ESPE Abstracts

Introduction: Early initiation of diazoxide (DZX) treatment in neonates with HH can prevent permanent hypoglycaemic brain injury. The DZX standard therapeutic dose (STD) is 5 mg/kg/day, and rarely associated with adverse events. There are limited data for the effectiveness and safety of DZX low-dose (<5mg/kg/day) for the treatment of HH neonates.

Aim: To assess efficacy and safety of low-dose DZX in HH newborns.

Methods: Observational study with data collection on HH neonates (<28 days) referred to our tertiary HH Service between November 2016-April 2021. As per our experience, neonates commenced DZX based on their weight and divided into 3 cohorts: i) C1 <2kg, DZX 2mg/kg/day, ii) C2 2-3.5kg, DZX 3mg/kg/day, iii) C3> 3.5kg, DZX 5mg/kg/day. DZX responsiveness defined as tolerating a 6-hour fasting study. Efficacy assessed based on number of patients responding to the DZX starting dose. Safety measured based on the number of adverse events in each cohort. Age of HH resolution after passing a fasting study off DZX reviewed.

Results: 99 neonates with gestational age (GA) ranging 30-41 weeks (C1 24; C2 67; C3 8). A safety fast achieved on the starting dose of DZX in 46% of C1, 61% of C2, and 62.5% of C3 neonates. Majority of moderate to late preterm infants (GA 34-38 weeks, n=31/47) responded well to low-dose DZX. All of the very preterm (GA <34weeks, n=5/5) and most of the term (GA>38 weeks, n=16/33) small for gestational age (SGA) neonates required dose increment, with 1/3 achieving safety fast at a dose lower than the STD. Side-effects noticed in 20% of C1; 25% of C2; and 33% of C3. Oedema was the most common side-effect. There were no cases of pulmonary hypertension. The majority of patients (n=97) achieved HH resolution at a similar mean age in all cohorts (C1 5.6 months, C2 5.2 months, C3 5 months). Infants in C2 who responded to DZX low-dose came off treatment earlier (mean age 4.6 months).

Conclusion: Our study demonstrates that DZX low-dose can effectively treat preterm and SGA HH neonates. Close supervision is needed in case dose increments required, especially in the very preterm and term-SGA infants. Adverse events can still be observed with DZX low doses, but at a lower incidence compared to the STD. We recommend starting DZX 2-3mg/kg/day in preterm or SGA HH neonates and up-titrate as needed, to achieve euglycaemia with minimum effective dose, while reducing the risk of side-effects.