Skip to main content
Journal of Epidemiology and Community Health logoLink to Journal of Epidemiology and Community Health
. 2002 Mar;56(3):209–217. doi: 10.1136/jech.56.3.209

Does a higher number of siblings protect against the development of allergy and asthma? A review

W Karmaus 1, C Botezan 1
PMCID: PMC1732088  PMID: 11854343

Abstract

Study objective: To review the "protective" effects of having a higher number of siblings for the risk of atopic eczema, asthma wheezing, hay fever, and allergic sensitisation.

Method: Review of the literature (Medline since 1965 and references).

Main results: 53 different studies were identified. For eczema, 9 of 11 studies reported an inverse relation with number of siblings; for asthma and wheezing, 21 of 31 reported the inverse association; for hay fever, all 17 studies showed the effect; for allergic sensitisation or immunoglobulin E reactivity 14 of 16 studies supported the "protective" effect of a higher number of siblings. The studies emphasise a "theory" that is based exclusively on epidemiological associations.

Conclusions: Research has not yet answered the question of which causal factors explain the sibling effect. Causal factors must meet two criteria; they must vary with sibship size and they must protect against atopic manifestations. The prevailing "hygiene hypothesis" failed to explain the findings adequately. Alternative explanations include in utero programming or endocrine explanatory models. The epidemiology research into siblings and atopic disorders has entered an intellectually challenging phase. Possessing sufficient knowledge about the causal factors might prevent at least 30% of all cases of asthma, eczema, and hay fever.

Full Text

The Full Text of this article is available as a PDF (167.0 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aaby P., Shaheen S. O., Heyes C. B., Goudiaby A., Hall A. J., Shiell A. W., Jensen H., Marchant A. Early BCG vaccination and reduction in atopy in Guinea-Bissau. Clin Exp Allergy. 2000 May;30(5):644–650. doi: 10.1046/j.1365-2222.2000.00803.x. [DOI] [PubMed] [Google Scholar]
  2. Aberer W., Geusau A., Pirkhammer D., Schreiber S. Epidemiologie und Diagnose allergischer Erkrankungen. Wien Klin Wochenschr. 1993;105(22):624–627. [PubMed] [Google Scholar]
  3. Alm J. S., Swartz J., Lilja G., Scheynius A., Pershagen G. Atopy in children of families with an anthroposophic lifestyle. Lancet. 1999 May 1;353(9163):1485–1488. doi: 10.1016/S0140-6736(98)09344-1. [DOI] [PubMed] [Google Scholar]
  4. Attena F., Agozzino E., Toscano G., Fedele N. Prevalence of asthma among young men in a military recruitment office of South Italy. Eur J Epidemiol. 1999 Jul;15(6):569–572. doi: 10.1023/a:1007564323390. [DOI] [PubMed] [Google Scholar]
  5. Backman A., Björkstén F., Ilmonen S., Juntunen K., Suoniemi I. Do infections in infancy affect sensitization to airborne allergens and development of atopic disease? A retrospective study of seven-year-old children. Allergy. 1984 May;39(4):309–315. doi: 10.1111/j.1398-9995.1984.tb00867.x. [DOI] [PubMed] [Google Scholar]
  6. Ball T. M., Castro-Rodriguez J. A., Griffith K. A., Holberg C. J., Martinez F. D., Wright A. L. Siblings, day-care attendance, and the risk of asthma and wheezing during childhood. N Engl J Med. 2000 Aug 24;343(8):538–543. doi: 10.1056/NEJM200008243430803. [DOI] [PubMed] [Google Scholar]
  7. Becklake M. R., Kauffmann F. Gender differences in airway behaviour over the human life span. Thorax. 1999 Dec;54(12):1119–1138. doi: 10.1136/thx.54.12.1119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Bennis A., el Fassy Fihry M. T., Fikri-Benbrahim N., Sayah-Moussaoui Z., Samir-Rafi A., Biaz A. Prévalence de l'asthme de l'adolescent à Rabat. Enquête dans les établissements de l'enseignement secondaire. Rev Mal Respir. 1992;9(2):163–169. [PubMed] [Google Scholar]
