Folic Acid Supplement Intake Research Articles

Associations of polycyclic aromatic hydrocarbons exposure with mortality and effect modification by folate biomarkers in a prospective population

The associations of folate biomarkers and polycyclic aromatic hydrocarbons (PAHs) in the general population remain unclear. Therefore, this study aimed to examine whether folate biomarkers are associated with PAHs, and whether folate biomarkers can mitigate adverse health outcome caused by PAHs. This prospective cohort study included 11,246 participants from the National Health and Nutrition Examination Survey (NHANES), which documented 1,303 deaths over a mean follow-up of 9.1 years. Multivariable linear regression models were used to examine the relationship between urinary individual PAHs and folate biomarkers. Multivariable Cox proportional hazards regression models were used to calculate hazard ratios and 95 % CIs for the associations of PAHs and folate biomarkers with CVDs mortality and all-cause mortality. We found negative associations between folate in red blood cells (RBC) and urinary 1-Hydroxyphenanthrene (percentage change for a 2·7 fold-increase in folate −4.19 %, 95 % CI -5.80 % to −2.56 %CI), 2-Hydroxyfluorene (−6.66 %, −7.84 % to −5.49 %), 3-Hydroxyfluorene (−5.78 %, −6.77 % to −4.78 %)) and 1-Hydroxynapthalene (−2.75 %, −3.48 % to −2.01 %). The associations between serum folate and PAHs were consistent with those observed for RBC folate, and negative associations were also found between serum folate and 2-Hydroxynapthalene (−4.10 %, −5.26 % to −2.94 %). Within the lowest quartile of folate levels in RBC, there are strong associations of 2-Hydroxyfluorene, 3-Hydroxyfluorene, 1-Hydroxynapthalene, and 2-Hydroxynapthalene with elevated risk of CVDs mortality [HRs (95 % CI) >1]. As folate levels in RBC increase to the third and fourth quartiles, these associations no longer exist [HRs (95 % CI) <1, P-interaction<0.05]. The positive associations between urinary PAHs and CVDs mortality are also eliminated as serum folate levels rise [HRs (95 % CI) <1, P-interaction<0.05]. Furthermore, we also found higher levels of folate in both RBC and serum can greatly reduce the adverse impact of 1-Hydroxynapthalene on all-cause mortality. Consistent results were also validated in daily dietary folate and the folic acid supplement intake. Our study highlighted a robust negative relationship between urinary PAHs and folate. Additionally, folate was found to effectively mitigate mortality caused by PAHs, although we did not observe a direct reduction in mortality attributable to folate.

Maternal Folic Acid and Dietary Folate Intake in Relation to Sex Ratio at Birth and Sex-Specific Birth Weight in China.

It is well-established that prenatal folic acid supplements can reduce neural tube defects. However, the associations between folic acid supplementation, dietary folate intake, and overall folate intake with sex-specific birth outcomes are not yet fully understood. This study aims to investigate the association of periconceptional folic acid supplement, dietary folate, and total folate intake with the sex ratio at birth and sex-specific birth weight. Data were sourced from a cross-sectional survey conducted between August and December 2013 in Northwest China, involving 7318 infants and their mothers, recruited using a stratified multistage random sampling method. Folic acid supplements (400 μg/d) were ascertained via a retrospective in-person interview. Dietary folate was evaluated using a validated food frequency questionnaire. Birth outcomes, including sex and weight at birth, were obtained from the Medical Certificate of Birth. Generalized linear models were employed to calculate relative risks (RRs) or differences with 95% confidence intervals (CIs). No association or dose-response relationship was observed between folic acid supplement, dietary folate, and total folate intake during periconception and the likelihood of male births. However, women who took folic acid supplements during pre- and post-conception were associated with an increased male birth weight by 52.8 (8.1 to 97.5) g. Additionally, the total folate intake during periconception was associated with birth weight for males (upper vs. lower tertile: β = 38.8, 95%CI: 5.0 to 72.5 g, p-trend = 0.024) and females (upper vs. lower tertile: β = 42.4, 95%CI: 6.7 to 78.1; p-trend = 0.022). Our findings indicate that periconceptional total folate intake does not correlate with sex ratio at birth but was positively linked to infant birth weights, regardless of gender. These findings offer novel insights into potential benefits of total folate intake, beyond the prevention of neural tube defects, for policymakers and public health.

