title: Prenatal exposure to anxiolytic and hypnotic medication in relation to behavioral problems in childhood: A population-based cohort study.
abstract: Benzodiazepines and benzodiazepine-related medications (BBRMs) are anxiolytics and hypnotics acting on γ-amino butyric acid (GABA)Areceptors. BBRMs are assumed to have a low potential for major congenital malformations, but research on more subtle and protracted developing symptoms of these medications is lacking. Therefore, we prospectively investigated the association between BBRM use in pregnancy and long-term effects on child behavior in a large population-based cohort study. The study population consisted of 104 children prenatally exposed to BBRM, 527 children exposed to maternal prenatal anxiety or phobic anxiety symptoms (without exposure to BBRM), and 5609 control children. At child age, 6years, Oppositional Defiant Disorder (ODD), Aggressive Behavior and Anxiety Problems were assessed by the Child Behavior Checklist (CBCL) reported by the mother and the Teacher Report Form (TRF). Children prenatally exposed to BBRM had higher scores of ODD and aggressive behavior, but not of anxiety. However, these associations were explained by maternal anxiety symptoms during pregnancy. Moreover, prenatal exposure to anxiety (without exposure to BBRM) was associated with increased scores of child ODD, aggressive behavior, and anxiety. In conclusion, the current study demonstrates that prenatal BBRM exposure was not independently associated with ODD and aggressive behavior in childhood when prenatal anxiety symptoms were taken into account.
authors.affiliation: Department of Child and Adolescent Psychiatry, Erasmus MC, Sophia Children's Hospital, Rotterdam, The Netherlands; Department of Pharmacokinetics and Clinical Pharmacy, Faculty of Pharmacy, Belgrade, Serbia.
authors.forename: Maja R
authors.initials: MR
authors.lastname: Radojčić
authors.affiliation: Department of Child and Adolescent Psychiatry, Erasmus MC, Sophia Children's Hospital, Rotterdam, The Netherlands; Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands; The Generation R Study Group, Erasmus MC, Rotterdam, The Netherlands. Electronic address: h.marrounel@erasmusmc.nl.
authors.forename: Hanan
authors.initials: H
authors.lastname: El Marroun
authors.affiliation: Department of Pharmacokinetics and Clinical Pharmacy, Faculty of Pharmacy, Belgrade, Serbia.
authors.forename: Branislava
authors.initials: B
authors.lastname: Miljković
authors.affiliation: Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands; Inspectorate of Healthcare, The Hague, The Netherlands.
authors.forename: Bruno H C
authors.initials: BHC
authors.lastname: Stricker
authors.affiliation: Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands; The Generation R Study Group, Erasmus MC, Rotterdam, The Netherlands; Department of Pediatrics, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Vincent W V
authors.initials: VWV
authors.lastname: Jaddoe
authors.affiliation: Department of Child and Adolescent Psychiatry, Erasmus MC, Sophia Children's Hospital, Rotterdam, The Netherlands.
authors.forename: Frank C
authors.initials: FC
authors.lastname: Verhulst
authors.affiliation: Department of Child and Adolescent Psychiatry, Erasmus MC, Sophia Children's Hospital, Rotterdam, The Netherlands; Department of Radiology, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Tonya
authors.initials: T
authors.lastname: White
authors.affiliation: Department of Child and Adolescent Psychiatry, Erasmus MC, Sophia Children's Hospital, Rotterdam, The Netherlands; Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Henning
authors.initials: H
authors.lastname: Tiemeier
mesh_terms: D000374:Aggression / Q000187:drug effects*; D014151:Anti-Anxiety Agents / Q000009:adverse effects*; D001007:Anxiety / Q000139:chemically induced* / Q000523:psychology; D019958:Attention Deficit and Disruptive Behavior Disorders / Q000139:chemically induced*; D001569:Benzodiazepines / Q000009:adverse effects*; D016022:Case-Control Studies; D002648:Child; D015331:Cohort Studies; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000009:adverse effects*; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000523:psychology*; D000066553:Problem Behavior / Q000523:psychology*
chemical_list: D014151:Anti-Anxiety Agents; D006993:Hypnotics and Sedatives; D001569:Benzodiazepines
keywords: Aggression; Benzodiazepine; Benzodiazepine related medications; Child behavior; Oppositional deviant disorder; Z-drugs, pregnancy