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Nutrients 2017, 9(3), 302; https://doi.org/10.3390/nu9030302

Article
Lactational Stage of Pasteurized Human Donor Milk Contributes to Nutrient Limitations for Infants
1
The Division of Obstetrics and Gynecology, The University of Cincinnati, Cincinnati, OH, 45220, USA2 OhioHealth Mothers’ Milk Bank of Ohio, Columbus, OH, 43215, USA3 Akron Children’s Hospital, Akron, OH, 44308, USA4 Biomolecular Mass Spectrometry and Proteomics, Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, Padualaan 8, 3584 CD, Utrecht, The Netherlands5 Cincinnati Children’s Hospital, Cincinnati, OH, 45229, USA6 Center for Perinatal Research, The Research Institute at Nationwide Children’s Hospital, Columbus, OH, 43215, USA
2
OhioHealth Mothers’ Milk Bank of Ohio, Columbus, OH, 43215, USA
3
Akron Children’s Hospital, Akron, OH, 44308, USA
4
Biomolecular Mass Spectrometry and Proteomics, Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, Padualaan 8, 3584 CD, Utrecht, The Netherlands
5
Cincinnati Children’s Hospital, Cincinnati, OH, 45229, USA
6
Center for Perinatal Research, The Research Institute at Nationwide Children’s Hospital, Columbus, OH, 43215, USA
*
Author to whom correspondence should be addressed.
Received: 12 January 2017 / Accepted: 14 March 2017 / Published: 18 March 2017

Abstract

:
Background. Mother’s own milk is the first choice for feeding preterm infants, but when not available, pasteurized human donor milk (PDM) is often used. Infants fed PDM have difficulties maintaining appropriate growth velocities. To assess the most basic elements of nutrition, we tested the hypotheses that fatty acid and amino acid composition of PDM is highly variable and standard pooling practices attenuate variability; however, total nutrients may be limiting without supplementation due to late lactational stage of the milk. Methods. A prospective cross-sectional sampling of milk was obtained from five donor milk banks located in Ohio, Michigan, Colorado, Texas-Ft Worth, and California. Milk samples were collected after Institutional Review Board (#07-0035) approval and informed consent. Fatty acid and amino acid contents were measured in milk from individual donors and donor pools (pooled per Human Milk Banking Association of North America guidelines). Statistical comparisons were performed using Kruskal–Wallis, Spearman’s, or Multivariate Regression analyses with center as the fixed factor and lactational stage as co-variate. Results. Ten of the fourteen fatty acids and seventeen of the nineteen amino acids analyzed differed across Banks in the individual milk samples. Pooling minimized these differences in amino acid and fatty acid contents. Concentrations of lysine and docosahexaenoic acid (DHA) were not different across Banks, but concentrations were low compared to recommended levels. Conclusions. Individual donor milk fatty acid and amino acid contents are highly variable. Standardized pooling practice reduces this variability. Lysine and DHA concentrations were consistently low across geographic regions in North America due to lactational stage of the milk, and thus not adequately addressed by pooling. Targeted supplementation is needed to optimize PDM, especially for the preterm or volume restricted infant.
Keywords:
preterm infants; human milk; nutrition; donor milk; DHA; lysine

1. Introduction

The American Academy of Pediatrics (AAP) [1] and the World Health Organization (WHO) [2] recommend mother’s own human milk feeding because of immunological benefits which lessen disease in the high-risk neonate [3,4]. Epidemiological investigations have determined that feeding mother’s own milk decreases the likelihood of necrotizing enterocolitis and late-onset sepsis in preterm infants [4,5,6], resulting in shorter hospital stays and decreased cost of care [7,8]. When mother’s own milk is not available, pasteurized donor milk (PDM) is used as a reasonable alternative for the preterm infant [9,10,11,12,13]. To achieve this practice, mother’s own milk is often augmented with pasteurized donor milk [14]. In fact, recent retrospective work demonstrated cost effectiveness in the intensive care unit that optimized human milk feeding [15]. However, a major gap in knowledge is the nutritional consequences of feeding infants with low volumes of PDM that is often provided by mothers feeding older term infants who consume much greater quantities of milk and receive food sources at 4–6 months [16]. Furthermore, whether from the mother or donor, specific human milk components can be influenced by maternal diet [17]. The reality is that many preterm infants fed even fortified human milk may demonstrate growth, meeting specified weight goals, but 43% are still documented as small for gestational age and are in the lower growth percentiles at discharge—unlike their term counterparts [18,19,20]. Most concerning is that growth failure—particularly linear velocity—is associated with neurodevelopmental morbidities [21,22,23]. In addition, a recent multi-site trial randomly assigning infants to donor milk or preterm formula did not find developmental advantages [24]. Consequently, understanding the nutrient characteristics of pooled human milk is essential to improving fortification strategies.
The composition of human milk changes throughout the course of lactation as the infant matures, and these changes are consistent with infants consuming increasing quantities of milk and ingesting other food sources [25,26]. Consequently, the nutrient composition of most PDM alone is not considered adequate to meet the needs of the preterm or volume-restricted infant due to the late lactational stage of the donor milk, which is nutritionally less concentrated than early milk [27,28], and there is consensus that PDM requires fortification [29,30,31,32]. Furthermore, a recent meta-analysis of term and preterm human milk composition confirmed that human milk is profoundly variable [33]. There are a multitude of factors that may contribute to this variability, including stage of lactation, diurnal cycles, exposure to environmental contaminants such as cigarette smoke, and the treatment of expressed milk (i.e., storage, containers, or tubing delivery) [33,34,35]. While many of these variables are normalized in mother’s own milk fed consistently around the clock and for months, milk obtained for donation is subject to the circumstances at that time. Expert opinion suggests more research is needed in the area of donor milk and fortification [11]. As a starting point to address the most basic elements in donor milk composition, we chose to measure fatty acid and amino acid contents. The purpose of this study was to determine the variability in fatty acid and amino acid composition in individual and pooled PDM using current pooling practices in place at milk banks compliant with Human Milk Banking Association of North America (HMBANA) guidelines, specifically for protein (0.7–1.0 g/100 mL) and caloric contents (67–81 kcal/100 mL) [36].

