Natasha Lelijveld

Chronic disease outcomes after severe acute malnutrition in Malawian children (ChroSAM): a cohort study

Summary Background Tackling severe acute malnutrition (SAM) is a global health priority. Heightened risk of non-communicable diseases (NCD) in children exposed to SAM at around 2 years of age is plausible in view of previously described consequences of other early nutritional insults. By applying developmental origins of health and disease (DOHaD) theory to this group, we aimed to explore the long-term effects of SAM. Methods We followed up 352 Malawian children (median age 9·3 years) who were still alive following SAM inpatient treatment between July 12, 2006, and March 7, 2007, (median age 24 months) and compared them with 217 sibling controls and 184 age-and-sex matched community controls. Our outcomes of interest were anthropometry, body composition, lung function, physical capacity (hand grip, step test, and physical activity), and blood markers of NCD risk. For comparisons of all outcomes, we used multivariable linear regression, adjusted for age, sex, HIV status, and socioeconomic status. We also adjusted for puberty in the body composition regression model. Findings Compared with controls, children who had survived SAM had lower height-for-age Z scores (adjusted difference vs community controls 0·4, 95% CI 0·6 to 0·2, p=0·001; adjusted difference vs sibling controls 0·2, 0·0 to 0·4, p=0·04), although they showed evidence of catch-up growth. These children also had shorter leg length (adjusted difference vs community controls 2·0 cm, 1·0 to 3·0, p<0·0001; adjusted difference vs sibling controls 1·4 cm, 0·5 to 2·3, p=0·002), smaller mid-upper arm circumference (adjusted difference vs community controls 5·6 mm, 1·9 to 9·4, p=0·001; adjusted difference vs sibling controls 5·7 mm, 2·3 to 9·1, p=0·02), calf circumference (adjusted difference vs community controls 0·49 cm, 0·1 to 0·9, p=0·01; adjusted difference vs sibling controls 0·62 cm, 0·2 to 1·0, p=0·001), and hip circumference (adjusted difference vs community controls 1·56 cm, 0·5 to 2·7, p=0·01; adjusted difference vs sibling controls 1·83 cm, 0·8 to 2·8, p<0·0001), and less lean mass (adjusted difference vs community controls −24·5, −43 to −5·5, p=0·01; adjusted difference vs sibling controls −11·5, −29 to −6, p=0·19) than did either sibling or community controls. Survivors of SAM had functional deficits consisting of weaker hand grip (adjusted difference vs community controls −1·7 kg, 95% CI −2·4 to −0·9, p<0·0001; adjusted difference vs sibling controls 1·01 kg, 0·3 to 1·7, p=0·005,)) and fewer minutes completed of an exercise test (sibling odds ratio [OR] 1·59, 95% CI 1·0 to 2·5, p=0·04; community OR 1·59, 95% CI 1·0 to 2·5, p=0·05). We did not detect significant differences between cases and controls in terms of lung function, lipid profile, glucose tolerance, glycated haemoglobin A1c, salivary cortisol, sitting height, and head circumference. Interpretation Our results suggest that SAM has long-term adverse effects. Survivors show patterns of so-called thrifty growth, which is associated with future cardiovascular and metabolic disease. The evidence of catch-up growth and largely preserved cardiometabolic and pulmonary functions suggest the potential for near-full rehabilitation. Future follow-up should try to establish the effects of puberty and later dietary or social transitions on these parameters, as well as explore how best to optimise recovery and quality of life for survivors. Funding The Wellcome Trust.

Long-term effects of severe acute malnutrition on lung function in Malawian children: a cohort study

Early nutritional insults may increase risk of adult lung disease. We aimed to quantify the impact of severe acute malnutrition (SAM) on spirometric outcomes 7 years post-treatment and explore predictors of impaired lung function. Spirometry and pulse oximetry were assessed in 237 Malawian children (median age: 9.3 years) who had been treated for SAM and compared with sibling and age/sex-matched community controls. Spirometry results were expressed as z-scores based on Global Lung Function Initiative reference data for the African–American population. Forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were low in all groups (mean FEV1 z-score: −0.47 for cases, −0.48 for siblings, −0.34 for community controls; mean FVC z-score: −0.32, −0.38, and −0.15 respectively). There were no differences in spirometric or oximetry outcomes between SAM survivors and controls. Leg length was shorter in SAM survivors but inter-group sitting heights were similar. HIV positive status or female sex was associated with poorer FEV1, by 0.55 and 0.31 z-scores, respectively. SAM in early childhood was not associated with subsequent reduced lung function compared to local controls. Preservation of sitting height and compromised leg length suggest “thrifty” or “lung-sparing” growth. Female sex and HIV positive status were identified as potentially high-risk groups. Despite stunting, survivors of acute malnutrition do not have worse lung function than controls http://ow.ly/2nvH308LroU

