Apolipoprotein E genotype and outcome in infants with hypoxic-ischemic encephalopathy.

BACKGROUND: Adults with the apolipoprotein E (APOE) gene alleles e4 and e2 are at high risk of poor neurological outcome after brain injury. The e4 allele has been associated with cerebral palsy (CP), and the e2 allele has been associated with worse neurological outcome with congenital heart disease. This study was done to test the hypothesis that the APOE genotype is associated with outcome among neonates who survive after hypoxic-ischemic encephalopathy (HIE). METHODS: We conducted a cohort study of infants who survived HIE and had 18-22 mo standardized neurodevelopmental evaluations to assess associations between disability and the APOE genotypes e3/e3, e4/-, and e2/-. RESULTS: A total of 139 survivors were genotyped. Of these, 86 (62%) were of the e3/e3, 41 (29%) were of the e4/-, and 14 (10%) were of the e2/- genotypes. One hundred and twenty-nine infants had genotype and follow-up data; 26% had moderate or severe disabilities. Disability prevalence was 30 and 19% among those with and without the 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, respectively. None of the differences were statistically significant. CP prevalence was also similar among genotype groups. CONCLUSION: Disability was not associated with the APOE genotype in this cohort of HIE survivors.

Outcome of extremely low birth weight infants who received delivery room cardiopulmonary resuscitation.

OBJECTIVE: To determine whether delivery room cardiopulmonary resuscitation (DR-CPR) independently predicts morbidities and neurodevelopmental impairment (NDI) in extremely low birth weight infants. STUDY DESIGN: We conducted a cohort study of infants born with birth weight of 401 to 1000 g and gestational age of 23 to 30 weeks. DR-CPR was defined as chest compressions, medications, or both. Logistic regression was used to determine associations among DR-CPR and morbidities, mortality, and NDI at 18 to 24 months of age (Bayley II mental or psychomotor index <70, cerebral palsy, blindness, or deafness). Data are adjusted ORs with 95% CIs. RESULTS: Of 8685 infants, 1333 (15%) received DR-CPR. Infants who received DR-CPR had lower birth weight (708±141 g versus 764±146g, P<.0001) and gestational age (25±2 weeks versus 26±2 weeks, P<.0001). Infants who received DR-CPR had more pneumothoraces (OR, 1.28; 95% CI, 1.48-2.99), grade 3 to 4 intraventricular hemorrhage (OR, 1.47; 95% CI, 1.23-1.74), bronchopulmonary dysplasia (OR, 1.34; 95% CI, 1.13-1.59), death by 12 hours (OR, 3.69; 95% CI, 2.98-4.57), and death by 120 days after birth (OR, 2.22; 95% CI, 1.93-2.57). Rates of NDI in survivors (OR, 1.23; 95% CI, 1.02-1.49) and death or NDI (OR, 1.70; 95% CI, 1.46-1.99) were higher for DR-CPR infants. Only 14% of DR-CPR recipients with 5-minute Apgar score <2 survived without NDI. CONCLUSIONS: DR-CPR is a prognostic marker for higher rates of mortality and NDI for extremely low birth weight infants. New DR-CPR strategies are needed for this population.

Aggressive vs. conservative phototherapy for infants with extremely low birth weight.

BACKGROUND: 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). METHODS: 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. RESULTS: 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 micromol 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. CONCLUSIONS: 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.)

Car seat or car bed for very low birth weight infants at discharge home.

OBJECTIVE: To compare the incidence of apnea, bradycardia, or desaturation in a car seat with that in a car bed for preterm very low birth weight (< or = 1500 g) infants. STUDY DESIGN: Infants were studied for 120 minutes in a car seat and in a car bed. Apnea (> 20 seconds), bradycardia (heart rate < 80/min for > 5 seconds), desaturation (SpO2 < 88% for > 10 seconds), and absent nasal flow were monitored. RESULTS: We assessed 151 infants (median birth weight, 1120 g [range, 437 to 3105]; median birth gestational age, 29 weeks [24 to 34]) in both devices. Twenty-three infants (15%) had > or = 1 event in the car seat compared with 29 (19%) in the car bed (P = .4). Time to first event was similar in the car seat and car bed (mean, 54 to 55 minutes). In logistic regression analyses, bronchopulmonary dysplasia was a significant predictor for a car seat event and a lower gestational age at birth was a risk factor for a car bed event. CONCLUSIONS: We found no evidence that an event is less likely in a car bed than in a car seat. Whichever device is used, very low birth weight infants require observation during travel.

Severe fetal acidemia and subsequent neonatal encephalopathy in the larger premature infant.

