Serum Folate Research Articles

Effect of Unmetabolized Folic Acid on Immunoinflammatory Markers in Sickle Cell Disease Patients Taking Folic Acid Supplementation.

Folic acid (FA) supplementation in sickle cell disease (SCD) patients lead to accumulation of unmetabolized folic acid (UMFA) which might influence the level of cytokines and NK cell activity and thus trigger the crisis event. The aim of the study was to investigate the effect of UMFA levels on immuno-inflammatory markers in SCD patients taking FA supplementation. The cross-sectional study was conducted on 60 HbSS confirmed SCD cases with 22 crisis and 38 cases at steady state of 15-40years age group. Serum FA, 5-Methyl Tetrahydrofolate (5-MTHF), Dihydrofolate reductase, Interleukin-6 (IL-6), Highly sensitive C-Reactive Protein (HsCRP), and natural killer (NK) cell activity were estimated. More than 50% of the study population depicted presence of UMFA. The median UMFA level was significantly elevated in crisis group (131.8ng/mL) as compared to the steady state group (36.31ng/mL) (p = 0.041). The median value of HsCRP was significantly higher in the crisis group (18.41mg/L) than the steady state group (2.04mg/L) (p = 0.003). Similarly, IL-6 was higher in crisis group (13.29pg/mL) than steady state group (5pg/mL) (p = 0.060). The median NK cell activity was 39.28nmol/L in crisis group and 35.31nmol/L in steady state groups (p = 0.889). In bivariate correlation analysis, UMFA showed a significant negative correlation with NK cell activity (r = - 0.638; p = < 0.001) and a positive correlation with IL-6 (r = 0.571; p = 0.001) and HsCRP (r = 0.237; p = 0.200). Accumulation of UMFA affect NK cell activity, thus influence the vulnerability for crisis state. Therefore, dosage modification for FA supplementation in SCD patients is suggested.

Effect of Antiepileptic Drugs on Serum Vitamin B12 and Folic Acid Among Children with Epilepsy in Bangalore

In India, there are more than 12 million people diagnosed with epilepsy, and contributes nearly to the one sixth of global burden. Over 60% of diagnosis for epilepsy is done in childhood; hence, it is of major importance to pediatricians. we aimed to assess the levels of Vitamin B12 and Folic acid among children with epilepsy receiving antiepileptic drugs like Carbamazepine, Sodium Valproate and Levetiracetam monotherapy for &gt;1 year. A total of 77 children with epilepsy (&lt;18 years), on monotherapy with SV, CBZ, LEV, for minimum one year, were enrolled after obtaining consent from the parent/guardian. Children with co morbid condition like chronic kidney disease, chronic liver disease, those children who were on multiple AED’s, and children receiving treatment for &lt;1year were excluded from the study. Out of the 77 patients, who were selected for the study, 46 were males and 31 were females. There has been a significant association between duration of treatment and Vitamin B12 and levels of Folic acid. There is also enough evidence to show that age of the patient and Folic acid levels are dependent variables. The proportion of children developing deficiency of Vitamin B12 or Folic acid after treatment with LEV is greater than the proportion treated with CBZ. The proportion of patients developing deficiency of Folic acid after treatment with LEV is greater than the same proportion after treatment with CBZ. Though there were a few significant findings as reported, we, the authors, feel that the study should be continued to ascertain if the AED’s have a significant role in Vitamin B12 and Folic acid metabolism and supplementation should be advised along with the AED’s.

The association between diverse serum folate with MAFLD and liver fibrosis based on NHANES 2017-2020.

Metabolically Associated Fatty Liver Disease (MAFLD) marks a progression from the previous paradigm of Non-Alcoholic Fatty Liver Disease (NAFLD), presenting a redefined diagnostic framework that accentuates metabolic factors while recognizing non-alcoholic contributors. In our investigation, our principal aim was to scrutinize the conceivable correlation between diverse serum folate levels and the prevalence of MAFLD and liver fibrosis. In our investigation, we conducted an extensive analysis utilizing data derived from the National Health and Nutrition Examination Survey (NHANES) across the years 2017-2020. We aimed to investigate the association between different serum folate concentrations and the prevalence of MAFLD and liver fibrosis by comprehensive multivariate analysis. This analytical approach considered various variables, encompassing sociodemographic characteristics, lifestyle factors, hypertension, and diabetes. By including these potential confounders in our analysis, we aimed to ensure the stability of the findings regarding the association between different serum folate concentrations and the development of MAFLD and liver fibrosis. In our investigation, we utilized multiple linear regression models to thoroughly analyze the data, revealing noteworthy insights. Evidently, elevated levels of both total folate and 5-MTHF exhibited a distinct negative correlation with CAP, while 5-MTHF demonstrated a notable negative correlation with LSM. Furthermore, multiple logistic regression models were employed for an in-depth examination of the data. As the concentrations of total folate and 5-MTHF in the serum increased, a substantial decrease in the likelihood of MAFLD and liver fibrosis occurrence was observed. The findings of this investigation robustly suggest the prevalence of MAFLD and liver fibrosis decreased significantly with the increase of serum concentrations of total folate and 5-MTHF.

