The purpose of this trial to find the best dose of N-acetylcysteine to decrease brain injury
in babies exposed to intrauterine infection without causing significant side effects.
Chorioamnionitits is an intrauterine infection—an infection in the fluid and membranes
surrounding the baby in utero. The infection, and the baby's response to the infection, can
cause inflammation in the baby's brain which affects development. Intrauterine infection is
associated with significant white and grey matter brain injury in newborns and is
particularly important in the pathogenesis of periventricular leukomalacia (PVL) and
cerebral palsy (CP). Brain injury, particularly CP, has been shown to be 4-9 times higher
in babies exposed to intrauterine infection than in normal infants. Treating both the
mother and baby with antibiotics is part of routine care, however this has not been shown to
change the risk for brain injury in the baby.
N-acetylcysteine (NAC) is a promising anti-oxidant therapy that has shown effective
neuroprotection in an animal model of chorioamnionitis, and has a favorable safety profile
with limited and manageable side effects. There are extensive clinical experience and safety
data in pregnant mothers and preterm infants, established from acetaminophen overdose and
European studies of NAC for prevention of chronic lung disease of prematurity.
In this pilot clinical trial, scientists will determine the safety of two different doses of
NAC given to pregnant women who present with chorioamnionitis at greater than 24 weeks
In the trial, intravenous NAC will be given to mothers antenatally (and to their infants
postnatally) who present with the diagnosis of chorioamnionitis, to evaluate safety and
pharmacokinetics (PK) in mothers and infants. Mothers at 24 weeks gestation or greater and
their infants will be randomized to receive either saline or one of two different doses of
NAC within 4 hours of a clinical diagnosis of chorioamnionitis. NAC will be given to the
mothers every 6 hours until delivery and every 12 hours to the infants after delivery for 2
Information gained from this trial will be used to determine the best dose of NAC and to
help estimate effect and sample sizes for a subsequent large clinical trial.
Participants must have all of the following to qualify:
- Chorioamnionitis, defined as either 1) clinical diagnosis of choriomanionitis 2)
maternal fever greater than or equal to 100 degrees F in the presence of rupture of
membranes or 2 of the following: uterine tenderness, maternal WBC > 15,000 cells/mm,
fetal tachycardia > 160 bpm, malodorous amniotic fluid, or in preterm group only,
rupture of membranes and active preterm labor.
- Gestational age > 24 completed weeks, by first trimester ultrasound or date of last
- No greater than 4 hours from onset of fever or diagnosis.
Participants must have none of the following:
- Clinical sepsis, whether viral or bacterial in nature, defined as fever with signs of
cardiovascular compromise in mother (blood pressure < 90/50, heart rate > 120 bpm,
need for oxygen due to maternal saturations below 92%, pneumonia, pyelonephritis, or
- Seizure disorder
- Fetal weight or biparietal diameter less than the 10th% for gestational age
- Suspected major genetic or congenital abnormality
- Fetal distress which demands immediate delivery (poor fetal biophysical profile, late
decelerations, sinusoidal fetal heart rate pattern)
- Participation in another therapeutic clinical trial