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Associations between markers of cobalamin and folate status and relative changes in MDI scores (Bayley II) in North Indian children. The vertical lines depict the 25th, 50th, and 75th percentiles of the plasma concentrations of the vitamins or metabolites. The concentration-developmental score responses were obtained from generalized additive models in R (r-project.org). In these models we adjusted for age, breastfeeding status, growth, and other predictors for developmental scores. The shaded area represents the 95% CI of the regression line/curve. The y axis is centered around the mean; thus, each plot represents how MDI scores changed relative to its mean with changes in the log-transformed concentrations of folate, cobalamin, tHcy, and MMA. MDI, mental development index; MMA, methylmalonic acid; tHcy, total homocysteine.
Source publication
Background:
Micronutrient deficiencies can affect cognitive function. Many young children in low- and middle-income countries have inadequate cobalamin (vitamin B-12) status.
Objective:
The objective was to measure the association of plasma concentrations of folate, cobalamin, total homocysteine, and methylmalonic acid with cognitive performance...
Similar publications
Background:
Vitamin B12 deficiency is diagnosed by measurements of total B12, holo-transcobalamin (holoTC), methylmalonic acid (MMA) and total homocysteine (Hcy) in blood. Results of the individual biochemical tests are often contradictory. Here the four markers are combined to achieve a more reliable indication of the B12 status. The results are...
Indian subcontinent has the highest child mortality rates along with a very high frequency of low birthweight (LBW). Folate and vitamin B12 (Vit-B12) are necessary during foetal development and their deficiency prevalence in Indians is very high. The objective of the present paper is to assess whether foetal homocysteine (Hcy)/folate metabolic path...
Pregnant women in resource-poor areas are at risk of multiple micronutrient deficiencies, and indicators of low vitamin B-12 status have been associated with adverse pregnancy outcomes, including anemia, low birth weight, and intrauterine growth retardation. To evaluate whether daily oral vitamin B-12 supplementation during pregnancy increases mate...
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Citations
... B 12 and FA deficiencies are associated with hyperhomocysteinemia, which is a CVD risk factor [10][11][12], and during pregnancy, an imbalance in FA/B 12 status has been associated with adverse birth outcomes [5] and adiposity and insulin resistance in the offspring [13]. Although a high prevalence of B 12 (27-67%) and FA (12-42%) deficiency has been reported in India [11,12,[14][15][16][17], the studies were not nationally representative. ...
... In the present study, the prevalence of B 12 deficiency in children and adolescents was lower, while the prevalence of FA deficiency was almost similar to estimates from previous Indian and other studies [14,15,[26][27][28]. However, except for the very recent study by Awasthi et al. [29], these previous studies had small sample sizes and were not nationally representative. ...
... In countries where animal foods constitute~5-10% of the energy intake, the prevalence of B 12 deficiency was high. For example, the prevalence of B 12 deficiency was >70% in school children in Kenya [33] and 27% in preschoolers in New Delhi [14]. A study in Nepal revealed 41% B 12 deficiency (serum B 12 < 150 pmol/L) plus 16% depletion (150-200 pmol/L) in 6-35-month-old children with acute diarrhea [26]. ...
Deficiencies of vitamin B12 (B12) and folate (FA) are of particular interest due to their pleiotropic role in 1-carbon metabolism. In addition to adverse birth outcomes, deficiencies of B12 and FA, or an imbalance in FA/B12 status, are linked to metabolic disorders. Indian diets that are predominantly plant food-based could be deficient in these vitamins, but there are no national estimates of the prevalence of B12 and FA deficiency in Indian children and adolescents, nor their associations with age, sex and growth indicators. The recent Comprehensive National Nutrition Survey (CNNS-2016-18) provided estimates of the prevalence of B12 and FA deficiency at the national and state levels among preschool (1–4 years: 9976 and 11,004 children, respectively), school-age children (5–9 years: 12,156 and 14,125) and adolescents (10–19 years: 11,748 and 13,621). Serum B12 and erythrocyte FA were measured by the direct chemiluminescence method and their deficiency was defined using WHO cut-offs. The prevalence of B12 and FA deficiency was high among adolescents (31.0%, CI: 28.7–33.5 and 35.6%, CI: 33.1–8.2) compared to school-age (17.3%, CI: 15.4–19.3 and 27.6%, CI: 25.5–29.9) and preschool children (13.8%, CI: 11.7–16.2 and 22.8%, CI: 20.5–25.2, respectively). The prevalence of both B12 and FA deficiency was significantly higher by 8% and 5%, respectively, in adolescent boys compared to girls. There was no association between anthropometric undernutrition and B12 and FA deficiency. There was wide regional variation in the prevalence of B12 and FA deficiency, but no rural–urban differences were observed across all age groups. The national prevalence of B12 deficiency among preschool or school-age children was <20% (the cut-off that indicates a public health problem). However, FA deficiency in these age groups and both FA and B12 deficiencies in adolescents were >20%, warranting further investigation.