Simultaneous Determination of One-Carbon Folate Metabolites and One-Carbon-Related Amino Acids in Biological Samples Using a UHPLC-MS/MS Method.

One-carbon folate metabolites and one-carbon-related amino acids play an important role in human physiology, and their detection in biological samples is essential. However, poor stability as well as low concentrations and occurrence in different species in various biological samples make their quantification very challenging. The aim of this study was to develop a simple, fast, and sensitive ultra-high-performance liquid chromatography MS/MS (UHPLC-MS/MS) method for the simultaneous quantification of various one-carbon folate metabolites (folic acid (FA), tetrahydrofolic acid (THF), p-aminobenzoyl-L-glutamic acid (pABG), 5-formyltetrahydrofolic acid (5-CHOTHF), 5-methyltetrahydrofolic acid (5-CH3THF), 10-formylfolic acid (10-CHOFA), 5,10-methenyl-5,6,7,8-tetrahydrofolic acid (5,10-CH+-THF), and 4-α-hydroxy-5-methyltetrahydrofolate (hmTHF)) and one-carbon-related amino acids (homocysteine (Hcy), methionine (Met), S-ade-L-homocysteine (SAH), and S-ade-L-methionine (SAM)). The method was standardized and validated by determining the selectivity, carryover, limits of detection, limits of quantitation, linearity, precision, accuracy, recovery, and matrix effects. The extraction methods were optimized with respect to several factors: protease-amylase treatment on embryos, deconjugation time, methanol precipitation, and proteins' isoelectric point precipitation on the folate recovery. Ten one-carbon folate metabolites and four one-carbon-related amino acids were detected using the UHPLC-MS/MS technique in various biological samples. The measured values of folate in human plasma, serum, and whole blood (WB) lay within the concentration range for normal donors. The contents of each analyte in mouse plasma were as follows: pABG (864.0 nmol/L), 5-CH3THF (202.2 nmol/L), hmTHF (122.2 nmol/L), Met (8.63 μmol/L), and SAH (0.06 μmol/L). The concentration of each analyte in mouse embryos were as follows: SAM (1.09 μg/g), SAH (0.13 μg/g), Met (16.5 μg/g), 5,10-CH+THF (74.3 ng/g), pABG (20.6 ng/g), and 5-CH3THF (185.4 ng/g). A simple and rapid sample preparation and UHPLC-MS/MS method was developed and validated for the simultaneous determination of the one-carbon-related folate metabolites and one-carbon-related amino acids in different biological samples.

The relationship between thiamin, folic acid and cognitive function in a rat model of uremia

End-stage renal disease is a worldwide health burden, but the pathogenesis of uremia-associated cognitive impairment (CI) is poorly recognized. We hypothesized that uremia brings about deficiency of thiamin and folic acid and causes CI by inducing oxidative stress. Therefore, 24 Sprague-Dawley rats were randomly divided into two groups: a 5/6 nephrectomy group (n = 12) and a sham-operated group (n = 12). The Morris water maze was used to assess the cognitive function eight weeks post-surgery, and serum levels of thiamin, folic acid and homocysteine were detected subsequently. Brain and kidney tissues were collected for pathological examination and 8-Hydroxy-2’-deoxyguanosine (8-OHdG) immunochemistry staining. Results showed that the escape latency on training days 1-2 was longer, and the time in quadrant IV on experimental day 6 was significantly shorter in 5/6 nephrectomy group. Meanwhile, the uremic rats showed decreased thiamin, folic acid and increased homocysteine. We also found the time in quadrant IV was positively correlated with thiamin and folic acid level, while negatively correlated with the blood urea nitrogen and 8-OHdG positive cell proportion. Furthermore, in 5/6 nephrectomy group, the hippocampal neuron count was significantly reduced, and a greater proportion of 8-OHdG positive cells were detected. Pretreating LPS-stimulated rat microglial cells with thiamin or folic acid in vitro alleviated the inflammatory impairment in terms of cell viability and oxidative stress. In summary, we applied a uremic rat model and proved that uremia causes serum thiamin and folic acid deficiency, homocysteine elevation, along with neuron reduction and severe oxidative stress in hippocampus, finally leading to CI.