  9. Bodner C., Anderson W. J., Reid T. S., Godden D. J. Childhood exposure to infection and risk of adult onset wheeze and atopy. Thorax. 2000 May;55(5):383–387. doi: 10.1136/thorax.55.5.383. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Bråbäck L., Breborowicz A., Julge K., Knutsson A., Riikjärv M. A., Vasar M., Björkstén B. Risk factors for respiratory symptoms and atopic sensitisation in the Baltic area. Arch Dis Child. 1995 Jun;72(6):487–493. doi: 10.1136/adc.72.6.487. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Bråbäck L., Hedberg A. Perinatal risk factors for atopic disease in conscripts. Clin Exp Allergy. 1998 Aug;28(8):936–942. doi: 10.1046/j.1365-2222.1998.00282.x. [DOI] [PubMed] [Google Scholar]
  12. Burr M. L., Merrett T. G., Dunstan F. D., Maguire M. J. The development of allergy in high-risk children. Clin Exp Allergy. 1997 Nov;27(11):1247–1253. [PubMed] [Google Scholar]
  13. Butland B. K., Strachan D. P., Lewis S., Bynner J., Butler N., Britton J. Investigation into the increase in hay fever and eczema at age 16 observed between the 1958 and 1970 British birth cohorts. BMJ. 1997 Sep 20;315(7110):717–721. doi: 10.1136/bmj.315.7110.717. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Carey O. J., Cookson J. B., Britton J., Tattersfield A. E. The effect of lifestyle on wheeze, atopy, and bronchial hyperreactivity in Asian and white children. Am J Respir Crit Care Med. 1996 Aug;154(2 Pt 1):537–540. doi: 10.1164/ajrccm.154.2.8756835. [DOI] [PubMed] [Google Scholar]
  15. Celedon J. C., Litonjua A. A., Weiss S. T., Gold D. R. Day care attendance in the first year of life and illnesses of the upper and lower respiratory tract in children with a familial history of atopy. Pediatrics. 1999 Sep;104(3 Pt 1):495–500. doi: 10.1542/peds.104.3.495. [DOI] [PubMed] [Google Scholar]
  16. Christie G. L., McDougall C. M., Helms P. J. Is the increase in asthma prevalence occurring in children without a family history of atopy? Scott Med J. 1998 Dec;43(6):180–182. doi: 10.1177/003693309804300607. [DOI] [PubMed] [Google Scholar]
  17. Crane J., Pearce N., Shaw R., Fitzharris P., Mayes C. Asthma and having siblings. BMJ. 1994 Jul 23;309(6949):272–272. doi: 10.1136/bmj.309.6949.272. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Davis J. B., Bulpitt C. J. Atopy and wheeze in children according to parental atopy and family size. Thorax. 1981 Mar;36(3):185–189. doi: 10.1136/thx.36.3.185. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Douwes J., McLean D., van der Maarl E., Heederik D., Pearce N. Worker exposures to airborne dust, endotoxin and beta(1,3)-glucan in two New Zealand sawmills. Am J Ind Med. 2000 Oct;38(4):426–430. doi: 10.1002/1097-0274(200010)38:4<426::aid-ajim8>3.0.co;2-r. [DOI] [PubMed] [Google Scholar]
  20. Erb K. J. Atopic disorders: a default pathway in the absence of infection? Immunol Today. 1999 Jul;20(7):317–322. doi: 10.1016/s0167-5699(99)01475-9. [DOI] [PubMed] [Google Scholar]
  21. Farooqi I. S., Hopkin J. M. Early childhood infection and atopic disorder. Thorax. 1998 Nov;53(11):927–932. doi: 10.1136/thx.53.11.927. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Forastiere F., Agabiti N., Corbo G. M., Dell'Orco V., Porta D., Pistelli R., Levenstein S., Perucci C. A. Socioeconomic status, number of siblings, and respiratory infections in early life as determinants of atopy in children. Epidemiology. 1997 Sep;8(5):566–570. doi: 10.1097/00001648-199709000-00015. [DOI] [PubMed] [Google Scholar]
