The objective of this study is to describe the role of periconceptional folic acid supplementation and assess it's potential in the prevention of foetal abnormalities, and consists of a review of the literature undertaken using an electronic and hand search. This includes research trials and methodology associated with folic acid supplementation. It is recommended that all women planning to conceive should supplement their diet with folic acid in order to prevent abnormalities in neural tube development, particularly if there is a history of a previously affected pregnancy. There is increasing evidence that folic acid supplementation may, in addition, reduce the incidence of oral facial clefting. Further research with multi-disciplinary approaches in biochemistry, genetics, gene/environment interactions, and embryology are indicated.

Cleft palate is the most common craniofacial anomaly. Affected individuals require extensive medical and psychosocial support. Although cleft palate has a complex and poorly understood etiology, low maternal folate is known to be a risk factor for craniofacial anomalies. Folate deficiency results in elevated homocysteine levels, which may disturb palatogenesis by several mechanisms, including oxidative stress and perturbation of matrix metabolism. We examined the effect of homocysteine-induced oxidative stress on human embryonic palatal mesenchyme (HEPM) cells and demonstrated that biologically relevant levels of homocysteine (20-100 microM) with copper (10 microM) resulted in dose-dependent apoptosis, which was prevented by addition of catalase but not superoxide dismutase. Incubation of murine palates in organ culture with homocysteine (100 micro) and CuSO(4) (10 microM) resulted in a decrease in palate fusion, which was not significant. Gelatin gel zymograms of HEPM cell-conditioned media and extracts of cultured murine palates, however, showed no change in the expression or activation of pro-matrix metalloproteinase-2 with homocysteine (20 microM-1 mM) with or without CuSO(4) (10 microM). We have demonstrated that biologically relevant levels of homocysteine in combination with copper can result in apoptosis as a result of oxidative stress; therefore, homocysteine has the potential to disrupt normal palate development.

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