{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T09:58:41Z","timestamp":1791539921000,"version":"4.3.4"},"reference-count":31,"publisher":"American Academy of Pediatrics (AAP)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2007,1,1]]},"abstract":"<jats:p>OBJECTIVES. Antibiotic exposure in early life may be associated with atopic disease development either by interfering with bacterial commensal flora or by modifying the course of bacterial infections. We evaluated early life exposure to antibiotics and the subsequent development of eczema, wheeze, and allergic sensitization in infancy.<\/jats:p>\n               <jats:p>METHODS. Information on antibiotic use in the first 6 months and eczema and wheeze until age 2 was collected by repeated questionnaires in 2764 families participating in the KOALA (Child, Parent and Health: Lifestyle and Genetic Constitution [in Dutch]) Birth Cohort Study in the Netherlands. Antibiotic intake was evaluated both as maternal antibiotic use during breastfeeding and infant oral medication. Venous blood samples taken from 815 infants at 2 years of age were analyzed for total and specific immunoglobulin E against common food and inhalant allergens using a radioallergosorbent test. Multivariate logistic regression analysis was used to adjust for confounding factors.<\/jats:p>\n               <jats:p>RESULTS. During the first 2 years, eczema was present in 32% of all infants, recurrent wheeze in 11%, and prolonged wheezing in 5%. At 2 years old, 27% of children were sensitized against \u22651 allergen. At 6 months old, 11% had been exposed to antibiotics through breast milk and 20% directly through medication. The risk for recurrent wheeze, and prolonged wheeze was higher in infants directly exposed to antibiotics through medication, also after excluding from the analyses children who wheezed in the same period as an antibiotic had been used (avoiding reverse causation). Antibiotic use through breastfeeding was associated with recurrent wheeze, but prolonged wheeze was not. Eczema and sensitization were not associated with antibiotic exposure.<\/jats:p>\n               <jats:p>CONCLUSIONS.We demonstrated that early antibiotic use preceded the manifestation of wheeze but not eczema or allergic sensitization during the first 2 years of life. Different biological mechanisms may underlie the etiology of wheeze compared with eczema or sensitization. Antibiotic exposure through breastfeeding enhanced the risk for recurrent wheeze, but this needs further confirmation.<\/jats:p>","DOI":"10.1542\/peds.2006-0896","type":"journal-article","created":{"date-parts":[[2007,1,3]],"date-time":"2007-01-03T15:47:33Z","timestamp":1167839253000},"page":"e225-e231","source":"Crossref","is-referenced-by-count":146,"title":["Early Life Exposure to Antibiotics and the Subsequent Development of Eczema, Wheeze, and Allergic Sensitization in the First 2 Years of Life: The KOALA Birth Cohort Study"],"prefix":"10.1542","volume":"119","author":[{"given":"Ischa","family":"Kummeling","sequence":"first","affiliation":[{"name":"Department of Epidemiology, Care and Public Health Research Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Foekje F.","family":"Stelma","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Care and Public Health Research Institute"},{"name":"Department of Medical Microbiology, University Hospital of Maastricht, Maastricht, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pieter C.","family":"Dagnelie","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Nutrition and Toxicology Research Institute, Maastricht University, Maastricht, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca