title: 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.
authors.affiliation: Hans Christian Andersen Children's Hospital, Odense University Hospital, Odense, Denmark; Clinical Institute, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark;
authors.forename: Sine
authors.initials: S
authors.lastname: Lykkedegn
authors.affiliation: Institute of Molecular Medicine, Department of Cardiovascular and Renal Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark.
authors.forename: Grith Lykke
authors.identifier: http://orcid.org/0000-0002-5273-1097
authors.initials: GL
authors.lastname: Sorensen
authors.affiliation: Hans Christian Andersen Children's Hospital, Odense University Hospital, Odense, Denmark; Clinical Institute, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark;
authors.forename: Signe Sparre
authors.initials: SS
authors.lastname: Beck-Nielsen
authors.affiliation: Hans Christian Andersen Children's Hospital, Odense University Hospital, Odense, Denmark; Clinical Institute, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark; henrik.christesen@rsyd.dk.
authors.forename: Henrik Thybo
authors.initials: HT
authors.lastname: Christesen
mesh_terms: D000818:Animals; D001997:Bronchopulmonary Dysplasia / Q000209:etiology*; D005260:Female; D047109:Fetal Development; D006801:Humans; D007231:Infant, Newborn; D008168:Lung / Q000196:embryology* / Q000254:growth & development; D011247:Pregnancy; D012127:Respiratory Distress Syndrome, Newborn / Q000209:etiology*; D014807:Vitamin D / Q000502:physiology*; D014808:Vitamin D Deficiency / Q000150:complications*
chemical_list: D014807:Vitamin D
keywords: fetus; lung; neonate; preterm; surfactant; vitamin D