Exposure to reactive intermediate-inducing drugs during pregnancy and the incident use of psychotropic medications among children

Yen-Hao Tran*, Henk Groen, Jorieke E H Bergman, Eelko Hak, Bob Wilffert

*Corresponding author for this work

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Purpose Our study aimed to investigate the association between prenatal exposure to reactive intermediate (RI)-inducing drugs and the initiation of psychotropic medications among children.

Methods We designed a cohort study using a pharmacy prescription database. Pregnant women were considered exposed when they received a prescription of RI-inducing drugs. These drugs could be either used alone (-I+/FAA-) or combined with drugs exhibiting folic acid antagonism (FAA, RI+/FAA+). The reference group included pregnant women who did not receive any RI-inducing drugs or FAA drugs.

Results We analyzed 4116 exposed and 30 422 reference pregnancies. The hazard ratio (HR) with 95% confidence interval (CI) was 1.27 (95% CI 1.15-1.41) for pregnancies exposed to RI-inducing drugs as a whole. Considering subgroups of RI-inducing drugs, prenatal exposure to both RI+/FAA+ and RI+/FAA- was associated with the children's initiation of psychotropic medications, HRs being 1.35 (95% CI 1.10-1.66) and 1.26 (1.13-1.41), respectively. The HRs were increased with prolonged exposure to RI-inducing drugs, especially in the first and second trimesters. In a detailed examination of the psychotropics, the incidences of receiving antimigraine preparations and psychostimulants were significantly increased for the exposed children, compared with the reference children. The incidences of receiving antipsychotics and hypnotics were also higher for the exposed children; however, the HRs did not reach significance after adjustment.

Conclusions We found a significantly increased incident use of psychotropic medications among children prenatally exposed to RI-inducing drugs, especially during the first and second trimesters. This suggests a detrimental effect during critical periods of brain development. Copyright (C) 2017 John Wiley & Sons, Ltd.

Original languageEnglish
Pages (from-to)265-273
Number of pages9
JournalPharmcoepidemiology and Drug Safety
Issue number3
Publication statusPublished - Mar-2017


  • reactive intermediates
  • folic acid antagonism
  • pregnancy
  • drug exposure
  • psychotropic medications
  • pharmacoepidemiology

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