PDF《and Iron》

Controversial Nutrients That Potentially Affect Preterm Neurodevelopment: Essential Fatty Acids and Iron MICHAEL K.

GEORGIEFF AND SHEILA M. INNIS University of Minnesota School of Medicine [M.K.G.],

420 Delaware St. SE, Minneapolis, MN USA 55455;

Nutrition Research Program [S.I.M.], B.C. Research Institute, Professor, Department of Pediatrics, University of British Columbia, Vancouver, BC V5Z 4H4, Canada Although all nutrients are needed for normal fetal and postnatal development, small preterm infants are particularly susceptible to nutrient de?ciencies. The potential for immediate and long-term consequences of de?ciency varies among nutrients. Essential fatty acids and iron are of particular interest because both are com- monly de?cient in the preterm infant, excessive or inadequate intakes are both of concern, and both are crucial to normal CNS development with the potential for long lasting effects that extend beyond the period of dietary insuf?ciency. Although seemingly diverse in physiologic roles, advances in the understanding of iron and essential fatty acid metabolism provide an exemplary illus- tration how different nutrients interact to support normal growth and development. The potential for adverse effect of inadequate or excess intake of any nutrient on any organ system is based on the timing, dose and duration of exposure (1). The vulnerability of a particular organ thus depends on the concurrence of two factors;

the pres- ence of a critical (or sensitive) period of growth and development that is dependent on the nutrient in question;

and de?ciency of the nutrient in the population at the time of this sensitive period. Effects that last beyond the period of exposure result from devi- ations from the normal developmental trajectory, involving mor- phologic process for example neuritogenesis, myelination, expres- sion of genes for key proteins or endocrine factors that regulate development, that are incompletely recovered at some later stage with restoration of normal nutrition. The brain between

6 mo postconception and

1 y of age undergoes a remarkable transfor- mation from a relatively primitive, poorly sulcated and gyrated structure into a complex, integrated organ. Important neurodevel- opmental processes at this time include the onset of myelination, organization of neurotransmitter systems, dendritic arborization and selective pruning, and synaptogenesis particularly in the visual system and the hippocampus (Fig. 1) (2). Iron and essential fatty acids impact on these developmental processes at multiple levels that have the potential for lasting effects in preterm infants inadequately nourished with these nutrients. ESSENTIAL FATTY ACID REQUIREMENTS OF THE PRETERM INFANT Docosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid (ARA, 20:4n-6) are required by preterm infants to support growth and development. DHA and ARA are formed from the essential fatty acids, linoleic acid (LA,18:2n-6) and ?-linolenic acid (LNA,18:3n-3), respectively, by elongation and desatura- tion (3) and are the major polyunsaturated fatty acids in fetal plasma. In contrast, LA and LNA are the most abundant n-6 and n-3 fatty acids in human milk, infant formula and IV lipids. Plasma LA increases, while ARA and DHA decrease rapidly with the initiation of feeding. LA and LNA are mutually competitive and their metabolism is inhibited by products of the autologous and opposing fatty acid series (4). Thus, inap- propriately high intakes of one of the n-6 and n-3 fatty acids can have deleterious effects on other n-6 and n-3 fatty acids. DHA and ARA are present in membrane phospholipids where they regulate membrane functions, and from which they are released to act directly or as precursors to molecules that modulate cell growth, inter- and intra-cellular communication and protein function (3). DHA is selectively accumulated in speci?c tissues that include the retina and brain grey matter. Depletion of DHA from the brain and retina results in reduced visual function, cognitive and behavioral abnormalities, altered monaminergic neurotransmitter metabolism, and decreased membrane protein and receptor activities (3). The monoamines dopamine and serotonin are important in many of the cognitive and behavior advances of early childhood;