Low Folate Status Research Articles

Docosahexaenoic acid, eicosapentaenoic acid, arachidonic acid, and neural tube defects in Tunisian population.

To determine the effect of maternal status in (plasma and red blood cell) folate, vitamin B12, homocysteine, and vitamin D, as well as their interaction with MTHFR (C677T and A1298C) and MTRR A66G polymorphisms, on maternal plasma docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and arachidonic acid (ARA) levels and the risk of neural tube defects (NTDs). ARA, EPA, and DHA composition was assessed using capillary gas chromatography. ARA and DHA levels were higher in controls than in case mothers for low plasma folate status. For low red blood cell folate status, DHA levels were higher in controls than in case mothers. For high homocysteine levels, ARA and DHA levels were higher in controls than in case mothers. NTD mothers had lower EPA and DHA levels for low vitamin B12 levels. NTD mothers had lower DHA levels for low vitamin D levels. For low plasma folate status, DHA levels in the MTHFR C677T gene and ARA and EPA levels in MTHFR A1298C gene were different among the three genotypes in case mothers. DHA levels in the MTHFR C677T gene were different among the three genotypes in case mothers for both low and high homocysteine levels. For low vitamin B12 levels, ARA and DHA levels were different among the three genotypes of the MTHFR C677T gene in case mothers. In the MTHFR C677T gene, ARA and DHA levels were different among the three genotypes in case mothers for low vitamin D levels. More advanced research is required to verify a suitable biochemical parameter status in relation to the genotypes in pregnant women.

Pregnancy, folic acid, and antiseizure medication

Abstract Background Although some antiseizure medications (ASMs) are teratogenic, most people with epilepsy need treatment in pregnancy. The risk of ASM fetotoxicity may be mitigated with folic acid. High-dose folic acid supplementation has traditionally been recommended before and during gestation despite little evidence of efficacy and safety for this patient group. Several studies have investigated the potential benefits and risks of folic acid supplements. Objective To provide an updated overview of the risks, benefits, and rationale for use of folic acid supplementation in relation to pregnant people of childbearing age using ASM. Materials and methods This is a narrative review based on an unstructured literature search of PubMed. We also scrutinized neurological and obstetrical guidelines. Results Antiseizure medication can decrease folate concentrations. In children exposed to ASM prenatally, those born to persons using folic acid supplements periconceptionally had lower risk of adverse neurodevelopment and preterm birth. It remains unclear whether the risk for congenital malformations can be equally alleviated. In studies of the general population, high plasma folate concentrations and/or high-dose folic acid supplements were associated with adverse neurodevelopmental outcomes. This has not been seen in children of mothers with epilepsy. However, an increased cancer risk has been found in children of mothers with epilepsy using high-dose folic acid supplements in pregnancy. Conclusion The optimal folic acid dose is not clear for persons of childbearing potential with epilepsy using ASM. Both low and excess folate status during pregnancy have been associated with adverse neurodevelopment. We propose an individual folic acid supplement dose that should be titrated based on maternal plasma folate concentrations during pregnancy.

Dolutegravir-induced neural tube defects in mice are folate responsive.

In 2018, the Botswana Tsepamo Study reported a nine-fold increased risk of neural tube defects in infants whose mothers were treated with dolutegravir (DTG) from the time of conception. As maternal folate supplementation and status is a well known modifier of neural tube defect (NTD) risk, we sought to evaluate birth outcomes in mice fed normal and low folic acid diets treated with DTG during pregnancy. DTG was evaluated for developmental toxicity using pregnant mice fed normal or low folic acid diet. CD-1 mice were provided diet with normal (3 mg/kg) or low (0.3 mg/kg) folic acid. They were treated with water, a human therapeutic-equivalent dose, or supratherapeutic dose of DTG from mouse embryonic day E6.5 to E12.5. Pregnant dams were sacrificed at term (E18.5) and fetuses were inspected for gross, internal, and skeletal defects. Fetuses with exencephaly, an NTD, were present in both therapeutic human equivalent and supratherapeutic exposures in dams fed low folic acid diet. Cleft palates were also found under both folate conditions. Recommended dietary folic acid levels during mouse pregnancy ameliorate developmental defects that arise from DTG exposure. Since low folate status in mice exposed to DTG increases the risk for NTDs, it is possible that DTG exposures in people living with HIV with low folate status during pregnancy may explain, at least in part, the elevated NTD risk signal observed in Botswana. Based on these results, future studies should consider folate status as a modifier for DTG-associated NTD risk.

