Morphine in Pregnancy and Breastfeeding

Risk Factor: CM*
Class: Central nervous system drugs / Narcotic agonist analgesics

Contents of this page:
Fetal Risk Summary
Breast Feeding Summary
References
Questions and Answers

Fetal Risk Summary

No reports linking the therapeutic use of morphine with major congenital defects have been located. The narcotic is not teratogenic in rats at a dose 35 times the usual human dose (1).

Bilateral horizontal nystagmus persisting for 1 year was reported in one addicted newborn (2). Like all narcotics, placental transfer of morphine is very rapid (3,4). Maternal addiction with subsequent neonatal withdrawal is well known following illicit use (see also Heroin) (2,5,6). Morphine was widely used in labor until the 1940s, when it was largely displaced by meperidine. Clinical impressions that meperidine caused less respiratory depression in the newborn were apparently confirmed (7,8). Other clinicians reported no difference between narcotics in the degree of neonatal depression when equianalgesic IV doses were used (4). Epidural use of morphine has been reported in women in labor but with unsatisfactory analgesic effects (9). The intrathecal route, however, has provided safe and effective analgesia without fetal or newborn toxicity (10,11 and 12).

The Collaborative Perinatal Project monitored 50,282 mother-child pairs, 70 of which had 1st trimester exposure to morphine (13, pp. 287295). For use anytime during pregnancy, 448 exposures were recorded (13, p. 434). No evidence was found to suggest a relationship to large categories of major or minor malformations. A possible association with inguinal hernia (10 cases) after anytime use was observed (13, p. 484). The statistical significance of this association is unknown and independent confirmation is required.

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

Breast Feeding Summary

Past reports have indicated that only trace amounts of morphine enter breast milk, and the clinical significance of this was unknown (14,15 and 16). In a 1990 report, however, much higher concentrations of morphine were measured in the breast milk of one woman and in her infant's serum (17). A 30-year-old, 75-kg woman with systemic lupus erythematosus and severe arthritic back pain was treated with morphine, 50 mg every 6 hours, during the 3rd trimester and then with tapering doses during breast feeding. At the time of the study, the normal, healthy 3.5-kg infant was 21 days of age. One day before the study, the dose was 10 mg every 6 hours and then was tapered to 5 mg every 6 hours on the study day. Milk sampling times and morphine concentrations were: 4.5 hours after a dose (before feeding), 100 ng/mL; 4.75 hours after a dose (at end of feeding), 10 ng/mL; and 0.5 hours after a dose, 12 ng/mL (reported as 12 ng/L). A blood sample drawn from the infant 1 hour after a feeding (4 hours after a dose) had a morphine concentration of 4 ng/mL, a close approximation to the estimated therapeutic level. It was presumed that the infant had been exposed to much higher morphine concentrations from the milk before dose tapering and, thus, had higher therapeutic serum concentrations. Using pharmacokinetic calculations, the authors estimated that the infant was receiving between 0.8% and 12% of the maternal dose (17). No adverse effects of the exposure were observed in the infant.

Although the American Academy of Pediatrics considers morphine to be compatible with breast feeding (18), the new data above, if confirmed, indicate that nursing infants of mothers consuming morphine could be exposed to clinically significant amounts of the narcotic. The long-term effects on neurobehavior and development are unknown but warrant study.

References

  1. Product information. Duramorph. Elkins-Sinn, 2000.
  2. Perlstein MA. Congenital morphinism. A rare cause of convulsions in the newborn. JAMA 1947;135:633.
  3. Fisher DE, Paton JB. The effect of maternal anesthetic and analgesic drugs on the fetus and newborn. Clin Obstet Gynaecol 1974;17:27587.
  4. Bonica JJ. Principles and Practice of Obstetric Analgesia and Anesthesia. Philadelphia, PA: FA Davis, 1967:247.
  5. McMullin GP, Mobarak AN. Congenital narcotic addiction. Arch Dis Child 1970;45:1401.
  6. Cobrinik RW, Hodd RT Jr, Chusid E. The effect of maternal narcotic addiction on the newborn infant. Pediatrics 1959;24:288304.
  7. Gilbert G, Dixon AB. Observations on Demerol as an obstetric analgesic. Am J Obstet Gynecol 1943;45:3206.
  8. Way WL, Costley EC, Way EL. Respiratory sensitivity of the newborn infant to meperidine and morphine. Clin Pharmacol Ther 1965;6:45461.
  9. Nybell-Lindahl G, Carlsson C, Ingemarsson I, Westgren M, Paalzow L. Maternal and fetal concentrations of morphine after epidural administration during labor. Am J Obstet Gynecol 1981;139:201.
  10. Baraka A, Noueihid R, Hajj S. Intrathecal injection of morphine for obstetric analgesia. Anesthesiology 1981;54:13640.
  11. Bonnardot JP, Maillet M, Colau JC, Millot F, Deligne P. Maternal and fetal concentration of morphine after intrathecal administration during labour. Br J Anaesth 1982;54:4879.
  12. Brizgys RV, Shnider SM. Hyperbaric intrathecal morphine analgesia during labor in a patient with Wolff-Parkinson-White syndrome. Obstet Gynecol 1984;64:44S6S.
  13. Heinonen OP, Slone D, Shapiro S. Birth Defects and Drugs in Pregnancy. Littleton, MA: Publishing Sciences Group, 1977.
  14. Terwilliger WG, Hatcher RA. The elimination of morphine and quinine in human milk. Surg Gynecol Obstet 1934;58:8236.
  15. Kwit NT, Hatcher RA. Excretion of drugs in milk. Am J Dis Child 1935;49:9004.
  16. Anonymous. Drugs in breast milk. Med Lett Drugs Ther 1979;21:214.
  17. Robieux I, Koren G, Vandenbergh H, Schneiderman J. Morphine excretion in breast milk and resultant exposure of a nursing infant. J Toxicol Clin Toxicol 1990;28:36570.
  18. Committee on Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 1994;93:13750.

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