A 24 year old first time mother brings her two week old son to your office for a well child examination. She is a single mother with strong family support. She will be returning to work in one week and has elected not to breastfeed. Today she is seeking your advice concerning her infant's nutrition.

In a 1986 policy statement, the American Academy of Pediatrics (AAP) reaffirmed its position on four issues pertinent to infant nutrition (1):

1. The AAP will continue to promote breastfeeding as the first form of infant nutrition.

2. The AAP will continue to work to maintain and improve the high quality of infant formulas in the United States because in some cases, breastfeeding is not practical or desired.

3. The AAP will continue to recommend against direct to consumer advertising of infant formula.

4. The AAP will continue to encourage the special supplement nutrition program for women, infants and children (WIC) and hospital nurseries, and programs to make available a diversity of formulas.

The AAP adheres to the belief that pediatricians have a responsibility for infant nutrition, have an obligation to be knowledgeable about the nutritional needs of both healthy normally developing infants as well as infants with unique nutritional needs such as those with metabolic, gastrointestinal, infectious and oncologic disease conditions (1).

Breast milk is considered to be the optimal nutrient for the term or near term infant as an exclusive source of nutrition during the first six months of life. Breast milk combined with the introduction of solids is recommended for the second six months of an infant's life (2).

There are indications for the use of infant formula:

1. As a supplement or substitute for breast milk when a mother cannot or chooses not to breast-feed.

2. Infants whose mothers are infected with organisms known to be transmittable by human milk (e.g., HIV)

3. Infants whose mothers are undergoing chemotherapy.

4. Infants whose mothers are receiving medication or drugs that are excreted into human milk.

5. Infants who are unable to tolerate human milk because of metabolic disorders (e.g., galactosemia).

In the event breast feeding is neither practical nor desired, there are a number of commercially available infant formulas that have been formulated to simulate human breast milk and provide an infant's nutritional requirements. On average, a neonate will drink about 165 cc of formula/kg/day (2.5 ounces/pound/day) and about 30-90 cc (1-3 ounces) per feeding. The caloric content of most infant formulas closely approximates that of human milk at 2/3 kcal/cc (20 kcal/oz). Infants are often their own best regulators, thus variation with each feeding should be expected. During the first 6 months of life, infants require 95-115 kcal/kg/day; 8-12% of these calories should be derived from protein, 30-50% from fat and 40-60% from carbohydrates. If these nutritional requirements are met, an infant will typically gain 25-40 grams per day (30 grams = 1 ounce) in the first 3 months and 15-20 grams in the second 3 months. Infant formulas are designed to mimic the nutritional composition of human milk, but in reality they contain a number of differences in the protein, fat and carbohydrate content.

Human milk contains approximately 1.1 g/dL of protein as compared to 1.5g/dL in most standard formulas. This represents 6-8% of an infant's total caloric intake. Milk protein can be divided into two classes based on relative solubility in acid: whey (acid soluble) and casein (acid insoluble). The whey:casein ratio of human milk is 70:30 as compared to a ratio of 18:82 for cow milk. The clinical significance of the difference in whey:casein ratio between human and bovine milk is illustrated when unmodified casein-predominant cow milk enters the acidic environment of the human stomach and forms a relatively hard curd of casein and minerals. This curd can be difficult for an infant to digest. Thus, the AAP recommends that cow's milk not be used until after the first birthday. Special toddler's milk is now being marketed as a transitional formula to whole cow's milk; however there are no proven special benefits compared to a toddler eating a balanced diet that includes milk and juice.

Lipid constitutes approximately 50% of the calories in human milk (5.7g/100 kcal) and standard infant formula (4.4-6.0g/100 kcal). The predominant portion of lipid in human and cow milk is triacyl glycerol. Triacyl glycerol is composed of a glycerol backbone with 3-hydroxyl group esterified to fatty acids.

Essential fatty acids lineoleic and alpha lineolinic acid play a crucial role in neurodevelopment. Approximately 5-7% of total calories in human milk and 1% of total calories in cow milk is lineoleic acid. The amount of lineoleic acid considered adequate is controversial but it in generally agreed it should not be more than 20%. For this reason all cow milk based formulas add vegetables oil (containing relatively large amounts of lineoleic and lineolinic) to their preparations. Most commercial infant formulas contain at least 10% of total fatty acids as lineoleic acid.

The primary carbohydrate source found in both human milk and formulas is lactose (except in lactose free formula). Lactose is a disaccharide that is converted to simple sugars, galactose and glucose by a lactase enzyme. Disaccharides require conversion to simple sugars to enable absorption through the gut via a monosaccharide transport system. The carbohydrate source in soy based formula is glucose polymers (also referred to as corn syrup solids) and/or sucrose. Sucrose is converted to simple sugars, fructose and galactose for absorption (3).

