Title of project

Umbilical cord glucose: A novel screening method for Congenital Hyperinsulinism to prevent brain damage

Abstract

Congenital hyperinsulinism (HI) causes persistent neonatal hypoglycemia that, if untreated, can lead to neurodevelopmental impairments (NDI) such as cognitive delays, cerebral palsy, epilepsy, and blindness. Despite being preventable with early diagnosis and treatment, 30-50% of affected infants still suffer NDI. Transient HI occurs in about 1 in 1,200 births, while persistent forms are rarer. Current screening focuses on high-risk groups but misses many infants with HI, resulting in delayed diagnosis and brain injury. Our pilot research suggests that measuring umbilical cord blood glucose (UCBG), already routinely collected for other purposes, can serve as a timely, non-invasive screening test for HI. Arterial UCBG below 3.5 mmol/L showed excellent accuracy in predicting pathological HI. This project aims to validate UCBG screening for neonatal HI, implement a national screening program, and assess the neurological outcomes of screen-positive infants. Planned studies: 1: A systematic review will analyze current screening strategies and the impact of delayed diagnosis on brain outcomes 2: A nationwide, prospective study in Denmark will implement UCBG screening in all newborns. Infants with arterial UCBG below 3.5 mmol/L will undergo standard hypoglycemia monitoring and diagnostic testing. Diagnostic accuracy and optimal thresholds will be evaluated. 3:Neurological follow-up at 6 months will assess development using standardized cognitive and motor tests, EEG, and MRI.

The study expects to identify most neonates with pathological HI early, enabling prompt treatment and reducing hypoglycemia severity. This early intervention should decrease the current high rate of neurodevelopmental impairment. The screening method’s simplicity and use of routine blood sampling make it feasible for global implementation. Umbilical cord blood glucose screening has the potential to revolutionize early detection of congenital hyperinsulinism, improving neonatal outcomes worldwide by preventing avoidable brain injury through timely diagnosis and treatment.