Background:Premature infants receiving alimentation with cow's milk formulas are at a considerably high risk of developing incipient late metabolic acidosis, an early stage in the development of manifest late metabolic acidosis. Is it possible to reduce this risk by modification of the composition of a standard formula?Methods:The mineral composition of a cow's milk preterm formula A was modified (formula B) with the aim of reducing the alimentary load to that of human milk. 160 premature infants were fed either mother's milk (n = 50) or the modified formula B (enriched with sodium and potassium) (n = 110), and their urine pH was tested twice a week. Randomly collected subgroups of infants were studied in detail for nutrient balances. The results were compared with earlier observations of 282 premature infants fed either mother's milk (n = 28) or the standard formula A (n = 254).Results:Incipient late metabolic acidosis was observed in nine of 78 premature infants receiving mother's milk, 53 of 254 premature infants receiving the standard formula A, and only one of 110 premature infants fed the modified formula B. Net acid excretion was 0.58 mmol/kg/day in 11 premature infants receiving alimentation with the modified formula B compared with 1.73 mmol/kg/day in 23 premature infants fed formula A. This reduction was mainly due to an increased alkali excess (sodium + potassium-chloride) in intake and urine.Conclusions:Reduction of renal acid load with the modified formula B had a preventive effect on the rate of development of incipient late metabolic acidosis in premature infants.