The epigenetic legacy of ICU feeding and its consequences

Many critically ill patients face physical, mental or neurocognitive impairments up to years later, the etiology remaining largely unexplained. Aberrant epigenetic changes have been linked to abnormal development and diseases resulting from adverse environmental exposures like major stress or inadequate nutrition. Theoretically, severe stress and artificial nutritional management of critical illness thus could induce epigenetic changes explaining long-term problems. We review supporting evidence.

Epigenetic abnormalities are found in various critical illness types, affecting DNA-methylation, histone-modification and noncoding RNAs. They at least partly arise de novo after ICU-admission. Many affect genes with functions relevant for and several associate with long-term impairments. As such, de novo DNA-methylation changes in critically ill children statistically explained part of their disturbed long-term physical/neurocognitive development. These methylation changes were in part evoked by early-parenteral-nutrition (early-PN) and statistically explained harm by early-PN on long-term neurocognitive development. Finally, long-term epigenetic abnormalities beyond hospital-discharge have been identified, affecting pathways highly relevant for long-term outcomes.

Epigenetic abnormalities induced by critical illness or its nutritional management provide a plausible molecular basis for their adverse effects on long-term outcomes. Identifying treatments to further attenuate these abnormalities opens perspectives to reduce the debilitating legacy of critical illness.