Paediatric asthma and wheeze : early life origins

Epidemiological evidence suggests poor fetal growth is associated with poor later respiratory health, including the important childhood disorders asthma and wheeze. Factors creating a suboptimal early environment may persistently alter the structure and function of the immune and respiratory systems. This thesis explored the early life origins of paediatric asthma and wheeze in a large, prospective mother-child cohort. In particular, the contributions of maternal nutrition, and fetal and postnatal growth were assessed. The mothers of healthy, term infants had their body composition, lifestyle and diet characterised before and during pregnancy. Serum anti-oxidants, vitamin D and polyunsaturated fatty acids were measured in late pregnancy. Fetal growth was recorded by longitudinal ultrasound scans. 1548 children were followed to age 3 years and 469 were seen at 6 years. Wheeze was assessed by questionnaire and skin prick testing and detailed lung function measures were performed. Late pregnancy fetal growth faltering was associated with an increased risk of atopy and atopic wheeze at age 3 years, and greater weight and adiposity gain in the first year of life were associated with increased risk of wheeze. In those children seen at 6 years, greater maternal adiposity, before and during pregnancy, was associated with increased risk of non-atopic wheeze. Lower maternal pre-pregnancy vitamin D intake was associated with increased risk of childhood asthma, recent wheeze, and non-atopic wheeze. Lower maternal serum 25(OH) vitamin D in late pregnancy was also associated with childhood asthma and wheeze. Higher late pregnancy energy-adjusted vitamin A intake was associated with higher forced expiratory volumes but also greater bronchial hyperresponsiveness. Higher arachidonic acid status during pregnancy was associated with markers of atopy and greater risk of atopic wheeze. These results suggest early life factors contribute to paediatric asthma and wheeze. Optimising the early environment may reduce the burden of childhood wheezeEThOS - Electronic Theses Online ServiceGBUnited Kingdo