Essential Nutrients for Infant Development

1. טעם החיים המוקדמיםנושאים בתזונת תינוקות וילדים דר' רון שאול מרכז רפואי בני ציון

4. מהי כלכלה ים תיכונית בריאה • מה כן • ירקות , פירות, קטניות, אגוזים ודגים, • אלכוהול בכמות מתונה. • מה לא • בשרים ומוצרי חלב עתירי שומן • ירידה בתמותה ממחלות לב ומסרטן

5. שעורי תמותה ביחס לצריכת כלכלה ים תיכונית

6. Introduction • Human milk is the most appropriate milk for the newborn infant. • Major research has been going on over the last years towards the development of enteral formulas that would be as close as possible to the composition of breast milk.

7. Introduction • The major nutrients of interest include • Glutamine • Taurine • ω-fatty acids • Nucleotides • probiotics, and prebiotics. • Antioxidants

9. ω-fatty acids

11. LC – PUFAω-3 AND ω-6 FATTY ACIDS • The ω-3 and ω-6 fatty acid families also are referred to as essential fatty acids because of absent de novo synthesis. • The ω-6 series are the precursors for arachidonic acid (AA), which has several biologic roles, including structural component of cell membranes and precursor for prostaglandins and leukotrienes

12. LC – PUFAω-3 AND ω-6 FATTY ACIDS • ω-3 Fatty acids, especially docosahexaenoic acid DHA, may be important for proper functioning of cellular membranes in neuronal tissues, such as the retina and the brain.

13. LC – PUFAω-3 AND ω-6 FATTY ACIDS • The brain and retina are rich in ω-3 fatty acids, particularly DHA. • These fatty acids are present in human milk • AA and DHA may be necessary for neural development, cognitive function

14. There are 14 controlled trials in term infants that have included formula feeding with or without LCPUFA and functional assessment of visual and other measures of neural development; in addition, 7 have evaluated specific measures related to cognitive development.

15. They examined the effect of DHA dose provided daily on the development of visual acuity to explain the differences in visual acuity responses across randomized studies. • Results indicate a strong and significant effect of DHA equivalent dose on magnitude of the visual acuity response at all conversions tested • Most studies showed no advantage for LCPUFA on neurodevelopment.

16. They concluded that there is a significant relation between the total DHA equivalents provided and effectiveness as defined by visual acuity measurements at 4 months of age. J Pediatr 2003;143:S17-S25

17. Long chain polyunsaturated fatty acid supplementation in infants born at term • Conclusions: At present there is little evidence from randomised trials to support the hypothesis that LCPUFA supplementation confers a benefit for visual or general development of term infants. • Minor effects on VEP acuity have been suggested but appear unlikely when all studies are reviewed. Cochrane Database of Systematic Reviews. 3, 2005

18. Long chain polyunsaturated fatty acid supplementation in infants born at term • A beneficial effect on information processing is possible but larger studies over longer periods are required. • Data from randomised trials do not suggest that LCPUFA supplements influence the growth of term infants. Cochrane Database of Systematic Reviews. 3, 2005

19. Objective: The objective was to determine the effect of supplementing infant formula with long-chain polyunsaturated fatty acids (LCPUFAs) on the growth of term infants. • Design: they reviewed all known randomized controlled trials that involved LCPUFA supplementation of infant formula fed to term infants. • Outcome measures were weight, length, and head circumference.

20. Results: They identified 14 eligible trials that had data available for meta-analysis (1846 infants). • Trial quality was generally high. • Meta-analysis showed no significant effect of LCPUFA supplementation on infant weight, length, or head circumference at any assessment age. • Similarly, subgroup analyses showed that supplementation with only n3 LCPUFAs or different sources of LCPUFA (phospholipid or triacylglycerol) also did not significantly affect infant growth.

22. Soy based formulas

23. Background • Soy-based infant formulae, initially developed for infants who were lactose intolerant or allergic to cow’s milk–based formulae, now account for >25% of the infant formulae sold in the United States. • Formulations have changed over the years to improve digestibility, the stability and availability of minerals, and protein quality.

