Maternal free fatty acid concentration during pregnancy is associated with newborn hypothalamic microstructure in humans

OBJECTIVE: This study tested the hypothesis, in a prospective cohort study design, that maternal saturated free fatty acid (sFFA) concentration during pregnancy is prospectively associated with offspring (newborn) hypothalamic (HTH) microstructure and to explore the functional relevance of this association with respect to early‐childhood body fat percentage (BF%). METHODS: In N = 94 healthy newborns (born mean 39.3 [SD 1.5] weeks gestation), diffusion‐weighted magnetic resonance imaging was performed shortly after birth (25.3 [12.5] postnatal days), and a subgroup (n = 37) underwent a dual‐energy x‐ray absorptiometry scan in early childhood (4.7 [SD 0.7] years). Maternal sFFA concentration during pregnancy was quantified in fasting blood samples via liquid chromatography‐mass spectrometry. Infant HTH microstructural integrity was characterized using mean diffusivity (MD). Multiple linear regression was used to test the association between maternal sFFA and HTH MD, accounting for newborn sex, age at scan, mean white matter MD, and image quality. Multiple linear regression models also tested the association between HTH MD and early‐childhood BF%, accounting for breastfeeding status. RESULTS: Maternal sFFA during pregnancy accounted for 8.3% of the variation in newborn HTH MD (β‐std = 0.25; p = 0.006). Furthermore, newborn HTH MD prospectively accounted for 15% of the variation in early‐childhood BF% (β‐std = 0.32; p = 0.019). CONCLUSIONS: These findings suggest that maternal overnutrition during pregnancy may influence the development of the fetal hypothalamus, which, in turn, may have clinical relevance for childhood obesity risk.