METHADONE

Fetal Risk Summary

Methadone use in pregnancy is almost exclusively related to the treatment of heroin addiction. No increase in congenital defects has been observed. However, since these patients normally consume a wide variety of drugs, it is not possible to separate completely the effects of methadone from the effects of other agents. Neonatal narcotic withdrawal and low birth weight seem to be the primary problems.

Withdrawal symptoms occur in approximately 60%–90% of the infants (1,2,3,4,5 and 6). One study concluded that the intensity of withdrawal was increased if the daily maternal dosage exceeded 20 mg (5). When withdrawal symptoms do occur, they normally start within 48 hours after delivery, but a small percentage may be delayed up to 7–14 days (1). One report observed initial withdrawal symptoms appearing up to 28 days after birth, but the authors do not mention if mothers of these infants were breast feeding (6). Methadone concentrations in breast milk are reported to be sufficient to prevent withdrawal in addicted infants (see Breast Feeding Summary below). Some authors believe methadone withdrawal is more intense than that occurring with heroin (1). Less than one-third of symptomatic infants require therapy (1,2,3,4 and 5). A lower incidence of hyaline membrane disease is seen in infants exposed in utero to chronic methadone and may be due to elevated blood levels of prolactin (7).

Infants of drug-addicted mothers are often small for gestational age. In some series, one-third or more of the infants weigh less than 2500 g (1,2,4). The newborns of methadone addicts may have a higher birth weights than comparable offspring of heroin addicts for reasons that remain unclear (4).

Other problems occurring in the offspring of methadone addicts are increased mortality, sudden infant death syndrome (SIDS), jaundice, and thrombocytosis. A correlation between drug addiction and SIDS has been suggested with 20 cases (2.8%) in a group of 702 infants, but the data could not attribute the increase to a single drug (8,9). Another study of 313 infants of methadone-addicted mothers reported 2 cases (0.6%) of SIDS, an incidence similar to the overall experience of that location (4). In one study, a positive correlation was found between severity of neonatal withdrawal and the incidence of SIDS (9). Maternal withdrawal during pregnancy has been observed to produce a marked response of the fetal adrenal glands and sympathetic nervous system (10). An increased stillborn and neonatal mortality rate has also been reported (11). Both reports recommend against detoxification of the mother during gestation. Jaundice is comparatively infrequent in both heroin- and methadone-exposed newborns. However, a higher rate of severe hyperbilirubinemia in methadone-exposed infants than in a comparable group of heroin-exposed infants has been observed (1). Thrombocytosis developing in the 2nd week of life, with some platelet counts exceeding 1,000,000/mm3 and persisting for more than 16 weeks, has been reported (12). The condition was not related to withdrawal symptoms or neonatal treatment. Some of these infants also had increased circulating platelet aggregates.

Respiratory depression is not a significant problem, and Apgar scores are comparable to those of a nonaddicted population (1,2,3,4 and 5). Long-term effects on the behavior and gross motor development skills are not known.

[*Risk Factor D if used for prolonged period or in high doses at term.]

Breast Feeding Summary

Methadone enters breast milk in concentrations approaching plasma levels and may prevent withdrawal symptoms in addicted infants. One study reported an average milk concentration in 10 patients of 0.27 µg/mL, representing an average milk:plasma ratio of 0.83 (13). The same investigators earlier reported levels ranging from 0.17 to 5.6 µg/mL in the milk of mothers on methadone maintenance (2). At least one infant death has been attributed to methadone obtained through breast milk (14). However, a recent report claimed that methadone enters breast milk in very low quantities that are clinically insignificant (15). The American Academy of Pediatrics considers methadone to be compatible with breast feeding with no adverse effects reported in the nursing infant when the mother was consuming 20 mg/24 hours or less (16).

References

1. Zelson C, Lee SJ, Casalino M. Neonatal narcotic addiction. N Engl J Med 1973;289:1216–20.
2. Blinick G, Jerez E, Wallach RC. Methadone maintenance, pregnancy and progeny. JAMA 1973;225:477–9.
3. Strauss ME, Andresko M, Stryker JC, Wardell JN, Dunkel LD. Methadone maintenance during pregnancy: pregnancy, birth and neonate characteristics. Am J Obstet Gynecol 1974;120:895–900.
4. Newman RG, Bashkow S, Calko D. Results of 313 consecutive live births of infants delivered to patients in the New York City methadone maintenance program. Am J Obstet Gynecol 1975;121:233–7.
5. Ostrea EM, Chavez CJ, Strauss ME. A study of factors that influence the severity of neonatal narcotic withdrawal. J Pediatr 1976;88:642–5.
6. Kandall SR, Gartner LM. Delayed presentation of neonatal methadone withdrawal. Pediatr Res 1973;7:320.
7. Parekh A, Mukherjee TK, Jhaveri R, Rosenfeld W, Glass L. Intrauterine exposure to narcotics and cord blood prolactin concentrations. Obstet Gynecol 1981;57:447–9.
8. Pierson PS, Howard P, Kleber HD. Sudden deaths in infants born to methadone-maintained addicts. JAMA 1972;220:1733–4.
9. Chavez CJ, Ostrea EM, Stryker JC, Smialek Z. Sudden infant death syndrome among infants of drug-dependent mothers. J Pediatr 1979;95:407–9.
10. Zuspan FP, Gumpel JA, Mejia-Zelaya A, Madden J, David R. Fetal stress from methadone withdrawal. Am J Obstet Gynecol 1975;122:43–6.
11. Rementeria JL, Nunag NN. Narcotic withdrawal in pregnancy: stillbirth incidence with a case report. Am J Obstet Gynecol 1973;116:1152–6.
12. Burstein Y, Giardina PJV, Rausen AR, Kandall SR, Siljestrom K, Peterson CM. Thrombocytosis and increased circulating platelet aggregates in newborn infants of polydrug users. J Pediatr 1979;94:895–9.
13. Blinick G, Inturrisi CE, Jerez E, Wallach RC. Methadone assays in pregnant women and progeny. Am J Obstet Gynecol 1975;121:617–21.
14. Smialek JE, Monforte JR, Aronow R, Spitz WU. Methadone deaths in children—a continuing problem. JAMA 1977;238:2516–7.
15. Anonymous. Methadone in breast milk. Med Lett Drugs Ther 1979;21:52.
16. Committee on Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 1994;93:137–50.