24. Introduction • Results suggest that modern soy-based formulae support normal growth and nutritional status in healthy term infants at the age of 1 year. • However, there are very limited data on sexual and reproductive development or outcomes such as immune function, visual acuity/cognitive development and thyroid function. Mendez MA, et al. J Nutr 2002; 132(8):2127-2130

25. Recent concerns have been raised regarding the phytoestrogenic isoflavone content (x40 in comparison to breast milk) of soy-based formula

26. Objective To examine the association between infant exposure to soy formula and health in young adulthood, with an emphasis on reproductive health. • Design, Setting, and Participants Retrospective cohort study among adults aged 20 to 34 years who, as infants, participated in controlled feeding studies conducted at the University of Iowa • 248 were fed soy formula and 563 were fed cow milk formula during infancy. JAMA 2001

27. Conclusions: Exposure to soy formula does not appear to lead to different general health or reproductive outcomes than exposure to cow milk formula. • The findings are reassuring about the safety of infant soy formula.

28. 1. In term infants whose nutritional needs are not being met from maternal breast milk or cow milk based formulas, • 2. They are appropriate for use in infants with galactosemia and hereditary lactase deficiency. • 3. Parents seeking a vegetarian-based diet for a term infant. • 4. Isolated soy protein-based formulas are indicated for acute gastroentitis when lactose intolerance has been documented.

29. 5. Soy protein-based formula has no proven value in the prevention or management of infantile colic. • 6. Soy protein-based formula has no proven value in the prevention of atopic disease in healthy or high-risk infants. • 7. Infants with documented cow milk protein-induced enteropathy or enterocolitis frequently are as sensitive to soy protein and should not be given isolated soy protein-based formula routinely. • 8. Most infants with documented IgE-mediated allergy to cow milk protein will do well on isolated soy protein-based formula. • 9. Soy protein-based formulas are not designed or recommended for preterm infants who weight <1800 g. Pediatrics, January 1998

30. Soy for allergy prevention • Conclusions: Feeding with a soy formula should not be recommended for the prevention of allergy or food intolerance in infants at high risk of allergy or food intolerance. Osborn DA, et al. Soy formula for prevention of allergy and food intolerance in infants. Cochrane Database Syst Rev 2004

31. Soy allergy occurs in only a small minority of young children with IgE-associated CMA. • As such, soy formula may provide a safe and growth-promoting alternative for the majority of these children. J Pediatr 1999;134:614-22

32. Infants (n = 170) with documented cow’s milk allergy were randomly assigned to receive either a soy formula or an extensively hydrolyzed formula. • If it was suspected that the formula caused symptoms, a double-blind, placebo-controlled challenge (DBPCFC) with the formula was performed. • The children were followed to the age of 2 years, and soy-specific IgE antibodies were measured at the time of diagnosis and at the ages of 1 and 2 years.

33. Conclusions: Soy formula was well tolerated by most infants with IgE associated and non–IgE-associated cow’s milk allergy. • Development of IgE-associated allergy to soy was rare. • Soy formula can be recommended as a first-choice alternative for infants >6 months of age with cow’s milk allergy.

34. המלצת הועדה המקצועית של משרד הבריאות • בהמלצות הועדה המקצועית מטעם משרד הבריאות, בראשות פרופ′ צבי ויצמן שסקרה את הנושא לעומקו הומלץ: • לעודד הנקה או שימוש בתרכובות חלב פרה באוכלוסיות הצורכות תכשירי סויה מטעמי כשרות, • להגביר הסברה בנושא הנזקים האפשריים משימוש בתכשירי סויה הן לציבור והן לכלל עובדי הרפואה (בעיקר רופאי ילדים, רופאי משפחה, דיאטניות ואחיות בריאות הציבור). • ביצוע מחקרים התערבותיים ארוכי טווח כדי לבחון את בטיחות השימוש בתכשירי סויה בתינוקות ובילדים • ניטור רמות הטירוקסין בדם בתינוקות ובפעוטות עם  תת-פעילות של בלוטת התריס, הניזונים מתכשירים על בסיס סויה.

