Effect of dietary intervention on the prevalence of asymptomatic malaria among 6-18-month-old children in rural Malawi.

BACKGROUND: The complex interaction between malaria and undernutrition leads to increased mortality and morbidity rate among young children in malaria-endemic regions. Results from previous interventions suggest that improving nutritional status of young children may reduce the burden of malaria. This study tested a hypothesis that provision of lipid-based nutrient supplements (LNS) or corn-soy blend (CSB) supplementation to 6-18-month-old children in Malawi would reduce the prevalence of asymptomatic malaria among them. METHODS: A total of 840 6-month-old children were enrolled in a randomized trial. The participants received 12-month supplementation with three different daily dietary supplementations: CSB, soy-LNS, or milk-LNS, and one control group without supplementation. The prevalence rate of asymptomatic Plasmodium falciparum was determined by real-time PCR from the participant's dried blood spots (DBS) collected at the baseline and every 3 months. The global null hypothesis was tested using modified Poisson regression to estimate the prevalence ratio (PR) between the control group and three intervention groups at all ages combined. All the models were adjusted for malaria at baseline, season of DBS sample collection, site of enrolment, and household asset Z-score. RESULTS: All children combined, the prevalence of P. falciparum was 14.1% at enrollment, 8.7% at 9 months, 11.2% at 12 months, 13.0% at 15 months and 22.4% at 18 months of age. Among all samples that were taken after enrolment, the prevalence was 12.1% in control group, 12.2% in milk-LNS, 14.0% in soy-LNS, and 17.2% in CSB group. Compared to children in the control group the prevalence ratio of positive malaria tests was 1.19 (95% CI 0.81-1.74; P = 0.372) in the milk-LNS group, 1.32 (95% CI 0.88-1.96; P = 0.177) in the soy-LNS group and 1.72 (95% CI 1.19-2.49; P = 0.004) in the CSB group. CONCLUSION: The study findings do not support a hypothesis that LNS or CSB supplementation would reduce the prevalence of asymptomatic malaria among Malawian children. In contrast, there was a signal of a possible increase in malaria prevalence among children supplemented with CSB.

Infant gut microbiota characteristics generally do not modify effects of lipid-based nutrient supplementation on growth or inflammation: secondary analysis of a randomized controlled trial in Malawi.

An unhealthy gut microbial community may act as a barrier to improvement in growth and health outcomes in response to nutritional interventions. The objective of this analysis was to determine whether the infant microbiota modified the effects of a randomized controlled trial of lipid-based nutrient supplements (LNS) in Malawi on growth and inflammation at 12 and 18 months, respectively. We characterized baseline microbiota composition of fecal samples at 6 months of age (n = 506, prior to infant supplementation, which extended to 18 months) using 16S rRNA gene sequencing of the V4 region. Features of the gut microbiota previously identified as being involved in fatty acid or micronutrient metabolism or in outcomes relating to growth and inflammation, especially in children, were investigated. Prior to correction for multiple hypothesis testing, the effects of LNS on growth appeared to be modified by Clostridium (p-for-interaction = 0.02), Ruminococcus (p-for-interaction = 0.007), and Firmicutes (p-for-interaction = 0.04) and effects on inflammation appeared to be modified by Faecalibacterium (p-for-interaction = 0.03) and Streptococcus (p-for-interaction = 0.004). However, after correction for multiple hypothesis testing these findings were not statistically significant, suggesting that the gut microbiota did not alter the effect of LNS on infant growth and inflammation in this cohort.

Provision of Lipid-Based Nutrient Supplements to Mothers During Pregnancy and 6 Months Postpartum and to Their Infants from 6 to 18 Months Promotes Infant Gut Microbiota Diversity at 18 Months of Age but Not Microbiota Maturation in a Rural Malawian Setting: Secondary Outcomes of a Randomized Trial.

BACKGROUND: Diet may alter the configuration of gut microbiota, but the impact of prenatal and postnatal nutritional interventions on infant gut microbiota has not been investigated. OBJECTIVE: We evaluated whether providing lipid-based nutrient supplements (LNSs) to mother-infant dyads promotes a more diverse and mature infant gut microbiota, compared to maternal supplementation with multiple micronutrients (MMN) or iron and folic acid (IFA). METHODS: We enrolled 869 pregnant women in a randomized trial in Malawi. There were 3 study groups, with women receiving 1 MMN capsule daily during pregnancy and 6 mo postpartum, or 1 LNS sachet (20 g) daily during pregnancy and 6 mo postpartum, or 1 IFA capsule daily (during pregnancy) then a placebo daily (postpartum). Infants in the LNS group received LNS from 6 to 18 mo; infants in the other groups did not receive supplements. The infants' fecal microbiota were characterized by PCR amplification and sequencing of the bacterial 16S rRNA gene (variable region 4). The primary outcomes were microbiota α diversity and maturation [as microbiota-for-age z score (MAZ)]. Specific associations of taxa with intervention were established with indicator species analysis (ISA). RESULTS: Primary outcomes did not differ between IFA and MMN groups, so these groups were combined (IFA + MMN). Mean ± SD α diversity was higher in the LNS group at 18 mo for Shannon index [3.01 ± 0.57 (LNS) compared with 2.91 ± 0.60 (IFA + MMN), P = 0.032] and Pielou's evenness index [0.61 ± 0.08 (LNS) compared with 0.60 ± 0.09 (IFA + MMN), P = 0.043]; no significant differences were observed at 1, 6, 12, or 30 mo. MAZ and ß diversity did not differ at any age. We found 10 and 3 operational taxonomic units (OTUs) positively associated with LNS and IFA + MMN, respectively; however, these associations became nonsignificant following false discovery rate correction at 10%. CONCLUSIONS: Prenatal and postnatal LNS intake promoted infant gut microbiota diversity at 18 mo, after 12 mo of child supplementation, but did not alter microbiota maturation. This trial was registered at clinicaltrials.gov as NCT01239693.

