Kitty W M Bloemenkamp

University of Amsterdam, Amsterdamo, North Holland, Netherlands

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Publications (142)854.8 Total impact

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    ABSTRACT: Preeclampsia is characterized by hypertension and proteinuria, and increased shedding of podocytes into the urine is a common finding. This finding raises the question of whether preeclamptic nephropathy involves podocyte damage. This study examined podocyte-related changes in a unique sample of renal tissues obtained from women who died of preeclampsia.DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: All patients with preeclampsia who died in The Netherlands since 1990 and had available autopsy tissue were identified using a nationwide database of the Dutch Pathology Registry (PALGA). This resulted in a cohort of 11 women who died from preeclampsia. Three control groups were also identified during the same time period, and consisted of normotensive women who died during pregnancy (n=25), and nonpregnant controls either with (n=14) or without (n=13) chronic hypertension. Glomerular lesions, including podocyte numbers, podocyte proliferation, and parietal cell activation, were measured.RESULTS: Patients with preeclampsia had prominent characteristic glomerular lesions. The results showed that the number of podocytes per glomerulus did not differ significantly between the patients with preeclampsia and the control groups. However, preeclampsia was associated with a significant increase in intraglomerular cell proliferation (7.3% [SD 9.4] of the glomeruli of patients with preeclampsia had Ki-67-positive cells versus 1.6% [SD 3.3] of the glomeruli of hypertensive controls and 1.1% [SD 1.3] of nonpregnant controls; P=0.004) and activated parietal epithelial cells on a podocyte location (34% [SD 13.1] of the glomeruli of patients with preeclampsia versus 18.0% [SD 15.3] of pregnant controls, 11.9% [SD 13.2] of hypertensive controls, and 10.8% [SD 13.4] of nonpregnant controls; P=0.01).CONCLUSIONS: These findings suggest that the recently described mechanisms of podocyte replacement play a role in preeclampsia. These results provide key new insights into the pathogenesis of preeclamptic nephropathy, and they open new possibilities for developing therapeutic modalities.
    Clinical journal of the American Society of Nephrology : CJASN. 07/2014;
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    ABSTRACT: To estimate the performance of combining cervical length measurement with fetal fibronectin testing in predicting delivery in women with symptoms of preterm labor. We conducted a prospective nationwide cohort study in all 10 perinatal centers in The Netherlands. Women with symptoms of preterm labor between 24 and 34 weeks of gestation with intact membranes were included. In all women, qualitative fibronectin testing (0.050-microgram/mL cutoff) and cervical length measurement were performed. Logistic regression was used to predict spontaneous preterm delivery within 7 days after testing. A risk less than 5%, corresponding to the risk for women with a cervical length of at least 25 mm, was considered as low risk. Between December 2009 and August 2012, 714 women were enrolled. Fibronectin results and cervical length were available for 665 women, of whom 80 (12%) delivered within 7 days. Women with a cervical length of at least 30 mm or with a cervical length between 15 and 30 mm with a negative fibronectin result were at low risk (less than 5%) of spontaneous delivery within 7 days. Fibronectin testing in case of a cervical length between 15 and 30 mm additionally classified 103 women (15% of the cohort) as low risk and 36 women (5% of the cohort) as high risk. Cervical length measurement, combined with fetal fibronectin testing in case of a cervical length between 15 and 30 mm, improves identification of women with a low risk to deliver spontaneously within 7 days. LEVEL OF EVIDENCE:: II.
