Prenatal paracetamol exposure and neurodevelopmental outcomes in preschool‐aged children
Background Recent studies have suggested an association between prenatal paracetamol exposure and adverse neurodevelopmental outcomes in children. However, these findings may be confounded by unmeasured factors related to maternal use of paracetamol and child outcomes. Objective To examine the assoc...
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| Veröffentlicht in: | Paediatric and perinatal epidemiology 2020-05, Vol.34 (3), p.247-256 |
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| creator | Trønnes, Johanne N. Wood, Mollie Lupattelli, Angela Ystrom, Eivind Nordeng, Hedvig |
| description | Background
Recent studies have suggested an association between prenatal paracetamol exposure and adverse neurodevelopmental outcomes in children. However, these findings may be confounded by unmeasured factors related to maternal use of paracetamol and child outcomes.
Objective
To examine the association between duration and timing of prenatal paracetamol exposure on parent‐reported communication skills, behaviour, and temperament in preschool‐aged children, with focus on the role of unmeasured confounding.
Methods
We used data from the Norwegian Mother and Child Cohort Study. Linear and generalised linear models with inverse probability weights and robust standard errors were used to quantify the association between prenatal paracetamol exposure and continuous and categorical outcomes.
Results
Of the 32 934 children included in our study, 8374 (25.4%), 4961 (15.1%), and 1791 (5.4%) were prenatally exposed to paracetamol in one, two, and three trimesters, respectively. Children exposed to paracetamol in two trimesters scored lower on shyness compared with unexposed children (β −0.62, 95% confidence interval [CI] −1.05, −0.19). Children exposed to paracetamol in three trimesters had a moderate increased risk of internalising behaviour problems (relative risk (RR) 1.36, 95% CI 1.02, 1.80) and borderline externalising behaviour problems (RR 1.22, 95% CI 0.93, 1.60) compared with unexposed children. Children exposed to paracetamol in 2nd/3rd trimester scored lower on shyness (β −0.32, 95% CI −0.66, 0.02) compared with unexposed children. Sensitivity analyses indicated that unmeasured confounders play an important role and may potentially bias the effect estimates away from the null.
Conclusions
Timing of exposure and short‐term use of paracetamol during pregnancy do not seem to pose any substantial risk of the outcomes examined. Although we found an association between paracetamol use in multiple trimesters and lower shyness and greater internalising behaviour in preschool‐aged children, we cannot rule out chance or unmeasured confounding as possible explanations for these findings. |
| doi_str_mv | 10.1111/ppe.12568 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8285062</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2280567486</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4678-bb468b3a5f37dd7da58ff926d497e97a81d9d4be1ba5c39ff13d161efd6da2a93</originalsourceid><addsrcrecordid>eNp1kc1u1DAURi1ERYfCgheASGxgkdb_sTeVUFUKUiVmARs2lhPfdFI5drCTQnc8As_Ik9TDtBVFwhsvfHS-e_0h9ILgQ1LO0TTBIaFCqkdoRZgUNcNEPkYrTKWuBaZ0Hz3N-RJjLIWmT9A-I5wrzvUKfV0nCHa2vppssh3Mdoy-gh9TzEuCygZXBVhSdHAFPk4jhC0bl7mLI-RqCNWUIHebGP3vn7_sBbiq2wzeFesztNdbn-H57X2Avrw__XzyoT7_dPbx5N153XHZqLptuVQts6JnjXONs0L1vabScd2AbqwiTjveAmmt6Jjue8IckQR6J52lVrMDdLzzTks7guvKiMl6M6VhtOnaRDuYhy9h2JiLeGUUVQJLWgSvdoIuDXkeggkxWUOwEtQ0XLKmEG9uI1L8tkCezTjkDry3AeKSDaUKC9lwJQv6-h_0Mi4plA8wlGnBFZZsG_n2LjLmnKC_H5dgs-3UlE7Nn04L-_Lv_e7JuxILcLQDvg8erv9vMuv16U55A4lmrgY</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2395480632</pqid></control><display><type>article</type><title>Prenatal paracetamol exposure and neurodevelopmental outcomes in preschool‐aged children</title><source>MEDLINE</source><source>NORA - Norwegian Open Research Archives</source><source>Wiley Online Library All Journals</source><creator>Trønnes, Johanne N. ; Wood, Mollie ; Lupattelli, Angela ; Ystrom, Eivind ; Nordeng, Hedvig</creator><creatorcontrib>Trønnes, Johanne N. ; Wood, Mollie ; Lupattelli, Angela ; Ystrom, Eivind ; Nordeng, Hedvig</creatorcontrib><description>Background
Recent studies have suggested an association between prenatal paracetamol exposure and adverse neurodevelopmental outcomes in children. However, these findings may be confounded by unmeasured factors related to maternal use of paracetamol and child outcomes.
