Docosahexaenoic acid infants

Human milk is rich in essential fatty acids of both the omega-3 and omega-6 families. This suggests that the activity of the A -desaturase may be too low in the infant to provide a sufficient amount of these fatty acids for development of tissues, particularly the brain and retina. It has been shown that development of visual acuity in infants is dependent upon the presence of docosahexaenoic acid in mother s milk. Hence, it is recommended that breastfeeding should be carried out for as long as 12 months after birth. These fatty acids are now added to commercial infant feeds (Chapter 15, Table 15.8). 

Another commercially available product containing naturally occurring marine products is Formulaid , produced by Martek Biosciences as a nutritional supplement for infant formulas. Formulaid contains two fatty acids, arachidonic acid (ARA) and docosahexaenoic acid (DHA), extracted from a variety of marine microalgae. ARA and DHA are the most abundant polyunsaturated fatty acids found in breast milk, and they are the most important fatty acids used in the development of brain gray matter. They are especially desirable for use in infant formulas because they come from nonmeat sources and can be advertised as vegetarian additives to the product. 

Smuts, C. M., H. Y. Tichelaar, M. A. Dhansay, M. Faber, J. Smith, and G. F. Kirsten. Smoking and alcohol use during pregnancy affects preterm infants docosahexaenoic acid (DHA) status. Acta Paediatr 1999 88(7) 757—762. Filippini, G., M. Farinotti, G. Lovicu, P. Maisonneuve, and P. Boyle. Mothers active and passive smoking during pregnancy and risk of brain tumours in children. Int J Cancer 1994 57(6) 769-774. 

Smit EN, Oelen EA, Seerat E, Boersma ER, Muskiet FAJ (2000) Fish oil supplementation improves docosahexaenoic acid status of malnourished infants. Arch Dis Child 82 366-369... 

Hogyes E., Nyakas C., Kiliaan A., Farkas T., Penke B., and Luiten P. G. M. (2003). Neuroprotective effect of developmental docosahexaenoic acid supplement against excitotoxic brain damage in infant rats. Neuroscience 119 999-1012. 

Valenzuela A. and Nieto M. S. (2001). Docosahexaenoic acid (DFIA) in fetal development and infant nutrition. Revista Med. Chile 129 1203-1211. 

Another marine product undergoing development is docosahexaenoic acid (DHA), developed via fermentation of a microalgae. DHA is a major component in human gray matter and is important for normal healthy development in infants. Various groups, such as the World Health Organization, have recommended DHA s inclusion in infant formulas at levels similar to those found in human milk. DHA is presently used in Belgium and Holland and is expected to gain approval in the United States. 

Jorgensen, M.H., Hernell, O., Lund, R, Holmer, G. and Michaelsen, K.F. (1996) Visual acuity and erythrocyte docosahexaenoic acid status in breast-fed and formular-fed term infants during the... 

Martinez, M. (1991) Developmental profiles of polyunsaturated fatty acids in the brain of normal infants and patients with peroxisomal diseases severe deficiency of docosahexaenoic acid in Zellweger s and pseudo-Zellweger s syndomes. World Rev. Nutr. Diet. 66 87-102. 

Salem, N.Jr., Wegher, B., Mena, P. and Uauy, R. (1996) Arachidonic and docosahexaenoic acids are biosynthesized from their 18-carbon precursors in human infants. Proc. Natl. Acad. Sci. USA. 93 49-54. 

Carnielli VP, WattimenaDJ. L., Luijendijk IH. T., Boerlage A, DegenhartHJ, Sauer PJJ. The very low birth weight premature infant is capable of synthesizing aiacidonic and docosahexaenoic acids from linoleic and linolenic acids. Pediatr Res 1996 40( 1) 169-174. 

Heird WC, Prager TC, Anderson RE. Docosahexaenoic acid and the development and function of the infant retina. Curr Opin Lipidol 1997 8(1) 12—16. 

Woods J, Ward G. Salem NJ. Is docosahexaenoic acid necessary in infant formula Evaluation of high linolenate diets in the neonatal rat. Pediatr Res 1996 40 687-694. 

Clandinin MT, Van Aerde IE, Parrott A, Field CJ, Euler A. R, Lien EL. Assessment of the efficacious dose of arachidonic and docosahexaenoic acids in preterm infant formulas fatty acid composition of erythrocyte membrane lipids. Pediatr Res 1997 42 819-825. 

Jorgenson MH, Hohner G, Lund P, Hernell O, Fleischer Michaelsen K. Effect of formula supplemented with docosahexaenoic acid and y-linolenic acid on fatty acid status and visual acuity in term infants. J Pediatr Gastroenterol Nutr 1998 26 412-421. 

Werkman SH, Carlson SE. A randomized trial of visual attention of preterm infants fed docosahexaenoic acid until nine months. Lipids 1996 31 91-97. 

