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. 2018 Jun 19;6(6):CD000341.
doi: 10.1002/14651858.CD000341.pub2.

Fat supplementation of human milk for promoting growth in preterm infants

Emma A Amissah  1 , Julie Brown, Jane E Harding
Affiliations

Fat supplementation of human milk for promoting growth in preterm infants

Emma A Amissah et al. Cochrane Database Syst Rev. .

Update in

Abstract

Background: As preterm infants do not experience the nutrient accretion and rapid growth phase of the third trimester of pregnancy, they are vulnerable to postnatal nutritional deficits, including of fat. Consequently, they require higher fat intakes compared to their full term counterparts to achieve adequate growth and development. Human milk fat provides the major energy needs of the preterm infant and also contributes to several metabolic and physiological functions. Although human milk has many benefits for this population, its fat content is highly variable and may be inadequate for their optimum growth and development. This is a 2018 update of a Cochrane Review last published in 2000.

Objectives: To determine whether supplementation of human milk with fat compared with unsupplemented human milk fed to preterm infants improves growth, body composition, cardio-metabolic, and neurodevelopmental outcomes without significant adverse effects.

Search methods: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2018, Issue 1), MEDLINE via PubMed (1966 to 08 February 2018), Embase (1980 to 08 February 2018), and CINAHL (1982 to 08 February 2018). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials.

Selection criteria: Published and unpublished randomised controlled trials were eligible if they used random or quasi-random methods to allocate preterm infants fed human milk in hospital to supplementation or no supplementation with additional fat.

Data collection and analysis: No new randomised controlled trials matching the selection criteria were found but we extracted data from the previously included trial due to changes in review outcomes from when the protocol was first published. Two reviewers independently abstracted data, assessed trial quality, and the quality of evidence at the outcome level using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. We planned to perform meta-analyses using risk ratio (RR) for dichotomous data and mean difference (MD) for continuous data, with their respective 95% confidence intervals (CIs). We planned to use a fixed-effect model and to explore potential causes of heterogeneity via sensitivity analyses.

Main results: One randomised trial involving 14 preterm infants was included. There was no evidence of a clear difference between the fat-supplemented and unsupplemented groups in in-hospital rates of growth in weight (MD 0.6 g/kg/day, 95% CI -2.4 to 3.6; 1 RCT, n = 14 infants, very low-quality evidence), length (MD 0.1 cm/week, 95% CI -0.08 to 0.3; 1 RCT, n = 14 infants, very low-quality evidence) and head circumference (MD 0.2 cm/week, 95% CI -0.07 to 0.4; 1 RCT n = 14 infants, very low-quality evidence). There was no clear evidence that fat supplementation increased the risk of feeding intolerance (RR 3.0, 95% CI 0.1 to 64.3; 1 RCT, n = 16 infants, very low-quality evidence). No data were available regarding the effects of fat supplementation on long-term growth, body mass index, body composition, neurodevelopmental, or cardio-metabolic outcomes.

Authors' conclusions: The one included trial suggests no evidence of an effect of fat supplementation of human milk on short-term growth and feeding intolerance in preterm infants. However, the very low-quality evidence, small sample size, few events, and low precision diminishes our confidence that these results reflect the true effect of fat supplementation of human milk in preterm infants, and no long-term outcomes were reported. Further high-quality research should evaluate the effect on short and long-term growth, neurodevelopmental and cardio-metabolic outcomes in the context of the development of multicomponent fortifiers. Optimal dosage, adverse effects, and delivery practices should also be evaluated.

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Conflict of interest statement

Emma Amissah: None known.

Julie Brown: None known.

Jane Harding: None known.

Figures

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1
81, Study flow diagram: review update
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Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
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Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
See this image and copyright information in PMC

Update of

References

References to studies included in this review

Polberger 1989 {published data only}
    1. Polberger SK, Axelsson IA, Räihä NC. Growth of very low birth weight infants on varying amounts of human milk protein. Pediatric Research 1989;25(4):414‐9. [DOI: 10.1203/00006450-198904000-00022; PUBMED: 2726319] - DOI - PubMed
    1. Polberger SK, Axelsson IE, Räihä NC. Amino acid concentrations in plasma and urine in very low birth weight infants fed protein‐unenriched or human milk protein‐enriched human milk. Pediatrics 1990;86(6):909‐15. [PUBMED: 2251029] - PubMed
    1. Polberger SK, Fex GA, Axelsson IE, Räihä NC. Eleven plasma proteins as indicators of protein nutritional status in very low birth weight infants. Pediatrics 1990;86(6):916‐21. [PUBMED: 2251030] - PubMed

