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Stunting affects almost one‐quarter of children globally, leading to reduced human capacity and increased long‐term risk of chronic disease. Despite intensive infant and young child feeding (IYCF) interventions, many children do not meet their requirements for essential nutrients. This study aimed to assess the feasibility of implementing an IYCF intervention utilizing nutrient‐dense powders from egg, biofortified sugar beans and Moringa oleifera leaf in rural Zimbabwe. A mixed‐methods formative study was conducted comprising the following: (i) a recipe formulation trial, (ii) trials of improved practices to assess acceptability of the intervention, and (iii) a participatory message formulation process to develop counselling modules for the IYCF‐plus intervention. Twenty‐seven mother–baby pairs were recruited between November 2019 and April 2020. Key domains affecting IYCF practices that emerged were time, emotional and physical space, cultural and religious beliefs, indigenous knowledge systems and gender dynamics. Household observations and sensory evaluation indicated high acceptability of the new ingredients. Recipe formulation and participatory message formulation by participants instilled community ownership and served to demystify existing misconceptions about the new food products. Families noted the potential for intervention sustainability because the foods could be grown locally. Supplementing complementary foods with nutrient‐dense local food ingredients as powders has the potential to sustainably address nutrient‐gaps in the diets of young children living in rural lower‐ and middle‐income countries. Comprehensive IYCF counselling utilizing a gender‐lens approach, family support and indigenous knowledge systems or resources are key elements to support positive behaviour change in complementary feeding interventions. Key messages: Incorporating locally available solid foods into complementary feeding is a major challenge for caregivers in rural communities. There are several barriers that hinder mothers from feeding nutrient‐dense solid foods such as animal source foods, fruits and vegetables, resulting in nondiversified complementary diets.Formulation of nutrient‐dense, high‐quality protein complementary meals using powdered locally available food supplements is feasible, well tolerated and allows young children to be fed nutrient‐dense complementary meals in rural LMICs.Utilizing traditionally recognized functional foods such as Moringa olifeira encourages the involvement of elderly women/grandmothers in infant and young child feeding, enabling support for mothers.Integrated complementary feeding interventions incorporating behaviour change communication, provision/promotion of specific nutrient‐dense complementary foods (SQ‐LNS and local foods as powdered supplements), family support and agricultural production has potential for success in rural settings. [ABSTRACT FROM AUTHOR]

Background: Inadequate food and water resources negatively affect child health and the efficiency of nutrition interventions. Methods: We used data from the SHINE trial to investigate the associations of food insecurity (FI) and water insecurity (WI) on mothers' implementation and maintenance of minimum infant dietary diversity (MIDD). We conducted factor analysis to identify and score dimensions of FI (poor access, household shocks, low availability & quality), and WI (poor access, poor quality and low reliability). MIDD implementation (n = 636) was adequate if infants aged 12 months (M12) ate ≥ four food groups. MIDD maintenance (n = 624) was categorized into four mutually exclusive groups: A (unmet MIDD at both M12 and M18), B (unmet MIDD at M12 only), C (unmet MIDD at M18 only), and D (met MIDD at both M12 and M18). We used multivariable-adjusted binary logistic and multinomial regressions to determine likelihood of MIDD implementation, and of belonging to MIDD maintenance groups A-C (poor maintenance groups), compared to group D, respectively. Results: Low food availability & quality were negatively associated with implementation (OR = 0.81; 0.69, 0.97), and maintenance (ORB = 1.29; 1.07, 1.56). Poor water quality was positively associated with implementation (OR = 1.25; 1.08, 1.44), but inconsistently associated with maintenance, with higher odds of infants being in group C (OR = 1.39; 1.08, 1.79), and lower odds of being in group B (OR = 0.80; 0.66, 0.96). Conclusion: Food security should be prioritized for adequate implementation and maintenance of infant diets during complementary feeding. The inconsistent findings with water quality indicate the need for further research on WI and infant feeding. [ABSTRACT FROM AUTHOR]

