Hyperinsulinemic hypoglycaemia (HH) is a common cause of severe and persistent hypoglycaemia during the neonatal period. Risk factors for neonatal transient hyperinsulinism are small-for-gestational age (SGA), perinatal asphyxia and maternal diabetes mellitus. This state of hyperinsulinism in SGA newborns could persist from weeks to years, resulting in an important comorbidity; its pathogenesis remains unknown.
Objective: To describe the clinical-genetic characteristics of SGA newborns with HH.
Methods: Review of our HH patient database and selection of SGA patients who presented hypoglycemia during neonatal period for more than 3 weeks. Definitions: SGA as birth weight and/or length ≤−2 S.D.. HH as insulin and/or C-peptide detectable during hypoglycaemia and/or suppressed or low concentrations of free fatty acids during hypoglycaemia, in patients with carbohydrate requirements >12 mg/kg per min. Genetic study included ABCC8, KCNJ11, GLUD1, GCK, HADH, SLC16A1, HNF4A, HNF1A, UCP2, HK1 and PGM1 genes. Patients with history of maternal diabetes mellitus, perinatal asphyxia and clinical-biochemical markers of infections were excluded.
Results: Eight patients (three girls). Mean gestational age 35.98 weeks (range 3039), 4 preterm newborns. Mean Z-scores of weight at birth −1.9 (range −1.23 to −3.25) and length −2.08 (range +0.78 to −3.01). All patients presented asymptomatic hypoglycemia from the first week of life (range 14 days). Echocardiographic study showed three patients with patent ductus arteriosus (PDA) (patient 2, 5 and 8), 2 of them were premature. Mean carbohydrate requirement was 17.63 mg/kg per min (range 1421). Five patients received diazoxide with a good response to treatment. Two patients continue on treatment (patients 5 and 8, currently aged 11 and 3 months respectively). In patient 5 the dose was reduced due to ductus reopening with subsequent spontaneous closure. In patient 2 treatment was suspended after 6 days due to pulmonary hypertension that required intubation (she had history of surgical ligation of PDA at 7 days of life). Nutritional and/or diazoxide treatment duration: mean 13.8 months (range 27 days28 months). Genetic study was conducted in 6 patients with one positive result (patient 7): mutation c.127-1G>T in UCP2 gene.
Conclusions: SGA newborns risk presenting transitory hyperinsulinism. The treatment with diazoxide was effective in all patients. Two complications were attributed to diazoxide: ductus reopening and pulmonary hypertension, observing high prevalence of adverse effects in this population. The genetic study was positive in only 1 of 6 patients (16.6%) in contrast to 60% of non SGA patients from our database.
27 Sep 2018 - 29 Sep 2018