2. Materials and Methods

2.1. Study Design/Participants

This is a prospective cross-sectional sampling of human milk from five HMBANA member milk banks: California, Colorado, Texas-Ft Worth, Michigan, and Ohio. Prospective enrollees were mothers donating to milk banks between December 2008 and June 2010. Participants were enrolled after Institutional Review Board approval and informed consent of the human milk donors. Milk samples from 15 to 16 individual mothers per Bank were collected from December 2008 through November of 2010. Collected samples were pasteurized, and 1 mL was removed and immediately stored at −80 °C for laboratory measurements. The remaining milk was pooled into five pools per bank to meet the required caloric content and protein concentrations following HMBANA guidelines [37]. The samples were shipped frozen to Nationwide Children’s Hospital, Columbus, OH, USA and stored at −80 °C until analyzed.

2.2. Nutrient Analyses

Fatty acid concentrations were determined by gas chromatography and included capric (C10:0), lauric (C12:0), myristic (C14:0), palmitic (C16:0), palmitoleic (C16:1ω7), steric (C18:0), oleic (C18:1ω9), vaccenic (C18:1ω7), linoleic (18:2ω6), α-linolenic (18:3ω3), γ-linolenic (C18:3ω3), arachidonic (20:4ω6), eicosapentaenoic (20:5ω3), and docosahexaenoic (22:6ω6) acids, as described previously [28]. Amino acid concentrations were measured by high pressure liquid chromatography and included phosphoserine, taurine, phosphoethanolamine, aspartic acid, threonine, serine, glutamic acid, alpha-aminoadipic, proline, glycine, alanine, valine, methionine, isoleucine, leucine, tyrosine, phenylalanine, tryptophan, lysine, histidine, and arginine, as described previously [28]. Each individual donor milk sample and the pooled samples from each milk bank were analyzed independently.

2.3. Statistical Analysis

Statistical comparisons were performed using Kruskal–Wallis for the demographic data (Table 1). Fatty acid and amino acid contents were compared across Centers with multivariate analysis of variance using a linear regression model. Results of the multivariate tests are reported in the figure legends, and coefficient of variation (adjusted R2) and the between-subject differences (p-values) are reported within the graph. All milk composition data were analyzed using lactational stage as a co-variate. Correlations between lactational stage and amino acids or fatty acids were performed by Spearman’s correlation. Statistical significance was set at p < 0.05 for all analyses.

3. Results

3.1. Participants

Women currently donating to HMBANA member banks were included in this study. Prior to donating, the participants received rigorous medical, dietary, and laboratory screening. No women refused participation. There were 16 women enrolled from California and Texas, and 15 women enrolled from each site in Colorado, Michigan, and Ohio. Participant median ages across Centers were 31.5–33.5 years (range 20–42 years) and median lactational stages were 1–5.5 months (range 0–13 months) (Table 1).

3.2. Nutrient Analyses

After caloric content and protein measurements were performed in the individual samples, the milk samples at each individual site were pooled to achieve an overall caloric content of 67–81 kcal per 100 mL and an overall total protein content of 0.7–1 g per 100 mL. Protein-to-calorie ratio with these combinations reaches 3.3 with standard fortification; however, baseline assumptions may change with mother’s lactational stage.
Fatty acid analysis of the individual samples revealed substantial differences across Banks in all fatty acids ranging from C16:0 to C20:5ω3 (Figure 1 and Table S1). Fatty acid analysis of the pooled samples indicated no differences between Centers (Table 2); however, the average docosahexaenoic acid (DHA) concentration in all samples was 7.1 mg/100 mL, which is substantially lower than the 65 mg/100 mL (0.8 mol %) required to match fetal accretion concentrations (based on intakes of 150 mL/kg/day) [38].
The composition of human milk is highly dependent upon lactational stage, which was highly significant in the multivariate regression analyses. Consequently, we analyzed both amino acids and fatty acids for correlation with lactational stage in individual and in pooled samples. In the individual samples, all amino acids were negatively correlated with lactational stage (p ≤ 0.006), but these correlations were no longer significant after the samples were pooled (p ≥ 0.131). Only the fatty acids eicosapentaenoic acid (EPA, 20:5ω3) (p = 0.029) and docosahexaenoic acid (DHA, 22:6ω3) (p = 0.025) were significantly correlated with lactational stage in the individual samples, and these correlations were no longer significant after the samples were pooled (p = 0.819 and p = 0.690, respectively).

