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Early oral exposure to house dust mite allergen through breast milk: A potential risk factor for allergic sensitization and respiratory allergies in children
2016; Elsevier BV; Volume: 139; Issue: 1 Linguagem: Inglês
10.1016/j.jaci.2016.07.021
ISSN1097-6825
AutoresNour Baïz, Patrícia Macchiaverni, Meri K. Tulić, Akila Rekima, Isabella Annesi‐Maesano, Valérie Verhasselt, I. Annesi‐Maesano, Jonathan Y. Bernard, Jérémie Botton, Marie‐Aline Charles, Patricia Dargent‐Molina, Blandine de Lauzon‐Guillain, Pierre Ducimetière, Maria De Agostini, B. Foliguet, Anne Forhan, Xavier Fritel, Alice Germa, V. Goua, R. Hankard, Barbara Heude, Monique Kaminski, Béatrice Larroque, N. Lelong, Johanna Lepeule, G Magnin, F. Pierre, Laetitia Marchand‐Martin, Cathy Nabet, Rémy Slama, Marie‐Josèphe Saurel‐Cubizolles, M. Schweitzer, O. Thiébaugeorges,
Tópico(s)Food Allergy and Anaphylaxis Research
ResumoHouse dust mites (HDMs) are found worldwide and are a major source of perennial aeroallergens. Allergic rhinitis and asthma have been attributed to sensitization to HDM allergens from Dermatophagoides pteronyssinus (Der p) and Dermatophagoides farinae (Der f) in up to 80% of patients.1Gregory L.G. Lloyd C.M. Orchestrating house dust mite-associated allergy in the lung.Trends Immunol. 2011; 32: 402-411Abstract Full Text Full Text PDF PubMed Scopus (290) Google Scholar Sensitization to HDMs is linked to HDM allergen exposure and is known to occur mostly during the first years of life (reviewed in Custovic2Custovic A. To what extent is allergen exposure a risk factor for the development of allergic disease?.Clin Exp Allergy. 2015; 45: 54-62Crossref PubMed Scopus (53) Google Scholar). These observations have led to early life environmental control studies in birth cohorts aimed at reducing domestic HDM exposure to prevent HDM sensitization and allergies; however, results of these studies have been conflicting (reviewed in Custovic2Custovic A. To what extent is allergen exposure a risk factor for the development of allergic disease?.Clin Exp Allergy. 2015; 45: 54-62Crossref PubMed Scopus (53) Google Scholar). Currently, no efficient strategy is available for the prevention of HDM-induced allergy, thus highlighting the necessity to better elucidate the source of exposures, risks, and protective factors. In recent years, the concept has emerged that early oral exposure to food antigens may be necessary for immune tolerance induction and long-term prevention of inappropriate immune reactions to food and this concept has been tested in recent interventional trials with some promising results.3Elizur A. Katz Y. Timing of allergen exposure and the development of food allergy: treating before the horse is out of the barn.Curr Opin Allergy Clin Immunol. 2016; 16: 157-164Crossref PubMed Scopus (9) Google Scholar, 4Grimshaw K.E. Maskell J. Oliver E.M. Morris R.C. Foote K.D. Mills E.N. et al.Introduction of complementary foods and the relationship to food allergy.Pediatrics. 2013; 132: e1529-e1538Crossref PubMed Scopus (70) Google Scholar Clinical trials have recently showed that introducing solid food while continuing to breast-feed may enhance chances of tolerance induction and prevent food allergy.5Perkin M.R. Logan K. Tseng A. Raji B. Ayis S. Peacock J. et al.Randomized trial of introduction of allergenic foods in breast-fed infants.N Engl J Med. 2016; 374: 1733-1743Crossref PubMed Scopus (532) Google Scholar We further proposed that oral exposure to aeroallergens through breast milk may affect the risk to develop respiratory allergies.6Verhasselt V. Neonatal tolerance under breastfeeding influence.Curr Opin Immunol. 2010; 22: 623-630Crossref PubMed Scopus (79) Google Scholar Recently, we demonstrated the presence of respiratory allergens from Der p and Blomia tropicalis HDM in human breast milk.7Macchiaverni P. Rekima A. Turfkruyer M. Mascarell L. Airouche S. Moingeon P. et al.Respiratory allergen from house dust mite is present in human milk and primes for allergic sensitization in a mouse model of asthma.Allergy. 2014; 69: 395-398Crossref PubMed Scopus (38) Google Scholar, 8Macchiaverni P. Ynoue L.H. Arslanian C. Verhasselt V. Condino-Neto A. Early exposure to respiratory allergens by placental transfer and breastfeeding.PLoS One. 2015; 10: e0139064Crossref PubMed Scopus (18) Google Scholar This surprising observation may be explained by the fact that Der p particules are ingested after lung mucociliary clearance of inhaled Der p particules and from food contaminated with dust2Custovic A. To what extent is allergen exposure a risk factor for the development of allergic disease?.Clin Exp Allergy. 2015; 45: 54-62Crossref PubMed Scopus (53) Google Scholar; Der p particules would then follow the same route as dietary antigens to maternal milk.7Macchiaverni P. Rekima A. Turfkruyer M. Mascarell L. Airouche S. Moingeon P. et al.Respiratory allergen from house dust mite is present in human milk and primes for allergic sensitization in a mouse model of asthma.Allergy. 