Showing papers in "Ultrasound in Obstetrics & Gynecology in 2016"

Zika virus intrauterine infection causes fetal brain abnormality and microcephaly: tip of the iceberg?

Abstract: An unexpected upsurge in diagnosis of fetal and pediatric microcephaly has been reported in the Brazilian press recently. Cases have been diagnosed in nine Brazilian states so far. By 28 November 2015, 646 cases had been reported in Pernambuco state alone. Although reports have circulated regarding the declaration of a state of national health emergency, there is no information on the imaging and clinical findings of affected cases. Authorities are considering different theories behind the ‘microcephaly outbreak’, including a possible association with the emergence of Zika virus disease within the region, the first case of which was detected in May 20151. Zika virus is a mosquito-borne disease closely related to yellow fever, dengue, West Nile and Japanese encephalitis viruses2. It was first identified in 1947 in the Zika Valley in Uganda and causes a mild disease with fever, erythema and arthralgia. Interestingly, vertical transmission to the fetus has not been reported previously, although two cases of perinatal transmission, occurring around the time of delivery and causing mild disease in the newborns, have been described3. We have examined recently two pregnant women from the state of Paraiba who were diagnosed with fetal microcephaly and were considered part of the ‘microcephaly cluster’ as both women suffered from symptoms related to Zika virus infection. Although both patients had negative blood results for Zika virus, amniocentesis and subsequent quantitative real-time polymerase chain reaction4, performed after ultrasound diagnosis of fetal microcephaly and analyzed at the Oswaldo Cruz Foundation, Rio de Janeiro, Brazil, was positive for Zika virus in both patients, most likely representing the first diagnoses of intrauterine transmission of the virus. The sequencing analysis identified in both cases a genotype of Asian origin. In Case 1, fetal ultrasound examination was performed at 30.1 weeks’ gestation. Head circumference (HC) was 246 mm (2.6 SD below expected value) and weight was estimated as 1179 g (21st percentile). Abdominal circumference (AC), femur length (FL) and transcranial Doppler were normal for gestational age as was the width of the lateral ventricles. Anomalies were limited to the brain and included brain atrophy with coarse calcifications involving the white matter of the frontal lobes, including the caudate, lentostriatal vessels and cerebellum. Corpus callosal and vermian dysgenesis and enlarged cisterna magna were observed (Figure 1). In Case 2, fetal ultrasound examination was performed at 29.2 weeks’ gestation. HC was 229 mm (3.1 SD below Figure 1 Case 1: (a) Transabdominal axial ultrasound image shows cerebral calcifications with failure of visualization of a normal vermis (large arrow). Calcifications are also present in the brain parenchyma (small arrow). (b) Transvaginal sagittal image shows dysgenesis of the corpus callosum (small arrow) and vermis (large arrow). (c) Coronal plane shows a wide interhemispheric fissure (large arrow) due to brain atrophy and bilateral parenchymatic coarse calcifications (small arrows). (d) Calcifications are visible in this more posterior coronal view and can be seen to involve the caudate (arrows).

Consensus definition of fetal growth restriction: a Delphi procedure

Abstract: Objective To determine, by expert consensus, a definition for early and late fetal growth restriction (FGR) through a Delphi procedure. Method A Delphi survey was conducted among an international panel of experts on FGR. Panel members were provided with 18 literature-based parameters for defining FGR and were asked to rate the importance of these parameters for the diagnosis of both early and late FGR on a 5-point Likert scale. Parameters were described as solitary parameters (parameters that are sufficient to diagnose FGR, even if all other parameters are normal) and contributory parameters (parameters that require other abnormal parameter(s) to be present for the diagnosis of FGR). Consensus was sought to determine the cut-off values for accepted parameters. Results A total of 106 experts were approached, of whom 56 agreed to participate and entered the first round, and 45 (80%) completed all four rounds. For early FGR ( 95th centile in either the UA or uterine artery) were agreed upon. For late FGR (≥ 32 weeks), two solitary parameters (AC or EFW two quartiles on growth charts and cerebroplacental ratio 95th centile) were defined. Conclusion Consensus-based definitions for early and late FGR, as well as cut-off values for parameters involved, were agreed upon by a panel of experts. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Systematic approach to sonographic evaluation of the pelvis in women with suspected endometriosis, including terms, definitions and measurements: a consensus opinion from the International Deep Endometriosis Analysis (IDEA) group

Abstract: The IDEA (International Deep Endometriosis Analysis group) statement is a consensus opinion on terms, definitions and measurements that may be used to describe the sonographic features of the different phenotypes of endometriosis. Currently, it is difficult to compare results between published studies because authors use different terms when describing the same structures and anatomical locations. We hope that the terms and definitions suggested herein will be adopted in centers around the world. This would result in consistent use of nomenclature when describing the ultrasound location and extent of endometriosis. We believe that the standardization of terminology will allow meaningful comparisons between future studies in women with an ultrasound diagnosis of endometriosis and should facilitate multicenter research. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

ISUOG Practice Guidelines: role of ultrasound in twin pregnancy.

Abstract: The International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) is a scientific organization that encourages sound clinical practice, and high quality teaching and research related to diagnostic imaging in women's healthcare. The ISUOG Clinical Standards Com mittee (CSC) has a remit to develop Practice Gui delines and Consensus Statements as educational recommendations that provide healthcare practit ioners with a consensus based approach, from experts, for diagnostic imaging. They are intended to reflect what is considered by ISUOG to be the best practice at the time at which they are issued. Although ISUOG has made every effort to ensure that Guidelines are accurate when issued, neither the Society nor any of its employees or members accepts any liability for the consequences of any inaccurate or misleading data, opinions or state ments issued by the CSC. The ISUOG CSC docu ments are not intended to establish a legal stan dard of care because interpretation of the eviden ce that underpins the Guidelines may be influen ced by individual circumstances, local protocol and available resources. Approved Guidelines can be distributed freely with the permission of ISUOG (info@isuog.org).

