laspeciali$e$patologia:$ unamalaa,$un$lae$speciale$ speciali e patologia... · casein-,...

La# speciali e patologia: una mala#a, un la3e speciale

Claudio Maffeis

UOC Diabetologia, Nutrizione Clinica e Obesità in Età Pediatrica

Università degli Studi di Verona

Formule: quali

•  Formule per la rialimentazione: senza la3osio •  Forumule e coliche: pre-‐, pro-‐, sinbioJci •  Formule per i sintomi: anJrigurgito •  Formule per la prevenzione (ipoallergeniche-‐HA) •  IdrolisaJ per la terapia (allergie) •  La# di altre specie

LATTE UMANO

PROTEINE

Proteine tot.: 0,9 g/100 ml (0,7 biodisponibili ) Caseine: 0,25 g/100ml (β prevalente, k ) Sieroproteine: 0,65 g/100ml

0,26 α la3oalbumina β la3oglobulina assente la3oferrina 0,17 lisozima 0,05 Ig 0,11 sieroalbumina 0,005

NucleoJdi: 5-‐8 mg/100ml

Le formule non possono ricopiare la composizione biochimica del la3e materno

Quale “riferimento” usare?

Riferimento: non la composizione biochimica del latte materno ma la crescita ed i marker biochimici

e funzionali dell’allattato al seno

à

FORMULE STANDARD (formule starJng, formule di inizio, formule 1)

casein-, whey-predominant & modified whey infant formula

A casein-‐ or a whey-‐predominant formula containing 2.5 g protein/100 kcal, provides an excess of most of the essenJal amino acids found in breast milk. Nevertheless, tryptophan and the condiJonally essenJal amino acid cysteine are limiJng factors for further reducing the protein quanJty in cow's milk formula. Term infants fed formulas with reduced protein content (1.8 g/100 kcal) and various whey/casein raJos had normal plasma cystein levels but depressed levels of tryptophan when compared with those fed human milk. The most recent proposal to increase the tryptophan level in the formula, maintaining the reduced protein content, is the modified sweet whey formula (whey/casein: 70/30), which has a closer essenJal amino acid profile to that of human milk.

LATTOSIO Favorisce uJlizzo proteine e AA liberi Incrementa assorbimento H2O, Na e Ca Contribuisce riduzione pH lume intesJnale

in piccole quanJtà in forma non idrolizzata nel lume, trasformato in la3ato, acetato e buJrrato

flora intesJnale bifidogena

Intolleranza al la3osio

Rara so3o i 2-‐3 anni di età Nei casi di intolleranza congenita, sintomi molto precoci a seguire l’introduzione di la3e Prematuri (<34 w deficit di la3asi) Secondaria a infezione intesJnale Più comune dopo i 3 aa (prevalenza ca. 15%) con esordio sintomatologia in adolescenza-‐età adulta Sintomi: distensione addominale, flatulenza, dolori addominali crampiformi, diarrea.

Dietary treatment of colic caused by excess gas in infants: biochemical evidence

Infante D, et al. World J Gastroenterol 2011;17(16):2104-‐8

Breasreeding may improve nocturnal sleep and reduce infanJle colic: PotenJal role of breast milk melatonin

Engler AC et al. Eur J Pediatr (2012) 171:729–732

Take Home Message

Le formule a rido3o contenuto di la3osio sono in grado di ridurre la produzione di gas nell’intesJno dovuta alla fermentazione del la3osio.

Physiological and Bifidogenic Effects of PrebioJc Supplements in Infant Formulae

Veereman-‐Wauters, G, et al. JPGN 2011;52:763-‐71

Orati Synergy1 (50 oligofructose:50 FOS), GOS:FOS (90:10) 0.8 g/dL

ProbioJc, zinc and lactose-‐free formula in children with rotavirus diarrhea: are they effecJve?

Dalzic Z, et al. Pediatr Int 2011;53:677-‐82

SynbioJcs, probioJcs or prebioJcs in infant formula for full term infants: a systemaJc review

Mugambi NM et al. NutriJon Journal 2012, 11:81

Synbio-cs (N = 475), failed to significantly increase growth, increased stool frequency, had no impact on stool consistency, colic, spi#ng up/regurgitaJon, crying, restlessness or vomiJng. Probio-cs in formula (N = 933) failed to have any significant effect on growth, stool frequency or consistency, did not lower the incidence of diarrhoea, colic, spi#ng up / regurgitaJon, crying, restlessness or vomiJng. Prebio-cs in formula (N = 1563) did increase weight gain but had no impact on length or head circumference gain. PrebioJcs increased stool frequency but had no impact on stool consistency, the incidence of colic, spi#ng up / regurgitaJon, crying, restlessness or vomiJng, the volume of formula tolerated, infecJons and gastrointesJnal microflora. Conclusions There is not enough evidence to state that supplementa5on of term infant formula with synbio5cs, probio5cs or prebio5cs does result in improved growth or clinical outcomes in term infants. There is no data available to establish if synbioJcs are superior to probioJcs or prebioJcs.

