Infant formulae are the only alternatives to breast milk for infants who are unable to continue breastfeeding through the first year of life. They aim to provide formula-fed infants with the same structural and functional benefits observed in breastfed infants. To achieve this, bioactive nutrients have been added to infant formulae in recent years: long-chain polyunsaturated fatty acids for neurodevelopment; probiotics and prebiotics for local gastrointestinal defence; and nucleotides for promoting the immune response. Changes in protein quantity and quality allow infant formulae to achieve a balance between providing the correct plasma amino acid profile and reducing the protein intake, which could prevent obesity in later life. Hydrolysed proteins may help prevent atopic disorders. Many short-term trials have been published but long-term follow-up data are needed in infants who have been fed the newer infant formulae, to fully understand the role of bioactive nutrients.
WHO Collaborative Study Team on the Role of Breastfeeding on the Prevention of Infant Mortality. Effect of breastfeeding on infant and child mortality due to infectious diseases in less developed countries: A pooled analysis. Lancet2000; 355: 451–455.
2.
JainAConcatoJLeventhalJM: How good is the evidence linking breastfeeding and intelligence?Pediatrics2002; 109: 1044–1053.
3.
ArenzSRuckerlRKoletzkoBvon KriesR: Breastfeeding and childhood obesity – a systematic review. Int J Obes Relat Metab Disord2004; 28: 1247–1256.
4.
SlyPDHoltPG: Breast is best for preventing asthma and allergies – or is it?Lancet2002; 360: 887–888.
5.
HaschkeFVan't HofMA: Euro-Growth references for breastfed boys and girls: Influence of breastfeeding and solids on growth until 36 months of age. Euro-Growth Study Group. J Pediatr Gastroenterol Nutr2000; 31 (suppl 1): S60–S71.
6.
GiovanniniMBanderaliGRadaelliGCarmineVRivaEAgostoniC: Monitoring breastfeeding rates in Italy: National surveys 1995 and 1999. Acta Paediatr2003; 92: 357–363.
7.
GiovanniniMRivaEBanderaliGScaglioniSVeehofSHSalaM: Feeding practices of infants through the first year of life in Italy. Acta Paediatr2004; 93: 492–497.
8.
NommsenLALoveladyCAHeinigMJLonnerdalBDeweyKG: Determinants of energy, protein, lipid, and lactose concentrations in human milk during the first 12 mo of lactation: The DARLING Study. Am J Clin Nutr1991; 53: 457–465.
9.
DeweyKGHeinigMJNommsenLAPeersonJMLonnerdalB: Breastfed infants are leaner than formula-fed infants at 1 yof age: The DARLING study. Am J Clin Nutr1993; 57: 140–145.
10.
EdwardsCAParrettAM: Intestinal flora during the first months of life: New perspectives. Br J Nutr2002; 88 (suppl 1): S11–S18.
11.
BosscherDVan Caillie-BertrandMRobberechtHVan DyckKVan CauwenberghRDeelstraH: In vitro availability of calcium, iron, and zinc from first-age infant formulae and human milk. J Pediatr Gastroenterol Nutr2001; 32: 54–58.
12.
von BergAKoletzkoSGrublAFilipiak-PittroffBWichmannHEBauerCP: The effect of hydrolyzed cow's milk formula for allergy prevention in the first year of life: The German Infant Nutritional Intervention Study, a randomized double-blind trial. J Allergy Clin Immunol2003; 111: 533–540.
13.
JanasLMPiccianoMFHatchTF: Indices of protein metabolism in term infants fed human milk, whey-predominant formula, or cow's milk formula. Pediatrics1985; 75: 775–784.
14.
JarvenpaaALRassinDKRaihaNCGaullGE: Milk protein quantity and quality in the term infant. II. Effects on acidic and neutral amino acids. Pediatrics1982; 70: 221–230.
15.
LucasABoyesSBloomSRAynsley-GreenA: Metabolic and endocrine responses to a milk feed in six-day-old term infants: Differences between breast and cow's milk formula feeding. Acta Paediatr Scand1981; 70: 195–200.
16.
AxelssonIEIvarssonSARaihaNC: Protein intake in early infancy: Effects on plasma amino acid concentrations, insulin metabolism, and growth. Pediatr Res1989; 26: 614–617.
