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.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
2R01EY010208-05A2
Application #
2859247
Study Section
Nutrition Study Section (NTN)
Project Start
1994-03-01
Project End
2003-03-31
Budget Start
1999-04-01
Budget End
2000-03-31
Support Year
5
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Cornell University
Department
Nutrition
Type
Other Domestic Higher Education
DUNS #
City
Ithaca
State
NY
Country
United States
Zip Code
14850
Hsieh, Andrea T; Brenna, J Thomas (2009) Dietary docosahexaenoic acid but not arachidonic acid influences central nervous system fatty acid status in baboon neonates. Prostaglandins Leukot Essent Fatty Acids 81:105-10
Diau, Guan-Yeu; Hsieh, Andrea T; Sarkadi-Nagy, Eszter A et al. (2005) The influence of long chain polyunsaturate supplementation on docosahexaenoic acid and arachidonic acid in baboon neonate central nervous system. BMC Med 3:11
Sarkadi-Nagy, Eszter; Wijendran, Vasuki; Diau, Guan Yeu et al. (2004) Formula feeding potentiates docosahexaenoic and arachidonic acid biosynthesis in term and preterm baboon neonates. J Lipid Res 45:71-80
Sarkadi-Nagy, Eszter; Wijendran, Vasuki; Diau, Guan-Yeu et al. (2003) The influence of prematurity and long chain polyunsaturate supplementation in 4-week adjusted age baboon neonate brain and related tissues. Pediatr Res 54:244-52
Diau, Guan-Yeu; Loew, Ellis R; Wijendran, Vasuki et al. (2003) Docosahexaenoic and arachidonic acid influence on preterm baboon retinal composition and function. Invest Ophthalmol Vis Sci 44:4559-66
Chao, Angela Chueh; Ziadeh, Bassem I; Diau, Guan-Yeu et al. (2003) Influence of dietary long-chain PUFA on premature baboon lung FA and dipalmitoyl PC composition. Lipids 38:425-9
Wijendran, Vasuki; Lawrence, Peter; Diau, Guan-Yeu et al. (2002) Significant utilization of dietary arachidonic acid is for brain adrenic acid in baboon neonates. J Lipid Res 43:762-7
Su, H M; Huang, M C; Saad, N M et al. (2001) Fetal baboons convert 18:3n-3 to 22:6n-3 in vivo. A stable isotope tracer study. J Lipid Res 42:581-6
Su, H M; Bernardo, L; Mirmiran, M et al. (1999) Bioequivalence of dietary alpha-linolenic and docosahexaenoic acids as sources of docosahexaenoate accretion in brain and associated organs of neonatal baboons. Pediatr Res 45:87-93
Cunnane, S C; Menard, C R; Likhodii, S S et al. (1999) Carbon recycling into de novo lipogenesis is a major pathway in neonatal metabolism of linoleate and alpha-linolenate. Prostaglandins Leukot Essent Fatty Acids 60:387-92

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