    Obstetrics and Gynecology 05/2014; · 4.80 Impact Factor
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    ABSTRACT: Objective The Disproportionate Intrauterine Growth Intervention Trial at Term (DIGITAT trial) showed that in women with suspected intrauterine growth restriction (IUGR) at term, there were no substantial outcome differences between induction of labour and expectant monitoring. The objective of the present analysis is to evaluate whether maternal or fetal markers could identify IUGR fetuses who would benefit from early labour induction. Study design The DIGITAT trial was a multicenter, parallel and open-label randomised controlled trial in women who had a singleton pregnancy beyond 36 + 0 weeks’ gestation with suspected IUGR (n = 650). Women had been randomly allocated to either labour induction or expectant monitoring. The primary outcome was a composite measure of adverse neonatal outcome, defined as neonatal death before hospital discharge, Apgar score <7, umbilical artery pH <7.05, or admission to neonatal intensive care. Using logistic regression modelling, we investigated associations between outcome and 17 markers, maternal characteristics and fetal sonographic and Doppler velocimetry measurements, all collected at study entry. Results 17 (5.3%) infants in the induction group had an adverse neonatal outcome compared to 20 (6.1%) in the expectant monitoring group. The only potentially informative marker for inducing labour was maternal pre-pregnancy body mass index (BMI). Otherwise, we observed at best weak associations between a benefit from labour induction and maternal age, ethnicity, smoking, parity, pregnancy-induced hypertension or preeclampsia, Bishop score and gestational age, or fetal sonographic markers (gender, estimated fetal weight, body measurements, oligohydramnios, or umbilical artery pulsatility index and end diastolic flow). Conclusion In late preterm and term pregnancies complicated by suspected intrauterine growth restriction, most of the known prognostic markers seem unlikely to be helpful in identifying women who could benefit from labour induction, except for maternal pre-pregnancy BMI.
    European journal of obstetrics, gynecology, and reproductive biology 01/2014; 172:20–25. · 1.97 Impact Factor
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    ABSTRACT: Objectives To assess the cost-effectiveness of post-partum screening on cardiovascular risk factors and subsequent treatment in women with a history of gestational hypertension or pre-eclampsia at term. Study design Two separate Markov models evaluated the cost-effectiveness analysis of hypertension (HT) screening and screening on metabolic syndrome (MetS), respectively, as compared to current practice in women with a history of term hypertensive pregnancy disorders. Analyses were performed from the Dutch health care perspective, using a lifetime horizon. One-way sensitivity analyses and Monte Carlo simulation evaluated the robustness of the results. Results Both screening on HT and MetS in women with a history of gestational hypertension or pre-eclampsia resulted in increase in life expectancy (HT screening 0.23 year (95% CI −0.06 to 0.54); MetS screening 0.14 years (95% CI −0.16 to 0.45)). The gain in QALYs was limited, with HT screening and MetS screening generating 0.04 QALYs (95% CI −0.12 to 0.20) and 0.03 QALYs (95% CI −0.14 to 0.19), resulting in costs to gain one QALY of €4228 and €28,148, respectively. Analyses for uncertainty showed a chance of 74% and 75%, respectively, that post-partum screening is cost-effective at a threshold of €60,000/QALY. Conclusions According to the available knowledge post-partum screening on cardiovascular risk factors and subsequent treatment in women with a history of gestational hypertension or pre-eclampsia at term is likely to be cost-effective.
    Pregnancy Hypertension: An International Journal of Women's Cardiovascular Health. 01/2014;
  • American Journal of Obstetrics and Gynecology. 01/2014; 210(1):S2–S3.
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    ABSTRACT: Objective The aim of this study is to investigate which non-classic cardiovascular biomarkers are associated with persistent endothelial dysfunction after pregnancy in women with a history of hypertensive pregnancy disorders compared to women with uncomplicated pregnancies. Study design Systematic review and meta-analysis of observational studies. A search was performed in PubMed, Embase, Cochrane and Cinahl including articles from inception to 27 February 2013. Included were cohort studies and case-control studies. Cases were women with a history of hypertension in pregnancy, control subjects were women with a history of uncomplicated pregnancies. Of the 3136 found, 21 studies on 16 non-classic cardiovascular biomarkers are described in this review; 12 studies on 5 biomarkers were included in the meta-analysis. Results Women with a history of hypertensive pregnancy disorders had a higher homocysteine level compared to women with a history of uncomplicated pregnancies (5 studies; pooled mean difference 0.77ng/ml; 95% confidence interval 0.27 to 1.26; p <0.01). For the other non-classic cardiovascular biomarkers including markers in areas of inflammation, thrombosis and angiogenesis, we found no significant differences. Conclusion This review and meta-analysis showed that women with a history of hypertensive pregnancy disorders have higher homocysteine levels compared to women with a history of uncomplicated pregnancies. These data suggest persistent endothelial alteration after pregnancies complicated by hypertensive disorders.
