Pediatric Allergy and Immunology
ORIGINAL ARTICLE
Asthma
Predicting risk for childhood asthma by pre-pregnancy, perinatal, and postnatal factors Hui-Ju Wen1,2, Tung-Liang Chiang3, Shio-Jean Lin4 & Yue Leon Guo2 1
Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Miaoli, Taiwan; 2Environmental and Occupational Medicine, National Taiwan University (NTU) College of Medicine and NTU Hospital, Taipei, Taiwan; 3Institute of Health Policy and Management, National Taiwan University, Taipei, Taiwan; 4Department of Pediatrics, Chi-Mei Medical Center, Tainan, Taiwan
To cite this article: Wen H-J, Chiang T-L, Lin S-J, Guo YL. Predicting risk for childhood asthma by pre-pregnancy, perinatal, and postnatal factors. Pediatr Allergy Immunol 2015: 26: 272–279.
Keywords asthma; birth cohort; prediction; childhood Correspondence Yue Leon Guo, MD, MPH, PHD, Environmental and Occupational Medicine, National Taiwan University (NTU) College of Medicine and NTU Hospital, Rm 339, 17 Syujhou Road, Taipei 100, Taiwan Tel.: 886 2 3366 8216 Fax: 886 2 2327 8515 E-mail: [email protected] Accepted for publication 12 March 2015 DOI:10.1111/pai.12374
Abstract Background: Symptoms of atopic disease start early in human life. Predicting risk for childhood asthma by early-life exposure would contribute to disease prevention. A birth cohort study was conducted to investigate early-life risk factors for childhood asthma and to develop a predictive model for the development of asthma. Methods: National representative samples of newborn babies were obtained by multistage stratified systematic sampling from the 2005 Taiwan Birth Registry. Information on potential risk factors and children’s health was collected by home interview when babies were 6 months old and 5 yr old, respectively. Backward stepwise regression analysis was used to identify the risk factors of childhood asthma for predictive models that were used to calculate the probability of childhood asthma. Results: A total of 19,192 children completed the study satisfactorily. Physiciandiagnosed asthma was reported in 6.6% of 5-yr-old children. Pre-pregnancy factors (parental atopy and socioeconomic status), perinatal factors (place of residence, exposure to indoor mold and painting/renovations during pregnancy), and postnatal factors (maternal postpartum depression and the presence of atopic dermatitis before 6 months of age) were chosen for the predictive models, and the highest predicted probability of asthma in 5-yr-old children was 68.1% in boys and 78.1% in girls; the lowest probability in boys and girls was 4.1% and 3.2%, respectively. Conclusions: This investigation provides a technique for predicting risk of childhood asthma that can be used to developing a preventive strategy against asthma.
Asthma is one of the most important chronic respiratory inflammatory diseases of childhood, and its socioeconomic consequences and effects on quality of life in children and their families are profound (1). The prevalence of asthma worldwide and in Taiwan has increased during the past two decades (2, 3). In Taiwan, the prevalence of physician-diagnosed asthma in school-age children increased from 4.5% in 1995–96 to 6.5% in 2001, 7.5% 2007 and had reached 11.7% by 2011 (3–5). While both environmental and genetic factors contribute to the development of asthma, environmental factors might be more important in the increased prevalence of asthma over a short period. Early childhood is considered the most critical stage for the development of atopy and asthma, and it is important to identify the significant early-life risk factors that predispose to later atopic disease. Most previous epidemiological studies on asthma have focused on preschool- or school-age children (3–5). However, as symptoms of atopic disease appear early in life (6),
272
important risk factors may be missed when participants are preschool-age or older. Moreover, it may be difficult to eliminate the causal relationship between early environmental exposure and disease in case–control and cross-sectional studies. A birth cohort study is therefore of value for investigating pre-pregnancy, perinatal, and early-postnatal risk factors for asthma. The aims of this study were to investigate pre-pregnancy, perinatal, and postnatal risk factors for asthma among 5-yr-old children enrolled in the Taiwan Birth Cohort Study (TBCS) (7) and to establish a model for predicting asthma risk in children.
Materials and methods Recruitment and sampling The study population was recruited from the TBCS, which is the first nationwide birth cohort study in Taiwan. The
Pediatric Allergy and Immunology 26 (2015) 272–279 ª 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Wen et al.
