Tarun Gera

Effect of iron supplementation on mental and motor development in children: systematic review of randomised controlled trials

OBJECTIVE To evaluate the effect of iron supplementation on mental and motor development in children through a systematic review of randomised controlled trials (RCTs). DATA SOURCES Electronic databases, personal files, hand search of reviews, bibliographies of books, abstracts and proceedings of international conferences. REVIEW METHODS RCTs with interventions that included oral or parenteral iron supplementation, fortified formula milk or cereals were evaluated. The outcomes studied were mental and motor development scores and various individual development tests employed, including Bayley mental and psychomotor development indices and intelligence quotient. RESULTS The pooled estimate (random effects model) of mental development score standardised mean difference (SMD) was 0.30 (95% confidence interval (CI) 0.15 to 0.46, P<0.001; P<0.001 for heterogeneity). Initial anaemia and iron-deficiency anaemia were significant explanatory variables for heterogeneity. The pooled estimate of Bayley Mental Development Index (weighted mean difference) in younger children (<27 months old) was 0.95 (95% CI -0.56 to 2.46, P=0.22; P=0.016 for heterogeneity). For intelligence quotient scores (> or =8 years age), the pooled SMD was 0.41 (95% CI 0.20 to 0.62, P<0.001; P=0.07 for heterogeneity). There was no effect of iron supplementation on motor development score (SMD 0.09, 95% CI -0.08 to 0.26, P=0.28; P=0.028 for heterogeneity). CONCLUSIONS Iron supplementation improves mental development score modestly. This effect is particularly apparent for intelligence tests above 7 years of age and in initially anaemic or iron-deficient anaemic subjects. There is no convincing evidence that iron treatment has an effect on mental development in children below 27 months of age or on motor development.

Multiple micronutrient supplementation for improving cognitive performance in children: systematic review of randomized controlled trials

BACKGROUND Although multiple micronutrient interventions have been shown to benefit childrens intellectual development, a thorough evaluation of the totality of evidence is currently lacking to direct public health policy. OBJECTIVE This study aimed to systematically review the present literature and to quantify the effect of multiple micronutrients on cognitive performance in schoolchildren. METHODS The Institute for Scientific Information Web of Knowledge and local medical databases were searched for trials published from 1970 to 2008. Randomized controlled trials that investigated the effect of > or =3 micronutrients compared with placebo on cognition in healthy children aged 0-18 y were included following protocol. Data were extracted by 2 independent researchers. The cognitive tests used in the trials were grouped into several cognitive domains (eg, fluid and crystallized intelligence), and pooled effect size estimates were calculated per domain. Heterogeneity was explored through sensitivity and meta-regression techniques. RESULTS Three trials were retrieved in children aged <5 y, and 17 trials were retrieved in children aged 5-16 y. For the older children, pooled random-effect estimates for intervention were 0.14 SD (95% CI: -0.02, 0.29; P = 0.083) for fluid intelligence and -0.03 SD (95% CI: -0.21, 0.15; P = 0.74) for crystallized intelligence, both of which were based on 12 trials. Four trials yielded an overall effect of 0.30 SD (95% CI: 0.01, 0.58; P = 0.044) for academic performance. For other cognitive domains, no significant effects were found. CONCLUSIONS Multiple micronutrient supplementation may be associated with a marginal increase in fluid intelligence and academic performance in healthy schoolchildren but not with crystallized intelligence. More research is required, however, before public health recommendations can be given.

Effect of iron supplementation on physical growth in children: systematic review of randomised controlled trials

OBJECTIVE To evaluate the effect of iron supplementation on physical growth in children through a systematic review of randomised controlled trials (RCTs). DATA SOURCES Electronic databases, personal files, and hand search of reviews, bibliographies of books, abstracts and proceedings of international conferences. REVIEW METHODS RCTs evaluating change in anthropometry with interventions that included oral or parenteral iron supplementation, or iron-fortified formula milk or cereals, were analysed. RESULTS Twenty-five trials (26 cohorts) had relevant information. There was no evidence of publication bias. The pooled estimates (random effects model) did not document a statistically significant (P>0.05) positive effect of iron supplementation on any anthropometric variable (weight-for-age, weight-for-height, height-for-age, mid upper-arm circumference, skinfold thickness, head circumference). Significant heterogeneity was evident, and its predictors included greater weight-for-age in supplemented children in malaria hyperendemic regions and greater weight-for-height for children above 5 years of age, but a negative effect on linear growth in developed countries and with supplementation for 6 months or longer. CONCLUSIONS This review did not document a positive effect of iron supplementation on the physical growth of children. The identified predictors of heterogeneity should be considered as exploratory and requiring confirmation, not conclusive.

