Journal of Asthma
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Breastfeeding and Timing of First Dietary Introduction in Relation to Childhood Asthma, Allergies, and Airway Diseases: A Cross-sectional Study Chen Huang PhD, Wei Liu PhD, Jiao Cai MSc, Louise B. Weschler BSc, Xueying Wang MSc, Yu Hu MSc, Zhijun Zou BSc, Li Shen MSc & Jan Sundell MD To cite this article: Chen Huang PhD, Wei Liu PhD, Jiao Cai MSc, Louise B. Weschler BSc, Xueying Wang MSc, Yu Hu MSc, Zhijun Zou BSc, Li Shen MSc & Jan Sundell MD (2016): Breastfeeding and Timing of First Dietary Introduction in Relation to Childhood Asthma, Allergies, and Airway Diseases: A Cross-sectional Study, Journal of Asthma, DOI: 10.1080/02770903.2016.1231203 To link to this article: http://dx.doi.org/10.1080/02770903.2016.1231203
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Date: 13 September 2016, At: 20:12
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Running Head Breastfeeding and Childhood Allergic Diseases
Breastfeeding and Timing of First Dietary Introduction in Relation to Childhood Asthma, Allergies, and Airway Diseases: A Cross-sectional Study
Chen Huang1, PhD; Wei Liu1,*, PhD; Jiao Cai, MSc; Louise B. Weschler2, BSc; Xueying Wang, MSc; Yu Hu1, MSc; Zhijun Zou1, BSc; Li Shen1, MSc; Jan Sundell1,3, MD 1 Department of Building Environment and Energy Engineering, School of Environment and Architecture, University of Shanghai for Science and Technology, Shanghai, PR China 2 161 Richdale Road, Colts Neck, New Jersey, 07722, United States of America 3 Department of Building Science, Tsinghua University, Beijing, PR China *
Corresponding Author: E-mail:
[email protected];
[email protected] School of
Environment and Architecture University of Shanghai for Science and Technology 516 Jungong Road, Yangpu District Shanghai, China. Tel: +86-021-55273409 Fax: +86-021-55270680
Abstract Objectives: We investigated associations of breastfeeding (BF) durations and patterns and of timing of other dietary introductions with prevalences of asthma, wheeze, hay fever, rhinitis,
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ACCEPTED MANUSCRIPT pneumonia, and eczema among preschool children. Methods: During April 2011-April 2012, we conducted a cross-sectional study in 72 kindergartens from five districts of Shanghai, China and obtained 13,335 questionnaires of children 4-6 year-old. We used multiple logistic regression models to evaluate the target associations. Results: Compared to children who were never BF, children who were exclusively breastfed for three-six months had the lowest risk of asthma (adjusted odds ratio and 95% confidence interval: 0.81, 0.72-0.91) and wheeze (0.93, 0.87-0.99); and exclusive BF >6 months was significantly associated with a reduced risk of hay fever (0.93, 0.89-0.97), rhinitis (0.97, 0.94-0.99), pneumonia (0.97, 0.94-0.99), and eczema (0.96, 0.93-0.99). No significant associations were found between time when fruits or vegetables were introduced and the studied diseases. Associations were independent of the child‟s sex and parent‟s ownership of the current residence. Longer duration BF was only significantly protective when there was no family history of atopy. Conclusions: This study suggests that heredity, but not sex and socioeconomic status, may negatively impact the effect of BF on childhood airway and allergic diseases. Our findings support China‟s national recommendation that mothers provide exclusive BF for the first four months, and continue partial BF for more than six months. Keywords Allergy, Breastfeeding, China, Pneumonia, Preschool children
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ACCEPTED MANUSCRIPT Introduction The prevalence of childhood asthma has increased rapidly in China [1, 2]. In Shanghai, the asthma prevalence among 3-7 year-old children in 1990 was 2.1% and increased to 10.2% in 2011 [2]. Numerous studies of associations between breastfeeding (BF) and childhood asthma, allergies, and airway diseases [3-28] have come to different conclusions with respect to the optimal BF duration and pattern and to BF‟s associations with these childhood diseases [3, 4]. Firstly, while many studies have found that longer BF duration was associated with reduced risk of these diseases in childhood [5-18], others found no significant associations [22-28] and some studies have even found that longer BF duration was associated with increased risk [19-21]. Secondly, while some studies have found that introducing foods in earlier age was associated with reduced risk of asthma and allergic diseases [8] and atopic sensitization [27, 30] among five year-old children, other studies have found no significant associations between the timing of introducing foods and childhood atopic diseases [23, 25-27, 31]. Several studies have found that BF‟s associations with childhood allergies were differ between boys and girls [6, 17], and depended on whether or not there was a family history of atopy [5, 12, 13, 17, 20, 29]. A study for preschool children in Beijing has reported that the lowest risk for asthma and allergies during childhood was for girls who did not have family history of atopy and who had exclusive BF >6 months [17].
Rapid development of economic status in large Chinese cities has accompanied by changes in
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ACCEPTED MANUSCRIPT family lifestyles and dietary behaviors in the past decades [32]. Changes in BF durations and patterns were included in these changes. A systematic review reported that BF rates in China decreased as breast milk substitutes became widely used during the 1970s, reaching a low point in the 1980s. In Shanghai, according to two questionnaire-based studies of infants in rural areas, the rate of “any BF” at four months decreased from 67.7% in 1983 to 49.7% in 1992 (p<0.001) [34]. Efforts to promote BF in the early 1990s successfully increased BF rates, and since the mid-1990s, the rate of “any BF” in the majority of Chinese provinces and in the large cities have been reported at greater than 80% [33]. A cross-sectional questionnaire-based study of Shanghai infants reported that the “any BF” rate was 92.99% and the averaged BF duration was 7.41 months in 2002 [35]. However, the national goal of “exclusive BF” for more than 4 months had not yet been reached [33]; only 56.8% of the surveyed mothers continued any BF to four months and 47.2% of the surveyed mothers continued any BF to six months, respectively [35].
