Placental Markers of Autism Spectrum Disorder

• In Event: 2-123 - The Placenta and Child Development

Integrative Statement

Introduction: Normal neurogenesis and healthy neuronal function is closely correlated with the structure and health of the local angiogenic network. That basic principle – alongside the recognition that the placenta is a fetal organ upon which fetal wellbeing is absolutely dependent in utero – guides our research program on assessing vascularization (among other features) in the placenta and child neurodevelopment. The placenta's unique anatomy presents us with challenges: it is a fetal organ that can be measured and dissected in every pregnancy and has an arterial and venous network laid out in a plane. No other of our viscera are "disposable" as medical waste, while the only other such circulatory anatomy is in the retina. A recent study identified abnormal angiogenesis rather than neurogenesis in brains of children with autism/autism spectrum disorder (ASD). We build on this and have focused our work on placental and autism on two main facts: 1. The placental 3D shape is effectively the shape of the bag that most closely fits the network of vessels that the placenta was able to grow. 2. The chorionic surface vessels determine the distribution of the stem vessels and capillary networks that are contained in the 3D placental shape, and these vessels' network structure is responsive to changes in the maternal and fetal environments.
Methods & Results: We have worked with two autism/ASD or high ASD-risk cohorts (the Avon Longitudinal Study of Parents and Children, ALSPAC and the Early Autism Risk Longitudinal Investigation, EARLI, respectively) with placentas from the National Children's study considered a population of low ASD risk controls. Our presentation will report on this program of study in which placenta structure and function have been characterized in detail and clinical assessments of the children have been carried out using established clinical protocols. In brief, our decades-long observations of the placenta and ASD can be summarized as follows:
Both cases with ASD diagnoses (ALSPAC) and ASD risk (EARLI) show placentas that can be reliably distinguished from non-case in several ways, including more centrally inserted cord; less variable perimeters; reduced maximal disk thickness; and significantly (42%) reduced chorionic surface vessel branch points. We interpret these features as reflecting a “constraint” (either genetic, environmental or both) on the natural ameboid nature of the placenta, growing where it can best, growing less well elsewhere, in order to provide an optimum environment for the fetus. These findings provide some of the first data to date linking placenta features to later neurodevelopmental disorder. In a separate, case-control study, we found that subclinical exposures to acute and/or chronic inflammation was associated with a > 3-fold risk of ASD status.
Conclusion: The data presented highlight reliable ways in which interrogation of the placenta may predict future neurodevelopmental disorder. Our presentation will also combine this work on vascularization with measures of gross and histopathology features to reflect a broader array of placenta markers for child health.

Authors

• Carolyn Salafia, Placental Analytics
  Presenting Author

• Ruchit Shah, Placental Analytics
  Non-Presenting Author