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OMEGA 3 FATTY ACIDS IN YOUNG CHILDREN
OBJECTIF NUTRITION 84 (JUNE 2007) by Prof. Alexandre Lapillonne, Université René Descartes Paris V, Department of Neonatology and Nutrition, Public Assistance/Hospitals of Paris, Hôpital Saint-Vincent de Paul (Paris, France)
Omega 3 and Omega 6 fatty acids are important nutrients for the neurosensory development of the fetus and infant. During gestation and the first two years of life, DHA, an Omega 3 long-chain polyunsaturated fatty acid, preferentially accumulates in the membranes of photoreceptive cells of the retina and neurons, where it plays an essential role. Breast milk provides for the child´s Omega 3 needs during the first months of life. If breastfeeding proves to be insufficient, it is recommended, in light of current knowledge, to prescribe DHA-enriched infant formula.
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FOCUS The study of metabolism and the role of Omega 3 and Omega 6 polyunsaturated fatty acids (PUFA) has been one of the most active areas of research in pediatric nutrition in the last two decades. Linoleic acid and Alpha-linolenic acid are considered to be essential PUFA because they cannot be synthesized by the human body, and therefore must be provided by food. On the other hand, the human body is able to synthesize from these precursors other Omega 3 and Omega 6 fatty acids that are more unsaturated and have longer chains, commonly referred to as long-chain PUFA (LCPUFA) (figure 1).
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The recommendations on dietary intake of Omega 3 and Omega 6 essential fatty acids have been well established for many years. All infant formulas contain adequate quantities of linoleic acid and Alpha-linolenic acid. The more recent interest for Omega 3 and Omega 6 PUFA in pediatrics comes from the recognition of the importance of LCPUFA in the development and maturation of the nervous system of the fetus and infant.
Omega 3 LCPUFA AND NORMAL DEVELOPMENT OF THE BRAIN AND RETINA
Docohexaenoic acid (C22:6n-3), a fatty acid better known by the name DHA, is a long-chain Omega 3 PUFA that accumulates preferentially in the membranes of the photoreceptive cells of the retina and neurons, where it plays an essential role.
DHA begins to accumulate in the fetal brain tissue during the last trimester of pregnancy, and continues after birth for the first two years of life.
The mother´s status during pregnancy and lactation is therefore essential to provide the fetus or neonate with an optimal amount of Omega 3 and Omega 6 fatty acids. Pregnant and nursing women must follow the recommended dietary intake (RDI). In France, the RDI for adults as well as pregnant or nursing women is a Omega 6/Omega 3 ratio close to 5. The intake of linoleic and Alpha-linolenic acid should be increased by 25% during pregnancy and 37% during nursing (figure 2). Sources of this intake are sunflower and corn oil, which are rich in linoleic acid, and canola, soy, nut and flax oil, which are rich in Alpha-linolenic acid. The RDI also specify that an adult´s diet should include 100 mg/d of preformed DHA, but that intake should be increased by 150% during pregnancy and lactation, to reach 250 mg/d. Foods that are rich in DHA are mainly fish oils. It is perhaps also important for any woman of childbearing potential to follow these recommendations in order to have an optimal PUFA status at the start of any pregnancy.
FIGURE 1: ROLES OF Omega 3 AND Omega 6 POLYUNSATURATED FATTY ACIDS 
OMEGA 3 AND OMEGA 6 LCPUFA AND BREAST MILK
Breast milk covers the child´s needs in terms of long-chain Omega 3 (mainly DHA) during the first months of life, because it naturally contains not only essential PUFA but also all of the derivatives. Levels of Omega 3 fatty acids in breast milk vary from one woman to another, as well as depending on the mother´s diet. For example, Inuit women who consume large quantities of fish rich in Omega 3 have DHA concentrations in their milk ten times higher than those of North American or European women. Therefore, a neonate´s Omega 3 status will be highly dependent on the DHA concentrations in the breast milk and the duration of breastfeeding. An infant receiving a baby formula designed for newborns that does not contain preformed DHA is totally dependent on its own capacities for endogenous synthesis and mobilization of hepatic and adipocyte reserves. In this context, children receiving infant formula, particularly children with low birth weight, who have limited reserves, will have a heightened risk of long-chain polyunsaturated acid deficiency.
FIGURE 2: RECOMMENDED DIETARY INTAKE IN PREGNANT AND NURSING MOTHERS

OMEGA 3 LCPUFA AND NEUROSENSORY DEVELOPMENT
Experimental studies have demonstrated that a deficiency of Omega 6 fatty acids during the key phases of development, during fetal life and immediately after birth, could significantly impair the development of visual and cognitive functions in animals. Can a deficiency of Omega 6 fatty acids in human infants also have a significant impact on their neurosensory development? This is an essential question.
▪ Breastfeeding: the studies are unanimous
The comparison between the neurosensory maturation of a breastfed child to that of a child receiving standard infant formula almost universally shows an advantage in favor of breastfeeding. In a meta-analysis of eight studies reporting an evaluation of cognitive functions determined between early childhood and adolescence, breastfeeding was associated with better cognitive performances even after adjustment for several variables known to significantly influence cognitive development. Nonetheless, this observation cannot make it possible to determine if any one of the nutrients in breast milk plays a particular role in neurosensory development, because the nutritional and non-nutritional differences between these two groups of children are so great.
