Progress in the Care of Extremely Preterm Infants

In this issue of JAMA, Stoll and colleagues report on care practices, morbidity, and mortality of 34 636 infants 22 through 28 weeks’ gestation, weighing 401 to 1500 g, born at 26 National Institute of Child Health and Human Development (NICHD) Neonatal Research Network centers between 1993 and 2012.1 This article provides an important historical perspective over the last 2 decades in neonatal-perinatal medicine and the most recent update on trends in neonatal care. For the overall population of these preterm infants, survival increased from 70% in 1993 to 79% in 2012. The improvement in survival was greatest between 2009 and 2012 among infants 23 weeks’ (reaching 33%) and 24 weeks’ (reaching 65%) gestational age; with smaller relative increases for infants 25 and 27 weeks’ gestation; and no change for infants aged 22, 26, and 28 weeks’ gestation. Perhaps not seeing substantial changes in survival in the more mature infants in this cohort is not surprising; these infants are no longer at high risk of dying. What is heartening is the improvement in survival without morbidity observed among infants at 27 and 28 weeks’ gestation (27 weeks: 35% in 1993 to 50% in 2012 among infants surviving to discharge; 28 weeks: 43% to 59%). The unfortunate corollary to this finding is that although survival improved in the least-mature infants, no improvement in survival without morbidity was seen in infants who were 22 to 24 weeks’ gestation. Details regarding the individual morbidities experienced by these infants over the past 20 years are less clear. Severe intracranial hemorrhage decreased, but these improvements were restricted to infants at 26 to 28 weeks’ gestation. Similarly, improvements in periventricular leukomalacia were limited to this more mature population. Little improvement was observed in necrotizing enterocolitis, and bronchopulmonary dysplasia increased. Late-onset sepsis presented a mixed picture; no changes were seen for the first 12 years and then substantial improvements occurred in the last 8 years. Similar findings have been reported by the Vermont Oxford Network (VON), a voluntary collaboration of health care professionals whose mission is to improve the quality and safety of medical care for newborns and their families.2 VON member centers are more diverse than the NICHD Neonatal Research Network, including both community and academic neonatal intensive care units and many of the Neonatal Research Network centers. Approximately 90% of very low–birth-weight infants born in the United States are currently included in the VON database. Trends over the past 20 years have been reported in 2 articles.3,4 The first detailed outcomes for a cohort of 118 448 infants who weighed 501 to 1500 g at birth from 362 neonatal intensive care units between 1991 and 1999.3 The rates of mortality, as well as many morbidities including pneumothorax, intraventricular hemorrhage, and severe intraventricular hemorrhage, declined between 1991 and 1995, but did not change significantly in the latter half of the 20th century. A second article reported outcomes between 2000 and 2009 and found meaningful but smaller changes in mortality and morbidity.4 Among infants weighing 501 to 1500 g at birth, mortality decreased from 14.3% to 12.4% and major morbidity in survivors decreased from 46.4% to 41.4%. As in the current study, changes in mortality were greatest in the smallest and least mature infants; for infants weighing 501 to 750 g at birth, mortality decreased by 5.3% (41.8%36.6%). Of note, rates of mortality and morbidity were lower in the VON database, likely due to differences in the populations reported (infants weighing 401-500 g at birth are not reported by VON) and perhaps reflecting differences in case mix. Certain outcomes seem to have been somewhat resistant to change in both networks; little change or worse outcomes were seen in chronic lung disease, periventricular leukomalacia, and necrotizing enterocolitis. What might account for these changes in outcome? Throughout these 20 years, there have beenmany changes in practice. Inboth theNeonatalResearchNetworkandVON,substantial differences were noted in obstetric practices, including the increased use of antenatal corticosteroids and cesareandelivery.1,3-5 Undoubtedly, evidence-based interventions, suchas the increaseduseofantenatal corticosteroids,havecontributed to improving many outcomes.6 Many other practices have changed, but the effect on outcomes seems less certain. In the past 10 years, delivery room intubation has decreased and the use of noninvasive respiratory support has increased.1,5 High-frequency ventilation has increased substantially throughout the past 2 decades. Yet little change has been seen in bronchopulmonary dysplasia, the outcome most linked to these respiraRelated article page 1039 Editorial Opinion