Mortality risk in infants receiving therapeutic care for malnutrition: A secondary analysis.

Small and nutritionally at-risk infants aged under 6 months (<6 months) are at high risk of death, but important evidence gaps exist on how to best identify them. We aimed to determine associations between anthropometric deficits and mortality among infants <6 months admitted to inpatient therapeutic care. A secondary analysis of 2002-2008 data included 5034 infants aged <6 months from 12 countries. We estimated the prevalence, concurrence, and severity of wasted, stunted, and underweight, as stand-alone indicators, and using the Composite Index of Anthropometric Failure (CIAF), which combines these indicators into six subgroups of single and multiple anthropometric deficits and into one combined indicator called CIAF. We used logistic regression to examine the association of different anthropometric deficits with in-programme mortality. Among 3692 infants aged <6 months with complete data, 3539 (95.8%) were underweight, 3058 (82.8%) were wasted, 2875 (77.8%) were stunted and 3575 (96.8%) had CIAF. Infants with multiple anthropometric deficits were presented with significantly lower anthropometric indices, that is, they were more severely wasted, stunted and underweight. A total of 141 infants died during inpatient therapeutic care. Among these, severely wasted (116) and severely underweight (138) infants had higher odds of mortality than normal infants (odds ratio [OR] = 2.1, 95% confidence interval [CI]: 1.2-2.7, p = 0.009, and OR = 3.3, 95% CI: 0.8-13.6, p = 0.09, respectively). Boys had higher odds of inpatient mortality than girls (OR = 1.40, 95% CI: 1.02-1.92, p = 0.03). Mortality was only observed in infants <6 months presenting multiple anthropometric deficits, although their odds of mortality were not significant, for example, OR = 2.4, 95% CI: 0.5-10.0, p = 0.21 for stunted, wasted and underweight infants <6 months. In conclusion, multiple anthropometric deficits (CIAF) is common among infants <6 months and may be reported in nutrition care programmes and surveys. Both weight-for-length/height z-score and weight-for-age z-score were found to be useful indicators for programme admission and in-programme prognosis. Future work needs to explore which better accounts for admission bias. Boys appear to be most at-risk of dying while receiving malnutrition therapeutic care. Programmes should ensure that all infants receive timely, evidence-based, effective care.

Duodenal Microbiota in Stunted Undernourished Children with Enteropathy.

BACKGROUND: Environmental enteric dysfunction (EED) is an enigmatic disorder of the small intestine that is postulated to play a role in childhood undernutrition, a pressing global health problem. Defining the incidence of this disorder, its pathophysiological features, and its contribution to impaired linear and ponderal growth has been hampered by the difficulty in directly sampling the small intestinal mucosa and microbial community (microbiota). METHODS: In this study, among 110 young children (mean age, 18 months) with linear growth stunting who were living in an urban slum in Dhaka, Bangladesh, and had not benefited from a nutritional intervention, we performed endoscopy in 80 children who had biopsy-confirmed EED and available plasma and duodenal samples. We quantified the levels of 4077 plasma proteins and 2619 proteins in duodenal biopsy samples obtained from these children. The levels of bacterial strains in microbiota recovered from duodenal aspirate from each child were determined with the use of culture-independent methods. In addition, we obtained 21 plasma samples and 27 fecal samples from age-matched healthy children living in the same area. Young germ-free mice that had been fed a Bangladeshi diet were colonized with bacterial strains cultured from the duodenal aspirates. RESULTS: Of the bacterial strains that were obtained from the children, the absolute levels of a shared group of 14 taxa (which are not typically classified as enteropathogens) were negatively correlated with linear growth (length-for-age z score, r = -0.49; P = 0.003) and positively correlated with duodenal proteins involved in immunoinflammatory responses. The representation of these 14 duodenal taxa in fecal microbiota was significantly different from that in samples obtained from healthy children (P<0.001 by permutational multivariate analysis of variance). Enteropathy of the small intestine developed in gnotobiotic mice that had been colonized with cultured duodenal strains obtained from children with EED. CONCLUSIONS: These results provide support for a causal relationship between growth stunting and components of the small intestinal microbiota and enteropathy and offer a rationale for developing therapies that target these microbial contributions to EED. (Funded by the Bill and Melinda Gates Foundation and others; ClinicalTrials.gov number, NCT02812615.).

Risk factors for early occurrence of malnutrition in infants with severe congenital heart disease.

