Pediatric Pulmonology
Breastfeeding Duration and Asthma in Puerto Rican Children Christian Rosas-Salazar, MD, MPH,1 Erick Forno, MD, MPH,2 John M. Brehm, MD, MPH,2 rez, PhD,3 Michelle M. Cloutier, MD,4 Yueh-Ying Han, PhD,2 Edna Acosta-Pe 5 Dorothy B. Wakefield, MA, Marı´a Alvarez, MD,3 Angel Colo n-Semidey, MD,3 3 Glorisa Canino, PhD, and Juan C. Celedo n, MD, DrPH2 Summary. Rationale: Little is known about breastfeeding and asthma in Puerto Ricans, the ethnic group most affected by this disease in the US. We examined the relation between the currently recommended duration of breastfeeding and asthma in school-aged Puerto Rican children. Methods: Case-control study of 1,127 Puerto Rican children aged 6–14 years living in Hartford, Connecticut (n ¼ 449) and San Juan, Puerto Rico (n ¼ 678). Parental recall of breastfeeding was categorized based on duration and according to current guidelines (i.e., none, 0–6 months, and >6 months). Asthma was defined as parental report of physician-diagnosed asthma and wheeze in the previous year. We used logistic regression for the multivariate analysis, which was conducted separately for each study site and for the combined cohort. All multivariate models were adjusted for age, gender, household income, atopy, maternal asthma, body mass index, early-life exposure to environmental tobacco smoke, and (for the combined cohort) study site. Results: After adjustment for covariates, children who were breastfed for up to 6 months had 30% lower odds of asthma (95% CI ¼ 0.5–1.0, P ¼ 0.04) than those who were not breastfed. In this analysis, breastfeeding for longer than 6 months was not significantly associated with asthma (OR ¼ 1.5, 95% CI ¼ 1.0–2.4, P ¼ 0.06). Conclusions: Our results suggest that breastfeeding for up to 6 months (as assessed by parental recall) is associated with decreased odds of asthma in Puerto Rican children, and that there is no additional beneficial effect of breastfeeding for over 6 months. These results support current recommendations on the duration of breastfeeding in an ethnic group at risk for asthma. Pediatr Pulmonol. ß 2014 Wiley Periodicals, Inc. Key words: breastfeeding; asthma; children; Puerto Rico. Funding source: US National Institutes of Health (NIH); Numbers: HL079966, HL117191, HD052892, Heinz Foundation.
INTRODUCTION
Breastfeeding has numerous advantages for the infant, the mother, and society, including developmental,
1 Division of Pediatric Allergy, Immunology, and Pulmonary Medicine, Monroe Carell Jr. Children’s Hospital at Vanderbilt, Vanderbilt University, Nashville, Tennessee.
nutritional, immunologic, psychological, social, and economic benefits.1 Although, the benefits of breastfeeding are widely acknowledged, there is still conflicting evidence on its optimal duration in developing and
5
Center for Public Health and Health Policy, University of Connecticut Health Center, Farmington, Connecticut. Conflict of interest: None.
2
Division of Pediatric Pulmonary Medicine, Allergy, and Immunology, Children’s Hospital of Pittsburgh of UPMC, University of Pittsburgh, Pittsburgh, Pennsylvania. 3 Department of Pediatrics, Behavioral Sciences Research Institute, University of Puerto Rico, San Juan, Puerto Rico. 4 Department of Pediatrics, University of Connecticut Health Center, Farmington, Connecticut.
ß 2014 Wiley Periodicals, Inc.
Correspondence to: Juan C. Celedo´n, MD, DrPH, Pulmonary Medicine, Allergy and Immunology, Children’s Hospital of Pittsburgh, 4401 Penn Ave, Pittsburgh, PA 15224. E-mail: [email protected] Received 3 January 2014; Accepted 31 March 2014. DOI 10.1002/ppul.23061 Published online in Wiley Online Library (wileyonlinelibrary.com).
