Direct antiglobulin test for the prediction of neonatal hyperbilirubinemia needing an intervention: a systematic review and diagnostic test accuracy meta-analysis

Abstract

Importance: The direct antiglobulin test (DAT) is commonly used as a screening test for predicting significant neonatal hyperbilirubinemia requiring intervention. However, evidence for this approach is limited. Objective: The aim of this study was to evaluate the diagnostic utility of DAT in predicting the need for phototherapy and double volume exchange transfusion (DVET) in neonates with ABO and Rhesus (Rh) incompatibility conditions. Methods: MEDLINE, Embase, CENTRAL, CINAHL, and Web of Science were searched from inception until 1 February 2024. Randomized controlled trials (RCTs) and non-RCTs were eligible for inclusion. Two reviewers screened the titles and abstracts blinded to each other. A Bayesian bivariate random-effects model was employed for the diagnostic test accuracy meta-analyses. Risk of bias was assessed using Quality Assessment for Studies of Diagnostic Accuracy 2 and certainty of evidence (CoE) was adjudged according to the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) guidelines. Results: In total, 53 studies were included in the systematic review and 28 were synthesized in the meta-analysis. For the need for phototherapy outcome, the pooled sensitivity [95% credible interval (CrI)] and specificity (95% CrI) of DAT in ABO incompatibility (18 studies, n = 10,110) were 56.1% (44.5%–67.8%) and 83.6% (71.6%–90.8%). For Rh incompatibility (three studies, n = 491), the sensitivity and specificity were 40.4% (12.2%–81.7%) and 89.9% (72.7%–94.6%). The CoE was predominantly low. For the need for DVET outcome, the pooled sensitivity and specificity of DAT in ABO incompatibility (three studies, n = 2,652) were 83.6% (35.8%–99.6%) and 74.5% (40.3%–92.7%). For Rh incompatibility (two studies, n = 240), the sensitivity and specificity were 80.3% (34.2%–97.3%) and 68.0% (25.3%–92.1%). The CoE was predominantly very low. Conclusion: In ABO and Rh incompatibility, DAT probably has moderate specificity and low sensitivity for predicting the need for phototherapy. For DVET, though DAT is possibly a better predictor due to its acceptable sensitivity, the predictive interval was wide. Thus, we do not suggest the routine use of DAT screening to predict the need for phototherapy and DVET. However, it may be used as a second-tier investigation for risk stratification of high-risk neonates. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022297785, PROSPERO (CRD42022297785).