Publication

P-Glycoprotein-Mediated Drug Interactions in Pregnancy and Changes in the Risk of Congenital Anomalies: A Case-Reference Study

Daud, A. N. A., Bergman, J. E. H., Bakker, M. K., Wang, H., Kerstjens-Frederikse, W. S., de Walle, H. E. K., Groen, H., Bos, J. H. J., Hak, E. & Wilffert, B., 2-Jul-2015, In : Drug Safety. 38, 7, p. 651-659 9 p.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Daud, A. N. A., Bergman, J. E. H., Bakker, M. K., Wang, H., Kerstjens-Frederikse, W. S., de Walle, H. E. K., ... Wilffert, B. (2015). P-Glycoprotein-Mediated Drug Interactions in Pregnancy and Changes in the Risk of Congenital Anomalies: A Case-Reference Study. Drug Safety, 38(7), 651-659. https://doi.org/10.1007/s40264-015-0299-3

Author

Daud, Aizati N.A. ; Bergman, Jorieke E.H. ; Bakker, Marian K. ; Wang, Hao ; Kerstjens-Frederikse, Wilhelmina S. ; de Walle, Hermien E.K. ; Groen, Henk ; Bos, Jens H. J. ; Hak, Eelko ; Wilffert, Bob. / P-Glycoprotein-Mediated Drug Interactions in Pregnancy and Changes in the Risk of Congenital Anomalies : A Case-Reference Study. In: Drug Safety. 2015 ; Vol. 38, No. 7. pp. 651-659.

Harvard

Daud, ANA, Bergman, JEH, Bakker, MK, Wang, H, Kerstjens-Frederikse, WS, de Walle, HEK, Groen, H, Bos, JHJ, Hak, E & Wilffert, B 2015, 'P-Glycoprotein-Mediated Drug Interactions in Pregnancy and Changes in the Risk of Congenital Anomalies: A Case-Reference Study', Drug Safety, vol. 38, no. 7, pp. 651-659. https://doi.org/10.1007/s40264-015-0299-3

Standard

P-Glycoprotein-Mediated Drug Interactions in Pregnancy and Changes in the Risk of Congenital Anomalies : A Case-Reference Study. / Daud, Aizati N.A.; Bergman, Jorieke E.H.; Bakker, Marian K.; Wang, Hao; Kerstjens-Frederikse, Wilhelmina S.; de Walle, Hermien E.K.; Groen, Henk; Bos, Jens H. J.; Hak, Eelko; Wilffert, Bob.

In: Drug Safety, Vol. 38, No. 7, 02.07.2015, p. 651-659.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Daud ANA, Bergman JEH, Bakker MK, Wang H, Kerstjens-Frederikse WS, de Walle HEK et al. P-Glycoprotein-Mediated Drug Interactions in Pregnancy and Changes in the Risk of Congenital Anomalies: A Case-Reference Study. Drug Safety. 2015 Jul 2;38(7):651-659. https://doi.org/10.1007/s40264-015-0299-3


BibTeX

@article{9cc84cb3b36f4ac0be8677c73c08e658,
title = "P-Glycoprotein-Mediated Drug Interactions in Pregnancy and Changes in the Risk of Congenital Anomalies: A Case-Reference Study",
abstract = "INTRODUCTION: 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.METHODS: 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).RESULTS: 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.CONCLUSIONS: 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.",
keywords = "HUMAN PLACENTA, CLINICAL-RELEVANCE, TRANSPORTERS, EXPRESSION, EXPOSURE, CHILDREN, FETAL, ABCB1, OUTCOMES",
author = "Daud, {Aizati N.A.} and Bergman, {Jorieke E.H.} and Bakker, {Marian K.} and Hao Wang and Kerstjens-Frederikse, {Wilhelmina S.} and {de Walle}, {Hermien E.K.} and Henk Groen and Bos, {Jens H. J.} and Eelko Hak and Bob Wilffert",
year = "2015",
month = "7",
day = "2",
doi = "10.1007/s40264-015-0299-3",
language = "English",
volume = "38",
pages = "651--659",
journal = "Drug Safety",
issn = "0114-5916",
publisher = "ADIS INT LTD",
number = "7",

}

RIS

TY - JOUR

T1 - P-Glycoprotein-Mediated Drug Interactions in Pregnancy and Changes in the Risk of Congenital Anomalies

T2 - A Case-Reference Study

AU - Daud, Aizati N.A.

AU - Bergman, Jorieke E.H.

AU - Bakker, Marian K.

AU - Wang, Hao

AU - Kerstjens-Frederikse, Wilhelmina S.

AU - de Walle, Hermien E.K.

AU - Groen, Henk

AU - Bos, Jens H. J.

AU - Hak, Eelko

AU - Wilffert, Bob

PY - 2015/7/2

Y1 - 2015/7/2

N2 - INTRODUCTION: 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.METHODS: 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).RESULTS: 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.CONCLUSIONS: 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.

AB - INTRODUCTION: 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.METHODS: 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).RESULTS: 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.CONCLUSIONS: 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.

KW - HUMAN PLACENTA

KW - CLINICAL-RELEVANCE

KW - TRANSPORTERS

KW - EXPRESSION

KW - EXPOSURE

KW - CHILDREN

KW - FETAL

KW - ABCB1

KW - OUTCOMES

U2 - 10.1007/s40264-015-0299-3

DO - 10.1007/s40264-015-0299-3

M3 - Article

VL - 38

SP - 651

EP - 659

JO - Drug Safety

JF - Drug Safety

SN - 0114-5916

IS - 7

ER -

ID: 20126145