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A prior report on hypothermia for neonatal hypoxic–ischemic encephalopathy showed a reduced rate of death or disability at 18 to 22 months of age. In this report of outcomes at 6 to 7 years, rates of death or an IQ below 70 were nonsignificantly lower with hypothermia than with usual care. Moderate or severe neonatal hypoxic–ischemic encephalopathy is associated with a high incidence of death or motor and sensory disability in children. 1 – 5 Children with encephalopathy are at risk for cognitive deficits even in the absence of functional deficits. Survivors without disability have delayed entry into primary school and fine-motor dysfunction and behavioral abnormalities. Hypothermia to 33 to 34°C for 72 hours, when initiated within 6 hours after birth among infants of more than 35 weeks' gestational age with hypoxic–ischemic encephalopathy, has been shown to reduce the risk of death or disability and increase the rate of survival free of disability . . .

Background Preterm very-low-birth-weight (PT-VLBW) infants are at risk of an elevated systolic blood pressure (SBP) in infancy and adulthood; however, the pathogenesis remains unclear. Altered renal development or function may be associated with increased SBP, but their contribution in PT-VLBW is unknown. Methods We determined renal function and its relationship to SBP in three groups of PT-VLBW at 1, 2, and 3 years of age, using serum cystatin-C to calculate the estimated glomerular filtration rate (eGFR). Results Cystatin-C levels decreased from 0.84 ± 0.2 (SD) within the 1-year group to 0.70 ± 0.1 mg/l (±SD; P  < 0.001) at 3 years and were unrelated to gender, fetal growth, and neonatal indomethacin exposure. eGFR rose from 121 ± 59 in the 1-year group to 138 ± 21 ml/min·1.73 m 2 ( P  < 0.001) at 3 years. At 1 year, cystatin-C levels decreased with increasing SBP ( P  < 0.007), and infants with SBP ≥ 90th% had lower cystatin-C and higher eGFR ( P  < 0.05). At 3 years, infants with lower birth weight ( P  < 0.03) and gestational age ( P  = 0.06) had reduced eGFR. Conclusions Preterm very-low-birth-weight infants demonstrate increasing renal function with advancing age. An elevated SBP and eGFR at 1 year suggests dysfunctional renal autoregulation and hyperfiltration, which may alter subsequent renal function and contribute to the lower eGFR seen at 3 years in infants with the lowest birth weight and gestational age.

Background Antibiotic exposure in term infants has been associated with later obesity. Premature, very-low-birth-weight (birth weight ≤ 1500 g) infants in the neonatal intensive care unit frequently are exposed to antibiotics. Our hypothesis was that in preterm infants, there is a positive linear and dose-dependent relationship between antibiotic exposure and growth from birth through 12 months’ corrected age. Methods Retrospective analysis of prospectively collected data of all antibiotic use among inborn, preterm (≤32 weeks’ gestation), very-low-birth-weight infants admitted to the neonatal intensive care unit at Parkland Memorial Hospital and followed in the Low Birth Weight Clinic at Children’s Medical Center, Dallas, TX. Antibiotic use was quantified by days of therapy which was compared with weight and length parameters at birth, 36 weeks’ postmenstrual age, and 2, 4, 6, and 12 months’ corrected age. The change in weight and length z-scores from birth to all subsequent age points was calculated. Stepwise multivariate regression analysis was performed to determine predictors of weight, length, and weight-for-length delta z-scores from birth to each subsequent age point. Results During the 18-month study, 161 infants received a median of 11 (IQR, 5.5–19.5) antibiotic days of therapy which was not associated with weight or length delta z-scores from birth through 12 months’ corrected age. Conclusion Association of prolonged antibiotic use and neonatal morbidities and mortality may override the potential association with increased weight gain in the NICU and beyond.

Background: Preterm, very-low-birth-weight (PT-VLBW) neonates are at-risk for metabolic syndrome later in life. At 1–3 y, they exhibit excessive weight-for-length z -scores (Wt-L Z ) and elevated systolic blood pressures (SBP). Serum adipokines are biomarkers of adiposity, but expression in PT-VLBW infants is unclear. We examined the correlation between serum adipokine levels, anthropometric measures and SBP in PT-VLBW neonates at follow-up. Methods: This was a cross-sectional cohort study of PT-VLBW infants at 1, 2, and 3 y of age (40/cohort). We measured SBP, abdominal circumference (AC) and anthropometrics; calculated age/gender-specific z -scores for Wt, L, Wt-L and subscapular skin fold (SS Z ), and measured serum adipokines. Results: Serum leptin was unaffected by chronologic age and gender, but was positively correlated with weight, Wt-L Z , AC, and SS Z at 1 and 3 y ( P < 0.01). Female infants at 1 and 3 y had a more significant relationship than males between serum leptin and SS Z ( P < 0.001, R = 0.75 and P < 0.001, R = 0.70, respectively). Adiponectin levels were 16–20% lower at 3 vs. 1–2 y ( P = 0.02, ANOVA) and negatively correlated with SBP. Conclusion: Although serum leptin was unrelated to advancing age, gender, and SBP in PT-VLBW infants, levels correlated with measures of adiposity at 1 and 3 y, females > males, suggesting leptin resistance may occur in early infancy.

