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Updated: Sep 15, 2025
High-resolution Structural Magnetic Resonance Imaging of the Human Subcortex In Vivo and Postmortem
Published on: December 30, 2015
MRI-Based Structural Development of the Human Newborn Hypothalamus
Elizabeth Yen1,2,3, Josepheen DeAsis-Cruz4,5, Jerod M Rasmussen6,7,8
1Tufts University School of Medicine, Boston, Massachusetts, USA.
Insights
Prenatal exposures like smoking impact newborn hypothalamus volume. This brain region
Area of Science:
- Neuroscience
- Developmental Biology
- Public Health
Background:
- Intrauterine exposures may affect early hypothalamic structure and future disease risk.
- Limited human data exist on the impact of prenatal factors on the developing hypothalamus.
Purpose of the Study:
- To investigate the associations between prenatal exposures and hypothalamic volume in newborns.
- To examine how factors like gestational age, sex, maternal BMI, and smoking influence early brain development.
Main Methods:
- Utilized T1-weighted MRI scans from 631 newborns in the Developing Human Connectome Project.
- Employed linear mixed-effects models to analyze associations with prenatal exposures.
- Partially replicated findings in the Adolescent Brain and Child Development (ABCD) Study.
Main Results:
- Hypothalamus volume increased with postmenstrual age but not when adjusted for brain volume.
- Males had larger absolute but smaller relative hypothalamus volumes.
- Lower gestational age was linked to larger relative hypothalamus volume, with sex-dependent effects.
- Prenatal smoking was associated with smaller hypothalamus volume in newborns and adolescents.
Conclusions:
- The hypothalamus is a sensitive target for perinatal influences.
- Early hypothalamic development is critical for understanding long-term health and disease origins.
Background:
Preclinical evidence suggests that intrauterine exposures can impact hypothalamic structure at birth and future disease risk, yet early human data are limited.
Methods:
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).
Results:
Absolute hypothalamus volume increased with PMA (+5.5%/week, t=39.9, p<10-10), 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<10-9), 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).
Conclusions:
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.
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