Paracetamol exposure in pregnancy and early childhood and development of childhood asthma: a systematic review and meta-analysis
Open accessAbstract
Background and objective: While paracetamol exposure in pregnancy and early infancy has been associated with asthma, it remains unclear whether this is confounded by respiratory tract infections, which have been suggested as an alternative explanation. We undertook a systematic review and meta-analysis of longitudinal studies that reported the association between paracetamol exposure during pregnancy or infancy and the subsequent development of childhood asthma (≥5 years). Methods: Two independent researchers searched the databases EMBASE and PUBMED on 12 August 2013 for relevant articles using predefined inclusion and exclusion criteria. Study quality was assessed and results were pooled using fixed effect models or random effect models when moderate between-study heterogeneity was observed. We explicitly assessed whether the observed associations are due to confounding by respiratory tract infections. Results: Eleven observational cohort studies met the inclusion criteria. Any paracetamol use during the first trimester was related to increased risk of childhood asthma (5 studies, pooled OR=1.39, 95% CI 1.01 to 1.91) but there was marked between-study heterogeneity (I 2=63%) and only one of these studies adjusted for maternal respiratory tract infections. Increasing frequency of use of paracetamol during infancy was associated with increased odds of childhood asthma (3 studies, pooled OR=1.15, 95% CI 1.00 to 1.31 per doubling of days exposure), but in these same three studies adjusting for respiratory tract infections reduced this association (OR=1.06, 95% CI 0.92 to 1.22). Discussion: The association during early pregnancy exposure was highly variable between studies and exposure during infancy appears to be moderately confounded by respiratory tract infections. There is insufficient evidence to warrant changing guidelines on early life paracetamol exposure at this time.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
A systematic review and meta-analysis found insufficient evidence to change guidelines on the association between paracetamol exposure in pregnancy or early infancy and childhood asthma.
“A systematic review and meta-analysis of studies reporting this association found that there was insufficient evidence to warrant changing guidelines.10”
From Paracetamol: pharmacology, prescribing and controversies (2016) · cites this paper as [10]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Measuring inconsistency in meta-analyses
Higgins, J. P. T., Thompson, S. G., Deeks, J. J., & Altman, D. G. (2003) · BMJ · doi:10.1136/bmj.327.7414.557 · Cited by 63,139 · see citing works
Preferred reporting items for systematic reviews and meta-analyses: the PRISMA Statement.
(2009) · PubMed Central · Cited by 44,859 · see citing works
Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement
Moher, D., Liberati, A., Tetzlaff, J., Altman, D. G., & the PRISMA Group* (2009) · Annals of Internal Medicine · doi:10.7326/0003-4819-151-4-200908180-00135 · Cited by 37,554 · see citing works
Stroup, D. F. (2000) · JAMA · doi:10.1001/jama.283.15.2008 · Cited by 20,623 · see citing works
Asher, M. I., Montefort, S., Björkstén, B., Lai, C. K., Strachan, D. P., Weiland, S. K., & Williams, H. (2006) · The Lancet · doi:10.1016/s0140-6736(06)69283-0 · Cited by 4,223 · see citing works
Asthma and Wheezing in the First Six Years of Life
Martinez, F. D., Wright, A. L., Taussig, L. M., Holberg, C. J., Halonen, M., & Morgan, W. J. (1995) · New England Journal of Medicine · doi:10.1056/nejm199501193320301 · Cited by 3,823 · see citing works
The global burden of asthma: executive summary of the GINA Dissemination Committee Report
Masoli, M., Fabian, D., Holt, S., Beasley, R. W., & Program, G. I. F. A. (. (2004) · Allergy · doi:10.1111/j.1398-9995.2004.00526.x · Cited by 3,521 · see citing works
