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Essential fatty acids and brain development: docosahexaenoic acid
Mental development in breast-fed infants
RICARDO UAUY AND ISIDORA DE ANDRACA2
1Prepared for the International Dietary Energy Consultative Group (IDECG) Task Force workshop on malnutrition and behavior at the University of California, Davis, CA, December 6-10, 1993. This workshop was supported by IDECG, the Nestle Foundation, Kraft Foods and the International Union for Nutritional Science. Guest editor for this supplement was Ernesto Pollitt, Department of Pediatrics, University of California, Davis, CA, 95616.
2To whom correspondence should be addressed: INTA University of Chile, Casilla 138-11, Santiago, Chile.
Instituto de Nutritión y Tecoología de los Alimentos (INTA), Universidad de Chile, Santiago, Chile
ABSTRACT Human milk has been characterized as the optimal food for human growth and development because of its nutritional, antiinfective and biological properties. Research conducted over the past decades provides further evidence on the uniqueness of human milk feeding for optimal brain development. The recognition of specific functions for the long chain essential fatty acids present in human milk as key components of neural membranes necessary for optimal brain development has provided a biological basis for this phenomenon. In addition the act of breast feeding provides unique mother-infant interactions opportunities that may have important implications for infant growth and development. These findings may have special relevance to populations in developing countries because this provides yet other very strong reasons to favor human milk feeding. J. Nutr. 125: 2278S-2280S, 1995.
INDEXING KEY WORDS:
human milk c breast
feeding essential fatty acids mental development infancy
Essential fatty acid deficiency is associated with specific findings in infants and young animals. The syndrome has been mostly related to linoleic acid deficiency, but, in most models, a deficiency in a-linolenic acid coexists. Recently v-3 fatty acids, especially docosahexaenoic acid (DHA)3 (C27:6 v-3] present in human milk were shown to be necessary for retinal and brain development in primates and humans (Anderson and Connor 1989, Simopoulus 1991, Uauy and Hoffman 1991). Rod photoreceptor function and the maturation of visual acuity of human low birth weight (LBW) infants are dependent on the supply of these essential nutrients (Birch et al. 1992, Birch BE et al. 1992, Uauy et al. 1990). Visual function of full-term infants fed human milk is enhanced for up to 3 y, supporting the concept of long-term benefits of human milk feeding on mental development (Birch et al. 1993). The LBW infants randomized to human milk or formula tube feeding served to demonstrate the benefits of human milk on IQ at age 8 y (Lucas et al. 1992).
3Abbreviations used: DHA, docosahexaenoic acid, LBW, low birth weight; OPL, operant preferential looking; RBC, red blood cell.
The plasma DHA concentrations of full-term infants fed formula are lower than that of breast-fed infants. This suggests that present formulas provide insufficient v-linolenic acid or chain elongation-desaturation enzymes are not sufficiently active during early life to support tissue accretion of DHA. Full-term infants may also be dependent on a dietary DHA source for optimal functional maturation of the retina and visual cortex (Birch et al. 1993). Furthermore, studies in infants born at term, dying from sudden infant death, revealed that brain composition is affected by human milk feeding in terms of higher DHA content in the brain cortex of breast-fed infants relative to infants receiving cow's milk-based formulas (Faquharson et al. 1992). However, no controlled trials of DHA supplementation of full-term infants are available to date.
We studied the effects of postnatal age on visual acuity maturation in full-term infants fed either human milk or cow milk formula containing 12-18% linoleic and 0.5-1.0% v-linolenic acid (Birch et al. 1993). These studies indicated that conceptional age, not postnatal age, determined visual maturation. Furthermore, indexes of visual acuity were more mature in 4-mo-old, exclusively breast-fed infants in comparison with formula-fed infants. At 4 mo of age, visual acuity measured using evoked potentials and expressed in Snellen equivalents, were mean 20/85 for the formula-fed and 20/65 for the human-milk fed infants. Behaviorally assessed acuities were mean 20/130 and 20/110, respectively (P < 0.01) (Birch et al. 1993).
We also completed a 3-y follow-up of
healthy, fullterm infants who participated in a controlled study of the effects of dietary
fat on lipoprotein metabolism (Birch et al. 1993). The cohorts were breast-fed from birth
to at least 4 mo or fed for 12 mo formula containing ample linoleic acid and 0.5% of the
total energy as a-linolenic acid. The breast-fed group was
weaned to an oleic acidpredominant formula and received egg yolk as a source of
cholesterol. The egg yolk also provided 80-100 mg DHA per day. The breast-fed group
maintained higher plasma and red blood cell (RBC) membrane phospholipid DHA concentrations
throughout the first year of life. At 3 y of age, stereo acuity, as measured by operant
preferential looking (OPL) techniques, was different between breast-fed and formula-fed
groups. Mean (+ SD) OPL stereo acuity was 42.1 ± 5 for the breast-fed and 92.8 ± 86.1 s
of arc for the formula-fed groups (P < 0.05). Because values varied greatly in the
formula group, the data were analyzed nonparametrically. This analysis showed that 92% of
the breast-fed group had OPL stereo acuity of < 40 s of arc (considered fully mature),
whereas only 35% of the formula-fed groups met that criteria (P < 0.001). Monocular
acuities assessed by OPL were similar in the breast-fed and formula-fed groups (mean
Snellen equivalents of 20/28 and 20/32, respectively) (P < 0.16). Visual recognition
was assessed by the child's ability to match three letters. In the breast-fed group, the
mean l+ SD) score was 2.71 ± 0.8, and in the formula-fed group, it was 1.82 ± 1.5 (P
< 0.04). Accordingly, 93% of the breast-fed group had a perfect score (3 of 3), whereas
only 61% in the formula-fed group met that criteria (P < 0.001). It is notable that
these differences could be found at 3 y of age in this select group by observers who were
blinded to the dietary group assignment (Birch et al. 1993).
