title: Fetal and Neonatal Effects of N-Acetylcysteine When Used for Neuroprotection in Maternal Chorioamnionitis.
abstract: OBJECTIVE
  To evaluate the clinical safety of antenatal and postnatal N-acetylcysteine (NAC) as a neuroprotective agent in maternal chorioamnionitis in a randomized, controlled, double-blinded trial.
  
  
  METHODS
  Twenty-two mothers >24 weeks gestation presenting within 4 hours of diagnosis of clinical chorioamnionitis were randomized with their 24 infants to NAC or saline treatment. Antenatal NAC (100 mg/kg/dose) or saline was given intravenously every 6 hours until delivery. Postnatally, NAC (12.5-25 mg/kg/dose, n = 12) or saline (n = 12) was given every 12 hours for 5 doses. Doppler studies of fetal umbilical and fetal and infant cerebral blood flow, cranial ultrasounds, echocardiograms, cerebral oxygenation, electroencephalograms, and serum cytokines were evaluated before and after treatment, and 12, 24, and 48 hours after birth. Magnetic resonance spectroscopy and diffusion imaging were performed at term age equivalent. Development was followed for cerebral palsy or autism to 4 years of age.
  
  
  RESULTS
  Cardiovascular measures, cerebral blood flow velocity and vascular resistance, and cerebral oxygenation did not differ between treatment groups. Cerebrovascular coupling was disrupted in infants with chorioamnionitis treated with saline but preserved in infants treated with NAC, suggesting improved vascular regulation in the presence of neuroinflammation. Infants treated with NAC had higher serum anti-inflammatory interleukin-1 receptor antagonist and lower proinflammatory vascular endothelial growth factor over time vs controls. No adverse events related to NAC administration were noted.
  
  
  CONCLUSIONS
  In this cohort of newborns exposed to chorioamnionitis, antenatal and postnatal NAC was safe, preserved cerebrovascular regulation, and increased an anti-inflammatory neuroprotective protein.
  
  
  BACKGROUND
  ClinicalTrials.gov: NCT00724594.
authors.affiliation: Department of Pediatrics, Medical University of South Carolina, Charleston, SC. Electronic address: jenkd@musc.edu.
authors.forename: Dorothea D
authors.initials: DD
authors.lastname: Jenkins
authors.affiliation: Department of Clinical Pharmacy and Outcome Science, Medical University of South Carolina, Charleston, SC.
authors.forename: Donald B
authors.initials: DB
authors.lastname: Wiest
authors.affiliation: Department of Pediatrics, Medical University of South Carolina, Charleston, SC.
authors.forename: Denise M
authors.initials: DM
authors.lastname: Mulvihill
authors.affiliation: Department of Pediatrics, Medical University of South Carolina, Charleston, SC.
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Hlavacek
authors.affiliation: Department of Pediatrics, Medical University of South Carolina, Charleston, SC.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Majstoravich
authors.affiliation: Department of Neuroscience's Center for Advanced Imaging Research, Medical University of South Carolina, Charleston, SC.
authors.forename: Truman R
authors.initials: TR
authors.lastname: Brown
authors.affiliation: Department of Neuroscience's Center for Advanced Imaging Research, Medical University of South Carolina, Charleston, SC; Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC.
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Taylor
authors.affiliation: Department of Pediatrics, Medical University of South Carolina, Charleston, SC.
authors.forename: Jason R
authors.initials: JR
authors.lastname: Buckley
authors.affiliation: Department of Clinical Pediatrics and Neurology, University of South Carolina School of Medicine and Palmetto Health Richland Children's Hospital, Columbia, SC.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Turner
authors.affiliation: Department of Clinical Psychology, University of Massachusetts, Boston, MA.
authors.forename: Laura Grace
authors.initials: LG
authors.lastname: Rollins
authors.affiliation: Department of Pediatrics, Medical University of South Carolina, Charleston, SC.
authors.forename: Jessica P
authors.initials: JP
authors.lastname: Bentzley
authors.affiliation: Department of Pediatrics, Medical University of South Carolina, Charleston, SC.
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Hope
authors.affiliation: Department of Pediatrics, Medical University of South Carolina, Charleston, SC.
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Barbour
authors.affiliation: Department of Pediatrics, Medical University of South Carolina, Charleston, SC.
authors.forename: Danielle W
authors.initials: DW
authors.lastname: Lowe
authors.affiliation: Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC.
authors.forename: Renee H
authors.initials: RH
authors.lastname: Martin
authors.affiliation: Department of Obstetrics and Gynecology, Medical University of South Carolina, Charleston, SC.
authors.forename: Eugene Y
authors.initials: EY
authors.lastname: Chang
mesh_terms: D000111:Acetylcysteine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D002821:Chorioamnionitis / Q000188:drug therapy*; D004311:Double-Blind Method; D004453:Echoencephalography; D004569:Electroencephalography; D005260:Female; D005333:Fetus; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008279:Magnetic Resonance Imaging; D008297:Male; D009035:Mothers; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011247:Pregnancy; D011446:Prospective Studies; D018608:Ultrasonography, Doppler
chemical_list: D018696:Neuroprotective Agents; D000111:Acetylcysteine