Donor Human Milk Implementation in a High-Mother’s-Own-Milk NICU: Impact on Feeding Progression and Clinical Outcomes in Extremely Low Birth Weight Infants
Abstract
1. Introduction
2. Material and Methods
2.1. Participants
2.2. Data Collection
2.3. Statistical Analysis
3. Results
3.1. Baseline Characteristics
3.2. Feeding Practices and Nutritional Outcomes
3.3. Clinical Outcomes
3.4. Exploratory Multivariable Analyses
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Stoll, B.J.; Hansen, N.I.; Bell, E.F.; Walsh, M.C.; Carlo, W.A.; Shankaran, S.; Laptook, A.R.; Sánchez, P.J.; Van Meurs, K.P.; Wyckoff, M.; et al. Trends in Care Practices, Morbidity, and Mortality of Extremely Preterm Neonates, 1993–2012. JAMA 2015, 314, 1039–1051. [Google Scholar] [CrossRef] [PubMed]
- Stoll, B.J.; Hansen, N.I.; Bell, E.F.; Shankaran, S.; Laptook, A.R.; Walsh, M.C.; Hale, E.C.; Newman, N.S.; Schibler, K.; Carlo, W.A.; et al. Neonatal outcomes of extremely preterm infants from the NICHD Neonatal Research Network. Pediatrics 2010, 126, 443–456. [Google Scholar] [CrossRef] [PubMed]
- Fanaroff, A.A.; Stoll, B.J.; Wright, L.L.; Carlo, W.A.; Ehrenkranz, R.A.; Stark, A.R.; Bauer, C.R.; Donovan, E.F.; Korones, S.B.; Laptook, A.R.; et al. Trends in neonatal morbidity and mortality for very low birthweight infants. Am. J. Obstet. Gynecol. 2007, 196, 147.e1–147.e8. [Google Scholar] [CrossRef] [PubMed]
- Alsaied, A.; Islam, N.; Thalib, L. Global incidence of Necrotizing Enterocolitis: A systematic review and Meta-analysis. BMC Pediatr. 2020, 20, 344. [Google Scholar] [CrossRef] [PubMed]
- Neu, J. Necrotizing enterocolitis. World Rev. Nutr. Diet. 2014, 110, 253–263. [Google Scholar] [CrossRef] [PubMed]
- Patel, B.K.; Shah, J.S. Necrotizing enterocolitis in very low birth weight infants: A systemic review. ISRN Gastroenterol. 2012, 2012, 562594. [Google Scholar] [CrossRef] [PubMed]
- Svenningsson, A.; Borg, H.; Hagander, L.; Lilja, H.E. Surgical management of necrotising enterocolitis in Sweden: A national cohort study. Acta Paediatr. 2023, 112, 1683–1688. [Google Scholar] [CrossRef] [PubMed]
- Robinson, J.R.; Rellinger, E.J.; Hatch, L.D.; Weitkamp, J.-H.; Speck, K.E.; Danko, M.; Blakely, M.L. Surgical necrotizing enterocolitis. Semin. Perinatol. 2017, 41, 70–79. [Google Scholar] [CrossRef] [PubMed]
- Quigley, M.; Embleton, N.D.; Meader, N.; McGuire, W. Donor human milk for preventing necrotising enterocolitis in very preterm or very low-birthweight infants. Cochrane Database Syst. Rev. 2024, 9, CD002971. [Google Scholar] [PubMed]
- Sullivan, S.; Schanler, R.J.; Kim, J.H.; Patel, A.L.; Trawöger, R.; Kiechl-Kohlendorfer, U.; Chan, G.M.; Blanco, C.L.; Abrams, S.; Cotton, M.C.; et al. An exclusively human milk-based diet is associated with a lower rate of necrotizing enterocolitis than a diet of human milk and bovine milk-based products. J. Pediatr. 2010, 156, 562–567.e1. [Google Scholar] [CrossRef] [PubMed]
- Altobelli, E.; Angeletti, P.M.; Verrotti, A.; Petrocelli, R. The Impact of Human Milk on Necrotizing Enterocolitis: A Systematic Review and Meta-Analysis. Nutrients 2020, 12, 1322. [Google Scholar] [CrossRef] [PubMed]
