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Folinic acid alleviates side effects of methotrexate in arthritis patients with side effects despite folic acid supplementation: an observational cohort study.
Fischer, EA, Hetland, ML, Krabbe, S
Rheumatology (Oxford, England). 2020;(11):3566-3568
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Effects of periconceptional folate on cognition in children of women with epilepsy: NEAD study.
Meador, KJ, Pennell, PB, May, RC, Brown, CA, Baker, G, Bromley, R, Loring, DW, Cohen, MJ, ,
Neurology. 2020;(7):e729-e740
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Abstract
OBJECTIVE Emerging evidence suggests potential positive neuropsychological effects of periconceptional folate in both healthy children and children exposed in utero to antiseizure medications (ASMs). In this report, we test the hypothesis that periconceptional folate improves neurodevelopment in children of women with epilepsy by re-examining data from the Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) study. METHODS The NEAD study was an NIH-funded, prospective, observational, multicenter investigation of pregnancy outcomes in 311 children of 305 women with epilepsy treated with ASM monotherapy. Missing data points were imputed with Markov chain Monte Carlo methods. Multivariate analyses adjusted for multiple factors (e.g., maternal IQ, ASM type, standardized ASM dose, and gestational birth age) were performed to assess the effects of periconceptional folate on cognitive outcomes (i.e., Full Scale Intelligence Quotient [FSIQ], Verbal and Nonverbal indexes, and Expressive and Receptive Language indexes at 3 and 6 years of age, and executive function and memory function at 6 years of age). RESULTS Periconceptional folate was associated with higher FSIQ at both 3 and 6 years of age. Significant effects for other measures included Nonverbal Index, Expressive Language Index, and Developmental Neuropsychological Assessment Executive Function at 6 years of age, and Verbal Index and Receptive Language Index at 3 years of age. Nonsignificant effects included Verbal Index, Receptive Index, Behavior Rating Inventory of Executive Function-Parent Questionnaire Executive Function, and General Memory Index at 6 years of age, and Nonverbal Index and Expressive Index at 3 years of age. CONCLUSIONS Use of periconceptional folate in pregnant women with epilepsy taking ASMs is associated with better cognitive development. CLINICALTRIALSGOV IDENTIFIER NCT00021866.
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Association Between Cognitive Impairment and Vitamin B12, Folate, and Homocysteine Status in Elderly Adults: A Retrospective Study.
Baroni, L, Bonetto, C, Rizzo, G, Bertola, C, Caberlotto, L, Bazzerla, G
Journal of Alzheimer's disease : JAD. 2019;(2):443-453
Abstract
BACKGROUND Cognitive disorders in old age have a serious impact on the health and social aspects of patients and their families. OBJECTIVE The scope of this paper is to explore the role of cobalamin and folate that has been linked to cognitive decline, not only as a deficiency state depending on malnutrition, but also a determinant in cognitive impairment. METHODS A 6-year observational, retrospective study was conducted by collecting the routine blood analyses and cognitive screening scores of patients aged 60 years or older, followed at our Centre for the Diagnosis and Treatment of Cognitive Disorders. RESULTS In a linear regression with a multi-vitamin model, higher folate concentrations were correlated with better cognitive performances through MMSE score, even after correction for sex, age, and years of education (beta = 0.144, p = 0.001). Estimated MMSE marginal means for folate versus homocysteine showed that folate deficiency was associated with worse cognitive performances, with a more severe cognitive impairment when hyperhomocysteinemia was present. CONCLUSION The assessment of B-vitamin status among elderly adults can contribute to an economic and practical approach to the prevention and management of cognitive decline. Future studies focused to define optimal vitamin status are warranted.
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Higher maternal plasma folate, vitamin B12 and homocysteine levels in women with preeclampsia.
Pisal, H, Dangat, K, Randhir, K, Khaire, A, Mehendale, S, Joshi, S
Journal of human hypertension. 2019;(5):393-399
Abstract
Micronutrients like vitamin B12 and folate play an important role in nucleic acid metabolism, cell growth, and are important determinants of fetal growth. The present study examined the levels of maternal and cord plasma folate, vitamin B12, homocysteine, and their association with birth outcome in women with preeclampsia (PE). This study includes 450 normotensive control (NC) and 350 women with PE. PE women were further classified into women delivering at term (n = 224) and preterm (n = 126). Maternal and cord blood was collected at delivery. The levels of maternal vitamin B12 (p < 0.05), folate (p < 0.01), and homocysteine (p < 0.01) were higher in the PE group as compared to the NC group. Maternal folate levels were higher in both term and preterm groups, while vitamin B12 levels were higher only in the preterm group as compared to NC group. In contrast, homocysteine was higher only in the term PE group. Similar changes were also observed in the cord plasma. There was a positive association of maternal plasma homocysteine with systolic (r = 0.151, p = 0.000, n = 578) and diastolic blood pressure (r = 0.213, p = 0.000, n = 578) in the whole cohort. A negative association of maternal folate with systolic blood pressure (r = -0.105, p = 0.048, n = 352) while a positive association with baby weight in the NC group (r = 0.116, p = 0.029, n = 352). The present study suggests that maternal and cord micronutrient levels are altered in women with PE.