Therefore, we hypothesized that the low rates of “exclusive BF” are associated with increases in the prevalences of childhood asthma, allergies, and airway diseases in Shanghai. In the present study, we investigated associations of BF duration and pattern, and the timing of other dietary introductions, with prevalences of these diseases. We further hypothesized that longer duration “exclusive BF” (longer than three months) and later dietary introductions are associated with lower likelihoods of the studied diseases. We also performed subanalyses which were stratified by sex, family history of atopy, and ownership of the current residence (a proxy of family
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ACCEPTED MANUSCRIPT socioeconomic status [36]).
Methods Questionnaire and Definitions The China, Children, Homes, Health (CCHH) study Phase One, a cross-sectional study, was conducted in five districts of Shanghai (urban district: Jing-An, Zha-Bei, and Hong-Kou; Suburban district: Bao-Shan and Feng-Xian) [2]. We randomly chose 72 kindergartens and distributed 17,898 questionnaires to children‟s parents or guardians during teacher-parent meetings at the schools or by post to the children‟s teachers, who distributed the questionnaires with an explanatory handout via the children to their parents/ guardians. We excluded those questionnaires in which the child‟s age was missed. We also excluded questionnaires from children 1-3 year-olds and 7-8 year-olds due to their sample sizes were small. Questions for children‟s health were taken from the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire [37] which has been validated in previous studies [38, 39]. Questions of environmental factors, which were previously validated [40, 41], were adapted for Chinese homes and cultured from questions used in a Swedish study [42] and used in CCHH studies in other cities [1]. Our previous articles [2, 43, 44] have provided more information on the survey methods and questionnaire of the Shanghai CCHH study. The questionnaire and proposal for the CCHH study were approved by the ethical committee of the School of Public Health, Fudan University in Shanghai, China. All parents or guardians voluntarily responded to the survey and
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ACCEPTED MANUSCRIPT consented for themselves and for their children. The Fudan ethical committee approved this procedure for obtaining consent. The CCHH survey in Shanghai was carried out in strict accordance with the approved guidelines.
Questions about dietary practices were as follows: 1) Duration of breastfeeding (BF): How long was the child breastfed? (Never vs. < 1 vs. 1-2 vs. 3-6 vs. > 6 months); 2) Time of introduction of infant formula, gruel or porridge: At what age was the child first given infant formula, gruel or porridge? (< 3 vs. 3-6 vs. > 6 months); 3) Time of introduction of fruits or vegetables: At what age was the child first given tasters (samples) of food, e.g. fruit purees, mashed root vegetables (e.g. potatoes)? (< 3 vs. 3-6 vs. > 6 months). Questions about asthma, allergies, and airway diseases were as follows: (1) Asthma: Has your child ever been diagnosed with asthma by a doctor (yes vs. no); (2) Wheeze: Has your child ever had wheeze or whistling in the chest at any time in the past years (yes vs. no); (3) Hay fever: Has your child been diagnosed with hay fever or allergic rhinitis by a doctor (yes vs. no); (4) Rhinitis: Has your child ever had a problem with sneezing, or a runny, or blocked nose when he/she did not have a cold or the flu in the past years (yes vs. no); (5) Pneumonia: Has your child ever been diagnosed with pneumonia by a doctor (yes vs. no); (6) Eczema: Has your child ever had an itchy skin rash (eczema) for at least 6 months (yes vs. no).
The duration of BF and the age for introduction of foods or liquids other than mother‟s milk
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ACCEPTED MANUSCRIPT were combined to determine the pattern of BF for various durations. Following Labbok et al.‟s suggestion [45], we defined exclusive BF as feeding solely by the mother‟s breast milk. If the BF duration was >6 months and other foods or liquids were introduced during this time, the child was classified as having had partial BF >6 months. If the BF duration was >6 months and no other foods or liquids were introduced until the child was >6 months-old, the child was classified as having had exclusive BF >6 months. Table 1 shows detailed stratification scheme for BF.
Covariates We used covariates which were identified in previous studies [43, 44, 46-49]: sex (boys vs. girls), age (4 vs. 5 vs. 6 years-old), family history of atopy (yes vs. no), location of the current residence (urban vs. suburban), ownership of the current residence (owner vs. renter), early pet-keeping (yes vs. no), early or current parental smoking (yes vs. no), and early or current home dampness exposures (yes vs. no). We defined “early” as the household at the child's birth; and “current” as the present home. Family history of atopy was defined as at least one of the child‟s family members (siblings, parents, and/or grandparents) having had at least one of the following diseases: asthma, eczema, and allergic nose or eye problems [43, 46-50]. Ownership of the current residence was used as a proxy of high socioeconomic status [36]. Early pet-keeping was defined as a report of at least one of the following pets in the early residence: dog, cat, rodent, bird, fish or any other animal [49]. Early and current parental smoking was defined as at least one smoking parent in the early or current residence, respectively [50]. Early home dampness
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ACCEPTED MANUSCRIPT exposure was defined as at least one of the following indicators in the early residence: visible mold spots or damp stains, windowpane condensation, and moldy odor. Current home dampness exposure was defined as at least one of the following indicators in the current residence: visible mold spots, visible damp stains, damp clothing/bedding, water damage, windowpane condensation, or moldy odor [43, 48]. The specific questions for these factors have been published in a previous article as supplementary materials [1].
Statistical analysis SPSS 17.0 (SPSS Ltd., USA) was used for statistical analyses. Pearson‟s chi-square test was used to compare differences in BF practices among children with different sex, ownership of the current residence, and family history of atopy. Pearson‟s chi-square test also was used to compare differences in prevalences of the studied diseases for different BF practices among all the children and among various subgroups which were stratified by sex, ownership of the current residence, or family history of atopy.