Maternal folate status and placental vascular malperfusion: Findings from a high-risk US minority birth cohort

IntroductionMaternal folate deficiency was associated with preeclampsia (PE) and PE was associated with placental maternal vascular malperfusion (MVM). However, no study has examined the association of maternal folate status with placental MVM. MethodsWe examined the association of maternal folate status and placental MVM in the Boston Birth Cohort. Primary exposure variables were maternal self-reported multivitamin supplement (<2, 3–5, >5 times/week) per trimester; and plasma folate levels (nmol/L) after birth. Primary outcome was presence/absence of placental MVM defined by the Amsterdam Placental Workshop Group standard classification. Covariates included demographics, chronic hypertension, clinically diagnosed PE, eclampsia and HELLP syndrome, gestational and pre-gestational diabetes, overweight/obesity, maternal cigarette smoking and alcohol use. Associations between folate and placental MVM were evaluated using multivariate logistic regressions. ResultsOf 3001 mothers in this study, 18.8% of mothers had PE, 37.5% had MVM. Mothers with the lowest self-reported frequency of folate intake had the highest risk of MVM (OR 1.45, 95% CI 1.03–2.05), after adjusting for the covariates. Consistently, among a subset of 939 mothers with plasma folate levels, folate insufficiency was associated with increased risk of MVM (OR 1.65, 95% CI 1.03–2.63), after adjusting for the covariables. As expected, mothers with low folate and placental MVM had highest rates of PE compared to those of high folate and no MVM (p < 0.001). DiscussionIn this high-risk birth cohort, low maternal folate status was associated with increased risk of placental MVM. Further investigation should explore the association between folate status, placental findings and the great obstetrical syndrome.

Association Between Atorvastatin Exposure and Low Folate Status: A Case-Control Study.

The objective of this study is to assess the association between exposure to atorvastatin (ATV) and low-plasma folate (PF) status. The sample consisted of patients admitted to the internal medicine service of a basic general hospital, located in Zaragoza (Spain). We adopted a pharmacoepidemiological case-control study design. For this, the number of treatment days (TDs) of all the drugs part of their treatment during the study period was obtained from each patient in the sample. The cases were comprised by the number of patient's TDs for which PF ≤3 mg/dl and the controls by the number of patient's TDs for which PF >3 mg/dl. To measure the strength of the association, the odds ratios (ORs) were calculated. The Chi-square test, using the Bonferroni correction, was used to calculate the statistical significance. The sample consisted of 640 polymedicated patients. The mean PF obtained were 8.0 ± 4.6 mg/dl and 2.1 ± 0.6 mg/dl, for the cases and controls, respectively; the total number of TDs for the cases and controls were 7615 and 57899, respectively. We obtained a U-shaped curve when representing the dose of ATV against the corresponding ORs when comparing cases with control. Exposure to ATV at 10 or 80 mg is associated with an augmented risk of low folate status. We recommend implementing guidelines for mandatory folic acid fortification in patients exposed to ATV doses of 10 or 80 mg.

Non-Linear Association between Folate/Vitamin B12 Status and Cognitive Function in Older Adults.

