Abstract

Background: Gestation is a critical window for neurodevelopmental vulnerability. This study examined whether the presence of trophoblast inclusions (TIs) in the placenta could serve as a predictor for children at elevated risk for autism spectrum disorder (ASD).

Methods: Placentas were obtained from 117 births in the MARBLES (Markers of Autism Risk in Babies – Learning Early Signs) cohort of families who have one or more previous biological children with ASD placing their newborn at elevated risk for neurodevelopmental compromise. Control samples were obtained from 100 uncomplicated term pregnancies of multiparous women with one or more typically developing biological children. Frequency of TIs was compared across the two groups.

Results: Placentas from at-risk pregnancies had an eight-fold increased odds of having two or more TIs compared to control samples (odds ratio 8.0, 95% confidence interval 3.6, 18.0). The presence of ≥2 TIs yielded a sensitivity of 41% and a specificity of 92% for predicting ASD risk status, while ≥4 TIs yielded a sensitivity of 19%, a specificity of 99.9%, a positive likelihood ratio of 242, and conservatively predicted an infant with a 74% probability of being at risk for ASD.

Conclusions: Our findings suggest that the placentas from women whose fetuses are at elevated risk for autism are markedly different from control placentas. These differences are manifested histologically as TIs. Their identification has the possibility of identifying newborns at risk for ASD who might benefit from targeted early interventions aimed at preventing or ameliorating behavioral symptoms and optimizing developmental outcomes.