- Herrmann, K.; Carroll, K. An exclusively human milk diet reduces necrotizing enterocolitis. Breastfeed. Med. 2014, 9, 184–190. [Google Scholar] [CrossRef] [PubMed]
- Miller, J.; Tonkin, E.; Damarell, R.A.; McPhee, A.J.; Suganuma, M.; Suganuma, H.; Middleton, P.F.; Makrides, M.; Collins, C.T. A Systematic Review and Meta-Analysis of Human Milk Feeding and Morbidity in Very Low Birth Weight Infants. Nutrients 2018, 10, 707. [Google Scholar] [CrossRef] [PubMed]
- Meek, J.Y.; Noble, L. Section on Breastfeeding. Policy statement: Breastfeeding and the use of human milk. Pediatrics 2022, 150, e2022057988. [Google Scholar] [CrossRef] [PubMed]
- Silano, M.; Milani, G.P.; Fattore, G.; Agostoni, C. Donor human milk and risk of surgical necrotizing enterocolitis: A meta-analysis. Clin. Nutr. 2019, 38, 1061–1066. [Google Scholar] [CrossRef] [PubMed]
- Carr, L.E.; Virmani, M.D.; Rosa, F.; Munblit, D.; Matazel, K.S.; Elolimy, A.A.; Yeruva, L. Role of human milk bioactives on infants’ gut and immune health. Front. Immunol. 2021, 12, 604080. [Google Scholar] [CrossRef] [PubMed]
- Underwood, M.A. Human milk for the premature infant. Pediatr. Clin. N. Am. 2013, 60, 189–207. [Google Scholar] [CrossRef] [PubMed]
- Granger, C.L.; Embleton, N.D.; Palmer, J.M.; Lamb, C.A.; Berrington, J.E.; Stewart, C.J. Maternal breastmilk, infant gut microbiome and the impact on preterm infant health. Acta Paediatr. 2021, 110, 450–457. [Google Scholar] [CrossRef] [PubMed]
- Johnson, T.J.; Patel, A.L.; Jegier, B.J.; Engstrom, J.L.; Meier, P.P. Cost of morbidities in very low birth weight infants. J. Pediatr. 2013, 162, 243–249.e1. [Google Scholar] [CrossRef] [PubMed]
- Herzlich, J.; Frumer, B.; Mandel, D.; Morag, S.; Halperin, A.; Mangel, L. Effects of donor human milk and formula supplementation on bone me-tabolism and clinical outcomes in preterm infants receiving mother’s own milk. Nutrients 2025, 17, 3263. [Google Scholar] [CrossRef] [PubMed]
- Dollberg, S.; Haklai, Z.; Mimouni, F.B.; Gorfein, I.; Gordon, E.-S. Birth weight standards in the live-born population in Israel. Isr. Med. Assoc. J. 2005, 7, 311–314. [Google Scholar] [PubMed]
- Parker, L.A.; Koernere, R.; Fordham, K.; Bubshait, H.; Eugene, A.; Gefre, A.; Bendixen, M. Mother’s own milk versus donor human milk: What’s the difference? Crit. Care Nurs. Clin. N. Am. 2024, 36, 119–133. [Google Scholar]
- Meier, P.; Patel, A.; Esquerra-Zwiers, A. Donor human milk update: Evidence, mechanisms, and priorities for research and practice. J. Pediatr. 2017, 180, 15–21. [Google Scholar] [CrossRef] [PubMed]
- Shah, T.A.; Meinzen-Derr, J.; Gratton, T.; Steichen, J.; Donovan, E.F.; Yolton, K.; Alexander, B.; Narendran, V.; Schibler, K.R. Hospital and neurodevelopmental outcomes of extremely low-birth-weight infants with necrotizing enterocolitis and spontaneous intestinal perforation. J. Perinatol. 2012, 32, 552–558. [Google Scholar] [CrossRef] [PubMed]
- Battersby, C.; Santhalingam, T.; Costeloe, K.; Modi, N. Incidence of neonatal necrotising enterocolitis in high-income countries: A systematic review. Arch. Dis. Child.-Fetal Neonatal Ed. 2018, 103, F182–F189. [Google Scholar] [CrossRef] [PubMed]
