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Low birthweight (LBW) is when an infant is born too soon or too small, and it affects one in seven infants in low- and middle-income countries. LBW has a significant impact on short-term morbidity and mortality, and it impairs long-term health and human capital. Antenatal microbial and inflammatory exposure may contribute to LBW. Ovid-Medline, Embase and Cochrane databases were searched for English-language articles evaluating inflammatory, microbial or infective causes of LBW, small-for-gestational age, intra-uterine growth restriction or prematurity. Inclusion criteria were human studies including published data; conference abstracts and grey literature were excluded. A narrative synthesis of the literature was conducted. Local infections may drive the underlying causes of LBW: for example, vaginitis and placental infection are associated with a greater risk of prematurity. Distal infection and inflammatory pathways are also associated with LBW, with an association between periodontitis and preterm delivery and environmental enteric dysfunction and reduced intra-uterine growth. Systemic maternal infections such as malaria and HIV are associated with LBW, even when infants are exposed to HIV but not infected. This latter association may be driven by chronic inflammation, co-infections and socio-economic confounders. Antimicrobial prophylaxis against other bacteria in pregnancy has shown minimal impact in most trials, though positive effects on birthweight have been found in some settings with a high infectious disease burden. Maternal inflammatory and infective processes underlie LBW, and provide treatable pathways for interventions. However, an improved understanding of the mechanisms and pathways underlying LBW is needed, given the impact of LBW on life-course. [ABSTRACT FROM AUTHOR]

Severe acute malnutrition (SAM) is the most high-risk form of undernutrition, particularly when children require hospitalization for complications. Complicated SAM is a multisystem disease with high inpatient and postdischarge mortality, especially in children with comorbidities such as HIV; however, the underlying pathogenesis of complicated SAM is poorly understood. Targeted multiplex biomarker analysis in children hospitalized with SAM (n = 264) was conducted on plasma samples, and inflammatory markers were assessed on stool samples taken at recruitment, discharge, and 12 to 24 and 48 weeks after discharge from three hospitals in Zimbabwe and Zambia. Compared with adequately nourished controls (n = 173), we found that at baseline, complicated SAM was characterized by systemic, endothelial, and intestinal inflammation, which was exacerbated by HIV infection. This persisted over 48 weeks despite nutritional recovery and was associated with children's outcomes. Baseline plasma concentrations of vascular endothelial growth factor, glucagon-like peptide-2, and intestinal fatty acid–binding protein were independently associated with lower mortality or hospital readmission over the following 48 weeks. Following principal components analysis of baseline biomarkers, higher scores of a component representing growth factors was associated with greater weight-for-height z score recovery and lower mortality or hospital readmission over the 48 weeks. Conversely, components representing higher gut and systemic inflammation were associated with higher mortality or hospital readmission. These findings highlight the interplay between inflammation, which damages tissues, and growth factors, which mediate endothelial and epithelial regeneration, and support further studies investigating interventions to reduce inflammation and promote epithelial repair as an approach to reducing mortality and improving nutritional recovery. Editor's summary: Complicated severe acute malnutrition (SAM) is associated with high mortality even after recovery of nutrition, but the underlying pathophysiology is still poorly understood. Here, Sturgeon and colleagues studied blood, urine, and stool samples from 264 children with SAM from hospitalization to 48 weeks after hospital discharge to better understand the disease. Principal components analyses and structural equation modeling revealed that SAM was characterized by inflammation, endothelial activation, and enteropathy that persisted over the 48 weeks after discharge and that were associated with higher mortality and hospital readmission. Conversely, growth factors indicative of endothelial and epithelial repair were associated with reduced mortality and hospital readmission over 48 weeks. These findings suggest that interventions to decrease inflammation and promote epithelial repair may be beneficial for the treatment of SAM. —Melissa L. Norton [ABSTRACT FROM AUTHOR]

HIV and severe wasting are associated with post-discharge mortality and hospital readmission among children with complicated severe acute malnutrition (SAM); however, the reasons remain unclear. We assessed body composition at hospital discharge, stratified by HIV and oedema status, in a cohort of children with complicated SAM in three hospitals in Zambia and Zimbabwe. We measured skinfold thicknesses and bioelectrical impedance analysis (BIA) to investigate whether fat and lean mass were independent predictors of time to death or readmission. Cox proportional hazards models were used to estimate the association between death/readmission and discharge body composition. Mixed effects models were fitted to compare longitudinal changes in body composition over 1 year. At discharge, 284 and 546 children had complete BIA and skinfold measurements, respectively. Low discharge lean and peripheral fat mass were independently associated with death/hospital readmission. Each unit Z -score increase in impedance index and triceps skinfolds was associated with 48 % (adjusted hazard ratio 0·52, 95 % CI (0·30, 0·90)) and 17 % (adjusted hazard ratio 0·83, 95 % CI (0·71, 0·96)) lower hazard of death/readmission, respectively. HIV-positive v. HIV-negative children had lower gains in sum of skinfolds (mean difference −1·49, 95 % CI (−2·01, −0·97)) and impedance index Z -scores (–0·13, 95 % CI (−0·24, −0·01)) over 52 weeks. Children with non-oedematous v. oedematous SAM had lower mean changes in the sum of skinfolds (–1·47, 95 % CI (−1·97, −0·97)) and impedance index Z -scores (–0·23, 95 % CI (−0·36, −0·09)). Risk stratification to identify children at risk for mortality or readmission, and interventions to increase lean and peripheral fat mass, should be considered in the post-discharge care of these children. [ABSTRACT FROM AUTHOR]