Proposal for standardized ultrasound descriptors of abnormally invasive placenta (AIP)

Abstract: *The Nuffield Department of Obstetrics & Gynaecology, University of Oxford, Oxford, UK; †The Fetal Medicine Unit, John Radcliffe Hospital, Oxford, UK; ‡Department of Obstetrics and Division of Experimental Obstetrics, Study Group Perinatal Programming, Charité Campus Virchow, Berlin, Germany; §Department of Obstetrics and Gynecology, General Faculty Hospital, Charles University, Prague, Czech Republic; ¶Department of Obstetrics, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; **Centre Hospitalier Régional Universitaire de Nancy, Université de Lorraine, Nancy, France; ††Fetomaternal Medical Center, Department of Obstetrics and Gynecology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland; ‡‡Prenatal Zürich, Zürich, Switzerland; §§Medical Faculty, Heinrich Heine University, Düsseldorf, Germany; ¶¶University of Liège, CHR de la Citadelle, Liège, Belgium *Correspondence. (e-mail: sally.collins@obs-gyn.ox.ac.uk)

Vaginal progesterone decreases preterm birth ≤ 34 weeks of gestation in women with a singleton pregnancy and a short cervix: an updated meta-analysis including data from the OPPTIMUM study.

Abstract: Objective To evaluate the efficacy of vaginal progesterone administration for preventing preterm birth and perinatal morbidity and mortality in asymptomatic women with a singleton gestation and a mid-trimester sonographic cervical length (CL) ≤ 25 mm. Methods This was an updated systematic review and meta-analysis of randomized controlled trials comparing the use of vaginal progesterone to placebo/no treatment in women with a singleton gestation and a mid-trimester sonographic CL ≤ 25 mm. Electronic databases, from their inception to May 2016, bibliographies and conference proceedings were searched. The primary outcome measure was preterm birth ≤ 34 weeks of gestation or fetal death. Two reviewers independently selected studies, assessed the risk of bias and extracted the data. Pooled relative risks (RRs) with 95% confidence intervals (CI) were calculated. Results Five trials involving 974 women were included. A meta-analysis, including data from the OPPTIMUM study, showed that vaginal progesterone significantly decreased the risk of preterm birth ≤ 34 weeks of gestation or fetal death compared to placebo (18.1% vs 27.5%; RR, 0.66 (95% CI, 0.52–0.83); P = 0.0005; five studies; 974 women). Meta-analyses of data from four trials (723 women) showed that vaginal progesterone administration was associated with a statistically significant reduction in the risk of preterm birth occurring at < 28 to < 36 gestational weeks (RRs from 0.51 to 0.79), respiratory distress syndrome (RR, 0.47 (95% CI, 0.27–0.81)), composite neonatal morbidity and mortality (RR, 0.59 (95% CI, 0.38–0.91)), birth weight < 1500 g (RR, 0.52 (95% CI, 0.34–0.81)) and admission to the neonatal intensive care unit (RR, 0.67 (95% CI, 0.50–0.91)). There were no significant differences in neurodevelopmental outcomes at 2 years of age between the vaginal progesterone and placebo groups. Conclusion This updated systematic review and meta-analysis reaffirms that vaginal progesterone reduces the risk of preterm birth and neonatal morbidity and mortality in women with a singleton gestation and a mid-trimester CL ≤ 25 mm, without any deleterious effects on neurodevelopmental outcome. Clinicians should continue to perform universal transvaginal CL screening at 18–24 weeks of gestation in women with a singleton gestation and to offer vaginal progesterone to those with a CL ≤ 25 mm. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

ISUOG Interim Guidance on ultrasound for Zika virus infection in pregnancy: information for healthcare professionals

Abstract: In response to the World Health Organization (WHO) statements and international concerns regarding the Zika virus (ZIKV) outbreak, ISUOG is publishing the following guidance for ultrasound during pregnancy. With the current uncertainty regarding many aspects of the diagnosis and clinical course of ZIKV infection in pregnancy, potentially valuable information may be obtained by ultrasound practitioners that may help in counseling pregnant women and further improve our understanding of the pathophysiology of ZIKV infection in pregnancy. This statement is not intended to replace previously published interim guidance on evaluation and management of ZIKV-exposed pregnant women. It should therefore be considered in conjunction with other relevant advice from organizations such as:

Risk of fetal loss associated with invasive testing following combined first-trimester screening for Down syndrome: a national cohort of 147,987 singleton pregnancies.

Abstract: Objective To assess prospectively the risk of fetal loss associated with chorionic villus sampling (CVS) and amniocentesis (AC) following combined first-trimester screening (cFTS) for Down syndrome. Methods This was a nationwide population-based study (Danish Fetal Medicine Database, 2008–2010) including 147 987 women with singleton pregnancy who underwent cFTS. Propensity score stratification was used to assess the risk of fetal loss with and without invasive testing. Analyses were performed between 3 and 21 days after cFTS for CVS and between 28 and 42 days after cFTS for AC. Results are reported as average risk differences with 95% CIs. Results The risks of miscarriage and stillbirth were not higher in women exposed to CVS or AC compared with unexposed women, independent of the analysis time-point. The average effect of CVS on risk of miscarriage was –0.08% (95% CI, −0.64; 0.47) at 3 days and –0.21% (95% CI, –0.58; 0.15) at 21 days after cFTS, while the effect on risk of stillbirth was –0.18% (95% CI, –0.50; 0.13) at 3 days and –0.27% (95% CI, –0.58; 0.04) at 21 days after cFTS. Regarding the effect of AC on risk of miscarriage, the analysis at 28 days after cFTS showed an average effect of 0.56% (95% CI, –0.21; 1.33), while the effect on risk of stillbirth was 0.09% (95% CI, –0.39; 0.58) at 42 days after cFTS. Conclusion Neither CVS nor AC was associated with increased risk of miscarriage or stillbirth. These findings indicate that the procedure-related risk of CVS and AC is very low. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Value of third-trimester cerebroplacental ratio and uterine artery Doppler indices as predictors of stillbirth and perinatal loss.

