Objectives To assess the association of head circumference (HC) <10th percentile at birth and discharge from the neonatal intensive care unit (NICU) with neurodevelopment in very preterm (24–32 weeks’ gestational age) neonates, and to compare the association of HC and total cerebral volume (TCV) with neurodevelopmental outcomes.

Design In a prospective cohort, semiautomatically segmented TCV and manually segmented white matter injury (WMI) volumes were obtained. Multivariable regressions were used to study the association of HC and TCV with neurodevelopmental outcomes, accounting for birth gestational age, WMI and postnatal illness.

Setting Participants born in 2006–2013 at British Columbia Women’s Hospital were recruited.

Patients 168 neonates had HC measurements at birth and discharge and MRI at term-equivalent age (TEA). 143 children were assessed at 4.5 years.

Main outcome measures Motor, cognitive and language outcomes at 4.5 years were assessed using the Movement Assessment Battery for Children Second Edition (M-ABC) and Wechsler Preschool and Primary Scale of Intelligence Third Edition Full Scale IQ (FSIQ) and Verbal IQ (VIQ).

Results Small birth HC was associated with lower M-ABC and FSIQ scores. In children with small birth HC, small discharge HC was associated with lower M-ABC, FSIQ and VIQ scores, while normal HC at discharge was no longer associated with adverse outcomes. HC strongly correlated with TCV at TEA. TCV did not correlate with outcomes.

Conclusions Small birth HC is associated with poorer neurodevelopment, independent of postnatal illness and WMI. Normalisation of HC during NICU care appears to moderate this risk.