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. Author manuscript; available in PMC: 2016 Apr 1.
Published in final edited form as: Curr Opin Pediatr. 2015 Apr;27(2):172–176. doi: 10.1097/MOP.0000000000000201

Donor Human Milk for VLBWs: Patterns of Usage, Outcomes, and Unanswered Questions

Tarah T Colaizy 1
PMCID: PMC4414040  NIHMSID: NIHMS679180  PMID: 25689453

Abstract

Purpose of Review

Donor milk (DM) usage in the United States has increased substantially over the past ten years. Between 2007–2011, DM use in level 3 and 4 NICUs increased from 25% to 45%.

Recent Findings

Most centers have written protocols based on birthweight or gestational age, and give DM in an effort to prevent necrotizing enterocolitis (NEC). Evidence for protection against NEC using bovine fortified DM vs. formula is limited, although the exclusive human milk diet seems to offer protection compared to diets containing formula. Adequate growth can be achieved with DM fortified with either bovine or human milk-derived fortifiers, but use of additional fortification and protein supplementation may be required. Several randomized trials of donor milk vs. formula are ongoing in the VLBW population in North America that can answer important questions.

Summary

Further research is needed before donor milk, and the exclusive human milk diet, are considered standard of care.

Keywords: Donor Human Milk, necrotizing enterocolitis, exclusive human milk diet

Introduction

Maternal milk diets are the ideal for all infants, particularly for vulnerable populations including VLBW infants. Observational studies over the past 30 years in preterm infants have reported myriad benefits to maternal milk diets compared with contemporary formula options, including: better feeding tolerance, lower rates of sepsis1,2, necrotizing enterocolitis NEC 1–5, and bronchopulmonary dysplasia 2,6, shorter length of hospital stay 7, fewer re-hospitalizations6 and superior developmental outcomes at 2–8 years of age 6,8,9, with demonstration of a significant dose-response relationship6,9.

With an increased understanding of the importance of human milk for VLBW infants, the use of pooled, pasteurized donor human milk (DM) has rapidly gained acceptance. Most DM used in the United States is obtained from the member banks of the Human Milk Banking Association of North America, a non-profit organization. In 2003, 6 banks were dispensing milk; in late 2014 there are now 18 banks, with 10 more banks in various stages of development10. Between 2007 and 2011, total volume of DM dispensed by HMBANA banks doubled from 1.1 to 2.18 million ounces 10.

Recent recommendations have been published from ESPGHAN11, the AAP12, and the WHO13 endorsing the use of human DM in preterm infants when maternal milk is unavailable. Despite these recommendations and wide-spread use, large scale studies of its use in VBLW infants during the era of routine human milk fortification are lacking. In 2011 the US Surgeon General called for further research to identify areas where the evidence regarding DM is inconclusive and to develop evidence-based clinical guidelines for its use14.

The use of DM in NICUs is well established, and data from the United States suggests an increasing acceptance of this product. Additionally, single center reports of short term nutritional and health outcomes of very low birthweight (VLBW) infants fed DM have been published that will inform future studies. The exclusive human milk diet, utilizing human milk fortifier derived from human DM rather than bovine sources also represents an emerging dietary option for VLBW infants which has been studied in limited populations.

Maternal and Donor Milk Use in US NICUs

Use of both maternal and donor human milk in US NICUs is common, and rates are increasing in recent years. An analysis of the Centers for Disease Control and Prevention’s National Maternity Practices in Infant Nutrition and Care (MPINC) survey for the years 2007 to 2011 was conducted to determine patterns of human milk (maternal and/or donor) use in US NICUS. Responses were available for >80% of all facilities providing delivery services in the US during the years surveyed. Among level 2 and level 3–4 NICUS combined, the rates of low human milk usage (0–9% of infants fed human milk) declined from 8% in 2007 to 7.3% in 2011, and rates of high human milk usage (>90% of infants fed human milk) increased from 21.2% in 2007 to 30.8% in 2011. Use of human DM increased faster than use of all human milk combined, with 11.5% of units reporting use in 2007, and 22% reporting use in 2011. This increase in DM use was most pronounced in the level 3 and 4 centers, where use increased from 25.1% in 2007 to 45.2% in 201115.

Building on this analysis, two groups have recently published reports of the prevalence of DM use, and the criteria for use in US NICUs. Parker and colleagues used purposive random sampling to conduct a mail survey of US level 3 NICU medical directors to assess patterns of DM use 16. 60.3% (182/302) of directors surveyed responded, distributed equally across all US regions. 42% of directors reported use of DM in their NICU, with higher rates of use in the West (62%) and Midwest (47%), and lower use in the Northeast (23%) and South (36%). Among users of DM (76/182), 85% had been using the intervention for less than 5 years. Factors associated with DM use in multivariable analysis included ≥ 800 annual NICU admissions and Midwest or West location. Availability of surgical care for NEC or designation as a safety net hospital were not associated with DM use in this analysis. Criteria used to initiate use were varied, but commonly included insufficient maternal milk supply, and infants below specified birthweight (83%) and gestational age (75%). At least 50% of respondents agreed that DM should be used in infants born at < 1500 g, and discontinued at 33–34 weeks postmenstrual age, and that it should be used after surgery for NEC. The majority of DM-using units had a specified guideline for use (73%), required signed parental consent for use (84%), and had high parental acceptance of DM (67% of units reported < 5% parental refusal)16.

