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Intrauterine growth retardation (IUGR) is an important cause of neonatal mortality, morbidity and poor neurological outcome.1 Hypoglycaemia as a consequence of IUGR is a major risk factor for neurodevelopmental impairment. The factors that predispose these patients to hypoglycaemia include failure of counter-regulation, immaturity of the enzyme systems regulating glycogenolysis, gluconeogenesis, ketogenesis, reduced adipose tissue stores, hyperinsulinism or increased sensitivity to insulin.2–4 Hypoglycaemia in patients with IUGR is usually thought to be transient, lasting for a few days. However, the precise duration of transient hyperinsulinaemic hypoglycaemia is unclear.
We report on our experience of prolonged hypofattyacidaemic hypoketotic hyperinsulinaemic hypoglycaemia (between 3 and 9 months’ duration) in 20 infants with symmetrical IUGR who required treatment with diazoxide and chlorothiazide. A total of 20 consecutive patients referred to the London Centre for Paediatric Endocrinology and Metabolism, Great Ormond Street Children’s Hospital NHS Trust, London, UK, with symmetrical IUGR (birth weight <3rd centile) and persistent hypoglycaemia (hypoglycaemia persisting for >10 days at the referring hospital) were recruited into the study. The mean birth weight and mean gestational age of the whole cohort were 2.1 kg and 38 weeks, respectively.
In each patient, the hypoglycaemia was characterised by inappropriate insulin secretion, increased glucose clearance (>10 mg/kg/min), blunting of the serum cortisol and glucagon counter-regulatory hormonal responses, and resistance to growth hormone as shown by low serum levels of insulin-like growth factor 1 and insulin-like growth factor-binding protein 3 and raised serum levels of growth hormone.
All patients required treatment with diazoxide (5–10 mg/kg/day) and chlorothiazide (7–10 mg/kg/day) to correct their hypoglycaemia. The mean age for starting diazoxide was 18 days. Each of these patients was then followed up at 3-monthly intervals to assess their response to diazoxide withdrawal. In 10 patients, administration of diazoxide and chlorothiazide was stopped at age 3 months, in seven patients at 6 months and in the remaining three patients at 9 months.
In summary, some infants with IUGR may continue to have hypofattyacidaemic hypoketotic hyperinsulinaemic hypoglycaemia beyond the first a few weeks of life. As this hypoglycaemia is associated with a lack of alternative substrates for the brain to use (such as ketone bodies), recognition and treatment of this group of patients is important. If unrecognised, this may have important implications for neurodevelopmental outcome of these patients. Further studies are needed to understand the underlying mechanism of these observations.
Footnotes
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Funding: Research at the Institute of Child Health and Great Ormond Street Hospital for Children NHS Trust benefits from R&D funding received from the NHS Executive.
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Competing interests: None declared.