Gender differences in nutritional status and determinants among infants (6-11 m): a cross-sectional study in two regions in Ethiopia.

BACKGROUND: A limited number of studies suggest that boys may have a higher risk of stunting than girls in low-income countries. Little is known about the causes of these gender differences. The objective of the study was to assess gender differences in nutritional status and its determinants among infants in Ethiopia. METHODS: We analyzed data for 2036 children (6-11 months old) collected as the baseline for a multiple micronutrient powders effectiveness study in two regions of Ethiopia in March-April 2015. Child, mother, and household characteristics were investigated as determinants of stunting and wasting. Multiple logistic regression models were used separately for boys and girls to check for gender differences while adjusting for confounders. The study is registered at http://www.clinicaltrials.gov/ with the clinical trials identifier of NCT02479815. RESULTS: Stunting and wasting prevalence is significantly higher among boys compared to girls, 18.7 vs 10.7% and 7.9 vs 5.4%, respectively. Untimely initiation of breastfeeding, not-exclusive breastfeeding at the age of 6 months, region of residence, and low maternal education are significant predictors of stunting in boys. Untimely introduction to complementary food and low consumption of legumes/nuts are significant predictors of stunting in both boys and girls, and low egg consumption only in girls. Region of residence and age of the mother are significant determinants of wasting in both sexes. Analysis of interaction terms for stunting, however, shows no differences in predictors between boys and girls; only for untimely initiation of breastfeeding do the results for boys (OR 1.46; 95%CI 1.02,2.08) and girls (OR 0.88; 95%CI 0.55,1.41) tend to be different (p = 0.12). CONCLUSION: In Ethiopia, boys are more malnourished than girls. Exclusive breastfeeding and adequate dietary diversity of complementary feeding are important determinants of stunting in boys and girls. There are no clear gender interactions for the main determinants of stunting and wasting. These findings suggest that appropriate gender-sensitive guidance on optimum infant and young child feeding practices is needed.

Determinants of adherence to micronutrient powder use among young children in Ethiopia.

In Ethiopia, home fortification of complementary foods with micronutrient powders (MNPs) was introduced in 2015 as a new approach to improve micronutrient intakes. The objective of this study was to assess factors associated with intake adherence and drivers for correct MNP use over time to inform scale-up of MNP interventions. Mixed methods including questionnaires, interviews and focus group discussions were used. Participants, 1,185 children (6-11 months), received bimonthly 30 MNP sachets for 8 months, with instruction to consume 15 sachets/month, that is, a sachet every other day and maximum of one sachet per day. Adherence to distribution (if child receives ≥14 sachets/month) and adherence to instruction (if child receives exactly 15[±1] sachets/month) were assessed monthly by counting used sachets. Factors associated with adherence were examined using generalized estimating equations. Adherence fluctuated over time, an average of 58% adherence to distribution and 28% for adherence to instruction. Average MNP consumption was 79% out of the total sachets provided. Factors positively associated with adherence included ease of use (instruction), child liking MNP and support from community (distribution and instruction) and mother's age >25 years (distribution). Distance to health post, knowledge of correct use (OR = 0.74, 95% CI = 0.66-0.81), perceived negative effects (OR = 0.73, 95% CI = 0.54-0.99) and living in Southern Nations, Nationalities and People Region (OR = 0.59, 95% CI = 0.52-0.67) were inversely associated with adherence to distribution. Free MNP provision, trust in the government and field staff played a role in successful implementation. MNP is promising to be scaled-up, by taking into account factors that positively and negatively determine adherence.

Identifying Dietary Strategies to Improve Nutrient Adequacy among Ethiopian Infants and Young Children Using Linear Modelling.

Nutrient adequacy of young children's diet and best possible strategies to improve nutrient adequacy were assessed. Data from the Ethiopian National Food Consumption Survey were analysed using Optifood (software for linear programming) to identify nutrient gaps in diets for children (6-8, 9-11 and 12-23 months), and to formulate feasible Food-Based Dietary Recommendations (FBDRs) in four regions which differ in culture and food practices. Alternative interventions including a local complementary food, micronutrient powders (MNPs), Small quantity Lipid-based Nutrient Supplement (Sq-LNS) and combinations of these were modelled in combination with the formulated FBDRs to compare their relative contributions. Risk of inadequate and excess nutrient intakes was simulated using the Estimated Average Requirement cut-point method and the full probability approach. Optimized local diets did not provide adequate zinc in all regions and age groups, iron for infants <12 months of age in all regions, and calcium, niacin, thiamine, folate, vitamin B12 and B6 in some regions and age-groups. The set of regional FBDRs, considerably different for four regions, increased nutrient adequacy but some nutrients remained sub-optimal. Combination of regional FBDRs with daily MNP supplementation for 6-12 months of age and every other day for 12-23 months of age, closed the identified nutrient gaps without leading to a substantial increase in the risk of excess intakes.