Hagadorn and colleagues used an online survey design of medical directors of level 3 and 4 NICUS in the US to describe policy-driven use of DM17. 33% of medical directors (153/459) completed the survey, 59% of whom reported use of DM in their unit. Similar to the earlier survey of medical directors undertaken by Parker et al16, use of DM was associated with more NICU beds, higher annual admissions, and higher VLBW admissions. Additionally, as noted in MPINC, higher level NICUs were more likely to provide DM (74% of level 4 NICUs vs. 53% of level 3 NICUs). Directors were also queried regarding reasons for DM use, with many citing desire to reduce the incidence of NEC (58%) as the most important reason. Directors of centers that did not provide DM reported expense as the most common reason for non-use. 79% of directors reported use of a formal policy to guide DM use, and policies were varied, but typically included birthweight and/or gestational age criteria for both initiation and discontinuation of DM. 91% of directors reported that DM was used outside of the written criteria at physician discretion17.

From these three studies, it is clear that donor human milk use in US NICUS is prevalent and growing, particularly over the past 5–10 years. NICUs caring for the smallest and sickest infants in the greatest numbers use DM more frequently, and often do so in an effort to reduce the incidence of necrotizing enterocolitis (NEC).

Evidence regarding NEC and fortified DM

Although the desire to prevent NEC is often cited as a reason to use DM by neonatologists, evidence for this effect is limited. The most often cited references for reduced NEC with DM compared to formula diets are meta-analyses of trials that were conducted prior to the routine use of multi-component bovine milk-derived human milk fortifiers which are now standard of care for VLBW infants 18,19. These trials compared unfortified DM to contemporary formulas. The only randomized trial of bovine-fortified DM compared to preterm formula was published by Schanler and colleagues in 2005 1. Infants were randomized to receive preterm formula or fortified DM if maternal milk was insufficient. Infants receiving formula had higher incidence of NEC (11%) than those receiving either entirely fortified maternal milk (6%), or fortified DM (6%), but this difference was not statistically different (p = 0.27, formula vs. DM). Therefore, we have no clear evidence that use of DM with bovine-derived fortifier will result in decreased NEC. Rather, evidence is commonly extrapolated from data that bovine-fortified maternal milk is associated with lower rates of NEC than preterm formula1,7,20 but the effects of pooling and pasteurization on DM, including decreased levels of secretory IgA21–23, lactoferrin, and lysozyme 23, make these extrapolations problematic.

Evidence regarding NEC and the exclusive human milk diet (EHM)

A recent published secondary analysis of the two previously published trials of the exclusive human milk diet (EHM) provide preliminary evidence that use of human milk-derived human milk fortifier (HHMF) in a human milk diet (maternal or donor) may offer protection against NEC when compared to preterm formula. The individual trials will be first reviewed as background. The first report of the EHM diet in VLBW infants published by Sullivan and colleagues in 2010 24was an unblinded trial that randomized infants to receive either bovine fortifier for all maternal milk feedings and preterm formula if a supplement to maternal milk was required, or HHMF for all maternal milk feedings and HHMF fortified donor milk if a supplement to maternal milk was required. The bovine group experienced a higher incidence of NEC (11/69, 16 % vs. 8/138, 6% in the human group, p =0.02). Additionally, surgical NEC was more common in the bovine group, (7/69, 10 % vs. 2/138, 1.4% in the human group, p = 0.007) 24. The combined outcome of NEC and/or late onset sepsis occurred at similar rates between bovine (30%) and human (30%) groups. The same group of investigators then conducted a blinded randomized trial of EHM vs. preterm formula in infants whose mothers never provided milk 25. 53 infants were included, 24 received formula, and 29 EHM. Five infants in the formula group (21%) developed NEC, compared to 1 (3%) in the bovine group (p = 0.08), and surgical NEC occurred in only the bovine group (4/5 cases, p = 0.04)25. Infants in the formula group in this trial experienced NEC at much higher rates than previously noted for exclusively formula fed infants (21% vs. an 11% incidence for infants exclusively fed formula in the NICHD “glutamine” trial20), which should be noted when interpreting these results.

The investigators then performed a post-hoc analysis of the datasets combined 26. They found that NEC occurred more frequently in the groups receiving formula and/or bovine HMF (16/93, 17%) than those receiving EHM (9/167, 5%, p=0.002). Surgical NEC (11/93, 12%) and mortality (7/93, 8%) were also more common in the bovine groups than those receiving EHM (surgical NEC 2/167, 1%, p = 0.0003; mortality 3/167, 2%, p = 0.04)26. Due to the small sample size of each trial, and the relatively high rates of NEC noted, these results should be interpreted with caution. However, taken together or separately they suggest that avoidance of formula results in lower incidence of NEC. There has not been a pure comparison of the use of HHMF and bovine HMF in diets that otherwise contain only maternal milk and/or donor milk, thus it is unknown if the EHM diet offers any benefit over a human milk diet fortified with bovine HMF with regards to NEC prevention.