Multiple logistic regression analyses, with adjusted for covariates listed above, were used to identify the target associations for all children, as well as for stratified subgroups. All associations were adjusted for the above covariates except for sex, ownership of the current residence, or family history of atopy when the data were stratified by these factors in the sub-analyses. All variables were treated as categorical in the multiple logistic regression models.
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ACCEPTED MANUSCRIPT For those independent variables that had more than two options, one option was selected as permanent reference. For example, that BF classified by duration (months) and pattern had seven options, thus we selected “no BF” as permanent reference and calculated odds ratios of the studied diseases among children with other options in the logistic regression analyses. All multiple analyses were restricted to children with complete data for the variables required in a specific analysis. Due to missing data for various items, the sums of children with different symptoms or different exposures in subgroups might not be equal to the total numbers. Adjusted associations were reported as adjusted odds ratio (AOR) with 95% confidence interval (CI). Significance was determined by p-value <0.05 in all statistical analyses.
Results Demographic data and prevalence Parents or guardians returned 15,266 questionnaires for 1-8 year-old children, with a response rate of 85.3%. We selected the 13,335 questionnaires for 4-6 year-old children for all analyses, excluding the questionnaires for 1-3 (n=782) and 7-8 (n=849) year-old children. We also excluded 300 questionnaires that lacked the child‟s age. Sample sizes for boys and girls were similar. Family history of atopy was reported for 23.9% of the 4-6 year-old children. Table 2 shows more demographic information. A total of 63.2% of the children were from families who own the current residences. A total of 58.0% and 56.5% of the children had at least one parental smoker in the early and current residences, respectively. A total of 60.3% and 86.1% of the
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ACCEPTED MANUSCRIPT children had home dampness exposure in the early and current residences, respectively. Prevalences of asthma and associated diseases and symptoms were asthma, 10.3%; wheeze, 28.3%; hay fever, 12.6%; rhinitis, 54.1%; pneumonia, 33.6%; and eczema, 16.4%.
BF practices and early dietary introductions A total of 86.8% had had any BF, and 41.8% of the children had BF >6 months. Of those who were breastfed >6 months, 14.0% were exclusively breastfed. A total of 26.7% did not have infant formula, gruel or porridge until they were >6 months-old, and 42.1% were not given fruits or vegetables until they were >6 months-old (Table 3). These dietary patterns did not differ between boys and girls. More children (88.5% vs. 86.2%) with family history of atopy were breastfed, but fewer (37.1% vs. 43.1%) were breastfed for >6 months (either partially or exclusively) than children without family history of atopy (p<0.001). However, more children with family history of atopy had earlier dietary introductions than children without family history of atopy (39.2% vs. 33.3%, p<0.001). Fewer children from families who own the current residence had BF >6 months (37.6% vs. 48.9%) and fewer of them had dietary introductions at >6 months (24.7% vs. 32.3% for infant formula/gruel/porridge introduction and 38.2% vs. 48.6% for fruits/vegetables introduction) than children from families who rent the current residence (p<0.001).
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ACCEPTED MANUSCRIPT Associations of BF and dietary introduction with the studied diseases Children with different BF practices had significant differences in the prevalences of asthma, hay fever, rhinitis, and pneumonia (Table 4). In general, the longer the BF duration and the more exclusive BF, the lower the prevalences of these diseases. Children with later introduction to foods had lower prevalences of all studied diseases (Table 4). Similar results were found among boys and girls (Online Table S1). Among children without family history of atopy (Online Table S2), children with longer BF had lower prevalences of all studied diseases except for eczema. Among children with family history of atopy, longer BF only was significantly associated with lower prevalences of hay fever and rhinitis; and the lowest prevalences of these diseases were found among children with exclusive BF >6 months.
Among children from families who owned the current residence (Online Table S3), prevalences of asthma, hay fever, rhinitis, and pneumonia had significant differences among children with different BF durations and patterns. No consistent trends were found between prevalences of these diseases and BF durations, the lowest prevalences of these diseases still were found among children with any BF >6 months. Among children from families who did not own the current residences, prevalences of all studied diseases (except for eczema) had significant differences among children with different BF practices. The lowest prevalences of these studied diseases were found among children with exclusive BF >6 months, except for asthma, for which the lowest prevalence was for children with exclusive BF 3-6 months.
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ACCEPTED MANUSCRIPT Besides, BF >6 months (reference: never BF) was associated with an 8% lower risk of asthma and hay fever, and a 5% lower risk of pneumonia (Table 5). Delaying the introduction of infant formula, gruel or porridge until after 6 months was associated with 22% lower risk of asthma, 12% lower risk of wheeze, 13% lower risk of hay fever, 5% lower risk of rhinitis, and 11% lower risk of pneumonia. However, there were no significant associations between ages at which fruits or vegetables were introduced and the risk of any studied disease. Compared to no BF, exclusive BF for 3-6 months was associated with the greatest decreased risk of asthma (19%) and wheeze (7%). Exclusive BF and partial BF > 6 months were associated with 6% and 5% lower risk of asthma as well as 5% and 7% lower risk of hay fever, respectively. Exclusive BF >6 months also was associated with 3% lower risk of both rhinitis and pneumonia, and with 4% lower risk of eczema.
With stratification by sex (Online Table S4) and ownership of the current residence (Online Table S5), 3-6 months of exclusive BF and >6 months exclusive or partial were associated with the reduced risk of asthma. Compared to no BF, exclusive BF for 3-6 months was associated the greatest decrease in the risk of asthma (44% lower in boys and 71% lower in girls; and 53% and 65% in children from families with and without ownership of the current residence, respectively). Exclusive BF >6 months was also associated with 5% lower risk of hay fever and pneumonia. For children without family history of atopy (Table 6), exclusive BF for 3-6 months was associated with 69% lower risk of asthma and 24% lower risk of wheeze compared to never BF.
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ACCEPTED MANUSCRIPT Partial and exclusive BF >6 months were also associated with 32% and 37% lower risk of asthma, 7% and 9% lower risk of rhinitis, 4% and 6% lower risk of pneumonia, respectively. However, among children with family history of atopy (Table S6), multiple logistic regression analyses showed no reduction of risk in the studied diseases for any duration of BF, whether exclusive or partial, compared to no BF.
