Severe malnutrition or famine exposure in childhood and cardiometabolic non-communicable disease later in life: a systematic review.

INTRODUCTION: Child malnutrition (undernutrition) and adult non-communicable diseases (NCDs) are major global public health problems. While convincing evidence links prenatal malnutrition with increased risk of NCDs, less is known about the long-term sequelae of malnutrition in childhood. We therefore examined evidence of associations between postnatal malnutrition, encompassing documented severe childhood malnutrition in low/middle-income countries (LMICs) or famine exposure, and later-life cardiometabolic NCDs. METHODS: Our peer-reviewed search strategy focused on 'severe childhood malnutrition', 'LMICs', 'famine', and 'cardiometabolic NCDs' to identify studies in Medline, Embase, Global Health, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases. We synthesised results narratively and assessed study quality with the UK National Institute for Health and Care Excellence checklist. RESULTS: We identified 57 studies of cardiometabolic NCD outcomes in survivors of documented severe childhood malnutrition in LMICs (n=14) and historical famines (n=43). Exposure to severe malnutrition or famine in childhood was consistently associated with increased risk of cardiovascular disease (7/8 studies), hypertension (8/11), impaired glucose metabolism (15/24) and metabolic syndrome (6/6) in later life. Evidence for effects on lipid metabolism (6/11 null, 5/11 mixed findings), obesity (3/13 null, 5/13 increased risk, 5/13 decreased risk) and other outcomes was less consistent. Sex-specific differences were observed in some cohorts, with women consistently at higher risk of glucose metabolism disorders and metabolic syndrome. CONCLUSION: Severe malnutrition or famine during childhood is associated with increased risk of cardiometabolic NCDs, suggesting that developmental plasticity extends beyond prenatal life. Severe malnutrition in childhood thus has serious implications not only for acute morbidity and mortality but also for survivors' long-term health. Heterogeneity across studies, confounding by prenatal malnutrition, and age effects in famine studies preclude firm conclusions on causality. Research to improve understanding of mechanisms linking postnatal malnutrition and NCDs is needed to inform policy and programming to improve the lifelong health of severe malnutrition survivors.