Risk Factors Predicting the Need for Phototherapy in Glucose 6 Phosphate Dehydrogenase-Deficient Infants in a Large Retrospective Cohort Study

<b><i>Introduction:</i></b> Glucose 6-phosphate dehydrogenase (G6PD) deficiency increases the risk of severe neonatal hyperbilirubinemia. This study evaluates the risk factors predicting the need for phototherapy in G6PD-deficient neonates after 72 h of age and assesses the safety of early discharge. <b><i>Methods:</i></b> A retrospective cohort study of 681 full-term G6PD-deficient infants with a birth weight ≥2,500 g over 4 years was conducted. We compared the baseline characteristics, bilirubin level on day 4 (after 72 h of life), day of peak bilirubin, G6PD levels, and concomitant ABO incompatibility between the group that required phototherapy (Group A) and those who did not (Group B). <b><i>Results:</i></b> 396 infants (58%), predominantly males, required phototherapy in the first week of life. The infants who required phototherapy had a lower median gestational age (38.3 vs. 38.7 weeks, <i>p</i> &#x3c; 0.01) and had lower G6PD levels (2.3 ± 2.5 vs. 3 ± 3.4 IU, <i>p</i> &#x3c; 0.05) compared to the controls. The mean day-four total serum bilirubin (TSB) levels were higher (213 ± 32 vs. 151 ± 37 µmol/L, <i>p</i> &#x3c; 0.01), with bilirubin level peaking earlier (3 vs. 4 days of life, <i>p</i> &#x3c; 0.01) in group A. Regression analysis identified TSB levels on day 4, Chinese race, lower gestation, and concomitant ABO incompatibility as the significant predictors for the need for phototherapy in the study population. In particular, coexisting ABO blood group incompatibility increased the risk of jaundice requiring phototherapy (OR 4.27, 95% CI: 1.98–121, <i>p</i> &#x3c; 0.01). Day four TSB values above 180 µmol/L predicted the need for phototherapy with 86% sensitivity and 80% specificity. The findings were similar across both male and female infants with G6PD deficiency. <b><i>Conclusion:</i></b> G6PD-deficient infants with day four TSB levels of &#x3e;180 µmol/L (10.5 mg/dL) and associated ABO blood group incompatibility have a higher risk of requiring phototherapy in the first week of life and should be closely monitored.