Association between Biomarkers of Phthalate Exposure and Serum Folate Concentrations in Children: A Population-Based Cross-Sectional Study of the NHANES from 2011 to 2016

BackgroundAlthough adverse health effects of phthalates have been reported, very few studies have assessed the associations between biomarkers of phthalate exposure and serum folate concentrations in children. ObjectivesWe aimed to examine the association between urinary phthalate metabolites, as biomarkers of exposure to phthalates, and total serum folate concentrations in children using national data from the United States. MethodsWe conducted cross-sectional analyses of 2100 individuals aged 6–18 y enrolled in the National Health and Nutrition Examination Survey, 2011–2016. Multivariable linear regression was applied to examine the relationship between natural logarithm (ln)-transformed urinary phthalate metabolites and serum folate concentrations. The quantile-based g-computation was used to assess the association of urinary phthalate metabolite mixture with serum folate levels. Subgroup analyses were conducted by sex, age, and race/ethnicity, and the interactions were assessed by adding interaction terms of these stratifying variables and phthalates and modeling through the Wald test. ResultsIn multiple linear regression models, for participants in the highest tertile of MEHHP, MEOHP, DEHP, MCPP, and MCOP, total serum folate concentrations were 1.566 [β: −1.566; 95% confidence interval: −2.935, −0.196], 1.423 (−1.423; −2.689, −0.157), 1.309 (−1.309; −2.573, −0.044), 1.530 (−1.530; −2.918, −0.142), and 1.381 (−1.381; −2.641, −0.122) ng/mL lower than those in the lowest tertile. The inverse associations were consistent in different subgroups by sex, age, and race/ethnicity (P for interaction ≥0.083 for all). In addition, the phthalate mixture showed a strong inverse correlation with serum folate; a quartile increase in the phthalate mixture on the ln scale was associated with 0.888 (−0.888; −1.677, −0.099) ng/mL decrease in the serum folate. ConclusionsHigher concentrations of urinary phthalate metabolites were associated with lower serum folate concentrations in children. Although our findings should be validated through additional population and mechanistic studies, they support a potential adverse effect of phthalate exposure on folate metabolism in children.

Optimal folic acid dosage in lowering homocysteine: Precision Folic Acid Trial to lower homocysteine (PFAT-Hcy)

BackgroundWhile folic acid (FA) is widely used to treat elevated total homocysteine (tHcy), promoting vascular health by reducing vascular oxidative stress and modulating endothelial nitric oxide synthase, the optimal daily dose and individual variation by MTHFR C677T genotypes have not been well studied. Therefore, this study aimed to explore the efficacy of eight different FA dosages on tHcy lowering in the overall sample and by MTHFR C677T genotypes.MethodsThis multicentered, randomized, double-blind, controlled clinical trial included 2697 eligible hypertensive adults with elevated tHcy (≥ 10 mmol/L) and without history of stroke and cardiovascular disease. Participants were randomized into eight dose groups of FA combined with 10 mg enalapril maleate, taken daily for 8 weeks of treatment.ResultsThe intent to treat analysis included 2163 participants. In the overall sample, increasing FA dosage led to steady tHcy reduction within the FA dosing range of 0–1.2 mg. However, a plateau in tHcy lowering was observed in FA dose range of 1.2–1.6 mg, indicating a ceiling effect. In contrast, FA doses were positively and linearly associated with serum folate levels without signs of plateau. Among MTHFR genotype subgroups, participants with the TT genotype showed greater efficacy of FA in tHcy lowering.ConclusionsThis randomized trial lent further support to the efficacy of FA in lowering tHcy; more importantly, it provided critically needed evidence to inform optimal FA dosage. We found that the efficacy of FA in lowering tHcy reaches a plateau if the daily dosage exceeds 1.2 mg, and only has a small gain by increasing the dosage from 0.8 to 1.2 mg.ClinicalTrials.gov IdentifierNCT03472508 (Registration Date: March 21, 2018).

Serum interleukin-17 A and homocysteine levels in children with autism

BackgroundAutism Spectrum Disorder (ASD) is a neurodevelopmental condition that typically emerges early in childhood. This study aimed to explore the potential link between serum levels of vitamin B12 and homocysteine (Hcy) and the severity of ASD symptoms in children.MethodsIn this study, 50 children diagnosed with ASD comprised the observation group, while 50 healthy children constituted the control group. Serum levels of IL-17 A, Hcy, folate, and vitamin B12 were compared between the study group and control group, as well as among children with different degrees of ASD severity. The correlation between the Childhood Autism Rating Scale (CARS) score and serum levels of IL-17 A, Hcy, folate, and vitamin B12 was examined. Additionally, the relationship between serum IL-17 A and Hcy levels and their association with the severity ASD were explored.ResultsCompared to the control group, the observation group demonstrated elevated serum Hcy and IL-17 A levels alongside decreased folate and vitamin B12 levels. Individuals with severe ASD exhibited higher Hcy and IL-17 A levels but lower folate and vitamin B12 levels compared to those with mild to moderate ASD. The CARS score showed negative correlations with serum folate and vitamin B12 levels and positive correlations with serum IL-17 A and Hcy levels in ASD patients. Additionally, serum Hcy and IL-17 A levels were correlated with ASD severity.ConclusionChildren diagnosed with ASD presented with reduced serum vitamin B12 levels and increased levels of Hcy, potentially contributing to the onset and severity of ASD.