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Folate pathway genetic polymorphisms modulate methotrexate-induced toxicity in childhood acute lymphoblastic leukemia.
Yousef, AM, Farhad, R, Alshamaseen, D, Alsheikh, A, Zawiah, M, Kadi, T
Cancer chemotherapy and pharmacology. 2019;(4):755-762
Abstract
BACKGROUND Acute lymphoblastic leukemia (ALL) is one of the major malignancies affecting children in Jordan. Methotrexate (MTX) is the cornerstone of chemotherapy for ALL, and works by targeting enzymes involved in the folate pathway. We hypothesize that genetic polymorphisms of the folate pathway are associated with MTX toxicity in children with ALL. METHODS A total of 64 children with ALL were included in this study; 31 (48.4%) boys and 33 (51.6%) girls aged 2-16 years. The folate pathway genes were genotyped using polymerase chain reaction followed by sequencing and studying the association between genetic polymorphisms and MTX toxicity. RESULTS The immunophenotype was B-lineage in 55 patients (85.9%) and T-lineage in nine patients (14.1%). All genetic polymorphisms, except for dihydropyrimidine dehydrogenase polymorphisms, were associated with hematological toxicities and did not appear to precipitate any non-hematological adverse events. Patients with ALL carrying dominant alleles of methylene tetrahydrofolate (MTHFR) C677T and dihydrofolate reductase 19 bp deletion were at a higher risk of developing severe leucopenia [OR (95% CI) = 4.5 (1.2-17), p = 0.03; 5.4 (1.6-17.8); p = 0.006] while minor allele carriers of MTHFR A1298C were more likely to develop neutropenia [OR (95% CI) = 6.1 (1.3-29.5); 0.04]. Furthermore, dominant allele carriers of thymidylate synthase 1494 del6 were at a higher risk of developing neutropenia [OR (95% CI) = 6 (1.2-31.1); p = 0.04]. CONCLUSION Genetic polymorphisms of the folate pathway may modulate MTX-induced toxicity in childhood ALL.
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Early pregnancy folate-cobalamin interactions and their effects on cobalamin status and hematologic variables throughout pregnancy.
Solé-Navais, P, Salat-Batlle, J, Cavallé-Busquets, P, Fernandez-Ballart, J, Ueland, PM, Ballesteros, M, Ornosa-Martín, G, Inglès-Puig, M, Colomina, JM, Murphy, MM
The American journal of clinical nutrition. 2018;(2):173-182
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Abstract
BACKGROUND Periconception folic acid supplementation is widespread, but how it interacts with cobalamin status is rarely considered. OBJECTIVE The aim of this study was to investigate whether first-trimester folate-cobalamin interactions affect pregnancy cobalamin status, hematologic variables, and pregnancy outcomes. DESIGN In the longitudinal Reus-Tarragona Birth Cohort study from <12 gestational weeks throughout pregnancy, fasting plasma and red blood cell (RBC) folate, plasma cobalamin, holotranscobalamin (holoTC), methylmalonic acid (MMA), total homocysteine (tHcy), hemoglobin, mean cell volume (MCV), postglucose-load serum glucose, gestational hypertension, gestational age at birth, and birth weight were recorded in 563 participants. RESULTS The highest plasma folate concentrations occurred in the first trimester when folic acid supplement use was extensive. Supplementation beyond the first trimester interacted with time of pregnancy on plasma folate, RBC folate, and tHcy throughout pregnancy (P-interaction <0.001). Plasma folate and RBC folate were higher and tHcy was lower in continued supplement users than in nonusers. Elevated plasma folate (≥30 nmol/L) occurred in 78.9% of women who exceeded the recommended 400 µg folic acid/d. First-trimester folate-cobalamin status interactions were associated with MMA (P-interaction <0.001) throughout pregnancy. When plasma cobalamin was suboptimal (≤221 pmol/L; n = 36), participants with elevated plasma folate (n = 11) had higher MMA concentrations than did those with nonelevated plasma folate (n = 23). First-trimester folate-MMA status interactions were associated with MCV throughout pregnancy (P-interaction <0.01) and with cord plasma holoTC (P-interaction <0.05). The mean difference (95% CI) in MCV (fL) between women with elevated and nonelevated plasma folate status was -2.12 (-3.71, -0.52) for top-quartile plasma MMA (≥0.139 µmol/L) and 0.60 (-0.39, 1.60) for plasma MMA <0.139 µmol/L. Cord plasma holoTC was higher in women with elevated compared with nonelevated plasma folate status only for MMA <0.139 µmol/L. Folate-cobalamin interactions were not associated with the other investigated outcomes. CONCLUSION First-trimester folate-cobalamin status interactions were associated with plasma MMA and MCV throughout pregnancy. This trial was registered at www.clinicaltrials.gov as NCT01778205.
