgical evacuation is a risk factor for IUAs. [ABSTRACT FROM AUTHOR]

Objective: Accurate assessment of gestational age (GA) is critical to paediatric care, but is limited in developing countries without access to ultrasound. Our objectives were to assess the accuracy of prediction of GA at birth and preterm birth classification using routinely collected anthropometry measures.Design: Prospective cohort study.Setting: United States.Population or Sample: A total of 2334 non-obese and 468 obese pregnant women.Methods: Enrolment GA was determined based on last menstrual period, confirmed by first-trimester ultrasound. Maternal anthropometry and fundal height (FH) were measured by a standardised protocol at study visits; FH alone was additionally abstracted from medical charts. Neonatal anthropometry measurements were obtained at birth. To estimate GA at delivery, we developed three predictor models using longitudinal FH alone and with maternal and neonatal anthropometry. For all predictors, we repeatedly sampled observations to construct training (60%) and test (40%) sets. Linear mixed models incorporated longitudinal maternal anthropometry and a shared parameter model incorporated neonatal anthropometry. We assessed models' accuracy under varied scenarios.Main Outcome Measures: Estimated GA at delivery.Results: Prediction error for various combinations of anthropometric measures ranged between 13.9 and 14.9 days. Longitudinal FH alone predicted GA within 14.9 days with relatively stable prediction errors across individual race/ethnicities [whites (13.9 days), blacks (15.1 days), Hispanics (15.5 days) and Asians (13.1 days)], and correctly identified 75% of preterm births. The model was robust to additional scenarios.Conclusions: In low-risk, non-obese women, longitudinal FH measures alone can provide a reasonably accurate assessment of GA when ultrasound measures are not available.Tweetable Abstract: Longitudinal fundal height alone predicts gestational age at birth when ultrasound measures are unavailable. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the cost-effectiveness of high-throughput, non-invasive prenatal testing (HT-NIPT) for fetal Rhesus D (RhD) genotype to guide antenatal prophylaxis with anti-D immunoglobulin compared with routine antenatal anti-D immunoglobulin prophylaxis (RAADP).Design: Cost-effectiveness decision-analytic modelling.Setting: Primary care.Participants: A simulated population of 100 000 RhD-negative women not known to be sensitised to the RhD antigen.Methods: A decision tree model was used to characterise the antenatal care pathway in England and the long-term consequences of sensitisation events. The diagnostic accuracy of HT-NIPT was derived from a systematic review and bivariate meta-analysis; estimates of other inputs were derived from relevant literature sources and databases. Women in whom the HT-NIPT was positive or inconclusive continued to receive RAADP, whereas women with a negative result received none. Five alternative strategies in which the use of HT-NIPT may affect the existing postpartum care pathway were considered.Main Outcome Measures: Costs expressed in 2015GBP and impact on health outcomes expressed in terms of quality-adjusted life-years over a lifetime.Results: The results suggested that HT-NIPT appears cost saving but also less effective than current practice, irrespective of the postpartum strategy evaluated. A postpartum strategy in which inconclusive test results are distinguished from positive results performed best. HT-NIPT is only cost-effective when the overall test cost is £26.60 or less.Conclusions: HT-NIPT would reduce unnecessary treatment with routine anti-D immunoglobulin and is cost saving when compared with current practice. The extent of any savings and cost-effectiveness is sensitive to the overall test cost.Tweetable Abstract: HT-NIPT is cost saving compared with providing anti-D to all RhD-negative pregnant women. [ABSTRACT FROM AUTHOR]

Pre-eclampsia is a complex disease with significant maternal and fetal morbidity and mortality. Its syndromic nature makes diagnosis and management difficult. The field is rapidly evolving with the definition of pre-eclampsia being challenged by some organisations, with proteinuria no longer being essential in the presence of other features. In the last decade, angiogenic factors, in particular soluble fms-like tyrosine kinase 1 (sFlt-1), have emerged as important molecules in the pathogenesis of pre-eclampsia. Here we review the most recent evidence regarding the potential of these factors as biomarkers and therapeutic targets for pre-eclampsia.Tweetable Abstract: A review of angiogenic factors, sFlt-1 and PlGF, in the diagnosis, prediction and management of pre-eclampsia. [ABSTRACT FROM AUTHOR]