NutriJonal Supplements and Other Complementary Medicines for InfanJle Colic: A SystemaJc Review

Perry R, et al. Pediatrics 2011;127:720–733

RESULTS: 15 RCTs met the inclusion criteria. 13 were placebo controlled. 8 were of good methodological quality. 11 indicated a significant result in favor of complementary and alterna-ve medicines. However, none of these randomized clinical trials were without flaws. Independent replica5ons were missing for most modali5es. CONCLUSIONS: Some encouraging results exist for fennel extract, mixed herbal tea *, and sugar soluJons, although it has to be stressed that all trials have major limitaJons. Thus, the no5on that any form of complementary and alterna5ve medicine is effec5ve for infan5le colic currently is not supported from the evidence from the included randomized clinical trials. Addi5onal replica5ons are needed before firm conclusions can be drawn.

* = chamomile, vervain, licorice, fennel, and balm-‐mint, or fennel, lemon balm, and German chamomile

The Effect of Thickened-‐Feed IntervenJons on GER in Infants: SystemaJc Review and Meta-‐analysis of

Randomized, Controlled Trials

Pediatrics 2008;122:e1268–e1277

Infants without regurgitaJon (n)



Pediatrics 2008;122:e1268–e1277

Episodes of regurgitaJon per day (n)



Pediatrics 2008;122:e1268–e1277

Episodes of vomiJng per day (n)

Weight gain (g/day)



Pediatrics 2008;122:e1268–e1277

DuraJon of the longest reflux episode

Reflux index (percentage of Jme pH<4): ns Number of reflux episodes lasJng >5 min: ns

Vandenplas Y Pediatrics 2009;123;e549

Thickened infant formula does what it has to do: decrease regurgitaJon

“….GER is healthy infants does not need treatment. GER is a normal physiologic process that occurs several Jmes per day in healthy infants, children, and adults. Approximately 50% of normal 3-‐ to 4-‐month-‐old infants regurgitate at least once per day . Up to 20% of caregivers in the United States seek medical help for this normal behavior.

Thickening agents such as rice cereal added to formula do not decrease esophageal acid exposure but do decrease the frequency of overt regurgitaJon. A combined impedance-‐pH-‐metry study showed a decreased reflux esophageal height with thickened formula, as well as a decrease in the overt frequency of regurgita5on, but no change in the frequency of reflux episodes.

A moderate increase of the reflux index (percent Jme of acid reflux) was reported with rice, an intermediate decrease with carob bean gum, and a clear significant beneficial effect of cornstarch….”

An eliminaJon diet in formula-‐fed infants usually starts with an extensively hydrolyzed infant formula (eHF) with proven efficacy in infants with CMPA. In infants with extremely severe or life-‐threatening symptoms, an AAF may be considered as the first choice. Soy protein–based formula may be an opJon in infants older than 6 months who do not accept the bi3er taste of an eHF, or in cases in which the higher cost of an eHF is a limiJng factor, provided that the tolerance to soy protein has been established. If there is no improvement within 2 weeks, then an allergic reacJon to the remaining pepJdes in the eHF must be considered, parJcularly in infants with sensiJzaJon against mulJple foods. In these cases, an AAF should be tried before CMPA is ruled out as cause of the symptoms.

Previous concerns that infants with CMPA would react to residual protein traces in lactose have oten resulted in complete avoidance of both lactose and CMP. Adverse reacJons to lactose in CMPA are not supported in the literature, and complete avoidance of lactose in CMPA is no longer warranted. eHFs containing purified lactose are now available and have been found safe and effecJve in the treatment of CMPA (50). These formulae may also be more palatable for infants older than 6 months. It is, however, possible for secondary lactose intolerance to coexist in infants who have enteropathy with diarrhea, and therefore a lactose-‐free eHF will be required iniJally in these cases.

