Postnatal Stature Does Not Largely Mediate the Relation between Adverse Birth Outcomes and Cognitive Development in Mid-Childhood and Early Adolescence in Rural Western China

Background: Preterm birth and fetal growth restriction are associated with linear growth faltering and suboptimal cognitive development in childhood. Objectives: We aimed to investigate whether and to what extent the associations between adverse birth outcomes and cognitive development in mid-childhood and early adolescence are mediated by postnatal stature. Methods: We used data from a prospective birth cohort of children born to women who participated in a large cluster-randomized trial of antenatal micronutrient supplementation in rural western China. Children were followed up for anthropometric assessments at 6, 12, and 24 mo of age and in mid-childhood (7-9 y). Cognitive development was assessed in mid-childhood (n = 669) and early adolescence (n = 735; 10-12 y) using the Wechsler Intelligence Scale for Children-IV. We conducted a causal mediation analysis to evaluate the proportion of the association of low birth weight (LBW; <2500 g), small-for-gestational age (SGA; <10th percentile), and preterm birth (<37 weeks of gestation) with cognitive development in mid-childhood and early adolescence that was mediated by postnatal length/height-for-age and -sex z score (LAZ/HAZ) during the first 2 y of life and in mid-childhood. Results: LBW and SGA, but not preterm birth, were associated with lower cognitive test scores in mid-childhood and early adolescence. The proportion of the total association of SGA with adolescent cognitive development that was mediated by LAZ/HAZ at 6, 12, and 24 mo of age and in mid-childhood was 25%, 32%, 32%, and 27%, respectively. The corresponding proportions for LBW were 25%, 32%, 16%, and 24%, respectively. Conclusions: The association of LBW and SGA with cognitive development in mid-childhood and adolescence is not largely mediated by postnatal stature during the first 2 y of life. Postnatal interventions that address the antecedent causes of poor child growth and development, rather than early childhood growth alone, are more likely to mitigate the risk of suboptimal development among SGA and LBW children.