4. Discussion

Mother’s own human milk is recommended by the AAP as a unique biologic source of nutrition for both term and preterm infants [1]. When mother’s milk is not available, PDM is a reasonable alternative for the preterm infant; however, PDM does not meet the nutritional needs of infants that are preterm or ingesting low volumes of milk if fed as the sole source of nutrition, and thus requires supplementation [9,10,11,39]. While women donating to human milk banks undergo extensive medical screening, there are many variables that are not controlled. The milk content of fatty acids of an individual woman may vary substantially depending upon her recent diet and/or other demographic factors. Human milk collection, storage, and fortification and biologic components are often described [40], but in light of the recent clinical practice of using donor milk, and publications on variability in human milk, the effectiveness of pooling to adequately address the nutritional differences in individual donor milk needs to be evaluated [33].
Our data indicate that donor milk protein-to-calorie ratio is within the range for nitrogen retention of 2.6–3.6 [41]; however, these studies were done with preterm formula, and other factors such as individual variation, heat treatment, absorption, or micronutrition may be limiting. We did find substantial differences between individuals and Banks in the nutrient contents of milk samples; these differences were largely overcome by pooling. These data demonstrate that infants fed DM that has not been pooled may experience dramatic differences from one day to the next in the composition of the milk they are fed—especially if the milk is from different individual donors. While the effects of nutrient variability are largely normalized in pooled PDM, there remain some deficiencies. This is especially important in the preterm population, because poor somatic growth correlates with low mental developmental scores and development of cerebral palsy [42].
Milk collected at milk banks in the United States is variable and is not a “single point in time”, but likely to have been collected longitudinally over several months. Each milk bank is pasteurizing different volumes of milk with varying mothers in a pool. For example, the OhioHealth Mothers’ Milk Bank typically pasteurizes 1500–2000 ounces per day from 4 to 10 different mothers, each having varying amounts of milk. The number of moms in a pool is dependent upon the available volume and calorie content of each. Current pooling practices utilizing HMBANA guidelines normalize the composition of PDM such that minimal differences in fatty acids or amino acids are observed among pooled samples and no correlations with lactational stage remain [36]. This observation may be explained by the fact that the sample size for pooled samples was one third that of the individual samples, and consequently there was less power to detect differences. Another explanation could be that the statistical differences between Banks Centers in the individual samples are largely driven by the outliers (up to five-fold different) and not actual differences from site to site. Despite the normalized contents in pooled samples, the absolute values vary two-to-three-fold and may still constitute a stressor on the infant. These findings would support customized supplementation for infants fed PDM to optimize nutrients.
DHA is a long chain poly-unsaturated omega-3 fatty acid that is a fundamental lipid in the human cortex and gray matter, and is correlated to developmental scores in preterm infants [43,44]. Furthermore, low concentrations of whole blood DHA have been correlated to late-onset sepsis and chronic lung disease, indicating the importance of DHA in overall infant health [45]. Throughout the last trimester of pregnancy, DHA is accreted at a rate of 50–75 mg/kg/day [46]. Infants born before the last trimester miss this accretion period and current DHA concentrations typically fed in the neonatal intensive care unit (NICU) fall short of the fetal accretion levels. Depending on diet, human milk concentrations of DHA can range from 0.2 to 2 mol % [28,47]. In the current study, measured levels of DHA in the regional PDM samples ranged between 2.22 and 20.20 mg/100 mL (equivalent to 0.08 and 0.67 mol %). This demonstrates that DHA levels in PDM are insufficient to consistently provide intrauterine accretion levels for preterm infants. In a previous study, supplementation of donors with 1 g of DHA per day resulted in human milk DHA concentrations that reached intrauterine accretion levels for the infant (0.8 mol %) [48]. These data suggest that mothers donating milk—especially milk to be used for preterm infants—should be advised to increase their daily intake of DHA, or direct supplementation of the PDM milk may be required.
Typical clinical practice is to increase total protein intake to improve growth without consideration of the concentrations of specific amino acids. Most requirements for amino acids are established for parenteral nutrition, and few address the needs for the enterally-fed infant [49]. Lysine is an essential amino acid used in protein synthesis and along with methionine is a precursor for carnitine synthesis, which is essential for fatty acid metabolism. After total protein, lysine is the amino acid most rate-limiting for growth and is essential to the biological value of food sources [49,50]. Huang et al. has demonstrated that infants require 130 mg/kg/day of lysine for optimal growth [50]. We observed substantial variability across Banks among amino acid contents in individual milk samples, but this variability was no longer evident in pooled milk samples. Several of the individual amino acids were lower than that recommended for parental nutrition (even in the pooled samples), but the relevance for enteral feeding is unknown (tyrosine, 74 mg/k/day; methionine, 49 mg/k/day; threonine, 33 mg/kg/day) [49]. Most importantly, lysine concentrations ranged from 52.1 to 66.3 mg/150 mL (the amount consumed by a healthy preterm per day), which is lower than the recommended 130 mg/kg/day assuming that most preterm infants weigh between 0.5 and 1 kg. Since many essential amino acids have defined functions, supplementing PDM with a specific quality of protein to ensure these amino acids are available may be as important as increasing total protein content.
One limitation of our study is that donated milk was from a wide range of lactational stages and included newborn milk to 12 months post-birth. Our study captured a median of 1 to 5.5 months, which can vary widely in protein and lipid content. A targeted donor process could perhaps improve the amino acid and fatty acid profile. The strength of our study is that it included a cross-sectional prospective examination of many regions in the United States to mimic current clinical practice to evaluate baseline nutrition in the donor milk.

