Amino acid-based formula and feeding outcomes in preterm infants with recurrent intolerance: A propensity score-matched study.

BACKGROUND AND AIMS: To evaluate whether transitioning from standard preterm formula to an amino acid-based formula (AAF) improves feeding outcomes in preterm infants with recurrent feeding intolerance (FI).

METHODS

This single-center retrospective cohort study included infants ≤34 weeks' gestation who developed recurrent FI between 2023 and 2024. Infants transitioned to AAF constituted the exposure group, while controls continued standard preterm formula. Propensity scores were derived from gestational age, birth weight, sex, delivery mode, 5-minute Apgar score, antenatal steroid exposure, and any early human milk intake, and 1:2 nearest-neighbor matching was performed using a caliper of 0.2 standard deviations. Primary outcomes were time to full enteral feeding (≥100 mL/kg/day for ≥48 hours) and duration of parenteral nutrition (PN). Secondary outcomes included recurrent FI, stage I necrotizing enterocolitis (suspected NEC), culture-proven sepsis, peak C-reactive protein (CRP) levels, eosinophil counts, and weight at 36 weeks' postmenstrual age. Given non-normal distributions, continuous outcomes were analyzed using nonparametric methods and are presented as medians with interquartile ranges (IQR).

RESULTS

Of 113 eligible infants, 37 were transitioned to AAF and 76 remained on standard formula. Propensity score matching yielded 33 AAF-treated infants and 66 matched controls with excellent baseline balance (all standardized mean differences <0.10). Infants receiving AAF achieved full enteral feeding earlier than controls (median 10 [IQR 9-12] versus 13 [IQR 12-15] days; P < 0.001) and required fewer days of PN (median 9 [IQR 8-10] versus 12 [IQR 11-13] days; P < 0.001). Recurrent FI occurred less frequently in the AAF group (15% versus 39%; P = 0.006). There were no significant differences between groups in suspected NEC, culture-proven sepsis, peak CRP levels, or weight at 36 weeks' postmenstrual age. No cases of proven NEC (Bell stage ≥II) were observed in either group. Median eosinophil counts were higher in the AAF group (0.38 [IQR 0.22-0.55] versus 0.29 [IQR 0.18-0.41] × 10³/mm³; P = 0.01), without clinical manifestations of allergy.

CONCLUSIONS

In preterm infants with recurrent feeding intolerance, transition to an amino acid-based formula was associated with faster progression to full enteral feeding, reduced parenteral nutrition exposure, and fewer recurrent FI episodes, without an increase in infectious or gastrointestinal complications.