Long-term effects of exposure to and recovery from severe acute malnutrition on growth, body composition, physical activity, and cardiometabolic health of Ethiopian children: a five-year prospective matched cohort study

Abstract

Background: Severe acute malnutrition (SAM) is a major global public health problem associated with a 12 times higher risk of mortality compared to healthy children. Ethiopia faces a significant burden of SAM and has made substantial investments in implementing the Community-based Management of Acute Malnutrition (CMAM) approach to tackle this issue. These efforts have dramatically increased the coverage and early identification of cases, reduced short-term SAM-related mortality and proven to be cost-effective. However, whilst the short-term nutritional and health outcomes have been well documented, limited data exists on the longer-term outcomes of SAM treatment; this includes minimizing the sequelae of SAM episodes by promoting physical growth, restoring normal body composition, enhancing physical activity, and reducing the risk of cardiometabolic disease later in life. The current lack of reliable evidence regarding the long-term nutritional and health impacts of SAM poses challenges in recommending effective strategies to achieve positive outcomes. Additionally, much of the existing research is outdated, which further limits the ability to propose appropriate actions. We hypothesized that SAM survivors would not achieve catch-up growth at five year post-recovery, and this could result in hierarchical preservation of some tissue relative to others, resulting in deficient lean mass that could, in turn, impact their physical activity level. Furthermore, the heterogeneity arising from case definitions for SAM and the variability in weight gain during nutritional recovery could be associated with cardiometabolic outcomes. We hypothesized that children exposed to SAM and treatment would have increased cardiometabolic risk, and that this would apply in particular to children with the most severe malnutrition who experienced the most rapid weight gain during the post-recovery period. Objective: The overall objective of this study was to close the knowledge gaps mentioned above and included a range of specific objectives including describing long-term effects of exposure to SAM and treatment on growth, body composition, physical activity and risk of cardiometabolic disease at five-year post-recovery comparative to that of matched community controls. Recognizing the heterogeneity of SAM case definitions and patterns of nutritional recovery, we also aimed to identify distinct BMI-for-age (BAZ) trajectories of SAM children in the first-year post-recovery and examine their associations with cardiometabolic risk markers five-years later. xii Method: This thesis is based on data collected during two periods of a prospective cohort study in 5 districts of Jimma zone, Ethiopia. The first study, called ENGINE (Empowering New Generations to Improve Nutrition and Economic Opportunities), was conducted in 2013. It involved children with SAM who had recovered from a Community-Based Management of Acute Malnutrition (CMAM) program. These children were matched by age and sex with community controls and were followed monthly for one year. The second study, named ACAM (Assessment of Long-Term Health Consequences of Acute Malnutrition), was conducted in 2018, five years after the SAM children were discharged as recovered from CMAM. A total of 405 children (203 children recovered from SAM and 202 non-wasted controls) aged 6-59 months from the first study were eligible for inclusion into the ACAM study. Anthropometry, body composition [using bioelectric impedance and deuterium dilution technical and expressed as fat-free mass index (FFMI) and fat-mass index (FMI)], physical activity [measured objectively using a tri-axial accelerometer and expressed as vector magnitude counts per minute (cpm)] and blood markers of cardiometabolic risk were assessed at five-year post recovery. Multiple linear regression models compared outcomes between children recovered from SAM and controls. We used latent class trajectory modelling to identify BAZ trajectories in the first-year post-recovery and compared these trajectory groups with controls for cardiometabolic risk markers at five-year post-recovery. Results: We traced 291 (71.9%) children (mean age 6.2 years) at five-year follow-up. Children recovered from SAM had higher stunting prevalence than controls at recovery (82.2% compared with 36.0%; P < 0.001), one year (80.2% compared with 53.7%; P < 0.001), and five year post-recovery (74.2% compared with 40.8%; P < 0.001). Children recovered from SAM remained 5 cm shorter at five year follow-up, indicating no catch-up in height-for-age z score (HAZ). Similarly, they had lower hip (-2.05 cm; 95% confidence interval: -2.73, -1.36), waist (-0.92 cm; CI: -1.59, -0.23) and mid-upper arm (-0.64 cm; CI: -0.90, -0.42) circumferences and lower-limb length (-1.57 cm; 95% CI: -2.21, -0.94) than controls at five year post-recovery. They also had persistent deficits in FFMI at discharge and 6-month and five year post-recovery (P < 0.001 for all), which was associated with lower physical activity levels at five year post-recovery compared to controls (436 cpm compared with 480.5 cpm, p=0.018). No difference was detected in head circumference, sitting height, or FMI. Overall, compared to controls, children who recovered from SAM did not differ in cardiometabolic risk. However, we identified four BMI-for-age z-score (BAZ) trajectories among children recovered from SAM: “Increase” (74.6%), “Decrease” (11.0%), “Decrease-increase” (5.0%), and xiii “Increase-decrease” (9.4%). Compared to controls, the “Decrease-increase” trajectory had lower glucose (-15.8 mg/dL; 95%CI: -31.2, -0.4), while the “Increase-decrease” trajectory had higher glucose (8.1 mg/dL; CI: -0.8, 16.9). Compared to controls, the “Decrease-increase” and “Decrease” trajectories had higher total cholesterol (24.3 mg/dL; CI: -9.4, 58.4) and LDL cholesterol (10.4 mg/dL; CI: -3.8, 24.7), respectively. The “Increase” trajectory had the lowest cardiometabolic risk. Conclusion: Five years after CMAM treatment for SAM, children maintained deficits in HAZ, lower-limb length, and FFMI, with preservation of FMI, sitting height, and head circumference indicating a “thrifty growth” pattern. Additionally, they spent more time in sedentary behavior. Moreover, both rapid BAZ increase and decrease during early post-recovery from SAM were associated with greater cardiometabolic risk five years later. The findings indicate the need to design post-recovery interventions to optimize healthy weight and height recovery.