  23. Gaudio S. A. Air pollution and its effects on adult asthmatics: a review. Mt Sinai J Med. 1980 May-Jun;47(3):329–334. [PubMed] [Google Scholar]
  24. Haby M. M., Marks G. B., Peat J. K., Leeder S. R. Daycare attendance before the age of two protects against atopy in preschool age children. Pediatr Pulmonol. 2000 Nov;30(5):377–384. doi: 10.1002/1099-0496(200011)30:5<377::aid-ppul3>3.0.co;2-3. [DOI] [PubMed] [Google Scholar]
  25. Henderson J., North K., Griffiths M., Harvey I., Golding J. Pertussis vaccination and wheezing illnesses in young children: prospective cohort study. The Longitudinal Study of Pregnancy and Childhood Team. BMJ. 1999 May 1;318(7192):1173–1176. doi: 10.1136/bmj.318.7192.1173. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Holt P. G. Programming for responsiveness to environmental antigens that trigger allergic respiratory disease in adulthood is initiated during the perinatal period. Environ Health Perspect. 1998 Jun;106 (Suppl 3):795–800. doi: 10.1289/ehp.98106795. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Infante-Rivard C., Amre D., Gautrin D., Malo J. L. Family size, day-care attendance, and breastfeeding in relation to the incidence of childhood asthma. Am J Epidemiol. 2001 Apr 1;153(7):653–658. doi: 10.1093/aje/153.7.653. [DOI] [PubMed] [Google Scholar]
  28. Jarvis D., Chinn S., Luczynska C., Burney P. The association of family size with atopy and atopic disease. Clin Exp Allergy. 1997 Mar;27(3):240–245. [PubMed] [Google Scholar]
  29. Kaijser M., Lichtenstein P., Granath F., Erlandsson G., Cnattingius S., Ekbom A. In utero exposures and breast cancer: a study of opposite-sexed twins. J Natl Cancer Inst. 2001 Jan 3;93(1):60–62. doi: 10.1093/jnci/93.1.60. [DOI] [PubMed] [Google Scholar]
  30. Kaprio J., Rimpelä A., Winter T., Viken R. J., Rimpelä M., Rose R. J. Common genetic influences on BMI and age at menarche. Hum Biol. 1995 Oct;67(5):739–753. [PubMed] [Google Scholar]
  31. Karmaus W., Arshad H., Mattes J. Does the sibling effect have its origin in utero? Investigating birth order, cord blood immunoglobulin E concentration, and allergic sensitization at age 4 years. Am J Epidemiol. 2001 Nov 15;154(10):909–915. doi: 10.1093/aje/154.10.909. [DOI] [PubMed] [Google Scholar]
  32. Kemp T., Pearce N., Fitzharris P., Crane J., Fergusson D., St George I., Wickens K., Beasley R. Is infant immunization a risk factor for childhood asthma or allergy? Epidemiology. 1997 Nov;8(6):678–680. doi: 10.1097/00001648-199710000-00011. [DOI] [PubMed] [Google Scholar]
  33. Kerrebijn K. F., Mourmans A. R. Study on the relationship of air pollution to respiratory disease in schoolchildren. Environ Res. 1975 Aug;10(1):14–28. doi: 10.1016/0013-9351(75)90070-5. [DOI] [PubMed] [Google Scholar]
  34. Krämer U., Heinrich J., Wjst M., Wichmann H. E. Age of entry to day nursery and allergy in later childhood. Lancet. 1999 Feb 6;353(9151):450–454. doi: 10.1016/S0140-6736(98)06329-6. [DOI] [PubMed] [Google Scholar]
  35. Kuehr J., Frischer T., Karmaus W., Meinert R., Barth R., Urbanek R. Clinical atopy and associated factors in primary-school pupils. Allergy. 1992 Dec;47(6):650–655. doi: 10.1111/j.1398-9995.1992.tb02390.x. [DOI] [PubMed] [Google Scholar]
  36. Leadbitter P., Pearce N., Cheng S., Sears M. R., Holdaway M. D., Flannery E. M., Herbison G. P., Beasley R. Relationship between fetal growth and the development of asthma and atopy in childhood. Thorax. 1999 Oct;54(10):905–910. doi: 10.1136/thx.54.10.905. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Levy D., Gent M., Newhouse M. T. Relationship between acute respiratory illness and air pollution levels in an industrial city. Am Rev Respir Dis. 1977 Aug;116(2):167–173. doi: 10.1164/arrd.1977.116.2.167. [DOI] [PubMed] [Google Scholar]
