Cost-effectiveness analysis of a first-trimester screening test for preterm preeclampsia in the Netherlands

Objectives: The risk of preterm preeclampsia (PT PE) can significantly be reduced by starting acetylsalicylic acid ≤ 16 weeks of gestational age. First trimester predictive models based on maternal risk factors to effectively start this therapy lacked sufficient power, but recent studies showed that these models can be improved by including test results of biochemical and/or -physical markers. To investigate whether testing a biochemical marker in the first trimester is cost-effective in the Netherlands, a cost-effectiveness analysis was performed in this study. Study design: The outcome of this study was expressed as an incremental cost-effectiveness ratio (ICER) with as effect prevented PT PE cases. To evaluate the impact of each model parameter and to determine model uncertainties, both univariate and probabilistic sensitivity analyses were performed. Results: When compared to the baseline strategy, the test strategy is estimated to save almost 4 million euros per year on a national scale and at the same time this would prevent an additional 228 PT PE cases. The sensitivity analyses showed that the major drivers of the result are the costs to monitor a high-risk pregnancy and the specificity and that most of the model simulations were in the southeast quadrant: cost saving and more prevented complications. Conclusions: This study showed that a first-trimester test strategy to screen for PT PE in the first trimester is potentially cost-effective in the Dutch healthcare setting. The fact that the specificity is a major driver of the ICER indicates the importance for a (new) screening model to correctly classify low-risk pregnancies.</p

Healthy and preeclamptic pregnancies show differences in Guanylate-Binding Protein-1 plasma levels

The large interferon-inducible anti-angiogenic pro-inflammatory GTPase Guanylate Binding Protein-1 (GBP-1) is produced and secreted by activated endothelial cells and is highly induced by inflammatory cytokines and inhibited by angiogenic growth factors. During pregnancy a generalized mild inflammatory response is observed. During preeclampsia this generalized inflammatory response is even further activated and activation of the endothelium occurs. We hypothesized that GBP-1 is increased in healthy pregnancy and will be even further increased during preeclampsia. In the first experiment, plasma and placentas were collected from healthy and preeclamptic pregnancies. Plasma was also collected from non-pregnant women. For the second experiment longitudinal blood samples from women with a healthy or preeclamptic pregnancy were collected from the end of the first trimester until birth and one sample postpartum. The plasma GBP-1 levels were measured by ELISA and GBP-1 mRNA and protein levels in the placenta were tested by qPCR and immunohistochemistry. During pregnancy higher plasma concentrations of GBP-1 compared with non-pregnant women were observed. Surprisingly, during preeclampsia, plasma GBP-1 levels were lower than in control pregnancies and similar to the level of non-pregnant controls. Placental GBP-1 mRNA levels were not different between healthy and preeclamptic pregnancies and GBP-1 protein was virtually undetectable in the trophoblast by immunohistochemistry in placental tissue. Evaluation of longitudinal samples showed that plasma GBP-1 concentrations increased towards the end of pregnancy in healthy pregnancies, but not in preeclampsia. In line with our hypothesis, we found higher GBP-1 plasma levels during healthy pregnancy. However, plasma GBP-1 did not further increase during preeclampsia, but was stable. Further studies are needed to evaluate why GBP-1 does not increase during preeclampsia

First trimester secreted Frizzled-Related Protein 4 and other adipokine serum concentrations in women developing gestational diabetes mellitus

