Addictive diseases最新文献

We studied the placental transfer of methadone, the relationship of neonatal plasma methadone concentrations to withdrawal symptomatology, and the relationship between maternal methadone dose and severity of neonatal withdrawal in 31 methadone-maintained mothers and their neonates. Methadone concentrations in maternal, cord and neonatal plasma were measured using a gas chromatographic micromethod. Neonatal plasma was assayed on days 0-5 of life. Urine methadone levels were measured for the first 3 days of neonatal life, using a similar assay. Twenty-five of the neonates experienced mild to severe withdrawal symptoms. There was no consistent relationship between the maternal methadone dose and the severity of neonatal symptoms. However, when neonatal withdrawal did occur, it began after plasma methadone levels fell below .06 mug/ml. The neonatal plasma methadone levels were consistently lower than those of the mother. Maternal methadone is transferred across the placenta and can induce significant withdrawal symptomatology in the newborn.

The neonatal withdrawal period was characterized by heightened auditory responsiveness and orientation, lowered overall alertness and poor attentiveness to and following of visual stimuli. Electroencephalographic recordings revealed high-frequency dysynchronous activity suggestive of cns irritability. Analysis of evoked response data further corroborated the behavioral findings with evidence for low arousal value of visual stimulation in the vertex frequency characteristics and poorly defined occipital responses. Auditory evoked responses appeared better integrated, and a significant correlation was found between auditory orienting ability and latency of the P2 component. The long-range developmental significance of these neonatal characteristics awaits further follow-up investigation.

1. History is unreliable in assessing maternal drug habit. Morphine was detected in significant amounts in maternal and fetal urine regardless of whether the mother was on a methadone program or whether she denied any use of heroin during the last trimester of pregnancy. 2. Infants born to drug-addicted mothers were, in general, of birthweight normal and appropriate for gestational age (i.e., greater that 10th percentile). The infants born to mothers on a methadone clinic program had a higher birthweight compared to those whose mothers were not on any methadone program. 3. In order of frequency, the signs and symptoms of withdrawal were: central nervous system manifestations-fist sucking, irritability, tremors, sneezing, high-pitch cry, hypertonia; vasomotor in the form of stuffy nose; and gastrointestinal in the form of sweating, diarrhea, vomiting and yawning. Convulsions were not noted. No death occurred. 4. The severity of neonatal narcotic withdrawal did not correlate with the infant's gestational age, APGAR, sex or race; nor with maternal age, parity, duration of heroin addiction or duration of methadone intake. Also, it did not correlate with the total morphine level measured either in infant's or mother's urine or in cord blood. The serum levels of calcium and glucose were normal and identical in either mild or severe withdrawal. 5. The severity of neonatal withdrawal correlated significantly with the methadone dose per day of the mother (in initial, final or average dose). A maternal methadone dose of more than 20 mg per day was associated with a higher incidence of moderate to severe withdrawal in their babies. As a corollary, it was also noted that infants whose mothers were on a high methadone dose (i.e., greater than 20 mg per day) had a greater postnatal weight loss despite a significantly higher birthweight initially, and stayed in the hospital longer. 6. Finally, the modification of the environment to reduce external stimuli to the infant born to a drug-dependent mother, does not prevent or diminish the severity of neonatal narcotic withdrawal. Thus, there is no need to manage these infants in a special nursery.

The injection of morphine sulfate into baby mice twice daily for 5 days increased their running reaponse to morphine when they were tested as adults. If treatment was completed before the mice were )5 days old there was no effect. Sensitization to morphine running was longer-lasting than either analgesic tolerance or tolerance to morphine running may be a form of denervation hypersensitivity that has several features in common with noise-induced sensitization to audiogenic seizures.

The semeiology and significance of neonatal "minor withdrawal" are developed. Its treatment and the consequent prevention of rebound, late, or classical withdrawal are proposed. Basic research implications are formulated.