N-acetylcysteine (NAC) facilitates motor learning in infants of diabetic mothers (IDM) failing oral feeds treated with transcutaneous auricular vagus nerve stimulation (taVNS)
Year: 2023
Type: article
Study design: Clinical Trial
Abstract: Introduction: taVNS improves oral feeding in newborns who are failing oral feeds but is ineffective in Infants of Diabetic Mothers (IDM) with lower CNS glutathione(GSH) concentrations in a prior trial. We hypothesized that mitigating oxidative stress with N-acetylcysteine(NAC) prior to taVNS would enhance motor learning in IDM and achieve full oral feeds. We measured PK and CNS GSH changes with NAC. Methods: Following informed consent, we enrolled 8 IDM slated to receive gastrotomy tubes. Infants received NAC 75 (n=4) or 100mg/kg/dose q6h (n=4) via nasogastric tube prior to feeds for 4 days alone, then with taVNS for up to 14 days. We obtained magnetic resonance spectroscopy (MRS) before NAC, after 4d of NAC, and the end of treatment, along with steady-state NAC serum concentrations for PK estimates around day 4 MRS. Feeding volumes were compared between IDM treated with NAC+taVNS (n=8) and taVNS alone (prior trial, n=12). Results: Mean (SD) postmenstrual age was 41±1wks, days attempting po were 39±8d, and 50% infants had CNS bleeds and infarcts due to birth asphyxia. The increase in daily oral feeds over 2 weeks was significantly greater during NAC+taVNS (+2.6ml/kg/d) than prior to treatment (0.5ml/kg/d, p<0.001) and greater than during taVNS alone (+1.5ml/kg/d, p<0.001). 62% IDM reached full oral feeds with NAC+taVNS, compared with 25% with taVNS alone. PK parameters included t½ = 1.8±0.4hours, AUC= 58.7±26.3 mcg-hr/mL, and CL= 1107±257mL/hr/kg. MRS showed increased [GSH] in basal ganglia in all infants at 1.5-2h after ng NAC. NAC was well tolerated. Conclusions: NAC improved CNS antioxidant status and facilitated taVNS effects on oral feeding volumes in Infants of Diabetic Mothers who have oxidative stress and largely did not respond to taVNS alone. This approach may enhance neuromodulation effects in other CNS neuroinflammatory conditions. Research Category and Technology and Methods Translational Research: 12. Vagus Nerve Stimulation (VNS); Keywords: NAC, taVNS, CNS oxidative stress, infants of diabetic mothers
Source: Brain stimulation
Institution: Medical University of South Carolina
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,830
OpenAlex ID: W4320898284