Abnormal Brain Development in Newborns with Congenital Heart Disease

Miller, Steven P.; McQuillen, Patrick S.; Hamrick, Shannon E. G.; Xu, Duan; Glidden, David V.; Charlton, Natalie N.; Karl, Tom R.; Azakie, Anthony; Ferriero, Donna M.; Barkovich, A. James; Vigneron, Daniel B.

doi:10.1056/nejmoa067393

Cited by 761 publications

(696 citation statements)

References 42 publications

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“…Mortality and G-tube placement data were available for 99 (94%) and 81 (78%) cases, respectively. A total of 53 infants were excluded for associated cardiac anatomy (29), prematurity (17), twinning (4), and genetic syndromes (3).…”

Section: Study Populationmentioning

confidence: 99%

“…The prevailing view is that chronic cyanosis and multiple cardiopulmonary bypass surgeries early in life lead to cognitive, motor, and behavioral deficits later in life (6,16). However, recent studies have implicated additional factors in the relationship between CNS abnormalities identified in neonates after birth but before surgery (17,18). Furthermore, early CNS abnormalities, including agenesis of the corpus callosum, as well as holoprosencephaly and microcephaly, have been identified in approximately one-quarter of HLHS neonates (5,15).…”

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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: Study Populationmentioning

confidence: 99%

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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.…”

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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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“…Multiple surgeries are often needed to correct the structural defects in subjects whose quality of life may remain compromised 1 . Children with CHD frequently develop neurological disorders even if they have not undergone surgery, indicating important in utero consequences on development 2,3 . Both genetic and environmental factors, such as exposure to viruses or chemicals (alcohol) during pregnancy, cause CHD.…”

Section: Introductionmentioning

confidence: 99%

<em>In utero</em> Measurement of Heart Rate in Mouse by Noninvasive M-mode Echocardiography

Kim

Seidah

Prat

2013

JoVE

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Congenital heart disease (CHD) is the most frequent noninfectious cause of death at birth. The incidence of CHD ranges from 4 to 50/1,000 births (Disease and injury regional estimates, World Health Organization, 2004). Surgeries that often compromise the quality of life are required to correct heart defects, reminding us of the importance of finding the causes of CHD. Mutant mouse models and live imaging technology have become essential tools to study the etiology of this disease. Although advanced methods allow live imaging of abnormal hearts in embryos, the physiological and hemodynamic states of the latter are often compromised due to surgical and/or lengthy procedures. Noninvasive ultrasound imaging, however, can be used without surgically exposing the embryos, thereby maintaining their physiology. Herein, we use simple M-mode ultrasound to assess heart rates of embryos at E18.5 in utero. The detection of abnormal heart rates is indeed a good indicator of dysfunction of the heart and thus constitutes a first step in the identification of developmental defects that may lead to heart failure. Video LinkThe video component of this article can be found at

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Abnormal Brain Development in Newborns with Congenital Heart Disease

Abstract: Term newborns with congenital heart disease have widespread brain abnormalities before they undergo cardiac surgery. The imaging findings in such newborns are similar to those in premature newborns and may reflect abnormal brain development in utero.

Cited by 761 publications

References 42 publications

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

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

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

<em>In utero</em> Measurement of Heart Rate in Mouse by Noninvasive M-mode Echocardiography

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