HUMAN MILK AND PREMATURE INFANTS
The Panel members agree on the statements from the American Academy of Pediatrics (1) and the ESPGHAN Committee on Nutrition (2) which state that because of the potential benefits all preterm infants should receive HM. OMM should be the primary diet, and if OMM is not available or not in sufficient quantity, pasteurized donor human milk obtained from a recognized HMB should be used.
The Panel agrees with these statements and strongly supports the recommendation that all preterm infants should receive HM.
WELL ESTABLISHED ADVANTAGES OF HUMAN MILK
The advantages of HM include protection against NEC and sepsis, and its trophic effects on the gastrointestinal tract.
- The protection against NEC was supported by studies of Schanler and coworkers in 1999 (3). More recent studies demonstrated that the feeding of HM protects against NEC in dose-dependent fashion (4,5).
- The protection of HM against sepsis has been well established over the years. A recent study confirmed that HM strongly protects premature babies against late-onset sepsis in dose-dependent fashion (6).
- The trophic effects of HM are attributable to multiple components that are known to stimulate maturation of the immature gut. Clinically trophic effects are manifested as lower gastric residual volumes, more rapid advancement of feedings and earlier achievement of full feedings (7).
There are limited data on protection against severe retinopathy and bronchopulmonary dysplasia, improvement of long term neurocognitive development and cardiovascular health outcomes. More studies are necessary to confirm these preliminary results.
The Panel agrees on the following statements about growth:
- The achievement of adequate growth in preterm infants is difficult, but extremely relevant in terms of long-term development.
- Reduction of the incidence and severity of extrauterine growth restriction represents one of the main goals in premature infant nutrition and efforts must begin immediately after birth.
- The aim of postnatal growth is not to lose more than 1 SDS in weight and head circumference from birth to discharge.
- Growth is not only weight gain. It includes also head circumference and length gains, although accurate length measurements are difficult to obtain.
FORTIFICATION OF HUMAN MILK
The WHO (8) recommends against HM fortification for preterm infants (1000 to 1500 g) unless growth faltering is noted. This recommendation is paradoxical as recent meta-analyses suggest benefits for multi-nutrient fortification (9).
The reported benefits are strong and the Panel feels that no further randomized trials need to be done and that attention now needs to be paid to the quality of the fortifier.
The practical recommendations on fortification of HM are the following:
- All preterm infants with a birth weight <1800 grams should be fed fortified HM (10).
- HM should be fortified with protein, vitamins and minerals.
- The quantity of HM fortification should be sufficient to enable appropriate growth throughout the NICU stay.
- HM fortification should start with standard fortification.
- If infants do not grow appropriately, individualized fortification is advisable.
- There are two types of individualized fortification: targeted fortification (based on milk analysis) (11,12) and adjustable fortification (based on BUN measurements) (13,14).
- Both are advisable depending on the NICU experience and facilities.
BIOENGINEERING OF HUMAN MILK AND QUALITY OF FORTIFIERS
Bioengineering of HM is the application of concepts and methods of biology (and secondarily of physics, chemistry, mathematics, and computer science) to solve problems related to feeding (premature) infants. In this context, while traditional engineering applies physical and mathematical sciences to analyze, design and manufacture inanimate tools, structures and processes, biological engineering uses primarily rapidly developing molecular biology to study and advance applications of HM and its components and to create biotechnology.
Bovine milk-based fortifiers are routinely used for fortification of HM. It has been speculated that bovine protein may be associated with intestinal inflammation in ELBW infants and that the concomitant use of DHM is inadequate to protect the host under these circumstances. These observations led to the investigation of exclusive HM diets (human milk-based human milk fortifier and donor human milk if OMM was unavailable), appropriately fortified to meet the needs of the ELBW infants (15,16). Both studies reported that an exclusive HM diet is associated with less NEC, less NEC requiring surgery, and lower mortality in ELBW infants than in those who receive OMM plus bovine milk-based products (17,18).
Based on the results from these randomized clinical trials, the Panel states:
- Studies for quality improvements of bovine milk-based fortifiers are in progress.
- Human milk-based fortifiers are available, probably are of better quality than cow's milk based fortifiers, but are very expensive at the moment.
- Optimizing human milk-based fortifiers, bioengineered to contain as many bioactive products as possible and including also pre- and probiotics, will enhance the use of OMM and potentially improve the outcome.
DONOR HUMAN MILK (DHM) BANK
OMM is the first choice in preterm infant feeding, and strong efforts should be made to promote lactation. When mother's milk is not available, DHM obtained from a well established HMB is the preferred choice.