Introduction: Infant and neonatal mortality estimates are typically derived from retrospective birth histories collected through surveys in countries with unreliable civil registration and vital statistics systems. Yet such data are subject to biases, including under-reporting of deaths and age misreporting, which impact mortality estimates. Prospective population-based cohort studies are an underutilized data source for mortality estimation that may offer strengths that avoid biases. Methods: We conducted a secondary analysis of data from the Child Health Epidemiology Reference Group, including 11 population-based pregnancy or birth cohort studies, to evaluate the appropriateness of vital event data for mortality estimation. Analyses were descriptive, summarizing study designs, populations, protocols, and internal checks to assess their impact on data quality. We calculated infant and neonatal morality rates and compared patterns with Demographic and Health Survey (DHS) data. Results: Studies yielded 71,760 pregnant women and 85,095 live births. Specific field protocols, especially pregnancy enrollment, limited exclusion criteria, and frequent follow-up visits after delivery, led to higher birth outcome ascertainment and fewer missing deaths. Most studies had low follow-up loss in pregnancy and the first month with little evidence of date heaping. Among studies in Asia and Latin America, neonatal mortality rates (NMR) were similar to DHS, while several studies in Sub-Saharan Africa had lower NMRs than DHS. Infant mortality varied by study and region between sources. Conclusions: Prospective, population-based cohort studies following rigorous protocols can yield high-quality vital event data to improve characterization of detailed mortality patterns of infants in low- and middle-income countries, especially in the early neonatal period where mortality risk is highest and changes rapidly. [ABSTRACT FROM AUTHOR]

Stunting affects one-in-five children globally and is associated with greater infectious morbidity, mortality and neurodevelopmental deficits. Recent evidence suggests that the early-life gut microbiome affects child growth through immune, metabolic and endocrine pathways. Using whole metagenomic sequencing, we map the assembly of the gut microbiome in 335 children from rural Zimbabwe from 1–18 months of age who were enrolled in the Sanitation, Hygiene, Infant Nutrition Efficacy Trial (SHINE; NCT01824940), a randomized trial of improved water, sanitation and hygiene (WASH) and infant and young child feeding (IYCF). Here, we show that the early-life gut microbiome undergoes programmed assembly that is unresponsive to the randomized interventions intended to improve linear growth. However, maternal HIV infection is associated with over-diversification and over-maturity of the early-life gut microbiome in their uninfected children, in addition to reduced abundance of Bifidobacterium species. Using machine learning models (XGBoost), we show that taxonomic microbiome features are poorly predictive of child growth, however functional metagenomic features, particularly B-vitamin and nucleotide biosynthesis pathways, moderately predict both attained linear and ponderal growth and growth velocity. New approaches targeting the gut microbiome in early childhood may complement efforts to combat child undernutrition.Here, using metagenomics, the authors show that the gut microbiome of rural Zimbabwean infants undergoes programmed maturation that is unresponsive to sanitation and nutrition interventions but is strongly associated with maternal HIV infection and can moderately predict linear growth. [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: 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]

