Longitudinal Pre- and Postnatal Brain Growth Trajectory in ASD: Evidence for a Late Gestation Critical Time Window

Background:

Longitudinal pre- and post-natal brain growth trajectory in ASD remains unexplored despite several pathophysiological findings targeting both gestational period and early post-natal life. Furthermore early brain overgrowth has been largely reported but more recent studies on large populations do not replicate this result, highlighting both physiopathological and clinical heterogeneity in ASD.

Objectives:

The aim of this study was to characterize longitudinal brain growth trajectory in ASD in both prenatal and postnatal periods to identify the critical time window for pathological neurodevelopmental processes.

Methods:

Prenatal and postnatal biometric parameters were collected in fetal Ultrasound records and medical records of 94 patients with ASD (87 males/7 females; mean age ± standard deviation 7.5 ±3.5 years) recruited and fully examined at the Center of Excellence in Autism in Tours (France). Diagnosis was made according to DSM-IV-R and DSM-5 criteria (American Psychiatric Association, 2000, 2013) and by using the Autism Diagnostic Interview or the Autism Diagnostic Observation Schedule-Generic. Diagnosis was complemented by the Childhood Autism Rating Scale, Behavioral Summarized Evaluation scale and Developmental Quotients using standardized tools. In utero parameters at 2^nd and 3^rdtrimester of gestation included Biparietal Diameter (BPD), Femur Length (FL) (N = 94: 87M / 7F) and Head Circumference (HC) (N = 70: 66M / 4F). Postnatal parameters included, HC, body length and birth weight (N = 70: 66M / 4F), HC at 1 year and 2 years (N = 54: 52M / 2F).

Results:

Compared to a French nationally recognized, normative database, ASD patients exhibited greater increase in HC between the 2^nd (t= 2.58; p=0.01) and 3^rd(t=3.37; p=0.001) trimesters of gestation, whereas BPD and femur length were not significantly increased. At birth, normal HC and weight were observed whereas body length was significantly larger (t=5.01; p<0.001). No brain overgrowth was observed during the first two years of life.

Conclusions:

This first longitudinal pre- and postnatal brain growth study in ASD suggests atypical neurodevelopmental processes during a critical time window between the 2^nd and 3^rd trimesters of gestation. This result opens discussions on pathophysiological tracks including genetic, inflammatory and structural pathways during this period. Accelerated postnatal brain growth seemed to be inconsistent and illustrates the clinical heterogeneity of ASD.