E. P.","family":"Snijders","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Care and Public Health Research Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Penders","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Care and Public Health Research Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Machteld","family":"Huber","sequence":"additional","affiliation":[{"name":"Louis Bolk Institute, Driebergen, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald","family":"van Ree","sequence":"additional","affiliation":[{"name":"Department of Experimental Immunology, Academic Medical Center, Amsterdam, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piet A.","family":"van den Brandt","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Care and Public Health Research Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carel","family":"Thijs","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Care and Public Health Research Institute"},{"name":"Department of Epidemiology, Nutrition and Toxicology Research Institute, Maastricht University, Maastricht, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"417","published-online":{"date-parts":[[2007,1,1]]},"reference":[{"key":"2021120902051277700_R1","doi-asserted-by":"crossref","unstructured":"Maziak W, Behrens T, Brasky TM, et al. Are asthma and allergies in children and adolescents increasing? Results from ISAAC phase I and phase III surveys in Munster, Germany. Allergy.\u20082003;58:572\u2013579","DOI":"10.1034\/j.1398-9995.2003.00161.x"},{"key":"2021120902051277700_R2","doi-asserted-by":"crossref","unstructured":"Beasley R, Crane J, Lai CK, Pearce N. Prevalence and etiology of asthma. J Allergy Clin Immunol.\u20082000;105:S466\u2013S472","DOI":"10.1016\/S0091-6749(00)90044-7"},{"key":"2021120902051277700_R3","doi-asserted-by":"crossref","unstructured":"The International Study of Asthma and Allergies in Childhood (ISAAC) Steering Committee. Worldwide variation in prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and atopic eczema: ISAAC. Lancet.\u20081998;351:1225\u20131232","DOI":"10.1016\/S0140-6736(97)07302-9"},{"key":"2021120902051277700_R4","doi-asserted-by":"crossref","unstructured":"Levy J. The effects of antibiotic use on gastrointestinal function. Am J Gastroenterol.\u20082000;95:S8\u2013S10","DOI":"10.1016\/S0002-9270(99)00808-4"},{"key":"2021120902051277700_R5","doi-asserted-by":"crossref","unstructured":"Brismar B, Edlund C, Nord CE. Impact of cefpodoxime proxetil and amoxicillin on the normal oral and intestinal microflora. Eur J Clin Microbiol Infect Dis.\u20081993;12:714\u2013719","DOI":"10.1007\/BF02009388"},{"key":"2021120902051277700_R6","doi-asserted-by":"crossref","unstructured":"Bjorksten B, Naaber P, Sepp E, Mikelsaar M. The intestinal microflora in allergic Estonian and Swedish 2-year-old children. Clin Exp Allergy.\u20081999;29:342\u2013346","DOI":"10.1046\/j.1365-2222.1999.00560.x"},{"key":"2021120902051277700_R7","doi-asserted-by":"crossref","unstructured":"Floistrup H, Swartz J, Bergstrom A, et al. Allergic disease and sensitization in Steiner school children. J Allergy Clin Immunol.\u20082006;117:59\u201366","DOI":"10.1016\/j.jaci.2005.09.039"},{"key":"2021120902051277700_R8","unstructured":"Wjst M, Hoelscher B, Frye C, Wichmann HE, Dold S, Heinrich J. Early antibiotic treatment and later asthma. Eur J Med Res.\u20082001;6:263\u2013271"},{"key":"2021120902051277700_R9","doi-asserted-by":"crossref","unstructured":"Droste JH, Wieringa MH, Weyler JJ, Nelen VJ, Vermeire PA, Van Bever HP. Does the use of antibiotics in early childhood increase the risk of asthma and allergic disease?Clin Exp Allergy.