Radojčić Maja R, El Marroun Hanan, Miljković Branislava, Stricker Bruno H C, Jaddoe Vincent W V, Verhulst Frank C, White Tonya, Tiemeier Henning
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.
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.
Neurotoxicol Teratol. 2017 May;61:58-65. doi: 10.1016/j.ntt.2017.02.005. Epub 2017 Mar 1.
Benzodiazepines and benzodiazepine-related medications (BBRMs) are anxiolytics and hypnotics acting on γ-amino butyric acid (GABA) receptors. 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.
苯二氮䓬类药物及苯二氮䓬类相关药物(BBRMs)是作用于γ-氨基丁酸(GABA)受体的抗焦虑药和催眠药。BBRMs被认为导致严重先天性畸形的可能性较低,但对于这些药物更细微和持久的发育症状的研究尚缺。因此,在一项基于人群的大型队列研究中,我们前瞻性地调查了孕期使用BBRMs与对儿童行为的长期影响之间的关联。研究人群包括104名产前暴露于BBRMs的儿童、527名暴露于母亲产前焦虑或恐惧焦虑症状(未暴露于BBRMs)的儿童以及5609名对照儿童。在儿童6岁时,通过母亲报告的儿童行为检查表(CBCL)和教师报告表(TRF)评估对立违抗障碍(ODD)、攻击行为和焦虑问题。产前暴露于BBRMs的儿童ODD和攻击行为得分较高,但焦虑得分不高。然而,这些关联可由孕期母亲的焦虑症状来解释。此外,产前暴露于焦虑(未暴露于BBRMs)与儿童ODD、攻击行为和焦虑得分增加有关。总之,本研究表明,在考虑产前焦虑症状时,产前暴露于BBRMs与儿童期的ODD和攻击行为并无独立关联。