OBJECTIVES: Maternal periconceptional folic acid supplement is by far the most effective primary prevention strategy to reduce the incidence of congenital heart disease (CHD) in offspring. It was revealed that the underlying mechanisms are complex, including a combination of genetic and environmental factors. The purpose of this study is to investigate the association between periconceptional folic acid supplement, the genetic polymorphisms of maternal folic acid receptor 1 gene (FOLR1) and folic acid receptor 2 gene (FOLR2) and the impact of their interaction on the risk of CHD in offspring, and to provide epidemiological evidence for individualized folic acid dosing in hygienic counseling. METHODS: A case-control study on 569 mothers of CHD infants and 652 mothers of health controls was performed. The interesting points were periconceptional folate supplements, single nucleotide polymorphisms (SNPs) of maternal FOLR1 gene and FOLR2 gene. RESULTS: Mothers who took folate in the periconceptional period were observed a decreased risk of CHD [adjusted odds ratio (aOR)=0.58, 95% CI 0.35 to 0.95]. Our study also found that polymorphisms of maternal FOLR1 gene at rs2071010 (G/A vs G/G: aOR=0.67, 95% CI 0.47 to 0.96) and FOLR2 gene at rs514933 (T/C vs T/T: aOR=0.60, 95% CI 0.43 to 0.84; C/C vs T/T: aOR=0.55, 95% CI 0.33 to 0.90; the dominant model: T/C+ C/C vs T/T: aOR=0.59, 95% CI 0.43 to 0.81; and the addictive model: C/C vs T/C vs T/T: aOR=0.70, 95% CI 0.56 to 0.88) were significantly associated with lower risk of CHD [all P<0.05, false discovery rate P value (FDR_P)<0.1]. Besides, significant interaction between periconceptional folate supplements and rs2071010 G→A (aOR=0.59, 95% CI 0.41-0.86) and rs514933 T→C (aOR=0.52, 95% CI 0.37 to 0.74) on CHD risk were observed (all P<0.05, FDR_P<0.1). CONCLUSIONS Periconceptional folate supplements, polymorphisms of FOLR1 gene and FOLR2 gene and their interactions are significantly associated with risk of CHD. However, more studies in different ethnic populations with a larger sample and prospective designs are required to confirm our findings.
Case-Control Studies ; Dietary Supplements ; Female ; Folate Receptor 1/genetics* ; Folate Receptor 2/genetics* ; Folic Acid/administration & dosage* ; Heart Defects, Congenital/genetics* ; Hospitals ; Humans ; Infant ; Polymorphism, Single Nucleotide ; Prospective Studies ; Risk Factors

Objective: To determine the prevalence and determinants of folic acid (FA) supplementation in Chinese couples planning for pregnancy and in women during early pregnancy. Methods: This was a cross-sectional study based on the Shanghai PreConception Cohort (SPCC) study. Data on FA supplementation and socio-demographic features were collected using questionnaires. Couples visiting clinics for pre-pregnancy examination and pregnant women at < 14 gestational weeks were recruited in Shanghai, China, between March 2016 and September 2018. Results: Among the pregnancy planners, 42.4% (4,710/11,099) women and 17.1% (1,377/8,045) men used FA supplements, while 93.4% (14,585/15,615) of the pregnant women used FA supplements. FA supplement use was higher in female pregnancy planners who were older ( : 1.13, 95% : 1.08-1.18), had higher education ( : 1.71, 95% : 1.53-1.92), and were residing in urban districts ( : 1.06, 95% : 1.01-1.11) of FA supplementation; female pregnancy planners with alcohol consumption ( : 0.95, 95% : 0.90-0.99) had lower odds of FA supplementation. In early pregnancy, women with higher educational level ( : 1.04, 95% : 1.03-1.06), who underwent pre-pregnancy examination ( : 1.02, 95% : 1.01-1.03) had higher odds of using an FA supplement; older aged ( : 0.99, 95% : 0.98-0.99), and multigravida ( : 0.97, 95% : 0.96-0.98) had lower odds of FA supplementation. Conclusion Although the majority of pregnant women took FA supplements, more than half of the women planning for pregnancy did not. Urgent strategies are needed to improve pre-conception FA supplementation.
Adult ; China ; Cohort Studies ; Cross-Sectional Studies ; Diet ; Dietary Supplements ; analysis ; Female ; Folic Acid ; administration & dosage ; Humans ; Male ; Pregnancy ; Surveys and Questionnaires ; Vitamin B Complex ; administration & dosage ; Young Adult

OBJECTIVETo investigate the status of folic acid (FA) supplementation and determinants of its use in pregnant Chinese women.

