Paracetamol exposure and asthma: What does the evidence say? An overview of systematic reviews
Manvi Singh MD
Department of Telemedicine, Postgraduate Institute of Medical Education and research, Chandigarh, India
Search for more papers by this authorSuresh Varukolu M.Pharm
Health Economics and Outcomes Research, Smartanalyst Pvt. Ltd., Hyderabad, Telangana, India
Search for more papers by this authorAnil Chauhan PhD
Department of Pediatrics, Postgraduate Institute of Medical Education and research, Advanced Center for Evidence Based Child Health, Chandigarh, India
Search for more papers by this authorNishant Jaiswal PhD
Health Economics and Health Technology Assessment, The University of Glasgow, Scotland, UK
Search for more papers by this authorPranita Pradhan M.Lib
Department of Pediatrics, Postgraduate Institute of Medical Education and research, Advanced Center for Evidence Based Child Health, Chandigarh, India
Search for more papers by this authorJoseph L. Mathew MD, PhD
Department of Pediatrics, Postgraduate Institute of Medical Education and research, Chandigarh, India
Search for more papers by this authorCorresponding Author
Meenu Singh MD
Department of Telemedicine, Postgraduate Institute of Medical Education and research, Chandigarh, India
Department of Pediatrics, Postgraduate Institute of Medical Education and research, Chandigarh, India
Correspondence Meenu Singh, Postgraduate Institute of Medical Education and research, Chandigarh, India.
Email: [email protected]
Search for more papers by this authorManvi Singh MD
Department of Telemedicine, Postgraduate Institute of Medical Education and research, Chandigarh, India
Search for more papers by this authorSuresh Varukolu M.Pharm
Health Economics and Outcomes Research, Smartanalyst Pvt. Ltd., Hyderabad, Telangana, India
Search for more papers by this authorAnil Chauhan PhD
Department of Pediatrics, Postgraduate Institute of Medical Education and research, Advanced Center for Evidence Based Child Health, Chandigarh, India
Search for more papers by this authorNishant Jaiswal PhD
Health Economics and Health Technology Assessment, The University of Glasgow, Scotland, UK
Search for more papers by this authorPranita Pradhan M.Lib
Department of Pediatrics, Postgraduate Institute of Medical Education and research, Advanced Center for Evidence Based Child Health, Chandigarh, India
Search for more papers by this authorJoseph L. Mathew MD, PhD
Department of Pediatrics, Postgraduate Institute of Medical Education and research, Chandigarh, India
Search for more papers by this authorCorresponding Author
Meenu Singh MD
Department of Telemedicine, Postgraduate Institute of Medical Education and research, Chandigarh, India
Department of Pediatrics, Postgraduate Institute of Medical Education and research, Chandigarh, India
Correspondence Meenu Singh, Postgraduate Institute of Medical Education and research, Chandigarh, India.
Email: [email protected]
Search for more papers by this authorAbstract
Objective
To conduct an umbrella review collating the existing evidence to determine whether there is an association between exposure of Paracetamol in-utero or in infancy and the development of childhood Asthma.
Methods
In this review, systematic reviews with or without meta-analysis that reported the association between paracetamol and asthma in children were included. To identify relevant reviews, a search was performed in the electronic databases PubMed, the Cochrane Library, and Ovid MEDLINE. The protocol was registered in PROSPERO CRD42020156023. A separate search was conducted for primary studies from the last 5 years not yet included in systematic reviews reporting the association from January 2016 to March 2021.
Results
The electronic searches identified 1966 review titles. After the removal of 493 duplicates, 1475 titles and abstracts were screened against the eligibility criteria. Full-text screening yielded six systematic reviews to be included in this review. The search for primary studies in the last 5 years yielded 1214 hits, out of which 5 studies were found suitable for inclusion. Three of them, that were not included in the systematic reviews, and have been summarised in this paper. The odds ratios (ORs) for the outcome of asthma in offspring of mothers with prenatal paracetamol consumption in any trimester were 1.28 (1.13–1.39) and 1.21 (1.02–1.44). For first trimester exposures, they were 1.12 (0.99–1.27), 1.39 (1.01–1.91), and 1.21 (1.14–1.28), for the second or third trimester, they were 1.49 (1.37–1.63) and 1.13 (1.04–1.23). For the third trimester only, the figure was 1.17 (1.04–1.31). Of the six reviews included, 1 had a low risk of bias, 2 had an unclear risk while 3 had a high risk of bias assessed using the ROBIS tool. There was no significant increased risk of asthma with early infancy exposure. The inter-study heterogeneity varied from I2 = 41% to I2 = 76% across reviews. In the primary studies, the OR for prenatal exposure ranged from 1.12 (0.25–4.98) to 4.66 (1.92–11.3) and for infancy exposure was 1.56 (1.06–2.30). All three included primary studies were adjudged to be of high quality using the Newcastle Ottawa scale.
Conclusions
There is a modest association between paracetamol exposure in-utero and the future development of asthma. Exposure in infancy has a less consistant association. All the studies done thus far are observational in nature, with their inherent biases. Further research, preferably randomized controlled trials are recommended to answer this pertinent question.
CONFLICT OF INTERESTS
The authors declare that there are no conflict of interests.
Open Research
DATA AVAILABILITY STATEMENT
The data that supports the findings of this study are available in the supplementary material of this article.
Supporting Information
| Filename | Description |
|---|---|
| ppul25595-sup-0001-R1Supplementary_Table_S1.docx22.6 KB | Supporting information. |
| ppul25595-sup-0002-Supplementary_Document_S1.docx256.9 KB | Supplementary Document S1: Search strategy for Systematic Reviews. |
| ppul25595-sup-0003-Supplementary_Document_S2a.docx14.7 KB | Supplementary Document S2a: Search strategy for Primary Studies (PubMed). |
| ppul25595-sup-0004-Supplementary_Document_S2b.pdf97.8 KB | Supplementary Document S2b: Search strategy for Primary Studies (EMBASE). |
| ppul25595-sup-0005-Supplementary_Document_S2c.docx12.4 KB | Supplementary Document S2c: Search strategy for Primary Studies (Ovid MEDLINE). |
| ppul25595-sup-0006-Supplementary_Document_S2d.docx10.5 KB | Supplementary Document S2d: Search strategy for Primary Studies (Cochrane). |
| ppul25595-sup-0007-Supplementary_Table_S2.docx15 KB | Supplementary Table S2: Hills causal criteria applied to the association between prenatal and early infancy paracetamol exposure and asthma. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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