Introduction: Over one billion people live with disability worldwide, of whom 80% are in developing countries. Robust childhood disability data are limited, particularly as tools for identifying disability function poorly at young ages. Methods: A subgroup of children enrolled in the Sanitation Hygiene Infant Nutrition Efficacy (SHINE) trial (a cluster-randomised, community-based, 2x2 factorial trial in two rural districts in Zimbabwe) had neurodevelopmental assessments at 2 years of age. We evaluated functional difficulty prevalence in HIV-exposed and HIV-unexposed children using the Washington Group Child Functioning Module (WGCFM), comparing absolute difference using chi-squared or Fisher's exact tests. Concurrent validity with the Malawi Developmental Assessment Tool (MDAT) was assessed using logistic regression with cohort MDAT score quartiles, linear regression for unit-increase in raw scores and a Generalised Estimating Equation approach (to adjust for clusters) to compare MDAT scores of those with and without functional difficulty. A 3-step, cluster-adjusted multivariable regression model was then carried out to examine risk factors for functional difficulty. Findings: Functional Difficulty prevalence was 4.2% (95%CI: 3.2%, 5.2%) in HIV-unexposed children (n = 1606) versus 6.1% (95%CI: 3.5%, 8.9%) in HIV-exposed children (n = 314) (absolute difference 1.9%, 95%CI: -0.93%, 4.69%; p = 0.14). Functional difficulty score correlated negatively with MDAT: for each unit increase in WGCFM score, children completed 2.6 (95%CI: 2.2, 3.1) fewer MDAT items (p = 0.001). Children from families with food insecurity and poorer housing were more at risk of functional difficulty. Interpretation: Functional difficulty was identified in approximately 1-in-20 children in rural Zimbabwe, which is comparable to prevalence in previous studies. WGCFM showed concurrent validity with the MDAT, supporting its use in early childhood. [ABSTRACT FROM AUTHOR]

Background: Children who are stunted (length-for-age Z-score<-2) are at greater risk of infectious morbidity and mortality. Previous studies suggest that stunted children have elevated inflammatory biomarkers, but no studies have characterised their capacity to respond to new infections (i.e., their immune function). We hypothesised that antibacterial immune function would differ between stunted and non-stunted children and relate to their health and environment during early life. Methods: We enrolled a cross-sectional cohort of 113 HIV-negative children nested within a longitudinal cluster-randomised controlled trial of household-level infant and young child feeding (IYCF) and water, sanitation and hygiene (WASH) interventions in rural Zimbabwe (SHINE; Clinical trials registration: NCT01824940). Venous blood was collected at 18 months of age and cultured for 24 h without antigen or with bacterial antigens: heat-killed Salmonella typhimurium (HKST) or Escherichia coli lipopolysaccharide (LPS). TNFα, IL-6, IL-8, IL-12p70, hepcidin, soluble (s)CD163, myeloperoxidase (MPO) and IFNβ were quantified in culture supernatants by ELISA to determine antigen-specific immune function. The effect of stunting status and early-life exposures (anthropometry, inflammation at 18 months, maternal health during pregnancy, household WASH) on immune function was tested in logit and censored log-normal (tobit) regression models. Results: Children who were stunted (n = 44) had higher proportions (86.4% vs. 65.2%; 88.6% vs. 73.4%) and concentrations of LPS-specific IL-6 (geometric mean difference (95% CI): 3.46 pg/mL (1.09, 10.80), p = 0.035) and IL-8 (3.52 pg/mL (1.20, 10.38), p = 0.022) than non-stunted children (n = 69). Bacterial antigen-specific pro-inflammatory cytokine concentrations were associated with biomarkers of child enteropathy at 18 months and biomarkers of systemic inflammation and enteropathy in their mothers during pregnancy. Children exposed to the WASH intervention (n = 33) produced higher LPS- (GMD (95% CI): 10.48 pg/mL (1.84, 60.31), p = 0.008) and HKST-specific MPO (5.10 pg/mL (1.77, 14.88), p = 0.003) than children in the no WASH group (n = 80). There was no difference in antigen-specific immune function between the IYCF (n = 55) and no IYCF groups (n = 58). Conclusions: Antibacterial immune function among 18-month-old children in a low-income setting was shaped by their stunting status and prior exposure to maternal inflammation and household WASH. Heterogeneity in immune function due to adverse exposures in early life could plausibly contribute to infection susceptibility. [ABSTRACT FROM AUTHOR]

Nutritional recovery and hospital readmission following inpatient management of complicated severe acute malnutrition (SAM) are poorly characterised. We aimed to ascertain patterns and factors associated with hospital readmission, nutritional recovery and morbidity, in children discharged from hospital following management of complicated SAM in Zambia and Zimbabwe over 52‐weeks posthospitalization. Multivariable Fine‐Gray subdistribution hazard models, with death and loss to follow‐up as competing risks, were used to identify factors associated with hospital readmission; negative binomial regression to assess time to hospitalisation and ordinal logistic regression to model factors associated with nutritional recovery. A total of 649 children (53% male, median age 18.2 months) were discharged to continue community nutritional rehabilitation. All‐cause hospital readmission was 15.4% (95% CI 12.7, 18.6) over 52 weeks. Independent risk factors for time to readmission were cerebral palsy (adjusted subhazard ratio (aSHR): 2.96, 95% CI 1.56, 5.61) and nonoedematous SAM (aSHR: 1.64, 95%CI 1.03, 2.64). Unit increases in height‐for‐age Z‐score (HAZ) (aSHR: 0.82, 95% CI 0.71, 0.95) and enrolment in Zambia (aSHR: 0.52, 95% CI 0.28, 0.97) were associated with reduced subhazard of time to readmission. Young age, SAM at discharge, nonoedematous SAM and cerebral palsy were associated with poor nutritional recovery throughout follow‐up. Collectively, nonoedematous SAM, ongoing SAM at discharge, cerebral palsy and low HAZ are independent risk factors for readmission and poor nutritional recovery following complicated SAM. Children with these high‐risk features should be prioritised for additional convalescent care to improve long‐term outcomes. Key messages: One‐in‐six children managed for SAM were readmitted into hospital over the first year after discharge and one‐in‐eight remained undernourished by 52 weeks of follow‐up.Nonoedematous SAM, ongoing SAM at the time of discharge and underlying cerebral palsy were independent risk factors for hospital readmission and poor nutritional recovery.Low HAZ was a risk factor for hospital readmission and poor nutritional recovery.Postdischarge care should focus on children with disability, nonoedematous SAM at initial hospitalisation and have ongoing SAM at the time of discharge.Stunting should be considered in the management of children with SAM. [ABSTRACT FROM AUTHOR]

