Long-Term Neurodevelopmental Outcomes After Intrauterine and Neonatal Insults

Abstract

A large proportion of mortality in children younger than 5 years occurs during the neonatal period, especially in resource-poor countries. The long-term effects of intrauterine and neonatal insults among surviving infants on the frequency and severity of neurocognitive impairment and other sequelae is unknown. Most neonatal interventions in neonates exposed to intrauterine and neonatal insults have largely focused on survival. This systematic review was designed to estimate the long-term effects of intrauterine and neonatal insults on neurocognitive and other sequelae, especially in low- and middle-income countries. The authors conducted a search of several databases (Medline, Cumulative Index to Nursing and Allied Health Literature, the Cochrane Library, and Embase) to identify studies published between 1966 and 2011 that reported neurodevelopmental sequelae after preterm or neonatal insult. A search of Dissertation Abstracts International and the World Health Organization library was performed for unpublished studies and gray literature. Studies reviewed reported data for long-term outcomes after identifiable and well-defined neonatal insults. The overall risk of each insult for at least 1 long-term impairment was summarized by calculating medians and interquartile range (IQR). Impairments were graded as severe, moderate, or mild. Of the 28,212 studies identified in the search, 153 met criteria for inclusion. The overall median risk of one or more impairment in any one domain was 39.4% (IQR, 20.0–54.8). The overall risk for at least 1 severe, moderate, or mild impairment was as follows: 18.5% (95% confidence interval [CI], 7.7–33.3) with a risk of severe impairment, 5.0% (95% CI, 0.0%–13.3%) with a risk of moderate impairment, and 10.0% (95% CI, 1.4%–17.9%) with risk of mild impairment. The pooled risk estimate of at least 1 impairment (weighted mean) for one or more insults (excluding human immunodeficiency virus) was 37.0% (95% CI, 27.0%–48.0%). No significant effect on risk was found for any of the 4 covariables tested: World Health Organization region, period of data collection, duration of follow-up, or study design. The most common impairments were learning difficulties, cognition, or developmental delay (59%); cerebral palsy (21%); hearing impairment (20%); and visual impairment (18%). Data for multidomain impairments were included in only 40 (26%) of the studies. Among the 2815 individuals included in the studies, 37% (n = 1048) had impairments and 32% (n = 334) had multiple impairments. These findings show a high risk of substantial long-term neurological morbidity among survivors of intrauterine and neonatal insults. The least data are available for resource-poor countries, which account for 98% of neonatal morbidity.