  38. Lewis S. A., Britton J. R. Consistent effects of high socioeconomic status and low birth order, and the modifying effect of maternal smoking on the risk of allergic disease during childhood. Respir Med. 1998 Oct;92(10):1237–1244. doi: 10.1016/s0954-6111(98)90427-9. [DOI] [PubMed] [Google Scholar]
  39. Lewis S. A., Britton J. R. Measles infection, measles vaccination and the effect of birth order in the aetiology of hay fever. Clin Exp Allergy. 1998 Dec;28(12):1493–1500. doi: 10.1046/j.1365-2222.1998.00436.x. [DOI] [PubMed] [Google Scholar]
  40. Lewis S., Richards D., Bynner J., Butler N., Britton J. Prospective study of risk factors for early and persistent wheezing in childhood. Eur Respir J. 1995 Mar;8(3):349–356. doi: 10.1183/09031936.95.08030349. [DOI] [PubMed] [Google Scholar]
  41. Martinez F. D., Holt P. G. Role of microbial burden in aetiology of allergy and asthma. Lancet. 1999 Sep;354 (Suppl 2):SII12–SII15. doi: 10.1016/s0140-6736(99)90437-3. [DOI] [PubMed] [Google Scholar]
  42. Martinez F. D. Role of respiratory infection in onset of asthma and chronic obstructive pulmonary disease. Clin Exp Allergy. 1999 Jun;29 (Suppl 2):53–58. doi: 10.1046/j.1365-2222.1999.00009.x. [DOI] [PubMed] [Google Scholar]
  43. Matricardi P. M., Franzinelli F., Franco A., Caprio G., Murru F., Cioffi D., Ferrigno L., Palermo A., Ciccarelli N., Rosmini F. Sibship size, birth order, and atopy in 11,371 Italian young men. J Allergy Clin Immunol. 1998 Apr;101(4 Pt 1):439–444. doi: 10.1016/s0091-6749(98)70350-1. [DOI] [PubMed] [Google Scholar]
  44. Matricardi P. M., Rosmini F., Ferrigno L., Nisini R., Rapicetta M., Chionne P., Stroffolini T., Pasquini P., D'Amelio R. Cross sectional retrospective study of prevalence of atopy among Italian military students with antibodies against hepatitis A virus. BMJ. 1997 Apr 5;314(7086):999–1003. doi: 10.1136/bmj.314.7086.999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Matricardi P. M., Rosmini F., Rapicetta M., Gasbarrini G., Stroffolini T. Atopy, hygiene, and anthroposophic lifestyle. San Marino Study Group. Lancet. 1999 Jul 31;354(9176):430–430. doi: 10.1016/s0140-6736(05)75853-0. [DOI] [PubMed] [Google Scholar]
  46. Matricardi P. M., Rosmini F., Riondino S., Fortini M., Ferrigno L., Rapicetta M., Bonini S. Exposure to foodborne and orofecal microbes versus airborne viruses in relation to atopy and allergic asthma: epidemiological study. BMJ. 2000 Feb 12;320(7232):412–417. doi: 10.1136/bmj.320.7232.412. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Mattes J., Karmaus W., Moseler M., Frischer T., Kuehr J. Accumulation of atopic disorders within families: a sibling effect only in the offspring of atopic fathers. Clin Exp Allergy. 1998 Dec;28(12):1480–1486. doi: 10.1046/j.1365-2222.1998.00420.x. [DOI] [PubMed] [Google Scholar]
  48. Mattes J., Karmaus W., Storm van's Gravesande K., Moseler M., Forster J., Kuehr J. Pulmonary function in children of school age is related to the number of siblings in their family. Pediatr Pulmonol. 1999 Dec;28(6):414–417. doi: 10.1002/(sici)1099-0496(199912)28:6<414::aid-ppul5>3.0.co;2-k. [DOI] [PubMed] [Google Scholar]
  49. Mosmann T. R., Sad S. The expanding universe of T-cell subsets: Th1, Th2 and more. Immunol Today. 1996 Mar;17(3):138–146. doi: 10.1016/0167-5699(96)80606-2. [DOI] [PubMed] [Google Scholar]
  50. Moyes C. D., Waldon J., Ramadas D., Crane J., Pearce N. Respiratory symptoms and environmental factors in schoolchildren in the Bay of Plenty. N Z Med J. 1995 Sep 8;108(1007):358–361. [PubMed] [Google Scholar]
  51. Nafstad P., Magnus P., Jaakkola J. J. Early respiratory infections and childhood asthma. Pediatrics. 2000 Sep;106(3):E38–E38. doi: 10.1542/peds.106.3.e38. [DOI] [PubMed] [Google Scholar]
