Folic Acid Supplementation Research Articles

Folate and cobalamin status, indicators, modulators, interactions, and reference ranges from early pregnancy until birth: the Reus–Tarragona birth cohort study

BackgroundFolate and cobalamin status, although essential for pregnancy, are not routinely monitored in prenatal care. ObjectivesTo investigate folate and cobalamin status and determinants throughout pregnancy, in the absence of mandatory folic acid (FA) fortification. MethodsIn a cohort study of 831 mothers recruited at <12 gestational weeks (GW), plasma folate, total homocysteine (tHcy), cobalamin, holotranscobalamin (holoTC), methylmalonic acid (MMA), red blood cell folate (RBCF), and the combined cobalamin status indicator (cB12) were determined at ≤12, 15, 24–27, 34 GW, labor and in the cord. Single nucleotide polymorphisms affecting folate and cobalamin status were determined. FA, cobalamin, micronutrient supplement use, and dietary folate and cobalamin intake (food frequency questionnaire) were recorded. Folate and cobalamin status predictors were assessed by multiple linear regression analysis. ResultsOnly 36.1% of the participants took FA preconceptionally and 47.4% and 7.3% had suboptimal RBCF (<906 nmol/L) and plasma cobalamin status (≤221 pmol/L), respectively, at ≤12 GW. RBCF determinants included planned pregnancy, FA supplementation, plasma cobalamin, and methylenetetrahydrofolate (MTHFR) 677C>T genotype. Cobalamin supplementation was positively associated with plasma cobalamin and early holoTC. Smoking and BMI were inversely associated with plasma cobalamin and early holoTC, but none were associated with MMA. Only participants with the MTHFR 677TT genotype, exceeding FA supplement recommendations, improved their folate status (interaction term: B (95% CI):0.15 (0.01, 0.29), P = 0.032). Smoking was inversely associated with plasma cobalamin status in participants with the methionine synthase reductase (MTRR) 524CC genotype only (interaction term:0.07 (0.01, 0.04), P = 0.014). Mothers with low early pregnancy cobalamin status and also those with bigger newborns, had lower cobalamin status at labor. ConclusionsSuboptimal early pregnancy folate or cobalamin status affected 47.4% and 7.3% of the participants, respectively. The MTHFR 677TT genotype predicted folate status throughout pregnancy. Smoking and BMI were negatively associated with cobalamin status throughout pregnancy.Clinical Trial Registry number and website where it was obtained: NCT01778205. www.clinicaltrials.gov

Effect of Folic Acid Supplementation on Glycemic Control in Patients with Type 2 Diabetes Mellitus.

Effect of Folic Acid Supplementation on Glycemic Control in Patients with Type 2 Diabetes Mellitus.

Issue Information

Gastroschisis (GS) and omphalocele (OC) are two prevalent congenital abdominal wall defects. This narrative review explores their global prevalence and the potential preventive role of maternal folic acid supplementation. The image includes clinical photographs (A, GS; C, OC) and schematic representations of inferior axial sections (B, GS; D, OC), illustrating key anatomical distinctions. Arrow indicates the abdominal wall membrane; I, intestine; K, kidney; UC, umbilical cord. image

Prevalence and Associated Risk Factors with Unawareness of Folic Acid Benefits Prior to Pregnancy: Results From Canadian Community Health Survey

Recent national studies on awareness of folic acid (FA) prior to pregnancy among Canadian women are lacking. Using the 2017–2018 Canadian Community Health Survey, we aimed to estimate prevalence and risk factors associated with Canadian women who reported they were unaware of the benefits of FA supplementation before pregnancy. Prevalence of unawareness of FA was 22.1%. Lower education, lack of a health care provider, low household income, and an immigrant background were associated with greater odds of unawareness of the benefits of FA supplementation. Persistent associations with measures of social disadvantage and social determinants of health emphasize the need for new targeted public health campaigns.

