IMPORTANCE Hypothermia at 33.5°C for 72 hours for neonatal hypoxic ischemic encephalopathy reduces death or disability to 44% to 55%; longer cooling and deeper cooling are neuroprotective in animal models. OBJECTIVE To determine if longer duration cooling (120 hours), deeper cooling (32.0°C), or both are superior to cooling at 33.5°C for 72 hours in neonates who are full-term with moderate or severe hypoxic ischemic encephalopathy. DESIGN, SETTING, AND PARTICIPANTS Arandomized, 2 × 2 factorial design clinical trial performed in 18 US centers in the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Neonatal Research Network between October 2010 and November 2013. INTERVENTIONS Neonates were assigned to 4 hypothermia groups; 33.5°C for 72 hours, 32.0°C for 72 hours, 33.5°C for 120 hours, and 32.0°C for 120 hours. MAIN OUTCOMES AND MEASURES The primary outcome of death or disability at 18 to 22 months is ongoing. The independent data and safety monitoring committee paused the trial to evaluate safety (cardiac arrhythmia, persistent acidosis, major vessel thrombosis and bleeding, and death in the neonatal intensive care unit [NICU]) after the first 50 neonates were enrolled, then after every subsequent 25 neonates. The trial was closed for emerging safety profile and futility analysis after the eighth review with 364 neonates enrolled (of 726 planned). This report focuses on safety and NICU deaths by marginal comparisons of 72 hours’ vs 120 hours’ duration and 33.5°C depth vs 32.0°C depth (predefined secondary outcomes). RESULTS The NICU death rates were 7 of 95 neonates (7%) for the 33.5°C for 72 hours group, 13 of 90 neonates (14%) for the 32.0°C for 72 hours group, 15 of 96 neonates (16%) for the 33.5°C for 120 hours group, and 14 of 83 neonates (17%) for the 32.0°C for 120 hours group. The adjusted risk ratio (RR) for NICU deaths for the 120 hours group vs 72 hours group was 1.37 (95% CI, 0.92–2.04) and for the 32.0°C group vs 33.5°C group was 1.24 (95% CI, 0.69–2.25). Safety outcomes were similar between the 120 hours group vs 72 hours group and the 32.0°C group vs 33.5°C group, except major bleeding occurred among 1% in the 120 hours group vs 3% in the 72 hours group (RR, 0.25 [95% CI, 0.07–0.91]). Futility analysis determined that the probability of detecting a statistically significant benefit for longer cooling, deeper cooling, or both for NICU death was less than 2%. CONCLUSIONS AND RELEVANCE Among neonates who were full-term with moderate or severe hypoxic ischemic encephalopathy, longer cooling, deeper cooling, or both compared with hypothermia at 33.5°C for 72 hours did not reduce NICU death. These results have implications for patient care and design of future trials.

Participation in a single SBME mastery learning session was insufficient to affect pediatric interns' subsequent procedural success.

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Objective We describe five neonates with enteroviral (EV) infection to demonstrate central nervous system (CNS) and cardiac complications and report successful treatment of myocarditis with immunoglobulin intravenous (IVIG) in two. Study Design Case series identified during three enteroviral seasons in one neonatal intensive care unit (NICU) by cerebral spinal fluid (CSF) reverse transcriptase polymerase chain reaction (PCR) testing for EV in neonates suspected to have sepsis, but with sterile bacterial cultures. Results Cases were identified in each of three sequential years in a NICU with 800 to 900 admissions/year. Two cases were likely acquired perinatally; all were symptomatic with lethargy and poor feeding by age 5 to 10 days. All had signs of sepsis and/or meningitis; one progressed to periventricular leukomalacia and encephalomalacia. Two recovered from myocarditis after treatment that included IVIG 3 to 5 g/kg. Conclusion Neonates who appear septic without bacterial etiology may have EV CNS infections that can be diagnosed rapidly by CSF PCR testing. Cases may be underdiagnosed in the early neonatal period if specific testing is not performed. Neonates with EV infection should be investigated for evidence of periventricular leukomalacia, screened for myocarditis, and considered for IVIG treatment.

HYPOTHESIS:Newborns with major congenital malformations (MCM) have contributed to a significant proportion of resource utilization in a regional referral neonatal intensive care unit (NICU). SETTING:The Children's Hospital Medical Center NICU, Cincinnati, OH. SUBJECTS:Newborns with and without MCM admitted from August 1, 1993 through July 31, 1994. Total patients studied were 572; 147 with and 385 without MCM. No intervention was performed in this observational study. STATISTICS:Statistics were t test, chi-squared, and rank sum analysis. RESULTS:MCM accounted for 27.6% of NICU referrals, 32.4% of total NICU days, and 39.6% of NICU costs. Both median cost per patient and length of stay were significantly (p Ͻ 0.01) higher for patients with MCM than those without MCM. Surgery was more frequent in MCM than non-MCM cases. Thirty-three percent of the newborns with MCM received ongoing medical support at discharge. CONCLUSION:Patients with MCM remain as one of the largest and costliest groups hospitalized in a referral NICU.Congenital malformations remain the leading cause of deaths in the United States for infants less than 1 year of age, with sudden infant death syndrome and disorders of prematurity being close behind. 1 Recently, advances in the care of premature infants, including antenatal steroids and surfactant therapy, have resulted in improved survival for this neonatal intensive care unit (NICU) population. Concurrently, newborns with major congenital malformations (MCM) have contributed to a consistent and relatively higher proportion of total NICU deaths than other hospitalized NICU patients. 2 Difficult decisions involving the provision of care for newborns with malformations were the basis for the development of the "Baby Doe" rulings by the U.S. Department of Health and Human Services in 1985. The regulations placed increasing responsibility on pediatricians to treat all infants with congenital malformations by requiring that reasonable measures be done to preserve the life of an infant with a serious condition. 3,4 Today, ethical considerations remain an integral part of the care of newborns with malformations.The combination of recent advancements in neonatal care and the responsibility to treat infants with life-threatening conditions may lead to an increased contribution to hospital resource use by newborns with major congenital malformations admitted to a regionalized NICU. In this study, we examined resource utilization in a population of infants with MCM admitted to a single referral children's hospital NICU over a 1-year time period. The comparison population consisted of newborns without MCM (non-MCM) admitted to the same NICU during the same time period.We hypothesized that newborns with MCMs would contribute significantly ( p Ͻ 0.05) to the median cost and median length of the initial hospitalization compared with those without MCMs. The purpose of the study was (1) to determine the duration and cost of the initial NICU hospitalization for newborn infants with MCM compared with non-MCM patien...