Hao Wang

University of Groningen, Groningen, Groningen, Netherlands

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Publications (8)23.22 Total impact

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    ABSTRACT: Background: Insulin analogues are commonly used in pregnant women with diabetes. It is not known if the use of insulin analogues in pregnancy is associated with any higher risk of congenital anomalies in the offspring compared with use of human insulin. Methods: We performed a literature search for studies of pregnant women with pregestational diabetes using insulin analogues in the first trimester and information on congenital anomalies. The studies were analyzed to compare the congenital anomaly rate among fetuses of mothers using insulin analogues with fetuses of mothers using human insulin. Results: Of 29 studies we included 1286 fetuses of mothers using short-acting insulin analogues with 1089 references of mothers using human insulin and 768 fetuses of mothers using long-acting insulin analogues with 685 references of mothers using long-acting human insulin (Neutral Protamine Hagedorn; NPH). The congenital anomaly rate was 4.84% and 4.29% among the fetuses of mothers using lispro and aspart. For glargine and detemir the congenital anomaly rate was 2.86% and 3.47% respectively. No studies on the use of insulin glulisine and degludec in pregnancy were found. There was no statistically significant difference in the congenital anomaly rate among fetuses exposed to insulin analogues (lispro, aspart, glargine or detemir) compared to those exposed to human insulin or NPH insulin. Conclusion: The total prevalence of congenital anomalies was not increased for fetuses exposed to insulin analogues. The small samples in the included studies provided insufficient statistical power to identify a moderate increased risk of specific congenital anomalies. This article is protected by copyright. All rights reserved.
    No preview · Article · Oct 2015 · Diabetes/Metabolism Research and Reviews
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    ABSTRACT: The aim of this study was to explore antiepileptic drug (AED) prescribing before, during and after pregnancy as recorded in seven population-based electronic healthcare databases. Databases in Denmark, Norway, the Netherlands, Italy (Emilia Romagna/Tuscany), Wales and the Clinical Practice Research Datalink, representing the rest of the UK, were accessed for the study. Women with a pregnancy starting and ending between 2004 and 2010, which ended in a delivery, were identified. AED prescriptions issued (UK) or dispensed (non-UK) at any time during pregnancy and the 6 months before and after pregnancy were identified in each of the databases. AED prescribing patterns were analysed, and the choice of AEDs and co-prescribing of folic acid were evaluated. In total, 978 957 women with 1 248 713 deliveries were identified. In all regions, AED prescribing declined during pregnancy and was lowest during the third trimester, before returning to pre-pregnancy levels by 6 months following delivery. For all deliveries, the prevalence of AED prescribing during pregnancy was 51 per 10 000 pregnancies (CI95 49-52%) and was lowest in the Netherlands (43/10 000; CI95 33-54%) and highest in Wales (60/10 000; CI95 54-66%). In Denmark, Norway and the two UK databases lamotrigine was the most commonly prescribed AED; whereas in the Italian and Dutch databases, carbamazepine, valproate and phenobarbital were most frequently prescribed. Few women prescribed with AEDs in the 3 months before pregnancy were co-prescribed with high-dose folic acid: ranging from 1.0% (CI95 0.3-1.8%) in Emilia Romagna to 33.5% (CI95 28.7-38.4%) in Wales. The country's differences in prescribing patterns may suggest different use, knowledge or interpretation of the scientific evidence base. The low co-prescribing of folic acid indicates that more needs to be done to better inform clinicians and women of childbearing age taking AEDs about the need to offer and receive complete preconception care. © 2015 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd. Copyright © 2015 John Wiley & Sons, Ltd.
    Full-text · Article · Aug 2015 · Pharmacoepidemiology and Drug Safety
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    ABSTRACT: Drug use in pregnancy is very common but may cause harm to the fetus. The teratogenic effect of a drug is partly dependent on the drug level in the fetal circulation, which is associated with the transport across the placenta. Many drugs are substrates of P-glycoprotein (P-gp), an efflux transporter that acts as a protective barrier for the fetus. We aim to identify whether drug interactions associated with P-gp promote any changes in fetal drug exposure, as measured by the risk of having children with congenital anomalies. In this study, cases (N = 4634) were mothers of children with congenital anomalies registered in the EUROCAT Northern Netherlands registry, and the reference population were mothers of children (N = 25,126) from a drug prescription database (IADB.nl). Drugs that are associated with P-gp transport were commonly used in pregnancy in cases (10 %) and population (12 %). Several drug classes, which are substrates for P-gp, were shown to have a higher user rate in mothers of cases with specific anomalies. The use of this subset of drugs in combination with other P-gp substrates increased the risk for specific anomalies (odds ratio [OR] 4.17, 95 % CI 1.75-9.91), and the addition of inhibitors further increased the risk (OR 13.03, 95 % CI 3.37-50.42). The same pattern of risk increment was observed when the drugs were analyzed separately according to substrate specificity. The use of drugs associated with P-gp transport was common during pregnancy. For several drug classes associated with specific anomalies, P-gp-mediated drug interactions are associated with an increased risk for those specific anomalies.
    Full-text · Article · May 2015 · Drug Safety
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    ABSTRACT: One of the ongoing issues in perinatal medicine is the risk of birth defects associated with maternal drug use. The teratogenic effect of a drug depends, apart from other factors, on the exposition of the fetus to the drug. Transporter proteins are known to be involved in the pharmacokinetics of drugs and have an effect on drug level and fetal drug exposure. This condition may subsequently alter the risk of teratogenicity, which occurs in a dose-dependent manner. This review focuses on the clinically important polymorphisms of transporter proteins and their effects on the mRNA and protein expression in placental tissue. We also propose a novel approach on how the different genotypes of the polymorphism can be translated into phenotypes to facilitate genetic association studies. The last section looks into the recent studies exploring the association between P-glycoprotein polymorphisms and the risk of fetal birth defects associated with medication use during pregnancy.
    Full-text · Article · May 2014 · Pharmacogenomics