5. Conclusions

The occurrence of failure to thrive currently witnessed in many infants fed PDM is concerning [18], and requires a further examination as to the adequacy of PDM as a sole source of nutrition. Our data indicate that individual PDM is highly variable, and that pooling lessens this variability; however, infants fed pooled PDM may still experience nutritional differences that may affect their overall growth. Our data supports the observed insufficiency of DHA and now lysine contents in most human milk across the United States and the need for supplementation—specifically in the case of the preterm infant. These findings support further studies on personalized maternal and infant supplementation strategies to meet the needs of high-risk infants receiving PDM [51].

Supplementary Materials

The following are available online at https://www.mdpi.com/2072-6643/9/3/302/s1, Table S1: Fatty acid levels in individual samples obtained from Regional Milk Banks. Table S2: Amino acid levels in individual samples obtained from Regional Milk Banks.

Acknowledgments

The authors would like to acknowledge the help and participation of the Human Milk Banking Association of North America and the donating mothers for sharing their milk.

Author Contributions

Christina Valentine and Lynette Rogers conceived and designed the experiments; Georgia Morrow, Amanda Reisinger, and Kelly Dingess performed the experiments; Christina Valentine, Ardythe Morrow and Lynette Rogers analyzed the data and wrote the paper.

Conflicts of Interest

The authors have no conflict of interest. Dr. Valentine is currently an Associate Professor at The University of Cincinnati, Cincinnati Ohio and Medical Director of Mead Johnson Nutrition, Evansville, IN, USA.

