STREPTOMYCIN

Fetal Risk Summary

Streptomycin is an aminoglycoside antibiotic. The drug rapidly crosses the placenta into the fetal circulation and amniotic fluid, obtaining concentrations that are usually less than 50% of the maternal serum level (1,2). Early investigators, well aware of streptomycin-induced ototoxicity, were unable to observe this defect in infants exposed in utero to the agent (3,4 and 5). Eventually, ototoxicity was described in a 2 1/2-month-old infant whose mother had been treated for tuberculosis with 30 g of streptomycin during the last month of pregnancy (6). The infant was deaf with a negative cochleopalpebral reflex. Several other case reports and small surveys describing similar toxicity followed this initial report (7,8). In general, however, the incidence of congenital ototoxicity, cochlear or vestibular, from streptomycin is low, especially with careful dosage calculations and if the duration of fetal exposure is limited (9).

Except for eighth cranial nerve damage, no reports of congenital defects caused by streptomycin have been located. The Collaborative Perinatal Project monitored 50,282 mother-child pairs, 135 of whom had 1st-trimester exposure to streptomycin (10, pp. 297–301). For use anytime during pregnancy, 355 exposures were recorded (10, p. 435). In neither group was evidence found to suggest a relationship to large categories of major or minor malformations or to individual defects.

In a group of 1,619 newborns whose mothers were treated for tuberculosis during pregnancy with multiple drugs, including streptomycin, the incidence of congenital defects was the same as in a healthy control group (2.34% vs. 2.56%) (11). Other investigators had previously concluded that the use of streptomycin in pregnant tuberculosis patients was not teratogenic (12).

The population-based dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities, covering the period of 1980–1996, was used to evaluate the teratogenicity of aminoglycoside antibiotics (parenteral gentamicin, streptomycin, tobramycin, and oral neomycin) in a study published in 2000 (13). A case group of 22,865 women who had fetuses or newborns with congenital malformations were compared to 38,151 women who had no newborns with structural defects. A total of 38 cases and 42 controls were treated with the aminoglycosides. There was one case, but no controls, treated with streptomycin (odds ratio 5.0, 95% confidence interval 0.2–122.9). The investigators concluded that there was no detectable teratogenic risk for structural defects for any of the aminoglycoside antibiotics (13). They also concluded, although it was not investigated in this study, that the risk of deafness after in utero aminoglycoside exposure was small.

Breast Feeding Summary

Streptomycin is excreted into breast milk. Milk:plasma ratios of 0.5–1.0 have been reported (14). Because the oral absorption of this antibiotic is poor, ototoxicity in the infant would not be expected. However, three potential problems exist for the nursing infant: modification of bowel flora, direct effects on the infant, and interference with the interpretation of culture results if a fever workup is required. The American Academy of Pediatrics considers the drug to be compatible with breast feeding (15).

References

1. Woltz J, Wiley M. Transmission of streptomycin from maternal blood to the fetal circulation and the amniotic fluid. Proc Soc Exp Biol Med 1945;60:106–7.
2. Heilman D, Heilman F, Hinshaw H, Nichols D, Herrell W. Streptomycin: absorption, diffusion, excretion and toxicity. Am J Med Sci 1945;210:576–84.
3. Watson E, Stow R. Streptomycin therapy: effects on fetus. JAMA 1948;137:1599–1600.
4. Rubin A, Winston J, Rutledge M. Effects of streptomycin upon the human fetus. Am J Dis Child 1951;82:14–6.
5. Kistner R. The use of streptomycin during pregnancy. Am J Obstet Gynecol 1950;60:422–6.
6. Leroux M. Existe-t-il une surdité congénitale acquise due á la streptomycine? Ann Otolaryngol 1950;67:194–6.
7. Nishimura H, Tanimura T. Clinical Aspects of the Teratogenicity of Drugs. New York, NY: Excerpta Medica, 1976:130.
8. Donald PR, Sellars SL. Streptomycin ototoxicity in the unborn child. S Afr Med J 1981;60:316–8.
9. Mann J, Moskowitz R. Plaque and pregnancy. A case report. JAMA 1977;237:1854–5.
10. Heinonen OP, Slone D, Shapiro S. Birth Defects and Drugs in Pregnancy. Littleton, MA: Publishing Sciences Group, 1977.
11. Marynowski A, Sianozecka E. Comparison of the incidence of congenital malformations in neonates from healthy mothers and from patients treated because of tuberculosis. Ginekol Pol 1972;43:713–5.
12. Lowe C. Congenital defects among children born under supervision or treatment for pulmonary tuberculosis. Br J Prev Soc Med 1964;18:14–6.
13. Czeizel AE, Rockenbauer M, Olsen J, Sorensen HT. A teratological study of aminoglycoside antibiotic treatment during pregnancy. Scand J Infect Dis 2000;32:309–13.
14. Wilson JT. Milk/plasma ratios and contraindicated drugs. In Wilson JT, ed. Drugs in Breast Milk. Balgowlah, Australia: ADIS Press, 1981:79.
15. Committee on Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 1994;93:137–50.