Neonatal Intensive Care - The Only Constant Is Change.

The rate of survival of infants born extremely early — previously considered to be periviable (≤24 weeks) — has increased with advances in perinatal–neonatal care. However, concerns regarding higher rates of neurodevelopmental impairment among survivors have been raised. A precise interpretation of outcomes in periviable neonates requires an understanding of competing outcomes bias, differences in outcome reporting, denominators used in the calculation of rates, and health care philosophies at the personal, institutional, regional, and national level that influence care provision. In this issue of the Journal, Younge et al.1 report data on 4227 neonates born at 22 to 24 weeks of gestation from 11 neonatal centers in the United States. The data were compared across three consecutive birth-year epochs (2000–2003 [epoch 1], 2004–2007 [epoch 2], and 2008–2011 [epoch 3]). Survival free of neurodevelopmental impairment increased between epoch 1 and epoch 3 (adjusted relative risk, 1.59; 95% confidence interval, 1.28 to 1.99). When the data are analyzed according to gestational age, improvements in survival are still not seen for infants born at 22 weeks; epoch 2 was the turning point for infants born at 23 weeks, and random variations in outcomes characterized infants born at 24 weeks of gestation. There was a 4 percentage point increase in the rate of survival without clinically significant neurodevelopmental impairment from epoch 1 to epoch 3 (P = 0.001) and a 1 percentage point increase in the rate of survival with clinically significant neurodevelopmental impairment from epoch 1 to epoch 3 (P = 0.29). The study attempts to signal a progressive change in neonatal intensive care by reporting on the largest cohort of periviable neonates from the United States and, more importantly, shows variability across centers. However, limitations include the exclusion of neonates not born in the 11 centers, evaluation of outcomes by arbitrary segmental epochs rather than by process control charts, and lack of generalizability — the study population represents only 4 to 5% of periviable neonates born in the United States. In addition to the study by Younge et al., other multicenter studies have reported on periviable neonates (Table 1). Reported rates of death or clinically significant neurodevelopmental impairment were greater than 94% for infants born at 22 weeks, between 80% and 90% for infants born at 23 weeks, and between 51% and 72% for infants born at 24 weeks of gestation, with the exception of Japan and Sweden (Table 1). There is wide variation in these rates, but the key to a correct interpretation lies in the denominator used, as well as the differing definitions of neurodevelopmental impairment in these reports. For example, in the study from Japan,7 data were from selected neonatal units, whereas in the studies from Sweden,4 France,3 and the United Kingdom,2 data included all births within a defined period. The classification of motor, cognitive, and sensory impairments that composed clinically significant neurodevelopmental impairment differed among studies. Therefore, it is difficult to counsel families on the basis of these different population bases and different outcomes. Studies from the United Kingdom and France have attempted to overcome such limitations and provided results using several denominators — all alive fetuses, all births, live births, neonates in whom active intervention was at-