2014; 69: 395-398Crossref PubMed Scopus (38) Google Scholar Der p 1 in maternal milk was found in similar quantities as dietary egg antigen ovalbumin and to be immunoreactive.7Macchiaverni P. Rekima A. Turfkruyer M. Mascarell L. Airouche S. Moingeon P. et al.Respiratory allergen from house dust mite is present in human milk and primes for allergic sensitization in a mouse model of asthma.Allergy. 2014; 69: 395-398Crossref PubMed Scopus (38) Google Scholar In a mouse model, we found that Der p in breast milk promoted subsequent allergic sensitization in the progeny.7Macchiaverni P. Rekima A. Turfkruyer M. Mascarell L. Airouche S. Moingeon P. et al.Respiratory allergen from house dust mite is present in human milk and primes for allergic sensitization in a mouse model of asthma.Allergy. 2014; 69: 395-398Crossref PubMed Scopus (38) Google Scholar In the present study, our main objective was to assess whether early exposure to Der p 1 transferred from the mother to the newborn through breast milk would affect child's subsequent development of allergic sensitization, asthma, and allergic rhinitis in the first 5 years of life, using prospective population-based data from the French Etude des Déterminants pré et post-natal du development et de la santé de l'Enfant birth cohort (http://eden.vjf.inserm.fr) (for mother-children pairs characteristics, see Table E1, Table E2, Table E3 in this article's Online Repository at www.jacionline.org). Der p 1 allergen was quantified by ELISA in milk of 255 mothers (see text in this article's Online Repository at www.jacionline.org and Macchiaverni et al7Macchiaverni P. Rekima A. Turfkruyer M. Mascarell L. Airouche S. Moingeon P. et al.Respiratory allergen from house dust mite is present in human milk and primes for allergic sensitization in a mouse model of asthma.Allergy. 2014; 69: 395-398Crossref PubMed Scopus (38) Google Scholar). Der p 1 was detected in two-thirds of all breast milk samples, and the median level was 52.1 pg/mL in the whole population (Fig 1; see Table E4 in this article's Online Repository at www.jacionline.org). Median Der p 1 level was higher in mothers with a history of asthma or allergies (Fig 1). In the whole population (n = 255), median Der p 1 level was higher in mothers younger than 34 years than in those older than 34 years (P = .02), in mothers whose milk was collected during winter compared with the other seasons (P = .04), and in mothers living in Nancy compared with those living in Poitiers (P = .0008) (see Table E5 in this article's Online Repository at www.jacionline.org). No significant association was found between Der p 1 levels in breast milk and proxies of exposure to HDM allergen, such as common HDM sources in the environment where the mother and the child have lived during the follow-up (see Table E6 in this article's Online Repository at www.jacionline.org) as well as the occupancy load (see Table E7 in this article's Online Repository at www.jacionline.org). To analyze possible associations between Der p 1 levels in breast milk and health outcomes at 5 years of age, exposure to Der p 1 was classified as a categorical variable, namely, "low" levels below or equal to median versus "high" levels above the median value obtained in the total population (=52.1 pg/mL) (for detailed statistical analysis method, see text in this article's Online Repository at www.jacionline.org). In the entire population, no significant association was found between Der p 1 levels and the risk of the studied health outcomes (Fig 2; see Table E8 in this article's Online Repository at www.jacionline.org). However, children breast-fed by mothers with a history of asthma or allergies with high Der p 1 levels in milk were at a significantly higher risk of asthma or allergic rhinitis compared with children from mothers with low Der p 1 in milk (odds ratio [OR], 3.4; P = .02; Fig 2 and Table E8). In this group, we also found a borderline significance of higher risk for asthma with high milk Der p 1 levels compared with those with low milk Der p 1 levels (OR, 7.8; P = .06). Both relationships persisted after adjustment for confounders (Table E8). Among the 255 mother-child pairs with Der p 1 quantification in breast milk, 142 children had available sera at 5 years for total and Der p 1 specific IgE assessment (ImmunoCAP Technology, Thermo Scientific/Phadia, Uppsala, Sweden) (for mother-child pair characteristics, see Table E3). We found that ORs for allergic sensitization in children breast-fed by mothers having high versus low levels of Der p 1 in milk were higher than 1 in the 3 groups we analyzed (whole population/children from mother with and without history of asthma and allergy, Fig 2 and Table E8). High Der p 1 in milk was associated with a significantly increased risk for having positive total IgE (adjusted OR [aOR], 3.87; P = .003) and a borderline significant trend for the risk of having specific IgE to Der p 1 (aOR, 2.21; P = .07) (Fig 2 and Table E8). An increased OR for having positive total IgE was found in children breast-fed by mothers both with and without allergic history (aOR, 2.85 and 4.34, respectively), with only the latter one being found to be statistically significant (P = .2 and .005, respectively) (Fig 2 and Table E8). Our study is the first in literature considering the presence of respiratory HDM Der p 1 allergen in human breast milk as a potential contributor to the development of allergic sensitization and asthma and allergic rhinitis in children. We observed an increased risk of allergic sensitization at 5 years in children breast-fed by mothers with Der p 1 levels in milk above the median value compared with children breast-fed by mothers with Der p 1 levels in milk below the median value. We further found that high levels of Der p 1 in milk were associated with an increased risk of asthma or allergic rhinitis in the first 5 years for children whose mothers had a history of asthma or allergy compared with those with low levels of Der p 1 in milk. This latter result suggests that a gene-environment interaction between familial asthma or allergy and Der p 1 in the milk is necessary for increasing the risk of asthma and rhinitis. Our findings are of relevance in the debate about the protective effect on the development of allergies conferred by breast milk, which is still controversial.9Victora C.G. Bahl R. Barros A.J. França G.V. Horton S. Krasevec J. et al.Breastfeeding in the 21st century: epidemiology, mechanisms, and lifelong effect.Lancet. 2016; 387: 475-490Abstract Full Text Full Text PDF PubMed Scopus (3336) Google Scholar The data presented in this report highlight that heterogeneity of breast-feeding–induced protection from atopic sensitization and respiratory allergies might depend on levels of respiratory Der p 1 antigen found in mother's milk. Whether Der p is a proxy for other exposures to environmental factors at the origin of the development of child's allergy cannot be excluded. However, high Der p 1 in breast milk was still a risk factor in subgroups of children when adjusting for environmental exposure to HDM in multivariate models and restricting the investigation to subgroups with low indoor sources of HDM, indicating that HDM allergen content is an independent risk factor for allergy (data not shown). There were also no differences observed in either breast-feeding behavior or population characteristics between parents with asthma and parents with allergy, except cat ownership, considered as a confounder. Importantly, data obtained in a mouse model where strict control of maternal and environmental parameters is possible, support the hypothesis of a causal role of Der p 1 in milk in allergic sensitization development.7Macchiaverni P. Rekima A. Turfkruyer M. Mascarell L. Airouche S. Moingeon P. et al.Respiratory allergen from house dust mite is present in human milk and primes for allergic sensitization in a mouse model of asthma.Allergy. 2014; 69: 395-398Crossref PubMed Scopus (38) Google Scholar Identification of factors governing Der p levels in breast milk and its proallergenic properties is needed to propose early intervention to counteract detrimental effects of Der p and prevent respiratory allergies. Here, we report significantly higher levels of Der p 1 in breast milk from mothers with a history of asthma or allergies, mothers living in Nancy versus Poitiers, mothers younger than 35 years, and in milk collected during winter. We found no association between Der p 1 levels in breast milk and proxies of indoor environmental HDM exposure. The apparent lack of association between indoor environmental exposure to Der p and levels of Der p 1 in breast milk is further supported by a report on levels of exposure to Der p in 6390 dwellings in France showing that levels of Der p exposure were much lower in Nancy than in Poitiers whereas we found that Der p 1 levels were significantly higher in milk from Nancy than from Poitiers.10Rocchi S. Reboux G. Frossard V. Scherer E. Valot B. Laboissiere A. et al.Microbiological characterization of 3193 French dwellings of Elfe cohort children.Sci Total Environ. 2015; 505: 1026-1035Crossref PubMed Scopus (35) Google Scholar This is consistent with studies showing no direct correlation between maternal food antigen intake and its presence in breast milk.11Palmer D.J. Gold M.S. Makrides M. Effect of maternal egg consumption on breast milk ovalbumin concentration.Clin Exp Allergy. 