The relationship of breast-feeding, overweight, and asthma in preadolescents

Article Outline

• Abstract
• Methods
  • Statistics
• Results
• Discussion
• Acknowledgment
• References
• Copyright

Background

Breast-feeding is suggested to be associated with overweight or asthma in children. Overweight and asthma may share common environmental influences of which breast-feeding may be one.

Objective

We evaluated whether short duration of exclusive breast-feeding and subsequent overweight were associated with asthma.

Methods

A nested case-control study included 246 children with pediatric allergist–diagnosed asthma and 477 controls without asthma at age 8 to 10 years. Information on exclusive breast-feeding was obtained from questionnaire data. Overweight at 8 to 10 years of age was defined as body mass index ≥85th percentile of age and sex-specific growth charts. The association between asthma and exclusive breast-feeding <12 weeks plus overweight, adjusted for sex, parental asthma, aboriginal origin, passive smoking at birth, residence location, and family income, was determined in logistic regression analyses.

Results

Exclusive breast-feeding <12 weeks was closely associated with overweight at age 8 to 10 years (P < .001). Exclusive breast-feeding <12 weeks plus overweight was significantly associated with asthma (adjusted OR, 1.81; 95% CI, 1.11-2.95; P = .018). This association appeared to be strong in children whose mothers had asthma (adjusted OR, 3.93; 95% CI, 1.17-13.2) and also in boys (adjusted OR, 2.22; 95% CI, 1.14-4.34). Asthma was not associated with either exclusive breast-feeding <12 weeks or overweight in the absence of the other.

Conclusion

Short duration of exclusive breast-feeding and subsequent overweight are associated with asthma in susceptible children, suggesting a common pathway.

Clinical implications

This finding adds to the importance of promoting prolonged breast-feeding for the prevention of overweight and asthma.

Key words: Asthma, breast-feeding, case-control studies, sex, heredity, leptin, overweight, preadolescent

Abbreviation used: OR, Odds ratio

The role of breast-feeding in the development of asthma remains controversial after more than 30 years of extensive investigation.¹, ² Breast-feeding has been reported to reduce the risk of asthma among toddlers diagnosed before 2 years of age³, ⁴, ⁵ and also in preschool children.⁶, ⁷ In contrast, breast-feeding in infancy has been related to an increased prevalence of asthma in preadolescents,⁸ adolescents, and young adults.⁹ Furthermore, several studies have investigated the relationship of breast-feeding and asthma in children with or without maternal history of allergic diseases. It has been suggested that the protective effect of breast-feeding on asthma at young age is strong in children whose mothers do not have a history of allergic disorders,⁶, ¹⁰, ¹¹ but the literature does not show consistency on this issue either.¹, ¹²

In addition, breast-feeding has been proposed to be a protective factor for childhood overweight.¹³, ¹⁴ The dramatic increase in child overweight has paralleled the rise in childhood asthma during the past few decades.¹⁵ There is also accumulating evidence of a positive association between overweight and asthma in children.¹⁶, ¹⁷, ¹⁸, ¹⁹, ²⁰ It has been hypothesized that overweight and asthma may have common genetic and environmental influences. However, there is scarcity in the literature to study what the common environmental factors are. We hypothesized that short duration of breast-feeding was a common influence on overweight and asthma. We sought to determine whether short duration of breast-feeding and subsequent overweight were associated with asthma.