Objective
To examine the association between duration and timing of prenatal paracetamol exposure on parent‐reported communication skills, behaviour, and temperament in preschool‐aged children, with focus on the role of unmeasured confounding.
Methods
We used data from the Norwegian Mother and Child Cohort Study. Linear and generalised linear models with inverse probability weights and robust standard errors were used to quantify the association between prenatal paracetamol exposure and continuous and categorical outcomes.
Results
Of the 32 934 children included in our study, 8374 (25.4%), 4961 (15.1%), and 1791 (5.4%) were prenatally exposed to paracetamol in one, two, and three trimesters, respectively. Children exposed to paracetamol in two trimesters scored lower on shyness compared with unexposed children (β −0.62, 95% confidence interval [CI] −1.05, −0.19). Children exposed to paracetamol in three trimesters had a moderate increased risk of internalising behaviour problems (relative risk (RR) 1.36, 95% CI 1.02, 1.80) and borderline externalising behaviour problems (RR 1.22, 95% CI 0.93, 1.60) compared with unexposed children. Children exposed to paracetamol in 2nd/3rd trimester scored lower on shyness (β −0.32, 95% CI −0.66, 0.02) compared with unexposed children. Sensitivity analyses indicated that unmeasured confounders play an important role and may potentially bias the effect estimates away from the null.
Conclusions
Timing of exposure and short‐term use of paracetamol during pregnancy do not seem to pose any substantial risk of the outcomes examined. Although we found an association between paracetamol use in multiple trimesters and lower shyness and greater internalising behaviour in preschool‐aged children, we cannot rule out chance or unmeasured confounding as possible explanations for these findings.</description><identifier>ISSN: 0269-5022</identifier><identifier>EISSN: 1365-3016</identifier><identifier>DOI: 10.1111/ppe.12568</identifier><identifier>PMID: 31448449</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>Acetaminophen - therapeutic use ; Analgesics ; Analgesics, Non-Narcotic - therapeutic use ; Child Behavior ; Child Behavior Disorders - diagnosis ; Child Behavior Disorders - epidemiology ; Child Development - drug effects ; child neurodevelopment ; Child, Preschool ; Children ; Communication skills ; Confidence intervals ; Confounding Factors, Epidemiologic ; Duration of Therapy ; Exposure ; Female ; Humans ; Male ; Migraine Disorders - drug therapy ; Migraine Disorders - epidemiology ; MoBa ; Norway - epidemiology ; Paracetamol ; Pregnancy ; Pregnancy Complications - drug therapy ; Pregnancy Complications - epidemiology ; Pregnancy Trimesters ; Prenatal experience ; Prenatal Exposure Delayed Effects - chemically induced ; Prenatal Exposure Delayed Effects - epidemiology ; Prenatal Exposure Delayed Effects - psychology ; Risk ; Risk Assessment ; Risk taking ; Sensitivity analysis ; Social Skills ; Statistical analysis</subject><ispartof>Paediatric and perinatal epidemiology, 2020-05, Vol.34 (3), p.247-256</ispartof><rights>2019 The Authors. Published by John Wiley & Sons Ltd</rights><rights>2019 The Authors. Paediatric and Perinatal Epidemiology Published by John Wiley & Sons Ltd.</rights><rights>2019. This article is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>info:eu-repo/semantics/openAccess</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4678-bb468b3a5f37dd7da58ff926d497e97a81d9d4be1ba5c39ff13d161efd6da2a93</citedby><cites>FETCH-LOGICAL-c4678-bb468b3a5f37dd7da58ff926d497e97a81d9d4be1ba5c39ff13d161efd6da2a93</cites><orcidid>0000-0001-6361-2918 ; 0000-0001-8462-0917 ; 0000-0003-4390-6171 ; 0000-0002-9302-2641 ; 0000-0002-8787-3183</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fppe.12568$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fppe.12568$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,1411,26544,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31448449$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Trønnes, Johanne N.</creatorcontrib><creatorcontrib>Wood, Mollie</creatorcontrib><creatorcontrib>Lupattelli, Angela</creatorcontrib><creatorcontrib>Ystrom, Eivind</creatorcontrib><creatorcontrib>Nordeng, Hedvig</creatorcontrib><title>Prenatal paracetamol exposure and neurodevelopmental outcomes in preschool‐aged children</title><title>Paediatric and perinatal epidemiology</title><addtitle>Paediatr Perinat Epidemiol</addtitle><description>Background
Recent studies have suggested an association between prenatal paracetamol exposure and adverse neurodevelopmental outcomes in children. However, these findings may be confounded by unmeasured factors related to maternal use of paracetamol and child outcomes.
