Folic Acid Supplements and Risk of Facial Clefts: National Population Based Case-Control Study

Wilcox, Allen J.; Lie, Rolv Terje; Solvoll, Kari; Taylor, Jack A.; McConnaughey, D. Robert; Åbyholm, Frank; Vindenes, Hallvard; Vollset, Stein Emil; Drevon, Christian A.

doi:10.1097/01.ogx.0000268659.58486.f4

Cited by 27 publications

(34 citation statements)

References 10 publications

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“…In this regard, it is interesting to note effects of maternal genotype and maternalspecific environmental modifiers such as smoking, drinking and vitamin intake during pregnancy on oral cleft susceptibility have been previously reported in various studies. 2,[10][11][12][13][14][15][16][17][18][19] However, it should be noted that the parental asymmetry tests we applied here do not specifically test for maternal effects which would be expected to occur via alterations of the in utero environment. Calculation of genomic inflation factors for the MAT and PAT tests showed a small increase for the MAT compared with the PAT in all categories, this increased inflation factor in the MAT does not discern the underlying cause, being consistent with either a true excess of biological associations with the maternally inherited alleles, or alternatively differing population structure between the two parental populations.…”

Section: Discussionmentioning

confidence: 99%

“…2,10,11 Similarly, according to several studies, multi-vitamin supplements with or without folic acid taken during pregnancy have been shown to decrease the risk of oral clefting, with a stronger effect seen in CL/P as compared with CPO. [12][13][14] If levels of circulating folate are influenced by genetic factors, then it can be hypothesized any maternal genes involved in dictating circulating folate levels could also alter the risk of OFCs in the fetus. Indeed, evidence in support of this idea has recently been published.…”

Section: Introductionmentioning

confidence: 99%

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Genome-wide analysis of parent-of-origin effects in non-syndromic orofacial clefts

et al. 2013

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Parent-of-origin (PofO) effects, such as imprinting are a phenomenon where the effect of variants depends on parental origin. Conventional association studies assume that phenotypic effects are independent of parental origin, and are thus severely underpowered to detect such non-Mendelian effects. Risk of orofacial clefts is influenced by genetic and environmental effects, the latter including maternal-specific factors such as perinatal smoking and folate intake. To identify variants showing PofO effects in orofacial clefts we have used a modification of the family-based transmission disequilibrium test to screen for biased transmission from mothers and fathers to affected offspring, biased ratios of maternal versus paternal transmission, and biased frequencies of reciprocal classes of heterozygotes among offspring. We applied these methods to analyze published genomewide single-nucleotide polymorphism (SNP) data from B2500 trios mainly of European and Asian ethnicity with non-syndromic orofacial clefts, followed by analysis of 64 candidate SNPs in a replication cohort of B1200 trios of European origin. In our combined analysis, we did not identify any SNPs achieving conventional genome-wide significance (Po5 Â 10 À8 ). However, we observed an overall excess of loci showing maternal versus paternal transmission bias (P ¼ 0.013), and identified two loci that showed nominally significant effects in the same direction in both the discovery and replication cohorts, raising the potential for PofO effects. These include a possible maternal-specific transmission bias associated with rs12543318 at 8q21.3, a locus identified in a recent meta-analysis of non-syndromic cleft (maternal-specific P ¼ 1.5 Â 10 À7 , paternal-specific P ¼ 0.17). Overall, we conclude from this analysis that there are subtle hints of PofO effects in orofacial clefting.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Genome-wide analysis of parent-of-origin effects in non-syndromic orofacial clefts

et al. 2013

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“…A low maternal serum folate concentration before conception and during the first weeks after conception is associated with an increased risk of fetal neural tube defects (NTD) and other non-NTD birth defects (1)(2)(3) and can be prevented by the intake of folic acid (4) . Adequate folic acid supplementation has been shown to substantially increase folate serum levels (5) .…”

mentioning

confidence: 99%

Validation of self-reported folic acid use in a multiethnic population: results of the Amsterdam Born Children and their Development study

Sikkens

Eijsden

Bonsel

et al. 2011

Public Health Nutr.

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Objective: To assess folic acid supplementation rates and validate the self-reporting of folic acid supplement use among pregnant women in a multiethnic cohort. Design: Secondary analysis of a prospective cohort study. Setting: Self-reported folic acid supplement use in the Amsterdam Born Children and their Development study cohort was compared with serum folate concentrations using non-parametric trend analysis and linear and logistic regression. Subjects: A total of 4234 pregnant women of various ethnic backgrounds. Results: Serum folate levels showed a significant positive linear trend as reported use of folic acid increased (P , 0?001), which was supported by linear regression (r 5 0?49). Odds of having low serum folate concentration decreased with reported early start of folic acid intake. Young, multiparous or non-Western women reported less pre-conception folic acid intake. Non-Western women showed lower serum folate concentrations. The overall rate of over-reporting, i.e. serum folate concentrations #20 nmol/l while reporting the use of folic acid supplements, was 20?7 %. Women of Surinamese and Moroccan ancestry had higher odds of overreporting (OR 5 2?3; 95 % CI 1?5, 3?5 and OR 5 2?3; 95 % CI 1?3, 4?0, respectively). The odds for Surinamese women remained significant after adjusting for the onset of supplement use, parity and age (OR 5 1?7; 95 % CI 1?1, 2?6). Conclusions: Although self-reporting is a valid method for assessing folic acid supplement use in a multiethnic population, some participants do over-report. Surinamese and possibly Moroccan women appear to over-report more often. Rates of supplementation are low, especially in non-Western women. This suggests the need for intensifying current campaigns or perhaps even additional advice to start or continue to use folic acid post-conceptionally.

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“…Low maternal B6 and B12 levels measured after pregnancy was reported to increase the risk of CL/P especially in cases associated with low serum folate. Animal studies have also confirmed the anti-teratogenic effects of prenatal folic acid supplementation and dietary folate [34][35][36].…”

Section: Prevention and Intervention Strategiesmentioning

confidence: 72%

Cleft Lip and Palate: Etiology, Epidemiology, Preventive and Intervention Strategies

Allam¹,

Stone²

2013

Anat Physiol

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Cleft lip and palate represent a major public health problem due to the possible associated life-long morbidity, complex etiology, and the extensive multidisciplinary commitment required for intervention. It affects about 1.5 per 1000 live births (250,000 new cases per year) worldwide, with tremendous variations across geographic areas and ethnic groups. It is considered a debilitating condition that is associated with significant feeding, hearing, speech, and psychological impairments. The wide surgical, dental, speech, social, and medical involvement emphasize the importance of understanding the underlying determinants of these defects to allow optimizing the treatment options and predicting the long-term course of the affected individuals development. Optimal and early surgical intervention is necessary and folic acid supplementation proved to be a highly efficient preventive strategy. However, there are still many challenges to be addressed for cleft care especially in the developing parts of the world.

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Folic Acid Supplements and Risk of Facial Clefts: National Population Based Case-Control Study

Cited by 27 publications

References 10 publications

Genome-wide analysis of parent-of-origin effects in non-syndromic orofacial clefts

Genome-wide analysis of parent-of-origin effects in non-syndromic orofacial clefts

Validation of self-reported folic acid use in a multiethnic population: results of the Amsterdam Born Children and their Development study

Cleft Lip and Palate: Etiology, Epidemiology, Preventive and Intervention Strategies

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