Is Gentamicin Ototoxic to the Fetus?

Background: Gentamicin is used in pregnancy to treat infections that cause complications to the mother and fetus if left untreated. In 2003, Schering, the manufacturer of Garamycin Injectable, amended the product monograph in the Compendium of Pharmaceuticals and Specialties to state that gentamicin should be avoided in pregnancy due to cases of total irreversible bilateral congenital deafness in babies exposed to gentamicin in utero. Because we have identified, after an intensive literature search, only two cases over many years of availability, it is questionable whether the outcome can be attributed to drug use rather than other factors. Objectives: The main objective of this study was to determine whether any infant exposed in utero to intravenous gentamicin and born between January 2002 and April 2006 at Victoria General Hospital demonstrated audiologic deficits on routine hearing testing. Such testing has been universally available since late 2001. Our secondary objectives were to examine patterns of gentamicin use, including indication, dosage, duration, and to determine whether or not monitoring of serum gentamicin levels was done. Methods: Women who had received gentamicin were identified through pharmacy records and their charts reviewed for factors that might contribute to fetal deafness including substance abuse, use of other potentially ototoxic medications, genetic predisposition, and intrauterine infections. We reviewed audiology test result and the infants' charts for potential confounding factors, including prematurity, low birth weight, low Apgar scores, anoxia, hyperbilirubinemia, sepsis, and meningitis. Results: Fifty-two charts were reviewed, 40 of which documented live births. There was no case of hearing loss documented. Of the eight fetal losses, six (11.5%) were preterm births before viability, and two were elective terminations. Pyelonephritis was the main indication for gentamicin use (48%), followed by chorioamnionitis (31%) and other miscellaneous indications (21%). Three times daily dosing was used for a mean duration of 2.7 +/- 2.3 days, resulting in an average cumulative dose of 764 +/- 600 mg gentamicin. The average gestational age at exposure was 28 weeks. Maternal serum gentamicin levels were obtained in 72.5% of cases, and no trough level was above 2 mg/L. Other potentially ototoxic medications were administered to the mother in 17.5% of pregnancies, and to 17.5% of babies in the immediate newborn period. With the exception of one infant who died before additional testing could be carried out, all the infants passed hearing tests, 89% on initial screening. Conclusion: In utero exposure to gentamicin did not cause an increase in audiologic impairment in the infants tested in this cohort.