Objective
To examine the association between duration and timing of prenatal paracetamol exposure on parent‐reported communication skills, behaviour, and temperament in preschool‐aged children, with focus on the role of unmeasured confounding.
Methods
We used data from the Norwegian Mother and Child Cohort Study. Linear and generalised linear models with inverse probability weights and robust standard errors were used to quantify the association between prenatal paracetamol exposure and continuous and categorical outcomes.
Results
Of the 32 934 children included in our study, 8374 (25.4%), 4961 (15.1%), and 1791 (5.4%) were prenatally exposed to paracetamol in one, two, and three trimesters, respectively. Children exposed to paracetamol in two trimesters scored lower on shyness compared with unexposed children (β −0.62, 95% confidence interval [CI] −1.05, −0.19). Children exposed to paracetamol in three trimesters had a moderate increased risk of internalising behaviour problems (relative risk (RR) 1.36, 95% CI 1.02, 1.80) and borderline externalising behaviour problems (RR 1.22, 95% CI 0.93, 1.60) compared with unexposed children. Children exposed to paracetamol in 2nd/3rd trimester scored lower on shyness (β −0.32, 95% CI −0.66, 0.02) compared with unexposed children. Sensitivity analyses indicated that unmeasured confounders play an important role and may potentially bias the effect estimates away from the null.
Conclusions
Timing of exposure and short‐term use of paracetamol during pregnancy do not seem to pose any substantial risk of the outcomes examined. Although we found an association between paracetamol use in multiple trimesters and lower shyness and greater internalising behaviour in preschool‐aged children, we cannot rule out chance or unmeasured confounding as possible explanations for these findings.</description><subject>Acetaminophen - therapeutic use</subject><subject>Analgesics</subject><subject>Analgesics, Non-Narcotic - therapeutic use</subject><subject>Child Behavior</subject><subject>Child Behavior Disorders - diagnosis</subject><subject>Child Behavior Disorders - epidemiology</subject><subject>Child Development - drug effects</subject><subject>child neurodevelopment</subject><subject>Child, Preschool</subject><subject>Children</subject><subject>Communication skills</subject><subject>Confidence intervals</subject><subject>Confounding Factors, Epidemiologic</subject><subject>Duration of Therapy</subject><subject>Exposure</subject><subject>Female</subject><subject>Humans</subject><subject>Male</subject><subject>Migraine Disorders - drug therapy</subject><subject>Migraine Disorders - epidemiology</subject><subject>MoBa</subject><subject>Norway - epidemiology</subject><subject>Paracetamol</subject><subject>Pregnancy</subject><subject>Pregnancy Complications - drug therapy</subject><subject>Pregnancy Complications - epidemiology</subject><subject>Pregnancy Trimesters</subject><subject>Prenatal experience</subject><subject>Prenatal Exposure Delayed Effects - chemically induced</subject><subject>Prenatal Exposure Delayed Effects - epidemiology</subject><subject>Prenatal Exposure Delayed Effects - psychology</subject><subject>Risk</subject><subject>Risk Assessment</subject><subject>Risk taking</subject><subject>Sensitivity analysis</subject><subject>Social Skills</subject><subject>Statistical analysis</subject><issn>0269-5022</issn><issn>1365-3016</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>EIF</sourceid><sourceid>3HK</sourceid><recordid>eNp1kc1u1DAURi1ERYfCgheASGxgkdb_sTeVUFUKUiVmARs2lhPfdFI5drCTQnc8As_Ik9TDtBVFwhsvfHS-e_0h9ILgQ1LO0TTBIaFCqkdoRZgUNcNEPkYrTKWuBaZ0Hz3N-RJjLIWmT9A-I5wrzvUKfV0nCHa2vppssh3Mdoy-gh9TzEuCygZXBVhSdHAFPk4jhC0bl7mLI-RqCNWUIHebGP3vn7_sBbiq2wzeFesztNdbn-H57X2Avrw__XzyoT7_dPbx5N153XHZqLptuVQts6JnjXONs0L1vabScd2AbqwiTjveAmmt6Jjue8IckQR6J52lVrMDdLzzTks7guvKiMl6M6VhtOnaRDuYhy9h2JiLeGUUVQJLWgSvdoIuDXkeggkxWUOwEtQ0XLKmEG9uI1L8tkCezTjkDry3AeKSDaUKC9lwJQv6-h_0Mi4plA8wlGnBFZZsG_n2LjLmnKC_H5dgs-3UlE7Nn04L-_Lv_e7JuxILcLQDvg8erv9vMuv16U55A4lmrgY</recordid><startdate>202005</startdate><enddate>202005</enddate><creator>Trønnes, Johanne N.