Maternal Use of Folic Acid and Other Supplements and Risk of Childhood Brain Tumors

Milne, Elizabeth; Greenop, Kathryn R.; Bower, Carol; Miller, Margaret; Bockxmeer, Frank M. van; Scott, Rodney J.; Klerk, Nicholas de; Ashton, Lesley J.; Gottardo, Nicholas G.; Armstrong, Bruce K.

doi:10.1158/1055-9965.epi-12-0803

Cited by 62 publications

(92 citation statements)

References 37 publications

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“…Among the studies, one considered folate supplements only [31] and 2 considered dietary folate intake only [29,30], while the other 7 studies considered both folate supplements and dietary folate intake [32][33][34][35][36][37][38]. Five studies reported maternal folate intake during pregnancy only [29-31, 34, 37], whereas the other 5 studies presented findings for maternal folate intake before and during pregnancy separately [32,33,35,36,38].…”

Section: Study Characteristicsmentioning

confidence: 99%

“…Five studies reported maternal folate intake during pregnancy only [29-31, 34, 37], whereas the other 5 studies presented findings for maternal folate intake before and during pregnancy separately [32,33,35,36,38].…”

Section: Study Characteristicsmentioning

confidence: 99%

“…Several studies have previously reported an inverse association between maternal folic acid supplementation in the periconceptional period and risk of CB-SCT [29][30][31][32], whereas others have reported largely null findings [33][34][35][36][37][38]. Therefore, the aim of this study was to conduct a systematic review and meta-analysis on maternal folate intake before and during pregnancy and the risk of CBSCT.…”

Section: Introductionmentioning

confidence: 99%

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Maternal Folate Intake and Risk of Childhood Brain and Spinal Cord Tumors: A Systematic Review and Meta-Analysis

2018

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Background: Many epidemiological studies have investigated the effect of maternal diet and prenatal multivitamin supplementation on pediatric cancer risk. Childhood brain and spinal cord tumors (CBSCT) have been attributed to different possible risk factors. Methods: We conducted a systematic review and meta-analysis on maternal folate intake before and during pregnancy and the risk of CBSCT. We systematically reviewed publications obtained by searching the Insitute for Scientific Information Web of Knowledge and PubMed literature databases. We extracted the risk estimate of the highest and the lowest reported categories of intake from each study and conducted a meta-analysis using a random-effects model. Results: The results of the pooled analysis of all 10 studies, 1 cohort and 9 case-control studies, indicated that maternal folate intake was inversely associated with CBSCT risk (OR 0.77; 95% CI 0.67–0.88, p < 0.001; I² = 51.22%, p = 0.001). Separate analyses on the basis of the source of folate (folic acid supplementation, dietary folate) and in relation to the timing of exposure (before pregnancy, during pregnancy) found that folic acid supplementation was associated with an approximately 23% reduction in CBSCT risk (OR 0.77, 95% CI 0.66–0.90, p = 0.001; I² = 53.18%, p = 0.001) and consumption during pregnancy was associated with an approximately 20% reduction in CBSCT risk (OR 0.80, 95% CI 0.67–0.97, p = 0.020; I² = 62.48%, p < 0·001). Conclusions: Maternal consumption of folic acid is associated with a reduced risk of CBSCT. Further investigations are necessary to increase the reliability of the results and estimate the relationship between dose-response and the best outcome.

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Section: Study Characteristicsmentioning

confidence: 99%

Section: Study Characteristicsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Maternal Folate Intake and Risk of Childhood Brain and Spinal Cord Tumors: A Systematic Review and Meta-Analysis

2018

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“…Detailed recruitment and participation rates have been published previously (1). Briefly, we were notified of 730 eligible CBT cases diagnosed from 2005 to 2010, of whom 568 (77.8%) were invited to participate by their treating clinician.…”

Section: Resultsmentioning

confidence: 99%

“…Tumor subtype analyses were conducted using models as above, limiting cases to specific subtypes compared with all controls. Maternal folic acid supplementation in the month before pregnancy was stratified by genotype; this period of use was most associated with reduced CBT risk in our previous work (1). Evidence for an interaction was assessed formally by fitting a product term to a model (Wald test P values of interaction terms are reported in tables).…”

Section: Genotypingmentioning

confidence: 99%

Folate Pathway Gene Polymorphisms and Risk of Childhood Brain Tumors: Results from an Australian Case–Control Study

Greenop¹,

Scott²,

Attia³

et al. 2015

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: Recent research suggests that maternal folic acid supplementation is associated with a reduced risk of childhood brain tumors (CBT); polymorphisms in folate pathway genes could modify this association or directly influence CBT risk.Methods: Associations between risk of CBT and folate pathway polymorphisms were investigated in a population-based casecontrol study in Australia (2005Australia ( -2010. Cases were recruited through all Australian pediatric oncology centers and controls by national random digit dialing. Data were available from 321 cases and 552 controls. Six polymorphisms were genotyped in children and parents (MTHFR 677C>T, MTHFR 1298A>C, MTRR 66A>G, MTR 2756A>G, MTR 5049C>A, and CBS 2199 T>C). Maternal folic acid use was ascertained via questionnaire. ORs were estimated using unconditional logistic regression. Caseparent trio analyses were also undertaken.

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

et al. 2022

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ImportanceWomen 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.ObjectiveTo assess whether high-dose folic acid supplementation in mothers with epilepsy is associated with childhood cancer.Design, Setting, and ParticipantsObservational 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.ExposuresMaternal prescription fills for high-dose folic acid tablets (≥1 mg daily) between 90 days before pregnancy start and birth.Main Outcomes and MeasuresFirst 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.ResultsThe 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 RelevancePrenatal exposure to high-dose folic acid was associated with increased risk of cancer in children of mothers with epilepsy.

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Maternal Use of Folic Acid and Other Supplements and Risk of Childhood Brain Tumors

Cited by 62 publications

References 37 publications

Maternal Folate Intake and Risk of Childhood Brain and Spinal Cord Tumors: A Systematic Review and Meta-Analysis

Maternal Folate Intake and Risk of Childhood Brain and Spinal Cord Tumors: A Systematic Review and Meta-Analysis

Folate Pathway Gene Polymorphisms and Risk of Childhood Brain Tumors: Results from an Australian Case–Control Study

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

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