2
Rosas-Salazar et al.
developed countries.2 Both the American Academy of Pediatrics and the World Health Organization recommend exclusive breastfeeding for the first 6 months of life.1,3 Asthma is the most common chronic disease of childhood in the US.4,5 In this country, the prevalence of childhood asthma is higher in Puerto Ricans (16.1%) than in non-Hispanic blacks (11.2%), non-Hispanic whites (7.7%), or Mexican Americans (5.4%).5 For unclear reasons, both Puerto Rican children living in the mainland US and those living in the island of Puerto Rico are disproportionately affected by asthma.6 Whereas, a protective effect of breastfeeding on asthma in preschool-aged children has been noted across numerous studies,7–9 studies in school-aged children (in whom a diagnosis of asthma is more likely to be accurate) have yielded conflicting results. Some10–17 but not all18–25 studies conducted in older children have found a detrimental effect of breastfeeding on asthma development, particularly in those breastfed for longer periods of time. In a meta-analysis of 31 observational studies published between January 2000 and June 2010, neither any breastfeeding (odds ratio [OR] ¼ 0.97, 95% confidence interval [CI] ¼ 0.90–1.04) nor exclusive breastfeeding (OR ¼ 0.96, 95% CI ¼ 0.86–1.06) was associated with wheezing illnesses (including asthma) in children aged 5–18 years.26 However, subgroup analysis revealed that any breastfeeding slightly increased the odds of asthma (OR ¼ 1.10, 95% CI ¼ 1.0–1.22) when asthma was defined by specific criteria (i.e., any two of the following: physician-diagnosed asthma, wheeze in the last 12 months, use of asthma medications in the last 12 months, or airway hyper-responsiveness). Most of the studies conducted to date have used 3 or 4 months as the cut point for the duration of breastfeeding. Therefore, the impact of the currently recommended duration of breastfeeding (i.e., 6 months [see above]) on asthma is still unknown, particularly in high-risk groups such as Puerto Ricans. We hypothesized that breastfeeding would be associated with asthma in school-aged Puerto Rican children, but that this association would differ according to how long the child was breastfed. To test this hypothesis, we examined breastfeeding and asthma in a case-control study of 1,127 Puerto Rican children aged 6–14 years
ABBREVIATIONS: CI Confidence interval ETS Environmental tobacco smoke FEV1 Forced expiratory volume in 1 sec FVC Forced vital capacity OR Odds ratio
Pediatric Pulmonology
living in Hartford, Connecticut (n ¼ 449), and San Juan, Puerto Rico (n ¼ 678). MATERIAL AND METHODS Subject Recruitment
From September of 2003 to July of 2008, children were recruited from 15 public elementary and middle schools in Hartford that enrolled a significant proportion (42–94%) of Puerto Rican children. As previously described,27 informational flyers with a study description were distributed to all parents of children in grades K to 8 of participating schools by mail (n ¼ 10,881) or in person during different school activities (n ¼ 885). Parents of 640 children completed a screening questionnaire. Of these 640 children, 585 (91.4%) met inclusion criteria (see below). Parents of 136 of these 585 eligible children refused to participate or could not be reached. There were no significant differences in age, gender, or area of residence between eligible children who did (n ¼ 449 [76.8%]) and did not (n ¼ 136 [23.2%]) agree to participate. From March of 2009 to June of 2010, children were recruited from randomly selected households in San Juan. As previously described,28 households in the metropolitan area of San Juan were selected by a multistage probability sampling design. Primary sampling units were randomly selected neighborhood clusters based on the 2000 US census. Secondary sampling units were randomly selected households within each primary sampling unit. A household was included if 1 resident was a child aged 6–14 years old. In households with >1 child of this age range, only one child was randomly selected for screening. On the basis of the sampling design, 7,073 households were selected and 6,401 (90.5%) were contacted. Of these 6,401 households, 1,111 had 1 child who met inclusion criteria (see below). In an effort to reach a target sample size of approximately 700 children, we attempted to enroll a random sample (n ¼ 783) of these 1,111 eligible children. Parents of 105 of these 783 eligible children refused to participate or could not be reached. There were no significant differences in age, gender, or area of residence between eligible children who did (n ¼ 678 [86.6%]) and did not (n ¼ 105 [13.4%]) agree to participate. At both study sites, the main recruitment tool was a screening questionnaire given to parents to obtain information about the child’s general and respiratory health. Children ages 6–14 years were included in the study if they had four Puerto Rican grandparents (to ensure their Puerto Rican descent). Cases had to have parental report of physician-diagnosed asthma and wheeze in the previous year (n ¼ 618). Control subjects had neither parental report of physician-diagnosed asthma nor wheeze in the prior year (n ¼ 509).
