Abstract
Neonatal nutritional supplements may improve early growth for infants born small, but effects on long-term growth are unclear and may differ by sex. We assessed the effects of early macronutrient supplements on later growth. We searched databases and clinical trials registers from inception 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 BMI in childhood (kg/m2: adjusted mean difference (aMD) −0.11[95% CI −0.47, 0.25], p = 0.54; 3 trials, n = 333). Supplementation increased length (cm: aMD 0.37[0.01, 0.72], p = 0.04; 18 trials, n = 2008) and bone mineral content (g: aMD 10.22[0.52, 19.92], p = 0.04; 6 trials, n = 313) in infancy, but not at older ages. There were no differences between supplemented and unsupplemented groups for other outcomes. In subgroup analysis, supplementation increased the height z-score in male toddlers (aMD 0.20[0.02, 0.37], p = 0.03; 10 trials, n = 595) but not in females, and no significant sex interaction was observed (p = 0.21). Macronutrient supplementation for infants born small may not alter BMI in childhood. Supplementation increased growth in infancy, but these effects did not persist in later life. The effects did not differ between boys and girls.
Highlights
The risk of poor growth, slow development and disability are increased in preterm and small-for-gestational-age (SGA) infants [1–4]
In trials conducted before 2000, supplementation increased weight, weight z-scores, length, head circumference, fat mass in infancy, fat mass index at >3 years, and bone mineral content (BMC) in infancy; supplemented children had increased lean mass and BMD in infancy, but these interaction terms were not significant. These effects were not due to changes over time in baseline macronutrient intake or quantity of the supplements (Text S2). In this meta-analysis, we found no evidence that early macronutrient supplements had any effect on Body Mass Index (BMI) in childhood
Macronutrient supplementation did slightly increase growth in infancy, but none of these effects persisted into later life, and there were no significant sex differences
Summary
The risk of poor growth, slow development and disability are increased in preterm and small-for-gestational-age (SGA) infants [1–4]. Providing preterm and SGA infants with more protein and energy during the first few weeks after birth may improve short-term growth and result in better developmental outcomes from infancy to adolescence [5–10]. Different prenatal growth patterns between girls and boys may potentially result in sex-specific responses to nutritional supplements [15]. Previous randomised trials have found sex-specific effects of early macronutrient supplements [6,16], and a recent systematic review found enhanced nutrition may improve length in toddler boys but not girls [17]. Thousands of infants have participated in randomised trials of enhanced nutrition, few trials have analysed girls and boys separately, and the long-term and the sex-specific effects of supplementation remain unclear
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