2008; 38: 1186-1191Crossref PubMed Scopus (55) Google Scholar To elucidate which factors are driving the presence of respiratory allergens in breast milk, we will need to better know how and when we get exposed to respiratory allergens ‡These authors contributed equally to this work as last authors. and to identify factors that affect transfer of antigen from maternal gut to milk. Clarification of mechanisms underlying priming activities of oral exposure to very low amounts of Der p 1 is necessary to delineate under which conditions early oral allergen exposure is safe and beneficial for allergy prevention. Our data obtained from mouse models clearly indicate that the nature of the antigen is critical in deciphering the long-term impact on allergy susceptibility.12Verhasselt V. Is infant immunization by breastfeeding possible?.Philos Trans R Soc Lond B Biol Sci. 2015; 370: 20140139Crossref PubMed Scopus (18) Google Scholar The data presented here highlight the need to be cautious in recommending early oral exposure to allergens. In contrast to antigens such as ovalbumin, Der p allergens have strong intrinsic adjuvant properties due to Toll-like receptor agonist and protease activities, which may be responsible for initiation of allergic immune responses. ∗These authors contributed equally to this work as first authors. Our ongoing studies in neonatal mice assess impacts of milk-transferred Der p on gut mucosal immune regulation and ways to counteract detrimental effects of Der p on allergy susceptibility. In conclusion, we have identified an environmental factor present in breast milk that may affect the risk of allergic sensitization and respiratory allergies in children. This original observation paves the way for future large cohort analyses of association between oral exposure to aeroallergens and the risk of respiratory allergies and for fostering mechanistic studies on factors affecting respiratory allergen levels and allergenicity in breast milk. We are indebted to the participating families and to the midwife research assistants (L. Douhaud, S. Bedel, B. Lortholary, S. Gabriel, M. Rogeon, and M. Malinbaum) for data collection. We thank Professor Antonio Condino Neto for providing grant support for salary of Patricia Macchiaverni. Members of the EDEN Mother-Child Cohort Study Group: I. Annesi-Maesano, J.Y. Bernard, J. Botton, M.A. Charles, P. Dargent-Molina, B. de Lauzon-Guillain, P. Ducimetière, M. de Agostini, B. Foliguet, A. Forhan, X. Fritel, A. Germa, V. Goua, R. Hankard, B. Heude, M. Kaminski, B. Larroque, N. Lelong, J. Lepeule, G. Magnin, F. Pierre, L. Marchand, C. Nabet, R. Slama, M.J. Saurel-Cubizolles, M. Schweitzer, and O. Thiebaugeorges. Mother-child pairs were drawn from the French "Etude des Déterminants pré et post-natal du development et de la santé de l'Enfant" prospective birth cohort study (http://eden.vjf.inserm.fr).E1Baiz N. Dargent-Molina P. Wark J.D. Souberbielle J.C. Annesi-Maesano I. Cord serum 25-hydroxyvitamin D and risk of early childhood transient wheezing and atopic dermatitis.J Allergy Clin Immunol. 2014; 133: 147-153Abstract Full Text Full Text PDF PubMed Scopus (131) Google Scholar Among 621 mother-child pairs with breast milk collected during the first week postpartum and their health status followed-up, 255 pairs whose breast milk was collected between day 3 and day 7 postpartum were randomly selected. The study received approval from the ethics committee (CCPPRB) of Kremlin Bicêtre University Hospital on December 12, 2002, and from Commission Nationale Informatique et Liberté, the French data privacy institution. Written consent was obtained from all mothers. Children were followed-up from birth to age 5 years. Parents completed an enriched version of the International Study of Asthma and Allergies in Childhood phase-I questionnaireE2Worldwide variations in the prevalence of asthma symptoms: the International Study of Asthma and Allergies in Childhood (ISAAC).Eur Respir J. 1998; 12: 315-335Crossref PubMed Scopus (1203) Google Scholar, E3Williams H. Robertson C. Stewart A. Aït-Khaled N. Anabwani G. Anderson R. et al.Worldwide variations in the prevalence of symptoms of atopic eczema in the International Study of Asthma and Allergies in Childhood.J Allergy Clin Immunol. 1999; 103: 125Abstract Full Text Full Text PDF PubMed Scopus (822) Google Scholar filled at different periods of the follow-up.E4Heude B. Forhan A. Slama R. Douhaud L. Bedel S. Saurel-Cubizolles M.J. et al.Cohort profile: the EDEN mother-child cohort on the prenatal and early postnatal determinants of child health and development.Int J Epidemiol. 