... B12 and FA deficiencies are associated with hyperhomocysteinemia, which is a CVD risk factor [9][10][11] and during pregnancy, an imbalance in FA/B12 status has been associated with adverse birth outcomes [4], and adiposity and insulin resistance in the offspring [12]. Although a high of prevalence of B12 (27% -67.2%) and FA (12% -42%) deficiencies have been reported in India [10,11,[13][14][15][16], the studies were not nationally representative. ...
... In the present study, the prevalence of B12 deficiency in children and adolescents was lower, while the prevalence of FA deficiency was almost similar to estimates from previous Indian and other studies [13,14,[25][26][27]. However, excepting the very recent study by Awasthi et al [28], these previous studies had small sample sizes and were not nationally representative. ...
... In countries where animal foods constitute ∼5-10% of the energy intake, the prevalence of B12 deficiency was high. For example, the prevalence of B12 deficiency was >70% in school children in Kenya [32], and 27% in pre-schoolers of New Delhi [13]. A study in Nepal revealed 41% of B12 deficiency (serum B12 <150 pmol/L) plus 16% depletion (150-200 pmol/L) in 6-35-monthold children with acute diarrhoea [25]. ...
Deficiencies of vitamin B12 (B12) and folate (FA) are of particular interest due to their pleiotropic role in 1-carbon metabolism. In addition to adverse birth outcomes, deficiencies of B12 and FA, or an imbalance in FA/B12 status, are linked to metabolic disorders. Indian diets that are predominantly plant food-based could be deficient in these vitamins, but there are no national estimates of the prevalence of B12 and FA deficiency in Indian children and adolescents, nor of their associations with age, sex, and growth indicators. The recent Comprehensive National Nutrition Survey (CNNS-2016-18) provided estimates of the prevalence of B12 and FA deficiency at the national and state level among preschool (1-4y: 9,976 and 11,004 children respectively), school-age children (5-9y: 12,156 and 14,125) and adolescents (10-19y: 11,748 and 13,621). Serum B12 and erythrocyte FA were measured by the direct chemiluminescence method and their deficiency was defined using WHO cut-offs. The prevalence of B12 and FA deficiency was high among adolescents (31.0%, CI: 28.7-33.5 and 35.6%, CI: 33.1-8.2), compared to school-age (17.3%, CI: 15.4-19.3 and 27.6%, CI: 25.5-29.9) and preschool children (13.8%, CI: 11.7-16.2 and 22.8%, CI: 20.5-25.2, respectively). The prevalence of both B12 and FA deficiency was significantly higher by 8 and 5% points respectively, in adolescent boys compared to girls. The prevalence of B12 deficiency was higher in moderately stunted school children (by 18.9% points) than in normal children, but no such difference was observed for FA deficiency. There was wide regional variation in the prevalence of B12 and FA deficiency, but no rural-urban differences were observed across all age groups. The national prevalence of B12 deficiency among preschool or school-age children was <20% (the cut-off that indicates a public health problem). However, FA deficiency in these age groups and both FA and B12 deficiencies in adolescents were >20%, which warrants further investigation.
