Can folic acid protect against congenital heart defects in down syndrome?

Meijer, Willemijn M.; Werler, Martha M.; Louik, Carol; Hernández–Dı́az, Sonia; Berg, Lolkje Theodora Wilhelmina de Jong-van den; Mitchell, Allen A.

doi:10.1002/bdra.20312

Cited by 12 publications

(15 citation statements)

References 17 publications

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“…Our results differ from that of Meijer et al(2006) who used a similar study design based on liveborn infants with DS and CHD (case) and DS and no CHD (control). They found no statistically significant association between use of folic acid-containing supplements and CHD in DS.…”

Section: Discussioncontrasting

confidence: 99%

Lack of maternal folic acid supplementation is associated with heart defects in Down syndrome: A report from the National Down Syndrome Project

Bean

Allen

Tinker

et al. 2011

Birth Defects Research Part A: Clinical and Molecular Teratolog

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BACKGROUND Maternal folic acid supplementation has been associated with a reduced risk for neural tube defects, and may be associated with a reduced risk for congenital heart defects, and other birth defects. Individuals with Down syndrome are at high risk for congenital heart defects and have been shown to have abnormal folate metabolism. METHODS As part of the population-based case-control National Down Syndrome Project, 1011 mothers of infants with Down syndrome reported their use of folic acid-containing supplements. These data were used to determine whether lack of periconceptional maternal folic acid supplementation is associated with congenital heart defects in Down syndrome. We used logistic regression to test the relationship between maternal folic acid supplementation and the frequency of specific heart defects correcting for maternal race/ethnicity, proband sex, maternal use of alcohol and cigarettes, and maternal age at conception. RESULTS Lack of maternal folic acid supplementation was more frequent among infants with Down syndrome and atrioventricular septal defects (OR=1.69; 95% CI, 1.08–2.63; P=0.011) or atrial septal defects (OR=1.69; 95% CI, 1.11–2.58; P=0.007) than among infants with Down syndrome and no heart defect. Preliminary evidence suggests that the patterns of association differ by race/ethnicity and sex of the proband. There was no statistically significant association with ventricular septal defects (OR=1.26; 95% CI, 0.85–1.87; P=0.124). CONCLUSIONS Our results suggest that lack of maternal folic acid supplementation is associated with septal defects in infants with Down syndrome.

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Section: Discussioncontrasting

confidence: 99%

Lack of maternal folic acid supplementation is associated with heart defects in Down syndrome: A report from the National Down Syndrome Project

Bean

Allen

Tinker

et al. 2011

Birth Defects Research Part A: Clinical and Molecular Teratolog

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“…According to the search strategy, a total of 20 citations were included in the meta-analysis. 4,14,15,19,[24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39] The characteristics and information of the eligible studies are shown in Supplemental Table I. Nine articles were written in English and 11 in Chinese.…”

Section: Resultsmentioning

confidence: 99%

“…18) Willemij, et al did not observe a protective effect of FA on heart defects among infants with Down syndrome. 19) There is a need for comprehensive analysis of this association.…”

mentioning

confidence: 99%

A Meta-Analysis of the Relationship Between Maternal Folic Acid Supplementation and the Risk of Congenital Heart Defects

Cao

et al. 2016

Int. Heart J.

