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Severe acute malnutrition (SAM) is the most life-threatening form of undernutrition and underlies at least 10% of all deaths among children younger than 5 years in low-income countries. SAM is a complex, multisystem disease, with physiological perturbations observed in conjunction with the loss of lean mass, including structural and functional changes in many organ systems. Despite the high mortality burden, predominantly due to infections, the underlying pathogenic pathways remain poorly understood. Intestinal and systemic inflammation is heightened in children with SAM. Chronic inflammation and its consequent immunomodulation may explain the increased morbidity and mortality from infections in children with SAM, both during hospitalization and in the longer term after discharge. Recognition of the role of inflammation in SAM is critical in considering new therapeutic targets in this disease, which has not seen a transformational approach to treatment for several decades. This review highlights the central role of inflammation in the wide-ranging pathophysiology of SAM, as well as identifying potential interventions that have biological plausibility based on evidence from other inflammatory syndromes. [ABSTRACT FROM AUTHOR]

Background Globally, 15 million children are born preterm each year and 10.7 million are born at term but with low birthweight (<2500 g). Methods The Sanitation Hygiene Infant Nutrition Efficacy (SHINE) cluster-randomized trial enrolled 5280 pregnant women between 22 November 2012 and 27 March 2015 to test the impact of improved water supply, sanitation and hygiene, and improved infant feeding, on child growth and anaemia. We conducted a secondary analysis to estimate the prevalence and risk factors of miscarriage, stillbirth, preterm birth, size small for gestational age (SGA), low birthweight (LBW), perinatal mortality, and neonatal mortality, and to estimate the effects of adverse birth outcomes on infant survival and growth.  Results The prevalence of adverse birth outcomes was: miscarriage: 5.0% [95% confidence interval (CI), 4.4, 5.7]; stillbirth: 2.3% (95% CI 1.9, 2.7); preterm birth: 18.2% (95% CI 16.9, 19.5); SGA: 16.1% (95% CI 15.0, 17.3); LBW: 9.8% (95% CI 9.0, 10.7); and neonatal mortality: 31.4/1000 live births (95% CI 26.7, 36.5). Modifiable risk factors included maternal HIV infection, anaemia, lack of antenatal care and non-institutional delivery. Preterm infants had higher neonatal mortality [risk ratio (RR): 6.1 (95% CI 4.0, 9.2)], post-neonatal infant mortality [hazard ratio (HR): 2.1 (95% CI 1.1, 4.1)] and stunting at 18 months of age [RR: 1.5 (95% CI 1.4, 1.7)] than term infants; 56% of stillbirths and 57% of neonatal deaths were among preterm births.  Conclusions Neonatal mortality and stillbirth are high in Zimbabwe and appear to be driven by high preterm birth. Interventions for primary prevention of preterm birth and strengthened management of preterm labour and ill and small neonates are required to reduce neonatal mortality in Zimbabwe and other African countries with similar profiles. [ABSTRACT FROM AUTHOR]

Background: Schistosoma haematobium is a parasitic helminth that causes urogenital pathology. The impact of urogenital schistosomiasis during pregnancy on birth outcomes and child growth is poorly understood.Methods: Risk factors for urogenital schistosomiasis were characterized among 4437 pregnant women enrolled in a cluster-randomized community-based trial in rural Zimbabwe. Infection was defined via urine microscopy (≥1 S. haematobium egg) and urinalysis (hematuria). Associations between infection and pregnancy outcomes were assessed in case-control analyses using conditional logistic regression. The association of maternal infection with birthweight and length-for-age Z scores (LAZ) at 1 and 18 months of age were assessed using generalized estimating equations.Results: Urogenital schistosomiasis (egg positive and/or hematuria positive) was detected in 26.8% of pregnant women. Risk factors significantly associated with infection were maternal age, education, marital status, and religion; household drinking water source and latrine; study region; and season. Urogenital schistosomiasis was not significantly associated with adverse pregnancy outcomes (miscarriage, stillbirth, preterm, and small-for-gestational age), birthweight, neonatal death, or LAZ.Conclusions: Including pregnant women in antihelminthic treatment programs would benefit a large number of women in rural Zimbabwe. However, clearance of the low-intensity infections that predominate in this context is unlikely to have additive benefits for pregnancy outcomes or child growth.Clinical Trials Registration: NCT01824940. [ABSTRACT FROM AUTHOR]

