Micronutrient fortification to improve growth and health of maternally HIV-unexposed and exposed Zambian infants: a randomised controlled trial.

BACKGROUND: The period of complementary feeding, starting around 6 months of age, is a time of high risk for growth faltering and morbidity. Low micronutrient density of locally available foods is a common problem in low income countries. Children of HIV-infected women are especially vulnerable. Although antiretroviral prophylaxis can reduce breast milk HIV transmission in early infancy, there are no clear feeding guidelines for after 6 months. There is a need for acceptable, feasible, affordable, sustainable and safe (AFASS by WHO terminology) foods for both HIV-exposed and unexposed children after 6 months of age. METHODS AND FINDINGS: We conducted in Lusaka, Zambia, a randomised double-blind trial of two locally made infant foods: porridges made of flour composed of maize, beans, bambaranuts and groundnuts. One flour contained a basal and the other a rich level of micronutrient fortification. Infants (n = 743) aged 6 months were randomised to receive either regime for 12 months. The primary outcome was stunting (length-for-age Z<-2) at age 18 months. No significant differences were seen between trial arms overall in proportion stunted at 18 months (adjusted odds ratio 0.87; 95% CI 0.50, 1.53; P = 0.63), mean length-for-age Z score, or rate of hospital referral or death. Among children of HIV-infected mothers who breastfed <6 months (53% of HIV-infected mothers), the richly-fortified porridge increased length-for-age and reduced stunting (adjusted odds ratio 0.17; 95% CI 0.04, 0.84; P = 0.03). Rich fortification improved iron status at 18 months as measured by hemoglobin, ferritin and serum transferrin receptors. CONCLUSIONS: In the whole study population, the rich micronutrient fortification did not reduce stunting or hospital referral but did improve iron status and reduce anemia. Importantly, in the infants of HIV-infected mothers who stopped breastfeeding before 6 months, the rich fortification improved linear growth. Provision of such fortified foods may benefit health of these high risk infants. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN37460449

Impact of food supplements on hemoglobin, iron status, and inflammation in children with moderate acute malnutrition: a 2 × 2 × 3 factorial randomized trial in Burkina Faso.

Background: Children with moderate acute malnutrition (MAM) are treated with lipid-based nutrient supplements (LNSs) or corn-soy blends (CSBs) but little is known about the impact of these supplements on hemoglobin, iron status, and inflammation. Objective: The objective of this study was to investigate the impact of supplementary foods for treatment of MAM on hemoglobin, iron status, inflammation, and malaria. Design: A randomized 2 × 2 × 3 factorial trial was conducted in Burkina Faso. Children aged 6-23 mo with MAM received 500 kcal/d as LNS or CSB, containing either dehulled soy (DS) or soy isolate (SI) and different quantities of dry skimmed milk (0%, 20% or 50% of total protein) for 12 wk. The trial was double-blind with regard to quality of soy and quantity of milk, but not matrix (CSB compared to LNS). Hemoglobin, serum ferritin (SF), serum soluble transferrin receptor (sTfR), serum C-reactive protein (CRP), serum α1-acid glycoprotein (AGP), and malaria antigens were measured at inclusion and after supplementation. Results: Between September 2013 and August 2014, 1609 children were enrolled. Among these, 61 (3.8%) were lost to follow-up. During the 12-wk supplementation period, prevalence of anemia, low SF adjusted for inflammation (SFAI), elevated sTfR, and iron-deficiency anemia decreased by 16.9, 8.7, 12.6 and 10.5 percentage points. Children who received LNS compared to CSB had higher hemoglobin (2 g/L; 95% CI: 1, 4 g/L), SFAI (4.2 µg/L; 95% CI: 2.9, 5.5 µg/L), and CRP (0.8 mg/L; 95% CI: 0.4, 1.2 mg/L) and lower sTfR (-0.9 mg/L, 95% CI: -1.3, -0.6 mg/L) after the intervention. Replacing DS with SI or increasing milk content did not affect hemoglobin, SFAI, sTfR, or CRP. Conclusion: Supplementation with LNS compared to CSB led to better hemoglobin and iron status, but overall prevalence of anemia remained high. The higher concentrations of acute-phase proteins in children who received LNSs requires further investigation. This trial was registered at www.controlled-trials.com as ISRCTN42569496

Micronutrient Fortification to Improve Growth and Health of Maternally HIV-Unexposed and Exposed Zambian Infants: A Randomised Controlled Trial

