On the Spectrum

A Prospective Study of Fetal Head Growth in Children, Autistic Traits and Autism Spectrum Disorder
INTRODUCTION
Autism Spectrum Disorder (ASD) is a developmental condition characterized by difficulties
in social communication and by restrictive and repetitive behaviors. ASD is thought to
be neurodevelopmental in origin and is associated with structural and functional brain
abnormalities (Minshew and Williams 2007). Traditionally, studies of early brain growth in
children with ASD have reported early brain overgrowth in the first year of life (Hazlett, Poe,
Gerig, Smith, Provenzale et al. 2005). More recently, the existence and exact timing of early
brain growth abnormalities have been disputed, as several studies used historic references
and most study samples are affected by ascertainment bias (Raznahan, Wallace, Antezana,
Greenstein, Lenroot et al. 2013). However, there seems to be at least some consensus that
children with ASD show subtly accelerated head growth in early life, resulting in larger head
circumference (HC) and brain volume by the age of two (Piven, Arndt, Bailey and Andreasen
1996; Courchesne, Karns, Davis, Ziccardi, Carper et al. 2001; Constantino, Majmudar, Bottini,
Arvin, Virkud et al. 2010; Green, Loesch and Dissanayake 2015). However, it remains unknown
whether postnatal head overgrowth is the first manifestation of altered neurodevelopment,
or whether changes start earlier. Postnatal overgrowth could reflect a reaction or adaptation
to earlier growth patterns during prenatal life (Hobbs, Kennedy, Dubray, Bigler, Petersen et al.
2007). Very few studies have measured head growth in prenatal life in children subsequently
diagnosed with ASD compared to those who develop typically. Two earlier studies identified
no group-level differences in second trimester prenatal HC between children later diagnosed
with ASD and controls (Hobbs et al. 2007; Whitehouse, Hickey, Stanley, Newnham and
Pennell 2011). Similarly, a study of high-risk siblings of children with confirmed ASD revealed
no differences in HC (Unwin, Maybery, Murphy, Lilje, Bellesini et al. 2015). However, these
studies all had relatively small samples sizes (