Phototherapy, Morbidity, and Mortality in Very Preterm Newborns

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.

To determine the associations between phototherapy and neonatal mortality or morbidity.

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.

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.

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.

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.

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.