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Drug Safety
Published in: Drug Safety 11/2013

01-11-2013 | Original Research Article

Identifying Associations between Maternal Medication Use and Birth Defects Using a Case-Population Approach: An Exploratory Study on Signal Detection

Authors: Linda de Jonge, Priscilla A. Zetstra-van der Woude, H. Jens Bos, Lolkje T. W. de Jong-van den Berg, Marian K. Bakker

Published in: Drug Safety | Issue 11/2013

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Abstract

Background

The effects of many drugs on the unborn child are unknown. In a case-population design, drug exposure of cases is compared with that of a source population; this kind of study can be useful for generating signals.

Objective

To see whether a comparison of drug use rates from the birth defect registry EUROCAT NNL (cases) with prescription rates from a population-based prescription database, the IADB (population), could be used to detect signals of teratogenic risk of drugs.

Methods

We defined 3,212 cases from the EUROCAT NNL database, a population-based birth defect registry in the Northern Netherlands and 29,223 population controls from the IADB, a prescription database with data from community pharmacies in the same geographical area, born between 1998 and 2008. We classified the malformations of the 3,212 cases into several malformation groups according to organ system (based on the International Classification of Diseases codes and the EUROCAT guidelines). If a child had multiple malformations in several organ systems (n = 253, 7.9 %), he/she was counted in all the categories represented. For several groups of malformations we calculated rate ratios (RR) and 95 % confidence intervals for drugs acting on the central nervous system and for drugs considered to be safe for use in pregnancy. The RRs were based on first-trimester drug use rates from the cases in the EUROCAT NNL database and prescription rates from the population controls in the IADB.

Results

For drugs acting on the central nervous system we found significantly increased RRs for the anti-epileptic drug valproic acid and for some selective serotonin reuptake inhibitors. For drugs considered to be safe only the anti-hypertensive methyldopa showed significantly increased RRs.

Conclusion

We show that a case-population study is a suitable method for detecting signals of possible teratogenicity, provided that the teratogenic effects and the drugs under study are as specific as possible and the drugs are widely used.
Appendix
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Metadata
Title
Identifying Associations between Maternal Medication Use and Birth Defects Using a Case-Population Approach: An Exploratory Study on Signal Detection
Authors
Linda de Jonge
Priscilla A. Zetstra-van der Woude
H. Jens Bos
Lolkje T. W. de Jong-van den Berg
Marian K. Bakker
Publication date
01-11-2013
Publisher
Springer International Publishing
Published in
Drug Safety / Issue 11/2013
Print ISSN: 0114-5916
Electronic ISSN: 1179-1942
DOI
https://doi.org/10.1007/s40264-013-0082-2

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