Review of the evidence regarding the use of antenatal multiple micronutrient supplementation in low- and middle-income countries.

Inadequate micronutrient intakes are relatively common in low- and middle-income countries (LMICs), especially among pregnant women, who have increased micronutrient requirements. This can lead to an increase in adverse pregnancy and birth outcomes. This review presents the conclusions of a task force that set out to assess the prevalence of inadequate micronutrient intakes and adverse birth outcomes in LMICs; the data from trials comparing multiple micronutrient supplements (MMS) that contain iron and folic acid (IFA) with IFA supplements alone; the risks of reaching the upper intake levels with MMS; and the cost-effectiveness of MMS compared with IFA. Recent meta-analyses demonstrate that MMS can reduce the risks of preterm birth, low birth weight, and small for gestational age in comparison with IFA alone. An individual-participant data meta-analysis also revealed even greater benefits for anemic and underweight women and female infants. Importantly, there was no increased risk of harm for the pregnant women or their infants with MMS. These data suggest that countries with inadequate micronutrient intakes should consider supplementing pregnant women with MMS as a cost-effective method to reduce the risk of adverse birth outcomes.

Micronutrient powder supplements combined with nutrition education marginally improve growth amongst children aged 6-23 months in rural Burkina Faso: A cluster randomized controlled trial.

Micronutrients powder (MNP) can prevent anaemia amongst children 6-23 months old. However, evidence of an effect on growth is limited and concerns about the safety of iron-containing MNP interventions limits their applicability. In a cluster randomized controlled intervention, we evaluated the effectiveness of a nutritional package including counselling and provision of MNP to improve the nutritional status of children aged 6-23 months and the effect of sustained use of MNP on morbidity in a malaria-endemic area. Child feeding practises and nutritional status were assessed through cross-sectional surveys. Biweekly morbidity surveillance and anthropometry measurements were carried out in a nested cohort study. No significant differences in the prevalence of wasting (-0.7% [-6.8, 5.3] points; p = .805), stunting (+4.6% [-2.9, 12.0] points; p = .201), or mean length-for-age z-score and weight-for-length z-score scores were found between study groups. The proportion of children with a minimum dietary diversity score and those with a minimum acceptable diet significantly increased in the intervention group compared with the control by 6.5% points (p = .043) and 5.8% points (p = .037), respectively. There were no significant differences in the risk of diarrhoea (RR: 1.68, 95% CI [0.94, 3.08]), fever (RR: 1.20 [0.82, 1.77]), and malaria (RR: 0.68 [0.37, 1.26]) between study groups. In the nested study, the rate of linear growth was higher in the intervention than in the control group by 0.013 SD/month (p = .027). In a programmatic intervention, MNP and nutrition education marginally improved child feeding practises and growth, without increasing morbidity from malaria or fever.

Effect of small-quantity lipid-based nutrient supplements on growth, psychomotor development, iron status, and morbidity among 6- to 12-mo-old infants in South Africa: a randomized controlled trial.

