Article

Is phototherapy exposure associated with better or worse outcomes in 501- to 1000-g-birth-weight infants?

Department of Pediatrics, Stanford University School of Medicine, Palo Alto, CA, USA.
Acta Paediatrica (Impact Factor: 1.84). 07/2011; 100(7):960-5. DOI: 10.1111/j.1651-2227.2011.02175.x
Source: PubMed

ABSTRACT  To compare risk-adjusted outcomes at 18- to 22-month-corrected age for extremely low birth weight (ELBW) infants who never received phototherapy (NoPTx) to those who received any phototherapy (PTx) in the NICHD Neonatal Research Network randomized trial of Aggressive vs. Conservative Phototherapy.
Outcomes at 18 to 22-month-corrected age included death, neurodevelopmental impairment (NDI) and Bayley Scales Mental Developmental Index (MDI). Regression models evaluated the independent association of PTx with adverse outcomes controlling for centre and other potentially confounding variables.
Of 1972 infants, 216 were NoPTx and 1756 were PTx. For the entire 501- to 1000-g-BW cohort, PTx was not independently associated with death or NDI (OR 0.85, 95% CI: 0.60-1.20), death or adverse neurodevelopmental endpoints. However, among infants 501-750 g BW, the rate of significant developmental impairment with MDI < 50 was significantly higher for NoPTx (29%) than PTx (12%) (p = 0.004).
Phototherapy did not appear to be independently associated with death or NDI for the overall ELBW group. Whether PTx increases mortality could not be excluded because of bias from deaths before reaching conservative treatment threshold. The higher rate of MDI < 50 in the 501- to 750-g-BW NoPTx group is concerning and consistent with NRN Trial results.

