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Sex-Specific Effects of Nutritional Supplements for Infants Born Early or Small: An Individual Participant Data Meta-Analysis (ESSENCE IPD-MA) II: Growth

Lookup NU author(s): Professor Nicholas EmbletonORCiD, Dr Claire Wood



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2022 by the authors. Licensee MDPI, Basel, Switzerland. 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 reg-isters 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. Supplemen-tation increased growth in infancy, but these effects did not persist in later life. The effects did not differ between boys and girls.

Publication metadata

Author(s): Lin L, Gamble GD, Crowther CA, Bloomfield FH, Agosti M, Atkinson SA, Biasini A, Embleton ND, Filho FL, Fusch C, Gianni ML, Kutman HGK, Koo W, Litmanovitz I, Morgan C, Mukhopadhyay K, Neri E, Picaud J-C, Rochow N, Roggero P, Stroemmen K, Tan MJ, Tandoi FM, Wood CL, Zachariassen G, Harding JE

Publication type: Review

Publication status: Published

Journal: Nutrients

Year: 2022

Volume: 14

Issue: 2

Online publication date: 17/01/2022

Acceptance date: 14/01/2022

ISSN (electronic): 2072-6643

Publisher: MDPI


DOI: 10.3390/nu14020392