Children with moderate acute malnutrition with no access to supplementary feeding programmes experience high rates of deterioration and no improvement: Results from a prospective cohort study in rural Ethiopia

Background Children with moderate acute malnutrition (MAM) have an increased risk of mortality, infections and impaired physical and cognitive development compared to well-nourished children. In parts of Ethiopia not considered chronically food insecure there are no supplementary feeding programmes (SFPs) for treating MAM. The short-term outcomes of children who have MAM in such areas are not currently described, and there remains an urgent need for evidence-based policy recommendations. Methods We defined MAM as mid-upper arm circumference (MUAC) of ≥11.0cm and <12.5cm with no bilateral pitting oedema to include Ethiopian government and World Health Organisation cut-offs. We prospectively surveyed 884 children aged 6-59 months living with MAM in a rural area of Ethiopia not eligible for a supplementary feeding programme. Weekly home visits were made for seven months (28 weeks), covering the end of peak malnutrition through to the post-harvest period (the most food secure window), collecting anthropometric, socio-demographic and food security data. Results By the end of the study follow up, 32.5%(287/884) remained with MAM, 9.3% (82/884) experienced at least one episode of SAM (MUAC <11cm and/or bilateral pitting oedema), and 0.9% (8/884) died. Only 54.2% of the children recovered with no episode of SAM by the end of the study. Of those who developed SAM half still had MAM at the end of the follow up period. The median (interquartile range) time to recovery was 9 (4-15) weeks. Children with the lowest MUAC at enrolment had a significantly higher risk of remaining with MAM and a lower chance of recovering. Conclusions Children with MAM during the post-harvest season in an area not eligible for SFP experience an extremely high incidence of SAM and a low recovery rate. Not having a targeted nutrition-specific intervention to address MAM in this context places children with MAM at excessive risk of adverse outcomes. Further preventive and curative approaches should urgently be considered. This was an observational, prospective cohort study of children aged 6–59 months with MAM living in a setting without SFP provision, followed weekly for seven months. Our primary objectives were to determine the proportion of recovery, non-response and deterioration to SAM; the incidence of mortality and SAM, and the average duration of the MAM episode. Our secondary objective was to identify child, household, and caretaker characteristics associated with the different outcomes and to compare the outcomes with reports from SFPs in food-insecure settings. MAM was defined as having mid-upper arm circumference (MUAC) of ≥11.0cm and <12.5cm with no bilateral pitting oedema. This definition comprises an expanded MUAC bracket to incorporate two cut-offs; the in-country criteria and the World Health Organisation (WHO) 2009 criteria. The Ethiopian Emergency Nutrition Coordination Unit (ENCU) defines MAM as MUAC ≥11.0cm and <12.0cm [27], whereas the WHO (2009) define MAM as MUAC ≥11.5cm and <12.5cm [28]. We therefore decided to use the expanded bracket in order to collect data that would be applicable to both the Ethiopian and international nutrition communities. Unless otherwise specified the definition of SAM in our main results section uses the ENCU definition of MUAC <11.0cm and/or bilateral pitting oedema [27]. The period of follow-up was set at 7 months (September 2013 –March 2014) in order to capture data from the end of the peak malnutrition period right through to the post-harvest period. The agricultural calendar for Jimma Zone indicating the study implementation period is shown in Fig 1. The study was conducted in Mana and Dedo woredas of Jimma Zone in South-western Ethiopia. These study areas were selected to represent rural settings with no access to SFPs, but where other health and nutrition services were delivered according to the national policy. These services included the Integrated Management of Maternal, Neonatal and Childhood Illnesses (IMNCI), the Integrated Community Case Management of illness (ICCM), and the Community-based Management of Acute Malnutrition (CMAM) to treat SAM. Through the Enhanced Outreach Strategy (EOS) vitamin A supplementation and deworming treatment was scheduled for distribution at 6-monthly campaigns. Immunisation, basic nutrition and sanitation counselling were provided through the health extension system. Subsistence farming is the dominant form of livelihood in the area. Major crops produced in the area are cereals (maize, teff, sorghum and barley), pulses (beans and peas), cash crops (coffee and khat), and root crops (false banana and potato) [29]. Mana