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Methods 

This was a nested case-control study that included 246 children with pediatric allergist–diagnosed asthma and 477 controls without asthma at 8 to 10 years of age. Cases and controls were recruited from the same cohort of children born in 1995 in the province of Manitoba, Canada, after parent response to a mailed survey on child health when these children were 8 to 10 years of age. The 1995 cohort was identified from the records of the Manitoba Health Services Insurance Plan, which was a population-based health care administrative and prescription database. From the 3500 received surveys, parent-declared asthma during the past 12 months was 11%, which mirrored the asthma prevalence in children at this age group in Manitoba. All children with parent-declared asthma in the past 12 months were selected for recruitment. A comparable number of children without parent-declared asthma (defined as control children) were randomly selected from the rest of participants after stratification by family income (low/high) and residence location (urban/rural) to ensure a balanced representation. All the recruited children were subsequently invited to undergo a clinical assessment. After clinical assessment for asthma by a pediatric allergist (A.B.B. or J.J.L.), there were ultimately 246 children with allergist-diagnosed asthma and 477 children without asthma among those who came and participated in the clinical examination. Diagnoses were based on the Canadian Asthma Consensus Guidelines in which symptoms and variable airway obstruction (responses to bronchodilators and corticosteroids) were 2 major criteria.²¹ To aid in the diagnosis, a standardized history was used including questions on cough, wheeze, shortness of breath, and response to current medications (ie, bronchodilators, corticosteroids), and the presence of other allergic conditions (eg, allergic rhinitis, atopic dermatitis, and food allergies) were elicited. Physical examination included examination for chest symptoms (hyperinflation, wheeze, prolonged expiration, and decreased breath sounds). Hospitalization and medical visits for breathing difficulty in the past year were also noted. All findings were recorded, and a diagnosis of asthma in the last 12 months was made.

Information on breast-feeding and other environmental factors was obtained from a detailed questionnaire answered by parents of participants at the clinical examination. Exclusive breast-feeding was derived from a question on the time of introduction of formula/cow's milk: “When did your child first have any formula/cow's milk?” Five options were given: <1 week, ≥1 week, ≥5 weeks, ≥9 weeks, and ≥12 weeks. The lower limit of each option was recorded in the data set (ie, 0, 1, 5, 9, and 12 weeks). Breast-feeding was categorized as a dichotomous variable. The highest limit of 12 weeks was used as the cutoff level to obtain an even number of children in each group. Children were categorized as follows: exclusive breast-feeding <12 weeks (n = 304; 44%) and exclusive breast-feeding ≥12 weeks (n = 381; 56%). The reliability of maternal report of breast-feeding was determined by comparison to reports of breast-feeding after birth in a sample of 40 study mothers who had participated in a prospective intervention study in 1995.²² Survey information on an exclusive breast-feeding measure was correlated with the same information collected prospectively after birth on these 40 children assessed by actual breast-feeding duration (correlation coefficient ρ, 0.45; P < .01). The correlation coefficients were similar in 20 children with asthma (ρ, 0.45; P = .05) and 20 controls (ρ, 0.53; P = .04), indicating there were no systematic (nonrandom) recall errors. When the 12-week cutoff was used, 65% of the survey information was in agreement with the prospective information, and there was no significant difference in the percentage of agreement between children with asthma and controls.

Data on parental asthma and child environmental factors, such as aboriginal origin, passive smoking at birth, residence location, and family income, were obtained from the same questionnaire data. Parental asthma was defined as mother or father report of asthma in the last 12 months. Aboriginal origin was defined as self-report of birth home located in a First Nation community. Passive smoking at birth was denoted as the presence of smoking in the home during the birth year. Residence location was categorized as urban/rural. Family income was classified as low if the annual household income was less than $30,000 Canadian. Parent report of mold at birth and the presence of cats or dogs in the home were used to create binary measures of these exposures. Birth weight information was obtained from provincial hospital database records after parental permission to link survey and clinic data to their child's database records.

At the time of clinical examination, skin prick tests to common relevant allergens were performed (tree pollen mix, weed pollen mix, ragweed [separate], grass pollen mix, Alternaria, Cladosporium, Penicillium, house dust mites [Dermatophagoides pteronyssinus, Dermatophagoides farinae], cockroach, cat, dog, feathers, and peanut). Methacholine bronchoprovocation tests were performed using the classic Juniper technique to define PC₂₀.²³ Bronchial hyperresponsiveness was defined as a PC₂₀ of <8 mg/mL methacholine. Height (in centimeters) and weight (in kilograms) were measured in triplicate and the mean recorded. Body mass index was calculated as weight in kilograms divided by the square of height in meters. Current overweight was defined as body mass index ≥85th percentile according to age and sex-specific growth charts.²⁴ Atopic asthma was defined as pediatric allergist–diagnosed asthma in combination with positive skin prick test to at least 1 common allergen. Nonatopic asthma was defined as pediatric allergist–diagnosed asthma in combination with negative skin prick test. The study was approved by the Health Research Ethics Board, University of Manitoba and the Health Information Privacy Committee.

