Hans Berger Department of Neurology, Jena University Hospital, Jena, Germany.
Department of Obstetrics, Jena University Hospital, Jena, Germany.
Acta Obstet Gynecol Scand. 2024 Aug;103(8):1530-1540. doi: 10.1111/aogs.14885. Epub 2024 Jun 14.
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.
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 gestational weeks). Thirty-five children not exposed to betamethasone served as the reference group (median 37 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.
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).
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.
产前暴露于超生理水平的糖皮质激素（GC）可能导致许多生物系统的持久发育变化。我们之前的研究表明，产前 GC 预防与 8-9 岁儿童的认知表现下降、脑电图变化以及自主神经系统（ANS）活动改变有关。本随访研究旨在探讨这些发现是否持续到青春期。
前瞻性观察性随访研究，纳入 21 名 14-15 岁青少年，其母亲在有早产风险时接受倍他米松促胎肺成熟，但出生时体重正常，与胎龄相符（中位数 37 孕周）。35 名未接受倍他米松治疗的儿童作为对照组（中位数 37 孕周）。主要终点是认知表现，通过智商（IQ）衡量。关键次要终点包括注意缺陷多动障碍（ADHD）症状和代谢标志物。此外，我们还测定了脑电图、下丘脑-垂体-肾上腺轴（HPAA）和自主神经系统对标准化应激范式的反应。
两组间总体智商无统计学显著差异（校正平均：倍他米松组 103.9 分，对照组 105.9 分，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 的整体和应激诱导活性在两组间无显著差异。然而，倍他米松组在前额脑区的脑电图活动减少（频谱边缘频率调整均值：16.0 Hz 比 17.8 Hz，平均差-1.83 Hz，95%CI：-3.21 至-0.45，p=0.01）。
在 14-15 岁青少年中，与未暴露组相比，产前 GC 暴露与智商评分或 ANS 活性无差异。然而，前区脑电图活动的减慢可能反映了皮质和/或皮质下脑结构成熟的障碍。这些变化的临床意义尚不清楚。由于样本量小、选择性参与/失访和潜在的残余混杂因素，这些发现应谨慎解释。需要在更大的队列中复制这些结果，才能得出明确的临床结论。
