Evaluation of the bioeffects of prenatal ultrasound exposure in the cynomolgus macaque (Macaca fascicularis): II. Growth and behavior during the first year.

The extensive use of ultrasonography for the prenatal assessment of growth and development continues to present questions regarding biological effects. We are currently evaluating a nonhuman primate model (Macaca fascicularis) exposed to ultrasound from gestational day (GD) 21 to 152 +/- 2. Exposures were performed with a commercial real-time sector scanner (ATL, MK 600); animals were scanned five times weekly on GD 21-35 +/- 2, three times weekly on GD 36-60 +/- 2, and once weekly on GD 61-150 +/- 2. The length of exposure was approximately the same as human exposure (GD 21-60 +/- 2 = 10 min/exam and GD 61-150 +/- 2 = 20 min/exam) although the frequency of the examinations was considerably greater. Initial reports indicated differences between control and treated animals including lower birth weight, higher simian Apgar scores, and changes in select hematologic parameters. Follow-up evaluations of growth during the first year included measurements of body weight, hand and foot lengths, humerus and femur lengths, biparietal and occipitofrontal diameters, head circumference, arm circumference, chest circumference, skinfold thickness, and crown-rump length. Results indicated a significant reduction in body weight in treated animals during the first three months, with nonsignificant differences during the following nine months. Hematologic analysis including complete blood counts (CBC) and clinical biochemistry at 6, 9, and 12 months of age were not significantly different. A series of behavioral evaluations including a neurobehavioral test battery (NBT) and tests assessing motor and cognitive skills were included. The NBT revealed increased muscle tone in treated animals at one, two, and four days. In an observation cage (week 1-14) more quiet activities were displayed by treated animals. Group differences in performance of motor and cognitive tasks were observed and may be attributable to agitation and difficulties in adjusting to test environments. There were no group differences observed in discrimination learning. When considering the possible implications to the human population, it is important to consider the amount of exposure these animals received, and the fact that most of the effects observed appeared to be transitory. Although human epidemiological studies have not revealed any significant bioeffects, the "prudent use" of diagnostic ultrasound should still be kept in mind. This is especially significant with the current rise in the use of endovaginal scanning and pulsed Doppler.