Background: Evidence on the effect of small-quantity lipid-based nutrient supplements (SQ-LNSs) on early child growth and development is mixed. Objective: This study assessed the effect of daily consumption of 2 different SQ-LNS formulations on linear growth (primary outcome), psychomotor development, iron status (secondary outcomes), and morbidity in infants from age 6 to 12 mo within the context of a maize-based complementary diet. Methods: Infants (n = 750) were randomly assigned to receive SQ-LNS, SQ-LNS-plus, or no supplement. Both SQ-LNS products contained micronutrients and essential fatty acids. SQ-LNS-plus contained, in addition, docosahexaenoic acid, arachidonic acid (important for brain and eye development), lysine (limiting amino acid in maize), phytase (enhances iron absorption), and other nutrients. Infants' weight and length were measured bimonthly. At age 6 and 12 mo, psychomotor development using the Kilifi Developmental Inventory and South African Parent Rating Scale and hemoglobin, plasma ferritin, C-reactive protein, and α1-acid glycoprotein were assessed. WHO Motor Milestone outcomes, adherence, and morbidity were monitored weekly through home visits. Primary analysis was by intention-to-treat, comparing each SQ-LNS group with the control. Results: SQ-LNS-plus had a positive effect on length-for-age zscore at age 8 mo (mean difference: 0.11; 95% CI: 0.01, 0.22; P = 0.032) and 10 mo (0.16; 95% CI: 0.04, 0.27; P = 0.008) but not at 12 mo (0.09; 95% CI: -0.02, 0.21; P = 0.115), locomotor development score (2.05; 95% CI: 0.72, 3.38; P = 0.003), and Parent Rating Score (1.10; 95% CI: 0.14, 2.07; P = 0.025), but no effect for weight-for-age zscore. Both SQ-LNS (P = 0.027) and SQ-LNS-plus (P = 0.005) improved hemoglobin concentration and reduced the risk of anemia, iron deficiency, and iron-deficiency anemia. Both SQ-LNS products reduced longitudinal prevalence of fever, coughing, and wheezing but increased incidence and longitudinal prevalence of diarrhea, vomiting, and rash/sores. Conclusions: Point-of-use fortification with SQ-LNS-plus showed an early transient effect on linear growth and improved locomotor development. Both SQ-LNS products had positive impacts on anemia and iron status. This trial was registered at clinicaltrials.gov as NCT01845610.

Effectiveness of a Program Intervention with Reduced-Iron Multiple Micronutrient Powders on Iron Status, Morbidity and Growth in Young Children in Ethiopia.

Despite the potential for improving iron status and child growth in low- and middle-income settings, concerns on the safety of high iron dosages of Micronutrient Powders (MNP currently limit their applicability in programs. We examined the effectiveness and risks of an integrated complementary feeding program with low iron dose (6 mg/serving) MNP among 6⁻23-month-old Ethiopian children using a quasi-experimental study design comparing children from five intervention districts (n = 1172) to those from four matched non-intervention districts (n = 1137). Haemoglobin concentrations increased in intervention and decreased in non-intervention children (group-difference +3.17 g/L), but without improvement in iron stores. Intervention children were 2.31 times more likely to have diarrhoea and 2.08 times more likely to have common cold and flu, but these differences decreased towards the end of the intervention. At end line, intervention children had higher mean Height-for-Age Zscore (HAZ) and a 51% reduced odds of being stunted compared to non-intervention children. MNP with low iron dose, when provided combined with other Infant and Young Child Feeding (IYCF) interventions, marginally improved haemoglobin status and resulted in a remarkable improvement in linear growth in 6⁻23-month-old children. These benefits likely outweigh the relatively small increase in the risk of diarrhoea.

Large-Scale Food Fortification and Biofortification in Low- and Middle-Income Countries: A Review of Programs, Trends, Challenges, and Evidence Gaps.

BACKGROUND: Food fortification and biofortification are well-established strategies to address micronutrient deficiencies in vulnerable populations. However, the effectiveness of fortification programs is not only determined by the biological efficacy of the fortified foods but also by effective and sustainable implementation, which requires continual monitoring, quality assurance and control, and corrective measures to ensure high compliance. OBJECTIVE: To provide an overview of efficacy, effectiveness, economics of food fortification and biofortification, and status of and challenges faced by large-scale food fortification programs in low- and middle-income countries (LMIC). METHODS: A literature review of PubMed publications in English from 2000 to 2017, as well as gray literature, targeting nongovernmental organizations whose work focuses on this topic, complemented by national reports and a "snowball" process of citation searching. The article describes remaining technical challenges, barriers, and evidence gap and prioritizes recommendations and next steps to further accelerate progress and potential of impact. RESULTS: The review identifies and highlights essential components of successful programs. It also points out issues that determine poor program performance, including lack of adequate monitoring and enforcement and poor compliance with standards by industry. CONCLUSIONS: In the last 17 years, large-scale food fortification initiatives have been reaching increasingly larger segments of populations in LMIC. Large-scale food fortification and biofortification should be part of other nutrition-specific and nutrition-sensitive efforts to prevent and control micronutrient deficiencies. There are remaining technical and food system challenges, especially in relation to improving coverage and quality of delivery and measuring progress of national programs.

Fortification of Complementary Foods: A Review of Products and Program Delivery.