The prevalence of overweight and obesity is increasing among reproductive-age women in sub-Saharan Africa. Whether maternal body mass index (BMI) influences the risk of infant infections in low- and middle-income countries (LMIC) is uncertain. We used data from a birth cohort of 5344 HIV-unexposed Zimbabwean infants with available data on maternal BMI, to calculate rates of sick clinic visits for infections during the first 12 months postpartum, and adjusted hazard ratios (aHR) for each maternal BMI group. Compared to infants of mothers with normal BMI, the rate of sick clinic visits for any infection progressively rose among infants of overweight (aHR 1.05; 95%CI 0.99, 1.11) and obese women (aHR 1.15; 95%CI 1.05, 1.25). Excess clinic attendances were particularly due to skin, respiratory and ear infections. Maternal obesity may therefore influence infant infectious morbidity in LMIC over the first year after birth. [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: Young children require high-quality care for healthy growth and development. We defined "maternal capabilities" as factors that influence mothers' caregiving ability (physical and mental health, social support, time, decision-making autonomy, gender norm attitudes, and mothering self-efficacy), and developed survey tools to assess them.Objectives: We hypothesized that mothers with stronger capabilities during pregnancy would be more likely to practice improved care behaviors after their child was born.Methods: We assessed maternal capabilities among 4667 pregnant women newly enrolled in the Sanitation Hygiene Infant Nutrition Efficacy (SHINE) trial. Several improved child-care practices were promoted until 18 mo postpartum, the trial endpoint. Care practices were assessed by survey, direct observation, or transcription from health records during postpartum research visits. We used logistic regression to determine the predictive association between maternal capabilities during pregnancy and child-care practices.Results: Mothers with more egalitarian gender norm attitudes were more likely to have an institutional delivery [adjusted OR (AOR), 2.06; 95% CI, 1.57-2.69], initiate breastfeeding within 1 h of delivery (AOR, 1.38; 95% CI, 1.03-1.84), exclusively breastfeed (EBF) from birth to 3 mo (AOR, 2.55; 95% CI, 1.95-3.35) and 3-6 mo (AOR, 1.75; 95% CI, 1.36-2.25), and, among households randomized to receive extra modules on sanitation and hygiene, have soap and water at a handwashing station (AOR, 1.76; 95% CI, 1.29-2.39). Mothers experiencing time stress were less likely to EBF from birth to 3 mo (AOR, 0.79; 95% CI, 0.66-0.93). Greater social support was associated with institutional delivery (AOR, 1.53; 95% CI, 1.37-1.98) and, among mothers randomized to receive extra complementary feeding modules, feeding children a minimally diverse diet (AOR, 1.18; 95% CI, 1.01-1.37). Depressed mothers were 37% and 33%, respectively, less likely to have an institutional delivery (AOR, 0.63; 95% CI, 0.44-0.88) and a fully immunized child (AOR, 0.67; 95% CI, 0.50-0.90).Conclusions: Interventions to reduce maternal depression, time stress, inadequate social support, and inequitable gender norms may improve maternal child caregiving. [ABSTRACT FROM AUTHOR]