Background: The period of complementary feeding, starting around 6 months of age, is a time of high risk for growth faltering and morbidity. Low micronutrient density of locally available foods is a common problem in low income countries. Children of HIV-infected women are especially vulnerable. Although antiretroviral prophylaxis can reduce breast milk HIV transmission in early infancy, there are no clear feeding guidelines for after 6 months. There is a need for acceptable, feasible, affordable, sustainable and safe (AFASS by WHO terminology) foods for both HIV-exposed and unexposed children after 6 months of age.Methods and Findings: We conducted in Lusaka, Zambia, a randomised double-blind trial of two locally made infant foods: porridges made of flour composed of maize, beans, bambaranuts and groundnuts. One flour contained a basal and the other a rich level of micronutrient fortification. Infants (n = 743) aged 6 months were randomised to receive either regime for 12 months. The primary outcome was stunting (length-for-age Z < -2) at age 18 months. No significant differences were seen between trial arms overall in proportion stunted at 18 months (adjusted odds ratio 0.87; 95% CI 0.50, 1.53; P = 0.63), mean length-for-age Z score, or rate of hospital referral or death. Among children of HIV-infected mothers who breastfed <6 months (53% of HIV-infected mothers), the richly-fortified porridge increased length-for-age and reduced stunting (adjusted odds ratio 0.17; 95% CI 0.04, 0.84; P = 0.03). Rich fortification improved iron status at 18 months as measured by hemoglobin, ferritin and serum transferrin receptors.Conclusions: In the whole study population, the rich micronutrient fortification did not reduce stunting or hospital referral but did improve iron status and reduce anemia. Importantly, in the infants of HIV-infected mothers who stopped breastfeeding before 6 months, the rich fortification improved linear growth. Provision of such fortified foods may benefit health of these high risk infants

Effect of multiple micronutrient-fortified food on mild morbidity and clinical symptoms in Zambian infants: results from a randomised controlled trial.

BACKGROUND/OBJECTIVES: We aimed to assess the effects on mild morbidity of a richly micronutrient-fortified complementary/replacement food given to Zambian infants aged 6-18 months. Previous results (The Chilenje Infant Growth, Nutrition and Infection Study Team, 2010) showed an increase in the rate of hospital referral for pneumonia in the same cohort. SUBJECT/METHODS: A total of 743 six-month-old healthy Zambian infants were randomised to receive either a richly or a basal micronutrient-fortified porridge for 12 months. Mild morbidity was defined as an illness that did not cause death or require hospitalisation and was diagnosed on clinical examination at scheduled visits. RESULTS: There was no evidence of an effect of trial arm on overall mild morbidity during the study (odds ratio (OR)=1.04, 95% confidence interval (CI)=0.90, 1.20, P=0.62). Infants in the richly fortified arm had significantly more visits in which they were diagnosed with lower respiratory tract infections/pneumonia (OR=1.65, 95% CI=1.06, 2.59, P=0.03) and fewer visits in which a diagnosis of urinary tract infection was made (OR=0.43, 95% CI=0.21, 0.87, P=0.02). Maternally reported symptoms were similar between trial arms. CONCLUSION: Compared with the basal diet, the richly micronutrient-fortified food was associated with more episodes of lower respiratory infections/pneumonia diagnosed at scheduled visits, which reinforces our previously reported findings of a higher incidence in hospital referral for pneumonia

Dietary diversity at 6 months of age is associated with subsequent growth and mediates the effect of maternal education on infant growth in urban Zambia.

BACKGROUND: Although numerous cross-sectional studies have shown an association between WHO infant and young child feeding (IYCF) indicators and child anthropometric measures, limited longitudinal evidence exists linking these indicators with subsequent growth. OBJECTIVES: The purpose of this study was to investigate whether meeting WHO IYCF indicators at 6 and 12 mo of age was associated with growth to 18 mo of age and if dietary diversity mediated the relation between household wealth, maternal education, and child growth. METHODS: We used longitudinal data on 811 infants in the CIGNIS (Chilenje Infant Growth, Nutrition, Infection Study), a randomized controlled trial comparing the effect of micronutrient-fortified porridges on infant growth in Lusaka, Zambia. Twenty-four-h diet recalls were conducted at 6 and 12 mo of age, and length and weight measurements at ages 6 and 18 mo were used to produce height-for-age Z-scores (HAZs) and weight-for-height Z-scores (WHZs). Information on household assets was used to generate a household wealth index, and level of maternal education was collected. RESULTS: In fully adjusted analyses, iron-rich food intake at 6 mo and greater household wealth and maternal education were positively associated with HAZ at 18 mo (all P ≤ 0.016). Iron-rich food intake at 6 and 12 mo, achieving a "minimum acceptable diet" at 12 mo, and higher maternal education were associated with greater WHZ at 18 mo (all P ≤ 0.044). Dietary diversity at 6 mo of age was positively associated with both HAZ and WHZ at 18 mo (both P ≤ 0.001) and mediated 13.4% and 25.9% of the total effect of maternal education on HAZ and WHZ, respectively, at 18 mo. CONCLUSIONS: Our findings indicate that IYCF programs should be targeted toward the early period of complementary food introduction and that policies aimed at increasing formal maternal education may benefit child growth through improved feeding practices. This trial was registered at www.controlled-trials.com as ISRCTN37460449