New infant formula additives approved by FDA

from the AAP Committee on Nutrition

Pediatricians should discuss with parents the potential benefits of adding long-chain polyunsaturated fatty acids to formulas for term infants and weigh this information against the increased costs of these new products.

Formulas containing the extra long-chain polyunsaturated fatty acids (LC-PUFAs) are now appearing in hospitals and at formula retail outlets throughout the United States.

Two products currently are available: Enfamil Lipil and Similac Advance with Iron. Both products utilize the same source of LC-PUFAs, which are derived from algae and fungi (Martek Biosciences Corporation). The data pertaining to this source of LC-PUFAs recently were reviewed by the U.S. Food and Drug Administration (FDA) and it was concluded that it probably was safe to add these to term infant formula.

With the wholesale prices for these products approximately 15% higher than standard formulas, this should translate into a higher sticker price at most retail outlets. Currently, no soy-based formulations of these products are available. Also, these new formulas presently are not supplied through the Special Supplemental Nutrition Program for Women, Infants and Children.

LC-PUFAs, by definition, are fatty acids that have chain lengths greater than 18 carbon atoms and contain two or more double bonds. Two such fatty acids are important in infant nutrition — arachidonic acid (ARA or AA) and docosahexonoic acid (DHA). These are present in small concentrations in human milk, but previously were not present in infant formulas.

ARA is derived from the essential fatty acid alpha-linoleic acid, and DHA is derived from the essential fatty acid linolenic acid. Both term and preterm infants can synthesize the LC-PUFAs from the respective essential fatty acids, but controversy has centered around the fact that breastfed infants have higher plasma concentrations of these LC-PUFAs than formula-fed infants. This information could be interpreted to imply that formula-fed infants cannot synthesize enough of these fatty acids to meet ongoing needs, though the plasma content of DHA and ARA is only a very small fraction of the total fatty acid pool available in other tissues.

DHA and ARA are major fatty acids in neural tissue. DHA also is an important component of the photoreceptor of the retina. These fatty acids are supplied to the fetus from maternal plasma during pregnancy, and it is believed that the preterm infant born during the third trimester is at much greater risk for deficiency of these LC-PUFAs than the term infant. It is hypothesized that the addition of DHA to infant formula will improve infant visual function, and that the addition of both DHA and ARA will improve cognitive development. However, to date, the relatively few studies testing these hypotheses have yielded variable results.

Is there any harm to adding DHA or ARA to infant formulas? In approving the addition of these oils to infant formula, the FDA expects infant formula manufacturers to sponsor scientific studies and to pursue rigorous post-marketing surveillance and monitoring of formulas containing DHA and ARA. This recommendation implies that infants may still be at risk for unknown adverse effects of these oils. A negative effect on growth of DHA supplements when provided alone has been reported in preterm infants, but when DHA is combined with ARA as a supplement for formula, no adverse effects on growth have been observed in either term or preterm infants. Concerns have been raised that the addition of LC-PUFAs to formulas for preterm infants will increase the likelihood of oxidant damage, but to date no differences have been reported in the incidence of bronchopulmonary dysplasia, necrotizing enterocolitis or other neonatal conditions in infants receiving supplements of either DHA or both ARA and DHA, compared with unsupplemented formula.

Expert panels from Life Sciences Research Organization assessed nutrient requirements for both term and preterm infant formulas and recommended neither a minimum nor maximum content of either ARA or DHA for term infant formula (Raiten DJ, et al. J Nutr. 1998;128:2059S-2093S). For preterm infant formula, they recommended maximum levels of 0.35% and 0.6% of total fatty acid intake for DHA and ARA, respectively. No minimum levels were recommended (according to a yet-to-be-published study). However, the report concludes that the benefits reported to date for preterm infants are modest and in part transient, thus supporting an optional rather than a mandatory addition of the LC-PUFA to preterm formula.

Given the relative paucity of data on this subject, the AAP Committee on Nutrition (CON) has recommended that the Academy not take an official stand at this time on the addition of LC-PUFAs to term infant formulas. Concerns are raised, however, that the recently introduced formulas are not intended for use in preterm infants, the group most likely to benefit from additional quantities of these fatty acids. (Further FDA approval is necessary for the addition of LC-PUFAs to preterm infant formula.) Though it recently granted approval for the addition of the LC-PUFA oils to infant formula (as noted previously), the FDA has expectations that the formula companies will continue to pursue post-marketing scientific studies and surveillance. As guidelines for such studies of infant formula are nonexistent, and it is yet unclear how the FDA will assure that such studies are completed, CON urges caution regarding the addition of other bioactive factors to formula with similar post-marketing expectations in the future.

What is the bottom line for pediatricians and families? Breast milk still remains the feeding of choice and the availability of these formulas does not change this fact. Pediatricians are urged to discuss with parents what is known about the potential benefits of adding LC-PUFAs to formulas for term infants, while weighing this information against the increased costs of these new products. It should be made clear that at this time these formulas are one of many alternative products available for infants.