Background Children discharged from hospital following management of complicated severe acute malnutrition (SAM) have a high risk of mortality, especially HIV-positive children. Few studies have examined mortality in the antiretroviral therapy (ART) era. Objectives Our objectives were to ascertain 52-wk mortality in children discharged from hospital for management of complicated SAM, and to identify independent predictors of mortality. Methods A prospective cohort study was conducted in children enrolled from 3 hospitals in Zambia and Zimbabwe between July 2016 and March 2018. The primary outcome was mortality at 52 wk. Univariable and multivariable Cox regression models were used to identify independent risk factors for death, and to investigate whether HIV modifies these associations. Results Of 745 children, median age at enrolment was 17.4 mo (IQR: 12.8, 22.1 mo), 21.7% were HIV-positive, and 64.4% had edema. Seventy children (9.4%; 95% CI: 7.4, 11.7%) died and 26 exited during hospitalization; 649 were followed postdischarge. At discharge, 43.9% had ongoing SAM and only 50.8% of HIV-positive children were receiving ART. Vital status was ascertained for 604 (93.1%), of whom 55 (9.1%; 95% CI: 6.9, 11.7%) died at median 16.6 wk (IQR: 9.4, 21.9 wk). Overall, 20.0% (95% CI: 13.5, 27.9%) and 5.6% (95% CI: 3.8, 7.9%) of HIV-positive and HIV-negative children, respectively, died [adjusted hazard ratio (aHR): 3.83; 95% CI: 2.15, 6.82]. Additional independent risk factors for mortality were ongoing SAM (aHR: 2.28; 95% CI: 1.22, 4.25), cerebral palsy (aHR: 5.60; 95% CI: 2.72, 11.50) and nonedematous SAM (aHR: 2.23; 95% CI: 1.24, 4.01), with no evidence of interaction with HIV status. Conclusions HIV-positive children have an almost 4-fold higher mortality than HIV-negative children in the year following hospitalization for complicated SAM. A better understanding of causes of death, an improved continuum of care for HIV and SAM, and targeted interventions to improve convalescence are needed. [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: There is a large treatment gap for common mental disorders in rural areas of low-income countries. We tested the Friendship Bench as a brief psychological intervention delivered by village health workers (VHWs) in rural Zimbabwe. Methods: Rural women identified with depression in a previous trial received weekly home-based problem-solving therapy from VHWs for 6 weeks, and joined a peer-support group. Depression was assessed using the Edinburgh Postnatal Depression Scale (EPDS) and Shona Symptom Questionnaire (SSQ). Acceptability was explored through in-depth interviews and focus group discussions. The proportion of women with depression pre- and post-intervention was compared using McNemar's test. Results: Ten VHWs delivered problem-solving therapy to 27 women of mean age 33 years; 25 completed six sessions. Women valued an established and trustful relationship with their VHW, which ensured confidentiality and prevented gossip, and reported finding individual problem-solving therapy beneficial. Peer-support meetings provided space to share problems, solutions and skills. The proportion of women with depression or suicidal ideation on the EPDS declined from 68% to 12% [difference 56% (95% confidence interval (CI) 27.0–85.0); p = 0.001], and the proportion scoring high (>7) on the SSQ declined from 52% to 4% [difference 48% (95% CI 24.4–71.6); p < 0.001] after the 6-week intervention. Conclusion: VHW-delivered problem-solving therapy and peer-support was acceptable and showed promising results in this pilot evaluation, leading to quantitative and qualitative improvements in mental health among rural Zimbabwean women. Scale-up of the Friendship Bench in rural areas would help close the treatment gap for common mental disorders. [ABSTRACT FROM AUTHOR]

Introduction: Exposure to maternal HIV may affect early child development (ECD), although previous studies have reported heterogeneous findings. We evaluated ECD among children who were HIV‐exposed uninfected (CHEU) and children who were HIV‐unexposed (CHU) recruited to the SHINE trial in rural Zimbabwe. Methods: SHINE was a community‐based cluster‐randomized trial of improved infant feeding and/or improved water, sanitation and hygiene. Pregnant women were enrolled between 2012 and 2015. We assessed ECD in a sub‐study at 24 months of age, between 2016 and 2017, using the Malawi Developmental Assessment Tool (MDAT; assessing motor, cognitive, language and social development); MacArthur‐Bates Communicative Development Inventory (CDI) (assessing vocabulary and grammar); A‐not‐B test (assessing object permanence); and a self‐control task. Mothers and infants were tested longitudinally for HIV. We used generalized estimating equations to compare ECD scores between CHEU and CHU, accounting for the cluster‐randomized design. Primary results were adjusted for trial‐related factors that could affect measurement reliability of ECD: study nurse, age of child, calendar month of birth, sex and randomized arm. Results: A total of 205 CHEU and 1175 CHU were evaluated. Mean total MDAT score was 90.6 (SD 8.7) in CHEU compared to 92.4 (9.1) in CHU (adjusted mean difference −1.3, 95% CI: −2.3, −0.3), driven mostly by differences in gross motor (−0.5, 95% CI: −0.9, −0.2) and language scores (−0.6, 95% CI: −1.1, −0.1). There was evidence that fine motor scores were lower in CHEU (adjusted mean difference −0.4, 95% CI: −0.8, 0.0) but no evidence of a difference in social scores (0.1, 95% CI: −0.2, 0.4). Mean MacArthur‐Bates CDI vocabulary score was 57.9 (SD 19.2) in CHEU compared to 61.3 (18.8) in CHU (adjusted mean difference −2.9 words, 95% CI: −5.7, −0.1). Object permanence and self‐control scores were similar between groups. Conclusions: CHEU in rural Zimbabwe had total child development and vocabulary scores that were approximately 0.15 standard deviations lower than CHU at two years of age. More detailed and specific studies are now needed to unravel the reasons for developmental delay in CHEU and the likelihood that these delays persist in the longer term. [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]

