|Joseph F. Borzelleca, Ph.D.
Medical College of Virginia
Dale J. Chodos, M.D.
Dean O. Cliver, Ph.D.
University of California, Davis
Michael A. Dubick, Ph.D.
Fort Sam Houston, TX
Ronald E. Kleinman, M.D.
Massachusetts General Hospital
Manfred Kroger, Ph.D.
Pennsylvania State University
|Roger P. Maickel, Ph.D.
Stuart Patton, Ph.D.
Pennsylvania State University
William O. Robertson, M.D.
University of Washington School of Medicine
Gilbert L. Ross, M.D.
Herbert P. Sarett, Ph.D.
Elizabeth M. Whelan, Sc.D., M.P.H.
Ekhard W. Ziegler, M.D.
University of Iowa
- Experts disagree about whether it is necessary to include the long-chain polyunsaturated fatty acids docosahexaenoic acid (DHA) and arachidonic acid (ARA) in infant formulas to promote optimal brain and visual development.
- It has been widely reported in the news media that breastfed children have higher IQs than formula-fed children, and that the presence of DHA and ARA in human milk is responsible for this difference. However, the scientific evidence does not conclusively support either of these statements. In actuality, it is uncertain whether there is any difference in IQ between breastfed and formula-fed children that cannot be accounted for by differences in parental education, family income, and related factors. If a true difference in IQ does exist, components of human milk other than DHA and ARA and/or aspects of breastfeeding other than milk composition may be responsible.
- Several research studies have compared the visual or neurological development of infants receiving formulas supplemented with DHA/ARA with that of infants receiving conventional formulas. The results of these studies have also been inconsistent. Because few of the studies have followed the children beyond the age of two years, the long-term effects of DHA/ARA supplementation on development continue to be unknown.
Some concerns have been raised about the safety of adding DHA/ARA to infant formulas. Actually, the safety issues in question appear to be relatively minor. But because infant formula is the sole source of nutrients for many infants, making changes in formula composition must always be approached with extreme caution. Based on extensive clinical testing, the U.S. Food and Drug Administration has approved supplementation of formulas intended for full-term infants with DHA and ARA.
The American Council on Science and Health has examined the issue, and has also concluded that such supplementation is safe. While currently available scientific evidence does not clearly establish the advantages of including DHA and ARA in infant formulas, such supplemented formulas have been used safely in many countries.
- Although breastfeeding is the preferred form of infant feeding, formula-feeding is an acceptable alternative that provides adequate nutrition. The infant formulas currently sold in the U.S. are designed to provide complete nutrition for young infants and to serve as a major source of nutrients for older infants. DHA- and ARA-supplemented formulas are now being offered in the United States. Their composition and production, like those of all infant formulas, are strictly controlled by federal law. Parents can be confident that the formulas that they feed to their infants are safe and nutritious, as long as they are prepared and handled correctly.
- Sigma Economic issues may also help determine the choice of infant formula. DHA/ARA-supplemented formulas may be expected to be somewhat more expensive than similar ones that do not contain these fatty acids.
- Currently, long-term studies that demonstrate a clear developmental advantage for infants fed DHA- and ARA-supplemented formulas are lacking. Thus, ACSH cannot urge all parents who elect to use formulas to choose the DHA- and ARA-supplemented varieties. Such decisions must be made on an individual basis with input from an infant's healthcare provider.
The question of whether it is beneficial to add certain fatty acids to infant formula remains controversial. These fatty acids, docosahexaenoic acid (DHA) and arachidonic acid (ARA), are present in human milk and are believed by some experts to play an important role in early visual and neurological development. Thus, some researchers think that any formula without DHA and ARA is a deficient product providing less-than-optimal nutrition. Others argue, however, that the addition of these fatty acids to infant formula has not been shown conclusively to be useful. The controversy has spilled over into the popular press as well as the scientific literature; even some formula manufacturers seem reluctant to urge universal use of the supplemented formulas (1).
This special report by the American Council on Science and Health (ACSH) reviews the current scientific evidence on the role of DHA and ARA in infant nutrition. The report focuses primarily on the nutritional needs of healthy, full-term infants. Premature infants and those with special health problems may have different nutritional needs.
Background: Basic Facts About Fats
The fats in our diet and in our bodies contain a variety of different types of fatty acids. Fatty acid molecules consist primarily of long hydrocarbon chains (chains of carbon atoms with hydrogen atoms bound to them) (2). Many of the common fatty acids contain 18 carbons. However, some fatty acids have longer chains, and others have shorter ones.
The links in the carbon chain of a fatty acid may consist of either single bonds or double bonds, as shown in Figure 1. The number and position of double bonds in fatty acids are very important in terms of their effects in the human body and their health implications.