The iron content of human milk is much less than that of iron fortified cow milk based formula, but the bioavailability of human milk iron is much higher. Guidelines from the committee on nutrition of the AAP recommends 2-3 mg/kg/day of elemental iron. In a term infant, iron deficiency is uncommon before 4-6 months of age because of the abundance of iron stores at birth. Iron deficiency is most common among children 6 months to 3 years of age. To compensate for the depletion of iron stores by growth, dietary iron must be provided. Exclusively breastfed infants may require diet supplementation with iron (1 mg/kg/day) and vitamin D (400 IU/day) at 4-6 months of age. Standard formulas (about 32 ounces per day) will meet 100% of RDA for vitamins and minerals for term infants. Low iron formulas defined by the FDA as containing less than 6.7 mg/L of iron, once contained less than 1.5mg/L of iron, resulting in an unacceptably high rate of iron deficiency and anemia. Over the past five years, formula manufacturers have increased the amount of iron in low iron formulas to 4-5mg/L. A public perception that iron causes constipation and other feeding problems has allowed for the continued market of low iron containing formulas. There is no data to support this belief and the AAP recommends iron-fortified formulas.

Symptoms of cow milk protein allergy typically begin between week 4 to 6, but the sensitivity may occur as early as 48 hours or may present in adulthood. The presence of gastrointestinal symptoms such as bloody stools, diarrhea and vomiting can indicate pathophysiological intolerance related to a specific component of cow milk formula. Symptoms such as flatus, fussiness and colic are less likely and difficult to directly relate to components of cow milk. True cow milk protein allergenicity as documented by a double-blinded study is present in less than 6% of the population (5,6). Some surveys show as high 30% of formula fed infants are switched to hypoallergenic formulas because of a perceived or suspected protein allergy (7). Hypoallergenic formulas are created by extensively hydrolyzing the cow milk protein (usually casein), thereby reducing its molecular weight to less than 1250 kDa. Proteins less than 1250 kDa are far less likely to produce a IgE-mediated allergic response (6). Hypoallergenic hydrolyzed casein formulas are effective in preventing protein allergy. It is however prudent to truly diagnose cow milk allergic infant before starting these formulas whose most significant disadvantage is a greater cost when compared to regular formula. Breastfeeding is even more strongly advocated in infants with milk hypersensitivity.

Primary lactose intolerance such as lactase deficiency and galactosemia, occurs approximately in 1:1000 infants. Secondary lactose intolerance by contrast is far more common and often presents with protracted diarrhea. The lactase enzyme is located at the villous tip of the intestine and appears to be more vulnerable than sucrase that is found deeper in the crypt. An infectious diarrhea may cause denuding and the lactase enzyme may take up to a week to fully recover. A low lactose or lactose free formula may reduce carbohydrate malabsorption (and subsequent exacerbation of diarrhea by an osmotic mechanism) during the illness. The lactose free cow-milk based formulas are designed to treat primarily secondary lactase deficiency. The contrast to lactose containing formulas is the substitution of its carbohydrate source. Instead of lactose, a corn syrup solid and/or sucrose is used.

Soy formulas support the growth of normal term infants through the first year of life. Soy formulas may be used in lieu of cow milk formula and in formula fed infants whose parents want their children to adhere to a vegetarian diet. Phytate in soy formula in addition to the absence of lactose diminish the absorption of divalent cations such as iron, calcium and zinc in the intestinal lumen. Supplementation of soy formula with iron, calcium and zinc has largely overcome these issues (8,9). Phytogens in soy formulas have the potential for hormonal action at critical points in development. The AAP has noted that limited human data does not support these concerns (10).

Summary of formulas:

Cow's milk based formulas:
. . . . Indications: Term or near term infant.
. . . . Protein: whey-predominant; carnitine and taurine usually added.
. . . . Carbohydrate: lactose.
. . . . Fat: vegetable oils.
. . . . Brands: Enfamil with iron, Similac with iron, Good Start (100% whey protein, thus may be used for constipation), Lacto-free (uses corn syrup and/or sucrose), Similac PM 60/40 (60:40 ratio of whey to casein, less Ca, P, K for cardiac and renal patients).