Although folate and vitamin B12 status have long been implicated in cognitive function, there is no consensus on the threshold of folate and vitamin B12 for assessing their impacts on cognition. The goal of this study was to detail the association between folate and vitamin B12 with cognitive performance. We analyzed cross-sectional data of older adults (≥60 y; n = 2204) from the NHANES (National Health and Nutrition Examination Surveys) cohort from 2011–2014. The restricted cubic spline model was used for describing the associations between serum total folate, RBC folate, 5-methyltetrahydrofolate, and vitamin B12 and the Consortium to Establish a Registry for Alzheimer’s Disease Word Learning (CERAD-WL) and Delayed Recall (CERAD-DR) tests, the Animal Fluency (AF) test, and the Digit Symbol Substitution Test (DSST), respectively. Older adults with a different folate and vitamin B12 status were clustered by artificial intelligence unsupervised learning. The statistically significant non-linear relationships between the markers of folate or vitamin B12 status and cognitive function were found after adjustments for potential confounders. Inverse U-shaped associations between folate/vitamin B12 status and cognitive function were observed, and the estimated breakpoint was described. No statistically significant interaction between vitamin B12 and folate status on cognitive function was observed in the current models. In addition, based on the biochemical examination of these four markers, older adults could be assigned into three clusters representing relatively low, medium, and high folate/vitamin B12 status with significantly different scores on the CERAD-DR and DSST. Low or high folate and vitamin B12 status affected selective domains of cognition, and was associated with suboptimal cognitive test outcomes.

Folate Deficiency Is Spatially Dependent and Associated with Local Farming Systems among Women in Ethiopia

ABSTRACTBackgroundFolate is essential for the synthesis and integrity of DNA, normal cell formation, and body growth. Folate deficiency among women of reproductive age (WRA) increases the risk of poor birth outcomes including neural tube defect (NTD)-affected pregnancies. Folate status is largely dependent on dietary intakes.ObjectivesWe aimed to explore the spatial distribution of biomarkers of folate status and their association with farming systems among nonpregnant WRA in Ethiopia.MethodsSerum and RBC folate concentration data were derived from the Ethiopia National Micronutrient Survey of 2015. The spatial dependencies of folate concentration of WRA were investigated and its relation with the dominant local farming system was explored.ResultsThe median serum folate and RBC folate concentrations were 12.3 nmol/L and 567.3 nmol/L, respectively. The national prevalence of folate deficiency using homocysteine concentration as a metabolic indicator based on serum and RBC folate concentration was 11.6% and 5.7%, respectively. The majority of women (77.9%) had low RBC folate concentrations consistent with increased risk of NTD-affected pregnancies. Folate nutrition was spatially dependent at distances of ≤ 300 km. A marked variability in folate concentration was observed between farming systems: greater RBC folate concentration (median: 1036 nmol/L) was found among women from the Lake Tana fish-based system, whereas the lowest RBC folate concentration (median: 386.7 nmol/L) was observed in the highland sorghum chat mixed system.ConclusionsThe majority (78%) of WRA in Ethiopia had low folate status potentially increasing the risk of NTD-affected pregnancies. These findings may help national and subnational nutrition intervention strategies to target the most affected areas in the country.

Demographic and biochemical risk factors of Down Syndrome in pregnant women: A pilot study in Sylhet division of Bangladesh