References

  1. Gartner, L.M.; Morton, J.; Lawrence, R.A.; Naylor, A.J.; O’Hare, D.; Schanler, R.J.; Eidelman, A.I.; American Academy of Pediatrics Section on Breastfeeding. Breastfeeding and the use of human milk. Pediatrics 2012, 129, e827–e841. [Google Scholar]
  2. World Health Organization; United Nations Children’s Fund. Protecting, Promoting and Supporting Breast-Feeding. The Special Role of Maternity Services; World Health Organization and United Nations Children’s Fund: Geneva, Switzerland, 1989; p. 32. [Google Scholar]
  3. Schanler, R.J.; Lau, C.; Hurst, N.M.; Smith, E.O. Randomized trial of donor human milk versus preterm formula as substitutes for mothers’ own milk in the feeding of extremely premature infants. Pediatrics 2005, 116, 400–406. [Google Scholar] [CrossRef] [PubMed]
  4. Ahrabi, A.F.; Schanler, R.J. Human milk is the only milk for premies in the nicu! Early Hum. Dev. 2013, 89 (Suppl. 2), S51–S53. [Google Scholar] [CrossRef] [PubMed]
  5. Sullivan, S.; Schanler, R.J.; Kim, J.H.; Patel, A.L.; Trawoger, R.; Kiechl-Kohlendorfer, U.; Chan, G.M.; Blanco, C.L.; Abrams, S.; Cotten, C.M.; 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, e561. [Google Scholar] [CrossRef] [PubMed]
  6. Cristofalo, E.A.; Schanler, R.J.; Blanco, C.L.; Sullivan, S.; Trawoeger, R.; Kiechl-Kohlendorfer, U.; Dudell, G.; Rechtman, D.J.; Lee, M.L.; Lucas, A.; et al. Randomized trial of exclusive human milk versus preterm formula diets in extremely premature infants. J. Pediatr. 2013, 163, 1592–1595.e1. [Google Scholar] [CrossRef] [PubMed]
  7. Younge, N.; Yang, Q.; Seed, P.C. Enteral high fat-polyunsaturated fatty acid blend alters the pathogen composition of the intestinal microbiome in premature infants with an enterostomy. J. Pediatr. 2016, 181, 93–101.e6. [Google Scholar] [CrossRef] [PubMed]
  8. Johnson, T.J.; Patel, A.L.; Bigger, H.R.; Engstrom, J.L.; Meier, P.P. Economic benefits and costs of human milk feedings: A strategy to reduce the risk of prematurity-related morbidities in very-low-birth-weight infants. Adv. Nutr. 2014, 5, 207–212. [Google Scholar] [CrossRef] [PubMed]
  9. Brent, N. The risks and benefits of human donor breast milk. Pediatr. Ann. 2013, 42, 84–90. [Google Scholar] [CrossRef] [PubMed]
  10. Arslanoglu, S.; Moro, G.E.; Ziegler, E.E. Preterm infants fed fortified human milk receive less protein than they need. J. Perinatol. 2009, 29, 489–492. [Google Scholar] [CrossRef] [PubMed]
  11. Arslanoglu, S.; Corpeleijn, W.; Moro, G.; Braegger, C.; Campoy, C.; Colomb, V.; Decsi, T.; Domellof, M.; Fewtrell, M.; et al.; Espghan Committee on Nutrition Donor human milk for preterm infants: Current evidence and research directions. J. Pediatr. Gastroenterol. Nutr. 2013, 57, 535–542. [Google Scholar] [CrossRef] [PubMed]
  12. Committee on Nutrition; Section on Breastfeeding; Committee on Fetus and Newborn. Donor human milk for the high-risk infant: Preparation, safety, and usage options in the united states. Pediatrics 2017, 139, e20163440. [Google Scholar]
  13. De Halleux, V.; Pieltain, C.; Senterre, T.; Rigo, J. Use of donor milk in the neonatal intensive care unit. Semin. Fetal Neonatal Med. 2017, 22, 23–29. [Google Scholar] [CrossRef] [PubMed]
  14. Valentine, C.J.; Dumm, M. Pasteurized donor human milk use in the neonatal intensive care unit. NeoReviews 2015, 16, e152–e159. [Google Scholar] [CrossRef]
  15. Assad, M.; Elliott, M.J.; Abraham, J.H. Decreased cost and improved feeding tolerance in vlbw infants fed an exclusive human milk diet. J. Perinatol. 2016, 36, 216–220. [Google Scholar] [CrossRef] [PubMed]
  16. Meier, P.; Patel, A.; Esquerra-Zwiers, A. Donor human milk update: Evidence, mechanisms, and priorities for research and practice. J. Pediatr. 2016, 180, 15–21. [Google Scholar] [CrossRef] [PubMed]
  17. Valentine, C.J.; Wagner, C.L. Nutritional management of the breastfeeding dyad. Pediatr. Clin. N. Am. 2013, 60, 261–274. [Google Scholar] [CrossRef] [PubMed]
  18. Colaizy, T.T.; Carlson, S.; Saftlas, A.F.; Morriss, F.H., Jr. Growth in vlbw infants fed predominantly fortified maternal and donor human milk diets: A retrospective cohort study. BMC Pediatr. 2012, 12, 124. [Google Scholar] [CrossRef] [PubMed]
  19. Schanler, R.J. Post-discharge nutrition for the preterm infant. Acta Paediatr. Suppl. 2005, 94, 68–73. [Google Scholar] [CrossRef] [PubMed]
  20. Schanler, R.J.; Shulman, R.J.; Lau, C.; Smith, E.O.; Heitkemper, M.M. Feeding strategies for premature infants: Randomized trial of gastrointestinal priming and tube-feeding method. Pediatrics 1999, 103, 434–439. [Google Scholar] [CrossRef] [PubMed]
  21. Ehrenkranz, R.A.; Das, A.; Wrage, L.A.; Poindexter, B.B.; Higgins, R.D.; Stoll, B.J.; Oh, W.; The Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Early nutrition mediates the influence of severity of illness on extremely LBW infants. Pediatr. Res. 2011, 69, 522–529. [Google Scholar] [CrossRef] [PubMed]