2015; 45: 353-363Crossref PubMed Scopus (171) Google Scholar Asthma was defined as parental report of doctor-diagnosis of asthma plus either 1 or more attacks of wheeze or use of asthma medication in the last 12 months. Allergic rhinitis was defined as having problem with sneezing or a runny nose or blocked nose without a cold or a flu, accompanied by itchy-watery eyes in the past 12 months.E5Asher M.I. Keil U. Anderson H.R. Beasley R. Crane J. Martinez F. et al.International Study of Asthma and Allergies in Childhood (ISAAC): rationale and methods.Eur Respir J. 1995; 8: 483-491Crossref PubMed Scopus (2802) Google Scholar Ever prevalence of asthma, allergic rhinitis, and asthma or allergic rhinitis (combined variable) was assessed as the presence of each health event at least once during the first 5 years of child's life. Maternal and paternal history of asthma or allergies was defined on the basis of a positive answer to a questionnaire administrated by a nurse on physician-diagnosed asthma, allergic rhinitis, eczema, or food allergies. In a subgroup of 142 children for whom blood serum was available, allergic sensitization was defined by assessing total and Der p 1 specific IgE using ImmunoCAP Technology (Thermo Scientific/Phadia). Total IgE levels were considered positive when more than 60 IU/mL and specific IgE to Der p 1 when 0.1 IU/mL or more. Transitional breast milk was collected using a sterile breast-pump from day 3 to 7 postdelivery. The samples were aliquoted and stored at −80°C. Before analysis, milk samples were thawed and centrifuged for 20 minutes at 160g at 4°C. The top layer of fat and the pellet were discarded and the intermediate fluid fraction used for Der p 1 measurement using a modified protocol of Der p 1 ELlSA kit 5H8/4Cl (EL-DP1, Indoor Biotechnologies, Charlottesville, Va) as previously described.E6Macchiaverni P. Arslanian C. Frazão J.B. Palmeira P. Russo M. Verhasselt V. et al.Mother to child transfer of IgG and IgA antibodies against Dermatophagoides pteronyssinus.Scand J Immunol. 2011; 74: 619-627Crossref PubMed Scopus (23) Google Scholar A typical dose-response curve of Der p 1 detection in PBS-Tween 0.05%-BSA 1% is shown in Fig 1. Der p 1 recovery in undiluted human milk or in milk diluted 2 or 4 times in PBS-Tween 0.05%-BSA 1% is also shown in Fig E1. For the analysis of Der p 1 levels in milk from this cohort, milk sample were diluted twice and an internal positive control was used in each ELISA plate. Samples with Der p 1 levels greater than 30 pg/mL were considered positive. For all the milk samples for which Der p 1 was undetectable by ELISA, we attributed the value of 0. The questionnaire allowed us to assess indoor environment sources of HDM as proxies of environmental HDME10Tobias K.R. Ferriani V.P. Chapman M.D. Arruda L.K. Exposure to indoor allergens in homes of patients with asthma and/or rhinitis in southeast Brazil: effect of mattress and pillow covers on mite allergen levels.Int Arch Allergy Immunol. 2004; 133: 365-370Crossref PubMed Scopus (23) Google Scholar, E7Bemt L. Vries M.P. Knapen L. Jansen M. Goossens M. Muris J.W. et al.Influence of mattress characteristics on house dust mite allergen concentration.Clin Exp Allergy. 2006; 36: 233-237Crossref PubMed Scopus (14) Google Scholar, E8Uchikoshi S. Kimura H. Nomura K. Chien C. Iida M. Miyake H. et al.A study of the ecology of the house dust mite in dwelling houses.Tokai J Exp Clin Med. 1982; 7: 233-243PubMed Google Scholar, E9Abbott J. Cameron J. Taylor B. House dust mite counts in different types of mattresses, sheepskins and carpets, and a comparison of brushing and vacuuming collection methods.Clin Allergy. 1981; 11: 589-595Crossref PubMed Scopus (36) Google Scholar to which mothers and children could have been exposed at least once during the follow-up. As an additional proxy of exposure to HDM in the dwelling, the occupancy load, which has been demonstrated to be a strong indicator of exposure to HDM allergen sources indoorsE11Hasselaar E. How healthy is the bedroom? Indoor Air Exposure Healthy Buildings.Proceedings. 2006; : 185-188Google Scholar and defined by the mean of the number of occupants divided by the number of rooms in the dwelling during the follow-up, was also used. A 2-class variable was introduced for the occupancy load to indicate low ( median value) exposure to indoor sources of HDM. The sample was described using frequencies of categorical variables, means, and SDs of continuous variables (median and interquartile range for Der p 1). We used chi-square tests to compare categorical data, t tests for normally distributed data, and Mann-Whitney U tests for skewed data. To quantify the relationships between exposure to Der p 1 allergen through lactation and health outcomes, and because of the nonnormal distribution of Der p 1 levels, exposure to Der p 1 was classified as a categorical variable, namely, "low" levels below or equal to median versus "high" levels above the median value obtained in the total population. Crude ORs between Der p 1 exposure and health outcomes and 95% CIs were evaluated with univariate logistic regression models and aORs and 95% CI with multivariate logistic regression models. In addition to the inclusion of confounders based on their statistically significant association with health outcomes, we selected other adjustment variables, on the basis of their known relationship to asthma and allergic rhinitis. To examine effect modification of maternal asthma or allergies in the association of health outcomes with Der p 1 levels, an interaction term between Der p 1 and maternal history of asthma or allergies