Fortified complementary foods (FCF) and home fortificants - single-sachet micronutrient powders (MNP) or small-quantity lipid-based nutrient supplements (SQ-LNS) to be added to a child's food immediately before consumption - have been shown to be efficacious to improve the micronutrient status and some functional outcomes in children 6-23 months of age. The objective of this chapter is to describe and discuss the latest advances related to the composition and delivery of FCF products, including home and commercial fortification. For FCF and MNPs, there is guidance to ensure that products are safe and aligned with recommendations. Impact, however, can be achieved only if adequate attention is paid to program design and implementation, including the choice of the delivery platform, and ensuring availability, accessibility, acceptability, coverage, and utilization by the target population. Well-targeted programs such as social protection programs, health services, community-based vendors (referred to as market based), child health weeks, and emergency programs have all been used as delivery platforms for FCF and MNPs. To date, guidance for formulation and programmatic experience with the distribution of SQ-LNS is limited. An in-depth understanding of the local context and culture, and the design and implementation of program components, including behavior change interventions that respond to those, can increase program coverage and product utilization. Using rigorous process evaluation would permit to adapt programs to increase their potential for impact, strengthen the evidence related to how programs work, and allow the development of program guidance to increase effective implementation.

Community-based grain banks using local foods for improved infant and young child feeding in Ethiopia.

The first thousand days of a child's life are critical for ensuring adequate nutrition to enable optimal health, development and growth. Inadequate infant and young child feeding (IYCF) practices likely contribute to Ethiopia's concerning malnutrition situation. Development partners in four regions of Ethiopia implemented community production of complementary food with women's groups processing local grains and legumes at grain banks to improve availability, accessibility, dietary diversity and timely introduction of complementary foods. The objective of this study was to establish the acceptability, perceived impact, feasibility and required inputs to sustain local grain bank interventions to improve IYCF. A subsidized barter system was used by mothers in the rural communities, and flour was sold in the semi-urban context. Purposive sampling guided the qualitative study design and selection of project stakeholders. A total of 51 key informant interviews and 33 focus group discussions (n = 237) were conducted. The grain bank flour was valued for its perceived diverse local ingredients; while the project was perceived as creating labour savings for women. The grain bank flour offered the potential to contribute to improved IYCF; however, further dietary modification or fortification is needed to improve the micronutrient content. Dependence upon external inputs to subsidize the barter model and the reliance on volunteer labour from women's groups in the rural context are the greatest risks to sustainability. This intervention illustrates how integrated agricultural and health interventions leveraging local production can appeal to diverse stakeholders as an acceptable approach to improve IYCF.

Complementary Feeding Diets Made of Local Foods Can Be Optimized, but Additional Interventions Will Be Needed to Meet Iron and Zinc Requirements in 6- to 23-Month-Old Children in Low- and Middle-Income Countries.

BACKGROUND: The question whether diets composed of local foods can meet recommended nutrient intakes in children aged 6 to 23 months living in low- and middle-income countries is contested. OBJECTIVE: To review evidence of studies evaluating whether (1) macro- and micronutrient requirements of children aged 6 to 23 months from low- and middle-income countries are met by the consumption of locally available foods ("observed intake") and (2) nutrient requirements can be met when the use of local foods is optimized, using modeling techniques ("modeled intake"). METHODS: Twenty-three articles were included after conducting a systematic literature search. To allow for comparisons between studies, findings of 15 observed intake studies were compared against their contribution to a standardized recommended nutrient intake from complementary foods. For studies with data on intake distribution, %< estimated average requirements were calculated. RESULTS: Data from the observed intake studies indicate that children aged 6 to 23 months meet requirements of protein, while diets are inadequate in calcium, iron, and zinc. Also for energy, vitamin A, thiamin, riboflavin, niacin, folate, and vitamin C, children did not always fulfill their requirements. Very few studies reported on vitamin B6, B12, and magnesium, and no conclusions can be drawn for these nutrients. When diets are optimized using modeling techniques, most of these nutrient requirements can be met, with the exception of iron and zinc and in some settings calcium, folate, and B vitamins. CONCLUSION: Our findings suggest that optimizing the use of local foods in diets of children aged 6 to 23 months can improve nutrient intakes; however, additional cost-effective strategies are needed to ensure adequate intakes of iron and zinc.

Current information and Asian perspectives on long-chain polyunsaturated fatty acids in pregnancy, lactation, and infancy: systematic review and practice recommendations from an early nutrition academy workshop.

