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Open Access 01-12-2022 | Nutrition | Consensus Paper

Infant formulas with synthetic oligosaccharides and respective marketing practices: Position Statement of the German Society for Child and Adolescent Medicine e.V. (DGKJ), Commission for Nutrition

Authors: Christoph Bührer, Regina Ensenauer, Frank Jochum, Hermann Kalhoff, Berthold Koletzko, Burkhard Lawrenz, Walter Mihatsch, Carsten Posovszky, Silvia Rudloff

Published in: Molecular and Cellular Pediatrics | Issue 1/2022

Abstract

Human milk contains more than 150 different oligosaccharides, which together are among to the quantitatively predominant solid components of breast milk. The oligosaccharide content and composition of human milk show large inter-individual differences. Oligosaccharide content is mostly influenced by genetic variants of the mother’s secretor status. Oligosaccharides in human milk are utilized by infants’ intestinal bacteria, affecting bacterial composition and metabolic activity. Maternal secretor status, and respective differing fucosylated oligosaccharide content, has been associated both with reduced and increased risk of infection in different populations of breastfed infants, possibly due to environmental conditions and the infant’s genotype. There are no safety concerns regarding the addition of previously approved oligosaccharides to infant formula; however, no firm conclusions can be drawn about clinically relevant benefits either. Therefore, infant formulas with synthetic oligosaccharide additives are currently not preferentially recommended over infant formulas without such additives. We consider the use of terms such as “human milk oligosaccharides” and corresponding abbreviations such as “HMO” in any advertising of infant formula to be an inappropriate idealization of infant formula. Manufacturers should stop this practice, and such marketing practices should be prevented by responsible supervisory authorities. Pediatricians should inform families that infant formulas supplemented with synthetic oligosaccharides do not resemble the complex oligosaccharide composition of human milk.

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Bode L (2012) Human milk oligosaccharides: every baby needs a sugar mama. Glycobiology 22:1147–1162. https://doi.org/10.1093/glycob/cws074CrossRefPubMedPubMedCentral

Rudloff S, Kunz C (2015) Oligosaccharide in Frauenmilch. Monatsschr Kinderheilkd 163:790–795. https://doi.org/10.1007/s00112-014-3292-5CrossRef

Asadpoor M, Peeters C, Henricks PAJ et al. (2020) Anti-pathogenic functions of non-digestible oligosaccharides in vitro. Nutrients 12.https://doi.org/10.3390/nu12061789

Urashima T, Hirabayashi J, Sato S et al (2018) Human milk oligosaccharides as essential tools for basic and application studies on galectins. Trends Glycosci Glycotechnol 30:SE51–SE65. https://doi.org/10.4052/tigg.1734.1SECrossRef

Prieto PA (2012) Profiles of human milk oligosaccharides and production of some human milk oligosaccharides in transgenic animals. Adv Nutr 3:456S-S464. https://doi.org/10.3945/an.111.001529CrossRefPubMedPubMedCentral

Lefebvre G, Shevlyakova M, Charpagne A et al (2020) Time of lactation and maternal fucosyltransferase genetic polymorphisms determine the variability in human milk oligosaccharides. Front Nutr 7:574459. https://doi.org/10.3389/fnut.2020.574459CrossRefPubMedPubMedCentral

Kunz C, Meyer C, Collado MC et al (2017) Influence of gestational age, secretor, and Lewis blood group status on the oligosaccharide content of human milk. J Pediatr Gastroenterol Nutr 64:789–798. https://doi.org/10.1097/MPG.0000000000001402CrossRefPubMed

McGuire MK, Meehan CL, McGuire MA et al (2017) What’s normal? Oligosaccharide concentrations and profiles in milk produced by healthy women vary geographically. Am J Clin Nutr 105:1086–1100. https://doi.org/10.3945/ajcn.116.139980CrossRefPubMedPubMedCentral

Nordgren J, Sharma S, Bucardo F et al (2014) Both Lewis and secretor status mediate susceptibility to rotavirus infections in a rotavirus genotype-dependent manner. Clin Infect Dis 59:1567–1573. https://doi.org/10.1093/cid/ciu633CrossRefPubMedPubMedCentral

10.

Payne DC, Currier RL, Staat MA et al (2015) Epidemiologic association between FUT2 secretor status and severe rotavirus gastroenteritis in children in the United States. JAMA Pediatr 169:1040–1045. https://doi.org/10.1001/jamapediatrics.2015.2002CrossRefPubMedPubMedCentral

11.