▪ Supplementation: varied results
The best-established data on the importance of intake of preformed DHA on infant development can only come from randomized, double-blind studies in which one group of children receives standard infant formula and another group receives infant formula with added DHA. These studies have become possible since industrial producers have developed usable sources to enrich infant formula.
To date, all studies on supplementation conducted on infants have demonstrated its efficacy in normalizing the DHA status of the full-term neonate, irrespective of the source used. Approximately 2/3 of studies comparing the visual acuity of children who did or did not received infant formula enriched with DHA and arachidonic acid (ARA) show a benefit of enrichment on visual acuity on the order of two-tenths during the first years of life. A correlation seems to exist between the cumulative dose of DHA received and the visual acuity of the infant during the first months of life.
Studies on supplementation aiming to study the neurological development of infants have produced results that are more varied than those on visual acuity: some studies reveal a positive effect of DHA supplementation, and others show no effect. It is possible that these differences between the studies are due, at least in part, to a difference in the composition of the infant formulas used. For example, supplementation with 0.36% fatty acids in the form of DHA and 0.72% in the form of ARA improves motor development at 18 months, while supplementation with 0.14% fatty acids in the form of DHA and 0.46% in the form of ARA has shown no efficacy on this score at one year.
▪ Weaning and supplementation
The question of weaning is also very important, particularly in France where the duration of breastfeeding is relatively short. Two studies on supplementation conducted after weaning from breast milk show that after weaning at six weeks or between four and six months the use of a formula supplemented with DHA and ARA concentrations similar to those observed in breast milk (0.36% DHA and 0.72% ARA) makes it possible to improve visual function at 17, 26 and 52 weeks in one study and at one year in another. These studies therefore plead in favor of the choice of an infant formula enriched with DHA and ARA at the time of weaning from breast milk.
OMEGA 6 LCPUFA AND NEUROSENSORY DEVELOPMENT
While DHA, Omega 3 fatty acid, is important for the infant´s development, arachidonic acid (ARA or C20:4n-6) also plays an important role in the body since it is a precursor of prostaglandins, leukotrienes and thromboxanes, molecules that are grouped under the general term eicosanoids. Synthesis of these long-chain PUFA uses the same enzymatic system, which makes the body sensitive to any significant imbalance between Omega 3 and Omega 6 levels.
Based on these data, several groups of experts who are specialists in PUFA recommend that infant formulas for newborns contain DHA and ARA levels similar to those observed on average in breast milk (Koletsko et al, 2005).
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INSET 1: PREMATURE INFANTS AND THOSE WITH LOW BIRTH WEIGHT
Premature infants and those with low birth weight have special metabolic characteristics including low reserves, a higher proportion of metabolically active tissues and an extremely fast growth rate. They are also children at high neurological risk with neurosensory development that is lower on average than that of full-term children. It is possible that part of this difference may be explained by suboptimal nutrition. In this context, the beneficial effects on neurosensory development of DHA supplementation have been studied.
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CHILDREN WITH HIGH NEUROLOGICAL RISK
In light of the positive results on neurosensory development of DHA supplementation in premature infants, all infant formulas for premature children in France and in Europe are enriched with DHA (inset 1). Nonetheless, it is important to emphasize that this enrichment must involve not only DHA but also ARA in order to preserve the equilibrium between the Omega 3 and Omega 6 families of fatty acids. Although the majority of clinical trials on premature children have provided supplementation during the first year of life, in practice in France children who were born prematurely only receive supplementation for a few weeks or months. Indeed, the majority of infant formulas used after formulas for children with low birth weight do not contain long-chain PUFA. However, for this category of children at high neurological risk, supplementation with DHA and ARA is essential for newborn formulas and probably desirable for 2nd stage formulas.
Conclusion
Omega 3 and Omega 6 fatty acids are biologically important nutrients, particularly for the infant´s neurosensory development. The mother´s status during pregnancy and lactation is essential for providing the fetus and infant an optimal amount of Omega 3 and Omega 6 fatty acids. Pregnant and nursing women should therefore respect the recommended dietary intake, both of precursors and long-chain PUFA. It may also be important for women of childbearing potential to follow these recommendations in order to have an optimal PUFA status at the start of any pregnancy.
Breastfeeding is the preferred method of nourishment for a healthy child, and should be strongly encouraged. The World Health Organization (WHO) recommends exclusive breastfeeding for six months. If breastfeeding is not possible, and also to take over for breast milk when weaning, prescribing infant formula enriched with DHA and ARA in full-term and premature infants is recommended in light of current data.
References
- HeirdWC, Lapillonne A. The Role of Essential Fatty Acids in Development. Annu. Rev. Nutr. 2005;25:549-71.
- Koletzko B, Baker S, Cleghorn G, et al. Global standard for the composition of infant formula: recommendations of an ESPGHAN coordinated international expert group. J Pediatr Gastroenterol Nutr. 2005;41: 584-99.
- Lapillonne A. Acides gras oméga 3 et oméga 6 au cours de la grossesse et de la petite enfance. Cahiers de Nutrition et Diététique, 2007;42(suppl1) :38-42.
- Lapillonne A. Les besoins en oméga 3 du prématuré et du nourrisson. La revue de Nutrition Pratique, 2007;21 :49-52.
- VidailhetM. Omega 3 : Une situation de carence chez le jeune enfant ? Arch Pédiatr. 2007;14:116-23.
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