The Early Nutrition Academy supported a systematic review of human studies on the roles of pre- and postnatal long-chain polyunsaturated fatty acids (LC-PUFA) published from 2008 to 2013 and an expert workshop that reviewed the information and developed recommendations, considering particularly Asian populations. An increased supply of n-3 LC-PUFA during pregnancy reduces the risk of preterm birth before 34 weeks of gestation. Pregnant women should achieve an additional supply ≥200 mg docosahexaenic acid (DHA)/day, usually achieving a total intake ≥300 mg DHA/day. Higher intakes (600-800 mg DHA/day) may provide greater protection against early preterm birth. Some studies indicate beneficial effects of pre- and postnatal DHA supply on child neurodevelopment and allergy risk. Breast-feeding is the best choice for infants. Breast-feeding women should get ≥200 mg DHA/day to achieve a human milk DHA content of ∼0.3% fatty acids. Infant formula for term infants should contain DHA and arachidonic acid (AA) to provide 100 mg DHA/day and 140 mg AA/day. A supply of 100 mg DHA/day should continue during the second half of infancy. We do not provide quantitative advice on AA levels in follow-on formula fed after the introduction of complimentary feeding due to a lack of sufficient data and considerable variation in the AA amounts provided by complimentary foods. Reasonable intakes for very-low-birth weight infants are 18-60 mg/kg/day DHA and 18-45 mg/kg/day AA, while higher intakes (55-60 mg/kg/day DHA, ∼1% fatty acids; 35-45 mg/kg/day AA, ∼0.6-0.75%) appear preferable. Research on the requirements and effects of LC-PUFA during pregnancy, lactation, and early childhood should continue. © 2014 S. Karger AG, Basel.

Intake of fatty acids in general populations worldwide does not meet dietary recommendations to prevent coronary heart disease: a systematic review of data from 40 countries.

AIM: To systematically review data from different countries on population intakes of total fat, saturated fatty acids (SFA) and polyunsaturated fatty acids (PUFA), and to compare these to recommendations from the Food and Agriculture Organization of the United Nations/the World Health Organization (FAO/WHO). METHODS: Data from national dietary surveys or population studies published from 1995 were searched via MEDLINE, Web of Science and websites of national public health institutes. RESULTS: Fatty acid intake data from 40 countries were included. Total fat intake ranged from 11.1 to 46.2 percent of energy intake (% E), SFA from 2.9 to 20.9% E and PUFA from 2.8 to 11.3% E. The mean intakes met the recommendation for total fat (20-35% E), SFA (<10% E) and PUFA (6-11% E) in 25, 11 and 20 countries, respectively. SFA intake correlated with total fat intake (r = 0.76, p < 0.01) but not with PUFA intake (r = 0.03, p = 0.84). Twenty-seven countries provided data on the distribution of fatty acids intake. In 18 of 27 countries, more than 50% of the population had SFA intakes >10% E and in 13 of 27 countries, the majority of the population had PUFA intakes <6% E. CONCLUSIONS: In many countries, the fatty acids intake of adults does not meet the levels that are recommended to prevent chronic diseases. The relation between SFA and PUFA intakes shows that lower intakes of SFA in the populations are not accompanied by higher intakes of PUFA, as is recommended for preventing coronary heart disease.

Effect of antenatal zinc supplementation on impetigo in infants in Bangladesh.

We sought to determine the effects of maternal zinc supplementation on skin infections among infants in poor urban areas of Dhaka, Bangladesh. A double-blind, placebo-controlled, randomized trial was conducted among 199 and 221 Bangladeshi infants whose mothers were administered 30 mg daily of zinc or placebo, respectively. The mothers received zinc supplementation from 12-16 weeks' gestation until delivery, and the infants were followed up until 6 months of age. Among the infants of mothers who received zinc supplementation during the antenatal period, 10.6% had at least 1 episode of impetigo compared with 19.6% of the infants of mothers in the placebo group (P = 0.01). Infants in the treatment group had a 54% reduction in incidence rate of episodes of impetigo when compared with infants in the placebo group (P = 0.01). The effect of zinc supplementation was more pronounced among male infants (64% reduction) and intrauterine growth restricted and low birth weight infants (73% reduction) and among infants of mothers with increased parity (60% reduction) or decreased socioeconomic status (71% reduction).