- Underwood, M.A. The fifty billion dollar question: Does formula cause necrotizing enterocolitis? J. Perinatol. 2025, 45, 565–571. [Google Scholar] [CrossRef] [PubMed]
- Williams, T.; Nair, H.; Simpson, J.; Embleton, N. Use of donor human milk and maternal breastfeeding rates: A systematic review. J. Hum. Lact. 2016, 32, 212–220. [Google Scholar] [CrossRef] [PubMed]
- Bagga, N.; Kurian, S.; Mohamed, A.; Reddy, P.; Chirla, D.K. Pasteurized donor human milk should not replace mother’s own milk in preterm neonates: A quality initiative toward decreasing the “PDHM dependency”. Breastfeed. Med. 2022, 17, 252–258. [Google Scholar] [CrossRef] [PubMed]
- Hård, A.-L.; Nilsson, A.K.; Lund, A.-M.; Hansen-Pupp, I.; Smith, L.E.H.; Hellström, A. Review shows that donor milk does not promote the growth and development of preterm infants as well as maternal milk. Acta Paediatr. 2019, 108, 998–1007. [Google Scholar] [CrossRef] [PubMed]
- Gates, A.; Hair, A.B.; Salas, A.A.; Thompson, A.B.; Stansfield, B.K. Nutrient composition of donor human milk and comparisons to preterm human milk. J. Nutr. 2023, 153, 2622–2630. [Google Scholar] [CrossRef] [PubMed]
- Perrin, M.T.; Belfort, M.B.; Hagadorn, J.I.; McGrath, J.M.; Taylor, S.N.; Tosi, L.M.; Brownell, E.A. The nutritional composition and energy content of donor human milk: A systematic review. Adv. Nutr. 2020, 11, 960–970. [Google Scholar]


| Characteristics | Epoch 1 (n = 58) | Epoch 2 (n = 58) | p-Value |
|---|---|---|---|
| Antenatal steroid | 40 (69) | 46 (79.3) | 0.203 |
| Pre-eclampsia | 11 (19) | 10 (17.2) | 0.844 |
| Gestational diabetes mellitus | 4 (6.9) | 6 (10.3) | 0.508 |
| Mode of delivery | 0.281 | ||
| Spontaneous vaginal delivery | 9 (15.5) | 17 (29.3) | |
| Emergency cesarean | 48 (82.8) | 40 (69) | |
| Elective cesarean | 1 (1.7) | 1 (1.7) | |
| Gestational age (weeks) | 27.1 ± 2.1 (24–32) | 26.6 ± 2 (23–32) | 0.231 |
| Birth weight (g) | 827.5 [698.8, 932.5] (500–995) | 827.5 [732.5, 980] (550–996) | 0.478 |
| Female sex | 30 (51.7) | 28 (48.3) | 0.710 |
| Small for gestational age | 32 (55.2) | 17 (29.3) | 0.005 |
| Surfactant use | 44 (75.9) | 35 (60.3) | 0.073 |
| Length of hospital stay (d) | 82 [55.8, 108.3] (40–224) | 83 [67.8, 105] (30–197) | 0.952 |
| Characteristics | Epoch 1 (n = 58) | Epoch 2 (n = 58) | p-Value |
|---|---|---|---|
| Start of enteral feeding (d) | 2.5 ± 1 2 [2, 3] | 2 ± 2.6 2 [1, 2] | <0.001 |
| Reaching birth weight (d) | 8 [5.8, 12] | 9.5 [6, 14] | 0.316 |
| Duration of parenteral nutrition (d) | 27 [13.8, 35.8] | 17.5 [12, 27.5] | 0.088 |
| Reaching full enteral feeding (d) | 24.5 [14, 35.5] | 14 [11, 22] | <0.001 |
| WG% at 14 days | 6.3 [−1.3, 17] | 8.4 [1, 14] | 0.903 |
| WG% at 28 days | 33.7 [17.3, 52.6] | 37.2 [23.1, 46.7] | 0.862 |
| Feeding regimen | <0.001 | ||
| MOM | 44 (75.9) | 21 (36.2) | |
| Formula | 5 (8.6) | 0 | |
| MOM + formula | 9 (15.5) | 0 | |
| MOM + DHM | 0 | 22 (37.9) | |
| MOM + DHM + formula | 0 | 13 (22.4) | |
| DHM | 0 | 2 (3.4) | |
| Exclusive MOM rate (%) | 44 (75.9) | 21 (36.2) | <0.001 |
| MOM exposure in mixed feeding regimen (% of feeds) | 75 [65, 87.5] | 82.5 [58, 90] | 0.775 |
| Formula exposure in mixed feeding regimen (% of feeds) | 25 [12.5, 35] | 14 [7.5, 28.5] | 0.144 |