Breastfeeding and Asthma in Puerto Rican Children
Study Procedures
Study participants completed a protocol that included questionnaires, spirometry, and collection of blood (for measurement of serum total and allergen-specific IgEs). One of the child’s parents (usually [>93%] the mother) completed a questionnaire that was slightly modified from the one used in the Collaborative Study of the Genetics of Asthma.29 This questionnaire was used to obtain information about the child’s general and respiratory health (including a history of any breastfeeding, prematurity, low birth weight, and mode of delivery), socio-demographic characteristics, maternal asthma, current exposure to environmental tobacco smoke (ETS), and early-life exposure to ETS (in utero or prior to 2 years of age). Height and weight were measured to the nearest centimeter and pound, respectively. Spirometry was conducted with an EasyOne spirometer (NDD Medical Technologies, Andover, MA). All participants had to be free of respiratory illnesses for 4 weeks, and they were also instructed to avoid (when possible) the use of inhaled shortand long-acting bronchodilators for 4 and 12 hr before testing, respectively. Forced expiratory maneuvers were judged to be acceptable if they met or exceeded the American Thoracic Society criteria modified for children.30 The best forced expiratory volume in 1 sec (FEV1) and forced vital capacity (FVC) were selected for data analyses. Serum levels of total IgE and IgEs specific to common allergens (dust mite [Der p 1], cockroach [Bla g 2], cat dander [Fel d 1], dog dander [Can f 1], and mouse urinary protein [Mus m 1]) were determined using the UniCAP 100 system (Pharmacia & Upjohn, Kalamazoo, MI). For each allergen, an IgE 0.35 IU/ml was considered positive. Written parental consent was obtained for participating children, from whom written assent was also obtained. The study was approved by the Institutional Review Boards of Connecticut Children’s Medical Center (Hartford, CT), the University of Puerto Rico (San Juan, PR), Brigham and Women’s Hospital (Boston, MA), and the University of Pittsburgh (Pittsburgh, PA). Statistical Analysis
The main exposure of interest was a history of any breastfeeding, which was categorized for our main analysis according to current guidelines as: none, 0–6, and >6 months.1,3 Our outcome of interest was asthma, defined as physician-diagnosed asthma, and wheeze in the previous year. The analysis of breastfeeding duration and asthma was first conducted for each study site and then for the combined cohort. Bivariate analyses were conducted using one-way analysis of variance (ANOVA) for continuous variables and the Cochran–Armitage trend tests for categorical variables. For the multivariate analysis, we used a stepwise approach to build the
3
logistic regression models. Because of their wellestablished association with breastfeeding and/or asthma, all models included age,5 gender,31 household income (< vs. $15,000/year [near the median income for households in Puerto Rico in 2008–200932]),33 maternal asthma,34 early-life exposure (in utero or prior to 2 years of age) to environmental tobacco smoke (ETS),35 and (for the combined cohort) study site.6 The following covariates were also included in the initial multivariate models if they were associated with asthma at P 0.20 in bivariate analyses: body mass index as a z-score (based on 2000 CDC growth charts36), prematurity, low birth weight (12 months) in the final models. Statistical significance was defined as a P < 0.05. All statistical analyses were performed using SAS version 9.3 (SAS Institute, Cary, NC). RESULTS
The baseline characteristics of study participants are summarized in Table 1. At each study site and in the combined cohort, cases were significantly more likely to have maternal asthma and to be atopic, and to have a higher total IgE and a lower FEV1/FVC than controls. Compared to controls in the combined cohort, cases were also significantly more likely to be male, premature, breastfed for over 6 months, exposed to ETS (currently or in early life), and to have a higher body mass index and a lower FEV1. Table 2 shows the bivariate analyses of breastfeeding duration and the covariates of interest. In the combined cohort, age, prematurity, low birth weight, low household income, low parental education, no private or employerbased insurance, and exposure to ETS in early life were all significantly and inversely associated with breastfeeding for over 6 months. Table 3 shows the results of the main analysis of breastfeeding duration and asthma. In the unadjusted analysis, breastfeeding duration was not significantly associated with asthma at either study site or in the Pediatric Pulmonology
4
Rosas-Salazar et al.