Wheezing Rhinovirus Illnesses in Early Life Predict Asthma Development in High-Risk Children
Jackson, D. J., Gangnon, R. E., Evans, M. D., Roberg, K. A., Anderson, E. L., Pappas, T., Printz, M. C., Lee, W.-M., Shult, P. A., Reisdorf, E. S., et al. (2008) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200802-309oc · Cited by 1,310 · see citing works
<i>Meta-analysis</i> Spurious precision? Meta-analysis of observational studies
Egger, M., Schneider, M., & Smith, G. D. (1998) · BMJ · doi:10.1136/bmj.316.7125.140 · Cited by 997 · see citing works
Brauer, M. D., Hoek, G., van Vliet, P., Meliefste, K., Fischer, P. H., Wijga, A. H., Koopman, L. P., Neijens, H. J., Gerritsen, J., Kerkhof, M., et al. (2002) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200108-007oc · Cited by 658 · see citing works
Self-citationBeasley, R. W., Clayton, T., Crane, J., von Mutius, E., Lai, C. K. W., Montefort, S., & Stewart, A. W. (2008) · The Lancet · doi:10.1016/s0140-6736(08)61445-2 · Cited by 429 · see citing works
Fowkes, F. J. I., Richards, J. S., Simpson, J. A., & Beeson, J. G. (2010) · PLoS Medicine · doi:10.1371/journal.pmed.1000218 · Cited by 345 · see citing works
Self-citationEllwood, P. E., Asher, M. I., Björkstén, B., Burr, M. L., Pearce, N. E., & Robertson, C. F. (2001) · European Respiratory Journal · doi:10.1183/09031936.01.17304360 · Cited by 254 · see citing works
The Safety of Acetaminophen and Ibuprofen Among Children Younger Than Two Years Old
Lesko, S. M., & Mitchell, A. A. (1999) · PEDIATRICS · doi:10.1542/peds.104.4.e39 · Cited by 251 · see citing works
Frequent paracetamol use and asthma in adults
Shaheen, S. O. (2000) · Thorax · doi:10.1136/thorax.55.4.266 · Cited by 226 · see citing works
The postnatal development and growth of the human lung. II. Morphology
Zeltner, T. B., & Burri, P. H. (1987) · Respiration Physiology · doi:10.1016/0034-5687(87)90058-2 · Cited by 221 · see citing works
Paracetamol use in pregnancy and wheezing in early childhood
Shaheen, S. O. (2002) · Thorax · doi:10.1136/thorax.57.11.958 · Cited by 208 · see citing works
Prenatal paracetamol exposure and risk of asthma and elevated immunoglobulin E in childhood
Shaheen, S. O., Newson, R. B., Henderson, A. J., Headley, J. E., Stratton, F. D., Jones, R. W., Strachan, D. P., & the ALSPAC Study Team (2005) · Clinical & Experimental Allergy · doi:10.1111/j.1365-2222.2005.02151.x · Cited by 206 · see citing works
The hygiene hypothesis in allergy and asthma
Brooks, C., Pearce, N. E., & Douwes, J. E. (2012) · Current Opinion in Allergy and Clinical Immunology · doi:10.1097/aci.0b013e32835ad0d2 · Cited by 167 · see citing works
Paracetamol sales and atopic disease in children and adults: an ecological analysis
Newson, R. B., Shaheen, S. O., Chinn, S., & Burney, P. (2000) · European Respiratory Journal · doi:10.1183/09031936.00.16581700 · Cited by 150 · see citing works
Acetaminophen Use and the Risk of Asthma in Children and Adults
Etminan, M., Sadatsafavi, M., Jafari, S., Doyle-Waters, M., Aminzadeh, K. K.-W., & FitzGerald, J. M. (2009) · CHEST Journal · doi:10.1378/chest.09-0865 · Cited by 138 · see citing works
Eyers, S., Weatherall, M., Jefferies, S., & Beasley, R. W. (2011) · Clinical & Experimental Allergy · doi:10.1111/j.1365-2222.2010.03691.x · Cited by 130 · see citing works
Prospective Study of Acetaminophen Use and Newly Diagnosed Asthma among Women
Barr, R. G., Wentowski, C. C., Curhan, G. C., Somers, S. C., Stampfer, M. J., Schwartz, J., Speizer, F. E., & Camargo, C. A. (2004) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200304-596oc · Cited by 125 · see citing works
Paracetamol use in early life and asthma: prospective birth cohort study
Lowe, A. J., Carlin, J. B., Bennett, C. M., Hosking, C. S., Allen, K. J., Robertson, C. F., Axelrad, C. M., Abramson, M. J., Hill, D. J., & Dharmage, S. C. (2010) · BMJ · doi:10.1136/bmj.c4616 · Cited by 125 · see citing works
