Supplementary Material for: Fetal Tricuspid Regurgitation in the First Trimester as a Screening Marker for Congenital Heart Defects: Systematic Review and Meta-Analysis

<p><b><i>Background:</i></b> Assessment of tricuspid flow has been reported to improve the performance of screening for aneuploidies and congenital heart defects (CHD). However, the performance of tricuspid regurgitation (TR) as a screening marker for CHD in euploid fetuses is yet to be established. The main aim of this meta-analysis was to establish the predictive accuracy of TR for CHD. <b><i>Methods:</i></b> MEDLINE, Embase, and the Cochrane Library were searched electronically utilizing combinations of the relevant medical subject heading for “fetus,” “tricuspid regurgitation,” and “first trimester.” The outcomes explored were prevalence of TR in an euploid population, strength of association between TR and CHD, and predictive accuracy of TR for CHD in euploid fetuses. Summary estimates of sensitivity, specificity, positive and negative likelihood ratios, and diagnostic odds ratio for the overall predictive accuracy of TR for the detection of CHD were computed using the hierarchical summary receiver-operating characteristics model. <b><i>Results:</i></b> A total of 452 articles were identified; 60 were assessed with respect to their eligibility for inclusion and a total of 4 studies were included in the study. TR was associated with an increased risk of CHD (RR: 9.6, 95% CI 2.8-33.5; I<sup>2</sup>: 92.7%). The strength of association between TR and CHD persisted when considering fetuses at risk for CHD, such as those with increased nuchal translucency (RR: 7.2, 95% CI 5.2-9.8; I<sup>2</sup>: 0%), while TR did not show any association with CHD when detected in a population at low risk for cardiac defects (RR: 9.3, 95% CI 0.8-111.8; I<sup>2</sup>: 93%). The overall diagnostic performance of TR in detecting CHD was poor in detecting CHD (sROC: 0.684, SE: 0.61) with a sensitivity of 35.2% (95% CI 26.9-44.1) and a specificity of 98.6% (95% CI 98.5-98.7). Detection of TR at the 11-14 weeks' scan showed a positive likelihood ratio of 7.2 (95% CI 5.3-9.8) in detecting CHD when applied to a population at risk for CHD such as fetuses with an increased nuchal translucency. <b><i>Conclusion:</i></b> The detection of TR in the first trimester increases the risk of CHD. However, isolated TR in the first trimester does not seem to be a strong predictor for CHD.</p>