In a saturated fatty acid, all of the links between carbon atoms are single bonds. In an unsaturated fatty acid, at least one link is a double bond. An unsaturated fatty acid that has only one double bond is called monounsaturated. An unsaturated fatty acid with two or more double bonds is called polyunsaturated. Figure 2 shows examples of saturated, monounsaturated, and polyunsaturated fatty acids. In numbering, the left-most carbon atom is number 1.
There are two different families of polyunsaturated fatty acids: the n-3 series and the n-6 series (2). The numbers refer to the location of the first double bond in the carbon chain either at the third or the sixth carbon atom. Figure 3 shows the locations of these double bonds. One n-3 and one n-6 polyunsaturated fatty acid are essential nutrients, meaning that they must be supplied by the diet. The human body can perform the biochemical reactions necessary to convert some of the fatty acids to others within a series, but it cannot convert an n-6 fatty acid into an n-3 fatty acid or vice versa. Table 1 lists some major food sources of n-3 and n-6 fatty acids. The n-6 fatty acid called linoleic acid and the n-3 fatty acid called alpha-linolenic acid are considered essential fatty acids.
Table 1: Food Sources of Polyunsaturated Fatty Acids
|n-6 Polyunsaturated Fatty Acids
- Vegetable oils such as corn, safflower, sunflower, and soybean oils
- Nuts and seeds
- Processed foods containing vegetable oils
n-3 Polyunsaturated Fatty Acids
- Fatty fish, such as herring, mackerel, sardines, and salmon (these foods contain very-long-chain n-3 fatty acids)
- Certain vegetable oils, including soybean and canola oils (these foods contain alpha-linolenic acid, which serves as a precursor to the very-long-chain n-3 fatty acids)
Both n-3 and n-6 fatty acids play important roles in the human body. In many of these roles, the two families of fatty acids have either complementary or contrary effects. It is possible, therefore, that the ratio of n-3 to n-6 fatty acids may be as important to health and nutrition as the absolute amounts present in the diet or in body tissues. Current Western diets tend to be relatively high in n-6 fatty acids and relatively low in n-3 fatty acids. This is due to our high intake of vegetable oils, which are rich in n-6 fatty acids, and our low intake of oils and foods rich in n-3 fatty acids, such as fatty fish.
Infant Formula: A Very Special Type of Food
Infant formula is a very special food product because it is intended to be used as the sole source of nourishment during the first four to six months of life (3). It must meet all of an infant's nutritional needs over this prolonged critical period, without any harmful inadequacies or excesses. Its composition is crucial to the infant's health.
Because human milk is considered to be the ideal food for full-term infants, it has served as the model for the composition of formulas. However, formulas need not exactly duplicate the composition of human milk. Formulas differ from human milk in several ways. For example, the levels of some nutrients in infant formula are deliberately made higher than those in human milk in order to compensate for differences in bioavailability (how well the body can absorb the nutrients).
Formulas intended for premature infants are a special case. After all, in the ideal situation, these infants wouldn't be eating at all. They would still be in the uterus, where they would receive nutrients through the placenta. The feeding of tiny infants who are not developmentally ready to eat is a particular challenge. Even human milk cannot fully meet certain of their nutritional needs (especially in the case of very low birth weight infants) and should be fortified with additional protein, certain vitamins, and minerals (3). Similarly, conventional formulas used in the feeding of full-term infants are not well suited for premature infants; for them, special fortified preterm formulas should be used (3).
|History of Infant Formulas
One hundred years ago, infants who weren't breastfed usually didn't survive. Today, thanks to modern infant formulas, practically all infants can thrive, even if it is impossible for their mothers to nurse them.
Commercial infant formulas were first widely marketed after World War II (45). The early formulas consisted of whole or evaporated cows' milk, water, and sugar. However, these formulas were found to be less than satisfactory for several reasons: the protein content was too high, the amounts of iron and nutritionally essential fatty acids were too low, and the fat was poorly absorbed. Over the decades, the composition of infant formulas has evolved as researchers learned how to meet infants' nutritional needs.
Most infant formulas are based on cows' milk, but the composition of the milk has been extensively modified to make it suitable for an infant. During the preparation of formula, the protein content of cows' milk is reduced, the butterfat is replaced by a mixture of animal and vegetable fats, and additional amounts of lactose or other carbohydrates are added (2). For infants who cannot tolerate cows' milk because of allergy, lactose intolerance, or other medical problems, formulas based on soy protein or hydrolyzed protein are available. All of these formulas are designed to provide complete nutrition for young infants and to serve as the major source of nutrients for older infants who have begun to eat other foods.
In the United States, the composition of infant formulas is strictly controlled, according to the provisions of the Infant Formula Act of 1980. Formulas must contain at least a required minimum amount of each of 29 nutrients, and they cannot contain more than a specified maximum level of nine nutrients (2). Experts review and revise the minimum and maximum nutrient level guidelines regularly to ensure that they reflect the most up-to-date scientific knowledge. Infant formula manufacturers are required to analyze every batch of formula to make sure that the correct levels of nutrients are present, to test samples for stability during the shelf life of the product, and to code every formula container so that individual batches can be identified (45).