Self-citationPre-natal exposure to paracetamol and risk of wheezing and asthma in children: A birth cohort study
Rebordosa, C., Kogevinas, M., Sørensen, H. T., & Olsen, J. H. (2008) · International Journal of Epidemiology · doi:10.1093/ije/dyn070 · Cited by 124 · see citing works
Prenatal acetaminophen exposure and risk of wheeze at age 5 years in an urban low-income cohort
Perzanowski, M. S., Miller, R. L., Tang, D. L., Ali, D., Garfinkel, R. S., Chew, G. L., Goldstein, I. F., Perera, F. P., & Barr, R. G. (2009) · Thorax · doi:10.1136/thx.2009.121459 · Cited by 119 · see citing works
Varner, A. E., Busse, W. W., & Lemanske, R. F. (1998) · Annals of Allergy Asthma & Immunology · doi:10.1016/s1081-1206(10)63127-4 · Cited by 111 · see citing works
Prenatal and infant acetaminophen exposure, antioxidant gene polymorphisms, and childhood asthma
Shaheen, S. O., Newson, R. B., Ring, S. M., Rose-Zerilli, M. J. J., Holloway, J. W., & Henderson, A. J. (2010) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2010.08.047 · Cited by 111 · see citing works
Delgado, J., Barranco, P., & Quirce, S. (2008) · PubMed · Cited by 85 · see citing works
Maternal infections in pregnancy and the development of asthma among offspring
Xu, B., Pekkanen, J., Järvelin, M., Olsén, P., & Hartikainen, A. (1999) · International Journal of Epidemiology · doi:10.1093/ije/28.4.723 · Cited by 81 · see citing works
Prenatal exposure to acetaminophen and respiratory symptoms in the first year of life
Persky, V., Piorkowski, J., Hernández, E., Chávez, N., Wagner-Cassanova, C., Vergara, C., Pelzel, D., Enriquez, R., Gutierrez, S., & Busso, A. (2008) · Annals of Allergy Asthma & Immunology · doi:10.1016/s1081-1206(10)60492-9 · Cited by 80 · see citing works
Prenatal paracetamol exposure and asthma: further evidence against confounding
Shaheen, S. O., Newson, R. B., Smith, G. D., & Henderson, A. J. (2010) · International Journal of Epidemiology · doi:10.1093/ije/dyq049 · Cited by 75 · see citing works
Prenatal Exposure to Acetaminophen and Asthma in Children
Kang, E. M., Lundsberg, L. S., Illuzzi, J. L., & Bracken, M. B. (2009) · Obstetrics and Gynecology · doi:10.1097/aog.0b013e3181c225c0 · Cited by 72 · see citing works
Anderson, H. R., Butland, B. K., van Donkelaar, A., Brauer, M. D., Strachan, D. P., Clayton, T. O., Dingenen, R. V., Amann, M., Brunekreef, B., Cohen, A., et al. (2012) · Environmental Health Perspectives · doi:10.1289/ehp.1104724 · Cited by 69 · see citing works
Paracetamol in early infancy: the risk of childhood allergy and asthma
Bakkeheim, E., Mowinckel, P., Carlsen, K. H., Håland, G., & Carlsen, K. C. L. (2010) · Acta Paediatrica · doi:10.1111/j.1651-2227.2010.01942.x · Cited by 66 · see citing works
Amberbir, A., Medhin, G., Alem, A., Britton, J. R., Davey, G., & Venn, A. J. (2010) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201006-0989oc · Cited by 66 · see citing works
Maternal drug use during pregnancy and asthma risk among children
Källén, B. A. J., Finnström, O., Nygren, K., et al. (2013) · Pediatric Allergy and Immunology · doi:10.1111/pai.12034 · Cited by 62 · see citing works
The effects of early and late paracetamol exposure on asthma and atopy: a birth cohort
Wickens, K. L., Beasley, R. W., Town, I. G., Epton, M., Pattemore, P., Ingham, T. R., Crane, J., & the New Zealand Asthma and Allergy Cohort Study Group (2010) · Clinical & Experimental Allergy · doi:10.1111/j.1365-2222.2010.03610.x · Cited by 62 · see citing works
Perinatal influences on the development of asthma and atopy in childhood
Illi, S., Weber, J., Zutavern, A., Genuneit, J., Schierl, R., Strunz-Lehner, C., & von Mutius, E. (2014) · Annals of Allergy, Asthma & Immunology · doi:10.1016/j.anai.2013.11.019 · Cited by 57 · see citing works
García‐Marcos, L., Sánchez‐Solís, M., Pérez‐Fernández, V., et al. (2008) · International Archives of Allergy and Immunology · doi:10.1159/000176304 · Cited by 52 · see citing works
