title: Sex differences in outcome and associations with neonatal brain morphology in extremely preterm children.
abstract: OBJECTIVE
  To investigate sex differences in neurologic and developmental outcomes in extremely preterm (EPT) children and explore associations with neonatal brain morphology.
  
  
  METHODS
  A population-based cohort of infants born at <27 weeks gestation underwent magnetic resonance imaging (MRI) at term equivalent age (n = 107). Voxel-based morphometry (n = 27) and tract-based spatial statistics (n = 29) were performed in infants with normal MRI findings. Neurologic and developmental assessment (using the Bayley Scales of Infant and Toddler Development-Third Edition [BSITD-III]) was performed at 30 months corrected age (n = 91).
  
  
  RESULTS
  EPT boys had lower mean cognitive composite scores (P = .03) and lower mean language composite scores (P = .04) compared with EPT girls. Rates of cerebral palsy were similar in the 2 sexes. No perinatal factor explained the variance in outcomes. Visual inspection of T1- and T2-weighted MRI images found that delayed myelination was found more frequently in boys, whereas cerebellar abnormalities were more common in girls. In the subgroup of children with normal MRI findings (n = 27), boys had poorer cognitive function (P = .015) and language function (P = .008), despite larger volumes of cerebellar tissue (P = .029). In boys, cerebellar volume was positively correlated with BSITD-III cognitive and motor scores (P = .04 for both). In girls, white matter volume (P = .02) and cortical gray matter volume (P = .03) were positively correlated with BSITD-III language score. At the regional level, significant correlations with outcomes were found only in girls.
  
  
  CONCLUSIONS
  Cognitive and language outcomes at age 30 months were poorer in boys. Sex-related differences were observed on neonatal structural MRI, including differences in the patterns of correlations between brain volumes and developmental scores at both global and regional levels.
authors: Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden; Department of Neonatology, Karolinska Institutet, Stockholm, Sweden. Electronic address: beatrice.skiold@karolinska.se.
authors: Béatrice
authors: B
authors: Skiöld
authors: Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
authors: Georgios
authors: G
authors: Alexandrou
authors: Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
authors: Nelly
authors: N
authors: Padilla
authors: Department of Neonatology, Karolinska Institutet, Stockholm, Sweden; Department of Clinical Sciences, Intervention, and Technology, Karolinska Institutet, Stockholm, Sweden.
authors: Mats
authors: M
authors: Blennow
authors: Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
authors: Brigitte
authors: B
authors: Vollmer
authors: Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden; Department of Neonatology, Karolinska Institutet, Stockholm, Sweden.
authors: Ulrika
authors: U
authors: Adén
mesh_terms: D001921:Brain / Q000473:pathology*; D002547:Cerebral Palsy / Q000175:diagnosis / Q000209:etiology* / Q000473:pathology; D002675:Child, Preschool; D003072:Cognition Disorders / Q000175:diagnosis / Q000209:etiology* / Q000473:pathology; D002658:Developmental Disabilities / Q000175:diagnosis / Q000209:etiology* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D062071:Infant, Extremely Premature; D007231:Infant, Newborn; D007235:Infant, Premature, Diseases / Q000175:diagnosis / Q000209:etiology* / Q000473:pathology; D007805:Language Development Disorders / Q000175:diagnosis / Q000209:etiology* / Q000473:pathology; D016014:Linear Models; D008279:Magnetic Resonance Imaging; D008297:Male; D015999:Multivariate Analysis; D009483:Neuropsychological Tests; D011446:Prospective Studies; D012307:Risk Factors; D012737:Sex Factors