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孕期使用糖皮质激素与后代注意缺陷多动障碍风险:一项全国性丹麦队列研究。

Use of glucocorticoids during pregnancy and risk of attention-deficit/hyperactivity disorder in offspring: a nationwide Danish cohort study.

机构信息

Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.

Department of Clinical Genetics, Rigshospitalet, Copenhagen, Denmark.

出版信息

BMJ Open. 2017 Sep 24;7(9):e016825. doi: 10.1136/bmjopen-2017-016825.

Abstract

OBJECTIVE

Prenatal exposure to excess endogenous glucocorticoid (GC) has been linked to attention-deficit/hyperactivity disorder (ADHD). We investigated whether prenatal exposure to exogenous GC is associated with ADHD.

DESIGN

Nationwide cohort study.

SETTING

A cohort of 875 996 singletons born alive between 1996 and 2009 in Denmark. Data were obtained from national registries.

EXPOSURES

We identified children exposed prenatally to GCs, children unexposed prenatally and born to maternal former users, and children unexposed and born to maternal never users.

MAIN OUTCOME MEASURES

We compared ADHD risk in children prenatally exposed to GCs and in children of former GC users with risk in unexposed children of never users. We computed cumulative incidence at 10 years of age and adjusted HRs (aHRs). In addition, we compared exposed children with unexposed siblings in a sibling design.

RESULTS

We identified 875 996 children, among whom 5319 were prenatally exposed to systemic GCs and 36 780 to local/inhaled GCs. Cumulative incidences of ADHD at 10 years of age were 2.65% in prenatally exposed children and 2.03% in unexposed children of never users. At the general population level, prenatal exposure was associated with ADHD compared with unexposed, with aHR of 1.43(95% CI 1.24 to 1.65) for systemic exposure and 1.23 (95% CI 1.15 to 1.31) for local/inhaled exposure. However, our former user analysis (aHR of 1.25 (95% CI 1.20 to 1.29)) and sibling design (aHR of 1.03 (95% CI 0.87 to 1.20)) indicated that these findings were due to confounding.

CONCLUSION

This study provides no evidence of a causal association between prenatal exposure to GCs and risk of ADHD.

摘要

目的

内源性糖皮质激素(GC)过量暴露与注意力缺陷多动障碍(ADHD)有关。我们研究了外源性 GC 暴露是否与 ADHD 相关。

设计

全国队列研究。

地点

丹麦 1996 年至 2009 年间出生的 875996 名活产单胎队列。数据来自国家登记处。

暴露

我们确定了产前暴露于 GC 的儿童、未暴露于 GC 的儿童和母亲既往使用者的儿童以及未暴露于 GC 的儿童和母亲从不使用者的儿童。

主要结果测量

我们比较了 GC 产前暴露的儿童与未暴露于 GC 的母亲既往使用者儿童的 ADHD 风险,并与未暴露于 GC 的母亲从不使用者儿童的风险进行比较。我们计算了 10 岁时的累积发病率和调整后的 HR(aHR)。此外,我们在同胞设计中比较了暴露儿童和未暴露的同胞。

结果

我们确定了 875996 名儿童,其中 5319 名儿童在产前暴露于全身 GC,36780 名儿童在产前暴露于局部/吸入性 GC。10 岁时 ADHD 的累积发病率在暴露于 GC 的儿童中为 2.65%,在未暴露于 GC 的母亲从不使用者的儿童中为 2.03%。在一般人群水平上,与未暴露的儿童相比,产前暴露与 ADHD 相关,全身暴露的 aHR 为 1.43(95%CI 1.24 至 1.65),局部/吸入性暴露的 aHR 为 1.23(95%CI 1.15 至 1.31)。然而,我们的既往使用者分析(aHR 为 1.25(95%CI 1.20 至 1.29))和同胞设计(aHR 为 1.03(95%CI 0.87 至 1.20))表明,这些发现是由于混杂因素造成的。

结论

本研究没有证据表明 GC 产前暴露与 ADHD 风险之间存在因果关系。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b2e/5623520/a1c96296ea1b/bmjopen-2017-016825f01.jpg

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