METHODSIn this cross-sectional study, questionnaires were used to collect information of participants and FA supplementation. Women were recruited between 6 and 12 weeks postpartum in Tianjin, China, between July 2015 and July 2016.

RESULTSA total of 1,921 women were recruited in the study. Approximately 93.1% of the study participants used FA, while 14.4% of the women taking FA from three months prior to preconception to three months post-conception. Women who took FA for three months prior to preconception through at least three months into their pregnancy were more likely to be between 30 and 34 years old (OR = 2.91, 95% CI: 1.15, 7.33), employed (OR = 2.07, 95% CI: 1.17, 3.67), primigravida (OR = 5.20, 95% CI: 3.02, 8.96), married to spouses with an intermediate education level (OR = 2.92, 95% CI: 1.45, 5.89), and earn a high family income (OR = 3.19, 95% CI: 1.57, 6.49).

CONCLUSIONThe prevalence of periconceptional FA intake was far below the requirements of the National Health and Family Planning Commission of China; therefore, knowledge of FA supplementation should be strengthened among women who are or planning to become pregnant.

Adolescent ; Adult ; China ; Cross-Sectional Studies ; Data Collection ; Dietary Supplements ; Female ; Folic Acid ; administration & dosage ; Health Knowledge, Attitudes, Practice ; Humans ; Neural Tube Defects ; Pregnancy ; Socioeconomic Factors ; Surveys and Questionnaires ; Vitamins ; administration & dosage ; Young Adult

Maternal nutrition during pregnancy plays a vital role in the health of the offspring. Methyl donor nutrients, including folate, vitamin B, choline, betaine, and methionine, directly affect DNA methylation and are closely associated with the health of the offspring. As an important part of epigenetics, DNA methylation plays an important role in the maintenance of normal cellular function, gene expression regulation, and embryonic development. Recent studies have shown that maternal nutrition may have a long-lasting effect on the health of the offspring via the changes in genomic DNA and/or methylation level in the promoter region in specific genes. Therefore, this review article focuses on the effect of maternal intake of methyl donor nutrients during pregnancy on DNA methylation, in order to explore the effect of the changed methylation status on the health of the offspring at the molecular level.
Betaine ; administration & dosage ; Choline ; administration & dosage ; DNA Methylation ; Female ; Folic Acid ; administration & dosage ; Humans ; Maternal Nutritional Physiological Phenomena ; Methionine ; administration & dosage ; Pregnancy ; Vitamin B 12 ; administration & dosage

OBJECTIVETo quantitatively and comprehensively investigate the association between maternal folate supplementation during pregnancy and the risk of autism spectrum disorder (ASD) in the offspring.

METHODSPubMed, Embase, Scopus, Cochrane Library, EBSCO, CNKI, Wanfang Data, VIP Database, and Chinese Biomedical Database were searched to collect the articles on maternal folate supplementation during pregnancy and the risk of ASD in children. Odds ratio (OR) and 95% confidence interval (CI) were used to determine the effect size. Stata 12.0 software was used for the Meta analysis. Publication bias evaluation and sensitivity analysis were also performed.

RESULTSA total of 10 articles were included according to the inclusion and exclusion criteria, including 15 studies which involved 4 459 cases and 1 225 835 controls. The Meta analysis showed that maternal folate supplementation during pregnancy significantly reduced the risk of ASD in the offspring in the total population (OR=0.798, 95%CI: 0.669-0.952, P=0.012). The subgroup analysis revealed that maternal folate supplementation during pregnancy was associated with a reduced risk of ASD in the offspring in both the Asian population (OR=0.664, 95%CI: 0.428-1.032, P=0.069) and the Western population (OR=0.817, 95%CI: 0.671-0.996, P=0.045).

CONCLUSIONSMaternal folate supplementation during pregnancy may reduce the risk of ASD in the offspring, especially in the Western population.

