Maternal Epilepsy, Prenatal Exposure to High-Dose Folic Acid, and Risk of Childhood Cancer: A Nordic Registry-Based Cohort Study
Abstract number :
2.13
Submission category :
4. Clinical Epilepsy / 4E. Women's Issues
Year :
2021
Submission ID :
1826503
Source :
www.aesnet.org
Presentation date :
12/5/2021 12:00:00 PM
Published date :
Nov 22, 2021, 06:55 AM
Authors :
Håkon Vegrim, MD - University of Bergen; Julie Werenberg Dreier, PhD - Senior scientist, Department of Economics and Business Economics, Aarhus University; Silje Alvestad, MD PhD - Postdoc, Department of Clinical Medicine 1, University of Bergen; Nils Erik Gilhus, MD PhD - Professor, Department of Clinical Medicine 1, University of Bergen; Mika Gissler, PhD - Professor, Information Services Department, Finnish Institute for Health and Welfare; Jannicke Igland, PhD - Senior engineer, Department of Clinical Medicine 1, University of Bergen; Maarit Leinonen, MD PhD - Project Manager, Information Services Department, Finnish Institute for Health and Welfare; Torbjörn Tomson, MD PhD - Professor, Department of Clinical Neuroscience, Karolinska Institutet; Yuelian Sun, MD PhD - Associate Professor, Department of Economics and Business Economics, Aarhus University; Helga Zoega, PhD - Professor, Centre of Public Health Sciences, University of Iceland; Jakob Christensen, MD PhD DrMedSci - Associate Professor, Department of Economics and Business Economics, Aarhus University; Marte-Helene Bjørk, MD PhD - Associate Professor, Department of Clinical Medicine 1, University of Bergen
Rationale: Folate is essential in the formation and repair of nucleic acids. Folic acid is recommended to all pregnant women to reduce risk of neural tube defects. Women with anti-seizure medication (ASM) are at increased risk of having a child with congenital malformations including neural tube defects. Therefore, high dose folic acid (1mg-5mg daily) is used before and during pregnancy in many pregnant women with epilepsy. Little is known about potential adverse effects of prenatal exposure to high doses of folic acid. There are concerns related to high serum levels of unmetabolized folic acid and future cancer risk for the child.
Methods: All filled prescriptions for high dose folic acid (1 or 5mg) from Denmark (1997-2017), Norway (2005-2017) and Sweden (2006-2017) were identified through the SCAN-AED project and linked with nationwide health and social registers. The International Classification of Childhood Cancer was used to define cancers identified in the national cancer registries with onset below age 20 years. Cox proportional model was used to calculate adjusted hazard ratios (aHR) with 95% confidence intervals, adjusting for sex, maternal age and education, prenatal ASM exposure, maternal smoking, number of maternal comorbidities, and birthweight. Stratification was done for country and birth year. Exposure-time was defined as a filled prescription for high dose folic acid between 90 days prior to the first day of the last menstrual period and birth.
Results: From a population of 3,325,277 children, we identified 27,527 children (0.8%) born to mothers with epilepsy. The median follow-up time from birth was 6.5 years (interquartile range 3.3-10.3 years). Among children of mothers with epilepsy, 5,881 (21.4%) were exposed to high dose folic acid and 21,646 (78.6%) unexposed.
Children of women with epilepsy exposed to high dose folic acid had an increased risk of childhood cancer when compared to such children unexposed to high dose folic acid (n=18, incidence rate 42.9/100,000, aHR 3.3 (95% CI: 1.7-7.9)). Children born to women without epilepsy exposed to high dose folic acid had no increased risk of childhood cancer when compared to such children unexposed to high dose folic acid (n=69, incidence rate 18.6/100,000, aHR 1.1 (95% CI: 0.8-1.4)).
Conclusions: Prenatal exposure to high dose folic acid was associated with an increased risk of childhood cancer among children to women with epilepsy. In contrast, high-dose folic acid was not associated with an increased risk of childhood cancer in children born to women without epilepsy. The results warrant further studies into the risks associated with maternal epilepsy, maternal comorbidities, and prenatal exposure to drugs including antiseizure medication.
Funding: Please list any funding that was received in support of this abstract.: This work was supported by the NordForsk Nordic Program on Health and Welfare (Project #83796).
Clinical Epilepsy