</creator><creator>Wood, Mollie</creator><creator>Lupattelli, Angela</creator><creator>Ystrom, Eivind</creator><creator>Nordeng, Hedvig</creator><general>Wiley Subscription Services, Inc</general><general>Blackwell Science Ltd</general><scope>24P</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7U9</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope><scope>3HK</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-6361-2918</orcidid><orcidid>https://orcid.org/0000-0001-8462-0917</orcidid><orcidid>https://orcid.org/0000-0003-4390-6171</orcidid><orcidid>https://orcid.org/0000-0002-9302-2641</orcidid><orcidid>https://orcid.org/0000-0002-8787-3183</orcidid></search><sort><creationdate>202005</creationdate><title>Prenatal paracetamol exposure and neurodevelopmental outcomes in preschool‐aged children</title><author>Trønnes, Johanne N. ; Wood, Mollie ; Lupattelli, Angela ; Ystrom, Eivind ; Nordeng, Hedvig</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4678-bb468b3a5f37dd7da58ff926d497e97a81d9d4be1ba5c39ff13d161efd6da2a93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Acetaminophen - therapeutic use</topic><topic>Analgesics</topic><topic>Analgesics, Non-Narcotic - therapeutic use</topic><topic>Child Behavior</topic><topic>Child Behavior Disorders - diagnosis</topic><topic>Child Behavior Disorders - epidemiology</topic><topic>Child Development - drug effects</topic><topic>child neurodevelopment</topic><topic>Child, Preschool</topic><topic>Children</topic><topic>Communication skills</topic><topic>Confidence intervals</topic><topic>Confounding Factors, Epidemiologic</topic><topic>Duration of Therapy</topic><topic>Exposure</topic><topic>Female</topic><topic>Humans</topic><topic>Male</topic><topic>Migraine Disorders - drug therapy</topic><topic>Migraine Disorders - epidemiology</topic><topic>MoBa</topic><topic>Norway - epidemiology</topic><topic>Paracetamol</topic><topic>Pregnancy</topic><topic>Pregnancy Complications - drug therapy</topic><topic>Pregnancy Complications - epidemiology</topic><topic>Pregnancy Trimesters</topic><topic>Prenatal experience</topic><topic>Prenatal Exposure Delayed Effects - chemically induced</topic><topic>Prenatal Exposure Delayed Effects - epidemiology</topic><topic>Prenatal Exposure Delayed Effects - psychology</topic><topic>Risk</topic><topic>Risk Assessment</topic><topic>Risk taking</topic><topic>Sensitivity analysis</topic><topic>Social Skills</topic><topic>Statistical analysis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Trønnes, Johanne N.</creatorcontrib><creatorcontrib>Wood, Mollie</creatorcontrib><creatorcontrib>Lupattelli, Angela</creatorcontrib><creatorcontrib>Ystrom, Eivind</creatorcontrib><creatorcontrib>Nordeng, Hedvig</creatorcontrib><collection>Wiley-Blackwell Open Access Titles</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><collection>NORA - Norwegian Open Research Archives</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Paediatric and perinatal epidemiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Trønnes, Johanne N.</au><au>Wood, Mollie</au><au>Lupattelli, Angela</au><au>Ystrom, Eivind</au><au>Nordeng, Hedvig</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Prenatal paracetamol exposure and neurodevelopmental outcomes in preschool‐aged children</atitle><jtitle>Paediatric and perinatal epidemiology</jtitle><addtitle>Paediatr Perinat Epidemiol</addtitle><date>2020-05</date><risdate>2020</risdate><volume>34</volume><issue>3</issue><spage>247</spage><epage>256</epage><pages>247-256</pages><issn>0269-5022</issn><eissn>1365-3016</eissn><abstract>Background
Recent studies have suggested an association between prenatal paracetamol exposure and adverse neurodevelopmental outcomes in children. However, these findings may be confounded by unmeasured factors related to maternal use of paracetamol and child outcomes.