  • No preview · Article · Nov 2012 · Birth Defects Research Part A Clinical and Molecular Teratology

  • No preview · Article · Mar 2012 · Contraception
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    ABSTRACT: Enzyme-inducing antiepileptic drugs (AEDs) reduce the efficacy of oral contraceptives. Little is known of contraceptive practice among reproductive-age women who receive AEDs. We explored the use of contraceptive methods among Dutch women aged 15 to 49 years with prescriptions of AEDs using pharmacy dispensing database. Drug dispensing data of AEDs and contraceptives in 2006 was retrieved from the InterAction Database (IADB.nl database). The prevalence of contraceptives use and distribution of different contraceptive methods were calculated. Of women who used enzyme-inducing AEDs in combination with any highly effective contraceptive method, over 40% were on an oral contraceptive (OC) containing <50 mcg estrogen. IUDs and injectable contraception were used in 22.5% of women receiving AEDs in combination with any highly effective contraceptive method, and 33.2% in those receiving enzyme-inducing AEDs in combination with any highly effective contraceptive method. Fertile-age women who received AEDs often relied on less effective contraceptive methods. Prescribers should be more aware of the interaction between AEDs and OCs.
    No preview · Article · Jun 2011 · Contraception
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    ABSTRACT: Infections have been suggested to play a role in the etiology of schizophrenia, but the evidence for this has been inconsistent. Schizophrenia patients have an increased risk of infections as a result of hospitalizations or life style factors. Therefore a study on early subclinical manifestations of psychosis in relation to virus infections is warranted. We examined whether serum antibodies against human Herpes viruses and Toxoplasma gondii were associated with subclinical symptoms of psychosis in adolescents. Data were collected as part of the TRacking Adolescents' Individual Lives Survey (TRAILS) cohort, a large prospective cohort of Dutch adolescents. A total of 1176 participants with an available Community Assessment of Psychic Experiences (CAPE) and an available blood sample were included in this analysis. Solid-enzyme immunoassay methods were used to measure the presence of immunoglobulin G (IgG) antibodies in serum to the Herpes virus family and to T. gondii. There was no significant association between serologic evidence of infection with human Herpes viruses or T. gondii and the risk of subclinical positive experience of psychosis. Subjects with a positive serological reaction to Epstein-Barr Virus (EBV) had higher scores on the positive dimension of psychosis measured by CAPE (b=0.03, P=0.02). This significant association was observed in males, but not in females. The current study suggests that there is no significant association between serological evidence of infection to human Herpes viruses and positive subclinical experience of psychosis, whereas there was an association between EBV infection and subclinical psychotic symptoms in boys.
    Full-text · Article · Mar 2011 · Schizophrenia Research