The Relationship Between Serum Folate and Homocysteine with Head and Neck Cancer: A Systematic Review and Meta-analysis

Context: Early diagnosis of head and neck squamous cell carcinomas (HNSCC) is critical for preventing further disease progression. This study aimed to compare the serum folate and homocysteine levels in patients with HNSCC and healthy controls through a systematic review and subsequent meta-analyses. Evidence Acquisition: The research question was: Is there a difference between serum folate and homocysteine levels (O) of patients with HNSCC (E) compared to healthy controls (C)? To conduct a systematic review, keywords were first identified and then searched in Medline/PubMed, Web of Science, ProQuest, EMBASE, Scopus, and Google Scholar databases within the period from January 2000 to November 2023. The searched studies were screened based on inclusion and exclusion criteria, and after assessing the quality of the selected articles using the Joanna Briggs Institute assessment checklist, 10 articles were finally included in the meta-analysis (nine articles for serum folate and eight for homocysteine). Due to the heterogeneity of studies, meta-analyses were conducted according to the random-effects model. Several meta-analyses were carried out because the selected articles were not uniform regarding smoking habits. Results: Regardless of smoking conditions, the serum folate levels of the HNSCC patients were significantly lower than those of the control groups. Similarly, the serum homocysteine levels were significantly higher in the patient groups compared to the control groups. Conclusions: The meta-analyses in this study showed an association between serum folate and homocysteine levels with HNSCC, indicating their possible use as biomarkers for the early detection of HNSCC.

Relationship between Different Hematological Parameters and Disease Activity in Patients with Rheumatoid Arthritis

Background and objectives: Rheumatoid arthritis is a type of immune disorder that has an impact on the entire body. The objective was to measure and compare various hematological parameter values between chronic and new cases also in new patients who exhibited varying degrees of disease activity. Methods: This study was a cross-sectional survey, conducted in Rizgary Hospital and private clinics in Erbil city/ Kurdistan Region of Iraq. Two groups each of 30 patients; with newly diagnosed the 2010 ACR/EULAR criteria are divided into four groups, each of which has a point score: joint symptoms, serology (including Rheumatoid factor and/or Anti-Citrullinated Peptide Antibody), duration of symptoms (less than or more than 6 weeks), and acute-phase reactants (c-reactive protein and/or erythrocyte sedimentation rate) and chronic Rheumatoid Arthritis cases enrolled in this study from October 2021 till September 2022. Hematological parameter and disease activity monitored and compared between both groups, in addition to comparison between cases in the same group. Results: The majority (81.7%) of patients were female and (18.3%) of them were male, mean age ± std. deviation of respondents was 48.80 ± 9.13 years. There was significant statistical association between study groups and joint swelling, multiple or single joint and disease activity (DAS 28), also, the difference between both groups was statistically significant regarding mean pain score, white blood cells, serum folate, and rheumatoid factor. Likewise; the association was significant between study groups and multiple or single joint. There was significant statistical association between study groups and DAS 28, the majority (86.7%) of newly diagnosed patients had low – moderate level of DAS 28 while 40% of chronic subjects measured high level of DAS 28. Conclusion: Hematological markers including disease activity score, white blood cells, serum folate, C-reactive protein and rheumatoid factor were good indicators for measurement of rheumatoid arthritis severity and activity in the selected sample of patients.

Folic Acid–Fortified Iodized Salt and Serum Folate Levels in Reproductive-Aged Women of Rural India

India has a disproportionately high prevalence of neural tube defects, including spina bifida and anencephaly (SBA), causing a high number of stillbirths, elective pregnancy terminations, and child mortality; India contributes a large proportion of the global burden of SBA. Thirty years after folic acid was shown to be effective in reducing SBA prevalence, only about one-quarter of such births are prevented globally through cereal grain fortification. To determine the association of folic acid-fortified iodized salt with serum folate concentrations among nonpregnant and nonlactating women of reproductive age. This nonrandomized controlled trial using a preintervention and postintervention design was conducted in 4 rural villages in Southern India from July 1 to November 30, 2022. All households in the villages agreed to participate in the study. Preintervention and postintervention serum folate levels were analyzed among study participants at baseline and after 4 months, respectively. Consumption of approximately 300 µg/d of folic acid using double fortified salt (folic acid plus iodine). Median serum folate concentrations were assessed at baseline and 4 months. Change in median serum folate levels between baseline and study end point as the primary outcome of the study. A total of 83 nonpregnant nonlactating women aged 20 to 44 years (mean [SD] age, 30.9 [5.1] years) were eligible for the study and provided serum samples for analysis at baseline and the end point of the intervention. The median serum folate concentration increased from 14.6 (IQR, 11.2-20.6) nmol/L at baseline to 54.4 (IQR, 43.5-54.4) nmol/L at end of study, a 3.7-fold increase from baseline to study end point. Two-tailed Wilcoxon signed rank test showed the median difference in preintervention and postintervention serum folate concentrations to be highly significant (P < .001). The participants found the salt acceptable in color and taste. Use of folic acid-fortified iodized salt was associated with increased serum folate concentrations in women of reproductive age. This novel evidence can inform public health policy to accelerate SBA prevention. ClinicalTrials.gov Identifier: NCT06174883.