Lipid-Based Nutrient Supplements During Pregnancy and Lactation Did Not Affect Human Milk Oligosaccharides and Bioactive Proteins in a Randomized Trial.

BACKGROUND: Human milk oligosaccharides (HMOs) and bioactive proteins are beneficial to infant health. Recent evidence suggests that maternal nutrition may affect the amount of HMOs and proteins in breast milk; however, the effect of nutrient supplementation on HMOs and bioactive proteins has not yet been well studied. OBJECTIVE: We aimed to determine whether lipid-based nutrient supplements (LNSs) affect milk bioactive protein and HMO concentrations at 6 mo postpartum in women in rural Malawi. These are secondary outcomes of a previously published randomized controlled trial. METHODS: Women were randomly assigned to consume either an iron and folic acid capsule (IFA) daily from ≤20 wk gestation until delivery, followed by placebo daily from delivery to 6 mo postpartum, or a multiple micronutrient (MMN) capsule or LNS daily from ≤20 wk gestation to 6 mo postpartum. Breast milk concentrations of total HMOs, sialylated HMOs, fucosylated HMOs, lactoferrin, lactalbumin, lysozymes, antitrypsin, immunoglobulin A, and osteopontin were analyzed at 6 mo postpartum (n = 647). Between-group differences in concentrations and in proportions of women classified as having low concentrations were tested. RESULTS: HMO and bioactive protein concentrations did not differ between groups (P > 0.10 for all comparisons). At 6 mo postpartum, the proportions of women with low HMOs or bioactive proteins were not different between groups except for osteopontin. A lower proportion of women in the IFA group had low osteopontin compared with the LNS group after adjusting for covariates (OR: 0.5; 95% CI: 0.3, 0.9; P = 0.016). CONCLUSION: The study findings do not support the hypothesis that supplementation with an LNS or MMN capsule during pregnancy and postpartum would increase HMO or bioactive milk proteins at 6 mo postpartum among Malawian women. This trial was registered at clinicaltrials.gov as NCT01239693.

Maternal cortisol and stress are associated with birth outcomes, but are not affected by lipid-based nutrient supplements during pregnancy: an analysis of data from a randomized controlled trial in rural Malawi.

BACKGROUND: Prenatal micronutrient supplements have been found to increase birth weight, but mechanisms for increased growth are poorly understood. Our hypotheses were that 1) women who receive lipid-based nutrient supplements (LNS) during pregnancy would have lower mean salivary cortisol concentration at 28 wk and 36 wk gestation compared to the multiple micronutrient (MMN) and iron-folic acid (IFA) supplement groups and 2) both salivary cortisol and perceived stress during pregnancy would be associated with shorter duration of gestation and smaller size at birth. METHODS: Women were enrolled in the trial in early pregnancy and randomized to receive LNS, MMN, or iron-folic acid (IFA) supplements daily throughout pregnancy. At enrollment, 28 wk and 36 wk gestation, saliva samples were collected and their cortisol concentration was measured. Self-report of perceived stress was measured using questionnaires. Gestation duration was indicated by ultrasound dating and newborn anthropometric measurements (weight, length, head circumference) provided indicators of intrauterine growth. RESULTS: Of the 1391 women enrolled in the trial, 1372, 906 and 1049 saliva samples were collected from women at baseline, 28 wk and 36 wk, respectively. There were no significant differences in mean cortisol concentrations by intervention group at 28 wk or 36 wk gestation. Cortisol concentrations were negatively associated with duration of gestation (Baseline: ß = -0.05, p = 0.039; 36 wk: ß = -0.04, p = 0.037) and birth weight (28 wk: ß = -0.08, p = 0.035; 36 wk: ß = -0.11, p = 0.003) but not associated with length-for-age or head circumference-for-age z-scores. Perceived stress at 36 wk was significantly associated with shorter newborn LAZ (p = 0.001). There were no significant associations with the risk of small for gestational age, preterm birth, or low birth weight. CONCLUSIONS: Maternal salivary cortisol concentration was strongly associated with birth weight and duration of gestation in rural Malawi, but these data do not support the hypothesis that LNS provision to pregnant women would influence their salivary cortisol concentrations. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT01239693.