[Oxidative DNA damage in mothers of children with isolated orofacial clefts].

Recently, there is increasing evidence suggesting that oxidative stress may contribute to birth defects. 8-Hydroxy-2'-deoxyguanosine (8-OHdG) is considered to be a sensitive biomarker of oxidative DNA damage. It would seem important to establish whether levels of 8-OHdG and antioxidants are different in mothers of children with orofacial clefts comparing to women who gave birth to healthy children. The present study was carried out to investigate this point. Total plasma antioxidant status (TAS), serum 8-OHdG, plasma alpha-tocopherol and retinol were determined in 27 healthy mothers of children with isolated orofacial clefts (cleft lip - 11, cleft lip and palate - 9, cleft palate - 7; mean age - 26.6+/-3.5 years; mean time after delivery - 6.5+/-8.4 months) and 14 control mothers of children without birth defect (mean age - 26.4+/-3.0 years, mean time after delivery - 5.7+/-5.8 months). 8-OHdG concentrations were significantly increased in mothers of children with clefts compared to controls (median - 4.7 ng/mL; range: 0.5-8.6 ng/mL vs. median 1.9 ng/mL; range: 0.1-3.2 ng/ mL; p<0.001 in Wilcoxon test). TAS (median - 1.03 micromol/L; range 0.87 - 1.26 micromol/L vs. median - 1.13 micromol/L; range: 1.03- 1.26 micromol/L; p<0,05) and alpha-tocopherol level (median - 15.8 micromol/L; range: 11.3-26.8 micromol/L vs. median - 20.6 micromol/L; range: 13.8-26.5 micromol/L; p<0,05) were significantly reduced in mothers of affected children. There were no differences in vitamin A levels between the study group and controls. The ratio of alpha-tocopherol to plasma total cholesterol was lower in women who gave birth to children with clefts compared to controls (median - 3.16 micromol/mmol vs. median - 3.7 micromol/ mmol; p>0.05). No correlation was found between TAS, the vitamins and 8-OHdG. We conclude that depletion of antioxidant systems as well as increased free radical generation are likely to be involved in the pathophysiology of orofacial clefts in humans. The results indicate the necessity of futher studies to establish whether peri-conceptional antioxidant supplementation will prevent these serious defects.