Worldwide research in down syndrome have shown that advanced maternal age (˃30 years) at conception, lower folate status and/or impaired folate metabolism, maternal weight gain during pregnancy, low socioeconomic conditions, radiation exposure, use of contraceptive pills, and taking tobacco/smoking are major maternal risk factors for giving birth child with DS. However, the occurrence of those factors in pregnant women at advanced age has not yet been investigated in Bangladesh. Therefore, a large scale study was needed to explore the overall scenario in Bangladesh. This pilot cross sectional study was aimed to determine the serum folate and homocysteine status at advanced age pregnant women. We measured serum folate and homocysteine concentrations using the Enzyme-Linked Immunosorbent Assay (ELISA). Out of 70 pregnant women, serumfolate level was low (&lt;5 ng/ml) in 13 (18.57%), intermediate (5-6.9 ng/ml) in 8 (11.43%) and normal in 49 (70%) whereas homocysteine concentrations were found low (&lt;5 ng/ml) in all participants. Finally, questionnaire data indicates, low socioeconomic status, overweight during pregnancy, taking contraceptive pills and taking tobacco/smoking was higher percentage in folate-deficient pregnant women than normal serum folate level women. Additionally, women (n=13) with low folate level belongs to low socioeconomic status, overweight, taking contraceptive pills and tobacco/smoking did not give birth child with DS phenotypes. Together, our preliminary findings give an overview of DS associated risk factors in Bangladeshi pregnant women. Large scale study is going on. In next study, we might able to investigate DS risk factors, their associations with serum folate and homocysteine levels and finally with DS phenotypes in child throughout the country. Keywords: Down syndrome; risk factors; folic acid; homocysteine; pregnant women; Bangladesh.

Effects of Inadequate Folate Intake on the Onset and Progression of Hypertensive Vascular Injury.

We investigated the effects of inadequate folate intake on the onset and progression of hypertensive organ injury. In the present study, 5-wk-old male stroke-prone spontaneously hypertensive rats (SHRSP) were fed with a normal-folate (control; 160-170 μg of folate/100 g diet) or low-folate (8-10 μg of folate/100 g diet) diet until they reached 25 wk of age. After the animals reached 10 wk of age, the bodyweight of the rats in the low-folate group was lower than that of the rats in the control group. Regarding blood pressure, both groups had severe hypertension of ≥230 mmHg at 12 wk of age that was not significantly different between the groups. At 16 wk of age, the low-folate group had a low number of blood cell types. The folate levels in the serum, liver, and kidneys of these rats were significantly lower (p<0.01) and the serum homocysteine level in the low-folate group was significantly higher than in the controls. The low-folate group had a significantly lower testicular weight than the control group (p<0.05) and arterial hypertrophy, spermatogenesis arrest, and interstitial connective tissue hyperplasia were observed. However, there was no clear difference in lesions in other organs. These results indicated that under low folate status, SHRSP causes hematopoietic disorders and exacerbates hypertensive vascular injury at various degrees by organ type.

Current nutritional status of mothers and children in Al Ain, United Arab Emirates

Forty-six mothers and children from the United Arab Emirates participated in a pilot study to determine possible micronutrient deficiencies in the country. Thirty-five per cent [35%] of the children and 21% of the mothers had low serum ferritin levels, while 30% of the mothers had low serum 25-hydroxyvitamin D with 28% of mothers having a low serum folate status. These deficiencies are widespread in the nationals of the United Arab Emirates. In view of the increasing importance of intrauterine and early infant nutrition, further investigation and a national study seem warranted

Perfluoroalkyl Substances (PFAS) and Red Blood Cell Folate Levels in the U.S. Adult Population, NHANES

BACKGROUND AND AIM: Adequate folate is essential for many physiological processes, and low folate levels have been associated with cardiovascular disease, anemia, and various health outcomes, including developmental outcomes in relation to low folate status during pregnancy. On the other hand, perfluoroalkyl substance (PFAS) have been associated with multiple health outcomes, with scarce data on the mechanistic pathways by which these substances exert their effects. Our objective is to investigate the individual and joint associations of a mixture of PFAS with red blood cell (RBC) folate concentrations in the adult U.S. population. METHODS: We assessed associations of five chemical biomarkers of 8961 participants ages 18-80 from the U.S. National Health and Nutrition Examination Survey (2007-2016). RBC folate were quantified using a micro bioassay and mass spectrometry. We estimated covariate-adjusted independent and joint associations between PFAS and RBC folate concentrations and triangulated evidence from three approaches developed to examine chemical mixtures: Exposome Wide Association (ExWAS), Bayesian Kernel Regression (BKMR), and Quantile G-Computation (QgComp). We additionally evaluated potential effect modification by sex. RESULTS:The geometric mean RBC folate was 468 µg/L (geometric standard deviation: 1.5 µg/L). In ExWAS analyses, all PFAS were associated with lower RBC folate concentrations. For instance, a twofold increase in Perfluorononanoic acid was associated with a 10% (95% CI: 9%, 11%) decrease in RBC folate concentrations. BKMR and QgComp showed convergent results with a one quartile increase in the PFAS mixture associated with comparable decreases in RBC folate concentrations. Associations did not differ between males and females. CONCLUSIONS:This study is the first to examine the associations between PFAS and RBC folate concentrations in a nationally representative sample. These results may deepen our understanding of the mechanistic pathways by which PFAS impact health outcomes. KEYWORDS: PFAS,Folate,Methods,BKMR,ExWAS,G-Computation