Exploring the causal associations of micronutrients on urate levels and the risk of gout: A Mendelian randomization study

Growing evidence has indicated a potential association between micronutrient levels, urate levels, and the risk of gout. However, the causal association underlying these associations still remains uncertain. Previous observational studies and randomized controlled trials investigating the association between micronutrients, urate levels, and the risk of gout have been limited in their scope and depth. The aim of this study was to utilize Mendelian randomization (MR) to investigate the causal associations between genetically predicted micronutrient levels, urate levels, and the risk of gout. In this study, we conducted a comprehensive examination of 10 specific micronutrients (vitamin B6, vitamin B12, vitamin C, vitamin D, folate, calcium, iron, copper, zinc, and selenium) as potential exposures. Two-sample MR analyses were performed to explore their causal associations with urate levels and the risk of gout. In these analyses, gout data were collected from the Global Biobank Meta-Analysis Initiative (N=1,069,839, N cases=30,549) and urate levels data from CKDGen Consortium (N=288,649) by utilizing publicly available summary statistics from independent cohorts of European ancestry. We performed inverse-variance weighted MR analyses as main analyses, along with a range of sensitivity analyses, such as MR-Egger, weighted median, simple mode, weighted mode, Steiger filtering, MR-PRESSO, and Radial MR analysis, to ensure the robustness of our findings. The results of our study indicate that there were negative associations between serum vitamin B12 and urate levels, as well as serum folate and the risk of gout. Specifically, we found a negative association between vitamin B12 levels and urate levels, with a β coefficient of-0.324 (95% CI -0.0581 to-0.0066, P=0.0137) per one standard deviation (SD) increase. Similarly, a negative association was observed between folate levels and gout risk, with an odds ratio of 0.8044 (95% CI 0.6637 to 0.9750, P=0.0265) per one SD increase. On the other hand, we identified positive associations between serum calcium levels and both urate levels and the risk of gout. Specifically, there was a positive association between serum calcium levels and urate levels (β coefficient: 0.0994, 95% CI 0.0519 to 0.1468, P=4.11E-05) per one SD increase. Furthermore, a positive association was found between serum calcium levels and the risk of gout, with an odds ratio of 1.1479 (95% CI 1.0460 to 1.2598, P=0.0036) per one SD increase. These findings were robust in extensive sensitivity analyses. By employing MR-PRESSO and Radial MR to eliminate outliers, the observed associations have been reinforced. No clear associations were found between the other micronutrients and the urate levels, as well as the risk of gout. Our findings provided evidence that there were negative associations between serum vitamin B12 and urate levels, as well as serum folate and the risk of gout, while positive associations existed between the serum calcium levels and urate levels, as well as the risk of gout.

Folate and vitamin B12 status and predicted neural tube defects risk among nonpregnant women of reproductive age from the Malawi National Micronutrient Survey, 2015-2016.

Maternal folate and vitamin B12 deficiency can lead to serious adverse pregnancy outcomes. There are no nationally representative estimates on folate and vitamin B12 status among women of reproductive age (WRA) in Malawi. We assessed folate and vitamin B12 status among nonpregnant WRA in Malawi and predicted the risk of folate-sensitive neural tube defects (NTDs) were they to become pregnant. Using data from the cross-sectional, nationally representative 2015-2016 Malawi Micronutrient Survey, we calculated the proportion of folate and vitamin B12 deficiency and insufficiency by demographic characteristics among 778 nonpregnant WRA (15-49 years). We predicted NTD prevalence using red blood cell (RBC) folate distributions and a published Bayesian model of the association between RBC folate and NTD risk. Analyses accounted for complex survey design. Among WRA, 8.5% (95% CI: 6.2, 11.6) and 13.3% (10.0, 17.4) had serum (<7 nmol/L) and RBC folate (<305 nmol/L) deficiency, respectively. The proportion of vitamin B12 deficiency (<148 pmol/L) and insufficiency (≤221 pmol/L) was 11.8% (8.6, 16.0) and 40.6% (34.1, 47.4), respectively. RBC folate insufficiency (<748 nmol/L, defined as the concentration associated with the threshold for elevated NTD risk: >8 cases per 10,000 births) was widespread: 81.4% (75.0, 86.4). The predicted NTD risk nationally was 24.7 cases per 10,000 live births. RBC folate insufficiency and higher predicted NTD risk were more common among WRA living in urban areas or with higher education. These findings highlight the importance of nutritional and NTD surveillance in Malawi and the opportunity for improving folate and vitamin B12 nutrition among Malawian WRA.

