Placental Structure in ASD: Does the Placenta Mirror the Diagnosis?

Background: The placenta is a fetal organ regulated in utero by fetal genes, but which is responsive to and may be altered by stressors in the maternal environment in which it grows and matures.

Objectives: We have speculated that the shape of the placenta, a vascular fractal, may be measurably altered in ASD cases as compared to controls.

Methods: Placentas from the Avon Longitudinal Study of Parents and Children were processed according to a standard protocol and photographs obtained of the fetal chorionic plate and serial slices of the placental disk. ASD cases were matched with controls from the source cohort.  All procedures were performed blinded to case status. Data regarding disk perimeter, site of cord insertion and disk thickness were extracted from traced photographs of surface (perimeter and cord insertion) and slides (3D depth/thickness) by dedicated algorithms and exported into SPSS 20.0 for analysis. Parametric or nonparametric tests were used, depending on variable distribution, with p<0.05 considered significant.

Results: In ASD, placental chorionic surface shape, with reduced maximum radius, and reduced standard deviation of the radius of the chorionic surface shape were statistically different from neurodevelopmentally normal controls (each p<0.05). There was also a statistically significant reduced eccentricity of the umbilical cord insertion In ASD placentas compared to those of normal controls.While mean disk thickness was not different between ASD and controls, there was reduced maximum disk thickness and reduced standard deviation of disk thickness that was observed subjacent to placental chorionic surface vessels of specific calibers(ech p<0.05).

Conclusions: Our findings support a global impression of ASD placentas as being more constrained, less variable in shape, less flexible in growth to permit asymmetry of cord insertion, with more restricted villous branching growth for any given caliber of overlying chorionic surface vessel. The reduced variability is not sufficient to yield an increased rate of fetal growth restriction,t, but may place an at risk fetus at a disadvantage of lesser compensatory capacity and greater vulnerability to gestational stressors including inflammation and/or oxidative stress, gestational exposures that have been associated with ASD risk. Thus, the abnormal placenta we have documented may be a perinatal biomarker and also on the causal pathway to the persistent neuronal injury that has been suggested to underlie ASD.