Therapeutic equivalence of intermittent and continuous phototherapy for neonatal jaundice: a systematic review & meta-analysis with regression and trial sequential analysis.

Phototherapy is the mainstay treatment for neonatal hyperbilirubinemia, but the optimal delivery strategy remains debated. Intermittent phototherapy (IMPT) has been proposed as an alternative to continuous phototherapy (CPT) that may achieve comparable bilirubin reduction with fewer adverse effects. This systematic review and meta-analysis evaluated the comparative efficacy and safety of IMPT versus CPT in neonates with hyperbilirubinemia. PubMed, Embase, Scopus, Cochrane Library, and ClinicalTrials.gov were searched through June 2026 for randomized controlled trials comparing IMPT and CPT. Outcomes included rate of fall in bilirubin, follow-up bilirubin, phototherapy duration, hospital stay, and mortality. Random-effects meta-analysis pooled mean differences (MD) and risk ratios (RR) with 95% confidence intervals (CI). Subgroup, meta-regression, and Trial Sequential Analysis (TSA) were performed, and certainty of evidence was graded using GRADE. Twenty-six RCTs (3,891 neonates) were included. No significant difference was found between IMPT and CPT for rate of bilirubin fall, follow-up bilirubin, hospital stay, or mortality. IMPT significantly reduced phototherapy duration (MD - 10.40 h, 95% CI - 18.91 to - 1.88). Heterogeneity was substantial across outcomes. TSA indicated conclusive evidence of equivalence for bilirubin-related and hospital stay outcomes, while evidence for the duration reduction had not yet reached the required information size. Certainty of evidence ranged from low to very low.

conclusionIMPT achieves outcomes comparable to CPT while significantly reducing treatment duration, supporting its use as a time-efficient alternative, though findings warrant cautious interpretation given low certainty of evidence. WHAT IS KNOWN: • IMPT and CPT show comparable bilirubin reduction, but prior comparisons relied on limited trials without assessing whether the evidence base is conclusive. WHAT IS NEW: • This review incorporates the latest trials, applies Cochrane-guided meta-regression, subgroup, leave-one-out, and Hartung-Knapp sensitivity analyses, and uses TSA to confirm conclusive equivalence across major outcomes.