  22. Ramel, S.E.; Demerath, E.W.; Gray, H.L.; Younge, N.; Boys, C.; Georgieff, M.K. The relationship of poor linear growth velocity with neonatal illness and two-year neurodevelopment in preterm infants. Neonatology 2012, 102, 19–24. [Google Scholar] [CrossRef] [PubMed]
  23. Ramel, S.E.; Georgieff, M.K. Preterm nutrition and the brain. World Rev. Nutr. Diet. 2014, 110, 190–200. [Google Scholar] [PubMed]
  24. O’Connor, D.L.; Gibbins, S.; Kiss, A.; Bando, N.; Brennan-Donnan, J.; Ng, E.; Campbell, D.M.; Vaz, S.; Fusch, C.; Asztalos, E.; et al. Effect of supplemental donor human milk compared with preterm formula on neurodevelopment of very low-birth-weight infants at 18 months: A randomized clinical trial. JAMA 2016, 316, 1897–1905. [Google Scholar] [CrossRef] [PubMed]
  25. Dewey, K.G. What is the optimal age for introduction of complementary foods? Nestle Nutr. Workshop Ser. Pediatr. Progr. 2006, 58, 161–170. [Google Scholar]
  26. Schanler, R.J.; Oh, W. Composition of breast milk obtained from mothers of premature infants as compared to breast milk obtained from donors. J. Pediatr. 1980, 96, 679–681. [Google Scholar] [CrossRef]
  27. Schanler, R.J. Mother’s own milk, donor human milk, and preterm formulas in the feeding of extremely premature infants. J. Pediatr. Gastroenterol. Nutr. 2007, 45 (Suppl. 3), S175–S177. [Google Scholar] [CrossRef] [PubMed]
  28. Valentine, C.J.; Morrow, G.; Fernandez, S.; Gulati, P.; Bartholomew, D.; Long, D.; Welty, S.E.; Morrow, A.L.; Rogers, L.K. Docosahexaenoic acid and amino acid contents in pasteurized donor milk are low for preterm infants. J. Pediatr. 2010, 157, 906–910. [Google Scholar] [CrossRef] [PubMed]
  29. Kuschel, C.A.; Harding, J.E. Protein supplementation of human milk for promoting growth in preterm infants. Cochrane Libr. 2000. [Google Scholar] [CrossRef]
  30. Kuschel, C.A.; Harding, J.E. Multicomponent fortified human milk for promoting growth in preterm infants. Cochrane Libr. 2004. [Google Scholar] [CrossRef]
  31. Kuschel, C.A.; Harding, J.E. Fat supplementation of human milk for promoting growth in preterm infants. Cochrane Libr. 2000. [Google Scholar] [CrossRef]
  32. Kuschel, C.A.; Harding, J.E. Carbohydrate supplementation of human milk to promote growth in preterm infants. Cochrane Libr. 1999. [Google Scholar] [CrossRef]
  33. Gidrewicz, D.A.; Fenton, T.R. A systematic review and meta-analysis of the nutrient content of preterm and term breast milk. BMC Pediatr. 2014, 14, 216. [Google Scholar] [CrossRef] [PubMed]
  34. Chung, M.Y. Factors affecting human milk composition. Pediatr. Neonatol. 2014, 55, 421–422. [Google Scholar] [CrossRef] [PubMed]
  35. Tudehope, D.I. Human milk and the nutritional needs of preterm infants. J. Pediatr. 2013, 162, S17–S25. [Google Scholar] [CrossRef] [PubMed]
  36. Human Milk Banking Association of North America. Guidelines for the Establishment and Operation of a Donor Human Milk Bank; Human Milk Banking Association of North America, Inc.: Raliegh, NC, USA, 2009. [Google Scholar]
  37. Human Milk Banking Association of North America. Best practice for expressing, storing and handling human milk in hospitals, homes, and child care settings, 3rd ed.; Human Milk Banking Association of North America, Inc.: Fort Worth, Texas, USA, 2011. [Google Scholar]
  38. Koletzko, B.; Agostoni, C.; Carlson, S.E.; Clandinin, T.; Hornstra, G.; Neuringer, M.; Uauy, R.; Yamashiro, Y.; Willatts, P. Long chain polyunsaturated fatty acids (LC-PUFA) and perinatal development. Acta Paediatr. 2001, 90, 460–464. [Google Scholar] [CrossRef] [PubMed]
  39. Hay, W.W., Jr.; Brown, L.D.; Denne, S.C. Energy requirements, protein-energy metabolism and balance, and carbohydrates in preterm infants. World Rev. Nutr. Diet. 2014, 110, 64–81. [Google Scholar] [PubMed]
  40. Valentine, C.J.; Morrow, A.L. Chapter 13: Human Milk Feeding of the High Risk NeonateGastroenterology and Nutrition, 2nd ed.; Elsevier: Philidephia, PA, USA, 2012. [Google Scholar]
  41. Fairey, A.K.; Butte, N.F.; Mehta, N.; Thotathuchery, M.; Schanler, R.J.; Heird, W.C. Nutrient accretion in preterm infants fed formula with different protein:Energy ratios. J. Pediatr. Gastroenterol. Nutr. 1997, 25, 37–45. [Google Scholar] [CrossRef] [PubMed]
  42. Ehrenkranz, R.A.; Dusick, A.M.; Vohr, B.R.; Wright, L.L.; Wrage, L.A.; Poole, W.K. Growth in the neonatal intensive care unit influences neurodevelopmental and growth outcomes of extremely low birth weight infants. Pediatrics 2006, 117, 1253–1261. [Google Scholar] [CrossRef] [PubMed]
  43. Makrides, M.; Smithers, L.G.; Gibson, R.A. Role of long-chain polyunsaturated fatty acids in neurodevelopment and growth. Nestle Nutr. Workshop Ser. Pediatr. Progr. 2010, 65, 123–133. [Google Scholar]