NEURAL TUBE CLOSURE ANOMALIES: EPIDEMIOLOGICAL STUDIES AND RISK FACTORS AT THE NEONATAL AND NEONATAL RESUSCITATION DEPARTMENT OF MOHAMMED VI UNIVERSITY HOSPITAL, OUJDA

Objective:This studyaims to identify the sociodemographic, maternal, and obstetricriskfactorsassociatedwith neural tube defects (NTDs) and determinetheirprevalenceamongnewbornshospitalized in the neonatology and neonatal intensive care unit at CHU Mohamed VI Oujda. Methods:Weconducted a descriptive retrospectivestudy over an 18-month period, including all newbornshospitalizedwithisolated or associatedNTDs. Incomplete records wereexcludedfrom the analysis. Results:Out of 797 hospitalizednewborns, 66 hadcongenital malformations, including 10 cases of NTDs (1.25%). The types of NTDsidentifiedwereanencephaly (1 case), spina bifida (6 cases), and encephalocele (3 cases). The majority of mothers had an average age of 34.3 years, with 80% coming from a low socioeconomic status and 60% having a history of consanguineous marriages. Additionally, fenugreek consumption during the first trimester of pregnancy was reported in 70% of cases, while only 20% of mothers had taken folic acid.Regarding the newborns, 70% presented with hypotonia, and 60% exhibited weak or absent primitive reflexes. The short-term postoperative mortality rate was 30%. Discussion:The prevalence of neural tube defects (NTDs) observed in this study is significantly higher than the global average, which may be explained by unfavorable socioeconomic conditions and maternal nutritional deficiencies. Fenugreek consumption and low folic acid supplementation were identified as significant risk factors. Conclusion:To reduce the incidence of NTDs, itis essential to Strengthening prenatal care, encouraging folic acid supplementation, and advising against the consumption of fenugreek during pregnancy are essential. A preventive strategy tailored to local specificities could significantly improve newborn health and reduce complications associated with neural tube defects (NTDs).

Role of folic acid supplementation in level of c-reactive protein in metabolic syndrome

Introduction: The prevalence of metabolic syndrome is increasing, its progression involves an inflammatory response that has an important impact on the initiation, progressivity, and complications of several diseases such as heart disease, stroke, type 2 diabetes mellitus, and cancer. C-reactive protein (CRP) is one of the inflammation markers increased in patients with metabolic syndrome. Folic acid has a role in metabolizing homocysteine and improving endothelial function. There have been many studies conducted, but the results are still inconsistent. Method: Literature searching was conducted using PubMed, Cochrane Library, and Embase databases. MeSH terms, advanced search and eligibility criteria were used for title/abstract screening before journal review. Results: One systematic review and meta-analysis (SR-MA) and one RCT met the PICO and eligibility criteria. The SR-MA found that folic acid administration can reduce CRP level (WMD -0.94 (95% CI -1.56 – 0.32; p=0.00) at a dose of 0.15 mg/day for 12 weeks to 10 mg/day for 2 weeks, while the RCT found an insignificant result. Conclusion: Folic acid supplementation has a potential benefit to decrease CRP levels in metabolic syndrome.

Influence of different forms of folic acid supplementation on pregnancy outcomes under various exposure factors.

Folic acid supplementation has been shown to provide benefits in preventing neural tube defects and other birth defects, as well as reducing adverse pregnancy outcomes. This study aimed to examine the impact of various folic acid supplementation methods on pregnancy. TaqMan-MGB technology was used to detect polymorphisms in the folate metabolism-related genes, MTHFR C677T and A1298C. Blood-related biochemical indicators, including HCY levels and history of adverse pregnancy, were examined in relation to different exposure factors (MTHFR gene polymorphism, HCY levels, and adverse pregnancy history) and their impact on pregnancy outcomes. Various forms of folic acid intervention were implemented in a population with an adverse pregnancy history and high HCY levels to analyze the effects of reducing HCY levels and improving pregnancy outcomes. Exposure factors, such as adverse pregnancy history, HCY, and medium-to-high risk of gene metabolism, were closely associated with pregnancy outcomes. Interestingly, methylfolate efficiently reduced the serum HCY levels. More importantly, the methylfolate group exhibited a significantly lower incidence of adverse pregnancies than the synthetic folic acid group. In this study, the risk factors, including adverse pregnancy history, HCY, and medium-to-high risk of gene metabolism, were confirmed to lead to the poorer pregnancy outcomes in our cohort. 5-methyltetrahydrofolate may be an effective approach for decreasing the incidence of adverse pregnancy outcomes.

