title: Nonsyndromic orofacial clefts: association with maternal hyperhomocysteinemia.
abstract: 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.
authors.affiliation: Department of Obstetrics and Gynecology, University Hospital Nijmegen St. Radboud, 6500 HB Nijmegen, The Netherlands.
authors.forename: W Y
authors.initials: WY
authors.lastname: Wong
authors.forename: T K
authors.initials: TK
authors.lastname: Eskes
authors.forename: A M
authors.initials: AM
authors.lastname: Kuijpers-Jagtman
authors.forename: P H
authors.initials: PH
authors.lastname: Spauwen
authors.forename: E A
authors.initials: EA
authors.lastname: Steegers
authors.forename: C M
authors.initials: CM
authors.lastname: Thomas
authors.forename: B C
authors.initials: BC
authors.lastname: Hamel
authors.forename: H J
authors.initials: HJ
authors.lastname: Blom
authors.forename: R P
authors.initials: RP
authors.lastname: Steegers-Theunissen
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002675:Child, Preschool; D002971:Cleft Lip / Q000209:etiology* / Q000517:prevention & control; D002972:Cleft Palate / Q000209:etiology* / Q000517:prevention & control; D004912:Erythrocytes / Q000378:metabolism; D005215:Fasting / Q000097:blood; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage / Q000097:blood; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D007223:Infant; D008431:Maternal-Fetal Exchange; D008715:Methionine / Q000008:administration & dosage; D011247:Pregnancy; D011736:Pyridoxine / Q000097:blood; D012307:Risk Factors; D014805:Vitamin B 12 / Q000097:blood
chemical_list: D006710:Homocysteine; D005492:Folic Acid; D008715:Methionine; D011736:Pyridoxine; D014805:Vitamin B 12