Vitamin D Deficiency at 16 to 20 Weeks’ Gestation Is Associated with Impaired Lung Function and Asthma at 6 Years of Age

Zosky, Graeme R.; Hart, Prue H.; Whitehouse, Andrew J. O.; Kusel, Merci; Ang, Wei; Foong, Rachel E.; Chen, Linping; Holt, Patrick G.; Sly, Peter D.; Hall, Graham L.

doi:10.1513/annalsats.201312-423oc

Cited by 115 publications

(129 citation statements)

References 38 publications

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“…In keeping with the animal data, a recent human study (109) showed that lower maternal vitamin D concentrations in pregnancy were after confounder control associated with current wheeze (both sexes, questionnaire data, P ϭ 0.05), current asthma (boys, doctor's diagnosis, P ϭ 0.04), decreased functional vital capacity (FVC) Z-score (both sexes, P ϭ 0.02, largely driven by decreased FVC in girls), a trend toward lower forced expiratory volume in 1 s (FEV1) Z-score at 6 yr (girls, P ϭ 0.09), and decreased FEV1/FVC Z-score in 14-yr-old girls (P ϭ 0.05). Whereas some other studies support an inverse relation between vitamin D status in pregnancy and offspring wheeze or asthma, others have found no associations, or U-shaped or direct associations, although many of these studies were of minor quality, e.g., in the diagnosis of childhood asthma (62,63).…”

Section: Discussionmentioning

confidence: 92%

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

Lykkedegn

Sørensen

Beck-Nielsen

et al. 2015

American Journal of Physiology-Lung Cellular and Molecular Phys

119

104

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-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...

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Section: Discussionmentioning

confidence: 92%

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

Lykkedegn

Sørensen

Beck-Nielsen

et al. 2015

American Journal of Physiology-Lung Cellular and Molecular Phys

119

104

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“…Dysanapsis is merely a reflection of the incongruence between a (faster) growth in lung volume and airway length, and the (slower) increase in airway caliber. Such incongruence may happen physiologically and may be accentuated by several mechanisms, including in utero exposures such as tobacco smoke or vitamin D deficiency (34,35), although it is unclear whether these effects would persist later in childhood. Chronic hypoxemia has been associated with a higher risk of dysanaptic lung growth (36); dysanapsis may also be present in breathhold divers, who use glossopharyngeal insufflation to force their lung volumes above TLC (providing extra oxygen and preventing compression when diving) (37).…”

Section: Discussionmentioning

confidence: 99%

Obesity and Airway Dysanapsis in Children with and without Asthma

Forno

Weiner

Mullen

et al. 2017

Am J Respir Crit Care Med

196

137

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Rationale: For unclear reasons, obese children with asthma have higher morbidity and reduced response to inhaled corticosteroids.Objectives: To assess whether childhood obesity is associated with airway dysanapsis (an incongruence between the growth of the lungs and the airways) and whether dysanapsis is associated with asthma morbidity.Methods: We examined the relationship between obesity and dysanapsis in six cohorts of children with and without asthma, as well as the relationship between dysanapsis and clinical outcomes in children with asthma. Adjusted odds ratios (ORs) were calculated for each cohort and in a combined analysis of all cohorts; longitudinal analyses were also performed for cohorts with available data. Hazard ratios (HRs) for clinical outcomes were calculated for children with asthma in the Childhood Asthma Management Program.Measurements and Main Results: Being overweight or obese was associated with dysanapsis in both the cross-sectional (OR, 1.95; 95% confidence interval [CI], 1.62-2.35 [for overweight/obese compared with normal weight children]) and the longitudinal (OR, 4.31; 95% CI, 2.99-6.22 [for children who were overweight/obese at all visits compared with normal weight children]) analyses. Dysanapsis was associated with greater lung volumes (FVC, vital capacity, and total lung capacity) and lesser flows (FEV 1 and forced expiratory flow, midexpiratory phase), and with indicators of ventilation inhomogeneity and anisotropic lung and airway growth. Among overweight/obese children with asthma, dysanapsis was associated with severe disease exacerbations (HR, 1.95; 95% CI, 1.38-2.75) and use of systemic steroids (HR, 3.22; 95% CI, 2.02-5.14).Conclusions: Obesity is associated with airway dysanapsis in children. Dysanapsis is associated with increased morbidity among obese children with asthma and may partly explain their reduced response to inhaled corticosteroids.

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“…33,47,48 The 9 studies with nonsignificant results used a variety of 25(OH)D thresholds. 29,30,32,[40][41][42][43][44]46 None of the 6 studies looking at the association between 25(OH)D and allergic rhinitis reported significant associations. 29,30,41,43,44,48 One study mentioned collecting data but did not report on the outcome.…”

Section: Allergic Diseasementioning

confidence: 99%

Maternal and cord blood vitamin D status and childhood infection and allergic disease: a systematic review

et al. 2016

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Context: It is unclear how in utero vitamin D deficiency affects the extraskeletal health of children, despite the known risks for adverse pregnancy/birth outcomes. Objective: This systematic review seeks to assess the effect of in utero vitamin D exposure on childhood allergy and infection outcomes using the PRISMA guidelines. Data Sources: MEDLINE, Cochrane Library, and Web of Science databases were searched. Study Selection: Literature published through April 2015 was searched for studies reporting on the association between maternal pregnancy or cord blood vitamin D status and childhood allergy and infection. Data Extraction: Of 4175 articles identified, 43 studies met the inclusion criteria. They examined a wide variety of outcomes, using many different vitamin D cutoff values in their analyses. Data Synthesis: For most outcomes, results were inconsistent, although there appeared to be a protective effect between higher in utero vitamin D status and childhood lower respiratory tract infection (5 of 10 studies). Conclusions: More research is needed on childhood allergy and infection outcomes, and future studies should standardize outcome reporting, especially with regard to cutoff values for vitamin D concentrations. Evidence of a protective association between in utero vitamin D exposure and lower respiratory tract infection was found, while the other outcomes were either understudied or showed inconsistent results. PROSPERO registration no. CRD42013006156.

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Vitamin D Deficiency at 16 to 20 Weeks’ Gestation Is Associated with Impaired Lung Function and Asthma at 6 Years of Age

Abstract: This study supports the notion that vitamin D deficiency during lung development may impact on postnatal lung growth and increase the risk of developing lung disease.

Cited by 115 publications

References 38 publications

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

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

Obesity and Airway Dysanapsis in Children with and without Asthma

Maternal and cord blood vitamin D status and childhood infection and allergic disease: a systematic review

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