and Dedo woredas have a similar agro-ecological pattern. Despite being known as one of the more food secure regions in Ethiopia the area experiences seasonal deterioration of food security. The sample size for the expected number of children deteriorating to SAM was calculated using the web-based OpenEpi software [30]. Anticipating a 10% deterioration to SAM with a 95% confidence level of ±2.5%, assuming a design effect of 1.5 and a loss to follow up of 20%, the required sample size was 996. The choice of 10% was based on the observed deterioration to SAM in a cohort of MAM children enrolled in a supplementary feeding programme in two regions of Ethiopia [31]. The sample size calculated for the proportion of recovered children was 691 children. This was calculated using the same loss to follow up proportion and design effect but assuming a 49± 5% recovery rate as in the evaluation mentioned above [31]. The target sample size of 996 was not reached but the loss to follow up was much lower than anticipated, making our sample size sufficient for the primary and secondary outcomes. Children were identified during a 10-day (5 days per woreda) exhaustive house-to-house MUAC and bilateral pitting oedema screening implemented by 82 trained community health volunteers (CHVs) in August-September 2013. Cohorts in Mana and Dedo woredas were started within two weeks of each other. During the initial screening 923 children were identified as eligible after determining the child’s MUAC met the MAM definition with no bilateral pitting oedema or medical complications and was not planning to move out of the study area. Forty data collectors then collected the baseline household questionnaire within the following week and performed weekly home visits for the subsequent 28 weeks. Fig 2 summarises the flow of participants through the study resulting in 884 children included for analysis. Final outcomes were assigned to children after 28 weeks of follow up. ‘Recovered’ was defined when a child obtained MUAC ≥12.5cm with no oedema by week 28 and had never experienced an episode of SAM throughout the follow up. ‘Deteriorated to SAM’ was defined as reaching a MUAC <11.0 cm or presenting bilateral pitting oedema any time during follow up. ‘Died’ was a death recorded during the study follow up, confirmed by a home visit. ‘Loss to follow up’ were those children who dropped out of the study due to moving away or refusal. ‘Remained MAM’ was defined as a child who never experienced a SAM episode but whose MUAC still remained below 12.5cm at the 28th week of follow up. We further categorised these children into those who remained with MAM throughout the entire follow up period, and those who relapsed to MAM. The relapsed children were defined as those who had reached the recovery criteria of MUAC ≥12.5cm for two consecutive weeks but deteriorated back to MAM before the 28th week of follow up. We designed a baseline questionnaire to capture potential predictors of the children’s final outcomes. The questionnaire included child, household and caretaker related variables. All predictors of outcomes are fully defined in the following section. Child-related variables included sex, age at enrolment, feeding index, immunization status, access to EOS, common illnesses in the previous two weeks (diarrhoea, fever, cough, difficulty breathing), hand washing practices, bed net use and baseline weight, height and MUAC. Household variables included questions to assess wealth index, household size, main income generating activity, food security status, water and sanitation questions, geographical access to primary health care, death of a family member and household head information. Caretaker-related variables included relationship to the child, age, educational status, occupation, work burden index, access to and source of information about recommended child feeding and care practices, hand washing practices, disposal of young child faeces, health seeking behaviour and MUAC. Weekly questionnaires were designed to track the cohort’s anthropometric, mortality and morbidity profile over the follow up period. We obtained information on common childhood illnesses, weight, MUAC and development of nutritional oedema. Height was taken monthly. Both the baseline and weekly questionnaires were pre-tested and translated into Amharic and Afan Oromo languages. Nutritional oedema was assessed by pressing the thumbs down on both feet, holding for three seconds and observing if any bilateral indentation remained. Weight was measured using SECA 874 digital floor scales to the nearest 50 grams. Weight of small children was taken together with their caretakers. Height was measured for children aged ≥2 years and length for children <2 years. Both measures were taken using locally produced wooden boards to the nearest 0.1cm. MUAC was