The Impact of the Dietary Intake of Vitamin B12, Folic Acid, and Vitamin D3 on Homocysteine Levels and the Health-Related Quality of Life of Levodopa-Treated Patients with Parkinson's Disease-A Pilot Study in Romania.

Previous studies have shown that the levodopa treatment of Parkinson's disease (PD) elevates circulating homocysteine levels, which are associated with an increased risk of cardiovascular and neurological disorders, or thrombosis. The present trial aimed to examine whether the intake of vitamin B12, folic acid, and vitamin D3 supplements improved homocysteine level and quality of life (QoL). An interventional prospective trial was conducted in multiple centers across Romania. Participants with clinically established PD taking at least 300 mg/day of levodopa for more than 1 year received a daily tablet of a supplement containing 800 UI of vitamin D3, 1000 µg of folic acid, and 15 µg of vitamin B12. They were followed for 6 months and their serum homocysteine, vitamin B12, vitamin D, and QoL scores were measured at baseline and at 6 months of treatment. QoL was measured using a 15D questionnaire, which assesses mobility, vision, hearing, breathing, sleeping, eating, speech, excretion, usual activities, mental function, discomfort and symptoms, depression, distress, vitality, and sexual activity. Twenty-four PD patients with a mean age of 71 ± 5.04 years (54.2% male and 45.8% female) finished the study. After the intervention, the mean score of speech, mental function, discomfort and symptoms, depression, and QoL significantly increased (p < 0.05 for all). Also, the serum homocysteine and vitamin D were significantly enhanced (p < 0.0001 and p = 0.025, respectively). Changes in vitamin B12 were not statistically significant at 6 months of treatment (p = 0.996). No gender differences were found among the changes that we have demonstrated for homocysteine, vitamin B12, vitamin D, and QoL levels (p < 0.05 for all). The findings of this study showed that the dietary intake of vitamin B12, folic acid, and vitamin D3 remarkably decreased the dimensions of homocysteine and finally increased the total score of QoL in PD patients. We have successfully captured the potential benefits of the supplementation regimen over time and provided insights into the broader implications for managing PD with a focus on nutritional support.

Gestational exposure to organochlorine compounds and metals and infant birth weight: effect modification by maternal hardships

BackgroundGestational exposure to toxic environmental chemicals and maternal social hardships are individually associated with impaired fetal growth, but it is unclear whether the effects of environmental chemical exposure on infant birth weight are modified by maternal hardships.MethodsWe used data from the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, a pan-Canadian cohort of 1982 pregnant females enrolled between 2008 and 2011. We quantified eleven environmental chemical concentrations from two chemical classes – six organochlorine compounds (OCs) and five metals – that were detected in ≥ 70% of blood samples collected during the first trimester. We examined fetal growth using birth weight adjusted for gestational age and assessed nine maternal hardships by questionnaire. Each maternal hardship variable was dichotomized to indicate whether the females experienced the hardship. In our analysis, we used elastic net to select the environmental chemicals, maternal hardships, and 2-way interactions between maternal hardships and environmental chemicals that were most predictive of birth weight. Next, we obtained effect estimates using multiple linear regression, and plotted the relationships by hardship status for visual interpretation.ResultsElastic net selected trans-nonachlor, lead, low educational status, racially minoritized background, and low supplemental folic acid intake. All were inversely associated with birth weight. Elastic net also selected interaction terms. Among those with increasing environmental chemical exposures and reported hardships, we observed stronger negative associations and a few positive associations. For example, every two-fold increase in lead concentrations was more strongly associated with reduced infant birth weight among participants with low educational status (β = -100 g (g); 95% confidence interval (CI): -215, 16), than those with higher educational status (β = -34 g; 95% CI: -63, -3). In contrast, every two-fold increase in mercury concentrations was associated with slightly higher birth weight among participants with low educational status (β = 23 g; 95% CI: -25, 71) compared to those with higher educational status (β = -9 g; 95% CI: -24, 6).ConclusionsOur findings suggest that maternal hardships can modify the associations of gestational exposure to some OCs and metals with infant birth weight.

Women in Canada are consuming above the upper intake level of folic acid but few are meeting dietary choline recommendations in the second trimester of pregnancy: data from the CHILD cohort study.

