Predictive value of brain MRI for neurodevelopmental outcome in infants with severe unconjugated hyperbilirubinemia: A systematic review

Context: Debate exists regarding predictive value of brain MRI for long-term neurodevelopmental outcome (NDO) in infants with severe unconjugated hyperbilirubinemia (above exchange transfusion levels).

Objective: To investigate whether MRI findings among (pre-)term infants with severe unconjugated hyperbilirubinemia can predict NDO at ≥ 12 months and determine optimal timing for MRI.

Data sources: PubMed and Embase. Last update: June 14, 2024.

Study selection: Studies in which (pre-)term infants with severe unconjugated hyperbilirubinemia who underwent an MRI before 24 months and had a reported NDO at ≥ 12 months were included.

Data extraction: Patient characteristics, MRI and NDO details were extracted.

Results: The search yielded 732 studies, of which 22 were included. Individual patient information was obtained for 120 infants (MRI-timing: early (≤6 weeks) n = 75, late (>6 weeks) n = 19, unknown n = 26). Positive predictive value (PPV) of abnormal MRI in the total group for impaired NDO was high (77.5 %). The PPV of late compared to early MRI was much higher, 92.3 % versus 71.7 %. Negative predictive value of normal MRI for normal NDO in the total group was low (29.0 %) and again higher in late compared to early MRI, 50.0 % versus 27.3 %.

Limitations: Quantitative synthesis of results was impossible due to large heterogeneity in study designs. Furthermore, selection bias towards patients with impaired outcome might have influenced our results.

Conclusions: Brain MRI can serve as prognostic tool for NDO in infants with severe unconjugated hyperbilirubinemia, both in early and late stages, but each timing has inherent constraints. Further prospective studies are necessary.