Background Clinical outcomes of children who are human immunodeficiency virus (HIV)–exposed in sub-Saharan Africa remain uncertain. Methods The Sanitation Hygiene Infant Nutrition Efficacy (SHINE) trial evaluated improved infant and young child feeding (IYCF) and/or improved water, sanitation, and hygiene in 2 rural Zimbabwean districts with 15% antenatal HIV prevalence and > 80% prevention of mother-to-child transmission (PMTCT) coverage. Children born between February 2013 and December 2015 had longitudinal HIV testing and anthropometry. We compared mortality and growth between children who were HIV-exposed and HIV-unexposed through 18 months. Children receiving IYCF were excluded from growth analyses. Results Fifty-one of 738 (7%) children who were HIV-exposed and 198 of 3989 (5%) children who were HIV-unexposed (CHU) died (hazard ratio, 1.41 [95% confidence interval {CI}, 1.02–1.93]). Twenty-five (3%) children who were HIV-exposed tested HIV positive, 596 (81%) were HIV-exposed uninfected (CHEU), and 117 (16%) had unknown HIV status by 18 months; overall transmission estimates were 4.3%–7.7%. Mean length-for-age z score at 18 months was 0.38 (95% CI,.24–.51) standard deviations lower among CHEU compared to CHU. Among 367 children exposed to HIV in non-IYCF arms, 147 (40%) were alive, HIV-free, and nonstunted at 18 months, compared to 1169 of 1956 (60%) CHU (absolute difference, 20% [95% CI, 15%–26%]). Conclusions In rural Zimbabwe, mortality remains 40% higher among children exposed to HIV, vertical transmission exceeds elimination targets, and half of CHEU are stunted. We propose the composite outcome of "alive, HIV free, and thriving" as the long-term goal of PMTCT programs. Clinical Trials Registration NCT01824940. [ABSTRACT FROM AUTHOR]

Background: We assessed the impact of water, sanitation, and hygiene (WASH) and infant and young child feeding (IYCF) interventions on enteric infections in the Sanitation Hygiene Infant Nutrition Efficacy (SHINE) trial in rural Zimbabwe.Methods: We tested stool samples collected at 1, 3, 6, and 12 months of age and during diarrhea using quantitative molecular diagnostics for 29 pathogens. We estimated the effects of the WASH, IYCF, and combined WASH + IYCF interventions on individual enteropathogen prevalence and quantity, total numbers of pathogens detected, and incidence of pathogen-attributable diarrhea.Results: WASH interventions decreased the number of parasites detected (difference in number compared to non-WASH arms, -0.07 [95% confidence interval, -.14 to -.02]), but had no statistically significant effects on bacteria, viruses, or the prevalence and quantity of individual enteropathogens after accounting for multiple comparisons. IYCF interventions had no significant effects on individual or total enteropathogens. Neither intervention had significant effects on pathogen-attributable diarrhea.Conclusions: The WASH interventions implemented in SHINE (improved pit latrine, hand-washing stations, liquid soap, point-of-use water chlorination, and clean play space) did not prevent enteric infections. Transformative WASH interventions are needed that are more efficacious in interrupting fecal-oral microbial transmission in children living in highly contaminated environments. [ABSTRACT FROM AUTHOR]