There is concern that during a low-risk pregnancy, women are consuming more than recommended (400 µg/day) supplemental folic acid and may not meet recommendations for other nutrients. The objective of this study was to determine folic acid supplement use and dietary folate intakes in the second trimester (week 18) of pregnancy in women (n=2996) in the Canadian CHILD cohort study. Vitamin B12 and choline intakes were also assessed because they are metabolically related to folate. The majority of participants (71.6%) were consuming a daily prenatal supplement. Twenty-eight percent of women (n=847) reported consuming a folic acid supplement and of these women, 45.3% had daily supplemental folic acid intakes above the upper intake level (UL; 1000 µg/day). Daily dietary folate intakes were (mean (SD)) 575 (235) DFE µg/day. In contrast, only 24.8% of women met the dietary choline adequate intake (AI) recommendation (AI ≥ 450mg/day) with a mean (SD) intake of 375 (151) mg/day. Further understanding of the impact of supplemental folic acid intake above the UL and low choline intake during pregnancy requires further investigation.

An association of deficiencies in balanced dietary practices and inadequate iron and folic acid supplement's intake during pregnancy and increasing risk of pre-eclampsia or eclampsia among Indian women.

Pre-eclampsia or eclampsia is a serious reproductive health problem which can cause maternal, fetal and neonatal morbidity and mortality worldwide. However till the notable reasons of it is not very clear at all. The main essence of the present study was to examine the association between dietary intake, iron and folic acid consumption during pregnancy and the chances of occurrences of pre-eclampsia or eclampsia among Indian women. A cross sectional observational study was performed by using NFHS-5 (2019-21) data. 190,797 ever married women aged between 15-49 years who had a live birth in the past five years preceding the survey were availed for this study. Multivariable logistic regression analysis was carried out to find out the association between dietary and supplementary intake and occurrences of eclampsia. About 3.6% of the sample women had pre-eclampsia or eclampsia. The results of the study indicated that the likelihood of the prevalence of pre-eclampsia or eclampsia was significantly higher among those women who did not take adequate diet and as well as not consumed iron and folic acid tablet or syrup for at least 90 days during pregnancy compared to those women who took adequate diet and iron and folic acid supplementation even after controlling some maternal, health and lifestyle, socio-economic and demographic characteristics. Integrated and quality ANC services can only ensure adequate nutritional intake in terms of healthy and balanced diet. So, quality ANC services and with this micronutrients intake could be an effective way to reduce the prevalence of pre-eclampsia or eclampsia.

Maternal folic acid supplementation and the risk of ankyloglossia (tongue-tie) in infants; a systematic review.

Maternal folic acid supplementation is protective against the development of neural tube defects (NTDs) in babies. However, recent public-facing communications have raised concerns about a causal relationship between folic acid supplementation, particularly after the first trimester, and ankyloglossia (tongue-tie) in infants. Non-evidence-based communications are potentially harmful because they could adversely affect adherence to folic acid supplementation, increasing NTD occurrence. This study aimed to review evidence on the relationships between maternal folic acid supplementation during preconception and/or pregnancy and the risk of ankyloglossia in infants. We searched the databases MEDLINE, EMBASE, Cochrane CENTRAL, and Scopus. We searched for observational, and interventional studies, and systematic reviews investigating the effect of maternal folic acid supplementation during preconception or pregnancy on the occurrence of ankyloglossia in offspring. The search was registered on PROSPERO on 01/12/2022, ID: CRD42022375862. The database searches yielded 93 articles. After removing duplicates and screening titles and abstracts, 26 remained. One article was judged relevant for inclusion in analyses; a case-control study that directly mentions the relationship between folic acid supplementation and ankyloglossia. This study reported that regular intake of folic acid supplements was higher in women with infants with ankyloglossia. However, this study has limitations regarding design, selection bias, and confounding, calling the findings into question. Insufficient evidence exists for a relationship between folic acid supplementation and ankyloglossia. Currently, the benefits of folic acid supplementation far outweigh the risks. This must be clearly communicated to patients by their clinicians during preconception and antenatal care.