Objective: To describe the incidence and nature of prenatal brain damage following fetoscopic laser selective coagulation (FLSC) of placental vessels for twin-to-twin transfusion syndrome (TTTS).Design: Retrospective observational study.Setting: Single center cohort.Population: All consecutive cases referred for TTTS treated by FLSC between 2003 and 2015.Methods: After the FLSC, patients were followed weekly by ultrasound. Fetal magnetic resonance imaging (MRI) scans were systematically planned at 30-32 weeks of gestation.Main Outcome Measures: Brain damage diagnosed prenatally by ultrasound or MRI.Results: In total, 1023 cases were reviewed. Brain damage was diagnosed prenatally in 22/1023 (2.1%) cases. Diagnosis was performed by ultrasound prior to MRI in 18 (82%) cases. All lesions were within the spectrum of ischaemic haemorrhagic lesions. Postoperative twin anaemia polycythaemia sequence and recurrence of TTTS were significantly associated with brain damage.Conclusion: The incidence of prenatal brain damage is low following FSLC, and is strongly associated with incomplete surgery.Tweetable Abstract: Following FSLC for TTTS, prenatal brain damage occurs in 2% of cases and is associated with incomplete surgery. [ABSTRACT FROM AUTHOR]

Objective: To investigate the pregnancy outcomes in a cohort of women who failed to obtain a result in non-invasive prenatal testing (NIPT).Design: Historical cohort study.Setting: A multicentre private practice in Sydney, Australia.Population: Women who failed to obtain a result from NIPT (n = 131).Methods: The maternal characteristics, antenatal investigations and pregnancy outcomes for these women were compared with those who obtained a result at the same practice and to the general Australian obstetric population.Main Outcome Measures: Antenatal investigations: pregnancy-associated plasma protein-A (PAPP-A), free β-human chorionic gonadotrophin (β-hCG), placental growth factor (PlGF), uterine artery pulsatility index (PI), mean arterial pressure (MAP). Pregnancy outcomes: chromosomal abnormality, pre-eclampsia, gestational diabetes, small-for-gestational-age (SGA), preterm delivery.Results: Only 1.1% of NIPT samples failed to return a result. This cohort was significantly older and had significantly increased weight compared with the general Australian obstetric population. Pregnancy outcomes were available for 94% of the cohort. There were significantly higher rates of chromosomal aneuploidies (6.5% versus 0.2%, P < 0.0001), pre-eclampsia (11% versus 1.5%, P < 0.0001) and gestational diabetes (23% versus 7.5%, P < 0.0001) compared with the general obstetric population. Rates of preterm delivery and SGA were elevated but did not reach significance. Antenatal investigations demonstrated decreased PAPP-A MoM (0.75 versus 1.14, P < 0.0001), decreased free β-hCG (0.71 versus 1.01, P < 0.0001) and increased uterine artery PI (1.79 versus 1.65, P = 0.02).Conclusion: Women who fail to obtain a result from NIPT are at increased risk of adverse pregnancy outcomes, in particular chromosomal aneuploidy, gestational diabetes and pre-eclampsia.Funding: None received.Tweetable Abstract: Women who fail to obtain a result from cell-free DNA NIPT are at increased risk of adverse pregnancy outcomes. [ABSTRACT FROM AUTHOR]

Objective: To estimate the association between lipoprotein particle concentrations in pregnancy and gestational age at delivery.Design: Prospective cohort study.Setting: The study was conducted in the USA at the University of North Carolina.Population: We assessed 715 women enrolled in the Pregnancy, Infection, and Nutrition study from 2001 to 2005.Methods: Fasting blood was collected at two time points (<20 and 24-29 weeks of gestation). Nuclear magnetic resonance (NMR) quantified lipoprotein particle concentrations [low-density lipoprotein (LDL), high-density lipoprotein (HDL), very-low density lipoprotein (VLDL)] and 10 subclasses of lipoproteins. Concentrations were assessed as continuous measures, with the exception of medium HDL which was classified as any or no detectable level, given its distribution. Cox proportional hazards models estimated hazard ratios (HR) for gestational age at delivery adjusting for covariates.Main Outcome Measures: Gestational age at delivery, preterm birth (<37 weeks of gestation), and spontaneous preterm birth.Results: At <20 weeks of gestation, three lipoproteins were associated with later gestational ages at delivery [large LDLNMR (HR 0.78, 95% CI 0.64-0.96), total VLDLNMR (HR 0.77, 95% CI 0.61-0.98), and small VLDLNMR (HR 0.78, 95% CI 0.62-0.98], whereas large VLDLNMR (HR 1.19, 95% CI 1.01-1.41) was associated with a greater hazard of earlier delivery. At 24-28 weeks of gestation, average VLDLNMR (HR 1.25, 95% CI 1.03-1.51) and a detectable level of medium HDLNMR (HR 1.90, 95% CI 1.19-3.02) were associated with earlier gestational ages at delivery.Conclusion: In this sample of pregnant women, particle concentrations of VLDLNMR , LDLNMR , IDLNMR , and HDLNMR were each independently associated with gestational age at delivery for all deliveries or spontaneous deliveries <37 weeks of gestation. These findings may help formulate hypotheses for future studies of the complex relationship between maternal lipoproteins and preterm birth.Tweetable Abstract: Nuclear magnetic resonance spectroscopy may identify lipoprotein particles associated with preterm delivery. [ABSTRACT FROM AUTHOR]

