Death or neurodevelopmental impairment at 18 to 22 months corrected age in a randomized trial of early dexamethasone to prevent death or chronic lung disease in extremely low birth weight infants.

OBJECTIVE: To evaluate the incidence of death or neurodevelopmental impairment (NDI) at 18-22 months corrected age in subjects enrolled in a trial of early dexamethasone treatment to prevent death or chronic lung disease in extremely low birth weight infants. STUDY DESIGN: Evaluation of infants at 18-22 months corrected age included anthropomorphic measurements, a standard neurological examination, and the Bayley Scales of Infant Development-II, including the Mental Developmental Index and the Psychomotor Developmental Index. NDI was defined as moderate or severe cerebral palsy, Mental Developmental Index or Psychomotor Developmental Index <70, blindness, or hearing impairment. RESULTS: Death or NDI at 18-22 months corrected age was similar in the dexamethasone and placebo groups (65% vs 66%, P = .99 among those with known outcome). The proportion of survivors with NDI was also similar, as were mean values for weight, length, and head circumference and the proportion of infants with poor growth (50% vs 41%, P = .42 for weight less than 10th percentile); 49% of infants in the placebo group received treatment with corticosteroid compared with 32% in the dexamethasone group (P = .02). CONCLUSION: The risk of death or NDI and rate of poor growth were high but similar in the dexamethasone and placebo groups. The lack of a discernible effect of early dexamethasone on neurodevelopmental outcome may be due to frequent clinical corticosteroid use in the placebo group.

Neurodevelopmental outcome of extremely low birth weight infants with Candida infection.

OBJECTIVE: Candida remains an important cause of late-onset infection in preterm infants. Mortality and neurodevelopmental outcome of extremely low birth weight (ELBW) infants enrolled in the Candida study were evaluated based on infection status. STUDY DESIGN: ELBW infants born at Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network (NRN) centers between March 2004 and July 2007 who were screened for suspected sepsis were eligible for inclusion in the Candida study. Primary outcome data for neurodevelopmental impairment (NDI) or death were available for 1317 of the 1515 infants (87%) enrolled in the Candida study. The Bayley Scales of Infant Development-II or -III was administered at 18 months' adjusted age. A secondary comparison was performed with 864 infants enrolled in the NRN Generic Database during the same cohort who were never screened for sepsis and therefore not eligible for the Candida study. RESULTS: Among ELBW infants enrolled in the Candida study, 31% with Candida and 31% with late-onset non-Candida sepsis had NDI at 18 months. Infants with Candida sepsis and/or meningitis had an increased risk of death and were more likely to have the composite outcome of death and/or NDI compared with uninfected infants in adjusted analysis. Compared with infants in the NRN registry never screened for sepsis, overall risk for death were similar but those with Candida infection were more likely to have NDI (OR 1.83, 95% CI 1.01-3.33, P = .047). CONCLUSIONS: In this cohort of ELBW infants, those with infection and/or meningitis were at increased risk for death and/or NDI. This risk was highest among those with Candida sepsis and/or meningitis.

Neurodevelopmental outcomes of premature infants with severe respiratory failure enrolled in a randomized controlled trial of inhaled nitric oxide.

OBJECTIVES: We hypothesized that inhaled nitric oxide (iNO) would not decrease death or neurodevelopmental impairment (NDI) in infants enrolled in the National Institute of Child Health and Human Development Preemie iNO Trial (PiNO) trial, nor improve neurodevelopmental outcomes in the follow-up group. STUDY DESIGN: Infants <34 weeks of age, weighing <1500 g, with severe respiratory failure were enrolled in the multicenter, randomized, controlled trial. NDI at 18 to 22 months corrected age was defined as: moderate to severe cerebral palsy (CP; Mental Developmental Index or Psychomotor score Developmental Index <70), blindness, or deafness. RESULTS: Of 420 patients enrolled, 109 who received iNO (52%) and 98 who received placebo (47%) died. The follow-up rate in survivors was 90%. iNO did not reduce death or NDI (78% versus 73%; relative risk [RR], 1.07; 95% CI, 0.95-1.19), or NDI or Mental Developmental Index <70 in the follow-up group. Moderate-severe CP was slightly higher with iNO (RR, 2.41; 95% CI, 1.01-5.75), as was death or CP in infants weighing <1000 g (RR, 1.22; 95% CI, 1.05-1.43). CONCLUSIONS: In this extremely ill cohort, iNO did not reduce death or NDI or improve neurodevelopmental outcomes. Routine iNO use in premature infants should be limited to research settings until further data are available.

Safety and immunogenicity of palivizumab (Synagis) administered for two seasons.

To evaluate the safety and immunogenicity of palivizumab, 55 children who received palivizumab in the IMpact-RSV trial received 5 monthly doses of 15 mg/kg palivizumab (Synagis) during the subsequent year. The single child with an antipalivizumab titer of >1/40 had no associated serious adverse events and had expected serum palivizumab trough concentrations. Second year palivizumab prophylaxis was safe and well-tolerated.

Visual perceptual skills in children born with very low birth weights.

INTRODUCTION: A disproportionate number of very low birth weight (VLBW; < or =1500 g) children require special education services and have school-related problems even when they are free from major disabilities and have average intelligence quotient scores. Visual-perceptual problems have been suggested as contributors to deficits in academic performance, but few data are available describing specific visual-perceptual problems. This study was designed to identify specific visual-perceptual skills in VLBW children. METHOD: Participants were 92 VLBW children aged 4 through 5 years who were free from major disability and appropriate for gestational age at birth. The Test of Visual-Perceptual Skills (non-motor)-Revised was used. RESULTS: Despite intelligent quotient scores in the average range, the majority (63% to 78.3%) of the children performed below age level on all seven subscales of a normed assessment of visual perceptual skills. DISCUSSION: Results suggest that visual perceptual screening should be considered as a part of routine evaluations of preschool-aged children born prematurely. Early identification of specific deficits could lead to interventions to improve achievement trajectories for these high-risk children.