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Prospective investigation of folic acid supplements before and during early pregnancy and paediatric and adult cancers in the Chinese children and families cohort: a pilot study in a sample of rural and urban families.
Linet, MS, Wang, L, Wang, N, Berry, RJ, Chao, A, Hao, L, Li, Z, Fang, L, Yin, P, Potischman, N, et al
BMJ open. 2018;(7):e022394
Abstract
OBJECTIVE To determine the feasibility of long-term prospective follow-up and ascertainment of cancer in offspring and mothers from the 1993-1995 Chinese Community Intervention Program that provided folic acid supplements before and during early pregnancy to reduce neural tube defects. DESIGN Feasibility pilot study for a prospective cohort study. SETTING Families residing during 2012-2013 in one rural and one urban county from 21 counties in 3 provinces in China included in the Community Intervention Program campaign. PARTICIPANTS The feasibility study targeted 560 families, including 280 from the rural and 280 from the urban county included in the large original study; about half of mothers in each group had taken and half had not taken folic acid supplements. INTERVENTION The planned new study is observational. PRIMARY AND SECONDARY OUTCOME MEASURES Primary: incidence of paediatric cancers in offspring; secondary: other chronic diseases in offspring and chronic diseases in mothers RESULTS Only 3.4% of pilot study families could not be found, 3.9% had moved out of the study area and 8.8% refused to participate. Interviews were completed by 82% of mothers, 79% of fathers and 83% of offspring in the 560 families. Almost all mothers and offspring who were interviewed also participated in anthropometric measurements. We found notable urban-rural differences in sociodemographic and lifestyle characteristics of the parents, but fewer differences among the offspring. In eight catchment area hospitals, we identified a broad range of paediatric cancers diagnosed during 1994-2013, although paediatric brain tumours, lymphomas and rarer cancers were likely under-represented. CONCLUSIONS Overall, 20 years after the original Community Intervention Program, the pilot study achieved high levels of follow-up and family member interview participation, and identified substantial numbers of paediatric malignancies during 1994-2013 in catchment area hospitals. Next steps and strategies for overcoming limitations are described.
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Association of Prenatal Exposure to Population-Wide Folic Acid Fortification With Altered Cerebral Cortex Maturation in Youths.
Eryilmaz, H, Dowling, KF, Huntington, FC, Rodriguez-Thompson, A, Soare, TW, Beard, LM, Lee, H, Blossom, JC, Gollub, RL, Susser, E, et al
JAMA psychiatry. 2018;(9):918-928
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Abstract
IMPORTANCE Presently, 81 countries mandate the fortification of grain products with folic acid to lessen the risk of neural tube defects in the developing fetus. Epidemiologic data on severe mental illness suggest potentially broader effects of prenatal folate exposure on postnatal brain development, but this link remains unsubstantiated by biological evidence. OBJECTIVE To evaluate associations among fetal folic acid exposure, cortical maturation, and psychiatric risk in youths. DESIGN, SETTING, AND PARTICIPANTS A retrospective, observational clinical cohort study was conducted at Massachusetts General Hospital (MGH) among 292 youths 8 to 18 years of age born between January 1993 and December 2001 (inclusive of folic acid fortification rollout ±3.5 years) with normative results of clinical magnetic resonance imaging, divided into 3 age-matched groups based on birthdate and related level of prenatal folic acid fortification exposure (none, partial, or full). Magnetic resonance imaging was performed between January 2005 and March 2015. Two independent, observational, community-based cohorts (Philadelphia Neurodevelopmental Cohort [PNC] and National Institutes of Health Magnetic Resonance Imaging Study of Normal Brain Development [NIH]) comprising 1078 youths 8 to 18 years of age born throughout (PNC, 1992-2003) or before (NIH, 1983-1995) the rollout of folic acid fortification were studied for replication, clinical extension, and specificity. Statistical analysis was conducted from 2015 to 2018. EXPOSURES United States-mandated grain product fortification with folic acid, introduced in late 1996 and fully in effect by mid-1997. MAIN OUTCOMES AND MEASURES Differences in cortical thickness among nonexposed, partially exposed, and fully exposed youths (MGH) and underlying associations between age and cortical thickness (all cohorts). Analysis of the PNC cohort also examined the association of age-cortical thickness slopes with the odds of psychotic symptoms. RESULTS The MGH cohort (139 girls and 153 boys; mean [SD] age, 13.3 [2.3] years) demonstrated exposure-associated cortical thickness increases in bilateral frontal and temporal regions (9.9% to 11.6%; corrected P < .001 to P = .03) and emergence of quadratic (delayed) age-associated thinning in temporal and parietal regions (β = -11.1 to -13.9; corrected P = .002). The contemporaneous PNC cohort (417 girls and 444 boys; mean [SD] age, 13.5 [2.7] years) also exhibited exposure-associated delays of cortical thinning (β = -1.59 to -1.73; corrected P < .001 to P = .02), located in similar regions and with similar durations of delay as in the MGH cohort. Flatter thinning profiles in frontal, temporal, and parietal regions were associated with lower odds of psychosis spectrum symptoms in the PNC cohort (odds ratio, 0.37-0.59; corrected P < .05). All identified regions displayed earlier thinning in the nonexposed NIH cohort (118 girls and 99 boys; mean [SD] age, 13.3 [2.6] years). CONCLUSIONS AND RELEVANCE The results of this study suggest an association between gestational exposure to fortification of grain products with folic acid and altered cortical development and, in turn, with reduction in the risk of psychosis in youths.
