Detection rates of first-trimester fetal anomalies ranged from 32% in low-risk groups to more than 60% in high-risk groups, demonstrating that first-trimester ultrasound has the potential to identify a large proportion of fetuses affected with structural anomalies. The use of a standardized anatomical protocol improves the sensitivity of first-trimester ultrasound screening for all anomalies and major anomalies in populations of varying risk. The development and introduction of international protocols with standard anatomical views should be undertaken in order to optimize first-trimester anomaly detection. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Table 1 -Characteristics of studies reporting on the detection of structural anomalies in low risk and unselected populations using first trimester ultrasound. Notes: (i). In studies where both TA and TV ultrasound were used, the number in parentheses adjacent to the ultrasound modality refers to the percentage of the study population which received this screening test (when available). (ii). In studies where aneuploid fetuses were included, the percentage of the study population confirmed by karyotyping as aneuploid was indicated in parentheses (where available). (iii). The subgroup analysis column identifies the group(s) in which the respective study's data was analyzed. * Highlights studies where TV ultrasound was only performed in situations where visualization with TA ultrasound was deemed suboptimal. **Cardiac exam performed at time of first trimester scan, but cardiac malformations excluded from study analysis. ***For the purposes of this review, only the cohort of known euploid fetuses was included in analysis (as insufficient data was provided on the entire cohort reported in the study). GroupYear N Gestation (weeks) Population Health-Care Setting Aneuploid Included? Index Test Anatomy Checklist Cardiac Exam Done? Subgroup for data Analysis Achiron (62) 1991 800 9-13 Mixed indications: vaginal bleeding, dating and early anomaly screening Unclear Yes TV/TA Basic Yes 2 Hernadi (37) 1997 3991 11-14 Unselected Unclear Yes (0.2%) TV Basic No 1 Bilardo (25) (Low risk) 1998 1543 10-14 Consecutive, Singleton pregnancies, Normal NT (<3.0mm),

Objectives: To determine the diagnostic accuracy of ultrasound at 11-14 weeks gestational age in the detection of fetal cardiac abnormalities, and to evaluate factors that impact detection rates.Methods: A systematic review of studies evaluating the diagnostic accuracy of ultrasound in the detection of fetal cardiac anomalies at 11-14 weeks gestational age was undertaken by two independent reviewers. Prospective and retrospective studies evaluating pregnancies at all levels of prior risk and in any healthcare setting were eligible for inclusion. The reference standard used was the detection of a major cardiac abnormality on postnatal or post-mortem examination. Data were extracted from included studies to populate 2 x 2 tables. Meta-analysis was performed using a random-effects model in order to determine the overall performance of first trimester ultrasound in the detection of major cardiac abnormalities overall and in addition, for individual types of cardiac abnormalities. Data were analysed separately for high-risk populations vs. non-high risk populations. Pre-planned secondary analyses were conducted in order to assess factors which may impact screening performance including: the imaging protocol used for cardiac assessment (including use of Colour Doppler), mode of ultrasound, publication year of study, and the index of sonographer suspicion at the time of scan. A risk of bias and quality assessment was undertaken for all included studies using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2).Results: An electronic search of four databases (Medline, Embase, Web of Science Core Collection and Cochrane Library) was conducted from January 1998 until July 2020 and identified 4108 citations. This led to 223 full text reviews from which a total of 63 studies were selected for inclusion. Data from a total of 328,214 screened fetuses were included. In non-high risk populations (45 studies, 306,872 fetuses), 1,445 major cardiac anomalies were identified (prevalence 0.41 (95% C.I. 0.39 -0.43)). Of these, 767 were correctly detected by first trimester examination of the heart and 678 were not detected. Pooled sensitivity was 55.80% (95% CI 45.87-65.50%,), specificity 99.98% (95% CI 99.97 -99.99%) and positive predictive value 94.85% (95% CI 91.63-97.32%). The cases diagnosed in the first trimester represent Accepted ArticleThis article is protected by copyright. All rights reserved.63.67% (95% CI 54.35 -72.49%) of all antenatally diagnosed major cardiac abnormalities. In high risk populations (18 studies, 21,342 fetuses) 480 major cardiac anomalies were identified (prevalence 1.36 (95% C.I. 1.20 -1.52)). Of these, 338 were correctly detected in the first trimester, and 142 were not detected. The sensitivity was 67.74% (95% CI 55.25 -79.06%), specificity 99.75% (95% CI 99.47 -99.92%) and positive predictive value 94.22% (95% CI 90.22 -97.22%). The cases diagnosed in the first trimester represent 79.86% (95% CI 69.89 -88.25%) of all antenatally diagnosed major cardiac abnormalities in high risk populati...