sampling method for the TBCS has been described previously (7). Briefly, nationally representative samples were obtained using a multistage stratified systematic sampling design based on national birth registration data in Taiwan in 2005. Beginning in January 2005, candidate pairs of mothers, and their newborn infants from 88 study areas were randomly sampled every month, and a total of 24,200 pairs were recruited. The infants, with informed consent from their parents or main caretakers, were evaluated by home interview at the ages of 6 months, 18 months, 3 yr, and 5 yr. The protocols used in this study were approved by the Institutional Review Board of the Bureau of Health Promotion, Taiwan. Data collection
Predicting childhood asthma
Results Among 24,200 sampled candidates, 2952 mother-infant pairs were excluded because of refusal to interview, incorrect address, move abroad, no one home after multiple visits, infant death, and other reasons. A total of 21,248 mother– newborn pairs (87.8%) completed the first (age 6 months) interview during July 2005 to July 2006. Multiparity and children lost to follow up at the 5-yr-old interview were also excluded, resulting in the inclusion of a total of 19,192 children (79.3%) in the final analysis (Fig. 1). The characteristics of the parents and children are shown in Table 1. Approximately 53% of the children were boys. The overall prevalence of asthma was 6.6% at 5 yr old, and asthma was more prevalent in boys (7.6%) than in girls (5.5%). The average parental age at birth was 29.3 yr for mothers and
Structured questionnaires were completed during each home interview to catalog physical data, parental histories of atopic disease (asthma, allergic rhinitis [AR], and atopic dermatitis [AD]), health status of children, and indoor environmental conditions. At the 5-yr interview, the main caretaker was asked if the child had ever had physician-diagnosed asthma, and an answer of ‘yes’ was considered to indicate that the child had asthma by 5 yr of age. Information about personal characteristics, breast-feeding, and vaccination was also collected by the questionnaires, as was information regarding environmental factors in the house, including pets, carpeting, cockroach sightings, incense burning, indoor mold, and painting/home renovation during pregnancy. Statistical analysis As boys and girls have different lifetime prevalence of asthma, the children were stratified by gender for determination of risk factors and establishment of predictive models. Odds ratios (OR) and 95% confidence interval (CI) were used to assess statistical relationships between potential risk factors and asthma. Backward stepwise regression was used to simply multiple regression model and select the predictive factors in predictive model. Factors with the highest p-value were eliminated one by one till all the remaining factors had p-value 12 yr Family income (*103 USD) 12 yr 4587 396 ≤12 yr 5478 368 Family income (*103 USD) ≥$40 1105 119 $20–$40 4786 379 12 yr ≤12 yr Family income (*103) ≥$40 $20–$40 12 yr) + 0.00 (if maternal education ≤12 yr) + 1.36 (if mother with asthma) + 0.26 (if mother with AD or AR) + 0.00 (if mother without atopy) + 1.49 (if father with asthma) + 0.26 (if father with AD or AR) + 0.00 (if father without atopy). The calculation was the same in model 2 and model 3.
and many of these compounds have been associated with allergic diseases (14). Hulin reported that exposure to high levels of acetaldehyde and toluene was associated with increased risk of childhood asthma (15), and Rumchev found that every 10 lg/m3 increase in toluene and benzene concentration was associated with a two- to threefold increase in asthma risk in children between the ages of 6 months and 3 yr
276
(16). Allergen-specific responses in asthma are attributed to a skew toward a Th2 phenotype with elevated levels of serum interleukin (IL)-4 and IgE, and animal experiments have shown that volatile organic compounds (VOCs) cross the placenta and affect neonatal immune status by increasing IL-4 production and reducing interferon-c production (17). Bonisch showed that VOCs may favor allergic responses by inducing
Pediatric Allergy and Immunology 26 (2015) 272–279 ª 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
32/1142 2.8% 43/592 7.3% 13/80 16.3% 49/1120 4.4% 50/607 8.2% 9/93 9.7%
oxidative stress and interfering with dendritic cell function in mice (18). Our finding that indoor painting during pregnancy could contribute to childhood asthma is also consistent with another birth cohort study that found higher levels of IL-4 and IL-5 in the cord blood of neonates who were exposed to home renovations during pregnancy (19). However, the exact causal agents and the exposure mechanisms will still warrant further study. Taiwan has a tropical/subtropical climate with an average year-round temperature of 15–30°C and 70–80% relative humidity, and this is conducive to mold. Our finding that indoor mold is a risk factor for childhood asthma agrees with previous studies that have associated indoor mold with early childhood asthma, including a meta-analysis of eight European birth cohorts in which exposure to residential mold during the first 2 yr of life showed significant association with childhood asthma, particularly among children of allergic parents (20). Children with greater exposure to fungal spores in the first 3 months of life have also shown increased risk of early wheezing (21). Penicillium, Aspergillus, and basidiospores are among the fungal species that are associated with asthma and atopy in children (4), and further investigation of the role of indoor mold in childhood asthma in Taiwan will be useful.
eP = Expected probability. *Probability (P) was calculated by the equation, P = 1
≥15.2% Very high
(1/[1 + E{training logical model}]).