  52. Nilsson L., Castor O., Löfman O., Magnusson A., Kjellman N. I. Allergic disease in teenagers in relation to urban or rural residence at various stages of childhood. Allergy. 1999 Jul;54(7):716–721. doi: 10.1034/j.1398-9995.1999.00896.x. [DOI] [PubMed] [Google Scholar]
  53. Nowak D., Heinrich J., Jörres R., Wassmer G., Berger J., Beck E., Boczor S., Claussen M., Wichmann H. E., Magnussen H. Prevalence of respiratory symptoms, bronchial hyperresponsiveness and atopy among adults: west and east Germany. Eur Respir J. 1996 Dec;9(12):2541–2552. doi: 10.1183/09031936.96.09122541. [DOI] [PubMed] [Google Scholar]
  54. Nystad W., Skrondal A., Magnus P. Day care attendance, recurrent respiratory tract infections and asthma. Int J Epidemiol. 1999 Oct;28(5):882–887. doi: 10.1093/ije/28.5.882. [DOI] [PubMed] [Google Scholar]
  55. Olesen A. B., Ellingsen A. R., Larsen F. S., Larsen P. O., Veien N. K., Thestrup-Pedersen K. Atopic dermatitis may be linked to whether a child is first- or second-born and/or the age of the mother. Acta Derm Venereol. 1996 Nov;76(6):457–460. doi: 10.2340/0001555576457460. [DOI] [PubMed] [Google Scholar]
  56. Omenaas E., Jentoft H. F., Vollmer W. M., Buist A. S., Gulsvik A. Absence of relationship between tuberculin reactivity and atopy in BCG vaccinated young adults. Thorax. 2000 Jun;55(6):454–458. doi: 10.1136/thorax.55.6.454. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Orgel H. A., Hamburger R. N., Bazaral M., Gorrin H., Groshong T., Lenoir M., Miller J. R., Wallace W. Development of IgE and allergy in infancy. J Allergy Clin Immunol. 1975 Oct;56(4):296–307. doi: 10.1016/0091-6749(75)90104-9. [DOI] [PubMed] [Google Scholar]
  58. Pekkanen J., Remes S., Kajosaari M., Husman T., Soininen L. Infections in early childhood and risk of atopic disease. Acta Paediatr. 1999 Jul;88(7):710–714. doi: 10.1080/08035259950168964. [DOI] [PubMed] [Google Scholar]
  59. Piccinni M. P., Bani D., Beloni L., Manuelli C., Mavilia C., Vocioni F., Bigazzi M., Sacchi T. B., Romagnani S., Maggi E. Relaxin favors the development of activated human T cells into Th1-like effectors. Eur J Immunol. 1999 Jul;29(7):2241–2247. doi: 10.1002/(SICI)1521-4141(199907)29:07<2241::AID-IMMU2241>3.0.CO;2-E. [DOI] [PubMed] [Google Scholar]
  60. Piccinni M. P., Giudizi M. G., Biagiotti R., Beloni L., Giannarini L., Sampognaro S., Parronchi P., Manetti R., Annunziato F., Livi C. Progesterone favors the development of human T helper cells producing Th2-type cytokines and promotes both IL-4 production and membrane CD30 expression in established Th1 cell clones. J Immunol. 1995 Jul 1;155(1):128–133. [PubMed] [Google Scholar]
  61. Pin I., Pilenko-McGuigan C., Cans C., Gousset M., Pison C. Epidémiologie de l'allergie respiratoire de l'enfant. Arch Pediatr. 1999;6 (Suppl 1):6S–13S. doi: 10.1016/s0929-693x(99)80240-1. [DOI] [PubMed] [Google Scholar]
  62. Ponsonby A. L., Couper D., Dwyer T., Carmichael A. Cross sectional study of the relation between sibling number and asthma, hay fever, and eczema. Arch Dis Child. 1998 Oct;79(4):328–333. doi: 10.1136/adc.79.4.328. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Ponsonby A. L., Couper D., Dwyer T., Carmichael A., Kemp A. Relationship between early life respiratory illness, family size over time, and the development of asthma and hay fever: a seven year follow up study. Thorax. 1999 Aug;54(8):664–669. doi: 10.1136/thx.54.8.664. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Reichrtová E., Ciznár P., Prachar V., Palkovicová L., Veningerová M. Cord serum immunoglobulin E related to the environmental contamination of human placentas with organochlorine compounds. Environ Health Perspect. 1999 Nov;107(11):895–899. doi: 10.1289/ehp.107-1566702. [DOI] [PMC free article] [PubMed] [Google Scholar]
