Obesity and overweight have been found as risk factors for asthma and asthma severity, although it is difficult to isolate exposure to obesity per se from sedentary activity and dietary factors associated with obesity(Beuther and Sutherland 2007). Furthermore, sedentary lifestyle and possibly even dietary indiscretion are thought to be mediators of this association. Unfortunately, both asthma and obesity have been increasing in prevalence(Chinn and Rona 2001). Little information exists about the potential effects of maternal obesity on the risk of asthma in their offspring. The lung branch of the National Health Lung and Blood Institute (NHLBI) has suggested studies explore in utero exposure to obesity as a possible causative factor in childhood asthma(Weiss and Shore 2004). Biologic plausibility exists for this association; obesity and asthma are both conditions with an increase in certain inflammatory markers. It has been hypothesized that obesity during pregnancy may cause immunologic changes (increase in TNF alpha, IL 4 and IL5) that can be transferred to the fetus resulting in increasing risk of atopy among offspring(L.-G. Hersoug 2007). Leptin levels known to be increased in obesity also exist in fetal lung and are associated with fetal lung maturation(Torday, Sun et al. 2002).

A study from the Fragile Families and Child Wellbeing study found an association between maternal pre-pregnancy weight and self-reported physician-diagnosed incident asthma in offspring up to age 3 years old(Reichman and Nepomnyaschy 2007). We propose to study the association of maternal weight (and weight gain during pregnancy) with incident asthma (and atopy) among offspring up to age 7 1/2 years old in the Avon Longitudinal Study of Parents and Children (ALSPAC). This analysis differs from the one study in this area, in that maternal weight at 18 weeks will be the exposure rather than pre-pregnancy weight, and the outcome of incident asthma will extend to 7 1/2 years rather than just 3 years. One advantage of ALSPAC is the phenotype of asthma is further validated in a subgroup of children through bronchial hyperresponsiveness testing with methocholine challenge. A disadvantage is that maternal weight was self-reported. Since we are relating asthma to in utero exposures, it is unlikely that follow-up beyond age 7 1/2 will be useful at this point, especially if there is no association in this age group.

Table 1 (see attached) shows the variables requested for this analysis. The main exposure will be self-reported weight and height at the week 18 pregnancy visit, maternal weight change during pregnancy, and self-reported physical activity level during pregnancy. The outcome of incident asthma will be defined in 3 separate ways and then also as a composite of these measures. First, asthma up to 3 years of age will be based on maternal responses about wheeze in their child up to that time. Second, asthma at age 7 1/2 years will be based on questions about symptoms of wheeze, treatment for asthma and a history of a physician diagnosis of asthma. Third, asthma will be defined by bronchial hyperresponsiveness (BHR) as tested with methacholine challenge. BHR testing was performed in those with a baseline FEV1 of at least 70%. A positive test indicative of BHR will be defined as a greater than 20 % reduction in FEV1 from the postsaline value prior to delivery of the maximum dose of methacholine (6.1 micro-mol). Atopy will be defined as a separate outcome based on positive responses to the pin prick skin testing. Atopic responses will be defined as those with a 2 mm or greater wheal reaction to selected common antigens and a negative reaction to the control.

Potential confounders for these analyses include maternal physical activity (hours per week participated in 11 specific exercise activities), maternal nutrition information, maternal age, maternal smoking, maternal history of asthma, maternal history of allergy/atopy, maternal housing inadequacy, maternal financial difficulties, maternal education, maternal psychopathology, and maternal social support, complications during pregnancy, pre-eclampsia, gestational diabetes, types of delivery (ie, vaginal, c-section), child's birth weight, child's gestational age at birth, child's gender, child length of time breastfed, BMI of child, child's sedentary behavior and TV viewing, child's exposure to pets, and child's exposure to environmental tobacco smoke.

References

Beuther, D. A. and E. R. Sutherland (2007). Overweight, Obesity, and Incident Asthma: A Meta-analysis of Prospective Epidemiologic Studies. 175: 661-666.

Chinn, S. and R. J. Rona (2001). Can the increase in body mass index explain the rising trend in asthma in children? 56: 845-850.

L.-G. Hersoug, A. L. (2007). "The link between the epidemics of obesity and allergic diseases: does obesity induce decreased immune tolerance?" Allergy 62(10): 1205-1213.

Reichman, N. E. and L. Nepomnyaschy (2007). "Maternal Pre-Pregnancy Obesity and Diagnosis of Asthma in Offspring at Age 3 Years." Matern Child Health J.

Torday, J. S., H. Sun, et al. (2002). "Leptin mediates the parathyroid hormone-related protein paracrine stimulation of fetal lung maturation." Am J Physiol Lung Cell Mol Physiol 282(3): L405-10.

Weiss, S. T. and S. Shore (2004). Obesity and Asthma: Directions for Research. 169: 963-968.