Objective: To evaluate whether targeted sequencing and relative mutation dosage can be used to diagnose correctly inheritance of maternal β-thalassaemia mutations in cell-free DNA.Design: Feasibility study using samples collected in a prenatal clinic.Setting: South East Asia.Population: Couples where both partners were known to be carriers of one of four common β-thalassaemia mutations or an HbE mutation, and therefore at risk of carrying a fetus affected with β-thalassaemia.Methods: 49 samples previously identified as having inherited a paternal β-thalassaemia mutation were amplified using nested polymerase chain reaction (PCR), and then sequencing. Relative mutation dosage was used to classify the fetus as having inherited the wild-type or mutant maternal allele.Main Outcome Measures: Classification of the fetus as 'unaffected' (if the maternal wild-type allele was inherited) or 'affected' with β-thalassaemia (if the maternal mutant allele was inherited).Results: A classification for inheritance of maternal allele was obtained in 48/49 samples (98.0%). A concordant call was made in 44/48 cases (91.7%): one false-positive and three false-negatives were obtained. Thus, we had an overall sensitivity of 87.5% [95% confidence interval (CI) 67.6-97.3%] and a specificity of 95.8% (95% CI 78.9-99.9%) for inheritance of maternal genotype.Conclusions: RMD for detection of inheritance of maternal β-thalassaemia mutations has potential for clinical use. Our sequential approach could be applied to other single-gene disorders.Tweetable Abstract: NIPT for β-thalassaemia achieved using nested-PCR followed by relative mutation dosage. [ABSTRACT FROM AUTHOR]

Objective: To examine preferences for follow-up testing in women screened with high or intermediate risk for Down syndrome in the first or second trimester.Design: Prospective cohort study.Setting: Three public hospitals in Hong Kong, China.Sample: Women with pregnancies termed as high risk (≥1:250; HR) or intermediate risk (1:251-1200; IR) for Down syndrome.Methods: Women with pregnancies screened as HR were offered the choices of: (1) an invasive test plus chromosomal microarray (CMA) to obtain more detailed fetal genetic information; (2) non-invasive cell-free prenatal DNA screening (NIPT) to detect trisomies 13, 18 and 21, and to avoid procedure-related miscarriage; and (3) to decline any further testing. Women received standardised counselling informing them that the reporting times were identical, the procedure miscarriage risk was 0.1-0.2% and that there was no charge for screening. Women with IR pregnancies (1:251-1200) were offered NIPT as a secondary screening test.Main Outcome Measures: Uptake rate for NIPT.Results: Three hundred and forty-seven women had pregnancies deemed as HR; 344 (99.1%) women opted for follow-up testing, 216 (62.2%) of whom chose NIPT. Five hundred and seven of 614 women (82.6%) with IR risk chose NIPT. Seven (21%) of 34 women with nuchal translucency ≥3.5 mm opted for NIPT.Conclusion: In a setting where reporting times are similar and there is no cost difference between options, approximately 60% of women with pregnancies classed as HR would opt for NIPT, offering simple but limited aneuploidy assessment, over a diagnostic procedure with comprehensive and more detailed assessment.Tweetable Abstract: 60% of pregnant Chinese women prefer NIPT over CMA when screened as high risk for Down syndrome. [ABSTRACT FROM AUTHOR]