  65. Ribon A., Perera S., Gavencak J. Air pollution: its effects on health and respiratory disease--a review. Ann Allergy. 1977 Oct;39(4):279–283. [PubMed] [Google Scholar]
  66. Rona R. J., Duran-Tauleria E., Chinn S. Family size, atopic disorders in parents, asthma in children, and ethnicity. J Allergy Clin Immunol. 1997 Apr;99(4):454–460. doi: 10.1016/s0091-6749(97)70070-8. [DOI] [PubMed] [Google Scholar]
  67. Rona R. J., Hughes J. M., Chinn S. Association between asthma and family size between 1977 and 1994. J Epidemiol Community Health. 1999 Jan;53(1):15–19. doi: 10.1136/jech.53.1.15. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Räsänen M., Kaprio J., Laitinen T., Winter T., Koskenvuo M., Laitinen L. A. Perinatal risk factors for asthma in Finnish adolescent twins. Thorax. 2000 Jan;55(1):25–31. doi: 10.1136/thorax.55.1.25. [DOI] [PMC free article] [PubMed] [Google Scholar]
  69. Räsänen M., Laitinen T., Kaprio J., Koskenvuo M., Laitinen L. A. Hay fever, asthma and number of older siblings--a twin study. Clin Exp Allergy. 1997 May;27(5):515–518. [PubMed] [Google Scholar]
  70. Schade G., Heinzow B. Organochlorine pesticides and polychlorinated biphenyls in human milk of mothers living in northern Germany: current extent of contamination, time trend from 1986 to 1997 and factors that influence the levels of contamination. Sci Total Environ. 1998 Apr 23;215(1-2):31–39. doi: 10.1016/s0048-9697(98)00008-4. [DOI] [PubMed] [Google Scholar]
  71. Schäfer T., Krämer U., Dockery D., Vieluf D., Behrendt H., Ring J. What makes a child allergic? Analysis of risk factors for allergic sensitization in preschool children from East and West Germany. Allergy Asthma Proc. 1999 Jan-Feb;20(1):23–27. doi: 10.2500/108854199778681477. [DOI] [PubMed] [Google Scholar]
  72. Shaheen S. O., Aaby P., Hall A. J., Barker D. J., Heyes C. B., Shiell A. W., Goudiaby A. Measles and atopy in Guinea-Bissau. Lancet. 1996 Jun 29;347(9018):1792–1796. doi: 10.1016/s0140-6736(96)91617-7. [DOI] [PubMed] [Google Scholar]
  73. Shaheen S. O., Sterne J. A., Tucker J. S., Florey C. D. Birth weight, childhood lower respiratory tract infection, and adult lung function. Thorax. 1998 Jul;53(7):549–553. doi: 10.1136/thx.53.7.549. [DOI] [PMC free article] [PubMed] [Google Scholar]
  74. Shaw R., Woodman K., Crane J., Moyes C., Kennedy J., Pearce N. Risk factors for asthma symptoms in Kawerau children. N Z Med J. 1994 Oct 12;107(987):387–391. [PubMed] [Google Scholar]
  75. Shirakawa T., Enomoto T., Shimazu S., Hopkin J. M. The inverse association between tuberculin responses and atopic disorder. Science. 1997 Jan 3;275(5296):77–79. doi: 10.1126/science.275.5296.77. [DOI] [PubMed] [Google Scholar]
  76. Shirakawa T., Morimoto K., Sasaki S., Taniguchi K., Motonaga M., Akahori W., Akahori S., Akahori T., Ohmori H., Kuroda E. Effect of maternal lifestyle on cord blood IgE factor. Eur J Epidemiol. 1997 Jun;13(4):395–402. doi: 10.1023/a:1007361013917. [DOI] [PubMed] [Google Scholar]
  77. Sprince N. L., Lewis M. Q., Whitten P. S., Reynolds S. J., Zwerling C. Respiratory symptoms: associations with pesticides, silos, and animal confinement in the Iowa Farm Family Health and Hazard Surveillance Project. Am J Ind Med. 2000 Oct;38(4):455–462. doi: 10.1002/1097-0274(200010)38:4<455::aid-ajim12>3.0.co;2-l. [DOI] [PubMed] [Google Scholar]
  78. Stein R. T., Sherrill D., Morgan W. J., Holberg C. J., Halonen M., Taussig L. M., Wright A. L., Martinez F. D. Respiratory syncytial virus in early life and risk of wheeze and allergy by age 13 years. Lancet. 1999 Aug 14;354(9178):541–545. doi: 10.1016/S0140-6736(98)10321-5. [DOI] [PubMed] [Google Scholar]