Background: Poverty and human capital development are inextricably linked and therefore research on human capital typically incorporates measures of economic well-being. In the context of randomized trials of health interventions, for example, such measures are used to: 1) assess baseline balance; 2) estimate covariate-adjusted analyses; and 3) conduct subgroup analyses. Many factors characterize economic well-being, however, and analysts often generate summary measures such as indices of household socio-economic status or wealth. In this paper, a household wealth index is developed and tested for participants in the cluster-randomized Sanitation, Hygiene, Infant Nutrition Efficacy (SHINE) trial in rural Zimbabwe. Methods: Building on the approach used in the Zimbabwe Demographic and Health Survey (ZDHS), we combined a set of housing characteristics, ownership of assets and agricultural resources into a wealth index using principal component analysis (PCA) on binary variables. The index was assessed for internal and external validity. Its sensitivity was examined considering an expanded set of variables and an alternative statistical approach of polychoric PCA. Correlation between indices was determined using the Spearman’s rank correlation coefficient and agreement between quintiles using a linear weighted Kappa statistic. Using the 2015 ZDHS data, we constructed a separate index and applied the loadings resulting from that analysis to the SHINE study population, to compare the wealth distribution in the SHINE study with rural Zimbabwe. Results: The derived indices using the different methods were highly correlated (r>0.9), and the wealth quintiles derived from the different indices had substantial to near perfect agreement (linear weighted Kappa>0.7). The indices were strongly associated with a range of assets and other wealth measures, indicating both internal and external validity. Households in SHINE were modestly wealthier than the overall population of households in rural Zimbabwe. Conclusion: The SHINE wealth index developed here is a valid and robust measure of wealth in the sample. [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: HIV-infected infants in sub-Saharan Africa have rapid disease progression. We hypothesized that co-infection with cytomegalovirus (CMV) or Epstein Barr virus (EBV) increases mortality in HIV-infected infants. Methods: 257 antiretroviral therapy-naïve HIV-infected Zimbabwean infants were tested for CMV and EBV at 6 weeks of age by real-time PCR; if positive, birth samples were retrieved where available to distinguish congenital and postnatal infection. The impact of co-infection on mortality through 6 months was estimated using Kaplan-Meier and Cox proportional hazards methods. Results: At 6 weeks, 203/257 (79%) HIV-infected infants were CMV-positive; 27 (11%) had congenital CMV, 108 (42%) postnatal CMV and 68 (26%) indeterminate timing of infection. By 6 months, 37/108 (34%) infants with postnatal CMV versus 16/54 (30%) CMV-negative infants died (adjusted hazard ratio (aHR) 1.1 [95%CI 0.6, 2.2]). At 6 weeks, 33/257 (13%) HIV-infected infants had EBV co-infection; 6 (2%) had congenital EBV, 18 (7%) postnatal EBV and 9 (4%) indeterminate timing of infection. By 6 months, 5/18 (28%) infants with postnatal EBV versus 72/224 (32%) EBV-negative infants died (aHR 0.8 [95%CI 0.3, 2.3]). Conclusions: The vast majority of HIV-infants had acquired CMV by 6 weeks, and EBV co-infection occurred earlier than expected, with one in eight HIV-infected infants positive for EBV by 6 weeks. There was a high prevalence of congenital CMV infection and we identified 6 infants with congenital EBV infection, which has not previously been reported in Africa or in the context of HIV infection. Neither CMV nor EBV co-infection was associated with increased mortality. [ABSTRACT FROM AUTHOR]