17.
DeweyKGHeinigMJNommsenLAPeersonJMLonnerdalB: Growth of breastfed and formula-fed infants from 0 to 18 months: The DARLING Study. Pediatrics1992; 89: 1035–1041.
18.
HedigerMLOverpeckMDRuanWJTroendleJF: Early infant feeding and growth status of US-born infants and children aged 4-71 mo: Analyses from the third National Health and Nutrition Examination Survey, 1988-1994. Am J Clin Nutr2000; 72: 159–167.
19.
AgostoniC: Breast feeding and childhood obesity. Pediatr Res2000; 47: 3.
20.
The EU Childhood Obesity Programme: EU childhood obesity. Available at: www.childhood-obesity.org (last accessed 21 June 2005).
21.
PiconeTABensonJDMoroGMinoliIFulconisFRassinDK: Growth, serum biochemistries, and amino acids of term infants fed formulas with amino acid and protein concentrations similar to human milk. J Pediatr Gastroenterol Nutr1989; 9: 351–360.
22.
RigoJBoehmGGeorgiGJelinekJNyambugaboKSawatzkiG: An infant formula free of glycomacropeptide prevents hyperthreoninemia in formula-fed preterm infants. J Pediatr Gastroenterol Nutr2001; 32: 127–130.
23.
HeineW: The significance of tryptophan in infant nutrition. Adv Exp Med Biol1999; 467: 705–710.
24.
HeineWRadkeMWutzkeKDPetersEKundtG: Alpha-lactalbumin-enriched low-protein infant formulas: A comparison to breast milk feeding. Acta Paediatr1996; 85: 1024–1028.
25.
SzajewskaHMrukowiczJZ: Probiotics in the treatment and prevention of acute infectious diarrhea in infants and children: A systematic review of published randomized, double-blind, placebo-controlled trials. J Pediatr Gastroenterol Nutr2001; 33 (suppl 2): S17–S25.
26.
Van NielCWFeudtnerCGarrisonMMChristakisDA: Lactobacillus therapy for acute infectious diarrhea in children: A meta-analysisPediatrics2002; 109: 678–684.
27.
KalliomakiMSalminenSArvilommiHKeroPKoskinenPIsolauriE: Probiotics in primary prevention of atopic disease: A randomised placebo-controlled trial. Lancet2001; 357: 1076–1079.
28.
AgostoniCAxelssonIGouletOKoletzkoBMichaelsenKFPuntisJW: Prebiotic oligosaccharides in dietetic products for infants: A commentary by the ESPGHAN Committee on Nutrition. J Pediatr Gastroenterol Nutr2004; 39: 465–473.
29.
MoroGMinoliIMoscaMFanaroSJelinekJStahlB: Dosage-related bifidogenic effects of galacto- and fructooligosaccharides in formula-fed term infants. J Pediatr Gastroenterol Nutr2002; 34: 291–295.
30.
SchmelzleHWirthSSkopnikHRadkeMKnolJBocklerHM: Randomized double-blind study of the nutritional efficacy and bifidogenicity of a new infant formula containing partially hydrolyzed protein, a high beta-palmitic acid and nondigestible oligosaccharides. J Pediatr Gastroenterol Nutr2003; 36: 343–351.
31.
AgostoniCAxelssonIBraeggerCGouletOKoletzkoBMichaelsenKF: Probiotic bacteria in dietetic products for infants: A commentary by the ESPGHAN Committee on Nutrition. J Pediatr Gastroenterol Nutr2004; 38: 365–374.
32.
MullieCYazourhAThibaultHOdouMFSingerEKalachN: Increased poliovirus specific intestinal antibody response coincides with promotion of Bifidobacterium longum-infantis and Bifidobacterium breve in infants: a randomized, double-blind, placebo-controlled trial. Pediatr Res2004; 56: 791–795.
33.
ThibaultHAubert-JacquinCGouletO: Effects of long-term consumption of a fermented infant formula (with Bifidobacterium breve c50 and Streptococcus thermophilus 065) on acute diarrhea in healthy infants. J Pediatr Gastroenterol Nutr2004; 39: 147–152.
