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母体内皮质醇在妊娠晚期与后代神经发育障碍的特征有关。欧登塞儿童队列研究。

Maternal cortisol in 3rd trimester is associated with traits of neurodevelopmental disorder in offspring. Odense Child Cohort.

机构信息

Department of Endocrinology and Metabolism, Odense University Hospital, Denmark; Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark; Department of Child and Adolescent Mental Health Odense, Mental Health Services in the Region of Southern Denmark, University of Southern Denmark, Odense, Denmark.

Department of Endocrinology and Metabolism, Odense University Hospital, Denmark; Department of Clinical Pharmacology, Pharmacy and Environmental Medicine, Odense University Hospital, Odense C, Denmark; Institute of Public Health, University of Southern Denmark, Odense, Denmark.

出版信息

Psychoneuroendocrinology. 2023 Aug;154:106293. doi: 10.1016/j.psyneuen.2023.106293. Epub 2023 May 15.

Abstract

BACKGROUND

Prenatal cortisol exposure is essential for neurodevelopment. Maternal cortisol levels could be associated with offspring autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD).

AIM

To investigate associations between maternal 3rd trimester cortisol and offspring traits of ASD and ADHD.

MATERIAL AND METHODS

Mother-child pairs were included from the prospective study Odense Child Cohort. Morning serum cortisol and 24-hour urine cortisol/cortisone were collected at gestational week 27-30. Offspring ASD and ADHD traits were assessed at age three and five years using the Child Behavior Checklist. Maternal cortisol measurements and offspring ASD and ADHD traits assessment were available in (n = 1131; 52% boys) mother-child pairs at age three and (n = 717; 54% boys) at five years of age. Maternal 24-hour urine measurement was available in a subset, at offspring three years of age (n = 300) and at five years of age (n = 217). Associations between maternal cortisol (continuous and tertiles) and offspring ASD or ADHD traits were examined in regression models adjusted for offspring sex, maternal age, pre-pregnancy BMI, parity, maternal education level, parental psychiatric disorders, and maternal smoking and stratified for offspring sex.

RESULTS

Maternal mean age ( ± SD) was 30 years ( ± 4.4) and median BMI (25%; 75% percentiles) 23.5 kg/m (21.3; 26.6). Higher maternal serum cortisol levels were associated with higher prevalence of offspring ASD traits at three years of age in the total study cohort and in boys after stratifying for offspring sex. In the total population, tertiles of serum cortisol showed a significant dose-response relationship to ASD traits in unadjusted and adjusted models (p-values for linear trend, p < 0.01 and p = 0.02, respectively). In offspring at five years, associations between maternal cortisol and offspring ASD traits were non-significant (all p-values > 0.2). Maternal cortisol was not associated with offspring ADHD traits (all p-values > 0.07) in offspring at three and five years. Maternal 24-hour urine cortisol, cortisone, or cortisol/cortisone ratio were not associated with offspring ASD or ADHD traits.

CONCLUSION

Higher maternal serum cortisol in 3rd trimester was associated with offspring ASD traits at three years of age in the whole study cohort and in boys, but not in girls. This association was non-significant at five years of age.

摘要

背景

产前皮质醇暴露对神经发育至关重要。母体皮质醇水平可能与后代自闭症谱系障碍(ASD)和注意缺陷多动障碍(ADHD)有关。

目的

研究母体 3 期末皮质醇与后代 ASD 和 ADHD 特征之间的关系。

材料和方法

从前瞻性奥登塞儿童队列研究中纳入母婴对子。在妊娠 27-30 周时采集清晨血清皮质醇和 24 小时尿液皮质醇/皮质酮。在三岁和五岁时使用儿童行为检查表评估后代的 ASD 和 ADHD 特征。在三岁(n=1131;52%男孩)和五岁(n=717;54%男孩)时,有母婴皮质醇测量和后代 ASD 和 ADHD 特征评估。在三岁(n=300)和五岁(n=217)的后代中,可获得母体 24 小时尿液测量的亚组。在调整后代性别、母体年龄、孕前 BMI、产次、母体教育水平、父母精神疾病和母体吸烟的回归模型中,检查母体皮质醇(连续和三分位)与后代 ASD 或 ADHD 特征之间的关系,并按后代性别分层。

结果

母体平均年龄(±标准差)为 30 岁(±4.4),中位数 BMI(25%;75%百分位)为 23.5kg/m(21.3;26.6)。在整个研究队列和按后代性别分层后,母体血清皮质醇水平较高与三岁时后代 ASD 特征的患病率较高相关。在总人口中,血清皮质醇三分位在未调整和调整模型中均与 ASD 特征呈显著剂量-反应关系(线性趋势的 p 值,p<0.01 和 p=0.02)。在五岁的后代中,母体皮质醇与后代 ASD 特征之间的关联无统计学意义(所有 p 值均>0.2)。在三岁和五岁的后代中,母体皮质醇与 ADHD 特征无关(所有 p 值均>0.07)。母体 24 小时尿液皮质醇、皮质酮或皮质醇/皮质酮比值与后代 ASD 或 ADHD 特征无关。

结论

在整个研究队列和男孩中,母体 3 期末血清皮质醇较高与三岁时后代 ASD 特征相关,但在女孩中则无相关性。这种关联在五岁时不显著。

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