Trisomy 13 as a risk factor for pulmonary hypertension induced by diazoxide

Diazoxide has been used globally for hyperinsulinemic hypoglycemia. However, serious adverse drug reactions, such as pulmonary hypertension (PH), are major concerns. This study aimed to determine the baseline risk of diazoxide administration leading to the development of PH.

A retrospective cohort study was conducted at a tertiary care institution in Tokyo, Japan. Children under 15 years old treated with diazoxide for congenital hyperinsulinemia between May 2015 and May 2024 were included. Data were extracted from electronic medical records. The primary endpoint was the development of PH, with cases that developed PH labeled as PH (+) and those that did not as PH (-). Patient backgrounds, including chromosomal abnormalities, congenital heart disease, gestational age, and birth weight, were extracted as explanatory variables for PH development. We adjunctively applied the Bayesian estimation for PH after diazoxide administration.

Among 65 children (median age 14 days), 3 (5%) children were PH (+). Comparing PH (+) and PH (-), trisomy 13 was identified as a significant risk factor (100% vs. 0%, P < 0.001). The birth weight also differed significantly (1491 vs. 2056 g, P = 0.049). There were no significant differences in gestational age or the presence of congenital heart disease. In the PH (+) group, the maximum doses of diazoxide ranged from 2.5 to 12 mg/kg/day, and all children received prophylactic diuretics. We estimated the posterior probability of PH complicated by diazoxide as 19% in the trisomy 13 group and 0.4% in the nontrisomy 13 group using the empirical Bayesian method.

Trisomy 13 significantly increased the risk of PH following diazoxide administration. Even low-dose diazoxide and prophylactic diuretics may not prevent PH in these patients. Caution is essential when prescribing diazoxide to children with trisomy 13 and low birth weight.