Ramani S, Stewart CJ, Laucirica DR et al (2018) Human milk oligosaccharides, milk microbiome and infant gut microbiome modulate neonatal rotavirus infection. Nat Commun 9:5010. https://doi.org/10.1038/s41467-018-07476-4CrossRefPubMedPubMedCentral

12.

Andreas NJ, Al-Khalidi A, Jaiteh M et al (2016) Role of human milk oligosaccharides in group B Streptococcus colonisation. Clin Transl Immunology 5. https://doi.org/10.1038/cti.2016.43CrossRefPubMedPubMedCentral

13.

Morrow AL, Ruiz-Palacios GM, Altaye M et al (2004) Human milk oligosaccharides are associated with protection against diarrhea in breast-fed infants. J Pediatr 145:297–303. https://doi.org/10.1016/j.jpeds.2004.04.054CrossRefPubMed

14.

Stepans MBF, Wilhelm SL, Hertzog M et al (2006) Early consumption of human milk oligosaccharides is inversely related to subsequent risk of respiratory and enteric disease in infants. Breastfeed Med 1:207–215. https://doi.org/10.1089/bfm.2006.1.207CrossRefPubMed

15.

Colston JM, Francois R, Pisanic N et al (2019) Effects of child and maternal histo-blood group antigen status on symptomatic and asymptomatic enteric infections in early childhood. J Infect Dis 220:151–162. https://doi.org/10.1093/infdis/jiz072CrossRefPubMedPubMedCentral

16.

Muthumuni D, Miliku K, Wade KH et al (2021) Enhanced protection against diarrhea among breastfed infants of nonsecretor mothers. Pediatr Infect Dis J 40:260–263. https://doi.org/10.1097/INF.0000000000003014CrossRefPubMed

17.

Larsson MW, Lind MV, Laursen RP et al (2019) Human milk oligosaccharide composition is associated with excessive weight gain during exclusive breastfeeding-an explorative study. Front Pediatr 7:297. https://doi.org/10.3389/fped.2019.00297CrossRefPubMedPubMedCentral

18.

Sakanaka M, Gotoh A, Yoshida K et al. (2019) Varied pathways of infant gut-associated bifidobacterium to assimilate human milk oligosaccharides: prevalence of the gene set and its correlation with bifidobacteria-rich microbiota formation. Nutrients 12https://doi.org/10.3390/nu12010071

19.

Davis EC, Dinsmoor AM, Wang M et al (2020) Microbiome composition in pediatric populations from birth to adolescence: impact of diet and prebiotic and probiotic interventions. Dig Dis Sci 65:706–722. https://doi.org/10.1007/s10620-020-06092-xCrossRefPubMedPubMedCentral

20.

Ackerman DL, Doster RS, Weitkamp J-H et al (2017) Human milk oligosaccharides exhibit antimicrobial and antibiofilm properties against group B Streptococcus. ACS Infect Dis 3:595–605. https://doi.org/10.1021/acsinfecdis.7b00064CrossRefPubMedPubMedCentral

21.

Cheng L, Akkerman R, Kong C et al. (2020) More than sugar in the milk: human milk oligosaccharides as essential bioactive molecules in breast milk and current insight in beneficial effects. Crit Rev Food Sci Nutr:1–17. https://doi.org/10.1080/10408398.2020.1754756.

22.

Autran CA, Kellman BP, Kim JH et al (2018) Human milk oligosaccharide composition predicts risk of necrotising enterocolitis in preterm infants. Gut 67:1064–1070. https://doi.org/10.1136/gutjnl-2016-312819CrossRefPubMed

23.

Wejryd E, Martí M, Marchini G et al. (2018) Low diversity of human milk oligosaccharides is associated with necrotising enterocolitis in extremely low birth weight infants. Nutrients 10https://doi.org/10.3390/nu10101556

24.

van Niekerk E, Autran CA, Nel DG et al (2014) Human milk oligosaccharides differ between HIV-infected and HIV-uninfected mothers and are related to necrotizing enterocolitis incidence in their preterm very-low-birth-weight infants. J Nutr 144:1227–1233. https://doi.org/10.3945/jn.113.187799CrossRefPubMed

25.

Masi AC, Embleton ND, Lamb CA et al (2020) Human milk oligosaccharide DSLNT and gut microbiome in preterm infants predicts necrotising enterocolitis. Gut. https://doi.org/10.1136/gutjnl-2020-322771CrossRefPubMed

26.

