Neurotoxicology andTeratology, Vol. 1 I, pp. 461-476. o Pergamon Press plc, 1989. Printed in the U.S.A. 0892-0362189 $3.00 + .00 Neurobehavioral Effects of Prenatal Alcohol: Part I. Research Strategy ANN P. STREISSGUTH,*§¶ 2 HELEN M. BARR,* PAUL D. SAMPSON,t FRED L. BOOKSTEIN~t AND BETI'Y L. DARBY* *Department of Psychiatry and Behavioral Sciences, §Alcoholism and Drug Abuse Institute ¶Child Development~Mental Retardation Center ~Department of Statistics of the University of Washington, Seattle, WA 98195 and the ~cCenter for Human Growth and Development of the University of Michigan, Ann Arbor, MI 48109 Received 16 November 1987 STREISSGUTH, A. P., H. M. BARR, P. D. SAMPSON, F. L. BOOKSTEIN AND B. L. DARBY. Neurobehavioraleffects of prenatalalcohol:Parti. Research strategy. NEUROTOXICOL TERATOL 11(5) 461--476, 1989.--This paper, Part I of a three-part series, reviews the literature on the neurobehavioral effects of prenatal alcohol exposure and describes a large group of tests assembled to assess neurobehavioral outcomes of alcohol teratogenesis in 7-year-old children. This paper presents the distribution of these test scores for our sample and discusses their relationships with an alcohol binge score and with full-scale IQ. This group of tests is suitable for children with a wide range of abilities and provides a broad assessment of neurobehavioral deficits. Part II of this series describes a new method of statistical analysis, Partial Least Squares (PLS), which is particularly well suited to complex multivariate data sets such as these, and with its aid, examines the effects of prenatal alcohol exposure on IQ, achievement, vigilance and classroom behavior, a total of 43 outcome scores. Part [ ] examines prenatal alcohol effects on outcomes from the broad group of 164 scores deriving from 17 neurepsychologic tests, using the Partial Least Squares methodology, and summarizes the implications of our findings for the behavioral teratology of alcohol. Behavioral teratology Alcohol teratogenesis Fetal Alcohol Syndrome Fetal alcohol effects Birth defects Neuropsychology Memory Alcohol use Partial least Squares Longitudinal research THIS is the fast in a trilogy of papers describing the effects of prenatal alcohol exposure on the neurobehavioral development of seven-year-old children. This first paper reviews the relevant literature, describes the rationale and methods in the study design, formulates the specific questions to be addressed, and presents descriptive statistics. The second paper (44) has two functions: a) to describe a method of statistical analysis called Partial Least Squares (PLS), which is particularly well suited to the complex multivariate data sets deriving from studies such as this one; and b) to use the PLS methods to analyze standardized outcomes, including IQ and achievement tests, in respect of prenatal alcohol exposure. The third paper (56) applies PLS analyses to a more complex data set deriving from neuropsychological assessment of these 7-year-old offspring. REVIEWOF THE LITERATURE Alcohol is well recognized as a teratogenic agent (63,65). It readily crosses the placenta so that fetal blood alcohol levels approximate those of the mothers. Alcohol crosses the blood-brain barrier, so it can alter the development of the central nervous system (CNS) in utero in a fashion depending on the dose, timing, and conditions of exposure (65). Children with Fetal Alcohol Syndrome (FAS) represent those most severely affected by prenatal alcohol exposure (11, 24, 25, 30). Their mothers abused alcohol during pregnancy or were clearly alcoholic. In addition to growth deficiency and physical anomalies, these children manifest a variety of CNS effects, including mental retardation, hyperactivity, poor impulse control, perceptual/motor problems, and delayed motor development (49). In addition, clinical observations have revealed difficulty with generalizations and abstract thinking, poor problem solving skills, poor social adaptation, and problems with attention and memory (57,58). Animal research has shown that while many areas of the brain are affected by prenatal alcohol exposure, the hippocampus is particularly at risk (65). Prenatal alcohol exposure produces changes in the mossy fibers of the hippocampus (65), a 20% reduction in the pyramidal cells in the CA1 region of the 'This work was primarily supported by grant number AA01455-01-13 from the National Institute of Alcohol Abuse and Alcoholism, with supplemental support from the University of Washington Alcoholism and Drug Abuse Institute and the Medical Student Research Training Program. Requests for reprints should be addressed to Ann. P. Su~issguth, Department of Psychiatry and Behavioral Sciences, GG-20, University of Washington, Seattle, WA 98195. 461