EPHEDRINE

Fetal Risk Summary

Ephedrine is a sympathomimetic used widely for bronchial asthma, allergic disorders, hypotension, and the alleviation of symptoms caused by upper respiratory infections. It is a common component of proprietary mixtures containing antihistamines, bronchodilators, and other ingredients. Thus it is difficult to separate the effects of ephedrine on the fetus from other drugs, disease states and viruses. Ephedrine-like drugs are teratogenic in some animal species, but human teratogenicity has not been suspected (1,2).

The Collaborative Perinatal Project monitored 50,282 mother-child pairs, 373 of whom had 1st trimester exposure to ephedrine (3, pp. 345–56). For use anytime during pregnancy, 873 exposures were recorded (3, p. 439). No evidence for a relationship to large categories of major or minor malformations or to individual defects was found. However, an association in the 1st trimester was found between the sympathomimetic class of drugs as a whole and minor malformations (not life-threatening or major cosmetic defects), inguinal hernia, and clubfoot (3, pp. 345–56).

Ephedrine is routinely used to treat or prevent maternal hypotension following spinal anesthesia (4,5,6 and 7). Significant increases in fetal heart rate and beat-to-beat variability may occur, but these effects may have been the result of normal reflexes following hypotension-associated bradycardias. A recent study, however, has demonstrated the placental passage of ephedrine with fetal levels at delivery approximately 70% of the maternal concentration (8). The presence of ephedrine in the fetal circulation is probably a major cause of the fetal heart rate changes.

Breast Feeding Summary

A single case report has been located describing adverse effects in a 3-month-old nursing infant of a mother consuming a long-acting preparation containing 120 mg of d-isoephedrine and 6 mg of dexbrompheniramine (9). The mother had begun taking the preparation on a twice-daily schedule 1 or 2 days prior to onset of the infant's symptoms. The infant exhibited irritability, excessive crying, and disturbed sleeping patterns that resolved spontaneously within 12 hours when breast feeding was stopped.

References

1. Nishimura H, Tanimura T. Clinical Aspects of The Teratogenicity of Drugs. New York, NY:American Elsevier, 1976:231.
2. Shepard TH. Catalog of Teratogenic Agents. 3rd ed. Baltimore, MD:Johns Hopkins University Press, 1980:134–5.
3. Heinonen OP, Slone D, Shapiro S. Birth Defects and Drugs in Pregnancy. Littleton, MA:Publishing Sciences Group, 1977.
4. Wright RG, Shnider SM, Levinson G, Rolbin SH, Parer JT. The effect of maternal administration of ephedrine on fetal heart rate and variability. Obstet Gynecol 1981;57:734–8.
5. Antoine C, Young BK. Fetal lactic acidosis with epidural anesthesia. Am J Obstet Gynecol 1982;142:55–9.
6. Datta S, Alper MH, Ostheimer GW, Weiss JB. Method of ephedrine administration and nausea and hypotension during spinal anesthesia for cesarean section. Anesthesiology 1982;56:68–70.
7. Antoine C, Young BK. Fetal lactic acidosis with epidural anesthesia. Am J Obstet Gynecol 1982;142:55–9.
8. Hughes SC, Ward MG, Levinson G, Shnider SM, Wright RG, Gruenke LD, Craig JC. Placental transfer of ephedrine does not affect neonatal outcome. Anesthesiology 1985;63:217–9.
9. Mortimer EA Jr. Drug toxicity from breast milk? Pediatrics 1977;60:780–1.