Fats in Breast Milk and Infant Formula
Almost 50% of the calories in human milk and infant formula come from fat (3,4). To people who are accustomed to thinking in terms of adults' nutritional needs, this may seem astonishingly high. However, infants need this high level of fat in their diets in order to grow properly. The reduced-fat diets that are healthful for adults are not appropriate during the first two years of life (3).
Both human milk and infant formula contain a variety of different fatty acids. The exact mixture of fatty acids in commercial formulas, however, differs from that of human milk (3).
The fats in human milk are absorbed very easily from the digestive tract into the bloodstream. The fats in cows' milk are not so easily absorbed by human babies, however. To provide infants with a more absorbable fat source, manufacturers remove the butterfat from the cows' milk used in the preparation of infant formulas and replace it with a blend of vegetable oils that provides appropriate proportions of saturated and unsaturated fatty acids (3). Infant formulas are required to contain sufficient amounts of the two fatty acids that are known to be essential in human nutrition linoleic acid and alpha-linolenic acid (4).
Fatty Acids and Neurological Development
Docosahexaenoic acid (DHA) is an n-3 fatty acid with 22 carbon atoms. Arachidonic acid (ARA) is an n-6 fatty acid with 20 carbon atoms. During the last trimester of pregnancy, large amounts of these fatty acids, especially DHA, are deposited in the brain and in the retina of the eyes of the fetus. The relative amounts of these fatty acids in the brain and eyes continue to increase in the months after birth, and thus they are believed to be important in normal neurological and visual development in the fetus and infant.
Fatty Acids in Human Milk and Formula
Human milk naturally contains DHA and ARA, with levels varying depending on the mother's diet (4). Women consuming typical North American diets usually have relatively low milk DHA levels (0.2-0.4% of total fatty acids) (4). In contrast, DHA levels as high as 1.4% of fatty acids have been found in the milk of women who eat large amounts of fish (4). ARA levels in human milk have also been found to vary in women from different parts of the world who eat different types of diets (5,6). Human milk content of these fatty acids can also be increased if a lactating mother's diet is supplemented with them (7).
Currently, most standard infant formulas sold in the United States contain no DHA or ARA, but they do contain other fatty acids (alpha-linolenic acid and linoleic acid) that the infant can convert into DHA and ARA. Both full-term and premature infants can synthesize DHA and ARA from these precursors (8-10). It is uncertain, however, whether infants can produce enough DHA and ARA in this way to completely meet their needs (11). It is this uncertainty that has prompted the controversy about whether or not DHA and ARA should be added directly to infant formulas.
Cognitive Development in Breastfed and Formula-fed Infants
More than 20 scientific studies have compared the mental development of breastfed infants with that of formula-fed infants (12). In most of these studies, the test scores of children who had been breastfed tended to be higher than those of children who had been formula-fed. However, it has been difficult for scientists to determine whether this difference was due to the type of milk per se. The mothers of the infants in these studies chose for themselves whether to breastfeed or formula-feed; they were not assigned randomly to one condition or the other. Surveys have shown that, at least in the United States, women who choose to breastfeed tend to be older and more highly educated than those who do not (3,13). They also have higher family incomes. These factors, rather than breastfeeding itself, might be responsible for differences in the infants' test scores.
To attempt to resolve this issue, a group of researchers conducted a combined analysis of 11 similar studies of infant feeding and cognitive development that considered other factors as well. (12). These included socioeconomic status and the mothers' levels of education (which are markers of the mothers' IQ and parenting skills). They found that the average IQ scores of the breastfed children in these studies were 5 points higher than those of the formula-fed children before the other factors were taken into account. After the other factors were considered, the difference narrowed to 3 points. In both instances, the differences between the breastfed and formula-fed groups were statistically significant.
This doesn't necessarily mean, however, that the DHA and ARA in human milk are responsible for even this small difference in IQ. Other components of human milk may also be involved (14). The experience of breastfeeding, rather than the composition of the milk, might also be a relevant factor (14). In addition, characteristics of the mothers that were not controlled in the combined analysis may play a role. For example, in a study that was completed too recently to be included in the combined analysis, no difference was found between the IQs of breastfed and formula-fed children when the mothers' IQs and their scores on a test of parenting skills were taken into account (15). None of the earlier studies of infant feeding and intelligence directly measured these two factors.
Thus, it is unclear whether the IQs of breastfed children are truly higher than those of formula-fed children, and if a difference does exist, it is uncertain whether the DHA or ARA content of human milk is even partially responsible.
