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Human milk macronutrient composition and intake in relation to preterm infant growth: a cohort study

Clin Exp Pediatr > Epub ahead of print
DOI: https://doi.org/10.3345/cep.2025.02509    [Epub ahead of print]
Published online April 22, 2026.
Human milk macronutrient composition and intake in relation to preterm infant growth: a cohort study
Eakkarin Mekangkul1,2  , Chonnikant Visuthranukul2  , Anongnart Sirisabya3  , Thaninee Chitsinchayakul3, Santi Punnahitananda3  , Sirinuch Chomtho2 
1Division of Nutrition, Department of Pediatrics, King Chulalongkorn Memorial Hospital, The Thai Red Cross Society, Bangkok, Thailand
2Center of Excellence in Pediatric Nutrition, Division of Nutrition, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
3Division of Neonatology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
Correspondence: 
Chonnikant Visuthranukul, Tel: chonnikant.v@chula.ac.th, 
Received: 18 October 2025   • Revised: 18 January 2026   • Accepted: 22 January 2026
Abstract
Background
Individualized targeted fortification based on human milk (HM) analysis reportedly achieves optimal outcomes in preterm infants. Therefore, understanding the effects of macronutrients in HM on preterm infant growth is essential.
Purpose
This study aimed to determine the association between HM macronutrients and the growth of preterm infants. We also compared macronutrient intake data obtained from an HM analyzer (HMA)–based calculation with those derived from a reference-based calculation.
Methods
This prospective-retrospective cohort study included infants born at 34 weeks' gestation or less. HM samples were collected weekly for up to 4 weeks or until discharge, whichever occurred first. Clinical outcomes were recorded. The macronutrient composition was analyzed using midinfrared HMA. Associations were determined using a linear regression model.
Results
Of 121 preterm infants, 65 (51.2%) were male. A total of 200 HM samples were analyzed. Fat composition showed a significant positive association with weight gain velocity, with an adjusted unstandardized coefficient (aB) of 3.07 (95% confidence interval [CI], 0.22–5.93). Total protein and fat intakes were positively associated with weight gain (aB, 3.41; 95% CI, 0.83–5.98; and aB, 7.07; 95% CI, 1.73–12.42, respectively). When using the HMA-based calculation, protein intake was lower and carbohydrate intake was higher throughout the 4-week period compared with those obtained based on the reference-based calculation.
Conclusion
Higher protein and fat intakes could potentially enhance weight gain in preterm infants. These findings provide further evidence to support the concept of individualized HM fortification. Our findings underscore the importance of using HMA-based methods to calculate macronutrient intakes among preterm infants.
Key Words: Preterm infants, Growth, Human milk, Macronutrient


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