Objective
To examine the association between duration and timing of prenatal paracetamol exposure on parent‐reported communication skills, behaviour, and temperament in preschool‐aged children, with focus on the role of unmeasured confounding.
Methods
We used data from the Norwegian Mother and Child Cohort Study. Linear and generalised linear models with inverse probability weights and robust standard errors were used to quantify the association between prenatal paracetamol exposure and continuous and categorical outcomes.
Results
Of the 32 934 children included in our study, 8374 (25.4%), 4961 (15.1%), and 1791 (5.4%) were prenatally exposed to paracetamol in one, two, and three trimesters, respectively. Children exposed to paracetamol in two trimesters scored lower on shyness compared with unexposed children (β −0.62, 95% confidence interval [CI] −1.05, −0.19). Children exposed to paracetamol in three trimesters had a moderate increased risk of internalising behaviour problems (relative risk (RR) 1.36, 95% CI 1.02, 1.80) and borderline externalising behaviour problems (RR 1.22, 95% CI 0.93, 1.60) compared with unexposed children. Children exposed to paracetamol in 2nd/3rd trimester scored lower on shyness (β −0.32, 95% CI −0.66, 0.02) compared with unexposed children. Sensitivity analyses indicated that unmeasured confounders play an important role and may potentially bias the effect estimates away from the null.
Conclusions
Timing of exposure and short‐term use of paracetamol during pregnancy do not seem to pose any substantial risk of the outcomes examined. Although we found an association between paracetamol use in multiple trimesters and lower shyness and greater internalising behaviour in preschool‐aged children, we cannot rule out chance or unmeasured confounding as possible explanations for these findings.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>31448449</pmid><doi>10.1111/ppe.12568</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0001-6361-2918</orcidid><orcidid>https://orcid.org/0000-0001-8462-0917</orcidid><orcidid>https://orcid.org/0000-0003-4390-6171</orcidid><orcidid>https://orcid.org/0000-0002-9302-2641</orcidid><orcidid>https://orcid.org/0000-0002-8787-3183</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Paediatric and perinatal epidemiology, 2020-05, Vol.34 (3), p.247-256 |
| issn | 0269-5022 1365-3016 |
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| source | MEDLINE; NORA - Norwegian Open Research Archives; Wiley Online Library All Journals |
| subjects | Acetaminophen - therapeutic use Analgesics Analgesics, Non-Narcotic - therapeutic use Child Behavior Child Behavior Disorders - diagnosis Child Behavior Disorders - epidemiology Child Development - drug effects child neurodevelopment Child, Preschool Children Communication skills Confidence intervals Confounding Factors, Epidemiologic Duration of Therapy Exposure Female Humans Male Migraine Disorders - drug therapy Migraine Disorders - epidemiology MoBa Norway - epidemiology Paracetamol Pregnancy Pregnancy Complications - drug therapy Pregnancy Complications - epidemiology Pregnancy Trimesters Prenatal experience Prenatal Exposure Delayed Effects - chemically induced Prenatal Exposure Delayed Effects - epidemiology Prenatal Exposure Delayed Effects - psychology Risk Risk Assessment Risk taking Sensitivity analysis Social Skills Statistical analysis |
| title | Prenatal paracetamol exposure and neurodevelopmental outcomes in preschool‐aged children |
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