Early bubble CPAP and outcomes in ELBW preterm infants.

OBJECTIVE: To test whether the introduction of early bubble continuous positive airway pressure (CPAP) results in improved respiratory outcomes in extremely low birth-weight infants. STUDY DESIGN: Outcomes of all infants between 401 and 1000 g born in a level 3 neonatal intensive care units (NICU) between July 2000 and October 2001 (period 2) were compared using historical controls (period 1). Early bubble (CPAP) was prospectively introduced in the NICU during period 1. Univariate and adjusted comparisons were made across time periods. RESULTS: Delivery room intubations, days on mechanical ventilation and use of postnatal steroids decreased (p<0.001) in period 2, while mean days on CPAP, number of babies on CPAP at 24 hours (p<0.001) and mean weight at 36 weeks corrected gestation also increased (p<0.05) after introduction of early bubble CPAP. CONCLUSIONS: Early bubble CPAP reduced delivery room intubations, days on mechanical ventilation, postnatal steroid use and was associated with increased postnatal weight gain with no increased complications.

Center differences and outcomes of extremely low birth weight infants.

OBJECTIVE: Previous multicenter studies have shown significant center differences in neonatal characteristics and morbidities. This study evaluated center differences in outcome at 18 to 22 months among extremely low birth weight (ELBW; 401-1000 g) infants after adjusting for demographics and antenatal interventions, and it identified neonatal interventions associated with outcome differences. METHODS: We assessed the outcome of 2478 liveborn infants who were admitted in 1993 and 1994 to the 12 centers of the Neonatal Research Network of the National Institute of Child Health and Human Development; 1483 (60%) infants survived to 18 to 22 months, and 1151 (78%) had comprehensive evaluations. Logistic regression analyses were performed to identify center differences and the association of 4 neonatal interventions--active resuscitation, postnatal steroids, ventilator treatment for < or =27 days, and full enteral feedings < or =24 days--with adverse outcomes (cerebral palsy, low Bayley scores, and neurodevelopmental impairment [NDI]), after adjusting for demographics and antenatal interventions. RESULTS: Using bivariate analyses, significant center differences were identified for mortality, antenatal and postnatal interventions, social and environmental variables, neonatal morbidities, and neurodevelopmental outcomes for the 12 centers. After adjustment for maternal and infant demographics and antenatal interventions, the percentage of ELBW infants who had died or had NDI at 18 to 22 months ranged from 52% to 85%. Active resuscitation and postnatal steroids were associated with increases of NDI of 11.8% and 19.3%, whereas shorter ventilation support and shorter time to achieve full enteral feeds were associated with decreases in NDI of 20.7% and 17.3%, respectively. CONCLUSION: There are large and disturbing differences among centers in outcomes at 18 to 22 months after adjusting for demographic and antenatal interventions. Center differences in postnatal interventions associated with differences in outcome can provide hypotheses for testing in clinical trials to improve outcome.

Neurodevelopmental outcome and growth at 18 to 22 months' corrected age in extremely low birth weight infants treated with early erythropoietin and iron.

BACKGROUND: Clinical trials evaluating the use of erythropoietin (Epo) have demonstrated a limited reduction in transfusions; however, long-term developmental follow-up data are scarce. OBJECTIVE: We compared anthropometric measurements, postdischarge events, need for transfusions, and developmental outcomes at 18 to 22 months' corrected age in extremely low birth weight (ELBW) infants treated with early Epo and supplemental iron therapy with that of placebo/control infants treated with supplemental iron alone. METHODS: The National Institute of Child Health and Human Development Neonatal Research Network completed a randomized, controlled trial of early Epo and iron therapy in preterm infants < or =1250 g. A total of 172 ELBW (< or =1000-g birth weight) infants were enrolled (87 Epo and 85 placebo/control). Of the 72 Epo-treated and 70 placebo/control ELBW infants surviving to discharge, follow-up data (growth, development, rehospitalization, transfusions) at 18 to 22 months' corrected age were collected on 51 of 72 Epo-treated infants (71%) and 51 of 70 placebo/controls (73%) by certified examiners masked to the treatment group. Statistical significance was determined using chi2 analysis. RESULTS: There were no significant differences between treatment groups in weight or length or in the percentage of infants weighing <10th percentile either at the time of discharge or at follow-up, and no difference was found in the mean head circumference between groups. A similar percentage of infants in each group was rehospitalized (38% Epo and 35% placebo/control) for similar reasons. There were no differences between groups with respect to the percentage of infants with Bayley-II Mental Developmental Index <70 (34% Epo and 36% placebo/control), blindness (0% Epo and 2% placebo/control), deafness or hearing loss requiring amplification (2% Epo and 2% placebo/control), moderate to severe cerebral palsy (16% Epo and 18% placebo/control) or the percentage of infants with any of the above-described neurodevelopmental impairments (42% Epo and 44% placebo/control). CONCLUSIONS: Treatment of ELBW infants with early Epo and iron does not significantly influence anthropometric measurements, need for rehospitalization, transfusions after discharge, or developmental outcome at 18 to 22 months' corrected age.