Background Micronutrient deficiencies may contribute to reduced oral vaccine immunogenicity in developing countries. We hypothesised that neonatal vitamin A supplementation (NVAS) would improve oral vaccine responses. Methods We performed a cross-sectional study of infants recruited at birth to the Zimbabwe Vitamin A for Mothers and Babies (ZVITAMBO) trial, a randomised controlled trial of single, high-dose NVAS vs placebo conducted in Zimbabwe between 1997–2001. We measured poliovirus-specific IgA to type 1–3 polio strains by semiquantitative capture ELISA in cryopreserved plasma samples collected at 6 months of age. Results A total of 181 infants fulfilled inclusion criteria, of whom 80 were randomised to NVAS and 101 to placebo. There were no significant differences in baseline characteristics between groups. At 6 months of age, median (IQR) vaccine titres for infants randomised to NVAS vs placebo were 932 (421–3001) vs 1774 (711–5431) for Sabin-1 (p=0.04); 1361 (705–3402) vs 2309 (1081–4283) for Sabin-2 (p=0.15); and 1584 (796–4216) vs 2260 (996–5723) for Sabin-3 (p=0.14), respectively. After adjusting for breast feeding status, birth weight, season and infant sex in a linear regression model, there was only weak evidence of difference in log mean titres between vitamin A and placebo groups for Sabin-1 (p=0.08) and no evidence of difference in log mean titres for Sabin-2 and Sabin-3. Conclusions NVAS did not augment oral polio vaccine responses in Zimbabwean infants. Further research is required to understand the impact of NVAS on responses to other oral vaccines. The trial is registered with clinicaltrials.gov identifier: NCT00198718. [ABSTRACT FROM AUTHOR]

Environmental enteric dysfunction (EED) is a virtually ubiquitous, but poorly defined, disorder of the small intestine among people living in conditions of poverty, which begins early in infancy and persists. EED is characterized by altered gut structure and function, leading to reduced absorptive surface area and impaired intestinal barrier function. It is hypothesized that recurrent exposure to fecal pathogens and changes in the composition of the intestinal microbiota initiate this process, which leads to a self-perpetuating cycle of pathology. We view EED as a primary gut disorder that drives chronic systemic inflammation, leading to growth hormone resistance and impaired linear growth. There is currently no accepted case definition or gold-standard biomarker of EED, making field studies challenging. The Sanitation Hygiene Infant Nutrition Efficacy (SHINE) trial in Zimbabwe is evaluating the independent and combined effects of a package of infant feeding and/or water, sanitation, and hygiene interventions on stunting and anemia. SHINE therefore provides an opportunity to longitudinally evaluate EED in a well-characterized cohort of infants, using a panel of biomarkers along the hypothesized causal pathway. Our aims are to describe the evolution of EED during infancy, ascertain its contribution to stunting, and investigate the impact of the randomized interventions on the EED pathway. In this article, we describe current concepts of EED, challenges in defining the condition, and our approach to evaluating EED in the SHINE trial. [ABSTRACT FROM AUTHOR]

Background: Human immunodeficiency virus (HIV)–infected pregnant women increasingly receive antiretroviral therapy (ART) to prevent mother-to-child transmission (PMTCT). Studies suggest HIV-exposed uninfected (HEU) children face higher mortality than HIV-unexposed children, but most evidence relates to the pre-ART era, breastfeeding of limited duration, and considerable maternal mortality. Maternal ART and prolonged breastfeeding while on ART may improve survival, although this has not been reliably quantified. Methods: Individual data on 19 219 HEU children from 21 PMTCT trials/cohorts undertaken from 1995 to 2015 in Africa and Asia were pooled to estimate the association between 24-month mortality and maternal/infant factors, using random-effects Cox proportional hazards models. Adjusted attributable fractions of risks computed using the predict function in the R package “frailtypack” were used to estimate the relative contribution of risk factors to overall mortality. Results: Cumulative incidence of death was 5.5% (95% confidence interval, 5.1–5.9) by age 24 months. Low birth weight (LBW <2500 g, adjusted hazard ratio (aHR, 2.9), no breastfeeding (aHR, 2.5), and maternal death (aHR, 11.1) were significantly associated with increased mortality. Maternal ART (aHR, 0.5) was significantly associated with lower mortality. At the population level, LBW accounted for 16.2% of 24-month mortality, never breastfeeding for 10.8%, mother not receiving ART for 45.6%, and maternal death for 4.3%; combined, these factors explained 63.6% of deaths by age 24 months. Conclusions: Survival of HEU children could be substantially improved if public health practices provided all HIV-infected mothers with ART and supported optimal infant feeding and care for LBW neonates.

