Effect of Maternal Vitamin B12 Supplementation on Cognitive Outcomes in South Indian Children: A Randomized Controlled Clinical Trial

Thomas, Simmy; Thomas, Tinku; Bosch, Ronald J.; Ramthal, Asha; Bellinger, David C.; Kurpad, Anura V; Duggan, Christopher; Srinivasan, Krishnamachari

doi:10.1007/s10995-018-2605-z

Cited by 35 publications

(46 citation statements)

References 24 publications

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“…None of the pooled estimates were significant. Among follow-up studies of nutritional supplementation, the pooled effect sizes were 0·03 (95% CI -0·05 to 0·11; 6 studies) for LAZ or HAZ score, -0·08 (-0·19 to 0·02; 6 studies) for 58 Nahar et al 48 Nahar et al 48 Jeon et al 41 Rosado et al 15 Phuka et al 21 Marchal et al 84 Adu-Afarwuah et al 18 Hess et al 16 Hess et al 16 Hess et al 16 Luby et al 23 Vazir et al 72 Phuka et al 21 Schmidt et al 53 Nahar et al 48 Nahar et al 48 Black et al 45 Lind et al 32 Hallammaa et al 82 Stewart et al 22 Thomas et al 60 Luby et al 23 Adu-Afarwuah et al 18 Schmidt et al 53 Shafique et al 24 Faber et al 14 Hallammaa et al 82 Maleta et al 17 Black et al 12 Black et al 12 Colombo et al 43 Husaini et al 50 Nguyen et al 34 Vazir et al 72 Black et al 63 Aboud et al 26 Gladstone et al 61 Yousafzai et al 42 Hamadani et al 74 Stewart et al 22 Dewey et al 20 Nguyen et al 34 Dewey et al 20 Lees cognitive score, and -0·03 (-0·18 to 0·12; 6 studies) for motor score. Among follow-up studies of interventions promoting nurturing care and learning opportunities, the pooled effect sizes were 0·06 (95% CI -0·12 to 0·25; 5 studies) for LAZ or HAZ score and 0·15 (-0·07 to 0·36; 5 studies) for cognitive or mental scores.…”

Section: Resultsmentioning

confidence: 99%

“…We calculated pooled effect sizes if at least five studies reported an intervention versus control group comparison in any category of intervention (eg, nutritional supplementation and promotion of responsive care and learning opportunities). We applied the same criterion to stratified 29 Ong et al 37 Jeon et al 41 Lind et al 31 Rosado et al 15 Oelofse et al 52 Nahar et al 48 Smuts et al 62 Husaini et al 50 Phuka et al 21 Maleta et al 17 Krebs et al 54 Bauserman et al 55 Faber et al 14 Hess et al 16 Dewey et al 20 77 Luby et al 23 Stewart et al 22 Gladstone et al 61 Lees et al 80 Hallamaa et al 82 Tomlinson et al 78 Tumwine et al 79 Dewey et al 20 Adu-Afarwuah et al 18 Ashorn et al 19 Zhang et al 59 Thomas et al 60 Gowachirapant et al 51 Hamadani et al 35 Jacobson et al 58 Schmidt et al 53 Hanieh 36 Zhu et al 56 Nguyen et al 34 Christian et al 40 Gonzalez-Casano 87 Tofail et al 49 In utero 3 6 9 12 15 18 Months Years 64 Nahar et al 48 Hamadani et al 70 Tofail et al…”

Section: Data Collection and Analysismentioning

confidence: 99%

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Do effects of early life interventions on linear growth correspond to effects on neurobehavioural development? A systematic review and meta-analysis