To identify the risk factors of early occurrence of malnutrition in infants with severe congenital heart disease (CHD) during their first year of life. Retrospective longitudinal multicenter study carried out from January 2014 to December 2020 in two tertiary care CHD centers. Four CHD hemodynamic groups were identified. Malnutrition was defined by a Waterlow score under 80% and/or underweight under -2 standard deviations. A total of 216 infants with a severe CHD, e.g., requiring cardiac surgery, cardiac catheterization, or hospitalization for heart failure during their first year of life, were included in the study. Malnutrition was observed among 43% of the cohort, with the highest prevalence in infants with increased pulmonary blood flow (71%) compared to the other hemodynamic groups (p < 0.001). In multivariate analysis, low birthweight (OR 0.62, 95% CI 0.44-0.89, p = 0.009), CHD with increased pulmonary blood flow (OR 4.80, 95% CI 1.42-16.20, p = 0.08), heart failure (OR 9.26, 95% CI 4.04-21.25, p < 0.001), and the number of hospitalizations (OR 1.35, 95% CI 1.08 l-1.69, p = 0.009) during the first year of life were associated with malnutrition (AUC 0.85, 95% CI 0.79-0.90).  Conclusions: In infants with a severe CHD, early occurrence of malnutrition during the first year of life affected a high proportion of subjects. CHD with increased pulmonary blood flow, low birthweight, heart failure, and repeated hospitalizations were risk factors for malnutrition. Further studies are required to identify optimal nutritional support in this population. What is Known: • Malnutrition is a known morbidity and mortality factor in children with severe congenital heart disease. What is New: • Early occurrence of malnutrition during the first year of life in infant severe congenital heart disease (CHD) was high (43%). • CHD with increased pulmonary blood flow, low birthweight, heart failure, and repeated hospitalizations during the first year of life were risk factors for malnutrition.

INTERGROWTH-21st versus a customized method for the prediction of neonatal nutritional status in hypertensive disorders of pregnancy.

BACKGROUND: Hypertensive disorders of pregnancy (HDP) generate complications and are one of the principal causes of maternal, foetal, and neonatal mortality worldwide. It has been observed that in pregnancies with HDP, the incidence of foetuses small for their gestational age (SGA) is twice as high as that in noncomplicated pregnancies. In women with HDP, the identification of foetuses (SGA) is substantially important, as management and follow-up are determined by this information. OBJECTIVE: The objective of this study was to evaluate whether the INTERGROWTH-21st method or customized birthweight references better identify newborns with an abnormal nutritional status resulting from HDP. METHOD: A comparative analysis study was designed with two diagnostic methods for the prediction of neonatal nutritional status in pregnancies with HDP. The performance of both methods in identifying neonatal malnutrition (defined by a neonatal body mass index < 10th centile or a ponderal index < 10th centile) was assessed by calculating sensitivity, specificity, positive predictive value, negative predictive value, diagnostic odds ratio, Youden's index and probability ratios. RESULTS: The study included 226 pregnant women diagnosed with HDP. The customized method identified 45 foetuses as small for gestational age (19.9%), while the INTERGROWTH-21st method identified 27 newborns with SGA (11.9%). The difference between proportions was statistically significant (p < 0.01). Using body mass index (< 10th centile) as a measure of nutritional status, newborns identified as SGA by the customized method showed a higher risk of malnutrition than those identified as SGA by INTERGROWTH-21st (RR: 4.87 (95% CI: 1.86-12.77) vs. 3.75 (95% CI: 1.49-9.43)) (DOR: 5.56 (95% CI: 1.82-16.98) vs. 4.84 (95% CI: 1.51-15.54)) Even when using Ponderal index (< 10th centile), newborns identified as SGA by the customized method showed a higher risk of malnutrition than those identified as SGA by INTERGROWTH-21st (RR 2.37 (95% CI: 1.11-5.05) vs. 1.68 (95% CI: 0.70-4.03))(DOR 2.62 (95% CI: 1.00-6.87) vs. 1.90 (95% CI: 0.61-5.92)). CONCLUSION: In pregnant women with HDP, the predictive ability of the customized foetal growth curves to identify neonatal malnutrition appears to surpass that of INTERGROWTH-21st.

Bile Acid Profiling Reveals Distinct Signatures in Undernourished Children with Environmental Enteric Dysfunction.

BACKGROUND: Intestinal inflammation and malabsorption in environmental enteric dysfunction (EED) are associated with early childhood growth faltering in impoverished settings worldwide. OBJECTIVES: The goal of this study was to identify candidate biomarkers associated with inflammation, EED histology, and as predictors of later growth outcomes by focusing on the liver-gut axis by investigating the bile acid metabolome. METHODS: Undernourished rural Pakistani infants (n = 365) with weight-for-height Z score (WHZ) < -2 were followed up to the age of 24 mo and monitored for growth, infections, and EED. Well-nourished local children (n = 51) were controls, based on consistent WHZ > 0 and height-for-age Z score (HAZ) > -1 on 2 consecutive visits at 3 and 6 mo. Serum bile acid (sBA) profiles were measured by tandem MS at the ages of 3-6 and 9 mo and before nutritional intervention. Biopsies and duodenal aspirates were obtained following upper gastrointestinal endoscopy from a subset of children (n = 63) that responded poorly to nutritional intervention. BA composition in paired plasma and duodenal aspirates was compared based on the severity of EED histopathological scores and correlated to clinical and growth outcomes. RESULTS: Remarkably, >70% of undernourished Pakistani infants displayed elevated sBA concentrations consistent with subclinical cholestasis. Serum glycocholic acid (GCA) correlated with linear growth faltering (HAZ, r = -0.252 and -0.295 at the age of 3-6 and 9 mo, respectively, P <0.001) and biomarkers of inflammation. The proportion of GCA positively correlated with EED severity for both plasma (rs = 0.324 P = 0.02) and duodenal aspirates (rs = 0.307 P = 0.06) in children with refractory wasting that underwent endoscopy, and the proportion of secondary BA was low in both undernourished and EED children. CONCLUSIONS: Dysregulated bile acid metabolism is associated with growth faltering and EED severity in undernourished children. Restoration of intestinal BA homeostasis may offer a novel therapeutic target for undernutrition in children with EED. This trial was registered at clinicaltrials.gov as NCT03588013.

