Placental transfer of N-acetylcysteine following human maternal acetaminophen toxicity.
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.


METHODS
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.
Horowitz
R S
RS
Rocky Mountain Poison and Drug Center, Denver, Colorado 80220-6800, USA. rivkah@pol.net
Dart
R C
RC
Jarvie
D R
DR
Bearer
C F
CF
Gupta
U
U
D000082:Acetaminophen / Q000506:poisoning*; D000111:Acetylcysteine / Q000097:blood* / Q000627:therapeutic use; D018712:Analgesics, Non-Narcotic / Q000506:poisoning*; D001692:Biological Transport; D002851:Chromatography, High Pressure Liquid; D062787:Drug Overdose; D017809:Fatal Outcome; D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D016166:Free Radical Scavengers / Q000097:blood* / Q000627:therapeutic use; D006801:Humans; D008431:Maternal-Fetal Exchange / Q000502:physiology; D010920:Placenta / Q000378:metabolism*; D011041:Poisoning / Q000097:blood* / Q000188:drug therapy; D011247:Pregnancy
D018712:Analgesics, Non-Narcotic; D016166:Free Radical Scavengers; D000082:Acetaminophen; D000111:Acetylcysteine