Munger Ronald G, Tamura Tsunenobu, Johnston Kelley E, Feldkamp Marcia L, Pfister Roxane, Cutler Richard, Murtaugh Maureen A, Carey John C
Department of Nutrition, Dietetics, and Food Sciences, Center for Epidemiologic Studies, Utah State University, Logan, UT 84322, USA.
Birth Defects Res A Clin Mol Teratol. 2011 Mar;91(3):153-61. doi: 10.1002/bdra.20762. Epub 2011 Feb 2.
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 B(6) ) 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 biomarker 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.
孕妇叶酸摄入量及相关生物标志物与口腔裂隙风险之间的关联并不一致。
在犹他州的一项研究中，对347例病例和469例对照的孕妇血浆叶酸（PF）、红细胞叶酸（EF）、血浆磷酸吡哆醛（PLP；活性维生素B6）和血浆总同型半胱氨酸（tHcy）浓度进行了测量。
包括唇裂伴或不伴腭裂（CL/P）和单纯腭裂（CP）在内的所有裂隙合并风险，在PF最高四分位数组与最低四分位数组相比降低了65%（优势比[OR]，0.35；95%置信区间[CI]，0.23 - 0.53；p趋势<0.001）。在孤立性CL/P和CP亚组中结果仍然显著（各亚组p趋势<0.001）。EF结果相似。在PLP最高四分位数组与最低四分位数组相比，CP合并其他畸形的风险较低（OR，0.25；95%CI，0.07 - 0.95）；然而，PLP或tHcy的其他关联均不显著。病例组和对照组之间平均生物标志物水平的差异随着分娩与孕妇采血之间间隔时间的增加而扩大。在索引儿童分娩与采血间隔时间较长的母亲中，随着PF、EF和PLP四分位数的增加以及tHcy的降低，裂隙风险降低更为明显。
孕妇血液叶酸浓度低与裂隙风险增加有关，病例组和对照组PF、EF、PLP和tHcy平均浓度的差异随时间扩大。有必要进行更多的机制研究，以阐明叶酸代谢的后天或遗传紊乱是否在裂隙病因中起作用。