Background Oral vaccines have lower efficacy in developing compared to developed countries. Poor water, sanitation, and hygiene (WASH) may contribute to reduced oral vaccine immunogenicity. Methods We conducted a cluster-randomized 2 × 2 factorial trial in rural Zimbabwe. Pregnant women and their infants were eligible if they lived in clusters randomized to (1) standard of care (52 clusters); (2) improved infant feeding (53 clusters); (3) WASH: ventilated improved pit latrine, 2 hand-washing stations, liquid soap, chlorine, infant play space, and hygiene counseling (53 clusters); or (4) feeding plus WASH (53 clusters). This substudy compared oral rotavirus vaccine (RVV) seroconversion (primary outcome), and seropositivity and geometric mean titer (GMT) (secondary outcomes), in WASH vs non-WASH infants by intention-to-treat analysis. Results We included 801 infants with documented RVV receipt and postvaccine titer measurements (329 from 84 WASH clusters; 472 from 102 non-WASH clusters); 328 infants with prevaccination titers were included in the primary outcome. Thirty-three of 109 (30.3%) infants in the WASH group seroconverted following rotavirus vaccination, compared to 43 of 219 (19.6%) in the non-WASH group (absolute difference, 10.6% [95% confidence interval {CI},.54%–20.7%]; P =.031). In the WASH vs non-WASH groups, 90 of 329 (27.4%) vs 107 of 472 (22.7%) were seropositive postvaccination (absolute difference, 4.7% [95% CI, –1.4% to 10.8%]; P =.130), and antirotavirus GMT was 18.4 (95% CI, 15.6–21.7) U/mL vs 14.9 (95% CI, 13.2–16.8) U/mL (P =.072). Conclusions Improvements in household WASH led to modest but significant increases in seroconversion to RVV in rural Zimbabwean infants. Clinical Trials Registration NCT01824940. [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]

Objective: Immune activation is associated with morbidity and mortality during human immunodeficiency virus (HIV) infection, despite receipt of antiretroviral therapy (ART). We investigated whether microbial translocation drives immune activation in HIV-infected Ugandan children.Methods: Nineteen markers of immune activation and inflammation were measured over 96 weeks in HIV-infected Ugandan children in the CHAPAS-3 Trial and HIV-uninfected age-matched controls. Microbial translocation was assessed using molecular techniques, including next-generation sequencing.Results: Of 249 children included, 142 were infected with HIV; of these, 120 were ART naive, with a median age of 2.8 years (interquartile range [IQR], 1.7-4.0 years) and a median baseline CD4+ T-cell percentage of 20% (IQR, 14%-24%), and 22 were ART experienced, with a median age of 6.5 years (IQR, 5.9-9.2 years) and a median baseline CD4+ T-cell percentage of 35% (IQR, 31%-39%). The control group comprised 107 children without HIV infection. The median increase in the CD4+ T-cell percentage was 17 percentage points (IQR, 12-22 percentage points) at week 96 among ART-naive children, and the viral load was <100 copies/mL in 76% of ART-naive children and 91% of ART-experienced children. Immune activation decreased with ART use. Children could be divided on the basis of immune activation markers into the following 3 clusters: in cluster 1, the majority of children were HIV uninfected; cluster 2 comprised a mix of HIV-uninfected children and HIV-infected ART-naive or ART-experienced children; and in cluster 3, the majority were ART naive. Immune activation was low in cluster 1, decreased in cluster 3, and persisted in cluster 2. Blood microbial DNA levels were negative or very low across groups, with no difference between clusters except for Enterobacteriaceae organisms (the level was higher in cluster 1; P < .0001).Conclusion: Immune activation decreased with ART use, with marker clustering indicating different activation patterns according to HIV and ART status. Levels of bacterial DNA in blood were low regardless of HIV status, ART status, and immune activation status. Microbial translocation did not drive immune activation in this setting.Clinical Trials Registration: ISRCTN69078957. [ABSTRACT FROM AUTHOR]