References to studies excluded from this review

Fewtrell 2011 {published data only}
    1. Fewtrell MS. Does early nutrition program later bone health in preterm infants?. American Journal of Clinical Nutrition 2011;94(6 Suppl):1870S‐3S. [DOI: 10.3945/ajcn.110.000844; PUBMED: 21543543] - DOI - PubMed
Lauterbach 2015 {published data only}
    1. Lauterbach R. A supplementation of DHA and AA to human milk‐fed VLBW infants has no significant cognitive improvement or measurable neuroanatomical effects when evaluated at 8 years of age. Evidence‐based Medicine 2015;20(5):177. [DOI: 10.1136/ebmed-2015-110242; PUBMED: 26282164] - DOI - PubMed
Makrides 1997 {published data only}
    1. Makrides M, Neumann M, Gibson R. Breast milk docosahexaenoic acid (DHA) and Infant outcomes: a randomised clinical trial. Journal of Pediatrics and Child Health 1997;33(4):A2.
Rönnholm 1984 {published data only}
    1. Rönnholm KA, Perheentupa J, Siimes MA. Supplementation with human milk protein improves growth of small premature infants fed human milk. Pediatrics 1986;77(5):649‐53. [PUBMED: 3703632] - PubMed
    1. Rönnholm KA, Simell O, Siimes MA. Human milk protein and medium‐chain triglyceride oil supplementation of human milk: plasma amino acids in very low‐birth‐weight infants. Pediatrics 1984;74(5):792‐9. [PUBMED: 6387613] - PubMed