Concordant fatal congenital anomaly in twin pregnancy: a case report and review of the literature

BackgroundWhen a pregnant mother finds out she has a fetus with a congenital defect, the parents feel profound worry, anxiety, and melancholy. Anomalies can happen in singleton or twin pregnancies, though they are more common in twin pregnancies. In twins, several congenital defects are typically discordant.Case summaryWe present a rare case of concordant fatal anomaly in twin pregnancy in a 22-year-old African patient primigravida mother from Western Ethiopia who presented for routine antenatal care. An obstetric ultrasound scan showed anencephaly, meningomyelocele, and severe ventriculomegaly. After receiving the counseling, the patient was admitted to the ward, and the pregnancy was terminated with the medical option. Following a successful in-patient stay, she was given folic acid supplements and instructed to get preconception counseling before getting pregnant again.ConclusionThe case demonstrates the importance of early obstetric ultrasound examination and detailed anatomic scanning, in twin pregnancies in particular. This case also calls for routine preconceptional care.

Unveiling the Therapeutic Potential of Folate-Dependent One-Carbon Metabolism in Cancer and Neurodegeneration.

Cellular metabolism is crucial for various physiological processes, with folate-dependent one-carbon (1C) metabolism playing a pivotal role. Folate, a B vitamin, is a key cofactor in this pathway, supporting DNA synthesis, methylation processes, and antioxidant defenses. In dividing cells, folate facilitates nucleotide biosynthesis, ensuring genomic stability and preventing carcinogenesis. Additionally, in neurodevelopment, folate is essential for neural tube closure and central nervous system formation. Thus, dysregulation of folate metabolism can contribute to pathologies such as cancer, severe birth defects, and neurodegenerative diseases. Epidemiological evidence highlights folate's impact on disease risk and its potential as a therapeutic target. In cancer, antifolate drugs that inhibit key enzymes of folate-dependent 1C metabolism and strategies targeting folate receptors are current therapeutic options. However, folate's impact on cancer risk is complex, varying among cancer types and dietary contexts. In neurodegenerative conditions, including Alzheimer's and Parkinson's diseases, folate deficiency exacerbates cognitive decline through elevated homocysteine levels, contributing to neuronal damage. Clinical trials of folic acid supplementation show mixed outcomes, underscoring the complexities of its neuroprotective effects. This review integrates current knowledge on folate metabolism in cancer and neurodegeneration, exploring molecular mechanisms, clinical implications, and therapeutic strategies, which can provide crucial information for advancing treatments.

Influence of lifestyle on female fertility. Review of the literature

Introduction Women who want to get pregnant soon often ask their doctors how to prepare best. During such a visit, doctors usually mention folic acid supplementation, a check-up with the dentist and gynaecologist or vaccinations. However, it is also worth pointing out the importance of lifestyle factors that affect fertility and fetal development. Modifying daily habits can improve fertility naturally and make getting pregnant faster. An increasing number of studies are being published on the importance of nutrition, physical activity, sleep, stress, stimulants and other factors on women's reproductive health. This article is a summary of the current state of knowledge in this area. Aim of the study The aim of this study is to review the literature and summarize current state of knowledge on the association between lifestyle factors and female reproductive function. Material and methods of research This literature review based on researches from PubMed platform. We searched articles describing connection between potentially modifiable lifestyle factors and women’s fertility. Search terms included keywords: „lifestyle”, „female fertility”, „obesity”, „sleep”, „nutrition”, „diet”, „stress”, „physical activity”, „smoking”, „alcohol”, „weight loss”, „reproductive health”.

Association of serum folate concentrations with the mortality of cancer: a prospective cohort study.