Soymilk based formulas:
. . . . Indications: Lactose deficiency or galactosemia, strict vegetarians, IgE mediated reaction to cow milk protein.
. . . . Protein: 2.2g/dl of protein from a plant source, cysteine and taurine as well as an additional methionine added.
. . . . Carbohydrate: corn syrup (glucose polymer), sucrose.
. . . . Fat: vegetable oils.
. . . . Brands: Isomil, ProSobee.

Casein Hydrosylate formulas:
. . . . Indications: Milk or soy protein intolerance, colic.
. . . . Protein: casein hydrolysate (hypoallergenic).
. . . . Carbohydrate: glucose oligosaccharides modified cornstarch.
. . . . Fat: MCT, corn oil.
. . . . Brands: Pregestimil, Nutramigen, Alimentum (increased MCT fat concentration; for cystic fibrosis patients).

Questions

1. The American Academy of Pediatrics recommends what form of nutrition for infants?

2. What is an appropriate quantity of formula for an infant?

3. When is iron supplementation required for an infant?

4. When comparing breast milk vs. cow's milk based formulas, which has a higher: a) kcal/cc? b) Concentration of casein protein? c) Carbohydrate content? d) Fat content?

5. What is the clinical significance of the whey:casein ratio in cow milk?

6. What is the main form of carbohydrate in breast milk? Cow's milk based formula? Soy based formula?

References

1. Breastfeeding and the use of human milk. American Academy of Pediatrics. Work Group on Breastfeeding. Pediatrics 1997;100(6):1035-1039.

2. Hall RT, Caroll RE. Infant feeding. Pediatr Rev 2000;21(6):191-200.

3. Greer FR. Formulas for the healthy term infant. Pediatr Rev 1995;16(3):107-113.

4. Blecker U, Sothern MS, Suskind RM. Iron-fortified infant formulas. Pediatr Rev 1999;20(10):359.

5. Oldaeus G, et al. Allergenicity screening of "hypoallergenic" milk-based formulas. J Allergy Clin Immunol 1992;90(1):133-135.

6. Oldaeus G, et al. Cow's milk IgE and IgG antibody responses to cow's milk formulas. Allergy 1999;54(4):352-357.

7. Schrander JJ, et al. Cow's milk protein intolerance in infants under 1 year of age: a prospective epidemiological study. Eur J Pediatr 1993;152(8):640-644.

8. Mimouni F, et al. Bone mineralization in the first year of life in infants fed human milk, cow-milk formula, or soy-based formula. J Pediatr 1993;122(3):348-354.

9. Hertrampf E, et al. Bioavailability of iron in soy-based formula and its effect on iron nutriture in infancy. Pediatrics, 1986;78(4):640-645.

10. American Academy of Pediatrics. Committee on Nutrition. Soy protein-based formulas: recommendations for use in infant feeding. Pediatrics 1998;101(1 Pt 1):148-153.

Answers to questions

1. Breastfeeding is regarded first and foremost except when it is not practical, desired or medically contraindicated.

2. From a practical standpoint, whether it is breast milk or infant formula, a healthy term infant is the best regulator of the frequency and quantity of their nutritional intake. However, since we are scientists at heart; during the first 6 months of life approximately 95-115 kcal/kg/day is recommended.

3. In a term infant, iron deficiency is uncommon before 4-6 months of age because of the abundance of iron stores at birth. To compensate for the depletion of iron stores by growth, dietary iron must be provided to exclusively breastfed infants. Iron fortified formulas can prevent iron deficiency in formula fed infants. Guidelines from the Committee on Nutrition of the AAP recommend 2-3 mg/kg/day of elemental iron.

4a. They are about the same. Human milk contains approximately 2/3 kcal/cc (20 kcal/oz). The standard infant formula usually remains close to this range.

4b. Whey:Casein of human milk is 70:30 as compared to a ratio of 18: 82 for cow milk. Please refer to the text to review the clinical significance of this profile difference.

4c. The carbohydrate content is about the same.

4d. Lipids constitute approximately 50% of the calories in human milk (5.7 g/100kcal) and standard infant formula (4.4-6.0 g/100kcal).

5. The clinical significance of the difference in whey:casein ratio between human and bovine milk is illustrated when unmodified casein-predominant cow milk enters the acidic environment of the human stomach and forms a relatively hard curd of casein and minerals. This curd can be difficult for an infant to digest. Thus, the AAP recommends that cow's milk not be used until after the first birthday.

6. Lactose is the main carbohydrate in mammalian milk. The lactose concentration of human milk is 7g/dL, cow milk contains 5 g/dL. Lactose is added to most standard infant formula to achieve the concentration of human milk. Soy formulas do not contain lactose; they contain sucrose, glucose polymers, or a mixture of the two.