Maternal hyperhomocysteinemia: a risk factor for neural-tube defects?
The maternal vitamin status, especially of folate, is involved in the pathogenesis of neural-tube defects (NTDs). Maternal folate administration can prevent these malformations. The precise metabolic mechanism of the beneficial effect of folate is unclear. In this study we focus on homocysteine accumulation, which may derive from abnormalities of metabolism of folate, vitamin B12, and vitamin B6. We studied nonpregnant women, 41 of whom had given birth to infants with NTDs and 50 control women who previously had normal offspring. The determinations included the plasma total homocysteine both in the fasting state and 6 hours after the ingestion of a methionine load. In addition, we measured the fasting blood levels of folate, vitamin B12, and vitamin B6. The mean values for both basal homocysteine and homocysteine following a methionine load were significantly increased in the group of women who previously had infants with NTDs. In nine of these subjects and two controls, the values after methionine ingestion exceeded the mean control by more than 2 standard deviations. Cystathionine synthase levels in skin fibroblasts derived from these methionine-intolerant women were within the normal range. Our findings suggest a disorder in the remethylation of homocysteine to methionine due to an acquired (ie, nutritional) or inherited derangement of folate or vitamin B12 metabolism. Increased homocysteine levels can be normalized by administration of vitamin B6 or folate. Therefore, we suggest that the prevention of NTDs by periconceptional folate administration may effectively correct a mild to moderate hyperhomocysteinemia.
Steegers-Theunissen
R P
RP
Department of Obstetrics and Gynecology, University Hospital St Radboud, Nijmegen, The Netherlands.
Boers
G H
GH
Trijbels
F J
FJ
Finkelstein
J D
JD
Blom
H J
HJ
Thomas
C M
CM
Borm
G F
GF
Wouters
M G
MG
Eskes
T K
TK
D000328:Adult; D000757:Anencephaly / Q000196:embryology; D003541:Cystathionine beta-Synthase / Q000378:metabolism; D004677:Encephalocele / Q000196:embryology; D005260:Female; D005492:Folic Acid / Q000097:blood; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D008591:Meningomyelocele / Q000196:embryology; D008715:Methionine; D009436:Neural Tube Defects / Q000196:embryology* / Q000201:enzymology; D011247:Pregnancy; D011248:Pregnancy Complications / Q000097:blood*; D012307:Risk Factors
D006710:Homocysteine; D005492:Folic Acid; D008715:Methionine; D003541:Cystathionine beta-Synthase