TABLE 1— Baseline Characteristics of Participating Puerto Rican Children According to Study Site and Case-Control Statusa,b Hartford
Covariate Age (years) Female sex Any breastfeeding No 0–6 months >6 months BMI (z-score) Obesity (BMI >95th percentile for age and sex) Total IgE (IU/ml)d Atopy (1 positive allergen-specific IgE) Current exposure to ETS Exposure to ETS in utero or prior to 2 years of age Household income 6 (n ¼ 49) (2.7) (46.6%) (1.1) (18.3%)
92 12 9 83 2.0 0.8
(34.6%) (4.5%) (3.4%) (31.2%) (0.7) (0.1)
152 (57.1%)
41 (15.4%)
142 (55.0%)
105 (39.5%) 118 (44.4%)
223.9 (5.0) 146 (63.2%)
10.1 124 0.6 43
0–6 (n ¼ 266) (2.4) (49.0%) (1.1) (27.0%)
(44.6%) (4.0%)c (1.0%)c (34.3%) (0.6) (0.1)
190 43 37 162 2.0 0.8
(36.3%) (8.1%) (7.2%) (34.8%) (0.7) (0.1)
391 (77.7%)
59 (57.8%)c 45 4 1 35 1.9 0.8
150 (28.2%)
350 (71.3%)
237 (44.6%) 280 (52.8%)
141.3 (5.0) 250 (54.7%)
(2.8) (47.4%) (1.3) (26.0%)
No (n ¼ 534) 10.3 253 0.7 132
Combined
(2.7) (47.8%) (1.2) (24.4%)
149 19 17 108 1.9 0.8
(36.9%) (4.7%) (4.2%) (27.9%) (0.7) (0.1)
246 (62.6%)
74 (18.3%)
219 (56.9%)
162 (40.1%) 193 (47.8%)
154.9 (5.4) 208 (59.4%)
9.8 193 0.7 91
0–6 (n ¼ 404)
(2.5)c (52.3%) (1.1) (29.7%)
65 5 1 44 1.9 0.8
(43.3%) (3.4%)c (0.7%)c (30.6%) (0.6) (0.1)
94 (63.5%)c
22 (14.6%)c
79 (54.5%)c
56 (37.1%) 58 (38.4%)c
162.2 (5.1) 73 (56.2%)
9.9 79 0.9 41
>6 (n ¼ 151)
Any breastfeeding (months)
12 (11.8%)c
61 (59.8%)c
35 (34.3%) 37 (36.3%)c
245.5 (4.5) 50 (60.2%)
9.9 50 0.8 24
>6 (n ¼ 102)
Any breastfeeding (months)
Any breastfeeding (months)
BMI, body mass index; ETS, environmental tobacco smoke; FEV1, forced expiratory volume in 1 sec; FVC, forced vital capacity. a Data presented as the number (%) for binary variables or mean (standard deviation) for continuous variables. b Percentages were calculated for children with complete data. c P < 0.05 for the comparison between breastfeeding groups. d Total IgE transformed to a logarithmic (log10) scale. Results shown as geometric mean (standard deviation). e FEV1 presented as absolute values because of lack of predicted values for Puerto Ricans.
