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Title: Prenatal vitamin D for the prevention of preschool wheezing : effect on early lung development
Author: Goldring, Stephen
ISNI:       0000 0005 0733 3948
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2014
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Background: Asthma is the commonest chronic disease of childhood. The earliest manifestation is often preschool wheezing, which affects up to 50% of young children, but is difficult to evaluate practically. Observational studies suggest that low prenatal vitamin D status may be a risk factor for childhood wheezing. Aims: To evaluate the measurement of preschool lung function using impulse oscillometry, and to test the hypotheses that prenatal vitamin D supplementation may promote lung development or prevent preschool wheezing. Methods: We recruited 3 to 5 year olds from outpatient clinics to evaluate the quality of impulse oscillometry readings and the relationship between lung function and wheezing. We then evaluated impulse oscillometry in a group of 3-year-old children whose mothers had participated in a prenatal vitamin D supplementation trial. Next we evaluated the effect of prenatal vitamin D supplementation on lung function parameters and on the prevalence of wheeze and atopy in the first 3 years of life in this population (ISRCTN 68645785). Findings: In 3 to 5 year old children, we successfully acquired high quality impulse oscillometry readings in 37/66 (56%). We found increased bronchodilator responses in those who had previously wheezed, with adjusted mean difference in respiratory resistance at 25Hz (95% confidence intervals) of -8.65 Kpa/Ls-1 (-16.63, -0.67), p=0.04. In 3-year-old children whose mothers participated in a prenatal vitamin D trial, we acquired high quality readings in 51/105 (49%), but found no relationship between wheezing history and bronchodilator response. In the randomised controlled trial of prenatal vitamin D supplementation, we evaluated 158/180 (88%) offspring at age 3 years and found no difference in wheeze, atopy, lung function or healthcare utilisation between vitamin D supplemented groups and controls. Conclusions: It is possible to acquire high quality lung function data using impulse oscillometry for half of preschool children, however we found no consistent relationship between lung function and wheezing history. There may be age related differences in the pathophysiology of wheezing and its relationship to lung function, which should be explored in future studies. Prenatal vitamin D supplementation in late pregnancy was not associated with differences in lung function or wheezing. Future research should explore the effect of higher doses and earlier administration of vitamin D in pregnancy.
Supervisor: Boyle, Robert; Warner, John Sponsor: Asthma UK
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral