Erythrocyte fatty acids and desaturase indices in early pregnancy are associated with risk of preeclampsia.

Preeclampsia (PE) is a pregnancy disorder that may be associated with inadequate maternal nutrition. Fatty acids are vital for placental and fetal growth. Fatty acid desaturases, key enzymes influencing the metabolism of polyunsaturated fatty acids, are reported to be associated with cardiometabolic risk. Any imbalance in the levels of omega-3 and omega-6 fatty acids can result in increased inflammatory response. The current study reports the levels of erythrocyte fatty acids and desaturase index across gestation in women who develop PE (n = 108) and compares them with non-PE women (n = 216). Maternal erythrocyte fatty acids were measured at 4 time points during pregnancy (i.e., 11-14, 18-22, 26-28 weeks and at delivery) using gas chromatography. Maternal total erythrocyte saturated fatty acids and omega-6/omega-3 fatty acid ratio was higher in the PE group as compared to the non-PE group at 11-14 weeks and 18-22 weeks respectively. Maternal Δ5 desaturase index was lower while Δ6 desaturase index was higher in the PE group at 11-14 and 18-22 weeks. Maternal stearoyl CoA desaturase-18 (SCD-18) index was lower at 11-14 weeks and at delivery. These changes were mainly observed in the early onset PE (EOP) group. Δ6 desaturase index at 11-14 weeks predicted the risk of EOP. Imbalance in fatty acid levels and desaturase indices predate the clinical diagnosis of PE, indicating their role in its pathophysiology. Measurement of fatty acids and desaturase indices in early pregnancy merits evaluation as predictors of risk of PE.

The Relationship of Birth Size and Postnatal Growth with Cellular Senescence in Adults: Data from the New Delhi Birth Cohort.

OBJECTIVE: To assess the effect of birth size and postnatal body mass index (BMI) gain from birth to adulthood on leucocytes cellular senescence in adult life. METHODS: Participants were aged 43.04 (± 0.92) y, and were enrolled from the New Delhi Birth Cohort study, who participated in phase 7 of the study (n = 210). Cellular senescence markers, p16 and p21 gene expression were determined by RT-qPCR in leucocytes and their association with birth size and conditional BMI gain at 2, 11, and 29 y were assessed in univariate and multivariate regression models. RESULTS: Birth weight (regression coefficient; B = -0.087, p = 0.011) and birth BMI (unadjusted B = -0.024, p = 0.026; adjusted B = -0.032, p = 0.022) were inversely associated with p21 gene expression in adult life. The p16 gene expression was not associated with any birth parameters. Conditional BMI gain at 2 y, 11 y, and 29 y was not associated with either p16 or p21 gene expression. The p21 gene expression was inversely associated with circulating insulin (B = -0.065, p = 0.026) and C-peptide levels (unadjusted B = -0.097, p = 0.014; adjusted B = -0.133, p = 0.003). CONCLUSION: Small size at birth is associated with accelerated cellular senescence in adult life. An altered senescent state is likely to be one of the links between LBW and adult chronic diseases.

Is iron status associated with markers of non-communicable disease in adolescent Indian children?

BACKGROUND: High body iron status has been associated with non-communicable diseases (NCD) like diabetes (high fasting blood glucose, FBG), hypertension (HTN) or dyslipidaemia (high total cholesterol, TC) in adults, but this has not been examined in adolescent children. This is relevant to iron supplementation and food iron fortification programs that are directed at Indian children. METHODS: The association of NCD with Serum Ferritin (SF) was examined using logistic additive models, adjusted for confounders such as age, body mass index, C-Reactive Protein, haemoglobin and sex, in adolescent (10-19 years old) participants of the Indian Comprehensive National Nutrition Survey. The interaction of these associations with wealth and co-existing prediabetes was also examined. A scenario analysis was also done to understand the impact of iron fortification of cereals on the prevalence NCD among adolescents. RESULTS: The odds ratio (OR) of high FBG, HTN and TC were 1.05 (95% CI: 1.01-1.08), 1.02 (95% CI: 1.001-1.03) and 1.04 (95% CI: 1.01-1.06) respectively for every 10 µg/L increase in SF. The odds for high TC increased with co-existing prediabetes. The scenario analysis showed that providing 10 mg of iron/day by fortification could increase the prevalence of high FBG by 2-14% across states of India. Similar increments in HTN and TC can also be expected. CONCLUSIONS: High SF is significantly associated with NCD in adolescents, dependent on wealth and co-existing prediabetes. This should be considered when enhancing iron intake in anaemia prevention programs, and the NCD relationship with body iron stores should be studied.

Indian Academy of Pediatrics Revised (2021) Guidelines on Prevention and Treatment of Vitamin D Deficiency and Rickets.

JUSTIFICATION: The emerging literature on prevalence of vitamin D deficiency in India, prevention and treatment strategies of rickets, and extra-skeletal benefits of vitamin D suggest the need for revising the existing guidelines for prevention and treatment of vitamin D deficiency in India. OBJECTIVES: To review the emerging literature on vitamin D prevalence and need for universal vitamin D supplementation. To suggest optimum vitamin D therapy for treatment of asymptomatic and symptomatic vitamin D deficiency, and rickets. To evaluate the extra-skeletal health benefits of vitamin D in children. PROCESS: A National consultative committee was formed that comprised of clinicians, epidemiologists, endocrinologists, and nutritionists. The Committee conducted deliberations on different aspects of vitamin D deficiency and rickets through ten online meetings between March and September, 2021. A draft guideline was formulated, which was reviewed and approved by all Committee members. RECOMMENDATIONS: The group reiterates the serum 25-hydroxy vitamin D cutoffs proposed for vitamin D deficiency, insufficiency, and sufficiency as <12 ng/mL, 12-20 ng/mL and >20 ng/mL, respectively. Vitamin D toxicity is defined as serum 25OHD >100 ng/mL with hypercalcemia and/or hypercalciuria. Vitamin D supplementation in doses of 400 IU/day is recommended during infancy; however, the estimated average requirement in older children and adolescents (400-600 IU/day, respectively) should be met from diet and natural sources like sunlight. Rickets and vitamin D deficiency should be treated with oral cholecalciferol, preferably in a daily dosing schedule (2000 IU below 1 year of age and 3000 IU in older children) for 12 weeks. If compliance to daily dosing cannot be ensured, intermittent regimens may be prescribed for children above 6 months of age. Universal vitamin D supplementation is not recommended in childhood pneumonia, diarrhea, tuberculosis, HIV and non-infectious conditions like asthma, atopic dermatitis, and developmental disorders. Serum 25-hydroxy vitamin D level of >20 ng/mL should be maintained in children with conditions at high-risk for vitamin deficiency, like nephrotic syndrome, chronic liver disease, chronic renal failure, and intake of anticonvulsants or glucocorticoids.

Childhood Head Growth and Educational Attainment in an Indian Cohort.

BACKGROUND: There is minimal information about the association of head growth at different stages of childhood with cognitive ability. OBJECTIVE: To determine the relationship of newborn head size and head growth during infancy, childhood and adolescence with attained education, a proxy for cognitive ability. STUDY DESIGN: Prospective birth cohort study. SETTING: Married women living in South Delhi between 1969 and 1973. PARTICIPANTS: The New Delhi Birth Cohort study followed up 8030 newborns born in 1969-1973 with head circumference, weight and height measurements at birth and 6-12 monthly until adulthood. Of these, 1526 men and women were followed up at the age of 26-32 years. OUTCOMES: Association between years of schooling, as an indicator of cognitive ability, and newborn head circumference and conditional measures of head growth during infancy, childhood and adolescence. RESULTS: In unadjusted analyses, newborn head size was positively associated with years of education [(b (95% CI)=0.30 (0.14 to 0.47) years per SD head circumference], as was head growth from birth to 6 months [b (95% CI)=0.44 (0.28 to 0.60) years per SD conditional head growth], 6 months to 2 years [b (95% CI)=0.31 (0.15 to 0.47) years per SD conditional head growth] and 2 to 11 years [b (95% CI)=0.20 (0.03 to 0.36) years per SD conditional head growth]. There were similar findings for height and body mass index (BMI). In the adjusted model containing all growth measures, gestational age, and socio-economic status (SES) at birth as predictors, only SES was positively associated with educational attainment. CONCLUSION: Educational attainment in this population is positively associated with socioeconomic status and its influence on inter-related early life (fetal, infant and childhood) factors like nutritional status and brain growth.

Research for Improving Patient Care.

Research is an integral part of medicine. Health research aims at generating evidence for development of new medicines, procedures and tools, all of which are directed at improved patient care. Research also aims at incorporating this evidence into clinical practice by developing clinical practice guidelines and developing robust health systems including governmental policies and systems. Health research not only allows doctors to decide how to best treat patients but also empowers patients to take active role in their health.

Characterisation of the types of anaemia prevalent among children and adolescents aged 1-19 years in India: a population-based study.

BACKGROUND: Anaemia is a serious public health concern in India. However, national estimates for its prevalence are not available for the 5-14 years age group, nor are estimates available for the types of anaemia among children and adolescents (1-19 years). We aimed to assess the prevalence of anaemia among children and adolescents in India and to categorise types of anaemia on the basis of micronutrient deficiencies. METHODS: We assessed the prevalence of anaemia among children (1-4 years and 5-9 years) and adolescents (10-19 years) using nationally representative data from the Comprehensive National Nutrition Survey. Anaemia was classified on the basis of age and sex-specific WHO cutoffs and serum ferritin, soluble transferrin receptor, folate, cyanocobalamin, and C-reactive protein concentrations as iron deficiency anaemia, folate or vitamin B12 deficiency anaemia, dimorphic anaemia (iron deficiency anaemia and folate or vitamin B12 deficiency anaemia), anaemia of other causes (anaemia not classified as iron deficiency anaemia and folate or vitamin B12 deficiency anaemia), and anaemia of inflammation. FINDINGS: We included 26 765 children (11 624 aged 1-4 years and 15 141 aged 5-9 years) and 14 669 adolescents. In the weighted sample, anaemia prevalence was 40·5% (4553 of 11 233) among 1-4 year-olds, 23·4% (3439 of 14 664) among 5-9 year-olds, and 28·4% (4064 of 14 300) among adolescents. Among 2862 children aged 1-4 years, iron deficiency anaemia (1045 [36·5%]) was the most prevalent type, followed by anaemia of other causes (702 [24·5%]), folate or vitamin B12 deficiency anaemia (542 [18·9%]), dimorphic anaemia (387 [13·5%]), and anaemia of inflammation (186 [6·5%]). Among 2261 children aged 5-9 years, anaemia of other causes was the most common (986 [43·6%]), followed by folate or vitamin B12 deficiency anaemia (558 [24·6%]), iron deficiency anaemia (353 [15·6%]), dimorphic anaemia (242 [10·7%]), and anaemia of inflammation (122 [5·4%]). 861 (31·4%) of 2740 adolescents had anaemia of other causes, 703 (25·6%) had folate or vitamin B12 deficiency anaemia, 584 (21·3%) had iron deficiency anaemia, 498 (18·2%) and dimorphic anaemia, and 94 (3·4%) had anaemia of inflammation. INTERPRETATION: Iron deficiency anaemia is the most common form of anaemia among younger children and anaemia of other causes among 5-9-year-old children and adolescents. Folate or vitamin B12 deficiency anaemia accounts for more than a third of anaemia prevalence. Anaemia prevention efforts should focus on strengthening the existing iron and folate supplementation programmes and prevention of folate or vitamin B12 deficiency anaemia. FUNDING: The Mittal Foundation.

Indian Academy of Pediatrics Guidelines on the Fast and Junk Foods, Sugar Sweetened Beverages, Fruit Juices, and Energy Drinks.

JUSTIFICATION: In view of easy availability and increasing trend of consumption of fast foods and sugar sweetened beverages (fruit juices and drinks, carbonated drinks, energy drinks) in Indian children, and their association with increasing obesity and related non-communicable diseases, there is a need to develop guidelines related to consumption of foods and drinks that have the potential to increase this problem in children and adolescents. OBJECTIVES: To review the evidence and formulate consensus statements related to terminology, magnitude of problem and possible ill effects of junk foods, fast foods, sugar-sweetened beverages and carbonated drinks; and to formulate recommendations for limiting consumption of these foods and beverages in Indian children and adolescents. PROCESS: A National Consultative group constituted by the Nutrition Chapter of the Indian Academy of Pediatrics (IAP), consisting of various stakeholders in private and public sector, reviewed the literature and existing guidelines and policy regulations. Detailed review of literature was circulated to the members, and the Group met on 11th March 2019 at New Delhi for a day-long deliberation on framing the guidelines. The consensus statements and recommendations formulated by the Group were circulated to the participants and a consensus document was finalized. CONCLUSIONS: The Group suggests a new acronym 'JUNCS' foods, to cover a wide variety of concepts related to unhealthy foods (Junk foods, Ultra-processed foods, Nutritionally inappropriate foods, Caffeinated/colored/carbonated foods/beverages, and Sugar-sweetened beverages). The Group concludes that consumption of these foods and beverages is associated with higher free sugar and energy intake; and is associated with higher body mass index (and possibly with adverse cardiometabolic consequences) in children and adolescents. Intake of caffeinated drinks may be associated with cardiac and sleep disturbances. The Group recommends avoiding consumption of the JUNCS by all children and adolescents as far as possible and limit their consumption to not more than one serving per week. The Group recommends intake of regional and seasonal whole fruits over fruit juices in children and adolescents, and advises no fruit juices/drinks to infants and young children (age <2y), whereas for children aged 2-5 y and >5-18 y, their intake should be limited to 125 mL/day and 250mL/day, respectively. The Group recommends that caffeinated energy drinks should not be consumed by children and adolescents. The Group supports recommendations of ban on sale of JUNCS foods in school canteens and in near vicinity, and suggests efforts to ensure availability and affordability of healthy snacks and foods. The Group supports traffic light coding of food available in school canteens and recommends legal ban of screen/print/digital advertisements of all the JUNCS foods for channels/magazines/websites/social media catering to children and adolescents. The Group further suggests communication, marketing and policy/taxation strategies to promote consumption of healthy foods, and limit availability and consumption of the JUNCS foods.

WASH practices and its association with nutritional status of adolescent girls in poverty pockets of eastern India.

BACKGROUND: Water, Sanitation, and Hygiene (WASH) practices may affect the growth and nutritional status among adolescents. Therefore, this paper assesses WASH practices and its association with nutritional status among adolescent girls. METHODS: As a part of an intervention programme, this study is based on baseline cross-sectional data. It was conducted between May 2016-April 2017 in three Indian states (Bihar, Odisha, and Chhattisgarh). From a sample of 6352 adolescent girls, information on WASH practices, accessibility to health services and anthropometric measurements (height, weight and mid upper arm circumference (MUAC)) was collected. Descriptive statistics were used to examine WASH practices, and nutritional status among adolescent girls. Determinants of open defecation and menstrual hygiene were assessed using logistic regression. Association between WASH and nutritional status of adolescent girls was determined using linear regression. RESULTS: Findings showed 82% of the adolescent girls were practicing open defecation and 76% were not using sanitary napkins. Significant predictors of open defecation and non use of sanitary napkin during menstruation were non Hindu households, households with poorer wealth, non availability of water within household premise, non visit to Anganwadi Centre, and non attendance in Kishori group meetings. One-third of adolescent girls were stunted, 17% were thin and 20% had MUAC < 19 cm. Poor WASH practices like water facility outside the household premise, unimproved sanitation facility, non use of soap after defecation had significant association with poor nutritional status of adolescent girls. CONCLUSIONS: Concerted convergent actions focusing on the provision of clean water within the household premise, measures to stop open defecation, promotion of hand washing, accessibility of sanitary napkins, poverty alleviation and behavior change are needed. Health, nutrition and livelihood programmes must be interspersed, and adolescents must be encouraged to take part in these programmes.

Effect of temperature and time delay in centrifugation on stability of select biomarkers of nutrition and non-communicable diseases in blood samples.

INTRODUCTION: Preanalytical conditions are critical for blood sample integrity and poses challenge in surveys involving biochemical measurements. A cross sectional study was conducted to assess the stability of select biomarkers at conditions that mimic field situations in surveys. MATERIAL AND METHODS: Blood from 420 volunteers was exposed to 2 - 8 °C, room temperature (RT), 22 - 30 °C and > 30 °C for 30 min, 6 hours, 12 hours and 24 hours prior to centrifugation. After different exposures, whole blood (N = 35) was used to assess stability of haemoglobin, HbA1c and erythrocyte folate; serum (N = 35) for assessing stability of ferritin, C-reactive protein (CRP), vitamins B12, A and D, zinc, soluble transferrin receptor (sTfR), total cholesterol, high density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol (LDL), tryglicerides, albumin, total protein and creatinine; and plasma (N = 35) was used for glucose. The mean % deviation of the analytes was compared with the total change limit (TCL), computed from analytical and intra-individual imprecision. Values that were within the TCL were deemed to be stable. RESULT: Creatinine (mean % deviation 14.6, TCL 5.9), haemoglobin (16.4%, TCL 4.4) and folate (33.6%, TCL 22.6) were unstable after 12 hours at 22-30°C, a temperature at which other analytes were stable. Creatinine was unstable even at RT for 12 hours (mean % deviation: 10.4). Albumin, CRP, glucose, cholesterol, LDL, triglycerides, vitamins B12 and A, sTfR and HbA1c were stable at all studied conditions. CONCLUSION: All analytes other than creatinine, folate and haemoglobin can be reliably estimated in blood samples exposed to 22-30°C for 12 hours in community-based studies.

Delivering an Integrated Package of Maternal Nutrition Services in Andhra Pradesh and Telangana (India).

BACKGROUND: Maternal spot feeding programs operational in southern Indian States are providing a package of nutrition services (food, micronutrient supplementation, deworming, gestation weight gain monitoring, and fortnightly nutrition health education) to pregnant women. These remain to be evaluated. OBJECTIVE: We evaluated the maternal spot feeding programs in 2 Southern Indian states. METHODS: Study design was cross-sectional entailing primary data collection (July to November 2016) on 360 pregnant and lactating women (of infants aged 0-6 months) per state and a review of the scheme's management information system (MIS) beneficiaries' records for the time period April 2014 to August 2017. To gain program functioning insights, open-ended interviews (n = 252) with state, district, and block program managers a state-level open space technology workshop was conducted. RESULTS: Average days of meal consumption ranged from 19 to 21 days per month; spot meal enhanced high dietary diversity (≥6 food groups; 57%-59%) and consumption of eggs and milk (74%-96%) among pregnant and lactating women. On-the-spot consumption of iron, folic acid, calcium, and deworming was 18%, 87%, and 56%, respectively; 94% attended at least 1 of the 2 nutrition monthly counseling sessions. Majority (68%) of the beneficiaries were motivated to enroll by self-help groups or family members, suggesting the crucial persuasive role of peers and family members. CONCLUSION: Maternal spot feeding schemes can potentially deliver nutrition interventions outlined in the World Health Organization antenatal care guidelines 2016 for a positive pregnancy outcome. Research on schemes' impact on birth outcomes, maternal depression, social norms, and its cost-effectiveness is needed.

Does India Need a Universal High-Dose Vitamin A Supplementation Program?

High dose vitamin A (HDVA) concentrate began to be distributed in India in 1970 as a short-term, stop-gap approach to reduce clinical signs of vitamin A deficiency. As this problem declined globally, the purpose of distributing them changed to the reduction of young child mortality. However, their impact on this has also declined, if not disappeared, as suggested in India by the enormous DEVTA study. This may be because of improved protection against and treatment of the main morbidity involved, measles and diarrhea. At the same time, semi-annual provision of mega-doses of vitamin A is not without risks, in particular linked to children's vaccination status. While a single dose is inexpensive, large-scale implementation of HDVA programs is expensive, particularly the opportunity cost involved in reducing the time health workers involved have to deal with their other commitments. Balancing potential benefits, risks and costs leads us to recommend an immediate cessation of the distribution of HDVA in India.

Context for layering women's nutrition interventions on a large scale poverty alleviation program: Evidence from three eastern Indian states.

Over 70 million women of reproductive age are undernourished in India. Most poverty alleviation programs have not been systematically evaluated to assess impact on women's empowerment and nutrition outcomes. National Rural Livelihoods Mission's poverty alleviation and livelihoods generation initiative is an opportune platform to layer women's nutrition interventions being tapped by project Swabhimaan in three eastern Indian states-Bihar, Chhattisgarh and Odisha. A cross-sectional baseline survey covering 8755 mothers of children under-two years of age, one of the three primary target groups of program are presented. Standardized questionnaire was administered and anthropometric measurements were undertaken from October 2016 to January 2017. 21 indicators on women's empowerment, Body Mass Index and Mid-upper Arm Circumference for nutrition status, food insecurity indicators as per the Food Insecurity Experience Scale and selected indicators for assessing women's access to basic health services were included. National Rural Livelihoods Mission operates in contexts with stark social and gender inequalities. Self-help group members exhibited better control on financial resources and participation in community activities than non-members. Using Body Mass Index, at least 45% mothers were undernourished irrespective of their enrolment in self-help groups. Higher proportion of self-help group members (77%-87%) belonged to food insecure households than non-members (66%-83%). Proportion of mothers reporting receipt of various components of antenatal care service package varied from over 90% for tetanus toxoid vaccination to less than 10% for height measurement. Current use of family planning methods was excruciatingly low (8.2%-32.4%) in all states but positively skewed towards self-help group members. Participation in monthly fixed day health camps was a concern in Bihar. Layering women's nutrition interventions as stipulated under Swabhimaan may yield better results for women's empowerment and nutrition status under National Rural Livelihoods Mission. While this opportunity exists in all three states, Bihar with a higher proportion of matured self-help groups offers more readiness for Swabhimaan implementation.

