rated fats and large amounts of iron without adding adequate antioxidants (Halliwell and Chirico, 1993; McCord, 1996).

The issue of the context or matrix in which nutrients are provided in milk remains a challenge to infant formula manufacturers as they try to match human-milk composition and breastfeeding performance (Benson and Masor, 1994). The matrix can highly influence the bioavailability of nutrients. In the simplest example, nutrients that are present in both milks may be present in different ratios. For many nutrients that do not interact chemically or compete for enzymatic or receptor binding sites, the relative amounts may not be important. However in situations where there is competition for enzymes (e.g., among n-3 and n-6 PUFAs) (Brenner, 1974) or receptor binding sites in the intestine (e.g., for zinc, iron, and copper), the relative proportions may have biological significance.

Manufacturers must also consider the form of the molecule in which a nutrient is presented to the intestine and its bioavailability. For example, the high bioavailability of iron from lactoferrin in human milk allows for a much lower concentration of iron in human milk (0.2–0.4 mg/L) compared with infant formulas (4.0–12 mg/L) and thereby decreases competition between iron and other divalent cations, such as copper and zinc (Lonnerdal and Hernell, 1994).

In the case of LC-PUFAs, care must be taken to ensure no toxicity from these compounds. Manufacturers must study the effects of fats, minerals, enzymes, or other factors on LC–PUFA bioavailability and processing. For example, newborn fat absorption can be highly variable because of the immaturity of several lipases, including pancreatic lipase (for review, see Hamosh, 1988). Human milk contains lipases that compensate for the lack of pancreatic lipases. Thus human-milk fat is more bioavailable than the vegetable oils found in infant formulas.

Finally, manufacturers must examine the effects of infant formulas in the context of mixed feedings (Ryan et al., 2002). Throughout the course of the day, an infant in the United States may consume both human milk and infant formulas in any number of combinations. For example, some infants of working mothers are breastfed during the morning and evening and fed formula during the day by a caregiver. Here the nutrients and their respective matrixes are kept quite separate and less interaction may be expected than in the situation where an infant is supplemented with formula directly after each nursing. In the latter case there is a theoretical concern that certain nutrients found in high concentration in infant formulas (e.g., iron) may interfere with the intended matrix delivery system found in human milk (e.g., lactoferrin). The nutritional consequence of mixed-feeding paradigms has not been adequately investigated, but should be targeted in future studies of the performance of infant formulas.

Matching Breastfeeding Performance

The alternative to matching human-milk composition is to match breastfeeding performance (Benson and Masor, 1994). Initially the goal of infant formulas was to match the growth rate of the breastfed infant. However over time it was recognized that breastfeeding may confer several other potential advantages to the infant (for review, see AAP, 1997), including:

  • prevention of infectious diseases (Beaudry et al., 1995; Dewey et al., 1995),

  • neurodevelopment (Mortensen et al., 2002), and

  • protection from chronic diseases in childhood (Saarinen and Kajosaari, 1995; Shu et al., 1995).

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