Abstract: Objective Placental insufficiency contributes to the risk of stillbirth. Cerebroplacental ratio (CPR) is an emerging marker of placental insufficiency. The aim of this study was to evaluate the association of third-trimester fetal CPR, uterine artery (UtA) Doppler and estimated fetal weight (EFW) with stillbirth and perinatal death. Methods This was a retrospective cohort study including 2812 women with a singleton pregnancy who underwent an ultrasound scan in the third trimester. EFWs were converted into centiles, and Doppler indices (UtA and CPR) were converted into multiples of the median (MoM), adjusting for gestational age. Regression analysis was performed to identify, and adjust for, potential confounders, and receiver–operating characteristics (ROC) curve analysis was used to assess the predictive value. Results When adjusting for EFW centile and UtA mean pulsatility index (UtA-PI) MoM, CPR-MoM remained an independent predictor of stillbirth (odds ratio (OR) = 0.003 (95% CI, 0.00–0.11), P = 0.003) and perinatal mortality (OR = 0.001 (95% CI, 0.00–0.03), P < 0.001). UtA-PI ≥ 1.5 MoM was significantly associated with low CPR-MoM, even after adjusting for EFW centile (OR = 5.22 (95% CI, 3.88–7.04), P < 0.001) or small-for-gestational age (SGA; OR = 4.73 (95% CI, 3.49–6.41), P < 0.001). These associations remained significant, even when excluding pregnancies with SGA or including only cases in which Doppler indices were recorded at term (P < 0.01). For prediction of stillbirth, the area under the ROC curve, using a combination of these three parameters, was 0.88 (95% CI, 0.77–0.99) with a sensitivity of 66.7%, specificity of 92.1%, positive likelihood ratio (LR) of 8.46 and negative LR of 0.36. Conclusions Third-trimester CPR is an independent predictor of stillbirth and perinatal mortality. The role of UtA Doppler, CPR and EFW in assessing risk of adverse pregnancy outcome should be evaluated prospectively. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Accuracy of transvaginal ultrasound for diagnosis of deep endometriosis in the rectosigmoid: systematic review and meta-analysis

Abstract: Objectives To review the diagnostic accuracy of transvaginal ultrasound (TVS) in the preoperative detection of rectosigmoid endometriosis in patients with clinical suspicion of deep infiltrating endometriosis (DIE), comparing enhanced (E-TVS) and non-enhanced approaches. Methods An extensive search was performed in MEDLINE (PubMed) and EMBASE for studies published between January 1989 and December 2014. The eligibility criterion was use of TVS for preoperative detection of rectosigmoid endometriosis in women with clinical suspicion of DIE, using surgical data as the reference standard. Study quality was assessed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. Results Our extended search identified a total of 801 citations, among which 19 studies (n = 2639) were considered eligible and included in the meta-analysis. Overall pooled sensitivity, specificity, positive likelihood ratio (LR+) and negative likelihood ratio (LR–) of TVS for detecting DIE in the rectosigmoid were 91% (95%CI, 85–94%), 97% (95%CI, 95–98%), 33.0 (95%CI, 18.6–58.6) and 0.10 (95%CI, 0.06–0.16), respectively. Significant heterogeneity was found for sensitivity (I2, 90.8%; Cochran Q, 195.2; P < 0.001) and specificity (I2, 76.8%; Cochran Q, 77.7; P < 0.001). We did not find statistical differences between non-enhanced TVS and E-TVS (P = 0.304). Conclusion Overall diagnostic performance of TVS for DIE of the rectosigmoid is good. However, further studies with improved quality in design are needed. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Screening for trisomies by cell-free DNA testing of maternal blood: consequences of a failed result

Abstract: Objectives First, to report the distribution of the fetal fraction of cell-free (cf) DNA and the rate of a failed cfDNA test result in trisomies 21, 18 and 13, by comparison with pregnancies unaffected by these trisomies, second, to examine the possible effects of maternal and fetal characteristics on the fetal fraction, and third, to consider the options for further management of pregnancies with a failed result. Methods This was a cohort study of 10 698 singleton pregnancies undergoing screening for fetal trisomies 21, 18 and 13 by cfDNA testing at 10–14 weeks' gestation. There were 160 cases of trisomy 21, 50 of trisomy 18, 16 of trisomy 13 and 10 472 were unaffected by these trisomies. Multivariate regression analysis was used to determine significant predictors of fetal fraction and a failed cfDNA test result amongst maternal and fetal characteristics. Results Fetal fraction decreased with increasing body mass index and maternal age, was lower in women of South Asian racial origin than in Caucasians and in assisted compared to natural conceptions. It increased with fetal crown–rump length and higher levels of serum pregnancy-associated plasma protein-A and free β-human chorionic gonadotropin. The median fetal fraction was 11.0% (interquartile range (IQR), 8.3–14.4%) in the unaffected group, 10.7% (IQR, 7.8–14.3%) in trisomy 21, 8.6% (IQR, 5.0–10.2%) in trisomy 18 and 7.0% (IQR, 6.0–9.4%) in trisomy 13. There was a failed result from cfDNA testing after first sampling in 2.9% of the unaffected group, 1.9% of trisomy 21, 8.0% of trisomy 18 and 6.3% of trisomy 13. In the cases with a failed result, 7% of women had invasive testing, mainly because of high risk from the combined test and/or presence of sonographic features suggestive of trisomies 18 and 13. All cases of trisomies were detected prenatally. Conclusions In cases of a failed cfDNA test, the rate of trisomies 18 and 13, but not trisomy 21, is higher than in those with a successful test. In the management of such cases, the decision in favor of invasive testing should depend on the risk of prior screening and the results of detailed ultrasound examination. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Ultrasound-based gestational-age estimation in late pregnancy.

Abstract: This project was supported by a generous grant from the Bill & Melinda Gates Foundation to the University of Oxford.

Clinical implementation of routine screening for fetal trisomies in the UK NHS: cell-free DNA test contingent on results from first-trimester combined test

