Antenatal diagnosis, neonatal brain volumes, and neurodevelopment in transposition of the great arteries.

AIM: To examine whether antenatal diagnosis modifies relationships between neonatal brain volumes and 18-month neurodevelopmental outcomes in children with transposition of the great arteries (TGA). METHOD: In a retrospective cohort of 139 children with TGA (77 antenatally diagnosed), we obtained total brain volumes (TBVs) on pre- (n = 102) and postoperative (n = 112) magnetic resonance imaging. Eighteen-month neurodevelopmental outcomes were assessed using the Bayley Scales of Infant and Toddler Development, Third Edition. Generalized estimating equations with interaction terms were used to determine whether antenatal diagnosis modified associations between TBVs and neurodevelopmental outcomes accounting for postmenstrual age at scan, brain injury, and ventricular septal defect. RESULTS: Infants with postnatal diagnosis had more preoperative hypotension (35% vs 14%, p = 0.004). The interactions between antenatal diagnosis and TBVs were significantly related to cognitive (p = 0.003) outcomes. Specifically, smaller TBVs were associated with lower cognitive scores in infants diagnosed postnatally; this association was attenuated in those diagnosed antenatally. INTERPRETATION: Antenatal diagnosis modifies associations between neonatal brain volume and 18-month cognitive outcome in infants with TGA. These findings suggest that antenatal diagnosis may be neuroprotective, possibly through improved preoperative clinical status. These data highlight the need to improve antenatal diagnosis rates. WHAT THIS PAPER ADDS: Antenatal diagnosis of transposition of the great arteries modified relationships between neonatal brain volume and neurodevelopment. Smaller brain volumes related to poorer cognitive scores with postnatal diagnosis only. There was more preoperative hypotension in the postnatal diagnosis group.

Ventricular Volume in Infants Born Very Preterm: Relationship with Brain Maturation and Neurodevelopment at Age 4.5 Years.

OBJECTIVE: To evaluate the relationship of quantitative ventricular volume with brain maturation and neurodevelopmental outcomes at age 4.5 years in children born very preterm. STUDY DESIGN: T1-weighted imaging, diffusion tensor imaging, and magnetic resonance spectroscopy were performed shortly after birth (n = 212) and at term-equivalent age (TEA) (n = 194). Intraventricular hemorrhage (IVH) grade and white matter injury (WMI) volume were measured on early T1-weighted magnetic resonance imaging (MRI) scans. Total cerebral volume and ventricular volume were quantified using the Multiple Automatically Generated Templates-Brain pipeline. At age 4.5 years, 178 children (84%) underwent cognitive and motor assessments. Multivariable linear regression was used to examine the relationships between ventricular volume and neurodevelopmental outcomes. Generalized estimating equations were used to account for repeated measures when analyzing neonatal MRI data. All models accounted for sex, postmenstrual age at scan, WMI volume, IVH grade, and total cerebral volume and were corrected for multiple comparisons. RESULTS: On early MRI, 97 infants had IVH (grade 1, n = 22; grade 2, n = 66; grade 3, n = 9), and 68 had WMI (median, 44 mm3; IQR, 21-296 mm3). IQ at 4.5 years was associated with MRI ventricular volume at the early (ß = -0.64; P < .001) and TEA (ß = -0.44, P < .001) time points. Motor outcomes were associated with ventricular volume at TEA (ß = -0.84, P = .01). Greater ventricular volume independently predicted lower fractional anisotropy in corpus callosum (genu: ß = -0.0008, P = .002; splenium: ß = -0.003, P < .001) and optic radiations (ß = -0.001, P = .004); ventricular volume did not predict the N-acetylaspartate/choline ratio. CONCLUSIONS: In children born very preterm, neonatal ventricular size was associated with 4.5-year neurodevelopmental outcomes. Our findings suggest that white matter maturation may be abnormal in the setting of enlarged ventricular size beyond that expected from concurrent brain injuries.

Interaction between Preterm White Matter Injury and Childhood Thalamic Growth.

OBJECTIVE: The purpose of this study was to determine how preterm white matter injury (WMI) and long-term thalamic growth interact to predict 8-year neurodevelopmental outcomes. METHODS: A prospective cohort of 114 children born at 24 to 32 weeks' gestational age (GA) underwent structural and diffusion tensor magnetic resonance imaging early in life (median 32 weeks), at term-equivalent age and at 8 years. Manual segmentation of neonatal WMI was performed on T1-weighted images and thalamic volumes were obtained using the MAGeT brain segmentation pipeline. Cognitive, motor, and visual-motor outcomes were evaluated at 8 years of age. Multivariable regression was used to examine the relationship among neonatal WMI volume, school-age thalamic volume, and neurodevelopmental outcomes. RESULTS: School-age thalamic volumes were predicted by neonatal thalamic growth rate, GA, sex, and neonatal WMI volume (p < 0.0001). After accounting for total cerebral volume, WMI volume remained associated with school-age thalamic volume (ß = -0.31, p = 0.005). In thalamocortical tracts, fractional anisotropy (FA) at term-equivalent age interacted with early WMI volume to predict school-age thalamic volumes (all p < 0.02). School-age thalamic volumes and neonatal WMI interacted to predict full-scale IQ (p = 0.002) and adverse motor scores among those with significant WMI (p = 0.01). Visual-motor scores were predicted by thalamic volumes (p = 0.04). INTERPRETATION: In very preterm-born children, neonatal thalamic growth and WMI volume predict school-age thalamic volumes. The emergence at term of an interaction between FA and WMI to impact school-age thalamic volume indicates dysmaturation as a mechanism of thalamic growth failure. Cognition is predicted by the interaction of WMI and thalamic growth, highlighting the need to consider multiple dimensions of brain injury in these children. ANN NEUROL 2021;90:584-594.