Extremely Low Birth Weight, Hyperbilirubinemia, Premature Newborns
Conditions
Keywords
hyperbilirubinemia, prematurity, extremely low birth weight (ELBW), phototherapy, cycled phototherapy, intermittent phototherapy
Brief summary
Cycled (intermittent) phototherapy will be compared to continuous (uninterrupted) phototherapy in the treatment of hyperbilirubinemia (newborn jaundice) in extremely low birth weight newborns in a pilot randomized controlled trial. Hypothesis: Cycled phototherapy (PT) will provide the same benefits as continuous phototherapy in extremely low birth weight (ELBW) infants without the risks that have been associated with continuous phototherapy.
Detailed description
Phototherapy (PT) is widely used and assumed to be safe as well as effective in reducing total bilirubin (TB) levels. Our recent NICHD Network Trial showed that aggressive use of phototherapy reduces neurodevelopmental impairment (NDI), but may increase deaths among ELBW infants. Among ventilator treated infants \<750 g birth weight (BW) (n =696), conservative Bayesian analyses (using a neutral prior probability) identified a 99% (posterior) probability that aggressive phototherapy reduced profound NDI but a 99% probability that it increased deaths relative to conservative phototherapy. The possibility that PT increases deaths among high risk infants is also suggested by the Collaborative Phototherapy trial (performed in the 1970s), the only large RCT in which LBW infants were randomly assigned to receive PT or no PT. The relative risk for death among those randomized to PT relative to those randomized to no PT was 1.32 (0.9-1.82) among all LBW infants and 1.49 (0.93-2.40) among ELBW infants. These findings are consistent with a major increase in mortality but have been ignored because the p was \>0.05, an error often made in ignoring important potential treatment hazards when power is limited. Multiple studies, most performed decades ago in larger infants, found that short on/off cycles of PT (e.g. 15 min on/60 min off, 1 h on/3 h off, or 1 h on/1 h off ) are as effective as uninterrupted PT to reduce TSB. (Cycles with \>6 h off PT do not appear to be as effective as uninterrupted PT). The clinical use of uninterrupted rather than cycled PT appears to be based largely on the assumption that PT is safe for all infants.
Interventions
OTHERphototherapy
Cycled versus continuous phototherapy during the first 2 wks after birth, both administered at bilirubin thresholds used in the NICHD Neonatal Network Phototherapy trial .
Sponsors
Stanford University
Lucile Packard Children's Hospital
The University of Texas Health Science Center, Houston
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 24 Hours
Healthy volunteers
No
Inclusion criteria
* birth weight 401-1000 grams * age less than or equal to 24 hours
Exclusion criteria
* hemolytic disease * major anomaly * overt nonbacterial infection
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Brain stem auditory evoked response wave V latency | 35 wks postmenstrual age or discharge | a measure of transient or permanent bilirubin neurotoxicity |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Peak Total Serum Bilirubin (tsb) | 14 days from birth | Total serum bilirubin (TSB) measurements will be obtained following a study protocol modeled on standard practice for monitoring TSB in ELBW newborns. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Neurodevelopmental status | 2 years adjusted age | The Network supports and assures carefully standardized neurodevelopmental testing at 2 years adjusted age for inborn ELBW patients. The reliability of these exams is verified annually in the Network. These assessments will provide data for survival rates without impairment |
| Survival | Before discharge from the neonatal ICU and at 2 years adjusted age | The Neonatal Research Network supports and assures outcome assessment at 2 years adjusted age for inborn ELBW patients. These assessments will provide data for survival rates and survival rates without impairment |
Countries
United States
Contacts
Primary ContactJon E Tyson, MD
Backup ContactCody C Arnold, MD
Outcome results
None listed