Adverse Fetal and Neonatal Outcomes Associated with a Life-Long High Fat Diet: Role of Altered Development of the Placental Vasculature

Maternal obesity results in a number of obstetrical and fetal complications with both immediate and long-term consequences. The increased prevalence of obesity has resulted in increasing numbers of women of reproductive age in this high-risk group. Since many of these obese women have been subjected to hypercaloric diets from early childhood we have developed a rodent model of life-long maternal obesity to more clearly understand the mechanisms that contribute to adverse pregnancy outcomes in obese women. Female Sprague Dawley rats were fed a control diet (CON - 16% of calories from fat) or high fat diet (HF - 45% of calories from fat) from 3 to 19 weeks of age. Prior to pregnancy HF-fed dams exhibited significant increases in body fat, serum leptin and triglycerides. A subset of dams was sacrificed at gestational day 15 to evaluate fetal and placental development. The remaining animals were allowed to deliver normally. HF-fed dams exhibited a more than 3-fold increase in fetal death and decreased neonatal survival. These outcomes were associated with altered vascular development in the placenta, as well as increased hypoxia in the labyrinth. We propose that the altered placental vasculature may result in reduced oxygenation of the fetal tissues contributing to premature demise and poor neonatal survival

Hyperhomocysteinaemia: a risk factor for pre-eclampsia?

Item does not contain fulltextPreeclampsia represents one of the most frequent complications of pregnancy, however, little is known about its aetiology. Damage of the endothelial layer lining the blood vessel wall is thought to play an important role in the pathophysiology of preeclampsia, accordingly, mild hyperhomocysteinaemia has been reported to be more prevalent among preeclamptic women. Therefore, we investigated the role of hyperhomocysteinaemia in preeclampsia by measuring plasma levels of homocysteine and studying the prevalence of the 677(C-->T) polymorphism in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, which may lead to reduced MTHFR enzyme activity and subsequently to higher plasma homocysteine levels.Plasma samples of 10 healthy non-pregnant women, 10 normotensive pregnant women, and 20 women with preeclampsia were analysed for total homocysteine levels by high performance liquid chromatography. Furthermore, 167 Dutch non-pregnant women previously hospitalised for preeclampsia and 403 population-based controls were analysed for the 677(C-->T) polymorphism by polymerase chain reaction followed by restriction fragment length polymorphism analysis (PCR/RFLP).In normotensive pregnancy homocysteine levels were lower compared with levels in healthy non-pregnant controls (8.4 versus 13.7micromol/l, PT) polymorphism in the MTHFR gene between preeclamptic women with or without HELLP syndrome and controls (13 and 9% homozygous for the less common T-allele, respectively; OR 1.5, 95% CI 0.8-2.6, P=0.17).In contrast with previous reports, we cannot confirm that mild hyperhomocysteinaemia is a risk factor for preeclampsia. Pregnancy induced hyperhomocysteinaemia found in preeclampsia might better be explained by fluctuations in plasma volume than by the presence of the 677(C-->T) polymorphism in the MTHFR gene

Gilbert's syndrome is not associated with HELLP syndrome

Item does not contain fulltextThe HELLP syndrome has been associated with postpartum unconjugated hyperbilirubinaemia. Several types of disorders cause unconjugated hyperbilirubinaemia, Gilbert's syndrome being the most common. In Caucasians a genetic defect in the TATA box of the promotor region of the gene encoding for bilirubin UDP-glucuronyltransferase is tightly associated with Gilbert's syndrome. This defect was assessed by polymerase chain reaction in 237 women with the HELLP syndrome in their obstetric history and 236 controls. Fifteen percent of the cases and 10% of the controls had a homozygous genetic defect (chi2 = 2.9; P = 0.23). No evidence was found that Gilbert's syndrome is associated with the HELLP syndrome

Polymorphism in the promoter region of the bilirubin UDP-glucuronosyltransferase (Gilbert's syndrome) in healthy Dutch subjects

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Correspondence:Premature Stop of the SOCceR Trial, a Multicenter Randomized Controlled Trial on Secondary Cytoreductive Surgery Netherlands Trial Register Number: NTR3337

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Surgery for Recurrent Epithelial Ovarian Cancer in the Netherlands:A Population-Based Cohort Study

Item does not contain fulltextOBJECTIVE: The value of secondary cytoreductive surgery (SCS) in patients with recurrent epithelial ovarian cancer is controversial. The aim of this population-based study was to investigate the role of SCS in the Netherlands. METHODS: Data of 408 patients who underwent SCS between 2000 and 2013 were retrospectively collected from 38 Dutch hospitals. Survival after complete and incomplete SCS was estimated by Kaplan-Meier curves. Factors associated with overall survival (OS) were explored with Cox regression. RESULTS: Median OS after SCS was 51 months (95% confidence interval [95% CI], 44.8-57.2). Complete SCS was achieved in 295 (72.3%) patients, with an OS of 57 months (95% CI, 49.0-65.0) compared with 28 months (95% CI, 20.8-35.2) in patients with incomplete SCS (log-rank test; P < 0.001). Nonserous histology (HR 0.65; 95% CI 0.45-0.95), a long progression free interval (hazard ratio [HR], 0.29; 95% CI, 0.07-1.18), a good performance status (HR, 0.68; 95% CI, 0.49-0.94), SCS without preoperative chemotherapy (HR, 0.72; 95% CI, 0.51-1.01), and complete SCS (HR, 0.46; 95% CI, 0.33-0.64) were prognostic factors for survival. CONCLUSIONS: This population-based retrospective study showed that there might be a role for SCS in recurrent epithelial ovarian cancer especially when complete SCS can be accomplished. However, before adopting SCS as a standard treatment modality for recurrent epithelial ovarian cancer, results of 3 ongoing prospectively randomized trials are needed