Premature birth is a significant cause of infant and child morbidity and mortality. In the United States, the premature birth rate, which had steadily increased during the 1990s and early 2000s, has decreased annually for four years and is now approximately 11.5%. Human viability, defined as gestational age at which the chance of survival is 50%, is currently approximately 23–24 weeks in developed countries. Infant girls, on average, have better outcomes than infant boys. A relatively uncomplicated course in the intensive care nursery for an extremely premature infant results in a discharge date close to the prenatal EDC. Despite technological advances and efforts of child health experts during the last generation, the extremely premature infant (less than 28 weeks gestation) and extremely low birth weight infant (ELBW) (< 1000 grams) remain at high risk for death and disability with 30–50% mortality and, in survivors, at least 20–50% risk of morbidity. The introduction of CPAP, mechanical ventilation, and exogenous surfactant increased survival and spurred the development of neonatal intensive care in the 1970s through the early 1990s. Routine administration of antenatal steroids during premature labor improved neonatal mortality and morbidity in the late 1990s. The recognition that chronic postnatal administration of steroids to infants should be avoided may have improved outcomes in the early 2000s. Evidence from recent trials attempting to define the appropriate target for oxygen saturation in preterm infants suggests arterial oxygen saturation between 91–95% (compared to 85–89%) avoids excess mortality. However, final analyses of data from these trials have not been published, so definitive recommendations are still pending The development of neonatal neurocognitive care visits may improve neurocognitive outcomes in this high-risk group. Long-term follow up to detect and address developmental, learning, behavioral, and social problems is critical for children born at these early gestational ages. The striking similarities in response to extreme prematurity in the lung and brain imply that agents and techniques that benefit one organ are likely to also benefit the other. Finally, since therapy and supportive care continue to change, the outcomes of ELBW infants are ever evolving. Efforts to minimize injury, preserve growth, and identify interventions focused on antioxidant and anti-inflammatory pathways are now being evaluated. Thus, treating and preventing long-term deficits must be developed in the context of a “moving target.”

Objective-To determine whether neonatal seizures are associated with neurodevelopmental outcome in infants with hypoxia-ischemia, independent of the presence and severity of brain injury on magnetic resonance imaging (MRI).Study Design-We used multivariate regression to examine the independent effect of clinical neonatal seizures and their treatment on neurodevelopment in 77 term newborns at risk for hypoxic-ischemic brain injury. Clinical seizures were recorded prospectively, and high-resolution newborn MRI was used to measure the severity of brain injury. The outcome measure was fullscale intelligence quotient (FSIQ) of the Wechsler Preschool and Primary Scale of IntelligenceRevised and the neuromotor score at four years.Results-After controlling for severity of injury on MRI, children with neonatal seizures had worse motor and cognitive outcomes than those without seizures. The magnitude of effect varied with seizure severity: children with severe seizures had a lower FSIQ than those with mild/ moderate seizures (P < 0.0001).Conclusions-Clinical neonatal seizures in the setting of birth asphyxia are associated with worse neurodevelopmental outcome, independent of the severity of hypoxic-ischemic brain injury. Randomized controlled trials are essential to determine whether differences in seizure treatment can improve outcome.

Objective To determine the contemporary etiology, burden, and short-term outcomes of seizures in neonates monitored with continuous video-electroencephalogram (cEEG). Study design We prospectively collected data from 426 consecutive neonates (56% male, 88% term) ≤44 weeks postmenstrual age with clinically suspected seizures and/or electrographic seizures. Subjects were assessed between January 2013 and April 2015 at seven U.S. tertiary care pediatric centers following American Clinical Neurophysiology Society (ACNS) guidelines for cEEG for at risk neonates. Seizure etiology, burden, management and outcome were determined by chart review using a case report form designed at study onset. Results The most common seizure etiologies were hypoxic-ischemic encephalopathy (38%), ischemic stroke (18%), and intracranial hemorrhage (11%). Seizure burden was high, with 59% having ≥7 electrographic seizures and 16% having status epilepticus; 52% received ≥2 anti-seizure medications. During the neonatal admission, 17% died; 49% of survivors had abnormal neurological examination at hospital discharge. In an adjusted analysis, high seizure burden was a significant risk factor for mortality, length of hospital stay, and abnormal neurological examination at discharge. Conclusions In this large contemporary profile of consecutively enrolled newborns with seizures treated at centers using cEEG per ACNS guidelines, about half had high seizure burden, received ≥2 anti-seizure medications, and/or died or had abnormal examination at discharge. Higher seizure burden was associated with increased morbidity and mortality. These findings underscore the importance of accurate determination of neonatal seizure frequency and etiology, and a potential for improved outcome if seizure burden is reduced.

An autosomal recessive syndrome of nonprogressive cerebellar ataxia and mental retardation is associated with inferior cerebellar hypoplasia and mild cerebral gyral simplification in the Hutterite population. An identity-by-descent mapping approach using eight patients from three interrelated Hutterite families localized the gene for this syndrome to chromosome region 9p24. Haplotype analysis identified familial and ancestral recombination events and refined the minimal region to a 2-Mb interval between markers D9S129 and D9S1871. A 199-kb homozygous deletion encompassing the entire very low density lipoprotein receptor (VLDLR) gene was present in all affected individuals. VLDLR is part of the reelin signaling pathway, which guides neuroblast migration in the cerebral cortex and cerebellum. To our knowledge, this syndrome represents the first human lipoprotein receptor malformation syndrome and the second human disease associated with a reelin pathway defect.