Background: Mother-to-child transmission (MTCT) is the main cause of HIV-1 infection in children worldwide. Given that the C-type lectin receptor, dendritic cell-specific ICAM-grabbing non-integrin-related (DC-SIGNR, also known as CD209L or liver/ lymph node-specific ICAM-grabbing non-integrin (L-SIGN)), can interact with pathogens including HIV-1 and is expressed at the maternal-fetal interface, we hypothesized that it could influence MTCT of HIV-1. Methods and Findings: To investigate the potential role of DC-SIGNR in MTCT of HIV-1, we carried out a genetic association study of DC-SIGNR in a well-characterized cohort of 197 HIV-infected mothers and their infants recruited in Harare, Zimbabwe. Infants harbouring two copies of DC-SIGNR H1 and/or H3 haplotypes (H1-H1, H1-H3, H3-H3) had a 3.6-fold increased risk of in utero (IU) (P = 0.013) HIV-1 infection and a 5.7-fold increased risk of intrapartum (IP) (P = 0.025) HIV-1 infection after adjusting for a number of maternal factors. The implicated H1 and H3 haplotypes share two single nucleotide polymorphisms (SNPs) in promoter region (p-198A) and intron 2 (int2-180A) that were associated with increased risk of both IU (P = 0.045 and P = 0.003, respectively) and IP (P = 0.025, for int2-180A) HIV-1 infection. The promoter variant reduced transcriptional activity in vitro. In homozygous H1 infants bearing both the p-198A and int2-180A mutations, we observed a 4-fold decrease in the level of placental DC-SIGNR transcripts, disproportionately affecting the expression of membrane-bound isoforms compared to infant noncarriers (P = 0.011). Conclusion: These results suggest that DC-SIGNR plays a crucial role in MTCT of HIV-1 and that impaired placental DC-SIGNR expression increases risk of transmission. [ABSTRACT FROM AUTHOR]

Little is known about mothers' perspectives and experiences of early breast-feeding cessation as a strategy to reduce postnatal HIV transmission in rural, resource-constrained settings. We conducted in-depth interviews (IDI) with 15 HIV-positive breast-feeding mothers of infants aged 3-5 mo about their plans for feeding their infants after age 6 mo. We also conducted IDI with 12 HIV-positive mothers who intended to stop breast-feeding after receiving their infant's HIV-PCR negative test result at age 6 mo. Twenty-four-hour dietary recalls were conducted with the same 12 mothers and 16 HIV-negative or status unknown mothers who were breast-feeding their 6- to 9-mo-old infants. Of the 12 mothers who intended to stop breast-feeding, 11 did so by 9 mo. Median energy intake (percent requirement) was 1382 kJ (54%) among weaned infants compared with 2234 kJ (87%) among breast-feeding infants. Median intakes were <67% of the recommended levels for 9 and 7 of the 12 micronutrients assessed for weaned and breast-feeding infants, respectively. Factors facilitating early breast-feeding cessation were mothers' knowledge about HIV transmission, family support, and disclosure of their HIV status; food unavailability was the primary barrier. HIV-positive mothers in resource-constrained settings may be so motivated to protect their child from HIV that they stop breast-feeding early even when they cannot provide an adequate replacement diet. As reflected in the new World Health Organization guidance, HIV-positive mothers should continue breastfeeding their infants beyond 6 mo if replacement feeding is still not acceptable, feasible, affordable, sustainable, and safe. [ABSTRACT FROM AUTHOR]