Higher Energy and Zinc Intakes from Complementary Feeding Are Associated with Decreased Risk of Undernutrition in Children from South America, Africa, and Asia.

BACKGROUND: Few studies have focused on quantitatively analyzing nutrients from infant diets, compromising complementary feeding evaluation and health promotion worldwide. OBJECTIVES: This study aimed to describe dietary intake in infants from 9 to 24 mo of age, determining nutrient intakes associated with the risk of underweight, wasting, and stunting. METHODS: Usual nutrient intakes from complementary feeding were determined by 24-h recalls collected when infants were 9-24 mo of age in communities from 7 low- and middle-income countries: Brazil (n = 169), Peru (n = 199), South Africa (n = 221), Tanzania (n = 210), Bangladesh (n = 208), India (n = 227), and Nepal (n = 229), totaling 1463 children and 22,282 food recalls. Intakes were corrected for within- and between-person variance and energy intake. Multivariable regression models were constructed to determine nutrient intakes associated with the development of underweight, wasting, and stunting at 12, 18, and 24 mo of age. RESULTS: Children with malnutrition presented significantly lower intakes of energy and zinc at 12, 18, and 24 mo of age, ranging from -16.4% to -25.9% for energy and -2.3% to -48.8% for zinc. Higher energy intakes decreased the risk of underweight at 12 [adjusted odds ratio (AOR): 0.90; 95% CI: 0.84, 0.96] and 24 mo (AOR: 0.91; 95% CI: 0.86, 0.96), and wasting at 18 (AOR: 0.91; 95% CI: 0.83, 0.99) and 24 mo (AOR: 0.83; 95% CI: 0.74, 0.92). Higher zinc intakes decreased the risk of underweight (AOR: 0.12; 95% CI: 0.03, 0.55) and wasting (AOR: 0.19; 95% CI: 0.04, 0.92) at 12 mo, and wasting (AOR: 0.05; 95% CI: 0.00, 0.76) at 24 mo. CONCLUSIONS: Higher intakes of energy and zinc in complementary feeding were associated with decreased risk of undernutrition in the studied children. Data suggest these are characteristics to be improved in children's complementary feeding across countries.

Interdisciplinary care of children with trisomy 13 and 18.

Children with trisomy 13 and 18 (previously deemed "incompatible with life") are living longer, warranting a comprehensive overview of their unique comorbidities and complex care needs. This Review Article provides a summation of the recent literature, informed by the study team's Interdisciplinary Trisomy Translational Program consisting of representatives from: cardiology, cardiothoracic surgery, neonatology, otolaryngology, intensive care, neurology, social work, chaplaincy, nursing, and palliative care. Medical interventions are discussed in the context of decisional-paradigms and whole-family considerations. The communication format, educational endeavors, and lessons learned from the study team's interdisciplinary care processes are shared with recognition of the potential for replication and implementation in other care settings.

Use of TaqMan Array Cards to investigate the aetiological agents of diarrhoea among young infants with severe acute malnutrition.

OBJECTIVE: Studies involving less sensitive conventional microscopy and culture-based approaches have identified distinct differences in diarrhoeal aetiology in childhood malnutrition. Our study involved the use of an advanced molecular biology technique, the TaqMan Array Cards (TAC), to elucidate the diarrhoeal aetiology among young infants with severe acute malnutrition (SAM). METHOD: A total of 113 faecal samples was collected from SAM infants, aged 2-6 months, upon admission to the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b) with complications of diarrhoea and related comorbidities. We used TAC for the detection of 29 different diarrhoeal enteropathogens from a single faecal sample. For comparison, we also analysed 25 diarrhoeal samples from well-nourished infants of similar age. RESULTS: Higher odds of detection of all bacterial enteropathogens were associated with diarrhoea among SAM infants. In particular, the detection of Aeromonas sp (aOR: 25.7, p = 0.011), Campylobacter sp (aOR: 9.6, p < 0.01) and ETEC (aOR: 5.2, p = 0.022) was significantly associated with diarrhoea among SAM infants in comparison to well-nourished infants. 80% higher odds of detection of rotavirus and norovirus GII were associated with diarrhoea among well-nourished infants in comparison to SAM infants (aOR: 0.2, p < 0.05). CONCLUSION: Our study findings demonstrate a difference in diarrhoeal aetiology among SAM and well-nourished young infants, which may be useful in providing an evidence-based logic for possible revision of treatment guidelines for treatment of young diarrhoeal infants with SAM in the early management of the menace of antimicrobial resistance.

