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Paul IM, Camera L, Zeiger RS, Guilbert TW, Bacharier LB, Taussig LM, Morgan WJ, Covar RA, Krawiec M, Bloomberg GR, Mauger DT, for the Childhood Asthma Research and Education (CARE) Network. Relationship between infant weight gain and later asthma. Pediatr Allergy Immunol 2010: 21: 82–89. © 2009 John Wiley & Sons A/S
Like obesity, the prevalence of asthma has increased over the past several decades. Accelerated patterns of infant growth have been associated with obesity and its co-morbidities. We aimed to determine if infant weight gain pattern is associated with asthma development later in childhood. Birth weight, growth, pulmonary function, and symptom data were collected in a trial of 2- to 3-yr-old children at-risk for asthma randomized to a 2-yr treatment with inhaled corticosteroids or placebo followed by a 1-yr observation period of study medication. Patterns of infant weight gain between birth and study enrollment were categorized as accelerated, average, or decelerated. Regression analyses were used to test the effects of infant weight gain pattern prior to study enrollment on outcomes during the observation year and at study conclusion while adjusting for demographics, baseline symptom severity, study treatment, and atopic indicators. Among the 197 study participants, early life weight gain pattern was not associated with daily asthma symptoms or lung function at the study’s conclusion. However, both prednisone courses (p = 0.01) and urgent physician visits (p < 0.001) were significantly associated with weight gain pattern with fewer exacerbations occurring amongst those with a decelerated weight gain pattern. We conclude that early life patterns of weight change were associated with subsequent asthma exacerbations, but were not associated with asthma symptoms or pulmonary function during the pre-school years for these children at-risk for asthma.
Accelerated or ‘rapid’ weight gain during infancy has emerged as a strong risk factor for obesity in both childhood and adulthood (1–16). Some co-morbid chronic conditions related to obesity have also been independently linked to rate of weight gain during infancy such as hypertension (17–20), coronary heart disease (21, 22), and type 2 diabetes mellitus (23, 24). Investigations into these associations began with the fetal growth restriction, or ‘Barker’ hypothesis (25). This hypothesis linked retarded growth in utero and catch-up growth to subsequent morbidities related to cardiovascular health and insulin resistance (26, 27). As studies continued to evaluate this hypothesis, recent data have revealed that the rate of growth in the months after birth may be more important in determining future outcomes (4, 28). It has been theorized that over-nutrition in infancy adversely ‘programs’ the components of the metabolic syndrome by promoting growth acceleration (29).
Like obesity, the prevalence of asthma has increased over the past several decades (30–33). While both low birth weight (34–42) and high body mass index in childhood (43–51) have been associated with an increased prevalence of asthma, a potential link between the two, rate of growth during childhood has received little attention. Therefore, we hypothesized that infant weight gain pattern would be associated with asthma development in a cohort of 2- to 3-yr-old children at high-risk for asthma enrolled in the Prevention of Early Asthma in Kids (PEAK) study (52). To test this hypothesis, asthma development was characterized by the two domains described in the new National Asthma Education and Prevention Program Guidelines: impairment and risk (53). The impairment domain is rooted in current burden of symptoms, quality of life, and functional capacity while the risk domain reflects adverse events, such as exacerbations of asthma and medication side effects.
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Through study of the developmental origins of adult diseases, early life weight gain has been explored for its relationship with numerous diseases later in life (70). Associations have previously been found with obesity (1–14), hypertension (17–20), coronary heart disease (21, 22), and type 2 diabetes mellitus (23, 24). The results of this study suggest that pattern of infant weight gain is associated with the risk domain of asthma morbidity for young children at high-risk for chronic asthma. Specifically, slower weight gain during the infant years relative to growth chart norms was protective for asthma exacerbations during the pre-school years. Though no association was found between weight gain pattern and components of the impairment domain of asthma morbidity, the data describing an association between early life weight gain and asthma exacerbations does provide evidence of a link between early life growth and subsequent asthma for children.
Given the small sample size, the findings should be viewed as preliminary, but the results of our study are consistent with the single other report examining the relationship between early life weight gain and asthma outcomes by Rona et al. (71). In that study, a cohort of 1232 Chilean children born between 1974 and 1978 were followed until a final study visit conducted between 2001 and 2003. Despite the collection of data on numerous variables related to birth and the infant period of life, only weight gain in the first year of life was significantly associated with wheezing illnesses during the 12 months prior to the final study assessment during adulthood.