The association between serum folate concentrations and the mortality of cancer remains unclear. We aim to investigate the association of serum folate concentrations with all-cause and cause-specific mortality among American adults with cancer. This cohort study included 4535 patients with cancer from National Health and Nutrition Examination Survey (NHANES) 1999 to 2016 and NHANES III (1988-1994). Death outcomes were ascertained by linkage to National Death Index records through 31 December 2019. Cox proportional hazards model and two-piecewise Cox proportional hazards model were used to calculate hazard ratios and 95% confidence intervals for the associations between folate concentrations and the risk of mortality. During a median follow-up of 37,792 person-years, there were 1998 all-cause deaths and 616 cancer deaths. Non-linear and L-shaped associations were observed between serum folate concentrations and the risk of all-cause and cancer mortality among patients with cancer. Notably, the mortality rates reached a plateau at 23.7ng/mL for all-cause mortality and 23.57ng/mL for cancer mortality. When folate levels fell below these thresholds, the risk of all-cause and cancer mortality decreased by approximately 2.1% (HR 0.979; 95% CI 0.969-0.989) and 3.6% (HR 0.964; 95% CI 0.948-0.981), respectively, with each unit increase in the folate concentration up to the thresholds. Our study reveals that low serum folate concentrations are linked to an elevated risk of cancer mortality among individuals with cancer within a certain range and supplementation of folate in cancer patients to achieve specific serum folate level threshold (23.7ng/mL) might reduce the risk of cancer mortality.

Prevention and management of anaemia in pregnancy: Community perceptions and facility readiness in Ghana and Uganda.

Anaemia is one of the most common conditions in low- and middle-income countries, with prevalence increasing during pregnancy. The highest burden is in Sub-Saharan Africa and South Asia, where the prevalence of anaemia in pregnancy is 41.7% and 40%, respectively. Anaemia in pregnancy can lead to complications such as prematurity, low birthweight, spontaneous abortion, and foetal death, as well as increasing the likelihood and severity of postpartum haemorrhage. Identifying and mitigating anaemia in pregnancy is a public health priority. Here we present a mixed-methods situational analysis of facility readiness and community understanding of anaemia in Ghana and Uganda. Quantitative health assessments (adapted from service availability and readiness assessments) and qualitative key informant interviews (KIIs) with district-level stakeholders, in-depth interviews (IDIs) with maternity staff, and focus group discussions (FGDs) with community members were held in 2021. We carried out facility assessments in nine facilities in Ghana and seven in Uganda. We carried out seven KIIs, 23 IDIs, and eight FGDs in Ghana and nine, 17, and five, respectively, in Uganda. Many good practices and general awareness of anaemia in pregnancy were identified. In terms of bottlenecks, there was broad consistency across both countries. In health facilities, there were gaps in the availability of haemoglobin testing-especially point-of-care testing-staffing numbers, availability of standard operating procedures/guidelines for anaemia in pregnancy, and poor staff attitudes during antenatal care. Amongst community members, there was a need for improved sensitisation around malaria and helminth infections as potential causes of anaemia and provision of education around the purpose of iron and folic acid supplementation for preventing or managing anaemia in pregnancy. Anaemia in pregnancy is a persistent challenge, but one with clear opportunities to intervene to yield improvements.

Qualitative evaluation of a package of implementation strategies codesigned to support the introduction of multiple micronutrient supplementation (MMS) for pregnant women in Bamako, Mali.

Mali national policy recommends that women take iron and folic acid supplements (IFA) from the time of the first antenatal care (ANC) visit, throughout pregnancyand during the first 3 months after delivery. In 2020, the World Health Organization (WHO) updated their ANC guidelines to recommend the United Nations International Multiple Micronutrient Antenatal Preparation (UNIMMAP) formulation of multiple micronutrient supplements (MMS) in the context of rigorous research, including implementation research. In Bamako, Mali, a codesign process was used to tailor antenatal care MMS packaging and counselling materials aimed at optimizing delivery and uptake of and adherence to MMS. This paper presents the codesign process along with the results of a post-intervention qualitative assessment to evaluate the behaviour change intervention. At the conclusion of the intervention, we conducted semistructured qualitative interviews with 24 women who had received the intervention and six pharmacy managers from the six health centres participating in the study. We conducted two focus groups with midwives who had delivered the intervention and two group discussions with family members of women who had received the intervention. Respondent perspectives reveal an easy experience transitioning from previously used IFA. Women and providers concur that the intervention counselling materials and visual aids were instrumental in influencing the perceived benefit and uptake of MMS. Family members play an influential role in pregnant women's decision-making regarding MMS uptake. MMSand the associated implementation strategies developed through the codesign process were found to be a highly acceptable intervention.

Is Oral Iron and Folate Supplementation during Pregnancy Protective against Low Birth Weight and Preterm Birth in Africa? A Systematic Review and Meta-Analysis.

