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  • Print publication year: 2010
  • Online publication date: February 2010

Chapter 18 - Nutrition, environment, and epigenetics

from Section 3 - Specialized requirements


This chapter presents a brief history of formula feeding to provide a historical perspective into the evolution of modern infant formulas. It discusses the types and composition of modern infant formulas available, and the regulation of infant formula composition and marketing. The chapter discusses the growth of formula-fed versus breast-fed infants, and the appropriate introduction of complementary foods for both breast-fed and formula-fed infants. The most commonly used infant formulas are standard cow's milk-based formulas. Infant formula is regulated as a food intended solely for infants. It simulates human milk or is suitable as a complete or partial substitute for human milk. Current recommendations for infants with a strong family history of food allergy are that they should be breast-fed for as long as possible and should not receive complementary foods until 6 months of age. The parents' approach to child feeding is central to the child's early feeding experience.


1. BirdA, Perceptions of epigenetics. Nature (2007), 447:396–8.
2. BirdA, DNA methylation patterns and epigenetic memory. Genes Dev (2002), 16:6–21.
3. Bourc'hisD and BestorTH, Meiotic catastrophe and retrotransposon reactivation in male germ cells lacking Dnmt3L. Nature (2004), 431:96–9.
4. EhrlichM, DNA methylation in cancer: too much, but also too little. Oncogene (2002), 12; 21:5400–13.
5. SaxonovS, BergP, and BrutlagDL, A genome-wide analysis of CpG dinucleotides in the human genome distinguishes two distinct classes of promoters. Proc Natl Acad Sci U S A (2006), 103:1412–7.
6. WeberM, HellmannI, StadlerMB, RamosL, PaaboS, RebhanM, et al., Distribution, silencing potential and evolutionary impact of promoter DNA methylation in the human genome. Nat Genet (2007), 39:457–66.
7. MorisonIM, RamsayJP, and SpencerHG, A census of mammalian imprinting. Trends Genet (2005), 21:457–65.
8. RazinA and RiggsAD, DNA methylation and gene function. Science (1980), 210:604–10.
9. HattoriN, NishinoK, KoYG, HattoriN, OhganeJ, and TanakaS, et al., Epigenetic control of mouse Oct-4 gene expression in embryonic stem cells and trophoblast stem cells. J Biol Chem (2004), 279:17063–9.
10. Deb-RinkerP, LyD, JezierskiA, SikorskaM, and WalkerPR, SequentialDNAmethylation of the Nanog and Oct-4 upstream regions in human NT2 cells during neuronal differentiation. J Biol Chem (2005), 280:6257–60.
11. FarthingCR, FiczG, NgRK, ChanC-F, AndrewsS, DeanW, et al., Global mapping of DNA methylation in mouse promoters reveals epigenetic reprogamming of pluripotency genes. PLoS Genet (2008), 4:e1000116.
12. BernsteinBE, MeissnerA, and LanderES, The mammalian epigenome. Cell (2007), 128:669–81.
13. PtashneM, On the use of the word “epigenetic.” Curr Biol (2007), 17:R233–6.
14. TurnerBM, Defining an epigenetic code. Nat Cell Biol (2007), 9:2–6.
15. StanchevaI, Caught in conspiracy: cooperation between DNA methylation and histone H3K9 methylation in the establishment and maintenance of heterochromatin. Biochem Cell Biol (2005), 83:385–95.
16. MorganHD, SantosF, GreenK, DeanW, and ReikW, Epigenetic reprogramming in mammals. Hum Mol Genet (2005), 14(Spec No 1):R47–58.
17. YoungLE and BeaujeanN, DNA methylation in the preimplantation embryo: the differing stories of the mouse and sheep. Anim Reprod Sci (2004), 82–83:61–78.
18. SinclairKD, AllegrucciC, SinghR, GardnerDS, SebastianS, BisphamJ, et al., DNA methylation, insulin resistance, and blood pressure in offspring determined by maternal periconceptional B vitamin and methionine status. Proc Natl Acad Sci U S A (2007), 104:19351–6.