Several previous studies have shown that increasing birth weight is inversely associated with subsequent asthma development (36, 37, 39, 40). Relating this fact to the current findings, children born heavier and near the upper percentile lines on the growth chart are less likely to upwardly cross major percentile lines due to the regression to the mean concept. Such children therefore are unlikely to have accelerated patterns of weight gain and more likely to have decelerated patterns of gain. The opposite is true for those born at lower weights who are unlikely to show decelerated patterns of growth and more likely to have accelerated weight gain during infancy. Though this study was underpowered to describe associations between asthma and birth weight, the current findings are related and consistent with an overall conceptual framework relating early life weight status to subsequent asthma outcomes.
Outside of infancy, the prevalence of asthma is associated with increased body mass index during childhood (43–51). Further, overweight children were recently shown to have a higher hospital admission rate when presenting to the emergency department when compared with normal weight children with asthma (72). In addition to the studies examining single point weight measurements, weight change over time has also been associated with asthma symptoms for children. The Tucson Children’s Respiratory Study demonstrated that females who became overweight or obese between ages 6 and 11 yr had an increased risk of developing new asthma symptoms and increased bronchial reactivity during the early adolescent period (73, 74). Similarly, the body mass index slope increases for those with unremitting asthma and unremitting wheezing were steeper than those with remitting asthma, remitting wheezing, or no wheezing (74). The investigators remarked that the prevention of accelerated weight gain during the school years could prevent asthma related morbidities.
Several mechanisms have been proposed to explain the relationship between obesity and asthma symptoms, and many of them can also be applied to weight gain pattern and accelerated weight gain during infancy, a time period where many confounders relevant to older subjects like sedentary lifestyle are not relevant. As recently reviewed by Shore (75), obesity is associated with mechanical factors, chronic systemic inflammation, and adipose tissue and energy-related hormones that all may be related to an individual’s asthma. Notably, accelerated weight gain during infancy has been associated with acquisition of adipose tissue as opposed to lean body mass (6, 9, 15, 76). The adipokines produced by adipose tissue may have a disease modifying effect (77). Further, co-morbidities of obesity such as gastroesophageal reflux disease can also contribute to asthma symptoms, and for infants, gastroesophageal reflux in particular is often clinically associated with overfeeding, which can lead to accelerated weight gain.
It is notable that the weight gain groups differed at baseline with respect to atopic status. Those in the decelerated group had higher IgE levels and were more likely to have aeroallergen skin test positivity. The fewer asthma exacerbations for this group is most likely explained by the fact that for toddlers, most exacerbations are induced by viral upper respiratory infections.
This analysis is limited by several factors. First, the data were generated from a prospective clinical trial, and the sample size and statistical power are therefore relatively small to describe associations between weight change and asthma outcomes. This fact may contribute to our inability to show any differences between the average weight gain group and those that had accelerated patterns of weight gain. Similarly, the lack of significant findings with asthma outcomes in the impairment domain should be viewed cautiously. Next, interval weight measurements between birth and study enrollment were not collected or available for analysis. It is possible that there is a critical early life period of growth that may have a stronger association with asthma outcomes than we were able to detect. A cohort followed from birth throughout childhood would be ideal to further evaluate the questions posed by this study. Further, data regarding other relevant perinatal covariates with relationships to infant weight status such as maternal body mass index and newborn gestational age were either unavailable or imprecise. Finally, this cohort was not representative of the general population or the overall population of asthmatic children, but rather a very specific cohort of young children with frequent intermittent wheezing at high-risk for asthma development. Therefore, this report cannot be generalized to other populations, but instead can be used to prompt further studies.
In summary, the results of this analysis describe a relationship between weight gain pattern during infancy and components of asthma later in childhood, specifically those related to exacerbations. While the overall contribution of weight change to asthma morbidity may be relatively minor compared with genetics, atopic status, and environmental exposures (78), weight status and weight change over time are modifiable. If future studies confirm that weight change is associated with asthma exacerbations, interventions could be developed with asthma prevention as a goal.