Evidence regarding growth in VBLW infants fed DM

Since growth is closely linked to long term neurodevelopmental outcomes27, any diet in widespread use in VLBWs needs to result in appropriate growth. Evidence for this is limited. However, there are two published trials of growth in VLBWs fed bovine fortified donor milk28. In the initial randomized trial of DM as a supplement to maternal milk published by Schanler1, growth was reported as a secondary outcome. A weight gain deficit of 3/g/kg was noted for infants fed maternal or donor milk compared to those fed formula, but no difference was noted between the donor and maternal groups, and length and head growth were similar across all three groups. Colaizy and colleagues specifically studied growth in a cohort of VLBW infants fed varying proportions of maternal and donor milk28. Infants receiving > 75% of the in-hospital diet as donor milk experienced a weight z-score change of – 0.84 vs. −0.56 for infants receiving > 75% maternal milk ( p = 0.28). Infants in this trial also received levels of protein fortification in excess of those produced with manufacturer-directed bovine HMF use, through additional bovine HMF use or as single component protein powders 28.

Hair and colleagues studied a similar cohort of VLBW infants fed the exclusive human milk diet, and report that with early use and rapid advancement of human HMF, weight gain of 24.8 g/kg/d was achieved, which exceeds most recommendations. Although 43% of their infants were SGA at discharge or 40 weeks PMA29, the growth rates achieved with their protocol were better than those achieved in either of the initial EHM studies 24,25.

Therefore, it has been demonstrated that appropriate growth can be achieved with use of donor milk diets, when both bovine and human HMF products are used, but that fortification beyond the traditional first step (24 kcal/oz) may be required.

Ongoing donor milk research

As called for by the US Surgeon General14, there are several ongoing randomized trials of donor milk vs. preterm formula in VLBW infants in North America. O’Connor and colleagues recently published the protocol for the randomized, blinded DoMINO trial, which is currently completing follow-up 30. VLBW infants were randomized at birth to receive donor milk or preterm formula as a supplement if maternal milk was insufficient, or as the sole diet if the mother chose not to provide milk for 90 days or the duration of hospitalization. The primary outcome of the trial is the Cognitive Scale score of the Bayley Scales of Infant Development III (BSID III) at age 18–22 months, and the investigators hypothesize that infants randomized to donor milk will score 5 points higher than those randomized to formula. This trial also collected extensive in-hospital growth and outcome data30. A similar trial is underway in Iowa, where Colaizy and colleagues also randomized VLBW infants at birth to donor milk or formula if maternal milk were insufficient or absent (clinicaltrials.gov NCT01232725), to assess the effect of DM on neurodevelopmental outcomes at 18–22months. Finally, the NICHD Neonatal Research Network is also conducting a blinded, randomized trial of donor milk vs. preterm formula in VLBW infants whose mothers do not provide milk, or provide only small amounts in the first days after birth (clinicaltrials.gov NCT01534481), to assess the impact of donor milk on neurodevelopmental outcomes at age 22–26 months.

These three trials will be the first to investigate the neurodevelopmental outcomes of VLBW infants fed donor milk compared to those fed formula using blinded randomized trial designs in the era of routine milk fortification. A total of over 1100 infants will be included in the three trials combined, allowing for secondary investigation of the growth and neonatal morbidity outcomes associated with donor milk diets.

Conclusions

What do we know about donor milk? Its use is common, and increasing rapidly. Although commonly used to prevent NEC, its ability to do so is not well studied in the era of routine milk fortification. The exclusive human milk diet is associated with lower incidence of NEC compared to diets containing any preterm formula, but it has not been directly compared to diets containing human milk and bovine fortifier. Donor milk diets fortified with bovine or human milk derived fortifier can result in appropriate growth for VLBW infants, if care is taken to provide adequate protein and calorie intake.

What questions remain? Further research is needed in a variety of areas to fully understand the role of donor milk in the nutritional care of VLBW infants. Current ongoing studies will assess the 18–24 month neurodevelopmental outcomes of former VLBW infants fed donor milk compared to those fed preterm formula. Additionally, we need to investigate the effects of donor milk fortified with bovine HMF on incidence of NEC compared to maternal milk. Further studies of the exclusive human milk diet are required to determine if this diet offers any added benefit for protection against NEC over a human milk diet fortified with bovine HMF but lacking formula.

Key Points.

  • Donor milk is commonly used to prevent NEC, but its ability to do so when fortified with bovine derived human milk fortifier is not well studied.

  • The exclusive human milk diet is associated with lower incidence of NEC than diets containing formula, but it has not been compared to a diet containing human milk and bovine fortifier in the absence of preterm formula.

  • Growth can be compromised with use of donor milk, but this can be overcome with careful attention to adequate protein and calorie fortification.

  • Further research is needed before donor milk and the exclusive human milk diet become the gold standard for VLBW nutritional management.

Footnotes

Conflicts of Interest: none

References

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