Background. In sub-Saharan Africa, 20%-25% of people starting antiretroviral therapy (ART) have severe immunosuppression; approximately 10% die within 3 months. In the Reduction of EArly mortaLITY (REALITY) randomized trial, a broad enhanced anti-infection prophylaxis bundle reduced mortality vs cotrimoxazole. We investigate the contribution and timing of different causes of mortality/morbidity. Methods. Participants started ART with a CD4 count <100 cells/µL; enhanced prophylaxis comprised cotrimoxazole plus 12 weeks of isoniazid + fluconazole, single-dose albendazole, and 5 days of azithromycin. A blinded committee adjudicated events and causes of death as (non--mutually exclusively) tuberculosis, cryptococcosis, severe bacterial infection (SBI), other potentially azithromycin-responsive infections, other events, and unknown. Results. Median pre-ART CD4 count was 37 cells/µL. Among 1805 participants, 225 (12.7%) died by week 48. Fatal/nonfatal events occurred early (median 4 weeks); rates then declined exponentially. One hundred fifty-four deaths had single and 71 had multiple causes, including tuberculosis in 4.5% participants, cryptococcosis in 1.1%, SBI in 1.9%, other potentially azithromycin-responsive infections in 1.3%, other events in 3.6%, and unknown in 5.0%. Enhanced prophylaxis reduced deaths from cryptococcosis and unknown causes (P < .05) but not tuberculosis, SBI, potentially azithromycin-responsive infections, or other causes (P > .3); and reduced nonfatal/fatal tuberculosis and cryptococcosis (P < .05), but not SBI, other potentially azithromycin-responsive infections, or other events (P > .2). Conclusions. Enhanced prophylaxis reduced mortality from cryptococcosis and unknown causes and nonfatal tuberculosis and cryptococcosis. High early incidence of fatal/nonfatal events highlights the need for starting enhanced-prophylaxis with ART in advanced disease. Clinical Trials Registration. ISRCTN43622374. [ABSTRACT FROM AUTHOR]

Background: Disease progression is rapid in human immunodeficiency virus (HIV)-infected infants. Whether intestinal damage and inflammation underlie mortality is unknown.Methods: We measured plasma intestinal fatty acid binding protein (I-FABP), soluble CD14 (sCD14), interleukin 6 (IL-6), and C-reactive protein (CRP) at 6 weeks and 6 months of age in 272 HIV-infected infants who either died (cases) or survived (controls), and in 194 HIV-exposed uninfected (HEU) and 197 HIV-unexposed infants. We estimated multivariable odds ratios for mortality and postnatal HIV transmission for each biomarker using logistic regression.Results: At 6 weeks, HIV-infected infants had higher sCD14 and IL-6 but lower I-FABP than HIV-exposed and HIV-unexposed infants (P < .001). CRP was higher in HIV-exposed than HIV-unexposed infants (P = .02). At 6 months, HIV-infected infants had highest sCD14, IL-6, and CRP concentrations (P < .001) and marginally higher I-FABP than other groups (P = .07). CRP remained higher in HIV-exposed vs HIV-unexposed infants (P = .04). No biomarker was associated with mortality in HIV-infected infants, or with odds of breast-milk HIV transmission in HIV-exposed infants.Conclusions: HIV-infected infants have elevated inflammatory markers by 6 weeks of age, which increase over time. In contrast to adults and older children, inflammatory biomarkers were not associated with mortality. HEU infants have higher inflammation than HIV-unexposed infants until at least 6 months, which may contribute to poor health outcomes. [ABSTRACT FROM AUTHOR]

Cytomegalovirus (CMV) acquisition and inflammation were evaluated in 231 human immunodeficiency virus (HIV)-exposed uninfected (HEU) and 100 HIV-unexposed Zimbabwean infants aged 6 weeks. The HEU and HIV-unexposed infants had a similarly high prevalence of CMV (81.4% vs 74.0%, respectively; P = .14), but HEU infants had higher CMV loads (P = .005) and >2-fold higher C-reactive protein (CRP) concentrations (P < .0001). The CMV-positive HEU infants had higher CRP than the CMV-negative HEU infants; this association disappeared after adjusting for maternal HIV load. Overall, CMV acquisition is high in early life, but HEU infants have higher CMV loads and a proinflammatory milieu, which may be driven partly by maternal HIV viremia. [ABSTRACT FROM AUTHOR]

