Hospitalized newborn foals had significantly lower vitamin D and antimicrobial peptide levels than healthy foals, and these deficiencies were associated with increased odds of death.
Low defensins predicted deathDecreased serum β-defensin-1 and cathelicidin-1 — the body's natural antimicrobial peptides — were independently associated with higher odds of mortality in hospitalized newborn foals.
What the researchers found
Serum 25(OH)D, 1,25(OH)₂D, vitamin D binding protein, β-defensin-1, and cathelicidin-1 concentrations were all significantly lower in hospitalized foals compared to healthy foals at multiple time points over 72 hours (p<0.05). Parathyroid hormone (PTH) was significantly higher in sick foals.
Septic foals showed decreased expression of vitamin D receptor (VDR) and CYP27B1 (the enzyme that activates vitamin D) genes, while pro-inflammatory genes TLR-4, TNF-α, and IL-1β were upregulated. Decreased serum 25(OH)D, β-defensin-1, cathelicidin-1, and elevated PTH were each independently associated with higher odds of death in hospitalized foals (p<0.05).
Why it matters
The vitamin D–antimicrobial peptide axis is a fundamental innate immune pathway conserved across mammals. While this study was conducted in foals, the same pathway operates in human newborns — low vitamin D in neonatal intensive care patients is also associated with higher infection rates and worse outcomes. These findings reinforce the biological importance of vitamin D in supporting antimicrobial peptide production and innate immunity during the critical neonatal period, with potential translational implications for both veterinary and human medicine.
How the study worked
This was a longitudinal observational study of 109 foals aged 72 hours or younger, divided into hospitalized (83 foals: 60 septic, 23 sick non-septic) and healthy (26 foals) groups. Blood samples were collected at admission and at 24, 48, and 72 hours. Researchers measured serum concentrations of vitamin D metabolites, vitamin D binding protein, PTH, β-defensin-1, and cathelicidin-1. Gene expression of VDR, CYP27B1, CYP24A1, TLR-4, TNF-α, and IL-1β was assessed from white blood cells. Data were analyzed using repeated measures statistical methods.
What this study cannot tell us
This is an observational study that demonstrates association, not causation — it cannot prove that low vitamin D or antimicrobial peptide levels directly cause death. The study was conducted in horses, and direct extrapolation to human neonates requires caution despite shared biology. The sample size of 109 foals with subgroups (septic, sick non-septic, healthy) limits statistical power for multivariate analyses. Whether vitamin D supplementation would improve antimicrobial peptide levels and outcomes was not tested.
How to read the evidence
This is a well-designed longitudinal observational study with 109 subjects, serial sampling over 72 hours, and comprehensive measurement of both protein levels and gene expression. The association between antimicrobial peptide levels and mortality is statistically significant. However, the observational design cannot establish causation, and the veterinary context limits direct clinical translation to human medicine.
When this study was published
Published in 2025, this study represents current research on the vitamin D–innate immunity axis in neonatal medicine. The findings align with and extend recent human studies on vitamin D and antimicrobial peptides in critical illness.
The bigger picture
The connection between vitamin D and antimicrobial peptide expression has been extensively studied in human medicine, particularly for cathelicidin (LL-37) and β-defensins. Vitamin D is known to directly upregulate the genes encoding these peptides. This study extends that understanding to equine neonatal medicine and provides a longitudinal view of how the axis behaves during acute illness. The parallel to human neonatal sepsis — where vitamin D deficiency is also prevalent and associated with poor outcomes — makes these findings broadly relevant to comparative medicine.
Questions still open
- Would vitamin D supplementation in critically ill newborn foals improve antimicrobial peptide levels and reduce mortality?
- Can serum cathelicidin-1 or β-defensin-1 levels be used as early prognostic biomarkers in neonatal sepsis across species?
- Do the same vitamin D–antimicrobial peptide associations hold in premature or septic human neonates with the same longitudinal pattern?
Common questions
What are antimicrobial peptides and why do they matter for newborn health?
How does vitamin D affect antimicrobial peptide levels?
Read the original research
Longitudinal Evaluation of Vitamin D, Parathyroid Hormone, Antimicrobial Peptides, and Immunomodulatory Genes in Hospitalized Foals.
Journal of veterinary internal medicine, 39(2), e70012
Citation
Kamr, Ahmed M; Bartish, Celine; Summers, Jamie; Horton, Julia; Hostnik, Laura D; Orr, Kindra; Browne, Nimet; Dembek, Katarzyna A; Saliba, Caroline; Gomez, Diego E; Toribio, Ramiro E. (2025). Longitudinal Evaluation of Vitamin D, Parathyroid Hormone, Antimicrobial Peptides, and Immunomodulatory Genes in Hospitalized Foals.. Journal of veterinary internal medicine, 39(2), e70012. https://doi.org/10.1111/jvim.70012