Individual and combined association analysis of famine exposure and serum uric acid with hypertension in the mid-aged and older adult: a population-based cross-sectional study.

BACKGROUND: Malnutrition in early life may affect health in later life. The associations between malnutrition and serum uric acid (SUA) and hypertension were inconsistent. The present study aimed to investigate the individual and combined association between famine exposure and serum uric acid and hypertension in middle-aged and older Chinese. METHODS: Data were selected from the China Health and Retirement Longitudinal Study (CHARLS) Wave2011. The analytic sample included 9368 individuals aged 45 to 90. Differences between baseline characteristics and famine exposure/SUA level were evaluated using the Chi-square test, t-test, and F-test. Then, the differences in the prevalence of hypertension between characteristic groups was also estimated by the Chi-square and t-test. Finally, multivariable-adjusted logistic regression models examined association of famine exposure and serum uric acid with odds of prevalence of hypertension. RESULTS: A total of 9368 individuals were enrolled in the study, 4366 (46.61%) and 5002 (53.39%) were male and female, respectively. Among males, 459 (10.51%) had been exposed to the Chinese famine during the fetal stage, whereas 1760 (40.31%) and 1645 (37.68%) had been exposed to the famine during childhood and adolescence/adult stage, respectively. Among females, 635 (12.69%) had been exposed to the Chinese famine during the fetal stage, whereas 1988 (39.74%) and 1569 (31.37%) had been exposed to the famine during childhood and adolescence/adult stage, respectively. Regarding the participants with SUA level measurements, 290 (6.64%) reported having Hyperuricemia (HUA) in males and 234 (4.68%) in the females. Furthermore, 1357 (31.08%) reported having hypertension in male and 1619 (32.37%) in the female. In multivariable-adjusted model, famine exposure and serum uric acid were associated with prevalence of hypertension independently in total populations [(1) Model fourd, fatal exposed group vs non-exposed group: 1.25 (95% CI 1.03, 1.52); childhood-exposed group vs non-exposed group:1.60 (95% CI 1.37, 1.87); adolescence/adult exposed group vs non-exposed group: 2.87 (95% CI 2.44, 3.37), P for trend < 0.001; (2) Model four e, high vs normal:1.73 (95% CI 1.44, 2.08)]. When stratified by sex, the results in both males and females were similar to those in the total population. In general, interaction analysis in the multivariable-adjusted model, compared with the combination of normal SUA level and no-exposed famine stage, all groups trended towards higher odds of prevalence of hypertension [the greatest increase in odds, adolescence/adult exposed stage and high SUA level in total participants: OR4.34; 95%CI 3.24, 5.81; P for interaction < 0.001]. When stratified by sex, the results in both males and females were also similar to those in the total population. CONCLUSION: Our data support a strongly positive individual and combined association of famine exposure and serum uric acid with hypertension in middle-aged and elderly Chinese.

Integrated community case management of childhood illness in low- and middle-income countries.