... When S-adenosylmethionine synthesis is blocked, DNA methylation and the generation of monoamine-based neurotransmitters, such as serotonine and catecholamines, may be reduced [59]. Deficiency in either folic acid or vitamin B 12 results in neurological or psychiatric disease [60][61][62][63]. Practically, folic acid and vitamin B 12 deficiencies are common among patients suffering from neuropsychiatric disease [64]. ...
The role of diet is gaining attention among the modifiable factors associated with depression; thus, this case–control study examined the association between nutrition and depression in young Korean adults. Dietary surveys in individuals with depression (n = 39) and age- and gender-matched controls (n = 76) were conducted using food records and food frequency questionnaires. Men with depression consumed less mushrooms and meat, while women consumed significantly less grains (p < 0.05). Overall, the depression group consumed less energy and nutrients, and the difference was more pronounced in men. The male depression group had lower nutrient adequacy ratio (NAR) for energy, protein, vitamin A, thiamine, niacin, folate, and phosphorus, whereas the female depression group had lower NARs for energy, protein, niacin, and vitamin B12. The depression group had a significantly lower mean adequacy ratio in both genders. Furthermore, the proportion of inappropriate nutrient intake was higher in both genders of the depression group, exhibiting significant differences in energy, protein, niacin, folate, and zinc in men and energy, riboflavin, folate, and vitamin C in women. Hence, both men and women in the depression group had poor nutrient intake and high rates of nutrient inadequacy and improper consumption. This suggests that the quantity and quality of meals should be improved for individuals with depressive symptoms.
... [4][5][6][7] Observational studies link vitamin B 12 status to neurodevelopment, growth and other outcomes. [8][9][10][11] Four randomised controlled trials (RCT) have investigated the effect of vitamin B 12 supplementation on neurodevelopment and growth in children. 6 7 12 13 Of these, two facility-based RCTs among Norwegian infants born with low birth weight or with developmental delay, demonstrated that a single intramuscular injection of 400 µg hydroxocobalamin substantially improved short-term motor development. ...
Introduction:
Vitamin B12 (cobalamin) is crucial for optimal child development and growth, yet deficiency is common worldwide. The aim of this study is twofold; (1) to describe vitamin B12 status and the status of other micronutrients in Norwegian infants, and (2) in a randomised controlled trial (RCT), investigate the effect of vitamin B12 supplementation on neurodevelopment in infants with subclinical vitamin B12 deficiency.
Methods and analysis:
Infant blood samples, collected at public healthcare clinics, are analysed for plasma cobalamin levels. Infants with plasma cobalamin <148 pmol/L are immediately treated with hydroxocobalamin and excluded from the RCT. Remaining infants (cobalamin ≥148 pmol/L) are randomly assigned (in a 1:1 ratio) to either a screening or a control group. In the screening group, baseline samples are immediately analysed for total homocysteine (tHcy), while in the control group, the baseline samples will be analysed after 12 months. Screening group infants with plasma tHcy >6.5 µmol/L, are given an intramuscular injection of hydroxocobalamin (400 µg). The primary outcomes are cognitive, language and motor development assessed using the Bayley Scales of Infant and Toddler Development at 12 months of age.
Ethics and dissemination:
The study has been approved by the Regional Committee for Medical and Health Research Ethics (ref: 186505). Investigators who meet the Vancouver requirements will be eligible for authorship and be responsible for dissemination of study findings. Results will extend current knowledge on consequences of subclinical vitamin B12 deficiency during infancy and may inform future infant feeding recommendations.
Trial registration number:
NCT05005897.
... 5,6 Results from several population-based studies show that even marginal vitamin B12 deficiency is associated with adverse pregnancy outcomes, 7 impaired infant growth, and poor neurodevelopment in early childhood. [8][9][10] Findings from three randomised controlled trials (RCTs) indicate positive effects of vitamin B12 supplementation starting before or during early pregnancy on child health and neurodevelopment in the first 2-3 years of life. [11][12][13][14] These findings, however, do not suffice to change the current recommendations on routine vitamin B12 supplementation in pregnant women from LMICs, which is in line with the current WHO antenatal pregnancy guidelines. ...