Age (years) Female sex BMI (z-score) Obesity (BMI >95th percentile for age and sex) Total IgE (IU/ml)d Atopy (1 positive allergen-specific IgE) Current exposure to ETS Exposure to ETS in utero or prior to 2 years of age Household income 6 months Maternal asthma BMI (z-score) Exposure to ETS in utero or prior to 2 years of age
Ref. 0.9 (0.6–1.4), 0.6 1.9 (0.9–3.8), 0.09
0.8 1.7 2.7 1.2 1.5
Ref. (0.5–1.3), (0.8–3.7), (1.6–4.4), (1.0–1.4), (0.9–2.4),
0.3 0.2
Breastfeeding Duration and Asthma in Puerto Rican Children Christian Rosas-Salazar, MD, MPH,1 Erick Forno, MD, MPH,2 John M. Brehm, MD, MPH,2 rez, PhD,3 Michelle M. Cloutier, MD,4 Yueh-Ying Han, PhD,2 Edna Acosta-Pe 5 Dorothy B. Wakefield, MA, Marı´a Alvarez, MD,3 Angel Colo n-Semidey, MD,3 3 Glorisa Canino, PhD, and Juan C. Celedo n, MD, DrPH2 Summary. Rationale: Little is known about breastfeeding and asthma in Puerto Ricans, the ethnic group most affected by this disease in the US. We examined the relation between the currently recommended duration of breastfeeding and asthma in school-aged Puerto Rican children. Methods: Case-control study of 1,127 Puerto Rican children aged 6–14 years living in Hartford, Connecticut (n ¼ 449) and San Juan, Puerto Rico (n ¼ 678). Parental recall of breastfeeding was categorized based on duration and according to current guidelines (i.e., none, 0–6 months, and >6 months). Asthma was defined as parental report of physician-diagnosed asthma and wheeze in the previous year. We used logistic regression for the multivariate analysis, which was conducted separately for each study site and for the combined cohort. All multivariate models were adjusted for age, gender, household income, atopy, maternal asthma, body mass index, early-life exposure to environmental tobacco smoke, and (for the combined cohort) study site. Results: After adjustment for covariates, children who were breastfed for up to 6 months had 30% lower odds of asthma (95% CI ¼ 0.5–1.0, P ¼ 0.04) than those who were not breastfed. In this analysis, breastfeeding for longer than 6 months was not significantly associated with asthma (OR ¼ 1.5, 95% CI ¼ 1.0–2.4, P ¼ 0.06). Conclusions: Our results suggest that breastfeeding for up to 6 months (as assessed by parental recall) is associated with decreased odds of asthma in Puerto Rican children, and that there is no additional beneficial effect of breastfeeding for over 6 months. These results support current recommendations on the duration of breastfeeding in an ethnic group at risk for asthma. Pediatr Pulmonol. ß 2014 Wiley Periodicals, Inc. Key words: breastfeeding; asthma; children; Puerto Rico. Funding source: US National Institutes of Health (NIH); Numbers: HL079966, HL117191, HD052892, Heinz Foundation.
INTRODUCTION
Breastfeeding has numerous advantages for the infant, the mother, and society, including developmental,
1 Division of Pediatric Allergy, Immunology, and Pulmonary Medicine, Monroe Carell Jr. Children’s Hospital at Vanderbilt, Vanderbilt University, Nashville, Tennessee.
nutritional, immunologic, psychological, social, and economic benefits.1 Although, the benefits of breastfeeding are widely acknowledged, there is still conflicting evidence on its optimal duration in developing and
5
Center for Public Health and Health Policy, University of Connecticut Health Center, Farmington, Connecticut. Conflict of interest: None.
2
Division of Pediatric Pulmonary Medicine, Allergy, and Immunology, Children’s Hospital of Pittsburgh of UPMC, University of Pittsburgh, Pittsburgh, Pennsylvania. 3 Department of Pediatrics, Behavioral Sciences Research Institute, University of Puerto Rico, San Juan, Puerto Rico. 4 Department of Pediatrics, University of Connecticut Health Center, Farmington, Connecticut.
ß 2014 Wiley Periodicals, Inc.
Correspondence to: Juan C. Celedo´n, MD, DrPH, Pulmonary Medicine, Allergy and Immunology, Children’s Hospital of Pittsburgh, 4401 Penn Ave, Pittsburgh, PA 15224. E-mail: [email protected] Received 3 January 2014; Accepted 31 March 2014. DOI 10.1002/ppul.23061 Published online in Wiley Online Library (wileyonlinelibrary.com).