An HMB is a service with the purpose of selecting, collecting, screening, storing, and distributing donated human milk to meet the specific needs of individuals for whom HM is prescribed by health care providers.
The Panel agrees that:
- DHM should be provided from an established HMB that follows specific safety guidelines.
- HMBs are essential for providing safe DHM to vulnerable infants, such as VLBW infants.
- Presence of an HMB does not compete with breast-feeding, but decreases the utilization of formula in a NICU and increases exclusive breast-feeding rates at discharge (19).
- The collection, treatment and distribution of DHM require technical processes which are differing depending on location, organization and resources.
- Universal core requirements and quality principles for all HMBs should be implemented. These are often based upon consensus between health professionals in each country.
- Further research is needed to help building universally accepted recommendations.
PROCESSING OF HUMAN MILK
Fresh OMM is the first choice for feeding preterm infants. Fresh OMM, when administered within 24 hours, does not require routine culturing or heat treatment. When OMM is not available, DHM is the first alternative. HM needs to be checked microbiologically and to undergo heat treatment in order to inactivate viral and bacterial agents present in milk. Processing of HM reduces some biological and nutritional components.
The Panel states that at the moment the following should be considered:
- Processing of HM includes pasteurization, freezing and thawing, and each of these phases influences the quality of HM. Special attention should be paid to all the three phases (20).
- Currently Holder pasteurization (62.5°C for 30 minutes) is the recommended method by all HMB guidelines (20–25).
- New methods of DHM treatment are under investigation and high-temperature-short-time pasteurization (HTST, 72°C for 5–15 seconds) seems to be the most promising.
CENTRALIZED HUMAN MILK HANDLING
The utilization of quality improvement measures with regards to safe handling of HM in NICUs is becoming a common practice in many centers (26).
The following recommendations are suggested to reduce the risk of HM errors and infant feeding contamination within the hospital setting:
- Centralized preparation of HM should be performed in a dedicated space designed to support aseptic techniques in every NICU.
- Presence of a dedicated and trained staff for the preparation of HM in this specific space is desirable.
- Technology (i.e. bar code scanning) to reduce risk of preparation and administration errors and for traceability of HM is highly suggested.
PROMOTION OF BREAST-FEEDING IN THE NICU
A strategy aiming to promote and support breast-feeding should be carried out in every maternity or children's hospital where premature infants are born or cared for after birth.
Hospital-based lactation programs and OMM bank to provide mother's milk to preterm infants should be adopted (27).
Early intervention with milk expression soon after delivery (ideally within 6 hours) is critical for milk production of NICU mothers; therefore, mothers should be taught a method of milk expression within this time frame.
Some clinicians use early colostrum care in their NICU patients. This indicates to mothers that their milk is critical for their infants. One study reported higher urinary sIgA and lactoferrin excretion in infants given oral colostrum care compared to controls (28).
HM utilization in premature infants can contribute to the development of an integrated system for providing optimal newborn care, together with kangaroo mother care (skin-to-skin contact), rooming-in, respecting the WHO/UNICEF Ten Steps to Successful Breast-feeding expanded in 2011 for use in NICUs, and other best practices for neonatal care (29).
EPIGENETICS AND NUTRITION
Studies suggest a new area of research in prematurity that is exploring developmental and feeding behavior problems of preterm infants via epigenetic mechanisms, namely Preterm Behavioral Epigenetics (PBE) (30). Benefits of HM for preterm infants’ health may be at least partly associated with its nutritional components, likely also by epigenetic mechanisms (31).
Although the epigenetic processes involved remain unclear, future research should be conducted to clarify the relationship between human breast milk and gene expression (32). Emerging research suggests that nutrition during infancy might contribute to later obesity via metabolic imprinting of epigenetic gene regulatory mechanisms (33,34), so future epigenetic research might investigate the associations between early nutrition in NICUs (e.g., HM vs. formula) and later eating disorders.
1. American Academy of Pediatrics. Breastfeeding and use of human milk. Pediatrics
2. Arslanoglu S, Corpeleijn W, Moro G, et al. ESPGHAN Committee on NutritionDonor Human Milk for Preterm Infants: Current Evidence and Research Directions. J Pediatr Gastroenterol Nutr
3. Schanler RJ, Shulman RJ, Lau C, et al. Feeding strategies for premature infants: randomized trial of gastrointestinal priming and tube-feeding method. Pediatrics
4. Meinzen-Derr J, Poindexter B, Wrage L, et al. for the NICHHD Neonatal Research NetworkRole of human milk in extremely low birth weight infants’ risk of necrotizing enterocolitis or death. J Perinatol
5. Corpeleijn WE, Kouwenhoven SM, Paap MC, et al. Intake of own mother's milk during the first days of life is associated with decreased morbidity and mortality in very low birth weight infants during the first 60 days of life. Neonatology
6. Patel AL, Johnson TJ, Engstrom JL, et al. Impact of early human milk on sepsis and health-care costs in very low birth weight infants. J Perinatol
2013; Jan 2013:1–6.
