Early life determinants of childhood wheezing disorders : evidence from Hong Kong’s “children of 1997” birth cohort

Abstract

Asthma is the most common chronic disease in children and a major cause of disability. The prevalence of asthma and wheeze varies widely across countries and is increasing in low-and-middle income countries for reasons that are poorly understood. As the respiratory system develops most rapidly in early life, exposures during this period could play a major role in the aetiology of childhood wheezing disorders. Nonetheless, existing evidence is predominantly based on observations in long-term developed Western populations, which may have different social patterns of exposures compared to developing or rapidly developed settings. These studies could also be residually confounded by socioeconomic position (SEP).

This thesis took advantage of the population-representative “Children of 1997” birth cohort (n=8,327) in Hong Kong, a recently developed, non-Western setting that is ethnically homogeneous and has a distinct lifestyle, history of economic development and confounding structure compared to Western settings. Adopting a life course approach, I examined the roles of exposures acting from the prenatal to infancy periods, as well as between generations, including parental migration, gestational age, birth weight, mode of delivery, breastfeeding, child care, and birth order. I used Cox regression to examine the time to first public hospital admission for asthma, bronchitis and bronchiolitis (International Classification of Diseases, Ninth Version Clinical Modification 466, 490 and 493) to 12 years. Using logistic and linear regression, I also examined the associations of parental and neighbourhood SEP with preterm birth (PTB) and birth weight.

Parental migration, late PTB and a higher birth order were associated with higher risk of hospitalization for childhood wheezing disorders. Conversely, being large for gestational age was associated with lower risk. Mode of delivery, breastfeeding and informal child care had no clear associations with childhood wheezing disorders. Parental and neighbourhood SEP had little associations with PTB, birth weight and SGA, suggesting that Hong Kong may provide a useful setting with less confounding by SEP to study outcomes associated with PTB and birth weight.

Taken together with existing evidence, this study supports a causal role of PTB in the aetiology of childhood wheezing disorders. The positive findings also highlight the health needs of migrants and may challenge the“hygiene hypothesis”. While an effect of mode of delivery could not be ruled out, positive results for late PTB emphasize the need to limit Caesarean sections without medical indications. On the other hand, the null results for breastfeeding suggest non-causality. Finally, results for informal child care suggest a potential role of the microbiome, which is an important area for future research.