Background: Anemia is prevalent in infants in developing countries. Its etiology is multifactorial and includes vitamin A deficiency. Objective: Our primary aim was to measure the effect of maternal or neonatal vitamin A supplementation (or both) on hemoglobin and anemia in Zimbabwean infants. Our secondary aim was to identify the underlying causes of postnatal anemia. Design: A randomized, placebo-controlled trial was conducted in 14 110 mothers and their infants; 2854 infants were randomly selected for the anemia substudy, of whom 1592 were successfully observed for 8-14 mo and formed the study sample. Infants were randomly assigned within 96 h of delivery to 1 of 4 treatment groups: mothers and infants received vitamin A; mothers received vitamin A and infants received placebo; mothers received placebo and infants received vitamin A; and mothers and infants received placebo. The vitamin A doses were 400 000 and 50 000 IU in the mothers and infants, respectively. Results: Vitamin A supplementation had no effect on hemoglobin or anemia (hemoglobin <105 g/L) in unadjusted or adjusted analyses. Infant HIV infection independently increased anemia risk >6-fold. Additional predictors of anemia in HIV-negative and -positive infants were male sex and lower total body iron at birth. In addition, in HIV-positive infants, the risk of anemia increased with early infection, low maternal CD4+ lymphocyte count at recruitment, and frequent morbidity. Six-month plasma ferritin concentrations <12 μg/L were a risk factor in HIV-negative but not in HIV-positive infants. Maternal HIV infection alone did not cause anemia. Conclusion: Prevention of infantile anemia should include efforts to increase the birth endowment of iron and prevent HIV infection. [ABSTRACT FROM AUTHOR]

Background. Low maternal serum retinol level is a risk factor for mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV). Multiple-large-dose vitamin A supplementation of HIV-positive children reduces mortality. The World Health Organization recommends single-large-dose vitamin A supplementation for postpartum women in areas of prevalent vitamin A deficiency; neonatal dosing is under consideration. We investigated the effect that single-large-dose maternal/neonatal vitamin A supplementation has on MTCT, HIV-free survival, and mortality in HIV-exposed infants. Methods. A total of 4495 HIV-positive women and their infants were enrolled ⩽96 h after delivery, and both mother and infant, mother only, infant only, or neither received vitamin A supplementation in a randomized, placebo-controlled trial with a 2 × 2 factorial design. Results. Neither maternal nor neonatal vitamin A supplementation significantly affected postnatal MTCT or overall infant mortality. However, the timing of infant HIV infection modified the effect that supplementation had on mortality. Vitamin A supplementation had no effect in infants who were polymerase chain reaction (PCR) negative for HIV at baseline. In infants who were PCR negative at baseline and PCR positive at 6 weeks, neonatal supplementation reduced mortality by 28% (P = .01), but maternal supplementation had no effect. In infants who were PCR negative at 6 weeks, all 3 vitamin A regimens were associated with ∼2-fold higher mortality (P⩽.05). Conclusions. Targeted vitamin A supplementation of HIV-positive children prolongs their survival. However, postpartum maternal and neonatal vitamin A supplementation may hasten progression to death in breast-fed infants who are PCR negative at 6 weeks. These findings raise concern about universal maternal or neonatal vitamin A supplementation in HIV-endemic areas. [ABSTRACT FROM AUTHOR]

Examines the delicate balance between life-saving benefits and the HIV infection risks of breastfeeding for babies born to HIV-positive women in Africa. Breastfeeding transmission of HIV; Safer breastfeeding practices to reduce HIV risks.

