Brain maturation is delayed in infants with complex congenital heart defects

Licht, Daniel J.; Shera, David; Clancy, Robert R.; Wernovsky, Gil; Montenegro, Lisa M.; Nicolson, Susan C.; Zimmerman, Robert A.; Spray, Thomas L.; Gaynor, J. William; Vossough, Arastoo

doi:10.1016/j.jtcvs.2008.10.025

Cited by 536 publications

(469 citation statements)

References 28 publications

(40 reference statements)

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“…Recently, however, the Pediatric Heart Network reported motor and cognitive developmental delays in HLHS survivors at the age of 14 mo that were independent of intraoperative management strategies (22). Furthermore, it has been shown that the CNS in term HLHS infants is immature and characterized by white matter injury (19,23). Microcephaly is an established risk factor for developmental delays in general, and in HLHS distinguishing primary from secondary microcephaly is challenging.…”

Section: Discussionmentioning

confidence: 99%

“…Fetal echocardiograms were performed on either Sequoia C512 (Siemens, Mountain View, CA) or Vivid 7 (General Electric, Milwaukee, WI) ultrasound systems with either a 2-6 MHz curvilinear or 3-5 MHz phased array transducer. Complete two-dimensional, color flow, and spectral Doppler studies were performed according to accepted standards (23). In recent years, Doppler profiles of the UA and MCA were included in the analysis, and this information is available for a subset of the cohort (n = 22).…”

Section: Echocardiographic Datamentioning

confidence: 99%

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Microcephaly is associated with early adverse neurologic outcomes in hypoplastic left heart syndrome

et al. 2013

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Background: Hypoplastic left heart syndrome (HLHS) is associated with significant mortality and morbidity. Fetal head growth abnormalities have been identified in a subset of HLHS fetuses, but it is unclear whether specific patterns of maladaptive growth affect clinical outcomes. We hypothesized that poor fetal head growth is associated with an increased frequency of adverse clinical outcomes. Methods: We retrospectively examined a cohort of HLHS patients from midgestation to 1 y of age. Fetal and birth anthropometric measurements were analyzed using the Olsen standard, and clinical outcomes were obtained. results: A total of 104 HLHS patients were identified over a 12-y period; fetal data were available in 38 cases. HLHS neonates demonstrated a high incidence of microcephaly (12%), small head size (27%), and poor head growth (32%). Allcause mortality was 31% at 30 d and 43% at 1 y. Neurologic outcomes were observed in 12% of patients and were significantly increased with microcephaly (43 vs. 4%; P = 0.02). The average length of hospital stay following stage I palliation was 33.4 ± 33 d, correcting for early death. conclusion: In term nonsyndromic HLHS, fetal and neonatal microcephaly are associated with early adverse neurologic outcomes but not mortality.

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Section: Discussionmentioning

confidence: 99%

Section: Echocardiographic Datamentioning

confidence: 99%

Microcephaly is associated with early adverse neurologic outcomes in hypoplastic left heart syndrome

et al. 2013

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“…WMI is not exclusively associated with prematurity and it is increasingly appreciated in term infants [23][24][25]. Infants with complex congenital heart disease are at particular risk for WMI and delayed brain maturation [26][27][28]. Because very low birth weight infants comprise approximately 1.5% of the 4 million live births in the United States alone each year, the worldwide social and economic burden is considerable.…”

mentioning

confidence: 99%

The Instrumented Fetal Sheep as a Model of Cerebral White Matter Injury in the Premature Infant

et al. 2012

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Despite advances in neonatal intensive care, survivors of premature birth remain highly susceptible to unique patterns of developmental brain injury that manifest as cerebral palsy and cognitive-learning disabilities. The developing brain is particularly susceptible to cerebral white matter injury related to hypoxia-ischemia. Cerebral white matter development in fetal sheep shares many anatomical and physiological similarities with humans. Thus, the fetal sheep has provided unique experimental access to the complex pathophysiological processes that contribute to injury to the human brain during successive periods in development. Recent refinements have resulted in models that replicate major features of acute and chronic human cerebral injury and have provided access to complex clinically relevant studies of cerebral blood flow and neuroimaging that are not feasible in smaller laboratory animals. Here, we focus on emerging insights and methodologies from studies in fetal sheep that have begun to define cellular and vascular factors that contribute to white matter injury. Recent advances include spatially defined measurements of cerebral blood flow in utero, the definition of cellular maturational factors that define the topography of injury and the application of high-field magnetic resonance imaging to define novel neuroimaging signatures for specific types of chronic white matter injury. Despite the higher costs and technical challenges of instrumented preterm fetal sheep models, they provide powerful access to clinically relevant studies that provide a more integrated analysis of the spectrum of insults that appear to contribute to cerebral injury in human preterm infants.

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“…These delays may result from preoperative microcephaly and structural brain immaturity, right-to-left intracardiac shunting that may result in decreased cerebral oxygen delivery, intraoperative or postoperative use of extracorporeal life support, or low cardiac output (Donofrio & Massaro, 2010;Licht et al, 2009;Marino et al, 2012;Wernovsky, 2006). Exposure to these risk factors may be a single occurrence, or may continue throughout life in children who require staged palliation.…”

Section: Introductionmentioning

confidence: 99%