2
Rosas-Salazar et al.
developed countries.2 Both the American Academy of Pediatrics and the World Health Organization recommend exclusive breastfeeding for the first 6 months of life.1,3 Asthma is the most common chronic disease of childhood in the US.4,5 In this country, the prevalence of childhood asthma is higher in Puerto Ricans (16.1%) than in non-Hispanic blacks (11.2%), non-Hispanic whites (7.7%), or Mexican Americans (5.4%).5 For unclear reasons, both Puerto Rican children living in the mainland US and those living in the island of Puerto Rico are disproportionately affected by asthma.6 Whereas, a protective effect of breastfeeding on asthma in preschool-aged children has been noted across numerous studies,7–9 studies in school-aged children (in whom a diagnosis of asthma is more likely to be accurate) have yielded conflicting results. Some10–17 but not all18–25 studies conducted in older children have found a detrimental effect of breastfeeding on asthma development, particularly in those breastfed for longer periods of time. In a meta-analysis of 31 observational studies published between January 2000 and June 2010, neither any breastfeeding (odds ratio [OR] ¼ 0.97, 95% confidence interval [CI] ¼ 0.90–1.04) nor exclusive breastfeeding (OR ¼ 0.96, 95% CI ¼ 0.86–1.06) was associated with wheezing illnesses (including asthma) in children aged 5–18 years.26 However, subgroup analysis revealed that any breastfeeding slightly increased the odds of asthma (OR ¼ 1.10, 95% CI ¼ 1.0–1.22) when asthma was defined by specific criteria (i.e., any two of the following: physician-diagnosed asthma, wheeze in the last 12 months, use of asthma medications in the last 12 months, or airway hyper-responsiveness). Most of the studies conducted to date have used 3 or 4 months as the cut point for the duration of breastfeeding. Therefore, the impact of the currently recommended duration of breastfeeding (i.e., 6 months [see above]) on asthma is still unknown, particularly in high-risk groups such as Puerto Ricans. We hypothesized that breastfeeding would be associated with asthma in school-aged Puerto Rican children, but that this association would differ according to how long the child was breastfed. To test this hypothesis, we examined breastfeeding and asthma in a case-control study of 1,127 Puerto Rican children aged 6–14 years
ABBREVIATIONS: CI Confidence interval ETS Environmental tobacco smoke FEV1 Forced expiratory volume in 1 sec FVC Forced vital capacity OR Odds ratio
Pediatric Pulmonology
living in Hartford, Connecticut (n ¼ 449), and San Juan, Puerto Rico (n ¼ 678). MATERIAL AND METHODS Subject Recruitment
From September of 2003 to July of 2008, children were recruited from 15 public elementary and middle schools in Hartford that enrolled a significant proportion (42–94%) of Puerto Rican children. As previously described,27 informational flyers with a study description were distributed to all parents of children in grades K to 8 of participating schools by mail (n ¼ 10,881) or in person during different school activities (n ¼ 885). Parents of 640 children completed a screening questionnaire. Of these 640 children, 585 (91.4%) met inclusion criteria (see below). Parents of 136 of these 585 eligible children refused to participate or could not be reached. There were no significant differences in age, gender, or area of residence between eligible children who did (n ¼ 449 [76.8%]) and did not (n ¼ 136 [23.2%]) agree to participate. From March of 2009 to June of 2010, children were recruited from randomly selected households in San Juan. As previously described,28 households in the metropolitan area of San Juan were selected by a multistage probability sampling design. Primary sampling units were randomly selected neighborhood clusters based on the 2000 US census. Secondary sampling units were randomly selected households within each primary sampling unit. A household was included if 1 resident was a child aged 6–14 years old. In households with >1 child of this age range, only one child was randomly selected for screening. On the basis of the sampling design, 7,073 households were selected and 6,401 (90.5%) were contacted. Of these 6,401 households, 1,111 had 1 child who met inclusion criteria (see below). In an effort to reach a target sample size of approximately 700 children, we attempted to enroll a random sample (n ¼ 783) of these 1,111 eligible children. Parents of 105 of these 783 eligible children refused to participate or could not be reached. There were no significant differences in age, gender, or area of residence between eligible children who did (n ¼ 678 [86.6%]) and did not (n ¼ 105 [13.4%]) agree to participate. At both study sites, the main recruitment tool was a screening questionnaire given to parents to obtain information about the child’s general and respiratory health. Children ages 6–14 years were included in the study if they had four Puerto Rican grandparents (to ensure their Puerto Rican descent). Cases had to have parental report of physician-diagnosed asthma and wheeze in the previous year (n ¼ 618). Control subjects had neither parental report of physician-diagnosed asthma nor wheeze in the prior year (n ¼ 509).
