Interactions between fecal gut microbiome, enteric pathogens, and energy regulating hormones among acutely malnourished rural Gambian children

Background: The specific roles that gut microbiota, known pathogens, and host energy-regulating hormones play in the pathogenesis of non-edematous severe acute malnutrition (marasmus SAM) and moderate acute malnutrition (MAM) during outpatient nutritional rehabilitation are yet to be explored. Methods: We applied an ensemble of sample-specific (intra- and inter-modality) association networks to gain deeper insights into the pathogenesis of acute malnutrition and its severity among children under 5 years of age in rural Gambia, where marasmus SAM is most prevalent. Findings: Children with marasmus SAM have distinct microbiome characteristics and biologically-relevant multimodal biomarkers not observed among children with moderate acute malnutrition. Marasmus SAM was characterized by lower microbial richness and biomass, significant enrichments in Enterobacteriaceae, altered interactions between specific Enterobacteriaceae and key energy regulating hormones and their receptors. Interpretation: Our findings suggest that marasmus SAM is characterized by the collapse of a complex system with nested interactions and key associations between the gut microbiome, enteric pathogens, and energy regulating hormones. Further exploration of these systems will help inform innovative preventive and therapeutic interventions. Funding: The work was supported by the UK Medical Research Council (MRC; MC-A760-5QX00) and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement; Bill and Melinda Gates Foundation (OPP 1066932) and the National Institute of Medical Research (NIMR), UK. This network analysis was supported by NIH U54GH009824 [CLD] and NSF OCE-1558453 [CLD]. © 2021 The Author(s). **Please note that there are multiple authors for this article therefore only the name of the first 5 including Federation University Australia affiliate “Richard Bradbury" is provided in this record*

Microbes and the malnourished child.

New research implicates a dysfunctional gut microbiome in the etiology of severe childhood malnutrition and confirms a role for antibiotics in its treatment

Growth faltering in rural Gambian children after four decades of interventions: a retrospective cohort study

Background Growth faltering remains common in children in sub-Saharan Africa and is associated with substantial morbidity and mortality. Due to a very slow decline in the prevalence of stunting, the total number of children with stunting continues to rise in sub-Saharan Africa. Identifi cation of eff ective interventions remains a challenge. Methods We analysed the eff ect of 36 years of intensive health interventions on growth in infants and young children from three rural Gambian villages. Routine growth data from birth to age 2 years were available for 3659 children between 1976 and 2012. Z scores for weight-for-age, length-for-age, weight-for-length, mid-upper-arm circumference, and head circumference were calculated using the WHO 2006 growth standards. Seasonal patterns of mean Z scores were obtained by Fourier regression. We additionally defi ned growth faltering as fall in Z score between 3 months and 21 months of age. Findings We noted secular improvements in all postnatal growth parameters (except weight-for-length), accompanied by declines over time in seasonal variability. The proportion of children with underweight or stunting at 2 years of age halved during four decades of the study period, from 38·7% (95% CI 33·5–44·0) for underweight and 57·1% (51·9–62·4) for stunting. However, despite unprecedented levels of intervention, postnatal growth faltering persisted, leading to poor nutritional status at 24 months (length-for-age Z score –1·36, 95% CI –1·44 to –1·27, weight-for-age Z score –1·20, –1·28 to –1·11, and head circumference Z score –0·51, –0·59 to –0·43). The prevalence of stunting and underweight remained unacceptably high (30·0%, 95% CI 27·0–33·0, for stunting and 22·1%, 19·4 to 24·8, for underweight). Interpretation A combination of nutrition-sensitive and nutrition-specifi c interventions has achieved a halving of undernutrition rates, but despite these intensive interventions substantial growth faltering remains. We need to understand the missing contributors to growth faltering to guide development of new interventions

Thresholds of socio-economic and environmental conditions necessary to escape from childhood malnutrition: a natural experiment in rural Gambia.

