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Effects of prenatal cocaine exposure on perinatal morbidity and postnatal growth in the rabbit
D E Weese-Mayer1, L M Klemka-Walden, M K Chan
1Department of Pediatrics, Rush Medical College, Rush University, Chicago, Ill.
Insights
Prenatal cocaine exposure in rabbits increased stillbirths but did not affect other pup development. This animal model for cocaine toxicity requires further study on respiratory control.
Area of Science:
- Reproductive toxicology
- Developmental neuroscience
- Pharmacology
Background:
- Prenatal cocaine exposure is linked to adverse outcomes including fetal loss and SIDS.
- Existing animal models struggle to isolate direct drug effects from nutritional or indirect factors.
- Understanding cocaine's specific toxicity to the developing respiratory system is crucial.
Purpose of the Study:
- To develop a rabbit model for prenatal cocaine exposure, differentiating direct drug effects.
- To investigate cocaine's toxicity on fetal development, particularly the respiratory control system.
- To assess pregnancy outcomes and pup development following controlled cocaine administration.
Main Methods:
- 38 pregnant New Zealand White rabbits were divided into cocaine (CC), pair-fed (PF), and free-fed (FF) groups.
- Cocaine hydrochloride (30 mg/kg/day) or saline was administered via osmotic pumps from day 10 of gestation.
- Pregnancy outcomes (stillbirth, malformations) and pup development (weight, length, head circumference) were assessed.
Main Results:
- A significant increase in stillbirths was observed in the cocaine-exposed group (18%) compared to controls (6-7%).
- No significant differences were found in maternal deaths, spontaneous abortions, or gross malformations.
- Postnatal pup development, including weight and physical measurements, did not differ among groups.
Conclusions:
- The developed rabbit model demonstrated increased stillbirths but did not replicate other human outcomes of prenatal cocaine exposure.
- Direct effects of prenatal cocaine in this model did not lead to observable developmental alterations.
- Further research is needed to explore cocaine's impact on physiological functions, especially the developing respiratory control system.
Abstract:
Prenatal cocaine (CC) exposure may result in increased fetal loss, growth retardation, altered neurodevelopment, and sudden infant death syndrome (SIDS). We sought to establish an animal model for prenatal cocaine exposure which (1) would allow us to distinguish the direct effects from the indirect and nutritional effects of the drug, and (2) might be used to address questions of cocaine's toxicity, specifically to the developing respiratory control system. The study design included 38 New Zealand White rabbit does among CC, pair-fed (PF), and free-fed (FF) groups. Miniosmotic pumps were implanted in each doe on day 10 of timed gestation providing continuous subcutaneous administration of either 30 mg/kg/day of cocaine HCl in H2O (CC) or sterile H2O alone (PF and FF). Mean (SEM) plasma cocaine concentration was 1.71 +/- 0.21 mumol/l (519.4 +/- 64.4 ng/ml). Pregnancy outcome compared for incidence of stillbirth, maternal death, spontaneous abortion, and gross malformation among 211 pups was significant only for increased stillbirths among CC pups (18%, p less than 0.04) as compared to PF (6%) and FF pups (7%). External and renal malformation and postnatal weight, crown-rump length, and snout-occiput head circumference for pups aged 4 and 5 days of age did not differ among groups. The direct effects of prenatal cocaine evaluated in our model do not reproduce the altered perinatal outcome observed among humans. However, our results do not determine if physiologic function has been altered. Investigation of the physiologic and pathologic abnormalities that are relevant to this human condition, specifically to the developing respiratory control system, should add clarity to the mechanism of action of cocaine during pregnancy.