Effects of Diet on Blood Levels of Fatty Acids
The amounts and proportions of fatty acids in the diet do influence the fatty acid composition of blood and body tissues. This is true in both infants and adults. Nursing mothers who consume large amounts of fatty fish have higher levels of DHA in their milk than do mothers whose diets do not include such foods (16,17).
The blood DHA and ARA levels of infants fed standard formulas are lower than those of breastfed infants (18-21). And in breastfed babies, one study found that blood levels of DHA were associated with somewhat improved visual and neural development (22). The feeding of formulas supplemented with DHA or ARA can increase blood levels of these fatty acids so that they more closely resemble those found in breastfed infants (20,21,23-26). It is unclear, however, whether these biochemical differences translate into meaningful effects on development and function. The mere fact that blood levels of fatty acids vary in infants receiving different diets does not mean that the levels of these fatty acids cause a specific functional outcome. To determine this, it is necessary to examine the relationship between dietary intake, blood or tissue levels of specific fatty acids, and measures of actual functioning such as visual acuity tests or cognitive tests.
Studies of Visual Acuity and Neurological Development in Full-Term Infants
Only a small number of studies have sought to evaluate the effects of formula supplementation with DHA (or DHA and ARA) on measures of visual function or neurological development in full-term infants, and their results have been inconsistent. Table 2 lists the results of these studies. Most of the studies listed in the table included only small numbers of infants and assessed their visual function or neurological development at only one or a few time points. None of the studies completed to date followed the children beyond the age of two years. Thus, nothing is really known about the effects of formula supplementation on long-term development into later childhood, adolescence, or adulthood. Clearly, further research, including longer-term studies, is needed. There have been a few recent review reports that combine results of smaller studies (see Table 2). One found benefit from supplementation on cognitive development at 18 months of age (27). Similarly, one review of visual acuity studies found a benefit from DHA supplementation for two month-old babies (28), but another did not (29).
Table 2: Results of Studies of Formula Supplementation in Full-Term Infants
|Studies that evaluated infants' vision
||No differences in visual acuity were found at several ages between 2 and 14 months between infants fed formulas with or without ARA + DHA supplementation or breastfed for the first 3 months of life. After 3 months, formula (supplemented or unsupplemented) was fed as a weaning formula.
||A review of both randomized and non-randomized comparisons of visual acuity found a positive effect of formula supplemented with DHA when infants were tested at 2 months of age.
||A review of 9 randomized studies found little evidence that formula supplementation with LCPUFA* benefits visual development of term infants.
||Infants who had received fish oil-supplemented formula showed better visual acuity at the ages of 16 and 30 weeks than those who received conventional formula.
||Infants who had received formulas supplemented either with DHA or DHA + ARA showed better visual acuity at 6, 17, and 52 weeks of age than those who had received conventional formula.
||Infants who had received ARA- and DHA-supplemented formula showed better visual acuity than those who had received conventional formula when tested at age 2 months but not at ages 4, 6, 9, and 12 months
||No differences in visual acuity were found at ages 2, 4, 6, 9, and 12 months between infants who had received supplemented formula (DHA or DHA + ARA) and those who had received conventional formula.
||No differences in visual acuity were found at age 4 months between infants who had received supplemented formula and those who had received conventional formula. The supplemented formula contained DHA and another long-chain fatty acid, gamma-linolenic acid.
||No differences in visual acuity were found at ages 16 and 34 weeks between infants who had received supplemented formula (with DHA or DHA + ARA) and those who had received conventional formula.
||Infants fed supplemented formula (with DHA or DHA + ARA) had more mature visual responses at 6 weeks of age than those fed unsupplemented formula; they also performed better on tests of visual function at 1 year of age than babies fed the unsupplemented formula.
|Studies that evaluated infants' neurological or intellectual development
||Infants fed formulas supplemented with DHA + ARA for the first year of life evidenced no improvement on several indices of growth and intellectual development compared to infants fed unsupplemented formulas. Both groups were similar to infants who were initially breastfed and later switched to formulas.
||Infants who received supplemented formulas (DHA + ARA) up to 17 weeks of age had better scores on several indices of mental development at 18 months of age than did babies who received unsupplemented formulas.
||A review of seven randomized studies of the effects of LCPUFA*supplementation on infant development found inconsistent results across studies. Reviewers considered that a beneficial effect on infants' information processing was possible but not strongly confirmed by these studies.
||No differences were found between infants who had received supplemented formula and those who had received conventional formula on developmental tests performed at ages 1 and 2 years. Supplemented formula contained DHA or DHA + ARA.
||Infants who had received supplemented formula (DHA + ARA) performed better on a problem-solving test at age 10 months than those who had received conventional formula.
||Infants who had received DHA + ARA-supplemented formula scored better than those who had received conventional formula on tests of neurological development administered at age 4 months but not at age 24 months.
||No differences were found between infants who had received DHA + ARA-supplemented formula and those who had received conventional formula on developmental tests performed at ages 9 and 18 months.
||Infants who had received supplemented formula (DHA or DHA + ARA) had poorer scores than those who had received conventional formula on a measure of vocabulary development at age 14 months. No other differences were found between the two groups in developmental tests administered at ages 12 and 14 months.