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SummaryControversial opinions exist with respect to the relationship between maternal folic acid (FA) supplementation and birth prevalence of congenital heart defects (CHDs).Eligible articles were retrieved by searching databases, including PubMed, Cochrane library, EMBASE, CNKI, and WanFang up to September 2015. A meta-analysis was performed to evaluate the effects of FA on CHDs. Odds ratios (ORs) and 95% confidence interval (CIs) were merged using STATA 12.0. Meta-regression analysis was used to explore the possible sources of heterogeneity. Subgroup analysis according to the selected sources was also performed. Publication bias was assessed by Egger's test.Twenty studies were included in the meta-analysis. The overall analysis showed that FA supplementation was significantly associated with decreased risk of CHDs. The meta-regression analysis showed that geographical area could be an important source of heterogeneity. The subgroup analysis based on the geographical area revealed that FA supplementation during pregnancy was a protective factor against CHDs in Chinese and European patients, but not in American patients. Subgroup analysis according to literature quality also displayed positive associations between FA supplementation and the decreased risk of CHDs of China.FA supplementation during pregnancy significantly decreases the risk of CHDs in newborns in China and Europe. (Int Heart J 2016; 57: 725-728) Key words: Literature search, Meta-regression analysis, Geographical area, Pregnancy C ongenital heart defects (CHDs) are the most common structural abnormalities presenting at birth, and they are also one of the leading causes of perinatal and infant mortality.1) It is reported that the prevalence of CHDs accounts for 6% of all neonatal death factors, and also accounts for 46% of all congenital lethal factors.2-4) Recently, the survival of newborns with CHDs has increased due to massive breakthroughs in cardiovascular diagnostics and cardiothoracic surgery, 5,6) however, this trend consequently generates a completely novel and steady increasing population with grown-up congenital heart disease (GUCH). Patients with GUCH often need long-term expert medical care with high healthcare-related costs. 7) Moreover, recently, an increasing number of women have postponed conception to an older age, which consequently results in a higher birth prevalence of congenital defects. 8,9) These defects lead to great economic pressure and mental burdens on society and the families, therefore, searching for effective prevention measures for CHDs is of great practical significance.Folic acid (FA) is an essential nutrient and plays an important role in the development of the cardiovascular system.10-12) The association of FA or multivitamins containing FA supplementation during the critical periods of organ formation with the risk of the occurrence of CHDs has been recognized in past decades. [13][14][15] Several studies have reported that FA or multivitamins containing FA supplementation taken during pregnancy could signifi...

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“…Epidemiologic studies have shown that periconceptional vitamin supplementation with folic acid reduces the risk of CHD among offspring [Shaw et al, 1995;Botto and Correa, 2003]. Only one case-control study has investigated a possible association between vitamins and CHD in children with DS, but with negative results [Meijer et al, 2006].In the general population, Wenstrom et al [2001] found a significant association of MTHFR 677T allele and CHD when studying 26 pregnant women with affected offspring compared to 116 control mothers of normal babies. Subsequent studies revealed controversial results, some supporting the positive association between MTHFR polymorphisms and CHD in offspring [van Beynum et al, 2006;Zhu et al, 2006], while others could not find such associations [Storti et al, 2003;Nurk et al, 2004;Hobbs et al, 2006].…”

mentioning

confidence: 97%

Evaluation of C677T and A1298C polymorphisms of the MTHFR gene as maternal risk factors for Down syndrome and congenital heart defects

Brandalize

Bandinelli

Santos

et al. 2009

American J of Med Genetics Pt A

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Abnormal folate/homocysteine metabolism due to polymorphisms in genes involved in this pathway has been implicated as an etiologic factor in Down syndrome (DS). This case-control study aimed to evaluate the effect of maternal C677T and A1298C polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) as risk factors for the development of DS and congenital heart defects (CHD). The distribution of these genotypic variants was similar between mothers of children with DS (n = 239) and control mothers of normal children (n = 197), but the combined genotypes 677CT or TT and 1298AA increased the risk of having offspring with DS (OR = 1.99; 95% CI 1.11-3.55). The presence of the 677T allele in case mothers resulted in a 2.07-fold higher odds of CHD in the offspring (P < 0.01). Among the 57 mothers of CHD-affected children with DS who carried the MTHFR 677CT or TT genotypes and did not have periconceptional folic acid intake, we observed a 2.26-fold increased odds (95% CI 1.25-4.09) of having any CHD-affected child with DS. Our results show that MTHFR genetic polymorphisms may be involved in the etiology of DS in our population when controlling for age. We noted a borderline significant association for the C677T polymorphism (P = 0.05). Maternal 677T allele may be associated with an increased occurrence of CHD in children with DS and we anticipate that women who carry this polymorphism would benefit from periconceptional folic acid supplementation. (c) 2009 Wiley-Liss, Inc.

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Can folic acid protect against congenital heart defects in down syndrome?

Abstract: Our study does not show a protective effect of FA on heart anomalies among infants with DS.

Cited by 12 publications

References 17 publications

Lack of maternal folic acid supplementation is associated with heart defects in Down syndrome: A report from the National Down Syndrome Project

Lack of maternal folic acid supplementation is associated with heart defects in Down syndrome: A report from the National Down Syndrome Project

A Meta-Analysis of the Relationship Between Maternal Folic Acid Supplementation and the Risk of Congenital Heart Defects

Evaluation of C677T and A1298C polymorphisms of the MTHFR gene as maternal risk factors for Down syndrome and congenital heart defects

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