Quigley M, Embleton ND, McGuire W (2019) Formula versus donor breast milk for feeding preterm or low birth weight infants. Cochrane Database Syst Rev 7:CD002971. https://doi.org/10.1002/14651858.CD002971.pub5CrossRefPubMed

27.

Goehring KC, Marriage BJ, Oliver JS et al (2016) Similar to those who are breastfed, infants fed a formula containing 2'-fucosyllactose have lower inflammatory cytokines in a randomized controlled trial. J Nutr 146:2559–2566. https://doi.org/10.3945/jn.116.236919CrossRefPubMed

28.

Vazquez E, Barranco A, Ramirez M et al (2016) Dietary 2'-fucosyllactose enhances operant conditioning and long-term potentiation via gut-brain communication through the vagus nerve in rodents. PLoS ONE 11:e0166070. https://doi.org/10.1371/journal.pone.0166070CrossRefPubMedPubMedCentral

29.

Fleming SA, Mudd AT, Hauser J et al (2020) Human and bovine milk oligosaccharides elicit improved recognition memory concurrent with alterations in regional brain volumes and hippocampal mRNA expression. Front Neurosci 14:770. https://doi.org/10.3389/fnins.2020.00770CrossRefPubMedPubMedCentral

30.

European-Commission (2016). Commission Delegated Regulation (EU) 2016/127 of 25 September 2015 supplementing Regulation (EU) No 609/2013 of the European Parliament and of the Council as regards the specific compositional and information requirements for infant formula and follow-on formula and as regards requirements on information relating to infant and young child feeding. Off J Eur Union: L 25/21/1–29.

31.

van Leeuwen SS, Te Poele EM, Chatziioannou AC et al (2020) Goat milk oligosaccharides: their diversity, quantity, and functional properties in comparison to human milk oligosaccharides. J Agric Food Chem 68:13469–13485. https://doi.org/10.1021/acs.jafc.0c03766CrossRefPubMedPubMedCentral

32.

Barile D, Rastall RA (2013) Human milk and related oligosaccharides as prebiotics. Curr Opin Biotechnol 24:214–219. https://doi.org/10.1016/j.copbio.2013.01.008CrossRefPubMed

33.

Austin S, Bénet T (2018) Quantitative determination of non-lactose milk oligosaccharides. Anal Chim Acta 1010:86–96. https://doi.org/10.1016/j.aca.2017.12.036CrossRefPubMed

34.

Eussen SRBM, Mank M, Kottler R et al. (2021) Presence and levels of galactosyllactoses and other oligosaccharides in human milk and their variation during lactation and according to maternal phenotype. Nutrients. 13https://doi.org/10.3390/nu13072324

35.

EFSA-Panel-on-Dietetic-Products (2014) Scientific opinion on the essential composition of infant and follow-on formulae. EFS2 12:3760. https://doi.org/10.2903/j.efsa.2014.3760CrossRef

36.

Skórka A, Pieścik-Lech M, Kołodziej M et al (2018) Infant formulae supplemented with prebiotics: are they better than unsupplemented formulae? An updated systematic review. Br J Nutr 119:810–825. https://doi.org/10.1017/S0007114518000120CrossRefPubMed

37.

EFSA (2011) Scientific opinion on the substantiation of health claims related to fructo-oligosaccharides (FOS) and decreasing potentially pathogenic gastro-intestinal microorganisms (ID 781) pursuant to Article 13(1) of Regulation (EC) No 1924/2006. EFSA J 9:2222CrossRef

38.

EFSA (2011) Scientific opinion on the substantiation of health claims related to galacto oligosaccharides (GOS) and reduction of gastro intestinal discomfort (ID 763) and decreasing potentially pathogenic microorganisms (ID 765) pursuant to Article 13(1) of Regulation (EC) No 1924/2006. EFSA J 9:2060CrossRef

39.

Bode L, Contractor N, Barile D et al (2016) Overcoming the limited availability of human milk oligosaccharides: challenges and opportunities for research and application. Nutr Rev 74:635–644. https://doi.org/10.1093/nutrit/nuw025CrossRefPubMedPubMedCentral

40.

Sprenger GA, Baumgärtner F, Albermann C (2017) Production of human milk oligosaccharides by enzymatic and whole-cell microbial biotransformations. J Biotechnol 258:79–91. https://doi.org/10.1016/j.jbiotec.2017.07.030CrossRefPubMed

41.