* LCPUFA stands for long chain polyunsaturated fatty acids. This category includes both DHA and ARA, and may include other fatty acids as well.
Sources of Supplemental DHA and ARA
DHA and ARA for use in infant formula can come from egg yolk lipids (a source of both DHA and ARA), fish oil (a source of DHA only), or oils derived from special strains of single-celled algae and fungi (the algae synthesize DHA and the fungi synthesize ARA). The DHA- and ARA-supplemented infant formulas currently on the U.S. market derive their fatty acids from algal, fungal, and tuna oil sources, not from egg yolk lipids (42,43).
The principal concern about oils derived from algae and fungi (also called single-cell oil) has been that they are new food ingredients without a history of safe use in infant feeding in this country. All new food ingredients must undergo formal safety testing before they can be allowed in the food supply. Extensive toxicological studies have been conducted on oils from algae and fungi, with generally favorable results (4), and authorities in several countries have approved their use in infant formula. The U.S. Food and Drug Administration (FDA), after being petitioned by one manufacturer of single-cell oil (as is the normal procedure), declared them to be Generally Recognized as Safe (GRAS), thereby permitting their use in infant formulas (44).
One important safety issue that may pertain to all sources of DHA is the possible adverse developmental effect reported in one study of infants receiving supplemented formula (41). In that study, infants who had received formula supplemented with DHA from fish oil had lower scores on one vocabulary measure at age 14 months than breastfed infants did. On another vocabulary measure, the scores of fish oil-supplemented infants were lower than those of infants fed conventional formula. In the same study, infants receiving a formula supplemented with both DHA and ARA (from egg yolk lipids) did not show any evidence of adverse effects. It is unclear from this single study whether the lower scores in the DHA-only group were due to a specific effect of DHA, to the lack of ARA in the fish oil-supplemented formula, to other factors, or simply to random chance.
Concerns have also been raised about the possibility that formulas supplemented with DHA might lead to slower growth in infants. Slower growth was observed in two studies of preterm infants who received formulas supplemented with fish oil (45,46). The lack of ARA in these formulas may have been responsible for the effect. No adverse effects on growth have been observed in any studies in which formulas were supplemented with both DHA and ARA or in any studies of full-term infants. In fact, four studies of full-term infants that specifically addressed the growth issue (all of which involved both DHA and ARA) found no evidence of any adverse effect (24,26,40,47).
It is important to emphasize that there is no substantial, replicated body of evidence that feeding infants formulas supplemented with any of the available sources of DHA or ARA causes any harm or developmental delay.
|Don't Try This at Home!
A few sites on the World Wide Web have suggested that parents can improve their infants' formula by adding dietary supplements that contain DHA to the bottles. ACSH strongly recommends against the addition of these supplements or any other substances to infant formula. Modern infant formula is a closely controlled, high-technology product containing a careful balance of specially prepared nutrients. To maintain its safety and nutritional value, parents should always prepare formula as the label directs, without any additions or modifications. Adding supplemental fatty acids to commercial formula could create a nutritional imbalance that might be harmful to an infant's health.
Divergent Views on the Addition of DHA and ARA to Infant Formula
Scientists, health professionals, and officials in various countries differ in their views on whether DHA and ARA should be added to infant formula. Although some people have claimed that these divergent views are attributable to ulterior economic motives, it seems more likely that they reflect honest disagreements on how best to interpret an incomplete body of scientific evidence.
On the basis of the currently available evidence, authorities in some Asian and European countries have decided to allow but not require the inclusion of DHA and ARA in infant formulas. Various international organizations including the European Society for Pediatric Gastroenterology and Nutrition, the British Nutrition Foundation, the WHO/FAO Expert Committee on Fats and Oils in Human Nutrition, and the International Society for the Study of Fatty Acids and Lipids, have also approved their use (48).
An expert panel that was commissioned by the FDA to assess nutrient requirements for formulas issued a report in 1998 that recommended against the addition of DHA and ARA to full-term infant formulas at that time (4). The panel members concluded that the evidence of benefits to visual acuity or neurodevelopment was still inconclusive. The panel recommended that the question of including DHA and ARA in infant formulas should be reassessed within five years, after additional research has been completed. While the agency usually follows the advice of its expert panels, in this case, when additional studies showed no evidence of harm, and some showed benefits, the FDA is allowing sales of ARA and DHA-supplemented formulas, as noted above.
