Congenital Hyperinsulinism (CHI)

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 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 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. 4. A retrospective observational study to investigate whether UCBG can provide improved risk stratification for hypoglycaemia in infants born to mothers with diabetes.

This purpose of this study is to determine the ability of an 18F-fluoro-L-dihydroxyphenylalanine (18F-DOPA) PET (Positron Emission Tomography) scan to detect a focal lesion of hyperinsulinism and determine the location in patients with congenital hyperinsulinism, Beckwith Wiedemann Syndrome and suspected insulinoma. Safety data will be collected.