| DHM use (% of feeds) | 0 | 10 [7, 32] | NA |
| Outcome | Epoch 1 | Epoch 2 | p-Value |
|---|---|---|---|
| Clinical Outcomes (28-day feeding cohort; n = 58 per epoch) | |||
| Total necrotizing enterocolitis (NEC) | 15 (25.9) | 12 (20.7) | 0.510 |
| Surgical NEC | 3 (5.2) | 5 (8.6) | 0.717 |
| Feeding intolerance | 18 (31) | 17 (29.3) | 0.840 |
| Bloodstream infection | 18 (31) | 17 (29.3) | 0.840 |
| Intraventricular hemorrhage (IVH) | 17 (29.3) | 24 (41.4) | 0.174 |
| Symptomatic hypoglycemia | 13 (22.4) | 27 (46.6) | 0.006 |
| Phototherapy | 39 (67.2) | 51 (87.9) | 0.008 |
| Mortality before discharge | 4 (6.9) | 5 (8.6) | 0.728 |
| Mortality (full ELBW cohort; epoch 1 n = 66, epoch 2 n = 65) | |||
| Mortality before day 28 | 8 (12.1) | 7 (10.8) | 0.808 |
| Total mortality rate | 12 (18.2) | 12 (18.5) | 0.967 |
| A. Exploratory Multivariable Logistic Regression Analysis for NEC (n = 116) | |||
|---|---|---|---|
| Variable | Adjusted OR | 95% CI | p-Value |
| Epoch 2 vs. epoch 1 | 0.76 | 0.30–1.93 | 0.569 |
| Gestational age (weeks) | 0.94 | 0.70–1.25 | 0.661 |
| Birth weight (per 100 g) | 0.88 | 0.57–1.35 | 0.555 |
| Feeding intolerance | 2.6 | 1.04–6.49 | 0.041 |
| Day of feeding initiation | 1.09 | 0.86–1.39 | 0.477 |
| Model statistics: Cox and Snell R2 = 0.066; Nagelkerke R2 = 0.100; omnibus χ2 = 7.91 (df = 5), p = 0.161. | |||
| B. Multivariable Linear Regression Analysis for Parenteral Nutrition Duration (n = 116) | |||
| Variable | β (days) | 95% CI | p-Value |
| Gestational age (weeks) | −3.67 | −6.07 to −1.27 | 0.003 |
| SGA | −1.76 | −11.23 to 8.73 | 0.805 |
| Feeding intolerance | 8.55 | −0.42 to 17.52 | 0.062 |
| Day of feeding initiation | −0.50 | −2.61 to 1.61 | 0.640 |
| Epoch 2 vs. epoch 1 | −5.39 | −13.88 to 3.10 | 0.211 |
| Model statistics: N = 116, R2 = 0.14, adjusted R2 = 0.10, F = 3.55, p = 0.005. | |||
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Herzlich, J.; Less, O.; Frumer, B.; Marom, R.; Mangel, L.; Mandel, D. Donor Human Milk Implementation in a High-Mother’s-Own-Milk NICU: Impact on Feeding Progression and Clinical Outcomes in Extremely Low Birth Weight Infants. Nutrients 2026, 18, 2608. https://doi.org/10.3390/nu18162608
Herzlich J, Less O, Frumer B, Marom R, Mangel L, Mandel D. Donor Human Milk Implementation in a High-Mother’s-Own-Milk NICU: Impact on Feeding Progression and Clinical Outcomes in Extremely Low Birth Weight Infants. Nutrients. 2026; 18(16):2608. https://doi.org/10.3390/nu18162608
Chicago/Turabian StyleHerzlich, Jacky, Omer Less, Bar Frumer, Ronella Marom, Laurence Mangel, and Dror Mandel. 2026. "Donor Human Milk Implementation in a High-Mother’s-Own-Milk NICU: Impact on Feeding Progression and Clinical Outcomes in Extremely Low Birth Weight Infants" Nutrients 18, no. 16: 2608. https://doi.org/10.3390/nu18162608
APA StyleHerzlich, J., Less, O., Frumer, B., Marom, R., Mangel, L., & Mandel, D. (2026). Donor Human Milk Implementation in a High-Mother’s-Own-Milk NICU: Impact on Feeding Progression and Clinical Outcomes in Extremely Low Birth Weight Infants. Nutrients, 18(16), 2608. https://doi.org/10.3390/nu18162608

