Micronutrient deficiency in children

Malnutrition increases morbidity and mortality and affects physical growth and development, some of these effects resulting from specific micronutrient deficiencies. While public health efforts must be targeted to improve dietary intakes in children through breast feeding and appropriate complementary feeding, there is a need for additional measures to increase the intake of certain micronutrients. Food-based approaches are regarded as the long-term strategy for improving nutrition, but for certain micronutrients, supplementation, be it to the general population or to high risk groups or as an adjunct to treatment must also be considered. Our understanding of the prevalence and consequences of iron, vitamin A and iodine deficiency in children and pregnant women has advanced considerably while there is still a need to generate more knowledge pertaining to many other micronutrients, including zinc, selenium and many of the B-vitamins. For iron and vitamin A, the challenge is to improve the delivery to target populations. For disease prevention and growth promotion, the need to deliver safe but effective amounts of micronutrients such as zinc to children and women of fertile age can be determined only after data on deficiency prevalence becomes available and the studies on mortality reduction following supplementation are completed. Individual or multiple micronutrients must be used as an adjunct to treatment of common infectious diseases and malnutrition only if the gains are substantial and the safety window sufficiently wide. The available data for zinc are promising with regard to the prevention of diarrhea and pneumonia. It should be emphasized that there must be no displacement of important treatment such as ORS in acute diarrhea by adjunct therapy such as zinc. Credible policy making requires description of not only the clinical effects but also the underlying biological mechanisms. As findings of experimental studies are not always feasible to extrapolate to humans, the biology of deficiency as well as excess of micronutrients in humans must continue to be investigated with vigour

Breast-feeding status alters the effect of vitamin A treatment during acute diarrhea in children

Vitamin A administration in children reduces the incidence of severe diarrhea during the subsequent few months. We therefore examined the effect of treatment with vitamin A during acute diarrhea on the episode duration and severity. In a double-blind controlled field trial, 900 children 1 to 5 y of age with acute diarrhea of ≤ 7 d duration were randomly assigned to receive vitamin A (60 mg) or a placebo. Children were followed up at home every alternate day until they recovered from the diarrheal episode. In all study children, those treated with vitamin A had a significantly lower risk of persistent diarrhea [odds ratio (OR) 0.30, 95% confidence interval (CI) 0.07-0.97], but there was no effect on the mean diarrheal duration or the mean stool frequency. In the subgroup of children who were not breast-fed, the mean diarrheal duration [ratio of geometric means (GM) 0.84, 95% CI 0.72-0.97], mean number of stools passed after the intervention (ratio of GM 0.73, 95% CI 0.56-0.95), the proportion of episodes lasting ≥ 14 d (P = 0.002) and the percentage of children who passed watery stools on any study day (OR 0.40, 95% CI 0.21-0.77) were significantly lower in those treated with vitamin A. We conclude that administration of vitamin A during acute diarrhea may reduce the severity of the episode and the risk of persistent diarrhea in non-breast-fed children. Similar benefit was not seen in breast-fed children

Careseeking for illness in young infants in an urban slum in India

Illness in infants in the first two months of life can take a precipitous life-threatening course, and requires timely and appropriate medical assessment and management. We conducted a focused ethnographic study of illness in young infants and associated careseeking practices in an urban slum in New Delhi, India, in order to identify the constraints in securing effective care for severe illness in this age group. The findings suggest that maternal recognition of illness is not a limiting factor in the use of health care services for sick young infants in this setting. Mothers respond to a number of important signs of illness, including changes in the young infant's sleeping or feeding behavior, and they are usually prompt in seeking care outside the home. They are not able, however, to discriminate among the many sources of health care available in this setting, and give preference to local unqualified private practitioners. Most practitioners, including qualified medical practitioners, display critical failures in the assessment and management of sick young infants. The continuity and effectiveness of care is further compromised by the caretakers' expectations of rapid cure, which result in discontinued treatment courses and frequent changes in practitioners, and by their reluctance to seek hospital care. The implications of these findings for the design of programs to reduce young infant mortality are discussed. In particular, the feasibility and acceptability of hospital referrals according to current program guidelines are called into question

Vitamin A Administered with measles vaccine to nine-month-old infants does not reduce vaccine immunogenicity