P05 Long-term effects of acute malnutrition on growth and body composition in malawian children

Aims Severe Acute malnutrition (SAM) is an important cause of child mortality worldwide and most treatment to date has focused on reducing those deaths. However, with emerging evidence that early nutritional adversity affects adult health, it is vital that treatment strategies also start looking beyond short term outcomes at programme discharge. To do this, improved evidence on the long term implications is needed; in this study, we examined growth and body composition 7 years after an episode of SAM. Methods We present latest data from a follow-up of 462 ex-malnourished Malawian children, comparing their growth and body composition to both siblings and age/sex matched community controls. These are the known survivors of an original cohort of 1024 children admitted to a large Malawian nutrition ward, from 2006 to 2007, for treatment of SAM. The current round of follow-up is 7 years after the original episode of malnutrition. Linear regression is used to analyse interim anthropometric data. Results To date, 321/412 (78%) of searches have been successful. Median age of the ex-malnourished ‘case’ children was 9 yrs 2 months (range: 7–20 years). 79/321 (25%) are HIV positive; 35/321 (11%) died in the last six years. Cases are significantly more stunted and underweight than community controls. Waist-hip ratio was significantly higher for cases suggestive of adverse body composition, however skinfold thickness ratio (subscapular+waist/tricep) was not significantly different between the groups. Sitting height ratio was also significantly higher for case children suggesting that torso length has been preserved and limb growth compromised. In addition, ex-malnourished case children had evidence of functional impairment with their hand-grip strength significantly weaker than that of community controls. Table 1 presents further details. Conclusions These results indicate that SAM may be associated with a number of adverse long-term effects, including stunting, abnormal body composition and functional impairment. It will be crucial to identify effective strategies, not only to prevent SAM in the first place, but to improve long-term outcomes in SAM survivors. Interventions might include more proactive case finding to encourage earlier detection and continued follow-up after the initial treatment to support high risk children and families. Abstract P05 Table 1 Linear regression of cases vs community controls

Carer and staff perspectives on supplementary suckling for treating infant malnutrition: qualitative findings from Malawi

Abstract Severe acute malnutrition (SAM) in infants aged <6 months is a major global health problem. Supplementary suckling (SS) is widely recommended as an inpatient treatment technique for infant <6 months SAM. Its aim is to re‐establish effective exclusive breastfeeding. Despite widespread support in guidelines, research suggests that field use of SS is limited in many settings. In this study, we aimed therefore to describe and understand the barriers and facilitating factors to SS as a treatment technique for infant SAM. We conducted qualitative interviews and focus group discussions in a hospital setting in Blantyre, Malawi, with ward staff and caregivers of infants <2 years. We created a conceptual framework based on five major themes identified from the data: (1) motivation; (2) breastfeeding views; (3) practicalities; (4) understanding; and (5) perceptions of hospital‐based medicine. Within each major theme, more setting‐specific subthemes can also be developed. Other health facilities considering SS roll‐out could consider their own barriers and facilitators using our framework; this will facilitate the implementation of SS, improve staff confidence and therefore give SS a better chance of success. Used to shape and guide discussions and inform action plans for implementing SS, the framework has the potential to facilitate SS roll‐out in settings other than Malawi, where this study was conducted. We hope that it will help pave the way to more widespread SS, more research into its use and effectiveness, and a stronger evidence‐base on malnutrition in infants aged <6 months.

The "ComPAS Trial" combined treatment model for acute malnutrition: study protocol for the economic evaluation

BackgroundAcute malnutrition is currently divided into severe (SAM) and moderate (MAM) based on level of wasting. SAM and MAM currently have separate treatment protocols and products, managed by separate international agencies. For SAM, the dose of treatment is allocated by the child’s weight. A combined and simplified protocol for SAM and MAM, with a standardised dose of ready-to-use therapeutic food (RUTF), is being trialled for non-inferior recovery rates and may be more cost-effective than the current standard protocols for treating SAM and MAM.MethodThis is the protocol for the economic evaluation of the ComPAS trial, a cluster-randomised controlled, non-inferiority trial that compares a novel combined protocol for treating uncomplicated acute malnutrition compared to the current standard protocol in South Sudan and Kenya. We will calculate the total economic costs of both protocols from a societal perspective, using accounting data, interviews and survey questionnaires. The incremental cost of implementing the combined protocol will be estimated, and all costs and outcomes will be presented as a cost-consequence analysis. Incremental cost-effectiveness ratio will be calculated for primary and secondary outcome, if statistically significant.DiscussionWe hypothesise that implementing the combined protocol will be cost-effective due to streamlined logistics at clinic level, reduced length of treatment, especially for MAM, and reduced dosages of RUTF. The findings of this economic evaluation will be important for policymakers, especially given the hypothesised non-inferiority of the main health outcomes. The publication of this protocol aims to improve rigour of conduct and transparency of data collection and analysis. It is also intended to promote inclusion of economic evaluation in other nutrition intervention studies, especially for MAM, and improve comparability with other studies.Trial RegistrationISRCTN 30393230, date: 16/03/2017.