The contribution of intrapartum hypoxia-ischemia to neonatal encephalopathy in the larger preterm infant remains poorly defined. Such infants could become potential candidates for neuroprotective strategies. The objective of this study was to determine in preterm infants of gestation 31 to 36 weeks, with severe fetal acidemia (i.e., cord arterial pH < 7.00) the incidence of moderate to severe neonatal encephalopathy as well as the perinatal characteristics that may facilitate early identification. The data of 61 preterm infants of mean birth weight 1998 gm and mean gestation of 33.6 weeks were retrieved. Short-term abnormal neurologic outcome measures included evidence of encephalopathy with or without seizures or neuroimaging abnormalities. Eight (13%) of 61 infants developed an abnormal neonatal neurologic outcome. More infants with abnormal vs normal outcome had 1-minute Apgar of 0, i.e., 4/8 vs 3/53, 5-minute Apgar score

Initial hypoglycemia and neonatal brain injury in term infants with severe fetal acidemia.

OBJECTIVE: To determine the potential contribution of initial hypoglycemia to the development of neonatal brain injury in term infants with severe fetal acidemia. METHODS: A retrospective chart review was conducted of 185 term infants who were admitted to the neonatal intensive care unit between January 1993 and December 2002 with an umbilical arterial pH <7.00. Short-term neurologic outcome measures include death as a consequence of severe encephalopathy and evidence of moderate to severe encephalopathy with or without seizures. Hypoglycemia was defined as an initial blood glucose < or =40 mg/dL. RESULTS: Forty-one (22%) infants developed an abnormal neurologic outcome, including 14 (34%) with severe hypoxic ischemic encephalopathy who died, 24 (59%) with moderate to severe hypoxic ischemic encephalopathy, and 3 (7%) with seizures. Twenty-seven (14.5%) of the 185 infants had an initial blood sugar < or =40 mg/dL. Fifteen (56%) of 27 infants with a blood sugar < or =40 mg/dL versus 26 (16%) of 158 infants with a blood sugar >40 mg/dL had an abnormal neurologic outcome (odds ratio [OR]: 6.3; 95% confidence interval [CI]: 2.6-15.3). Infants with abnormal outcomes and a blood sugar < or =40 mg/dL versus >40 mg/dL had a higher pH (6.86 +/- 0.07 vs 6.75 +/- 0.09), a lesser base deficit (-19 +/- 4 vs -23.8 +/- 4 mEq/L), and lower mean arterial blood pressure (34 +/- 10 vs 45 +/- 14 mm Hg), respectively. There was no difference between groups in the proportion of infants who required cardiopulmonary resuscitation (7 [46%] vs 15 [57%]) and those with a 5-minute Apgar score <5 (11 [73%] vs 22 [85%]). By multivariate logistic analysis, 4 variables were significantly associated with abnormal outcome: initial blood glucose < or =40 mg/dL versus >40 mg/dL (OR: 18.5; 95% CI: 3.1-111.9), cord arterial pH < or =6.90 versus >6.90 (OR: 9.8; 95% CI: 2.1-44.7), a 5-minute Apgar score < or =5 versus >5 (OR: 6.4; 95% CI: 1.7-24.5), and the requirement for intubation with or without cardiopulmonary resuscitation versus neither (OR: 4.7; 95% CI: 1.2-17.9). CONCLUSION: Initial hypoglycemia is an important risk factor for perinatal brain injury, particularly in depressed term infants who require resuscitation and have severe fetal acidemia. It remains unclear, however, whether earlier detection of hypoglycemia, such as in the delivery room, in this population could modify subsequent neurologic outcome.

Necrotizing enterocolitis and neurodevelopmental outcome in extremely low birth weight infants <1000 g.

OBJECTIVE: To determine the growth and neurodevelopmental outcome, as well as predictors of the latter in extremely low-birth-weight (ELBW) infants with definitive necrotizing enterocolitis (NEC). STUDY DESIGN: Case - control analysis. In all, 17 ELBW infants <1000 g with Stage 2 or 3 NEC were matched to 51 control infants without NEC. Demographics, clinical course, growth, and neurodevelopmental outcome were compared. RESULTS: Demographic and clinical characteristics of both groups were similar except that NEC infants had more culture-proven sepsis (59 vs 24%, p=0.02), longer intubation (36 vs 16 days, p=0.003) and longer hospital stay (134 vs 86 days, p<0.001). At 18 to 22 months corrected age BSID-II mental scores (MDI) were similar between groups (74+/-14 vs 81+/-13, p=0.2). However, the psychomotor index (PDI) (66+/-18 vs 88+/-14), the proportion with abnormal neurologic examination (54 vs 9%), subnormal height (38 vs 3%) and head circumference (23 vs 0%) were significantly higher in NEC infants (p<0.05). A logistic model identified NEC and chronic lung disease as predictors for abnormal PDI and MDI, respectively. CONCLUSIONS: NEC and its comorbidities are associated with severe neurodevelopmental and growth delay in ELBW infants.

