Umbilical Cord Glucose

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.

Inclusion Criteria: Study 2: * Live-born neonates delivered at participating Danish hospitals during the study period. * arterial umbilical cord blood glucose (UCBG) ≤3.5 mmol/L. * Written informed consent obtained from parent(s) or legal guardian(s). Study 3: * Infants diagnosed with pathological neonatal hyperinsulinism (HI) following UCBG screening in Study 2. * Written informed consent obtained from parent(s) or legal guardian(s) for participation in the follow-up study. Exclusion Criteria: Study 2: * No predefined clinical exclusion criteria. * Missing or unsuccessful arterial umbilical cord blood sampling resulting in an unavailable UCBG measurement. * Withdrawal of parental consent. Study 3: * No predefined clinical exclusion criteria. * Withdrawal of parental consent.