Journal
DRUG SAFETY
Volume 38, Issue 7, Pages 651-659Publisher
ADIS INT LTD
DOI: 10.1007/s40264-015-0299-3
Keywords
-
Funding
- Ministry of Health, Welfare and Sports, The Netherlands
- University of Groningen, Groningen, The Netherlands
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available