Abstract

Hyperhomocysteinemia is a risk factor in obstetrical complications such as pre-eclampsia, ‘hemolysis, elevated liver enzymes, low platelet’ (HELLP)-syndrome and placental insufficiency. The aim of our study was to investigate the alterations of homocysteine catabolism in these patients in relation to serum B-vitamins and renal function. Maternal fasting serum from preeclampsia (n = 24), HELLP (n = 20) and placental insufficiency (n = 25) patients at the time of diagnosis and pregnant controls (n = 34) was analyzed for homocysteine and its metabolites cystathionine and methylmalonic acid, the vitamins B₆, B₁₂ and folate, renal and additional parameters. Cystathionine, a parameter of homocysteine catabolism, was significantly increased in pre-eclampsia and HELLP compared with controls and placental insufficiency patients (mean concentrations: 343, 324, 248, 227 nmol/l; p=0.001). Homocysteine, folic acid, vitamin B₆ and methylmalonic acid, however, did not differ significantly between groups. The main determinants of cystathionine are cystatin C and vitamin B₆, whereas the main determinants of homocysteine are folate and uric acid. The strongest dependency of cystathionine on vitamin B₆ was observed in pre-eclampsia and HELLP patients. The results suggest that the vitamin B₆-dependent trans-sulfuration pathway is activated in pre-eclampsia and HELLP syndrome, probably by oxidative stress. Therefore, the demand for vitamin B₆ is increased in these patients. Furthermore, renal dysfunction and low vitamin B₆ levels contribute to the increase of cystathionine in pre-eclampsia and HELLP patients.