Brain Maturation is Delayed in Infants with Complex Congenital Heart Defects
Daniel J. Licht, David M. Shera, Robert R. Clancy, Gil Wernovsky, Lisa M. Montenegro, Susan C. Nicolson, J. W. Gaynor, Arastoo Vossough; Children's Hospital of Philadelphia, Philadelphia, PA
Comment on this Abstract
Objective: Periventricular leukomalacia (PVL) is a risk factor for neuro-cognitive dysfunction in premature infants and has been attributed to maturation-dependent vulnerability of the cerebral white matter to hypoxic-ischemic injury. Neuroimaging studies have identified PVL in >50% of neonates with congenital heart disease (CHD) after surgical intervention. This study was undertaken to test the hypothesis that the presence of CHD alters in-utero brain development leading to delayed brain maturation, even in full term infants.
Methods: Full-term infants with hypoplastic left heart syndrome (HLHS) or transposition of the great arteries (TGA) were prospectively evaluated with pre-operative brain magnetic resonance imaging (MRI). Exclusion criteria included acidosis at birth (pH <7.10) and gestational age (GA) <36 weeks. Brain maturation was independently measured by two MRI readers blinded to clinical data, using the “total maturation score” (TMS), a previously validated semi-quantitative anatomical scoring system. The TMS evaluates four developmentally-sensitive parameters of maturity: (i) myelination, (ii) cortical infolding, (iii) involution of glial cell migration bands and (iv) the presence of germinal matrix tissue.
Results: Infants with HLHS (n = 25) and TGA (n = 11) with an average GA of 39.0 ± 1.1weeks underwent MRI prior to surgery, on day of life 4.0 ± 2.3. Mean head circumference (HC) and birth weight (BW) were 34.6 ± 1.2cm (z = -0.6) and 3.41 ± 0.56kg (z = -0.2). There was good agreement of TMS values between the blinded MRI readers (intra-class correlation: r = 0.73), with a mean score for the cohort of was 10.19 ± 1.0. This is significantly lower than reported mean TMS scores in non-cardiac infants with GA of 36 to 37 weeks (n = 28, mean TMS =11.1 ± 1.5, p = 0.009) and from 38 to 43 weeks (n = 16, mean TMS = 13.0 ± 2.3, p <0.0001).
Conclusion: Brain development at birth is significantly delayed in full term neonates with HLHS and TGA, both on semiquantitative interpretation of MRI and by HC measurements. This finding suggests that in-utero brain development is altered in fetuses with CHD, possibly secondary to altered cerebral oxygen delivery or other sequelae of CHD. Delay in maturation of cerebral white matter may increase susceptibility to hypoxic-ischemic injury and thus the risk of PVL during the peri-operative period in these patients.
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