Consequences of General Anesthesia in Infancy on Behavior and Brain Structure : Anesthesia & Analgesia

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Consequences of General Anesthesia in Infancy on Behavior and Brain Structure

Salaün, Jean-Philippe MD, PhD*,†; Chagnot, Audrey PhD*; Cachia, Arnaud PhD‡,§; Poirel, Nicolas PhD‡,§,∥; Datin-Dorrière, Valérie MD, PhD‡,∥,¶; Dujarrier, Cléo MSc*; Lemarchand, Eloïse PhD*; Rolland, Marine MD*,†; Delalande, Lisa PhD; Gressens, Pierre MD, PhD#; Guillois, Bernard MD§; Houdé, Olivier PhD‡,§,∥; Levard, Damien MSc*; Gakuba, Clément MD, PhD*,†; Moyon, Marine PhD; Naveau, Mikael PhD**; Orliac, François MD, PhD‡,∥; Orliaguet, Gilles MD, PhD††; Hanouz, Jean-Luc MD, PhD†,‡‡; Agin, Véronique PhD*; Borst, Grégoire PhD‡,§; Vivien, Denis PhD*,§§

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Anesthesia & Analgesia 136(2):p 240-250, February 2023. | DOI: 10.1213/ANE.0000000000006233



One in 7 children will need general anesthesia (GA) before the age of 3. Brain toxicity of anesthetics is controversial. Our objective was to clarify whether exposure of GA to the developing brain could lead to lasting behavioral and structural brain changes.


A first study was performed in mice. The behaviors (fear conditioning, Y-maze, and actimetry) and brain anatomy (high-resolution magnetic resonance imaging) of 6- to 8-week-old Swiss mice exposed or not exposed to GA from 4 to 10 days old were evaluated. A second study was a complementary analysis from the preexisting APprentissages EXécutifs et cerveau chez les enfants d’âge scolaire (APEX) cohort to assess the replicability of our data in humans. The behaviors (behavior rating inventory of executive function, emotional control, and working memory score, Backward Digit Span, and Raven 36) and brain anatomy (high-resolution magnetic resonance imaging) were compared in 102 children 9 to 10 years of age exposed or not exposed to a single GA (surgery) during infancy.


The animal study revealed chronic exacerbated fear behavior in the adult mice (95% confidence interval [CI], 4–80; P = .03) exposed to postnatal GA; this was associated with an 11% (95% CI, 7.5–14.5) reduction of the periaqueductal gray matter (P = .046). The study in humans suggested lower emotional control (95% CI, 0.33–9.10; P = .06) and a 6.1% (95% CI, 4.3–7.8) reduction in the posterior part of the right inferior frontal gyrus (P = .019) in the children who had been exposed to a single GA procedure.


The preclinical and clinical findings of these independent studies suggest lasting effects of early life exposure to anesthetics on later emotional control behaviors and brain structures.

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