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1.  Apolipoprotein E (APOE) Genotype and Outcome in Infants with Hypoxic-Ischemic Encephalopathy (HIE) 
Pediatric research  2013;75(3):424-430.
Adults with the apolipoprotein E gene (APOE) alleles e4 and e2 are at high risk of poor neurologic outcome after brain injury. The e4 allele has been associated with cerebral palsy and the e2 allele has been associated with worse neurologic outcome with congenital heart disease. This study was done to test the hypothesis that APOE genotype is associated with outcome among neonates who survive after hypoxic-ischemic encephalopathy (HIE).
We conducted a cohort study of infants who survived HIE and had 18 – 22 month standardized neurodevelopmental evaluations to assess associations between disability and APOE genotypes e3/e3, e4/-, and e2/-
139 survivors were genotyped. 86 (62%) were e3/e3, 41 (29%) were e4/-, and 14 (10%) were e2/-. 129 infants had genotype and follow-up data; 26% had moderate or severe disabilities. Disability prevalence was 30% and 19% among those with and without e3/e3 genotype, 25% and 26% among those with and without the e2 allele, and 18% and 29% among those with and without the e4 allele. None of the differences were statistically significant. Cerebral palsy prevalence was also similar among genotype groups.
Disability was not associated with APOE genotype in this cohort of HIE survivors.
PMCID: PMC4095992  PMID: 24322171
2.  Outcome of Extremely Low Birth Weight Infants Who Received Delivery Room Cardiopulmonary Resuscitation 
The Journal of Pediatrics  2011;160(2):239-244.e2.
To determine whether delivery room cardiopulmonary resuscitation (DR-CPR) independently predicts morbidities and neurodevelopmental impairment (NI) in extremely low birth weight (ELBW) infants.
Study design
Cohort study of infants born with birth weight (BW) 401-1000g and gestational age (GA) 23-30wks. DR-CPR was defined as chest compressions and/or drugs. Logistic regression was used to determine associations between DR-CPR and morbidities, mortality and NI at 18-24 months (Bayley II mental or psychomotor index < 70, cerebral palsy, blindness or deafness). Data are adjusted Odds Ratio (OR) with 95% confidence interval.
Of 8685 infants, 1333(15%) received DR-CPR. DR-CPR infants had lower BW (708±141vs 764±146g, p<0.0001) and GA (25±2 vs 26±2 wks, p<0.0001). DR-CPR infants had more pneumothoraces (OR 1.28, 1.48-2.99), Grade 3-4 intraventricular hemorrhage (OR 1.47, 1.23-1.74), bronchopulmonary dysplasia (OR 1.34, 1.13-1.59), death by 12 hours (OR 3.69, 2.98-4.57) and by 120 days after birth (OR 2.22, 1.93-2.57). NI among survivors (OR 1.23, 1.02-1.49), and death or NI (OR 1.70, 1.46-1.99) were higher for DR-CPR infants. Only 14% of DR-CPR recipients with 5-minute Apgar score<2 survived without NI.
DR-CPR is a prognostic marker for higher mortality and NI for ELBW survivors. New DR-CPR strategies are needed for this population.
PMCID: PMC3258355  PMID: 21930284
cardiac compressions; epinephrine; neurodevelopmental outcomes
3.  Predictive Value of an Early Amplitude Integrated Electroencephalogram and Neurologic Examination 
Pediatrics  2011;128(1):e112-e120.
To examine the predictive validity of the amplitude integrated electroencephalogram (aEEG) and stage of encephalopathy among infants with hypoxic-ischemic encephalopathy (HIE) eligible for therapeutic whole-body hypothermia.
Neonates were eligible for this prospective study if moderate or severe HIE occurred at <6 hours and an aEEG was obtained at <9 hours of age. The primary outcome was death or moderate/severe disability at 18 months.
There were 108 infants (71 with moderate HIE and 37 with severe HIE) enrolled in the study. aEEG findings were categorized as normal, with continuous normal voltage (n = 12) or discontinuous normal voltage (n = 12), or abnormal, with burst suppression (n = 22), continuous low voltage (n = 26), or flat tracing (n = 36). At 18 months, 53 infants (49%) experienced death or disability. Severe HIE and an abnormal aEEG were related to the primary outcome with univariate analysis, whereas severe HIE alone was predictive of outcome with multivariate analysis. Addition of aEEG pattern to HIE stage did not add to the predictive value of the model; the area under the curve changed from 0.72 to 0.75 (P = .19).
The aEEG background pattern did not significantly enhance the value of the stage of encephalopathy at study entry in predicting death and disability among infants with HIE.
PMCID: PMC3124102  PMID: 21669899
neonatal hypoxic-ischemic encephalopathy; amplitude integrated EEG
4.  Aggressive vs. Conservative Phototherapy for Infants with Extremely Low Birth Weight 
It is unclear whether aggressive phototherapy to prevent neurotoxic effects of bilirubin benefits or harms infants with extremely low birth weight (1000 g or less).
We randomly assigned 1974 infants with extremely low birth weight at 12 to 36 hours of age to undergo either aggressive or conservative phototherapy. The primary outcome was a composite of death or neurodevelopmental impairment determined for 91% of the infants by investigators who were unaware of the treatment assignments.
Aggressive phototherapy, as compared with conservative phototherapy, significantly reduced the mean peak serum bilirubin level (7.0 vs. 9.8 mg per deciliter [120 vs. 168 μmol per liter], P<0.01) but not the rate of the primary outcome (52% vs. 55%; relative risk, 0.94; 95% confidence interval [CI], 0.87 to 1.02; P = 0.15). Aggressive phototherapy did reduce rates of neurodevelopmental impairment (26%, vs. 30% for conservative phototherapy; relative risk, 0.86; 95% CI, 0.74 to 0.99). Rates of death in the aggressive-phototherapy and conservative-phototherapy groups were 24% and 23%, respectively (relative risk, 1.05; 95% CI, 0.90 to 1.22). In preplanned subgroup analyses, the rates of death were 13% with aggressive phototherapy and 14% with conservative phototherapy for infants with a birth weight of 751 to 1000 g and 39% and 34%, respectively (relative risk, 1.13; 95% CI, 0.96 to 1.34), for infants with a birth weight of 501 to 750 g.
Aggressive phototherapy did not significantly reduce the rate of death or neurodevelopmental impairment. The rate of neurodevelopmental impairment alone was significantly reduced with aggressive phototherapy. This reduction may be offset by an increase in mortality among infants weighing 501 to 750 g at birth. (ClinicalTrials. gov number, NCT00114543.)
PMCID: PMC2821221  PMID: 18971491

Results 1-4 (4)