Statistics 

To investigate the study question, the following categories were created: (1) exclusive breast-feeding ≥12 weeks and no overweight (reference group); (2) exclusive breast-feeding ≥12 weeks and overweight; (3) exclusive breast-feeding <12 weeks and no overweight; (4) exclusive breast-feeding <12 weeks and overweight. Subsequent to 38 missing values for exclusive breast-feeding and 1 missing value for overweight, 684 children were included in multivariate logistic regression analyses. Separate analyses were conducted for boys and girls, for children with and without maternal asthma, and for atopic and nonatopic asthma. Models were adjusted for sex, maternal asthma, paternal asthma, aboriginal origin, passive smoking at birth, residence location, and family income.²⁵, ²⁶, ²⁷, ²⁸ A P value < .05 was used as the significance level, and 2-sided tests were applied. All statistical analyses were performed with STATA 9.0 (College Station, Tex).

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Results 

Sex, maternal asthma, paternal asthma, aboriginal origin, passive smoking at birth, residence location, and family income were significantly associated with exclusive breast-feeding and/or overweight and/or asthma (Table I) and thus were included in the multivariate logistic regression analyses. No significant associations were found between low birth weight or exposure to pets and exclusive breast-feeding, overweight, or asthma, and these factors were excluded from multivariate models.

Table I. Possible confounding factors in relation to exclusive breast-feeding, current overweight, and asthma§

Comparison between yes and no for ∗maternal asthma or †paternal asthma.

In general, children who were exclusively breast-fed <12 weeks were more likely to have pediatric allergist–diagnosed asthma than children who were exclusively breast-fed ≥12 weeks (38% vs 31%; P < .05, crude odds ratio [OR], 1.38; 95% CI, 1.00-1.89). Moreover, exclusive breast-feeding <12 weeks was closely associated with overweight at 8 to 10 years of age (P < .001). There was no significant difference in asthma frequency among children who were currently overweight and those who were not currently overweight (37% vs 33%; P = .22; crude OR, 1.23; 95% CI, 0.88-1.70). The OR for asthma in children exclusively breast-fed <12 weeks decreased nominally after adjustment for overweight (OR, 1.34; 95% CI, 0.97-1.85, and a 9% change in the estimated coefficient) and after adjustment for additional covariates of sex, maternal asthma, paternal asthma, aboriginal origin, passive smoking at birth, residence location, and family income (OR, 1.37; 95% CI, 0.97-1.94, and a 1% change in the estimated coefficient).

Children who were exclusively breast-fed <12 weeks and currently overweight had the highest frequency of asthma compared with children who were exclusively breast-fed ≥12 weeks and not currently overweight (42% vs 31%; P = .03; Table II). Children with either exclusive breast-feeding <12 weeks or with overweight had an intermediate frequency of asthma (36% and 33%, respectively), but these rates were not significantly higher than those children with neither status (P > .2 for both). After adjustment for sex, maternal asthma, paternal asthma, aboriginal origin, passive smoking at birth, residence location, and family income, the combination of exclusive breast-feeding <12 weeks and overweight remained significantly associated with asthma (OR, 1.81; 95% CI, 1.11-2.95; P = .018). Exclusive breast-feeding <12 weeks or overweight alone was not significantly associated with asthma in multivariate analyses (Table II). The association between breast-feeding–overweight status and asthma was significant in children whose mothers had asthma (adjusted OR, 3.93; 95% CI, 1.17-13.15), but not in those whose mothers did not have asthma (Table II), and it was significant in boys but not in girls (Table II). Moreover, combined exclusive breast-feeding <12 weeks and overweight was significantly associated with atopic asthma (adjusted OR, 2.02; 95% CI, 1.14-3.55; Table III). No association was found between allergist-diagnosed asthma concomitant with bronchial hyperresponsiveness and exclusive breast-feeding <12 weeks plus overweight (data not shown).