  44. McNamara, R.K.; Carlson, S.E. Role of omega-3 fatty acids in brain development and function: Potential implications for the pathogenesis and prevention of psychopathology. Prostaglandins Leukot Essent Fat. Acids 2006, 75, 329–349. [Google Scholar] [CrossRef] [PubMed]
  45. Martin, C.R.; Dasilva, D.A.; Cluette-Brown, J.E.; Dimonda, C.; Hamill, A.; Bhutta, A.Q.; Coronel, E.; Wilschanski, M.; Stephens, A.J.; Driscoll, D.F.; et al. Decreased postnatal docosahexaenoic and arachidonic acid blood levels in premature infants are associated with neonatal morbidities. J. Pediatr. 2011, 159, 743–749, e741–e742. [Google Scholar] [CrossRef] [PubMed]
  46. Innis, S.M. Essential fatty acid transfer and fetal development. Placenta 2005, 26 (Suppl. A), S70–S75. [Google Scholar] [CrossRef] [PubMed]
  47. Brenna, J.T.; Varamini, B.; Jensen, R.G.; Diersen-Schade, D.A.; Boettcher, J.A.; Arterburn, L.M. Docosahexaenoic and arachidonic acid concentrations in human breast milk worldwide. Am. J. Clin. Nutr. 2007, 85, 1457–1464. [Google Scholar] [PubMed]
  48. Valentine, C.J.; Morrow, G.; Pennell, M.; Morrow, A.L.; Hodge, A.; Haban-Bartz, A.; Collins, K.; Rogers, L.K. Randomized controlled trial of docosahexaenoic acid supplementation in midwestern U.S. Human milk donors. Breastfeed. Med. 2013, 8, 86–91. [Google Scholar] [CrossRef] [PubMed]
  49. Chapman, K.P.; Courtney-Martin, G.; Moore, A.M.; Langer, J.C.; Tomlinson, C.; Ball, R.O.; Pencharz, P.B. Lysine requirement in parenterally fed postsurgical human neonates. Am. J. Clin. Nutr. 2010, 91, 958–965. [Google Scholar] [CrossRef] [PubMed]
  50. Huang, L.; Hogewind-Schoonenboom, J.E.; de Groof, F.; Twisk, J.W.; Voortman, G.J.; Dorst, K.; Schierbeek, H.; Boehm, G.; Huang, Y.; Chen, C.; et al. Lysine requirement of the enterally fed term infant in the first month of life. Am. J. Clin. Nutr. 2011, 94, 1496–1503. [Google Scholar] [CrossRef] [PubMed]
  51. Radmacher, P.G.; Adamkin, D.H. Fortification of human milk for preterm infants. Semin. Fetal Neonatal Med. 2016, 22, 30–35. [Google Scholar] [CrossRef] [PubMed]
Figure 1. Fatty acid levels in pasteurized donor milk samples. The individual variability of linoleic acid, linolenic acid, arachidonic acid, and docosahexaenoic acid (DHA) were calculated as mg/kg/day, assuming 150 mL per day and a 1 kg infant. Individuals within each Bank are represented by the small symbols. The boxes represent the median and range for the pooled samples. Data are representative of 15–16 amino acids; analyses in individual milk samples revealed that all but two of the measured amino acids were different across Banks—these were taurine and tryptophan (Figure 2 and Table S2). Once samples were pooled, no statistical differences in amino acid contents across Banks were indicated (Table 3).
Figure 1. Fatty acid levels in pasteurized donor milk samples. The individual variability of linoleic acid, linolenic acid, arachidonic acid, and docosahexaenoic acid (DHA) were calculated as mg/kg/day, assuming 150 mL per day and a 1 kg infant. Individuals within each Bank are represented by the small symbols. The boxes represent the median and range for the pooled samples. Data are representative of 15–16 amino acids; analyses in individual milk samples revealed that all but two of the measured amino acids were different across Banks—these were taurine and tryptophan (Figure 2 and Table S2). Once samples were pooled, no statistical differences in amino acid contents across Banks were indicated (Table 3).
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Figure 2. Amino acid levels in pasteurized donor milk samples. The individual variability of arginine, leucine, methionine, and lysine were calculated as mg/kg/day, assuming 150 mL per day and a 1 kg infant. Individuals within each Bank are represented by the small symbols. The boxes represent the median and range for the pooled samples. Data are representative of 15–16 individual samples and five pooled samples per Bank.
Figure 2. Amino acid levels in pasteurized donor milk samples. The individual variability of arginine, leucine, methionine, and lysine were calculated as mg/kg/day, assuming 150 mL per day and a 1 kg infant. Individuals within each Bank are represented by the small symbols. The boxes represent the median and range for the pooled samples. Data are representative of 15–16 individual samples and five pooled samples per Bank.
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Table 1. Age and lactational stage of donors by milk bank.
Table 1. Age and lactational stage of donors by milk bank.
RegionnAgeLactational Stage (months) *
MedianRangeMeanStd. Dev.MedianRangeMeanStd. Dev.
