Janneke Jentink

University of Groningen, Groningen, Groningen, Netherlands

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Publications (10)94.94 Total impact

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    ABSTRACT: Anti-epileptic drugs are known to be teratogenic, yet many women do need to continue the anti-epileptic drug use during pregnancy. Objectives: To perform an economic evaluation of the anti-epileptic drug choice in young women who potentially wish to become pregnant. In particular, to estimate the impact of teratogenicity on the costs per quality adjusted life year (QALY). A decision-tree model is used to calculate the costs per QALY, taking into account the malformation risk in offspring due to the exposure to carbamazepine, lamotrigine or valproic acid, based on the European birth cohort of 2007. Probabilistic sensitivity analyses were performed using Monte Carlo simulation. Valproic acid is dominated by carbamazepine after rank ordering on costs. The incremental cost-effectiveness of lamotrigine vs carbamazepine was estimated at €175,534 per QALY. Although valproic acid was dominated by carbamazepine in terms of costs and related effects, it is clinically relevant to compare lamotrigine with valproic acid. In particular, treatment options are dependent on several individual and clinical characteristics and these agents are therefore not always considered as interchangeable for all specified populations. The incremental cost-effectiveness for lamotrigine vs valproic acid was estimated at €13,370 per QALY. With assuming a willingness to pay threshold of €50,000 per QALY, results from the probabilistic analysis resulted in an acceptance level for lamotrigine vs carbamazepine and lamotrigine vs valproic acid of 4% and 99%, respectively. Based on epidemiological data it is advised to whenever possible avoid valproic acid during pregnancy. Both carbamazepine and lamotrigine are estimated to be cost-effective treatment options vs valproic acid if focused on teratogenicity.
    Journal of Medical Economics 04/2012; 15(5):862-8. DOI:10.3111/13696998.2012.684366
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    ABSTRACT: A case-control study is the most powerful design to test the risk of specific congenital malformations associated with a specific drug. However, malformation registries often lack non-malformed controls. For the Dutch EUROCAT, we collected a non-malformed control group: the 'Healthy Pregnant'. The aim of this study was to evaluate the representativeness of this control group for the general pregnant population in the northern part of the Netherlands. The Healthy Pregnant data set includes data from two midwife practices. The baseline characteristics of mother and child including smoking status, drinking status, body mass index, maternal age, educational level, exposures to several drugs for chronic diseases and pregnancy related symptoms were evaluated. Compared with the general population, mothers in Healthy Pregnant group (n = 556) were from either low or high education level, were more likely to have a body mass index > 25 kg/m² (26% versus 22%, p = 0.08) or to smoke (19% versus 10%, p < 0.01) but were less likely to consume alcohol (20% versus 29%, p < 0.01). The use of drugs for chronic conditions was lower in Healthy Pregnant group. Furthermore, drugs for occasional use were prescribed less frequently, and a significant underreporting of children with a low birth weight and a short duration of gestation was found. The Healthy Pregnant data set was not representative of the general pregnant population in the northern part of the Netherlands. Specifically, the exposure to (chronic) drugs was underestimated, possibly a result of second-line care on the basis of medical indication. Thus, continuous investigation of options for improvement of the Healthy Pregnant database is required.
    Pharmacoepidemiology and Drug Safety 09/2011; 20(11):1217-23. DOI:10.1002/pds.2254 · 3.17 Impact Factor
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    ABSTRACT: To compare the distribution of congenital anomalies within the VACTERL association (vertebral defects, anal atresia, cardiac, tracheoesophageal, renal, and limb abnormalities) between patients exposed to tumor necrosis factor-α (TNF-α) antagonist and the general population. Analysis for comparison of proportional differences to a previous publication between anomaly subgroups, according to subgroup definitions of the European Surveillance of Congenital Anomalies (EUROCAT), a population-based database. Most EUROCAT subgroups belonging to the VACTERL association contained only one or 2 records of TNF-α antagonist exposure, so comparison of proportions was imprecise. Only the category "limb abnormalities" showed a significantly higher proportion in the general population. The high number of congenital anomalies belonging to the VACTERL association from a report of pregnancies exposed to TNF-α antagonists could not be confirmed using a population-based congenital anomaly database.
