Autism spectrum disorders in extremely preterm infants and placental pathology findings: a matched case–control study

Background: The prevalence of autism spectrum disorders (ASD) is 5-fold higher in preterm (PT) infants born ≤28 weeks gestational age (GA) as compared to the general population. The relationship between placental pathologic lesions and ASD in PT infants has not been studied. Objectives: The objective of this study was to determine the association of placental pathology with the occurrence of ASD in PT infants born ≤28 weeks GA. Study design: A matched case–control study to identify confirmed ASD cases (n = 16) and matched controls (n = 48) born at Parkland Hospital between January 2012 and December 2015. Patients were matched using known variables associated with increased risk of ASD in PT infants. Placental histology from all births was reviewed. Results: Children with ASD had 2-fold greater incidence of multiple placental pathologic lesions vs. matched controls [11/16 (69%) vs.16/48 (33%), respectively; P = 0.01]. In contrast, single placental pathologic lesions were not associated with ASD [5/16 (31%) vs. 21/48 (43%), respectively; P = 0.1]. Conclusions: In this study, we have demonstrated an association between the increasing complexity of histologic placental lesions and the later risk for ASD in infants born ≤28 weeks GA. Thus, placental pathology findings may be valuable in further understanding the prenatal pathologic processes underlying ASD in PT infants. Impact: PT infants with ASD have a 2-fold greater incidence of multiple placental pathologies.This is the first study to report an association between the complexity of histologic placental lesions and later risk of ASD in infant born extremely PT (i.e., ≤28 weeks GA).This study reiterates the importance of examining placental pathologic lesions, since placental evidence of antenatal insults correlates with postnatal morbidities and mortality in PT infants.