Abstract: Objectives Cell-free DNA (cfDNA) analysis of maternal blood for detection of trisomies 21, 18 and 13 is superior to other methods of screening but is expensive. One strategy to maximize performance at reduced cost is to offer cfDNA testing contingent on the results of the first-trimester combined test that is used currently. The objectives of this study were to report the feasibility of implementing such screening, to examine the factors affecting patient decisions concerning their options for screening and decisions on the management of affected pregnancies and to report the prenatal diagnosis of fetal trisomies and outcome of affected pregnancies following the introduction of contingent screening. Methods We examined routine clinical implementation of contingent screening in 11 692 singleton pregnancies in two National Health Service (NHS) hospitals in the UK. Women with a risk ≥ 1 in 100 (high-risk group) were offered options of invasive testing, cfDNA testing or no further testing, and those with a risk between 1 in 101 and 1 in 2500 (intermediate-risk group) were offered cfDNA testing or no further testing. The trisomic status of the pregnancies was determined by prenatal or postnatal karyotyping or by examination of the neonates. Results In the study population of 11 692 pregnancies, there were 47 cases of trisomy 21 and 28 of trisomies 18 or 13. Screening with the combined test followed by invasive testing for all patients in the high-risk group potentially could have detected 87% of trisomy 21 and 93% of trisomies 18 or 13, at a false-positive rate of 3.4%; the respective values for cfDNA testing in the high- and intermediate-risk groups were 98%, 82% and 0.25%. However, in the high-risk group, 38% of women chose invasive testing and 60% chose cfDNA testing; in the intermediate-risk group 92% opted for cfDNA testing. A prenatal diagnosis was made in 43 (91.5%) pregnancies with trisomy 21 and all pregnancies with trisomies 18 or 13. In many affected pregnancies the parents chose to avoid testing or termination and 32% of pregnancies with trisomy 21 resulted in live births. Conclusions Screening for fetal trisomies by cfDNA analysis of maternal blood, contingent on the results of the combined test, can be implemented easily in routine clinical practice. In the high-risk group from the combined test, most but not all women chose cfDNA testing rather than invasive testing. Performance of screening for trisomy 21 was superior by the cfDNA test than by the combined test. However, prenatal detection of trisomies and pregnancy outcome depend not only on performance of screening tests but also on parental choice. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Clinical experience with single-nucleotide polymorphism-based non-invasive prenatal screening for 22q11.2 deletion syndrome.

Abstract: Objectives To evaluate the performance of a single-nucleotide polymorphism (SNP)-based non-invasive prenatal test (NIPT) for the detection of fetal 22q11.2 deletion syndrome in clinical practice, assess clinical follow-up and review patient choices for women with high-risk results. Methods In this study, 21 948 samples were submitted for screening for 22q11.2 deletion syndrome using a SNP-based NIPT and subsequently evaluated. Follow-up was conducted for all cases with a high-risk result. Results Ninety-five cases were reported as high risk for fetal 22q11.2 deletion. Diagnostic testing results were available for 61 (64.2%) cases, which confirmed 11 (18.0%) true positives and identified 50 (82.0%) false positives, resulting in a positive predictive value (PPV) of 18.0%. Information regarding invasive testing was available for 84 (88.4%) high-risk cases: 57.1% (48/84) had invasive testing and 42.9% (36/84) did not. Ultrasound anomalies were present in 81.8% of true-positive and 18.0% of false-positive cases. Two additional cases were high risk for a maternal 22q11.2 deletion; one was confirmed by diagnostic testing and one had a positive family history. There were three pregnancy terminations related to screening results of 22q11.2 deletion, two of which were confirmed as true positive by invasive testing. Conclusions Clinical experience with this SNP-based non-invasive screening test for 22q11.2 deletion syndrome indicates that these deletions have a frequency of approximately 1 in 1000 in the referral population with most identifiable through this test. Use of this screening method requires the availability of counseling and other management resources for high-risk pregnancies. © 2015 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd. on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Birthweight in live births and stillbirths

Abstract: Objective To establish a normal range of birthweight with gestational age at delivery and compare the proportion of live births and stillbirths that are classified as small for gestational age (SGA) according to our normal range versus that of the INTERGROWTH-21st standard. Methods The study population comprised of 113,019 live births and 437 (0.4%) stillbirths. The inclusion criteria for establishment of a normal range of birthweight for gestational age were: firstly, delivery of live birth of phenotypically normal neonate at ≥ 24 weeks’ gestation, secondly, no smoking and no maternal pre-pregnancy hypertension, diabetes mellitus, systemic lupus erythematosus or antiphospholipid syndrome and thirdly, no preeclampsia, gestational hypertension, gestational diabetes mellitus or iatrogenic preterm birth for fetal growth restriction in the current pregnancy. These criteria were met by 92,018 live births. The proportion of live births and stillbirths with birthweight below the 5th and 10th percentiles of our normal range and that according to the INTERGROWTH-21st standard were determined and compared by the Chi-square test and McNemar test. Results The proportion of live births and stillbirths with birthweight <5th percentile according to our standard (5.6% and 37.2%, respectively) were significantly higher than and discordant to those according to the INTERGROWTH-21st standard (3.4% and 22.7%, respectively). Similarly, the proportion of live births and stillbirths with birthweight <10th percentile according to our standard (11.2% and 44.3%, respectively) were significantly higher than and discordant to those according to the INTERGROWTH-21st standard (6.9% and 32.6%, respectively). Conclusion The INTERGROWTH-21st standard underestimates the proportion of SGA in live births and stillbirths in our population.

ISUOG Practice Guidelines: invasive procedures for prenatal diagnosis

Abstract: The International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) is a scientific organization that encourages sound clinical practice, and high-quality teaching and research related to diagnostic imaging in women’s healthcare. The ISUOG Clinical Standards Committee (CSC) has a remit to develop Practice Guidelines and Consensus Statements that provide healthcare practitioners with a consensus-based approach. They are intended to reflect what is considered by ISUOG to be the best practice at the time at which they are issued. Although ISUOG has made every effort to ensure that Guidelines are accurate when issued, neither the Society nor any of its employees or members accepts any liability for the consequences of any inaccurate or misleading data, opinions or statements issued by the CSC. The ISUOG CSC documents are not intended to establish a legal standard of care because interpretation of the evidence that underpins the Guidelines may be influenced by individual circumstances, local protocol and available resources. Approved Guidelines can be distributed freely with the permission of ISUOG (info@isuog.org).

Synthesizing Evidence from Diagnostic Accuracy TEsts: the SEDATE guideline.

Abstract: Although commonly overlooked during the writing and reporting process, most readers will look at only the abstract, so it is essential to convey as much quantitative information as possible, given the space limitations set by the journal. Suggested subheadings include ‘Introduction’ (specifying the current state of knowledge in the field, the gap that this study aims to cover, i.e. objectives), ‘Methods’ (search strategy, eligibility criteria, outcomes and statistical analysis), ‘Results’ (study selection and main results with numerical estimates) and ‘Conclusion’ (clinical interpretation of results and suggestions for future research).

Surgical treatment of Cesarean scar ectopic pregnancy: efficacy and safety of ultrasound-guided suction curettage.

