Steegers E.A.R Department of Obstetrics and Gynaecology, University Hospital Nijmegen St Radboud, The Netherlands
Introduction: The remethylation of homocysteine into methionine depends on enzyme activities and the availability of betaine and vitamins. The folate and vitamin B12 dependent remethylation of homocysteine takes place in most tissues as well as in embryonic and trophoblast tissues. Hyperhomocysteinaemia results from a diminished activity of enzymes due to genetic abnormalities, ie., methylenetetrahydrofolate reductase (MTHFR), or folate and vitamin B 12 deficiencies. Last two decades evidence is increasing that elevated plasma total homocysteine concentration should be regarded as a risk factor for cardiovascular diseases. More recently maternal hyperhomocysteinemia has been associated with an increased risk for recurrent spontaneous miscarriage, abruptio placentae, thromboembolic events and preeclampsia. Moreover, hyperhomocysteinaemia seems to be more prevalent in mothers having had ottspring with a neural tube defect, orofacial cleft, heart detect, hypospadia and Down syndrome. An update will be given of the available evidence of these associations by identification of studies through OVID Medline between 1966 and February 2001. The importance of maternal hyperhomocysteinaemia in underlying mechanisms of these outcomes will be highlighted as well as the benefit of preconceptional diagnosis and treatment.
Results: So far, observational studies strongly suggest that folate deficiency, hyperhomocysteinaemia and MTHFR polymorphisms are risk factors tor placenta-related abnormalities and several midline defects. In vitro studies are not supporting the teratogenicity of moderate hyperhomocysteinaemia, however do support the role of folate in early pregnancy. Plasma total homocysteine is the most sensitive biomarker of a functional tolate deficiency. Therefore, maternal hyperhomocysteinaemia should be regarded as an epiphenomenon more than as a primary cause for abnormalities in the course and outcome of pregnancy. The beneficial effect of periconceptional folate treatment can partly be explained by the treatment of a functional maternal folate deficiency.
Conclusion: However, before large scale intervention programmes and recommendations are launched to prevent abnormal pregnancy and midline defects, other than neural tube defects, the effectiveness and safety of periconceptional and antenatal folate or combined vitamin treatment should be proven.