The Role of Folate-supplementation in Depression: A Narrative Review

Background: There is a relationship between the etiology and management of clinical depression and vitamin deficiencies. Aim: To review the effect of dietary folic acid supplementation on cause, severity and treatment of depression. Methods: A narrative review of empirical and theoretical literature on the effect of folic acid supplementation on the se-verity and treatment outcomes of depression. Result: Many enzymes and neurotransmitters depend on folic acid for optimal functions. The monoamine hypothesis of depression confirms the depletion of serotonin, dopamine, and norepinephrine. The systemic level of methyl folate is dependent upon the enzyme methylenetetrahydrofolate reductase [MTHFR], which is encoded by a polymorphic gene [C677T-MTHFR], as well as being dependent on dietary folic acid intake. However, folate has procarcinogenic properties because its coenzymes are involved in de novo purine and thymine nucleotide biosynthesis. Besides, folate deficiency in normal tissues may also predispose to neoplastic transformation, while folate supplementation may suppress the development of tumors in normal tissues. Epidemiological studies revealed that low folate status is associated with depression; especially in terms of severity and the outcome of antidepressant use. Conclusion: The role of folic acid in the etiology and the management of depression cannot be overemphasized. Folate supplementation has been yielding positive results in the management of depression.

Ischemia-Reperfusion Injury Reduces Kidney Folate Transporter Expression and Plasma Folate Levels.

Acute or chronic kidney disease can cause micronutrient deficiency. Patients with end-stage renal disease, kidney transplantation or on dialysis have reduced circulating levels of folate, an essential B vitamin. However, the molecular mechanism is not well understood. Reabsorption of folate in renal proximal tubules through folate transporters is an important process to prevent urinary loss of folate. The present study investigated the impact of acute kidney injury (AKI) on folate transporter expression and the underlying mechanism. AKI was induced in Sprague-Dawley rats that were subjected to kidney ischemia (45 min)-reperfusion (24 h). Both male and female rats displayed kidney injury and low plasma folate levels compared with sham-operated rats. The plasma folate levels were inversely correlated to plasma creatinine levels. There was a significant increase in neutrophil gelatinase-associated lipocalin (NGAL) and IL-6 mRNA expression in the kidneys of rats with ischemia-reperfusion, indicating kidney injury and increased inflammatory cytokine expression. Ischemia-reperfusion decreased mRNA and protein expression of folate transporters including folate receptor 1 (FOLR1) and reduced folate carrier (RFC); and inhibited transcription factor Sp1/DNA binding activity in the kidneys. Simulated ischemia-reperfusion through hypoxia-reoxygenation or Sp1 siRNA transfection in human proximal tubular cells inhibited folate transporter expression and reduced intracellular folate levels. These results suggest that ischemia-reperfusion injury downregulates renal folate transporter expression and decreases folate uptake by tubular cells, which may contribute to low folate status in AKI. In conclusion, ischemia-reperfusion injury can downregulate Sp1 mediated-folate transporter expression in tubular cells, which may reduce folate reabsorption and lead to low folate status.

