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孕期接触诱导反应性中间体的药物与儿童精神药物的使用情况

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

作者信息

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

机构信息

Groningen Research Institute of Pharmacy, Unit of Pharmacotherapy, Epidemiology and Economics, University of Groningen, Groningen, The Netherlands.

Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

出版信息

Pharmacoepidemiol Drug Saf. 2017 Mar;26(3):265-273. doi: 10.1002/pds.4161. Epub 2017 Jan 18.

Abstract

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 (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.

摘要

目的

我们的研究旨在调查产前暴露于可诱导反应中间体(RI)的药物与儿童开始使用精神药物之间的关联。

方法

我们利用药房处方数据库设计了一项队列研究。当孕妇接受可诱导RI的药物处方时,她们被视为暴露组。这些药物可以单独使用(RI+/FAA-),也可以与表现出叶酸拮抗作用的药物联合使用(FAA,RI+/FAA+)。对照组包括未接受任何可诱导RI的药物或FAA药物的孕妇。

结果

我们分析了4116例暴露组妊娠和30422例对照组妊娠。整体暴露于可诱导RI的药物的妊娠的风险比(HR)及95%置信区间(CI)为1.27(95%CI 1.15 - 1.41)。考虑可诱导RI的药物亚组,产前暴露于RI+/FAA+和RI+/FAA-均与儿童开始使用精神药物有关,HR分别为1.35(95%CI 1.10 - 1.66)和1.26(1.13 - 1.41)。HR随着暴露于可诱导RI的药物时间延长而增加,尤其是在孕早期和孕中期。在对精神药物的详细检查中,与对照组儿童相比,暴露组儿童接受抗偏头痛制剂和精神兴奋剂的发生率显著增加。暴露组儿童接受抗精神病药物和催眠药的发生率也较高;然而,调整后HR未达到显著水平。

结论

我们发现产前暴露于可诱导RI的药物的儿童中,精神药物的使用发生率显著增加,尤其是在孕早期和孕中期。这表明在大脑发育的关键时期存在有害影响。版权所有© 2017约翰威立父子有限公司。

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