Breastfeeding and Asthma in Puerto Rican Children
Study Procedures
Study participants completed a protocol that included questionnaires, spirometry, and collection of blood (for measurement of serum total and allergen-specific IgEs). One of the child’s parents (usually [>93%] the mother) completed a questionnaire that was slightly modified from the one used in the Collaborative Study of the Genetics of Asthma.29 This questionnaire was used to obtain information about the child’s general and respiratory health (including a history of any breastfeeding, prematurity, low birth weight, and mode of delivery), socio-demographic characteristics, maternal asthma, current exposure to environmental tobacco smoke (ETS), and early-life exposure to ETS (in utero or prior to 2 years of age). Height and weight were measured to the nearest centimeter and pound, respectively. Spirometry was conducted with an EasyOne spirometer (NDD Medical Technologies, Andover, MA). All participants had to be free of respiratory illnesses for 4 weeks, and they were also instructed to avoid (when possible) the use of inhaled shortand long-acting bronchodilators for 4 and 12 hr before testing, respectively. Forced expiratory maneuvers were judged to be acceptable if they met or exceeded the American Thoracic Society criteria modified for children.30 The best forced expiratory volume in 1 sec (FEV1) and forced vital capacity (FVC) were selected for data analyses. Serum levels of total IgE and IgEs specific to common allergens (dust mite [Der p 1], cockroach [Bla g 2], cat dander [Fel d 1], dog dander [Can f 1], and mouse urinary protein [Mus m 1]) were determined using the UniCAP 100 system (Pharmacia & Upjohn, Kalamazoo, MI). For each allergen, an IgE 0.35 IU/ml was considered positive. Written parental consent was obtained for participating children, from whom written assent was also obtained. The study was approved by the Institutional Review Boards of Connecticut Children’s Medical Center (Hartford, CT), the University of Puerto Rico (San Juan, PR), Brigham and Women’s Hospital (Boston, MA), and the University of Pittsburgh (Pittsburgh, PA). Statistical Analysis
The main exposure of interest was a history of any breastfeeding, which was categorized for our main analysis according to current guidelines as: none, 0–6, and >6 months.1,3 Our outcome of interest was asthma, defined as physician-diagnosed asthma, and wheeze in the previous year. The analysis of breastfeeding duration and asthma was first conducted for each study site and then for the combined cohort. Bivariate analyses were conducted using one-way analysis of variance (ANOVA) for continuous variables and the Cochran–Armitage trend tests for categorical variables. For the multivariate analysis, we used a stepwise approach to build the
3
logistic regression models. Because of their wellestablished association with breastfeeding and/or asthma, all models included age,5 gender,31 household income (< vs. $15,000/year [near the median income for households in Puerto Rico in 2008–200932]),33 maternal asthma,34 early-life exposure (in utero or prior to 2 years of age) to environmental tobacco smoke (ETS),35 and (for the combined cohort) study site.6 The following covariates were also included in the initial multivariate models if they were associated with asthma at P 0.20 in bivariate analyses: body mass index as a z-score (based on 2000 CDC growth charts36), prematurity, low birth weight (12 months) in the final models. Statistical significance was defined as a P < 0.05. All statistical analyses were performed using SAS version 9.3 (SAS Institute, Cary, NC). RESULTS
The baseline characteristics of study participants are summarized in Table 1. At each study site and in the combined cohort, cases were significantly more likely to have maternal asthma and to be atopic, and to have a higher total IgE and a lower FEV1/FVC than controls. Compared to controls in the combined cohort, cases were also significantly more likely to be male, premature, breastfed for over 6 months, exposed to ETS (currently or in early life), and to have a higher body mass index and a lower FEV1. Table 2 shows the bivariate analyses of breastfeeding duration and the covariates of interest. In the combined cohort, age, prematurity, low birth weight, low household income, low parental education, no private or employerbased insurance, and exposure to ETS in early life were all significantly and inversely associated with breastfeeding for over 6 months. Table 3 shows the results of the main analysis of breastfeeding duration and asthma. In the unadjusted analysis, breastfeeding duration was not significantly associated with asthma at either study site or in the Pediatric Pulmonology
4
Rosas-Salazar et al.