19. WaterlandRA and MichelsKB, Epigenetic epidemiology of the developmental origins hypothesis. Annu Rev Nutr (2007), 27:363–88.
20. WolffGL, KodellRL, MooreSR, and CooneyCA, Maternal epigenetics and methyl supplements affect agouti gene expression in Avy/a mice. FASEB J (1998), 12:949–57.
21. WaterlandRA and JirtleRL, Transposable elements: targets for early nutritional effects on epigenetic gene regulation. Mol Cell Biol (2003), 23:5293–300.
22. MorganHD, SutherlandHG, MartinDI, and WhitelawE, Epigenetic inheritance at the agouti locus in the mouse. Nat Genet (1999), 23:314–18.
23. TakimotoH, MitoN, UmegakiK, IshiwakiA, KusamaK, AbeS, et al., Relationship between dietary folate intakes, maternal plasma total homocysteine and B-vitamins during pregnancy and fetal growth in Japan. Eur J Nutr (2007), 46:300–6.
24. DolinoyDC, WeidmanJR, WaterlandRA, and JirtleRL, Maternal genistein alters coat color and protects Avy mouse offspring from obesity by modifying the fetal epigenome. Environ Health Perspect (2006), 114:567–72.
25. RakyanVK, ChongS, ChampME, CuthbertPC, MorganHD, LuuKV, et al., Transgenerational inheritance of epigenetic states at the murine Axin(Fu) allele occurs after maternal and paternal transmission. Proc Natl Acad Sci U S A (2003), 100:2538–43.
26. WaterlandRA, DolinoyDC, LinJR, SmithCA, ShiX, and TahilianiKG, Maternal methyl supplements increase offspring DNA methylation at Axin Fused. Genesis (2006), 44:401–6.
27. OatesNA, van VlietJ, DuffyDL, KroesHY, MartinNG, BoomsmaDI, et al., Increased DNA methylation at the AXIN1 gene in a monozygotic twin from a pair discordant for a caudal duplication anomaly. Am J Hum Genet (2006), 79:155–62.
28. DunlevyLP, BurrenKA, ChittyLS, CoppAJ, and GreeneND, Excess methionine suppresses the methylation cycle and inhibits neural tube closure in mouse embryos. FEBS Lett (2006), 580:2803–7.
29. ErnestS, CarterM, ShaoH, HosackA, LernerN, ColmenaresC, et al., Parallel changes in metabolite and expression profiles in crooked-tail mutant and folate-reduced wild-type mice. Hum Mol Genet (2006), 15:3387–93.
30. Paoloni-GiacobinoA, Epigenetics in reproductive medicine. Pediatr Res (2007), 61(5 Pt 2):51R–7R.
31. MilesHL, HofmanPL, PeekJ, HarrisM, WilsonD, RobinsonEM, et al., In vitro fertilization improves childhood growth and metabolism. J Clin Endocrinol Metab (2007), 92:3441–5.
32. ReikW, RomerI, BartonSC, SuraniMA, HowlettSK, and KloseJ, Adult phenotype in the mouse can be affected by epigenetic events in the early embryo. Development (1993), 119:933–42.
33. RiveraRM, SteinP, WeaverJR, MagerJ, SchultzRM, Bartolomei MS, Manipulations of mouse embryos prior to implantation result in aberrant expression of imprinted genes on day 9.5 of development. Hum Mol Genet (2008), 17:1–14.
34. FauqueP, JouannetP, LesaffreC, RipocheMA, DandoloL, VaimanD, et al., Assisted reproductive technology affects developmental kinetics, H19 imprinting control region methylation and H19 gene expression in individual mouse embryos. BMC Dev Biol (2007), 7:116.