Effect of iron supplementation on haemoglobin response in children: systematic review of randomised controlled trials.

Objective: To evaluate the effect of iron supplementation on haemoglobin (Hb) in children through a systematic review of randomised controlled trials. Materials and Methods: Electronic databases, personal files, hand search of reviews, bibliographies of books, and abstracts and proceedings of international conferences were reviewed. Randomised controlled trials evaluating change in Hb levels with interventions that included oral or parenteral iron supplementation or iron-fortified formula milk or cereals were analysed. Results: A total of 55 trials (56 cohorts) provided relevant information. Publication bias was evident (P < 0.001). The pooled estimate (random-effects model) for change in Hb with iron supplementation (weighted mean difference) was 0.74 g/dL (95% CI, 0.61–0.87; P < 0.001; P < 0.001 for heterogeneity). Lower baseline Hb level, oral medicinal iron supplementation, and malarial nonhyperendemic region were significant predictors of greater Hb response and heterogeneity. Projections suggested that, on average, between 37.9% and 62.3% of baseline anaemia (Hb <11 g/dL) was responsive to iron supplementation among children under 6 years of age; the corresponding range for malarial hyperendemic regions was 5.8% to 31.8%. Conclusions: This systematic review indicates that iron supplementation increases Hb levels in children significantly but modestly. The increase is greater in subjects who are anaemic at the start of the trial and lower in malarial hyperendemic areas and in those consuming iron-fortified food. The projected reductions in prevalence of anaemia with iron supplementation alone highlight the need for additional area-specific interventions, particularly in malaria-prone regions.

Effect of iron-fortified foods on hematologic and biological outcomes: systematic review of randomized controlled trials

BACKGROUND The utility of iron fortification of food to improve iron deficiency, anemia, and biological outcomes is not proven unequivocally. OBJECTIVES The objectives were to evaluate 1) the effect of iron fortification on hemoglobin and serum ferritin and the prevalence of iron deficiency and anemia, 2) the possible predictors of a positive hemoglobin response, 3) the effect of iron fortification on zinc and iron status, and 4) the effect of iron-fortified foods on mental and motor development, anthropometric measures, and infections. DESIGN Randomized and pseudorandomized controlled trials that included food fortification or biofortification with iron were included. RESULTS Data from 60 trials showed that iron fortification of foods resulted in a significant increase in hemoglobin (0.42 g/dL; 95% CI: 0.28, 0.56; P < 0.001) and serum ferritin (1.36 μg/L; 95% CI: 1.23, 1.52; P < 0.001), a reduced risk of anemia (RR: 0.59; 95% CI: 0.48, 0.71; P < 0.001) and iron deficiency (RR: 0.48; 95% CI: 0.38, 0.62; P < 0.001), improvement in other indicators of iron nutriture, and no effect on serum zinc concentrations, infections, physical growth, and mental and motor development. Significant heterogeneity was observed for most of the evaluated outcomes. Sensitivity analyses and meta-regression for hemoglobin suggested a higher response with lower trial quality (suboptimal allocation concealment and blinding), use of condiments, and sodium iron edetate and a lower response when adults were included. CONCLUSION Consumption of iron-fortified foods results in an improvement in hemoglobin, serum ferritin, and iron nutriture and a reduced risk of remaining anemic and iron deficient.

Incidence of cardiovascular risk factors in an Indian urban cohort results from the New Delhi birth cohort.

