Abstract
Background: We recently reported links between frequent paracetamol (acetaminophen) use and wheezing and asthma in adults and children, but data are lacking on possible effects of prenatal exposure on wheezing in early childhood.
Methods: In the population based Avon Longitudinal Study of Parents and Children (ALSPAC) women were asked twice during pregnancy (at 18–20 weeks and 32 weeks) about their usage of paracetamol and aspirin. Six months after birth, and at yearly intervals thereafter, mothers were asked about wheezing and eczema symptoms in their child. The effects of paracetamol and aspirin use in pregnancy on the risk in the offspring of wheezing at 30–42 months (n=9400) and eczema at 18–30 months (n=10 216) and on their risk of different wheezing patterns (defined by presence or absence of wheezing at <6 months and at 30–42 months) were examined.
Results: Paracetamol was taken frequently (most days/daily) by only 1% of women. After controlling for potential confounders, frequent paracetamol use in late pregnancy (20–32 weeks), but not in early pregnancy (<18–20 weeks), was associated with an increased risk of wheezing in the offspring at 30–42 months (adjusted odds ratio (OR) compared with no use 2.10 (95% CI 1.30 to 3.41); p=0.003), particularly if wheezing started before 6 months (OR 2.34 (95% CI 1.24 to 4.40); p=0.008). Assuming a causal relation, only about 1% of wheezing at 30–42 months was attributable to this exposure. Frequent paracetamol use in pregnancy was not associated with an increased risk of eczema. Frequent aspirin use in pregnancy was associated with an increased risk of wheezing only at <6 months.
Conclusions: Frequent use of paracetamol in late pregnancy may increase the risk of wheezing in the offspring, although such an effect could explain only about 1% of the population prevalence of wheezing in early childhood.
Full Text
The Full Text of this article is available as a PDF (114.6 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Barnes P. J. Reactive oxygen species and airway inflammation. Free Radic Biol Med. 1990;9(3):235–243. doi: 10.1016/0891-5849(90)90034-g. [DOI] [PubMed] [Google Scholar]
- Bousquet J., Yssel H., Vignola A. M. Is allergic asthma associated with delayed fetal maturation or the persistence of conserved fetal genes? Allergy. 2000 Dec;55(12):1194–1197. doi: 10.1034/j.1398-9995.2000.00923.x. [DOI] [PubMed] [Google Scholar]
- 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]
- Chen T. C., Leviton A. Asthma and eczema in children born to women with migraine. Arch Neurol. 1990 Nov;47(11):1227–1230. doi: 10.1001/archneur.1990.00530110087022. [DOI] [PubMed] [Google Scholar]
- Chen T. S., Richie J. P., Jr, Lang C. A. Life span profiles of glutathione and acetaminophen detoxification. Drug Metab Dispos. 1990 Nov-Dec;18(6):882–887. [PubMed] [Google Scholar]
- Comhair S. A., Bhathena P. R., Dweik R. A., Kavuru M., Erzurum S. C. Rapid loss of superoxide dismutase activity during antigen-induced asthmatic response. Lancet. 2000 Feb 19;355(9204):624–624. doi: 10.1016/S0140-6736(99)04736-4. [DOI] [PubMed] [Google Scholar]
- Cossar D., Bell J., Strange R., Jones M., Sandison A., Hume R. The alpha and pi isoenzymes of glutathione S-transferase in human fetal lung: in utero ontogeny compared with differentiation in lung organ culture. Biochim Biophys Acta. 1990 Feb 9;1037(2):221–226. doi: 10.1016/0167-4838(90)90171-b. [DOI] [PubMed] [Google Scholar]
