Auditory Function in Rat Pups Exposed Perinatally to Zidovudine (ZDV)† 693

Abstract

Prenatal and postnatal treatment of HIV-infected pregnant women and their newborns with zidovudine is routinely used to reduce transmission of the virus to the fetus/newborn. However, little is known about the effects of ZDV-treatment on the fetus. A high incidence of auditory dysfunction has been noted among children in the Pediatrics AIDS Program at USF. The purpose of this study was to determine whether differences exist in the auditory development of rat pups treated in utero and throughout infancy with ZDV as compared with untreated pups. METHODS: ZDV syrup was added to the water supply (2mg/ml)of six timed pregnant rats throughout pregnancy and lactation beginning on day three of pregnancy. A control group of six pregnant rats was provided with plain water. Intake was measured. After a normal gestation, all rats delivered within a ten hour period. On postnatal day (pnd) three, pups within the two groups were randomly cross-fostered to five dams (8 pups/dam; 40 pups/group) to control for litter effects. On pnd 21, auditory brainstem responses were recorded under light sedation and auditory brainstem conduction time (ABCTs) were measured. On pnd 28, cochlear function (sensory cell) was assessed using distortion product otoacoustic emissions (DPOAEs). Analyses of variance (ANOVA) of pup weights, ABCTs and DPOAEs and analyses of covariance (ANCOVA) with weight as the covariant were performed on the measures of auditory function. RESULTS: Weights of pups treated with ZDV were significantly lower on pnd 3, 21 and 28. ANOVA of ABCTs revealed significantly slower conduction times in the ZDV treated pups. When weight was controlled for by ANCOVA, these differences were not statistically significant. DPOAEs in the lower end of the frequency range (below 6k Hz) were significantly lower (decibels, sound pressure level) in the ZDV treated group even after controlling statistically for weight differences. CONCLUSION: These findings suggest that ZDV may have no direct effect on the development of the brainstem auditory pathway, but cochlear development in rats may be altered by perinatal exposure to ZDV. Table