Development, Health and Disease Research Program, University of California, Irvine, CA, 92697, USA.
Department of Pediatrics, University of California, Irvine, CA, 92697, USA.
BMC Med. 2023 Feb 14;21(1):57. doi: 10.1186/s12916-023-02743-8.
An extensive body of animal literature supports the premise that maternal obesity during pregnancy can alter the development of the fetal hypothalamus (HTH, a critical regulator of energy balance) with implications for offspring obesity risk (i.e., long-term energy imbalance). Yet, the relationship in humans between maternal overweight/obesity during pregnancy and fetal hypothalamic development remains largely unknown. Here, using an international (Finland and California, USA) multi-site diffusion tensor imaging (DTI) dataset, we test the hypothesis that maternal pre-pregnancy BMI is associated with newborn offspring HTH mean diffusivity (HTH MD, a replicable neural correlate of BMI in adults).
HTH MD was independently quantified in two separate BMI-matched cohorts (up to class II obesity; BMI = 17-35) using a high-resolution atlas-based definition of HTH. A total of n = 231 mother-child dyads were available for this analysis (n = 152, age at MRI = 26.7 ± 8.1 days, gestational age at birth = 39.9 ± 1.2 weeks, n = 82/70, BMI = 24.2 ± 3.8; n = 79, age at MRI = 25.6 ± 12.5 days, gestational age at birth = 39.3 ± 1.5 weeks, n = 45/34, BMI = 25.1 ± 4.0). The association between maternal pre-pregnancy BMI and newborn offspring HTH MD was examined separately in each cohort using linear regression adjusting for gestational age at birth, postnatal age at scan, sex, whole white matter mean diffusivity, and DTI quality control criteria. In post hoc analyses, additional potentially confounding factors including socioeconomic status, ethnicity, and obstetric risk were adjusted where appropriate.
The distribution of maternal pre-pregnancy BMI was comparable across sites but differed by ethnicity and socioeconomic status. A positive linear association between maternal pre-pregnancy BMI and newborn offspring HTH MD was observed at both sites ([Formula: see text] = 0.17, p = 0.01; [Formula: see text] = 0.22, p = 0.03) and remained significant after adjusting for cohort-relevant covariates.
These findings translate the preclinically established association between maternal obesity during pregnancy and offspring hypothalamic microstructure to the human context. In addition to further replication/generalization, future efforts to identify biological mediators of the association between maternal obesity and fetal HTH development are warranted to develop targeted strategies for the primary prevention of childhood obesity.
大量动物文献支持这样一种前提，即孕期母体肥胖会改变胎儿下丘脑（HTH，能量平衡的关键调节剂）的发育，这与后代肥胖风险（即长期能量失衡）有关。然而，在人类中，孕期母体超重/肥胖与胎儿下丘脑发育之间的关系在很大程度上仍不清楚。在这里，我们使用国际（芬兰和美国加利福尼亚）多地点扩散张量成像（DTI）数据集，检验了以下假设，即母体孕前 BMI 与新生儿后代 HTH 平均扩散率（HTH MD，成人 BMI 的可重复神经相关性）相关。
使用基于高分辨率图谱的 HTH 定义，在两个单独的 BMI 匹配队列中（最高至 II 类肥胖；BMI=17-35）独立定量 HTH MD。共有 231 对母婴对子（n=152，MRI 年龄=26.7±8.1 天，出生时的胎龄=39.9±1.2 周，n=82/70，BMI=24.2±3.8；n=79，MRI 年龄=25.6±12.5 天，出生时的胎龄=39.3±1.5 周，n=45/34，BMI=25.1±4.0）可用于此分析。在每个队列中，使用线性回归分别调整出生时的胎龄、扫描时的产后年龄、性别、全白质平均扩散率和 DTI 质量控制标准，分别检验母体孕前 BMI 与新生儿后代 HTH MD 之间的关联。在事后分析中，根据需要调整了包括社会经济地位、种族和产科风险在内的其他潜在混杂因素。
母体孕前 BMI 的分布在各地点相似，但因种族和社会经济地位而异。在两个地点都观察到母体孕前 BMI 与新生儿后代 HTH MD 之间存在正线性关联（[Formula: see text]=0.17，p=0.01；[Formula: see text]=0.22，p=0.03），并且在调整了与队列相关的协变量后仍然显著。
这些发现将临床前已建立的孕期母体肥胖与后代下丘脑结构之间的关联转化到人类环境中。除了进一步的复制/推广之外，还需要努力确定母体肥胖与胎儿 HTH 发育之间关联的生物学介质，以制定针对儿童肥胖的一级预防的针对性策略。
