Evidence for a Causal Association of Low Birth Weight and Attention Problems

Abstract

Low birth weight (LBW) is associated with attention problems (AP) and attention-deficit/hyperactivity disorder (ADHD). The etiology of this association is unclear. We investigate whether there is a causal influence of birth weight (BW) on AP and whether the BW effect is mediated by catch-up growth (CUG) in low-BW children. Longitudinal data from >29,000 twins registered with the Netherlands Twin Register with BW ≥1,500 g and gestational age (GA) ≥32 weeks were analyzed with the cotwin control method. Hyperactivity and AP were assessed at ages 3, 7, 10, and 12 years; weight was assessed at birth and age 2 years. Children in the lowest BW category of 1,500 to 2,000 g scored 0.18 to 0.37 standard deviations (SD) higher on AP than children in the reference category of 3,000 to 3,500 g. This effect was present in term-born and preterm-born children. Importantly, in BW discordant monozygotic (MZ), dizygotic (DZ), and unrelated (UR) pairs, the child with the lower BW scored higher on hyperactivity and AP than the child with the higher BW and within-pair differences were similar for MZ, DZ, and UR pairs. This pattern is consistent with a causal effect of BW on AP. MZ and DZ twin pairs concordant for LBW but discordant for CUG showed similar AP scores, thus ruling out any effect of CUG on AP. These results strongly indicate that the association of birth weight and AP represents a causal relationship. The effects of BW are not explained by CUG in LBW children.