Current preconception care practice in the Netherlands — An evaluation study among birth care professionals

ObjectiveTo evaluate the current practice of preconception care in the Netherlands and the perceptions of birth care professionals concerning preconception care. MethodsWe have developed a digital questionnaire and conducted a cross-sectional study by distributing the questionnaire among 102 organisations: 90 primary care midwifery practices and obstetric departments of 12 hospitals in the Southwest region of the Netherlands between December 2020 and March 2021. One birth care professional per organization was asked to complete the questionnaire. Descriptive statistics were used to present the results. FindingsRespondents of eighty-three organisations (81.4 %) filled in the questionnaire, of whom 74 respondents were independent primary care midwives and 9 respondents were obstetricians. Preconception care mostly consisted of an individual consultation in which personalized health and lifestyle advice was given. Among the respondents, 44.4 % reported that the organization had a preconception care protocol. The way in which the consultation was carried out, as well as the health and lifestyle related questions asked, differed between respondents. More than 85 % of the respondents inquire about the following possible risk factors for complications: maternal illnesses, obstetric history, folic acid supplement intake, alcohol intake, smoking, substance abuse, hereditary disease, prescription medication, dietary habits, overweight, and birth defects in the family. The respondents acknowledged that preconception care should be offered to all couples who wish to become pregnant, as opposed to offering preconception care only to those with an increased risk of complications. Still, respondents do not receive many questions regarding the preconception period or requests for preconception care consultations. Key conclusionBirth care professionals acknowledge the need for preconception care for all couples. In the Netherlands, preconception care consists mostly of an individual consultation with recommendations for health and lifestyle advice. However, the identification of risk factors varies between birth care professionals and less than half of the respondents indicate that they have a protocol available in their practice. Furthermore, the demand of parents-to-be for preconception care is low. More research, that includes more obstetricians, is necessary to investigate if there is a difference between the care provided by primary care midwives and obstetricians. Implications for practice: To increase the awareness and uptake of preconception care, it would be prudent to emphasize its importance to parents-to-be and professionals, and actively promote the use of widespread, standardized protocols for birth care professionals.

Enhanced recovery in patients with gestational diabetes mellitus and MTHFR 677 TT genotype after taking high-dose folic acid supplements during mid-late pregnancy: an open-label interventional study.

To explore the relationship between folic acid supplementation and the recovery rate of gestational diabetes mellitus (GDM) in women with methylenetetrahydrofolate (MTHFR) 677 TT genotypes in mid-late pregnancy. 9, 096 pregnant women were recruited with their MTHFR gene genotyped. 5,111 women underwent a 75-g oral glucose tolerance test (OGTT) and 2,097 were confirmed with GDM. The association between MTHFR genotypes and GDM risk was estimated using logistic and log-binomial regression, with age and parity set as the covariates to control their confounding effects. Further assessment of GDM risk on glucose levels was done using the ANCOVA model. As an open-label intervention study, 53 GDM patients with TT genotype were prescribed 800μg/day of folic acid as the high-dose group, while 201 GDM patients were given 400μg/day as the standard-dose group at their 24-28 weeks of pregnancy. A rate ratio (RR) of GDM recovery was estimated at each available time point for both groups. The time-to-GDM persistence events were analyzed with the Kaplan-Meier method and Cox-regression model. The trend of glucose levels over time was estimated using the linear model. MTHFR 677 TT genotype has no significant association with the glucose levels and GDM risk, with an adjusted OR of 1.105 (95% CI 0.853, 1.431; p=0.452) and an adjusted PR of 1.050 (95% CI 0.906, 1.216; p=0.518) compared to the wildtype CC group. Patients in the high-dose group (n=38; 15 drop-outs; 40.69 days (95% CI 33.22, 48.15)) recovered from GDM approximately 27 days faster than those in the standard-dose group (n=133; 68 drop-outs; 68.09 days (95% CI 63.08, 73.11)). Concomitantly, the RR of GDM recovery rose and reached 1.247 (95% CI 1.026, 1.515) at 100 days of treatment with the standard-dose group as reference. High-dose folic acid supplement intake in mid-late pregnancy is associated with faster GDM relief in patients with MTHFR 677 TT genotype compared to the standard dose, which would be served as a novel and low-cost alternative therapy for the treatment of GDM.

Opportunities and barriers for maternal nutrition behavior change: an in-depth qualitative analysis of pregnant women and their families in Uttar Pradesh, India.

