Are fetal growth impairment and preterm birth causally related to child attention problems and ADHD? Evidence from a comparison between high-income and middle-income cohorts

Background Cross-cohort comparison is an established method for improving causal inference. This study compared 2 cohorts, 1 from a high-income country and another from a middle-income country, to (1) establish whether birth exposures may play a causal role in the development of childhood attention problems; and (2) identify whether confounding structures play a different role in parent-reported attention difficulties compared with attention deficit hyperactivity disorder (ADHD) diagnoses. Methods Birth exposures included low birth weight (LBW), small-for-gestational age (SGA), small head circumference (HC) and preterm birth (PTB)). Outcomes of interest were attention difficulties (Strengths and Difficulties Questionnaire, SDQ) and ADHD (Development and Well-Being Assessment, DAWBA). Associations between exposures and outcomes were compared between 7-year-old children from the Avon Longitudinal Study of Parents and Children (ALSPAC) in the UK (N = 6849) and the 2004 Pelotas cohort in Brazil (N = 3509). Results For attention difficulties (SDQ), the pattern of association with birth exposures was similar between cohorts: following adjustment, attention difficulties were associated with SGA (OR = 1.59, 95% CI 1.20 to 2.19) and small HC (OR = 1.64, 95% CI 1.11 to 2.41) in ALSPAC and SGA (OR = 1.35, 95% CI 1.04 to 1.75) in Pelotas. For ADHD, however, the pattern of association following adjustment differed markedly between cohorts. In ALSPAC, ADHD was associated with LBW (OR= 2.29, 95% CI 1.09 to 4.80) and PTB (OR = 2.33, 95% CI 1.23 to 4.42). In the Pelotas cohort, however, ADHD was associated with SGA (OR = 1.69, 95% CI 1.02 to 2.82). Conclusions The findings suggest that fetal growth impairment may play a causal role in the development of attention difficulties in childhood, as similar associations were identified across both cohorts. Confounding structures, however, appear to play a greater role in determining whether a child meets the full diagnostic criteria for ADHD.