Phototherapy-Associated Changes in Ionized Calcium Among Neonates Born at ≥35 Weeks of Gestation

Background  Phototherapy is the standard treatment for clinically significant unconjugated neonatal hyperbilirubinemia. Although generally safe and effective, phototherapy has been associated with alterations in calcium homeostasis. The magnitude and clinical relevance of phototherapy-associated reductions in ionized calcium (iCa) remain uncertain, particularly among neonates born at ≥35 weeks of gestation. Objective  To evaluate changes in iCa before and after phototherapy in neonates born at ≥35 weeks with unconjugated hyperbilirubinemia. Methods  This prospective cohort study included 145 neonates born at ≥35 weeks who received phototherapy for at least 24 hours for unconjugated hyperbilirubinemia at the Department of Pediatrics, Baba Raghav Das (BRD) Medical College, Gorakhpur, India, from August 2021 to August 2022. Ionized calcium was measured immediately before the initiation of phototherapy and after 24 hours of phototherapy using an ion-selective electrode (ISE) method and was categorized as <1.20, 1.20-1.40, and >1.40 mmol/L. Changes in the paired distribution of iCa categories were assessed using the Stuart-Maxwell test of marginal homogeneity. Results  The mean gestational age was 36.93 ± 1.49 weeks; 64 (44.1%) neonates were born before 37 weeks, and 82 (56.6%) were male. Before phototherapy, 12/145 (8.3%) neonates had iCa <1.20 mmol/L, compared with 54/145 (37.2%) after 24 hours of phototherapy, representing an absolute increase of 28.9 percentage points. Among 133 neonates with baseline iCa ≥1.20 mmol/L, 44 (33.1%) developed iCa <1.20 mmol/L after 24 hours of phototherapy. The proportion with iCa >1.40 mmol/L decreased from 109/145 (75.2%) before treatment to 30/145 (20.7%) after 24 hours. The overall shift in paired iCa categories was statistically significant (Stuart-Maxwell χ² = 83.808, df = 2, p < 0.001). Conclusion  Phototherapy was associated with a significant downward shift in iCa among neonates born at ≥35 weeks of gestation. Among neonates without low iCa at baseline, 33.1% developed concentrations <1.20 mmol/L after 24 hours of phototherapy. These findings demonstrate an important biochemical association; however, further studies are needed to determine its clinical significance and identify neonates who may benefit from targeted iCa monitoring.