    American journal of obstetrics and gynecology 01/2014; · 3.28 Impact Factor
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    ABSTRACT: Objective Women with late preterm premature rupture of membranes (PROM) have an increased risk that their child will develop neonatal sepsis. We evaluated whether neonatal sepsis can be predicted from antepartum parameters in these women. Study design: We used multivariable logistic regression to develop a prediction model. Data were obtained from two recent randomized controlled trials on induction of labor versus expectant management in late preterm PROM (PPROMEXIL trials, (ISRCTN29313500 and ISRCTN05689407). Data from randomized as well as non-randomized women, who consented to the use of their medical data, were used. We evaluated 13 potential antepartum predictors for neonatal sepsis. Missing data were imputed. Discriminative ability of the model was expressed as the area under the receiver operating characteristic (ROC) curve and a calibration with both a calibration plot and the Hosmer and Lemeshow goodness-of-fit test. Overall performance of the prediction model was quantified as the scaled Brier score. Results We studied 970 women. Thirty-three (3.4%) neonates suffered neonatal sepsis. Maternal age (OR 1.09 per year), maternal CRP level (OR 1.01 per mmol/l), maternal temperature (OR 1.80 per °Celsius) and positive GBS culture (OR 2.20) were associated with an increased risk of neonatal sepsis. The model had an area under the ROC-curve of 0.71. The model had both a good calibration and accuracy. Conclusions Antepartum parameters aid in the more precise prediction of the risk of neonatal sepsis in women with late preterm PPROM.
    European journal of obstetrics, gynecology, and reproductive biology 01/2014; · 1.97 Impact Factor
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    ABSTRACT: Objective Increasingly, maternal administration of 17-α-hydroxyprogesterone caproate (17-OHPC) is utilized to prevent preterm birth, but the fetal safety of 17-OHPC is still a matter of concern. This study aimed to assess whether exposure to 17-OHPC during the second and third trimesters of pregnancy affects fetal biometry in twin gestations. Methods This study included a subset of women with a twin pregnancy who had been previously included in a randomized clinical trial comparing the effectiveness of 17-OHPC and placebo on neonatal outcomes and preterm birth rates in multiple pregnancy. In the present study, the individual growth patterns of femur length, head circumference and abdominal circumference were compared between fetuses of women who had been randomized to receive weekly injections of either 17-OHPC (n = 52) or placebo (n = 58) at between 16–20 and 36 weeks' gestation. ResultsThe three biometric variables assessed developed similarly in fetuses in both the group exposed to 17-OHPC and the placebo group during the second half of pregnancy. Birth weight adjusted for parity and fetal sex was also comparable between groups. Conclusion The use of 17-OHPC has no adverse effects on fetal biometry and birth weight in twins. Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd.
    Ultrasound in Obstetrics and Gynecology 09/2013; 42(3). · 3.56 Impact Factor
  • Mieke Ten Eikelder, Ben Willem J Mol, Kitty Bloemenkamp
    American journal of obstetrics and gynecology 08/2013; · 3.28 Impact Factor
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    ABSTRACT: Cardiovascular disease (CVD) is the leading cause of death in women in the western world. Several studies have described the association between hypertensive pregnancy disorders and CVD in later life. Our aim was to compare postpartum cardiovascular risk factors in women who had a shorter and women who had a longer exposure to endothelial activation during their term hypertensive pregnancy. We studied a subsample of women with pregnancy-induced hypertension or mild preeclampsia at term, who had participated in the randomized HYPITAT trial comparing induction of labour (IOL cohort) (n=110) or expectant monitoring (EM cohort) (n=91). We assessed, 2.5 years postpartum, cardiovascular risk factors, i.e. blood pressure, anthropometrics, glucose, HbA1C, insulin, HOMA score, total cholesterol, HDL cholesterol, triglycerides, high sensitive CRP, micro-albumin and metabolic syndrome, and compared these risk factors between the induction and expectant groups. The mean time from randomization to delivery was 3.3 days in the induction group and 10.3 days in the expectant group (p<.001), generating a difference in exposure of 7 days. After a mean follow-up period of 2.5 years, the prevalence of hypertension (IOL 34%; EM 37%, p=.66) and metabolic syndrome (IOL 26%; EM 27%, p=1.0) was similar in both groups. Furthermore, systolic and diastolic blood pressure, BMI, waist circumference, glucose, HbA1C, insulin, HOMA score, lipids, HsCRP-levels and micro-albumin were all comparable between women who had induction of labour and those who had expectant monitoring. In women with hypertensive disorders in pregnancy at term, induction of labour does not affect the clinical and biochemical cardiovascular profile at 2.5 years postpartum.