  79. Stoddard J. J., Miller T. Impact of parental smoking on the prevalence of wheezing respiratory illness in children. Am J Epidemiol. 1995 Jan 15;141(2):96–102. doi: 10.1093/oxfordjournals.aje.a117418. [DOI] [PubMed] [Google Scholar]
  80. Strachan D. P. Epidemiology of hay fever: towards a community diagnosis. Clin Exp Allergy. 1995 Apr;25(4):296–303. doi: 10.1111/j.1365-2222.1995.tb01046.x. [DOI] [PubMed] [Google Scholar]
  81. Strachan D. P. Family size, infection and atopy: the first decade of the "hygiene hypothesis". Thorax. 2000 Aug;55 (Suppl 1):S2–10. doi: 10.1136/thorax.55.suppl_1.s2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  82. Strachan D. P., Harkins L. S., Golding J. Sibship size and self-reported inhalant allergy among adult women. ALSPAC Study Team. Clin Exp Allergy. 1997 Feb;27(2):151–155. [PubMed] [Google Scholar]
  83. Strachan D. P., Harkins L. S., Johnston I. D., Anderson H. R. Childhood antecedents of allergic sensitization in young British adults. J Allergy Clin Immunol. 1997 Jan;99(1 Pt 1):6–12. doi: 10.1016/s0091-6749(97)70294-x. [DOI] [PubMed] [Google Scholar]
  84. Strachan D. P. Hay fever, hygiene, and household size. BMJ. 1989 Nov 18;299(6710):1259–1260. doi: 10.1136/bmj.299.6710.1259. [DOI] [PMC free article] [PubMed] [Google Scholar]
  85. Strachan D. P., Moran S. E., McInneny K., Smalls M. Reduced risk of hospital admission for childhood asthma among Scottish twins: record linkage study. BMJ. 2000 Sep 23;321(7263):732–733. doi: 10.1136/bmj.321.7263.732. [DOI] [PMC free article] [PubMed] [Google Scholar]
  86. Strachan D. P., Taylor E. M., Carpenter R. G. Family structure, neonatal infection, and hay fever in adolescence. Arch Dis Child. 1996 May;74(5):422–426. doi: 10.1136/adc.74.5.422. [DOI] [PMC free article] [PubMed] [Google Scholar]
  87. Strannegård I. L., Larsson L. O., Wennergren G., Strannegård O. Prevalence of allergy in children in relation to prior BCG vaccination and infection with atypical mycobacteria. Allergy. 1998 Mar;53(3):249–254. doi: 10.1111/j.1398-9995.1998.tb03884.x. [DOI] [PubMed] [Google Scholar]
  88. Sunyer J., Antó J. M., Kogevinas M., Barceló M. A., Soriano J. B., Tobías A., Muniozguren N., Martínez-Moratalla J., Payo F., Maldonado J. A. Risk factors for asthma in young adults. Spanish Group of the European Community Respiratory Health Survey. Eur Respir J. 1997 Nov;10(11):2490–2494. doi: 10.1183/09031936.97.10112490. [DOI] [PubMed] [Google Scholar]
  89. Szekeres-Bartho J., Wegmann T. G. A progesterone-dependent immunomodulatory protein alters the Th1/Th2 balance. J Reprod Immunol. 1996 Aug;31(1-2):81–95. doi: 10.1016/0165-0378(96)00964-3. [DOI] [PubMed] [Google Scholar]
  90. Tariq S. M., Matthews S. M., Hakim E. A., Stevens M., Arshad S. H., Hide D. W. The prevalence of and risk factors for atopy in early childhood: a whole population birth cohort study. J Allergy Clin Immunol. 1998 May;101(5):587–593. doi: 10.1016/S0091-6749(98)70164-2. [DOI] [PubMed] [Google Scholar]
  91. Taylor B., Wadsworth J., Golding J., Butler N. Breast feeding, eczema, asthma, and hayfever. J Epidemiol Community Health. 1983 Jun;37(2):95–99. doi: 10.1136/jech.37.2.95. [DOI] [PMC free article] [PubMed] [Google Scholar]
  92. Vaz R., Slorach S. A., Hofvander Y. Organochlorine contaminants in Swedish human milk: studies conducted at the National Food Administration 1981-1990. Food Addit Contam. 1993 Jul-Aug;10(4):407–418. doi: 10.1080/02652039309374164. [DOI] [PubMed] [Google Scholar]
