Abnormal second-trimester biometrics and risk of neurodevelopmental disorders

Neurodevelopmental disorders are assumed to be mostly caused by impaired development during pregnancy. Therefore, we aimed to investigate relationships between abnormal second-trimester biometrics and neurodevelopmental disorders in childhood. Population-based register study using data from the Danish Fetal Medicine Database, including all singleton liveborn children in Denmark from 2008–2013 who had undergone routine second-trimester screening at gestational weeks 18+0 to 21+6 and were alive after the first year of life. All were followed in the first six years of life for the diagnosis of cerebral palsy (CP), epilepsy, intellectual disability and autism spectrum disorders (ASD). The biometrics were biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), femur length (FL), estimated fetal weight (EFW), and HC/AC-ratio. Mean z-scores and proportions < 10th and > 90th centiles were compared in cases and controls, calculated by linear regression adjusted for sex and gestational age at scan. We comprised a total of 249,131 children and found 78 with ASD, 130 with intellectual disability, 381 with CP, and 1515 with epilepsy. Some children had more than one diagnosis. Second-trimester biometrics of children who developed CP were not different from children without. In contrast, children with epilepsy in childhood had a higher mean z-score of the BPD and the HC/AC-ratio (p= 0.01 and 0.03), a higher fraction of HC measurements > 90th (10.6% vs. 8.9%, p = 0.04), and a lower proportion of BPD measurements < 10th centile (8.4% vs. 10.1%, p = 0.04). Additionally, children with ASD had a lower mean z-score of FL (p = 0.02) and a higher fraction of FL measurements < 10th centile (18.0% vs. 8.9%, p = 0.02). Interestingly, intellectual disability was associated with higher proportions of HC measurements < 10th centile (15.4% vs. 8.1%, p = 0.01) and higher proportions of HC/AC-ratio < 10th centile (16.9% vs. 9.5%, p = 0.02). Abnormal second-trimester biometrics are associated with the diagnosis of neurodevelopmental disorders in childhood.