Background: Identifying determinants of morbidity and mortality may help target future interventions for human immunodeficiency virus (HIV)-infected children.Methods: CD4(+) T-cell count, HIV viral load, and levels of biomarkers (C-reactive protein, tumor necrosis factor α [TNF-α], interleukin 6 [IL-6], and soluble CD14) and interleukin 7 were measured at antiretroviral therapy (ART) initiation in the ARROW trial (case-cohort design). Cases were individuals who died, had new or recurrent World Health Organization clinical stage 4 events, or had poor immunological response to ART.Results: There were 115 cases (54 died, 45 had World Health Organization clinical stage 4 events, and 49 had poor immunological response) and 485 controls. Before ART initiation, the median ages of cases and controls were 8.2 years (interquartile range [IQR], 4.4-11.4 years) and 5.8 years (IQR, 2.3-9.3 years), respectively, and the median percentages of lymphocytes expressing CD4 were 4% (IQR, 1%-9%) and 13% (IQR, 8%-18%), respectively. In multivariable logistic regression, cases had lower age-associated CD4(+) T-cell count ratio (calculated as the ratio of the subject's CD4(+) T-cell count to the count expected in healthy individuals of the same age; P < .0001) and higher IL-6 level (P = .002) than controls. Clustering biomarkers and age-associated CD4(+) and CD8(+) T-cell count ratios identified 4 groups of children. Group 1 had the highest frequency of cases (41% cases; 16% died) and profound immunosuppression; group 2 had similar mortality (23% cases; 15% died), but children were younger, with less profound immunosuppression and high levels of inflammatory biomarkers and malnutrition; group 3 comprised young children with moderate immunosuppression, high TNF-α levels, and high age-associated CD8(+) T-cell count ratios but lower frequencies of events (12% cases; 7% died); and group 4 comprised older children with low inflammatory biomarker levels, lower HIV viral loads, and good clinical outcomes (11% cases; 5% died).Conclusions: While immunosuppression is the major determinant of poor outcomes during ART, baseline inflammation is an additional important factor, identifying a subgroup of young children with similar mortality. Antiinflammatory interventions may help improve outcomes. [ABSTRACT FROM AUTHOR]

Advances in DNA sequencing technology now allow us to explore the dynamics and functions of the microbes that inhabit the human body, the microbiota. Recent studies involving experimental animal models suggest a role of the gut microbiota in growth. However, the specific changes in the human gut microbiota that contribute to growth remain unclear, and studies investigating the gut microbiota as a determinant of environmental enteric dysfunction (EED) and child stunting are lacking. In this article, we review the evidence for a link between the developing infant gutmicrobiota, infant feeding, EED, and stunting, and discuss the potential causal pathways relating these variables. We outline the analytic approaches we will use to investigate these relationships, by capitalizing on the longitudinal design and randomized interventions of the Sanitation Hygiene Infant Nutrition Efficacy trial in Zimbabwe. [ABSTRACT FROM AUTHOR]

Children in developing countries experience multiple exposures that are harmful to their growth and development. An emerging concern is frequent exposure to mycotoxins that contaminate a wide range of staple foods, including maize and groundnuts. Three mycotoxins are suspected to contribute to poor child health and development: aflatoxin, fumonisin, and deoxynivalenol. We summarize the evidence that mycotoxin exposure is associated with stunting, and propose that the causal pathway may be through environmental enteric dysfunction (EED) and disturbance of the insulin-like growth factor 1 (IGF-1) axis. The objectives of this substudy are to assess the relationship between agricultural and harvest practices and mycotoxin exposure; to evaluate associations between mycotoxin exposure and child stunting; and to investigate EED as a potential pathway linking mycotoxin exposure to child stunting, to inform potential areas for intervention. [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]

