Supplemental folic acid in pregnancy and childhood cancer risk

Mortensen, Jan Helge Seglem; Øyen, Nina; Fomina, Tatiana; Melbye, Mads; Tretli, Steinar; Vollset, Stein Emil; Bjørge, Tone

doi:10.1038/bjc.2015.446

Cited by 23 publications

(19 citation statements)

References 19 publications

(27 reference statements)

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“…Hence in some subgroup analyses, the numbers of included studies were too small and may influence the conclusions. Since the included studies in our meta-analysis were almost all casecontrol studies [29][30][31][32][33][34][35][36]38] and only one a cohort study [37], recall bias and selection bias could have restricted the precision of our results. The preventive effect suggested by the case-control studies may be due to potential confounding factors and exposure misclassification.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, only 10 studies met the inclusion criteria: nine were case-control design studies [29][30][31][32][33][34][35][36]38] and one was a cohort study [37] (Fig. 1).…”

Section: Literature Searchmentioning

confidence: 99%

“…Four studies were conducted in Europe (in particular, one was conducted in France [38], one in Norway [37], one in Sweden [34] and one in Spain [35]), 3 studies in North America [29,30,33], 2 studies in Australia [32,36], and the remaining one was a multisite study [31].…”

Section: Study Characteristicsmentioning

confidence: 99%

“…Four studies reported tumors occurred in children aged 0-15 years [34][35][36]38], 3 studies tumors occurred in children aged 0-6 years [29,30,33], one study considered tumors occurred in children aged less than 5 years [31], one study tumors occurred in children aged 0-14 years [32], while the cohort study evaluated risk of CBSCT in children among all live births from 1 January 1999 through 31 December 2010 [37].…”

Section: Study Characteristicsmentioning

confidence: 99%

“…The quality scores varied in the range from 6 to 8 (median: 7.5). High-quality studies (i.e., those studies that had a score ≥7) included the cohort study [37] and 7 case-control studies [30-32, 34-36, 38].…”

Section: Quality Assessmentmentioning

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: Discussionmentioning

confidence: 99%

“…Therefore, only 10 studies met the inclusion criteria: nine were case-control design studies [29][30][31][32][33][34][35][36]38] and one was a cohort study [37] (Fig. 1).…”

Section: Literature Searchmentioning

confidence: 99%

Section: Study Characteristicsmentioning

confidence: 99%

Section: Study Characteristicsmentioning

confidence: 99%

Section: Quality Assessmentmentioning

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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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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Risk of neuroblastoma, birth‐related characteristics, congenital malformations and perinatal exposures: A pooled analysis of the ESCALE and ESTELLE French studies (SFCE)

Rios

Bailey

Orsi

et al. 2016

Intl Journal of Cancer

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Neuroblastoma (NB), an embryonic tumour arising from neural crest cells, is the most common malignancy among infants. The aetiology of NB is largely unknown. We conducted a pooled analysis to explore whether there is an association between NB and preconception and perinatal factors using data from two French national population-based case-control studies. The mothers of 357 NB cases and 1783 controls younger than 6 years, frequency-matched by age and gender, responded to a telephone interview that focused on demographic, socioeconomic and perinatal characteristics, childhood environment, life-style and maternal reproductive history. Unconditional logistic regression was used to estimate pooled odds ratios and 95% confidence intervals. After controlling for matching variables, study of origin and potential confounders, being born either small (OR 1.4 95% CI 1.0-2.0) or large (OR 1.5 95% CI 1.1-2.2) for gestational age and, among children younger than 18 months, having congenital malformations (OR 3.6 95% CI 1.3-8.9), were significantly associated with NB. Inverse associations were observed with breastfeeding (OR 0.7 95% CI 0.5-1.0) and maternal use of any supplements containing folic acid, vitamins or minerals (OR 0.5 95% CI 0.3-0.9) during the preconception period. Our findings reinforce the hypothesis that fetal growth anomalies and congenital malformations may be associated with an increased risk of NB. Further investigations are needed in order to clarify the role of folic acid supplementation and breastfeeding, given their potential importance in NB prevention.

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Supplemental folic acid in pregnancy and childhood cancer risk

Cited by 23 publications

References 19 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

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

Risk of neuroblastoma, birth‐related characteristics, congenital malformations and perinatal exposures: A pooled analysis of the ESCALE and ESTELLE French studies (SFCE)

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