... The absence of an effect of vitamin B12 supplementation on our primary outcomes contrasts with previous studies that suggest that even marginal vitamin B12 status contributes to impaired growth 9,21 and neurodevelopment. 8,10 However, our findings are supported by results from a previous RCT conducted in the same area, in which 1 year of daily B12 supplementation starting from infancy had no effect on infant growth and neurodevelopment. 20 Two RCTs published between 2017 and 2021 from India, which involved vitamin B12 supplementation during pregnancy, found positive effects on specific neurodevelopmental domains. ...
Background:
Vitamin B12 is required for healthy infant growth and development, but low and marginal vitamin B12 status is endemic in low-income and middle-income countries. We aimed to measure the effect of vitamin B12 supplementation from early pregnancy until 6 months post partum on infant growth and neurodevelopment.
Methods:
In this community-based, double-blind, placebo-controlled trial, we randomly assigned (1:1) 800 pregnant women (aged 20-40 years) who were up to 15 weeks pregnant-recruited from home visits and outpatient departments at three hospitals in Nepal-to daily supplementation with 50 μg oral vitamin B12 or placebo until 6 months postpartum. Independent scientists generated the list that linked allocation to participants' study identification number. Participants were masked to group assignment and all investigators were masked until data cleaning was completed. The primary outcomes were length-for-age Z score (LAZ) at age 12 months and the cognitive composite score of the Bayley Scales of Infant and Toddler Development (3rd edition) at age 6 months and 12 months. The primary and secondary outcomes, including adverse events, were assessed in the intention-to-treat population, for all participants with available outcome data. This trial is registered with ClinicalTrials.gov, NCT03071666.
Findings:
800 eligible pregnant women were enrolled in the trial between March 28, 2017, and Oct 15, 2020, with 400 women randomly assigned to each group. Follow-up was completed on May 18, 2022. At baseline, 569 (71%) of 800 women had plasma vitamin B12 indicating low or marginal status (<221 pmol/L). We found no effect of vitamin B12 on the primary outcomes. The mean LAZ at age 12 months were -0·57 (SD 1·03) in the B12 group and -0·55 (1.03) in the placebo group (366 infants in the vitamin B12 group vs 363 infants in the placebo group) with a mean difference of -0·02 (95% CI -0·16 to 0·13). The mean cognitive composite scores were 97·7 (SD 10·5) in the B12 group and 97·1 (10·2) in the placebo group, with a mean difference of 0·5 (95% CI -0·6 to 1·7) measured in 364 and 361 infants. Stillbirths or infant deaths occurred in three (1%) of 374 women in the vitamin B12 group and nine (2%) of 379 women in the placebo group.
Interpretation:
Although vitamin B12 deficiency was prevalent in our study population and vitamin B12 supplementation from early pregnancy substantially improved vitamin B12 status, supplementation did not improve infant growth or neurodevelopment. Our findings support the current WHO recommendations of no routine vitamin B12 supplementation during pregnancy.
Funding:
Research Council of Norway.
... During the embryonic and fetal periods, the lack of folate has been linked to an increased risk of numerous negative reproductive outcomes such as neural tube defects (NTDs), small for gestational age and preterm delivery [5][6][7]. Studies have also shown that folate may promote neural development in the brain during infancy and early childhood, which are sensitive and rapid periods of brain growth [8][9][10]. ...
Folate is an essential nutrient for growth in early life. This study aimed to determine the levels and compositions of folate in Chinese breast milk samples. This study was part of the Maternal Nutrition and Infant Investigation (MUAI) study. A total of 205 healthy mothers were randomly recruited in Chengdu over 1–400 days postpartum. Five different species of folate, including tetrahydrofolate (THF), 5-methyl-THF, 5,10-methenyl-THF,5-formyl-THF and unmetabolized folic acid (UMFA), were measured for liquid chromatography–tandem mass spectrometry (LC-MS). The median levels of total folate ranged from 12.86 to 56.77 ng/mL in the breast milk of mothers at 1–400 days postpartum, gradually increasing throughout the lactating periods. The median levels of 5-methyl-THF, minor reduced folate (the sum of THF, 5,10-methenyl-THF and 5-formyl-THF) and UMFA were in the ranges of 8.52–40.65 ng/mL, 3.48–16.15 ng/mL and 0.00–1.24 ng/mL during 1–400 days postpartum, respectively. 5-Methyl-THF accounted for more than 65% of the total folate in all breast milk samples. The levels of UMFA in mature breast milk samples were higher in supplement users than nonusers, but not for colostrum and transitional milk samples (p < 0.05). In conclusion, the level of total folate in the breast milk changed along with the prolonged lactating periods, but 5-methyl-THF remains the dominant species of folate in the breast milk of Chinese populations across all entire lactating periods.