- Dimova S., Hoet P. H., Nemery B. Paracetamol (acetaminophen) cytotoxicity in rat type II pneumocytes and alveolar macrophages in vitro. Biochem Pharmacol. 2000 Jun 1;59(11):1467–1475. doi: 10.1016/s0006-2952(00)00257-4. [DOI] [PubMed] [Google Scholar]
- Fryer A. A., Hume R., Strange R. C. The development of glutathione S-transferase and glutathione peroxidase activities in human lung. Biochim Biophys Acta. 1986 Oct 1;883(3):448–453. doi: 10.1016/0304-4165(86)90283-7. [DOI] [PubMed] [Google Scholar]
- Golding J., Pembrey M., Jones R., ALSPAC Study Team ALSPAC--the Avon Longitudinal Study of Parents and Children. I. Study methodology. Paediatr Perinat Epidemiol. 2001 Jan;15(1):74–87. doi: 10.1046/j.1365-3016.2001.00325.x. [DOI] [PubMed] [Google Scholar]
- Greenland S., Drescher K. Maximum likelihood estimation of the attributable fraction from logistic models. Biometrics. 1993 Sep;49(3):865–872. [PubMed] [Google Scholar]
- Halliwell B. Free radicals, antioxidants, and human disease: curiosity, cause, or consequence? Lancet. 1994 Sep 10;344(8924):721–724. doi: 10.1016/s0140-6736(94)92211-x. [DOI] [PubMed] [Google Scholar]
- Hart S. G., Cartun R. W., Wyand D. S., Khairallah E. A., Cohen S. D. Immunohistochemical localization of acetaminophen in target tissues of the CD-1 mouse: correspondence of covalent binding with toxicity. Fundam Appl Toxicol. 1995 Feb;24(2):260–274. doi: 10.1006/faat.1995.1029. [DOI] [PubMed] [Google Scholar]
- Holgate S. T., Davies D. E., Lackie P. M., Wilson S. J., Puddicombe S. M., Lordan J. L. Epithelial-mesenchymal interactions in the pathogenesis of asthma. J Allergy Clin Immunol. 2000 Feb;105(2 Pt 1):193–204. doi: 10.1016/s0091-6749(00)90066-6. [DOI] [PubMed] [Google Scholar]
- Hulsmann A. R., Raatgeep H. R., den Hollander J. C., Stijnen T., Saxena P. R., Kerrebijn K. F., de Jongste J. C. Oxidative epithelial damage produces hyperresponsiveness of human peripheral airways. Am J Respir Crit Care Med. 1994 Feb;149(2 Pt 1):519–525. doi: 10.1164/ajrccm.149.2.8306055. [DOI] [PubMed] [Google Scholar]
- Jeffery E. H., Haschek W. M. Protection by dimethylsulfoxide against acetaminophen-induced hepatic, but not respiratory toxicity in the mouse. Toxicol Appl Pharmacol. 1988 May;93(3):452–461. doi: 10.1016/0041-008x(88)90048-8. [DOI] [PubMed] [Google Scholar]
- Kelly F. J., Mudway I., Blomberg A., Frew A., Sandström T. Altered lung antioxidant status in patients with mild asthma. Lancet. 1999 Aug 7;354(9177):482–483. doi: 10.1016/S0140-6736(99)01812-7. [DOI] [PubMed] [Google Scholar]
- Levy G., Garrettson L. K., Soda D. M. Letter: Evidence of placental transfer of acetaminophen. Pediatrics. 1975 Jun;55(6):895–895. [PubMed] [Google Scholar]
- Martinez F. D., Wright A. L., Taussig L. M., Holberg C. J., Halonen M., Morgan W. J. Asthma and wheezing in the first six years of life. The Group Health Medical Associates. N Engl J Med. 1995 Jan 19;332(3):133–138. doi: 10.1056/NEJM199501193320301. [DOI] [PubMed] [Google Scholar]