BACKGROUND: The aim of this study was to evaluate whether soluble frizzled-related protein 4 (sFRP4) concentration in the first trimester of pregnancy is individually, or in combination with Leptin, Chemerin and/or Adiponectin, associated with the development of gestational diabetes (GDM). METHODS: In a nested case-control study, 50 women with GDM who spontaneously conceived and delivered a live-born infant were matched with a total of 100 uncomplicated singleton control pregnancies based on body mass index (± 2 kg/m2), gestational age at sampling (exact day) and maternal age (± 2 years). In serum samples, obtained between 70-90 days gestational age, sFRP4, Chemerin, Leptin and Adiponectin concentrations were determined by ELISA. Statistical comparisons were performed using univariate and multi-variate logistic regression analysis after logarithmic transformation of the concentrations. Discrimination of the models was assessed by the area under the curve (AUC). RESULTS: First trimester sFRP4 concentrations were significantly increased in GDM cases (2.04 vs 1.93 ng/ml; p<0.05), just as Chemerin (3.19 vs 3.15 ng/ml; p<0.05) and Leptin (1.44 vs 1.32 ng/ml; p<0.01). Adiponectin concentrations were significantly decreased (2.83 vs 2.94 ng/ml; p<0.01) in GDM cases. Further analysis only showed a weak, though significant, correlation of sFRP4 with Chemerin (R2 = 0.124; p<0.001) and Leptin (R2 = 0.145; p<0.001), and Chemerin with Leptin (R2 = 0.282; p<0.001) in the control group. In a multivariate logistic regression model of these four markers, only Adiponectin showed to be significantly associated with GDM (odds ratio 0.12, 95%CI 0.02-0.68). The AUC of this model was 0.699 (95%CI 0.605-0.793). CONCLUSION: In the first trimester of pregnancy, a multi-marker model with sFRP4, Leptin, Chemerin and Adiponectin is associated with the development of GDM. Therefore, this panel seems to be an interesting candidate to further evaluate for prediction of GDM in a prospective study

Het effect van de CBG-waarschuwing op de trend in SSRI-gebruik in Nederland van 1998 tot 2010

OBJECTIVE: To determine the effect of the warning by the Dutch Medicines Evaluation Board (CBG) in 2004 concerning SSRI use by children on the trend of SSRI utilization in the Dutch population in the period 1998-2010. DESIGN: Interrupted time series analysis. METHODS: Yearly prevalence of SSRI utilization (excluding fluoxetine) was calculated for the age categories 12-18, 19-24, 25-49, 50-64 and 65-84 years. Regression was used to determine whether the trend in SSRI utilization after 2004 changed significantly from the trend before 2004. RESULTS: Prevalence in SSRI utilization in age groups 12-18, 19-24 and 25-49 years increased in the period 1998 to 2004 and started to decline after 2004 (P <0.001) until 2010. Prevalence in age categories 50-64 and 64-84 years increased in the period 1998 to 2004 and the increase in prevalence afterwards is not significantly different from 0. Prevalence of fluoxetine utilization declined throughout the study period. CONCLUSION: The CBG warning appears to strongly affect the trends in the utilization of SSRIs (excluding fluoxetine) in the Netherlands. It is noteworthy that the trends in SSRI utilization in age categories above 24 years, at which the warning was not aimed, significantly changed after 2004

The effect of the warning by the Dutch Medicines Evaluation Board on the trend in SSRI utilization in the Netherlands from 1998 to 2010

OBJECTIVE: To determine the effect of the warning by the Dutch Medicines Evaluation Board (CBG) in 2004 concerning SSRI use by children on the trend of SSRI utilization in the Dutch population in the period 1998-2010. DESIGN: Interrupted time series analysis. METHODS: Yearly prevalence of SSRI utilization (excluding fluoxetine) was calculated for the age categories 12-18, 19-24, 25-49, 50-64 and 65-84 years. Regression was used to determine whether the trend in SSRI utilization after 2004 changed significantly from the trend before 2004. RESULTS: Prevalence in SSRI utilization in age groups 12-18, 19-24 and 25-49 years increased in the period 1998 to 2004 and started to decline after 2004 (P &lt;0.001) until 2010. Prevalence in age categories 50-64 and 64-84 years increased in the period 1998 to 2004 and the increase in prevalence afterwards is not significantly different from 0. Prevalence of fluoxetine utilization declined throughout the study period. CONCLUSION: The CBG warning appears to strongly affect the trends in the utilization of SSRIs (excluding fluoxetine) in the Netherlands. It is noteworthy that the trends in SSRI utilization in age categories above 24 years, at which the warning was not aimed, significantly changed after 2004