FOLATE STATUS IN INTRAUTERINE GROWTH RETARDED INFANTS

点击翻译按钮获取中文摘要

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The role of folate deficiency in IUGR is uncertain. This study will provide preliminary evidence for the roles of folate, folate cofactors and the enzymes of folate regulation in human intrauterine growth restricted neonates. It is hypothesized that IUGR newborns will have abnormalities of folate and vitamin B12 metabolism compared to appropriately grown newborns. Cord blood will be collected on 30 IUGR newborns and 90 control newborns. After delivery, 5-15 cc of cord blood will be collected in prechilled EDTA tubes (5-15 cc) separated, brought to (vol/wt) 1% ascorbic acid, snap frozen and stored at -20 C until analysis for folate cofactors. 5 cc will be placed in a prechilled red top, allowed to clot and serum separated, aliquoted to 750 l aliquots, snap frozen and stored at -20 C until analysis for metabolites.We will use novel and sensitive assays developed in our laboratories to confirm observations made in a fetal sheep model of IUGR. Metabolite assay: Serum methionine, SAM and SAH will be determined by the stable isotope dilution method in the laboratory of Dr. Stabler 13. In addition, this method yields the concentrations for other metabolites of folate and vitamin B12 that aid in distinguishing folate from vitamin B12 deficiency: dimethylglycine, methylglycine, homocysteine, serine, glycine, cysteine, methyl- malonic acid, tryptophan, and cystathionine. Folate coenzyme assay: Plasma will be assayed for total folate, 5-methyl-THF, 5,10 methylene THF and the formyl groups of THF (5-formyl-THF, 10-formyl-THF, 5,10 methenyl-THF) by direct probe MS using a technique that we have developed in Dr. Kolhouse's laboratory 12. We hypothesize that IUGR infants will have evidence for folate deficiency compared to controls. We anticipate that we will generate normative data for folate and metabolite values and using these new more sensitive assays directly determine the potential association between folate deficiency and IUGR. The metabolite assays have been validated in animal and human testing and are very reproducible.