Discussion In this questionnaire-based cross-sectional study, our main findings included that exclusive BF >6 months had significant association with the decreased risk of childhood asthma, hay fever, rhinitis, pneumonia, and eczema; and this association was not notably different between boys and girls as well as among children with different socioeconomic status (indicated by ownership of the current residence), but was only significant among children without family history of atopy. We also found that delayed food introductions, with the exception of fruits and vegetables, was associated with reduced risk of asthma, wheeze, hay fever, rhinitis, and pneumonia. These findings supported our hypothesis that exclusive BF for at least >3 months and later introduction of the complementary foods was associated with lower risk for the studied diseases. Besides, our finding that “more” BF was only associated with the lower risk of asthma, hay fever, and pneumonia in the absence of family history of atopy, is consistent with the conclusion of several studies [17, 21, 24], and this finding suggested that the strength of heredity with respect to asthma and allergy might be greater than BF‟s possible protective effects. We also found that
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ACCEPTED MANUSCRIPT 86.8% of Shanghai children aged 4-6 year-old during 2011-2012 had “any BF” and 41.8% had BF >6 months. These rates were lower than the 92.99% for “any BF” and 47.16% for BF >6 months reported in the cross-sectional questionnaire-based study of Shanghai infants in 2002 [35]. Thus we infer that BF rates in Shanghai infants probably have decreased since 2002.
Our findings that “more” BF, in terms of either duration or pattern (exclusive versus partial) was associated with a decreased risk of asthma, hay fever, and pneumonia in children without family history of atopy were consistent with previous studies in different countries [6, 11, 13, 17]. Our findings also agree with those of the parallel CCHH study in Beijing [17] with one notable exception: for the Shanghai children, children with exclusive BF for 3-6 months had lower risk for asthma and wheeze during childhood than either exclusive or partial BF > 6 months (Table 5). Although our finding might be affected by the small sample size (n = 447; 3.6% of the total children), it might also be possible that introducing foods before a child is six months old, while continuing BF, might decrease the risk of asthma and wheeze [7, 8, 18]. A systematic review concluded that exclusive BF for at least 4 months and introduction of complementary diets between four and six months of age may induce greater IL-10 and TGFb production and expression of interferon gamma, which protected against asthma and allergies [18]. Regardless, our findings support China‟s national recommendation that mothers provide exclusive BF for at least four months for their children, and then start introducing complementary foods and continuing partial BF for more than six months [33].
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ACCEPTED MANUSCRIPT Our finding that the age for introduction of fruits or vegetables was not associated with prevalences of any of the studied diseases was consistent with some previous studies [23, 31], but inconsistent with findings from a Finnish birth-cohort study, in which early introduction of complementary foods was associated with a reduced risk of childhood atopic sensitization [27]. Other studies have noted that lack of diversity in the child‟s food at three months may increase the risk of atopic sensitization for 5 year-old children [27, 30].
Reverse causation must be considered in studies of BF with asthma, allergies, and airway diseases in childhood [9, 17, 22]. A previous study found that early signs of atopic disease among infants might prompt mothers to prolong exclusive BF, which could mask a protective effect of BF or even cause BF to appear to be a risk factor for these diseases [9]. We had one finding suggestive of reverse causation, namely that more children were breastfed in families with family history of atopy than in families without family history of atopy. However, we found that children with a family history of atopy were less likely to be exclusively breastfed > 6 months (Table 3). We also found that the rate of exclusive BF >6 months was significantly lower for those children whose mothers had a history of atopy (9.0% vs. 15.4%; p<0.001). It is possible that some mothers aware of family history of atopy might think certain foods to be more protective than mother‟s milk or those mothers with history of atopy had lower capacity in providing exclusive BF for their children than the health mothers [33]. These possibilities deserve further investigation [33, 51-53].
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ACCEPTED MANUSCRIPT This study had some limitations. Firstly, we cannot infer causal relationships between BF or other dietary behaviors and the studied diseases due to the cross-sectional design. Secondly, all data we used to analyze were obtained from parents-responded questionnaires. Besides, although asthma, hay fever, and pneumonia were doctor-diagnosed, reports of wheeze, rhinitis, and eczema were determined by parents‟ observation, and were therefore particularly vulnerable to reported error. Thirdly, during our survey, parents-reported BF practices occurred up to six years ago and thus increasing the possibility of recall error among parents. This recall error also could decrease the reliability of our results. Nevertheless, this study had several strengths. Firstly, this study of 13,335 multistage hierarchical sampled preschool children was one of the largest cross-sectional studies of children‟s asthma and allergy in China [1]. Secondly, we used a questionnaire that has been validated in studies in several other countries [38, 40, 41] and in other cities of China [1, 17]. Our high response rate (85.3%) also made it probable that the present study gives a valid, reliable picture of BF and early dietary introduction in current Shanghai preschool children.
Conclusions This cross-sectional questionnaire-based study found that for 4-6 year-old Shanghai children with no family history of atopy, BF was associated with reduced risk of asthma, allergies, and associated symptoms. Exclusive BF for 3-6 months and either partial or exclusive BF for >6 months were associated with significantly reduced risk of these diseases. Risk was reduced
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ACCEPTED MANUSCRIPT equally for boys and girls, and among children with different socioeconomic status as indicated by home ownership against these diseases. However, BF was not associated with a reduced risk of asthma for children with family history of atopy.
Declaration of interests The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
Acknowledgements The authors thank the Shanghai Municipal and District Bureau of Education for their supports, and greatly appreciate the work of Prof. Yinping Zhang (Tsinghua University), Prof. Baizhan Li (Chongqing University), and Dr. Yuexia Sun (Tianjin University) in preparing the questionnaire, and Dr. Zhuohui Zhao (Fudan University) for obtaining the ethical approval for CCHH project, and we express our thanks to all who participated in the survey.