Despite recent evidence demonstrating iron and folate supplementation reduces the risk of low birth weight and preterm births, synthesis of the evidence is not sufficient to understand their impacts in Africa. MEDLINE, PsycINFO, Embase, Scopus, CHINAL, Web of Science, Cochrane databases, and Google Scholar were searched for the published and grey literature. Either iron-only, folate-only, or iron-folic acid (IFA) oral supplementation during pregnancy was the primary exposure/intervention. The focus of this review was low birth weight and preterm births in the African region. Qualitative synthesis, meta-analysis, and subgroup analysis were employed. In the qualitative synthesis (n = 4), IFA supplementation showed a positive impact on reducing preterm birth. Additionally, the meta-analysis showed that IFA and iron-only supplementation reduced the odds of low birth weight by 63% (OR 0.37; 95% CI: 0.29, 0.48) and 68% (OR 0.32; 95% CI: 0.21 to 0.50), respectively. Both iron-only and IFA supplementation are effective in reducing the risk of low birth weight in Africa. There is also promising evidence suggesting a potential reduction in preterm births. Consequently, further research is needed, particularly targeting high-risk groups such as women residing in rural areas with limited support and low levels of literacy.

Dietary folic acid intake, 13 genetic variants and other factors with red blood cell folate concentration in pregnancy-preparing population

PurposeThis study aims to evaluate a combined effect of dietary folic acid intake, multiple genetic polymorphisms in folate metabolism, and other environmental factors on red blood cell (RBC) folate concentration in pregnancy-preparing population.Methods519 pregnancy-preparing subjects (260 couples) were investigated. Dietary intake was measured by 3-day dietary recalls. 13 Single Nucleotide polymorphisms (SNPs) reported in association with one-carbon metabolism including the methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C were genotyped. RBC folate concentration was measured using chemiluminescence assay. Hierarchical regression was applied for covariate selection. Factors showed significance(p < 0.0125) on RBC folate level was included for prediction model construction and R2 estimation. Validation cohort analysis was performed as post-hoc analysis if applicable.ResultsThe median RBC folate was 212.8 ng/ml. Only 10% took folic acid supplementation within three months. Based on hierarchical selection, folic acid supplementation, genetic polymorphism (especially TT genotype of MTHFR C677T), serum folate level were determinants of the variance of RBC folate concentrations, with adjusted R2 of 0.178–0.242. MTHFR A1298C polymorphism, sex difference with other socio-demographic and lifestyle factors (age, BMI, alcohol drinking, smoking, education, occupation) explained little to change in RBC folate level. Validation in another sub-cohort(n = 8105) had adjusted R2 of 0.273.ConclusionIn pregnancy-preparing subjects, folic acid supplementation, serum folate level and TT allele of MTHFR C677T polymorphism were determinants of the total variance of RBC folate level, which explained 19.8% variance in our subjects and 27.3% in the validation cohort. Food folate intake, sex and other environmental factors explained little to RBC folate level.

Treatment of anaemia in pregnancy with oral iron, folic acid or iron, folic acid and vitamin B12 supplementation: A hospital-based open randomized study

: National iron plus initiative recommended that anaemic pregnant women should be treated with 200 mg of elemental iron and 1 mg folic acid. An increase in vitamin B12 deficiency has been reported in last two decades. An open randomised study was taken up in urban antenatal clinics to assess the impact of addition of vitamin B12 to the iron and folic acid supplementation.: Anaemic pregnant women willing to participate in the study were randomised into Group 1 (240 iron mg and 5 mg folic acid) or Group 2 (240 mg iron, 1.5 mg of folic acid and 15 µg vitamin B12); the impact of supplementation on Hb, ferritin, folic acid and vitamin B12 was assessed.: In both groups mean Hb improved by 1g/dL at 8 weeks and by 1.5g/dL by 38 weeks of pregnancy; at 38 weeks only 30% were anaemic. Mean ferritin and folic acid levels improved in both groups. There was a fall in the mean vitamin B12 levels in the group which received 5 mg of folic acid.: With assured supply and supportive supervision, the supplementation achieved substantial reduction in anaemia in both groups. Supplementation with folic acid 5 mg should not be done because it causes a fall in vitamin B12 levels. The reason why addition of vitamin B12 to iron folic acid supplementation did not result in improvement in mean Hb, or vitamin B12 levels has to be investigated.

