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Association between inhibited binding of folic acid to folate receptor alpha in maternal serum and folate-related birth defects in Norway.

ABSTRACT: Folic acid intake during pregnancy can reduce the risk of neural tube defects (NTDs) and perhaps also oral facial clefts. Maternal autoantibodies to folate receptors can impair folic acid binding. We explored the relationship of these birth defects to inhibition of folic acid binding to folate receptor ? (FR?), as well as possible effects of parental demographics or prenatal exposures.We conducted a nested case-control study within the Norwegian Mother and Child Cohort Study. The study included mothers of children with an NTD (n = 11), cleft lip with or without cleft palate (CL/P, n= 72), or cleft palate only (CPO, n= 27), and randomly selected mothers of controls (n = 221). The inhibition of folic acid binding to FR? was measured in maternal plasma collected around 17 weeks of gestation. On the basis of prior literature, the maternal age, gravidity, education, smoking, periconception folic acid supplement use and milk consumption were considered as potential confounding factors.There was an increased risk of NTDs with increased binding inhibition [adjusted odds ratio (aOR) = 1.4, 95% confidence interval (CI) 1.0-1.8]. There was no increased risk of oral facial clefts from inhibited folic acid binding to FR? (CL/P aOR = 0.7, 95% CI 0.6-1.0; CPO aOR = 1.1, 95% CI 0.8-1.4). No association was seen between smoking, folate supplementation or other cofactors and inhibition of folic acid binding to FR?.Inhibition of folic acid binding to FR? in maternal plasma collected during pregnancy was associated with increased risk of NTDs but not oral facial clefts.

SUBMITTER: Boyles AL

PROVIDER: S-EPMC3137385 | biostudies-other | 2011 Aug

REPOSITORIES: biostudies-other

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Association between inhibited binding of folic acid to folate receptor alpha in maternal serum and folate-related birth defects in Norway.

Boyles A L AL Ballard J L JL Gorman E B EB McConnaughey D R DR Cabrera R M RM Wilcox A J AJ Lie R T RT Finnell R H RH

Human reproduction (Oxford, England) 20110515 8

<h4>Background</h4>Folic acid intake during pregnancy can reduce the risk of neural tube defects (NTDs) and perhaps also oral facial clefts. Maternal autoantibodies to folate receptors can impair folic acid binding. We explored the relationship of these birth defects to inhibition of folic acid binding to folate receptor α (FRα), as well as possible effects of parental demographics or prenatal exposures.<h4>Methods</h4>We conducted a nested case-control study within the Norwegian Mother and Chil ...[more]

PMID: 21576080

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Project description:BackgroundThe main objective was to investigate the burden of birth defects among alive infants and explore the impact of maternal lifestyle during pregnancy on the burden of birth defects in Northwest China.MethodsA stratified multi-stage sampling method was used to study infants born during 2010-2013 (and their mothers) in Shaanxi province of Northwest China. Socio-demographic information was collected using a structured questionnaire, and medical records from the local hospitals were used to determine the final diagnosis of birth defects. Poisson regression analysis was performed to assess the association between maternal lifestyles during pregnancy and the burden of birth defects, while adjusting for potential confounders.ResultsWe sampled 29098 infants, of whom 629 (i.e. 216.17 per 10000) were observed to have congenital defects. Cardiovascular system defects (77.32 per 10000) were found to be the most common. Mothers who had ever consumed alcohol during pregnancy were found to have infants with a higher prevalence of some categories of birth defects, including nervous system (Prevalence Rate Ratio, PRR:14.67, 95% CI: 1.94, 110.92), cardiovascular system (PRR:3.22, 95% CI: 1.02, 10.16) and oral clefts (PRR:9.02, 95% CI: 2.08, 39.10) in contrast to infants of mothers without any alcohol consumption. Maternal passive smoking during pregnancy lead to the increased burden of malformations of eye, ear, face and neck (PRR:1.95, 95% CI: 1.15, 3.33), cardiovascular system (PRR:1.70, 95% CI: 1.25, 2.31) and respiratory system (PRR:9.94, 95% CI: 2.37, 41.76) in their newborns. Further, tea or coffee consumption during pregnancy was positively correlated with the burden of specific birth defects, such as cardiovascular system (PRR: 2.44, 95% CI: 1.33, 4.46) and genital organs (PRR:14.72, 95% CI: 1.87, 116.11) among infants.ConclusionsThe prevalence of birth defects was high in Shaanxi province of Northwest China. The unhealthy lifestyles of mothers during pregnancy may increase the prevalence of congenital malformations. These findings in future may have some important implications for prevention of birth defects in Northwest China.

Project description:BackgroundIt has been reported that neural tube defects can be prevented with periconceptional folic acid supplementation. The effects of different doses, forms and schemes of folate supplementation for the prevention of other birth defects and maternal and infant outcomes are unclear.ObjectivesThis review updates and expands a previous Cochrane Review assessing the effects of periconceptional supplementation with folic acid to reduce neural tube defects (NTDs). We examined whether folate supplementation before and during early pregnancy can reduce neural tube and other birth defects (including cleft palate) without causing adverse outcomes for mothers or babies.Search strategyWe searched the Cochrane Pregnancy and Childbirth Group's Trials Register (July 2010). Additionally, we searched the international clinical trials registry platform and contacted relevant organisations to identify ongoing and unpublished studies.Selection criteriaWe included all randomised or quasi-randomised trials evaluating the effect of periconceptional folate supplementation alone, or in combination with other vitamins and minerals, in women independent of age and parity.Data collection and analysisWe assessed trials for methodological quality using the standard Cochrane criteria. Two authors independently assessed the trials for inclusion, one author extracted data and a second checked for accuracy.Main resultsFive trials involving 6105 women (1949 with a history of a pregnancy affected by a NTD and 4156 with no history of NTDs) were included. Overall, the results are consistent in showing a protective effect of daily folic acid supplementation (alone or in combination with other vitamins and minerals) in preventing NTDs compared with no interventions/placebo or vitamins and minerals without folic acid (risk ratio (RR) 0.28, 95% confidence interval (CI) 0.15 to 0.52). Only one study assessed the incidence of NTDs and the effect was not statistically significant (RR 0.08, 95% CI 0.00 to 1.33) although no events were found in the group that received folic acid. Folic acid had a significant protective effect for reoccurrence (RR 0.32, 95% CI 0.17 to 0.60). There is no statistically significant evidence of any effects on prevention of cleft palate, cleft lip, congenital cardiovascular defects, miscarriages or any other birth defects. There were no included trials assessing the effects of this intervention on maternal blood folate or anaemia at term.We found no evidence of short-term side effects.Authors' conclusionsFolic acid, alone or in combination with vitamins and minerals, prevents NTDs but does not have a clear effect on other birth defects.

Dataset Information

Association between inhibited binding of folic acid to folate receptor alpha in maternal serum and folate-related birth defects in Norway.

Publications

Association between inhibited binding of folic acid to folate receptor alpha in maternal serum and folate-related birth defects in Norway.

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