The correlation of folic acid and homocysteine serum with vascular density and retinal non-perfusion area in diabetic retinopathy

Background : Diabetic Retinopathy (DR) is the most common microvascular complication of Diabetes Mellitus (DM). Homocysteine has been studied as a biomarker in DR, while folic acid exhibits anti-proliferative effects in DR.&#x0D; Objective : To analyze the correlation between folic acid and homocysteine serum with vascular density and retinal non-perfusion area in healthy individuals and patients with diabetic retinopathy.&#x0D; Methods : This is an observational study with a cross-sectional design, conducted in Dr. Kariadi Hospital and GAKI laboratory in Semarang in January 2023. This study included 60 samples: 15 healthy individuals, 15 patients with DM but no DR, 15 patients with Non-Proliferative Diabetic Retinopathy (NPDR), and 15 patients with Proliferative Diabetic Retinopathy (PDR). Patients were examined for serum folic acid and homocysteine using blood laboratory tests, vessel density and retinal non-perfusion areas using optical coherence tomography angiography (OCTA).&#x0D; Results : There was a negative correlation with weak strength between folic acid levels and retinal non-perfusion area of the retina in all samples (Folic acid levels vs retinal non-perfusion area, p = 0.009, Spearman correlation = -0.335). There was a positive correlation with weak strength between folic acid levels and vascular density in all samples (Folic acid levels vs vascular density, p = 0.009, Spearman correlation = 0.337). There was a positive correlation with moderate strength between homocysteine levels and retinal non-perfusion area in all samples (Homocysteine levels vs non–perfusion area of the retina, p = 0.001, Spearman correlation = 0.426). There was a positive correlation with moderate strength between homocysteine levels and vascular density in all samples (Homocysteine levels vs vascular density, p = 0.001, Spearman correlation = -0.414).&#x0D; Conclusion : There was a correlation between folic acid and homocysteine serum with vascular density and retinal non-perfusion areas.

Risk Factors for Neural-Tube Defects Detected in Utero: A Prospective Community-Based Study from Addis Ababa

BackgroundA recent community-based study from Addis Ababa identifying NTD cases by ultrasound examination of pregnant women showed a higher prevalence of 17 per 1000 foetuses. The risk factors behind the high prevalence remain unclear. MethodsAltogether 891 of the 958 women participated in the ultrasound examination. Thirteen with unaffected twin pregnancies were excluded. Among 878 singleton pregnancies, 15 NTD cases were identified. Serum Folate, vitamin B12 and homocysteine levels were measured in case-mothers and a sub-set of 28 non-case mothers. Because of the modest sample size, exact logistic regression analysis was used to estimate associations between risk factors and NTDs. ResultsSerum vitamin status was generally poor for participants in the study. Still, relatively higher values of folate or vitamin B12 in serum, appeared to be protective for NTD (OR=0.61 per ng/ml, 95% CI: 0.42-0.85 and OR=0.67 per 100 pg/ml, 95% CI: 0.41-1.02, respectively). High serum homocysteine was associated with higher risk of NTD (OR=1.3 per μmol/l, 95% CI: 1.02-1.8). Women aged 30 years or more had an odds ratio of 3.5 (95% CI: 1.1-12) for having a NTD child, and families with NTD children had lower household income. Women in the NTD group also had more spontaneous abortions or stillbirths in previous pregnancies. Self-reported intake of folate did not appear to protect against NTDs. ConclusionWithin this high-prevalence community, poor vitamin status was identified as a risk factor for NTDs detected at ultrasound examination. Improving food security and fortification of foods or food ingredients could be alternative measures.

Verification of the analytical performance of the serum Folate assay on the Abbott Alinity ci®

In the evolving landscape of clinical diagnostics, the significance of folate takes center stage as precision and innovation shape advancements in analytical methodologies. Folate, a pivotal element in cellular metabolism, governs physiological processes and serves as an indicator for various medical conditions. This study employs the Chemiluminescent Microparticle Immunoassay (CMIA), known for its accuracy, to assess the reproducibility and repeatability of serum folate levels. Folate's role in cellular metabolism influences diverse physiological functions, making its precise quantification crucial for identifying and monitoring conditions such as folate deficiency. The CMIA method emerges as a robust approach, leveraging immunological specificity for high precision and reliability. Utilizing the Abbott Alinity ci® Analyzer, a technologically advanced clinical chemistry instrument, this study incorporates a systematic analytical method verification procedure. This involves quantification through a standardized protocol and a comparative analysis against criteria set by esteemed societies (RICOS and FSCB), ensuring comprehensive insights into analysis techniques. The reproducibility test, evaluating the impact of various factors on assay results, reveals low Coefficient of Variation (CV) values (CV1: 10.25%, CV2: 8.58%, CV3: 9.13%) across different levels. The results align with quality control limits, emphasizing the method's reliability. Repeatability assessment demonstrates exceptionally low CV values (CV1: 4.84%, CV2: 3.41%, CV3: 1.89%), highlighting the method's stability and precision under controlled conditions.