34.
AndersonJWJohnstoneBMRemleyDT: Breastfeeding and cognitive development: A meta-analysis. Am J Clin Nutr1999; 70: 525–535.
35.
LarqueEDemmelmairHKoletzkoB: Perinatal supply and metabolism of long-chain polyunsaturated fatty acids: Importance for the early development of the nervous system. Ann N Y Acad Sci2002; 967: 299–310.
36.
InnisSM: The role of dietary n-6 and n-3 fatty acids in the developing brain. Dev Neurosci2000; 22: 474–480.
37.
UdellTGibsonRAMakridesM: The effect of alpha-linolenic acid and linoleic acid on the growth and development of formula-fed infants: A systematic review and meta-analysis of randomized controlled trials. Lipids2005; 40: 1–11.
BirchEEGarfieldSHoffmanDRUauyRBirchDG: A randomized controlled trial of early dietary supply of long-chain polyunsaturated fatty acids and mental development in term infants. Dev Med Child Neurol2000; 42: 174–181.
40.
CarnielliVPWattimenaDJLuijendijkIHBoerlageADegenhartHJSauerPJ: The very low birth weight premature infant is capable of synthesizing arachidonic and docosahexaenoic acids from linoleic and linolenic acids. Pediatr Res1996; 40: 169–174.
41.
SimmerK: Long chain polyunsaturated fatty acid supplementation in infants born at term. Cochrane Database Syst Rev2001; (4): CD000376.
42.
SanGiovanniJPBerkeyCSDwyerJTColditzGA: Dietary essential fatty acids, long-chain polyunsaturated fatty acids, and visual resolution acuity in healthy fullterm infants: A systematic review. Early Hum Dev2000; 57: 165–188.
43.
KoletzkoBAgostoniCCarlsonSEClandininTHornstraGNeuringerM: Long chain polyunsaturated fatty acids (LCPUFA) and perinatal development. Acta Paediatr2001; 90: 460–464.
44.
ForsythJSCarlsonSE: Long-chain polyunsaturated fatty acids in infant nutrition: Effects on infant development. Curr Opin Clin Nutr Metab Care2001; 4: 123–126.
45.
MakridesMGibsonRAUdellTRiedKInternational LCPUFA Investigators: Supplementation of infant formula with long-chain polyunsaturated fatty acids does not influence the growth of term infants. Am J Clin Nutr2005; 81: 1094–1101.
46.
SchlimmeEMartinDMeiselH: Nucleosides and nucleotides: Natural bioactive substances in milk and colostrum. Br J Nutr2000; 84 (suppl 1): S59–S68.
47.
CosgroveM: Perinatal and infant nutrition. Nucleotides. Nutrition1998; 14: 748–751.
48.
SugawaraMSatoNNakanoTIdotaTNakajimaI: Profile of nucleotides and nucleosides of human milk. J Nutr Sci Vitaminol (Tokyo)1995; 41: 409–418.
49.
MerollaR: Gruppo Pediatri Sperimentatori: Evaluation of the effects of a nucleotide-enriched formula on the incidence of diarrhea. Italian multicenter national study (in Italian). Minerva Pediatr2000; 52: 699–711.
50.
PickeringLKGranoffDMEricksonJRMasorMLCordleCTSchallerJP: Modulation of the immune system by human milk and infant formula containing nucleotides. Pediatrics1998; 101: 242–249.
51.
GilA: Modulation of the immune response mediated by dietary nucleotides. Eur J Clin Nutr2002; 56 (suppl 3): S1–S4.
52.
BaumgartnerMBrownCAExlBMSecretinMCvan't HofMHaschkeF: Controlled trials investigating the use of one partially hydrolyzed whey formula for dietary prevention of atopic manifestations until 60 months of age: An overview using meta-analytical techniques. Nutrition Res1998; 18: 1425–1442.
53.
van OdijkJKullIBorresMPBrandtzaegPEdbergUHansonLA: Breastfeeding and allergic disease: A multidisciplinary review of the literature (1966-2001) on the mode of early feeding in infancy and its impact on later atopic manifestations. Allergy2003; 58: 833–843.
54.