Modifiers of the effect of maternal multiple micronutrient supplementation on stillbirth, birth outcomes, and infant mortality: a meta-analysis of individual patient data from 17 randomised trials in low-income and middle-income countries.

BACKGROUND: Micronutrient deficiencies are common among women in low-income and middle-income countries. Data from randomised trials suggest that maternal multiple micronutrient supplementation decreases the risk of low birthweight and potentially improves other infant health outcomes. However, heterogeneity across studies suggests influence from effect modifiers. We aimed to identify individual-level modifiers of the effect of multiple micronutrient supplements on stillbirth, birth outcomes, and infant mortality in low-income and middle-income countries. METHODS: This two-stage meta-analysis of individual patient included data from 17 randomised controlled trials done in 14 low-income and middle-income countries, which compared multiple micronutrient supplements containing iron-folic acid versus iron-folic acid alone in 112 953 pregnant women. We generated study-specific estimates and pooled subgroup estimates using fixed-effects models and assessed heterogeneity between subgroups with the χ2 test for heterogeneity. We did sensitivity analyses using random-effects models, stratifying by iron-folic acid dose, and exploring individual study effect. FINDINGS: Multiple micronutrient supplements containing iron-folic acid provided significantly greater reductions in neonatal mortality for female neonates compared with male neonates than did iron-folic acid supplementation alone (RR 0·85, 95% CI 0·75-0·96 vs 1·06, 0·95-1·17; p value for interaction 0·007). Multiple micronutrient supplements resulted in greater reductions in low birthweight (RR 0·81, 95% CI 0·74-0·89; p value for interaction 0·049), small-for-gestational-age births (0·92, 0·87-0·97; p=0·03), and 6-month mortality (0·71, 0·60-0·86; p=0·04) in anaemic pregnant women (haemoglobin <110g/L) as compared with non-anaemic pregnant women. Multiple micronutrient supplements also had a greater effect on preterm births among underweight pregnant women (BMI <18·5 kg/m2; RR 0·84, 95% CI 0·78-0·91; p=0·01). Initiation of multiple micronutrient supplements before 20 weeks gestation provided greater reductions in preterm birth (RR 0·89, 95% CI 0·85-0·93; p=0·03). Generally, the survival and birth outcome effects of multiple micronutrient supplementation were greater with high adherence (≥95%) to supplementation. Multiple micronutrient supplements did not significantly increase the risk of stillbirth or neonatal, 6-month, or infant mortality, neither overall or in any of the 26 examined subgroups. INTERPRETATION: Antenatal multiple micronutrient supplements improved survival for female neonates and provided greater birth-outcome benefits for infants born to undernourished and anaemic pregnant women. Early initiation in pregnancy and high adherence to multiple micronutrient supplements also provided greater overall benefits. Studies should now aim to elucidate the mechanisms accounting for differences in the effect of antenatal multiple micronutrient supplements on infant health by maternal nutrition status and sex. FUNDING: None.

Effect of participatory women's groups and counselling through home visits on children's linear growth in rural eastern India (CARING trial): a cluster-randomised controlled trial.