A Cross-Sectional Study for the Spectrum of Clinical Diagnosis in Patients Presenting With Macrocytosis.

Objective The objectives of this study were to determine the frequency of the clinical spectrum of diseases in patients with macrocytosis and to summarize the diagnostic evaluation of patients found to have macrocytosis on laboratory testing. Background This was a cross-sectional study that took place at the Department of Medicine in Combined Military Hospital, Rawalpindi, Pakistan, from January to June 2023. Methodology One hundred and five patients with macrocytosis with mean corpuscular volume (MCV) values > 100 fL (80 to 100 fL) were inducted as per inclusion and exclusion criteria. Informed consent was obtained from all patients. Complete blood counts (CBC), peripheral blood film, serum vitamin B12 levels, serum folate levels, renal function tests (RFTs), liver function tests (LFTs), and thyroid function tests (TFTs) were performed during the assessment. Results The commonest cause of macrocytosis was vitamin B12 deficiency followed by folate deficiency, combined vitamin B12 and folate deficiency, and other causes were also found in a few cases. Conclusion Serum vitamin B12 and folate deficiency are the most common preventable causes of macrocytosis.

Assessment of blood one-carbon metabolism indexes during mid-to-late pregnancy in 397 Chinese pregnant women.

One-carbon metabolism (OCM) significantly influences fetal growth and neurodevelopment through transferring methyl group to biomolecules, during which folate, methionine, choline and betaine function as methyl donor nutrients, while vitamin B2, B6, B12 function as enzyme cofactors, and homocysteine (Hcy) and S-adenosyl methionine (SAM) are functional metabolites. This study aimed to assess blood OCM index levels and explore their relationships among Chinese pregnant women. Data were obtained from the baseline of the Mother-Child Nutrition and Health Cohort Study. Pregnant women, voluntarily recruited from September 2020 to June 2022 during antenatal examinations in five Chinese cities at 24-32 gestational weeks, provided fasting venous blood samples. Measurements included RBC and serum folate, serum vitamin B2, B6, B12, choline, betaine, methionine, total Hcy (tHcy), and plasma SAM. Sociodemographic characteristics and pregnancy-related conditions were collected via a self-designed questionnaire. Of 397 participants, 82.6% were in mid-pregnancy (24-27 gestational weeks) and 17.4% were in late-pregnancy (28-32 gestational weeks). Serum folate, vitamin B6, and B12 deficiencies were 2.5, 1.3, and 8.3%, respectively. Elevated tHcy (≥10 μmol/L) was observed in 1.8% of pregnant women. Elderly pregnant women (aged 35 and above) exhibited significantly lower serum methionine levels (p < 0.05), while multiparous women had lower RBC folate levels (p < 0.05), and lower serum methionine and vitamin B12 levels (p < 0.10, not statistically significant). Partial correlation analysis revealed positive associations between RBC folate and cofactor vitamin B12 (r = 0.244, p < 0.05) in the folate cycle, as well as significant correlations between two methyl donor paths [serum folate was significantly related to serum choline (r = 0.172) and betaine (r = 0.193)]. As functional biomarkers of OCM, serum tHcy exhibited negative associations with RBC folate (β = -0.330, p < 0.05) and vitamin B6 (β = -0.317, p < 0.05), and plasma SAM displayed a positive association with serum betaine (β = 0.610, p < 0.05), while negatively associated with serum vitamin B6 (β = -0.181, p < 0.05). The blood OCM exhibited imbalances during mid-to-late pregnancy, characterized by lower levels of folate, vitamin B6, and B12, alongside elevated tHcy levels. Adequate folate and vitamin B6 emerged as significant predictors of lower tHcy levels. Additionally, serum betaine showed a positive correlation with plasma SAM. This suggests the importance of not only ensuring sufficient folate but also optimizing other OCM-related nutrients throughout pregnancy.

Periconceptional maternal homocysteine and birth weight outcomes in offspring: a prospective cohort study