Perquin, M., Oster, T., Maul, A., Froment, N., Untereiner, M., & Bagrel, D. (2001) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s004320000228 · Cited by 51 · see citing works
Reye's syndrome and aspirin: lest we forget
McGovern, M., Glasgow, J. F. T., & Stewart, M. C. (2001) · BMJ · doi:10.1136/bmj.322.7302.1591 · Cited by 46 · see citing works
Foliaki, S., Annesi‐Maesano, I., Tuuau‐Potoi, N., Waqatakirewa, L., Cheng, S.-L., Douwes, J. E., & Pearce, N. E. (2008) · PubMed · Cited by 44 · see citing works
Prevalence and risk factors for wheezing in children from rural areas of north India
Sharma, S. K., & Banga, A. (2007) · Allergy and Asthma Proceedings · doi:10.2500/aap.2007.28.3059 · Cited by 43 · see citing works
Prenatal paracetamol exposure and risk of wheeze at preschool age*
Goksör, E., Thengilsdottir, H., Alm, B., et al. (2011) · Acta Paediatrica · doi:10.1111/j.1651-2227.2011.02403.x · Cited by 39 · see citing works
Schnabel, E., & Heinrich, J. (2010) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2010.08.023 · Cited by 39 · see citing works
Self-citationAndersen, A. B., Pedersen, L. H., Mehnert, F., Ehrenstein, V., & Erichsen, R. (2012) · Clinical Epidemiology · doi:10.2147/clep.s28312 · Cited by 39 · see citing works
Kang, S. H., Jung, Y.-H., Kim, H. Y., Seo, J., Lee, J.-Y., Kwon, J., Kim, B., Kim, H. B., Lee, S. Y., Jang, G. C., et al. (2013) · Annals of Allergy Asthma & Immunology · doi:10.1016/j.anai.2013.03.008 · Cited by 38 · see citing works
Intake of Paracetamol and Risk of Asthma in Adults
Thomsen, S. F., Kyvik, K. O., Skadhauge, L. R., Steffensen, I., & Backer, V. (2008) · Journal of Asthma · doi:10.1080/02770900802165998 · Cited by 37 · see citing works
Asthma Severity and Prevalence: An Ongoing Interaction between Exposure, Hygiene, and Lifestyle
Platts‐Mills, T. A. E. (2005) · PLoS Medicine · doi:10.1371/journal.pmed.0020034 · Cited by 36 · see citing works
Exposure to paracetamol and asthma symptoms
González‐Barcala, F. J., Pértega-Díaz, S., Pérez-Castro, T. R., et al. (2012) · European Journal of Public Health · doi:10.1093/eurpub/cks061 · Cited by 35 · see citing works
Kreiner‐Møller, E., Sevelsted, A., Vissing, N. H., et al. (2012) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2012.09.017 · Cited by 33 · see citing works
Early exposure to acetaminophen and allergic disorders
García‐Marcos, L., Sánchez‐Solís, M., & Pérez‐Fernández, V. (2011) · Current Opinion in Allergy and Clinical Immunology · doi:10.1097/aci.0b013e3283464c28 · Cited by 26 · see citing works
Tapiainen, T., Dunder, T., Möttönen, M. I., Pokka, T. M.-L., & Uhari, M. K. (2010) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2009.11.039 · Cited by 24 · see citing works
The Effect of a Single Dose of Acetaminophen on Airways Response in Children With Asthma
Soferman, R., Tsivion, A., Farber, M., & Sivan, Y. (2012) · Clinical Pediatrics · doi:10.1177/0009922812462764 · Cited by 23 · see citing works
Barragán-Meijueiro, M. M., Morfín-Maciel, B. M., & Nava‐Ocampo, A. A. (2006) · PubMed · Cited by 21 · see citing works
Factors Associated with Severe Disease in a Population of Asthmatic Children of Bogota, Colombia
Martínez, C., Sossa, M., & Goss, C. (2008) · Journal of Asthma · doi:10.1080/02770900701840253 · Cited by 20 · see citing works
Prevalence and risk factors for early presentation of asthma among preschool children in Taiwan.
Yeh, K., Ou, L.-S., Yao, T., et al. (2011) · PubMed · Cited by 19 · see citing works
Frequent Use of Paracetamol and Risk of Allergic Disease Among Women in an Ethiopian Population
Amberbir, A., Medhin, G., Hanlon, C., Britton, J. R., Venn, A. J., & Davey, G. (2011) · PLoS ONE · doi:10.1371/journal.pone.0022551 · Cited by 19 · see citing works
Del-Rio-Navarro, B. E., Ito-Tsuchiya, F. M., Berber, A. C., Zepeda-Ortega, B., Sienra-Monge, J. J. L., García-Almaráz, R., & Baeza-Bacab, M. A. (2008) · PubMed · Cited by 18 · see citing works
The association between acetaminophen and asthma: should its pediatric use be banned?
