The Effect of Unadjusted Mineral Supplementation on Bone Health of Preterm Infants Fed Fortified Human Milk: An Exploratory Analysis

In standard fortification of human milk (HM), the HM macronutrient content is assumed, and a fixed amount of a multinutrient fortifier is added to achieve recommended nutrient intakes. In target fortification, the HM macronutrient content is regularly measured, guiding the addition of modular macronutrient supplements to the fortified HM, to achieve the nutritional targets more precisely. The study aimed to investigate whether this addition of modular supplements, unaccompanied by mineral supplementation, predispose to metabolic bone disease (MBD). This is a secondary analysis of a larger study of infants born with <33 weeks gestational age. Fortifications based on the assumed (Group 1) or measured (Group 2) of the HM macronutrient content were compared, using low serum phosphate levels as an indicator of MBD, and length growth as a surrogate of bone growth. Eighty-four infants were included, 35 in Group 1 and 49 in Group 2. During the exposure period, infants of Group 2 received higher mean fat (6.1 vs. 5.3 g/kg/day, P < 0.001) and carbohydrate (13.0 vs. 11.7 g/kg/day, P < 0.001) intakes; in addition, they exhibited lower mean serum phosphate (5.5 vs. 6.0 mg/dL, P = 0.022) and faster mean length velocity (1.06 vs. 0.89 cm/week, P = 0.003). These findings suggest that feeding fortified HM with extra fat and carbohydrate content, unaccompanied by mineral supplementation, promotes increased bone growth, as indicated by accelerated length growth, but with insufficiently mineralized osteoid, indicated by low serum phosphate levels. Intervention studies using direct biomarkers of bone mass content and mineral density are necessary to corroborate our findings.