AAF Formulae containing free AA as the only nitrogen source are the best opJon in infants reacJng to eHF. This risk is esJmated to be <10% of all infants with CMPA (higher in the presence of severe enteropathy or with mulJple food allergies). For that reason, AAF may be considered a first-‐line treatment despite limited evidence in infants with severe anaphylacJc reacJons and infants with severe enteropathy indicated by hypoproteinemia and faltering growth. ParJally or extensively HF based on rice protein are also an opJon provided that they have been proven safe and efficient in infants with CMPA. Because of the limited short-‐ and long-‐term data on allergic reacJons (not sensiJzaJon) to rice-‐based formulae, a hydrolyzed rice formula may be considered in selected infants, which are either refusing or not toleraJng an eHF based on CMP, or in vegan families.

Soy protein–based formulae are tolerated by the majority of infants with CMPA, but 10-‐14% of affected infants react to soy protein (especially infants <6 mo). The ESPGHAN and the AAP recommend that cow’s-‐milk based formulae should be preferred over soy formula in healthy infants, and soy protein– based formulae should not usually be used during the first 6 mo. Soy formulae have nutriJonal disadvantages because their absorpJon of minerals and trace elements may be lower because of their phytate content, and they contain appreciable amounts of isoflavones with a weak estrogenic acJon that can lead to high serum concentraJons in infants. ESPGHAN & AAP consider eHF based on CMP or AAF if eHF is not tolerated preferable over soy protein–based formulae for the dietary treatment of infants with CMPA; however, a soy formula may be considered in an infant with CMPA >6 mo if eHF is not accepted or tolerated by the child, if these formulae are too expensive for the parents, or if there are strong parental preferences (eg, vegan diet).

Skin prick tests, patch tests and serum specific IgE are only indicaJve of CMPA.

EliminaJon diet by a double-‐blind placebo controlled food challenge is the gold standard for diagnosis.

EliminaJon of the offending allergen from the infants' diet is the main treatment principle.

Breasred infants have a decreased risk of developing CMPA; an eliminaJon diet for the mother is indicated if CMPA is confirmed.

If a food challenge is posiJve in formula fed infants, an extensively hydrolysed formula and cow's milk-‐free diet is recommended.

If symptoms do not improve, an amino acid based formula should be considered.

In severe CMPA with life-‐threatening symptoms, an amino-‐acid formula is recommended.

Diagnosis and management of cow's milk protein allergy (CMPA) in infants

De Greef E, et al. World J Pediatr 2012;8:19-‐24

How diagnosis and raJonale for acJon against cow’s milk allergy (DRACMA) changes clinical decision for the individual paJent in cow’s milk allergy therapy

Terraciano L, et al. Curr Opin Allergy Clin Immunol 2012;12:316-‐22

Lowe AJ, et al. J Allergy Clin Immunol 2011;128:360-‐5

Effect of a parJally hydrolyzed whey infant formula at weaning on risk of allergic disease in high-‐risk children: a randomized controlled trial

Effect of a parJally hydrolyzed whey infant formula at weaning on risk of allergic disease in high-‐risk children: a randomized controlled trial

Clinical implicaJons The authors found no evidence to support the use of pHWF at weaning for the prevenJopn of allergic disease in infants with a family history of allergic disease.

Lowe AJ, et al. J Allergy Clin Immunol 2011;128:360-‐5

Allergies in high-‐risk schoolchildren ater early intervenJon with cow’s milk protein hydrolisates: 10-‐year results from the German Infant NutriJon IntervenJon study

Von Berg A, et al. J Allergy Clin Immunol 2013;131:1565-‐73

Allergies in high-‐risk schoolchildren ater early intervenJon with cow’s milk protein hydrolisates: 10-‐year results from the German Infant NutriJon IntervenJon study

Clinical implicaJons Our results support the present recommendaJon to use certain CMPHIFs in high-‐risk infants to reduce the risk for atopic eczema but not for respiratory allergies. Von Berg A, et al. J Allergy Clin Immunol 2013;131:1565-‐73

FDA's health claim review: whey-‐protein parJally hydrolyzed infant formula

and atopic dermaJJs.

Chung CS, et al. Pediatrics 2012;e408-‐14.

The FDA concluded there is liGle to very liGle evidence, respecJvely, to support a

qualified health claim concerning the relaJonship between intake of W-‐PHF and

a reduced risk of AD in parJally breasred and exclusively formula-‐fed infants

throughout the first year ater birth and up to 3 years of age.

In addiJon, the FDA required a warning statement be displayed along with the

health claim to indicate to consumers that parJally hydrolyzed infant formulas

are not hypoallergenic and should not be fed to infants who are allergic to milk

or to infants with exisJng milk allergy symptoms.

Formula SelecJon for Management of Children with Cow's Milk Allergy Influences the Rate of AcquisiJon of Tolerance: A ProspecJve MulJcenter Study

J Pediatr 2013;163:771-‐7)

Results of allergy screening test during the study. .