The experimental study of FA deficit has been characterized by investigations that utilize food deprivation or restrictions on nutritional intake, and by designs that have provided for dietary supplementation of the FA and/or their metaboUtes (especially DHA and its precursors EPA and LNA). Metabolic studies continue to address many of the unexplained complexities associated with the behavior performance observations in the laboratory. Among the questions of interest are How do the EFAs get into the brain and other organs What is the basis for the apparent selectivity of various organs, cells, and subcellular organelles for particular lipids and FA Why is DHA (docosahexaenoic acid 22 6n-3) concentrated in the brain How can the adult brain maintain its DHA even when there is little support in the diet How much can the metabolism of the precursors of DHA (e.g., LNA, EPA, etc.) support DHA composition in the brain in comparison to the incorporation of preformed DHA taken in the diet In addition to their basic science value, these issues have practical implications for public health policy, such as the design of infant formulas. 

Docosahexaenoic acid (DHA) and arachidonic acid (ARA) are two fatty acids abundant in human milk, but until recently, were not contained in commercial infant formulas. While the role of ARA supplementation is unclear, DHA is known to be important in both brain and eye development. In some studies, DHA and ARA supplementation has been shown to provide benefits to a child s visual function and/or cognitive and behavioral development. " Other studies have shown no difference with DHA and ARA supplementation. The FDA has classified the plant-based fatty acid blends of DHA and ARA (DHASCO, ARASCO Martek Biosciences Corporation) as generally recognized as safe in infant formulas. 

Innis SM, Adamkin DH, Hall RT, et al. Docosahexaenoic acid and arachi-donic acid enhance growth with no adverse effects in preterm infants fed formula. J Pediatr 2002 140 547-554. 

Infante, J.P., and Huszagh, V.A. (2001) Zellweger Syndrome Knockout Mouse Models Challenge Putative Peroxisomal p-Oxidation Involvement in Docosahexaenoic Acid (22 6n-3) Biosynthesis, Mol. Genet. Metab. 72,1-7. 

Fig. 6. Effect of dietary treatment on arachidonic acid (ARA) as wt% of total fatty acids in mucosal phosphatidylcholine. Values shown are means + SD, n = 6. Bars with different superscript letters differ, (P< 0.05). Baseline (BL), piglets killed at 1 d of age before initiation of dietary treatment SOW, piglets naturally reared on sow s milk FF(STD), piglets formula-fed a milk replacer formula containing a standard (STD) fat blend similar to that in conventional Infant formula FF + ARA, piglets formula-fed a milk replacer formula containing a standard fat supplemented with ARA FF + ARA/DHA, piglets formula-fed a milk replacer formula containing a standard fat blend supplemented with ARA and docosahexaenoic acid (DHA).

Fig. 1. The n-3 and n-6 polyunsaturates in the four formulas. Diet designations correspond to multiples of the long-chain docosahexaenoic acid (DHA) and arachidonic acid (AA) concentrations in Diet 1, which contains levels recommended for human infant formulas. Diet 0 is a long-chain polyunsaturated fatty acid (LC-PUFA)-free control. Diets 2 and 5 had 2- and 5-fold greater concentrations of DHA and AA than Diet 1.

Clandinin, M. T., Van Aerde, J. E., Parrott, A., Field, C. J., Euler, A.R., and Lien, E.L. (1997) Assessment of the Efficacious Dose of Arachidonic and Docosahexaenoic Acids in Preterm Infant Formulas Fatty Acid Composition of Erythrocyte Membrane Lipids, Pediatr. Res. 42, 819-825. 

Birch, E.E., Hoffman, D.R., Uauy, R., Birch, D.G., and Prestidge, C. (1998) Visual Acuity and the Essentiality of Docosahexaenoic Acid and Arachidonic Acid in the Diet of Term Infants, Pediatr. Res. 44,201-209. 

Sleep Patterns of Infants Immediately After Birth Reflect Docosahexaenoic Acid Status and Central Nervous System Maturity... 

Reliable characterization and description of sleeping and waking states of infants offer the potential for assessment of the functional integrity of the central nervous system (CNS) (1). As a basis for our work, the premise has been that because the phospholipids of the nervous system are characterized by high concentrations of docosahexaenoic acid (DHA), assessment of the sleep-wake states offers an instrument for defining infant functional outcome at birth as it relates to DHA status (2). We further propose that immediate postnatal sleep-wake patterns are arehable measure of CNS maturity. 

Fig. 2. Association of maternal plasma (PL) docosahexaenoic acid (DHA) with infant sleep parameters. (A) Maternal DHA vs. infant active sleep (AS) on postnatal day (PND) 2. (B) Maternal DHA vs. infant active sleep to quiet sleep ratio (AS/QS) on PND 2. (C) Maternal DHA vs. infant wakefulness (W) on PND 2. (D) Maternal DHA vs. infant sleep-wake transitional sleep (T) on PND 2. (Reprinted with permission from Ref. 2).

Carlson, S.E., and Werkman, S.H. (1996) A Randomized Trial of Visual Attention of Preterm Infants Fed Docosahexaenoic Acid Until Two Months, Lipids 31,85-90. 

---