TABLE 1— Baseline Characteristics of Participating Puerto Rican Children According to Study Site and Case-Control Statusa,b Hartford
Covariate Age (years) Female sex Any breastfeeding No 0–6 months >6 months BMI (z-score) Obesity (BMI >95th percentile for age and sex) Total IgE (IU/ml)d Atopy (1 positive allergen-specific IgE) Current exposure to ETS Exposure to ETS in utero or prior to 2 years of age Household income 6 (n ¼ 49) (2.7) (46.6%) (1.1) (18.3%)
92 12 9 83 2.0 0.8
(34.6%) (4.5%) (3.4%) (31.2%) (0.7) (0.1)
152 (57.1%)
41 (15.4%)
142 (55.0%)
105 (39.5%) 118 (44.4%)
223.9 (5.0) 146 (63.2%)
10.1 124 0.6 43
0–6 (n ¼ 266) (2.4) (49.0%) (1.1) (27.0%)
(44.6%) (4.0%)c (1.0%)c (34.3%) (0.6) (0.1)
190 43 37 162 2.0 0.8
(36.3%) (8.1%) (7.2%) (34.8%) (0.7) (0.1)
391 (77.7%)
59 (57.8%)c 45 4 1 35 1.9 0.8
150 (28.2%)
350 (71.3%)
237 (44.6%) 280 (52.8%)
141.3 (5.0) 250 (54.7%)
(2.8) (47.4%) (1.3) (26.0%)
No (n ¼ 534) 10.3 253 0.7 132
Combined
(2.7) (47.8%) (1.2) (24.4%)
149 19 17 108 1.9 0.8
(36.9%) (4.7%) (4.2%) (27.9%) (0.7) (0.1)
246 (62.6%)
74 (18.3%)
219 (56.9%)
162 (40.1%) 193 (47.8%)
154.9 (5.4) 208 (59.4%)
9.8 193 0.7 91
0–6 (n ¼ 404)
(2.5)c (52.3%) (1.1) (29.7%)
65 5 1 44 1.9 0.8
(43.3%) (3.4%)c (0.7%)c (30.6%) (0.6) (0.1)
94 (63.5%)c
22 (14.6%)c
79 (54.5%)c
56 (37.1%) 58 (38.4%)c
162.2 (5.1) 73 (56.2%)
9.9 79 0.9 41
>6 (n ¼ 151)
Any breastfeeding (months)
12 (11.8%)c
61 (59.8%)c
35 (34.3%) 37 (36.3%)c
245.5 (4.5) 50 (60.2%)
9.9 50 0.8 24
>6 (n ¼ 102)
Any breastfeeding (months)
Any breastfeeding (months)
BMI, body mass index; ETS, environmental tobacco smoke; FEV1, forced expiratory volume in 1 sec; FVC, forced vital capacity. a Data presented as the number (%) for binary variables or mean (standard deviation) for continuous variables. b Percentages were calculated for children with complete data. c P < 0.05 for the comparison between breastfeeding groups. d Total IgE transformed to a logarithmic (log10) scale. Results shown as geometric mean (standard deviation). e FEV1 presented as absolute values because of lack of predicted values for Puerto Ricans.
Age (years) Female sex BMI (z-score) Obesity (BMI >95th percentile for age and sex) Total IgE (IU/ml)d Atopy (1 positive allergen-specific IgE) Current exposure to ETS Exposure to ETS in utero or prior to 2 years of age Household income 6 months Maternal asthma BMI (z-score) Exposure to ETS in utero or prior to 2 years of age
Ref. 0.9 (0.6–1.4), 0.6 1.9 (0.9–3.8), 0.09
0.8 1.7 2.7 1.2 1.5
Ref. (0.5–1.3), (0.8–3.7), (1.6–4.4), (1.0–1.4), (0.9–2.4),
0.3 0.2
