Autism/ASD reflects a range of disordered and impaired brain development that leads to a lifelong course of behavioral and cognitive abnormalities. Diagnosis cannot formally be made prior to age two, and at this point there is a lack of behavioral and biologic markers that we can use to predict its onset. Early predictors could lead to early interventions which might significantly improve the lives of those affected. We intend to use the fact that the same biochemistry that controls the branching of nerves also controls branching of blood vessels. Unlike the nerve networks in the living human brain, the branching of the blood vessels in a child's placenta (which is generally discarded after birth without any examination) can be photographed and dissected. Our methods have expressly focused on capture of potentially key placental vascular features using equipment and procedures that could be performed at any hospital delivering a baby in the US. Thus, if successful, our work could lead to the routine examinations of placentas at birth to provide a noninvasive newborn screening test to identify children at high risk for developing autism/ASD. In this project we will measure the branching of larger blood vessels on the surface of the placenta (2D), the placental shape (which contains the placental vascular fractal), and the branching structure of the fine vessels of the thickness of the placenta (3D), and analyze the maternal medical and gestational factors that may have led to differences observed between the autism/ASD group, a group of children with other special educational needs, and healthy control children. We have developed and will apply new tools to analyze digital images of placental blood vessel branching, and the mathematics required to analyze the complex patterns of this placental branching architecture. In addition to its use as a biomarker, the application of these techniques has the potential both to clarify the pathologic anatomy of autism/ASD, and to determine when during pregnancy autism/ASD might have developed. Any model generated in a single population will require validation prior to its general use in public health screening. Collection of a new cohort, and confirmation of positive results from this study would likely be 3-5 years in the future (given needs for study recruitment, births, and diagnosis of children at ~ age two years). However, this research tool could be applied very quickly in current studies of high-autism risk siblings (HAR), such as the E.A.R.L.I. (PI, Craig Newschaffer, Ph.D.) and M.A.R.B.L.E.S. (PI: Cheryl Walker, M.D.) networks, both of which currently work closely with Dr. Salafia in placental analysis in autism/ASD, and could rapidly contribute to our understanding of likely pathways of disordered neurodevelopment in this highly heterogeneous spectrum of autism/ASD.