Hyperhomocysteinemia and recurrent early pregnancy loss: a meta-analysis.
OBJECTIVE
To quantify the risk of recurrent early pregnancy loss in the presence of elevated fasting or afterload homocysteine concentrations or homozygosity for the 677C-->T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene (T/T genotype).


METHODS
Case-control studies published between January 1992 and November 1999 were identified with a MEDLINE-search. These studies were combined with a recent case-control study performed by our own research group.


METHODS
Academic research environment.


METHODS
Studies published in the English language, concerning two or more pregnancy losses before 16 weeks' menstrual age were included.


METHODS
Meta-analysis of all of the studies included.


METHODS
The number of subjects with and without hyperhomocysteinemia or with the T/T genotype were derived, if necessary the study was supplemented by personal communication with the original authors.


RESULTS
Pooled risk estimates of 2.7 (1.4 to 5.2) and 4.2 (2.0 to 8.8) were calculated for fasting and afterload plasma homocysteine concentrations, respectively. For the MTHFR T/T genotype a pooled risk estimate of 1.4 (1.0 to 2.0) was found.


CONCLUSIONS
These data support hyperhomocysteinemia as a risk factor for recurrent early pregnancy loss. Further research should be focused on the pathophysiology of this relationship and on the clinical efficacy of B vitamin supplementation.
Nelen
W L
WL
Department of Obstetrics and Gynecology, Nijmegen, The Netherlands. w.nelen@obgyn.AZN.NL
Blom
H J
HJ
Steegers
E A
EA
den Heijer
M
M
Eskes
T K
TK
D000026:Abortion, Habitual / Q000209:etiology* / Q000235:genetics; D001483:Base Sequence / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D020138:Hyperhomocysteinemia / Q000150:complications*; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D009154:Mutation / Q000235:genetics / Q000502:physiology; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics; D011247:Pregnancy; D012307:Risk Factors
D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)