Essential fats: how do they affect growth and development of infants and young children in developing countries? A literature review.

Omega-3 and omega-6 fatty acids, particularly docosahexaenoic acid (DHA), are known to play an essential role in the development of the brain and retina. Intakes in pregnancy and early life affect growth and cognitive performance later in childhood. However, total fat intake, alpha-linolenic acid (ALA) and DHA intakes are often low among pregnant and lactating women, infants and young children in developing countries. As breast milk is one of the best sources of ALA and DHA, breastfed infants are less likely to be at risk of insufficient intakes than those not breastfed. Enhancing intake of ALA through plant food products (soy beans and oil, canola oil, and foods containing these products such as lipid-based nutrient supplements) has been shown to be feasible. However, because of the low conversion rates of ALA to DHA, it may be more efficient to increase DHA status through increasing fish consumption or DHA fortification, but these approaches may be more costly. In addition, breastfeeding up to 2 years and beyond is recommended to ensure an adequate essential fat intake in early life. Data from developing countries have shown that a higher omega-3 fatty acid intake or supplementation during pregnancy may result in small improvements in birthweight, length and gestational age based on two randomized controlled trials and one cross-sectional study. More rigorous randomized controlled trials are needed to confirm this effect. Limited data from developing countries suggest that ALA or DHA supplementation during lactation and in infants may be beneficial for growth and development of young children 6-24 months of age in these settings. These benefits are more pronounced in undernourished children. However, there is no evidence for improvements in growth following omega-3 fatty acid supplementation in children >2 years of age.

Effect of fortification with multiple micronutrients and n-3 fatty acids on growth and cognitive performance in Indian schoolchildren: the CHAMPION (Children's Health and Mental Performance Influenced by Optimal Nutrition) Study.

BACKGROUND: Fortification with multiple micronutrients has been shown to improve growth and cognitive performance among children in developing countries, but it is unknown whether higher concentrations are more effective than lower concentrations. OBJECTIVE: We compared the effect of 2 different concentrations of a combination of micronutrients and n-3 (omega-3) fatty acids on indicators of growth and cognitive performance in low-income, marginally nourished schoolchildren in Bangalore, India. DESIGN: In a 2-by-2 factorial, double-blind, randomized controlled trial, 598 children aged 6-10 y were individually allocated to 1 of 4 intervention groups to receive foods fortified with either 100% or 15% of the Recommended Dietary Allowance of micronutrients in combination with either 900 mg alpha-linolenic acid plus 100 mg docosahexaenoic acid or 140 mg alpha-linolenic acid for 12 mo. Anthropometric and biochemical assessments were performed at baseline and 12 mo. Cognitive performance was measured at baseline and at 6 and 12 mo. RESULTS: The high micronutrient treatment significantly improved linear growth at 12 mo (0.19 cm; 0.01, 0.36) and short-term memory at 6 mo (0.11 SD; 0.01, 0.20) and was less beneficial on fluid reasoning at 6 (-0.10 SD; -0.17, -0.03) and 12 (-0.12 SD; -0.20, -0.04) mo than was the low micronutrient treatment, whereas no differences were observed on weight, retrieval ability, cognitive speediness, and overall cognitive performance. No significant differences were found between the n-3 treatments. CONCLUSIONS: The high micronutrient treatment was more beneficial for linear growth than was the low micronutrient treatment. However, with some small differential effects, higher micronutrient concentrations were as effective as lower concentrations on cognitive performance. This trial was registered at clinicaltrials.gov as NCT00467909.

Effect of a 12-mo micronutrient intervention on learning and memory in well-nourished and marginally nourished school-aged children: 2 parallel, randomized, placebo-controlled studies in Australia and Indonesia.