After a report of reduced seroconversion to measles in infants, aged 6 mo, given vitamin A with their measles vaccination, serious concerns were raised regarding the safety of the WHO's recommendation that infants be supplemented with vitamin A at the time of measles immunization. To determine the impact of coadministered vitamin A on the antibody response to measles vaccine given to infants aged 9 mo, the more common age for immunization in developing countries, we conducted a randomized, double-blind, placebo-controlled trial in an urban slum community in Delhi. Infants (618) were randomly allocated to receive 30 mg vitamin A or a placebo with the measles immunization. Antibodies to measles were measured by ELISA in serum samples obtained at before (baseline) and 12 wk after immunization. Overall, the seroconversion rates did not differ between vitamin A (89.5%) and placebo (87.6%) groups. There were no significant differences in the geometric mean titers in the two groups (ratio of geometric means, 1.19; 95% confidence interval, 0.97-1.46). Among malnourished infants, the geometric mean titer was significantly greater in the vitamin A group compared to the placebo group (ratio of geometric means, 1.57; 95% confidence interval, 1.18-2.0), but seroconversion rates did not differ. There were no differences in seroconversion rates and geometric mean titers in the two study groups among the well-nourished children. These results indicate that 30 mg vitamin A does not reduce the immune response to the coadministered vaccine and, therefore, can be continued to be given safely in public health programs

Use of multiple opportunities for improving feeding practices in under-twos within child health programmes

Objectives: In a community randomized trial, we aimed to promote exclusive breastfeeding and appropriate complementary feeding practices in under-twos to ascertain the feasibility of using available channels for nutrition counselling, their relative performance and the relationship between intensity of counselling and behaviour change. We also assessed whether using multiple opportunities to impart nutrition education adversely affected routine activities. Methods: We conducted a community randomized, controlled effectiveness trial in rural Haryana, India, with four intervention and four control communities. We trained health and nutrition workers in the intervention communities to counsel mothers at multiple contacts on breastfeeding exclusively for 6 months and on appropriate complementary feeding practices thereafter. The intervention was not just training health and nutrition workers in counselling but included community and health worker mobilization. Findings: In the intervention group, about 32% of caregivers were counselled by traditional birth attendants at birth. The most frequent sources of counselling from birth to 3 months were immunization sessions (45.1%) and home visits (32.1%), followed closely by weighing sessions (25.5%); from 7 to 12 months, home visits (42.6%) became more important than the other two. An increase in the number of channels through which caregivers were counselled was positively associated with exclusive breastfeeding prevalence at 3 months (p = 0.002), consumption of milk/cereal gruel or mix use at 9 months (p = 0.004) and 18 months (p = 0.003), undiluted milk at 9 months (p < 0.0001) and 24 hour non-breast-milk energy intakes at 18 months (p = 0.023), after controlling for potential confounding factors. Intervention areas, compared with the control, had higher coverage for vitamin A (45% vs. 11.5%) and iron folic acid (45% vs. 0.4%) supplementation. Conclusions: Using multiple available opportunities and workers for counselling caregivers was feasible, resulted in high coverage and impact, and instead of disrupting ongoing services, resulted in their improvement

Use of multiple opportunities for improving feeding practices in under-twos within child health programmes

Objectives: In a community randomized trial, we aimed to promote exclusive breastfeeding and appropriate complementary feeding practices in under-twos to ascertain the feasibility of using available channels for nutrition counselling, their relative performance and the relationship between intensity of counselling and behaviour change. We also assessed whether using multiple opportunities to impart nutrition education adversely affected routine activities. Methods: We conducted a community randomized, controlled effectiveness trial in rural Haryana, India, with four intervention and four control communities. We trained health and nutrition workers in the intervention communities to counsel mothers at multiple contacts on breastfeeding exclusively for 6 months and on appropriate complementary feeding practices thereafter. The intervention was not just training health and nutrition workers in counselling but included community and health worker mobilization. Findings: In the intervention group, about 32% of caregivers were counselled by traditional birth attendants at birth. The most frequent sources of counselling from birth to 3 months were immunization sessions (45.1%) and home visits (32.1%), followed closely by weighing sessions (25.5%); from 7 to 12 months, home visits (42.6%) became more important than the other two. An increase in the number of channels through which caregivers were counselled was positively associated with exclusive breastfeeding prevalence at 3 months (p = 0.002), consumption of milk/cereal gruel or mix use at 9 months (p = 0.004) and 18 months (p = 0.003), undiluted milk at 9 months (p<0.0001) and 24 hour non-breast-milk energy intakes at 18 months (p = 0.023), after controlling for potential confounding factors. Intervention areas, compared with the control, had higher coverage for vitamin A (45% vs. 11.5%) and iron folic acid (45% vs. 0.4%) supplementation. Conclusions: Using multiple available opportunities and workers for counselling caregivers was feasible, resulted in high coverage and impact, and instead of disrupting ongoing services, resulted in their improvemen

Rotavirus nonstructural protein NSP4 induces heterotypic antibody responses during natural infection in children