BACKGROUND: The leading causes of mortality globally in children younger than five years of age (under-fives), and particularly in the regions of sub-Saharan Africa (SSA) and Southern Asia, in 2018 were infectious diseases, including pneumonia (15%), diarrhoea (8%), malaria (5%) and newborn sepsis (7%) (UNICEF 2019). Nutrition-related factors contributed to 45% of under-five deaths (UNICEF 2019). World Health Organization (WHO) and United Nations Children's Fund (UNICEF), in collaboration with other development partners, have developed an approach - now known as integrated community case management (iCCM) - to bring treatment services for children 'closer to home'. The iCCM approach provides integrated case management services for two or more illnesses - including diarrhoea, pneumonia, malaria, severe acute malnutrition or neonatal sepsis - among under-fives at community level (i.e. outside of healthcare facilities) by lay health workers where there is limited access to health facility-based case management services (WHO/UNICEF 2012). OBJECTIVES: To assess the effects of the integrated community case management (iCCM) strategy on coverage of appropriate treatment for childhood illness by an appropriate provider, quality of care, case load or severity of illness at health facilities, mortality, adverse events and coverage of careseeking for children younger than five years of age in low- and middle-income countries. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase and CINAHL on 7 November 2019, Virtual Health Library on 8 November 2019, and Popline on 5 December 2018, three other databases on 22 March 2019 and two trial registers on 8 November 2019. We performed reference checking, and citation searching, and contacted study authors to identify additional studies. SELECTION CRITERIA: Randomized controlled trials (RCTs), cluster-RCTs, controlled before-after studies (CBAs), interrupted time series (ITS) studies and repeated measures studies comparing generic WHO/UNICEF iCCM (or local adaptation thereof) for at least two iCCM diseases with usual facility services (facility treatment services) with or without single disease community case management (CCM). We included studies reporting on coverage of appropriate treatment for childhood illness by an appropriate provider, quality of care, case load or severity of illness at health facilities, mortality, adverse events and coverage of careseeking for under-fives in low- and middle-income countries. DATA COLLECTION AND ANALYSIS: At least two review authors independently screened abstracts, screened full texts and extracted data using a standardised data collection form adapted from the EPOC Good Practice Data Collection Form. We resolved any disagreements through discussion or, if required, we consulted a third review author not involved in the original screening. We contacted study authors for clarification or additional details when necessary. We reported risk ratios (RR) for dichotomous outcomes and hazard ratios (HR) for time to event outcomes, with 95% confidence intervals (CI), adjusted for clustering, where possible. We used estimates of effect from the primary analysis reported by the investigators, where possible. We analysed the effects of randomized trials and other study types separately. We used the GRADE approach to assess the certainty of evidence. MAIN RESULTS: We included seven studies, of which three were cluster RCTs and four were CBAs. Six of the seven studies were in SSA and one study was in Southern Asia. The iCCM components and inputs were fairly consistent across the seven studies with notable variation for the training and deployment component (e.g. on payment of iCCM providers) and the system component (e.g. on improving information systems). When compared to usual facility services, we are uncertain of the effect of iCCM on coverage of appropriate treatment from an appropriate provider for any iCCM illness (RR 0.96, 95% CI 0.77 to 1.19; 2 CBA studies, 5898 children; very low-certainty evidence). iCCM may have little to no effect on neonatal mortality (HR 1.01, 95% 0.73 to 1.28; 2 trials, 65,209 children; low-certainty evidence). We are uncertain of the effect of iCCM on infant mortality (HR 1.02, 95% CI 0.83 to 1.26; 2 trials, 60,480 children; very low-certainty evidence) and under-five mortality (HR 1.18, 95% CI 1.01 to 1.37; 1 trial, 4729 children; very low-certainty evidence). iCCM probably increases coverage of careseeking to an appropriate provider for any iCCM illness by 68% (RR 1.68, 95% CI 1.24 to 2.27; 2 trials, 9853 children; moderate-certainty evidence). None of the studies reported quality of care, severity of illness or adverse events for this comparison. When compared to usual facility services plus CCM for malaria, we are uncertain of the effect of iCCM on coverage of appropriate treatment from an appropriate provider for any iCCM illness (very low-certainty evidence) and iCCM may have little or no effect on careseeking to an appropriate provider for any iCCM illness (RR 1.06, 95% CI 0.97 to 1.17; 1 trial, 811 children; low-certainty evidence). None of the studies reported quality of care, case load or severity of illness at health facilities, mortality or adverse events for this comparison. AUTHORS' CONCLUSIONS: iCCM probably increases coverage of careseeking to an appropriate provider for any iCCM illness. However, the evidence presented here underscores the importance of moving beyond training and deployment to valuing iCCM providers, strengthening health systems and engaging community systems.

Infant malnutrition treatment in Kenya: Health worker and breastfeeding peer supporter experiences.

Acute malnutrition in infants under 6 months (u6m) is increasingly recognised as a global public health problem. The World Health Organisation (WHO) guidelines for inpatient nutritional rehabilitation of infants u6m is re-lactation: the re-establishment of exclusive breastfeeding. Evidence suggests these guidelines are rarely followed in many low-income settings. Two studies of infant nutritional rehabilitation undertaken in three public hospitals in coastal Kenya employed breastfeeding peer supporters (BFPSs) to facilitate WHO guideline implementation. To explore the acceptability of the strategy to health workers (HWs) and the BFPSs, in-depth interviews were conducted with 20 HWs and five BFPSs in the three study hospitals. The HWs reported that the presence of the BFPSs changed the way infant nutritional rehabilitation was managed, increasing efforts at relactation and decreasing reliance on supplemental milk. BFPSs were said to help address staff shortages and had dedicated time to support and assist the mothers. Key to the success of the BFPSs was the social relationships they were able to establish with the mothers due to the similarity in their experiences and backgrounds. Despite the success of the BFPSs, human resource management and infrastructure challenges remained. BFPSs can successfully be employed to facilitate the implementation of the WHO guidelines for the nutritional rehabilitation of acutely malnourished infants u6m in hospitals in Kenya, establishing supportive social relationships and trust with the mothers of the acutely malnourished infants and helping to address the issue of human resource shortages.