Metabolism-Disrupting Chemical Mixtures during Pregnancy, Folic Acid Supplementation, and Liver Injury in Mother-Child Pairs

Metabolism-Disrupting Chemical Mixtures during Pregnancy, Folic Acid Supplementation, and Liver Injury in Mother-Child Pairs

Advances in DNA methylation of imprinted genes and folic acid regulation of growth and development.

DNA methylation is closely related to folate levels and acts as a mechanism linking developmental disorders to chronic diseases. Folic acid supplementation can impact DNA methylation levels of imprinted genes crucial for neonatal development. Imprinted genes are vital for regulating embryonic and postnatal fetal growth. This review summarizes imprinted genes, DNA methylation, folic acid's influence on growth and development and their correlation. It aims to provide a comprehensive overview of research advancements on imprinted genes, DNA methylation and folic acid regulation concerning growth and development.

Folic acid supplement prescribing practice during the protective period and its associated factors among health professionals in selected governmental health centers in Addis Ababa, Ethiopia, 2023: A cross-sectional study.

Background: Supplementing folic acid (FA) before and in the first month of conception is an essential preventive factor, especially for neural tube defects (NTDs) and other congenital anomalies. Aim: The research aimed to assess FA supplement prescribing practice during the protective period and its associated factors among health professionals in selected governmental health centers in Addis Ababa, Ethiopia, in 2023. Methods: An institutionalized cross-sectional survey was carried out in Addis Ababa public health centers with a total sample size of 396 in February 2023. Systematic random sampling methods were used, and after each respondent's signed consent, a row of data was gathered using pretested self-administered questionnaires. The data was coded, interred to Epi Data 4.6.0.6 and transferred to Statistical Package for Social Sciences 27 software. Then a binary and multivariable logistic regression analysis method was used to show the associated variables with FA prescribing practice using a confidence interval (CI) of 95% and a significance value < 0.05. Results: The total prevalence of FA prescribing practice during the periconceptional period was 64.4% [95% CI (59.68-69.12)]. But those prescribed during the protective period were 26.7%. Ever since the birth of a neonate with NTDs, not prescribing a dose of 4 mg of FA for women with NTD, the type of women for whom FA was prescribed were associated with FA prescribing practice during the protective period. Conclusion: The healthcare professional's prescribing practice during the protective period was still low and needs more attention to strengthen FA supplements.

Vitamin D, Folate, Vitamin B12, and Iron Status in Pregnant/Postpartum Old Order Anabaptist Women in Southwestern Ontario.

Purpose: To assess vitamin D, folate, vitamin B12, and iron status in Old Order Anabaptist (OOA) pregnant/postpartum women.Methods: Blood was analyzed for plasma 25 hydroxy vitamin D (25(OH)D), red blood cell (RBC) folate, serum vitamin B12, and iron status indicators. Dietary intakes (food and supplements) from 3-day estimated records were compared to Dietary Reference Intakes and Canada's Food Guide (2007).Results: Fifty women participated in this descriptive cross-sectional study. Concentrations of 25(OH)D were low (<50 nmol/L for 20% and < 75 nmol/L for 63%); 42% had total vitamin D intakes < estimated average requirement (EAR). All women had RBC folate above the 1360 mmol/L cut-off. Nineteen percent had folate intakes <EAR; 80% had folic acid supplement intakes >upper limit. One woman had low serum vitamin B12 (<148 pmol/L); serum vitamin B12 was high (>652 pmol/L) for 24%. None had vitamin B12 intakes <EAR; intakes were high compared to the recommended dietary intake. One woman had low hemoglobin; 13% had ferritin <15 μg/L. Thirteen percent had total iron intake <EAR.Conclusions: Overall, dietary intake and serum micronutrient status of OOA pregnant and postpartum women in our study were similar to those reported in previous studies of Canadian women. While some women had low intakes of vitamin D and iron, most had high intakes of folate and vitamin B12. These findings provide guidance to ensure appropriate dietary and supplement intakes in this potentially vulnerable and rarely studied population.