Foetal growth determines cerebral ventricular volume in infants The Generation R Study Sabine J. Roza, a,b Paul P. Govaert, c Henri A. Vrooman, d,e Maarten H. Lequin, d Albert Hofman, f Eric A.P. Steegers, g Henriette A. Moll, h Vincent W.V. Jaddoe, a,f,h Frank C. Verhulst, b and Henning Tiemeier b,f, ⁎ a The Generation R Study Group, Erasmus MC University Medical Center Rotterdam, The Netherlands b Department of Child and Adolescent Psychiatry, Erasmus MC University Medical Center Rotterdam, The Netherlands c Department of Neonatology, Erasmus MC University Medical Center Rotterdam, The Netherlands d Department of Radiology, Erasmus MC University Medical Center Rotterdam, The Netherlands e Biomedical Imaging Group Rotterdam, Erasmus MC University Medical Center Rotterdam, The Netherlands f Department of Epidemiology & Biostatistics, Erasmus MC University Medical Center Rotterdam, The Netherlands g Department of Obstetrics & Gynaecology, Erasmus MC University Medical Center Rotterdam, The Netherlands h Department of Paediatrics, Erasmus MC University Medical Center Rotterdam, The Netherlands Received 12 April 2007; revised 22 October 2007; accepted 7 November 2007 Available online 21 November 2007 The cerebral ventricular system is a marker of brain development and a predictor of neurodevelopmental outcome. In premature or dysmature neonates, neuroanatomical structures including the ven- tricular system appear to be altered. The present study aims to provide information on the association between foetal growth and neonatal cerebral ventricular size in the normal population. Within the Generation R Study, a population-based cohort study, we used three-dimensional cranial ultrasound to determine lateral ventricular volume in 778 term infants aged 4–12 weeks. Foetal growth characteristics were repeatedly measured in early, mid- and late pregnancy and analysed in relation to ventricular volume divided by head circumference. Results revealed positive associations between foetal head circumference in late pregnancy and log-transformed ventricular volume (β = 0.077, 95% confidence interval (0.017; 0.136), equivalent to a 7.7% increase in ventricular volume per standard deviation of head circumference). Similarly, in a per week-longer gestational duration, ventricular volume in infancy was 6.0% larger. Multilevel modelling demonstrated that reduced growth of foetal head circumference and biparietal diameter during pregnancy were associated with decreased ventricular volume in infancy. In conclusion, foetal maturation is positively associated to cerebral ventricular size in term infants. Larger ventricular size in term infants needs to be distinguished from ventricular enlargement due to intraventricular haemorrhage or white matter damage in premature or dysmature infants. Moreover, the naturally occurring enlargement of ventricles during infancy should be considered in interpreting reports on increased ventricular volumes in several neuropsychiatric disorders. © 2007 Elsevier Inc. All rights reserved. Keywords: Brain anatomy; Neuroimaging; Foetal growth; Infant; Cerebral ventricular system Introduction The size of the cerebral ventricular system is a marker of brain development (Gilmore et al., 1998) and can be reliably explored by ultrasound in prenatal and early postnatal life (Garel, 2005; Gilmore et al., 2001). Ventricular size in infancy has mainly been studied in premature born infants (Davies et al., 2000; Haiden et al., 2005; Saliba et al., 1990). These children with (very) short gestational duration, even those without gross evidence of brain injury, have subtle structural signs of altered brain development such as lower cortical grey matter volumes, and overall reduction in cerebral tissue volume (Inder et al., 2005; Kesler et al., 2004; MacKendrick, 2006; Peterson et al., 2002). However, it is unclear whether brain structure is determined by gestational duration across the entire range in the general population. Irrespective of the degree of prematurity, small for gestational age infants are at greater risk for neurodevelopmental impairments than appropriate for gestational age infants (McCarton et al., 1996). In contrast to gestational duration, birth weight has been described to be a continuous risk factor for developmental disabilities in the www.elsevier.com/locate/ynimg NeuroImage 39 (2008) 1491 – 1498 ⁎ Corresponding author. Department of Child and Adolescent Psychiatry, P.O. Box 2060, 3000 CB Rotterdam, The Netherlands. E-mail address: h.tiemeier@erasmusmc.nl (H. Tiemeier). Available online on ScienceDirect (www.sciencedirect.com). 1053-8119/$ - see front matter © 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.neuroimage.2007.11.004