Improving nutritional status among urban poor children in sub-Saharan Africa: An evidence-informed Delphi-based consultation.

In sub-Saharan Africa (SSA), rapid urbanisation coupled with the high prevalence of infant and young child (IYC) undernutrition in low-income settings means that interventions to support IYC nutrition are a priority. Little is known about how urbanisation influences IYC feeding (IYCF) practices, and evidence-based interventions to improve IYC health/nutrition in the urban poor are lacking. Therefore, this research aimed to (a) systematically review evidence on interventions for improving the nutritional status of IYC aged 6-23 months living in urban poor areas (PROSPERO CRD42018091265) and (b) engage stakeholders to identify the highest ranking evidence gaps for improving IYCF programmes/policies. First, a rapid systematic review was conducted. This focused on the literature published regarding nutrition-specific and nutrition-sensitive complementary feeding interventions in urban poor areas, specifically low-income informal settlements, in low- and middle-income countries (LMICs). Six intervention studies met the review inclusion criteria. Intervention adherence was generally high, and indicators of maternal knowledge and IYC nutritional intake typically increased because of the interventions, but the impact on anthropometric status was small. Second, stakeholders working across SSA were engaged via a Delphi-based approach to identify priority areas for future intervention. Stakeholders reported that a situational analysis was required to better understand IYCF in urban poor areas, particularly the causes of IYC undernutrition, and highlighted the need to involve local communities in defining how future work should proceed. Together, these findings indicate a need for more evidence regarding IYCF and the factors that drive it in urban poor areas across LMIC settings, but particularly in SSA.

Impact of food supplements on early child development in children with moderate acute malnutrition: A randomised 2 x 2 x 3 factorial trial in Burkina Faso.

BACKGROUND: Lipid-based nutrient supplements (LNS) and corn-soy blends (CSBs) with varying soy and milk content are used in treatment of moderate acute malnutrition (MAM). We assessed the impact of these supplements on child development. METHODS AND FINDINGS: We conducted a randomised 2 × 2 × 3 factorial trial to assess the effectiveness of 12 weeks' supplementation with LNS or CSB, with either soy isolate or dehulled soy, and either 0%, 20%, or 50% of protein from milk, on child development among 6-23-month-old children with MAM. Recruitment took place at 5 health centres in Province du Passoré, Burkina Faso between September 2013 and August 2014. The study was fully blinded with respect to soy quality and milk content, while study participants were not blinded with respect to matrix. This analysis presents secondary trial outcomes: Gross motor, fine motor, and language development were assessed using the Malawi Development Assessment Tool (MDAT). Of 1,609 children enrolled, 54.7% were girls, and median age was 11.3 months (interquartile range [IQR] 8.2-16.0). Twelve weeks follow-up was completed by 1,548 (96.2%), and 24 weeks follow-up was completed by 1,503 (93.4%); follow-up was similar between randomised groups. During the study, 4 children died, and 102 children developed severe acute malnutrition (SAM). There was no difference in adverse events between randomised groups. At 12 weeks, the mean MDAT z-scores in the whole cohort had increased by 0.33 (95% CI: 0.28, 0.37), p < 0.001 for gross motor; 0.26 (0.20, 0.31), p < 0.001 for fine motor; and 0.14 (0.09, 0.20), p < 0.001 for language development. Children had larger improvement in language z-scores if receiving supplements with milk (20%: 0.09 [-0.01, 0.19], p = 0.08 and 50%: 0.11 [0.01, 0.21], p = 0.02), although the difference only reached statistical significance for 50% milk. Post hoc analyses suggested that this effect was specific to boys (interaction p = 0.02). The fine motor z-scores were also improved in children receiving milk, but only when 20% milk was added to CSB (0.18 [0.03, 0.33], p = 0.02). Soy isolate over dehulled soy increased language z-scores by 0.07 (-0.01, 0.15), p = 0.10, although not statistically significant. Post hoc analyses suggested that LNS benefited gross motor development among boys more than did CSB (interaction p = 0.04). Differences between supplement groups did not persist at 24 weeks, but MDAT z-scores continued to increase post-supplementation. The lack of an unsupplemented control group limits us from determining the overall effects of nutritional supplementation for children with MAM. CONCLUSIONS: In this study, we found that child development improved during and after supplementation for treatment of MAM. Milk protein was beneficial for language and fine motor development, while suggested benefits related to soy quality and supplement matrix merit further investigation. Supplement-specific effects were not found post-intervention, but z-scores continued to improve, suggesting a sustained overall effect of supplementation. TRIAL REGISTRATION: ISRCTN42569496.

Incidence Correction Factors for Moderate and Severe Acute Child Malnutrition From 2 Longitudinal Cohorts in Mali and Burkina Faso.