Additional references

Arslanoglu 2013
    1. Arslanoglu S, Corpeleijn W, Moro G, Braegger C, Campoy C, Colomb V, et al. ESPGHAN Committee on Nutrition. Donor human milk for preterm infants: current evidence and research directions. Journal of Pediatric Gastroenterology and Nutrition 2013;57(4):535‐42. [DOI: 10.1097/MPG.0b013e3182a3af0a; PUBMED: 24084373] - DOI - PubMed
Berseth 2014
    1. Berseth CL, Harris CL, Wampler JL, Hoffman DR, Diersen‐Schade DA. Liquid human milk fortifier significantly improves docosahexaenoic and arachidonic acid status in preterm infants. Prostaglandins, Leukotrienes, and Essential Fatty Acids 2014;91(3):97‐103. [DOI: 10.1016/j.plefa.2014.03.002; PUBMED: 24863250] - DOI - PubMed
Bhatia 2016
    1. Bhatia J. Human milk for preterm infants and fortification. Nestle Nutrition Workshop Series 2016;86:109‐19. [DOI: 10.1159/000442730; PUBMED: 27347886] - DOI - PubMed
Brown 2016
    1. Brown JV, Embleton ND, Harding JE, McGuire W. Multi‐nutrient fortification of human milk for preterm infants. Cochrane Database of Systematic Reviews 2016, Issue 5. [DOI: 10.1002/14651858.CD000343.pub3] - DOI - PubMed
Chang 2012
    1. Chang YC, Chen CH, Lin MC. The macro‐nutrients in human milk change after storage in various containers. Pediatrics and Neonatology 2012;53(3):205‐9. - PubMed
Choi 2016
    1. Choi A, Fusch G, Rochow N, Fusch C. Target fortification of breast milk: predicting the final osmolality of the feeds. PLOS One 2016;11(2):e0148941. [DOI: 10.1371/journal.pone.0148941; PUBMED: 26863130] - DOI - PMC - PubMed
Delplanque 2015
    1. Delplanque B, Gibson R, Koletzko B, Lapillonne A, Strandvik B. Lipid quality in infant nutrition: current knowledge and future opportunities. Journal of Pediatric Gastroenterology and Nutrition 2015;61(1):8‐17. [DOI: 10.1097/MPG.0000000000000818; PUBMED: 25883056] - DOI - PMC - PubMed
Deshpande 2011
    1. Deshpande G, Simmer K. Lipids for parenteral nutrition in neonates. Current Opinion in Clinical Nutrition and Metabolic Care 2011;14(2):145‐50. [DOI: 10.1097/MCO.0b013e3283434562; PUBMED: 21192257] - DOI - PubMed
Fenton 2013
    1. Fenton TR, Nasser R, Eliasziw M, Kim JH, Bilan D, Sauve R. Validating the weight gain of preterm infants between the reference growth curve of the fetus and the term infant. BMC Pediatrics 2013;13:92. [DOI: 10.1186/1471-2431-13-92; PUBMED: 23758808] - DOI - PMC - PubMed
Geddes 2013
    1. Geddes D, Hartmann P, Jones E. Preterm birth: strategies for establishing adequate milk production and successful lactation. Seminars in Fetal & Neonatal Medicine 2013;18(3):155‐9. [DOI: 10.1016/j.siny.2013.04.001; PUBMED: 23623976] - DOI - PubMed
Georgieff 2005
    1. Georgieff MK, Innis SM. Controversial nutrients that potentially affect preterm neurodevelopment: essential fatty acids and iron. Pediatric Research 2005;57(5 Pt 2):99R‐103R. [DOI: 10.1203/01.PDR.0000160542.69840.0F; PUBMED: 15817493] - DOI - PubMed
GRADEpro GDT [Computer program]
    1. McMaster University (developed by Evidence Prime). GRADEpro GDT. Version accessed 01 September 2017. Hamilton (ON): McMaster University (developed by Evidence Prime), 2015.
Hadley 2016
    1. Hadley KB, Ryan AS, Forsyth S, Gautier S, Salem N. The essentiality of arachidonic acid in infant development. Nutrients 2016;8(4):216. [DOI: 10.3390/nu8040216; PUBMED: 27077882] - DOI - PMC - PubMed
Higgins 2017
    1. Higgins JP, Green S, (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.2.0 (updated June 2017). The Cochrane Collaboration, 2017. Available from training.cochrane.org/handbook.
Howles 1999
    1. Howles PN, Stemmerman GN, Fenoglio‐Preiser CM, Hui DY. Carboxyl ester lipase activity in milk prevents fat‐derived intestinal injury in neonatal mice. American Journal of Physiology 1999;277(3 Pt 1):G653‐61. [PUBMED: 10484391] - PMC - PubMed
Innis 2003
    1. Innis SM. Perinatal biochemistry and physiology of long‐chain polyunsaturated fatty acids. Journal of Pediatrics 2003;143(4 Suppl):S1‐8. [PUBMED: 14597908] - PubMed
Innis 2014
    1. Innis SM. Impact of maternal diet on human milk composition and neurological development of infants. American Journal of Clinical Nutrition 2014;99(3):734S‐41S. [DOI: 10.3945/ajcn.113.072595; PUBMED: 24500153] - DOI - PubMed
Isaacs 2009
    1. Isaacs EB, Morley R, Lucas A. Early diet and general cognitive outcome at adolescence in children born at or below 30 weeks gestation. Journal of Pediatrics 2009;155(2):229‐34. [DOI: 10.1016/j.jpeds.2009.02.030; PUBMED: 19446846] - DOI - PubMed
Kenner 2014
    1. Kenner C, Lott J, editor(s). Comprehensive Neonatal Nursing Care. 5th Edition. New York (NY): Springer Publishing Company, 2014.
Koletzko 2014
    1. Koletzko B, Poindexter B, Uauy R, editor(s). Defining the Nutritional Needs of Preterm Infants: Scientific Basis and Practical Guidelines. Vol. 110, Karger Publishers, 2014.
Kuschel 2000
    1. Kuschel CA, Harding JE. Protein supplementation of human milk for promoting growth in preterm infants. Cochrane Database of Systematic Reviews 2000, Issue 2. [DOI: 10.1002/14651858.CD000433] - DOI - PubMed
Lapillonne 2014
    1. Lapillonne A. Enteral and parenteral lipid requirements of preterm infants. World Review of Nutrition and Dietetics 2014;110:82‐98. [DOI: 10.1159/000358460; PUBMED: 24751623] - DOI - PubMed
