Association Between Ultrasonography Fetal Anomalies and Autism Spectrum Disorder

Abstracts Background Prenatal ultrasound is frequently used to monitor fetal growth and identify fetal anomalies that may suggest genetic or developmental abnormalities which may develop into congenital anomalies and diseases. Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder, associated with a wide range of congenital anomalies. Nevertheless, very little has been done to investigate organ development using prenatal ultrasound as a means to identify fetuses with ASD susceptibility. Methods A retrospective matched case-sibling-control study. ASD cases were matched to two control groups: typically developing sibling (TDS) closest in age to ASD child; and typically developing population (TDP), matched for age, sex, and ethnicity. The study comprised 659 children: 229 ASD, 201 TDS, and 229 TDP; 471 (71.5%) males. Results Ultrasonography fetal anomalies (UFAs) were found in 29.3% of ASD cases vs. only 15.9% and 9.6% in the TDS and TDP groups (aOR=2.23, 95%CI=1.32-3.78, and OR=3.50, 95%CI=2.07-5.91, respectively). Also, multiple co-occurring UFAs were significantly more prevalent among ASD cases. UFAs in the urinary system, heart, and head&brain were the most significantly associated with ASD diagnosis (aOR Urinary =2.08, 95%CI=0.96-4.50 and aOR Urinary =2.90, 95%CI=1.41-5.95; aOR Heart =3.72, 95%CI=1.50-9.24 and aORHeart=8.67, 95%CI=2.62-28.63; and aOR Head&Brain =1.96, 95%CI=0.72-5.30 and aOR Head&Brain =4.67, 95%CI=1.34-16.24; vs. TDS and TDP, respectively). ASD females had significantly more UFAs than ASD males (43.1% vs. 25.3%, p =0.013) as well as higher prevalence of multiple co-occurring UFAs (15.7% vs. 4.5%, p =0.011), while no sex differences were seen among TDS and TDP controls. ASD fetuses were characterized by a narrower head and a relatively wider ocular-distance vs. TDP fetuses (aOR BPD =0.81, 95%CI=0.70-0.94, and aOR Ocular-Distance =1.29, 95%CI=1.06-1.57). Finally, UFAs were associated with more severe ASD symptoms. Conclusions Our findings shed important light on the abnormal multiorgan embryonic development of ASD and suggest fetal ultrasonography biomarkers for ASD.