Child acute malnutrition (AM) is an important cause of child mortality. Accurately estimating its burden requires cumulative incidence data from longitudinal studies, which are rarely available in low-income settings. In the absence of such data, the AM burden is approximated using prevalence estimates from cross-sectional surveys and the incidence correction factor $K$, obtained from the few available cohorts that measured AM. We estimated $K$ factors for severe acute malnutrition (SAM) and moderate acute malnutrition (MAM) from AM incidence and prevalence using representative cross-sectional baseline and longitudinal data from 2 cluster-randomized controlled trials (Innovative Approaches for the Prevention of Childhood Malnutrition-PROMIS) conducted between 2014 and 2017 in Burkina Faso and Mali. We compared K estimates using complete (weight-for-length z score, mid-upper arm circumference (MUAC), and edema) and partial (MUAC, edema) definitions of SAM and MAM. $K$ estimates for SAM were 9.4 and 5.7 in Burkina Faso and in Mali, respectively; K estimates for MAM were 4.7 in Burkina Faso and 5.1 in Mali. The MUAC and edema-based definition of AM did not lead to different $K$ estimates. Our results suggest that $K$ can be reliably estimated when only MUAC and edema-based data are available. Additional studies, however, are required to confirm this finding in different settings.

The Microbiota and Malnutrition: Impact of Nutritional Status During Early Life.

According to the developmental origins of health and disease hypothesis, our health is determined by events experienced in utero and during early infancy. Indeed, both our prenatal and postnatal nutrition conditions have an impact on the initial architecture and activity of our microbiota. Recent evidence has underlined the importance of the composition of the early gut microbiota in relation to malnutrition, whether it be undernutrition or overnutrition, that is, in terms of both stunted and overweight development. It remains unclear how early microbial contact is linked to the risk of disease, as well as whether alterations in the microbiome underlie the pathogenesis of malnutrition or are merely the end result of it, which indicates that thequestion of causality must urgently be answered. This review provides information on the complex interaction between the microbiota and nutrition during the first 1,000 days of life, taking into account the impact of both undernutrition and overnutrition on the microbiota and on infants' health outcomes in the short- and long-term.

Impact Evaluation of a Comprehensive Nutrition Program for Reducing Stunting in Children Aged 6-23 Months in Rural Malawi.

BACKGROUND: The prevalence of stunting in central rural Malawi is ∼50%, which prompted a multipronged nutrition program in 1 district from 2014 to 2016. The program distributed a daily, fortified, small-quantity lipid-based nutritional supplement, providing 110 kcal and 2.6 g of protein to children aged 6-23 mo, and behavior change messages around optimal infant and young child feeding (IYCF) and water, sanitation, and hygiene. OBJECTIVES: Our objective was to perform an impact evaluation of the program using a neighboring district as comparison. METHODS: Using a quasi-experimental study design, with cross-sectional baseline (January-March, 2014; n = 2404) and endline (January-March, 2017; n = 2453) surveys, we evaluated the program's impact using a neighboring district as comparison. Impact on stunting was estimated using propensity score weighted difference-in-differences regression analyses to account for baseline differences between districts. RESULTS: No differences in mean length-for-age z-score or prevalence of stunting were found at endline. However, mean weight, weight-for-length z-score, and mid-upper arm circumference were higher at endline by 150 g, 0.22, and 0.19 cm, respectively, in the program compared with the comparison district (all P < 0.05). Weekly reports of high fever and malaria were also lower by 6.4 and 4.7 percentage points, respectively, in the program compared with the comparison district (both P < 0.05). There was no impact on anemia. Children's dietary diversity score improved by 0.17, and caregivers' infant and young child feeding and hand-washing practices improved by 8-11% in the program compared with the comparison district (all P < 0.05). CONCLUSIONS: An impact evaluation of a comprehensive nutrition program in rural Malawi demonstrated benefit for child ponderal growth and health, improved maternal IYCF and hand-washing practices, but a reduction in stunting prevalence was not observed.

Environmental exposures and child and maternal gut microbiota in rural Malawi.

BACKGROUND: Gut microbiota composition is associated with child health, but the effect of the environment on microbiota composition is not well understood. Few studies have been conducted in low-income settings where childhood malnutrition is common and possibly related to microbiota composition. OBJECTIVES: To investigate whether gut microbiota composition in young children and their mothers is associated with different environmental exposures in rural Malawi. We hypothesized that more adverse environmental exposures would be associated with lower levels of microbiota maturity and diversity. METHODS: Faecal samples from up to 631 children and mothers participating in a nutrition intervention trial were collected at 1, 6, 12, 18, and 30 months (children) and at 1 month (mothers) after birth and analysed for microbiota composition with 16S rRNA sequencing. Bacterial OTU and genus abundances, measures of microbiota maturity and diversity, and UniFrac distances were compared between participants with different environmental exposures. The exposure variables included socio-economic status, water source, sanitary facility, domestic animals, maternal characteristics, season, antibiotic use, and delivery mode. RESULTS: Measures of microbiota maturity and diversity in children were inversely associated with maternal education at 6, 18, and 30 months and did not otherwise differ consistently between participants with different environmental exposures. Phylogenetic distance was related to season of stool sample collection at all time points. At the level of individual OTUs and genera, season of stool sample collection, type of water source, and maternal education showed most associations with child gut microbiota, while HIV status was the most important predictor of relative OTU and genus abundances in mothers. CONCLUSION: The results do not support the hypothesis that adverse environmental exposures are broadly associated with lower microbiota maturity and diversity but suggest that environmental exposures influence the abundance of several bacterial OTUs and genera and that low maternal education is associated with higher microbiota maturity and diversity.

