Background The nature and contribution of different pregnancy related complications to future cardiovascular disease (CVD) and its risk factors, as well as mechanisms underlying these associations remain unclear. Methods and Results We studied associations of pregnancy diabetes, hypertensive disorders of pregnancy (HDP), preterm delivery and size for gestational age with calculated 10 year CVD risk (based on the Framingham score) and a wide range of cardiovascular risk factors measured 18 years after pregnancy (mean age at outcome assessment: 48 years) in a prospective cohort of 3,416 women. Gestational diabetes (GDM) was positively associated with fasting glucose and insulin, even after adjusting for potential confounders whilst HDP were associated with BMI, waist circumference, blood pressure, lipids and insulin. Large for gestational age (LGA) was associated with greater waist circumference and glucose concentrations, whilst small for gestational age (SGA) and preterm delivery were associated with higher blood pressure. The association with the calculated 10 year CVD risk based on the Framingham prediction score was OR=1.31 (95%CI: 1.11, 1.53) for preeclampsia and 1.26 (0.95, 1.68) for GDM compared to women without preeclampsia and GDM respectively. Conclusions HDP and pregnancy diabetes are independently associated with an increased calculated 10 year CVD risk. Preeclampsia may be the better predictor of future CVD since it was associated with a wider range of cardiovascular risk factors. Our results suggest that pregnancy may be an important opportunity for early identification of women at increased risk of CVD later in life.

Summary:Purpose: P-glycoprotein (P-gp) has been implicated in the causation of refractory epilepsy. The expression and efflux efficiency of P-gp is influenced by a polymorphism (C3435T) in the encoding gene (MDR1). Recent evidence suggests that the homozygous C-variant, which is associated with higher expression and increased activity of P-gp, is more common in patients with pharmacoresistant epilepsy. We have investigated the prevalence of this polymorphism in a series of patients attending a specialist epilepsy clinic.Methods: DNA samples were obtained from 400 patients, irrespective of seizure type or drug treatment. Genotype of the C3435T polymorphism was determined by traditional polymerase chain reaction (PCR) followed by restriction digest. Classification of response to treatment was determined in a blinded fashion by an independent physician. Results were expressed as genotype and allele frequencies per response group and compared by logistic regression analysis. Results:In total, 170 patients were classified as responders, with ≥12 months seizure freedom on current treatment. The remaining 230 patients were classified as nonresponders. Comparison of responders and nonresponders revealed no significant difference in allele frequency (C vs. T; odds ratio, 1.03; 95% CI, 0.78-1.37; p = 0.83) or genotype frequency (CC vs TT; odds ratio, 1.07; 95% CI, 0.60-1.91; p = 0.81). Subanalyses of individual seizure types were similarly unremarkable.Conclusions: This study failed to corroborate a previously reported association between the C3435T polymorphism in the human MDR1 gene and pharmacoresistant epilepsy. Whether the C3435T polymorphism can act as a marker for the natural history of treated epilepsy remains to be determined.