Infants who survive birth at the edge of viability: how are they doing at school age?

Thepast 20 yearshavewitnessed a dramatic improvement in survival after extremely preterm birth. Currently, most infants born between 25 and 28 weeks’ gestation can survive when provided with delivery room resuscitation followed by neonatal intensive care, including positivepressure ventilation, surfactant replacement, and nutritional support.At least forbabiesbornatorafter 25completedweeks’ gestation, theexpected long-termoutcomeisgoodenoughthat mostneonatologists considerdelivery roomresuscitationand neonatal intensive care obligatory, regardless of the parents’ preference.1 For babies bornbefore 25 completedweeks’ gestation, deciding what care to provide is less straightforward. As compared with more mature infants, the survival rate for babies born in the“grayzone” (approximately23-24weeks’gestation)1 is considerably lower and long-term morbidities affecting health anddevelopment aremore frequent and severe. Intensive care and comfort or palliative care may both be acceptable approaches for neonatologists and parents, and neonatologists are encouraged topursuean individualizedapproach reflecting the preferences of the parents.2 To determine which approach is right for their baby, expectant parents need accurate information about the anticipated sequelae of pretermbirth, should their baby survive the initial resuscitationandneonatalhospitalization.Typically, this information is communicated to parents by neonatologists in the context of an antenatal consultation, andmostneonatologists rely on published data to inform these discussions. Most widely available information describes the probability of survival to age 18 to 22 months, as well as the expected level of cognitive ability and degree of neurosensory impairment in survivors at that age. Although reasonably easy to find in the published literature, extremely preterm infant outcome measures at age 18 to 22 months are relatively poor predictors of a child’s abilities at school age and beyond. Many children scoring less than 70 on the Bayley Scales of Infant Development Mental Development Index at age 18 to 22 months perform in the normal range on cognitive testing at age 8 years.3 Measures in infancy, then, may substantially overestimate the expected degree of long-term impairment. Reports of adult outcomes are also relevant but are particularly limited with respect to babies born at the edge of viability because they reflect outdated neonatal care practices of the presurfactant era, during which only a tiny proportion of “gray zone” babies survived. Compared with outcomes in infancy, school-age outcomesbetter reflect deficits that are likely to be sustained and have an advantage over adult outcomes of reflecting contemporarymedical practices. Fine-grained information about the expectedoutcome for infants bornafter each completedweek of gestation is critical for informing decisions, but such data fromanygivenneonatal intensivecareunit (NICU)orevennetwork of NICUs are limited because extremely pretermbirth is rare, the probability of survival is relatively low, and following up survivors to school age is logistically challenging and costly. In this issueof JAMAPediatrics,Moore andcolleagues4 attempt to fill this gap with their meta-analysis of neurodevelopmental outcomes at 4 to 8 years of age for children born at 22 to 25 weeks’ gestation. Moore et al performed a comprehensive systematic review and included in themeta-analysis studies with school-age outcomes stratified by gestational week, or they obtained primary data from the authors and stratified it themselves.Theprimaryoutcomesweresevereand moderate to severe neurodevelopmental impairment, defined on the basis of IQ, motor, or sensory deficits. Moore et al included only studies with more than 75% follow-up. The final meta-analysis included 8 studies from the United Kingdom, Finland, Germany, Czech Republic, Norway, and New Zealand. For the 441 infants born at 25 weeks’ gestation, Moore et al found that 24% had moderate to severe impairment at age 4 to 8 years. That is, 76% were either mildly impaired or unimpaired, an estimate that is more favorable than previously published 18to 22-month outcomes. For example, based on data from the Eunice Kennedy Shriver National Institute of ChildHealthNeonatal ResearchNetwork,5 about 30% to 40% of surviving infants born at 25weeks’ gestationhaveneurodevelopmental impairment at age 18 to 22 months. The schoolage data presented byMoore and colleagues seem to support the general consensus among US neonatologists that for babies born at or after 25 weeks’ gestation, neonatal resuscitation is not optional. Outcomes for infants born before 25 weeks’ gestation— the “gray zone”—are of particular interest with respect to decision making about use of life-sustaining therapies. For the infants born at 23weeks’ (n = 75) and 24weeks’ (n = 210) gestation,meta-analysis estimates of school-agemoderate to severe impairment rateswere40%and28%, respectively.While manyneonatologists consider the resuscitationof infantsborn at 22 weeks’ gestation to be futile, Moore and colleagues report that 43% of the 12 infants included in the meta-analysis were impairedat school age, that is,more thanhalfwereeither mildly impaired or unimpaired. How should clinicians and parents use this information? First, the outcomes reported by Moore et al must be placed in the context of everyday decision making in the NICU. By definition, school-age outcomes represent only the survivors, a small proportion of all births at 22 to 24 weeks’ gestation. Some infants are too immature to survive, regardless of technological support in the NICU. However, for many, survival is contingent on decisions to initiate resuscitation and Related article page 967 Editorial Opinion