    The Journal of Rheumatology 07/2011; 38(9):1871-4. DOI:10.3899/jrheum.101316 · 3.17 Impact Factor
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    ABSTRACT: To identify specific major congenital malformations associated with use of carbamazepine in the first trimester of pregnancy. A review of all published cohort studies to identify key indications and a population based case-control study to test these indications. Review of PubMed, Web of Science, and Embase for papers about carbamazepine exposure in the first trimester of pregnancy and specific malformations, and the EUROCAT Antiepileptic Study Database, including data from 19 European population based congenital anomaly registries, 1995-2005. The literature review covered eight cohort studies of 2680 pregnancies with carbamazepine monotherapy exposure, and the EUROCAT dataset included 98 075 registrations of malformations covering over 3.8 million births. Overall prevalence for a major congenital malformation after exposure to carbamazepine monotherapy in the first trimester. Odds ratios for malformations with exposure to carbamazepine among cases (five types of malformation identified in the literature review) compared with two groups of controls: other non-chromosomal registrations of malformations and chromosomal syndromes. The literature review yielded an overall prevalence for a major congenital malformation of 3.3% (95% confidence interval 2.7 to 4.2) after exposure to carbamazepine monotherapy in the first trimester. In 131 registrations of malformations, the fetus had been exposed to carbamazepine monotherapy. Spina bifida was the only specific major congenital malformation significantly associated with exposure to carbamazepine monotherapy (odds ratio 2.6 (95% confidence interval 1.2 to 5.3) compared with no antiepileptic drug), but the risk was smaller for carbamazepine than for valproic acid (0.2, 0.1 to 0.6). There was no evidence for an association with total anomalous pulmonary venous return (no cases with carbamazepine exposure), cleft lip (with or without palate) (0.2, 0.0 to 1.3), diaphragmatic hernia (0.9, 0.1 to 6.6), or hypospadias (0.7, 0.3 to 1.6) compared with no exposure to antiepileptic drugs. Further exploratory analysis suggested a higher risk of single ventricle and atrioventricular septal defect. Carbamazepine teratogenicity is relatively specific to spina bifida, though the risk is less than with valproic acid. Despite the large dataset, there was not enough power to detect moderate risks for some rare major congenital malformations.
    BMJ (online) 12/2010; 341:c6581. DOI:10.1136/bmj.c6581 · 16.38 Impact Factor
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    ABSTRACT: Women with child wish are advised to take folic acid supplements to reduce the risk for spina bifida. However, there is less evidence for this protective effect in women using valproic acid (VPA). We investigated the effect of folic acid in women exposed to VPA in the first trimester of pregnancy. A case-control study was performed with data from a population-based registry of congenital malformations. Our cases were spina bifida registrations and all other malformed registrations (excluding folic acid sensitive malformations) were used as controls. The ORs for the effect of correct folic acid use were calculated among antiepileptic drug (AED) unexposed pregnancies 0.5 [95%CI: 0.3-0.7] and among VPA exposed pregnancies 1.0 [95%CI: 0.1-7.6]. Due to power-reasons, we cannot conclude that folic acid has no effect on the risk for spina bifida among VPA exposed pregnancies. Although for AED unexposed pregnancies we found a decreased risk. Results from (animal) studies support a biologically plausible association between VPA, folic acid and spina bifida. While folic acid might not be able to reduce the risk for lower spina bifida lesions caused by VPA, the use of folic acid might be important to reduce the risk for higher, folic acid sensitive spina bifida lesions. Further research is needed to get more insight in the most effective form and dose of FA in women that use VPA to reduce the risk for (higher forms of) spina bifida.
    Pharmacoepidemiology and Drug Safety 08/2010; 19(8):803-7. DOI:10.1002/pds.1975 · 3.17 Impact Factor
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    ABSTRACT: The use of valproic acid in the first trimester of pregnancy is associated with an increased risk of spina bifida, but data on the risks of other congenital malformations are limited. We first combined data from eight published cohort studies (1565 pregnancies in which the women were exposed to valproic acid, among which 118 major malformations were observed) and identified 14 malformations that were significantly more common among the offspring of women who had received valproic acid during the first trimester. We then assessed the associations between use of valproic acid during the first trimester and these 14 malformations by performing a case-control study with the use of the European Surveillance of Congenital Anomalies (EUROCAT) antiepileptic-study database, which is derived from population-based congenital-anomaly registries. Registrations (i.e., pregnancy outcomes with malformations included in EUROCAT) with any of these 14 malformations were compared with two control groups, one consisting of infants with malformations not previously linked to valproic acid use (control group 1), and one consisting of infants with chromosomal abnormalities (control group 2). The data set included 98,075 live births, stillbirths, or terminations with malformations among 3.8 million births in 14 European countries from 1995 through 2005. Exposure to valproic acid monotherapy was recorded for a total of 180 registrations, with 122 registrations in the case group, 45 in control group 1, and 13 in control group 2. As compared with no use of an antiepileptic drug during the first trimester (control group 1), use of valproic acid monotherapy was associated with significantly increased risks for 6 of the 14 malformations under consideration; the adjusted odds ratios were as follows: spina bifida, 12.7 (95% confidence interval [CI], 7.7 to 20.7); atrial septal defect, 2.5 (95% CI, 1.4 to 4.4); cleft palate, 5.2 (95% CI, 2.8 to 9.9); hypospadias, 4.8 (95% CI, 2.9 to 8.1); polydactyly, 2.2 (95% CI, 1.0 to 4.5); and craniosynostosis, 6.8 (95% CI, 1.8 to 18.8). Results for exposure to valproic acid were similar to results for exposure to other antiepileptic drugs. The use of valproic acid monotherapy in the first trimester was associated with significantly increased risks of several congenital malformations, as compared with no use of antiepileptic drugs or with use of other antiepileptic drugs.