Autism Spectrum Disorder ; etiology ; Dietary Supplements ; Female ; Folic Acid ; administration & dosage ; Humans ; Pregnancy ; Risk

In this study, we sought to determine the association between environmental factors and nonsyndromic cleft of the lip and/or palate (NSCLP) to understand the etiology of the disease. A total of 200 NSCLP cases and 327 controls were recruited at the Maternal and Child Health Hospital of Xuzhou City. We conducted face-to-face interviews with the mothers of both cases and controls. The factors increasing the risk of NSCLP were a positive family history [odds ratio (OR)=56.74], pesticide exposure (OR=8.90), and indoor decoration pollution (OR=4.32). On the other hand, the factors decreasing the risk of NSCLP were a high education level (OR=0.22) and supplementation of folic acid (OR=0.23) and multivitamins (OR=0.16). Positive family history, pesticide exposure, and indoor decoration pollution are associated with the risk of NSCLP. In contrast, high education level and folic acid and multivitamin supplementation are protective factors against NSCLP.
Case-Control Studies ; China ; epidemiology ; Cleft Lip ; epidemiology ; etiology ; prevention & control ; Cleft Palate ; epidemiology ; etiology ; prevention & control ; Environmental Pollutants ; toxicity ; Female ; Folic Acid ; administration & dosage ; therapeutic use ; Humans ; Infant, Newborn ; Logistic Models ; Maternal Exposure ; adverse effects ; Pregnancy ; Risk Factors ; Socioeconomic Factors ; Surveys and Questionnaires

PURPOSE: The purpose of this study was to estimate dietary folate intake and food sources of children and adolescents using a nutrient database revised based on measured folate in selected foods. METHODS: Folate content in 51 foods known as folate sources was measured by microbiological assay after trienzyme extraction. Folate intake was estimated from a part of the data of 'Dietary Intake Survey of Infants, Children and Adolescents in 2007~2008' conducted by the Korea Food and Drug Administration (KFDA) and the Korea Health Industry Development Institute (KHIDI). The study subjects were 567 children aged 1~19 years living in the Chungcheong area who completed two 24-hour recalls. RESULTS: Folate values were revised by replacing the values in the current database with the analyzed values except when the value in the current database was between the analytical values or was not different from the mean analytical value by more than 10%. Among the revised values of 40 food items, folate values of 36 foods were lower than the current values. Mean folate intakes estimated with the revised database were approximately 70~80% lower than those estimated with the current database. Mean folate intakes of males aged 12~14 and females aged 12~19 were lower than the 2010 Recommended Nutrient Intakes (RNIs). Chicken's eggs, Kimchi, rice, mandarin, and laver were found to be main food sources of folate. CONCLUSION: In this study, mean dietary folate intakes were lower than those estimated with the current database. Further analyses for folate content especially in cooked foods commonly consumed in Korea are needed using a reliable assay in order to accurately assess folate intake of the Korean population. In addition, nutrition education should be provided for adolescent females in order to increase consumption of folate-rich foods.
Adolescent* ; Child* ; Education ; Eggs ; Female ; Folic Acid* ; Humans ; Infant ; Korea ; Male ; Ovum ; United States Food and Drug Administration

OBJECTIVETo describe the epidemiological characteristics on the supplement of folic acid in progestation and early pregnancy, and to probe the protective effects of supplement of folic acid in early pregnancy against pregnant depression, in Ma'anshan city, Anhui province.

METHODSIn this cohort study, 5 150 subjects who had their first antenatal examination at Ma'anshan Maternal and Child Care Centers were recruited under informed consent, from October 2008 to October 2010. All the information were collected through questionnaires in the first, second and third trimesters respectively. A "Center for Epidemiological Studies Depression Scale (CES-D)" was used to assess the mood of depression in the second questionnaire. Single factor analysis and the unconditional multivariate logistic regression were applied to analyze the association of supplement folic acid in peri-conceptional period and pregnancy depression.

RESULTSIn the study, the prevalence of those who had never taken the supplement folic acid but only the supplement folic acid in progestation and supplement in the first-trimester, or supplement in the peri-conceptional period were 27.3%,0.5%, 27.4% and 17.9%, respectively. The incidence of pregnancy depression was 4.8% (247/5 150). Data from logistic regression analysis showed that, supplement of folic acid only in the first-trimester or in the peri-conceptional period were negatively associated with pregnancy depression even after adjustment for potential confounders. The adjusted odds ratio were 0.63 (95%CI:0.44-0.90) and 0.61 (95%CI:0.39-0.95) respectively.

CONCLUSIONSupplement of folic acid in peri-conceptional period could be a preventive factor for pregnancy depression.

Adult ; Cohort Studies ; Depression ; prevention & control ; Female ; Folic Acid ; administration & dosage ; therapeutic use ; Humans ; Pregnancy ; Prenatal Care ; Prospective Studies ; Surveys and Questionnaires

OBJECTIVETo evaluate whether or not administration of folic acid and resveratrol have preventive effects on cleft palate formation as well as the comparison of the two drugs' s effects.