Funding This study was financially supported by National Natural Science Foundation of China (51278302), Innovation Program of Shanghai Municipal Education Commission (14ZZ132), Hujiang Foundation of China (D14003), and the Innovation Fund Project for Graduate Student of Shanghai (JWCXSL1401). The funder provided support in the form of salaries for authors, but
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ACCEPTED MANUSCRIPT did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of the authors are articulated in the authors‟ contributions‟ section.
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ACCEPTED MANUSCRIPT 5-11. 19. Sears MR, Greene JM, Willan AR, Taylor DR, Flannery EM, Cowan JO, et al. Long-term relation between breastfeeding and development of atopy and asthma in children and young adults: a longitudinal study. Lancet 2002; 360(9337): 901-907. 20. Siltanen M, Kajosaari M, Poussa T, Saarinen KM & Savilahti E. A dual long-term effect of breastfeeding on atopy in relation to heredity in children at 4 years of age. Allergy 2003; 58(6): 524-530. 21. Kramer MS, Matush L, Vanilovich I, Platt R, Bogdanovich N, Sevkovskaya Z, et al. Effect of prolonged and exclusive breast feeding on risk of allergy and asthma: cluster randomised trial. BMJ 2007; 335(7624): 815-820. 22. Kusunoki T, Morimoto T, Nishikomori R, Yasumi T, Heike T, Mukaida K, et al. Breastfeeding and the prevalence of allergic diseases in schoolchildren: does reverse causation matter? Pediatric and Allergy Immunology 2010; 21: 60-66. 23. Hörnell A, Lagström H, Lande B & Thorsdottir I. Breastfeeding, introduction of other foods and effects on health: a systematic literature review for the 5th Nordic Nutrition Recommendations. Food & Nutrition Research 2013; 57: e20823. 24. Lee KS, Choi SH, Choi YS, Oh IH & Rha YH. Relationship between breast-feeding and wheeze risk in early childhood in Korean children: based on the fifth Korea National Health
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ACCEPTED MANUSCRIPT and Nutrition Examination Survey 2010-2012. Allergy, Asthma & Respiratory Disease 2014; 2(2): 103-107. 25. Mihrshahi S, Ampon R, Webb K, Almqvist C, Kemp AS, Hector D, et al. The association between infant feeding practices and subsequent atopy among children with a family history of asthma. Clinical & Experimental Allergy 2007; 37(5): 671-679. 26. Nwaru BI, Craig LC, Allan K, Prabhu N, Turner SW, McNeill G, et al. Breastfeeding and introduction of complementary foods during infancy in relation to the risk of asthma and atopic diseases up to 10 years. Clinical & Experimental Allergy 2013; 43: 1263-1273. 27. Nwaru BI, Takkinen HM, Niemelä O, Kaila M, Erkkola M, Ahonen S, et al. Introduction of complementary foods in infancy and atopic sensitization at the age of 5 years: timing and food diversity in a Finnish birth cohort. Allergy 2013; 68(4): 507-516. 28. Jelding-Dannemand E, Schoos AMM. & Bisgaard H. Breast-feeding does not protect against allergic sensitization in early childhood and allergy-associated disease at age 7 years. The Journal of Allergy and Clinical Immunology 2015; 136(5): 1302-1308. 29. Nwaru BI, Takkinen HM, Niemelä O, Kaila M, Erkkola M, Ahonen S, et al. Timing of infant feeding in relation to childhood asthma and allergic diseases. The Journal of Allergy and Clinical Immunology 2013; 131(1): 78-86. 30. Nwaru BI, Erkkola M, Ahonen S, Kaila M, Haapala AM, Kronberg-Kippilä C, et al. Age at
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ACCEPTED MANUSCRIPT the introduction of solid foods during the first year and allergic sensitization at age 5 years. Pediatrics 2010; 125(1): 50-59. 31. Greer FR, Sicherer SH & Burks AW. Effects of early nutritional interventions on the development of atopic disease in infants and children: the role of maternal dietary restriction, breastfeeding, timing of introduction of complementary foods, and hydrolyzed formulas. Pediatrics 2008; 121(1): 183-191. 32. Tilman D. & Clark M. Global diets link environmental sustainability and human health. Nature 2014; 515: 518-522. 33. Xu F, Qiu L, Binns CW & Liu X. Breastfeeding in China: a review. International Breastfeeding Journal 2009; 4: 6. Doi: 10.1186/1746-4358-4-6. 34. Zhang LH, Chen HX & Yao PH. Comparison of breastfeeding rate in Shanghai rural areas during 10 years. Shanghai Preventive Medicine 1996; 8(4): 183-186. (in Chinese) 35. Hu BS, Zhang CC, Li Y, Zhang Y & Feng ZC. Influential factors of breast feeding in married woman at child- bearing age in five cities of China. Maternal and Child Health Care of China 2004; 19(9): 18-20. (in Chinese) 36. Hiroshi S, Sicular T & Yue X. Housing Ownership, Incomes, and Inequality in China, 2002-2007. Rising Inequality in China: Key Issues and Findings. Cambridge University Press, UK. 2013.
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ACCEPTED MANUSCRIPT 37. Asher MI, Keil U, Anderson HR, Beasley R, Crane J, Martinez F, et al. International Study of Asthma and Allergies in Childhood (ISAAC): rationale and methods. European Respiratory Journal 1995; 8(3): 483-491. 38. Jenkins M, Clarke J, Carlin J, Robertson C, Hopper J, Dalton M, et al. Validation of questionnaire and bronchial hyper-responsiveness against respiratory physician assessment in the diagnosis of asthma. International Journal of Epidemiology 1996; 25: 609–616. 39. Chan HH, Pei A, Van Krevel C, Wong WK & Lai CKW. Validation of the Chinese translated version of ISAAC core questions for atopic eczema. Clinical and Experimental Allergy 2001; 31: 903-907. 40. Sun YX, Sundell J & Zhang YF. Validity of building characteristics and dorm dampness obtained in a self-administrated questionnaire. Science of the Total Environment 2007; 387: 276-282. 41. Hagerhed-Engman L, Bornehag CG, Sundell J. How valid are parents‟ questionnaire responses regarding building characteristics, mouldy odour, and signs of moisture problems in Swedish homes?. Scandinavian Journal of Public Health 2007; 35: 125-132. 42. Bornehag CG, Sundell J, Hagerhed-Engman L, Sigsggard T, Janson S, Aberg N, et al. „Dampness‟ at home and its association with airway, nose, and skin symptoms among 10,851 preschool children in Sweden: a cross-sectional study. Indoor Air 2005; 15: 48-55.
