Homocysteine: biomarker or cause of adverse pregnancy outcome?

Total fasting plasma homocysteine (tHcy) is significantly reduced during early-mid normal pregnancy. Elevated tHcy during or outside of pregnancy has been associated with adverse pregnancy outcomes, affecting either the fetus or the evolution of the pregnancy. Examples of direct adverse effects on the fetus are neural tube defects, Down's syndrome, congenital heart defects and intrauterine growth retardation. Both fetal and maternal wellbeing can be affected by other adverse outcomes reported to be associated with elevated tHcy, such as recurrent spontaneous abortion, pre-eclampsia or placental vasculopathy. To date, endothelial activation of the placental vascularization system, apoptosis, toxicity and stimulation of uterine contractions have been proposed as possible modes of adverse action of homocysteine. The strength of the clinical evidence for a pathological role of elevated homocysteine in the evolution of pregnancy is examined in this review.