EFSA (2015) Safety of 2′-O-fucosyllactose as a novel food ingredient pursuant to Regulation (EC) No 258/97. EFS2 13. https://doi.org/10.2903/j.efsa.2015.4184

42.

EFSA (2015) Safety of lacto-N-neotetraose as a novel food ingredient pursuant to Regulation (EC) No 258/97. EFS2 13. https://doi.org/10.2903/j.efsa.2015.4183

43.

Turck D, Castenmiller J, de Henauw S et al (2019) Safety of 2'-fucosyllactose/difucosyllactose mixture as a novel food pursuant to Regulation (EU) 2015/2283. EFS2. 17:e05717. https://doi.org/10.2903/j.efsa.2019.5717CrossRef

44.

Turck D, Castenmiller J, de Henauw S et al (2019) Safety of lacto-N-tetraose (LNT) as a novel food pursuant to Regulation (EU) 2015/2283. EFS2 17:e05907. https://doi.org/10.2903/j.efsa.2019.5907CrossRef

45.

Turck D, Castenmiller J, Henauw S de et al. (2020) Safety of 3’-sialyllactose (3’-SL) sodium salt as a novel food pursuant to Regulation (EU) 2015/2283. EFS2 18. https://doi.org/10.2903/j.efsa.2020.6098

46.

Turck D, Castenmiller J, Henauw S de et al. (2020) Safety of 6′-sialyllactose (6′-SL) sodium salt as a novel food pursuant to Regulation (EU) 2015/2283. EFS2 18. https://doi.org/10.2903/j.efsa.2020.6097

47.

Marriage BJ, Buck RH, Goehring KC et al (2015) Infants fed a lower calorie formula with 2'FL show growth and 2'FL uptake like breast-fed infants. J Pediatr Gastroenterol Nutr 61:649–658. https://doi.org/10.1097/MPG.0000000000000889CrossRefPubMedPubMedCentral

48.

Puccio G, Alliet P, Cajozzo C et al (2017) Effects of infant formula with human milk oligosaccharides on growth and morbidity: a randomized multicenter trial. J Pediatr Gastroenterol Nutr 64:624–631. https://doi.org/10.1097/MPG.0000000000001520CrossRefPubMedPubMedCentral

49.

Berger B, Porta N, Foata F et al. (2020) Linking human milk oligosaccharides, infant fecal community types, and later risk to require antibiotics. mBio 11. https://doi.org/10.1128/mBio.03196-19

50.

Storm HM, Shepard J, Czerkies LM et al (2019) 2'-Fucosyllactose is well tolerated in a 100% whey, partially hydrolyzed infant formula with Bifidobacterium lactis: a randomized controlled trial. Glob Pediatr Health 6:2333794X19833995. https://doi.org/10.1177/2333794X19833995CrossRefPubMedPubMedCentral

51.

Bode L (2019) Human milk oligosaccharides: next-generation functions and questions. Nestle Nutr Inst Workshop Ser 90:191–201. https://doi.org/10.1159/000490306CrossRefPubMed

52.

Kommission E (1999) RICHTLINIE 1999/21/EG DER KOMMISSION vom 25. März 1999 über diätetische Lebensmittel für besondere medizinische Zwecke. Amtsblatt der Europäischen Kommission L 091:29–36

53.

Bundesministerium der Justiz und für Verbraucherschutz (2017) Verordnung über diätetische Lebensmittel (Diätverordnung). https://www.gesetze-im-internet.de/di_tv/BJNR004150963.html.

Title: Infant formulas with synthetic oligosaccharides and respective marketing practices: Position Statement of the German Society for Child and Adolescent Medicine e.V. (DGKJ), Commission for Nutrition
Authors: Christoph Bührer
Regina Ensenauer
Frank Jochum
Hermann Kalhoff
Berthold Koletzko
Burkhard Lawrenz
Walter Mihatsch
Carsten Posovszky
Silvia Rudloff
Publication date: 01-12-2022
Publisher: Springer International Publishing
Keyword: Nutrition
Published in: Molecular and Cellular Pediatrics / Issue 1/2022
Electronic ISSN: 2194-7791
DOI: https://doi.org/10.1186/s40348-022-00146-y

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Infant formulas with synthetic oligosaccharides and respective marketing practices: Position Statement of the German Society for Child and Adolescent Medicine e.V. (DGKJ), Commission for Nutrition

Abstract

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Abstract

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