Seroconversion of immunoglobulin A (IgA) and immunoglobulin G (IgG) (≥4-fold rise) to rotavirus nonstructural protein 4 (NSP4) was determined, by use of enzyme-linked immunosorbent assay with fusion proteins glutathione S-transferase (GST)-NSP4 from strains SA11 (A), 116E (B), and RRV (C), in 40 children with acute rotavirus gastroenteritis and in 30 with the same disease due to other pathogens. The IgG seroconversion rates in the rotavirus group were 67.5%, 70%, and 60% when recombinant (r) NSP4A, -B, and -C, respectively, were used as antigen in the assay, and, for rotavirus-uninfected children, rates were 10%, 13%, and 7%. IgA seroconversion occurred in 57%, 70%, and 50%, respectively, of children with rotavirus gastroenteritis; in rotavirus-uninfected children, 1 child each seroconverted to the different rNSP4s. Among 9 children infected with strain NSP4A, 7, 6, and 5 children showed IgG seroconversion, and, among 18 infected with NSP4A, -B, and -C, 16, 17, and 15, respectively, showed IgG seroconversion. Between NSP4A-infected and NSP4B-infected children, IgA responses were similar to IgG responses. In conclusion, significant NSP4-specific antibody response occurs in natural rotavirus infection, and the antibody response appears to be broad and heterotypic in nature

Effect of Zinc Added to Multivitamin Supplementation Containing Low-dose Vitamin A on Plasma Retinol Level in Children—A Double-blind Randomized, Controlled Trial

In a community-based double-blind randomized trial in children aged 6–35 months, both intervention and control groups received a multi-vitamin syrup containing vitamin A, while the intervention group had zinc gluconate (equivalent to 10 mg of elemental zinc) additional in the syrup. There was a significant decrease in diarrhoea and pneumonia in the intervention group. This study was undertaken to investigate if addition of zinc to vitamin A had improved plasma retinol levels, which, in turn, was responsible for the effects observed in the intervention group. In a randomly-selected subsample of 200 children—100 each from the intervention and the control group, plasma retinol levels after 120 days of supplementation were measured. There was no difference in the mean plasma retinol levels [the difference in the mean 0.46 μg/dL (95% confidence interval -1.42–2.36)] between the two groups following supplementation. No difference in plasma retinol levels was observed in the subgroups based on baseline nutritional status and plasma zinc levels. Addition of zinc to low-dose vitamin A in this study did not improve the vitamin A status of children and cannot explain morbidity effects of the intervention

Adding zinc to supplemental iron and folic acid does not affect mortality and severe morbidity in young children

Studies have found a substantial reduction in diarrhea and respiratory morbidity in young children receiving zinc supplementation. The impact of daily zinc supplementation administered with iron plus folic acid (IFA) in young children on all-cause hospitalizations and mortality in comparison with IFA alone was evaluated. In a double blind cluster-randomized controlled trial, 94,359 subjects aged 1-23 mo were administered a daily dose of zinc plus IFA or IFA alone for a duration of 12 mo after enrollment. The intervention group tablet contained 10 mg of elemental zinc, 12.5 mg of iron, and 50 &#956;g of folic acid. The control group tablets were similar except that they contained a placebo for zinc. Infants aged &lt;6 mo were administered half a tablet, and those older received 1 tablet dissolved in breast milk or water. Hospitalizations were captured by trained study physicians through the surveillance of 8 hospitals. Deaths and hospitalizations were ascertained through visits to households by study supervisors once every 2 mo. The overall death rates did not differ significantly between the 2 groups when adjusted for cluster randomization (hazard ratio = 1.02, 95% CI 0.87, 1.19). Zinc and IFA supplementation compared with IFA alone did not affect adjusted hospitalization rates (overall rate ratio = 1.08, 95% CI 0.98, 1.19; diarrhea-specific rate ratio = 1.15, 95% CI 0.99, 1.34; or pneumonia-specific rate ratio = 1.09, 95% CI 0.94, 1.25). The lack of impact of zinc on mortality and hospitalization rates in this study may have been due to the use of lower daily zinc dosing than used in some of the morbidity prevention trials or from an interaction between zinc and iron, where the addition of iron may have adversely affected potential effects of zinc on immune function and morbidity. Future research should address iron and zinc interaction effects on important functional outcomes

Association between Helicobacter pylori infection and increased risk of typhoid fever

Helicobacter pylori infection has been reported to increase the risk of cholera. This nested case-control study was conducted to determine whether H. pylori infection is associated with occurrence of typhoid fever. Eighty-three case subjects of culture-proven typhoid fever were identified through a 1-year surveillance of subjects aged 0-40 years in an urban slum. Two age- and sex-matched neighborhood control subjects were concurrently selected for each case subject. Serum anti-H. pylori immunoglobulin G antibodies were measured in case and neighborhood control subjects. For determining other risk factors, 2 additional community control subjects per case were selected. There was a significant association between the presence of serum anti-H. pylori immunoglobulin G antibodies and typhoid fever (adjusted odds ratio, 2.03; 95% confidence interval, 1.02-4.01). Illiteracy, being part of a nuclear family, nonuse of soap, and consumption of ice cream were also associated with a significantly greater risk of typhoid fever. This study provides the first empiric evidence that H. pylori infection is associated with an increased risk of typhoid fever