title: Exposure to reactive intermediate-inducing drugs during pregnancy and the incident use of psychotropic medications among children.
abstract: OBJECTIVE
  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 (RI+/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 © 2017 John Wiley & Sons, Ltd.
authors.affiliation: Groningen Research Institute of Pharmacy, Unit of Pharmacotherapy, Epidemiology and Economics, University of Groningen, Groningen, The Netherlands.
authors.forename: Yen-Hao
authors.identifier: http://orcid.org/0000-0003-2614-8073
authors.initials: YH
authors.lastname: Tran
authors.affiliation: Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Henk
authors.initials: H
authors.lastname: Groen
authors.affiliation: Eurocat Registration Northern Netherlands, Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Jorieke E H
authors.initials: JE
authors.lastname: Bergman
authors.affiliation: Groningen Research Institute of Pharmacy, Unit of Pharmacotherapy, Epidemiology and Economics, University of Groningen, Groningen, The Netherlands.
authors.forename: Eelko
authors.initials: E
authors.lastname: Hak
authors.affiliation: Groningen Research Institute of Pharmacy, Unit of Pharmacotherapy, Epidemiology and Economics, University of Groningen, Groningen, The Netherlands.|Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Bob
authors.initials: B
authors.lastname: Wilffert
mesh_terms: D000328:Adult; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D016208:Databases, Factual; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D011247:Pregnancy; D011264:Pregnancy Trimesters; D011297:Prenatal Exposure Delayed Effects / Q000453:epidemiology*; D055553:Prescription Drugs / Q000008:administration & dosage* / Q000009:adverse effects; D011619:Psychotropic Drugs / Q000008:administration & dosage*; D013997:Time Factors
chemical_list: D055553:Prescription Drugs; D011619:Psychotropic Drugs
keywords: drug exposure; folic acid antagonism; pharmacoepidemiology; pregnancy; psychotropic medications; reactive intermediates