Brain maturation is delayed in infants with complex congenital heart defects

Divison of Neurology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
The Journal of thoracic and cardiovascular surgery (Impact Factor: 4.17). 04/2009; 137(3):529-36; discussion 536-7. DOI: 10.1016/j.jtcvs.2008.10.025
Source: PubMed


Small head circumferences and white matter injury in the form of periventricular leukomalacia have been observed in populations of infants with severe forms of congenital heart defects. This study tests the hypothesis that congenital heart defects delay in utero structural brain development.
Full-term infants with hypoplastic left heart syndrome or transposition of the great arteries were prospectively evaluated with preoperative brain magnetic resonance imaging. Patients with independent risk factors for abnormal brain development (shock, end-organ injury, or intrauterine growth retardation) were excluded. Outcome measures included head circumferences and the total maturation score on magnetic resonance imaging. Total maturation score is a previously validated semiquantitative anatomic scoring system used to assess whole brain maturity. The total maturation score evaluates 4 parameters of maturity: (1) myelination, (2) cortical infolding, (3) involution of glial cell migration bands, and (4) presence of germinal matrix tissue.
The study cohort included 29 neonates with hypoplastic left heart syndrome and 13 neonates with transposition of the great arteries at a mean gestational age of 38.9 +/- 1.1 weeks. Mean head circumference was 1 standard deviation below normal. The mean total maturation score for the cohort was 10.15 +/- 0.94, significantly lower than reported normative data in infants without congenital heart defects, corresponding to a delay of 1 month in structural brain development.
Before surgery, term infants with hypoplastic left heart syndrome and transposition of the great arteries have brains that are smaller and structurally less mature than expected. This delay in brain development may foster susceptibility to periventricular leukomalacia in the preoperative, intraoperative, and postoperative periods.

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Available from: Daniel J Licht, Oct 04, 2015
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    • "The majority of infants with CCHD are now living into adulthood and the focus has become neurodevelopmental outcomes. Infants with CCHD are more likely to have neurological impairments as a result of brain immaturity and injury before and after surgery, contributing to developmental impairments (Clouchoux et al., 2012; Licht et al., 2009; Mahle et al., 2002). Brain injuries in infants with CCHD may be a result of hypoxia/ischemia during the fetal stage or during post-natal stages because of impaired circulatory function and post-surgery sequelae (Mahle et al., 2002). "
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    ABSTRACT: The purpose of this study was to examine learning, short-term memory and general development including cognitive, motor, and language domains in infants with Complex Congenital Heart Defects (CCDH). Ten infants with CCHD (4 males, 6 females) and 14 infants with typical development (TD) were examined at 3 months of age. The mobile paradigm, where an infant's leg is tethered to an overhead mobile, was used to evaluate learning and short-term memory. The Bayley Scales of Infant Development 3rd edition (Bayley-III) was used to evaluate general development in cognitive, motor, and language domains. Infants with CCHD and infants with TD both showed learning with significant increase in kicking rate (p<0.001) across periods of the mobile paradigm, but only infants with TD demonstrated short-term memory (p=0.017) in the mobile paradigm. There were no differences on cognitive, motor, and language development between infants with CCHD and infants with TD on the Bayley-III. Early assessment is necessary to guide targeted treatment in infants with CCHD. One-time assessment may fail to detect potential cognitive impairments during early infancy in infants with CCHD. Supportive intervention programs for infants with CCHD that focuses on enhancing short-term memory are recommended. Copyright © 2015 Elsevier Inc. All rights reserved.
    Infant behavior & development 04/2015; 40:12-19. DOI:10.1016/j.infbeh.2015.02.007 · 1.34 Impact Factor
    • "Infants with CHD exhibit high rates of microcephaly, hypotonia, and atypical state regulation on clinical examination, and neuroimaging abnormalities such as ischemic infarcts and white matter injury (periventricular leukomalacia) are present in up to 59% before surgery (Owen, Shevell, Majnemer, & Limperopoulos, 2011). Relative to controls, the brains of full-term infants with TGA or HLHS are smaller and less mature structurally than those of typically developing infants (Licht et al., 2009), with reduced grey matter volumes particularly in the frontal lobe (Watanabe et al., 2009). Adolescents with corrected TGA (Bellinger et al., 2011) and those with TOF (Bellinger et al., 2014a) exhibit much higher rates of structural MRI abnormalities than controls. "
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    ABSTRACT: Children and adolescents with critical cyanotic congenital heart disease (CHD) are at risk for deficits in aspects of executive function (EF). The primary aim of this investigation was to compare EF outcomes in three groups of children/adolescents with severe CHD and controls (ages 10-19 years). Participants included 463 children/adolescents with CHD [dextro-transposition of the great arteries (TGA), n=139; tetralogy of Fallot (TOF), n=68; and, single-ventricle anatomy requiring Fontan procedure (SVF), n=145] and 111 controls, who underwent laboratory and informant-based evaluation of EF skills. Rates of EF impairment on D-KEFS measures were nearly twice as high for CHD groups (75-81%) than controls (43%). Distinct EF profiles were documented between CHD groups on D-KEFS tasks. Deficits in flexibility/problem-solving and verbally mediated EF skills were documented in all three CHD groups; visuo-spatially mediated EF abilities were impaired in TOF and SVF groups, but preserved in TGA. Parent, teacher, and self-report ratings on the BRIEF highlighted unique patterns of metacognitive and self-regulatory concerns across informants. CHD poses a serious threat to EF development. Greater severity of CHD is associated with worse EF outcomes. With increased understanding of the cognitive and self-regulatory vulnerabilities experienced by children and adolescents with CHD, it may be possible to identify risks early and provide individualized supports to promote optimal neurodevelopment. (JINS, 2014, 20, 1-16).
    Journal of the International Neuropsychological Society 12/2014; 21(01):1-16. DOI:10.1017/S1355617714001027 · 2.96 Impact Factor
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    • "The imaging findings of their study are similar to those in premature newborns and may reflect abnormal brain development in utero. Licht et al. [4] showed that before surgery, term infants with hypoplastic left heart syndrome and transposition of the great arteries have brains that are smaller and structurally less mature than expected. Periventricular leukomalacia (PVL) is a type of brain injury that affects infants. "
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    ABSTRACT: This paper is concerned with predicting the occurrence of Periventricular Leukomalacia (PVL) using vital data which are collected over a period of twelve hours after neonatal cardiac surgery. The vital data contain heart rate (HR), mean arterial pressure (MAP), right atrium pressure (RAP), and oxygen saturation (SpO2). Various features are extracted from the data and are then ranked so that an optimal subset of features that have the highest discriminative capabilities can be selected. A decision tree (DT) is then developed for the vital data in order to identify the most important vital measurements. The DT result shows that high amplitude 20 minutes variations and low sample entropy in the data is an important factor for prediction of PVL. Low sample entropy represents lack of variability in hemodynamic measurement, and constant blood pressure with small fluctuations is an important indicator of PVL occurrence. Finally, using the different time frames of the collected data, we show that the first six hours of data contain sufficient information for PVL occurrence prediction.
    Conference proceedings: ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference 07/2013; 2013:7080-7083. DOI:10.1109/EMBC.2013.6611189
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