Prado

Larson

Cox

et al. 2019

The Lancet Global Health

138

146

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Background Faltering in linear growth and neurobehavioural development during early childhood are often assumed to have common causes because of their consistent association. This notion has contributed to a global focus on the promotion of nutrition during pregnancy and childhood to improve both conditions. Our aim was to assess whether effects of interventions on linear growth are associated with effects on developmental scores and to quantify these associations.Methods In this systematic review and meta-analysis, we included randomised trials done during pregnancy and in children aged 0-5 years that reported effects of any intervention on length-for-age or height-for-age Z scores (LAZ or HAZ) and on any of the following outcomes: motor, cognitive or mental, language, and social-emotional or behavioural development. We searched MEDLINE (Ovid), CINAHL (EBSCO), and PsycINFO (EBSCO) from database inception to June 25, 2019. Study-level data were extracted and, when required, authors were contacted for missing information. We calculated weighted meta-regression coefficients of the association between standardised effect sizes of interventions on LAZ or HAZ and developmental outcome scores and calculated pooled effect sizes for different types of intervention.Findings Of the 7207 studies identified, we included 75 studies with 122 comparisons between intervention and control groups and outcomes reported for 72 275 children. Across all interventions, effect sizes on LAZ or HAZ were significantly associated with effect sizes on social-emotional scores (β 0·23, 95% CI 0·05 to 0·41; p=0·02), but not on cognitive (0·18, -0·36 to 0·72; p=0·51), language (0·12, -0·07 to 0·31; p=0·21), or motor development scores (0·23, -0·05 to 0·50; p=0·11). In studies that provided nutritional supplements, we observed positive significant pooled effect sizes on all five outcomes of LAZ or HAZ (effect size 0·05, 95% CI 0·01-0·09; p=0·01; n=50), cognitive or mental (0·06, 0·03-0·10; p<0·01; n=38), language (0·08, 0·03-0·13; p=0·01; n=21), motor (0·08, 0·04-0·12; p<0·01; n=41), and social-emotional (0·07, 0·02-0·12; p=0·01; n=20) scores. The effect sizes of nutritional supplementation on LAZ or HAZ scores were significantly associated with effect sizes on cognitive (β 0·40, 95% CI 0·04-0·77; p=0·049) and motor (0·43, 0·11-0·75; p=0·01) scores. In the 14 interventions promoting responsive care and learning opportunities, the pooled effect size on LAZ or HAZ score was not significant (-0·01, 95% CI -0·07 to 0·05; p=0·74), but pooled effect sizes on cognitive, language, and motor scores were 4 to 5 times larger (range 0·38-0·48) than the pooled effect sizes of nutritional supplementation (0·05-0·08). Interpretation In nutritional supplementation interventions, improvements in linear growth were associated with small improvements in child development, whereas nurturing and stimulation interventions had significant effects on child development but no effectson linear growth. The determinants of linear growth and neurodevelopment are only partly ...

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Section: Resultsmentioning

confidence: 99%

Section: Data Collection and Analysismentioning

confidence: 99%

Do effects of early life interventions on linear growth correspond to effects on neurobehavioural development? A systematic review and meta-analysis

Prado

Larson

Cox

et al. 2019

The Lancet Global Health

138

146

View full text Add to dashboard Cite

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“…Two intervention studies (60,61) reported an effect of B12 supplementation on offspring cognitive status at 9 months and 30 months of age in the context of a randomized controlled trial (Supplementary Table 8). In this trial, mothers were randomized to receive either 50mcg oral vitamin B12 supplementation or placebo from the 1 st trimester of pregnancy till 6 weeks postpartum.…”

Section: Intervention Studiesmentioning

confidence: 99%

Maternal Vitamin B12 Status During Pregnancy and Its Association With Outcomes of Pregnancy and Health of the Offspring: A Systematic Review and Implications for Policy in India