Follow-up between 6 and 24 months after discharge from treatment for severe acute malnutrition in children aged 6-59 months: A systematic review

Background Severe acute malnutrition (SAM) is a major global health problem affecting some 16.9 million children under five. Little is known about what happens to children 6–24 months post-discharge as this window often falls through the gap between studies on SFPs and those focusing on longer-term effects. Methods A protocol was registered on PROSPERO (PROSPERO 2017:CRD42017065650). Embase, Global Health and MEDLINE In-Process and Non-Indexed Citations were systematically searched with terms related to SAM, nutritional intervention and follow-up between June and August 2017. Studies were selected if they included children who experienced an episode of SAM, received a therapeutic feeding intervention, were discharged as cured and presented any outcome from follow-up between 6–24 months later. Results 3,691 articles were retrieved from the search, 55 full-texts were screened and seven met the inclusion criteria. Loss-to-follow-up, mortality, relapse, morbidity and anthropometry were outcomes reported. Between 0.0% and 45.1% of cohorts were lost-to-follow-up. Of those discharged as nutritionally cured, mortality ranged from 0.06% to 10.4% at an average of 12 months post-discharge. Relapse was inconsistently defined, measured, and reported, ranging from 0% to 6.3%. Two studies reported improved weight-for-height z-scores, whilst three studies that reported height-for-age z-scores found either limited or no improvement. Conclusions Overall, there is a scarcity of studies that follow-up children 6–24 months post-discharge from SAM treatment. Limited data that exists suggest that children may exhibit sustained vulnerability even after achieving nutritional cure, including heightened mortality and morbidity risk and persistent stunting. Prospective cohort studies assessing a wider range of outcomes in children post-SAM treatment are a priority, as are intervention studies exploring how to improve post-SAM outcomes and identify high-risk children.

Children who are both wasted and stunted are also underweight and have a high risk of death: a descriptive epidemiology of multiple anthropometric deficits using data from 51 countries

BackgroundWasting and stunting are common. They are implicated in the deaths of almost two million children each year and account for over 12% of disability-adjusted life years lost in young children. Wasting and stunting tend to be addressed as separate issues despite evidence of common causality and the fact that children may suffer simultaneously from both conditions (WaSt). Questions remain regarding the risks associated with WaSt, which children are most affected, and how best to reach them.MethodsA database of cross-sectional survey datasets containing data for almost 1.8 million children was compiled. This was analysed to determine the intersection between sets of wasted, stunted, and underweight children; the association between being wasted and being stunted; the severity of wasting and stunting in WaSt children; the prevalence of WaSt by age and sex, and to identify weight-for-age z-score and mid-upper arm circumference thresholds for detecting cases of WaSt. An additional analysis of the WHO Growth Standards sought the maximum possible weight-for-age z-score for WaSt children.ResultsAll children who were simultaneously wasted and stunted were also underweight. The maximum possible weight-for-age z-score in these children was below − 2.35. Low WHZ and low HAZ have a joint effect on WAZ which varies with age and sex. WaSt and “multiple anthropometric deficits” (i.e. being simultaneously wasted, stunted, and underweight) are identical conditions. The conditions of being wasted and being stunted are positively associated with each other. WaSt cases have more severe wasting than wasted only cases. WaSt cases have more severe stunting than stunted only cases. WaSt is largely a disease of younger children and of males. Cases of WaSt can be detected with excellent sensitivity and good specificity using weight-for-age.ConclusionsThe category “multiple anthropometric deficits” can be abandoned in favour of WaSt. Therapeutic feeding programs should cover WaSt cases given the high mortality risk associated with this condition. Work on treatment effectiveness, duration of treatment, and relapse after cure for WaSt cases should be undertaken. Routine reporting of the prevalence of WaSt should be encouraged. Further work on the aetiology, prevention, case-finding, and treatment of WaSt cases as well as the extent to which current interventions are reaching WaSt cases is required.