title: Maternal biomarkers of methylation status and non-syndromic orofacial cleft risk: a meta-analysis.
abstract: Animal models have shown evidence of the role of maternal methyl donor status and its metabolism (one-carbon metabolism) in normal embryonic maxillofacial development. Nevertheless, studies in humans have shown conflicting results for the association of maternal methylation status biomarkers in the aetiology of the main craniofacial birth defects: non-syndromic orofacial clefts (NSOFCs). The aim of this study was to perform a meta-analysis assessing the relationship between maternal levels of methylation status biomarkers (plasma and erythrocyte folates and plasma vitamin B12 and homocysteine) and the risk of NSOFCs. A literature search of the conventional and grey medical-scientific databases identified 12 studies considering these variables. Based on standardized differences between means among cases and controls (Cohen's d test), evidence was found of an association only with high plasma homocysteine (d=0.37; P=0.026) when single effects were pooled. In addition to its usefulness as a marker of poor methyl-donor intake and/or metabolism, homocysteine appears to have a teratogenic effect. Although the results are based on a relatively small number of reports and/or studies of small sample sizes showing between-study heterogeneity, these problems were resolved by including an additional analysis. Therefore these findings constitute a real contribution towards explaining the complex aetiology of orofacial clefts.
authors.affiliation: Program of Human Genetics, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, Santiago, Chile.
authors.forename: R
authors.initials: R
authors.lastname: Blanco
authors.affiliation: Program of Anatomy and Developmental Biology, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, Santiago, Chile.
authors.forename: A
authors.initials: A
authors.lastname: Colombo
authors.affiliation: Sección de Genética, Hospital Clínico Universidad de Chile, Santiago, Chile; Unidad de Neonatología, Hospital Clínico Universidad de Chile, Santiago, Chile; Unidad de Genética, Hospital Dr. Sótero del Río, Santiago, Chile.
authors.forename: R
authors.initials: R
authors.lastname: Pardo
authors.affiliation: Institute for Research in Dental Sciences, Faculty of Dentistry, Universidad de Chile, Santiago, Chile. Electronic address: jsuazo@odontologia.uchile.cl.
authors.forename: J
authors.initials: J
authors.lastname: Suazo
mesh_terms: D015415:Biomarkers / Q000097:blood; D002971:Cleft Lip / Q000209:etiology* / Q000378:metabolism; D002972:Cleft Palate / Q000209:etiology* / Q000378:metabolism; D005260:Female; D005492:Folic Acid / Q000378:metabolism*; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D008745:Methylation; D011247:Pregnancy; D014805:Vitamin B 12 / Q000097:blood*
chemical_list: D015415:Biomarkers; D006710:Homocysteine; D005492:Folic Acid; D014805:Vitamin B 12
keywords: folate; homocysteine; meta-analysis; orofacial clefts; vitamin B12