1.
Prospective investigation of folic acid supplements before and during early pregnancy and paediatric and adult cancers in the Chinese children and families cohort: a pilot study in a sample of rural and urban families.
Linet, MS, Wang, L, Wang, N, Berry, RJ, Chao, A, Hao, L, Li, Z, Fang, L, Yin, P, Potischman, N, et al
BMJ open. 2018;(7):e022394
Abstract
OBJECTIVE To determine the feasibility of long-term prospective follow-up and ascertainment of cancer in offspring and mothers from the 1993-1995 Chinese Community Intervention Program that provided folic acid supplements before and during early pregnancy to reduce neural tube defects. DESIGN Feasibility pilot study for a prospective cohort study. SETTING Families residing during 2012-2013 in one rural and one urban county from 21 counties in 3 provinces in China included in the Community Intervention Program campaign. PARTICIPANTS The feasibility study targeted 560 families, including 280 from the rural and 280 from the urban county included in the large original study; about half of mothers in each group had taken and half had not taken folic acid supplements. INTERVENTION The planned new study is observational. PRIMARY AND SECONDARY OUTCOME MEASURES Primary: incidence of paediatric cancers in offspring; secondary: other chronic diseases in offspring and chronic diseases in mothers RESULTS Only 3.4% of pilot study families could not be found, 3.9% had moved out of the study area and 8.8% refused to participate. Interviews were completed by 82% of mothers, 79% of fathers and 83% of offspring in the 560 families. Almost all mothers and offspring who were interviewed also participated in anthropometric measurements. We found notable urban-rural differences in sociodemographic and lifestyle characteristics of the parents, but fewer differences among the offspring. In eight catchment area hospitals, we identified a broad range of paediatric cancers diagnosed during 1994-2013, although paediatric brain tumours, lymphomas and rarer cancers were likely under-represented. CONCLUSIONS Overall, 20 years after the original Community Intervention Program, the pilot study achieved high levels of follow-up and family member interview participation, and identified substantial numbers of paediatric malignancies during 1994-2013 in catchment area hospitals. Next steps and strategies for overcoming limitations are described.
2.
Folic acid supplementation during early pregnancy and the risk of gestational hypertension and preeclampsia.
Li, Z, Ye, R, Zhang, L, Li, H, Liu, J, Ren, A
Hypertension (Dallas, Tex. : 1979). 2013;(4):873-9
Abstract
Emerging evidence has suggested that folic acid-containing multivitamins may markedly reduce the risk of gestational hypertension or preeclampsia. We examined whether maternal supplementation with folic acid alone during early pregnancy can prevent the occurrence of gestational hypertension and preeclampsia. The data are from a large population-based cohort study established to evaluate the effectiveness of the campaign to prevent neural tube defects with folic acid supplementation in China. We selected participants who were registered in 2 southern provinces, had exact information on folic acid use, and were not affected by chronic hypertension or diabetes mellitus before 20 weeks gestation. A logistic regression model was used to adjust for the effects of the main potential confounders, including age, body mass index, education, occupation, parity, and multiple births. The study size had 99.9% power (α=0.05) to detect a decrease of 10% over the unexposed rate of 9.4% for gestational hypertension. Among the 193 554 women (47.9% took folic acid, 52.1% did not), the overall incidence of gestational hypertension and preeclampsia was 9.5% and 2.5%, respectively. The incidence of gestational hypertension and preeclampsia was 9.7% and 2.5% for women who took folic acid, and 9.4% and 2.4% for women who did not use it. The adjusted risk ratio associated with folic acid use was 1.08 (95% confidence interval, 1.04-1.11) for gestational hypertension and 1.11 (95% confidence interval, 1.04-1.18) for preeclampsia. Our findings suggest that daily consumption of 400 μg folic acid alone during early pregnancy cannot prevent the occurrence of gestational hypertension and preeclampsia.
3.
Genomic DNA methylation changes in response to folic acid supplementation in a population-based intervention study among women of reproductive age.
Crider, KS, Quinlivan, EP, Berry, RJ, Hao, L, Li, Z, Maneval, D, Yang, TP, Rasmussen, SA, Yang, Q, Zhu, JH, et al
PloS one. 2011;(12):e28144
Abstract
Folate is a source of one-carbons necessary for DNA methylation, a critical epigenetic modification necessary for genomic structure and function. The use of supplemental folic acid is widespread however; the potential influence on DNA methylation is unclear. We measured global DNA methylation using DNA extracted from samples from a population-based, double-blind randomized trial of folic acid supplementation (100, 400, 4000 µg per day) taken for 6 months; including a 3 month post-supplementation sample. We observed no changes in global DNA methylation in response to up to 4,000 µg/day for 6 months supplementation in DNA extracted from uncoagulated blood (approximates circulating blood). However, when DNA methylation was determined in coagulated samples from the same individuals at the same time, significant time, dose, and MTHFR genotype-dependent changes were observed. The baseline level of DNA methylation was the same for uncoagulated and coagulated samples; marked differences between sample types were observed only after intervention. In DNA from coagulated blood, DNA methylation decreased (-14%; P<0.001) after 1 month of supplementation and 3 months after supplement withdrawal, methylation decreased an additional 23% (P<0.001) with significant variation among individuals (max+17%; min-94%). Decreases in methylation of ≥25% (vs. <25%) after discontinuation of supplementation were strongly associated with genotype: MTHFR CC vs. TT (adjusted odds ratio [aOR] 12.9, 95%CI 6.4, 26.0). The unexpected difference in DNA methylation between DNA extracted from coagulated and uncoagulated samples in response to folic acid supplementation is an important finding for evaluating use of folic acid and investigating the potential effects of folic acid supplementation on coagulation.
4.
[Advances in the study of the etiologic relationship between reduced folate carrier gene (RFC1) and neural tube and craniofacial defects].
Pei, LJ, Li, Z
Yi chuan = Hereditas. 2004;(2):239-43
Abstract
Neural tube and craniofacial defects are common birth defects which are ascribed to the combination of genetic and environmental factors. The population epidemiological studies suggested that periconceptional use of multivitamins containing folic acid can reduce a woman's risk of having a child with neural tube and craniofacial defects. It's a major environmental factor that periconceptional women with deficiency of folic acid may increase their risk for delivering babies with neural tube and craniofacial defects, but the mechanism by which folic acid facilitates this risk reduction is unknown. This paper reviews folate transport carrier, Reduced Folate Carrier (RFC)'s characteristics in biological chemistry, physiological function, the folate transport mechanism, structure, function, regulation and expression of reduced folate carrier gene (RFC1), and the relationship between RFC1 with plasm or erythrocyte folate level and neural tube defects, et al. It is suggested a etiologic hypothesis in investigation of candidate gene encoding specific folate-related pathways of neural tube and craniofacial defects.