Red blood cell folate, high-risk human papillomavirus risk and cervical intraepithelial neoplasia development: A large Chinese community-based cohort study of cervical screening.

10547 Background: Although low folate status has been implicated in cervical carcinogenesis, large-scale population-based prospective cohort studies controlling for high-risk types of human papillomavirus (hrHPV) infection are lacking. The aim of this study is to evaluate the associations of red blood cell (RBC) folate, hrHPV infection risk and cervical intraepithelial neoplasia (CIN) development. Methods: In this prospective, population-based cohort study, we analyzed the cross-sectional data of 2304 women from a large cervical cancer screening program of 40,000 women aged 19-65 years in the Chinese rural area from 2014-2015. We conducted a nested case-control study including 35 CIN1 progression cases and 105 CIN1 regression controls. A logistic regression model was used to evaluate the associations of RBC folate and hrHPV infection risk and CIN1 development. Results: The median RBC folate concentration decreased gradually with cervical lesion severity. The risks of CIN 1 and CIN2 or worse (CIN 2+) in the 1st quartile of RBC folate concentration were significantly higher than those in the 4th quartile (Odds Ratio [OR], 2.27; 95% confidence interval [CI], 1.71-3.01 and OR, 2.33; 95% CI,1.52-3.56; respectively). We did not observe a significant relationship between hrHPV infection and CIN1 risk in the unadjusted and adjusted models, however, a statistically significant association was observed for CIN2+. Interestingly, RBC folate concentration was not associated with hrHPV infection among women with CIN1 or CIN2+. After full adjustment for potential confounders, a highly significant inverse linear relation between RBC folate concentration and CIN2+ was observed ( P-overall＜0.001, P-nonlinearity = 0.969). We further observed a positive additive interaction between RBC folate concentration and hrHPV infection on the risk of CIN2+ ( P-interaction＜0.01). Moreover, during the 21-month follow-up, CIN1 progression risk was significantly higher in the lowest RBC folate quartile (1st quartile compared with 4th quartile: OR, 3.86; 95% CI,1.01-14.76). Conclusions: Our findings indicates that RBC folate is inversely associated with the risk of higher-grade CIN and CIN1 progression in the Chinese rural population, either with or without hrHPV infection. Therefore, improving folate status has the potential to prevent higher-grade CIN and cervical cancer among women in the areas without mandatory folic acid food fortification. Clinical trial information: ChiCTR-ROC-15006479 .

The Inclusion of Folic Acid in Weekly Iron-Folic Acid Supplements Confers no Additional Benefit on Anemia Reduction in Nonpregnant Women: A Randomized Controlled Trial in Malaysia.

Weekly iron-folic acid (IFA) supplements are recommended for all menstruating women in countries where anemia prevalence is ≥20%; however, it is unknown whether the inclusion of folic acid in weekly IFA supplements reduces anemia. We examined whether the inclusion of folic acid in weekly IFA supplements conferred any benefit on hemoglobin (Hb) concentration, anemia reduction, or iron status [ferritin and soluble transferrin receptor (sTfR)], over iron alone. In this secondary analysis of a randomized controlled trial in Malaysia, n=311 nonpregnant women (18-45 y old) received 60mg Fe with either 0, 0.4, or 2.8mg folic acid once-weekly for 16 wk. Fasting blood was collected at baseline and 16 wk. A generalized linear model (normal distribution with identity link) was used to assess Hb concentration at 16 wk (primary outcome). At baseline, 84% of women had low folate status (plasma folate<14nmol/L). At 16 wk, marginal mean (95% CI) Hb was 131 (130, 133), 131 (129, 132), and 132 (130, 133) g/L; ferritin was 58.2 (53.9, 62.5), 56.5 (52.2, 60.9), and 58.0 (53.7, 62.3) μg/L; and sTfR was 5.8 (5.5, 6.1), 5.8 (5.5, 6.1), and 5.9 (5.6, 6.2) mg/L in the 0, 0.4, and 2.8mg/wk groups, respectively, with no differences between groups (P>0.05). Baseline plasma folate concentration did not modify the effect of treatment on Hb concentration at 16 wk. Among all women, the risks of anemia [risk ratio (RR): 0.65; 95% CI: 0.45, 0.96; P=0.03] and iron deficiency based on ferritin (RR: 0.30; 95% CI: 0.20, 0.44; P<0.001) were lower at 16 wk than at baseline. Despite the low folate status among these nonpregnant Malaysian women, the inclusion of folic acid in weekly IFA supplements did not reduce anemia or improve iron status, over iron alone. However, the benefits of folic acid for neural tube defect prevention still warrant its retention in weekly IFA supplements.This trial was registered at www.anzctr.org.au as ACTRN12619000818134.