Objective: To quantify the associations between periconceptional maternal homocysteine (HCY) and offspring's birth weight and risk of small for gestational age (SGA) infant. Methods: The 19 984 mother-child pairs in this prospective cohort study were recruited from the Shanghai preconception cohort; the infants were delivered from 1st September 2016 to 11th November 2022. A standardized questionnaire was used to collect the mothers' demographic information, medical history, dietary supplement use, and maternal complications during pregnancy, and their serum samples were collected. Serum HCY, folate, and vitamin B12 were measured using chemiluminescent microparticle immunoassay based on serum sample drawn at enrollment. Birth weight data were obtained from medical records. Multiple imputation methods were applied to handle missing data in key variables. Multivariable linear regression and Poisson regression models were used to analyze the relationship between maternal HCY concentration during the periconceptional period and the birth weight and SGA risk of the offspring. Results: A total of 9 452 pairs were enrolled preconceptionally and the remaining 10 532 pairs were enrolled in early pregnancy. The proportion of mothers whose pregnancy age was greater than 35 years was 9.2% (1 832/19 984), the proportion of primiparous women was 76.5% (15 283/19 984), the proportion of pre-pregnancy overweight and obesity was 14.0% (2 804/19 984), the proportion of using folic acid supplements before pregnancy was 21.4% (4 272/19 984), and the proportion of those who supplemented with folic acid during early pregnancy was 85.2% (8 976/10 532); gestational diabetes mellitus was in 6.2% (1 245/19 984), gestational hypertensive syndrome in 3.6% (711/19 984). The birth weight of the offspring was (3 297±468) g, and there were 1 962 SGA children (9.8%). The HCY concentration in the overall population in appropriate for gestational age during the periconceptional period was (7.9±3.2) μmol/L, with (8.3±3.7) μmol/L in the preconception subgroup and (7.3±2.4) μmol/L in the early pregnancy subgroup. After adjustment for the covariates of perinatal demographic information, adverse pregnancy outcomes, serum folate and vitamin B12, increased maternal periconceptional HCY was significantly associated with lower offspring birth weight (β=-2.30, 95%CI -4.43--0.16, P=0.035). Only the early pregnancy subgroup was significantly associated with lower offspring birth weight (β=-7.39, 95%CI-11.50--3.21, P<0.001). No association was found between peripregnancy HCY and offspring SGA risk. However, elevated HCY in early pregnancy was associated with an increased risk of SGA in the offspring (RR=1.05, 95%CI 1.01-1.08, P=0.002). Periconceptional vitamin B12 was a mediator of the association between HCY and offspring birth weight, accounting for 16.5%, 41.2% and 5.4% of its total effect in the overall periconceptional population, the pre-pregnancy subgroup and the early pregnancy subgroup, respectively. Conclusions: Maternal periconceptional HCY level is associated with lower birth weight in offspring, but not with the risk of SGA. Elevated maternal HCY in early pregnancy subgroup may be associated with increased risk of SGA in offspring.

Association of serum folic acid levels in response to fasting blood glucose in early pregnancy with the risk of gestational diabetes mellitus: A retrospective cohort study

ObjectiveWith increasingly prevalent folic acid consumption in early pregnancy, concerns about its potentially negative effect on maternal metabolism have been raised. Recent findings regarding folic acid levels in the first trimester and the risk of gestational diabetes mellitus have been inconclusive. The aim of this study was to investigate the association of folic acid status in early pregnancy with gestational diabetes mellitus as well as examine whether glucose levels can be modulated by folic acid status during the same first trimester. MethodsThis was a retrospective cohort study based on 27 128 Chinese pregnant women who registered during their first prenatal visit from January 2015 to December 2019. Serum folic acid and fasting blood glucose concentrations were measured during the 9th to 13th gestational weeks. Binary logistic regression was applied to estimate the odds ratios of gestational diabetes mellitus by using the serum folic acid levels quartiles with adjustment for major confounders. To investigate the potential effect of modifying key risk factors for gestational diabetes mellitus, we established subgroups, in which analyses were stratified by age (<25, 25–29, 30–34, and ≥35 y), parity (nulliparous and parous), prepregnancy body mass index (< 18.5, 18.5–23.9, and ≥ 24 kg/m2), and family history of diabetes (yes and no). ResultsThe positive association between maternal folate concentrations and fasting blood glucose was observed: the risk for hyperglycemia was higher in those in the middle (Q3) and higher (Q4) quartiles compared with those in Q1 and Q2. A higher risk for gestational diabetes mellitus was found in hyperglycemia of early pregnant women with high folate concentrations (Q3: odds ratio = 5.63; 95% CI, 4.56–6.95, and Q4: odds ratio = 5.57; 95% CI, 4.68–6.64) compared with normal fasting glucose mothers with folate concentrations in Q1 and Q2 after accounting for multiple covariables. Similar patterns were observed for different subgroups. Restricted cubic spline plots had a positive correlation of serum folic acid level with fasting blood glucose concentration as well as risk of gestational diabetes mellitus in a nonlinear pattern, with 32.5 nmol/L as the cutoff point for folic acid level. ConclusionsOur findings underscore the importance of maintaining an appropriate folic acid concentration for preserving a lower risk of gestational diabetes mellitus, especially in women with relatively higher blood glucose in early pregnancy. Additionally, folic acid concentration > 32.5 nmol/L may be considered a risk factor for gestational diabetes mellitus. This research suggested that folic acid levels should be monitored during the first trimester from the first prenatal checkup to prevent adverse effects of excessive folic acid intake.