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Background and Objective: The causal role of maternal nutrition in orofacial clefts is uncertain. We tested hypotheses that low maternal vitamin B12 and low folate status are each associated with an increased risk of isolated cleft lip with or without cleft palate (CL±P) in a case–control study in Tamil Nadu state, India. Methods: Case-mothers of CL±P children (n = 47) and control-mothers of unaffected children (n = 50) were recruited an average of 1.4 years after birth of the index child and plasma vitamin B12, methylmalonic acid (MMA), total homocysteine (tHcy), and folate were measured at that time. Logistic regression analyses estimated associations between nutrient biomarkers and case–control status. Results: Odds ratios (ORs) contrasting biomarker levels showed associations between case-mothers and low versus high plasma vitamin B12 (OR = 2.48, 95% CI, 1.02-6.01) and high versus low plasma MMA, an indicator of poor B12 status (OR = 3.65 95% CI, 1.21-11.05). Case–control status was not consistently associated with folate or tHcy levels. Low vitamin B12 status, when defined by a combination of both plasma vitamin B12 and MMA levels, had an even stronger association with case-mothers (OR = 6.54, 95% CI, 1.33-32.09). Conclusions: Mothers of CL±P children in southern India were 6.5 times more likely to have poor vitamin B12 status, defined by multiple biomarkers, compared to control-mothers. Further studies in populations with diverse nutritional backgrounds are required to determine whether poor maternal vitamin B12 or folate levels or their interactions are causally related to CL±P. [ABSTRACT FROM AUTHOR]

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 methyl-malonic acid with cognitive performance at 2 occasions, 4 mo apart, in North Indian children aged 12-18 mo. Design: Bayley Scales of Infant Development II were used to assess cognition. In multiple regression models adjusted for several potential confounders, we measured the association between, biomarkers for folate and cobalamin status and psychomotor or mental development scores on the day of blood sampling and 4 ?no thereafter. Results: Each 2-fold increment in plasma cobalamin concentration was associated with a significant increment in the mental development index score of 1.3 (95% CI: 0.2, 2.4; P = 0.021). Furthermore, each 2-fold increment in homocysteine or methylmalonic acid concentration was associated with a decrement in mental development index score of 2.0 (95% CI: 0.5, 3.4; P = 0.007) or 1.1 (95% CI: 0.3, 1.8; P = 0.004) points, respectively. Plasma folate concentration was significantly and independently associated with mental development index scores only when children with poor cobalamin status were excluded, ie, in those who had cobalamin concentrations below the 25th percentile. None of these markers was associated with psychomotor scores in the multiple regression models. Conclusions: Cobalamin and folate status showed a statistically significant association with cognitive performance. Given the high prevalence of deficiencies in these nutrients, folate and cobalamin supplementation trials are required to measure any beneficial effect on cognition. The study was registered at www.clinicaltrials.gov under the identifier number NCT00272116. [ABSTRACT FROM AUTHOR]

Poor micronutrient status is associated with diarrheal illness, but it is not known whether low folate and/or cobalamin status are independent risk factors for diarrhea. We measured the association between plasma folate and cobalamin and subsequent diarrheal morbidity in a prospective cohort study of 2296 children aged 6-30 mo in New Delhi, India. Plasma concentrations of folate, cobalamin, total homocysteine (tHcy), and methylmalonic acid were determined at baseline. Whether a child had diarrhea was recorded during weekly visits in a 4-mo zinc supplementation trial. Diarrhea episodes lasting <7, ≥7, and ≥14 d were classified as acute, prolonged, and persistent, respectively. There was a total of 4596 child periods with acute, 633 with prolonged, and 117 with persistent diarrhea during follow-up. Children with plasma folate concentrations in the lowest quartile had higher odds of persistent diarrhea than children in the other quartiles [adjusted OR = 1.77 (95% CI = 1.14, 2.75); P = 0.01]. This effect differed between boys [adjusted OR = 2.51 (95% CI = 1.47, 4.28)] and girls [adjusted OR = 1.03 (95% CI = 0.53, 2.01); P-interaction = 0.030]. We found a small but significant association between high plasma tHcy concentration and acute diarrhea [adjusted OR = 1.14 (95% CI = 1.04, 1.24); P = 0.006]. Plasma cobalamin concentration was not a predictor of diarrheal morbidity. In conclusion, poor folate status was an independent predictor of persistent diarrhea in this population. [ABSTRACT FROM AUTHOR]