Maternal Vitamin B12 Status and Risk of Cleft Lip and Cleft Palate Birth Defects in Tamil Nadu State, India.

The causal role of maternal nutrition in orofacial clefts is uncertain. We tested hypotheses that low maternal vitamin B12 and low folate status are each associated with an increased risk of isolated cleft lip with or without cleft palate (CL±P) in a case-control study in Tamil Nadu state, India. Case-mothers of CL±P children (n = 47) and control-mothers of unaffected children (n = 50) were recruited an average of 1.4 years after birth of the index child and plasma vitamin B12, methylmalonic acid (MMA), total homocysteine (tHcy), and folate were measured at that time. Logistic regression analyses estimated associations between nutrient biomarkers and case-control status. Odds ratios (ORs) contrasting biomarker levels showed associations between case-mothers and low versus high plasma vitamin B12 (OR = 2.48, 95% CI, 1.02-6.01) and high versus low plasma MMA, an indicator of poor B12 status (OR = 3.65 95% CI, 1.21-11.05). Case-control status was not consistently associated with folate or tHcy levels. Low vitamin B12 status, when defined by a combination of both plasma vitamin B12 and MMA levels, had an even stronger association with case-mothers (OR = 6.54, 95% CI, 1.33-32.09). Mothers of CL±P children in southern India were 6.5 times more likely to have poor vitamin B12 status, defined by multiple biomarkers, compared to control-mothers. Further studies in populations with diverse nutritional backgrounds are required to determine whether poor maternal vitamin B12 or folate levels or their interactions are causally related to CL±P.

Folic Acid Status and Associated Factors for Pregnant Chinese Women - China, 2015.

What is already known on this topic?Low folate status in pregnancy has been associated with multiple adverse pregnancy outcomes, including neural tube defects, congenital heart defects, fetal growth restriction, low birth weight, and preterm delivery. Low folate status is common in China, especially in northern areas.What is added by this report?Folate status remains suboptimal among pregnant Chinese women in 2015. Folate concentration was in the widespread in rural area (9.88ng/mL) and especially in the northern of China (9.10ng/mL). Pregnant women in the last trimester had the lowest folic acid concentration (9.18 ng/mL). Taking folic acid supplements every day would achieve adequate serum folate concentrations (10.87 ng/mL vs. 10.11 ng/mL vs. 9.38 ng/mL, P<0.001). What are the implications for public health practice?Folic acid interventions should be strengthened, especially for pregnant women in rural areas and in northern China, those with junior school or below education, those pregnant during spring and winter, or those with late pregnancy.

