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

BACKGROUND: 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. OBJECTIVE: To determine whether maternal VDD is sufficient to impair lung structure and function and whether VDD increases the impact of hyperoxia (HX) on the developing rat lung. DESIGN/METHODS: 4-week-old rats were fed VDD chow and housed in UV-A/B shielded room to achieve 25-OHD levels <10 ng/ml at mating and throughout lactation. Lung structure was assessed at 2 weeks for radial alveolar counts (RAC), mean linear intercepts (MLI), pulmonary vessel density (PVD), and lung function (lung compliance and resistance). The effects of HX for 2 weeks after birth were assessed after exposure to FiO2, 0.95. RESULTS: At 2 weeks, VDD offspring have decreased alveolar and vascular growth, abnormal airways reactivity and lung function. Impaired lung structure and function in VDD offspring was similar to that observed in control rats exposed to postnatal hyperoxia alone. CONCLUSIONS: Maternal VDD causes sustained abnormalities of distal lung growth, increases in airways hyper-reactivity and abnormal lung mechanics during infancy. These changes in VDD pups were as severe as those measured after exposure to postnatal HX alone. We speculate that antenatal disruption of VD signaling increases the risk for late childhood respiratory disease.