The observed effect of zinc supplementation on diarrheal morbidity varies between trials and there is a need to identify subgroups most likely to benefit from improved zinc nutriture. In a randomized, double-blind trial in 2296 children in New Delhi, India, we assessed whether baseline cobalamin or folate status modified the effect of zinc supplementation on the incidence of prolonged (≥7 d duration) and acute diarrhea. Children aged 6-30 mo received zinc or placebo daily for 4 mo. We measured plasma concentrations of folate, cobalamin, total homocysteine (tHcy), and methylmalonic acid (MMA) at enrollment and assessed the efficacy of zinc supplementation in subgroups based on these variables. The efficacy of zinc on reducing the risk of prolonged diarrhea was higher in those with plasma cobalamin concentrations below the 25th percentile and in those with tHcy and MMA concentrations above the 75th percentile. The OR (95% Cl) for children below and above the 25th percentile for cobalamin were 0.53 (0.35-0.78) and 0.90 (0.73-1.11), respectively IP-interaction = 0.015). There were similar differences for the OR when comparing efficacy in those above and below the 75th percentile for tHcy and MMA IP-interaction = 0.045 and 0.188, respectively). Baseline folate status did not modify the effect of zinc on prolonged diarrhea. Neither cobalamin nor folate status influenced the effect of zinc on acute diarrhea. Children with poor cobalamin status benefited more from zinc supplementation for the prevention of prolonged diarrhea. [ABSTRACT FROM AUTHOR]

Background and Objective: The causal role of maternal nutrition in orofacial clefts is uncertain. We tested hypotheses that low maternal vitamin B 12 and low folate status are each associated with an increased risk of isolated cleft lip with or without cleft palate (CL±P) in a case-control study in Tamil Nadu state, India., Methods: Case-mothers of CL±P children (n = 47) and control-mothers of unaffected children (n = 50) were recruited an average of 1.4 years after birth of the index child and plasma vitamin B 12 , methylmalonic acid (MMA), total homocysteine (tHcy), and folate were measured at that time. Logistic regression analyses estimated associations between nutrient biomarkers and case-control status., Results: Odds ratios (ORs) contrasting biomarker levels showed associations between case-mothers and low versus high plasma vitamin B 12 (OR = 2.48, 95% CI, 1.02-6.01) and high versus low plasma MMA, an indicator of poor B 12 status (OR = 3.65 95% CI, 1.21-11.05). Case-control status was not consistently associated with folate or tHcy levels. Low vitamin B 12 status, when defined by a combination of both plasma vitamin B 12 and MMA levels, had an even stronger association with case-mothers (OR = 6.54, 95% CI, 1.33-32.09)., Conclusions: Mothers of CL±P children in southern India were 6.5 times more likely to have poor vitamin B 12 status, defined by multiple biomarkers, compared to control-mothers. Further studies in populations with diverse nutritional backgrounds are required to determine whether poor maternal vitamin B 12 or folate levels or their interactions are causally related to CL±P.

High-quality protein has been associated with child growth; however, the role of the amino acid cysteine remains unclear. The aim was to measure the extent to which plasma total cysteine (tCys) concentration is associated with anthropometric status in children aged 6-30 months living in New Delhi, India. The study was a prospective cohort study including 2102 children. We calculated Z-scores for height-for-age (HAZ), weight-for-height (WHZ), or weight-for-age (WAZ) according to the WHO Child Growth Standards. We used multiple regression models to estimate the association between tCys and the anthropometric indices. A high proportion of the children were categorized as malnourished at enrolment; 41% were stunted (HAZ ≤ -2), 19% were wasted (WHZ ≤ -2) and 42% underweight (WAZ ≤ -2). Plasma total cysteine (tCys) was significantly associated with HAZ, WHZ and WAZ after adjusting for relevant confounders ( p < 0.001). Low tCys (≤25th percentile) was associated with a decrease of 0.28 Z-scores for HAZ, 0.10 Z-scores for WHZ, and 0.21 Z-scores for WAZ compared to being >25th percentile. In young Indian children from low-to-middle socioeconomic neighborhoods, a low plasma total cysteine concentration was associated with an increased risk of poor anthropometric status.