was included in the multivariate models. A stratified analysis was also performed to assess whether the associations between Der p 1 exposure and health outcomes differed according to maternal history of asthma or allergies. All statistical analyses were performed using SAS statistical software version 9.3 (SAS Institute Inc, Cary, NC).Table E1Characteristics of the study population with Der p I assessed in breast milk compared with the rest of the populationVariableWhole population (n = 621)Study population (n = 255)Rest of the population (n = 366)P value∗P value for χ2 tests (categorical variables) or Mann-Whitney U tests (continuous variables) comparing the 3 groups.City (%) Poitiers38.139.636.9 Nancy61.960.463.1.77Maternal age (y), mean ± SD31.5 ± 4.630.3 ± 4.430.7 ± 4.7.50 34 (%)17.217.717.0.99BMI, mean ± SD (kg/m2)25.8 ± 4.426.3 ± 4.725.5 ± 4.1.19 Normal (%)50.246.852.3 Overweight (%)35.735.736.1 Moderate obesity (%)10.312.38.8 Severe obesity (%)3.75.22.8.55Maternal history of asthma or allergies (%)29.733.027.1.26Paternal history of asthma or allergies (%)24.823.925.5.91Maternal gestational diabetes (%)7.05.97.9.59Maternal educational level (%) Primary school or less3.32.83.6 Secondary school53.654.053.4 University degree or higher43.243.242.8.99Paternal educational level (%) Primary school or less5.64.86.2 Secondary school60.262.758.9 University degree or higher34.232.534.8.92Any smoking during pregnancy (%)32.331.033.5.73Household income (euros) (%) ≤ 230065.466.365.0 >230034.633.735.0.97Presence of a pet in the house during pregnancy (%)53.953.354.4.96Presence of a pet in the house (0-5 y) (%)64.464.764.4.99Presence of a cat in the house during pregnancy (%)25.825.126.2.95Presence of a cat in the house (0-5 y) (%)35.833.737.2.68Any smoking (0-3 y) (%)43.842.844.5.91Dampness in housing (0-3 y) (%)7.78.27.4.94Daycare attendance first started (%) Before 1 y67.067.566.7.97Older siblings (%) 049.451.847.5 1-246.244.747.5 ≥34.33.54.9.79Gestational age at birth (wk), mean ± SD39.3 ± 1.639.2 ± 1.839.3 ± 1.5.99Preterm birth†<37 completed weeks of gestation. (%)5.45.55.2.95Birth weight (kg), mean ± SD3.3 ± 0.53.3 ± 0.63.3 ± 0.5.58Low birth weight‡<2500 g. (%)5.45.55.2.95Cesarian delivery (%)14.916.513.7.60Sex of the newborn (%) Female49.145.551.4.41Season of birth (%) Summer24.823.525.4 Autumn19.220.018.6 Winter23.724.323.2 Spring32.332.232.8.99Duration of breast-feeding (mo), mean ± SD4.7 ± 3.74.8 ± 3.74.7 ± 3.7.96Exclusively breast-fed for ≥6 mo (%)12.312.212.6.98Respiratory outcomes (%) Asthma ever11.212.910.1.59 Allergic rhinitis ever19.822.018.3.52 Asthma or allergic rhinitis ever27.429.325.9.65BMI, Body mass index.∗ P value for χ2 tests (categorical variables) or Mann-Whitney U tests (continuous variables) comparing the 3 groups.† <37 completed weeks of gestation.‡ <2500 g. Open table in a new tab Table E2Characteristics of mothers with and without a history of asthma or allergiesVariableMothers with a history of asthma or allergies (n = 84)Mothers without a history of asthma or allergies (n = 171)P value∗P value for χ2 tests (categorical variables) or Mann-Whitney U tests (continuous variables). P values <.05 were considered significant and are in boldface.City (%) Poitiers41.738.6 Nancy58.361.4.64Maternal age (y), mean ± SD30.3 ± 4.230.3 ± 4.6.99 34 (%)15.518.7.72BMI (kg/m2), mean ± SD26.3 ± 4.626.3 ± 4.7.82 Normal (%)43.948.2 Overweight (%)39.034.1 Moderate obesity (%)12.212.4 Severe obesity (%)4.95.3.89Paternal history of asthma or allergies (%)29.821.1.13Maternal gestational diabetes (%)4.86.4.59Maternal educational level (%) Primary school or less2.43.0 Secondary school50.056.0 University degree or higher47.641.1.62Paternal educational level (%) Primary school or less1.26.6 Secondary school69.559.3 University degree or higher29.334.1.10Any smoking during pregnancy (%)32.530.2.70Household income (euros) (%) ≤ 230054.861.9 >230045.238.1.37Presence of a pet in the house during pregnancy (%)51.254.4.63Presence of a pet in the house (0-5 y) (%)59.567.3.22Presence of a cat in the house during pregnancy (%)17.228.1.02Presence of a cat in the house (0-5 y) (%)33.333.9.93Any smoking (0-3 y) (%)39.344.4.43Dampness in housing (0-3 y) (%)10.77.0.31Daycare attendance first started (%) Before 1 y63.169.6.30Older siblings (%) 058.348.5 1-240.546.8 ≥31.24.7.17Gestational age at birth (wk), mean ± SD39.5 ± 1.739.1 ± 1.8.27Preterm birth†<37 completed weeks of gestation. (%)4.85.9.72Birth weight (kg), mean ± SD3.3 ± 0.63.3 ± 0.5.44Low birth weight‡<2500 g. (%)3.66.4.35Cesarian delivery (%)15.517.0.76Sex of the newborn (%) Female46.842.9.55Season of birth (%) Summer24.022.6 Autumn17.026.2 Winter24.623.8 Spring34.527.4.34Duration of breast-feeding (mo), mean ± SD4.7 ± 3.74.8 ± 3.7.96Exclusively breast-fed for ≥6 mo (%)14.311.1.47Respiratory outcomes (%) Asthma ever13.112.9.96 Allergic rhinitis ever26.219.9.25 Asthma or allergic rhinitis ever33.327.5.34BMI, Body mass index.