California1633.524–4132.95.34.01–134.83.4
Colorado1631.525–3831.73.61.0 #1–82.21.9
Michigan1532.026–4133.54.93.01–124.43.8
Ohio1530.020–4231.75.92.0 #0–112.72.8
Texas-Ft Worth1632.025–3731.24.45.52–116.12.7
* Data analyzed by Kruskal–Wallis, p = 0.002, with Dunn’s Multiple Comparison test; # different than Texas. Std. Dev. = standard deviation.
Table 2. Fatty acid levels in pooled samples obtained from Regional Milk Banks.
Table 2. Fatty acid levels in pooled samples obtained from Regional Milk Banks.
mg/100 mLCaliforniaColoradoMichiganOhioTexasr2 (Adjusted)p
mean ± SDmed.mean ± SDmed.mean ± SDmed.mean ± SDmed.mean ± SDmed.
C10:019.0 ± 8.517.626.1 ± 10.823.722.2 ± 7.321.115.3 ± 5.012.228.9 ± 13.631.60.0550.314
C12:0118 ± 31.0117130 ± 60.0108134 ± 28.5125123 ± 35.1116151 ± 45.81340.1510.864
C14:0144 ± 32.5142156 ± 63.8135182 ± 33.6184162 ± 43.6147172 ± 37.81530.1400..835
C16:0553 ± 86.8580614 ± 159577666 ± 1125651570 ± 79.6569677 ± 1796010.0050.456
C16:1ω768.4 ± 14.471.368.9 ± 20.359.376.1 ± 13.875.154.1 ± 8.2158.374.0 ± 26.068.10.0470.331
C18:0184 ± 34.1191193 ± 36.8178214 ± 55.4195193 ± 32.0197239 ± 67.72020.0510.322
C18:1ω9935 ± 189983923 ± 1578801019 ± 17310041008 ± 2169751134 ± 27510330.0190.396
C18:1ω769.5 ± 15.863.381.9 ± 18.072.885.6 ± 20.975.474.1 ± 16.979.289.7 ± 35.781.30.0500.581
C18:2ω6494 ± 90483510 ± 57506593 ± 82584661 ± 171626603 ± 1565620.1270.184
C18:3ω66.64 ± 0.686.496.63 ± 0.626.587.16 ± 0.827.134.42 ± 1.044.556.49 ± 2.455.730.2410.065
C18:3ω344.2 ± 7.4746.844.9 ± 3.2645.348.5 ± 7.4647.352.1 ± 12.851.757.8 ± 21.451.10.0440.338
C20:4ω618.1 ± 4.9718.114.9 ± 2.5013.915.4 ± 1.4115.116.3 ± 4.2315.812.7 ± 1.5612.70.0740.274
C20:5ω33.74 ± 0.473.553.80 ± 0.533.533.15 ± 0.822.942.20 ± 0.442.353.56 ± 2.512.360.0160.403
C22:6ω37.81 ± 1.627.827.29 ± 1.587.466.17 ± 2.005.628.20 ± 3.026.896.09 ± 2.635.480.0660.627
Data were analyzed by multivariate regression with Bank as the fixed variable and lactational stage as a co-variate. Multivariate tests (Pillai’s Trace) revealed statistical differences between Banks (p = 0.000) across the model. Between-subject effects are indicated on the table. Data are representative of five pooled samples perBank; med = median. Data in gray indicates statistical significance at 0.05.
Table 3. Amino acid levels in pooled samples obtained from Regional Milk Banks.
Table 3. Amino acid levels in pooled samples obtained from Regional Milk Banks.
mg/100 mLCaliforniaColoradoMichiganOhioTexasr2 (Adjusted)p
mean ± SDmed.mean ± SDmed.mean ± SDmed.mean ± SDmed.mean ± SDmed.
Phosphoserine97.8 ± 41.480.485.5 ± 28.084.480.2 ± 13.473.382.2 ± 23.181.183.1 ± 17.274.90.0500.333
Taurine8.44 ± 3.638.177.00 ± 4.728.064.89 ± 3.422.595.5 ± 2.69.008.3 ± 4.96.570.0510.332
Aspartic Acid102 ± 24.494.488.2 ± 26.182.683.6 ± 13.079.983.4 ± 8.874.687.5 ± 22.885.90.0970.240
Threonine44.1 ± 13.039.833.4 ± 10.029.335.9 ± 3.2534.835.0 ± 6.5834.034.4 ± 7.9632.50.1300.185
Serine56.9 ± 14.452.746.2 ± 14.144.444.8 ± 8.2141.144.8 ± 5.0238.447.3 ± 14.443.50.1050.227
Glutamic Acid206 ± 43.4185173.8 ± 37.0162171 ± 14.2164179 ± 23.46151164 ± 23.71750.1520.156
Proline101 ± 25.883.578.9 ± 25.266.281.4 ± 5.7179.779.3 ± 20.167.166.6 ± 6.8170.30.2050.096
Glycine25.2 ± 5.923.022.3 ± 5.8520.521.3 ± 2.2621.020.5 ± 3.520.023.4 ± 7.1721.00.0270.385
Alanine47.1 ± 11.444.739.5 ± 13.137.938.1 ± 7.5135.037.4 ± 3.8731.640.3 ± 13.536.40.0660.299
Valine41.1 ± 12.636.930.9 ± 9.4530.732.2 ± 4.3233.027.2 ± 9.9623.425.9 ± 7.5628.10.1400.172
Methionine19.7 ± 5.817.615.1 ± 6.4814.614.2 ± 3.8611.914.4 ± 1.3811.513.8 ± 4.5914.30.2120.090
Isoleucine37.4 ± 12.732.927.0 ± 8.6925.128.8 ± 3.0827.728.4 ± 6.7123.623.8 ± 3.3525.50.1990.102
Leucine99.1 ± 24.088.176.8 ± 21.268.679.4 ± 7.8577.576.5 ± 16.867.872.6 ± 10.871.20.2210.082
Tyrosine55.6 ± 20.952.144.1 ± 19.544.640.4 ± 11.633.144.6 ± 6.632.242.1 ± 17.045.10.0060.469
Phenylalanine38.1 ± 11.434.429.7 ± 8.9026.530.0 ± 3.6529.329.8 ± 5.1025.130.4 ± 9.0329.80.0980.238
Tryptophan188.7 ± 39.6176172 ± 28.6169173 ± 9.39173173 ± 29.8161157 ± 16.41580.0640.624
Lysine66.3 ± 23.262.954.8 ± 16.750.154.0 ± 7.4151.154.5 ± 8.845.352.1 ± 11.453.20.0220.399
Histidine22.4 ± 6.318.718.1 ± 4.7816.453.2 ± 78.218.619.0 ± 4.1416.117.5 ± 3.3117.50.0420.564
Arginine38.7 ± 9.836.031.7 ± 10.329.231.3 ± 7.627.633.8 ± 3.8529.337.3 ± 15.534.10.0380.360
Data were analyzed by multivariate regression with Banks as the fixed variable and lactational stage as a co-variate. Multivariate tests (Pillai’s Trace) revealed no statistical differences between Banks or lactational stage across the model. Between-subject effects are indicated on the table. Data are representative of five pooled samples perBank; med = median. Data in gray indicates statistical significance at 0.05.
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