BergmannRLDiepgenTLKussOBergmannKEKujatJDudenhausenJW: Breastfeeding duration is a risk factor for atopic eczema. Clin Exp Allergy2002; 32: 205–209.
55.
JarvinenKMLaineSTJarvenpaaALSuomalainenHK: Does low IgA in human milk predispose the infant to development of cow's milk allergy?Pediatr Res2000, 48: 457–462.
56.
American Academy of Pediatrics. Committee on Nutrition: Hypoallergenic infant formula. Pediatrics2000; 106: 346–349.
57.
von BergAKoletzkoSGrublAFilipiak-PittroffBWichmannHEBauerCP: The effect of hydrolyzed cow's milk formula for allergy prevention in the first year of life: The German Infant Nutritional Intervention Study, a randomized double-blind trial. J Allergy Clin Immunol2003; 111: 533–540.
58.
ExlBMDelandUSecretinMCPreyschUWallMShmerlingDH: Improved general health status in an unselected infant population following an allergen-reduced dietary intervention programme: The ZUFF-STUDY-PROGRAMME, part II: Infant growth and health status to age 6 months. ZUg-FrauenFeld. Eur J Nutr2000; 39: 145–156.
59.
HostAHalkenS: Hypoallergenic formulas – when, to whom and how long: After more than 15 years we know the right indication. Allergy2004; 59 (suppl 78): 45–52.
60.
GiovanniniMAgostoniCFiocchiABelluRTrojanSRivaE: Antigen-reduced infant formulas versus human milk: Growth and metabolic parameters in the first 6 months of life. J Am Coll Nutr1994; 13: 357–363.
61.
AgostoniCTrojanSBelluRRivaEGiovanniniM: Neurodevelopmental quotient of healthy term infants at 4 months and feeding practice: The role of long-chain polyunsaturated fatty acids. Pediatr Res1995; 38: 262–266.
62.
AgostoniCRivaETrojanSBelluRGiovanniniM: Docosahexaenoic acid status and developmental quotient of healthy term infants. Lancet1995; 346: 638.
63.
AgostoniCRivaEBelluRTrojanSLuottiDGiovanniniM: Effects of diet on the lipid and fatty acid status of full-term infants at 4 months. J Am Coll Nutr1994; 13: 658–664.
64.
AgostoniCTrojanSBelluRRivaEBruzzeseMGGiovanniniM: Developmental quotient at 24 months and fatty acid composition of diet in early infancy: A follow up study. Arch Dis Child1997; 76: 421–424.
65.
CarnielliVPVerlatoGPederziniFLuijendijkIBoerlageAPedrottiD: Intestinal absorption of long-chain polyunsaturated fatty acids in preterm infants fed breast milk or formula. Am J Clin Nutr1998; 67: 97–103.
66.
FaldellaGGovoniMAlessandroniRMarchianiESalvioliGPBiagiPL: Visual evoked potentials and dietary long chain polyunsaturated fatty acids in preterm infants. Arch Dis Child Fetal Neonatal Ed1996; 75: F108–F112.
67.
MariniANegrettiFBoehmGLi DestriMClerici-BagozziDMoscaF: Pro- and prebiotics administration in preterm infants: Colonization and influence on faecal flora. Acta Paediatr Suppl2003; 91: 80–81.
68.
MoroGEMoscaFMinielloVFanaroSJelinekJStahlB: Effects of a new mixture of prebiotics on faecal flora and stools in term infants. Acta Paediatr Suppl2003; 91: 77–79.
69.
BoehmGLidestriMCasettaPJelinekJNegrettiFStahlB: Supplementation of a bovine milk formula with an oligosaccharide mixture increases counts of faecal bifidobacteria in preterm infants. Arch Dis Child Fetal Neonatal Ed2002; 86: F178–F181.
70.
DaniCBiadaioliRBertiniGMartelliERubaltelliFF: Probiotics feeding in prevention of urinary tract infection, bacterial sepsis and necrotizing enterocolitis in preterm infants. A prospective double-blind study. Biol Neonate2002; 82: 103–108.
71.
MakridesMNeumannMSimmerKPaterJGibsonR: Are long-chain polyunsaturated fatty acids essential nutrients in infancy?Lancet1995; 345: 1463–1468.
