Relationship between markers of inflammation and anaemia in children of Papua New Guinea.

OBJECTIVE: To assess the association of the acute-phase protein biomarkers, C-reactive protein (CRP) and α1-acid glycoprotein (AGP), with anaemia in children aged 6-59·9 months in Papua New Guinea. DESIGN: A nationally representative household-based cross-sectional survey of children aged 6-59·9 months was used to assess the relationships between various combinations of elevated CRP (>5 mg/l) and AGP (>1·2 g/l) with anaemia. Logistic regression was used to determine if other factors, such as age, sex, measures of anthropometry, region, urban/rural residence and household size, modified or confounded the acute-phase protein-anaemia association. SETTING: Papua New Guinea. SUBJECTS: A total of 870 children aged 6-59·9 months from the 2005 Papua New Guinea National Micronutrient Survey were assessed. RESULTS: The following prevalence estimates were found: anaemia 48 %; elevated CRP 32 %; and elevated AGP 33 %. Children with elevated CRP had a prevalence of anaemia of 66 % compared with children with normal CRP who had a prevalence of 40 %. Corresponding estimates for AGP were 61 % and 42 %, respectively. Similar results were found with combinations of elevated CRP and AGP. The higher prevalence of anaemia in children with elevated CRP and/or AGP was still present after controlling for confounders. CONCLUSIONS: Elevated levels of CRP and AGP were significantly associated with a higher prevalence of anaemia in the children surveyed. There are no expert group recommendations on whether to or how to account for markers of inflammation in presenting results on anaemia prevalence. Additional research would be helpful to clarify this issue.

Development and Validation of a New Low-Cost Enzyme-Linked Immunoassay for Serum and Dried Blood Spot Thyroglobulin.

BACKGROUND: Thyroglobulin (Tg), a biomarker of iodine nutrition, can be measured on dried blood spots (DBS), which simplifies collection and transport in surveys. The World Health Organization recommends DBS-Tg for monitoring iodine status in children. It could also be a useful iodine biomarker during pregnancy. However, the Tg antibody (Ab) used in earlier DBS-Tg assays is no longer commercially available. The aims of the present study were: (i) to develop a new low-cost serum and DBS-Tg sandwich enzyme-linked immunosorbent assay for assessment of Tg in population studies; (ii) to check the stability of DBS-Tg during long-term storage; and (iii) to assess within-subject variability in DBS-Tg. METHODS: Serum and DBS samples were measured from healthy pregnant women (n = 424) with the new assays, as well as the Immulite 2000 (Siemens), including TgAb positive (n = 150) and TgAb negative (n = 274) women. DBS-Tg stability was tested over 15 weeks of storage at -20 °C. Within-subject variability was evaluated over four weeks in four healthy adults. RESULTS: Intra-assay and interassay variability was 4.4-7.3% and 10.1-12.9% for the new serum Tg assay, and 7.6-12.3% and 7.6-16.5% for the DBS-Tg assay. Correlation between the two serum methods was high (r = 0.68, p < 0.01). Assay performance in all women and those TgAb negative was comparable. Correlation between the new serum Tg assay and the DBS-Tg assay was high (r = 0.78, p < 0.01), and agreement expressed as a function of the average Tg concentration for the two methods (X) was 0.59X -4.59 µg/L. DBS-Tg was stable for 15 weeks stored at -20 °C. Within-subject variability in DBS-Tg was 21.1%. Reagents and antibodies costs for the new serum and DBS assays are ∼ US$1. CONCLUSIONS: These new low-cost serum and DBS-Tg assays perform well over a wide range of Tg concentrations, and the field-friendly DBS assay may be particularly useful in population studies of iodine nutrition.

IRIS. I: a FOODlet-based multiple-micronutrient intervention in 6- to 12-month-old infants at high risk of micronutrient malnutrition in four contrasting populations: description of a multicenter field trial.

Infants in developing countries are at risk of concurrent micronutrient deficiencies, because the same causative factors may lead to deficiencies of different micronutrients. Inadequate dietary intake is considered one of the major causes of micronutrient deficiencies, especially among poor and underprivileged children in developing countries. Operational strategies and distribution systems are often duplicated when supplementation programs for single micronutrients are implemented at the same time. The International Research on Infant Supplementation (IRIS) trial was conducted in four distinct populations on three continents: Africa, Latin America, and Asia. The participating countries were South Africa, Peru, Vietnam, and Indonesia. The study had a randomized, doubleblind, placebo-controlled design. Each country aimed to enroll at least 70 infants per intervention group (65 + 5 anticipated dropouts). The micronutrient vehicle was in the form of a "foodlet" (food-like tablet) manufactured as chewable tablets, which were easy to break and dissolve, and which had the same taste, color, and flavor for all countries. Children were randomly assigned to one of four 6-month intervention groups: group 1 received a daily foodlet containing multiple micronutrients; group 2 received a daily placebo foodlet containing no micronutrients; group 3 received a weekly foodlet that contained multiple micronutrients (twice the dose of the daily foodlet) and placebo foodlets on the other days of the week; group 4 received a daily foodlet containing only 10 mg of elemental iron. The IRIS Trial aimed to examine the prevalence of multi-micronutrient deficiencies in 6- to 12-month-old infants from rural populations, and to examine the efficacy of multi-micronutrient supplementation in infants from the different countries included in the study. This paper describes the general methodology of the IRIS trial and the operational differences among the country sites.

Efficacy of a foodlet-based multiple micronutrient supplement for preventing growth faltering, anemia, and micronutrient deficiency of infants: the four country IRIS trial pooled data analysis.

