Placental transfer of N-acetylcysteine following human maternal acetaminophen toxicity

J Toxicol Clin Toxicol. 1997;35(5):447-51. doi: 10.3109/15563659709001226.

Abstract

Objective: To determine whether the antidote for acetaminophen poisoning, N-acetylcysteine, administered to pregnant women with acetaminophen toxicity, crosses the placenta and can be measured in the newborn circulation following delivery.

Design: Over a 15-month period, four pregnant women with acetaminophen toxicity, who delivered their infants while receiving the antidote N-acetylcysteine, were studied. Maternal and cord blood from three viable infants, and cardiac blood sampled during an autopsy on the fourth, were analyzed for the presence of N-acetylcysteine using high-performance liquid chromatography. Maternal and cord blood aminotransferase activities, and autopsy findings on the nonviable infant were used to assess hepatic injury.

Results: N-Acetylcysteine was detected in the cord blood of three viable infants and in cardiac blood of a fourth, sampled at the time of autopsy. The mean N-acetylcysteine concentration in cord blood was 9.4 micrograms/mL (+/-1.3). This is well within the range associated with therapeutic doses of N-acetylcysteine typically administered to adults with acetaminophen poisoning. No adverse sequelae developed in the three viable infants. The fourth infant, delivered at 22 weeks gestational age died 3 h after birth. All mothers recovered and none of the four infants had evidence of acetaminophen-related toxicity.

Conclusions: This is the first study documenting placental transfer of N-acetylcysteine in humans and provides impetus for research establishing a direct antidotal effect of N-acetylcysteine in the fetus.

Publication types

  • Case Reports

MeSH terms

  • Acetaminophen / poisoning*
  • Acetylcysteine / blood*
  • Acetylcysteine / therapeutic use
  • Analgesics, Non-Narcotic / poisoning*
  • Biological Transport
  • Chromatography, High Pressure Liquid
  • Drug Overdose
  • Fatal Outcome
  • Female
  • Fetal Blood / metabolism
  • Free Radical Scavengers / blood*
  • Free Radical Scavengers / therapeutic use
  • Humans
  • Maternal-Fetal Exchange* / physiology
  • Placenta / metabolism*
  • Poisoning / blood*
  • Poisoning / drug therapy
  • Pregnancy

Substances

  • Analgesics, Non-Narcotic
  • Free Radical Scavengers
  • Acetaminophen
  • Acetylcysteine