Postnatal Stature does not Largely Mediate the Relationship 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. OBJECTIVE 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, 24 months of age and mid-childhood (7-9 years). Cognitive development was assessed at mid-childhood (n = 669) and early adolescence (n = 735, 10-12 years) 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, <2500g),  small-for-gestational age (SGA, <10th percentile) and preterm birth (<37 gestational weeks) with cognitive development at mid-childhood and early adolescence that was mediated by postnatal length/height-for- age and sex Z-score (LAZ/HAZ) during the first two years of life and mid-childhood. RESULTS LBW and SGA, but not preterm birth, were associated with lower cognitive test scores at mid-childhood and early adolescence. The proportion of total association of SGA on adolescent cognitive development that was mediated by LAZ/HAZ at 6, 12, 24 months of age and mid-childhood was 25%, 32%, 32%, and 27%, respectively. The corresponding proportions for LBW was 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 two years 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.