Evaluation and management of neonatal onset hyperinsulinemic hypoglycemia: a single neonatal center experience

Abstract

Objectives

To evaluate the clinical characteristics and treatment options of neonates requiring prolonged hospitalization due to persistent hyperinsulinemic hypoglycemia (HH).

Methods

This retrospective cohort study included infants >34 weeks of gestation at birth who were born in our hospital between 2018 and 2021, diagnosed with HH, and required diazoxide within the first 28 days of life. The baseline clinical characteristics, age at the time of diagnosis and treatment options in diazoxide resistance cases were recorded. Genetic mutation analysis, if performed, was also included.

Results

A total of 32 infants diagnosed with neonatal HH were followed up. Among the cohort, 25 infants were classified as having transient form of HH and seven infants were classified as having congenital hyperinsulinemic hypoglycemia (CHI). Thirty-one percent of the infants had no risk factors. The median birth weight was significantly higher in the CHI group, whereas no differences were found in other baseline characteristics. Patients diagnosed with CHI required higher glucose infusion rate, higher doses, and longer duration of diazoxide treatment than those in the transient HH group. Eight patients were resistant to diazoxide, and six of them required treatment with octreotide and finally sirolimus. Sirolimus prevented the need of pancreatectomy in five of six patients without causing major side effects. Homozygous mutations in the ABCC8 gene were found in four patients with CHI.

Conclusions

The risk of persistent neonatal hyperinsulinism should be considered in hypoglycemic neonates particularly located in regions with high rates of consanguinity. Our study demonstrated sirolimus as an effective treatment option in avoiding pancreatectomy in severe cases.

Keywords:

• Hyperinsulinemic hypoglycemia
• sirolimus
• diazoxide
• ABCC8 mutation
• neonate

Author contributions

HB and NO were primarily responsible for protocol development and the analytic framework of the study, outcome assessment, and manuscript preparation. HB, KC, and FFT had primary responsibility for reviewing the files, patient screening, enrollment, and data entry, and prepared the manuscript with NO. MNO contributed to preparation and revision of the manuscript.

Disclosure statement

The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper.

Data availability statement

The authors confirm that the data supporting the findings of this study are available within the article.

Additional information

Funding

This research did not receive any specific grants from funding agencies in the public, commercial, or not-for-profit sectors.