Maternal Vitamin D Deficiency Causes Sustained Impairment of Lung Structure and Function and Increases Susceptibility to Hyperoxia-induced Lung Injury in Infant Rats

Am J Respir Cell Mol Biol. 2020 Jul;63(1):79-91. doi: 10.1165/rcmb.2019-0295OC.


Vitamin D deficiency (VDD) during pregnancy is associated with increased respiratory morbidities and risk for chronic lung disease after preterm birth. However, the direct effects of maternal VDD on perinatal lung structure and function and whether maternal VDD increases the susceptibility of lung injury due to hyperoxia are uncertain. In the present study, we sought to determine whether maternal VDD is sufficient to impair lung structure and function and whether VDD increases the impact of hyperoxia on the developing rat lung. Four-week-old rats were fed VDD chow and housed in a room shielded from ultraviolet A/B light to achieve 25-hydroxyvitamin D concentrations <10 ng/ml at mating and throughout lactation. Lung structure was assessed at 2 weeks for radial alveolar count, mean linear intercept, pulmonary vessel density, and lung function (lung compliance and resistance). The effects of hyperoxia for 2 weeks after birth were assessed after exposure to fraction of inspired oxygen of 0.95. At 2 weeks, VDD offspring had decreased alveolar and vascular growth and abnormal airway reactivity and lung function. Impaired lung structure and function in VDD offspring were similar to those observed in control rats exposed to postnatal hyperoxia alone. Maternal VDD causes sustained abnormalities of distal lung growth, increases in airway hyperreactivity, and abnormal lung mechanics during infancy. These changes in VDD pups were as severe as those measured after exposure to postnatal hyperoxia alone. We speculate that antenatal disruption of vitamin D signaling increases the risk for late-childhood respiratory disease.

Keywords: hyperoxia; lung development; maternal vitamin D deficiency; vitamin D deficiency.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Female
  • Hyperoxia / complications*
  • Hyperoxia / metabolism
  • Lung / metabolism
  • Lung / physiopathology*
  • Lung Compliance / physiology*
  • Lung Injury / etiology*
  • Lung Injury / metabolism
  • Pregnancy
  • Rats
  • Vitamin D / analogs & derivatives*
  • Vitamin D / metabolism
  • Vitamin D Deficiency / complications*


  • Vitamin D
  • 25-hydroxyvitamin D