The goals of this continuation project are to couple biochemical tracer studies of essential fatty acid metabolism with functional outcomes related to retinal and brain development in preterm baboons, and including a randomized breastfed term group, to generate highly applicable information to aid in nutritional management of human preterm infants. The proposed work focuses on preterm (153 days gestation) and term (185 days) neonates and the effects of diet on conversion and organ accretion of linoleic acid (LA), alpha-linolenic acid (LNA), and docosahexaenoic acid (DHA), and on functional outcomes of importance to vision. A completely randomized design is proposed with 5 groups total: 3 preterm, (P)and 2 term (T). Three diets similar to those tested in experimental clinical settings will be studied in premature neonates for 11 weeks: Group """"""""PN""""""""-LA/LNA ration of 9:1, long chain polyunsaturated (LCP)-free; Group """"""""PR""""""""-LA/LNA=4, LCP-free; Group """"""""PL""""""""-LA/LNA=9, supplemented with 0.3%en DHA and 0.6%/en arachidonic acid (AA). The control groups are term (T) groups: Group """"""""TN""""""""-identical diet to PN: LA/LNA ratio of 9:1, LCP-free;Group """"""""TB""""""""-A randomized group of breastfed term baboons will serve as the gold-standard control, which is never available in human studies. The primary outcomes to be measured are: i) The bioequivalence of dietary LNA and DNA as precursors for brain DNA accretion using stable isotope tracers, ii) Fractional conversion of LNA and LA to LCP in brain, retina and liver, iii) Electroretinograms (ERG) a- and b- wave implicit times and amplitudes, with calculation of """"""""A"""""""", the amplification factor associated with initial photoreceptor transduction, iv) flash and pattern-reversal visual evoked potentials, v) development of circadian rhythm-dependent sleep/wake states, v) eye focusing properties. The combination of biochemical and functional outcomes in a well controlled intervention study with a randomized breastfed group will permit correlations to be drawn between physiology and function which are not possible in humans. Because of the similarity of baboons to humans, the dietary bioequivalence of LNA and DHA for brain DHA accretion will apply to preterm humans and will facilitate calculation of adequate dietary n-3 fatty acid levels. Sub-normal development will be directly revealed via functional tests to assess the impact of low omega-3 fatty acid status on develop of vision acid status on development of vision and related health parameters.
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