ACSH's View: Parents' Decision
After reviewing the scientific evidence, ACSH believes that the evidence for benefits of DHA and ARA-supplemented infant formulas is still equivocal at this time. The studies that have been completed to date have not consistently shown that supplementation of formulas with DHA and ARA has a lasting beneficial effect on infant development. It must be noted, however, that not all studies used the same methodologies supplementation levels, identity of fatty acid(s) added, ratio of n-3 to n-6 fatty acids, outcome measures, and ages differed and this fact may have influenced the lack of consistency in results. It does seem clear that such supplementation does not retard developmental progress. The Nutrition Committee of the American Academy of Pediatrics has noted the lack of a clear beneficial effect of DHA and ARA on infant development. The committee has suggested that the Academy not take an official stand on formula supplementation until more data on its effects has been collected (49).
At present, both supplemented and unsupplemented versions of the same formulas are available to American parents, and thus they will be able to choose which one they use. The supplemented versions will likely be more expensive than the unsupplemented ones (49). ACSH urges parents who choose to feed formula to discuss their choices with their infant's healthcare provider before opting for one type over the other.
The Special Situation of Premature Infants
The balance of risks, costs, and benefits of DHA/ARA supplementation for premature infants may prove to be different from that for full-term infants. Some experts believe that premature infants may have a greater need for dietary sources of DHA because they miss out on the DHA transfer from their mothers that ordinarily occurs near the end of pregnancy. On the other hand, because premature infants are fragile, they may be especially vulnerable to any adverse effects that might result from changes in formula composition.
Several studies have shown that premature infants who received formulas supplemented with DHA alone or DHA plus ARA had better scores on measures of visual function than those receiving unsupplemented formulas (34,39-43). In some of these studies, however, the effects were transient, disappearing as the infants grew older (34,39). Overall, the evidence for a potential benefit of DHA and ARA is stronger for premature infants than for full-term infants. Nevertheless, uncertainties remain because most of the studies have involved only small numbers of infants, who were followed for relatively short periods of time.
There is an urgent need for additional, longer-term studies of DHA and ARA supplementation in premature infants. Unlike full-term infants, many premature infants (especially those born very early or at very low birth weights) do not thrive. Providing them with the best possible nutrition may help to increase their chances of survival and decrease the risk of long-term health problems.
Putting the Fatty Acid Controversy into Perspective
Modern infant formulas are safe and nutritious. They contain all of the nutrients known to be essential to infants' health, including essential fatty acids. Practically all formula-fed full-term infants thrive, just as practically all breastfed full-term infants thrive.
It may be helpful to parents to know that enhanced cognitive development is not advocated as a major reason why breastfeeding is considered superior to formula feeding. The number one argument in favor of breastfeeding is that it substantially reduces the risk of infectious diseases, such as ear infections, lower respiratory tract infections, and gastrointestinal illnesses (3,37,44).
Although breastfeeding is the preferred method of infant feeding, formula-feeding is certainly an acceptable alternative. Parents who feed their infants any of the commercial iron-fortified infant formulas currently available in the United States and that now includes ARA- and DHA-supplemented versions can be confident that they are providing their infants with appropriate and adequate nutrition.
1. Rubin R. Formula for bright babies?; experts consider whether fatty acids can affect IQ. USA Today Feb. 21, 2002.
2. American Council on Science and Health, Facts about fats. Health effects of dietary fats and oils, New York: ACSH, 1995.
3. AAP (American Academy of Pediatrics), Pediatric nutrition handbook, Elk Grove Village, IL: American Academy of Pediatrics, 1998.
4. LSRO (Life Sciences Research Office) Report: Assessment of nutrient requirements for infant formulas, J Nutr 1998;128:2059S-2293S.
5. Chen ZY, Kwan KY, Tong KK, Ratnayake WM, Li HO, Leung SS, Breast milk fatty acid composition: a comparative study between Hong Kong and Chongqing Chinese, Lipids 1997;32:1061-1067.
6. Ruan C, Liu X, Man H, Ma X, Lu G, Duan G, DeFrancesco CA, Connor WE, Milk composition in women from five different regions of China: the great diversity of milk fatty acids, J Nutr 1995;125:2993-2998.
7. Helland IB, Saugstad OD, Smith L, Saarem K, Solovoll K, Ganes T, Drevon CA. Similar effects on infants on n-3 and n-6 fatty acids supplementation to pregnant and lactating women. Pediatrics 2001; 108(5):E82.
8. Demmelmair H, von Schenck U, Behrendt E, Sauerwald T, Koletzko B, Estimation of arachidonic acid synthesis in full term neonates using natural variation of 13C content, J Pediatr Gastroenterol Nutr 1995;21:31-36.
9. Sauerwald TU, Hachey DL, Jensen CL, Chen H, Anderson RE, Heird WC, Effect of dietary alpha-linolenic acid intake on incorporation of docosahexaenoic and arachidonic acids into plasma phospholipids of term infants, Lipids 1996;31:S131-S135.
