vitamin-b-12 and Cleft-Lip

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.

Topics: Biomarkers; Cleft Lip; Cleft Palate; Female; Folic Acid; Homocysteine; Humans; Methylation; Pregnancy; Vitamin B 12

The aims of this study were to assess the association between polymorphisms within genes involved in vitamin B12 transport and nonsyndromic cleft lip with or without cleft palate (NSCL/P) and global DNA methylation in Chile. From 247 cases and 453 controls, we obtained variant genotypes for CBLIF, CUBN, AMN, ABCC1, CD320, and TCN2 from a single nucleotide polymorphisms array. Global DNA methylation in 95 controls was obtained through LINE-1 methylation. After multiple comparison corrections, only rs780807 in CUBN remains associated with NSCL/P at dominant model (OR 0.564, p-value = 0.0006, q-value = 0.0450). Carriers of protective allele showed lower levels of DNA methylation than non-carriers (p = 0.0259). Further studies are necessary in order to explain relations with the phenotype and DNA methylation due to the absence of functional evidence for rs780807 in CUBN.

Topics: Case-Control Studies; Chile; Cleft Lip; Cleft Palate; Genetic Predisposition to Disease; Genotype; Humans; Polymorphism, Single Nucleotide; Vitamin B 12

The causal role of maternal nutrition in orofacial clefts is uncertain. We tested hypotheses that low maternal vitamin B. Case-mothers of CL±P children (n = 47) and control-mothers of unaffected children (n = 50) were recruited an average of 1.4 years after birth of the index child and plasma vitamin B. Odds ratios (ORs) contrasting biomarker levels showed associations between case-mothers and low versus high plasma vitamin B. Mothers of CL±P children in southern India were 6.5 times more likely to have poor vitamin B

Topics: Case-Control Studies; Child; Cleft Lip; Cleft Palate; Female; Folic Acid; Humans; India; Risk Factors; Vitamin B 12; Vitamins

The cobalamin type C deficiency is a rare condition that results from impaired biosynthesis of both methylcobalamin (MeCbl) and adenosylcobalamin (AdoCbl). Hemizygous mutations of the HCFC1 gene explain the majority of clinically and biologically compatible cblC patients without MMACHC mutations (OMIM 309541). We report a family with two maternal half-brothers with multiple congenital anomalies and HCFC1 gene mutation in the second Kelch domain. Both presented with dysmorphic features (flat profile, cleft lip for one), increased nuchal translucency, prenatal onset microcephaly and hypospadias. Additionally to early onset intractable epilepsy and profound neurocognitive impairment, this familial observation suggests that HCFC1 gene should be considered in boys with midline malformations, even without proven cobalamin C deficiency.

Topics: Abnormalities, Multiple; Carrier Proteins; Child, Preschool; Cleft Lip; Cobamides; Comparative Genomic Hybridization; Genetic Testing; Host Cell Factor C1; Humans; Karyotyping; Male; Mutation; Oxidoreductases; Vitamin B 12; Vitamin B 12 Deficiency

Riboflavin is a cofactor for the 5,10-methylenetetrahydrofolate reductase (MTHFR) enzyme involved in the homocysteine pathway. The aim of this study was to investigate the effects of maternal riboflavin intake and two MTHFR polymorphisms (677C>T; Ala222Val and 1298A>C; Glu429Ala substitutions) on the biomarkers of the homocysteine pathway, and investigate the risk of having offspring with an orofacial cleft (OFC).. In a case-control study design, dietary riboflavin intake and the MTHFR 677C>T and 1298A>C polymorphisms were evaluated in 123 OFC and 108 control mothers by using food frequency questionnaires and blood samples. Homocysteine (tHcy), folate and vitamin B12 concentrations in blood were analyzed in 70 cases and 68 controls. Linear and logistic regression analyses were applied.. At 14 months postpartum riboflavin intake and MTHFR 677C>T and 1298A>C genotypes were not significantly different between cases and controls. The 677TT genotype showed lower folate concentrations compared to C-allele carriers with a mean difference of 2.8 nmol/l in serum and 174 nmol/l in red blood cell (both P's=0.01). Every mg per day increase of dietary riboflavin intake was positively associated with increase in vitamin B12 concentration by 52.1% (P<0.01). This effect was most pronounced in MTHFR 677TT homozygotes (205.1%, P=0.03). The riboflavin-adjusted MTHFR 677TT and 1298CC genotypes showed a trend toward an increasing risk for OFC, adjusted odds ratio 1.7 (confidence interval (95% CI), 0.7-4.5) and 1.6 (95% CI, 0.7-4.2), respectively.. Maternal riboflavin intake is significantly associated with biomarkers of the homocysteine pathway, with the strongest effects in MTHFR 677TT homozygotes. The maternal risk of having OFC offspring, however, is not associated with dietary riboflavin intake.

Topics: Biomarkers; Case-Control Studies; Cleft Lip; Cleft Palate; Female; Folic Acid; Genetic Predisposition to Disease; Genotype; Homocysteine; Humans; Linear Models; Logistic Models; Methylenetetrahydrofolate Reductase (NADPH2); Nutrigenomics; Odds Ratio; Polymorphism, Genetic; Riboflavin; Risk Factors; Surveys and Questionnaires; Vitamin B 12

Metabonomic analysis has been increasingly used to monitor metabolic abnormalities in cells and their micro-environment in order to detect the biomarkers recently. This study evaluated the feasibility of applying 1H-nuclear magnetic resonance (1H-NMR) based metabonomic method to detect the differences of the early development of cleft palate in the plasma from control group and experimental group.. Pregnant mice (inbred C57BL/6J strain) with vitamin B12 injected only were assigned as the control group, pregnant mice with excessive Dex, injected after vitamin B12 as the experimental group, each group includes 12 mice. And the effect of B12 to rate of cleft palate was observed. The technology of nuclear magnetic resonance (NMR) was used to detect the endogenous small molecule metabolites. Finally, changes of metabolites ingredients were ascertained by using the method of principal component analysis (PCA).. There was significant difference in PCA scores plot between the two groups according to whether cleft palate occurred.. The 1H-NMR based metabonomic approach might be used as a feasible and efficient method for a deep exploration of the pathogenesis of cleft lip and palate and an early exploration of the mechanism of vitamin B12.

