Pulmonary Hypertension and Necrotizing Enterocolitis in Neonates Treated with Diazoxide

This study aimed to evaluate the prevalence of adverse outcomes, specifically pulmonary hypertension (PH) and suspected or confirmed necrotizing enterocolitis (NEC), and their associated risk factors, in neonates treated with diazoxide.

A retrospective study in infants born ≥ 31^6/7 weeks and admitted between January 2014 and June 2020. Combined adverse outcomes possibly associated to diazoxide were PH (systolic pulmonary pressure of ≥40 mm Hg or an eccentricity index ≥1.3) and suspected or confirmed NEC (suspected: stop feeds and antibiotics and confirmed: modified Bell stage ≥2). Echocardiography data extractors were masked to infants' characteristics.

A total of 63 infants were included; 7 (11%) with suspected and 1 (2%) with confirmed NEC. Of the 36 infants with an available echocardiography after initiation of diazoxide treatment, 12 (33%) had PH. All infants with suspected or confirmed NEC were males (p = 0.01), whereas PH occurred mostly in females (75%, p = 0.02). The combined adverse outcome occurred in 14/26 (54%) infants exposed to >10 mg/kg/day, compared to 6/37 (16%) exposed to ≤10 mg/kg/day (p = 0.006). This association remained significant after adjustment for sex, small for gestational age status, and gestational age at birth (odds ratio: 6.1, 95% confidence interval: 1.7-21.7, p = 0.005). Left ventricular dysfunction was found in 19 infants (30%) but was not discriminative for the combined outcome.

PH and suspected or confirmed NEC were identified frequently in neonates treated with diazoxide. A total dose >10 mg/kg/day was associated with an increased occurrence of these complications.

· PH and suspected or confirmed NEC were frequently found in neonates treated with diazoxide.. · A total dose >10 mg/kg/day was associated with an increased occurrence of these complications.. · Echocardiography screening should be considered in neonates exposed to diazoxide..