10. Carnielli VP, Wattimena DJ, Luijendijk IH, Boerlage A, Degenhart HJ, Sauer PJ, The very low birth weight premature infant is capable of synthesizing arachidonic and docosahexaenoic acids from linoleic and linolenic acids, Pediatr Res 1996;40:169-174.
11. Gibson RA, Makrides M, The role of long chain polyunsaturated fatty acids (LCPUFA) in neonatal nutrition, Acta Paediatr 1998;87:1017-1022.
12. Anderson JW, Johnstone BM, Remley DT, Breast-feeding and cognitive development: a meta-analysis, Am J Clin Nutr 1999;70:525-535.
13. Ryan AS, The resurgence of breastfeeding in the United States, Pediatrics 1997;99:E12.
14. Uauy R, Peirano P, Breast is best: human milk is the optimal food for brain development, Am J Clin Nutr 1999;70:433-434.
15. Jacobson SW, Chiodo LM, Jacobson JL, Breastfeeding effects on intelligence quotient in 4- and 11-year-old children, Pediatrics 1999;103:E71.
16. Jorgensen MH, Hernell O, Hughes E, Michaelsen KF. Is there a relation between docosahexaenoic acid concentration in mothers' milk and visual development in term infants? J Pediatr Gastroenterol Nutr 2001; 32(3):293-6.
17. Williams C, Birch EE, Emmett PM, Northstone K; Avon Longitudinal Study of Pregnancy and Childhood Study Team. Stereoacuity at age 3.5 y in children born full-term is associated with prenatal and postnatal dietary factors: a report from a population-based cohort study, Am J Clin Nutr 2001; 73(2):316-22.
18. Sanders TAB, Naismith DJ, A comparison of the influence of breast-feeding and bottle-feeding on the fatty acid composition of the erythrocytes, Br J Nutr 1979;41:619-623.
19. Putnam JC, Carlson SE, DeVoe PW, Barness LA, The effect of variations in dietary fatty acids on the fatty acid composition of erythrocyte phosphatidylcholine and phosphatidylethanolamine in human infants, Am J Clin Nutr 1982;36:106-114.
20. Innis SM, Auestad N, Siegman JS, Blood lipid docosahexaenoic and arachidonic acid in term gestation infants fed formulas with high docosahexaenoic acid, low eicosapentaenoic acid fish oil, Lipids 1996;31:617-625.
21. Bondia-Martinez E, Lopez-Sabater MC, Castellote-Bargallo AI, Rodriguez-Palmero M, Gonzalez-Corbella MJ, Rivero-Urgell M, Campoy-Folgoso C, Bayes-Garcia R, Fatty acid composition of plasma and erythrocytes in term infants fed human milk and formulae with and without docosahexaenoic and arachidonic acids from egg yolk lecithin, Early Hum Dev 1998;53:S109-S119.
22. Innis SM, Gilley J, Werker J. Are human milk long-chain polyunsaturated fatty acids related to visual and neural development in breast-fed term infants? J Pediatr 2001; 139(4):532-8.
23. Koletzko B, Decsi T, Demmelmair H, Arachidonic acid supply and metabolism in human infants born at full term, Lipids 1996;31:79-83.
24. Decsi T, Koletzko B, Growth, fatty acid composition of plasma lipid classes, and plasma retinol and alpha-tocopherol concentrations in full-term infants fed formula enriched with omega-6 and omega-3 long-chain polyunsaturated fatty acids, Acta Paediatr 1995;84:725-732.
25. Makrides M, Neumann MA, Simmer K, Gibson RA, Erythrocyte fatty acids of term infants fed either breast milk, standard formula, or formula supplemented with long-chain polyunsaturates, Lipids 1995;30:941-948.
26. Auestad N, Halter R, Hall RT, Blatter M, Bogle ML, et al. Growth and development in term infants fed long-chain polyunsaturated fatty acids: a double-masked, randomized, parallel, prospective, multivariate study, Pediatrics 2001; 108:372-381.
27. Birch EE., Garfield S, Hoffman DR, Uauy R, Birch DG. A randomized controlled trial of early dietary supply of long-chain polyunsaturated fatty acids and mental development in term infants, Dev Med Child Neurol 2000; 42(3): 174-81.
28. SanGiovanni JP, Berkey CS, Dwyer JT, Colditz GA. Dietary essential fatty acids, long-chain fatty acids, and visual resolution acuity in healthy fullterm infants: a systemic review, Early Hum Dev 2000; 57:165-88.
29. Simmer K, Longchain polyunsaturated fatty acid supplementation in infants born at term (Cochrane Review), Cochrane Database Syst Rev 2001; 4:CD000376.
30. Makrides M, Neumann M, Simmer K, Pater J, Gibson R, Are long-chain polyunsaturated fatty acids essential nutrients in infancy? Lancet 1995;345:1463-1468.