METHODSPregnant mice were randomly divided into 9 groups, with 8 mice in each group. The TCDD group mice were dosed with TCDD 28 microg/kg body weight on gestation day 10 (GD 10) animals in folic acid group were respectively dosed with folic acid 15, 10, 5 mg/kg and TCDD 28 microg/kg; resveratrol treated mice were divided into 3 groups: resveratrol 50 mg/kg were orally administered for 6 consecutive days, from gestational day GD 8 to GD13 in resveratrol (GD8-13 ) group; resveratrol 50 mg/kg were orally administered for 6 consecutive days, from gestational day GD 8 to GD13, followed hy an oral administered with TCDD on GD10 in resveratrol (GD8-13) + TCDD group; resveratrol 50mg/kg and TCDD 28 microg/kg were used by gavage administration at GD10 in resveratrol (GD10) + TCDD group. Control mice were treated with the same volume of water for 6 consecutive days from GD8 to GD13 and were given a single dose of corn oil on GD10. The pregnant mice weight and embryos, the number of live, cleft palate, dead and resorption fetal mice were recorded on GD 17.5. The coronal sections of the fetal mice heads were prepared at GD 17.5 and observed by microscopy.

RESULTSTotal frequency of clefts was 92.86% in TCDD group, 84.00% (15 mg), 73.08% (10 mg), 84.00% (5 mg) in folic acid + TCDD groups, 0% in resveratrol (GD10) group, 74.51% (GD10), 57.78% (GD8-13) in resveratrol + TCDD groups. The frequency of cleft was 0% in the control group. Compared with the control and the TCDD groups, there were significant differences in the number of live, dead and resorption fetal mice in TCCD + resveratrol (GD8-13) group (P < 0.05). No significant differences in embryonic weight, live fetuses weight, the number of live, dead and resorption fetal mice were found in the other groups (P > 0.05).

CONCLUSIONTest dose of folic acid and resveratrol both had certain antagonistic effect on cleft palate in mice induced by TCDD, with folic acid 10 mg/kg, resveratrol 50 mg/kg GD8-13 doses having stronger antagonistic action. Effects of both the two drugs have no significant difference, but resveratrol (50 mg/kg, GD8-13) significantly affects the fetal mice's growth and development under TCDD exposure in utero.

Abnormalities, Drug-Induced ; prevention & control ; Animals ; Cleft Palate ; chemically induced ; prevention & control ; Female ; Fetus ; Folic Acid ; administration & dosage ; pharmacology ; Humans ; Mice ; Mice, Inbred C57BL ; Polychlorinated Dibenzodioxins ; antagonists & inhibitors ; Pregnancy ; Random Allocation ; Stilbenes ; administration & dosage ; pharmacology ; Teratogens

BACKGROUNDFolate plays a critical role in nucleotide synthesis and DNA methylation, and was considered to be associated with anti-carcinogenesis.

RESULTSfrom studies that concern the relationship between the folate intake or serum folate levels and lung cancer risk showed no consistency, which requires our further comprehensive meta-analysis.

METHODSSystematic literature search was conducted to identify the relevant studies (published prior to February 2013) according to standard protocol. Estimated effects were calculated under both random-effects and fixed-effects models. Heterogeneity between studies and publication bias were also evaluated.

RESULTSA total of 4390 cases and 6138 controls from 6 case-control studies revealed a significant overall inverse association between folate intake and lung cancer risk (OR = 0.74, 95%CI = 0.65 - 0.84, P < 0.001). Summary of 1438 cases and 2582 controls from 4 case-control studies and 44 cases out of a cohort of 1988 participants suggested a marginal association without significance (OR = 0.78, 95%CI = 0.60 - 1.02, P = 0.075) between high serum folate levels and less lung cancer susceptibility; however, subgroup analysis about population-based case-control studies showed that high serum folate levels significantly associated with the reduced lung cancer risk (OR = 0.76, 95%CI = 0.58 - 1.00, P = 0.048).

CONCLUSIONHigher folate intake can be a protective factor against lung cancer risk, and higher serum folate level is probably associated with reduced lung cancer risk in marginal manner, though more studies are warranted to confirm these associations.

Folic Acid ; administration & dosage ; blood ; Humans ; Lung Neoplasms ; blood ; epidemiology ; Risk Factors