India has one of the highest burdens of cardiovascular disease (CVD) worldwide. The annual number of deaths from CVD in India is projected to rise from 2.26 million (1990) to 4.77 million (2020) ([1][1]). Coronary heart disease prevalence rates in India have been estimated over the past several

Promoting appropriate management of diarrhea: A systematic review of literature for advocacy and action: UNICEF-PHFI series on newborn and child health, India

BackgroundScaling up of evidence-based management and prevention of childhood diarrhea is a public health priority in India, and necessitates robust literature review, for advocacy and action.ObjectiveTo identify, synthesize and summarize current evidence to guide scaling up of management of diarrhea among under-five children in India, and identify existing knowledge gaps.MethodsA set of questions pertaining to the management (prevention, treatment, and control) of childhood diarrhea was identified through a consultative process. A modified systematic review process developed a priori was used to identify, synthesize and summarize, research evidence and operational information, pertaining to the problem in India. Areas with limited or no evidence were identified as knowledge gaps.ResultsChildhood diarrhea is a significant public health problem in India; the point (two-weeks) prevalence is 9–20%. Diarrhea accounts for 14% of the total deaths in under-five children in India. Infants aged 6–24 months are at the highest risk of diarrhea. There is a lack of robust nation-wide data on etiology; rotavirus and diarrheogenic E.coli are the most common organisms identified. The current National Guidelines are sufficient for case-management of childhood diarrhea. Exclusive breastfeeding, handwashing and point-of-use water treatment are effective strategies for prevention of all-cause diarrhea; rotavirus vaccines are efficacious to prevent rotavirus specific diarrhea. ORS and zinc are the mainstay of management during an episode of childhood diarrhea but have low coverage in India due to policy and programmatic barriers, whereas indiscriminate use of antibiotics and other drugs is common. Zinc therapy given during diarrhea can be upscaled through existing infrastructure is introducing the training component and information, education and communication activities.ConclusionThis systematic review summarizes current evidence on childhood diarrhea and provides evidence to inform child health programs in India.

Impact of Water, Sanitation and Hygiene Interventions on Growth, Non-diarrheal Morbidity and Mortality in Children Residing in Low- and Middle-income Countries: A Systematic Review

ObjectiveTo evaluate the impact of water, sanitation and hygiene (WASH) interventions in children (age <18 y) on growth, non-diarrheal morbidity and mortality in children.DesignSystematic review of randomized controlled trials, non-randomized controlled trials and controlled before-after studies.SettingLow- and middle-income countries.Participants41 trials with WASH intervention, incorporating data on 113055 children.InterventionHygiene promotion and education (15 trials), water intervention (10 trials), sanitation improvement (7 trials), all three components of WASH (4 trials), combined water and sanitation (1 trial), and sanitation and hygiene (1 trial).Outcome Measures(i) Anthropometry: weight, height, weight-for-height, mid-arm circumference; (ii) Prevalence of malnutrition; (iii) Non-diarrheal morbidity; and (iv) mortality.ResultsThere may be little or no effect of hygiene intervention on most anthropometric parameters (low- to very-low quality evidence). Hygiene intervention reduced the risk of developing Acute respiratory infections by 24% (RR 0.76; 95% CI 0.59, 0.98; moderate quality evidence), cough by 10% (RR 0.90; 95% CI 0.83, 0.97; moderate quality evidence), laboratory-confirmed influenza by 50% (RR 0.5; 95% CI 0.41, 0.62; very low quality evidence), fever by 13% (RR 0.87; 95% CI 0.74, 1.02; moderate quality evidence), and conjunctivitis by 51% (RR 0.49; 95% CI 0.45, 0.55; low quality evidence). There was low quality evidence to suggest no impact of hygiene intervention on mortality (RR 0.65; 95% CI 0.25, 1.7). Improvement in water supply and quality was associated with slightly higher weight-for-age Z-score (MD 0.03; 95% CI 0, 0.06; low quality evidence), but no significant impact on other anthropometric parameters or infectious morbidity (low to very low quality evidence). There was very low quality evidence to suggest reduction in mortality (RR 0.45; 95% CI 0.25, 0.81). Improvement in sanitation had a variable effect on the anthropometry and infectious morbidity. Combined water, sanitation and hygiene intervention improved height-for-age Z scores (MD 0.22; 95% CI 0.12, 0.32) and decreased the risk of stunting by 13% (RR 0.87; 95% CI 0.81, 0.94) (very low quality of evidence). There was no evidence of significant effect of combined WASH interventions on non-diarrheal morbidity (fever, respiratory infections, intestinal helminth infection and school absenteeism) (low- to very-low quality of evidence). Any WASH intervention (considered together) resulted in lower risk of underweight (RR 0.81; 95% CI 0.69, 0.96), stunting (RR 0.77; 95% CI 0.68, 0.86) and wasting (RR 0.12, 0.85) (low- to very-low quality of evidence).ConclusionAvailable evidence suggests that there may be little or no effect of WASH interventions on the anthropometric indices in children from low- and middle-income countries. There is low- to very-low quality of evidence to suggest decrease in prevalence of wasting, stunting and underweight. WASH interventions (especially hygiene intervention) were associated with lower risk of non-diarrheal morbidity (very low to moderate quality evidence). There was very low quality evidence to suggest some decrease to no change in mortality. These potential health benefits lend support to the ongoing efforts for provision of safe and adequate water supply, sanitation and hygiene.

