Presentation (CTI)

OBJECTIVES: The impact of early-life hypoglycemia on later neurological sequelae remains unclear. This study explores their longitudinal relationship to inform a disease model.
METHODS: Sequence analysis was conducted using claims data (2016-2024) from 815 individuals with congenital hyperinsulinism, with first claims at age zero. Each year, individuals were classified into one of three health states: hypoglycemia, hypoglycemia with neurological sequelae, or neurological sequelae. Health states were defined using the International Classification of Diseases-10th Revision codes for hypoglycemia (E16.0, E16.1, E16.2, P70.4) and for neurological conditions including attention-deficit/hyperactivity disorder, autism, cerebral palsy, epilepsy, hearing loss, language and learning disorders, vision impairment, development coordination disorder, and intellectual disabilities. We estimated yearly state distributions and transition probabilities.
RESULTS: The proportion of children with hypoglycemia remained high between ages 0 and 3 (0.85 to 0.50), then declined from 0.44 to 0.05 between ages 4 and 8. The proportion with both hypoglycemia and neurological sequelae increased slightly between ages 0 and 5 (0.12 to 0.14), then declined from 0.10 to 0.02 between ages 6 and 8. The proportion with neurological sequelae alone increased steadily from 0.03 at age 0 to 0.93 at age 8. The probability of transitioning from hypoglycemia to hypoglycemia with neurological sequelae was 0.15, and to neurological sequelae alone was 0.09, indicating a 0.24 probability of developing neurological sequelae following early-life hypoglycemia.
CONCLUSIONS: Findings suggest a possible association between early hypoglycemia and later neurological sequelae. The persistence of hypoglycemia highlights the need for early diagnosis and more effective management. Future research should account for confounders and use robust designs to better assess causal relationships.