Full-text

Available from: Ronald J Wong, May 29, 2015
0 Followers
 · 
146 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Hemolytic conditions in preterm neonates, including Rhesus (Rh) disease, can lead to mortality and long-term impairments due to bilirubin neurotoxicity. Universal access to Rh immunoprophylaxis, coordinated perinatal-neonatal care, and effective phototherapy has virtually eliminated the risk of kernicterus in many countries. In the absence of jaundice due to isoimmunization and without access to phototherapy or exchange transfusion (in 1955), kernicterus was reported at 10.1%, 5.5%, and 1.2% in babies <30, 31-32, and 33-34 wks gestational age, respectively. Phototherapy initiated at 24±12 hr effectively prevented hyperbilirubinemia in infants <2,000 g even in the presence of hemolysis. This approach (in 1985) reduced exchange transfusions from 23.9% to 4.8%. Now with 3 decades of experience in implementing effective phototherapy, the need for exchange transfusions has virtually been eliminated. However, bilirubin neurotoxicity continues to be associated with prematurity alone. The ability to better predict this risk, other than birthweight and gestation, has been elusive. Objective tests such as total bilirubin, unbound or free bilirubin, albumin levels, and albumin-bilirubin binding, together with observations of concurrent hemolysis, sepsis, and rapid rate of bilirubin rise have been considered, but their individual or combined predictive utility has yet to be refined. The disruptive effects of immaturity, concurrent neonatal disease, cholestasis, use of total parenteral nutrition or drugs that alter bilirubin-binding abilities augment the clinical risk of neurotoxicity. Current management options rely on the "fine-tuning" of each infant's exposure to beneficial antioxidants and avoidance of silent neurotoxic properties of bilirubin navigated within the safe spectrum of operational thresholds demarcated by experts.
    03/2013; 2(2):61-69. DOI:10.4103/2249-4847.116402
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Structural brain abnormalities identified at near-term age have been recognized as potential predictors of neurodevelopment in children born preterm. The aim of this study was to examine the relationship between neonatal physiological risk factors and early brain structure in very-low-birth-weight (VLBW) preterm infants using structural MRI and diffusion tensor imaging (DTI) at near-term age. Structural brain MRI, diffusion-weighted scans, and neonatal physiological risk factors were analyzed in a cross-sectional sample of 102 VLBW preterm infants (BW ≤ 1500 g, gestational age (GA) ≤ 32 wks), who were admitted to the Lucile Packard Children’s Hospital, Stanford NICU and recruited to participate prior to routine near-term brain MRI conducted at 36.6 ± 1.8 weeks postmenstrual age (PMA) from 2010–2011; 66/102 also underwent a diffusion-weighted scan. Brain abnormalities were assessed qualitatively on structural MRI, and white matter (WM) microstructure was analyzed quantitatively on DTI in six subcortical regions defined by DiffeoMap neonatal brain atlas. Specific regions of interest included the genu and splenium of the corpus callosum, anterior and posterior limbs of the internal capsule, the thalamus, and the globus pallidus. Regional fractional anisotropy (FA) and mean diffusivity (MD) were calculated using DTI data and examined in relation to neonatal physiological risk factors including gestational age (GA), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), and sepsis, as well as serum levels of C-reactive protein (CRP), glucose, albumin, and total bilirubin. Brain abnormalities were observed on structural MRI in 38/102 infants including 35% of females and 40% of males. Infants with brain abnormalities observed on MRI had higher incidence of BPD (42% vs. 25%) and sepsis (21% vs. 6%) and higher mean and peak serum CRP levels, respectively, (0.64 vs. 0.34 mg/dL, p = .008; 1.57 vs. 0.67 mg/dL, p = .006) compared to those without. The number of signal abnormalities observed on structural MRI correlated to mean and peak CRP (rho = .316, p = .002; rho = .318, p = .002). The number of signal abnormalities observed on MRI correlated with thalamus MD (left: r = .382, p = .002; right: r = .400, p = .001), controlling for PMA-at-scan. Thalamus WM microstructure demonstrated the strongest associations with neonatal risk factors. Higher thalamus MD on the left and right, respectively, was associated with lower GA (r = –.322, p = .009; r = –.381, p = .002), lower mean albumin (r = –.276, p = .029; r = –.385, p = .002), and lower mean bilirubin (r = –.293, p = .020; r = –.337 p = .007). Results suggest that at near-term age, thalamus WM microstructure may be particularly vulnerable to certain neonatal risk factors. Interactions between albumin, bilirubin, phototherapy, and brain development warrant further investigation. Identification of physiological risk factors associated with selective vulnerability of certain brain regions at near-term age may clarify the etiology of neurodevelopmental impairment and inform neuroprotective treatment for VLBW preterm infants.
    01/2014; 5. DOI:10.1016/j.nicl.2014.05.013
  • [Show abstract] [Hide abstract]
    ABSTRACT: Phototherapy is assumed to be both effective and safe for extremely low-birth-weight infants. Our objective was to critically assess the relevant evidence from randomized trials. In the decades-old Collaborative Phototherapy Trial, phototherapy reduced serum bilirubin but not neurodevelopmental impairments. In the recent and larger Neonatal Network Trial, aggressive phototherapy compared to conservative phototherapy reduced both peak serum bilirubin (7.0 vs. 9.8 mg/dL) and profound impairment at 18–22 months adjusted age (relative risk = 0.68). However, both trials suggested that phototherapy increased deaths among the smallest infants. Conservative Bayesian analyses of ventilator-treated infants under 751 g birth weight in the Network trial identified a 99% probability of increased deaths and 99% probability of reduced profound impairment with aggressive phototherapy. Potential strategies to optimize the risk/benefit ratio in achieving low serum bilirubin levels, e.g., use of lowered irradiance levels, light-emitting diode phototherapy units, cycled phototherapy, and/or porphyrin compounds, deserve rigorous evaluation.
    Seminars in Perinatology 10/2014; 38(7). DOI:10.1053/j.semperi.2014.08.008 · 2.42 Impact Factor