Oral Clefts and Maternal Biomarkers of Folate-Dependent One-Carbon Metabolism in Utah
Published Date:Feb 02 2011
Source:Birth Defects Res A Clin Mol Teratol. 91(3):153-161.
Pubmed Central ID:PMC4703080
Funding:1R21-DE016877/DE/NIDCR NIH HHS/United States
1UO1DD000698/DD/NCBDD CDC HHS/United States
5-RO1-HD39061/HD/NICHD NIH HHS/United States
R01 HD039061/HD/NICHD NIH HHS/United States
Maternal folate intake and related biomarkers have been inconsistently associated with a risk of oral clefts.
Maternal concentrations of plasma folate (PF) and erythrocyte folate (EF), plasma pyridoxal-5′-phosphate (PLP; active vitamin B6) and total plasma homocysteine (tHcy) were measured in a Utah study with 347 cases and 469 controls.
Risk of all clefts combined, including cleft lip with or without cleft palate (CL/P) and cleft palate only (CP), was 65% lower in the highest versus lowest PF quartile (odds ratio [OR], 0.35; 95% confidence interval [CI], 0.23–0.53; p-trend < 0.001). Results remained significant in the subgroups with isolated CL/P and CP (p-trend < 0.001 in each). EF results were similar. In the highest versus lowest PLP quartile, risk of CP with other malformations was lower (OR, 0.25; 95% CI, 0.07–0.95); however, no other associations were significant for PLP or tHcy. Differences in mean bio-marker levels between cases and controls widened with an increasing interval between delivery and maternal blood collection. Decreased cleft risk with increasing quartiles of PF, EF, and PLP and decreasing tHcy was more apparent in mothers with a longer versus shorter interval between the index child delivery and blood collection.
Low maternal blood folate concentration was associated with an increased risk of clefts, and the differences in mean case and control PF, EF, PLP, and tHcy concentrations widened over time. Additional mechanistic studies are warranted to elucidate whether an acquired or inherited disorder of folate metabolism plays a role in the etiology of clefts.
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