Yen Elizabeth, DeAsis-Cruz Josepheen, Rasmussen Jerod M
Tufts University School of Medicine, Boston, Massachusetts, USA.
Woman, Mother + Baby Research Institute, Tufts Medical Center, Boston, Massachusetts, USA.
bioRxiv. 2025 Jun 21:2025.06.20.660741. doi: 10.1101/2025.06.20.660741.
Preclinical evidence suggests that intrauterine exposures can impact hypothalamic structure at birth and future disease risk, yet early human data are limited.
Hypothalamic volumes were measured from 699 T1-weighted MRI scans from 631 newborns (54% female; 27-45 weeks postmenstrual age/PMA) in the Developing Human Connectome Project. Linear mixed-effects models tested associations with prenatal exposures: gestational age (GA) at birth, PMA at scan, sex, maternal body mass index (BMI), and smoking. Findings were partially replicated in the Adolescent Brain and Child Development (ABCD) Study (release 5.1) data (16,934 observations from 11,207 participants).
Absolute hypothalamus volume increased with PMA (+5.5%/week, t=39.9, p<10), but not after adjusting for brain volume (t=1.2, p=0.24). Males showed larger absolute (+3.3%, t=3.2, p=0.002) but smaller relative hypothalamus volume (t=-2.8, p=0.005). Lower GA was linked to larger relative hypothalamus volume (t=-6.5, p<10), with evidence for sex moderation (t=-2.4, p=0.019). Smoking during pregnancy was associated with smaller hypothalamus volume in newborns (t=-2.05, p=0.04; dose dependence: t=-2.9, p<0.01). Smoking remained associated with reduced hypothalamus volume in adolescents (t=-2.8, p=0.005).
The findings suggest that the hypothalamus is a crucial and underexplored target of perinatal influences for understanding the origins of long-term health and disease.
临床前证据表明，子宫内暴露会影响出生时的下丘脑结构以及未来的疾病风险，但早期人类数据有限。
在人类连接组发育项目中，对631名新生儿（54%为女性；月经龄/胎龄27 - 45周）的699次T1加权磁共振成像扫描测量下丘脑体积。线性混合效应模型测试与产前暴露的关联：出生时的胎龄（GA）、扫描时的月经龄、性别、母亲体重指数（BMI）和吸烟情况。研究结果在青少年大脑与儿童发育（ABCD）研究（版本5.1）数据（来自11207名参与者的16934条观察数据）中部分得到重复验证。
下丘脑绝对体积随月经龄增加（每周增加5.5%，t = 39.9，p < 10），但在调整脑体积后则无此变化（t = 1.2，p = 0.24）。男性的下丘脑绝对体积较大（增加3.3%，t = 3.2，p = 0.002），但相对体积较小（t = -2.8，p = 0.005）。较低的胎龄与较大的下丘脑相对体积相关（t = -6.5，p < 10），有证据表明存在性别差异（t = -2.4，p = 0.019）。孕期吸烟与新生儿下丘脑体积较小有关（t = -2.05，p = 0.04；剂量依赖性：t = -2.9，p < 0.01）。吸烟在青少年中仍与下丘脑体积减小有关（t = -2.8，p = 0.005）。
研究结果表明，下丘脑是围产期影响的一个关键且未被充分探索的靶点，对于理解长期健康和疾病的起源具有重要意义。