35. Lactose Free formulas

36. Background • Although few infants are likely to manifest lactose intolerance, the use of lactose-free formulas has increased rapidly in the past several years. • Many parents prefer lactose-free formula, apparently because they believe infants tolerate it better than they do formulas containing lactose.

37. Introduction • Lactose is a disaccharide that is present in almost all mammalian milks. • It is digested in the small bowel by the lactase located on the brush border of the enterocyte. • On digestion, lactose is broken down into two components, glucose and galactose. • If lactose is not digested or is digested minimally, the intact sugar moves into the large bowel where it is fermented by enteric bacteria. • This fermentation produces acids, carbon dioxide, methane, and hydrogen, and usually results in borborygmi and abdominal discomfort.

38. Introduction • Lack of digestion of lactose results in an increased number of solute particles in the large bowel with a concomitant increase in osmotic pressure. • It has been suggested that the diarrhea associated with lactose intolerance occurs when the capacity of the bacteria to metabolize carbohydrate in the colon has been exceeded. • Most of the people of the world are unable to digest lactose in adult life.

39. Introduction • In general, evidence for malabsorption of lactose as a clinical problem is not manifest until after 5 to 7 years of age, although this age can be variable. • Individuals can increase their tolerance to dairy products by ingesting fermented products such as yogurt, hard cheeses and cottage cheese. • Even children hypersensitive to CM are clinically tolerant to lactose and can safely consume foods and drugs with lactose from bovine sources.

40. Although reduction in intestinal brush-border lactase levels is often associated with diarrhea, most infants with decreased lactase levels will not have clinical signs or symptoms of malabsorption. • Infants fed human milk can be nursed safely during episodes of diarrhea

41. Recently, a major comprehensive report concluded that it is unwise to discourage the use of milk in children from a population with a high rate of lactose malabsorption unless these children are suffering from severe diarrhea or show a definite intolerance to milk or milk products. American Academy of Pediatrics Committee on Nutrition: Practical significance of lactose intolerance in children: supplement. Pediatrics 1990; 86:643-644

42. A meta-analysis was performed to evaluate the use of lactose-containing feedings in children with diarrhea and concluded that 80% or more of children with acute diarrhea can tolerate full-strength milk safely Brown KH, et al. Pediatrics 1994; 93(1):17-27

43. Despite the lack of proven efficacy, lactose free formula is also widely used in diarrheal illnesses. • The growth of infants fed lactose-free formulas is comparable to that of infants fed lactose-containing formulas • Questions remain, however, regarding the mineral bioavailability and optimal mineral contents of these lactose-free formulas.

44. The formula should not be used for galactosemia patients !!!!!

45. So who should get the formula ? • It might be helpful in cases of diarrhea among malnourished children or among children with a severe enteropathy

46. Hypoallergenic formulas

47. Background • Hypoallergenic formulas are processed by enzymatic hydrolysis of different protein sources followed by further processing ( heat treatment and/or ultrafiltration), or they are based on amino acid mixtures. • The products have been classified according to the degree of protein hydrolysis as extensively or partially hydrolysed protein products

48. Background • Only pure amino acid mixtures are considered to be nonallergenic. • Other hypoallergenic products contain residual allergenicity. • Hypoallergenic formulas for treatment of cow’s milk protein allergy should be tolerated by at least 90% of infants with documented cow’s milk protein allergy.

49. Feeding high-risk infants hypoallergenic formula combined with avoidance of solid foods during the first 4–6 months reduces the cumulative incidence of cow’s milk protein allergy and atopic dermatitis as compared with a standard cow’s-milk-based formula. • Partially hydrolysed formulas may have an effect, though it seems to be less than that of extensively hydrolysed formulas at present. Host A et al. Allergy 2004

50. Thus, if exclusive breastfeeding for 4–6 months is not possible in high- risk infants, a documented hypoallergenic formula and avoidance of solid foods are recommended for the first 4 months of life