340 - Sex-Specific Association between Neonatal Deep Grey Nuclei Growth and Neurodevelopmental Outcomes at 4.5 Years in Very Preterm Children

Poster Number: 340
Publication Number: 340.442

Connor Mabbott, The Hospital for Sick Children, Toronto, ON, Canada; Ting Guo, The Hospital for Sick Children, Toronto, ON, Canada; Min Sheng, SickKids Hospital, Toronto, ON, Canada; Vann Chau, The Hospital for Sick Children, Toronto, ON, Canada; Helen Branson, The Hospital for Sick Children, Toronto, ON, Canada; Anne Synnes, University of British Columbia Faculty of Medicine, Salt Spring Island, BC, Canada; Ruth E. Grunau, University of British Columbia Faculty of Medicine, Vancouver, BC, Canada; Steven P. Miller, The Hospital for Sick Children, Toronto, ON, Canada

Background: Male and female preterm neonates respond differently to early-life exposures that contribute to brain maturation and neurodevelopmental outcomes. Deep grey nuclei (DGN) growth is associated with outcomes. However, whether neonatal DGN growth is related to preschool outcomes differently in male and female preterm children is unclear. 

Objective: To determine how the child’s sex modifies the relationship between neonatal DGN growth with cognitive and motor outcomes at 4.5 years of age in very preterm children.

Design/Methods: A prospective cohort of 234 very preterm neonates (122 males) were scanned twice: early in life (median post-menstrual age [PMA] 32 wks) and at term equivalent age (median PMA 40.3 wks). The total cerebral volume (TCV), caudate, putamen, globus pallidus, and thalamus volumes, and each nucleus/TCV percentage were assessed at both time points. At 4.5 years, cognitive and motor abilities (n=168) were examined with Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III), Movement Assessment Battery for Children (MABC-2), and Beery-Buktenica Developmental Test of Visual-Motor Integration (Beery VMI). General estimating equations (GEE) were used to assess the association between the interaction of sex and each nucleus/TCV percentage with outcomes at 4.5 years, adjusting for birth GA, PMA at MRI, and white matter injury (WMI) volume/TCV percentage. False discovery rate was used to correct for multiple comparisons.

Results: Male and female preterm children were not different by key clinical features. Interaction of sex and caudate percentage predicted Verbal IQ (q=0.028), and interaction of sex and thalamus percentage predicted Beery VMI (q=0.038), adjusting for key covariates and correcting for multiple comparisons. Further analysis using GEE models stratified by sex showed that in females, greater caudate volume predicted higher Verbal IQ (ß= 0.035, p=0.0031), adjusting for TCV, birth GA, PMA at MRI, and WMI volume. However, in males, TCV (ß= 1.17e-4, p=0.022), but not caudate (p >0.05) predicted Verbal IQ. Similarly, higher Beery VMI was predicted by thalamus volume (ß= 0.012, p=0.11) in females, while by TCV (ß= 8.2e-5, p=0.048) in males.Conclusion(s): In very preterm children, sex significantly modifies the relationship between neonatal DGN growth and preschool outcomes, suggesting the need to consider sex-dependent strategies to improve neurodevelopmental outcomes.