Abstract: Objectives To assess the efficacy of ultrasound-guided suction curettage for management of pregnancies implanted into the lower uterine segment Cesarean section scar. Methods This was a retrospective study including women diagnosed with Cesarean section scar pregnancy at two large tertiary referral early pregnancy units between 1997 and 2014. Surgical evacuation was offered to selected women presenting in the first trimester ≤ 14 weeks' gestation. All procedures were performed transcervically under ultrasound guidance using suction curettage. A modified Shirodkar cervical suture was used in women who required additional measures to secure hemostasis. Results A total of 232 women with Cesarean section scar pregnancy were seen at the referral units; 191/232 (82.3%) women were treated surgically. The median intraoperative blood loss was 100 mL (range, 10–3000 mL); 9/191 (4.7% (95% CI, 1.7–7.7%)) women required blood transfusion and, in one (0.5% (95% CI, 0–1.5%)), life-saving hysterectomy had to be performed because of uncontrollable intraoperative bleeding. Of the women who attended for follow-up, 7/116 (6.0% (95% CI, 1.7–10.3%)) required a repeat surgical procedure because of retained products of conception. Multivariable analysis showed that the gestational sac diameter (odds ratio (OR), 1.10 (95% CI, 1.03–1.17)) and pregnancy vascularity on Doppler examination (OR, 3.41 (95% CI, 1.39–8.33)) were significant predictors of heavy intraoperative blood loss (> 1000 mL). Conclusions Ultrasound-guided suction curettage is an effective method for the treatment of pregnancies implanted into a lower uterine segment Cesarean section scar and is associated with a low risk of blood transfusion and hysterectomy. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Fetal cardiovascular remodeling persists at 6 months in infants with intrauterine growth restriction.

Abstract: This work was supported by grants from Instituto de Salud Carlos III (grant numbers PI11/00051, PI12/00801, PI11/01709) and from the Ministerio de Economia y Competitividad (grant number SAF2012‐37196), and cofinanced by the Fondo Europeo de Desarrollo Regional de la Union Europea ‘Una manera de hacer Europa’, Fundacion Mutua Madrilena, Fundacio Agrupacio Premi Ambit de la Infancia (Spain) and Cerebra Foundation for the Brain Injured Child (Carmarthen, Wales, UK). B.V.A. was supported by Programa de Ayudas Postdoctorales FI Agaur (2013FI_B 00667). M.C.L. and B.V.A. wish to express their gratitude to the Mexican National Council of Science and Technology (CONACyT, Mexico City, Mexico) for partially supporting their predoctoral studies at Hospital Clinic, Barcelona, Spain.

Prevention of pre-eclampsia by low-molecular-weight heparin in addition to aspirin: a meta-analysis.

Abstract: Objective To estimate the impact of adding low-molecular-weight heparin (LMWH) or unfractionated heparin to low-dose aspirin started ≤ 16 weeks' gestation on the prevalence of pre-eclampsia (PE) and the delivery of a small-for-gestational-age (SGA) neonate. Methods A systematic review and meta-analysis of randomized controlled trials (RCTs) was performed by searching the medical databases PubMed, EMBASE, Web of Science and Cochrane Central. Pregnant women randomized to receive LMWH or unfractionated heparin in addition to low-dose aspirin were compared with those who received low-dose aspirin alone. Outcome measures were PE, severe PE, early-onset PE and SGA. Pooled relative risks (RRs) with 95% CI were calculated using a random-effects model. Results Eight RCTs met the inclusion criteria; the indication for recruitment was previous recurrent miscarriage in five studies (three included women with thrombophilia) and a history of severe or early-onset PE in three studies (including women with thrombophilia in one). LMWH was administered in seven studies and unfractionated heparin in one. In women with a history of PE, treatment with LMWH and aspirin, compared with aspirin alone, was associated with a significant reduction in development of PE (three trials (n = 379); RR, 0.54 (95% CI, 0.31–0.92); P = 0.03) and in delivery of SGA neonates (two trials (n = 363); RR, 0.54 (95% CI, 0.32–0.91); P = 0.02). These outcomes were not significantly reduced in women with recurrent miscarriage who received LMWH and aspirin, compared with aspirin alone. The small number of studies precluded sensitivity analyses and the evaluation of publication biases. Blinding to the allocation treatment was absent in all RCTs. Conclusions Based on limited evidence, the addition of LMWH to low-dose aspirin could reduce the prevalence of PE and SGA in women with a history of PE. This observation should be the basis of a well-conducted future trial rather than a recommendation for immediate clinical application. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Competing-risks model in screening for pre-eclampsia by maternal factors and biomarkers at 35–37 weeks' gestation

Abstract: Objective To develop a model for prediction of term pre-eclampsia (PE) based on a combination of maternal factors and late third-trimester biomarkers. Methods Data were derived from prospective screening for adverse obstetric outcomes in women attending their routine hospital visit at 35–37 weeks' gestation in two maternity hospitals in the UK. Uterine artery pulsatility index (UtA-PI) was measured in 5362 pregnancies, mean arterial pressure (MAP) in 5386 and serum placental growth factor (PlGF) and serum soluble fms-like tyrosine kinase-1 (sFlt-1) in 3920. Bayes' theorem was used to combine the a-priori risk of PE from maternal factors with various combinations of biomarkers, expressed as multiples of the median (MoM). Five-fold cross-validation was used to estimate the performance of screening for PE, requiring delivery at some stage after assessment. The empirical performance of screening was compared to model predictions. Results In pregnancies that developed PE, the values of MAP, UtA-PI and sFlt-1 were increased and PlGF was decreased compared to unaffected pregnancies. For all biomarkers evaluated, the deviation from normal was inversely related to the gestational age at which delivery became necessary for maternal or fetal indications. Screening by maternal factors and by a combination of maternal factors with all biomarkers predicted 35% and 84% of PE, respectively, at a 10% false-positive rate. Conclusion A combination of maternal factors and biomarkers at 35–37 weeks' gestation can provide effective screening for term PE. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Stillbirth and intrauterine fetal death: role of routine histopathological placental findings to determine cause of death.

