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Trimethoprim use before pregnancy and risk of congenital malformation: reanalyzed using a case‐crossover design and a case‐time‐control design
Author(s) -
Sun Yuelian,
Wu Chun Sen,
Olsen Jørn
Publication year - 2014
Publication title -
pharmacoepidemiology and drug safety
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.023
H-Index - 96
eISSN - 1099-1557
pISSN - 1053-8569
DOI - 10.1002/pds.3691
Subject(s) - medicine , pregnancy , odds ratio , medical prescription , confidence interval , obstetrics , pharmacoepidemiology , crossover study , cohort study , population , pediatrics , trimethoprim , environmental health , genetics , alternative medicine , pathology , microbiology and biotechnology , pharmacology , biology , placebo , antibiotics
Purpose Studies on the safety of drugs used during pregnancy are necessary and important but prone to bias. Using cases as their own controls can reduce bias. We used a case‐crossover design and a case‐time‐control design to estimate the risk of congenital malformation (CM) for children born to mothers who redeemed a trimethoprim prescription shortly before pregnancy. Methods The study was based on all live born singletons (N = 685 600) in Denmark whose mothers had available information on prescriptions in the Danish National Prescription Registry between 1996 and 2008. We defined 1–3 months before pregnancy as a potential risk period and 13–15 months before pregnancy as a reference period. Two other reference periods were used (7–9 months before pregnancy and months 4–6 of pregnancy). The case‐crossover design is dependent on the assumption of a stable trimethoprim prescription over the study period in the source population. To estimate the trend of trimethoprim prescriptions, we used a control group comprising children without CMs. Results Both study designs showed children had a higher risk of overall CM [odds ratio of 1.66, 95% confidence interval (CI): 1.10–2.53 and 1.50, 95%CI: 0.66–3.38, respectively] if their mothers had a trimethoprim prescription in the 3 months before pregnancy and subtypes of CM for example in the musculoskeletal system, which were consistent to the previous findings from a cohort study. Conclusions This study corroborates that trimethoprim is a potential teratogen when used 3 months before pregnancy and demonstrates the value of case‐only approaches for studying, for example, adverse effects of antibiotics in reproductive epidemiology. Copyright © 2014 John Wiley & Sons, Ltd.