    European journal of obstetrics, gynecology, and reproductive biology 08/2013; · 1.97 Impact Factor
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    ABSTRACT: In women with a multiple pregnancy, spontaneous preterm delivery is the leading cause of perinatal morbidity and mortality. Interventions to reduce preterm birth in these women have not been successful. We assessed whether a cervical pessary could effectively prevent poor perinatal outcomes. We undertook a multicentre, open-label randomised controlled trial in 40 hospitals in the Netherlands. We randomly assigned women with a multiple pregnancy between 12 and 20 weeks' gestation (1:1) to pessary or control groups, using a web-based application with a computer-generated list with random block sizes of two to four, stratified by hospital. Participants and investigators were aware of group allocation. For women in the pessary group, a midwife or obstetrician inserted a cervical pessary between 16 and 20 weeks' gestation. Women in the control group did not receive the pessary, but otherwise received similar obstetrical care to those in the pessary group. The primary outcome was a composite of poor perinatal outcome: stillbirth, periventricular leucomalacia, severe respiratory distress syndrome, bronchopulmonary dysplasia, intraventricular haemorrhage, necrotising enterocolitis, proven sepsis, and neonatal death. Analyses were by modified intention to treat. This trial is registered in the Dutch trial registry, number NTR1858. Between Sept 21, 2009, and March 9, 2012, 813 women underwent randomisation, of whom 808 were analysed (401 in the pessary group; 407 in the control group). At least one child of 53 women (13%) in the pessary group had poor perinatal outcome, compared with 55 (14%) in the control group (relative risk 0·98, 95% CI 0·69-1·39). In unselected women with a multiple pregnancy, prophylactic use of a cervical pessary does not reduce poor perinatal outcome. The Netherlands Organisation for Health Research and Development.
    The Lancet 08/2013; · 39.06 Impact Factor
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    ABSTRACT: Pregnancies complicated by intrauterine growth restriction (IUGR) are at increased risk for neonatal morbidity and mortality. The Dutch nationwide disproportionate intrauterine growth intervention trial at term (DIGITAT trial) showed that induction of labour and expectant monitoring were comparable with respect to composite adverse neonatal outcome and operative delivery. In this study we compare the costs of both strategies. A cost analysis was performed alongside the DIGITAT trial, which was a randomized controlled trial in which 650 women with a singleton pregnancy with suspected IUGR beyond 36 weeks of pregnancy were allocated to induction or expectant management. Resource utilization was documented by specific items in the case report forms. Unit costs for clinical resources were calculated from the financial reports of participating hospitals. For primary care costs Dutch standardized prices were used. All costs are presented in Euros converted to the year 2009. Antepartum expectant monitoring generated more costs, mainly due to longer antepartum maternal stays in hospital. During delivery and the postpartum stage, induction generated more direct medical costs, due to longer stay in the labour room and longer duration of neonatal high care/medium care admissions. From a health care perspective, both strategies generated comparable costs: on average €7106 per patient for the induction group (N=321) and €6995 for the expectant management group (N=329) with a cost difference of €111 (95%CI: €-1296 to 1641). Induction of labour and expectant monitoring in IUGR at term have comparable outcomes immediately after birth in terms of obstetrical outcomes, maternal quality of life and costs. Costs are lower, however, in the expectant monitoring group before 38 weeks of gestation and costs are lower in the induction of labour group after 38 weeks of gestation. So if induction of labour is considered to pre-empt possible stillbirth in suspected IUGR, it is reasonable to delay until 38 weeks, with watchful monitoring.