Topics: Animals; Cleft Lip; Cleft Palate; Dexamethasone; Female; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Metabolomics; Mice; Mice, Inbred C57BL; Pregnancy; Principal Component Analysis; Vitamin B 12

Periconceptional folic acid supplementation is suggested to prevent orofacial clefts (OFCs). Other B vitamins however may be beneficial as well.. To investigate the maternal periconceptional dietary intake of thiamine, riboflavin, niacin, pyridoxine and cobalamin in association with the occurrence of OFC.. Two hundred and six mothers of a child with nonsyndromic OFC and 203 control mothers filled out a general questionnaire and a food frequency questionnaire around 14 months postpartum as a proxy for periconceptional intake. After exclusion of known pregnant and lactating mothers, those who reported to have altered their diet compared to the periconceptional period, and mothers with incidental folic acid supplement use periconceptionally, data of 182 OFC mothers and 173 controls were analysed. After logarithmic transformation, geometric means (P5-P95) were calculated and compared between the groups. After subsequent adjustment for energy, quintiles of dietary B vitamin intake were created.. The periconceptional intake of thiamine, niacin and pyridoxine was significantly lower in mothers of an OFC child. A trend towards risk reduction for OFC with increasing dietary intake was demonstrated for thiamine (p = 0.04) and pyridoxine (p = 0.03). Risk reductions were only demonstrated in women using folic acid supplements periconceptionally. Supplement users tended to consume a diet richer in B vitamins.. Periconceptional intake of thiamine, niacin and pyridoxine seems to contribute to the prevention of OFC.

Topics: Adult; Case-Control Studies; Cleft Lip; Cleft Palate; Diet; Energy Intake; Female; Folic Acid; Humans; Infant, Newborn; Niacin; Preconception Care; Pregnancy; Prenatal Care; Pyridoxine; Riboflavin; Risk Reduction Behavior; Surveys and Questionnaires; Thiamine; Vitamin B 12; Vitamin B Complex

This study was undertaken to investigate the involvement of maternal and infant B vitamins and homocysteine as risk factors for orofacial clefting.. Venous blood samples were taken from 96 infants with nonsyndromic orofacial clefts and 88 infants without a congenital malformation and from their mothers at approximately 14 months after the index pregnancy. Red blood cell and serum folate, serum vitamin B(12), whole blood vitamin B(6) as pyridoxal-5'-phosphate (PLP), and plasma homocysteine concentrations were measured.. A vitamin B(12) concentration of 185 pmol/L or less and a PLP concentration of 44 nmol/L or less in mothers increased the risk of having a child with an orofacial cleft (odds ratio [OR]=3.1; 95% CI: 1.3-7.4, OR=2.9; 95% CI: 1.2-7.1, respectively). Infants with orofacial clefts had a 15% lower serum folate concentration compared with controls (P=.06).. A low vitamin B(12) and PLP concentration in mothers increased the risk of orofacial clefts in the offspring. A possible role of the infant's folate status is suggested.

Topics: Cleft Lip; Cleft Palate; Female; Folic Acid; Homocysteine; Humans; Infant; Mothers; Pyridoxal Phosphate; Risk Factors; Vitamin B 12; Vitamin B 6

Maternal folic acid supplementation has been suggested to play a role in the prevention of nonsyndromic orofacial clefts, i.e., cleft lip +/- cleft palate. Using a case-control design, we investigated vitamin-dependent homocysteine metabolism in 35 mothers with nonsyndromic orofacial cleft offspring and 56 control mothers with nonmalformed offspring. A standardized oral methionine loading test was performed, in which fasting and afterload plasma total homocysteine, serum and red-cell folate, serum vitamin B12, and whole-blood vitamin B6 levels were determined. We found that both fasting (P < 0.01) as well as afterload (P < 0.05) homocysteine concentrations were significantly higher in cases compared to controls. Hyperhomocysteinemia, defined by a fasting and/or afterload homocysteine concentration above the 97.5th percentile, was present in 15.6% of the cases and in 3.6% of controls (odds ratio, 5.3 (1.1-24.2)). The median concentrations of serum (P < 0. 01) and red-cell (P < 0.05) folate were significantly higher, and vitamin B6 concentrations appeared to be significantly lower (P < 0. 05), in cases compared with controls. No significant difference was observed between groups for vitamin B12. These preliminary data offer evidence that maternal hyperhomocysteinemia may be a risk factor for having nonsyndromic orofacial cleft offspring.

Topics: Adult; Case-Control Studies; Child, Preschool; Cleft Lip; Cleft Palate; Erythrocytes; Fasting; Female; Folic Acid; Homocysteine; Humans; Infant; Maternal-Fetal Exchange; Methionine; Pregnancy; Pyridoxine; Risk Factors; Vitamin B 12

Topics: Animals; Cleft Lip; Cleft Palate; Mice; Mice, Inbred Strains; Vitamin B 12

Topics: Ascorbic Acid; Calcium; Cleft Lip; Cleft Palate; Female; Folic Acid; Humans; Infant, Newborn; Maternal-Fetal Exchange; Niacinamide; Pregnancy; Pregnancy Trimester, First; Pyridoxine; Riboflavin; Thiamine; Vitamin B 12; Vitamins