Exclusive Human Milk Diet for Extremely Premature Infants: A Novel Fortification Strategy with Human Milk-Derived Fortifiers to Enhance the Bioactive Properties of Donor Milk

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A recent study at the University Maternity Hospital Limerick in Ireland sheds light on the benefits of human milk-derived fortifiers (HMDF) for extremely preterm and low-birthweight infants. Results show that, unlike cow’s milk-derived fortifiers (CMDF), HMDF significantly improves human milk’s nutritional content, including higher fat, protein, and antioxidant activity. Moreover, certain bioactive proteins found to be lacking in donor human milk were enhanced with HMDF. Researchers concluded that fresh mother’s own milk (FreMOM) fortified with HMDF and given early, enterally, and exclusively (3E) is an optimal nutritional option for preterm infants.

Preterm birth is a global concern, with about one in 10 infants born preterm worldwide and 8.7% of births in Europe being preterm. While human milk (HM) is considered the optimal choice for preterm infants, those born at extremely early gestational ages or extremely low-birthweight often require additional nutritional support to approximate the levels of growth and development comparable to the womb. The traditional practice in neonatal nutrition in the neonatal intensive care unit (NICU) has been to supplement HM with cow’s milk-derived fortifiers. However, concerns have arisen about the nutritional limitations and potential risks of using cow-origin protein supplementation. As a result, researchers have turned to human milk-derived fortifiers (HMDF) as a safer and potentially more beneficial alternative.

A recent study conducted at the University Maternity Hospital Limerick (UMHL) in Ireland has shed light on the benefits of using a human milk-derived fortifier for extremely preterm and extremely low-birthweight infants. The Irish Neonatal Health Alliance (INHA)(@INHA), a patient advocacy group representing parents of preterm infants, was involved from the conception to the completion of the study.

The study, which explored the biochemical and immunochemical characteristics of HM supplemented with either HMDF or traditional cow’s milk-derived fortifier, aimed to evaluate the potential advantages for neonatal nutrition when using one over the other. Researchers analysed gestation-specific specimens for macronutrients, pH, total solids, antioxidant activity (AA), α-lactalbumin, lactoferrin, lysozyme, and α- and β-caseins in various types of HM, both with and without CMDF and HMDF fortification. The types of HM used were freshly expressed mother’s own milk (FreMOM), frozen mother’s own milk (FroMOM), preterm donor human milk (PTDHM), and full-term donor human milk (FTDHM). Researchers also included commercially available preterm-formula and term-formula as comparators.

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The study results revealed that HMDF significantly improved the nutritional content of HM, enhancing fat and total protein levels when compared to CMDF. Moreover, HMDF substantially increased the antioxidant activity of the milk, which is crucial in reducing oxidative damage to developing tissue. Certain bioactive proteins, such as α-lactalbumin, lactoferrin, and lysozyme, protect preterm infants from infections and support their immune systems. The study found that pasteurised donor human milk (PTDHM and FTDHM) had lower concentrations of these bioactive proteins compared to fresh and frozen mother’s own milk. However, when HMDF was added to DHM, the levels of these protective proteins increased significantly, suggesting that HMDF can help reinstate and enhance the bioactive properties of DHM, which has been attenuated through pasteurisation.

Analyses concluded that FreMOM fortified with HMDF and given early, enterally, and exclusively (3E) appears to be an optimal nutritional choice for extremely preterm and extremely low-birthweight infants during the early critical period after birth. Additionally, this approach could potentially reduce the risk of complications such as necrotising enterocolitis (NEC), late-onset neonatal sepsis, bronchopulmonary dysplasia, retinopathy of prematurity (ROP), and total parenteral nutrition usage.

The findings of this study provide valuable insights into the significance of HMDF for neonatal care. Regardless of the small sample and the lack of in-vivo bioactivity measures used for the study, it contributes to the growing body of evidence supporting the benefits of HM and HMDF for improving the health and development of newborns, especially when it comes to the most vulnerable preterm babies. Further evidence is needed to evaluate the long-term benefits of HMDF.


Paper available at: Breastfeeding Medicine

Full list of authors: Roy K. Philip, Ehab Romeih, Elizabeth Bailie, Mandy Daly, Kieran D. McGourty, Andreas M. Grabrucker, Colum P. Dunne, and Gavin Walker


For more on the importance of optimal neonatal nutrition, visit our campaigns Human Milk Matters – Human Milk Cares” and “Healthy Early Nutrition – Healthy Future

Our position paper about parenteral nutrition is available for download as well: