Natural history and neurodevelopmental outcomes in perinatal stress induced hyperinsulinism

Abstract

ObjectiveTo describe perinatal stress induced hyperinsulinism (PSIHI), determine the prevalence of neurodevelopmental differences, and identify risk factors for poor developmental prognosis.MethodsSubjects with a history of hyperinsulinism (HI) and perinatal stress and in whom resolution of the HI was demonstrated were included. Medical record review, caregiver interview, and three validated developmental assessments were completed.ResultsOf the 107 subjects (75% male), 36% were born between 32 and 37 weeks. Median age of hypoglycemia presentation was 0 days. Median age at HI diagnosis was 12 days (IQR 13.5). Median length of time for initiation of definitive treatment was 14 days (IQR 14).Caregiver interviews were completed for 53 of 79 eligible subjects. Developmental concerns were reported by 51%. Neurodevelopmental assessments were completed by caregivers of 37 of the 53 enrolled subjects. The proportion of subjects scoring >1 SD and >2 SD away from the mean in the direction of concern on the major composite scores was significantly greater than in the general population (40.5% vs. 15.8%, P ≤ 0.0001 and 18.9% vs. 2.2%, P ≤ 0.0001, respectively).Male sex, small for gestational age status (SGA), and treatment with continuous feeds were associated with assessment scores >1 SD from the mean (P < 0.05). SGA and preeclampsia were associated with assessment scores >2 SD from the mean (P < 0.05).ConclusionWhile the majority of infants presented with hypoglycemia in the first day of life, diagnosis and treatment occurred 12–14 days later. Children with PSIHI are at high risk of neurodevelopmental deficits and are more likely to perform below average on developmental assessment.

Factors Associated with Need for Intravenous Glucose Infusion for the Treatment of Early Neonatal Hypoglycemia in Late Preterm and Term Neonates

“…Unauthorized distribution is strictly prohibited. maximum GIR reported were 11.7 and 10.0 mg • kg -1 • min -1 , respectively, in a recent study [13].…”

“…Neonatal hypoglycemia may have long-term consequences that may not be detected until school age [25][26][27][28]. Higher target levels of glucose concentration are currently used for patients with hyperinsulinemia because of lack of alternative fuels [12,13]. There is considerable heterogeneity across studies about which level of hypoglycemia is associated with longterm consequences; controversy may not be resolved until school age outcomes are available for the randomized trial by van Kempen et al [29].…”

“…12 Neonates with stress-induced hyperinsulinism (e.g., due to sepsis, perinatal asphyxia, IUGR) typically require a high GIR; the mean and median maximum GIR reported were 11.7 and 10.0 mg/kg / min, respectively, in a recent study. 13 The current study was designed in 2013 to determine the incidence of early-onset hypoglycemia among late-preterm and term neonates admitted to the Mother-Baby Unit (MBU) at Parkland Hospital. Neonates had to have laboratory-documented and carefully validated evidence of early-onset hypoglycemia.…”

Variability in Diagnosis and Management of Hypoglycemia in Neonatal Intensive Care Unit

“…The use of concentrated dextrose, continuously via gastric tube in infants with hyperinsulinism who are not responsive to medication or pancreatectomy 22 or newborns diagnosed with perinatal stress-induced hyperinulinism 23 has been reported and almost one-fifth of respondents reported use of enteral dextrose, not gel, as treatment. While there are no data on the efficacy and safety of enteral dextrose use in transient hypoglycemia, especially in premature newborns, we speculate this finding might be due to an attempt to avoid the use of intravenous dextrose.…”

Bridging the gaps: recent advances in diagnosis, care, and outcomes in congenital hyperinsulinism

“…The reported prevalence of neurodevelopmental differences in children with HI ranges 26–48% in different cohorts from around the world [38]. Sigal et al showed that children with perinatal stress-induced HI (in whom hypoglycemia exposure is limited to the first months of life) experience similar rates of adverse neurodevelopment [39 ▪ ]. Rapid advances in the monitoring and therapeutic landscape for HI holds promise to improve these outcomes, and new approaches to assess long-term impact have emerged.…”