31. Birch EE, Hoffman DR, Uauy R, Birch DG, Prestidge C, Visual acuity and the essentiality of docosahexaenoic acid and arachidonic acid in the diet of term infants, Pediatr Res 1998;44:201-209.
32. Carlson SE, Ford AJ, Werkman SH, Peeples JM, Koo WW, Visual acuity and fatty acid status of term infants fed human milk and formulas with and without docosahexaenoate and arachidonate from egg yolk lecithin, Pediatr Res 1996;39:882-888.
33. Auestad N, Montalto MB, Hall RT, Fitzgerald KM, Wheeler RE, Connor WE, Neuringer M, Connor SL, Taylor JA, Hartmann EE, Visual acuity, erythrocyte fatty acid composition, and growth in term infants fed formulas with long chain polyunsaturated fatty acids for one year. Ross Pediatric Lipid Study, Pediatr Res 1997;41:1-10.
34. Horby Jorgensen M, Holmer G, Lund P, Hernell O, Michaelsen KF, Effect of formula supplemented with docosahexaenoic acid and gamma-linolenic acid on fatty acid status and visual acuity in term infants, J Pediatr Gastroenterol Nutr 1998;26:412-421.
35. Makrides M, Neumann MA, Simmer K, Gibson RA, A critical appraisal of the role of dietary long-chain polyunsaturated fatty acids on neural indices of term infants: a randomized, controlled trial, Pediatrics 2000;105:32-38.
36. Hoffman DR, Birch EE, Birch DG, Uauy R, Castaneda YS, Lapus MG, Wheaton DH, Impact of early dietary intake and blood lipid composition of long-chain polyiunsaturated fatty acids on later visual development, J Pediatr Gastroenterol Nutr 2000; 31(5):540-53.
37. Willatts P, Forsyth JS, DiModugno MK, Varma S, Colvin M, Effect of long-chain polyunsaturated fatty acids in infant formula on problem solving at 10 months of age, Lancet 1998;52:688-691.
38. Agostoni C, Trojan S, Bellu R, Riva E, Giovannini M, Neurodevelopmental quotient of healthy term infants at 4 months and feeding practice: the role of long-chain polyunsaturated fatty acids, Pediatr Res 1995;38:262-266.
39. Agostoni C, Trojan S, Bellu R, Riva E, Bruzzese MG, Giovannini M, Developmental quotient at 24 months and fatty acid composition of diet in early infancy: a follow up study, Arch Dis Child 1997;76:421-424.
40. Lucas A, Stafford M, Morley R, Abbott R, Stephenson T, MacFadyen U, Elias-Jones A, Clements H, Efficacy and safety of long-chain polyunsaturated fatty acid supplementation of infant-formula milk: a randomised trial, Lancet 1999;354:1948-1954.
41. Scott DT, Janowsky JS, Carroll RE, Taylor JA, Auestad N, Montalto MB, Formula supplementation with long-chain polyunsaturated fatty acids: are there developmental benefits? Pediatrics 1998;102:E59.
42. Ross Products Division, Abbott Laboratories. Ross Products to launch Infant Formula Supplemented with two new fatty acids. Jan. 10, 2002. http://www.abbott.com/ross/index.cfm?id=334. Accessed March 6, 2002.
43. Mead-Johnson Co. press release. New Enfamil Lipil with Iron. http://www.enfamil.com/lipip/index.html. Accessed April 11, 2002.
44. FDA (U.S. Food and Drug Administration), Agency Response Letter, GRAS Notice No. GRN 000041, addressed to Mr. Henry Linsert, Jr. of Martek Biosciences Corporation International and dated May21, 2001. Available on the FDA's web site at: http://www.cfsan.fda.gov/~rdb/opa-g041.html.
45. Carlson SE, Cooke RJ, Werkman SH, Tolley EA, First year growth of preterm infants fed standard compared to marine oil n-3 supplemented formula, Lipids 1992;27:901-907.
46. Carlson SE, Werkman SH, Tolley EA, Effect of long-chain n-3 fatty acid supplementation on visual acuity and growth of preterm infants with and without bronchopulmonary dysplasia, Am J Clin Nutr 1996;63:687-697.
47. Makrides M, Neumann MA, Simmer K, Gibson RA, Dietary long-chain polyunsaturated fatty acids do not influence growth of term infants: a randomized clinical trial, Pediatrics 1999;104:468-475.
48. Anonymous, International Society for the Study of Fatty Acids and Lipids (ISSFAL) Board Statement: recommendations for the essential fatty acid requirement for infant formulas (June 1994), Nutrition Today 1995;30:46.
49. The Committee on Nutrition, American Academy of Pediatrics. New infant formula additives approved by FDA. AAP News 2002; 20(5):209. http://www.aapnews.org/cgi/content/full/20/5/209.