Analysis OF C677T polymorphism in methylene tetrahydrofolate reductase (MTHFR) gene as a risk factor for congenital talipes equino varus (CTEV)

BackgroundClubfoot is a common congenital foot deformity. Low folate status in mothers has been associated with CTEV. Folate metabolism might be affected by Methylene Tetrahydrofolate Reductase (MTHFR) gene polymorphism. The present study was aimed to investigate MTHFR C677T polymorphism and its association with CTEV. MethodsThis is a Case-mother-Dyad study with 30 pairs of cases and controls. Single Nucleotide Polymorphism (SNP) analysis of the MTHFR gene was done in this hospital-based study by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). ResultsIn this study, we observed less relative risk of CTEV in presence of C allele as compared to T allele in children, with Relative Risk- 0.6281 and likelihood ratio of 0.5714. While analysing the correlation of genotype variation in cases (CC = 8(26.66%) and CT = 22(73.33%)) with there biological mother (CC = 13(43.33%) and CT = 17(56.66%)), no significant correlation (p = 0.3110) was found between cases and their biological mother genotype. ConclusionAmong the enrolled cases, there was a significant association of increased CTEV risk with 677T variant allele of MTHFR gene. Also, maternal MTHFR genotype was not found to influence CTEV risk of offspring.

Association of antenatal vitamin B complex supplementation with neonatal vitamin B12 status: evidence from a cluster randomized controlled trial.

Evidence about the effect of maternal vitamin B12 supplementation on offspring's vitamin B12 status is limited. The present interventional study sought to evaluate the association of antenatal vitamin B complex supplementation with neonatal vitamin B12 status. In an ongoing cluster randomized controlled trial conducted in three rural counties in northwest China, pregnant women < 20weeks of gestation were randomized to three treatment groups: blank control, iron supplements, or vitamin B complex supplements. All women were administered folic acid supplements during the periconceptional period. In a sub-study, we collected cord blood samples of 331 participants from the control or vitamin B complex groups in the Xunyi county from January 2017 to December 2017. Plasma concentrations of folate, vitamin B12, and homocysteine were measured. Linear mixed models with a random intercept for cluster were used to compare biochemical indexes between groups after controlling for covariates. Compared with newborns whose mothers were in the control group, newborns of the vitamin B complex-supplemented women had significantly higher cord plasma vitamin B12 (P = 0.001) and lower homocysteine concentrations (P = 0.043). The association of antenatal vitamin B complex supplementation with cord blood vitamin B12 concentrations appeared to be more pronounced among newborns with high folate status than those with low folate status (Pinteraction = 0.060). Maternal vitamin B complex supplementation during pregnancy was associated with better neonatal vitamin B12 status in rural northwest China.

Plasma concentrations of vitamin B12 and folate and global cognitive function in an older population: cross-sectional findings from The Irish Longitudinal Study on Ageing (TILDA).

The uncertainty surrounding high intakes of folic acid and associations with cognitive decline in older adults with low vitamin B12 status has been an obstacle to mandatory folic acid fortification for many years. We estimated the prevalence of combinations of low/normal/high vitamin B12 and folate status and compared associations with global cognitive function using two approaches, of individuals in a population-based study of those aged ≥50 years in the Republic of Ireland. Cross-sectional data from 3781 men and women from Wave 1 of The Irish Longitudinal Study on Ageing were analysed. Global cognitive function was assessed by the Mini Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Prevalence estimates for combinations of vitamin B12 (plasma vitamin B12 < or ≥258 pmol/l) and folate (plasma folate ≤ or >45·3 nmol/l) concentrations were generated. Negative binomial regression models were used to investigate the associations of vitamin B12 and folate status with global cognitive function. Of the participants, 1·5 % (n 51) had low vitamin B12 (<258 pmol/l) and high folate (>45·3 nmol/l) status. Global cognitive performance was not significantly reduced in these individuals when compared with those with normal status for both B-vitamins (n 2433). Those with normal vitamin B12/high folate status (7·6 %) had better cognitive performance (MMSE: incidence rate ratio (IRR) 0·82, 95 % CI 0·68, 0·99; P = 0·043, MoCA: IRR 0·89, 95 % CI 0·80, 0·99; P = 0·025). We demonstrated that high folate status was not associated with lower cognitive scores in older adults with low vitamin B12 status. These findings provide important safety information that could guide fortification policy recommendations in Europe.