Trial of Aggressive Versus Conservative Phototherapy in Infants <1,000 Grams Birth Weight
Condition: Hyperbilirubinemia, Neonatal; Jaundice, Neonatal; Infant, Newborn; Infant, Low Birth Weight; Infant, Small for Gestational Age; Infant, Premature
MeSH terms: Hyperbilirubinemia, Neonatal; Jaundice, Neonatal; Body Weight; Birth Weight; Jaundice; Hyperbilirubinemia
Study type: Interventional
Phase: Phase 3

Summary: 
      This multi-center, randomized clinical trial compared different bilirubin levels as
      thresholds for timing of phototherapy in extremely low birth weight infants. The primary
      hypothesis was that there would be no difference in death or neurodevelopmental impairment at
      18-22 months corrected age in infants treated by either aggressive or conservative threshold
      limits. 1,978 infants were enrolled.
    

Detailed description: 
      In NICHD Neonatal Research Network (NRN) centers in 2002, phototherapy was administered to 94
      percent of the extremely low birth weight (ELBW) infants who survive more than 12 hours. Yet,
      it is unclear what level of bilirubin in the blood is harmful for these very tiny infants --
      no data existed from large or recent clinical trials to define the risks, benefits, and
      appropriate indications for phototherapy in these infants. The largest and most recent trial
      was the NICHD Collaborative Phototherapy Trial which involved infants treated in 1974-1976
      and included only 77 ELBW infants. Data from this study and others suggested that
      phototherapy could have important hazards as well as benefits for ELBW infants.

      This NRN study used two different bilirubin levels as thresholds for timing of phototherapy
      in 1,978 extremely low birth weight infants, examining the primary hypothesis that there
      would be no difference in death or neurodevelopmental impairment at 18-22 months corrected
      age between the aggressively and conservatively treated groups.

      Enrolled infants were stratified by birth weight (501-750g and 751-1,000g) and randomized to
      receive phototherapy regimens based on either an aggressive threshold or a conservative
      threshold of total serum bilirubin.

      In the Aggressive group:

        -  501-750 grams birth weight infants, phototherapy was started, stopped, and restarted
           based on a total serum bilirubin threshold level of 5 mg/dl for day of life 1-14.

        -  751-1,000 grams birth weight infants, phototherapy was started, stopped, and restarted
           based on a total serum bilirubin threshold level of 5 mg/dl for day of life 1-7 and 7
           mg/dl for day of life 8-14.

      In the Conservative group:

        -  501-750 grams birth weight infants, phototherapy was started, stopped, and restarted
           based on a total serum bilirubin threshold level of 8 mg/dl for day of life 1-14.

        -  751-1,000 grams birth weight infants, phototherapy was started, stopped, and restarted
           based on a total serum bilirubin threshold level of 10 mg/dl for day of life 1-14.

      The phototherapy regimens are designed to fall within the range of clinical practice and to
      assure a sizable difference between groups in total serum bilirubin levels and duration of
      phototherapy.

      The primary outcome was death or neurodevelopmental impairment at 18-22 months corrected age
      determined at an outpatient clinic visit. Secondary outcomes included death, abnormal
      neurodevelopmental outcome, severe hearing loss, cerebral palsy, blindness, and important
      medical outcomes.
    

Intervention name(s): Aggressive Phototherapy 501-750g; Aggressive Phototherapy 751-1000g; Conservative Phototherapy 501-750g; Conservative Phototherapy 751-1000g
Intervention type(s): Procedure; Procedure; Procedure; Procedure
Intervention description(s): Phototherapy started, stopped, and/or restarted when total serum bilirubin levels reach 5 mg/dl during days of life 1-14.; Phototherapy started, stopped, and/or restarted when total serum bilirubin levels reach 5 mg/dl during days of life 1-7, and started, stopped, and/or restarted when levels reach 7 mg/dl during days of life 8-14.; Phototherapy started, stopped, and/or restarted when total serum bilirubin levels reach ≥8.0 mg/dl during days of life 1-14.; Phototherapy started, stopped, and/or restarted when total serum bilirubin levels reach ≥10.0 mg/dl during days of life 1-14.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Treatment
Keywords: NICHD Neonatal Research Network; Bilirubin; Phototherapy; Very Low Birth Weight (VLBW); Extremely Low Birth Weight (ELBW); Prematurity; Neurodevelopmental outcome