35. WatkinsAJ, PlattD, PapenbrockT, WilkinsA, EckertJJ, KwongWY, et al., Mouse embryo culture induces changes in postnatal phenotype including raised systolic blood pressure. Proc Natl Acad Sci U S A (2007), 104:5449–54.
36. KhoslaS, DeanW, BrownD, ReikW, FeilR, Culture of preimplantation mouse embryos affects fetal development and the expression of imprinted genes. Biol Reprod (2001), 64: 918–26.
37. DoornbosME, MaasSM, McDonnellJ, VermeidenJP, HennekamRC, Infertility, assisted reproduction technologies and imprinting disturbances: a Dutch study. Hum Reprod (2007), 22:2476–80.
38. YoungLE, FernandesK, McEvoyTG, ButterwithSC, GutierrezCG, and CarolanC, et al., Epigenetic change in IGF2R is associated with fetal overgrowth after sheep embryo culture. Nat Genet (2001), 27:153–4.
39. YoungLE, SinclairKD, and WilmutI, Large offspring syndrome in cattle and sheep. Rev Reprod (1998), 3:155–63.
40. MikkelsenTS, KuM, JaffeDB, IssacB, LiebermanE, GiannoukosG, et al., Genome-wide maps of chromatin state in pluripotent and lineage-committed cells. Nature (2007), 448:553–60.
41. SakamotoH, KogoY, OhganeJ, HattoriN, YagiS, TanakaS, et al., Sequential changes in genome-wide DNA methylation status during adipocyte differentiation. Biochem Biophys Res Commun (2008), 366:360–6.
42. SimmonsRA, Role of metabolic programming in the pathogenesis of beta-cell failure in postnatal life. Rev Endocr Metab Disord (2007), 8:95–104.
43. SimmonsRA, Developmental origins of beta-cell failure in type 2 diabetes: the role of epigenetic mechanisms. Pediatr Res (2007), 61(5 Pt 2):64R–7R.
44. StirzakerC, SongJZ, DavidsonB, and ClarkSJ, Transcriptional gene silencing promotes DNA hypermethylation through a sequential change in chromatin modifications in cancer cells. Cancer Res (2004) 64:3871–7.
45. LiB, CareyM, and WorkmanJL, The role of chromatin during transcription. Cell (2007), 128:707–19.
46. LillycropKA, PhillipsES, TorrensC, HansonMA, JacksonAA, BurdgeGC, Feeding pregnant rats a protein-restricted diet persistently alters the methylation of specific cytosines in the hepatic PPARalpha promoter of the offspring. Br J Nutr (2008), 11:1–5.
47. YajnikCS, DeshpandeSS, JacksonAA, RefsumH, RaoS, FisherDJ, et al., Vitamin B and folate concentrations during pregnancy and insulin resistance in the offspring: the Pune Maternal Nutrition Study. Diabetologia (2008), 51:29–38.
48. McMillenIC and RobinsonJS, Developmental origins of the metabolic syndrome: prediction, plasticity, and programming. Physiol Rev (2005), 85:571–633.
49. BogdarinaI, WelhamS, KingPJ, BurnsSP, and ClarkAJ, Epigenetic modification of the renin-angiotensin system in the fetal programming of hypertension. Circ Res (2007), 100:520–6.
50. WelhamSJ, WadeA, and WoolfAS, Protein restriction in pregnancy is associated with increased apoptosis of mesenchymal cells at the start of rat metanephrogenesis. Kidney Int (2002), 61:1231–42.
51. KellerG, ZimmerG, MallG, RitzE, and AmannK, Nephron number in patients with primary hypertension. N Engl J Med (2003), 348:101–8.
52. WelhamSJ, RileyPR, WadeA, HubankM, WoolfAS, Maternal diet programs embryonic kidney gene expression. Physiol Genomics (2005), 22:48–56.
53. WeaverIC, CervoniN, ChampagneFA, D'AlessioAC, SharmaS, SecklJR, et al., Epigenetic programming by maternal behavior. Nat Neurosci (2004), 7:847–54.
