Necrotizing Enterocolitis in Neonates With Hyperinsulinemic Hypoglycemia Treated With Diazoxide

Abstract

The most common cause of persistent hypoglycemia in the neonatal period is hyperinsulinism. Severe, refractory hypoglycemia resulting from hyperinsulinism can lead to significant brain injury and permanent cognitive disability. Diazoxide is the first-line and only US Food and Drug Administration-approved, pharmacologic treatment for refractory hyperinsulinism. In recent years, the use of diazoxide in neonates with persistent hyperinsulinemic hypoglycemia has increased in the United States. Known adverse effects of diazoxide include fluid retention, hypertrichosis, neutropenia, thrombocytopenia, and more recently, pulmonary hypertension. It is currently unknown if diazoxide exposure is associated with an increased risk of necrotizing enterocolitis (NEC) in neonates. We reviewed the cases of 24 patients in a level IV NICU at Massachusetts General Hospital who received diazoxide over 12 years (April 2006-April 2018). All 24 patients received enteral diazoxide for refractory hyperinsulinemic hypoglycemia. A total of 5 patients developed NEC after initiation of diazoxide based on clinical and radiographic findings, corresponding to 20% of infants exposed to diazoxide. This is above our baseline incidence of NEC (1% for all inborn infants and 6% for all inborn very low birth weight infants). More research and monitoring are necessary to characterize the potential risk of NEC associated with the use of diazoxide in the neonatal period.

FIGURE 1

AXR 10 days after diazoxide initiation reveals portal venous gas and pneumatosis intestinalis in case 1.

FIGURE 2

AXR 18 days after diazoxide reintroduction reveals pneumatosis intestinalis and portal venous gas in case 2.

FIGURE 3

AXR 2 days after starting diazoxide reveals pneumatosis in the left and right abdomen, and distension of multiple bowel loops in case 3.

FIGURE 4

AXR 6 days after starting diazoxide reveals pneumatosis intestinalis is observed in the right abdomen in case 4.

FIGURE 5

AXR 11 days after starting diazoxide reveals colonic distension and pneumatosis in the transverse and descending colon in case 5.