Memory deficits following neonatal critical illness: a common neurodevelopmental pathway

Abstract

Over the past decade, evidence has emerged that children growing up after neonatal critical illness, irrespective of underlying diagnosis, are at risk of memory impairment and academic problems. These difficulties are manifest even when intelligence is within the normal range. In this Review, we propose a common neurodevelopmental pathway following neonatal critical illness by showing that survivors of preterm birth, congenital heart disease, and severe respiratory failure share an increased risk of long-term memory deficits and associated hippocampal alterations. Rather than a consequence of underlying diagnosis, we suggest that this shared vulnerability is probably related to common conditions associated with neonatal critical illness, including hypoxia, neuroinflammation, stress, exposure to anaesthetics, or a complex interplay of these factors at different postconceptional ages. Future work should be aimed at improvement of early identification of patients at risk and evaluation of intervention modalities, such as exercise or cognitive training.

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

“…A complex interplay among these factors may lead to (subtle) brain injuries early in life, which become evident only later in life when those brain regions are required for higher cognitive functioning. In particular, the hippocampus, the main hub for memory formation in the brain, has been found to show pronounced vulnerability to factors associated with critical illness, including exposure to sedatives . This “growing into deficit” phenomenon, where early hippocampal alterations lead to memory deficits later in life, has recently been identified by our group across survivors of neonatal critical illness .…”

“…Within this context, interaction with age and developmental stage are essential. Furthermore, given the high incidence of memory deficits following neonatal critical illness, early identification of patients at risk of memory deficits may become possible using hippocampal volume as a neurobiological marker. The hippocampus can be accurately and noninvasively delineated using structural MRI and is the brain's critical hub for long‐term memory formation .…”

“…In particular, the hippocampus, the main hub for memory formation in the brain, has been found to show pronounced vulnerability to factors associated with critical illness, including exposure to sedatives. 6,80 This "growing into deficit" phenomenon, 111 where early hippocampal alterations lead to memory deficits later in life, has recently been identified by our group across survivors of neonatal critical illness. 80 To what extent exposure to analgosedatives contribute to early brain injury in these patients needs further research that combines information on analgosedative exposure and exposure to confounding factors, such as pain, with neuroimaging and elaborate neuropsychological assessment.…”

Working Memory Training Following Neonatal Critical Illness: A Randomized Controlled Trial*

“…These deficits become more evident as children mature, suggesting they 'grow into deficit' (9). This mechanism -where subtle brain injuries acquired in early life become evident only later in life when higher cognitive functioning is required -has recently been described by our group across survivors of neonatal critical illness (10). As more educational problems occur following neonatal critical illness than in the general population (4,11), it is imperative to find intervention strategies to prevent or diminish impaired outcome.…”

“…11 (9)(10)(11)(12)(13)(14)(15)(16)(17) 12 ( .824 N (%), mean ± SD or median (interquartile range) is reported where appropriate for the group as a whole ('All' in column 1), the control group (Controls in column 2) and the CWMT group (CWMT in column 3) separately. Dutch refers to children with two native Dutch parents.…”