7. Tyson JA, Kennedy KA. Trophic feedings for parenterally fed infants Review). Cochrane Database System Rev
9. Kuschel CA, Harding JE. Multicomponent fortified human milk for promoting growth in preterm infants. Cochrane Library
10. Agostoni C, Buonocore G, Carnielli VP, et al. Enteral nutrient supply for preterm infants: commentary from the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) Committee on Nutrition. J Pediatr Gastroenterol Nutr
11. Polberger S, Räihä NCR, Juvonen P, et al. Individualized protein fortification of human milk for preterm infants: Comparison of ultrafiltrated human milk protein and a bovine whey fortifier. J Pediatr Gastroenterol Nutr
12. Rochow N, Fusch G, Choi A, et al. Target fortification of breast milk with fat, protein and carbohydrates for preterm infants. J Pediatr
13. Arslanoglu S, Moro GE, Ziegler EE. Adjustable fortification of human milk fed to preterm infants: does it make a difference? J Perinatol
14. Arslanoglu S, Bertino E, Coscia A, et al. Update of adjustable fortification regimen for preterm infants: a new protocol. J Biol Regul Homeost Agents
2012; 26 (3 Suppl):65–67.
15. Sullivan S, Schanler RJ, Kim JH, 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
16. Cristofalo EA, Schanler RJ, Blanco CL, et al. Randomized trial of exclusive human milk versus preterm formula diets in extremely premature infants. J Pediatr
17. Eidelman A, Schanler R. Breastfeeding and the use of human milk. Pediatrics
18. Abrams SA, Schanler RJ, Lee ML, et al. Greater mortality and morbidity in extremely preterm infants fed a diet containing cow milk protein products. Breastfeed Med
19. Arslanoglu S, Moro GE, Bellù R, et al. Presence of human milk bank is associated with elevated rate of exclusive breastfeeding in VLBW infants. J Perinat Med
20. Arslanoglu S, Bertino E, Tonetto P, et al. Guidelines for the establishment and operation of a donor human milk bank. J Matern Fetal Neonatal Med
2010; 23 (Suppl 2):l–20.
21. Frischknecht K, Wälchli C, Annen C, et al. Recommandations pour l’organisation et le fonctionnement d’une banque de lait en Suisse. Paediatrica
22. Grøvslien AH, Grønn M. Donor milk banking and breastfeeding in Norway. J Hum Lact
23. Hartmann BT, Pang WW, Keil AD, et al. Australian Neonatal Clinical Care UnitBest practice guidelines for the operation of a donor human milk bank in an Australian NICU. Early Hum Dev
24. Human Milk Bank Association North America. Guidelines for the Establishment and Operation of a Donor Human Milk Bank” 2013. https://www.hmbana.org/publications
. Accessed April 2015.
26. Steele C, Bixby C. Centralized breastmilk handling and bar code scanning improve safety and reduce breastmilk administration errors. Breastfeeding Med
27. Hurst NM, Myatt A, Schanler RJ. Growth and development of a hospital-based lactation program and mother's own milk bank. J Obstet Gynecol Neonatal Nurs
28. Rodriguez NA, Meier PP, Groer MW, et al. A pilot study to determine the safety and feasibility of oropharyngeal administration of own mother's colostrum to extremely low birth weight infants. Adv Neonatal Care
29. Nyqvist KH, Häggkvist AP, Hansen MN, et al. Expansion of the Baby-Friendly Hospital Initiative Ten Steps to Successful Breastfeeding into neonatal intensive care: expert group recommendations. J Hum Lact
30. Montirosso R, Provenzi L. Implications of epigenetics and stress regulation on research and developmental care of preterm infants. J Obstet Gynecol Neonatal Nurs
31. Verduci E, Banderali G, Barberi S, et al. Epigenetic effects of human breast milk. Nutrients
32. Simeoni U, Yzydorczyk C, Siddeek B, et al. Epigenetics and neonatal nutrition. Early Hum Dev
33. Anderson OS, Sant KE, Dolinoy DC. Nutrition and epigenetics: An interplay of dietary methyl donors, one-carbon metabolism and DNA methylation. J Nutr Biochem
34. Burdge GC, Hanson MA, Slater-Jefferies JL, et al. Epigenetic regulation of transcription: A mechanism for inducing variations in phenotype (fetal programming) by differences in nutrition during early life? Br J Nutr