\u20082000;30:1547\u20131553","DOI":"10.1046\/j.1365-2222.2000.00939.x"},{"key":"2021120902051277700_R10","doi-asserted-by":"crossref","unstructured":"von Mutius E, Illi S, Hirsch T, Leupold W, Keil U, Weiland SK. Frequency of infections and risk of asthma, atopy and airway hyperresponsiveness in children. Eur Respir J.\u20081999;14:4\u201311","DOI":"10.1034\/j.1399-3003.1999.14a03.x"},{"key":"2021120902051277700_R11","doi-asserted-by":"crossref","unstructured":"Wickens K, Pearce N, Crane J, Beasley R. Antibiotic use in early childhood and the development of asthma. Clin Exp Allergy.\u20081999;29:766\u2013771","DOI":"10.1046\/j.1365-2222.1999.00536.x"},{"key":"2021120902051277700_R12","doi-asserted-by":"crossref","unstructured":"Alm JS, Swartz J, Lilja G, Scheynius A, Pershagen G. Atopy in children of families with an anthroposophic lifestyle. Lancet.\u20081999;353:1485\u20131488","DOI":"10.1016\/S0140-6736(98)09344-1"},{"key":"2021120902051277700_R13","doi-asserted-by":"crossref","unstructured":"Farooqi IS, Hopkin JM. Early childhood infection and atopic disorder. Thorax.\u20081998;53:927\u2013932","DOI":"10.1136\/thx.53.11.927"},{"key":"2021120902051277700_R14","doi-asserted-by":"crossref","unstructured":"Cohet C, Cheng S, MacDonald C, et al. Infections, medication use, and the prevalence of symptoms of asthma, rhinitis, and eczema in childhood. J Epidemiol Community Health.\u20082004;58:852\u2013857","DOI":"10.1136\/jech.2003.019182"},{"key":"2021120902051277700_R15","doi-asserted-by":"crossref","unstructured":"Mathew JL. Effect of maternal antibiotics on breast feeding infants. Postgrad Med J.\u20082004;80:196\u2013200","DOI":"10.1136\/pgmj.2003.011973"},{"key":"2021120902051277700_R16","doi-asserted-by":"crossref","unstructured":"Chung AM, Reed MD, Blumer JL. Antibiotics and breast-feeding: a critical review of the literature. Paediatr Drugs.\u20082002;4:817\u2013837","DOI":"10.2165\/00128072-200204120-00006"},{"key":"2021120902051277700_R17","doi-asserted-by":"crossref","unstructured":"Kummeling I, Thijs C, Penders J, et al. Etiology of atopy in infancy: the KOALA Birth Cohort Study. Pediatr Allergy Immunol.\u20082005;16:679\u2013684","DOI":"10.1111\/j.1399-3038.2005.00333.x"},{"key":"2021120902051277700_R18","doi-asserted-by":"crossref","unstructured":"Bastiaanssen JM, de Bie RA, Bastiaenen CH, et al. Etiology and prognosis of pregnancy-related pelvic girdle pain; design of a longitudinal study. BMC Public Health.\u20082005;5:1\u20138","DOI":"10.1186\/1471-2458-5-1"},{"key":"2021120902051277700_R19","doi-asserted-by":"crossref","unstructured":"Stallman PJ, Aalberse RC. Estimation of basophil-bound IgE by quantitative immunofluorescence microscopy. Int Arch Allergy Appl Immunol.\u20081977;54:9\u201318","DOI":"10.1159\/000231803"},{"key":"2021120902051277700_R20","doi-asserted-by":"crossref","unstructured":"Akkerdaas JH, Wensing M, Asero R, et al. IgE binding to pepsin-digested food extracts. Int Arch Allergy Immunol.\u20082005;138:203\u2013208","DOI":"10.1159\/000088720"},{"key":"2021120902051277700_R21","doi-asserted-by":"crossref","unstructured":"Schuurman J, Perdok GJ, Lourens TE, et al. Production of a mouse\/human chimeric IgE monoclonal antibody to the house dust mite allergen Der p 2 and its use for the absolute quantification of allergen-specific IgE. J Allergy Clin Immunol.\u20081997;99:545\u2013550","DOI":"10.1016\/S0091-6749(97)70083-6"},{"key":"2021120902051277700_R22","doi-asserted-by":"crossref","unstructured":"Remes ST, Castro Rodriguez JA, Holberg CJ, Martinez FD, Wright AL. Dog exposure in infancy decreases the subsequent risk of frequent wheeze but not of atopy. J Allergy Clin Immunol.