Placental Transfer ofN-Acetylcysteine Following Human Maternal Acetaminophen Toxicity

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Abstract
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. 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. 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. 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.