≥11%
7.6–15.2% High
72/1347 5.4% 62/557 11.1% 14/107 13.1% 65/1272 5.1% 65/624 10.4% 22/110 20.0%
ORIGINAL ARTICLE
Asthma
Predicting risk for childhood asthma by pre-pregnancy, perinatal, and postnatal factors Hui-Ju Wen1,2, Tung-Liang Chiang3, Shio-Jean Lin4 & Yue Leon Guo2 1
Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Miaoli, Taiwan; 2Environmental and Occupational Medicine, National Taiwan University (NTU) College of Medicine and NTU Hospital, Taipei, Taiwan; 3Institute of Health Policy and Management, National Taiwan University, Taipei, Taiwan; 4Department of Pediatrics, Chi-Mei Medical Center, Tainan, Taiwan
To cite this article: Wen H-J, Chiang T-L, Lin S-J, Guo YL. Predicting risk for childhood asthma by pre-pregnancy, perinatal, and postnatal factors. Pediatr Allergy Immunol 2015: 26: 272–279.
Keywords asthma; birth cohort; prediction; childhood Correspondence Yue Leon Guo, MD, MPH, PHD, Environmental and Occupational Medicine, National Taiwan University (NTU) College of Medicine and NTU Hospital, Rm 339, 17 Syujhou Road, Taipei 100, Taiwan Tel.: 886 2 3366 8216 Fax: 886 2 2327 8515 E-mail: [email protected] Accepted for publication 12 March 2015 DOI:10.1111/pai.12374
Abstract Background: Symptoms of atopic disease start early in human life. Predicting risk for childhood asthma by early-life exposure would contribute to disease prevention. A birth cohort study was conducted to investigate early-life risk factors for childhood asthma and to develop a predictive model for the development of asthma. Methods: National representative samples of newborn babies were obtained by multistage stratified systematic sampling from the 2005 Taiwan Birth Registry. Information on potential risk factors and children’s health was collected by home interview when babies were 6 months old and 5 yr old, respectively. Backward stepwise regression analysis was used to identify the risk factors of childhood asthma for predictive models that were used to calculate the probability of childhood asthma. Results: A total of 19,192 children completed the study satisfactorily. Physiciandiagnosed asthma was reported in 6.6% of 5-yr-old children. Pre-pregnancy factors (parental atopy and socioeconomic status), perinatal factors (place of residence, exposure to indoor mold and painting/renovations during pregnancy), and postnatal factors (maternal postpartum depression and the presence of atopic dermatitis before 6 months of age) were chosen for the predictive models, and the highest predicted probability of asthma in 5-yr-old children was 68.1% in boys and 78.1% in girls; the lowest probability in boys and girls was 4.1% and 3.2%, respectively. Conclusions: This investigation provides a technique for predicting risk of childhood asthma that can be used to developing a preventive strategy against asthma.
Asthma is one of the most important chronic respiratory inflammatory diseases of childhood, and its socioeconomic consequences and effects on quality of life in children and their families are profound (1). The prevalence of asthma worldwide and in Taiwan has increased during the past two decades (2, 3). In Taiwan, the prevalence of physician-diagnosed asthma in school-age children increased from 4.5% in 1995–96 to 6.5% in 2001, 7.5% 2007 and had reached 11.7% by 2011 (3–5). While both environmental and genetic factors contribute to the development of asthma, environmental factors might be more important in the increased prevalence of asthma over a short period. Early childhood is considered the most critical stage for the development of atopy and asthma, and it is important to identify the significant early-life risk factors that predispose to later atopic disease. Most previous epidemiological studies on asthma have focused on preschool- or school-age children (3–5). However, as symptoms of atopic disease appear early in life (6),
272
important risk factors may be missed when participants are preschool-age or older. Moreover, it may be difficult to eliminate the causal relationship between early environmental exposure and disease in case–control and cross-sectional studies. A birth cohort study is therefore of value for investigating pre-pregnancy, perinatal, and early-postnatal risk factors for asthma. The aims of this study were to investigate pre-pregnancy, perinatal, and postnatal risk factors for asthma among 5-yr-old children enrolled in the Taiwan Birth Cohort Study (TBCS) (7) and to establish a model for predicting asthma risk in children.
Materials and methods Recruitment and sampling The study population was recruited from the TBCS, which is the first nationwide birth cohort study in Taiwan. The
Pediatric Allergy and Immunology 26 (2015) 272–279 ª 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Wen et al.
