Pediatric thiamine deficiency disorders in high‐income countries between 2000 and 2020: a clinical reappraisal

Abstract

Often thought to be a nutritional issue limited to low-and middle-income countries (LMICs), pediatric thiamine deficiency (PTD) is perceived as being eradicated or anecdotal in high-income countries (HICs). In HICs, classic beriberi cases in breastfed infants by thiamine-deficient mothers living in disadvantaged socioeconomic conditions are thought to be rare. This study aims to assess PTD in HICs in the 21st century. Literature searches were conducted to identify case reports of PTD observed in HICs and published between 2000 and 2020. The analyzed variables were age, country, underlying conditions, clinical manifestations of PTD, and response to thiamine supplementation. One hundred and ten articles were identified, totaling 389 PTD cases that were classified into four age groups: neonates, infants, children, and adolescents. Eleven categories of PTD-predisposing factors were identified, including genetic causes, lifestyle (diabetes, obesity, and excessive consumption of sweetened beverages), eating disorders, cancer, gastrointestinal disorders/surgeries, critical illness, and artificial nutrition. TD-associated hyperlactatemia and Wernicke encephalopathy were the most frequent clinical manifestations. The circumstances surrounding PTD in HICs differ from classic PTD observed in LMICs and this study delineates its mutiple predisposing factors. Further studies are required to estimate its magnitude. Awareness is of utmost importance in clinical practice.

Thiamine as a Possible Neuroprotective Strategy in Neonatal Hypoxic-Ischemic Encephalopathy

“…In the neonatal period (birth to 28 days) TD is rare, as usually thiamine levels are higher in newborns and in cord blood due to the preferential delivery of this vitamin to the fetus at the expense of the mother [ 85 , 86 , 87 , 88 ]. This biological mechanism, which in humans is the preferential distribution of thiamine to the developing tissues, highlights the importance of optimizing the intake and status of this vitamin in the mother and the newborn in order to foster, in this crucial period for acquisition of fundamental cognitive skills, an optimal neurodevelopmental outcome [ 89 , 90 , 91 ].…”

“…However, this mechanism does not preclude in the newborn the occurrence of TD when the mother, and her breast milk, are deficient in this vitamin and the infant is exclusively breastfed, as may frequently happen in low-and middle-income countries [ 87 ]. Other clinical settings that may predispose to TD in this age group, also in high-income countries, are total parenteral nutrition or enteral nutrition, genetic inborn errors of thiamine metabolism, gastrointestinal disorders and acute critical illness, including pediatric emergency room, surgical settings, pediatric cardiology and nephrology/dialysis [ 88 ].…”

“…Considering that the body’s stores of thiamine in humans are only sufficient for up to 18 days [ 24 ] after birth, in a full-term infant with deficient intake of this vitamin, it is conceivable that the earliest clinical manifestations of TD usually present at about one month of age [ 87 , 88 ]. Early clinical signs may be refusal to breastfed, irritability, vomiting and persistent crying that is difficult to console.…”

“…Early clinical signs may be refusal to breastfed, irritability, vomiting and persistent crying that is difficult to console. [ 87 , 88 ]. Importantly, the progression of clinical symptoms/signs to overt infantile beriberi is a medical emergency, as infants can die within hours of clinical presentation if not promptly treated [ 88 ].…”

“…Importantly, the progression of clinical symptoms/signs to overt infantile beriberi is a medical emergency, as infants can die within hours of clinical presentation if not promptly treated [ 88 ]. The clinical presentation is broad and may include cardiovascular disturbances, such as critical heart failure, shock and pulmonary arterial hypertension, aphonia, absent deep-tendon reflexes, nystagmus, ophthalmoplegia, altered consciousness, seizures, respiratory symptoms and hyperlactatemia with acidosis [ 87 , 88 ]. High doses of parenteral thiamine supplementation promptly reverses these clinical disturbances and the hyperlactatemia [ 24 , 87 , 88 ].…”