Pulmonary Hypertension and Necrotizing Enterocolitis in Neonates Treated with Diazoxide

Abstract

Objective 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.

Study Design 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.

Results 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.

Conclusion 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.

Key Points

• 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.

Keywords

diazoxide - hypoglycemia - necrotizing enterocolitis - pulmonary hypertension - neonates

^* These authors contributed equally to this publication.

Ethical Approval and Patient Consent

The study was performed in accordance with the Declaration of Helsinki and was approved by the McGill University Health Centre research ethics boards.

Authors' Contributions

M.D. participated in conceptualizing and design of the study, collected the data, analyzed the data, drafted the manuscript, and adjusted the manuscript according to the comments of co-authors. S.S.M. collected the data, critically appraised the analysis of the data, and adjusted and revised the final manuscript. J.S. reviewed the data. J.E.vonO. critically appraised the analysis of the data and reviewed and revised the manuscript. G.G. provided the list of patients from the pharmacy registry, critically appraised the analysis of the data, reviewed, and revised the manuscript. I.G. provided the list of patients from the pharmacy registry, critically appraised the analysis of the data, reviewed, and revised the manuscript. G.S. critically appraised the analysis of the data, reviewed, and revised the manuscript. G.A. conceptualized and designed the study, supervised data collection, critically appraised the analysis of the data, and critically reviewed the manuscript for important intellectual content. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

Publication History

Received: 12 July 2022

Accepted: 03 February 2023

Article published online:
07 March 2023

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