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Original Investigation
April 27, 2020

Cycled Phototherapy Dose-Finding Study for Extremely Low-Birth-Weight Infants: A Randomized Clinical Trial

Author Affiliations
  • 1McGovern Medical School, University of Texas, Houston
  • 2Birmingham School of Medicine, University of Alabama, Birmingham
  • 3Stanford University School of Medicine, Stanford, California
  • 4Now at University of Colorado School of Medicine, Aurora
  • 5University of Texas Medical Branch at Galveston
  • 6University of Texas Southwestern Medical School, Dallas
  • 7University of Texas Health Science Center at San Antonio
JAMA Pediatr. 2020;174(7):649-656. doi:10.1001/jamapediatrics.2020.0559
Key Points

Question  Can cycled phototherapy control total serum bilirubin levels while reducing phototherapy exposure to potentially avoid increased mortality with continuous phototherapy among extremely low-birth-weight newborns?

Findings  In this dose-finding randomized clinical trial of 305 infants, cycled phototherapy (≥15 min/h titrated to total serum bilirubin level) compared with continuous phototherapy substantially decreased mean phototherapy hours (34 vs 72) with a minimally higher mean peak total serum bilirubin level (7.1 vs 6.4 mg/dL), similar mean brainstem auditory-evoked response mean wave V latency (7.42 vs 7.32 milliseconds), and fewer deaths (10.2% vs 13.4%).

Meaning  A large, randomized trial is needed to assess whether cycled phototherapy would increase survival and survival without impairment in small, preterm infants.

Abstract

Importance  Cycled (intermittent) phototherapy (PT) might adequately control peak total serum bilirubin (TSB) level and avoid mortality associated with usual care (continuous PT) among extremely low-birth-weight (ELBW) infants (401-1000 g).

Objective  To identify a cycled PT regimen that substantially reduces PT exposure, with an increase in mean peak TSB level lower than 1.5 mg/dL in ELBW infants.

Design, Setting, and Participants  This dose-finding randomized clinical trial of cycled PT vs continuous PT among 305 ELBW infants in 6 US newborn intensive care units was conducted from March 12, 2014, to November 14, 2018.

Interventions  Two cycled PT regimens (≥15 min/h and ≥30 min/h) were provided using a simple, commercially available timer to titrate PT minutes per hour against TSB level. The comparator arm was usual care (continuous PT).

Main Outcomes and Measures  Mean peak TSB level and total PT hours through day 14 in all 6 centers and predischarge brainstem auditory-evoked response wave V latency in 1 center. Mortality and major morbidities were secondary outcomes despite limited power.

Results  Consent was requested for 452 eligible infants and obtained for 305 (all enrolled) (mean [SD] birth weight, 749 [152] g; gestational age, 25.7 [1.9] weeks; 81 infants [27%] were multiple births; 137 infants [45%] were male; 112 [37%] were black infants; and 107 [35%] were Hispanic infants). Clinical and demographic characteristics of the groups were similar at baseline. After a preplanned interim analysis of 100 infants, the regimen of 30 min/h or more was discontinued, and the study proceeded with 2 arms. Comparing 128 infants receiving PT of 15 min/h or more with 128 infants receiving continuous PT among those surviving to 14 days, mean peak TSB levels were 7.1 vs 6.4 mg/dL (adjusted difference, 0.7; 95% CI, 0.4-1.1 mg/dL) and mean total PT hours were 34 vs 72 (adjusted difference, −39; 95% CI, −45 to −32). Wave V latency adjusted for postmenstrual age was similar in 37 infants receiving 15 min/h or more of PT and 33 infants receiving continuous PT: 7.42 vs 7.32 milliseconds (difference, 0.10; 95% CI, −0.11 to 0.30 millisecond). The relative risk for death was 0.79 (95% CI, 0.40-1.54), with a risk difference of −4.5% (95% CI, −10.9 to 2.0). Morbidities did not differ between groups.

Conclusions and Relevance  Cycled PT can substantially reduce total PT with little increase in peak TSB level. A large, randomized trial is needed to assess whether cycled PT would increase survival and survival without impairment in small, preterm infants.

Trial Registration  ClinicalTrials.gov Identifier: NCT01944696

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