Table II. Exclusive breast-feeding and current overweight in relation to asthma∗

Table III. Exclusive breast-feeding and current overweight in relation to atopic asthma and nonatopic asthma∗

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Discussion 

In our study, short duration of exclusive breast-feeding had a marginal association with asthma in preadolescents after adjustment for overweight and other covariates, which was consistent with findings in children at a younger age.³, ⁴, ⁵, ⁶, ⁷, ²⁹ More interestingly, we found that combined exclusive breast-feeding <12 weeks and overweight was significantly associated with asthma. Because exclusive breast-feeding <12 weeks was closely associated with overweight in our study and that of others,¹³, ¹⁴, ³⁰ our finding suggests that overweight as a consequence of short duration of breast-feeding is associated with asthma in susceptible children. To our knowledge, this is one of the few studies to evaluate the interrelationship of breast-feeding, overweight, and asthma²⁹ and the first study to assess breast-feeding as a common environmental influence on overweight and asthma.

The comorbid condition of overweight and asthma related to a short duration of exclusive breast-feeding suggests a common pathway, which can possibly be explained by a hormone called leptin. Leptin is present in breast milk and is produced by mammary epithelial cells.³¹ Higher levels of serum leptin are detected in breast-fed than in bottle-fed infants during the first years of life.³², ³³ Leptin acts on the hypothalamus to inhibit food intake and in turn control body weight.³⁴ Serum leptin levels have been reported to be inversely related to weight gain in infancy.³⁵ In addition, there is evidence that leptin affects immune responses in the periphery by favoring T_H1 responses and inhibiting T_H2 cytokines.³⁴, ³⁶ We speculate that low levels of circulating leptin in early life caused by short duration of exclusive breast-feeding increase the risk of overweight and asthma in children. Moreover, we showed that combined short duration of exclusive breast-feeding and overweight was associated with asthma, particularly in boys and in children whose mothers had asthma. Children with a family history of allergy have delayed maturation of T_H1 immunity.³⁷ Recent evidence shows that boys have lower levels of leptin than girls in cord blood and during the first years of life,³³, ³⁵ which may lead to delayed T_H1 immune responses in boys. Short duration of exclusive breast-feeding and the resultant low leptin levels could thus exert an additional role in the development of a more imbalanced immune response in these children.

Despite the fact that our findings were independent of many risk factors for asthma, additional factors such as maternal history of obesity might play a role in the relationship among breast-feeding, overweight, and childhood asthma. Parental history of obesity is one of the strongest risk factors for obesity in the offspring, more than doubling the risk.³⁸ Maternal obesity is associated with a decreased likelihood of successful breast-feeding initiation and higher discontinuation rates.³⁹ However, there is no evidence that maternal obesity is associated with childhood asthma.

The strength of our study design was that it was a case-control study nested within a cohort of children. Unlike a standard case-control study, both cases and controls were selected from the same population, which reduces the likelihood of selection bias. Controls were randomly selected after stratification by residence location and family income to ensure representation of urban and rural areas, as well as high-income and low-income families. Cases of asthma were diagnosed by 2 pediatric allergists according to disease history, clinical symptoms, physical examination, and variable airway obstruction following Canadian Asthma Consensus Guidelines.²¹ Our child population also represented the typical presentation of asthma in this age group.⁴⁰ Further, although doctor-diagnosed asthma with bronchial hyperresponsiveness was not associated with short duration of exclusive breast-feeding and overweight, the association was noteworthy with atopic asthma, the phenotype of persistent asthma. Information on biomarkers of inflammation such as T_H2 cytokine levels was not available during this analysis and may increase our understanding of the relationship among breast-feeding, overweight, and asthma. Finally, although our study was based on retrospective report of breast-feeding, we found maternal recall of breast-feeding to be acceptable and free from systematic bias.

There are many benefits of breast-feeding, including optimum infant nutrition, reduction in risk of infant infections, and close bonding of mother and child.⁴¹, ⁴² Our study indicates that short duration of exclusive breast-feeding may be a common environmental influence for child overweight and asthma, adding to the importance of promoting prolonged breast-feeding for the prevention of overweight and asthma in children.

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We thank all of the participating children and their parents. We also acknowledge our research nurses and assistants involved in the project: Marilyn Lilley, Tanya Lilley-Chan, Rishma Chooniedass, Miriam Clement, Shamima Huq, Donna Everette, Brenda Gerwing, Ingrid Loewen, Mellissa Moyen, Diane Stewart, Michelle Tillett, and John Weselake.

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