Phototherapy, Morbidity, and Mortality in Very Preterm Newborns.

Importance: Phototherapy is widely used in the care of preterm newborns to prevent brain damage resulting from hyperbilirubinemia. However, concerns regarding its safety have been raised. Objective: To determine the associations between phototherapy and neonatal mortality or morbidity. Design, Setting, and Participants: This population-based cohort study from the Swedish Neonatal Quality Register included preterm newborns (gestational age, 22-31 weeks) admitted for care between November 2015 and December 2024, and followed up to hospital discharge. Deaths before 7 days of age, major congenital anomalies, or newborns without data on phototherapy were excluded. Exposures: Duration of phototherapy categorized as 0 to 3, 4 to 5, and 6 to 7 days. Peak bilirubin levels in the first week were categorized as less than 25th, 25th to 50th, 51st to 75th, and greater than 75th percentiles. Main Outcomes and Measures: The primary outcome was late neonatal mortality (LNM) on postnatal days 8 to 27 with a composite of severe neonatal morbidity as secondary outcome: intraventricular hemorrhage (IVH) grade 3 to 4; treated patent ductus arteriosus; necrotizing enterocolitis stage IIa or higher; severe bronchopulmonary dysplasia (BPD); or retinopathy of prematurity. Adjusted odds ratios (aORs) were calculated and adjusted for multiple pregnancy, preeclampsia, cesarean delivery, newborn sex, gestational age, Apgar score less than 4 at 5 minutes, and being small for gestational age or large for gestational age. Results: This study included a total of 4970 newborns. Median (IQR) gestational age was 29.1 (26.7-30.7) weeks, the median (IQR) birth weight was 1180 (860-1510) g, 2741 newborns (55.2%) were male, and 4746 newborns (95.5%) were treated with phototherapy. LNM occurred in 34 of 1995 newborns (1.7%) treated with phototherapy for 0 to 3 days, in 55 of 1921 newborns (2.9%) treated 4 to 5 days, and in 48 of 1054 newborns (4.6%) treated 6 to 7 days. Compared with 0 to 3 days of phototherapy, the aOR for LNM after 4 to 5 was 1.13 (95% CI, 0.71-1.78), and that for 6 to 7 days of treatment was 1.01 (95% CI, 0.62-1.65). Excluding newborns with IVH, hemolytic disease, or Apgar score below 4 at 5 minutes did not alter the results; neither did an evaluation of phototherapy duration and LNM stratified by peak bilirubin categories. Compared with 0 to 3 days, the aOR for composite morbidity after 4 to 5 days of phototherapy was 1.29 (95% CI, 1.04-1.59), and that for 6 to 7 days of phototherapy was 1.66 (95% CI, 1.31-2.09), which could be attributed to more prevalent IVH and severe BPD in newborns with longer treatment durations. Conclusions and Relevance: In this cohort study of very preterm newborns, the duration of phototherapy for hyperbilirubinemia was not associated with neonatal mortality. Nevertheless, prolonged phototherapy in very preterm newborns should be avoided.