    European journal of obstetrics, gynecology, and reproductive biology 08/2013; · 1.97 Impact Factor
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    ABSTRACT: To assess the safety and effectiveness of a transcervical Foley catheter compared to vaginal prostaglandin E2 inserts for term induction of labour. We conducted an open-label randomized controlled trial in five hospitals in the Netherlands. Women with a singleton term pregnancy in cephalic presentation, intact membranes, unfavourable cervix, and no prior caesarean section were enrolled. Participants were randomly allocated by a web-based randomization system to induction of labour with a 30ml Foley catheter or 10mg slow-release vaginal prostaglandin E2 inserts in a 1:1 ratio. Due to the nature of the intervention this study was not blinded. The primary outcome was the caesarean section rate. Secondary outcomes were maternal and neonatal morbidity and time from intervention to birth. Additionally, we carried out a systematic review and meta-analysis of similar studies. We analyzed 226 women: 107 received a Foley catheter and 119 inserts. Caesarean section rates were comparable (20% versus 22%, RR 0.90, 95% CI 0.54-1.50). Secondary outcomes showed no differences. We observed no serious maternal or neonatal morbidity. Meta-analysis showed comparable caesarean section rates, but significantly fewer cases of hyperstimulation during the ripening phase when a Foley catheter was used. We found, in this relatively small study, no differences in effectiveness and safety of induction of labour with a Foley catheter and 10mg slow release vaginal prostaglandin E2 inserts. Meta-analysis confirmed a comparable caesarean section rate, and showed fewer cases of hyperstimulation when a Foley catheter was used.
    European journal of obstetrics, gynecology, and reproductive biology 07/2013; · 1.97 Impact Factor
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    ABSTRACT: Preeclampsia is associated with increased levels of the circulating antiangiogenic factor sFlt-1 and with an excessive shedding of placenta-derived multinucleated syncytial aggregates into the maternal circulation. However, it remains unclear whether these aggregates are transcriptionally active in the maternal organs and can, therefore, contribute to the systemic manifestations of preeclampsia. In this study, we measured placental soluble fms-like tyrosine kinase-1 (sFlt-1) mRNA levels in preeclamptic- and control placentas and performed RNA in situ hybridization to localize the main placental expression site of sFlt-1 mRNA. Because the maternal lung is the first capillary bed that circulating syncytial aggregates traverse, we studied the presence and persistence of placental material in lungs of preeclamptic and control subjects. To confirm the placental origin of these aggregates in maternal lungs, immunohistochemistry for the placenta-specific marker hCG (human chorionic ghonadotropin) and Y chromosome in situ hybridization were performed. Using human placental tissue, we found that syncytial knots are the principal site of expression of the antiangiogenic factor sFlt-1. In addition, autopsy material obtained from women with preeclampsia (n=9) showed significantly more placenta-derived syncytial aggregates in the lungs than in control subjects (n=26). Importantly, these aggregates still contained the antiangiogenic factor sFlt-1 after their entrapment in the maternal lungs. The current study confirms the important role of syncytial knots in placental sFlt-1 mRNA production. In addition, it shows a significant association between preeclampsia and larger quantities of sFlt-1 containing syncytial aggregates in maternal lungs, suggesting that the transfer of syncytial aggregates to the maternal compartment may contribute to the systemic endothelial dysfunction that characterizes preeclampsia.
    Hypertension 07/2013; · 6.87 Impact Factor
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    ABSTRACT: Objectives To assess effectiveness and safety of Foley catheter versus vaginal misoprostol for term induction of labor.Study Design This trial randomly allocated women with singleton term pregnancy to 30-mL Foley catheter or 25-μg vaginal misoprostol tablets. Primary outcome was cesarean delivery rate. Secondary outcomes were maternal and neonatal morbidity and time to birth. Additionally, a systematic review was conducted.Results Fifty-six women were allocated to Foley catheter, 64 to vaginal misoprostol tablets. Cesarean delivery rates did not differ significantly (25% Foley versus 17% misoprostol; relative risk [RR] 1.46, 95% confidence interval [CI] 0.72 to 2.94), with more cesarean deliveries due to failure to progress in the Foley group (14% versus 3%; RR 4.57, 95% CI 1.01 to 20.64). Maternal and neonatal outcomes were comparable. Time from induction to birth was longer in the Foley catheter group (36 hours versus 25 hours; p < 0.001). Meta-analysis showed no difference in cesarean delivery rate and reduced vaginal instrumental deliveries and hyperstimulation in the Foley catheter group. Other outcomes were not different.Conclusion Our trial and meta-analysis showed no difference in cesarean delivery rates and less hyperstimulation with fetal heart rate changes and vaginal instrumental deliveries when using Foley catheter, thereby supporting potential advantages of the Foley catheter over misoprostol as ripening agent.
