Impaired development of the cerebral cortex in infants with congenital heart disease is correlated to reduced cerebral oxygen delivery

Kelly, Christopher; Makropoulos, Antonios; Cordero‐Grande, Lucilio; Hutter, Jana; Price, Anthony N.; Hughes, Emer; Murgasova, Maria; Teixeira, Rui Pedro A. G.; Steinweg, Johannes K.; Kulkarni, Sagar; Rahman, Loay; Zhang, Hui; Alexander, Daniel C.; Pushparajah, Kuberan; Rueckert, Daniel; Hajnal, Joseph V.; Simpson, John; Edwards, A. David; Rutherford, Mary; Counsell, Serena J.

doi:10.1038/s41598-017-14939-z

Cited by 68 publications

(66 citation statements)

References 51 publications

(62 reference statements)

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“…These changes were further associated with reduced cerebral oxygen delivery. 77,78 This therefore highlights the importance of understanding the additional and as yet unexplored, effects of a CHD on brain development in Down syndrome. Mouse models are also useful for this as the Ts65Dn, 79 Ts1Cje, 80 Tc1, 81 Dp1Tyb, 70 and the genetically similar Dp16 mouse strains all develop CHD, which are identifiable by embryonic day 14.5.…”

Section: What We Do Not Knowmentioning

confidence: 98%

New approaches to studying early brain development in Down syndrome

Baburamani

Patkee

Arichi

et al. 2019

Develop Med Child Neuro

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Down syndrome is the most common genetic developmental disorder in humans and is caused by partial or complete triplication of human chromosome 21 (trisomy 21). It is a complex condition which results in multiple lifelong health problems, including varying degrees of intellectual disability and delays in speech, memory, and learning. As both length and quality of life are improving for individuals with Down syndrome, attention is now being directed to understanding and potentially treating the associated cognitive difficulties and their underlying biological substrates. These have included imaging and postmortem studies which have identified decreased regional brain volumes and histological anomalies that accompany early onset dementia. In addition, advances in genome‐wide analysis and Down syndrome mouse models are providing valuable insight into potential targets for intervention that could improve neurogenesis and long‐term cognition. As little is known about early brain development in human Down syndrome, we review recent advances in magnetic resonance imaging that allow non‐invasive visualization of brain macro‐ and microstructure, even in utero. It is hoped that together these advances may enable Down syndrome to become one of the first genetic disorders to be targeted by antenatal treatments designed to ‘normalize’ brain development. What this paper adds Magnetic resonance imaging can provide non‐invasive characterization of early brain development in Down syndrome. Down syndrome mouse models enable study of underlying pathology and potential intervention strategies. Potential therapies could modify brain structure and improve early cognitive levels. Down syndrome may be the first genetic disorder to have targeted therapies which alter antenatal brain development.

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Section: What We Do Not Knowmentioning

confidence: 98%

New approaches to studying early brain development in Down syndrome

Baburamani

Patkee

Arichi

et al. 2019

Develop Med Child Neuro

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“…A limitation of this study is the assessment of all CHD cases combined. We acknowledge that fetuses with lower oxygen delivery to the brain might be prone to delayed cortical development, reduced head circumference and brain lesions . However, reduced head circumference, as a proxy for brain development, has been reported in fetuses with only a single ventricular septal defect .…”

Section: Discussionmentioning

confidence: 87%

Cortical development in fetuses with congenital heart defects using an automated brain‐age prediction algorithm

Everwijn

Namburete

Geloven

et al. 2019

Acta Obstet Gynecol Scand

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Introduction Congenital heart defects are associated with neurodevelopmental delay. It is hypothesized that fetuses affected by congenital heart defect have altered cerebral oxygen perfusion and are therefore prone to delay in cortical maturation. The aim of this study was to determine the difference in fetal brain age between consecutive congenital heart defect cases and controls in the second and third trimester using ultrasound. Material and methods Since 2014, we have included 90 isolated severe congenital heart defect cases in the Heart And Neurodevelopment (HAND)‐study. Every 4 weeks, detailed neurosonography was performed in these fetuses, including the recording of a 3D volume of the fetal brain, from 20 weeks onwards. In all, 75 healthy fetuses underwent the same protocol to serve as a control group. The volumes were analyzed by automated age prediction software which determines gestational age by the assessment of cortical maturation. Results In total, 477 volumes were analyzed using the age prediction software (199 volumes of 90 congenital heart defect cases; 278 volumes of 75 controls). Of these, 16 (3.2%) volume recordings were excluded because of imaging quality. The age distribution was 19‐33 weeks. Mixed model analysis showed that the age predicted by brain maturation was 3 days delayed compared with the control group (P = .002). Conclusions This study shows that fetuses with isolated cases of congenital heart defects show some delay in cortical maturation as compared with healthy control cases. The clinical relevance of this small difference is debatable. This finding was consistent throughout pregnancy and did not progress during the third trimester.

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“…Children with congenital heart disease are at an increased risk of experiencing developmental delay or other neurocognitive disabilities such as mild cognitive impairment, impaired social skills, impulsive behavior, or impaired executive function (65,66). It is suggested this may be related to abnormal neurogenesis from a decrease in cerebral oxygen delivery during gestation and is positively associated with decreased brain volume and decreased gyrification (67).…”

Section: Biomarkers Of Cerebral Injurymentioning

confidence: 99%

Recent innovations in perfusion and cardiopulmonary bypass for neonatal and infant cardiac surgery

Sturmer¹,

Beaty²,

Clingan³

et al. 2018

Transl Pediatr

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Abstract:The development and refinement of cardiopulmonary bypass (CPB) has made the repair of complex congenital heart defects possible in neonates and infants. In the past, the primary goal for these procedures was patient survival. Now that substantial survival rates have been achieved for even the most complex of repairs in these patients, focus has been given to the reduction of morbidity. Although a necessity for these complex neonatal and infant heart defect repairs, CPB can also be an important source of perioperative complications. Recent innovations have been developed to mitigate these risks and is the topic of this review. Specifically, we will discuss improvements in minimizing blood transfusions, CPB circuit design, monitoring, perfusion techniques, temperature management, and myocardial protection, and then conclude with a brief discussion of how further systematic improvements can be made in these areas.

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Impaired development of the cerebral cortex in infants with congenital heart disease is correlated to reduced cerebral oxygen delivery

Cited by 68 publications

References 51 publications

New approaches to studying early brain development in Down syndrome

New approaches to studying early brain development in Down syndrome

Cortical development in fetuses with congenital heart defects using an automated brain‐age prediction algorithm

Recent innovations in perfusion and cardiopulmonary bypass for neonatal and infant cardiac surgery

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