Vitamin D beyond the blood: Tissue distribution of vitamin D metabolites after supplementation.

Vitamin D3's role in mineral homeostasis through its endocrine function, associated with the main circulating metabolite 25-hydroxyvitamin D3, is well characterized. However, the increasing recognition of vitamin D3's paracrine and autocrine functions-such as cell growth, immune function, and hormone regulation-necessitates examining vitamin D3 levels across different tissues post-supplementation. Hence, this review explores the biodistribution of vitamin D3 in blood and key tissues following oral supplementation in humans and animal models, highlighting the biologically active metabolite, 1,25-dihydroxyvitamin D3, and the primary clearance metabolite, 24,25-dihydroxyvitamin D3. While our findings indicate significant progress in understanding how circulating metabolite levels respond to supplementation, comprehensive insight into their tissue concentrations remains limited. The gap is particularly significant during pregnancy, a period of drastically increased vitamin D3 needs and metabolic alterations, where data remains sparse. Within the examined dosage ranges, both human and animal studies indicate that vitamin D3 and its metabolites are retained in tissues selectively. Notably, vitamin D3 concentrations in tissues show greater variability in response to administered doses. In contrast, its metabolites maintain a more consistent concentration range, albeit different among tissues, reflecting their tighter regulatory mechanisms following supplementation. These observations suggest that serum 25-hydroxyvitamin D3 levels may not adequately reflect vitamin D3 and its metabolite concentrations in different tissues. Therefore, future research should aim to generate robust human data on the tissue distribution of vitamin D3 and its principal metabolites post-supplementation. Relating this data to clinically appropriate exposure metrics will enhance our understanding of vitamin D3's cellular effects and guide refinement of clinical trial methodologies.

Early-Life Weight Status and Risk of Childhood Asthma or Recurrent Wheeze in Preterm and Term Offspring.

BACKGROUND: Excessive weight is associated with the development of childhood asthma. However, trends among preterm and term offspring may differ. OBJECTIVE: To assess whether the association of longitudinal weight for age (WFA) and odds of asthma/recurrent wheeze in early life differs between children born preterm and those born at term. METHODS: This study used prospectively collected data from the Vitamin D Antenatal Asthma Reduction Trial. Children (n = 804) were followed-up and anthropometric measurements, including WFA, were taken at birth and annually until the age of 6 years. The primary outcome was asthma/recurrent wheeze by age 3 and 6 years. RESULTS: Among the offspring, 71 (8.8%) were premature. In all the children, the odds of asthma/recurrent wheeze increased by 15% (adjusted odds ratio [aOR], 1.15; 95% CI, 1.10-1.20; P < .001) by age 3 years and 9% (aOR, 1.09; 95% CI, 1.07-1.11; P < .001) by age 6 years for each unit increase in WFA z score. Odds were different between term and preterm offspring (Pinteraction < .001). In term offspring, the odds of having asthma/recurrent wheeze by age 3 and 6 years increased by 22% and 15%, respectively (aOR, 1.22, 95% CI, 1.16-1.27, P < .001, and aOR, 1.15, 95% CI, 1.11-1.18, P < .001). In preterm offspring, by age 3 years, odds of asthma/recurrent wheeze decreased by 10% for each unit increase in WFA z score (aOR, 0.90; 95% CI, 0.81-0.99; P = .030) and decreased by 27% by age 6 years (aOR, .73; 95% CI, 0.61-0.86; P < .001). CONCLUSIONS: During early life, increasing standardized WFA is associated with higher odds of asthma/recurrent wheeze in term children. In contrast, in preterm children, a higher standardized WFA during catch-up growth may decrease the odds of asthma/recurrent wheeze associated with prematurity.

Early life gut microbiome in children following spontaneous preterm birth and maternal preeclampsia.

The early life microbiome plays an important role in developmental and long-term health outcomes. However, it is unknown whether adverse pregnancy complications affect the offspring's gut microbiome postnatally and in early years. In a longitudinal cohort with a five-year follow-up of mother-child pairs affected by preeclampsia (PE) or spontaneous preterm birth (sPTB), we evaluated offspring gut alpha and beta diversity as well as taxa abundances considering factors like breastfeeding and mode of delivery. Our study highlights a trend where microbiome diversity exhibits comparable development across adverse and normal pregnancies. However, specific taxa at genus level emerge with distinctive abundances, showing enrichment and/or depletion over time in relation to PE or sPTB. These findings underscore the potential for certain adverse pregnancy complications to induce alterations in the offspring's microbiome over the course of early life. The implications of these findings on the immediate and long-term health of offspring should be investigated in future studies.