SPT in children with IgE-‐mediated CMA.

APT in children with non-‐IgE-‐mediated CMA.

Formula SelecJon for Management of Children with Cow's Milk Allergy Influences the Rate of AcquisiJon of Tolerance: A ProspecJve MulJcenter Study

J Pediatr 2013;163:771-‐7)

Rate of paJents acquiring tolerance to oral food challenge ater 12 mo of exclusion diet with different formulas

The effect of a parJally hydrolised formula based on rice protein in the treatment of infants with cows milk protein allergy

Reche M. Pediatr Allergy and Immunol 2010;21(4 Pt 1):577-85

PARTIALLY HYDROLIZED PROTEIN-‐BASED RISE FORMULA Growth, tolerance and biochemical measures in healthy infants fed a parJally hydrolized rice protein based formula: a randomized, blinded, prospecJve trial. “... Healthy infants fed an experimental parJally hydrolized rice protein-‐based formula had normal growth, tolerance, and plasma biochemistry comparable to those of infants fed a standard intact milk protein based formula, despite some differences in amino acid profiles (lysine & threonine)”.

Lasekan JB, et al. J Am Coll Nutr 2006

Tolerance to a rice hydrolysate formula in children allergic to cow's milk and soy. “...Children allergic to cow's milk and soy tolerate an HRF clinically. This suggest that rice hydrolysate may be used as a protein source for children with mulJple food-‐induced reacJons but also for children with CMA”.

Fiocchi A, et al. Clin Exp Allergy 2003; 2006

“Analysis of studies comparing soy to a hydrolysed formula found a significant increase in infant and childhood allergy cumulaJve incidence, infant eczema cumulaJve incidence and childhood food allergy period prevalence. Feeding with a soy formula should not be recommended for the prevenJon of allergy of food intolerance in infants at high risk of allergy or food intolerance”.

Soy formula for prevenJon of allergy and food intolerance in infants

Cochrane Database Systemic Review, 2004

LATTE DI ASINA (donkey’s milk) Proteine: 1.5-‐1.8 (g/100g) Lipidi: 0.3-‐1.8 (più probabilmente 1) La3osio: 5.8-‐7.4 -‐Molto simile al la3e di donna -‐Proteine: sieroproteine 0,75 g/100 g; caseina 0,66 g/100 g (il contenuto minore in caseine può essere un fa3ore determinante l’ipoallergenicità del la3e di asina) -‐Lisozima 1g/litro : ad azione ba3ericida, perme3e migliore conservazione delle proprietà organole#che e microbiologiche -‐Lipidi: il rido3o contenuto in lipidi determina un rido3o apporto energeJco perciò va integrato con oli; saturi 46.7-‐67.6%, mono 15.3-‐28.2%, poli 16-‐22.8% (più ricco in n-‐3 e n-‐6 a lunga catena rispe3o al la3e vaccino) -‐Reperibilità: la produzione e la commercializzazione in Italia sono svolte solo nell’azienda zootecnica di produzione per cui non è facilmente reperibile e il costo è stabilito sostanzialmente dal produ3ore, oscilla fra 5 e 15 euro al litro -‐Palatabilità: ok per i bambini APLV

Pediatr Allergy Immunol. 2007 May;18(3):258-‐64. Efficacy of donkey's milk in trea5ng highly problema5c cow's milk allergic children: an in vivo and in vitro study.

LATTE DI CAPRA (goat’s milk) Proteine: 3,4 (g7100g) Lipidi: 3,8 La3osio: 4,1 -‐Molto simile al la3e vaccino come composizione totale -‐Proteine: molte varianJ proteiche delle caseine, esiste una certa variabilità anche per le sieroproteine; questo potrebbe rendere il la3e di alcune capre più simile a quello di donna; più ricco di aa essenziali rispe3o al vaccino -‐Lipidi: le dimensioni minori (rispe3o al la3e vaccino ) dei globuli di trigliceridi rendono il la3e di capra più facilmente a3accabile da parte degli enzimi digesJvi quindi più digeribile; ricco di a.g. a corta/media catena (caproico, caprilico, caprinico) che conferiscono il sapore cara3erisJco e non sempre gradito; nel la3e degli animali al pascolo ci sono discrete quanJtà di CLA (coniugaJ dell’acido linoleico). Non indicato per sogge# APLV (cross rea#vità) perché bisognerebbe selezionare l’animale che produce la3e ad esempio senza una parJcolare caseina,… Ci sono inoltre sogge# allergici al la3e di capra e non al vaccino. Non indicato per intolleranJ al la3osio perché ne conJene in quanJtà poco inferiore al vaccino Goat milk allergenicity as a funcJon of αs₁-‐casein geneJc polymorphism. Ballabio C, et al, J Dairy Science 2011; 94(2):998-‐1004.