Background: Population-based data on the prevalence of cobalamin and folate deficiency in India are lacking., Objective: The objective was to measure the prevalence of cobalamin and folate deficiency among children aged 6-30 mo residing in a low-to-middle income community in North India., Design: Children aged 6-30 mo (n = 2482) were identified through a community survey in a low-to-middle socioeconomic area in New Delhi, India. Non-fasting venous blood samples were collected before enrollment in another trial., Results: The median (interquartile range; IQR) cobalamin concentration in 6-11-mo-old children was substantially lower in breastfed (183; 120-263 pmol/L) than in nonbreastfed (334; 235-463 pmol/L) children. Cobalamin concentrations decreased progressively with increasing age in the nonbreastfed children. Median (IQR) plasma folate concentrations in the 6-11-mo-old group were higher in breastfed (20.3; 11.7-34.4 nmol/L) than in nonbreastfed (5.3; 3.4-7.7 nmol/L) children (P < 0.001). Folate concentrations decreased with increasing age in the breastfed children. In the nonbreastfed children, folate concentrations increased with increasing age. Low concentrations of plasma cobalamin (<150 pmol/L) were detected in 36% of breastfed and 9% of nonbreastfed children (P < 0.001). The proportions of children with plasma folate concentrations <5 nmol/L in these 2 subgroups were 6% and 33%, respectively (P < 0.001)., Conclusions: In north Indian preschool children, cobalamin and folate concentrations were commonly low and were associated with elevated total homocysteine and methylmalonic acid concentrations. Because low cobalamin and folate concentrations have functional consequences, population-based measures for improving cobalamin and folate concentrations need to be seriously considered.

Background: Vitamin deficiencies are often part of malnutrition, which predisposes to acute lower respiratory tract infections., Objective: The objective was to measure the association between cobalamin and folate status and subsequent respiratory morbidity., Design: A prospective cohort study was conducted in 2482 children aged 6-30 mo nested in a zinc supplementation trial. We measured plasma concentrations of folate, cobalamin, methylmalonic acid, and total homocysteine (tHcy) and followed the children for 4 mo., Results: We observed 1176 episodes of acute lower respiratory tract infections. Children with folate concentrations in the lowest quartile (interquartile range: 6.4-20.0 nmol/L) had a 44% higher incidence [adjusted incidence rate ratio (IRR): 1.44; 95% CI: 1.23, 1.70] of acute lower respiratory tract infections than did children in the other 3 quartiles. For tHcy, the IRR was 1.24 (1.07, 1.40) in a comparison of those in the highest quartile with those in the other quartiles. Breastfeeding was associated with high folate concentrations and protection against subsequent respiratory tract infections. This protection was significantly and substantially reduced after adjustment for plasma folate concentrations at baseline. Compared with the children in the other 3 quartiles, the IRR for being in the lowest quartile of cobalamin was 1.13 (0.76, 1.03) and for being in the highest quartile of methylmalonic acid was 1.12 (0.96, 1.31)., Conclusions: Poor folate status appears to be an independent risk factor for lower respiratory tract infections in young children. This study also suggests that the protective effect of breastfeeding is partly mediated by folate provided through breast milk.

This population-based cross-sectional study in South London looks at the total homocysteine (tHcy) levels in groups of different ethnic background and the possible role of environmental factors and the 677C-->T genetic polymorphism of the methylenetetrahydrofolate reductase (MTHFR). Fasting plasma tHcy was measured in 1392 men and women, age 40-59 years; 475 were white, 465 of African origin (of whom 180 were West Africans and 280 Caribbeans) and 452 South Asian (of whom 222 were Hindus and 167 Muslims). The homozygous MTHFR TT variant had observed frequencies of 0.10 in whites, 0.01 in people of African origin and 0.02 in South Asians (P<0.001). tHcy levels were 16% (95% CI 8-26) higher amongst TT than CC. tHcy levels were 25% (21-29) higher in men than women. Levels were significantly higher in South Asians than whites (8% [3-13]). Vegetarians had higher levels than non-vegetarians (25% [18-33]). These differences were present after adjustments for age, sex, smoking, body mass index (BMI), MTHFR 677C-->T polymorphism and socio-economic status. Compared with whites (10.0 [9.7-10.3] micromol/l), and allowing for confounders, Hindus had significantly higher levels of tHcy (12.1 [11.6-12.6] micromol/l). This difference was attenuated by the inclusion of vegetarianism in the model (11.3 [10.8-11.9] micromol/l). In contrast Muslims had similar tHcy levels to whites while both West Africans and Caribbeans had slightly lower levels, though differences were not significant. The reported higher levels of tHcy in South Asians are due to high levels amongst Hindus only. They are in part accounted for by their vegetarianism. These differences in tHcy are large enough to be important contributors to the risk of vascular disease and may be preventable by simple targeted population strategies.