Intermittent phototherapy in neonatal hyperbilirubinemia: A pilot randomized controlled trial in Taiwan

Continuous phototherapy (CPT) is standard for neonatal hyperbilirubinemia, but intermittent phototherapy (IPT) regimens may produce fewer side effects with comparable efficacy.

This prospective randomized controlled study enrolled neonates (GA ≥ 35 weeks) conducted between September 2023 and April 2025. Neonates received IPT (12 h on/12 h off) or CPT until bilirubin fell below threshold. The primary outcome was phototherapy duration. The secondary outcomes were length of hospital stay, bilirubin decline rate and threshold deviation and short-term adverse events.

A total of 69 infants were randomized into IPT (n = 35) and CPT (n = 34) groups. No significant differences were observed in duration of phototherapy (3.31 vs. 3.35 days; p = 0.91) or hospitalization length (5.31 vs. 5.26 days; p = 0.91). TSB levels markedly declined in both groups in the first 3 days and successfully reduced levels below the limit by Day 2. While daily TSB decline rates were comparable (p = 0.97), the IPT group demonstrated a significantly faster hourly response on Day 1 (p = 0.018). Conversely, the CPT group achieved a significantly greater negative deviation from the threshold on Day 3 (-3.92 vs. -2.98 mg/dL; p = 0.047). Notably, rebound hyperbilirubinemia requiring retreatment occurred only in the CPT group (n = 2, 5.9%), while the IPT group remained stable. Adverse events were infrequent and similar.

Our findings suggest that a 12-h IPT regimen may be comparable to CPT, exhibiting potential advantages in the initial hourly response and post-treatment rebound stability within this study cohort. While CPT achieves a deeper mid-treatment clearance, IPT's paced clearance appeared to maintain clinical safety margins without prolonging treatment. Thus, IPT may serve as a feasible alternative to CPT. Further large-scale studies are needed to refine individualized strategies.