\u20082001;108:509\u2013515","DOI":"10.1067\/mai.2001.117797"},{"key":"2021120902051277700_R23","doi-asserted-by":"crossref","unstructured":"Wright AL, Sherrill D, Holberg CJ, Halonen M, Martinez FD. Breast-feeding, maternal IgE, and total serum IgE in childhood. J Allergy Clin Immunol.\u20081999;104:589\u2013594","DOI":"10.1016\/S0091-6749(99)70328-3"},{"key":"2021120902051277700_R24","doi-asserted-by":"crossref","unstructured":"Koopman LP, Brunekreef B, de Jongste JC, Neijens HJ. Definition of respiratory symptoms and disease in early childhood in large prospective birth cohort studies that predict the development of asthma. Pediatr Allergy Immunol.\u20082001;12:118\u2013124","DOI":"10.1034\/j.1399-3038.2001.012003118.x"},{"key":"2021120902051277700_R25","doi-asserted-by":"crossref","unstructured":"Lowe L, Murray CS, Martin L, et al. Reported versus confirmed wheeze and lung function in early life. Arch Dis Child.\u20082004;89:540\u2013543","DOI":"10.1136\/adc.2003.038539"},{"key":"2021120902051277700_R26","doi-asserted-by":"crossref","unstructured":"Kusel MM, Holt PG, de Klerk N, Sly PD. Support for 2 variants of eczema. J Allergy Clin Immunol.\u20082005;116:1067\u20131072","DOI":"10.1016\/j.jaci.2005.06.038"},{"key":"2021120902051277700_R27","doi-asserted-by":"crossref","unstructured":"Nyquist AC, Gonzales R, Steiner JF, Sande MA. Antibiotic prescribing for children with colds, upper respiratory tract infections, and bronchitis. JAMA.\u20081998;279:875\u2013877","DOI":"10.1001\/jama.279.11.875"},{"key":"2021120902051277700_R28","doi-asserted-by":"crossref","unstructured":"Everard ML. The relationship between respiratory syncytial virus infections and the development of wheezing and asthma in children. Curr Opin Allergy Clin Immunol.\u20082006;6:56\u201361","DOI":"10.1097\/01.all.0000200506.62048.06"},{"key":"2021120902051277700_R29","doi-asserted-by":"crossref","unstructured":"Celedon JC, Litonjua AA, Ryan L, Weiss ST, Gold DR. Lack of association between antibiotic use in the first year of life and asthma, allergic rhinitis, or eczema at age 5 years. Am J Respir Crit Care Med.\u20082002;166:72\u201375","DOI":"10.1164\/rccm.2109074"},{"key":"2021120902051277700_R30","unstructured":"Van Eldere J. The role of bacteria as a local defence mechanism in the ear, nose and throat. Acta Otorhinolaryngol Belg.\u20082000;54:243\u2013247"},{"key":"2021120902051277700_R31","doi-asserted-by":"crossref","unstructured":"McKeever TM, Lewis SA, Smith C, et al. Early exposure to infections and antibiotics and the incidence of allergic disease: a birth cohort study with the West Midlands General Practice Research Database. J Allergy Clin Immunol.\u20082002;109:43\u201350","DOI":"10.1067\/mai.2002.121016"}],"container-title":["Pediatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/publications.aap.org\/pediatrics\/article-pdf\/119\/1\/e225\/1117857\/zpe0010700e225.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/publications.aap.org\/pediatrics\/article-pdf\/119\/1\/e225\/1117857\/zpe0010700e225.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,9]],"date-time":"2021-12-09T09:13:41Z","timestamp":1639041221000},"score":1,"resource":{"primary":{"URL":"https:\/\/publications.aap.org\/pediatrics\/article\/119\/1\/e225\/70693\/Early-Life-Exposure-to-Antibiotics-and-the"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,1,1]]},"references-count":31,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2007,1,1]]},"published-print":{"date-parts":[[2007,1,1]]}},"URL":"https:\/\/doi.org\/10.1542\/peds.2006-0896","relation":{},"ISSN":["0031-4005","1098-4275"],"issn-type":[{"value":"0031-4005","type":"print"},{"value":"1098-4275","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,1,1]]}}}