Martínez, A., & García‐Marcos, L. (2013) · Expert Review of Respiratory Medicine · doi:10.1586/ers.13.8 · Cited by 12 · see citing works
Acetaminophen intake and risk of asthma, hay fever and eczema in early adolescence.
Vlaski, E., Stavric, K., Isjanovska, R. D., Seckova, L., & Kimovska, M. (2007) · PubMed · Cited by 8 · see citing works
Effects of Acetaminophen consumption in asthmatic children.
Oshnouei, S., Sh, S., Khalkhali, H. R., et al. (2012) · PubMed · Cited by 5 · see citing works
The Association Between Dietary Fat Intake and Allergic Diseases
Standl, M., & Heinrich, J. (2012) · Current Nutrition & Food Science · doi:10.2174/157340112803832200 · Cited by 3 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 2
- [26]26. Stroup DF, Berlin JA, Morton SC, et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. JAMA 2000;283:2008-12.
- [39]39. Kodgule R, Kapoor S, Pawar R, et al. Paracetamol increases airway resistance in stable asthmatics: a double blind, randomized, placebo controlled study. Eur Respir J 2010;36:A3872.
Cited by
Sorted by citations
Long‐term adverse effects of paracetamol – a review
McCrae, J. C., Morrison, E. E., MacIntyre, I. M., Dear, J. W., & Webb, D. J. (2018) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.13656 · Cited by 308 · see citing works
Paracetamol use during pregnancy — a call for precautionary action
Bauer, A. Z., Swan, S. H., Kriebel, D., Liew, Z., Taylor, H. S., Bornehag, C.-G., Andrade, A. M., Olsen, J., Jensen, R. H., Mitchell, R. T., et al. (2021) · Nature Reviews Endocrinology · doi:10.1038/s41574-021-00553-7 · Cited by 228 · see citing works
Toxicological Property of Acetaminophen: The Dark Side of a Safe Antipyretic/Analgesic Drug?
Ishitsuka, Y., Kondo, Y., & Kadowaki, D. (2020) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.b19-00722 · Cited by 63 · see citing works
Paracetamol: pharmacology, prescribing and controversies
Moriarty, C., & Carroll, W. (2016) · Archives of disease in childhood - Education & practice edition · doi:10.1136/archdischild-2014-307287 · Cited by 24 · see citing works
Star, K., & Choonara, I. (2015) · Archives of Disease in Childhood · doi:10.1136/archdischild-2014-307431 · Cited by 14 · see citing works
- Authors
- Cheelo, M., Lodge, C. J., Dharmage, S. C., Simpson, J. A., Matheson, M., Heinrich, J., & Lowe, A. J.
- Affiliations
- The University of Melbourne (AU)
- Royal Children's Hospital (AU)
- Helmholtz Munich (DE)
- Venue
- Archives of Disease in Childhood
- Publisher
- BMJ
- Published
- 2014-11-26
- Volume
- 100
- Issue
- 1
- Pages
- 81-89
- ISSN
- 0003-9888 (ISSN-L)
- 1468-2044
- OpenAlex
- W2162858999
- Cited by
- 110
- References
- 64
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 5 · 2023: 4 · 2022: 8 · 2021: 8 · 2020: 18 · 2019: 10 · 2018: 11 · 2017: 6 · 2016: 19 · 2015: 12 · 2014: 1
- FWCI
- 1.48
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Archives of Disease in Childhood (publishedVersion)
- PubMed (publishedVersion)
- Open access LMU (Ludwid Maxmilian's Universitat Munchen) (submittedVersion)
- HighWire Press Open Archive (submittedVersion)
- Site cant be reached (submittedVersion)
- PuSH - Publication Server of Helmholtz Zentrum München (submittedVersion)
- Funders
- Medical Research Council
- National Health and Medical Research Council
- Topics
- Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Pregnancy and Medication Impact
- Health Sciences › Medicine › Pharmacology › Inflammatory mediators and NSAID effects
- Keywords
- paracetamol, childhood asthma, first trimester, infancy, respiratory infections, confounding, early life exposure, asthma risk
- MeSH terms
- Acetaminophen, Asthma, Child, Preschool, Female, Humans, Infant, Pregnancy, Prenatal Exposure Delayed Effects, Risk Factors, Analgesics, Non-Narcotic
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