    American Journal of Perinatology 04/2013; · 1.57 Impact Factor
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    ABSTRACT: Introduction In preeclampsia (PE), the kidney is one of the major target organs. Growing evidence suggests PE increases the risk of subsequent microalbuminuria and end-stage renal disease (ESRD). Endotheliosis and podocyte changes due to anti-angiogenic factors seem to be salient features of PE. However, it is unknown whether chronic lesions are present in PE patients that could contribute to this increased risk. Objectives We hypothesized that women with PE and young women with chronic hypertension might show similarity in renal lesions. Furthermore, we investigated if the number of podocytes within the kidney is decreased under these different circumstances. Methods We performed a search for renal autopsy-tissues using a nationwide computerized database (PALGA) to collect a unique large cohort of preeclamptic patients (n = 11). Three control groups were included consisting of young women who died during pregnancy without hypertension (n = 25) and non-pregnant controls with (n = 14) and without (n = 13) chronic hypertension. WT-1 staining was used to quantify the number of podocytes. Results Women with PE had MPGN-like lesions without immune-deposits. Tram tracking and podocyte changes were exclusively observed in these patients. Endotheliosis was significantly more present in PE, but sporadically seen in pregnant- and hypertensive controls. Chronic ischaemic lesions were predominantly found in young women with chronic hypertension, and not in PE and other controls. No differences were found in glomerular podocyte number between the study groups. Conclusion All women with PE had MPGN-like lesions in their kidneys which was therefore regarded characteristic for PE. In contrast, no chronic lesions were observed in PE which could explain the increased risk of impaired renal function later in life. Interestingly, we demonstrated no difference in podocyte number between study groups. These results might suggest that neither persistent hypertension or dysbalance in angiogenic factors (i.e. preeclampsia) cause an observable change in podocyte number within the kidney.
    Pregnancy Hypertension: An International Journal of Women's Cardiovascular Health. 04/2013; 3(2):79.
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    ABSTRACT: BACKGROUND: Induction of labour is a common obstetric procedure. At present, different methods are used for induction of labour in women with an unfavourable cervix. Recently, we showed that in term women with an unfavorable cervix the use of a Foley catheter in comparison with vaginal Prostaglandin E2 gel, results in a comparable vaginal delivery rate. A meta-analysis on the subject indicated lower rates of hyperstimulation, and probably as a sequel fewer cases of postpartum haemorrhage. Misoprostol (PgE1) is another type of prostaglandin frequently used for labour induction, recommended by the international federation of gynaecology and obstetrics (FIGO). Misoprostol can be administered by vaginal, rectal and oral route. There is evidence that oral administration results in less asphyxia and hyperstimulation than vaginal administration. At present, valid comparisons between oral misoprostol and Foley catheter are lacking. Therefore, we propose a randomised controlled trial comparing Foley catheter to oral misoprostol in order to assess safety and cost-effectiveness. METHODS: We plan a multicentre, randomised, controlled, open-label clinical trial among term pregnant women with a vital singleton in cephalic presentation, unfavorable cervix, intact membranes and an indication for induction of labour. After informed consent, women will be randomly allocated by a webbased randomisation system to transcervical Foley catheter or oral misoprostol (50 mcg every 4 hours). The primary outcome will be a composite of complications of uterine hyperstimulation, i.e. post partum haemorrhage and asphyxia. Secondary outcomes are mode of delivery, maternal and neonatal morbidity, costs and women's preference. Serious adverse events such as severe maternal or neonatal morbitity or mortality will be monitored and reported to an independent data safety monitory board. With a sample size of 1860 women we will be able to demonstrate a 5% non-inferiority of the Foley catheter as compared to misoprostol for the composite outcome. DISCUSSION: Worldwide, various methods are being used for labour induction. Results of the proposed trial will contribute to the answer which method of induction of labour is most safe, cost-effective, and patient friendly and will help to construct evidence based guidelines.Trial registration: The Netherlands Trial Register NTR3466,
    BMC Pregnancy and Childbirth 03/2013; 13(1):67. · 2.52 Impact Factor
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    ABSTRACT: OBJECTIVE: The purpose of this study was to determine cardiovascular risk factors in women with a history of hypertensive pregnancy disorders at term, 2.5 years after pregnancy. STUDY DESIGN: In a multicenter cohort study in the Netherlands between June 2008 and November 2010, cardiovascular risk factors were compared between women with a history of hypertensive pregnancy disorders at term (HTP cohort, n=306) and women with a history of normotensive pregnancies at term (NTP cohort, n=99). HTP women had participated in a randomized, longitudinal trial assessing the effectiveness of induction of labor in women with hypertensive pregnancy disorders at term. All women were assessed 2.5 years after pregnancy for blood pressure, anthropometrics, glucose, HbA1C, insulin, HOMA score, total cholesterol, HDL cholesterol, triglycerides, high sensitive CRP and micro-albumin and metabolic syndrome. RESULTS: After a mean follow-up period of 2.5 years, hypertension (HTP, 34%; NTP, 1%; P<.001) and metabolic syndrome (HTP, 25%; NTP, 5%; P<.001) were more prevalent in HTP women compared with NTP women. HTP women had significantly higher systolic and diastolic blood pressure, higher BMI and waist circumference. Glucose, HbA1C, insulin, HOMA score, total cholesterol, triglycerides and high sensitive CRP-levels were significantly higher and HDL cholesterol was significantly lower in HTP women. CONCLUSIONS: In women with a history of hypertensive pregnancy disorders at term hypertension and metabolic syndrome are more common, and they have higher levels of biochemical cardiovascular risk factors 2.5 years after pregnancy.
