Most infant formulas provide ample alpha-linolenic acid (LNA) but formula fed infants are at risk for docosahexaenoic acid (DHA) deficiency due to their limited ability to metabolize this long-chain polyunsaturated fatty acid (LCP) from LNA during the first months of life. Formula-fed infants have abnormal fatty acid composition of red blood cells, retina and brain when compared with breast-fed infants, who obtain pre-formed DHA via human milk. Formula-fed infants whose diets lack both LNA and DHA exhibit less sensitive rod electroretinographic (ERG) function, poorer cortical visual evoked potential (VEP) acuity, poorer preferential-looking (PL) acuity, and lower scores on Fagan and Bayley tests. A specific need for dietary DHA in preterm and term infants is the focus of studies during the current grant period and the PI interim results support the essentiality of DHA for optimal maturation of visual function. 1. To delineate the role of DHA in supporting optimal maturation of cortical function. VEP and especially PL acuity have been widely used as indices of general maturation of the cortex or central nervous system; the motivation for these studies has been the quantification of subtle differences related to LCP composition of neural membranes. The PI proposes a series of studies to more directly evaluate cortical function via random dot stereoacuity and tests of cognitive function administered at 39 weeks, 4 years and 9 years of age. These data, coupled with VEP and PL acuity data, will also be used to examine the validity of the hypothesis that VEP and PL acuity provide indices of cortical maturation through analyses of concurrent and predictive validity for cognitive performance. 2. To evaluate the need for dietary supplementation following early weaning. Based on our data which support the essentiality of DHA in the term diet, we will address the question of whether DHA is essential in the post-weaning diet. Common practice in the US is a short 6-8 week period of breast-feeding; yet preliminary evidence suggests that a dietary supply of DHA is essential for at least 17 weeks. This study will be the first test of the essentiality of DHA in the post-weaning diet in the context of a randomized trial. 3. To evaluate the functional role of DHA in the neural retinal membranes of human infants. While there have been a number of studies on the role of DHA in neural membranes in vertebrates, little is known about the role of DHA in the neural membranes of the human infant. The functional effects of dietary DHA supply on activation and inactivation phases of the phototransduction cascade and the synaptic efficiency of the photo-receptor-bipolar junction will be evaluated in the context of a randomized trial. These data will provide the first test of the hypothesis that changes in neural membrane fatty acid composition lead to altered transduction and neurotransmission in the human infant. 4. To assess the capacity of human infants to synthesize DHA in vivo and in vitro. Based on the PI recent finding that in vivo elongation/desaturation of essential fatty acids (EFAs) in infants is limited, he plans to evaluate the impact of fetal growth, gestational age and diet on in vivo EFA conversion. in vivo studies will be complemented by in vitro investigations of LCP biosynthesis in fetal retinal tissue as a function of time in culture, gestational age and fatty acid substrate. Data from the in vivo and in vitro studies will assist in defining endogenous LCP biosynthetic capacity and optimal lipid composition for routine and specialty infant formulas.
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