The methadone-maintained pregnancy.

Methadone treatment during pregnancy offers overwhelming advantages compared with the less acceptable option of medical detoxification or the unacceptably dangerous option of leaving heroin-addicted women dependent on street drugs. General agreement exists that pregnancy offers a unique opportunity to bring women into medical, obstetric, and drug treatment. Methadone maintenance in the setting of comprehensive service provision during pregnancy reduces maternal morbidity and mortality and promotes fetal stability and growth. With an accumulated experience of over 25 years, methadone maintenance has been shown to be an invaluable and often an essential ingredient in bettering the health of women during pregnancy, in improving the outcomes of those pregnancies, and in offering opiate-addicted women a chance to improve both their lives and the lives of their families.

Relationship between maternal methadone dosage, maternal-neonatal methadone levels, and neonatal withdrawal.

OBJECTIVE: To define the relationships between neonatal opiate withdrawal and drug-related factors such as maternal methadone dosage, maternal and neonatal plasma levels, and rate of decline of methadone in neonatal plasma. METHODS: Twenty-one methadone-dependent women and their newborn infants were studied. Fourteen of the women used other illicit drugs. The severity of neonatal withdrawal was assessed with a standardized scoring system. Venous blood samples for methadone levels were collected from the mothers within 24 hours of delivery and from their newborns within 24 hours of birth and on day 3-4 of life. RESULTS: The maternal methadone dosage at delivery correlated significantly with the maternal plasma level drawn at 16 hours postpartum (r = 0.512, P < .05), and the maternal methadone level in turn correlated significantly with the neonatal plasma methadone level on day 1 of life (r = 0.545, P < .05). A positive correlation was found between the severity of central nervous system signs of withdrawal and the rate of decline of the neonatal plasma methadone level from day 1 to day 4 of life (r = 0.550, P < .05). CONCLUSION: This spectrum of relationships supports the concept that careful reduction of the maternal methadone dosage during pregnancy under intensive medical and psychosocial surveillance may benefit the drug-exposed new-born infant clinically.

Neonatal opiate abstinence syndrome in term and preterm infants.

Data on 178 term and 34 preterm infants born to methadone-maintained mothers were analyzed to assess the effects of neonatal opiate abstinence in infants of varying gestational ages. More mothers in the term group (79%) than in the preterm group (53%) had abused other drugs during pregnancy (p less than 0.001). Mean (+/- SD) gestational age was 39.5 weeks +/- 1.4 for term infants and 34.3 weeks +/- 2.6 for preterm infants. On the basis of a semiobjective symptom scoring scale, term infants had more severe abstinence symptoms and more prominent central nervous system manifestations than preterm infants. The severity of abstinence symptoms correlated with maternal methadone dosage in both term and preterm infants. Maternal multiple drug abuse (e.g., heroin, cocaine) did not influence severity of abstinence symptoms in either group. More term infants (145/178) than preterm infants (20/34) required treatment for these symptoms (p less than 0.005). In 13 of 178 term infants, compared with 1 of 34 preterm infants, abstinence-related seizures developed. Peak severity occurred 1 to 2 days earlier in term than in preterm infants. A less severe abstinence syndrome in preterm infants may be due to (1) developmental immaturity of either dendritic ramifications, specific opiate receptors, or neurotransmitter function, or (2) reduced total drug exposure during the intrauterine period.

Neonatal neurologic and electroencephalographic effects of intrauterine cocaine exposure.

Thirty-nine infants with intrauterine exposure to cocaine were examined for neurologic and electroencephalographic (EEG) abnormalities. Of the 39 infants, 34 displayed central nervous system irritability, but only two of the infants required sedation. The EEGs were abnormal in 17 of 38 infants during the first week of life; abnormalities were characterized as showing central nervous system irritability. The EEG abnormalities could not be predicted on the basis of clinical neurologic dysfunction or perinatal variables. On follow-up, 9 of the 17 abnormal EEGs remained abnormal during the second week of life. One infant had an abnormal first EEG at 13 days of age. By 3 to 12 months of age, however, 9 of the 10 previously abnormal tracing had normalized and one is pending. These transient clinical and EEG abnormalities may be the result of changes in neurotransmitter availability and function.

One-year follow-up of infants with abstinence-associated seizures.