In low-income countries, children ≥4 years and adults with low CD4 count have equally high mortality risk in the 3 months after initiation of antiretroviral therapy, similar to that of untreated individuals. Bacterial infections play a major role; targeted interventions could have important benefits.Background. Adult mortality in the first 3 months on antiretroviral therapy (ART) is higher in low-income than in high-income countries, with more similar mortality after 6 months. However, the specific patterns of changing risk and causes of death have rarely been investigated in adults, nor compared with children in low-income countries.Methods. We used flexible parametric hazard models to investigate how mortality risks varied over the first year on ART in human immunodeficiency virus–infected adults (aged 18–73 years) and children (aged 4 months to 15 years) in 2 trials in Zimbabwe and Uganda.Results. One hundred seventy-nine of 3316 (5.4%) adults and 39 of 1199 (3.3%) children died; half of adult/pediatric deaths occurred in the first 3 months. Mortality variation over year 1 was similar; at all CD4 counts/CD4%, mortality risk was greatest between days 30 and 50, declined rapidly to day 180, then declined more slowly. One-year mortality after initiating ART with 0–49, 50–99 or ≥100 CD4 cells/μL was 9.4%, 4.5%, and 2.9%, respectively, in adults, and 10.1%, 4.4%, and 1.3%, respectively, in children aged 4–15 years. Mortality in children aged 4 months to 3 years initiating ART in equivalent CD4% strata was also similar (0%–4%: 9.1%; 5%–9%: 4.5%; ≥10%: 2.8%). Only 10 of 179 (6%) adult deaths and 1 of 39 (3%) child deaths were probably medication-related. The most common cause of death was septicemia/meningitis in adults (20%, median 76 days) and children (36%, median 79 days); pneumonia also commonly caused child deaths (28%, median 41 days).Conclusions. Children ≥4 years and adults with low CD4 values have remarkably similar, and high, mortality risks in the first 3 months after ART initiation in low-income countries, similar to cohorts of untreated individuals. Bacterial infections are a major cause of death in both adults and children; targeted interventions could have important benefits. [ABSTRACT FROM AUTHOR]

Background Suboptimal breastfeeding contributes to >800,000 global child deaths annually. Optimal breastfeeding includes early initiation (EI) and exclusive breastfeeding (EBF) for the first 6 mo. Objectives We tested the hypothesis that an intervention targeting context and infant age-specific barriers to EI and EBF will achieve a higher EI and EBF prevalence than those of women participating in the concurrently conducted 2015 Zimbabwe Demographic Health Survey (Z-DHS). Methods We designed an intervention to promote EI and EBF, and implemented it within the Sanitation Hygiene Infant Nutrition Efficacy (SHINE) trial in rural Zimbabwe. Intervention modules were delivered at 4 perinatal time points by government-employed village health workers. We compared EI and EBF prevalence among SHINE women who provided outcomes at 1 mo (n  = 2442) and 3 mo (n  = 2728), with women in the 2015 Z-DHS. Results In cross-sectional analyses EI prevalence was 86.6% and 64.3% in the SHINE and Z-DHS samples, respectively; absolute difference (95% CI) = 22.4% (17.5%, 27.3%). EBF prevalence was similarly high (>80%) in both surveys during the first month of life; during 1 to <2 mo, 2 to <3 mo, 3 to <4 mo, 4 to <5 mo, and 5 to <6 mo, EBF prevalence was, respectively, 85%, 90%, 90%, 84%, and 75% in SHINE, and 71%, 65%, 35%, 26%, and 25% in Z-DHS; absolute difference (95% CI) = 50.2% (34.7%, 65.7%) at 5 to <6 mo. Cesarean delivery, mother's belief that intimate partner violence was sometimes justifiable, and having a male infant negatively modified the effects of the intervention. Conclusions The SHINE intervention achieved a high prevalence of EI and EBF. Concurrently addressing gender norms will be critical to make further progress. Formative studies to identify context- and infant age-specific barriers to EI and EBF may inform improvement of breastfeeding practices elsewhere. Important work remains to scale up this intervention beyond a research setting. SHINE was registered at www.clinicaltrials.gov as NCT01824940. [ABSTRACT FROM AUTHOR]