Do effects of early life interventions on linear growth correspond to effects on neurobehavioural development. A systematic review and meta-analysis

Background Faltering in linear growth and neurobehavioural development during early childhood are often assumed to have common causes because of their consistent association. This notion has contributed to a global focus on the promotion of nutrition during pregnancy and childhood to improve both conditions. Our aim was to assess whether effects of interventions on linear growth are associated with effects on developmental scores and to quantify these associations. Methods In this systematic review and meta-analysis, we included randomised trials done during pregnancy and in children aged 0-5 years that reported effects of any intervention on length-for-age or height-for-age Z scores (LAZ or HAZ) and on any of the following outcomes: motor, cognitive or mental, language, and social-emotional or behavioural development. We searched MEDLINE (Ovid), CINAHL (EBSCO), and PsycINFO (EBSCO) from database inception to June 25, 2019. Study-level data were extracted and, when required, authors were contacted for missing information. We calculated weighted meta-regression coefficients of the association between standardised effect sizes of interventions on LAZ or HAZ and developmental outcome scores and calculated pooled effect sizes for different types of intervention. Findings Of the 7207 studies identified, we included 75 studies with 122 comparisons between intervention and control groups and outcomes reported for 72 275 children. Across all interventions, effect sizes on LAZ or HAZ were significantly associated with effect sizes on social-emotional scores (beta 0.23, 95% CI 0.05 to 0.41; p=0.02), but not on cognitive (0.18, -0.36 to 0.72; p=0.51), language (0.12, -0.07 to 0.31; p=0- 21), or motor development scores (0.23, -0.05 to 0.50; p=0.11). In studies that provided nutritional supplements, we observed positive significant pooled effect sizes on all five outcomes of LAZ or HAZ (effect size 0.05, 95% CI 0.01-0-09; p=0. 01; n=50), cognitive or mental (0.06, 0.03-0.10; p<0.01; n=38), language (0-08, 0-03-0-13; p=0.01; n=21), motor (0-08,0-04-0-12; p<0.01; n=41), and social-emotional (0.07, 0.02-0.12; p=0 . 01; n=20) scores. The effect sizes of nutritional supplementation on LAZ or HAZ scores were significantly associated with effect sizes on cognitive (beta 0.40, 95% CI 0.04-0.77; p=0 . 049) and motor (0.43, 0.11-0 - 75; p=0 . 01) scores. In the 14 interventions promoting responsive care and learning opportunities, the pooled effect size on LAZ or HAZ score was not significant (-0.01, 95% CI -0.07 to 0.05; p=0 . 74), but pooled effect sizes on cognitive, language, and motor scores were 4 to 5 times larger (range 0.38-0.48) than the pooled effect sizes of nutritional supplementation (0.05-0.08). Interpretation In nutritional supplementation interventions, improvements in linear growth were associated with small improvements in child development, whereas nurturing and stimulation interventions had significant effects on child development but no effects on linear growth. The determinants of linear growth and neurodevelopment are only partly shared. To nurture thriving individuals and communities, interventions should specifically target determinants of neurodevelopment and not simply linear growth. Copyright (C) 2019 The Author(s). Published by Elsevier Ltd.