Persistent Effects of Antenatal Synthetic Glucocorticoids on Endocrine Stress Reactivity From Childhood to Adolescence
Persistent Effects of Antenatal Synthetic Glucocorticoids on Endocrine Stress Reactivity From Childhood to Adolescence
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DOI：
10.1210/jc.2018-01566
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发表时间：
2019-03-01
影响因子：
5.8
通讯作者：
Alexander, Nina
中科院分区：
文献类型：
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作者：
Ilg, Liesa;Kirschbaum, Clemens;Alexander, Nina
内容：已确定产前合成糖皮质激素（sGC）治疗是下丘脑-垂体-肾上腺（HPA）轴的有效编程因子。我们先前观察到，与对照组相比，6至11岁的足月出生儿童暴露于产前sGC的皮质醇应激反应显着增加。鉴于青春期HPA轴功能的显著变化，这些发现需要进行纵向随访研究，以评估产前sGC的长期影响。目的：本研究旨在纵向研究产前sGC相关影响的稳定性，从儿童期到青春期皮质醇应激反应。设计、设置和参与者：为了评估产前sGC的长期轨迹，我们纵向跟踪了我们儿童队列的子样本（n = 44）到青春期（14至18岁）进行第二次评估。为此，22名产前暴露于sGC的青少年和22名未接受治疗的对照组接受了标准化的实验室应激源[特里尔社会应激测试（TSST）]。除了从儿童到青春期HPA轴反应性普遍增加外，（P < 0.05），在两个发育阶段，与对照组相比，接受产前sGC治疗的参与者对TSST的反应显示出显著更高的皮质醇水平（P < 0.05）。此外，我们观察到sGCs对儿童期至青春期皮质醇应激反应的等级顺序稳定性的调节作用（P < 0.05）有趋势（P = 0.07）暴露于sGC的个体中的秩序稳定性较高（r = 0.37）与对照组相比结论：产前sGC可导致HPA轴反应性的长期变化，这种变化持续到青春期，并可能增加发生应激相关疾病的脆弱性。
Context: Antenatal synthetic glucocorticoid (sGC) therapy has been identified as a potent programming factor of the hypothalamic-pituitary-adrenal (HPA) axis. We previously observed significantly increased cortisol stress responses in 6- to 11-year-old, term-born children exposed to antenatal sGCs compared with controls. These findings call for longitudinal follow-up studies to evaluate long-term effects of antenatal sGCs, given that adolescence is marked by a substantial shift of HPA axis functioning.Objective: This study aimed to longitudinally investigate the stability of antenatal sGC-related effects on cortisol stress reactivity from childhood to adolescence.Design, Setting, and Participant: To evaluate long-term trajectories of antenatal sGCs, we longitudinally followed a subsample (n = 44) of our children's cohort into adolescence (14 to 18 years old) for a second assessment. To this end, 22 adolescents with antenatal sGC exposure and 22 untreated controls underwent a standardized laboratory stressor [Trier Social Stress Test (TSST)].Results: Besides a general increase in HPA axis reactivity from childhood to adolescence (P < 0.05), participants treated with antenatal sGCs showed significantly higher cortisol levels in response to the TSST compared with controls during both developmental stages (P < 0.05). Furthermore, we observed a moderating effect of sGCs on rank-order stability of cortisol stress reactivity from childhood to adolescence (P < 0.05) with a trend (P = 0.07) for higher rank-order stability in sGC-exposed individuals (r = 0.37) compared with controls (r = -0.20).Conclusion: These findings suggest that antenatal sGCs yield long-term changes of HPA axis reactivity that persist into adolescence and may confer increased vulnerability for developing stress-related disorders.