Fourteen infants with neonatal abstinence-associated seizures were assessed neurodevelopmentally during the first year of life. Despite abnormal neurologic examination results in eight of 12 infants at 2 to 4 months of age, nine of 12 infants had normal neurologic examination results at follow-up (two infants were unavailable for follow-up; one infant died of acquired immunodeficiency syndrome). Nine neonatal electroencephalograms were abnormal; seven of eight of these abnormal tracings normalized during the follow-up period. Bayley developmental scores remained normal during the first year of life and did not differ from either passively addicted infants without seizures or from published population norms. This short-term favorable prognosis for abstinence-associated seizures differs from that associated with neonatal seizures due to other causes. This observed improvement in neurologic function may be based on replenishment of neurotransmitters following transient depletion in the neonatal period.

Impact of maternal drug dependency on birth weight and head circumference of offspring.

The impact of maternal opiate dependency on birth weight and head circumference of offspring was studied in 150 mother-infant pairs and 150 controls. Mean birth weight and head circumference of drug-dependent offspring were reduced symmetrically compared with drug-free controls of similar socioeconomic status. Although mean gestational ages and rates of prematurity were similar, intrauterine growth retardation occurred in 20% of passively addicted infants vs 4% of controls. A longer period of methadone maintenance was associated with longer gestation and increased birth weight, while higher methadone dosages were associated with higher birth weights and larger head circumferences. Smoking was associated with reduced birth weight by an average of 160 g per pack of cigarettes smoked per day; longer duration of smoking was associated with reductions in both birth weight and head circumference. These data suggest therapeutic strategies to improve these fetal growth characteristics and perhaps improve neurobehavioral outcome of drug-dependent newborns.

Early weight-change patterns in neonatal abstinence.

Early weight-change patterns were studied in 101 passively addicted neonates. Newborns showing mild abstinence and not requiring pharmacologic treatment lost an average of 4.0% of birth weight, reached a weight nadir on day 3, and regained birth weight by days 7 to 8. Newborns treated with either paregoric or phenobarbital for more severe signs of abstinence lost an average of 6.3% of birth weight, reached a nadir on days 6 to 7, and regained birth weight only by days 13 to 14. Despite comparable birth weights and energy intakes, treated newborns weighed 95 g less than untreated neonates on day 10 when the untreated neonates were discharged. In light of abnormal early weight-change patterns seen with more severe abstinence, both strict control of abstinence and provision of additional individualized nutritional support seem warranted.

Peripheral nerve conduction studies in passively addicted neonates.

Neurologic signs dominate the manifestations of the neonatal abstinence syndrome (NAS). To help delineate this dysfunction, peripheral nerve conduction studies (NCS) were made in 25 neonates born to methadone-maintained mothers; 12 of the mothers abused other controlled substances concomitantly. Median and common peroneal motor nerve conduction velocities (NCV) in these infants were normal, both at three to seven days and three to four weeks of age, and were unaffected by maternal drug intake pattern, severity of neonatal abstinence symptoms, treatment with either camphorated tincture of opium or phenobarbital, intrauterine growth retardation, or abstinence-associated seizurer. Electromyographic findings were normal in 21/23 infants; two others showed minimal partial denervation, characterized by fibrillations and positive sharp waves. NCV in the NAS may enhance gestational age assessment and therefore increase validity of neurobehavioral follow-up. Our studies continue to point to a central rather than a peripheral motor dysfunction exhibited by passively addicted infants at birth, which may persist on two-to-five-year follow-up.

Opiate v CNS depressant therapy in neonatal drug abstinence syndrome.

Paregoric and phenobarbital, administered randomly in 153 passively addicted neonates, initially appeared to control neonatal abstinence signs equally well. However, seven of the 62 phenobarbital-treated newborns had abstinence-associated seizures within the first month of life, while none of 49 paregoric-treated neonates had seizures. Forty-two neonates initially requiring no specific pharmacotherapy for abstinence signs were born to mothers taking less methadone hydrochloride just before delivery. Five of those 42 neonates, however, had seizures within the first 14 days of life. Seizure occurrence could not be predicted from analysis of early abstinence patterns. We consider paregoric to be the treatment of choice for the neonatal abstinence syndrome. Phenobarbital use should be monitored with serum drug levels and modification of recommended dosage regimens considered.