Sustainable under nutrition reduction program and dietary diversity among children's aged 6-23 months, Northwest Ethiopia: Comparative cross-sectional study.

INTRODUCTION: Adequate dietary diversity is vital for the survival, growth and development of infants and children. Inadequate dietary diversity is the major cause of micronutrient deficiency in Sub-saharan Africa, including Ethiopia, where only less than one-fourth of the children aged 6-23 months obtain adequate diversified diet. Thus country implemented a strategy known as the Sustainable Undernutrtion Reduction (SUR) programs to alleviate the problem. However, empirical evidences are scarce on the impact of the program on children aged 6-23 months. Therefore, this study aimed to compare the level of dietary diversity among children aged 6-23 months in districts covered and not covered by SURE program in West Gojjam zone. METHODS: A community based comparative cross-sectional study was conducted in three districts of West Gojjam zone, Ethiopia, from February 29 to April 20, 2019. A total of 832 mother and child pairs were selected by the simple random sampling technique. A pretested and structured interviewer-administered questionnaire was used to collect data. A binary logistic regression model was fitted to identify factors associated with dietary diversity. Crude odds and adjusted odds ratios with 95% confidence intervals (CI) were calculated to assess the strength of associations and significance of the identified factors for dietary diversity score. RESULT: The overall proportion of adequate dietary diversity among children aged 6-23 months was 29.9% (95% CI: 27.0-33.0), whereas in SURE covered and uncovered districts it was 33.4% (95%CI: 29.0-38.and 26.4%(95% CI: 22.0, 31.0), respectively. ANC (Antenatal care) (AOR = 1.7; 95% CI: 1.16, 2.55) and postnatal care services (AOR = 2.1; 95% CI: 1.38, 3.28), participating in food preparation programs (AOR = 1.9; 95% CI: 1.19, 2.96), GMP (AOR = 2.74,95%CI:1.80, 4.18), vitamin A supplementation (AOR = 2.10,95%CI:1.22, 3.61) and household visits by health extension workers (AOR = 2.0; 95% CI: 1.25, 3.21) were significantly associated with dietary diversity. CONCLUSION: The proportion of adequate dietary diversity was higher among children in the program than those out of the program. ANC visits, PNC follow-ups, women's participating in food preparation programs and household visits by health extension workers were significantly associated with dietary diversity. Therefore, and strengthening and scaling up the program to non covered districts and providing health and nutrition counseling on Infant and Young Child Feeding (IYCF) during ANC and PNC services are recommended for achieving the recommended dietary diversity.

Persistent gut microbiota immaturity in malnourished Bangladeshi children.

Therapeutic food interventions have reduced mortality in children with severe acute malnutrition (SAM), but incomplete restoration of healthy growth remains a major problem. The relationships between the type of nutritional intervention, the gut microbiota, and therapeutic responses are unclear. In the current study, bacterial species whose proportional representation define a healthy gut microbiota as it assembles during the first two postnatal years were identified by applying a machine-learning-based approach to 16S ribosomal RNA data sets generated from monthly faecal samples obtained from birth onwards in a cohort of children living in an urban slum of Dhaka, Bangladesh, who exhibited consistently healthy growth. These age-discriminatory bacterial species were incorporated into a model that computes a 'relative microbiota maturity index' and 'microbiota-for-age Z-score' that compare postnatal assembly (defined here as maturation) of a child's faecal microbiota relative to healthy children of similar chronologic age. The model was applied to twins and triplets (to test for associations of these indices with genetic and environmental factors, including diarrhoea), children with SAM enrolled in a randomized trial of two food interventions, and children with moderate acute malnutrition. Our results indicate that SAM is associated with significant relative microbiota immaturity that is only partially ameliorated following two widely used nutritional interventions. Immaturity is also evident in less severe forms of malnutrition and correlates with anthropometric measurements. Microbiota maturity indices provide a microbial measure of human postnatal development, a way of classifying malnourished states, and a parameter for judging therapeutic efficacy. More prolonged interventions with existing or new therapeutic foods and/or addition of gut microbes may be needed to achieve enduring repair of gut microbiota immaturity in childhood malnutrition and improve clinical outcomes.