BACKGROUND: Little is known about the combined effect of micronutrients and essential fatty acids on cognitive function in school-aged children. OBJECTIVE: We assessed the effect of micronutrients, long-chain n-3 fatty acids, or both on indicators of cognitive performance in well-nourished and marginally nourished school-aged children. DESIGN: Two 2-by-2 factorial randomized controlled double-blind trials were performed home-based in Adelaide, South Australia, and at 6 primary schools in Jakarta, Indonesia. A total of 396 children (aged 6-10 y) in Australia and 384 children in Indonesia were randomly allocated to receive a drink with a micronutrient mix (iron, zinc, folate, and vitamins A, B-6, B-12, and C), with docosahexanoic acid (DHA, 88 mg/d) and eicosapentaenoic acid (EPA, 22 mg/d), or with both or placebo 6 d/wk for 12 mo. Biochemical indicators were determined at baseline and 12 mo. Cognitive performance was measured at baseline, 6 mo, and 12 mo. RESULTS: The micronutrient treatment significantly improved plasma micronutrient concentrations in Australian and Indonesian children. DHA+EPA treatment increased plasma DHA and total plasma n-3 fatty acids in both countries. The micronutrient treatment resulted in significant increases in scores on tests representing verbal learning and memory in Australia (estimated effect size: 0.23; 95% CI: 0.01, 0.46). A similar effect was observed among Indonesian girls (estimated effect size: 0.32; 95% CI: -0.01, 0.64). No effects were found on tests measuring general intelligence or attention. No effects of DHA+EPA on the factors of cognitive tests were observed. CONCLUSION: In well-nourished school-aged children, fortification with multiple micronutrients can result in improvements in verbal learning and memory.

Immunization with the heptavalent pneumococcal conjugate vaccine in Bangladeshi infants and effects of zinc supplementation.

BACKGROUND: Zinc deficiency is known to impair immunologic functions. However, the effect of zinc supplementation on immune response to polysaccharide vaccines is not known. OBJECTIVE: To determine the immunogenicity of the heptavalent Pneumococcal protein conjugate (PNC) vaccine in poor Bangladeshi infants and to assess the effect of zinc supplementation on immune response to the PNC vaccine. DESIGN: We immunized a sub-cohort of 241 infants who had previously received three doses of a Hib conjugate vaccine with three doses of the heptavalent PNC vaccine at 4 weeks intervals beginning at 18+/-1 weeks of age. The infants were supplemented with daily 5 mg zinc or placebo from 4 to 33 weeks of age. Response to each of the seven PNC serotypes were assessed at 4, 24 and 33 weeks of age. RESULTS: After three doses of PNC, at 29 weeks of age, geometric mean titres for the pneumococcal serotypes ranged from 3.68 to 13.34 microg/ml. Titres were significantly higher for infants who had received PNC compared to infants who had only received DTP-Hib. Zinc supplementation resulted in higher titres for serotype 9V (4.09 microg/ml; [95% CI: 3.27; 5.10] and 3.33 microg/ml; [95% CI: 2.79; 3.96] for zinc and placebo group, respectively; p<0.05) after three doses but had no effect on other serotypes. CONCLUSIONS: A heptavalent PNC vaccine proved to be safe and immunogenic in Bangladeshi infants. Zinc supplementation enhanced the immune response to only one of the serotypes (9V). However, there was no effect on other serotypes.

The effect of zinc supplementation during pregnancy on immune response to Hib and BCG vaccines in Bangladesh.

An essential role for zinc in development of the fetal immune system has been documented. However, the effect of antenatal zinc supplementation on infants' postnatal immune response to vaccinations is unknown. The objective of this study was to evaluate the effect of zinc supplementation during pregnancy on immune response to the Bacillus Calmette-Guerin (BCG) vaccine and the Haemophilus influenzae type b (Hib) component of the combined diphtheria, tetanus toxoid and pertussis (DTP)-Haemophilus influenzae type-b (Hib)- conjugate vaccine in poor Bangladeshi infants. We immunized 405 infants whose mothers were supplemented daily with 30 mg elemental zinc or placebo beginning at 12-16 weeks gestation with the standard BCG vaccine at birth. A subcohort of 203 infants were in addition immunized at 1-month intervals with three doses of DTP-Hib vaccine starting at 9 weeks of age. The delayed hypersensitivity (PPD) skin test was performed in 345 infants at 24 weeks of age. Hib polysaccharide (PRP) antibodies were assessed for 91 infants at 4 and 24 weeks of age. In infants born with low birth weight (LBW) a lower proportion of negative responses to PPD skin test were observed in the zinc (66.2%) compared to placebo (78.5%) group (p = 0.07). No differences were observed in normal birth weight infants. There were no differences in proportion of infants above the protective thresholds for anti-PRP antibodies between zinc (81%) and placebo (89%) group. Geometric mean PRP antibody titres at 4 and 24 weeks of age were not different between groups. Zinc supplementation during pregnancy did not enhance immune response to Hib-conjugate vaccine but there was a suggestion of improved delayed hypersensitivity immune responses to BCG-vaccine in Bangladeshi LBW infants.