et al. 2021

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BackgroundVitamins B12 and folate participate in the one-carbon metabolism cycle and hence regulate fetal growth. Though vitamin B12 deficiency is widely prevalent, the current public health policy in India is to supplement only iron and folic acid for the prevention of anaemia. Prompted by our research findings of the importance of maternal vitamin B12 status for a healthy pregnancy, birth and offspring health outcomes, we evaluated available literature evidence using a systematic review approach, to inform policy.MethodsA systematic search was performed for relevant Indian studies in the MEDLINE/PubMed and IndMed databases. We selected studies reporting maternal vitamin B12 status (dietary intake or blood concentrations), and/or metabolic markers of vitamin B12 deficiency (homocysteine, methylmalonic acid) or haematological indices during pregnancy and their associations with outcomes of pregnancy, infancy or in later life. Intervention trials of vitamin B12 during pregnancy were also included. Quality of evidence was assessed on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.ResultsOf the 635 articles identified, 46 studies met the inclusion criteria (cohort studies-26, case-control studies-13, RCT’s -7). There is a high prevalence of vitamin B12 deficiency in Indian women during pregnancy (40-70%) (3 studies). Observational studies support associations (adjusted for potential sociodemographic confounders, maternal body size, postnatal factors) of lower maternal B12, higher homocysteine or an imbalance between vitamin B12-folate status with a higher risk of NTDs (6 studies), pregnancy complications (recurrent pregnancy losses, gestational diabetes, pre-eclampsia) (9 studies), lower birth weight (10 studies) and adverse longer-term health outcomes in the offspring (cognitive functions, adiposity, insulin resistance) (11 studies). Vitamin B12 supplementation (7 RCT’s) in pregnancy showed a beneficial effect on offspring neurocognitive development and an effect on birth weight was inconclusive. There is a high quality evidence to support the role of low maternal vitamin B12 in higher risk for NTD and low birth weight and moderate-quality evidence for higher risk of gestational diabetes and later life adverse health outcomes (cognitive functions, risk for diabetes) in offspring.ConclusionIn the Indian population low maternal vitaminB12 status, is associated with adverse maternal and child health outcomes. The level of evidence supports adding vitamin B12 to existing nutritional programs in India for extended benefits on outcomes in pregnancy and offspring health besides control of anaemia.Systematic Review Registration[website], identifier [registration number]

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“…There is evidence that some vitamins and minerals, like vitamin B12, have a direct effect on brain development and function (19). A recent trial in India determined that children of mothers who received vitamin B12 supplementation in pregnancy had significantly higher scores on expressive language scores as compared to children of mothers who received placebo (20). There are also many indirect pathways through which micronutrients may potentially provide benefit, including increases in birthweight, reduction in risk of prematurity, and reductions in maternal and fetal inflammation that may subsequently influence child development (18, 21).…”

Section: Discussionmentioning

confidence: 99%

Effect of antenatal and infant micronutrient supplementation on middle childhood and early adolescent development outcomes in Tanzania

et al. 2019

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Background: There is growing evidence that nutritional interventions in the first 1,000 days of life may influence long-term health and development outcomes. Few studies have examined the effect of maternal and infant micronutrient supplementation on development outcomes in sub-Saharan Africa. Methods: We conducted a follow-up study of two randomized trials of antenatal and infant micronutrient supplementation conducted in Dar es Salaam, Tanzania. We assessed the effect of maternal multiple micronutrient (MMN) supplementation in pregnancy on development of children at 11–14 years of age. We also examined the effect of infant zinc and MMN supplementation on development at 6–8 years of age. We use generalized linear models to assess standardized mean differences (SMDs) in general intelligence, executive function and mental health scores. Results: We followed-up 446 children whose mothers were enrolled in the maternal MMN supplementation trial and 365 children who were enrolled in the infant zinc and MMN supplementation trial. We found no effect of maternal MMN supplementation on general intelligence (SMD: −0.03; 95% CI: −0.15, 0.09), executive function (SMD: 0.00; 95% CI: −0.11, 0.11) and mental health scores (SMD: 0.06; 95% CI: −0.10, 0.22). We also found no effect of either infant zinc or MMN supplementation on any of the three development domains (p-values >0.05). Conclusions: We found that antenatal MMN supplementation and infant zinc and MMN supplementation did not have a large effect on development outcomes in middle childhood and early adolescence in Tanzania.

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Effect of Maternal Vitamin B12 Supplementation on Cognitive Outcomes in South Indian Children: A Randomized Controlled Clinical Trial

Cited by 35 publications

References 24 publications

Do effects of early life interventions on linear growth correspond to effects on neurobehavioural development? A systematic review and meta-analysis

Do effects of early life interventions on linear growth correspond to effects on neurobehavioural development? A systematic review and meta-analysis

Maternal Vitamin B12 Status During Pregnancy and Its Association With Outcomes of Pregnancy and Health of the Offspring: A Systematic Review and Implications for Policy in India

Effect of antenatal and infant micronutrient supplementation on middle childhood and early adolescent development outcomes in Tanzania

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