Auditory brainstem response (ABR) abnormalities across the life span of rats prenatally exposed to alcohol.

BACKGROUND: Fetal alcohol syndrome (FAS) is a leading cause of neurodevelopmental impairments (NDIs) in developed countries. Sensory deficits can play a major role in NDI, yet few studies have investigated the effects of prenatal alcohol exposure on sensory function. In addition, there is a paucity of information on the lifelong effects of prenatal alcohol exposure. Thus, we sought to investigate the effects of prenatal alcohol exposure on auditory function across the life span in an animal model. Based on prior findings with prenatal alcohol exposure and other forms of adverse prenatal environments, we hypothesized that animals prenatally exposed to alcohol would show an age-dependent pattern of (i) hearing and neurological abnormalities as postweanling pups, (ii) a substantial dissipation of such abnormalities in young adulthood, and (iii) a resurgence of such abnormalities in middle-aged adulthood. METHODS: Pregnant rats were randomly assigned to an untreated control (CON), a pair-fed control (PFC), or an alcohol-treated (ALC) group. The ALC dams were gavaged with 6 mg/kg alcohol daily from gestation day (GD) 6 to 21. The PFC dams were gavaged daily from GD6 to GD21 with an isocaloric and isovolumetric water-based solution of maltose-dextrins and pair-fed to the ALC dams. The CON dams were the untreated group to which the ALC and CON groups were compared. Hearing and neurological functions in the offspring were assessed with the auditory brainstem response (ABR) at the postnatal ages of 22, 220, and 520 days. RESULTS: In accord with our hypothesis, ABR abnormalities were first observed in the postweanling pups, largely dissipated in young adulthood, and then resurged in middle-aged adulthood. This age-related pattern suggests that the ALC pups had a developmental delay that dissipated in young adulthood and an enhanced age-related deterioration that occurred in middle-aged adulthood. Such a pattern is consistent with the fetal programming hypothesis of adult-onset diseases (the Barker hypothesis). CONCLUSIONS: Our findings have important clinical implications for the assessment and management of (i) childhood hearing disorders and their comorbidities (i.e., speech-and-language, learning, and attention deficit disorders) and (ii) enhanced age-related hearing and neurological degeneration in middle-aged adulthood that can result from prenatal alcohol exposure. We recommend hearing evaluation be a part of any long-term follow-up for FAS patients and patients exposed to any adverse prenatal environment.

Prenatal cocaine exposure influences the growth and life span of laboratory rats.

Laboratory rats prenatally exposed to alcohol, nicotine, amphetamine, undernutrition or hypoxia can exhibit shortened life span and other signs of enhanced age-related degeneration. We evaluated the possibility of similar effects following prenatal cocaine exposure. Pregnant rats received 20 or 40 mg/kg cocaine HCl subcutaneously (C20, C40), twice daily, from gestation days (GD) 7-20. Untreated control (UTC) and pair-fed control (PFC) groups were also used. The pregnant C40, C20, and PFC dams ate less food and gained less weight than the UTC dams did. The pregnant C40 and C20 dams drank more water than the UTC dams did, and the pregnant PFC dams drank less than the UTC dams did. The C40 and PFC offspring had delayed earflap openings. The C40 male and female offspring had lower birth weights than their cohorts in the other three groups. The C40 female and male offspring remained significantly underweight until postnatal day (PND) 28 and PND56, respectively. During young adulthood, the males and females in the C20, C40, and PFC groups had normal body weights. During old adulthood, however, the C20 and C40 males and the C20, C40, and PFC females developed reduced body weights as compared with their UTC cohorts. The C20 and C40 male offspring and the C20, C40, and PFC female offspring also had life spans that were 7-12% shorter than that of their UTC cohorts. Thus, groups that showed reduced body weights in old age also showed shorter life spans. These results provided converging evidence that prenatal cocaine exposure caused enhanced age-related degeneration. Observations on cardiac and other organ pathology were also made. Health implications for children born to cocaine-abusing women are discussed.

Effects of Prenatal Cocaine on Hearing, Vision, Growth, and Behaviora.

The illicit use of cocaine has increased dramatically over the last 10-12 years. There has been a corresponding increase in cocaine abuse among obstetric patients and in the number of "cocaine babies." According to some estimates, these children make up more than half of the drug-associated births. This problem is therefore a major public health concern. Consequently, our laboratory investigated the effects of prenatal cocaine exposure on hearing, vision, growth, and exploratory/stress behavior. This chapter summarizes the literature on animals and humans on these topics and presents new observations from our laboratory. In terms of maternal toxicity, prenatal cocaine exposure causes hypertension, placental abruption, spontaneous abortion, poor pregnancy weight gain, and undernutrition secondary to appetite suppression. Some offspring effects include in utero growth retardation, cephalic hemorrhage, fetal edema, altered body composition, congenital malformations, and even pre- and postnatal death. The offspring can also exhibit a variety of behavioral, visual, hearing, and language disorders. Differential effects of animal strain and late gestational cocaine exposure are discussed. Comparisons are made between prenatal cocaine, the fetal alcohol syndrome, and the effects of prenatal undernutrition. Recommendations for clinical assessment and intervention are made.