Abstract: Objectives Placental abnormalities are a common cause of death in stillbirth, ranking second only to unexplained deaths, though there is wide variation in the proportion attributed to placental disease In clinical practice, interpretation of the significance of placental findings is difficult, since many placental features in stillbirths overlap with those in live births Our aim was to examine objectively classified placental findings from a series of > 1000 autopsies following intrauterine death in order to evaluate the role of placental histological examination in determining the cause of death Methods As part of a larger study evaluating several aspects of autopsy findings in intrauterine death, a dedicated database was used to collate antenatal and postmortem examination details for all cases examined between 2005 and 2013 at two tertiary specialist centers in London, UK Histological findings for placentas were evaluated in relation to the final cause of death Results Among 1064 intrauterine deaths, 946 (89%) cases had the placenta submitted for examination as part of the autopsy Of these, 307 (32%) cases had the cause of death assigned to abnormalities of the placenta, cord or membranes Around one third of stillbirths (≥ 24 weeks) had some isolated placental histological abnormality identified, many of uncertain significance, a significantly greater proportion than in cases of second-trimester intrauterine fetal demise (P < 00001) The cause of death was ascending infection in 176/946 (19%) cases, peaking at 22 weeks' gestation, with significantly more black mothers having ascending infection compared with other ethnicities (P < 00001) Maternal vascular malperfusion was the largest category of placental abnormalities in stillbirth, with peak prevalence in the early third trimester There were 18 (2%) cases with specific histological abnormalities, including chronic histiocytic intervillositis and massive perivillous fibrin deposition Conclusions Placental pathologies represent the largest category of cause of intrauterine death Placental histological examination is the single most useful component of the autopsy process in this clinical setting A minority of cases are associated with specific placental pathologies, often with high recurrence rates, that can be diagnosed only on microscopic examination of the placenta Many deaths remain unexplained, although placental histological lesions may be present which are of uncertain significance A rigorous, systematic approach to placental pathology research and classification may yield better understanding of the significance of placental findings and reduce the rate of unexplained intrauterine deaths Copyright © 2016 ISUOG Published by John Wiley & Sons Ltd

Fetal lower urinary tract obstruction: proposal for standardized multidisciplinary prenatal management based on disease severity.

Abstract: Objective To present a single center experience of a standardized prenatal multidisciplinary management protocol for fetal lower urinary tract obstruction (LUTO) and to propose a classification of fetal LUTO based on disease severity. Methods This was a retrospective cohort study of 25 consecutive fetal patients with prenatal diagnosis of primary LUTO. Fetal intervention was offered after evaluation by a multidisciplinary team. Analyses were conducted using Bayesian methodology to determine predictors of survival at 6 months postpartum. Odds ratios (ORs) with 95% credibility intervals are reported. Results Fifteen (60.0%) of the 25 patients referred for assessment survived to postnatal evaluation. Fetal vesicoamniotic shunt was placed in 14 (56.0%) patients with 12 survivors. Multivariable analysis suggested that fetal intervention (OR, 6.97 (0.88-70.16), Pr(OR > 1) = 96.7%), anhydramnios (OR, 0.12 (0.04-0.35), Pr(OR 1) = 92.7%) and absence of renal cortical cysts (OR, 3.9 (0.66-24.2), Pr(OR > 1) = 93.3%) were predictors of survival. Conclusions Fetal intervention and fetal renal function were independently associated with postnatal survival of fetuses with LUTO. A classification based on the severity of disease is proposed. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Counseling in fetal medicine: evidence-based answers to clinical questions on morbidly adherent placenta

Abstract: Although the incidence of morbidly adherent placenta (MAP) has risen progressively in the last two decades, there remains uncertainty about the diagnosis and management of this condition. The aim of this review is to provide up-to-date and evidence-based answers to common clinical questions regarding the diagnosis and management of MAP. Different risk factors have been associated with MAP; however, previous Cesarean section and placenta previa are the most frequently associated. Ultrasound is the primary method for diagnosing MAP and has a good overall diagnostic accuracy for its detection. When considering the different ultrasound signs of MAP, color Doppler seems to provide the best diagnostic performance. Magnetic resonance imaging has the same accuracy in diagnosing MAP as does ultrasound examination; its use should be considered when a resective procedure, such as hysterectomy, is planned as it can provide detailed information about the topography of placental invasion and predict difficulties that may arise in surgery. The optimal gestational age for delivery in pregnancies with MAP is yet to be established; planning surgery between 35 and 36 weeks of gestation provides the best balance between fetal maturity and the risk of unexpected episodes of heavy bleeding, which are more likely to occur with delivery after this timepoint, especially in severe cases of MAP. The optimal surgical approach to MAP depends on multiple factors, including availability of an experienced team, specific surgical skills and hospital resources. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Pro forma for ultrasound reporting in suspected abnormally invasive placenta (AIP): an international consensus