... These are essential throughout the life but the period of childhood and adolescence is more important, as it is marked by rapid growth and development. Review of literature suggests that deficiency of minerals (calcium, iron, selenium and zinc) and Vitamins (Vitamin A, 25 Hydroxy Vitamin D, Vitamin B12 and Folate) during childhood and adolescence have negative impact on general health, growth, neuropsychological behavior, cognitive and motor development, intelligence quotient, attention, learning, memory, language ability and educational achievement [1][2][3][4][5][6][7][8][9]. Iron, folate or vitamin B12 deficiency results in anaemia which has a negative impact on work capacity, intellectual performance, and child cognitive development [1]. ...
Introduction
Childhood and adolescence require adequate amount of micronutrients for normal growth and development. The primary objective of study was to assess the prevalence of deficiencies of Vitamins (Vitamin A, 25 Hydroxy Vitamin D, Vitamin B12 and Folate) and minerals (Calcium, Zinc, Selenium and Iron), among urban school going children aged 6–11 and 12–16 years in ten cities of India. Secondary objective was to find the association between micronutrient deficiencies with sociodemographic and anthropometric indicators.
Methods
A multi-center cross-sectional study was conducted across India. Participants in the age groups of 6 to 11 years (group 1) and 12 to 16 years (group 2) were selected from randomly chosen schools from each center. Data on socio economic status, anthropometric measures was collected. Blood samples were collected for biochemical analysis of micronutrients. Point estimates and 95% confidence intervals was used to assess the prevalence of deficiencies. Associations were observed using chi square, student t test and ANOVA test.
Results
From April 2019 to February 2020, 2428 participants (1235 in group 1 and 1193 group 2) were recruited from 60 schools across ten cites. The prevalence of calcium and iron deficiency was 59.9% and 49.4% respectively. 25 Hydroxy Vitamin D deficiency was seen in 39.7% and vitamin B12 in 33.4% of subjects. Folate, Selenium and Zinc were deficient in 22.2%, 10.4% and 6.8% of subjects respectively. Vitamin A deficiency least (1.6%). Anemia was prevalent in 17.6% subjects and was more common among females.
Conclusion
One or more micronutrient deficiencies are found in almost one half of school going children in urban area. Hence efforts must be made to combat these on priority.
Trial registration number
CTRI/2019/02/017783 .
... Studies conducted among children in age group other than 6-59 months of age in Northern India have reported the prevalence of cobalamin deficiency ranging range between 17% and 97.5%. [1,11,13,[17][18][19][20][21][22][23][24] Studies done in other parts of India have reported a lower prevalence in the range of 2.3% to 14%. [10,12,25] Probable reasons for such a wide range of prevalence could be the use of different laboratory methods, different cut-off values, different geographic locations, and different age groups for estimating cobalamin levels. ...
... [16] The prevalence of folate deficiency has been reported in the range of 1% to 63% across various regions of India. [10][11][12][13][18][19][20][21][22]25] We did not find any other study on serum folate level in children aged 6-59 months from India. However, a community-based cross-sectional study by Gupta et al. [2] reported folate deficiency among 1.5% adolescents. ...
Context:
Cobalamin and folate are essential for the synthesis of nucleic acids and in the maintenance of myelin. They are required during the period of the rapid growth of infancy and childhood. Their deficiency may result in nutritional anemia and neurological manifestations. There is paucity of literature regarding the prevalence of cobalamin and folate deficiency among North Indian children aged 6-59 months.
