Abstract
Neonatal nutritional supplements are widely used to improve growth and development but may increase risk of later metabolic disease, and effects may differ by sex. We assessed effects of supplements on later development and metabolism. We searched databases and clinical trials registers up to April 2019. Participant-level data from randomised trials were included if the intention was to increase macronutrient intake to improve growth or development of infants born preterm or small-for-gestational-age. Co-primary outcomes were cognitive impairment and metabolic risk. Supplementation did not alter cognitive impairment in toddlers (13 trials, n = 1410; adjusted relative risk (aRR) 0.88 [95% CI 0.68, 1.13]; p = 0.31) or older ages, nor alter metabolic risk beyond 3 years (5 trials, n = 438; aRR 0.94 [0.76, 1.17]; p = 0.59). However, supplementation reduced motor impairment in toddlers (13 trials, n = 1406; aRR 0.76 [0.60, 0.97]; p = 0.03), and improved motor scores overall (13 trials, n = 1406; adjusted mean difference 1.57 [0.14, 2.99]; p = 0.03) and in girls not boys (p = 0.03 for interaction). Supplementation lowered triglyceride concentrations but did not affect other metabolic outcomes (high-density and low-density lipoproteins, cholesterol, fasting glucose, blood pressure, body mass index). Macronutrient supplementation for infants born small may not alter later cognitive function or metabolic risk, but may improve early motor function, especially for girls.
Highlights
As the mortality of infants born preterm or small-for-gestational-age (SGA) has decreased, there is a greater focus on improving their quality of life
2110 infants from 15 trials were included in analysis of individual participant data (IPD) only and 1996 infants from 10 trials were included in the analysis of combined IPD and aggregate data (AD)
We found that early macronutrient supplementation of preterm and SGA infants did not alter cognitive function nor increase metabolic risk in toddlers and older children, the data are limited for older ages
Summary
As the mortality of infants born preterm or small-for-gestational-age (SGA) has decreased, there is a greater focus on improving their quality of life. Such infants are at increased risk of poor growth, disability and delayed development [1,2,3], and as adults, they are at increased risk of obesity, diabetes and heart disease [4]. Provision of enhanced early nutritional supplement is reported to improve early growth and cognitive development [5,6,7], findings from observational studies suggest that early rapid growth may contribute to adiposity, metabolic and cardiovascular diseases in later life [8,9,10]. The long-term and the sex-specific effects of enhanced nutrition have not been adequately explored, with few trials separately analysing outcomes of girls and boys
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