PLACENTAL IDENTIFICATION AND IMMUNE QUANTIFICATION OF ACUTE AND/OR CHRONIC INFLAMMATION IN CHILDREN DIAGNOSED WITH PLACENTAL AUTISM IN UNIVERSITY AND COMMUNITY HOSPITALS
autism spectrum disorder is a developmental disorder that is defined by behaviors including impaired social interaction, delayed and disordered language, and having isolated areas of interest. It is still not well understood. We know that autism is expressed within the first 2 to 3 years of life. The placenta is an organ that connects the developing fetus to the mother and allows for nutrient uptake, waste elimination, and gas exchange, by way of the mother's blood. In most hospitals this organ is discarded as medical waste, after the baby is delivered. The placenta may hold a wealth of underutilized information. Because the placentas of apparently healthy newborns are generally discarded, data on prenatal inflammatory exposures must be retrospectively derived from routine, and often limited, records. Placental tissue samples archived as stained slides and as tissue embedded in laboratory wax blocks could be used to generate additional analyses such as stains for specific molecules that are part of the inflammatory response or its companion oxidative stress may provide direct evidence of otherwise clinically silent prenatal inflammation and/or oxidative stress. We need both a sensitive and a specific test. As part of prevention, specific screening could enable early intervention; this could be achieved if we could better understand the causes of autism. While there is an increased risk to develop autism in children who are born into a family where a brother or sister already has a diagnosis of autism, or who were born prematurely or who may have been born with a low birth weight, most children who develop autism are not siblings of other children diagnosed with autism nor are they born prematurely or with low birth weight, but rather are apparently healthy term newborns. When the mother is pregnant, exposure to acute and chronic inflammation has been linked with some origins of autism. Its close companion is a state known as oxidative stress, and it has independently been linked to autism risk. Both inflammation and oxidative stress have been associated with an unusual formation of the smallest vessels in the placenta that supply nutrients and to the developing baby. This is known as villous maldevelopment, and abnormal shapes of the placenta that may be present when performing histological cross-section evaluation of stained slides for the presence of inclusions. Our study will pilot the relationships between an autism diagnosis and the presence and distribution of molecules related to inflammation and/or oxidative and quantitative assessment of villous maldevelopment. We propose to examine these relationships in two specific groups from two community hospitals located in New York and New Jersey. In two established autism groups, one at Saint Peter's University Hospital, New Brunswick, New Jersey and the second at New York Methodist Hospital, Brooklyn, New York, a novel universal placental pathology study reported at birth histological evidence of prenatal exposures to inflammation, oxidative stress, and villous maldevelopment for these children and their matched controls (three control cases/autism case, at each site). Placental tissue will be archived. Semiquantitative scores will be generated by the two site pathologists in tandem review; we will first test whether either/both autism case groups are more likely have evidence of prenatal inflammation, oxidative stress, or villous maldevelopment than their site-specific controls. We will then map the feto-placental distribution of cytokines and specific markers of oxidative stress by immunohistochemistry (IHC), using the archived tissue. Combined routine placental diagnosis with immunolocalization of key molecules may lead to perinatal diagnoses of inflammatory, oxidative stress, or villous maldevelopment exposures refined for autism risk phenotype. Identification of placental biomarkers such as prenatal exposures to inflammation and/or oxidative stress may elucidate the causes of autism and may lead to earlier initiation of intervention strategies and potential improved outcomes.
Interagency Autism Coordinating Committee (IACC)
Autism Research Database (AFD)
