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Cancer Risk in Children of Mothers With Epilepsy and High-Dose Folic Acid Use During Pregnancy

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 unknow...

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Autores principales: Vegrim, Håkon Magne, Dreier, Julie Werenberg, Alvestad, Silje, Gilhus, Nils Erik, Gissler, Mika, Igland, Jannicke, Leinonen, Maarit K., Tomson, Torbjörn, Sun, Yuelian, Zoega, Helga, Christensen, Jakob, Bjørk, Marte-Helene
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Medical Association 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9513705/
https://www.ncbi.nlm.nih.gov/pubmed/36156660
http://dx.doi.org/10.1001/jamaneurol.2022.2977
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author Vegrim, Håkon Magne
Dreier, Julie Werenberg
Alvestad, Silje
Gilhus, Nils Erik
Gissler, Mika
Igland, Jannicke
Leinonen, Maarit K.
Tomson, Torbjörn
Sun, Yuelian
Zoega, Helga
Christensen, Jakob
Bjørk, Marte-Helene
author_facet Vegrim, Håkon Magne
Dreier, Julie Werenberg
Alvestad, Silje
Gilhus, Nils Erik
Gissler, Mika
Igland, Jannicke
Leinonen, Maarit K.
Tomson, Torbjörn
Sun, Yuelian
Zoega, Helga
Christensen, Jakob
Bjørk, Marte-Helene
author_sort Vegrim, Håkon Magne
collection PubMed
description 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 3 379 171 children after exclusion of 126 711 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 3 379 171 children was 7.3 years (IQR, 3.5-10.9 years). Among the 27 784 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, 46 646 (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.
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spelling pubmed-95137052022-10-14 Cancer Risk in Children of Mothers With Epilepsy and High-Dose Folic Acid Use During Pregnancy Vegrim, Håkon Magne Dreier, Julie Werenberg Alvestad, Silje Gilhus, Nils Erik Gissler, Mika Igland, Jannicke Leinonen, Maarit K. Tomson, Torbjörn Sun, Yuelian Zoega, Helga Christensen, Jakob Bjørk, Marte-Helene JAMA Neurol Original Investigation 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 3 379 171 children after exclusion of 126 711 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 3 379 171 children was 7.3 years (IQR, 3.5-10.9 years). Among the 27 784 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, 46 646 (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. American Medical Association 2022-09-26 2022-11 /pmc/articles/PMC9513705/ /pubmed/36156660 http://dx.doi.org/10.1001/jamaneurol.2022.2977 Text en Copyright 2022 Vegrim HM et al. JAMA Neurology. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the CC-BY License.
spellingShingle Original Investigation
Vegrim, Håkon Magne
Dreier, Julie Werenberg
Alvestad, Silje
Gilhus, Nils Erik
Gissler, Mika
Igland, Jannicke
Leinonen, Maarit K.
Tomson, Torbjörn
Sun, Yuelian
Zoega, Helga
Christensen, Jakob
Bjørk, Marte-Helene
Cancer Risk in Children of Mothers With Epilepsy and High-Dose Folic Acid Use During Pregnancy
title Cancer Risk in Children of Mothers With Epilepsy and High-Dose Folic Acid Use During Pregnancy
title_full Cancer Risk in Children of Mothers With Epilepsy and High-Dose Folic Acid Use During Pregnancy
title_fullStr Cancer Risk in Children of Mothers With Epilepsy and High-Dose Folic Acid Use During Pregnancy
title_full_unstemmed Cancer Risk in Children of Mothers With Epilepsy and High-Dose Folic Acid Use During Pregnancy
title_short Cancer Risk in Children of Mothers With Epilepsy and High-Dose Folic Acid Use During Pregnancy
title_sort cancer risk in children of mothers with epilepsy and high-dose folic acid use during pregnancy
topic Original Investigation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9513705/
https://www.ncbi.nlm.nih.gov/pubmed/36156660
http://dx.doi.org/10.1001/jamaneurol.2022.2977
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