Maternal undernutrition during pregnancy remains a critical public health issue in India. While evidence-based interventions exist, poor program implementation and limited uptake of behavior change interventions make addressing undernutrition complex. To address this challenge, Alive & Thrive implemented interventions to strengthen interpersonal counseling, micronutrient supplement provision, and community mobilization through the government antenatal care (ANC) platform in Uttar Pradesh, India. This qualitative study aimed to: (1) examine pregnant women's experiences of key nutrition-related behaviors (ANC attendance, consuming a diverse diet, supplement intake, weight gain monitoring, and breastfeeding intentions); (2) examine the influence of family members on these behaviors; and (3) identify key facilitators and barriers that affect behavioral adoption. We conducted a qualitative study with in-depth interviews with 24 pregnant women, 13 husbands, and 15 mothers-in-law (MIL). We analyzed data through a thematic approach using the Capability-Opportunity-Motivation-Behavior (COM-B) framework. For ANC checkups and maternal weight gain monitoring, key facilitators were frontline worker home visits, convenient transportation, and family support, while the primary barrier was low motivation and lack understanding of the importance of ANC checkups. For dietary diversity, there was high reported capability (knowledge related to the key behavior) and most family members were aware of key recommendations; however, structural opportunity barriers (financial strain, lack of food availability and accessibility) prevented behavioral change. Opportunity ranked high for iron and folic acid supplement (IFA) intake, but was not consistently consumed due to side effects. Conversely, lack of supply was the largest barrier for calcium supplement intake. For breastfeeding, there was low overall capability and several participants described receiving inaccurate counseling messages. Key drivers of maternal nutrition behavior adoption were indicator specific and varied across the capability-opportunity-motivation behavior change spectrum. Findings from this study can help to strengthen future program effectiveness by identifying specific areas of program improvement.

Folate Intake and Ovarian Cancer Risk among Women with Endometriosis: A Case-Control Study from the Ovarian Cancer Association Consortium.

Although folate intake has not been associated with an increased risk of ovarian cancer overall, studies of other cancer types have suggested that high folate intake may promote carcinogenesis in precancerous lesions. Women with endometriosis (a potential precancerous lesion) have an increased risk of developing ovarian cancer; however, whether high folate intake increases risk in this group is unknown. We conducted a pooled analysis of six case-control studies from the Ovarian Cancer Association Consortium to investigate the association between folate intake and risk of ovarian cancer among women with and without self-reported endometriosis. We included 570 cases/558 controls with and 5,171/7,559 without endometriosis. We used logistic regression to estimate odds ratios (OR) and 95% confidence intervals for the association between folate intake (dietary, supplemental, and total) and ovarian cancer risk. Finally, we used Mendelian randomization (MR) to evaluate our results using genetic markers as a proxy for folate status. Higher dietary folate intake was associated with an increased risk of ovarian cancer for women with endometriosis [OR, 1.37 (1.01-1.86)] but not for women without endometriosis. There was no association between supplemental folate intake and ovarian cancer risk for women with or without endometriosis. A similar pattern was seen using MR. High dietary folate intake may be associated with an increased risk of ovarian cancer among women with endometriosis. Women with endometriosis with high folate diets may be at increased risk of ovarian cancer. Further research is needed on the potential cancer-promoting effects of folate in this group.

Traffic-related air pollution and supplemental folic acid intake in relation to DNA methylation in granulosa cells

BackgroundHigher exposure to traffic-related air pollution (TRAP) is related to lower fertility, with specific adverse effects on the ovary. Folic acid may attenuate these effects. Our goal was to explore the relation of TRAP exposure and supplemental folic acid intake with epigenetic aging and CpG-specific DNA methylation (DNAm) in granulosa cells (GC). Our study included 61 women undergoing ovarian stimulation at a fertility center (2005–2015). DNAm levels were profiled in GC using the Infinium MethylationEPIC BeadChip. TRAP was defined using a spatiotemporal model to estimate residence-based nitrogen dioxide (NO2) exposure. Supplemental folic acid intake was measured with a validated food frequency questionnaire. We used linear regression to evaluate whether NO2 or supplemental folic acid was associated with epigenetic age acceleration according to the Pan-tissue, mural GC, and GrimAge clocks or DNAm across the genome adjusting for potential confounders and accounting for multiple testing with a false discovery rate < 0.1.ResultsThere were no associations between NO2 or supplemental folic acid intake and epigenetic age acceleration of GC. NO2 and supplemental folic acid were associated with 9 and 11 differentially methylated CpG sites. Among these CpGs, only cg07287107 exhibited a significant interaction (p-value = 0.037). In women with low supplemental folic acid, high NO2 exposure was associated with 1.7% higher DNAm. There was no association between NO2 and DNAm in women with high supplemental folic acid. The genes annotated to the top 250 NO2-associated CpGs were enriched for carbohydrate and protein metabolism, postsynaptic potential and dendrite development, and membrane components and exocytosis. The genes annotated to the top 250 supplemental folic acid-associated CpGs were enriched for estrous cycle, learning, cognition, synaptic organization and transmission, and size and composition of neuronal cell bodies.ConclusionsWe found no associations between NO2, supplemental folic acid, and DNAm age acceleration of GC. However, there were 20 differentially methylated CpGs and multiple enriched GO terms associated with both exposures suggesting that differences in GC DNAm could be a plausible mechanism underlying the effects of TRAP and supplemental folic acid on ovarian function.

