Unexplained Pregnancy Loss

With the start of the homocysteine research in relation to NTD and the genetic mutations found, it was logical to also explore this fascinating field in early embryonic development. Hibbard (3) was the first to suggest a possible relationship between miscarriage and folate deficiency. An increased

FIGLU excretion was found after histidine loading in 32% of women with an isolated unexplained "abortion" and in 60.5% of women with two or more recurrent events.

Mild hyperhomocysteinemia was suggested in patients with recurrent early pregnancy loss (122). In later studies, mild homocysteinemia was confirmed (81,84). The odds ratio of both studies for mild hyperhomocysteinemia was 2.9 (95% CI: 0.9-10.2).

The common mutation C677T was found (82) in 16% of 185 Dutch women with unexplained recurrent early loss and in 5% of 113 case-controls (OR: 3.3; 95% CI:1.3-10.1) and 1250 population controls (OR: 2.0; 95% CI: 1.2-3.2)]. This was confirmed in a small French retrospective study (123).

Homozygotes for the mutant gene of thermolabile MTHFR were sensitive to 0.5 mg of folic acid per day and normalized their plasma homocysteine concentrations (71).

The higher prevalence of the C677T mutation in women with recurrent early pregnancy loss was confirmed in the Norwegian Hordaland study (124).

It is important to realize that the possibly preventive effect of folic acid on the recurrence of early pregnancy loss cannot be investigated anymore in a placebo-randomized fashion because of the evidence-based prevention of NTD with folic acid, a preventive approach that has to start around conception. Therefore, more in-depth research is necessary into the mechanisms that interfere with embryonic development.

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