P0705 - Adverse Effects Associated with Diazoxide Use in Neonates

Background: Hyperinsulinism (HI) is the most common cause of persistent or recurrent hypoglycemia in infants. Diazoxide is the first-line treatment used to manage infants with hypoglycemia secondary to HI after initial stabilization of blood glucose. Recent changes in definition of and in guidelines for screening for hypoglycemia in neonates led to an increase in the number of infants being treated with diazoxide. Previous studies have noted various side effects of diazoxide. With the increased use of this drug in neonates, our aim is to further evaluate these side effects.

Objective: To evaluate the type and frequency of adverse effects associated with the use of diazoxide for treatment of hyperinsulinemic hypoglycemia (HIH) in neonates.

Methods: An IRB approved retrospective case control study was performed of all neonates admitted to a single tertiary care center who were treated with diazoxide after a diagnosis of HIH between 1/1/2015 and 9/1/2019. All subjects were younger than 6 months of age at treatment initiation. Data regarding general patient characteristics and diazoxide dosing was collected. In addition, findings on echocardiogram, blood counts, episodes of emesis, and intake amounts were collected at time points before and after diazoxide initiation.

Results: A total of 25 patients (64% males) were included, with a mean gestational age of 35.7 weeks (median 36.1; 24.9-41.0, ±4), and mean birthweight of 2112 grams (median 2052; 662-4035, ±954). Diazoxide was initiated at mean 13.8 postnatal days (median 9; 2-58) and mean weight of 2376 grams (median 2150; 987-3980). Average length of treatment was 19.6 (median 14; 6-78, ±15.9) days. Based on echocardiogram results, 4% of babies had pulmonary hypertension (PHN) before and 20% after diazoxide administration, with 5 cases (20%) of reopening of patent ductus arteriosus (PDA). Nine patients (36%) required a diuretic dose increase after diazoxide initiation. There was a significant increase in the number of emesis events after diazoxide initiation compared to before (p=0.006), and a week after initiation there was no expected improvement in the percent of total intake that was taken by mouth.

Conclusions: New onset pulmonary hypertension and re-opening of the PDA were associated with initiation of diazoxide treatment. The significant increase in emesis events after diazoxide initiation suggests that infants may experience feeding difficulties after initiation of the drug. As diazoxide appears to be used more liberally, larger studies are needed to further evaluate the extent and severity of side effects seen with this medication.