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ACCEPTED MANUSCRIPT 43. Hu Y, Liu W, Huang C, Zou ZJ, Zhao ZH, Shen L, et al. Home dampness, childhood asthma, hay fever, and airway symptoms in Shanghai, China: associations, dose-response relationships, and lifestyle's influences. Indoor Air 2014; 24: 450-463. 44. Liu W, Huang C, Hu Y, Zou ZJ & Sundell J. Associations between indoor environmental smoke and respiratory symptoms among preschool children in Shanghai, China. Chinese Science Bulletin 2013; 58(34): 4211-4216. 45. Labbok MH & Coffin CJ. A call for consistency in definition of breastfeeding behaviors. Social Science & Medicine 1997; 44(12): 1931-1932. 46. Nurmatov U, Nwaru BI, Devereux G & Sheikh A. Confounding and effect modification in studies of diet and childhood asthma and allergies. Allergy 2012; 67(8): 1041-1059. 47. Wang XY, Liu W, Hu Y, Zou ZJ, Shen L & Huang C. Home environment, lifestyles behaviors, and rhinitis in childhood. International Journal of Hygiene and Environmental Health 2016; 219: 220-231. 48. Cai J, Liu W, Hu Y, Zou ZJ, Shen L & Huang C. Associations between home dampness-related exposures and childhood eczema among 13,335 preschool children in Shanghai, China: A cross-sectional study. Environmental Research 2016; 146: 18–26. 49. Huang C, Hu Y, Liu W, Zou ZJ & Sundell J. Pet-keeping and its impact on asthma and allergies among preschool children in Shanghai, China. Chinese Science Bulletin 2013; 58:
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ACCEPTED MANUSCRIPT 4203-4210. 50. Liu W, Huang C, Hu Y, et al. Associations between indoor environmental smoke and respiratory symptoms among preschool children in Shanghai, China. Chinese Science Bulletin 2013; 58: 4211-4216, 51. Balogun OO, Dagvadorj A, Anigo KM, Ota E & Sasaki S. Factors influencing breastfeeding exclusivity during the first 6 months of life in developing countries: a quantitative and qualitative systematic review. Maternal & Child Nutrition 2015; Doi: 10.1111/mcn.12180. 52. Brown A & Rowan H. Maternal and infant factors associated with reasons for introducing solid foods. Maternal & Child Nutrition 2015; Doi: 10.1111/mcn.12166. 53. Munblit D, Boyle RJ & Warner J.O. Factors affecting breast milk composition and potential consequences for development of the allergic phenotype. Clinical & Experimental Allergy 2014; 45: 583-601.
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Table 1. Definitions of Breastfeeding (BF) according to duration and pattern. Durations and patterns of BF (months)
No BF Partial BF < 3 Exclusive BF < 3 Partial BF = 3-6 Exclusive BF = 3-6 Partial BF > 6
BF (months)
No ne
< 3a
3-6
> 6
<3
3-6
>6
Exclusive BF > 6 a
Age for first introduction of infant formula, gruel or porridge (months)
Age for first introduction of fruits or vegetables (months) < 3 3-6 >6
Includes < 1 month and 1-2 months.
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ACCEPTED MANUSCRIPT Table 2. Demographic data for the studied children. Items Sample size, n (%) Age (years) 4 5561 (41.7) 5 4399 (33.0) 6 3375 (25.3) Sex Boys 6536 (49.2) Girls 6753 (50.8) District of the current residence urban 7576 (56.8) suburban 5759 (43.2) Ownership of the current residence Owner 8224 (63.2) Renter 4795 (36.8) Family history of atopy Yes 3097 (23.9) No 9837 (76.1) Early pet-keeping Yes 1628 (12.4) No 11515 (87.6) Early parental smoking Yes 7631 (58.0) No 5524 (42.0) Current parental smoking Yes 7319 (56.5) No 5637 (43.5) Early home dampness exposure Yes 7596 (60.3) No 5006 (39.7) Current home dampness exposure Yes 10137 (86.1) No 1634 (13.9)
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ACCEPTED MANUSCRIPT Table 3. BF strata and early dietary introductions.