BACKGROUND: Around 30% of the world's stunted children live in India. The Government of India has proposed a new cadre of community-based workers to improve nutrition in 200 districts. We aimed to find out the effect of such a worker carrying out home visits and participatory group meetings on children's linear growth. METHODS: We did a cluster-randomised controlled trial in two adjoining districts of Jharkhand and Odisha, India. 120 clusters (around 1000 people each) were randomly allocated to intervention or control using a lottery. Randomisation took place in July, 2013, and was stratified by district and number of hamlets per cluster (0, 1-2, or ≥3), resulting in six strata. In each intervention cluster, a worker carried out one home visit in the third trimester of pregnancy, monthly visits to children younger than 2 years to support feeding, hygiene, care, and stimulation, as well as monthly women's group meetings to promote individual and community action for nutrition. Participants were pregnant women identified and recruited in the study clusters and their children. We excluded stillbirths and neonatal deaths, infants whose mothers died, those with congenital abnormalities, multiple births, and mother and infant pairs who migrated out of the study area permanently during the trial period. Data collectors visited each woman in pregnancy, within 72 h of her baby's birth, and at 3, 6, 9, 12, and 18 months after birth. The primary outcome was children's length-for-age Z score at 18 months of age. Analyses were by intention to treat. Due to the nature of the intervention, participants and the intervention team were not masked to allocation. Data collectors and the data manager were masked to allocation. The trial is registered as ISCRTN (51505201) and with the Clinical Trials Registry of India (number 2014/06/004664). RESULTS: Between Oct 1, 2013, and Dec 31, 2015, we recruited 5781 pregnant women. 3001 infants were born to pregnant women recruited between Oct 1, 2013, and Feb 10, 2015, and were therefore eligible for follow-up (1460 assigned to intervention; 1541 assigned to control). Three groups of children could not be included in the final analysis: 147 migrated out of the study area (67 in intervention clusters; 80 in control clusters), 77 died after the neonatal period and before 18 months (31 in intervention clusters; 46 in control clusters), and seven had implausible length-for-age Z scores (<-5 SD; one in intervention cluster; six in control clusters). We measured 1253 (92%) of 1362 eligible children at 18 months in intervention clusters, and 1308 (92%) of 1415 eligible children in control clusters. Mean length-for-age Z score at 18 months was -2·31 (SD 1·12) in intervention clusters and -2·40 (SD 1·10) in control clusters (adjusted difference 0·107, 95% CI -0·011 to 0·226, p=0·08). The intervention did not significantly affect exclusive breastfeeding, timely introduction of complementary foods, morbidity, appropriate home care or care-seeking during childhood illnesses. In intervention clusters, more pregnant women and children attained minimum dietary diversity (adjusted odds ratio [aOR] for women 1·39, 95% CI 1·03-1·90; for children 1·47, 1·07-2·02), more mothers washed their hands before feeding children (5·23, 2·61-10·5), fewer children were underweight at 18 months (0·81, 0·66-0·99), and fewer infants died (0·63, 0·39-1·00). INTERPRETATION: Introduction of a new worker in areas with a high burden of undernutrition in rural eastern India did not significantly increase children's length. However, certain secondary outcomes such as self-reported dietary diversity and handwashing, as well as infant survival were improved. The interventions tested in this trial can be further optimised for use at scale, but substantial improvements in growth will require investment in nutrition-sensitive interventions, including clean water, sanitation, family planning, girls' education, and social safety nets. FUNDING: UK Medical Research Council, Wellcome Trust, UK Department for International Development (DFID).

Supplementation of vitamin B12 or folic acid on hemoglobin concentration in children 6-36 months of age: A randomized placebo controlled trial.

BACKGROUND & AIMS: The main objective of this report is to measure to what extent folate or vitamin B12 given daily for 6 months to young North Indian Children improves hemoglobin (Hb) concentration. METHODS: In a randomized placebo controlled trial in low-to-middle income neighborhoods in New Delhi, India, children were randomized into four groups in a 1:1:1:1 ratio and supplemented daily for 6 months with 2 RDAs of vitamin B12, folic acid, both, or placebo. All children with anemia at baseline were given iron supplementation daily for 2 months. We measured the plasma concentrations of soluble transferrin receptor (sTfR), folate, vitamin B12, total homocysteine (tHcy) and Hb in 262 children. RESULTS: Mean Hb concentration decreased in all four study groups during the six months of follow up and supplementation of either or both of the vitamins did not improve the Hb concentration. Iron supplements for the initial 2 mo had limited effect on anemia at 6 mo as almost 90% were still anemic at study end. CONCLUSION: Supplementation of folic acid and/or vitamin B12 for 6 months does not improve Hb concentration in young children. Our findings do not argue for widespread vitamin B12 or folic acid supplementation to combat anemia. Our results also call for alternative strategies to improve iron status and treat iron deficiency anemia. CLINICAL TRIAL REGISTRY: NCT00717730 at www.clinicaltrials.gov, CTRI No.: CTRI/2010/091/001090 at www.ctri.nic.in.