  93. Vogelzang P. F., van der Gulden J. W., Folgering H., Heederik D., Tielen M. J., van Schayck C. P. Longitudinal changes in bronchial responsiveness associated with swine confinement dust exposure. Chest. 2000 May;117(5):1488–1495. doi: 10.1378/chest.117.5.1488. [DOI] [PubMed] [Google Scholar]
  94. Von Ehrenstein O. S., Von Mutius E., Illi S., Baumann L., Böhm O., von Kries R. Reduced risk of hay fever and asthma among children of farmers. Clin Exp Allergy. 2000 Feb;30(2):187–193. doi: 10.1046/j.1365-2222.2000.00801.x. [DOI] [PubMed] [Google Scholar]
  95. Warner J. A., Jones A. C., Miles E. A., Colwell B. M., Warner J. O. Maternofetal interaction and allergy. Allergy. 1996 Jul;51(7):447–451. [PubMed] [Google Scholar]
  96. Warner J. O. Bronchial hyperresponsiveness, atopy, airway inflammation, and asthma. Pediatr Allergy Immunol. 1998 May;9(2):56–60. doi: 10.1111/j.1399-3038.1998.tb00304.x. [DOI] [PubMed] [Google Scholar]
  97. Weiss S. T., Tager I. B., Muñoz A., Speizer F. E. The relationship of respiratory infections in early childhood to the occurrence of increased levels of bronchial responsiveness and atopy. Am Rev Respir Dis. 1985 Apr;131(4):573–578. doi: 10.1164/arrd.1985.131.4.573. [DOI] [PubMed] [Google Scholar]
  98. Weitzman M., Gortmaker S., Sobol A. Racial, social, and environmental risks for childhood asthma. Am J Dis Child. 1990 Nov;144(11):1189–1194. doi: 10.1001/archpedi.1990.02150350021016. [DOI] [PubMed] [Google Scholar]
  99. Whitacre C. C., Reingold S. C., O'Looney P. A. A gender gap in autoimmunity. Science. 1999 Feb 26;283(5406):1277–1278. doi: 10.1126/science.283.5406.1277. [DOI] [PubMed] [Google Scholar]
  100. Wickens K. L., Crane J., Kemp T. J., Lewis S. J., D'Souza W. J., Sawyer G. M., Stone M. L., Tohill S. J., Kennedy J. C., Slater T. M. Family size, infections, and asthma prevalence in New Zealand children. Epidemiology. 1999 Nov;10(6):699–705. [PubMed] [Google Scholar]
  101. Wickens K., Pearce N., Crane J., Beasley R. Antibiotic use in early childhood and the development of asthma. Clin Exp Allergy. 1999 Jun;29(6):766–771. doi: 10.1046/j.1365-2222.1999.00536.x. [DOI] [PubMed] [Google Scholar]
  102. Xu B., Järvelin M. R., Hartikainen A. L., Pekkanen J. Maternal age at menarche and atopy among offspring at the age of 31 years. Thorax. 2000 Aug;55(8):691–693. doi: 10.1136/thorax.55.8.691. [DOI] [PMC free article] [PubMed] [Google Scholar]
  103. Xu B., Järvelin M. R., Pekkanen J. Prenatal factors and occurrence of rhinitis and eczema among offspring. Allergy. 1999 Aug;54(8):829–836. doi: 10.1034/j.1398-9995.1999.00117.x. [DOI] [PubMed] [Google Scholar]
  104. Xu X., Yang J., Chen C., Wang B., Jin Y., Fang Z., Wang X., Weiss S. T. Familial aggregation of pulmonary function in a rural Chinese community. Am J Respir Crit Care Med. 1999 Dec;160(6):1928–1933. doi: 10.1164/ajrccm.160.6.9902013. [DOI] [PubMed] [Google Scholar]
  105. von Mutius E., Illi S., Hirsch T., Leupold W., Keil U., Weiland S. K. Frequency of infections and risk of asthma, atopy and airway hyperresponsiveness in children. Eur Respir J. 1999 Jul;14(1):4–11. doi: 10.1034/j.1399-3003.1999.14a03.x. [DOI] [PubMed] [Google Scholar]
  106. von Mutius E., Martinez F. D., Fritzsch C., Nicolai T., Reitmeir P., Thiemann H. H. Skin test reactivity and number of siblings. BMJ. 1994 Mar 12;308(6930):692–695. doi: 10.1136/bmj.308.6930.692. [DOI] [PMC free article] [PubMed] [Google Scholar]
  107. von Mutius E., Pearce N., Beasley R., Cheng S., von Ehrenstein O., Björkstén B., Weiland S. International patterns of tuberculosis and the prevalence of symptoms of asthma, rhinitis, and eczema. Thorax. 2000 Jun;55(6):449–453. doi: 10.1136/thorax.55.6.449. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Epidemiology and Community Health are provided here courtesy of BMJ Publishing Group

RESOURCES