Association of Folic Acid Supplementation, Dietary Folate Intake and Serum Folate Levels with Risk of Gestational Diabetes Mellitus: A Matched Case-Control Study.

Periconceptional folate supplementation is prevalent, raising concerns about possible side effects. The aim of this study was to investigate the associations of folic acid supplementation, dietary folate, serum folate with gestational diabetes mellitus (GDM) risk. In this matched case-control study, 81 pregnant women with GDM (cases) and 81 pregnant women with non-GDM (controls) were identified through age difference (≤3 y) and parity (Both primipara or multipara women) matching, and serum folate levels were measured during the GDM screening (24-28 gestational wk). Folic acid supplementation and dietary folate intake from three months prepregnancy through midpregnancy were assessed using a self-reported questionnaire and food frequency questionnaire. Multivariate binary logistic regression models were used to evaluate the association between folate and GDM. After adjusting for confounding factors, we observed that compared with folic acid supplementation dose ≤400 μg/d, pregnancies without folic acid supplementation and supplemental dose >800 μg/d were associated with GDM risk (adjusted odds ratio=7.25, 95% confidence interval: 1.34-39.36; adjusted odds ratio=4.20, 95% confidence interval: 1.03-17.22), while no significant association with a 400-800 μg/d dose of folic acid supplementation and GDM. Compared with folic acid supplementation dose ≤24 wk, pregnancies without folic acid supplementation were associated with GDM risk (adjusted odds ratio=6.70, 95% confidence interval: 1.22-36.77), while no significant association with folic acid supplementation dose >24 wk and GDM. No significant association of dietary folate and serum folate with GDM was found. No or a higher dose of folic acid supplementation would increase GDM risk and a dose of <800 μg/d is the safe dose.

Zinc Status is not Adversely Affected by Folic Acid Supplementation and Zinc Intake does not Impair Folate Utilization in Human Subjects

Changes in zinc status in response to folic acid supplementation and the effect of zinc intake on folate utilization were evaluated in 12 men (20–34 y old) consuming a diet containing 3.5 or 14.5 mg zinc/d for two 25-d intervals. Deuterium-labeled folic acid (800 μg/d) or a placebo was administered orally during each phase. No differences in plasma zinc, erythrocyte zinc, urinary zinc, erythrocyte metallothionein or serum alkaline phosphatase, due to supplemental folic acid, were detected at either level of zinc intake. Differences in the response to folic acid supplementation, due to the level of zinc intake, were not detected for serum, erythrocyte or urinary (labeled and unlabeled) folate. Within the constraints of this short-term folic acid supplementation study, adverse effects on zinc status were not observed and our data suggest that folic acid utilization was not influenced by level of zinc intake.

Maternal gestational diabetes in singleton pregnancies conceived by ART may be modified by periconceptional B vitamins.