In one of the few long-term follow-up studies of mental development comparing breast-fed with formula-fed children, where family, social and economic variables were controlled, early breast feeding was associated with better picture intelligence at 8 y of age, better scores in mathematics, nonverbal ability and sentence completion at 15 y of age (Rodgers 1978). The study cohorts were selected from all live births occurring during 1 wk in 1946 in Great Britain. On the basis of confirmed records of early diet, 1133 individuals were considered entirely bottle-fed and 1291 individuals were never bottle-fed. The functional benefits were proportional to the duration of breast feeding and remained statistically significant after controlling for social, cultural and demographic variables by multivariate analysis (Rodgers 1978). These observations could not be extrapolated to today's formula-fed infants because during the observation period children were fed unmodified, diluted cow's milk with the sole addition of sugar. Protein may have been excessive, and essential fatty acids may have been inadequate. However, a recent study from a cohort of 855 newborns, enrolled from 1978 to 1982 and followed through school age, using present day formula and modern methodology to assess cognitive development confirmed the results of the earlier British study (Rodgers 1978, Rogan and Gladen 1993). Breast-fed infants had significantly higher scores in the Bayley scale mental development index at 2 y and in the McCarthy scale at 3 and 4 y. In addition, slightly higher English grades on report cards were found in the breast-fed. Although the effects are not of a great magnitude (3-7%), they consistently show a statistically significant advantage for the human milk-fed group even 'after adjusting for the relevant confounding variables (Rogan and Gladen 1993). Other studies with less controlled designs point in the same direction in terms of improved mental abilities in the breast-fed infants. The effects are less pronounced but remain significant after controlling by multiple confounders (Morrow-Tlucak et al. 1988, Taylor and Wadsworth 1984).
In evaluating these results it is important to consider that the comparison of breast feeding vs. formula feeding becomes complex because there are differences in what is fed, who feeds it and how it is fed.
Formula differs from human milk in several nutritional components that may affect the biological basis of mental function: protein, nonprotein nitrogen choline, nucleotides and nucleic acids, polyamines, free amino acids, carnitine, minerals, cholesterol, fats phospholipids, essential fats, carotene and oligosaccharides. In addition, hormones and growth factors present in human milk such as IGF I and IGF II, insulin, cytokines, epidermal GF, thyroxine, cortisol and prolactin may play a role in the development of the nervous system.
There are also differences in parents who choose breast milk over formula. The decision of whether to breast-feed is linked to the mother's intelligence, education, socioeconomic level and infant birth weight. In addition, parents of breast-fed infants have a greater preoccupation for their infants development and educational achievement. Mothers are less authoritarian, have greater ego strength and provide an enhanced home environment (Jacobson et al. 1988, Jacobson and Jacobson 1992, Lucas et al. 1992). These factors may affect developmental outcome favorably, confounding the relationship between type of feeding and mental function.
In addition there are differences in taking the milk from the breast. The act of breast feeding itself has profound effects on the behavior and physiology of mothers and infants. Infant sucking determines in large part lactational performance due to prolactin and oxytocin release, which participate in mothering behavior. Breast odors induce specific behavioral responses in the infant, and close skin contact with the mother reduces stress and irritability, promoting improved maternal infant interaction (Porter 1989). Skin contact was found to exert a positive impact in strengthening maternal child bonds that will affect cognitive and emotional development. Close contact also favors a more gradual transition to the extrauterine environment because mother's heart sounds and temperature resembles that of the uterine milieu (Klaus and Kennel 1979). The fact that breast output matches infant intake tightly and that satiety is regulated by breast milk composition because fore milk is lower in fat than hinde milk illustrates the unique interactions that arise during the act of breast feeding (Woolridge and Fisher 1988). Educational programs can attempt to improve the quality of the feeding situation when using formula, but there are qualitative aspects in the physiologic process of breast feeding that cannot be reproduced by providing even optimal maternal support. The act of breast feeding cannot be reproduced by bottle feeding no matter how good the formula is or how interested the mother is on infant well-being.
Specific physiologic and interactive characteristics of breast feeding elicit a cascade of events that multiplies its potential immediate effects. It also suggests that there may well be potential long-term consequences of breast feeding that favor optimal mental development. Present criteria to judge adequacy of infant diets should not only include somatic growth but also the effect on the development of key organ systems such as the nervous system.
Most of the studies that approach the relation between mental development and breast feeding examine the effect of sociodemographic confounders, with less emphasis in interactive variables. It would be important to include in future studies confounding variables such as quality of the family environment in terms of infant needs, mother-infant interactions style and specific personality traits of mothers (that is, empathy, depression and anxiety). These and other variables need to be assessed during the period of breast feeding and later during different stages of follow-up.
The potential benefits of breast
feeding in economically developed societies remain to be fully determined, yet the case
for breast feeding in developing countries is certainly strengthened by the information
reviewed here. This is especially relevant for low birth weight and small for gestational
infants. Under conditions prevailing in developing countries one would expect that breast
feeding not only improves infant survival but that the quality of life of the survivors is
enhanced. As a final conclusion we suggest that the burden of proof should be placed on
those proposing that artificial formula may be equal to human milk feeding. Breast is best
unless proven otherwise.
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