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Cancer Risk in Children of Mothers with Epilepsy and High-Dose Folic Acid Use during Pregnancy

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dc.contributor.author Vegrim, Håkon Magne
dc.contributor.author Dreier, Julie Werenberg
dc.contributor.author Alvestad, Silje
dc.contributor.author Gilhus, Nils Erik
dc.contributor.author Gissler, Mika
dc.contributor.author Igland, Jannicke
dc.contributor.author Leinonen, Maarit K.
dc.contributor.author Tomson, Torbjörn
dc.contributor.author Sun, Yuelian
dc.contributor.author Zoega, Helga
dc.contributor.author Christensen, Jakob
dc.contributor.author Bjørk, Marte Helene
dc.date.accessioned 2022-12-21T01:05:45Z
dc.date.available 2022-12-21T01:05:45Z
dc.date.issued 2022-11-14
dc.identifier.citation Vegrim , H M , Dreier , J W , Alvestad , S , Gilhus , N E , Gissler , M , Igland , J , Leinonen , M K , Tomson , T , Sun , Y , Zoega , H , Christensen , J & Bjørk , M H 2022 , ' Cancer Risk in Children of Mothers with Epilepsy and High-Dose Folic Acid Use during Pregnancy ' , JAMA Neurology , vol. 79 , no. 11 , pp. 1-10 . https://doi.org/10.1001/jamaneurol.2022.2977
dc.identifier.issn 2168-6149
dc.identifier.other PURE: 68092042
dc.identifier.other PURE UUID: 12ee7a39-4b5e-405e-9f41-a74ac2a9fa4b
dc.identifier.other Scopus: 85139198796
dc.identifier.uri https://hdl.handle.net/20.500.11815/3755
dc.description Funding Information: Funding/Support: This work was supported by the NordForsk Nordic Program on Health and Welfare (project 83796). Publisher Copyright: © 2022 American Medical Association. All rights reserved.
dc.description.abstract Importance: Women with epilepsy are recommended high doses of folic acid before and during pregnancy owing to risk of congenital anomalies associated with antiseizure medications. Whether prenatal exposure to high-dose folic acid is associated with increases in the risk of childhood cancer is unknown. Objective: To assess whether high-dose folic acid supplementation in mothers with epilepsy is associated with childhood cancer. Design, Setting, and Participants: Observational cohort study conducted with nationwide registers in Denmark, Norway, and Sweden from 1997 to 2017. Analyses were performed during January 10, 2022, to January 31, 2022. Mother-child pairs were identified in medical birth registers and linked with information from patient, prescription, and cancer registers, as well as with sociodemographic information from statistical agencies, and were categorized by maternal diagnosis of epilepsy. The study population consisted of 3379171 children after exclusion of 126711 children because of stillbirth or missing or erroneous values on important covariates. Exposures: Maternal prescription fills for high-dose folic acid tablets (≥1 mg daily) between 90 days before pregnancy start and birth. Main Outcomes and Measures: First onset of childhood cancer at younger than 20 years. Cox proportional hazards models were used to calculate adjusted hazard ratios with corresponding 95% CIs, adjusted for potential confounders. Cumulative incidence at aged 20 years was used as a measure of absolute risk. Results: The median age at the end of follow-up in the study population of 3379171 children was 7.3 years (IQR, 3.5-10.9 years). Among the 27784 children (51.4% male) born to mothers with epilepsy, 5934 (21.4%) were exposed to high-dose folic acid (mean dose, 4.3 mg), with 18 exposed cancer cases compared with 29 unexposed, producing an adjusted hazard ratio of 2.7 (95% CI, 1.2-6.3), absolute risk if exposed of 1.4% (95% CI, 0.5%-3.6%), and absolute risk if unexposed of 0.6% (95% CI, 0.3%-1.1%). In children of mothers without epilepsy, 46646 (1.4%) were exposed to high-dose folic acid (mean dose, 2.9 mg), with 69 exposed and 4927 unexposed cancer cases and an adjusted hazard ratio of 1.1 (95% CI, 0.9-1.4; absolute risk, 0.4% [95% CI, 0.3%-0.5%]). There was no association between children born to mothers with epilepsy who were prenatally exposed to antiseizure medications, but not high-dose folic acid, and an increased risk of cancer (absolute risk, 0.6%; 95% CI, 0.2%-1.3%). Conclusions and Relevance: Prenatal exposure to high-dose folic acid was associated with increased risk of cancer in children of mothers with epilepsy.
dc.format.extent 10
dc.format.extent 1-10
dc.language.iso en
dc.relation.ispartofseries JAMA Neurology; 79(11)
dc.rights info:eu-repo/semantics/openAccess
dc.subject Pregnancy
dc.subject Humans
dc.subject Male
dc.subject Female
dc.subject Child, Preschool
dc.subject Child
dc.subject Folic Acid/therapeutic use
dc.subject Prenatal Exposure Delayed Effects/chemically induced
dc.subject Epilepsy/drug therapy
dc.subject Risk
dc.subject Cohort Studies
dc.subject Neoplasms/chemically induced
dc.subject Neurology (clinical)
dc.title Cancer Risk in Children of Mothers with Epilepsy and High-Dose Folic Acid Use during Pregnancy
dc.type /dk/atira/pure/researchoutput/researchoutputtypes/contributiontojournal/article
dc.description.version Peer reviewed
dc.identifier.pmid 36156660
dc.identifier.doi https://doi.org/10.1001/jamaneurol.2022.2977
dc.relation.url http://www.scopus.com/inward/record.url?scp=85139198796&partnerID=8YFLogxK
dc.contributor.department Faculty of Medicine

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