Aim:
The aim of this study was to estimate the prevalence of serum cobalamin and folate deficiency among children aged 6-59 months, attending a secondary care hospital.
Settings and design:
Children were recruited from pediatrics OPD of the sub-district hospital (SDH), Ballabgarh, Haryana, through systematic random sampling. Hemoglobin was measured by an automated analyzer. Serum cobalamin and serum folate were estimated using enhanced chemiluminescence based immunoassay.
Results:
A total of 420 children were recruited, of which 392 provided a blood specimen. Prevalence of cobalamin, folate deficiency, and anemia were 22.3% (95% CI: 18.3-26.7), 10.9% (95% CI: 8.2-14.6), and 81.9% (95% CI 77.7-85.4), respectively. The proportion of children with cobalamin deficiency who had anemia was 97.7% compared to 95.7% among those with no cobalamin deficiency (P = 0.396). Similarly, the proportion of children with folate deficiency who had anemia was 95.2% compared to 96.2% among those with no folate deficiency (P = 0.765).
Conclusion:
We found that almost one in five children aged 6-59 were deficient in cobalamin, and one in ten were deficient in folate.
... Vitamin B 12 is required for cell division and differentiation, energy production and the generation of methionine, which is needed to produce neurotransmitters and myelin in the brain (7,8) . Subclinical vitamin B 12 deficiency is associated with poor cognitive performance in both the elderly and children (1,9,10) . Results from an Indian cohort study suggested that children with inadequate vitamin B 12 status had lower scores on the Bayley Scales of Infant and Toddler Development 2nd edition (Bayley-II) than replete children (9) . ...
... Subclinical vitamin B 12 deficiency is associated with poor cognitive performance in both the elderly and children (1,9,10) . Results from an Indian cohort study suggested that children with inadequate vitamin B 12 status had lower scores on the Bayley Scales of Infant and Toddler Development 2nd edition (Bayley-II) than replete children (9) . Moreover, in a cohort of Nepalese children, we found that vitamin B 12 status in infancy was positively associated with cognitive function when the children were 5 years old (11) . ...
The most critical period for brain development is before a child’s 2 nd birthday. Standardized tests measuring neurodevelopment are more reliable when administered after this period. Severe vitamin B12 deficiency affects brain development and function. In a randomized, double-blind, placebo-controlled trial in 600 Nepalese infants (6-11 months at enrolment), we found no effect of 2 µg vitamin B12 daily or a placebo for a year on neurodevelopment. The primary objective of the current study was to measure the effect the intervention on the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-IV) full scale intelligence quotient (FSIQ) two years after end of supplementation. We also measured the effect on the Bayley Scales of Infant and Toddler Development 3 rd edition (at age 30-35 months, n=555). At the final visit (age 42-47 months, n=533), we used the WPPSI-IV and subtests from the NEPSY-II. We used the FSIQ to estimate subgroup specific effects. The mean (SD) WPPSI-IV FSIQ in the vitamin B12 group was 84.4 (8.4) and 85.0 (8.6) in the placebo group (mean difference −0.5 (95% CI-1.97, 0.94), p =0.48). There were no effect of the vitamin B12 on any of the other neurodevelopmental outcomes, and no beneficial effect in any of the subgroups. In conclusion, providing 2 µg of vitamin B12 for a year in infants at risk of vitamin B12 deficiency does not improve preschool cognitive function.
... Independent of cobalamin status, folate levels in plasma were positively associated with mental development index scores. [32] Evidence from clinical studies supports the relevance of certain vital nutrients in supporting executive functions and higher-order cognitive functions among infants and children ( Table 2). [25][26][27][28][29][30][31][32][33][34][35][36][37][38][39] ...
... [32] Evidence from clinical studies supports the relevance of certain vital nutrients in supporting executive functions and higher-order cognitive functions among infants and children ( Table 2). [25][26][27][28][29][30][31][32][33][34][35][36][37][38][39] ...
... Role of critical nutrients in executive functions of the brain[26][27][28][29][30][31][32]. ...