Only 5.8% of Zimbabwean infants are exclusively breastfed for the first 6 mo of life despite substantial investment in exclusive breastfeeding (EBF) promotion throughout the country. We conducted a survey of 295 mothers of infants <6 mo of age who were recruited from rural immunization clinics and outreach sites in the Midlands Province of Zimbabwe. We explored infant feeding knowledge, beliefs and attitudes, and details regarding facilitators for EBF mothers and first foods fed by non-EBF mothers to identify and understand barriers to EBF. Among mothers of infants <1 mo, 1 to <2 mo, and 2-6 mo of age, 54%, 30%, and 12%, respectively, were practicing EBF. In adjusted multivariate analyses, EBF practice was positively associated with belief in the sufficiency of EBF (P = 0.05), belief in the avoidance of cooking oil feeding (a common traditional practice) in the first 6 mo (P = 0.001), and perceived pressure from others regarding infant feeding and traditional medicine use (P = 0.03). Psychosocial support and viewing breast milk as sufficient were reported as primary facilitators of EBF practice. Maternal responses to open-ended questions identified protection, nutrition, and crying as the main reasons for EBF interruption. During the first 2 mo of life, "protection feedings" using traditional oral remedies (such as cooking oil and water) to prevent or treat perceived illness, specifically colic and sunken/depressed fontanel, made up 78.5% of the non-breast milk feeds. From the second month of life, "nutrition feedings," mainly of water and porridge, were given when mothers believed their breast milk was insufficient in quantity or quality to meet the hunger or thirst needs of their infants. Our findings underscore the importance of exploring cultural beliefs and practices as they pertain to infant feeding and care and present insights for designing and targeting EBF promotion interventions. [ABSTRACT FROM AUTHOR]

Background: Stunting affects one-third of children in developing countries, but the causes remain unclear. We hypothesized that enteropathy leads to low-grade inflammation, which suppresses the growth hormone-IGF axis and mediates stunting. Methods: We conducted a case-control study of 202 HIV-unexposed Zimbabwean infants who were stunted (height-for-age Z-score (HAZ) <−2; cases) or non-stunted (HAZ >−0.5; controls) at 18 months. We measured biomarkers of intestinal damage (I-FABP), inflammation (CRP, AGP, IL-6) and growth hormone-IGF axis (IGF-1, IGFBP3) in infant plasma at 6 weeks and 3, 6, 12 and 18 months, and in paired maternal-infant plasma at birth. Adjusted mean differences between biomarkers were estimated using regression models. Multivariate odds ratios of stunting were estimated by logistic regression. Results: At birth, cases were shorter (median (IQR) HAZ −1.00 (−1.53, −0.08) vs 0.03 (−0.57, 0.62,); P<0.001) than controls and their mothers had lower levels of IGF-1 (adjusted mean difference (95%CI) −21.4 (−39.8, −3.1) ng/mL). From 6 weeks to 12 months of age, levels of CRP and AGP were consistently higher and IGF-1 and IGFBP3 lower in cases versus controls; IGF-1 correlated inversely with inflammatory markers at all time-points. I-FABP increased between 3–12 months, indicating extensive intestinal damage during infancy, which was similar in cases and controls. In multivariate analysis, higher log10 levels of CRP (aOR 3.06 (95%CI 1.34, 6.99); P = 0.008) and AGP (aOR 7.87 (95%CI 0.74, 83.74); P = 0.087) during infancy were associated with stunting. There were no associations between levels of I-FABP, IL-6, sCD14 or EndoCAb and stunting. Conclusions: Stunting began in utero and was associated with low maternal IGF-1 levels at birth. Inflammatory markers were higher in cases than controls from 6 weeks of age and were associated with lower levels of IGF-1 throughout infancy. Higher levels of CRP and AGP during infancy were associated with stunting. These findings suggest that an extensive enteropathy occurs during infancy and that low-grade chronic inflammation may impair infant growth. [ABSTRACT FROM AUTHOR]

As the World Health Organization ( WHO) infant and young child feeding ( IYCF) indicators are increasingly adopted, a comparison of country-specific analyses of the indicators' associations with child growth is needed to examine the consistency of these relationships across contexts and to assess the strengths and potential limitations of the indicators. This study aims to determine cross-country patterns of associations of each of these indicators with child stunting, wasting, height-for-age z-score ( HAZ) and weight-for-height z-score ( WHZ). Eight studies using recent Demographic and Health Surveys data from a total of nine countries in sub- Saharan Africa (nine), Asia (three) and the Caribbean (one) were identified. The WHO indicators showed mixed associations with child anthropometric indicators across countries. Breastfeeding indicators demonstrated negative associations with HAZ, while indicators of diet diversity and overall diet quality were positively associated with HAZ in Bangladesh, Ethiopia, India and Zambia ( P < 0.05). These same complementary feeding indicators did not show consistent relationships with child stunting. Exclusive breastfeeding under 6 months of age was associated with greater WHZ in Bangladesh and Zambia ( P < 0.05), although CF indicators did not show strong associations with WHZ or wasting. The lack of sensitivity and specificity of many of the IYCF indicators may contribute to the inconsistent associations observed. The WHO indicators are clearly valuable tools for broadly assessing the quality of child diets and for monitoring population trends in IYCF practices over time. However, additional measures of dietary quality and quantity may be necessary to understand how specific IYCF behaviours relate to child growth faltering. [ABSTRACT FROM AUTHOR]

