Oral contraceptives and the absolute risk of venous thromboembolism in women with single or multiple thrombophilic defects: results from a retrospective family cohort study.

BACKGROUND: The risk of venous thromboembolism (VTE) in women taking combined oral contraceptives (COCs) is attributed to changes in coagulation and fibrinolysis. Their impact may be greater in women with preexistent thrombophilic defects. METHODS: We assessed the effects of COCs on absolute VTE risk in women with single or multiple thrombophilic defects in a retrospective family cohort study. Female relatives of probands with VTE and hereditary deficiencies of protein S, protein C, or antithrombin were tested for known thrombophilic defects, including the index deficiency. Absolute incidences of VTE were compared in deficient vs nondeficient women, in deficient and nondeficient women who ever or never used COCs, and in deficient and nondeficient women with 0, 1, or more than 1 other thrombophilic defect during exposure to COCs. RESULTS: Of 222 women, 135 (61%) ever used COCs. Overall, annual incidences of VTE were 1.64% and 0.18% in deficient and nondeficient women, respectively; the adjusted relative risk was 11.9 (95% confidence interval, 3.9-36.2). The risk was comparable in deficient ever and never users (1.73% vs 1.54%). Annual incidences during actual COC use were 4.62% in deficient women and 0.48% in nondeficient women; the relative risk was 9.7 (95% confidence interval, 3.0-42.4). The incidence increased by concomitant thrombophilic defects, from 3.49% to 12.00% in deficient women and from 0% to 3.13% in nondeficient women. CONCLUSIONS: Women with hereditary deficiencies of protein S, protein C, or antithrombin are at high risk of VTE during use of COCs, particularly when other thrombophilic defects are present. They have VTE at a younger age, but the overall risk is not increased by COCs.

High-resolution 1H NMR spectroscopy of amniotic fluids from spina bifida fetuses and controls.

OBJECTIVE: To quantify proton containing metabolites by in vitro 1H NMR spectroscopy of amniotic fluids from fetuses with spina bifida and controls. STUDY DESIGN: Fourteen amniotic fluids from spina bifida fetuses and 18 controls were obtained. Concentrations of carbohydrates, organic acids and amino acids were determined. Multiple linear regression analysis was used to evaluate the data. RESULTS: At 15 and 39 weeks amenorrhea, the estimated median amniotic fluid concentrations of succinic acid and glutamine were significantly higher in the spina bifida group compared to controls, 37 and 64%, respectively. Whereas creatine and creatinine were significantly lower, 27 and 36%, respectively. Amenorrhea influenced the concentrations of most compounds with the exception of lactic acid. CONCLUSION: 1H NMR spectroscopy shows significantly higher succinic acid and glutamine concentrations in amniotic fluids derived from spina bifida fetuses compared with controls. A derangement in amino acid metabolism is suggested.

Decreased relative brain tissue levels of inositol in fetal hydrocephalus.

OBJECTIVE: Inositol seems to play a role in the development of the central nervous system. In this study, the brain tissue level of inositol in fetal hydrocephalus was compared with that of healthy control subjects. STUDY DESIGN: Proton magnetic resonance spectroscopy was used to examine the inositol over creatine ratio in the brain of 10 hydrocephalic human fetuses and 36 normal control subjects. RESULTS: Resolved signals for inositol and creatine were detected successfully in six hydrocephalic fetuses and in all control subjects. The inositol over creatine ratio was significantly lower in fetuses with hydrocephalus (P <.01). CONCLUSION: This result supports speculations concerning the role of inositol in central nervous system development.