- Micheli L., Cerretani D., Fiaschi A. I., Giorgi G., Romeo M. R., Runci F. M. Effect of acetaminophen on glutathione levels in rat testis and lung. Environ Health Perspect. 1994 Nov;102 (Suppl 9):63–64. doi: 10.1289/ehp.94102s963. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Newson R. B., Shaheen S. O., Chinn S., Burney P. G. Paracetamol sales and atopic disease in children and adults: an ecological analysis. Eur Respir J. 2000 Nov;16(5):817–823. doi: 10.1183/09031936.00.16581700. [DOI] [PubMed] [Google Scholar]
- Peterson J. D., Herzenberg L. A., Vasquez K., Waltenbaugh C. Glutathione levels in antigen-presenting cells modulate Th1 versus Th2 response patterns. Proc Natl Acad Sci U S A. 1998 Mar 17;95(6):3071–3076. doi: 10.1073/pnas.95.6.3071. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Placke M. E., Wyand D. S., Cohen S. D. Extrahepatic lesions induced by acetaminophen in the mouse. Toxicol Pathol. 1987;15(4):381–387. doi: 10.1177/019262338701500401. [DOI] [PubMed] [Google Scholar]
- Rollins D. E., von Bahr C., Glaumann H., Moldéus P., Rane A. Acetaminophen: potentially toxic metabolite formed by human fetal and adult liver microsomes and isolated fetal liver cells. Science. 1979 Sep 28;205(4413):1414–1416. doi: 10.1126/science.38505. [DOI] [PubMed] [Google Scholar]
- Rusconi F., Galassi C., Corbo G. M., Forastiere F., Biggeri A., Ciccone G., Renzoni E. Risk factors for early, persistent, and late-onset wheezing in young children. SIDRIA Collaborative Group. Am J Respir Crit Care Med. 1999 Nov;160(5 Pt 1):1617–1622. doi: 10.1164/ajrccm.160.5.9811002. [DOI] [PubMed] [Google Scholar]
- Shaheen S. O., Sterne J. A., Songhurst C. E., Burney P. G. Frequent paracetamol use and asthma in adults. Thorax. 2000 Apr;55(4):266–270. doi: 10.1136/thorax.55.4.266. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sherriff A., Peters T. J., Henderson J., Strachan D., ALSPAC Study Team. Avon Longitudinal Study of Parents and Children Risk factor associations with wheezing patterns in children followed longitudinally from birth to 3(1/2) years. Int J Epidemiol. 2001 Dec;30(6):1473–1484. doi: 10.1093/ije/30.6.1473. [DOI] [PubMed] [Google Scholar]
- Smith L. J., Houston M., Anderson J. Increased levels of glutathione in bronchoalveolar lavage fluid from patients with asthma. Am Rev Respir Dis. 1993 Jun;147(6 Pt 1):1461–1464. doi: 10.1164/ajrccm/147.6_Pt_1.1461. [DOI] [PubMed] [Google Scholar]
- Strachan D. P., Butland B. K., Anderson H. R. Incidence and prognosis of asthma and wheezing illness from early childhood to age 33 in a national British cohort. BMJ. 1996 May 11;312(7040):1195–1199. doi: 10.1136/bmj.312.7040.1195. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Terwindt G. M., Ferrari M. D., Tijhuis M., Groenen S. M., Picavet H. S., Launer L. J. The impact of migraine on quality of life in the general population: the GEM study. Neurology. 2000 Sep 12;55(5):624–629. doi: 10.1212/wnl.55.5.624. [DOI] [PubMed] [Google Scholar]
- Warner J. A., Jones C. A., Jones A. C., Warner J. O. Prenatal origins of allergic disease. J Allergy Clin Immunol. 2000 Feb;105(2 Pt 2):S493–S498. doi: 10.1016/s0091-6749(00)90049-6. [DOI] [PubMed] [Google Scholar]
- Williams H. C., Burney P. G., Hay R. J., Archer C. B., Shipley M. J., Hunter J. J., Bingham E. A., Finlay A. Y., Pembroke A. C., Graham-Brown R. A. The U.K. Working Party's Diagnostic Criteria for Atopic Dermatitis. I. Derivation of a minimum set of discriminators for atopic dermatitis. Br J Dermatol. 1994 Sep;131(3):383–396. doi: 10.1111/j.1365-2133.1994.tb08530.x. [DOI] [PubMed] [Google Scholar]