Objective: To assess the potential of screening for pre-eclampsia (PE) in a Chinese population.Design: Case-control study.Setting: Teaching hospital in Hong Kong.Population: A total of 3330 women having a viable singleton pregnancy attending first-trimester Down-syndrome screening.Methods: Mean arterial pressure (MAP), bilateral uterine artery pulsatility index (UtA-PI), and placental growth factor (PlGF) were measured. Screening markers were transformed to multiples of the gestational median (MoM) and adjusted for maternal and pregnancy characteristics. MoM distributions in PE and non-PE pregnancies were compared with published expected values. PE screening performance was assessed using area under receiver operating curves (AUROC).Main Outcome Measures: PE detection rate.Results: A total of 30 (0.9%) women developed either early (<34 weeks) or late (≥34 weeks) onset PE. MAP was dependent on maternal BMI, UtA-PI on fetal crown rump length, uterine artery peak systolic velocity (UtA-PSV) on maternal age and gestation, and PlGF on gestation in non-PE pregnancies. MoM distributions determined using published Fetal Medicine Foundation models deviated significantly from one for both MAP (P < 0.0001) and PI (P < 0.0001), but not PlGF (P = 0.52) in non-PE pregnancies, whilst PlGF MoM distributions in those who developed early as opposed to late onset PE were significantly higher (P = <0.05). AUROC for any PE using multiple markers was 0.72 (95% CI: 0.64-0.81) with detection rates of 72 and 55% for early and late PE, respectively, for a 10% false positive rate.Conclusion: Detection rates for PE in our Chinese population were lower than the expected 90-95% even after adjusting MoM for local women's characteristics.Funding: General Research Fund (Project number 470513).Tweetable Abstract: Pre-eclampsia screening in the Chinese population had detection rates lower than previously published results. [ABSTRACT FROM AUTHOR]

The article explores opportunities for improving risk communication about noninvasive prenatal tests (NIPT) for having a child affected by Down syndrome to help pregnant women make informed decisions about their pregnancy. The suggested strategies discussed include discouraging the use of the 1-in-X format, use of the same denominator such as number of babies tested when comparing ratios, use of visual aids to explain possible test outcomes, and discussing test failure as an outcome.

Objective: Gestational diabetes mellitus (GDM) potentially harms the child before birth. We previously found GDM to be associated with developmental changes in the central nervous system. We now hypothesise that GDM may also impact on the fetal autonomic nervous system under metabolic stress like an oral glucose tolerance test (OGTT).Design: We measured heart rate variability (HRV) of mothers and fetuses during a three-point OGTT using fetal magnetocardiography (fMCG).Setting: Measurements were performed in the fMEG Centre in Tübingen.Population: After exclusion of 23 participants, 13 pregnant women with GDM and 36 pregnant women with normal glucose tolerance were examined.Methods: All women underwent the same examination setting with OGTT during which fMCG was recorded three times.Main Outcome Measure(s): Parameters of heart rate variability were measured.Results: Compared with mothers with normal glucose regulation, mothers with GDM showed increased heart rate but no significant differences of maternal HRV. In contrast, HRV in fetuses of mothers with GDM differed from those in the metabolically healthy group regarding standard deviation normal to normal beat (SDNN) (P = 0.012), low-frequency band (P = 0.008) and high-frequency band (P = 0.031). These HRV parameters exhibit a decrease only in GDM fetuses during the second hour of the OGTT.Conclusions: These results show an altered response of the fetal autonomic nervous system to metabolic stress in GDM-complicated pregnancies. Hence, disturbances in maternal glucose metabolism might not only impact on the central nervous system of the fetus but may also affect the fetal autonomic nervous system.Tweetable Abstract: Metabolic stress reveals a different response of fetal autonomic nervous system in GDM-complicated pregnancies. [ABSTRACT FROM AUTHOR]