BACKGROUND: Childhood malnutrition remains highly prevalent in low-income countries, and a 40% reduction in under-5 year stunting is WHO's top Global Target 2025. Disappointingly, meta-analyses of intensive nutrition interventions reveal that they generally have low efficacy at improving growth. Unhygienic environments also contribute to growth failure, but large WASH Benefits and SHINE trials of improved water, sanitation and hygiene (WASH) recently reported no benefits to child growth. METHODS: To explore the thresholds of socio-economic status (SES) and living standards associated with malnutrition, we exploited a natural experiment in which the location of our research centre within a remote rural village created a wide diversity of wealth, education and housing conditions within the same ecological setting and with free health services to all. A composite SES score was generated by grading occupation, education, income, water and sanitation, and housing and families were allocated to 5 groups (SES1 = highest). SES ranged from very poor subsistence-farming villagers to post graduate staff with overseas training. Nutritional status at 24 m was obtained from clinic records for 230 children and expressed relative to WHO Growth Standards. RESULTS: Height-for-age (HAZ) and weight-for-age (WAZ) Z-scores were strongly predicted by SES group. HAZ varied from - 0.67 to - 2.23 (P < 0.001) and WAZ varied from - 0.90 to - 1.64 (P < 0.001), from SES1 to SES5, respectively. Weight-for-height (WHZ) showed no gradient. Children in SES1 showed greater dispersion so were further divided in a post hoc analysis. Children resident in Western housing on the research compound (SES1A) had HAZ = + 0.68 and WAZ = + 0.36. The residual gradient between those in SES1B and SES5 spanned only 0.65 Z-score for HAZ (- 1.58 to - 2.23) and was not significant for WAZ or WHZ. CONCLUSIONS: The large difference in growth between children in SES1A living in Western-type housing and SES1B children living in the village, and the very shallow gradient between SES1B and SES5, implies a very high SES threshold before stunting and underweight will be eliminated. This may help to explain the lack of efficacy of the recent WASH interventions and points to the need for what is termed 'Transformative WASH'. Good quality housing, with piped water into the home, may be key to eliminating malnutrition

Design and implementation of a community-based mother-to-mother peer support programme for the follow-up of low birthweight infants in rural western Kenya

Background: Globally, low birthweight (LBW) infants ( Methods: Key informant interviews were conducted with 10 mothers of neonates (infants days) from two rural communities in western Kenya. These data informed the identification of key characteristics required for mother-to-mother peer supporters (peer mothers) following up LBW infants post discharge. Forty potential peer mothers were invited to attend a 5-day training programme that focused on three main themes: supportive care using appropriate communication, identification of severe illness, and recommended care strategies for LBW infants. Sixteen peer mothers were mentored to conduct seven community follow-up visits to each mother-LBW infant pair with fifteen completing all the visits over a 6-month period. A mixed methods approach was used to evaluate the implementation of the programme. Quantitative data of peer mother socio-demographic characteristics, recruitment, and retention was collected. Two post-training focus group discussions were conducted with the peer mothers to explore their experiences of the programme. Descriptive statistics were generated from the quantitative data and the qualitative data was analysed using a thematic framework. Results: The median age of the peer mothers was 26 years (range 21–43). From March-August 2019, each peer mother conducted a median of 28 visits (range 7–77) with fourteen (88%) completing all their assigned follow-up visits. Post training, our interviews suggest that peer mothers felt empowered to promote appropriate infant feeding practices. They gave multiple examples of improved health seeking behaviours as a result of the peer mother training programme. Conclusion: Our peer mother training programme equipped peer mothers with the knowledge and skills for the post-discharge follow-up of LBW infants in this rural community in Kenya. Community-based interventions for LBW infants, delivered by appropriately trained peer mothers, have the potential to address the current gaps in post-discharge care for these infants

A mixed-methods study to investigate feasibility and acceptability of an early warning score for preterm infants in neonatal units in Kenya: results of the NEWS-K study

Preterm birth (\u3c 37 weeks gestation) complications are the leading cause of neonatal mortality. Early-warning scores (EWS) are charts where vital signs (e.g., temperature, heart rate, respiratory rate) are recorded, triggering action. To evaluate whether a neonatal EWS improves clinical outcomes in low-middle income countries, a randomised trial is needed. Determining whether the use of a neonatal EWS is feasible and acceptable in newborn units, is a prerequisite to conducting a trial. We implemented a neonatal EWS in three newborn units in Kenya. Staff were asked to record infants’ vital signs on the EWS during the study, triggering additional interventions as per existing local guidelines. No other aspects of care were altered. Feasibility criteria were pre-specified. We also interviewed health professionals (n = 28) and parents/family members (n = 42) to hear their opinions of the EWS. Data were collected on 465 preterm and/or low birthweight (\u3c 2.5 kg) infants. In addition to qualitative study participants, 45 health professionals in participating hospitals also completed an online survey to share their views on the EWS. 94% of infants had the EWS completed at least once during their newborn unit admission. EWS completion was highest on the day of admission (93%). Completion rates were similar across shifts. 15% of vital signs triggered escalation to a more senior member of staff. Health professionals reported liking the EWS, though recognised the biggest barrier to implementation was poor staffing. Newborn unit infant to staff ratios varied between 10 and 53 staff per 1 infant, depending upon time of shift and staff type. A randomised trial of neonatal EWS in Kenya is possible and acceptable, though adaptations are required to the form before implementation