∗ P value for χ2 tests (categorical variables) or Mann-Whitney U tests (continuous variables). P values <.05 were considered significant and are in boldface.† <37 completed weeks of gestation.‡ <2500 g. Open table in a new tab Table E3Characteristics of children with and without IgE assessmentsVariableSample with IgE assessment (n = 142)Sample without IgE assessment (n = 113)P value∗P value for χ2 tests (categorical variables) or Mann-Whitney U tests (continuous variables). P values <.05 were considered significant and are in boldface.City (%) Poitiers62.011.5 Nancy38.088.5<.0001Maternal age (y), mean ± SD30.5 ± 4.830.0 ± 4.0.72 34 (%)20.414.2.60BMI (kg/m2), mean ± SD26.7 ± 4.825.7 ± 4.5.11 Normal (%)40.055.4 Overweight (%)41.428.6 Moderate obesity (%)12.911.6 Severe obesity (%)5.74.5.39Maternal history of asthma or allergies (%)30.336.3.60Paternal history of asthma or allergies (%)21.127.4.50Maternal gestational diabetes (%)6.35.3.94Maternal educational level (%) Primary school or less3.61.8 Secondary school58.648.2 University degree or higher37.950.0.40Paternal educational level (%) Primary school or less6.62.7 Secondary school65.758.9 University degree or higher27.738.4.34Any smoking during pregnancy (%)33.827.3.54Household income (euros) (%) ≤ 230071.160.2 >230028.939.8.18Presence of a pet in the house during pregnancy (%)58.546.9.19Presence of a pet in the house (0-5 y) (%)72.554.9.01Presence of a cat in the house during pregnancy (%)26.123.9.69Presence of a cat in the house (0-5 y) (%)38.727.4.06Any smoking (0-3 y) (%)45.838.9.55Dampness in housing (0-3 y) (%)7.88.9.95Daycare attendance first started (%) Before 1 y63.472.6.30Older siblings (%) 048.655.8 1-247.940.7 ≥33.53.5.85Gestational age at birth (wk), mean ± SD39.3 ± 1.839.2 ± 1.7.65Preterm birth†<37 completed weeks of gestation. (%)4.27.1.61Birth weight (kg), mean ± SD3.3 ± 0.63.3 ± 0.5.62Low birth weight‡<2500 g. (%)6.34.4.80Cesarian delivery (%)11.323.0.04Sex of the newborn (%) Female45.146.0.99Season of birth (%) Summer23.923.0 Autumn20.419.5 Winter22.526.6 Spring33.131.0.99Duration of breast-feeding (mo), mean ± SD4.3 ± 3.65.4 ± 3.8.06Exclusively breast-fed for ≥6 mo (%)10.614.2.68Respiratory outcomes (%) Asthma ever12.713.3.99 Allergic rhinitis ever22.521.2.97 Asthma or allergic rhinitis ever28.930.1.98BMI, Body mass index.∗ P value for χ2 tests (categorical variables) or Mann-Whitney U tests (continuous variables). P values <.05 were considered significant and are in boldface.† <37 completed weeks of gestation.‡ <2500 g. Open table in a new tab Table E4Der p 1 levels in breast milk according to maternal history of asthma or allergiesTotal population (n = 255)Mothers with a history of asthma or allergies (n = 84)Mothers without a history of asthma or allergies (n = 171)P value∗P value of Mann-Whitney U test and χ2 test for comparison of continuous variables and percentages, respectively, between mothers with or without a history of asthma or allergies. P values <.05 were considered significant and are in boldface.% of positive samples (n)69.8 (178)73.8 (62)67.8 (116).30Median (IQR) (pg/mL)52.1 (0.0-109.3)67.6 (0.0-137.4)48.2 (0.0-95.4).05Median (IQR) among positive samples (pg/mL)73.8 (49.0-146.8)90.0 (57.4-150.7)67.8 (48.1-127.5).05% of samples (n) above median value obtained from the total population50.20 (128)60.7 (51)45.03 (77).02IQR, Interquartile range.∗ P value of Mann-Whitney U test and χ2 test for comparison of continuous variables and percentages, respectively, between mothers with or without a history of asthma or allergies. P values <.05 were considered significant and are in boldface. Open table in a new tab Table E5Factors associated with Der p 1 concentration in breast milk according to maternal history of asthma or allergiesVariableTotal population (n = 255)Mothers with a history of asthma or allergies (n = 84)Mothers without a history of asthma or allergies (n = 171)Der p 1 (pg/mL), median (IQR)P value∗P value of Mann-Whitney U test or Kruskal-Wallis test. P values <.05 were considered significant and are in boldface.Der p 1 (pg/mL), median (IQR)P value∗P value of Mann-Whitney U test or Kruskal-Wallis test. P values <.05 were considered significant and are in boldface.Der p 1 (pg/mL), median (IQR)P value∗P value of Mann-Whitney U test or Kruskal-Wallis test. P values <.05 were considered significant and are in boldface.City Poitiers44.4 (0.0-70.6)48.9 (0.0-102.6)38.5 (0.0-64.2) Nancy61.4 (0.0-125.5).00871.5 (33.0-141.9).1650.3 (0.0-113.6).03Maternal age (y) 3434.3 (0.0-65.2).0237.4 (0.0-67.6).2934.1 (0.0-60.8).08Smoking during pregnancy No smoking54.5 (0.0-116.0)67.3 (15.4-139.8)50.6 (0.0-106.9) Smoking44.4 (0.0-73.9).0670.8 (0.0-111.7).9530.8 (0.0-50.3).01Season of birth Summer41.6 (0.0-86.2)69.2 (33.0-167.2)34.3 (0.0-61.8) Autumn48.1 (0.0-81.9)60.4 (0.0-84.9)35.0 (0.0-73.7) Winter64.9 (42.4-144.9)69.2 (37.8-115.1)60.3 (42.4-158.1) Spring54.4 (0.0-116.0).0467.6 (0.0-152.1).4949.0 (0.0-98.2).01IQR, Interquartile range.