Hypoglycaemia and hypoxic–ischaemic encephalopathy

Abstract

HIE Hypoxic-ischaemic encephalopathyThe transition from fetal to neonatal life requires metabolic adaptation to ensure that energy supply to vital organs and systems is maintained after separation from the placental circulation. Under normal conditions, this is achieved through the mobilization and use of alternative cerebral fuels (fatty acids, ketone bodies, and lactate) when blood glucose concentration falls. Severe hypoxia-ischaemia is associated with impaired metabolic adaptation, and animal and human data suggest that levels of hypoglycaemia that are tolerated under normal conditions can be harmful in association with hypoxia-ischaemia. The optimal target blood glucose level for ensuring adequate energy provision in hypoxic-ischaemic encephalopathy (HIE) remains unknown. However, recent data support guidance to maintain a blood glucose concentration of 2.5mmol/L or more in neonates with signs of acute neurological dysfunction, which includes those with HIE, and this is higher than the accepted threshold of 2mmol/L in infants without signs of neurological dysfunction or hyperinsulinism. CEREBRAL ENERGY SUFFICIENCY AND METABOLIC ADAPTATION AT BIRTHDuring fetal life, the predominant source of brain energy is glucose, which crosses the placenta by facilitated diffusion; there is very little endogenous glucose production under normal circumstances, although this increases in cases of intrauterine growth restriction and placental insufficiency. Ketone bodies and lactate may also be cerebral energy substrates in the healthy fetus. Amino acids, free fatty acids, and glycerol from the placental circulation are typically used for growth and the accumulation of fuel stores in preparation for birth, but they can serve as brain energy substrates if there is fetal growth restriction. 1,2During labour, the fetus is exposed to physiological challenges that require metabolic adaptation to occur if cerebral energy sufficiency is to be preserved. Anaerobic metabolism occurs under the transient hypoxic conditions of a typical labour, and this consumes more substrate than oxidative metabolism would. There is an abrupt cessation of continuous substrate supply when the placental circulation is divided, with a consequent drop in blood glucose concentration, and the fetus must then adapt to use lipids as the predominant energy substrate. A healthy infant successfully manages the postnatal transition by mobilizing and using alternative cerebral fuels including ketone bodies, fatty acids, and lactate. After birth, there is a rapid surge in catecholamine and glucagon levels, and a steady decrease in insulin, at the same time as blood glucose levels decline. These hormonal changes induce enzyme activities that lead to glycogenolysis, gluconeogenesis, lipolysis, and ketogenesis, which, in turn, provide endogenous glucose, free fatty acids, and ketone bodies.2,3 These substrates, together with lactate, meet the energy requirements of the neonatal brain in most situations. In some circumstances, this metabolic adaptation can be predicted...

Neuro Developmental Consequences of Neonatal Hypoglycemia

“…The age of the test performed was 11.3 months and 12.2 months, respectively. [3][4][5]. We undertook to investigate the neurological and developmental outcomes in children with neonatal HG.…”

Swedish national guideline for prevention and treatment of neonatal hypoglycaemia in newborn infants with gestational age ≥35 weeks

“…This is probably due to a higher peripheral energy demand, which results in faster consumption of the infant's glycogen depots. In addition, the brain cells have an increased sensitivity to energy deficiencies …”

2. Neonatal hypoglycaemia: History, clinical picture, investigations, management and outcome

“…Most often it is the consequence of unregulated maternal diabetes (type 1, type 2 or gestational) (25,26). Moreover, a transient increase in insulin concentration may be seen in some other conditions: in IUGR (7,18,27,28), after a stressful peripartum event (2,7,22,29), after maternal treatment with insulin or glucose during labour (30), and in the case of some foetal disorders: haemolytic disease of the newborn, hypothermia, heart failure (2, 7, 22) and in Beckwith-Wiedemann syndrome (BWS) (24,31,32).…”

“…Congenital central nervous system malformations may be diagnosed using ultrasound (US) and magnetic resonance imaging (MRI) of the brain (29,(39)(40)(41). Adrenal haemorrhage, pancreas hypertrophy and hepatomegaly may be visualized by US or MRI of the abdomen (42).…”