    New England Journal of Medicine 06/2010; 362(23):2185-93. DOI:10.1056/NEJMoa0907328 · 54.42 Impact Factor
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    ABSTRACT: To investigate whether first trimester exposure to lamotrigine (LTG) monotherapy is specifically associated with an increased risk of orofacial clefts (OCs) relative to other malformations, in response to a signal regarding increased OC risk. Population-based case-control study with malformed controls based on EUROCAT congenital anomaly registers. The study population covered 3.9 million births from 19 registries 1995-2005. Registrations included congenital anomaly among livebirths, stillbirths, and terminations of pregnancy following prenatal diagnosis. Cases were 5,511 nonsyndromic OC registrations, of whom 4,571 were isolated, 1,969 were cleft palate (CP), and 1,532 were isolated CP. Controls were 80,052 nonchromosomal, non-OC registrations. We compared first trimester LTG and antiepileptic drug (AED) use vs nonepileptic non-AED use, for mono and polytherapy, adjusting for maternal age. An additional exploratory analysis compared the observed and expected distribution of malformation types associated with LTG use. There were 72 LTG exposed (40 mono- and 32 polytherapy) registrations. The ORs for LTG monotherapy vs no AED use were 0.67 (95% CI 0.10-2.34) for OC relative to other malformations, 0.80 (95% CI 0.11-2.85) for isolated OC, 0.79 (95% CI 0.03-4.35) for CP, and 1.01 (95% CI 0.03-5.57) for isolated CP. ORs for any AED use vs no AED use were 1.43 (95% CI 1.03-1.93) for OC, 1.21 (95% CI 0.82-1.72) for isolated OC, 2.37 (95% CI 1.54-3.43) for CP, and 1.86 (95% CI 1.07-2.94) for isolated CP. The distribution of other nonchromosomal malformation types with LTG exposure was similar to non-AED exposed. We find no evidence of a specific increased risk of isolated orofacial clefts relative to other malformations due to lamotrigine (LTG) monotherapy. Our study is not designed to assess whether there is a generalized increased risk of malformations with LTG exposure.
    Neurology 09/2008; 71(10):714-22. DOI:10.1212/01.wnl.0000316194.98475.d8 · 8.30 Impact Factor
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    ABSTRACT: Folic acid intake before and during pregnancy reduces neural tube defects (NTD). Therefore, several countries have enriched bulk food with folic acid resulting in a 26-48% decrease in the prevalence of NTDs. In 2000, the Dutch Health Council advised against folic acid enrichment based on literature research; yet formal cost-effectiveness information was absent. We designed our study to estimate cost-effectiveness of folic acid food fortification in the Netherlands. Prevalence of NTD at birth, life-time costs of care, and folic acid fortification costs were estimated using Dutch registrations, Dutch guidelines for costing, (inter)national literature and expert opinions. Both net cost per discounted life year gained and net cost per discounted quality adjusted life year (QALY) gained were estimated for the base case and sensitivity analyses. In the base case and most sensitivity analyses, folic acid enrichment was estimated to be cost-saving. Bulk food fortification with folic acid remains cost-effective as long as enrichment costs do not exceed euro5.5 million (threshold at euro20 000 per QALY). Our model suggests that folic acid fortification of bulk food to prevent cases of NTD in newborns might be a cost-saving intervention in the Netherlands. Additionally, besides the evidence that folic acid reduces the number of NTDs, there are indications that folic acid is associated with the prevention of other birth defects, cardiovascular diseases and cancer. Our model did not yet include these possibly beneficial effects.
    The European Journal of Public Health 07/2008; 18(3):270-4. DOI:10.1093/eurpub/ckm129 · 2.46 Impact Factor
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    ABSTRACT: To compare the prescription of drugs in women over a period from 2 years before until 3 months after pregnancy, regarding the type of drugs used and the fetal risk. A cohort study based on pharmacy records of women giving birth to a child between 1994 and 2003. The study was performed with data from the InterAction database, containing prescription-drug-dispensing data from community pharmacies. The study population included 5412 women for whom complete pharmacy records were available. Drugs were classified into three categories: (1) drugs for chronic conditions, (2) drugs for occasional use and (3) drugs for pregnancy-related symptoms and also classified according to the Australian classification system. The prescription rate was calculated as the number of women per 100 women who received one or more prescriptions for a given drug within a specified time period. About 79.1% of the women received at least one prescription during pregnancy. The prescription rate for most drugs for chronic diseases and for occasional use decreased during pregnancy, whereas, as expected, the prescription rate for pregnancy-related drugs increased. During the first trimester of pregnancy, 1.7% of all drugs prescribed for chronic conditions and 2.3% of the occasional drugs were classified as harmful. The increase in prescription rate during pregnancy is caused by an increase in prescription rate of drugs for pregnancy-related symptoms. The prescription of harmful drugs is more commonly associated with drugs for occasional use rather than with drugs for chronic conditions. Therefore, a more cautious prescribing of drugs to healthy women in the fertile age is necessary.
    BJOG An International Journal of Obstetrics & Gynaecology 06/2006; 113(5):559-68. DOI:10.1111/j.1471-0528.2006.00927.x · 3.86 Impact Factor