∗ P value of Mann-Whitney U test or Kruskal-Wallis test. P values <.05 were considered significant and are in boldface. Open table in a new tab Table E6Relationships between HDM sources in the environment where the mother and the child lived during the follow-up and Der p 1 levels in breast milkPotential HDM sourceLow HDM in milk, % (n)High HDM in milk, % (n)P-χ2/FisherDo it yourself activities (n = 251) Never54.0 (68)44.8 (56) Rarely34.9 (44)42.4 (53) Often11.1 (14)12.8 (16).35Presence of a carpet at home (n = 239)37.1 (43)26.0 (32).07Double curtains or wall fabrics (n = 236)22.2 (26)19.3 (23).58Child's mattress (n = 52) New54.6 (12)50.0 (15) Bought 1-3 y ago18.2 (4)33.3 (10) Bought more than 3 y ago22.7 (5)13.3 (4) Do not know4.6 (1)3.3 (1).61Child's type of pillow (n = 51) Synthetic18.2 (4)6.9 (2) Do not use pillow81.8 (18)93.1 (27).22Child's type of blanket (n = 51) Synthetic22.7 (5)10.3 (3) Wool4.6 (1)0.0 (0) Other9.1( 2)10.3 (3) Do not use blanket63.6 (14)79.3 (23).39 Open table in a new tab Table E7Relationship between the occupancy load in the dwellings where the mother and the child have lived and Der p 1 levels in the breast milkOccupancy loadLow HDM in milk, % (n)High HDM in milk, % (n)P-χ2n = 255 Low42.4 (53)42.2 (51) High57.6 (72)57.9 (70).97n = 142 Low39.5 (30)45.0 (27) High60.5 (46)55.0 (33).52Occupancy load was defined as the mean of the number of occupants divided by the number of rooms in the dwelling during the follow-up.E11Hasselaar E. How healthy is the bedroom? Indoor Air Exposure Healthy Buildings.Proceedings. 2006; : 185-188Google Scholar Open table in a new tab Table E8Unadjusted and adjusted relationships of Der p 1 levels (above vs below the median value; 52.1 pg/mL) in breast milk to respiratory outcomes and total and specific IgE levelsMaternal statusHealth outcomecOR95% CIP value∗aOR for city, mother's age, maternal history of asthma or allergies (in nonstratified model-whole population only), any smoking during pregnancy, any passive smoke exposure during the first 3 y of life, season of birth, and newborn's sex.aOR∗aOR for city, mother's age, maternal history of asthma or allergies (in nonstratified model-whole population only), any smoking during pregnancy, any passive smoke exposure during the first 3 y of life, season of birth, and newborn's sex.95% CIP valueWhole population (n = 255) Total populationAsthma ever1.220.59-2.55.591.580.72-3.48.26AR ever0.990.55-1.80.971.140.60-2.18.69Asthma or AR ever1.110.65-1.90.711.290.72-2.32.40 Mothers with a history of asthma or allergies (n = 84)Asthma ever7.800.95-64.17.068.250.90-74.95.08AR ever2.060.71-5.96.181.960.60-6.34.26Asthma or AR ever3.411.20-9.70.023.401.07-10.8.04 Mothers without a history of asthma or allergies (n = 171)Asthma ever0.660.26-1.67.380.790.29-2.16.64AR ever0.600.28-1.32.210.710.31-1.65.43Asthma or AR ever0.600.30-1.21.150.690.33-1.46.33Subpopulation with IgE assessments (n = 142) Total populationPositive total IgE1.950.97-3.89.063.871.57-9.54.003Positive Der p 1 IgE1.930.88-4.25.102.210.93-5.23.07 Mothers with a history of asthma or allergies (n = 43)Positive total IgE1.670.41-6.63.482.850.58-14.12.20Positive Der p 1 IgE1.650.41-6.63.482.150.46-10.10.33 Mothers without a history of asthma or allergies (n = 99)Positive total IgE2.461.07-5.65.034.341.54-12.24.005Positive Der p 1 IgE1.810.67-4.91.252.050.72-5.82.18cOR, Crude odds ratio (unadjusted). P values <.05 were considered significant and are in boldface.∗ aOR for city, mother's age, maternal history of asthma or allergies (in nonstratified model-whole population only), any smoking during pregnancy, any passive smoke exposure during the first 3 y of life, season of birth, and newborn's sex. Open table in a new tab BMI, Body mass index. BMI, Body mass index. BMI, Body mass index. IQR, Interquartile range. IQR, Interquartile range. Occupancy load was defined as the mean of the number of occupants divided by the number of rooms in the dwelling during the follow-up.E11Hasselaar E. How healthy is the bedroom? Indoor Air Exposure Healthy Buildings.Proceedings. 2006; : 185-188Google Scholar cOR, Crude odds ratio (unadjusted). P values <.05 were considered significant and are in boldface. Oral exposure to mite allergens: Sensitizer or tolerogenic?Journal of Allergy and Clinical ImmunologyVol. 143Issue 2PreviewIn a recent article, Baïz et al1 reported on the presence of Der p 1 mite allergen in two-thirds of breast milk samples from French lactating mothers. Allergen levels in the milk were higher in mothers with a history of asthma or allergies, and children breast-fed by such mothers with high Der p 1 levels in the milk were at a significantly higher risk of asthma or allergic rhinitis when compared with children from mothers with low Der p 1 levels in the milk. In addition, a high amount of Der p 1 in the milk was associated with increased total serum IgE. Full-Text PDF
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