The article focuses on a study to examine normal hepcidin levels in healthy, non-anaemic, Zimbabwean infants. According to the study, cryopreserved plasma samples from the project Zimbabwe Vitamin A for Mothers and Babies (ZTAMBO), a randomized controlled trial (RCT) of maternal and neonatal vitamin supplementation were used for the analysis. The study also mentions that various techniques were used to analyse hemoglobin and hepcidin levels such as enzyme immunoassay and haemoglobinometer.

A letter to the editor is presented about the effectiveness of vitamin A supplementation in improving infant survival.

Oral rotavirus vaccine (RVV) immunogenicity is considerably lower in low- versus high-income populations; however, the mechanisms underlying this remain unclear. Previous evidence suggests that the gut microbiota may contribute to differences in oral vaccine efficacy. We performed whole metagenome shotgun sequencing on stool samples and measured anti-rotavirus immunoglobulin A in plasma samples from a subset of infants enrolled in a cluster randomized 2 × 2 factorial trial of improved water, sanitation and hygiene and infant feeding in rural Zimbabwe (SHINE trial: NCT01824940). We examined taxonomic microbiome composition and functional metagenome features using random forest models, differential abundance testing and regression analyses to explored associations with RVV immunogenicity. Among 158 infants with stool samples and anti-rotavirus IgA titres, 34 were RVV seroconverters. The median age at stool collection was 43 days (IQR: 35–68), corresponding to a median of 4 days before the first RVV dose. The infant microbiome was dominated by Bifidobacterium longum. The gut microbiome differed significantly between early (≤42 days) and later samples (>42 days) however, we observed no meaningful differences in alpha diversity, beta diversity, species composition or functional metagenomic features by RVV seroconversion status. Bacteroides thetaiotaomicron was the only species associated with anti-rotavirus IgA titre. Random forest models poorly classified seroconversion status by both composition and functional microbiome variables. RVV immunogenicity is low in this rural Zimbabwean setting, however it was not associated with the composition or function of the early-life gut microbiome in this study. Further research is warranted to examine the mechanisms of poor oral RVV efficacy in low-income countries. [ABSTRACT FROM AUTHOR]

Oral rotavirus vaccines (RVV) have poor immunogenicity in low-income countries, for reasons that remain unclear. This study identified the determinants of RVV immunogenicity among infants in rural Zimbabwe. Anti-rotavirus IgA titres were measured among a sub-group of infants enrolled in the Sanitation Hygiene Infant Nutrition Efficacy (SHINE) trial (NCT01824940). SHINE was a cluster-randomized trial of improved infant and young child feeding, and improved water, sanitation and hygiene (WASH) in two rural Zimbabwean districts. Infants received RVV as part of the national immunisation programme. Among HIV-unexposed infants in the non-WASH trial arms, we evaluated associations between potential risk factors (vaccine schedule and dose, maternal and infant nutritional status, infant diarrhoea, and household environment) and RVV immunogenicity (seroconversion, seropositivity and geometric mean titres) using multivariable regression. Among 219 infants with seroconversion data, 43 (20%) successfully seroconverted and 176 (80%) failed to seroconvert to RVV. Seroconversion was positively associated with a higher length-for-age Z-score (LAZ) around the time of vaccination (adjusted RR 1.27 (95% CI 1.04, 1.55), P = 0.021), and negatively associated with concurrent OPV and RVV administration (adjusted RR 0.36 (0.19, 0.71), P = 0.003). Among 472 infants with post-vaccination titres, a higher LAZ score was associated with increased seropositivity (aRR 1.21 (95% CI 1.06, 1.38), P = 0.004), and higher birthweight was associated with increased IgA titres (0.45 (95%CI 0.18, 1.09) U/mL greater per 100 g gain in birthweight; P = 0.001). Infant ponderal and linear growth were positively associated with RVV immunogenicity, while concurrent administration of OPV was negatively associated with RVV immunogenicity. Together, these findings suggest that improving foetal growth and separating RVV and OPV administration are plausible approaches to increasing RVV immunogenicity. [ABSTRACT FROM AUTHOR]