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Growth Efficiency of Donor Human Milk Compared With Maternal Milk and Formula in Preterm Infants

Chou, J. H.; Berken, J. A.; Nelson, B. D.; Matute, J. D.

2025-10-07 pediatrics
10.1101/2025.10.03.25337279 medRxiv
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ImportanceHuman milk is beneficial for preterm newborns, and pasteurized donor human milk (PDHM) is increasingly used when mothers own milk (MM) is insufficient. However, PDHM has been associated with suboptimal growth outcomes. ObjectiveTo quantify the comparative clinical effectiveness of PDHM, MM, and formula in supporting daily weight gain and growth outcomes during the birth hospitalization. DesignRetrospective cohort study of infants born before 34 weeks gestation between 2016 and 2024 SettingFive newborn nurseries across the Mass General Brigham healthcare system (Boston, MA), including one Level IV, one Level III, and three Level II newborn units. ParticipantsA total of 2,635 preterm infants born before 34 weeks gestation between 2016 and late 2024 were included in the daily weight gain analysis, contributing 40,007 days of eligible enteral intake data for evaluation of in-hospital growth outcomes. For the analysis examining the association between PDHM use and discharge weight, 2,719 infants met eligibility criteria. ExposuresPDHM, MM, formula Main Outcomes and MeasuresThe primary outcome was daily weight gain (g/kg/day). The secondary outcome was the change in weight Z-score from birth to discharge. ResultsIn adjusted analyses, an equal volume of PDHM was associated with 74% of the daily weight gain achieved with MM (p < 0.0001, 95% CI 70%-77%), and formula with 115% of MM (p < 0.0001, 95% CI 111%-119%). During the birth hospitalization, infants in the highest quartile of PDHM exposure had a significantly greater decline in weight-for-age Z-score compared with those with no exposure (-0.09, p = 0.005), while no differences were observed in the lower quartiles. Conclusions and RelevanceGrowth outcomes varied by PDHM exposure, with a significant decline observed only in the highest quartile, while lower exposure levels showed no significant effect. Formula-fed infants were observed to have greater weight gain than either PDHM or MM. These results highlight the need for close growth monitoring and timely nutritional adjustments in preterm infants, particularly when PDHM is the primary source of enteral nutrition. QuestionHow does pasteurized donor human milk (PDHM) compare with mothers own milk (MM) and formula in supporting in-hospital growth among preterm infants born at or before 34 weeks gestation? FindingsIn this multicenter retrospective cohort study involving > 2500 preterm infants contributing over 40,000 infant-days of enteral data, PDHM correlated with significantly reduced daily weight gain compared with MM, whereas formula supported greater weight gain than either human milk source. At discharge, infants with the highest quartile of PDHM exposure showed a greater reduction in weight-for-age Z-score than infants with no PDHM exposure. No association was observed in the lower quartiles. MeaningOur findings underscore the need for close growth monitoring and potentially greater nutritional supplementation in relation to PDHM exposure.

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