Li 2013
    1. Li J, Wang Y, Tang L, Villiers WJ, Cohen D, Woodward J, et al. Dietary medium‐chain triglycerides promote oral allergic sensitization and orally induced anaphylaxis to peanut protein in mice. Journal of Allergy and Clinical Immunology 2013;131(2):442‐50. [DOI: 10.1016/j.jaci.2012.10.011; PUBMED: 23182172] - DOI - PMC - PubMed
Lindquist 2010
    1. Lindquist S, Hernell O. Lipid digestion and absorption in early life: an update. Current Opinion in Clinical Nutrition and Metabolic Care 2010;13(3):314‐20. [DOI: 10.1097/MCO.0b013e328337bbf0; PUBMED: 20179589] - DOI - PubMed
Longo 2016
    1. Longo N, Frigeni M, Pasquali M. Carnitine transport and fatty acid oxidation. Biochimica et Biophysica Acta 2016;1863(10):2422‐35. [DOI: 10.1016/j.bbamcr.2016.01.023; PUBMED: 26828774] - DOI - PMC - PubMed
Martin 2015
    1. Martin CR. Lipids and fatty acids in the preterm infant, part 2: clinical considerations. NeoReviews 2015;16(3):e169‐80.
Moon 2016
    1. Moon K, Rao SC, Schulzke SM, Patole SK, Simmer K. Longchain polyunsaturated fatty acid supplementation in preterm infants. Cochrane Database of Systematic Reviews 2016, Issue 12. [DOI: 10.1002/14651858.CD000375.pub5] - DOI - PMC - PubMed
Patel 2016
    1. Patel P, Bhatia J. Human milk: the preferred first food for premature infants. Journal of Human Nutrition & Food Science 2016;4(5):1098.
Peila 2016
    1. Peila C, Moro GE, Bertino E, Cavallarin L, Giribaldi M, Giuliani F, et al. The effect of holder pasteurization on nutrients and biologically‐active components in donor human milk: a review. Nutrients 2016;8(8):E477. [DOI: 10.3390/nu8080477; PUBMED: 27490567] - DOI - PMC - PubMed
Pereira‐da‐Silva 2008
    1. Pereira‐da‐Silva L, Dias MP, Virella D, Moreira AC, Serelha M. Osmolality of preterm formulas supplemented with non‐protein energy supplements. European Journal of Clinical Nutrition 2008;62(2):274‐8. [DOI: 10.1038/sj.ejcn.1602736; PUBMED: 17375112] - DOI - PubMed
Review Manager 2014 [Computer program]
    1. Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager 5 (RevMan 5). Version 5.3. Copenhagen: Nordic Cochrane Centre, The Cochrane Collaboration, 2014.
Robinson 2017
    1. Robinson DT, Martin CR. Fatty acid requirements for the preterm infant. Seminars in Fetal & Neonatal Medicine 2017;22(1):8‐14. [DOI: 10.1016/j.siny.2016.08.009; PUBMED: 27599697] - DOI - PubMed
Schünemann 2013
    1. Schünemann H, Brożek J, Guyatt G, Oxman A, editor(s), GRADE Working Group. Handbook for grading the quality of evidence and the strength of recommendations using the GRADE approach (updated October 2013). gdt.guidelinedevelopment.org/app/handbook/handbook.html (accessed prior to 22 May 2018).
Section on Breastfeeding 2012
    1. Section on Breastfeeding. Breastfeeding and the use of human milk. Pediatrics 2012;129(3):e827‐41. [DOI: 10.1542/peds.2011-3552; PUBMED: 22371471] - DOI - PubMed
Stocks 1985
    1. Stocks RJ, Davies DP, Allen F, Sewell D. Loss of breast milk nutrients during tube feeding. Archives of Disease in Childhood 1985;60(2):164‐6. [PUBMED: 3919654] - PMC - PubMed
Su 2014
    1. Su B. Optimizing nutrition in preterm infants. Pediatrics and Neonatology 2014;55(1):5‐13. [DOI: 10.1016/j.pedneo.2013.07.003; PUBMED: 24050843] - DOI - PubMed
Underwood 2013
    1. Underwood MA. Human milk for the premature infant. Pediatric Clinics of North America 2013;60(1):189‐207. [DOI: 10.1016/j.pcl.2012.09.008; PUBMED: 23178065] - DOI - PMC - PubMed
Vieira 2011
    1. Vieira AA, Soares FV, Pimenta HP, Abranches AD, Moreira ME. Analysis of the influence of pasteurization, freezing/thawing, and offer processes on human milk's macronutrient concentrations. Early Human Development 2011;87(8):577‐80. [DOI: 10.1016/j.earlhumdev.2011.04.016; PUBMED: 21592688] - DOI - PubMed
WHO 1995
    1. World Health Organization. Physical status: The use of and interpretation of anthropometry: report of a WHO expert committee. www.who.int/nutrition/publications/growth_physical_status/en/ (accessed prior to 22 March 2018).
Yang 2013
    1. Yang Q, Ayers K, Chen Y, Helderman J, Welch CD, O'Shea TM. Early enteral fat supplement and fish oil increases fat absorption in the premature infant with an enterostomy. Journal of Pediatrics 2013;163(2):429‐34. [DOI: 10.1016/j.jpeds.2013.01.056; NCT01306838; PUBMED: 23453547] - DOI - PubMed
Younge 2017
    1. Younge N, Yang Q, Seed PC. Enteral high fat‐polyunsaturated fatty acid blend alters the pathogen composition of the intestinal microbiome in premature infants with an enterostomy. Journal of Pediatrics 2017;181:93‐101.e6. [DOI: 10.1016/j.jpeds.2016.10.053; NCT01306838; PUBMED: 27856001] - DOI - PMC - PubMed

References to other published versions of this review

Kuschel 1999
    1. Kuschel CA, Harding JE. Fat supplementation of human milk for promoting growth in preterm infants. Cochrane Database of Systematic Reviews 1999, Issue 3. [DOI: 10.1002/14651858.CD000341] - DOI - PubMed
Kuschel 2000
    1. Kuschel CA, Harding JE. Fat supplementation of human milk for promoting growth in preterm infants. Cochrane Database of Systematic Reviews 2000, Issue 1. [DOI: 10.1002/14651858.CD000341] - DOI - PubMed

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