Lipid based nutrient supplements (LNS) for treatment of children (6 months to 59 months) with moderate acute malnutrition (MAM): A systematic review

Background Moderate acute malnutrition is a major public health problem affecting children from low- and middle-income countries. Lipid nutrient supplements have been proposed as a nutritional intervention for its treatment. Objectives To evaluate the effectiveness and safety of LNS for the treatment of MAM in infants and children 6 to 59 months of age. Study design Systematic review of randomized-controlled trials and controlled before-after studies. Results Data from nine trials showed that use of LNS, in comparison to specially formulated foods, improved the recovery rate (RR 1.08; 95% CI 1.02–1.14, 8 RCTs, 8934 participants, low quality evidence); decreased the chances of no recovery (RR 0.70; 95% CI 0.58–0.85, 7 RCTs, 8364 participants, low quality evidence) and the risk of deterioration into severe acute malnutrition (RR 0.87; 95% CI 0.73–1.03, 6 RCTs, 6788 participants, low quality evidence). There was little impact on mortality (RR 0.94, 95% CI 0.54–1.52, 8 RCTs, 8364 participants, very-low- quality evidence) or default rate (RR 1.32; 95% CI 0.73–2.4, 7 studies, 7570 participants, low quality evidence). There was improvement in weight gain, weight-for-height z-scores, height-for-age z-scores and mid-upper arm circumference. Subset analyses suggested higher recovery rates with greater amount of calories provided and with ready-to-use therapeutic foods, in comparison to ready-to-use supplementary foods. One study comparing LNS with nutritional counselling (very low quality evidence) showed higher chance of recovery, lower risk of deteriorating into severe acute malnutrition and lower default rate, with no impact on mortality, and no recovery. Conclusions Evidence restricted to the African regions suggests that LNS may be slightly more effective than specially formulated fortified foods or nutritional counselling in recovery from MAM, lowering the risk of deterioration into SAM, and improving weight gain with little impact on mortality or default rate.

Association between anthropometry, cardiometabolic risk factors, & early life factors & adult measures of endothelial function: Results from the New Delhi Birth Cohort

Background & objectives: Abnormal endothelial function represents a preclinical marker of atherosclerosis. This study was conducted to evaluate associations between anthropometry, cardiometabolic risk factors, and early life factors and adult measures of endothelial function in a young urban Indian cohort free of clinical cardiovascular disease. Methods: Absolute changes in brachial artery diameter following cuff inflation and sublingual nitroglycerin (400 µg) were recorded to evaluate endothelium-dependent and -independent measures of endothelial function in 600 participants (362 men; 238 women) from the New Delhi Birth Cohort (2006-2009). Data on anthropometry, cardiometabolic risk factors, medical history, socio-economic position, and lifestyle habits were collected. Height and weight were recorded at birth, two and 11 yr of age. Age- and sex-adjusted linear regression models were developed to evaluate these associations. Results: The mean age of participants was 36±1 yr. Twenty two per cent men and 29 per cent women were obese (BMI > 30 kg/m2). Mean systolic blood pressure (SBP) was 131±14 and 119±13 mmHg, and diabetes prevalence was 12 and 8 per cent for men and women, respectively. Brachial artery diameter was higher for men compared with women both before (3.48±0.37 and 2.95±0.35 cm) and after hyperaemia (3.87±0.37 vs. 3.37±0.35 cm). A similar difference was seen before and after nitroglycerin. Markers of increased adiposity, smoking, SBP, and metabolic syndrome, but not early life anthropometry, were inversely associated with endothelial function after adjustment for age and sex. Interpretation & conclusions: The analysis of the current prospective data from a young urban Indian cohort showed that cardiometabolic risk factors, but not early life anthropometry, were associated with worse endothelial function.