Author Affiliations: Departments of Pediatrics (Drs Bhutta, Cleves, Casey, Cradock, and Anand), Biostatistics (Dr Cleves), Anesthesiology (Dr Anand), Pharmacology (Dr Anand), and Neurobiology (Dr Anand) and Arkansas Center for Birth Defects Research and Prevention (Dr Cleves), University of Arkansas for Medical Sciences, Little Rock.
Context The cognitive and behavioral outcomes of school-aged children who were
born preterm have been reported extensively. Many of these studies have methodological
flaws that preclude an accurate estimate of the long-term outcomes of prematurity.
Objective To estimate the effect of preterm birth on cognition and behavior in
Data Sources MEDLINE search (1980 to November 2001) for English-language articles,
supplemented by a manual search of personal files maintained by 2 of the authors.
Study Selection We included case-control studies reporting cognitive and/or behavioral
data of children who were born preterm and who were evaluated after their
fifth birthday if the attrition rate was less than 30%. From the 227 reviewed
studies, cognitive data from 15 studies and behavioral data from 16 studies
Data Extraction Data on population demographics, study characteristics, and cognitive
and behavioral outcomes were extracted from each study, entered in a customized
database, and reviewed twice to minimize error. Differences between the mean
cognitive scores of cases and controls were pooled. Homogeneity across studies
was formally tested using a general variance-based method and graphically
using Galbraith plots. Linear meta-analysis regression models were fitted
to explore the impact of birth weight and gestational age on cognitive outcomes.
Study-specific relative risks (RRs) were calculated for the incidence of attention-deficit/hyperactivity
disorder (ADHD) and pooled. Quality assessment of the studies was performed
based on a 10-point scale. Publication bias was examined using Begg modified
funnel plots and formally tested using the Egger weighted-linear regression
Data Synthesis Among 1556 cases and 1720 controls, controls had significantly higher
cognitive scores compared with children who were born preterm (weighted mean
difference, 10.9; 95% confidence interval [CI], 9.2-12.5). The mean cognitive
scores of preterm-born cases and term-born controls were directly proportional
to their birth weight (R2 = 0.51; P<.001) and gestational age (R2 = 0.49; P<.001). Age at evaluation had
no significant correlation with mean difference in cognitive scores (R2 = 0.12; P = .20).
Preterm-born children showed increases in externalizing and internalizing
behaviors in 81% of studies and had more than twice the RR for developing
ADHD (pooled RR, 2.64; 95% CI, 1.85-3.78). No differences were noted in cognition
and behaviors based on the quality of the study.
Conclusions Children who were born preterm are at risk for reduced cognitive test
scores and their immaturity at birth is directly proportional to the mean
cognitive scores at school age. Preterm-born children also show an increased
incidence of ADHD and other behaviors.
Bhutta AT, Cleves MA, Casey PH, Cradock MM, Anand KJS. Cognitive and Behavioral Outcomes of School-Aged Children Who Were Born Preterm: A Meta-analysis. JAMA. 2002;288(6):728–737. doi:10.1001/jama.288.6.728
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