    American journal of obstetrics and gynecology 02/2013; · 3.28 Impact Factor
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    ABSTRACT: BACKGROUND Pre-eclampsia has a clear familial component, suggesting that the condition may be partly attributable to genetic susceptibility. The search for susceptibility genes has led to a drastic increase in the number of published studies associating genetic factors with pre-eclampsia. However, attempts to replicate these findings have yielded inconsistent results. This meta-analysis assessed the pooled effect of each genetic variant that is reproducibly associated with pre-eclampsia.METHODS Studies that assessed the association between genes and pre-eclampsia were searched in PubMed, Embase and Web of Science. We selected all genetic variants that were significantly associated with pre-eclampsia in an initial study and were subsequently independently reproduced in at least one additional study. All studies that assessed these reproduced variants were then included. The association between genetic variants and pre-eclampsia was calculated at the allele level, and the main measure of effect was a pooled odds ratio in a random-effects model.RESULTSThe literature search yielded 2965 articles, of which 542 investigated genetic associations in pre-eclampsia. We identified 22 replicated genetic variants, of which 7 remained significantly associated with pre-eclampsia following meta-analysis. These variants were in or near the following genes: ACE, CTLA4, F2, FV, LPL and SERPINE1.CONCLUSIONS This meta-analysis identified seven genetic variants associated with pre-eclampsia. Importantly, many of these variants are also risk factors for developing cardiovascular disease, revealing that pre-eclampsia and cardiovascular disease have shared genetic risk factors. The contribution of the identified genetic variants in the pathogenesis of pre-eclampsia should be the focus of future studies.
    Human Reproduction Update 01/2013; · 9.23 Impact Factor

Publication Stats

2k Citations
854.80 Total Impact Points


  • 2014
    • University of Amsterdam
      • Department of Obstetrics and Gynaecology
      Amsterdamo, North Holland, Netherlands
  • 1995–2014
    • Leiden University Medical Centre
      • • Department of Obstetrics
      • • Department of Clinical Epidemiology
      Leyden, South Holland, Netherlands
  • 2011–2013
    • Academisch Medisch Centrum Universiteit van Amsterdam
      • • Academic Medical Center
      • • Department of Obstetrics & Gynecology
      Amsterdam, North Holland, Netherlands
    • Groene Hart Ziekenhuis
      Guda, South Holland, Netherlands
  • 2010–2013
    • VU University Medical Center
      • Department of Obstetrics and Gynecology
      Amsterdam, North Holland, Netherlands
  • 2012
    • Bronovo Hospital
      's-Gravenhage, South Holland, Netherlands
  • 2007–2011
    • University of Groningen
      • Department of Obstetrics and Gynaecology
      Groningen, Province of Groningen, Netherlands
  • 2004–2011
    • Erasmus MC
      • • Department of Internal Medicine
      • • Department of Obstetrics and Gynaecology
      Rotterdam, South Holland, Netherlands
  • 1998
    • Saint Joseph Hospital
      Chicago, Illinois, United States
  • 1997
    • Leiden University
      Leyden, South Holland, Netherlands
    • St. Joseph's Hospital
      Savannah, Georgia, United States