Abstract: Accurate antenatal diagnosis of an abnormally invasive placenta (AIP), allowing multidisciplinary management at the time of delivery, has been shown to improve maternal and fetal outcomes1–3. AIP can be predicted as early as in the first trimester, by identifying cases of suspected Cesarean scar pregnancy (CSP), as there is evidence that CSP in the first trimester and AIP in the second and third trimesters may represent different stages of a similar pathology4. Grayscale ultrasonography, with or without color Doppler and performed both transabdominally and transvaginally, has been used widely for antenatal screening and diagnosis of AIP. Many signs have been suggested, with reports varying as to their sensitivity and specificity5. Most of these ‘signs’ are poorly defined and, consequently, it is difficult to assess which are the most robust. To address this, the European Working Group on AIP (EW-AIP) have produced a consensus proposal to standardize the ultrasound descriptions used to define each sign, published in this issue of the Journal6. We assembled an international group of experts in the field with the specific aim of reaching an agreement regarding a standardized means of reporting ultrasound assessment of suspected AIP. If adopted by sonographers, clinicians and researchers worldwide, such a pro forma may facilitate better communication, and better evaluation of our diagnostic performance, in cases of suspected AIP. The group of international experts comprised an e-mail discussion group (n = 50) led by Jose Palacios Jaraquemada, members of the EW-AIP (n = 19) and members of the ISUOG (International Society of Ultrasound in Obstetrics and Gynecology) Clinical Standards Committee (n = 7). Each expert was asked to participate in a survey which involved completion of an online questionnaire to indicate what they believed should be included in the pro forma for reporting ultrasound assessment of suspected AIP. The online questionnaire, created using Survey Monkey, included risk factors known to be associated with AIP and all commonly reported ultrasound signs and definitions related to the diagnosis of AIP5–11. Ultrasound signs were divided into three subgroups according to modality: grayscale ultrasound, color Doppler and three-dimensional (3D) power Doppler. Each ultrasound sign in each subgroup had between one and six associated definitions reported in the published literature. To each selected demographic characteristic and ultrasound sign we assigned three options: (i) definitely include in report; (ii) include optionally in report and (iii) do not include in report. The definitions for each ultrasound sign were also assigned three options: (i) include; (ii) do not include and (iii) unsure. Participants were also asked whether clinical interpretation and relevance of the ultrasound findings should be included in the report. Options for preferred method of reporting clinical interpretation included: (i) give probability of clinically significant AIP, (ii) state whether manual removal of placenta should be attempted, and (iii) give free text description to provide guidance to the local team. There was the opportunity to provide free text comments for each section. A reminder to complete the questionnaire was sent out after 2 weeks, and we allowed 4 weeks for a response. All demographic characteristics and ultrasound signs for which >50% respondents selected ‘definitely include in report’ were incorporated into the standardized report, while those for which >50% respondents selected ‘do not include in report’ were excluded. For each ultrasound sign, the definitions for which >50% of respondents selected either ‘include’ or ‘unsure’ were kept for further evaluation. A second questionnaire was created for such items requiring further evaluation, in which respondents could specify first and second choice for definition of the ultrasound sign, and included additional suggestions from the free text comments, such as assessment for suspected parametrial involvement. For confirmation, we distributed a third and final round of the survey, with three domains, addressing: demographic and risk factors, ultrasound signs and clinical interpretation. At this round, consensus was sought from all participants that the ultrasound signs previously agreed on should be defined using the standardized descriptors proposed by the EW-AIP6. There were 42 respondents in the first round of the survey (response rate, 55%). For all of the demographic characteristics, placental location and grayscale ultrasound parameters, and for all but one color Doppler parameter, >50% of respondents chose ‘definitely include in report’. Only seven respondents thought that 3D power Doppler volumes should definitely be included and thus this criterion was excluded. All

Placental magnetic resonance imaging T2* measurements in normal pregnancies and in those complicated by fetal growth restriction

Abstract: Objectives The magnetic resonance imaging (MRI) variable transverse relaxation time (T2*) depends on multiple factors, one important one being the presence of deoxyhemoglobin. We aimed to describe placental T2* measurements in normal pregnancies and in those with fetal growth restriction (FGR). Methods We included 24 normal pregnancies at 24–40 weeks' gestation and four FGR cases with an estimated fetal weight below the 1st centile. Prior to MRI, an ultrasound examination, including Doppler flow measurements, was performed. The T2* value was calculated using a gradient echo MRI sequence with readout at 16 different echo times. In normal pregnancies, repeat T2* measurements were performed and interobserver reproducibility was assessed in order to estimate the reproducibility of the method. Placental histological examination was performed in the FGR cases. Results The method was robust regarding the technical and interobserver reproducibility. However, some slice-to-slice variation existed owing to the heterogeneous nature of the normal placenta. We therefore based T2* estimations on the average of two slices from each placenta. In normal pregnancies, the placental T2* value decreased significantly with increasing gestational age, with mean ± SD values of 120 ± 17 ms at 24 weeks' gestation, 84 ± 16 ms at 32 weeks and 47 ± 17 ms at 40 weeks. Three FGR cases had abnormal Doppler flow, histological signs of maternal hypoperfusion and a reduced T2* value (Z-score < –3.5). In the fourth FGR case, Doppler flow, placental histology and T2* value (Z-score, −0.34) were normal. Conclusions The established reference values for placental T2* may be clinically useful, as T2* values were significantly lower in FGR cases with histological signs of maternal hypoperfusion. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Prospective first-trimester screening for trisomies by cell-free DNA testing of maternal blood in twin pregnancy.

Abstract: OBJECTIVES First, to examine in twin pregnancies the performance of first-trimester screening for fetal trisomies 21, 18 and 13 by cell-free (cf) DNA testing of maternal blood and, second, to compare twin and singleton pregnancies regarding the distribution of fetal fraction of cfDNA and rate of failure to obtain a result. METHODS This was a prospective study in 438 twin and 10 698 singleton pregnancies undergoing screening for fetal trisomies by cfDNA testing at 10 + 0 to 13 + 6 weeks' gestation. Chromosome-selective sequencing of cfDNA was used and, in twin pregnancies, an algorithm was applied that relies on the lower fetal fraction contributed by the two fetuses. Multivariate regression analysis was used to determine significant predictors of fetal fraction and a failed result. RESULTS In twin pregnancies, the median fetal fraction was lower (8.0% (interquartile range (IQR), 6.0-10.4%) vs 11.0% (IQR, 8.3-14.4%); P < 0.0001) and failure rate after first sampling was higher (9.4% vs 2.9%; P < 0.0001) compared to in singletons. Multivariate logistic regression analysis demonstrated that the risk of test failure increased with increasing maternal age and body mass index and decreased with fetal crown-rump length. The risk was increased in women of South Asian racial origin and in pregnancies conceived by in-vitro fertilization (IVF). The main contributor to the higher rate of failure in twins was conception by IVF which was observed in 9.5% of singletons and 56.2% of twins. In the 417 twin pregnancies with a cfDNA result after first or second sampling, the detection rate was 100% (8/8) for trisomy 21 and 60% (3/5) for trisomies 18 or 13, at a false-positive rate (FPR) of 0.25% (1/404). In the 10 530 singleton pregnancies with a cfDNA result after first or second sampling, the detection rate was 98.7% (156/158) for trisomy 21 and 80.3% (49/61) for trisomies 18 or 13, at a FPR of 0.22% (23/10 311). CONCLUSIONS In twin pregnancies undergoing first-trimester screening for trisomies by cfDNA testing, the fetal fraction is lower and failure rate higher compared to in singletons. The number of trisomic twin pregnancies examined was too small for an accurate assessment of performance of screening, but it may be similar to that in singleton pregnancies. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Single deepest vertical pocket or amniotic fluid index as evaluation test for predicting adverse pregnancy outcome (SAFE trial): a multicenter, open-label, randomized controlled trial

