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

Background: 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. Methods:
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. Results: 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; I2:
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; I2: 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; I2:
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. Conclusion: 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.