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Nutritional factors and metabolic variables in relation to the risk of coronary heart disease: A case control study in Armenian adults.
Fazeli Moghadam, E, Tadevosyan, A, Fallahi, E, Goodarzi, R
Diabetes & metabolic syndrome. 2017;(1):7-11
Abstract
INTRODUCTION Dietary factors can affect the coronary heart disease (CHD). Results of previous studies on the association between the diet and CHD are not consistent in different countries. There were no data on this association in Armenia. OBJECTIVE Aims of this case-control study were to evaluate the association between nutritional factors and CHD among Armenians in Yerevan. METHODS During 2010 and 2011, we randomly selected 320 CHD patients with a diagnosis of CHD less than 6 months and 320 subjects without CHD (≥30years old) from the hospitals and polyclinics in Yerevan. Dietary intakes with 135 food items over the previous 12 months were evaluated using a semi-quantitative food frequency questionnaire. RESULTS After adjusting for some CHD risk factors higher intakes of polyunsaturated fatty acids (PUFA) and monounsaturated fatty acids (MUFA) were associated with a reduced risk of CHD, while this association was not witnessed for saturated fatty acids (SFA). In addition, findings indicated an inverse relation between vitamins (E, B6 and B12, folic acid) and fiber with CHD. In this population, smoking, hypertension, and metabolic syndrome (MetS) were significantly more common among patients with CHD. CONCLUSION The intake of vitamins E, B6 and B12, folic acid, PUFA, MUFA and fiber appeared to be predictors of CHD, independently of other risk factors.
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Antenatal nutritional supplementation and autism spectrum disorders in the Stockholm youth cohort: population based cohort study.
DeVilbiss, EA, Magnusson, C, Gardner, RM, Rai, D, Newschaffer, CJ, Lyall, K, Dalman, C, Lee, BK
BMJ (Clinical research ed.). 2017;:j4273
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Objective To determine whether nutritional supplementation during pregnancy is associated with a reduced risk of autism spectrum disorder (ASD) with and without intellectual disability in offspring.Design Observational prospective cohort study using multivariable logistic regression, sibling controls, and propensity score matching.Setting Stockholm County, Sweden.Participants 273 107 mother-child pairs identified through population registers. The study sample was restricted to children who were aged 4 to 15 years by the end of follow-up on 31 December 2011 and were born between 1996 and 2007.Exposures Multivitamin, iron, and folic acid supplement use was reported at the first antenatal visit.Main outcome measure Diagnosis of ASD with and without intellectual disability in children determined from register data up to 31 December 2011.Results Prevalence of ASD with intellectual disability was 0.26% (158 cases in 61 934) in the maternal multivitamin use group and 0.48% (430 cases in 90 480) in the no nutritional supplementation use group. Maternal multivitamin use with or without additional iron or folic acid, or both was associated with lower odds of ASD with intellectual disability in the child compared with mothers who did not use multivitamins, iron, and folic acid (odds ratio 0.69, 95% confidence interval 0.57 to 0.84). Similar estimates were found in propensity score matched (0.68, 0.54 to 0.86) and sibling control (0.77, 0.52 to 1.15) matched analyses, though the confidence interval for the latter association included 1.0 and was therefore not statistically significant. There was no consistent evidence that either iron or folic acid use were inversely associated with ASD prevalence.Conclusions Maternal multivitamin supplementation during pregnancy may be inversely associated with ASD with intellectual disability in offspring. Further scrutiny of maternal nutrition and its role in the cause of autism is recommended.