Hyperhomocysteinaemia and protein S deficiency in complicated pregnancies

Objective The aim of our study was to investigate whether women with placental abruption, intrauterine fetal death or small for gestational age infants have metabolic and/or haemostatic abnormalities which are known to be risk factors for intravascular thrombosis. Design For two years blood tests were performed at > 10 weeks after delivery on all women without hypertensive disorders either before or during pregnancy, who had been consecutively admitted to our hospital with placental abruption, intrauterine fetal death and small for gestational age. Sample A total of 62 women who had placental abruption (n= 13), intrauterine fetal death (n = 18) and a small for gestational age infant (n= 13). Setting Obstetric outpatient clinic in a university hospital (Free University Hospital, Amsterdam). Methods Presence of hyperhomocysteinaemia, various coagulation abnormalities and anticardiolipins was investigated. Results Abnormalities were found in 20 women in the placental abruption group (20/31, 65%), in 10 women in the intrauterine fetal death group (10/18, 56%) and in 11 women in the small for gestational age group (11/13, 85%). Eight out of these 31 women had more than one abnormality. In the group of 62 women protein S deficiency was demonstrated in 26%, hyperhomocysteinaemia in 24%, Protein C deficiency in 6%, anticardiolipin IgG in 11%, anticardiolipin IgM in 5%, Lupus anticoagulant in 2%. An antithrombin III deficiency was not found. Thirty-three women were tested for activated protein C resistance (9% positive) and factor V Leiden mutation (6% positive). Hyperhomocysteinaemia was treated with a daily oral dose of 250 mg pyridoxine and 5 mg folic acid. After six weeks of vitamin supplementation homocysteine levels were tested again. At that tune a mean reduction of fasting homocysteine value of 68% (95% CI 57–79) was found and of post-load value of 65% (95% CI 55–76). Conclusions Based on the results of our study, it can be concluded that women whose pregnancies are complicated by either placental abruption, intrauterine fetal death or small for gestational age, even if there is no history of thrombo-embolic disorders or hypertension during pregnancy, should be advised to undergo an examination for metabolic and/or haemostatic abnormalities.