Abstract: Objective To determine whether the amniotic fluid index (AFI) or the single deepest vertical pocket (SDP) technique for estimating amniotic fluid volume is superior for predicting adverse pregnancy outcome. Methods This was a multicenter randomized controlled trial including 1052 pregnant women with a term singleton pregnancy across four hospitals in Germany. Women were assigned randomly, according to a computer-generated allocation sequence, to AFI or SDP measurement for estimation of amniotic fluid volume. Oligohydramnios was defined as AFI ≤ 5 cm or the absence of a pocket measuring at least 2 × 1 cm. The diagnosis of oligohydramnios was followed by labor induction. The primary outcome measure was postpartum admission to a neonatal intensive care unit. Further outcome parameters were the rates of diagnosis of oligohydramnios and induction of labor (for oligohydramnios or without specific indication), and mode of delivery. Results Postpartum admission to a neonatal intensive care unit was similar between groups (4.2% (n = 21) vs 5.0% (n = 25); relative risk (RR), 0.85 (95% CI, 0.48–1.50); P = 0.57). In the AFI group, there were more cases of oligohydramnios (9.8% (n = 49) vs 2.2% (n = 11); RR, 4.51 (95% CI, 2.2–8.57); P < 0.01) and more cases of labor induction for oligohydramnios (12.7% (n = 33) vs 3.6% (n = 10); RR, 3.50 (95% CI, 1.76–6.96); P < 0.01) than in the SDP group. Moreover, an abnormal cardiotocography was seen more often in the AFI group than in the SDP group (32.3% (n = 161) vs 26.2% (n = 132); RR, 1.23 (95% CI, 1.02–1.50); P = 0.03). The other outcome measures were not significantly different between the two groups. Conclusions Use of the AFI method increased the rate of diagnosis of oligohydramnios and labor induction for oligohydramnios without improving perinatal outcome. The SDP method is therefore the favorable method to estimate amniotic fluid volume, especially in a population with many low-risk pregnancies. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Prevalence of prenatal brain abnormalities in fetuses with congenital heart disease: a systematic review

Abstract: Objectives Studies have shown an association between congenital heart defects (CHDs) and postnatal brain abnormalities and neurodevelopmental delay. Recent evidence suggests that some of these brain abnormalities are present before birth. The primary aim of this study was to perform a systematic review to quantify the prevalence of prenatal brain abnormalities in fetuses with CHDs. Methods MEDLINE, EMBASE and The Cochrane Library were searched electronically. Reference lists within each article were hand-searched for additional reports. The outcomes observed included structural brain abnormalities (on magnetic resonance imaging (MRI)) and changes in brain volume (on MRI, three-dimensional (3D) volumetric MRI, 3D ultrasound and phase-contrast MRI), brain metabolism or maturation (on magnetic resonance spectroscopy and phase-contrast MRI) and brain blood flow (on Doppler ultrasound, phase-contrast MRI and 3D power Doppler ultrasound) in fetuses with CHDs. Cohort and case–control studies were included and cases of chromosomal or genetic abnormalities, case reports and editorials were excluded. Proportion meta-analysis was used for analysis. Between-study heterogeneity was assessed using the I2 test. Results The search yielded 1943 citations, and 20 studies (n = 1175 cases) were included in the review. Three studies reported data on structural brain abnormalities, while data on altered brain volume, metabolism and blood flow were reported in seven, three and 14 studies, respectively. The three studies (221 cases) reporting on structural brain abnormalities were suitable for inclusion in a meta-analysis. The prevalence of prenatal structural brain abnormalities in fetuses with CHD was 28% (95% CI, 18–40%), with a similar prevalence (25% (95% CI, 14–39%)) when tetralogy of Fallot was considered alone. These abnormalities included ventriculomegaly (most common), agenesis of the corpus callosum, ventricular bleeding, increased extra-axial space, vermian hypoplasia, white-matter abnormalities and delayed brain development. Fetuses with CHD were more likely than those without CHD to have reduced brain volume, delay in brain maturation and altered brain circulation, most commonly in the form of reduced middle cerebral artery pulsatility index and cerebroplacental ratio. These changes were usually evident in the third trimester, but some studies reported them from as early as the second trimester. Conclusion In the absence of known major aneuploidy or genetic syndromes, fetuses with CHD are at increased risk of brain abnormalities, which are discernible prenatally. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Fetuses with right aortic arch: a multicenter cohort study and meta-analysis.

Abstract: Objectives Use of recent antenatal screening guidelines for cardiac abnormalities has increased fetal diagnoses of right aortic arch (RAA). We aimed to establish the outcome of fetal RAA without intracardiac abnormalities (ICA) to guide postnatal management. Methods In the retrospective cohort part of our study, outcome measures were rates of chromosomal abnormalities, 22q11.2 deletion, fetal extracardiac abnormalities (ECA), postnatal ICA and ECA, and symptoms of and surgery for vascular ring. A systematic review and meta-analysis was also performed; results are reported as proportions. Kaplan–Meier analysis of vascular ring cases with surgery as endpoint was performed. Results Our cohort included 86 cases; 41 had a vascular ring. Rates of chromosomal abnormalities, 22q11.2 deletion and fetal ECA were 14.1%, 6.4% and 17.4%, respectively. Sixteen studies including our cohort (312 fetuses) were included in the systematic review. Overall rates of chromosomal abnormalities and 22q11.2 deletion were 9.0% (95% CI, 6.0–12.5%) and 6.1% (95% CI, 3.6–9.3%), whilst the respective rates for cases with no ECA were 4.6% (95% CI, 2.3–7.8%) and 5.1% (95% CI, 2.4–8.6%). ECA were seen in 14.6% (95% CI, 10.6–19.0%) prenatally and in 4.0% (95% CI, 1.5–7.6%) after birth. Postnatal ICA were identified in 5.0% (95% CI, 2.7–7.9%). Rate of symptoms of vascular rings (follow-up ≥ 24 months postpartum) was 25.2% (95% CI, 16.6–35.0%), and 17.1% (95% CI, 9.9–25.7%) had surgery. Two-year freedom from surgery was 83.0% (95% CI, 74.3–90.1%). Conclusions Fetal RAA without ICA is more frequently associated with ECA than with chromosomal abnormalities. Most cases, however, are isolated. Vascular-ring symptoms occur in about 25% of cases. Postnatal surveillance is required mainly in the first 2 years after delivery. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.