ObjectiveTo determine the association of persistent pulmonary hypertension of the newborn (PPHN) with death or disability among infants with moderate or severe hypoxic ischemic encephalopathy (HIE) treated with therapeutic hypothermia.MethodsWe compared infants with and without PPHN enrolled in the hypothermia arm from three randomized controlled trials (RCTs): Induced Hypothermia trial, “usual care” arm of Optimizing Cooling trial, and Late Hypothermia trial. Primary outcome was death or disability at 18–22 months adjusted for severity of HIE, center, and RCT.ResultsAmong 280 infants, 67 (24%) were diagnosed with PPHN. Among infants with and without PPHN, death or disability was 47% vs. 29% (adjusted OR: 1.65, 0.86–3.14) and death was 26% vs. 12% (adjusted OR: 2.04, 0.92–4.53), respectively.ConclusionsPPHN in infants with moderate or severe HIE was not associated with a statistically significant increase in primary outcome. These results should be interpreted with caution given the limited sample size.

Preterm, very-low-birth-weight neonates (≤1500 gm, VLBW) exhibit elevated systolic blood pressures (SBP) in adolescence and adulthood; however, the age of onset and causes are unknown. We assessed SBP in a cross-sectional study of VLBW infants at 1, 2 and 3 years of age ( n = 40 per cohort). SBP was manually measured using Doppler amplification (observed), and calm values were compared to reference ranges used for clinical purposes (expected). SBP was converted to age-, gender- and height-specific z -scores (SBPz). Perinatal variables and growth parameters measured between 6 and 36 months were assessed as predictors of an elevated SBP. Observed SBP and SBPz exceeded the expected value at each age ( P  < 0.01); for example 1 year SBP was 94 ± 10 (standard deviation) vs. 85 ± 3 mmHg, respectively. Although the expected SBP rose from 85 ± 3 to 90 ± 3 mmHg with advancing age ( P  < 0.05), VLBW SBP was unchanged ( P  > 0.1), averaging 93 mmHg across ages. Height and weight z -scores were below expected ( P  < 0.01), while weight-for-height z -scores exceeded zero at 6, 12 and 24 months ( P  < 0.05). Male subscapular skinfold thickness:abdominal circumference ratio decreased with advancing age, paralleling the decreases in SBPz. The VLBW neonates demonstrated an elevated SBP as early as 1 year of age. Although predictive perinatal variables were not identified, gender-specific relationships between infant growth and SBP were observed.

This multicenter trial showed no significant differences in the composite outcome of death or neurodevelopmental impairment among extremely preterm infants randomly assigned to early CPAP or early surfactant and to lower or higher oxygen saturation. Extremely premature infants are at high risk for death and neurosensory or developmental impairment in early childhood. 1 – 3 The risk of neurodevelopmental impairment increases with decreasing gestational age and greater severity of illness. Neurodevelopmental impairment is often a consequence of neonatal complications. 4 – 12 Although surfactant administration decreases the risk of death and bronchopulmonary dysplasia, randomized, controlled trials of various respiratory interventions have not shown significant reductions in mortality and morbidity or improvement in developmental outcomes. 13 – 17 We previously reported results of the multicenter, randomized, controlled Surfactant, Positive Pressure, and Pulse Oximetry Randomized Trial (SUPPORT), which involved extremely premature infants (from . . .

Objective: Bayley-III scales are currently used to evaluate outcomes of term infants following hypothermia therapy, while all before reported outcomes in this population have used Bayley-II. Our objectives were to determine the incidence of abnormal neurodevelopmental outcomes using Bayley III and the predictive value of Magnetic resonance imaging (MRI) in infants who received systemic hypothermia. Study Design: We conducted a prospective cohort study of inborn infants who underwent hypothermia for moderate/severe neonatal encephalopathy from October 2005–November 2011. Result: Eighty newborns underwent hypothermia (incidence of 1/1000). Of the survivors, 89% had Bayley-III performed around 24 months of age. An abnormal outcome using Bayley-III <85 occurred in 50%, while Bayley III <70 occurred in 13%. MRI predicted Bayley III<85 with sensitivity of 73%, specificity of 84%, positive-predictive value of 84% and negative-predictive value of 74%. Conclusion: A Bayley-III 85 cutoff identifies a disability rate of 50%, and MRI was predictive of abnormal outcomes. Findings can be useful for counseling of families and planning of future studies using Bayley III.

Objective: To determine whether a Bayley-III motor composite score of 85 may overestimate moderate–severe motor impairment by analyzing Bayley-III motor components and developing cut-point scores for each. Study Design: Retrospective study of 1183 children born <27 weeks gestation at NICHD Neonatal Research Network centers and evaluated at 18–22 months corrected age. Gross Motor Function Classification System determined gross motor impairment. Statistical analyses included linear and logistic regression and sensitivity/specificity. Results: Bayley-III motor composite scores were strong indicators of gross/fine motor impairment. A motor composite cut-point of 73 markedly improved the specificity for identifying gross and/or fine motor impairment (94% compared with a specificity of 76% for the proposed new cut-point of 85). A Fine Motor Scaled Score <3 differentiated mild from moderate–severe fine motor impairment. Conclusions: This study indicates that a Bayley-III motor composite score of 85 may overestimate impairment. Further studies are needed employing term controls and longer follow-up.

ObjectiveExtremely low birth weight children are at high risk for cognitive impairment.Study designCognitive outcome of extremely low birth weight children participating in a Neonatal Research Network, randomized trial was evaluated at 18 and 30 months corrected age using the Bayley Scales of Infant Development, 2nd ed. Family resources and social support were assessed using a Family Resource Scale parent questionnaire. Regression analysis was used to determine independent demographic, medical, and family resource factors influencing longitudinal cognitive outcome.ResultHigher Family Resource Scale scores at 18 months were associated with greater improvement in cognitive scores between 18 and 30 months. Cognitive outcome was most adversely affected in children whose families had the least resources and social support. The adverse effect of poor social support was independent of family income.ConclusionPoor interpersonal social support has an independent, adverse impact on cognitive outcomes of extremely low birth weight infants.