Hospital survival of very-low-birth-weight neonates from 1977 to 2000.

OBJECTIVE: To determine patterns of survival for very low birth weight (VLBW, birth weight 501 to 1500 g) neonates over 23 years. STUDY DESIGN: Data for 4873 VLBW neonates born from 1977 to 2000 were divided into five epochs. The primary outcome was survival to hospital discharge. Birth weight-specific survival rates were estimated by race and gender for each epoch. Presence of comorbidities and congenital anomalies, delivery mode, and provision of artificial ventilation were investigated to determine whether they could explain observed survival patterns. RESULTS: From 1977 to 1995, survival increased from 50.2% to 81.0% as the proportion of VLBW neonates receiving artificial ventilation rose from 59.0% to 80.9%. Survival was unchanged between 1990 to 1995 and 1996 to 2000. Black females maintained a survival advantage over the entire study period. Survival improved for neonates with congenital anomalies over time, but had little impact on race/gender survival patterns. Survival patterns also could not be explained by comorbidity status, delivery mode, or access to artificial ventilation. CONCLUSION: The survival advantage of VLBW black females persists and remains unexplained.

Partial or complete antenatal steroids treatment and neonatal outcome in extremely low birth weight infants < or =1000 g: is there a dose-dependent effect?

OBJECTIVES: To assess the outcome of extremely low birth weight (ELBW) infants < or =1000 g as it relates to antenatal steroids (ANS) therapy. STUDY DESIGN: A retrospective analysis of 124 infants born between January 1995 and December 1997. Infants born to mothers with pregnancy-induced hypertension, diabetes, and severe growth restriction were excluded. In all, 77 (62%) infants were exposed to ANS, of whom 31 (25%) received one to two doses (partial course), and 46 (37%) received three to four doses (complete course). A total of 47 infants (38%) were not exposed to ANS. RESULTS: Infants not exposed to ANS, who exhibited more HMD, PDA, and IVH, were administered more surfactants, and were more likely to die versus infants with complete ANS dosing. Regression models revealed a dose-dependent effect of ANS on HMD, surfactant use, IVH, and CLD or death, with a significant decrease in HMD with > or =2 ANS doses. CONCLUSIONS: ANS, in a dose-dependent way, are associated with improved outcome in ELBW infants < or =1000 g, with the best outcome seen after a complete course.

Association of antenatal and postnatal dexamethasone exposure with outcomes in extremely low birth weight neonates.

BACKGROUND: Recent studies of preterm neonates have indicated that antenatal dexamethasone (ADX) may have adverse effects on cranial ultrasound findings at the time of hospital discharge, including periventricular leukomalacia. Furthermore, both ADX and postnatal dexamethasone (PDX) may have adverse effects on subsequent neurodevelopmental outcome. OBJECTIVES: 1) To assess the effects of ADX exposure on cranial ultrasound findings at the time of hospital discharge and 2) to evaluate the individual effects of ADX and/or PDX exposure on subsequent neurodevelopmental outcome in extremely low birth weight (ELBW) neonates in whom confounding risk factors known to influence outcome were controlled. METHODS: One hundred seventy-three ELBW (< or =1000 g) neonates were studied using a prospectively collected database and hospital and clinic records. Study patients were assigned to 1 of 4 groups according to dexamethasone exposure: group I, no dexamethasone exposure; group II, ADX exposure to hasten fetal lung maturity; group III, PDX exposure for chronic lung disease; group IV, both ADX and PDX exposure. The 4 groups were compared using multinomial logistic regression or analysis of covariance to control for confounding variables. Primary outcome variables were cranial ultrasound findings at hospital discharge and results of developmental testing at 18 to 22 months' corrected age (Bayley Scales of Infant Development). RESULTS: Cranial ultrasound results as well as Bayley Scales of Infant Development scores were similar in groups I and II and in groups III and IV. The likelihood of abnormal cranial ultrasound studies and lower scores on neurodevelopmental testing was greater in groups III and IV versus groups I and II. In this study, ADX did not seem to increase the risk of periventricular leukomalacia. CONCLUSIONS: ADX exposure is not associated with an increase in abnormal cranial ultrasound findings in ELBW neonates. PDX exposure, but not ADX exposure, is associated with worse neurodevelopmental outcome in this population. These results are supportive of the recent statement by the American Academy of Pediatrics (Committee on Fetus and Newborn) and the Canadian Paediatric Society (Fetus and Newborn Committee) and emphasize that PDX should be used with caution in ELBW neonates.