sampling method for the TBCS has been described previously (7). Briefly, nationally representative samples were obtained using a multistage stratified systematic sampling design based on national birth registration data in Taiwan in 2005. Beginning in January 2005, candidate pairs of mothers, and their newborn infants from 88 study areas were randomly sampled every month, and a total of 24,200 pairs were recruited. The infants, with informed consent from their parents or main caretakers, were evaluated by home interview at the ages of 6 months, 18 months, 3 yr, and 5 yr. The protocols used in this study were approved by the Institutional Review Board of the Bureau of Health Promotion, Taiwan. Data collection
Predicting childhood asthma
Results Among 24,200 sampled candidates, 2952 mother-infant pairs were excluded because of refusal to interview, incorrect address, move abroad, no one home after multiple visits, infant death, and other reasons. A total of 21,248 mother– newborn pairs (87.8%) completed the first (age 6 months) interview during July 2005 to July 2006. Multiparity and children lost to follow up at the 5-yr-old interview were also excluded, resulting in the inclusion of a total of 19,192 children (79.3%) in the final analysis (Fig. 1). The characteristics of the parents and children are shown in Table 1. Approximately 53% of the children were boys. The overall prevalence of asthma was 6.6% at 5 yr old, and asthma was more prevalent in boys (7.6%) than in girls (5.5%). The average parental age at birth was 29.3 yr for mothers and
Structured questionnaires were completed during each home interview to catalog physical data, parental histories of atopic disease (asthma, allergic rhinitis [AR], and atopic dermatitis [AD]), health status of children, and indoor environmental conditions. At the 5-yr interview, the main caretaker was asked if the child had ever had physician-diagnosed asthma, and an answer of ‘yes’ was considered to indicate that the child had asthma by 5 yr of age. Information about personal characteristics, breast-feeding, and vaccination was also collected by the questionnaires, as was information regarding environmental factors in the house, including pets, carpeting, cockroach sightings, incense burning, indoor mold, and painting/home renovation during pregnancy. Statistical analysis As boys and girls have different lifetime prevalence of asthma, the children were stratified by gender for determination of risk factors and establishment of predictive models. Odds ratios (OR) and 95% confidence interval (CI) were used to assess statistical relationships between potential risk factors and asthma. Backward stepwise regression was used to simply multiple regression model and select the predictive factors in predictive model. Factors with the highest p-value were eliminated one by one till all the remaining factors had p-value 12 yr Family income (*103 USD) 12 yr 4587 396 ≤12 yr 5478 368 Family income (*103 USD) ≥$40 1105 119 $20–$40 4786 379 12 yr ≤12 yr Family income (*103) ≥$40 $20–$40 12 yr) + 0.00 (if maternal education ≤12 yr) + 1.36 (if mother with asthma) + 0.26 (if mother with AD or AR) + 0.00 (if mother without atopy) + 1.49 (if father with asthma) + 0.26 (if father with AD or AR) + 0.00 (if father without atopy). The calculation was the same in model 2 and model 3.
and many of these compounds have been associated with allergic diseases (14). Hulin reported that exposure to high levels of acetaldehyde and toluene was associated with increased risk of childhood asthma (15), and Rumchev found that every 10 lg/m3 increase in toluene and benzene concentration was associated with a two- to threefold increase in asthma risk in children between the ages of 6 months and 3 yr
276
(16). Allergen-specific responses in asthma are attributed to a skew toward a Th2 phenotype with elevated levels of serum interleukin (IL)-4 and IgE, and animal experiments have shown that volatile organic compounds (VOCs) cross the placenta and affect neonatal immune status by increasing IL-4 production and reducing interferon-c production (17). Bonisch showed that VOCs may favor allergic responses by inducing
Pediatric Allergy and Immunology 26 (2015) 272–279 ª 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
32/1142 2.8% 43/592 7.3% 13/80 16.3% 49/1120 4.4% 50/607 8.2% 9/93 9.7%
oxidative stress and interfering with dendritic cell function in mice (18). Our finding that indoor painting during pregnancy could contribute to childhood asthma is also consistent with another birth cohort study that found higher levels of IL-4 and IL-5 in the cord blood of neonates who were exposed to home renovations during pregnancy (19). However, the exact causal agents and the exposure mechanisms will still warrant further study. Taiwan has a tropical/subtropical climate with an average year-round temperature of 15–30°C and 70–80% relative humidity, and this is conducive to mold. Our finding that indoor mold is a risk factor for childhood asthma agrees with previous studies that have associated indoor mold with early childhood asthma, including a meta-analysis of eight European birth cohorts in which exposure to residential mold during the first 2 yr of life showed significant association with childhood asthma, particularly among children of allergic parents (20). Children with greater exposure to fungal spores in the first 3 months of life have also shown increased risk of early wheezing (21). Penicillium, Aspergillus, and basidiospores are among the fungal species that are associated with asthma and atopy in children (4), and further investigation of the role of indoor mold in childhood asthma in Taiwan will be useful.
eP = Expected probability. *Probability (P) was calculated by the equation, P = 1
≥15.2% Very high
(1/[1 + E{training logical model}]).
≥11%
7.6–15.2% High
72/1347 5.4% 62/557 11.1% 14/107 13.1% 65/1272 5.1% 65/624 10.4% 22/110 20.0%
