Segmenting hypothalamic subunits in human newborn magnetic resonance imaging data.

Preclinical evidence suggests that inter-individual variation in the structure of the hypothalamus at birth is associated with variation in the intrauterine environment, with downstream implications for future disease susceptibility. However, scientific advancement in humans is limited by a lack of validated methods for the automatic segmentation of the newborn hypothalamus. N = 215 healthy full-term infants with paired T1-/T2-weighted MR images across four sites were considered for primary analyses (mean postmenstrual age = 44.3 ± 3.5 weeks, nmale /nfemale = 110/106). The outputs of FreeSurfer's hypothalamic subunit segmentation tools designed for adults (segFS) were compared against those of a novel registration-based pipeline developed here (segATLAS) and against manually edited segmentations (segMAN) as reference. Comparisons were made using Dice Similarity Coefficients (DSCs) and through expected associations with postmenstrual age at scan. In addition, we aimed to demonstrate the validity of the segATLAS pipeline by testing for the stability of inter-individual variation in hypothalamic volume across the first year of life (n = 41 longitudinal datasets available). SegFS and segATLAS segmentations demonstrated a wide spread in agreement (mean DSC = 0.65 ± 0.14 SD; range = {0.03-0.80}). SegATLAS volumes were more highly correlated with postmenstrual age at scan than segFS volumes (n = 215 infants; RsegATLAS 2 = 65% vs. RsegFS 2 = 40%), and segATLAS volumes demonstrated a higher degree of agreement with segMAN reference segmentations at the whole hypothalamus (segATLAS DSC = 0.89 ± 0.06 SD; segFS DSC = 0.68 ± 0.14 SD) and subunit levels (segATLAS DSC = 0.80 ± 0.16 SD; segFS DSC = 0.40 ± 0.26 SD). In addition, segATLAS (but not segFS) volumes demonstrated stability from near birth to ~1 years age (n = 41; R2 = 25%; p < 10-3 ). These findings highlight segATLAS as a valid and publicly available (https://github.com/jerodras/neonate_hypothalamus_seg) pipeline for the segmentation of hypothalamic subunits using human newborn MRI up to 3 months of age collected at resolutions on the order of 1 mm isotropic. Because the hypothalamus is traditionally understudied due to a lack of high-quality segmentation tools during the early life period, and because the hypothalamus is of high biological relevance to human growth and development, this tool may stimulate developmental and clinical research by providing new insight into the unique role of the hypothalamus and its subunits in shaping trajectories of early life health and disease.

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 (ß-std = 0.25; p = 0.006). Furthermore, newborn HTH MD prospectively accounted for 15% of the variation in early-childhood BF% (ß-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.

The Interplay between Maternal Nutrition and Stress during Pregnancy: Issues and Considerations.

BACKGROUND: Several studies about humans and animals have separately examined the effects of prenatal nutrition and stress on fetal development, pregnancy, and birth outcomes, and subsequent child health and disease risk. Although substantial evidence from non-pregnant literature supports the presence of bidirectional interactions between nutrition and stress at various psychological, behavioral, and physiological levels, such interaction effects have not yet been systematically examined in the context of pregnancy. SUMMARY: This paper discusses the multifaceted and multilevel relationship between nutrition and stress. It then reviews the currently available observational and experimental evidence in animals and humans regarding the interplay between maternal psychosocial stress, dietary intake, and nutritional state during pregnancy, and implications for maternal and child health-related outcomes. Key Messages: During pregnancy, maternal psychosocial stress, dietary behavior, and nutritional state likely regulate and counter-regulate one another. Emerging evidence suggests that omega-3 fatty acids may attenuate maternal psychosocial stress, and that high maternal pre-pregnancy body mass index exacerbates unhealthy dietary behaviors under high-stress conditions. Longitudinal studies are warranted in order to understand the interplay between prenatal psychosocial stress, diet, and stress- and nutrition-related biomarkers to obtain further insight and inform the development and design of future, more effective intervention trials for improved maternal and child health outcomes.