The risk of maternal gestational diabetes mellitus (GDM) may be influenced by pregnancies conceived through assisted reproductive technology (ART). However, the influence of the dosage of B vitamins (folate, vitamin B6 and vitamin B12) on GDM weren't considered. Thus, we hypothesized that periconceptional B vitamins could modify maternal GDM in singleton pregnancies conceived by ART. This study is a prospective cohort study using data from 3,252 women with singleton pregnancies and received a 75 g oral glucose tolerance test (OGTT) at 24-28 weeks of gestation. We included an interaction term in the multivariable logistic and linear regression models, respectively, to test our hypothesis. Women who underwent ART were significantly associated with the incidence of GDM compared with spontaneous pregnancy women. The adjusted odds ratio (aOR) was 1.59, and the 95% confidence interval (CI) was 1.08-2.34. ART pregnancies also elevated OGTT (oral glucose tolerance test) 1-h blood glucose levels and OGTT 2-h blood glucose levels (P < 0.05). A positive association between dietary vitamin B6 (aOR = 1.60, 95% CI: 1.13-2.27), dietary vitamin B12 (aOR = 1.88, 95% CI: 1.34-2.64) and dietary folate (aOR = 1.66, 95% CI: 1.19-2.32) with GDM risk comparing the highest to the lowest quartile (all P trend < 0.001). The aORs of GDM for inadequate (< 400 μg/day), adequate (400-800 μg/day), and excessive (> 800 μg/day) supplemental folate intake were 1.00, 0.93, and 1.30, respectively (P trend = 0.033). Since only the supplemental folate illustrates a statistically significant interaction with ART (P for interaction < 0.05), the association between ART and GDM and OGTT blood glucose levels stratifying by supplemental folate were further evaluated. These increased risks of GDM (aOR = 1.62, 95% CI: 1.39-3.39) and the regression coefficients (β) of 1-h blood glucose (β = 0.76, 95% CI: 0.39-1.13) and 2-h blood glucose (β = 0.60, 95% CI: 0.29-0.92) in the multiple linear regression model were significant only in the ART group with excessive supplemental folate (> 800 μg/day). The risk of GDM is significantly elevated, particularly among those women who conceived ART with the intake of excessive supplemental folate (> 800 μg/day).

The compliance of free folic acid supplements among pregnant women in rural areas of Northwestern China: The role of related knowledge.

High prevalence of neural tube defects remains one of the major threats to newborns in rural China. Folic acid supplementation before and during early pregnancy can effectively reduce the risk of neural tube defects. Despite the efforts of the free folic acid mass distribution, the actual usage of folic acid supplements was still suboptimal among rural pregnant women in China. The objective of this study is to investigate if and how knowledge can influence the picking up and intake of the free folic acid supplements distributed by the government. We collected survey data from 821 pregnant women in rural areas of Shaanxi, China, in March and December of 2021. Face-to-face interviews and questionnaire surveys were conducted with every participant. Univariate and multivariate logistic regression analyses were performed to test the relationship between knowledge and dependent variables. Our study found that there were 76.4% of pregnant women would pick up folic acid supplements distributed by the government and only 44.5% of women would use folic acid before current pregnancy. Awareness of folic acid policy both affects the picking up (OR: 6.708, 95% CI: 4.672-9.632) and periconceptional intake (OR: 1.912, 95% CI:1.326-2.758) of folic acid supplements. Knowledge of health and nutrition in pregnancy showed no significant relationship with the picking up and periconceptional intake of folic acid supplements but was positively associated with the intake duration (Coefficient: 9.278, 95% CI: 2.966-15.591). Despite the relatively high level of picking up, the actual folic acid usage was not ideal among pregnant women in rural areas of China. Folic acid policy awareness was positively associated with the picking up and intake of folic acid before and during conception. Knowledge of health and nutrition about pregnancy was related to a longer duration of folic acid intake but had no impact on the picking up rate and periconceptional intake of folic acid supplements.

Periconceptional folate intake influences DNA methylation at birth based on dietary source in an analysis of pediatric acute lymphoblastic leukemia cases and controls

Periconceptional folate intake is associated with the establishment of DNA methylation in offspring; however, variations in this relation by food sources compared with folic acid supplements are not described. Also, maternal folate intake is associated with decreased risk of pediatric acute lymphoblastic leukemia (ALL), but the mechanism is not known. We evaluated the relation between periconceptional folate intake by source and DNA methylation at birth in a cohort of pediatric ALL cases and controls in an epigenome-wide association study. Genome-wide DNA methylation status obtained from archived neonatal blood spots from pediatric ALL cases (n=189) and controls (n=205) in the California Childhood Leukemia Study (CCLS) from 1995-2008 was compared with periconceptional folate from total, food, and supplemental sources using multivariable linear regression. Further stratification was performed by income, education, ethnicity, and total folate intake. We evaluated variable DNA methylation response to periconceptional folate by ALL case status through an interaction term. Two significant differentially methylated probes (DMPs) were associated with food and supplemental periconceptional folate intake in all subjects (n=394). The top differentially methylated region at the promoter region of DUSP22(dual specificity phosphatase 22) demonstrated DNA hypermethylation in ALL cases but not in controls in response to total and food folate intake. We further identified 8 interaction term DMPs with variable DNA methylation response to folate intake by ALL case status. Further stratification of the cohort by education and ethnicity revealed a substantially higher number of DMPs associated with supplemental folic acid intake in Hispanic subjects with lower income and educational level. We identified modest associations between periconceptional folate intake and DNA methylation differing by source, including variation by ALL case status. Hispanic subjects of lower income and education appear uniquely responsive to periconceptional folate supplementation.