LATTE DI PECORA (sheep’s milk)

Proteine: 5,3-‐6,2 (g/100g) Lipidi: 6,9-‐7,9 La3osio: 4,9-‐5,2 OSSERVAZIONI: -‐Alto apporto di proteine e grassi -‐Difficilmente reperibile in commercio come tale; usato spesso per produzione formaggi -‐Proteine: -‐Lipidi: gli acidi grassi più rappresentaJ sono il palmiJco e l’oleico, ma anche quelli a catena corta e media come il caprinico e il caprilico

LATTE DI AVENA Proteine: 1,35 (g/100g) Lipidi: 1,6 CarboidraJ: 6,6, di cui 1,4 amido-‐5.2zuccheri; la3osio :0 Kcal: 47/100 g OSSERVAZIONI: -‐Proteine: apporto minimo -‐Cho: ricco di zuccheri semplici -‐Lipidi: viene spesso aggiunto di olio di girasole; conJene prevalentemente a.g. poliinsaturi -‐Vitamine: E, acido folico -‐0.8 g fibra/100 g

LATTE DI MANDORLE Proteine: 1 (g/100g) Lipidi: 2,3 CarboidraJ: 6,6, di cui 3,7 amido-‐2,9zuccheri; la3osio :0 Kcal: 51/100 g OSSERVAZIONI: -‐Non può sosJtuire le formulazioni per l’infanzia a base di soia; viene dato come integrazione -‐Lipidi prevalentemente poliinsaturi

VII° CONGRESSO NAZIONALE:

NUTRIZIONE, METABOLISMO E DIABETE NEL BAMBINO E NELL’ADOLESCENTE

Dalla ricerca all'ambulatorio del pediatra

Aula Magna Policlinico G. B. Rossi -‐ Piazzale L. Scuro, 10

Verona, 12 – 13 se3embre 2014

SAVE THE DATE

Allergenicity of goat's milk in children with cow's milk allergy.

“... GM is not an appropriate cow's milk substitute for children with IgE-mediated cow's milk allergy”.

Bellioni-Businco B, et al. J Allergy Clin Immunol 1999

GOAT'S MILK

Goat milk is less immunogenic than cow milk in a murine model of atopy.

“... GM, when used as the first source of protein after a breast-feeding period, is less allergenic than CM in mice”.

Lara-Villoslada F, et al. JPGN 2004 Randomized, doube-blind comparison of growth in infants receiving goat milk formula versus cow milk infant formula.

“...Growth of infants fed GMF is not different to that of infants-fed CMF”.

Grant C, et al. J Pediatr Child Health 2005

Postnatal fish oil supplementaJon in high-‐risk infants to prevent allergy: randomized controlled trial.

D’Vaz N, et al. Pediatrics 2012;130:674-‐82

«LATTI» VEGETALI: legalmente non sono la# LATTE DI SOIA COMPOSIZIONE BROMATOLOGICA (g/100 g) Proteine: 2.9 Lipidi: 1.9 CarboidraJ: 0.8 ; La3osio: 0 Kcal: 32/100 g OSSERVAZIONI: -‐Proteine: di buon valore biologico; caseina:0 -‐Lipidi: gli acidi grassi più rappresentaJ sono i poliinsaturi, compresi n-‐3; i saturi sono molto rido#; colesterolo:0 -‐Il ferro è contenuto in misura doppia rispe3o al la3e vaccino (0.4-‐0.5 mg/100 g) -‐ConJene vitamina A, E del gruppo B ma non B12 -‐Viene addizionato di Ca (naturalmente ne conJene 13mg/100 g) e/o B12 LATTE DI RISO COMPOSIZIONE BROMATOLOGICA (g/100 g) Proteine: 0.3 Lipidi: 1 CarboidraJ: 15, di cui 8 amido-‐7 zuccheri; la3osio :0 Kcal: 70/100g OSSERVAZIONI: -‐Proteine: apporto minimo -‐Cho: ricco di zuccheri semplici -‐Lipidi: viene spesso aggiunto di olio di girasole; conJene prevalentemente a.g. poliinsaturi -‐Vitamine: A, B, D

laspeciali$e$patologia:$ unamalaa,$un$lae$speciale$ speciali e patologia... · casein-,...

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