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- Title
P-Glycoprotein-Mediated Drug Interactions in Pregnancy and Changes in the Risk of Congenital Anomalies: A Case-Reference Study.
- Authors
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
- Abstract
<bold>Introduction: </bold>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.<bold>Methods: </bold>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).<bold>Results: </bold>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.<bold>Conclusions: </bold>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.
- Publication
Drug Safety, 2015, Vol 38, Issue 7, p651
- ISSN
0114-5916
- Publication type
journal article
- DOI
10.1007/s40264-015-0299-3