measured on the left arm using standard numbered insertion tapes to the nearest 0.1cm. The anthropometric measures were taken of the children in minimal clothing and without shoes using standard measurement techniques [32]. Immunisation status was only recorded for children with an immunisation record card. As measures of child morbidity we asked the caretaker if the child had experienced diarrhoea, fever, cough or difficulty breathing in the prior two weeks. Diarrhoea was defined as 3 or more loose stools per day and fever as being hot to the touch. The household wealth index was assessed using the standard criteria from the Ethiopia 2011 Demographic and Health Survey [22], which included a durable asset list, recording the land and animals owned and observation of housing materials. Healthcare accessibility was captured by recording the transportation used to reach the nearest health facility and the time taken to reach there. To minimise bias, all data collectors received a standardised training for conducting the anthropometry and questionnaires. CHVs received a one-day refresher on MUAC screening techniques, and data collectors received 8 days of training on anthropometry and questionnaire delivery. The study was preceded by pilot testing all of the data collection tools, conducted within the study area but in households not selected for the study. The data collectors were closely supervised to confirm adherence to the interview procedures. Anthropometric indices (weight-for-height, height-for-age and weight-for-age) were calculated in Stata according to WHO (2006) growth standards [33] using the zscore06 command [34]. Weight-for-height z-score (WHZ), height-for-age z-score (HAZ) and weight-for-age z-score (WAZ) at enrolment were categorised into <-3 z-scores, ≥-3 and <-2 z-scores and >-2 z-scores. Child MUAC was split into 11.0–11.4cm, 11.5–11.9cm and 12.0–12.4cm categories. Caretaker MUAC was categorised into MUAC <23cm and ≥23cm. A respiratory illness variable was created and 3 categories defined: those having no cough, those with cough but no difficulty breathing and those with cough and difficulty breathing. The feeding practice of children was summarised using the Infant and Child Feeding Index (ICFI) score [35]. The ICFI creates three categories based on a final score derived from the caretaker’s previous day recall of breastfeeding, dietary diversity in 7 food groups as per methodology in Arimond and Ruel [36] and feeding frequency [37]. The scores are assigned according to the child’s age category, with each age category scoring a maximum of 6 (S1 Table). The final three ICFI categories were then grouped so that those with scores of 0–2 were assigned to the lowest group, 3–4 to the middle group and 5–6 to the highest group. Hand washing scores for the child and caretaker were created by assigning no = “0” and yes = “1” for seven hand washing questions, totalling the scores and dividing into three categories with the lowest category containing scores 0–2, the middle one containing scores 3–5 and the highest category containing scores 6 and 7. Hand washing questions for the caregiver were for after defecation, before preparing food, before breastfeeding, after cleaning child’s faeces, before eating, after eating and when hands are dirty. Hand washing questions for the child were regarding before and after defecation, before eating, after eating, after crawling and after touching dirty things. The caretaker’s work index was created using responses to questions on how many days in the preceding week the caretaker had worked on herding animals, farm work, fetching water, washing clothes, cooking, child care, grinding grain and carrying a heavy load. The answers were summed and divided into tertiles to form ‘least heavy’, ‘middle’ and ‘most heavy’ categories. Wealth index scores and resulting quintiles were generated from the data collected on wealth using the criteria listed above by principal components analysis using the methodology described in detail in Vyas and Kumaranayake [38]. Healthcare accessibility categories were defined based on the time taken to reach the nearest health facility as ≤30 minutes, >30–60 minutes and >60 minutes. The number of different topics covered in counselling sessions from a health extension worker in the past month was summarised in three categories: none received, 1–2 topics, and 3 or more topics. Caretakers’ knowledge of danger signs was summarised into three categories: zero, 1–3, and 4 or more signs (out of a total of 7 possible answers). Two health-seeking behaviour variables were created regarding what the caregiver did when the child was ill. ‘Good’ health-seeking behaviours were defined as taking the child to the health facility, giving the child modern medicine, giving more food, giving more clean water, having a separate plate