背景:产前暴露于超生理糖皮质激素(GC)水平可能导致许多生物系统的长期发育变化。我们先前的研究确定了产前GC预防和认知能力降低之间的关联,电皮质改变,8-9岁儿童的自主神经系统(ANS)活动改变。这项后续研究旨在检查这些发现是否持续到青春期。
方法:前瞻性观察性随访研究,涉及21名14至15岁的青少年,这些青少年是在先兆早产中接受倍他米松诱导胎儿肺成熟的母亲所生,但出生时体重正常,适合其孕龄(中位数37+4孕周)。35名未接触倍他米松的儿童作为参照组(中位37+6孕周)。主要终点是认知表现,以智商(IQ)衡量。关键次要终点包括注意力缺陷/多动障碍(ADHD)和代谢标志物的症状。此外,我们确定了皮层电(脑电图),下丘脑-垂体-肾上腺轴(HPAA),和ANS活动,以响应标准化的压力范式。
结果:在总体智商方面没有观察到统计学上的显著差异(调整平均值:倍他米松103.9与参考105.9,平均差-2.0,95%置信区间[CI]:-7.12至3.12,p=0.44)。同样,ADHD症状,代谢标志物,HPAA和ANS的总体活性和应激诱导活性在组间没有显著差异.然而,倍他米松组显示额脑区域的皮质电活动减少(光谱边缘频率调整平均值:16.0Hz对17.8Hz,平均差-1.83Hz,95%CI:-3.21至-0.45,p=0.01)。
结论:在14至15岁的青少年中,与未暴露对照组相比,产前GC暴露与IQ评分或ANS活性差异无关.然而,额叶区域皮质电活动减速可能反映了皮质和/或皮质下脑结构成熟的紊乱。这些变化的临床意义仍然未知。鉴于样本量小,选择性参与/失去随访和潜在的残余混杂,这些发现应谨慎解释.在得出确切的临床结论之前,需要进一步的研究才能在更大的队列中复制这些结果。
BACKGROUND: Prenatal exposure to supraphysiological glucocorticoid (GC) levels may lead to long-lasting developmental changes in numerous biological systems. Our prior study identified an association between prenatal GC prophylaxis and reduced cognitive performance, electrocortical changes, and altered autonomic nervous system (ANS) activity in children aged 8-9 years. This follow-up study aimed to examine whether these findings persisted into adolescence.
METHODS: Prospective observational follow-up study involving twenty-one 14- to 15-year-old adolescents born to mothers who received
betamethasone for induction of fetal lung maturation in threatened preterm birth, but who were born with a normal weight appropriate for their gestational age (median 37+4 gestational weeks). Thirty-five children not exposed to
betamethasone served as the reference group (median 37+6 gestational weeks). The primary endpoint was cognitive performance, measured by intelligence quotient (IQ). Key secondary endpoints included symptoms of attention-deficit/hyperactivity disorder (ADHD) and metabolic markers. Additionally, we determined electrocortical (electroencephalogram), hypothalamus-pituitary-adrenal axis (HPAA), and ANS activity in response to a standardized stress paradigm.
RESULTS: No statistically significant group difference was observed in global IQ (adjusted mean:
betamethasone 103.9 vs references 105.9, mean difference -2.0, 95% confidence interval [CI]: -7.12 to 3.12, p = 0.44). Similarly, ADHD symptoms, metabolic markers, the overall and stress-induced activity of the HPAA and the ANS did not differ significantly between groups. However, the
betamethasone group exhibited reduced electrocortical activity in the frontal brain region (spectral edge frequency-adjusted means: 16.0 Hz vs 17.8 Hz, mean difference -1.83 Hz, 95% CI: -3.21 to -0.45, p = 0.01).
CONCLUSIONS: In 14- to 15-year-old adolescents, prenatal GC exposure was not associated with differences in IQ scores or ANS activity compared to unexposed controls. However, decelerated electrocortical activity in the frontal region potentially reflects disturbances in the maturation of cortical and/or subcortical brain structures. The clinical significance of these changes remains unknown. Given the small sample size, selective participation/loss of follow-up and potential residual confounding, these findings should be interpreted cautiously. Further research is required to replicate these results in larger cohorts before drawing firm clinical conclusions.