New Insights into the Pathogenesis and Treatment of Malnutrition

Malnutrition affects 52 million children under age 5 years, contributing to 45% of child mortality. Chronic malnutrition results in stunting (low height for age), present in 155 million children—87 million in Asia and 59 million in Africa. The 16.9 million children with severe wasting (low weight for height), including 12.6 million in Asia and 4.1 million in Africa,1 have a 9.4-fold greater chance of dying compared with healthy-weight children.2 The World Health Organization (WHO) defines severe acute malnutrition (SAM) as mid-upper arm circumference (MUAC) less than 115 mm or weight-for-height z score (WHZ) less than −3 for ages 6 months to 59 months. Both acute and chronic malnutrition can cause long-term cognitive deficits. Low birthweight, stunting, and wasting correlate with lower scores on intelligence tests, developmental delays, and decreased lifetime earnings, perpetuating the poverty-malnutrition cycle.3 The WHO recommends that all children with SAM are treated with therapeutic foods. Children with minimal appetite or medical complications should receive inpatient treatment with therapeutic milk (F-75 and later F-100) and an antibiotic with gram-negative coverage and then be transitioned to community-based treatment with ready-to-use therapeutic food (RUTF). Children should be monitored until recovery, defined as WHZ greater than or equal to −2 or MUAC greater than or equal to 125 mm and greater than or equal to 2 weeks without edema.4 Despite these guidelines, SAM mortality rates in the hospital setting remain as high as 10% to 40%, and meta-analyses examining long-term outcomes reveal mixed results.5,6 Among the key barriers to improving care is an incomplete understanding of mechanisms underlying the metabolic and physiologic abnormalities of SAM. Recent insights into the pathogenesis of malnutrition instill hope that better outcomes might soon be possible. This review highlights new evidence relevant to 5 topics, including early-life determinants of malnutrition, the role of protein deficiency in the development and perpetuation of malnutrition, the drivers of malnutrition-associated immune deficiencies, impaired gut barrier function and resulting inflammation, and potential roles of the intestinal microbiota in the pathogenesis and treatment of malnutrition.