Items
Total, n (%)
Stratified by sex, n (%)
Stratified by family history of atopy, n (%)
Boys
Yes
Girls
No
Stratified by ownership of the current residence, n (%) Owner Renter
(1) Duration of BF Never
1727 (13.2)
868 (13.1) 855 (13.4)
< 1 month 1-2 months
885 (6.8) 1363 (10.4)
442 (6.7) 440 (6.9) 702 (10.6) 655 (10.3)
3-6 months
3630 (27.8)
1810 (27.3) 1813 (28.4)
> 6 months
5456 (41.8)
2807 (42.3) 2625 (41.1)
1325 (13.8) 242 (7.9) 621 (6.4) 365 (12.0) 961 (10.0) 2576 960 (31.5) (26.7) 4153 1132 (37.1) (43.1)# 352 (11.5)
1055 (13.1) 619 (13.2) 594 (7.4) 265 (5.6) 908 (11.2) 431 (9.2) 2480 (30.7) 1085 (23.1) 3036 (37.6) 2295 (48.9)#
(2) Introduction of infant formula, gruel or porridge < 3 months-old
4483 (34.6)
2287 (34.9) 2190 (34.5)
3-6 months-old
4890 (36.7)
2510 (38.3) 2364 (37.2)
> 6 months-old
3569 (26.7)
1755 (26.8) 1795 (28.3)
(3) Introduction of fruits or vegetables < 3 months-old 700 (5.5) 356 (5.5)
344 (5.5)
3-6 months-old
6682 (52.4)
3370 (52.2) 3295 (52.7)
> 6 months-old
5361 (42.1)
2729 (42.3) 2612 (41.8)
3177 (33.3) 3624 1129 (37.2) (38.0) 2737 716 (23.6) (28.7)# 1188 (39.2)
199 (6.6)
483 (5.2) 4785 1719 (57.2) (51.0) 4110 1085 (36.1) (43.8)#
2964 (36.8) 1422 (30.9) 3094 (38.4) 1696 (36.8) 1992 (24.7) 1488 (32.3)# 467 (5.9)
221 (4.9)
4434 (55.9) 2112 (46.5) 3027 (38.2) 2205 (48.6)#
(4) BF classified by duration (months) and pattern No BF
1727 (13.8)
868 (13.6) 855 (14.0)
352 (11.9)
Partial BF < 3
1532 (12.2)
792 (12.5) 738 (12.0)
433 (14.7)
Exclusive BF < 3
512 (4.1)
254 (4.0)
125 (4.2)
Partial BF = 3-6
3117 (24.9)
1553 (24.4) 1559 (25.4)
848 (28.8)
Exclusive BF = 3-6
447 (3.6)
230 (3.6)
91 (3.1)
Partial BF > 6
3432 (27.4)
1787 (28.1) 1633 (26.7)
783 (26.6)
Exclusive BF > 6
1754 (14.0)
875 (13.8) 873 (14.2)
317 (10.7)
254 (4.1)
215 (3.5)
1325 (14.4) 1059 (11.5) 375 (4.1) 2191 (23.7) 343 (3.7) 2551 (27.6) 1385 (15.0)#
1055 (13.5) 619 (13.9) 1044 (13.3) 455 (10.2) 333 (4.3)
173 (3.9)
2160 (27.6) 901 (20.3) 285 (3.6)
158 (3.6)
2056 (26.3) 1311 (29.5) 888 (11.4) 827 (18.6)#
BF, Breastfeeding. #p <0.001 in chi-square test (two-tailed) for the differences in BF strata and
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ACCEPTED MANUSCRIPT early dietary introductions among different subgroups which were stratified by sex, family history of atopy, and ownership of the current residence (n*2 tables), where n is the number of options for various items. Bold indicates significant difference.
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ACCEPTED MANUSCRIPT Table 4. Prevalence of the studied diseases for different levels of BF and timing of dietary introductions. Items
Prevalence, n (%) Asthma Wheeze
Hay fever Rhinitis
Pneumonia Eczema
(1) Duration of BF Never 205 (12.2) 485 (28.5) 224 (13.3) 921 (54.2) 589 (35.4) 260 (16.3) < 1 month 108 (12.5) 273 (31.1) 127 (14.8) 491 (56.5) 302 (35.0) 150 (18.2) 1-2 months 146 (11.0) 395 (29.3) 208 (15.7) 759 (56.8) 518 (39.0) 209 (16.3) 3-6 months 387 (10.9) 1017 (28.5) 517 (14.6) 2016 (56.4) 1272 (36.0) 574 (16.9) > 6 months 470 (8.9) # 1478 (27.5) 523 (9.9) # 2743 (51.2) # 1573 (29.8) # 796 (15.8) (2) Introduction of infant formula, gruel or porridge < 3 months-old 534 (12.2) 1313 (29.6) 639 (14.7) 2481 (56.1) 1595 (36.6) 739 (17.6) 3-6 months-old 505 (10.6) 1419 (29.4) 614 (12.9) 2604 (54.2) 1631 (34.4) 745 (16.4) > 6 months-old 280 (8.1) # 896 (25.5) # 340 (9.8) # 1790 (51.2) # 1016 (29.6) # 499 (15.2)* (3) Introduction of fruits or vegetables < 3 months-old 74 (10.8) 191 (27.5) 79 (11.6) 401 (58.3) 228 (33.5) 113 (17.3) 3-6 months-old 724 (11.1) 1946 (29.4) 915 (14.1) 3626 (55.0) 2292 (35.3) 1112 (17.8) > 6 months-old 490 (9.4)* 1432 (27.1)* 578 (11.1) # 2758 (52.6)** 1624 (31.4) # 721 (14.6) # (4) BF classified by duration and pattern (month) No BF 205 (12.2) 485 (28.5) 224 (13.3) 921 (54.2) 589 (35.4) 260 (16.3) Partial BF < 3 167 (11.2) 454 (29.8) 229 (15.4) 851 (56.4) 561 (37.5) 260 (18.0) Exclusive BF < 3 64 (12.8) 160 (31.5) 81 (16.3) 285 (57.0) 195 (38.9) 75 (15.7) Partial BF = 3-6 349 (11.4) 895 (29.2) 455 (15.0) 1746 (56.8) 1108 (36.5) 500 (17.1) Exclusive BF = 3-6 30 (6.9) 101 (22.9) 51 (11.8) 236 (53.4) 147 (33.9) 64 (15.2) Partial BF > 6 321 (9.6) 978 (28.8) 368 (11.0) 1785 (52.8) 1054 (31.7) 561 (17.6) Exclusive BF > 6 140 (8.2) # 430 (24.8)** 138 (8.1) # 820 (47.8) # 452 (26.7) # 205 (12.8)** BF, Breastfeeding. *0.01 ≤ p <0.05, **0.001 ≤ p <0.01, #p <0.001 in chi-square test (two-tailed) for the difference in prevalence of the diseases (lifetime-ever) for different levels of BF and timing of dietary introductions (n*2 tables), herein n is the number of options for various items. Bold indicates significant difference.
