Neurobiologic Correlates of Attention and Memory Deficits Following Critical Illness in Early Life*

Abstract

Design A prospective follow-up study.Setting Erasmus MC-Sophia Children's Hospital, Rotterdam, the Netherlands.Patients Thirty-eight school-age (8-12 years) survivors of neonatal extracorporeal membrane oxygenation (ECMO) and/or congenital diaphragmatic hernia (CDH) with an IQ ≥ 80 and a below average score (z-score≤ -1.5) on one or more memory tests.Interventions None. Hippocampal volume was positively associated with verbal memory delayed recall (left:β=0.44, p=.037; right:β=0.67, p=.012). ECMO treatment or ECMO type did not influence the structure-function relationships. Measurements and Main ResultsConclusions Our findings indicate specific neurobiological correlates of attention and memory deficits in school-age survivors of neonatal ECMO and CDH. A better understanding of the neurobiology following critical illness, both in early and in adult life, may lead to earlier identification of patients at risk for impaired neuropsychological outcome with the use of neurobiological markers.2

Memory deficits following neonatal critical illness: a common neurodevelopmental pathway

“…6,7,9,[14][15][16] This is highly suggestive of an alternative explanation related to specific neuropsychological deficit rather than general intellectual functioning ( Table 1). Memory deficits can greatly affect daily life activities and academic achievement, and have been reported in 19-41% of children born preterm 7,25 , in 28-64% of children with CHD 15,37 , and in 50-70% of children treated with neonatal ECMO 41 , compared to 16% in the general population. These deficits become particularly evident as these children get older, suggesting that they 'grow into their deficits'.…”

Analgesics and Sedatives in Critically Ill Newborns and Infants: The Impact on Long‐Term Neurodevelopment

“…91 This may contribute to the long-term neuropsychological deficits and brain alterations observed in these patients at school age and even in adolescence. 66,67,92 In 8-year-old extracorporeal membrane oxygenation survivors, specific attention problems were found irrespective of generally average intelligence. 65 However, outcome at 8 years was not associated with the time children had been exposed to opioids or other sedatives.…”

“…Children treated with neonatal extracorporeal membrane oxygenation treatment are often exposed to prolonged continuous opioids and sedatives in the absence of major pain . This may contribute to the long‐term neuropsychological deficits and brain alterations observed in these patients at school age and even in adolescence . In 8‐year‐old extracorporeal membrane oxygenation survivors, specific attention problems were found irrespective of generally average intelligence .…”

“…Although studies in humans are scarce, findings from experimental studies suggest that, in particular, hippocampal development and long‐term learning memory are affected after exposure to these agents . Interestingly, studies have shown long‐term hippocampal alterations and associated memory deficits across survivors of neonatal critical illness, irrespective of gestation age or underlying disease . The hippocampus is the brain's central hub for memory encoding, consolidation, and retrieval .…”

“…100,101 Interestingly, S145 studies have shown long-term hippocampal alterations and associated memory deficits across survivors of neonatal critical illness, irrespective of gestation age or underlying disease. 92,102,103 The hippocampus is the brain's central hub for memory encoding, consolidation, and retrieval. 79 Benzodiazepines, such as midazolam, potentiate the neuronal inhibitory pathways or inhibit the excitatory pathways by binding to gamma-aminobutyric acid or glutamatergic N-methyl-D-aspartate (NMDA) receptors in the brain.…”