The impact of vitamin D on fetal and neonatal lung maturation. A systematic review

Abstract

-Respiratory distress syndrome (RDS) and bronchopulmonary dysplasia (BPD) are major complications to preterm birth. Hypovitaminosis D is prevalent in pregnancy. We systematically reviewed the evidence of the impact of vitamin D on lung development, surfactant synthesis, RDS, and BPD searching PubMed, Embase, and Cochrane databases with the terms vitamin D AND (surfactant OR lung maturation OR lung development OR respiratory distress syndrome OR fetal lung OR prematurity OR bronchopulmonary dysplasia). Three human studies, ten animal studies, two laboratory studies, and one combined animal and laboratory study were included. Human evidence was sparse, allowing no conclusions. BPD was not associated with vitamin D receptor polymorphism in a fully adjusted analysis. Animal and laboratory studies showed substantial positive effects of vitamin D on the alveolar type II cell, fibroblast proliferation, surfactant synthesis, and alveolarization. These data support the hypothesis of hypovitaminosis D as a frequent, modifiable risk factor of RDS and BPD, which should be tested in randomized controlled trials on pregnant women, those with threatening preterm delivery, or in the preterm neonates. Future experimental and human studies should aim to identify optimal time windows, vitamin D doses, and cut-off levels for 25-hydroxyvitamin D in interventions against RDS, BPD, and later adverse respiratory outcomes. vitamin D; fetus; lung; surfactant; preterm; neonate THE IMPORTANCE OF VITAMIN D in nonskeletal fetal and childhood health has become increasingly recognized in the last decades (19,65). The impact of vitamin D on early lung development and maturation and lung diseases of early life is an emerging field of research. Hypovitaminosis D during pregnancy is associated with reduced placental development and weight, leading to a presumed risk of preterm birth (24,25), which per se may lead to respiratory distress syndrome (RDS) and bronchopulmonary dysplasia (BPD). Moreover, vitamin D is suggested to play a role in the embryogenesis and in cellular growth and differentiation, including lung development and regulation of lung maturation in the fetus (23,29,38,70,71,108), whereby hypovitaminosis D could be hypothesized to aggravate premature neonatal lung diseases.Vitamin D is involved in the development of the innate and adaptive immune system, and, because of its unique capacity to bind to the vitamin D receptor (VDR) and thereby to serve as a transcriptional factor, vitamin D can regulate gene expression and exert widespread immunomodulatory effects including proliferation, differentiation, and complex regulation (19, 56, 58 -61, 64, 65, 68, 69, 105). Evidence suggests that vitamin D may stimulate regulatory T cell development and T cell function to suppress inappropriate Th1 and Th2 responses to environmental exposure (i.e., allergens, infection load), leading to a more balanced immune response inhibiting autoimmune diseases (with Th1 dominance) and allergic diseases (Th2 dominance) (55). Vitamin D could therefore be inv...

Can We Understand the Pathobiology of Bronchopulmonary Dysplasia?

“…Further, the postnatal growth restriction resulting from insufficient total calories that is commonly observed in premature infants 98, 99 may represent an additional risk factor 100 , with evidence suggesting that adequate intake of protein 101 , fat 102 , and specific vitamins 103–106 are particularly important. Data from animals models 107–109 suggest that pre- and postnatal growth restriction alters antioxidant activity 110 , surfactant production 111 , pulmonary endothelial function 112 , and biologic pathways that regulate pulmonary vascular growth 113 .…”

Vitamin D Depletion in Pregnancy Decreases Survival Time, Oxygen Saturation, Lung Weight and Body Weight in Preterm Rat Offspring

“…In preterm neonates inadequate lung maturation leads to respiratory distress syndrome (RDS) characterized by structural immaturity and inadequate synthesis and secretion of surfactant [2]. Antenatal corticosteroids [3, 4], intratracheal surfactant [5] and nasal continuous positive airway pressure (nCPAP) or mechanical ventilation [6, 7] are important in modern treatment of RDS. Yet, respiratory insufficiency due to lung immaturity is still a major cause of mortality in extremely preterm neonates [6], and research in other treatment modalities are needed.…”

Maternal high-fat diet is associated with impaired fetal lung development

“…Importantly, it has not been established if the maternal diet, specifically a diet high in fat (HFD), impacts fetal lung development. There are other nutritional components that have been shown to impact fetal lung development (24,36), but the focus of this manuscript will be on the maternal HFD. The fetal lung is particularly susceptible to in utero insults (27).…”