Background We sought to disentangle the contributions of hyperthyrotropinemia (an indicator of thyroid dysfunction) (HTT) and intermittent or sustained systemic inflammation (ISSI) to structural and functional indicators of brain damage. Methods We measured the concentrations of TSH on day 14, and of 25 inflammation-related proteins in blood collected during the first 2 postnatal weeks from 786 infants born before the 28th week of gestation who were not considered to have hypothyroidism. We defined hyperthyrotropinemia (HTT) as a TSH concentration in the highest quartile for gestational age on postnatal day 14 and ISSI was defined as a concentration in the top quartile for gestational age of a specific inflammation-related protein on two separate days a week apart during the first two postnatal weeks. We first assessed the risk of brain damage indicators comparing 1) neonates who had HTT to those without (regardless of ISSI), and 2) neonates with HTT only, ISSI only, or HTT+ ISSI, to those who were exposed to neither HTT nor ISSI. HTT was defined as a TSH concentration in the highest quartile for gestational age on postnatal day 14. Results In univariable models that compared those with HTT to those without, HTT was not significantly associated with any indicator of brain damage. In models that compared HTT only, ISSI only, and HTT+ISSI, to those with neither, children with ISSI only or with HTT+ISSI were at significantly higher risk of ventriculomegaly [odds ratios (OR) ranged from 2–6], while those with HTT only were at significantly reduced risk of a hypoechoic lesion [ORs ranged from 0.2–0.4]. Children with HTT only had a higher risk of quadriparesis and those with ISSI alone had a higher risk of hemiparesis [ORs ranged from 1.6–2.4]. Elevated risk of a very low mental development score was associated with both ISSI only and with HTT+ISSI while a very low motor development score and microcephaly were associated with HTT+ISSI. Conclusions The association of HTT with increased or decreased risk of indicators of brain damage depends upon the presence or absence of ISSI.

Objectives The objectives of this review are to discuss the pathophysiology, clinical impact and treatment of hyperglycemia and disturbances in thyroid and adrenal function prior to and following cardiac surgery in children. Data Source MEDLINE, PubMed Conclusions Disturbances in glucose metabolism and thyroid and adrenal function are common in critically ill children with cardiac disease and in particular in children undergoing cardiac surgery for complex congenital heart disease. An understanding of the pathophysiology, clinical impact and treatment of these disturbances is essential for the management of these at risk patients.

Objectives Test whether hyperglycemic critically ill children with cardiovascular and/or respiratory failure experience more ICU-free days when assigned to tight glycemic control with a normoglycemic versus hyperglycemic blood glucose target range. Design Multi-center randomized clinical trial. Setting Pediatric ICUs at 35 academic hospitals. Patients Children aged 2 weeks to 17 years receiving inotropic support and/or acute mechanical ventilation, excluding cardiac surgical patients. Interventions Patients receive intravenous insulin titrated to either 80–110 mg/dL (4.4–6.1 mmol/L) or 150–180 mg/dL (8.3–10.0 mmol/L). The intervention begins upon confirmed hyperglycemia and ends when the patient meets study-defined ICU discharge criteria or after 28 days. Continuous glucose monitoring, a minimum glucose infusion, and an explicit insulin infusion algorithm are deployed to achieve the BG targets while minimizing hypoglycemia risk. Measurements and main results The primary outcome is ICU-free days (equivalent to 28-day hospital mortality-adjusted ICU length of stay). Secondary outcomes include 90-day hospital mortality, organ dysfunction scores, ventilator-free days, nosocomial infection rate, neurodevelopmental outcomes, and nursing workload. To detect an increase of 1.25 ICU-free days (corresponding to a 20% relative reduction in 28-day hospital mortality and a one-day reduction in ICU length of stay), 1414 patients are needed for 80% power using a two-sided 0.05 level test. Conclusions This trial tests whether hyperglycemic critically ill children randomized to 80–110 mg/dL benefit more than those randomized to 150–180 mg/dL. This study implements validated bedside support tools including continuous glucose monitoring and a computerized algorithm to enhance patient safety and ensure reproducible bedside decision-making in achieving glycemic control.