The impact of growth monitoring and promotion on health indicators in children under five years of age in low- and middle-income countries

Undernutrition in the critical first 1000 days of life is the most common form of childhood malnutrition, and a significant problem in low- and middle-income countries (LMICs). The effects of undernutrition in children aged under five years are wide-ranging and include increased susceptibility to and severity of infections; impaired physical and cognitive development, which diminishes school and work performance later in life; and death. Growth monitoring and promotion (GMP) is a complex intervention that comprises regular measurement and charting of growth combined with promotion activities. Policymakers, particularly in international aid agencies, have differing and changeable interpretations and perceptions of the purpose of GMP. The effectiveness of GMP as an approach to preventing malnutrition remains a subject of debate, particularly regarding the added value of growth monitoring compared with promotion alone. To evaluate the effectiveness of child growth monitoring and promotion for identifying and addressing faltering growth, improving infant and child feeding practices, and promoting contact with and use of health services in children under five years of age in low- and middle-income countries. We used standard, extensive Cochrane search methods. The latest search date was 3 November 2022. We included randomised controlled trials (RCTs), cohort studies, and controlled before-after studies that compared GMP with standard care or nutrition education alone in non-hospitalised children aged under five years. We used standard Cochrane methods to conduct a narrative synthesis. Our primary outcomes were anthropometric indicators, infant and child feeding practices, and health service usage. Secondary outcomes were frequency and severity of childhood illnesses, and mortality. We used GRADE to assess the certainty of evidence for each primary outcome. We included six studies reported in eight publications. We grouped the findings according to intervention. Community-based growth monitoring and promotion (without supplementary feeding) versus standard care We are unsure if GMP compared to standard care improves infant and child feeding practices, as measured at 24 months by the proportion of infants who have fluids other than breast milk introduced early (49.7% versus 70.5%; 1 study; 4296 observations; very low-certainty evidence). We are unsure if GMP improves health service usage, as measured at 24 months by the proportion of children who receive vitamin A (72.5% versus 62.9%; 1 study; 4296 observations; very low-certainty evidence) and the proportion of children who receive deworming (29.2% versus 14.6%; 1 study; 4296 observations; very low-certainty evidence). No studies reported selected anthropometric indicators (weight-for-age z-score or height-for-age z-score) at 12 or 24 months, infant and child feeding practices at 12 months, or health service usage at 12 months. Community-based growth monitoring and promotion (with supplementary feeding) versus standard care Two studies (with 569 participants) reported the mean weight-for-age z-score at 12 months, providing very low-certainty evidence: in one study, there was little or no difference between GMP and standard care (mean difference (MD) -0.07, 95% confidence interval (CI) -0.19 to 0.06); in the other study, mean weight-for-age z-score worsened in both groups, but we were unable to calculate a relative effect. GMP versus standard care may make little to no difference to the mean height-for-age z-score at 12 months (MD -0.15, 95% CI -0.34 to 0.04; 1 study, 337 participants; low-certainty evidence). Two studies (with 564 participants) reported a range of outcome measures related to infant and child feeding practices at 12 months, showing little or no difference between the groups (very low-certainty evidence). No studies reported health service usage at 12 or 24 months, feeding practices at 24 months, or selected anthropometric indicators at 24 months. There is limited uncertain evidence on the effectiveness of GMP for identifying and addressing faltering growth, improving infant and child feeding practices, and promoting contact with and use of health services in children aged under five years in LMICs. Future studies should explore the reasons for the apparent limited impact of GMP on key child health indicators. Reporting of GMP interventions and important outcomes must be transparent and consistent

Time to full enteral feeds in hospitalised preterm and very low birth weight infants in Nigeria and Kenya