Exclusive breastfeeding (EBF) is rarely practiced despite its significant child survival benefits. A key constraint to increasing EBF rates in Zimbabwe and most of the developing world is that key decision makers (fathers/partners and other family members) are often poorly informed about EBF and do not attend antenatal clinics where health information is routinely provided. Informed by formative research, a district-wide campaign was conducted in rural Zimbabwe to encourage EBF and expressing and heat treating (EHT) breast milk as a means to maintain EBF. The campaign combined traditional strategies of education, counselling and outreach through health service delivery with a novel road show 'edutainment' intervention to reach men and other community members. A post campaign evaluation measured the association of road show exposure with 20 knowledge items and summative scores of social norms, beliefs and attitudes obtained through exploratory factor analysis. In adjusted models, road show exposure was associated with correct EBF knowledge ( β = 1.0, 0.001), EHT knowledge ( β = 1.3, P < 0.001) and greater perceived benefits of condom use during pregnancy and breastfeeding ( β = 0.5, P < 0.001), and more positive EBF social norms ( β = 0.6, P < 0.001), EBF beliefs and attitudes ( β = 1.0, P < 0.001) and attitudes towards condom use during breastfeeding ( β = 0.6, P < 0.001). Road show exposure was more strongly associated with EBF knowledge among men ( P-value for gender × exposure group interaction = 0.03), suggesting that it also closed the knowledge gap between men and women. Longitudinal studies will determine whether road shows were associated with changes in EBF practices. [ABSTRACT FROM AUTHOR]

Supplementation with lipid-based nutrient supplements (LiNS) is promoted as an approach to prevent child undernutrition and growth faltering. Previous LiNS studies have not tested the effects of improving the underlying diet prior to providing LiNS. Formative research was conducted in rural Zimbabwe to develop feeding messages to improve complementary feeding with and without LiNS. Two rounds of Trials of Improved Practices were conducted with mothers of infants aged 6-12 months to assess the feasibility of improving infant diets using (1) only locally available resources and (2) locally available resources plus 20 g of LiNS as Nutributter®/day. Common feeding problems were poor dietary diversity and low energy density. Popular improved practices were to process locally available foods so that infants could swallow them and add processed local foods to enrich porridges. Consumption of beans, fruits, green leafy vegetables, and peanut/seed butters increased after counselling ( P < 0.05). Intakes of energy, protein, vitamin A, folate, calcium, iron and zinc from complementary foods increased significantly after counselling with or without the provision of Nutributter ( P < 0.05). Intakes of fat, folate, iron, and zinc increased only (fat) or more so (folate, iron, and zinc) with the provision of Nutributter ( P < 0.05). While provision of LiNS was crucial to ensure adequate intakes of iron and zinc, educational messages that were barrier-specific and delivered directly to mothers were crucial to improving the underlying diet. [ABSTRACT FROM AUTHOR]

In the context of a prevention of mother to child transmission of HIV program promoting exclusive breast-feeding (EBF) to 6 mo and offering HIV-PCR testing at ∼6 mo, we ascertained the feasibility of expressing and heat-treating (EHT) all breast milk fed to HIV-exposed, uninfected infants following 6 mo of EBF. Twenty mother-baby pairs were enrolled from a hospital in rural Zimbabwe. Research nurses provided lactation, EHT, and complementary feeding counseling through 21 home visits conducted over an 8-wk period and collected quantitative and qualitative data on the mothers' EHT experiences, children's diets, and anthropometric measurements. Mothers kept daily logs of EHT volumes and direct breast-feeding episodes. Mothers successfully initiated and sustained EHT for 4.5 mo (range, 1-11 mo), feeding 426 ± 227 mL/d (mean ± SD). By wk 2 of follow-up, children were receiving EHT and Nutributter-enriched complementary foods that satisfied 100% of their energy requirements. During the 8-wk follow-up period, no growth faltering was experienced [changes in weight-for-age, weight-for-length, and length-for-age Z scores = +0.03 ± 0.50; +0.77 ± 1.59; and +0.02 ± 0.85 (mean ± SD), respectively]. Stigma was not a major deterrent, likely due to a social marketing campaign for EBF that promoted EHT as a practice to sustain breast-feeding for all women. This study provides evidence that resource-poor rural women can initiate and sustain EHT given family and health systems support. EHT provides a strategy for improving the diets of HIV-exposed but uninfected children after direct breast-feeding has ceased. [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]

A letter to the editor is presented in response to the correspondence "Is the Strength of Association Between Indicators of Dietary Quality and the Nutritional Status of Children Being Underestimated?" by A. Thorne-Lyman et al. in the January 2014 issue.