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

Schiller, Raisa M. MSc1,2; IJsselstijn, Hanneke MD, PhD1; Madderom, Marlous J. PhD1; Rietman, André B. MSc1,2; Smits, Marion MD, PhD3; van Heijst, Arno F. J. MD, PhD4; Tibboel, Dick MD, PhD1; White, Tonya MD, PhD2,3; Muetzel, Ryan L. PhD2

doi: 10.1097/CCM.0000000000002553
Pediatric Critical Care

Objectives: Survivors of critical illness in early life are at risk of long-term–memory and attention impairments. However, their neurobiologic substrates remain largely unknown.

Design: A prospective follow-up study.

Setting: Erasmus MC-Sophia Children’s Hospital, Rotterdam, the Netherlands.

Patients: Thirty-eight school-age (8–12 yr) survivors of neonatal extracorporeal membrane oxygenation and/or congenital diaphragmatic hernia with an intelligence quotient greater than or equal to 80 and a below average score (z score ≤ –1.5) on one or more memory tests.

Interventions: None.

Measurements and Main Results: Intelligence, attention, memory, executive functioning, and visuospatial processing were assessed and compared with reference data. White matter microstructure and hippocampal volume were assessed using diffusion tensor imaging and structural MRI, respectively. Global fractional anisotropy was positively associated with selective attention (β = 0.53; p = 0.030) and sustained attention (β = 0.48; p = 0.018). Mean diffusivity in the left parahippocampal region of the cingulum was negatively associated with visuospatial memory, both immediate (β = –0.48; p = 0.030) and delayed recall (β = –0.47; p = 0.030). Mean diffusivity in the parahippocampal region of the cingulum was negatively associated with verbal memory delayed recall (left: β = –0.52, p = 0.021; right: β = –0.52, p = 0.021). Hippocampal volume was positively associated with verbal memory delayed recall (left: β = 0.44, p = 0.037; right: β = 0.67, p = 0.012). Extracorporeal membrane oxygenation treatment or extracorporeal membrane oxygenation type did not influence the structure-function relationships.

Conclusions: Our findings indicate specific neurobiologic correlates of attention and memory deficits in school-age survivors of neonatal extracorporeal membrane oxygenation and congenital diaphragmatic hernia. 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 neurobiologic markers.

1Intensive Care and Department of Pediatric Surgery, Erasmus MC-Sophia Children’s Hospital, Rotterdam, The Netherlands.

2Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC-Sophia Children’s Hospital, Rotterdam, The Netherlands.

3Department of Radiology and Nuclear Medicine, Erasmus MC-Sophia Children’s Hospital, Rotterdam, The Netherlands.

4Department of Neonatology, Radboud University Medical Center, Nijmegen, The Netherlands.

*See also p. 1791.

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Supported, in part, by the Sophia Stichting Wetenschappelijk Onderzoek: S14–21.

Dr. Schiller’s institution received funding from Sophia Stichting Wetenschappelijk Onderzoek (SSWO). Dr. IJsselstijn received support for article research from SSWO. Dr. White’s institution received funding from SSWO: S14–213. The remaining authors have disclosed that they do not have any potential conflicts of interest.

For information regarding this article, E-mail: t.white@erasmusmc.nl

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