Background: Preterm (born \u3c 37 weeks’ gestation) and very low birthweight (VLBW; \u3c1.5kg) infants are at the greatest risk of morbidity and mortality within the first 28 days of life. Establishing full enteral feeds is a vital aspect of their clinical care. Evidence predominantly from high income countries shows that early and rapid advancement of feeds is safe and reduces length of hospital stay and adverse health outcomes. However, there are limited data on feeding practices and factors that influence the attainment of full enteral feeds among these vulnera- ble infants in sub-Saharan Africa. Aim: To identify factors that influence the time to full enteral feeds, defined as tolerance of 120ml/ kg/day, in hospitalised preterm and VLBW infants in neonatal units in two sub-Saharan Afri- can countries. Methods: Demographic and clinical variables were collected for newborns admitted to 7 neonatal units in Nigeria and Kenya over 6-months. Multiple linear regression analysis was conducted to identify factors independently associated with time to full enteral feeds. Results: Of the 2280 newborn infants admitted, 484 were preterm and VLBW. Overall, 222/484 (45.8%) infants died with over half of the deaths (136/222; 61.7%) occurring before the first feed. The median (inter-quartile range) time to first feed was 46 (27, 72) hours of life and time to full enteral feeds (tFEF) was 8 (4.5,12) days with marked variation between neonatal units. Independent predictors of tFEF were time to first feed (unstandardised coefficient B 1.69; 95% CI 1.11 to 2.26; p value \u3c0.001), gestational age (1.77; 0.72 to 2.81; \u3c0.001), the occurrence of respiratory distress (-1.89; -3.50 to -0.79; \u3c0.002) and necrotising enterocoli- tis (4.31; 1.00 to 7.62; \u3c0.011). Conclusion: The use of standardised feeding guidelines may decrease variations in clinical practice, shorten tFEF and thereby improve preterm and VLBW outcome

A rite of passage: a mixed methodology study about knowledge, perceptions and practices of menstrual hygiene management in rural Gambia.

BACKGROUND: Appropriate menstrual hygiene management (MHM) is impeded by taboos and secrecy surrounding menstruation. Unhygienic menstrual practices and unpreparedness for managing menstruation has been associated with adverse health and social outcomes among adolescent girls. In The Gambia, there is limited data on menstrual practices among girls and women in rural communities and the sources of information about menstruation for the adolescents. This study aimed to explore knowledge, preparedness and practices of menstruation and its management among adolescents, mothers and teachers in rural Gambia. METHODS: A mixed methods study was conducted in the rural Kiang West district of The Gambia. Twenty focus group discussions and thirteen in-depth interviews were conducted among mothers, adolescents and teachers to explore their views on menstruation, cultural beliefs, sources and level of knowledge on menstruation and MHM practices. In addition, a survey was done among 331 school girls to assess their knowledge, practices and attitudes of menstruation and its management. Inductive content analysis was used to analyse the qualitative data, and descriptive analysis and chi-squared tests were used to analyse quantitative data. RESULTS: All participants had different levels of knowledge about menstruation. Knowledge score was higher among post-menarche girls compare with pre-menarche girls (p = 0.0001). All groups expressed difficulties, embarrassment and shame in relation to discussing menstruation. Two thirds of the surveyed girls reported having learnt about menstruation before menarche, however at menarche most felt unprepared. Teachers were the main source of information, but when asking for advice most girls preferred to ask their mothers. Mothers reported facing difficulties in discussing menstruation with their children and felt that boys did not need to be taught about it, however boys were very curious to know about. Most girls used reusable cloth unless they are given free pads from school. CONCLUSION: Taboos, secrecy and embarrassment associated with discussing menstruation hinder adolescents from seeking advice from parents and teachers on appropriate MHM practices. Strategies to encourage positive social norms towards menstruation would help to promote more open discussions about it at the family, community and national level, which will support improvements in MHM in this and similar communities in low and middle income settings

Impact of COVID-19 lockdown measures on institutional delivery, neonatal admissions and prematurity: a reflection from Lagos, Nigeria

We assessed the effect of COVID-19 lockdown on deliveries and neonatal admissions according to gestation in Lagos, Nigeria. During lockdown (April–June 2020), there was a marked fall of about 50% in in-hospital deliveries and admissions to the neonatal wards for both in and outborn infants compared with prelockdown (January–March 2020) and a comparison period (April–June 2019). However, the proportion of preterm infants was broadly similar in each period. Lockdown markedly reduced hospital deliveries and healthcare-seeking for sick newborns but did not influence the overall proportion of preterm births among in-house deliveries and outborn neonatal admissions