Inhaled Vitamin D: A Novel Strategy to Enhance Neonatal Lung Maturation

Abstract

Introduction The physiologic vitamin D (VD), 1α,25(OH)2 D3 (1,25D) is a local paracrine/autocrine effecter of fetal lung maturation. By stimulating alveolar type II cell and lipofibroblast proliferation and differentiation, parenterally administered 1,25D has been shown to enhance neonatal lung maturation; but due to the potential systemic side effects of the parenteral route, the translational value of these findings might be limited. To minimize the possibility of systemic toxicity, we examined the effects of VD on neonatal lung maturation, when delivered directly to lungs via nebulization. Methods One-day-old rat pups were administered three different doses of 1,25D and its physiologic precursor 25(OH)D (25D), or the diluent, via nebulization daily for 14 days. Pups were sacrificed for lung, kidneys, and blood collection to determine markers of lung maturation, and serum 25D and calcium levels. Results Compared to controls, nebulized 25D and 1,25D enhanced lung maturation as evidenced by the increased expression of markers of alveolar epithelial (SP-B, leptin receptor), mesenchymal (PPARγ, C/EBPα), and endothelial (VEGF, FLK-1) differentiation, surfactant phospholipid synthesis, and lung morphology without any significant increases in serum 25D and calcium levels. Conclusions Inhaled VD is a potentially safe and effective novel strategy to enhance neonatal lung maturation.

The Implications of Vitamin D Status During Pregnancy on Mother and her Developing Child

“…Other in vivo studies support the role of vitamin D in pulmonary function. Taylor, et al, showed promising and provocative results utilizing a neonatal rat model ( 41 ). The investigators randomized one-day-old rat pups to one of three different doses of the active hormone, 1,25(OH)D 2 and its physiologic precursor 25(OH)D, or the diluent, via nebulization daily for 14 days.…”

Prenatal vitamin D status and respiratory and allergic outcomes in childhood: A meta‐analysis of observational studies

“…Vitamin D has also effects on lung development and function. Experimental and human studies have revealed vitamin D to play a key role in lung maturation by modulating type II alveolar cell differentiation and by stimulating surfactant synthesis and release . Antenatal vitamin D deficiency impairs airway and alveolar development and limits lung function in mice .…”

“…Experimental and human studies have revealed vitamin D to play a key role in lung maturation by modulating type II alveolar cell differentiation and by stimulating surfactant synthesis and release. [62][63][64][65] Antenatal vitamin D deficiency impairs airway and alveolar development and limits lung function in mice. 9 Moreover, vitamin D deficiency may provoke proliferation and hypertrophy of smooth muscle, contributing to airway remodeling and increased airway smooth muscle mass.…”

Perinatal Undernutrition, Metabolic Hormones, and Lung Development

“…In addition, calcitriol supplementation during lactation in rodents with previous deficiency during gestation improves alveolar septation and lung function [95]. Even in pups from normal pregnant rats, the aerosol administration of calcitriol precursors contributes to lung maturity by increasing the expression of markers of epithelial, mesenchymal, and vascular differentiation that is followed by an increase in the synthesis of surfactant phospholipids [96]. In human studies, there is an association between a reduction of calcitriol levels in 18 WG and a reduced lung function in childhood [97].…”

“…Formation of bronchial tubules during pseudoglandular phase [57] Lung maturation [62,69,70,72,[77][78][79] In vitro Proliferation of ATII cells and differentiation to ATI cells [62,81] In vitro and in vivo SFTPs expression [62,63] Cholecalciferol Branching morphogenesis [91] In vitro proliferation of ATII cells [96] In vitro surfactant phospholipids secretion [96] In vitro SFTPs expression [96] Lung maturation [95,96] Abbreviations Funding: This research received no external funding.…”