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Sex-Specific Effects of Nutritional Supplements for Infants Born Early or Small: An Individual Participant Data
Luling Lin1, Greg D Gamble1, Caroline A Crowther1
1Liggins Institute, University of Auckland, Auckland 1023, New Zealand.
Insights
Neonatal nutritional supplements for small infants improved early growth but did not affect childhood BMI. These growth benefits in infancy did not persist into later life and showed no significant sex differences.
Area of Science:
- Pediatrics
- Neonatology
- Nutritional Science
Background:
- Infants born small require nutritional support for optimal growth.
- Long-term effects of neonatal nutritional supplements on growth are not well-established.
- Potential sex-based differences in response to supplementation warrant investigation.
Purpose of the Study:
- To assess the long-term effects of early macronutrient supplementation on growth in infants born small.
- To investigate potential sex differences in the response to neonatal nutritional supplements.
- To evaluate the impact of supplementation on childhood BMI, length, bone mineral content, cognitive impairment, and metabolic risk.
Main Methods:
- Systematic review and meta-analysis of participant-level data from randomized controlled trials.
- Included trials focused on preterm or small-for-gestational-age infants receiving macronutrient supplements.
- Co-primary outcomes included cognitive impairment and metabolic risk; secondary outcomes assessed growth parameters.
Main Results:
- Supplementation did not alter childhood Body Mass Index (BMI).
- Infancy length and bone mineral content were increased by supplementation, but these effects did not persist.
- Subgroup analysis showed increased height z-score in male toddlers, but no significant sex interaction was observed.
Conclusions:
- Early macronutrient supplementation for small infants does not appear to alter childhood BMI.
- While infancy growth parameters improved, these benefits were not sustained long-term.
- The study found no significant sex differences in the overall effects of neonatal nutritional supplementation on growth.
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.
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