Necrotising enterocolitis in newborns receiving diazoxide

Arch Dis Child Fetal Neonatal Ed. 2021 May;106(3):306-310. doi: 10.1136/archdischild-2020-319057. Epub 2020 Nov 10.

Abstract

Background: Frequent and severe gastrointestinal disturbances have been reported with the use of diazoxide in adults and older children. However, no studies have investigated the incidence of necrotising enterocolitis (NEC) in diazoxide-exposed newborns.

Objective: To evaluate a possible association between diazoxide treatment for neonatal hypoglycaemia and the occurrence of NEC.

Design: Multicentre retrospective cohort study.

Setting: Three tertiary neonatal intensive care units in Toronto, Canada.

Patients: All patients treated with diazoxide for persistent hypoglycaemia between July 2012 and June 2017 were included. Overall incidence of NEC during those years on the participating units was obtained for comparison from the Canadian Neonatal Network database.

Main outcome: Incidence of NEC after diazoxide exposure.

Results: Fifty-five neonates were exposed to diazoxide during the study period. Eighteen patients (33%) showed signs of feeding intolerance, and 7 developed NEC (13%). A diagnosis of NEC was more prevalent in the diazoxide-exposed, as compared with non-exposed infants of similar gestational age (OR 5.07, 95% CI 2.27 to 11.27; p<0.001), and greatest among infants born at 33-36 weeks' gestation (OR 13.76, 95% CI 3.77 to 50.23; p<0.001). All but one of the neonates diagnosed with NEC developed the disease within 7 days from initiation of diazoxide treatment.

Conclusion: The present data suggest a possible association between diazoxide exposure and the development of NEC in neonates. Further evaluation of the diazoxide-associated risk of NEC in neonates treated for persistent hypoglycaemia is warranted.

Keywords: intensive care; neonatology; pharmacology.

MeSH terms

  • Canada / epidemiology
  • Correlation of Data
  • Diazoxide* / administration & dosage
  • Diazoxide* / adverse effects
  • Enterocolitis, Necrotizing* / chemically induced
  • Enterocolitis, Necrotizing* / diagnosis
  • Enterocolitis, Necrotizing* / epidemiology
  • Female
  • Gastrointestinal Tract / drug effects*
  • Gestational Age
  • Humans
  • Hypoglycemia / blood
  • Hypoglycemia / diagnosis
  • Hypoglycemia / drug therapy*
  • Hypoglycemia / etiology
  • Infant, Newborn
  • Infant, Premature, Diseases / blood
  • Infant, Premature, Diseases / diagnosis
  • Infant, Premature, Diseases / drug therapy*
  • Male
  • Membrane Transport Modulators / administration & dosage
  • Membrane Transport Modulators / adverse effects
  • Neonatology / methods
  • Prevalence
  • Retrospective Studies
  • Risk Assessment

Substances

  • Membrane Transport Modulators
  • Diazoxide