54. ChampagneFA, WeaverIC, DiorioJ, DymovS, SzyfM, MeaneyMJ, Maternal care associated with methylation of the estrogen receptor-alpha1b promoter and estrogen receptor-alpha expression in the medial preoptic area of female offspring. Endocrinology (2006), 147:2909–15.
55. OngKK, AhmedML, EmmettPM, PreeceMA, DungerDB, Association between postnatal catch-up growth and obesity in childhood: prospective cohort study. BMJ (2000), 320:967–71.
56. LiuL, van GroenT, KadishI, TollefsbolTO, DNA methylation impacts on learning and memory in aging. Neurobiol Aging (2007), 10.
57. SekiY, HayashiK, ItohK, MizugakiM, SaitouM, and MatsuiY, Extensive and orderly reprogramming of genome-wide chromatin modifications associated with specification and early development of germ cells in mice. Dev Biol (2005), 278:440–58.
58. ConstânciaM, HembergerM, HughesJ, DeanW, Ferguson-SmithA, FundeleR, et al., Placental-specific IGF-II is a major modulator of placental and fetal growth. Nature (2002), 417:945–8.
59. ReikW, ConstanciaM, FowdenA, AndersonN, DeanW, Ferguson-SmithA, et al., Regulation of supply and demand for maternal nutrients in mammals by imprinted genes. J Physiol (2003), 547(Pt 1):35–44.
60. AngioliniE, FowdenA, CoanP, SandoviciI, SmithP, DeanW, et al. Regulation of placental efficiency for nutrient transport by imprinted genes. Placenta (2006), 27(Suppl A):S98–102.
61. ConstanciaM, AngioliniE, SandoviciI, SmithP, SmithR, KelseyG, et al., Adaptation of nutrient supply to fetal demand in the mouse involves interaction between the Igf2 gene and placental transporter systems. Proc Natl Acad Sci U S A (2005) 102:19219–24.
62. BertoliniM, MoyerAL, MasonJB, BatchelderCA, HoffertKA, BertoliniLR, et al., Evidence of increased substrate availability to in vitro-derived bovine foetuses and association with accelerated conceptus growth. Reproduction (2004), 128:341–54.
63. MartinezY and MartinezR, Clinical features in the Wiedemann-Beckwith syndrome. Clin Genet (1996), 50:272–4.
64. KaatiG, BygrenLO, PembreyM, and SjöströmM, Transgenerational response to nutrition, early life circumstances and longevity. Eur J Hum Genet (2007), 15:784–90.
65. SkinnerMK, What is an epigenetic transgenerational phenotype? F3 or F2. Reprod Toxicol (2008), 25:2–6.
66. LaneN, DeanW, ErhardtS, HajkovaP, SuraniA, WalterJ, et al., Resistance of IAPs to methylation reprogramming may provide a mechanism for epigenetic inheritance in the mouse. Genesis (2003 Feb), 35:88–93.
67. SteinAD and LumeyLH, The relationship between maternal and offspring birth weights after maternal prenatal famine exposure: the Dutch Famine Birth Cohort Study. Hum Biol (2000), 72:641–54.
68. RoemerI, ReikW, DeanW, and KloseJ, Epigenetic inheritance in the mouse. Curr Biol (1997), 7:277–80.
69. BlewittME, VickaryousNK, PaldiA, KosekiH, and WhitelawE, Dynamic reprogramming of DNA methylation at an epigenetically sensitive allele in mice. PLoS Genet (2006), 2:e49.
70. CropleyJE, SuterCM, BeckmanKB, and MartinDI, Germ-line epigenetic modification of the murine A vy allele by nutritional supplementation. Proc Natl Acad Sci U S A (2006), 103:17308–12.
71. AnwayMD, CuppAS, UzumcuM, and SkinnerMK, Epigenetic transgenerational actions of endocrine disruptors and male fertility. Science (2005), 308:1466–9.