Objectives: To assess in pregnant women with HIV the rates of amniocentesis and chorionic villus sampling (CVS), and the outcomes associated with such procedures.Design: Observational study. Data from the Italian National Program on Surveillance on Antiretroviral Treatment in Pregnancy were used.Setting: University and hospital clinics.Population: Pregnant women with HIV.Methods: Temporal trends were analysed by analysis of variance and by the Chi-square test for trend. Quantitative variables were compared by Student's t-test and categorical data by the Chi-square test, with odds ratios and 95% confidence intervals calculated.Main Outcome Measures: Rate of invasive testing, intrauterine death, HIV transmission.Results: Between 2001 and 2015, among 2065 pregnancies in women with HIV, 113 (5.5%) had invasive tests performed. The procedures were conducted under antiretroviral treatment in 99 cases (87.6%), with a significant increase over time in the proportion of tests performed under highly active antiretroviral therapy (HAART) (100% in 2011-2015). Three intrauterine deaths were observed (2.6%), and 14 pregnancies were terminated because of fetal anomalies. Among 96 live newborns, eight had no information available on HIV status. Among the remaining 88 cases with either amniocentesis (n = 75), CVS (n = 12), or both (n = 1), two HIV transmissions occurred (2.3%). No HIV transmission occurred among the women who were on HAART at the time of invasive testing, and none after 2005.Conclusions: The findings reinforce the assumption that invasive prenatal testing does not increase the risk of HIV vertical transmission among pregnant women under suppressive antiretroviral treatment.Tweetable Abstract: No HIV transmission occurred among women who underwent amniocentesis or CVS under effective anti-HIV regimens. [ABSTRACT FROM AUTHOR]

Objective: To validate a symptom-based fistula screening questionnaire and estimate obstetric fistula (OF) prevalence in rural Nepal.Design: Cross-sectional and nested case-control study.Setting: Sarlahi District, Nepal.Population: Parous, reproductive age women.Methods: The questionnaire assessed symptoms of vesicovaginal and rectovaginal fistula (VVF and RVF, respectively), stress and urge urinary incontinence (SUI and UUI, respectively), fecal incontinence (FI), and included interviewer observations on the smell and presence of urine and/or stool. All women who screened positive for OF and a randomly selected group of women who screened negative for OF were included in a nested case-control study (one case, four normal controls, and four incontinent controls) and underwent confirmatory clinical examinations.Main Outcome Measures: Clinically confirmed OF, and questionnaire sensitivity (Se) and specificity (Sp).Results: Of the 16 893 women who completed cross-sectional screening, 68 were screened-positive cases. Fifty-five (82%) screened-positive cases, 203 screened-negative normal controls, and 203 screened-incontinent controls participated in the case-control study, which confirmed one case of VVF and one case of both VVF and RVF without any false-negative cases. For VVF, the screening tool demonstrated Se 100% (95% CI 34.2-100.0%), Sp 86.9% (95% CI 83.3-89.9%), and estimated VVF prevalence as 12 per 100 000 (95% CI 3-43); for RVF, it demonstrated Se 100% (95% CI 20.7-100.0), Sp 99.8% (95% CI 98.6-100.0), and estimated RVF prevalence as 6 per 100 000 (95% CI 1-34).Conclusions: The OF screening questionnaire demonstrated high sensitivity and specificity in this low-prevalence setting.Tweetable Abstract: Community-based obstetric fistula screening tool validation study, Nepal, n = 16 893: High Se, Sp & feasibility. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the national antenatal syphilis screening programme and provide evidence for improving screening and management strategies.Design: National population-based surveillance.Setting: United Kingdom (UK).Population: All pregnant women screening positive for syphilis, 2010-2011.Methods: Demographic, laboratory and treatment details for each pregnancy were collected from UK antenatal units (~210), along with follow-up information on all infants born to women requiring syphilis treatment in pregnancy.Main Outcome Measures: Proportion of women with newly or previously diagnosed syphilis among those with positive screening tests in pregnancy; proportion requiring treatment.Results: Overall, 77% (1425/1840) of reported pregnancies were confirmed syphilis screen-positive. Of these, 71% (1010/1425) were in women with previously diagnosed syphilis (155 requiring treatment), 26% (374/1425) with newly diagnosed syphilis (all requiring treatment) and 3% (41/1425) required treatment but the reason for treatment was unclear. Thus 40% (570/1425) required treatment overall; of these, 96% (516/537) were treated (missing data: 33/570), although for 18% (83/456), this was not until the third trimester (missing data: 60/537). Follow up of infants born to treated women was poor, with at least a third not followed. Six infants were diagnosed with congenital syphilis; two mothers were untreated, three had delayed treatment and one had incomplete treatment (first trimester).Conclusion: Over 2 years, among pregnant women with confirmed positive syphilis screening results in the UK, a quarter had newly diagnosed infections and 40% required treatment. Despite high uptake of treatment, antenatal syphilis management could be improved by earlier detection, earlier treatment, and stronger links between healthcare teams.Tweetable Abstract: 25% of pregnant women screening positive for syphilis in the UK were newly diagnosed and 40% needed treatment. [ABSTRACT FROM AUTHOR]