Prenatal Exposures As Measured By Routine Placental Histopathology in a Community Cohort of ASD

Friday, May 13, 2016: 5:30 PM-7:00 PM
Hall A (Baltimore Convention Center)



Autism Spectrum Disorder (ASD) is a set of neurodevelopmental disorders expressed in early life as stereotypic behaviors and language and social-emotional deficits. Exposure to inflammation and oxidative stress have each emerged as prenatal risk factors. These processes can be identified at birth in the baby's placenta by routine histologic methods. 

Objectives:  We will study a unique contemporary population based birth cohort for which placental examination was performed at birth for all newborns. Does histologic evidence of prenatal exposure to acute, chronic or both acute and chronic inflammation and evidence of maternal underperfusion of the placenta, a condition that may involve oxidative stress, correlate with subsequent ASD diagnosis?

Methods:  Our case-control sample was drawn from a broad population based sample of nearly all births occurring at a large urban community based hospital (New York Methodist Hospital, NYMH)  from 2007 to 2013, during which time there was universal placental examination of births at NYMH. Coupled with access to links to billing data for children who remain in the system for pediatric care has yielded a unique population based cohort with (currently) 55 population based cases (42 males, 13 females) and 199 controls (150 males, 49 females). Pathology diagnostic reports reviewed by a single observer at birth were extracted for coding of markers of AI, CI and maternal underperfusion as “present/absent”.  Conditional logistic regression accounted for our matched case-control design.  

Results:  As expected with matched data, there were no significant differences in genders or gestational ages between ASD cases and controls.  There were substantial significant differences in several measures of inflammation between cases and controls.  Placentas of cases were much more likely to have acute fetal chorionic vessel inflammation (23.6% cases vs. 6.5% controls; conditional logistic regression odds ratio (COR), 95% CI:  4.88, 1.99, 11.96).  There was a higher risk of chronic inflammation as measured by uteroplacental chronic vasculitis in the placentas of cases (7.3% cases vs. 1.5% controls; COR, 95% CI:  6.36, 1.13, 35.90).  There was also a higher risk of chronic choriodeciduitis but this difference was not statistically significant (p=0.14).  Finally, the finding of histologic evidence of poor maternal perfusion (villous fibrosis, hypovascularity and Tenney-Parker changes of trophoblast (considered to reflect local hypoxia) was also much more likely in cases (7.3% cases vs. 0.5% controls; COR, 95% CI: 13.54, 1.51, 121.6).  

Conclusions: Children who eventually are diagnosed with ASD have significantly more histologic placental evidence of prenatal exposures to both acute and chronic inflammation, and features that are typically attributed to chronic maternal perfusion pathology and oxidative stress. These diagnoses are gleaned from routine histopathology slide preparations that can be performed in any hospital laboratory. These findings may point to a universally available and inexpensive screen for ASD risk at birth.

See more of: Epidemiology
See more of: Epidemiology