A growing body of evidence supports prenatal onset of autism spectrum disorder (ASD).  Nevertheless, robust data about abnormalities in fetal development associated with ASD is lacking. Prenatal ultrasound is an excellent tool to study abnormal fetal development as it frequently used to monitor fetal growth and identify fetal anomalies throughout pregnancy. 

To identify fetal abnormalities associated with ASD, we compared data from prenatal ultrasound scans of children diagnosed with ASD (cases); their own typically developing, closest-in-age siblings (TDS); and typically developing children from the general population (TDP), matched by year of birth, sex and ethnicity. Fetal ultrasound data from the 2nd and 3rd trimesters of gestation were obtained from prenatal ultrasound clinics of Clalit Health Services (CHS) in southern Israel.

Both ASD and TDS fetuses had significantly narrower heads (smaller biparietal diameter; BPD) during the 2nd trimester compared to the TDP group (aORzBPD=0.685, 95%CI=0.527-0.890 and aORzBPD=0.587, 95%CI=0.459-0.751, respectively). However, TDS fetuses managed to close this gap during the 3rd trimester while the heads of ASD fetuses remained relatively smaller. In addition, ultrasonography fetal anomalies (UFAs) comprised of both structural anomalies and soft markers, were significantly more frequent in ASD cases than in the TDS and TDP groups (29.3% vs. 15.9% and 9.6% respectively; p<0.01).  Interestingly, UFAs associated with ASD were found mostly in the urinary system, heart, and head&brain. 

Our findings highlight several fetal anomalies associated with ASD that could, if confirmed, form a basis for future prenatal screening of ASD.