Biomarkers Make the Case for a Comprehensive Approach to Diagnosing Severe Acute Malnutrition.

Abstract

Aim 2.2 of the 2015 United Nations Sustainable Development Goals is to “end all forms of malnutrition” by 2030.1 Nevertheless, severe acute malnutrition (SAM) continues to pose a major threat to global child health, especially throughout sub-Saharan Africa and South Asia, even in nonconflict and nonfamine areas. Malnutrition is linked to approximately one-half of the deaths of children <5 years old worldwide,2 and an estimated 10 000 additional malnutrition-associated deaths among children are expected to be occurring globally during the coronavirus disease 2019 pandemic, because of interruptions in health and nutrition services.3 Food insecurity, household size, rural–urban disparities, and gaps in health literacy are commonly cited risk factors for SAM in low- and middle-income countries.4SAM and its complications can be difficult to recognize unless objective diagnostic measures are applied, namely weight-for-height z score (WHZ) and mid-upper arm circumference (MUAC). Use of the MUAC dates back to the 1950s, an innovation of post–World War II humanitarianism. It was first proposed to the World Health Organization as a metric for the nutritional assessment of children <5 years of age in 1966,5 but MUAC was progressively abandoned when its assumptions of age and sex independence were called into question.6,7In the past several decades, however, renewed support has emerged for the routine use of MUAC as an easily scalable field test in resource-limited settings where scales and height boards are scarce.8 In 2009, the World Health Organization and United Nations International Children’s Emergency Fund endorsed a MUAC cutoff point of <11.5 cm (previously <11.0 cm) as an independent hospital admission criterion for SAM.9 As MUAC became increasingly popular, in a growing body of evidence, researchers pointed to its superiority as a predictor of mortality, energizing its proponents and fueling MUAC-only approaches.10–12In this issue of Pediatrics, using a 3-country multicentric cohort study of children with uncomplicated, nonedematous SAM, Dailey-Chwalibóg et al13 call into question the safety of MUAC-only approaches. They note a significantly higher odds of complications (in all categories except malaria diagnosis) detected in the combined WHZ-MUAC group, as compared with the MUAC-only group, suggesting that the children at risk for the worst complications may have been missed if it were not for additional consideration of WHZ. With these findings, Dailey-Chwalibóg et al13 validate conclusions in a 2018 systematic review that revealed that only a minority of SAM patients fulfill both WHZ and MUAC criteria, yet mortality is similarly high for patients diagnosed by using either WHZ-only or MUAC-only approaches.14Dailey-Chwalibóg et al13 were innovative in their use of a biomarker (leptin) drawn at the time of SAM diagnosis as a surrogate variable for mortality risk. Leptin is a marker of adipose tissue reserve and critical modulator of immune function.15 In SAM, hypoleptinemia is a biochemical predictor of mortality both at the time of diagnosis and after hospital discharge.16 However, there are lingering questions about exactly why so much heterogeneity exists in the literature regarding MUAC sensitivity, including whether age and sex do in fact significantly influence MUAC17 and whether observed geographic differences for edematous-SAM prevalence may also underpin regional differences in MUAC performance.18 For example, in this study of children with nonedematous SAM, Dailey-Chwalibóg et al13 observed that the difference in leptin levels among MUAC-only and WHZ-only groups were most the pronounced in Bangladesh and less so in West Africa. Furthermore, it remains to be seen whether leptin fluctuations in response to certain infections (including malaria) may be confounding the leptin-survival association.19MUAC has been an indispensable diagnostic innovation that has likely saved tens of thousands of lives through mass screening campaigns. However, MUAC-only screening programs are only temporizing measures. We agree with the assessment by Dailey-Chwalibóg et al13 that WHZ and MUAC should be used in tandem whenever possible, and, in settings where there are no scales or height boards, children with borderline MUACs should be referred to bridging facilities for a more thorough anthropometric evaluation.Dailey-Chwalibóg et al13 should be commended for applying scientific rigor to an often-neglected field of pediatric health; this work and others like it will undoubtedly save lives. However, we must also finally acknowledge that the most daunting challenge of childhood malnutrition (its elimination) still looms. The rapid development of several highly effective vaccines against severe acute respiratory syndrome coronavirus 2 over the past year has been a stunning example of what can happen when scientists and governments mobilize to make public health a priority. In the same way, the problem of childhood malnutrition demands multinational urgency, innovation, and accountability among both scientists and policy makers. Perhaps what is needed now, as Dailey-Chwalibóg et al13 would likely agree, is not necessarily the discovery of the next great SAM biomarker but, rather, a renewed and substantiated commitment by international governments and organizations to end malnutrition and dismantle the systems of global inequity perpetuating it.