for the child and increasing the amount attention given. ‘Poor’ behaviours included giving traditional medicine, giving less food and water, and prioritising a traditional healer or other faith healing practices. Water, sanitation and hygiene (WASH) questions were summarised as recommended by the WHO & UNICEF (2006) methodology [39], producing the standard binary variables of improved/unimproved drinking water sources and latrine type, and safe/unsafe water treatment and disposal of youngest child’s faeces. Household food security status was summarised using the nine questions and scoring methodology from the Household Food Insecurity Access Scale (HFIAS), described in detail by Coates et al. [40]. We described baseline characteristics of the cohort using proportions for categorical variables, means for normally distributed continuous variables and medians for non-normal continuous variables. For our main analysis we present results using the MAM and SAM definitions as per our study design, using Ethiopian government cut-offs. However, in order to also present data that can be externally validated using WHO (2009) cut-offs, we also analysed our primary objectives using a subsample of our cohort. Here we defined SAM as MUAC <11.5cm and MAM as MUAC 11.5–12.4cm, therefore excluding children enrolled with MUAC 11.0–11.4cm (n = 111). We calculated deterioration to SAM incidence using the first episode only. Since deterioration to SAM was the primary outcome, we listed any child who experienced an episode of SAM under that category, and listed any further details as sub-categories (i.e. those who had SAM who then recovered, became MAM, died, or were lost to follow up). We stratified Kaplan-Meier survival plots for deterioration to SAM by MUAC admission category and compared curves using the log-rank test with Bonferroni correction in the case of multiple comparisons. To analyse potential predictors for the outcomes we performed univariable and multivariable Cox regression for deterioration to SAM and recovery, and multinomial univariable and multivariable logistic regression for the ‘remaining MAM’ outcomes. In the case of the latter we included two levels in our multinomial outcome: children who recovered but then relapsed before the 28th week of follow up, and those who remained MAM throughout the follow up. These outcomes were compared against children who recovered. Children who died and were lost to follow up were excluded from our multinomial logistic regression models. The models provided relative risk ratios and their 95% confidence intervals. For the cox regression analyses we checked whether proportional hazards assumptions were met using three methods. Firstly, we inspected the -ln(-n(survival)) versus ln(analysis time) plots (stphplot command in Stata) to look at convergence of curves. Secondly, we used the smoothed scaled Schoenfeld residuals versus time plots to test for a non-zero slope (estat phtest Stata command). Thirdly, we plotted a lowess curve to assess how much the scaled Schoenfeld residuals versus time plots deviated from the horizontal reference line at y = 0 (stphtest Stata command). The proportional hazards ratio assumptions were not met for some explanatory variables (MUAC category, gender and HAZ category) and so we performed extended Cox proportional hazards models that took into account the non-proportionality of these variables. Since the results of the extended models had little influence on the interpretation of the results the simpler models (with proportional hazards violations) were reported for ease of interpretation, as suggested by Allison (1995)[41]. For completeness we present the extended models in Tables A-C of S1 File, which include details on the time*covariate interaction terms fitted for the violating variables. Given that our goal was to identify primary predictors whilst controlling for putative confounding variables, variable selection was done manually using the p-value and the change-in-estimate method [42,43]. Robust standard errors were used throughout. No imputation method for missing values was used. We restricted all the analysis to children with complete information. Data were double entered at the field level using Epi Data version 3.2 [44]. Data cleaning and all data analyses were performed using Stata 13.0 [45]. The study was approved by the ethical review board of Jimma University (reference RPGC/131/2013). Enrolment into the study was voluntary and data collection was initiated after obtaining written consent or thumbprint from the caregiver of the child. Any child who deteriorated to SAM (MUAC <11.0cm or bilateral pitting oedema) at any point during the follow up was referred to the nearest health facility for outpatient therapeutic feeding programmes as per existing national protocol, and continued to be followed up.