Maternal use of cystitis medication and childhood epilepsy in a danish population-based cohort.
BACKGROUND
Maternal infections during pregnancy have been associated with an increased risk for neurological outcomes in the child, including epilepsy. We examined cystitis antibiotics commonly used during pregnancy, as a marker of cystitis, and the risk of childhood epilepsy in a population-based cohort in Denmark.


METHODS
We examined all liveborn singletons born in Denmark between January 1996 and September 2004, identified from the Danish National Birth Registry. Epilepsy diagnoses were obtained from the Danish National Hospital Register and maternal antibiotic use from the National Register of Medicinal Product Statistics. Cystitis antibiotics consisted of pivmecillinam, sulphamethizole and nitrofurantoin. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated with Cox proportional hazard regression models.


RESULTS
The study followed 447629 singletons for up to 9.9 years and identified 2848 children diagnosed with epilepsy. We found slightly increased risks of epilepsy in children whose mothers had redeemed prescriptions during pregnancy for pivmecillinam HR=1.2 [95% CI 1.0, 1.4], sulphamethizole HR=1.2 [95% CI 1.1, 1.4] or nitrofurantoin HR=1.1 [95% CI 0.8, 1.5], compared with those unexposed. Among mothers with multiple redeemed prescriptions during pregnancy, adjusted HR were for pivmecillinam HR=1.3 [95% CI 1.1, 1.5], sulphamethizole HR=1.3 [95% CI 1.1, 1.5] and nitrofurantoin HR=1.3 [95% CI 1.0, 1.8].


CONCLUSIONS
Similar magnitudes of associations between chemically different drugs, used almost exclusively to treat cystitis, may suggest an impact of maternal infection on the fetal brain. However, direct drug effects or confounding factors are also possible explanations.
Department of Epidemiology, School of Public Health, University of California, Los Angeles, CA 90095-1772, USA. jemille@ucla.edu
Jessica E
JE
Miller
Lars Henning
LH
Pedersen
Yuelian
Y
Sun
Jørn
J
Olsen
D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003556:Cystitis / Q000188:drug therapy*; D003718:Denmark; D011307:Drug Prescriptions / Q000706:statistics & numerical data; D004827:Epilepsy / Q000139:chemically induced*; D005260:Female; D006801:Humans; D007223:Infant; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced*; D012044:Regression Analysis; D012307:Risk Factors
D000900:Anti-Bacterial Agents