Sex Differences in Outcome and Associations with Neonatal Brain Morphology in Extremely Preterm Children

doi:10.1016/j.jpeds.2013.12.051

The Journal of Pediatrics

Volume 164, Issue 5, May 2014, Pages 1012-1018

https://doi.org/10.1016/j.jpeds.2013.12.051 Get rights and content

Objective

To investigate sex differences in neurologic and developmental outcomes in extremely preterm (EPT) children and explore associations with neonatal brain morphology.

Study design

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.

Conclusion

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.

Section snippets

Methods

Study subjects were participants in the Extremely Preterm Infants in Sweden Study (EXPRESS) project,¹¹ a prospective population-based study of EPT infants in Sweden investigating neurodevelopmental outcomes at 30 months corrected age, with a subcohort in Stockholm undergoing MRI at term equivalent age.⁸ All infants born between January 2004 and April 2007 at gestational age <27 weeks + 0 days were eligible for inclusion in the study (Figure 1). Children with malformations, chromosome

Sex and Outcomes at 30 Months

At corrected age 30 months, 6 of the 91 children (3 boys and 3 girls) met the criteria for CP. Unspecific neurologic signs were distributed similarly between boys and girls, present in 12 boys and 14 girls. Boys had lower mean composite scores for cognitive function (94 ± 7 vs 98 ± 11; P = .03) and language function (94 ± 13 vs 101 ± 15; P = .04) compared with girls (Table II), whereas motor scores were not significantly different between the sexes.

Sex and Findings on Visual Analysis of MRI

According to the composite white matter score,

Discussion

The purpose of this study was to investigate sex differences in outcomes at 30 months corrected age in EPT infants and to explore associations with brain structure revealed by neonatal MRI. We found that boys had lower cognitive and language scores compared with girls, whereas motor function outcome was similar in the 2 sexes. Sex-related differences were observed on MRI, including differences in the patterns of correlation between brain volume and developmental score at both global and

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: Supported by Swedish Medical Research Council (2011-3981), Marianne and Marcus Wallenberg Foundation (2011-MWW.0085), the regional agreement on medical training and clinical research between Stockholm County Council and Karolinska Institutet (ALF 20120450), Linnea and Josef Carlsson's Foundation, Swedish Order of Freemasons in Stockholm, Swedish Medical Society, Swedish Brain Foundation, and Sällskapet Barnavård. The authors declare no conflicts of interest.

^∗: Present address: Clinical and Experimental Sciences, University of Southampton, Southampton, United Kingdom.

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Original ArticleSex Differences in Outcome and Associations with Neonatal Brain Morphology in Extremely Preterm Children

Objective

Study design

Results

Conclusion

Section snippets

Methods

Sex and Outcomes at 30 Months

Sex and Findings on Visual Analysis of MRI

Discussion

Early Hum Dev

J Pediatr

Neuroimage

Neuroimage

Neuroimage

J Biol Chem

Brain Res Mol Brain Res

Int J Dev Neurosci

Neuroimage

The rise and fall of excess male infant mortality

Proc Natl Acad Sci U S A

Gender differences in neurodevelopmental outcomes among extremely preterm, extremely-low-birthweight infants

Acta Paediatr

The EPICure study: associations and antecedents of neurological and developmental disability at 30 months of age following extremely preterm birth

Arch Dis Child Fetal Neonatal Ed

Adverse neurodevelopmental outcomes among extremely low birth weight infants with a normal head ultrasound: prevalence and antecedents

Pediatrics

Prematurely born children demonstrate white matter microstructural differences at 12 years of age, relative to term control subjects: an investigation of group and gender effects

Pediatrics

White matter changes in extremely preterm infants, a population-based diffusion tensor imaging study

Acta Paediatr

Impaired brain growth and neurodevelopment in preterm infants with posthaemorrhagic ventricular dilatation

Acta Paediatr

Neonatal tract-based spatial statistics findings and outcome in preterm infants

AJNR Am J Neuroradiol

Original Article
Sex Differences in Outcome and Associations with Neonatal Brain Morphology in Extremely Preterm Children