Prevalence of Anemia Among Pregnant Women of Tribal Community in Kashmir: A Prospective Observational Study

Background: A lack of nutrition is one of the most frequent causes of anaemia. Anemia is a significant but preventable public health issue that affects pregnant women all over the world. The present study has been objectively conducted to ascertain the prevalence of anaemia among tribal pregnant women of J &amp; K. Methods: The study was a prospective observational study conducted over a period of one and a half year. Around 200 admitted antenatal Gujjar and Bakarwal women were included in this study. Results: We observed that the overall prevalence of anemic patients among the studied subjects was 35.5%. Of them 53.5% had mild anemia, 26.8% had moderate anemia and 19.7% had severe anemia. The prevalence of anemic rates increased significantly with age and parity. Conclusion: The present study revealed that the prevalence of anemia among pregnant women of tribal community increases significantly with age and parity of patient. The relative prevalence of mild, moderate and severe anemia was observed as 53.5%, 26.8% and 19.7% respectively. The reason for high anemic rates among such patients is multifaceted which includes low family income, illiteracy, high parity, poor dietary habits and irregular intake of iron and folic acid supplements. Keywords: Anaemia, tribal population, Pregnant Women, Prevalence

Association of Folic Acid Supplementation in Early Pregnancy with Risk of Gestational Diabetes Mellitus: A Longitudinal Study.

Background: Gestational diabetes mellitus (GDM) may lead to many adverse effects on women and their offspring. Method: 24,429 pregnant women were enrolled during early pregnancy from January 2018 to December 2021. The self-reported intake of folic acid supplements was assessed via a questionnaire. Oral glucose tolerance tests were used for the diagnosis of GDM. The association between intake or not, dose, and duration of folic acid and GDM risk was assessed. Results: 6396 (26.18%) women were diagnosed with GDM. In the univariate models, folic acid was found to be correlated with total GDM risk (OR = 0.82, 95% CI: 0.70~0.95, p = 0.009). After adjusting for potential confounders, the association with total GDM risk was not significant, but the association of folic acid with 2-h PBG diagnosed GDM risk was consistently significant (OR = 0.75, 95% CI: 0.63~0.90, p = 0.002). No significant association between the dose and duration of folic acid supplementation and GDM risk was observed in the analyses. Conclusion: Folic acid supplementation might be a protective factor for the risk of GDM caused by the high level of postprandial blood glucose, but the dose or duration-related association between folic acid supplementation and GDM risk is not clear.

Maternal Folate Status and the Relation between Gestational Arsenic Exposure and Child Health Outcomes.

Gestational arsenic exposure adversely impacts child health. Folate-mediated 1-carbon metabolism facilitates urinary excretion of arsenic and may prevent arsenic-related adverse health outcomes. We investigated the potential for maternal folate status to modify associations between gestational arsenic exposure and child health. We used data from 364 mother–child pairs in the MIREC study, a prospective pan-Canadian cohort. During pregnancy, we measured first trimester urinary arsenic concentrations, plasma folate biomarkers, and folic acid supplementation intake. At age 3 years, we evaluated twelve neurodevelopmental and anthropometric features. Using latent profile analysis and multinomial regression, we developed phenotypic profiles of child health, estimated covariate-adjusted associations between arsenic and these phenotypic profiles, and evaluated whether folate status modified these associations. We identified three phenotypic profiles of neurodevelopment and three of anthropometry, ranging from less to more optimal child health. Gestational arsenic was associated with decreased odds of optimal neurodevelopment. Maternal folate status did not modify associations of arsenic with neurodevelopmental phenotypic profiles, but gestational arsenic was associated with increased odds of excess adiposity among those who exceed recommendations for folic acid (>1000 /day). However, arsenic exposure was low and folate status was high. Gestational arsenic exposure may adversely impact child neurodevelopment and anthropometry, and maternal folate status may not modify these associations; however, future work should examine these associations in more arsenic-exposed or lower folate-status populations.