Diets of infants across the world are commonly deficient in multiple micronutrients during the period of growth faltering and dietary transition from milk to solid foods. A randomized placebo controlled trial was carried out in Indonesia, Peru, South Africa, and Vietnam, using a common protocol to investigate whether improving status for multiple micronutrients prevented growth faltering and anemia during infancy. The results of the pooled data analysis of the 4 countries for growth, anemia, and micronutrient status are reported. A total of 1134 infants were randomized to 4 treatment groups, with 283 receiving a daily placebo (P), 283 receiving a weekly multiple micronutrient supplement (WMM), 280 received a daily multiple micronutrient (DMM) supplement, and 288 received daily iron (DI) supplements. The DMM group had a significantly greater weight gain, growing at an average rate of 207 g/mo compared with 192 g/mo for the WMM group, and 186 g/mo for the DI and P groups. There were no differences in height gain. DMM was also the most effective treatment for controlling anemia and iron deficiency, besides improving zinc, retinol, tocopherol, and riboflavin status. DI supplementation alone increased zinc deficiency. The prevalence of multiple micronutrient deficiencies at baseline was high, with anemia affecting the majority, and was not fully controlled even after 6 mo of supplementation. These positive results indicate the need for larger effectiveness trials to examine how to deliver supplements at the program scale and to estimate cost benefits. Consideration should also be given to increasing the dosages of micronutrients being delivered in the foodlets.

beta-Carotene and alpha-tocopherol concentration and antioxidant status in buccal mucosal cells and plasma after oral supplementation.

The uptake of alpha-tocopherol and beta-carotene and their antioxidative effect in plasma and buccal mucosal cells after oral application in twelve subjects is demonstrated in our study. The effect on the antioxidative status was evaluated using a modified thiobarbituric acid-reactive substance (TBARS) method. As expected, the supplement of 134.2 mg alpha-tocopherol/d and 25 mg beta-carotene/d for 7 d resulted in a significant increase of alpha-tocopherol and beta-carotene concentration in plasma (P<0.05). In buccal mucosal cells, the concentration of beta-carotene increased after supplementation (P<0.05), whereas the concentration of alpha-tocopherol remained constant. A decrease in TBARS (P<0.05) was found in buccal mucosal cells but not in plasma. In conclusion, an uptake of the supplemented antioxidants was detected in plasma and in buccal mucosal cells. There was significant change in beta-carotene concentration and oxidative stress as measured using a modified TBARS test in buccal mucosal cells, but not in the plasma.

Vitamin A capsule distribution to control vitamin A deficiency in Indonesia: effect of supplementation in pre-school children and compliance with the programme.

OBJECTIVE: The aim of this study was to evaluate the effectiveness of a widespread vitamin A supplementation programme and to describe indicators of compliance with the programme in Indonesia. DESIGN: Prospective cohort study. Children's anthropometric data were gathered at baseline (June 2000) and 4 months later (2 months after supplementation in August 2000). Serum retinol, haemoglobin, ferritin, alpha1-acid glycoprotein and C-reactive protein were measured at baseline and at follow-up. Caregivers of the children were interviewed using a questionnaire. SETTING: Semi-urban and rural areas of Semarang district, Central Java, Indonesia. SUBJECTS: Children aged 1-5 years. RESULTS: After the supplementation, the proportion of children with a low concentration of retinol decreased in recipients from 18.8 to 14.5%. However, in non-recipients, the prevalence of vitamin A deficiency increased from 31.9 to 37.5%, this prevalence being significantly higher than in recipients. A significant decrease occurred in the proportion of recipients with low ferritin (26.5 to 16.2%) and haemoglobin (25.7 to 15.3%), whereas the proportions did not show a significant change after supplementation for non-recipients. Modest linear growth was detected in recipients after supplementation but there was no effect on ponderal growth. The coverage rate of the supplementation in the study areas was 60%. There was an association between compliance of the caregivers and their knowledge about the potential benefit of vitamin A supplementation, the place where sick children were taken and age of the children. CONCLUSIONS: The vitamin A supplementation programme marginally decreased the proportion of vitamin A deficiency and had a marginal effect on the nutritional status of recipients. More than one micronutrient intervention is needed to increase the effectiveness of the supplementation programme. To increase compliance and coverage in the supplementation programme, nutrition communication and private healthcare practices need to be included in the programme.

Socioeconomic and familial characteristics influence caretakers' adherence to the periodic vitamin A capsule supplementation program in Central Java, Indonesia.

The adherence of program participants to periodic vitamin A capsule (VAC) supplementation among children aged 1-5 years (n = 677) in Central Java, Indonesia was assessed. Fourteen villages from five sub-districts and one ward from one sub-district in Central Java were included in the study to represent rural and suburban areas. All questions about demographic factors, socioeconomic conditions, current dietary practice and healthcare-seeking attitudes for common childhood illnesses, previous breastfeeding experience, their knowledge about vitamin A and adherence to the VAC program after capsule distribution (two periods in 2000) were asked. Caretakers with limited knowledge about the health benefits of vitamin A, households with more than one preschool child, and households with older children (> 36 months) were associated with a decreased likelihood of regular participation in the program with odds ratios of 0.38, 0.55, and 0.26, respectively (p < 0.01). The percentage of caretakers who utilized community health centers, village health posts or midwives' practices in rural areas, was significantly higher (86.6 per cent, p < 0.001) than in suburban areas (62.8 per cent). Living in a rural location was associated with an increased adherence to participate in the program regularly with an odds ratio of 2.02 (p < 0.01). In conclusion, nutritional education and periodic social marketing should be re-emphasized and other potential delivery channels, such as private healthcare practices, could also contribute to an increase adherence of supplementation program.