Epidemiology and Infection

Original Papers

Other infections

Trimethoprim use in early pregnancy and the risk of miscarriage: a register-based nationwide cohort study

J. T. ANDERSENa1a2 c1, M. PETERSENa1a2, E. JIMENEZ-SOLEMa1a2, K. BROEDBAEKa1a2, E. W. ANDERSENa3, N. L. ANDERSENa4, S. AFZALa1a2, C. TORP-PEDERSENa5a6, N. KEIDINGa3 and H. E. POULSENa1a2a6

a1 Laboratory of Clinical Pharmacology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark

a2 Department of Clinical Pharmacology, Bispebjerg Hospital, Copenhagen, Denmark

a3 Department of Biostatistics, University of Copenhagen, Copenhagen, Denmark

a4 Mental Health Centre Copenhagen, Copenhagen, Denmark

a5 Department of Cardiology, Gentofte University Hospital, Hellerup, Denmark

a6 Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark

SUMMARY

The antibiotic trimethoprim acts as a folate antagonist. Since trophoblasts are very sensitive to drugs that interfere with the folic acid cycle and thereby inhibit DNA synthesis, use of trimethoprim during the first trimester could be associated with miscarriage. A nationwide cohort study including all women in Denmark with a registered pregnancy between 1997 and 2005 was conducted. We used nationwide registers to identify all women giving birth, having a record of miscarriage or induced abortion. Data on exposure to trimethoprim were obtained from the National Prescription Register. Cox proportional hazard regression analysis with exposure to trimethoprim as a time-dependent variable was used to estimate the risk of miscarriage. The adjusted hazard ratio of having a miscarriage after exposure to trimethoprim in the first trimester compared to non-exposure was 2·04 (95% confidence interval 1·43–2·91). Our results indicate that trimethoprim exposure in the first trimester is associated with a doubling of the hazard of miscarriage.

(Received May 01 2012)

(Revised July 30 2012)

(Accepted August 29 2012)

(Online publication September 25 2012)

Key words

  • Antibiotics;
  • birth defects;
  • epidemiology;
  • pregnancy

Correspondence

c1 Author for correspondence: Dr J. T. Andersen, Laboratory of Clinical Pharmacology, Copenhagen University Hospital Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. (Email: jta@rh.dk)

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