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ACCEPTED MANUSCRIPT Table 5. Associations of breastfeeding (BF) and timing of dietary introduction with the studied diseases. Adjusted OR a, 95%CI Items Asthma Wheeze Hay fever Rhinitis Pneumonia Eczema (1) Duration of BF (reference: Never BF) < 1 month 0.90, 0.67-1.20 1.12, 0.91-1.37 0.96, 0.72-1.27 1.06, 0.88-1.29 0.95, 0.78-1.16 1.08, 0.84-1.39 0.96, 1-2 months 0.98, 0.89-1.07 1.03, 0.91-1.16 1.04, 0.96-1.14 1.03, 0.95-1.12 0.93, 0.83-1.04 0.94-0.98** 0.93, 3-6 months 0.98, 0.93-1.03 0.98, 0.92-1.05 1.02, 0.97-1.06 0.99, 0.95-1.04 0.95, 0.89-1.01 0.87-0.99* 0.92, 0.92, 0.95, > 6 months 0.97, 0.84-1.11 0.98, 0.95-1.01 0.99, 0.95-1.04 0.87-0.97** 0.88-0.97** 0.92-0.98** (2) Introduction of infant formula, gruel or porridge (reference: < 3 months-old) 3-6 months-old 0.98, 0.85-1.13 1.02, 0.92-1.13 0.95, 0.83-1.10 0.97, 0.88-1.06 0.97, 0.88-1.07 0.95, 0.84-1.08 0.78, 0.88, 0.87, 0.95, 0.89, > 6 months-old 0.99, 0.92-1.06 ** * ** * 0.66-0.93 0.78-0.99 0.80-0.94 0.90-1.00 0.84-0.94# (3) Introduction of fruits or vegetables (reference: < 3 months-old) 3-6 months-old 1.04, 0.79-1.37 1.12, 0.92-1.36 1.26, 0.96-1.65 0.88, 0.73-1.05 1.07, 0.89-1.29 1.09, 0.86-1.38 > 6 months-old 1.01, 0.87-1.17 1.03, 0.93-1.14 1.07, 0.93-1.24 0.92, 0.84-1.01 0.99, 0.90-1.09 0.98, 0.87-1.11 (4) BF classified by duration and pattern (month) (reference: Never BF) 0.93, Partial BF < 3 1.01, 0.84-1.20 1.03, 0.81-1.30 1.05, 0.89-1.24 1.00, 0.85-1.18 0.97, 0.78-1.20 0.87-0.99* Exclusive BF < 3 0.98, 0.83-1.17 1.03, 0.91-1.17 1.04, 0.88-1.23 1.04, 0.93-1.17 1.05, 0.94-1.18 0.95, 0.81-1.11 Partial BF = 3-6 0.93, 0.87-1.00 0.99, 0.94-1.04 0.99, 0.92-1.06 1.02, 0.97-1.07 1.00, 0.95-1.05 0.95, 0.89-1.01 0.93, Exclusive BF = 0.81, 0.95, 0.86-1.04 1.00, 0.94-1.06 0.98, 0.92-1.04 0.96, 0.88-1.05 # 3-6 0.72-0.91 0.87-0.99* 0.94, 0.95, Partial BF > 6 1.00, 0.97-1.03 0.99, 0.96-1.02 1.07, 0.83-1.38 1.01, 0.98-1.05 ** 0.90-0.98 0.91-0.99* 0.95, 0.93, 0.97, 0.97, 0.96, Exclusive BF > 6 0.99, 0.96-1.02 * ** * * 0.91-0.99 0.89-0.97 0.94-0.99 0.94-0.99 0.93-0.99* a
Adjusted for family history of atopy, sex, age, district of the current residence, ownership of the
current residence, early pet-keeping, early and current parental smoking, as well as early and
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ACCEPTED MANUSCRIPT current home dampness exposure. * 0.01 ≤ p <0.05, ** 0.001 ≤ p <0.01, # p <0.001. Bold indicates statistical significance.
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ACCEPTED MANUSCRIPT Table 6. Adjusted associations of durations and patterns of breastfeeding (BF) with the studied diseases among children without family history of atopy. BF pattern and Adjusted OR a, 95%CI (reference: No BF) duration (Months) Asthma Wheeze Hay fever
Eczema 0.93, Partial BF < 3 0.77, 0.55-1.09 1.22, 0.98-1.50 1.10, 0.79-1.54 1.00, 0.83-1.20 1.00, 0.82-1.21 0.71-1.22 0.96, Exclusive BF < 3 1.09, 0.71-1.69 1.22, 0.91-1.64 1.14, 0.92-1.43 1.03, 0.90-1.17 1.03, 0.89-1.18 0.79-1.17 0.96, Partial BF = 3-6 0.89, 0.68-1.18 1.07, 0.89-1.29 1.04, 0.95-1.15 1.04, 0.99-1.09 0.99, 0.94-1.05 0.89-1.04 Exclusive BF = 0.31, 0.98, 0.76, 0.88, 0.75-1.02 1.00, 0.94-1.07 0.96, 0.89-1.03 ** * 3-6 0.89-1.08 0.15-0.62 0.55-0.99 1.00, 0.68, 0.93, 0.96, Partial BF > 6 1.06, 0.89-1.27 0.99, 0.96-1.02 ** * ** 0.95-1.04 0.52-0.91 0.88-0.99 0.93-0.99 0.97, 0.63, 0.91, 0.94, Exclusive BF > 6 0.97, 0.78-1.19 0.97, 0.95-1.00 ** ** # 0.92-1.01 0.45-0.89 0.85-0.97 0.91-0.97 a
Rhinitis
Pneumonia
Adjusted for sex, age, district of the current residence, ownership of the current residence, early
pet-keeping, early and current parental smoking, and early and current home dampness exposure. *
0.01 ≤ p <0.05, ** 0.001 ≤ p <0.01, # p <0.001. Bold indicates statistical significance.
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