Up to half of the 3.5 million babies born annually in the United States are exposed to diagnostic ultrasound in utero. No adverse effects, and many benefits, have accrued to ultrasound's proper use during pregnancy, but these are lingering concerns about its possible effects on subtle aspects of intrauterine brain ontogeny and subsequent behavioral and intellectual development. The goal of this research is to evaluate the possible biobehavioral effects of ultrasound on the developing central nervous system by exposure of rat embryos and fetuses to ultrasound and evaluating the offspring with tests recently developed here and elsewhere to detect behavioral teratogenicity. The structural and ponderal teratogenicity of ultrasound in separate groups identically exposed will also be evaluated. A unique feature of the proposal is that we will insonate rats without subjecting them to long periods of anesthesia or other forced restraint during gestation by using a behavioral approach in which we will train the rats to voluntarily remain stationary while propping themselves in a water vessel. We already have data that this can be done successfully. In the course of 5 years we propose to examine the dose-response effects of continuous wave (yr-01) and pulsed wave (yr-02) ultrasound (4 levels of each type, 2-3 of which are in the clinical range). Exposure will be during most of pregnancy (postimplantation to parturition). The structural, ponderal, neurological, and behavioral development of the offspring will be evaluated in detail. We will also determine if ultrasound produces any residual maternal effects lasting until after delivery that might affect the dam's rearing of her young (yr-03). Finally, we will assess whether ultrasound at one of four very specific stages of gestation has any effects on postnatal neurological, behavioral, and intellectual development (yr-04 & 05). The stages of exposure for this last 2-year study will be preimplantation, early-mid organogenesis, late organogenesis, and fetogenesis, all stages that are clinically relevant.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD021806-05
Application #
3320956
Study Section
Diagnostic Radiology Study Section (RNM)
Project Start
1987-02-01
Project End
1993-01-31
Budget Start
1991-02-01
Budget End
1993-01-31
Support Year
5
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Cincinnati Children's Hospital Medical Center
Department
Type
DUNS #
071284913
City
Cincinnati
State
OH
Country
United States
Zip Code
45229
Schilling, M A; Inman, S L; Morford, L L et al. (1999) Prenatal phenytoin exposure and spatial navigation in offspring: effects on reference and working memory and on discrimination learning. Neurotoxicol Teratol 21:567-78
Vorhees, C V (1997) Methods for detecting long-term CNS dysfunction after prenatal exposure to neurotoxins. Drug Chem Toxicol 20:387-99
Fisher Jr, J E; Acuff-Smith, K D; Schilling, M A et al. (1996) Behavioral effects of prenatal exposure to pulsed-wave ultrasound in unanesthetized rats. Teratology 54:65-72
Vorhees, C V; Acuff-Smith, K D; Schilling, M A et al. (1995) Prenatal exposure to sodium phenytoin in rats induces complex maze learning deficits comparable to those induced by exposure to phenytoin acid at half the dose. Neurotoxicol Teratol 17:627-32
Vorhees, C V; Acuff-Smith, K D; Moran, M S et al. (1994) A new method for evaluating air-righting reflex ontogeny in rats using prenatal exposure to phenytoin to demonstrate delayed development. Neurotoxicol Teratol 16:563-73
Fisher Jr, J E; Acuff-Smith, K D; Schilling, M A et al. (1994) Teratologic evaluation of rats prenatally exposed to pulsed-wave ultrasound. Teratology 49:150-5
Vorhees, C V; Acuff-Smith, K D; Schilling, M A et al. (1994) Behavioral teratologic effects of prenatal exposure to continuous-wave ultrasound in unanesthetized rats. Teratology 50:238-49
Minck, D R; Acuff-Smith, K D; Vorhees, C V (1991) Comparison of the behavioral teratogenic potential of phenytoin, mephenytoin, ethotoin, and hydantoin in rats. Teratology 43:279-93
Vorhees, C V; Acuff-Smith, K D; Weisenburger, W P et al. (1991) A teratologic evaluation of continuous-wave, daily ultrasound exposure in unanesthetized pregnant rats. Teratology 44:667-74
Vorhees, C V; Acuff-Smith, K D; Weisenburger, W P et al. (1991) Lack of teratogenicity of trans-2-ene-valproic acid compared to valproic acid in rats. Teratology 43:583-90

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