Elsevier

Seminars in Pediatric Neurology

Volume 28, December 2018, Pages 60-65
Seminars in Pediatric Neurology

Brain Injury During Transition in the Newborn With Congenital Heart Disease: Hazards of the Preoperative Period

https://doi.org/10.1016/j.spen.2018.05.007Get rights and content

Infants born with critical congenital heart disease are at risk for neurodevelopmental morbidities later in life. In-utero differences in fetal circulation lead to vulnerabilities which lead to an increased incidence of stroke, white matter injury, and brain immaturity. Recent work has shown these infants may be most vulnerable to brain injury during the early neonatal period when they are awaiting their cardiac surgeries. Novel imaging and monitoring modalities are being employed to investigate this crucial time period and elucidate the precise timing and cause of brain injury in this population.

Introduction

Congenital heart defects (CHD) are the most common birth defect, affecting approximately 30,000 newborns each year. Nearly one-third of these children require cardiac surgery during the neonatal period.1 Although surgical advancements over the last several decades have improved survival, neurodevelopmental disabilities remain a significant morbidity among survivors. As a result, clinical and investigative focus has shifted from survival beyond the neonatal period toward neurologic sequelae. Magnetic resonance imaging (MRI) studies during the neonatal period in this population reveal abnormal development including microcephaly, decreased folding, and white matter immaturity.2 This immaturity leads to a high prevalence of a specific form of hypoxic-ischemic white matter injury (WMI), which is similar, if not identical to, periventricular leukomalacia (PVL) and has identical MRI signal properties to the PVL that commonly occurs in infants born prematurely.3 School-age survivors of various forms of CHD demonstrate problems with academic achievement, fine and gross motor function, visual-spatial skills, and executive function.4, 5

Newborn infants are a particular challenge to study; their examination is poorly informative and most information on brain health has to be obtained from neuromonitoring. Furthermore, neurodevelopmental testing (ie, Bayley scales of infant development) when conducted too early work poorly at predicting academic achievement of performance later in life. Thus, during early infancy, we rely on imaging which shows immaturity and injury, and infer that early abnormal findings contribute to the negative, long-term cognitive outcomes.

Section snippets

White Matter Injury

The underlying cause of the neurobehavioral symptoms seen in children with CHD is believed to be the high prevalence of WMI.3 Specifically, these infants are prone to a form of hypoxic-ischemic WMI which commonly occurs in a vascular watershed zone near the lateral ventricles (Fig. 1). Vulnerability to this WMI in these full-term infants with CHD occurs as a consequence of in utero differences in cerebral oxygen delivery that result in delayed maturation of the entire fetal brain and the glial

Magnetic Resonance Imaging

As mentioned above, infants with CHD are at an increased risk for developing periventricular WMI that can be detected as hyperintense lesions on T1-weighted MR images. A study by Mahle et al3 in 2002 investigated preoperative and postoperative MRIs of infants with CHD and was the first study to report preoperative WMI in 16% of subjects and new postoperative WMI in nearly half of the subjects. The finding that WMI was present before surgery, raised the possibility that surgery was not the main

Prenatal and Postnatal Circulation

The topic of fetal and transitional circulation in CHD is covered in detail elsewhere in this special edition. Briefly, studies have investigated in utero CBF and compensatory mechanisms and the relationship of these with specific congenital heart defects and fetal circulation.29 Prenatal studies using Doppler ultrasound have shown fetuses with HLHS have lower than normal cerebral vascular resistance (CVR).30, 31 Lower fetal CVR is likely due to decreased oxygen delivery to the brain caused by

Preoperative Risk for Brain Injury

Although studies have traditionally focused on investigating risk factors for brain injury in critical CHD related to surgery and the use of cardiopulmonary bypass, a growing body of evidence supports the notion that preoperative risks may be more significant. This was first observed in infants with TGA. In a study on preoperative brain injury in 22 neonates with TGA, McQuillen et al12 observed that 41% of these neonates had evidence of brain injury on preoperative MRI. Additionally, this study

Anticipatory Management Aimed at Neuroprotection

As longer time between birth and surgery is a risk factor for WMI, it is imperative to identify reasons for delayed timing of surgery. Timing of surgery may be delayed due to postnatal diagnosis, and consequently prenatal diagnosis has been shown to improve neurologic morbidities.34 Prenatal diagnosis also allows for earlier treatment with prostaglandins to prevent circulatory failure and there is ample evidence on how this has mitigated some brain injury.38 However, prostaglandins now appear

Summary

There is a growing body of evidence that the preoperative period carries the greatest risk for development of WMI and consequent neurodevelopmental disabilities. Furthermore, a time-to-surgery of 3-4 days appears to be a threshold beyond which the risk for neurologic morbidity increases.9, 35 This optimal time for surgery needs to be validated in different cardiac diagnoses and also across different institutions with varying preoperative, perioperative, and postoperative care strategies. Once

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      Citation Excerpt :

      Children born with CHD, particularly cyanotic disease, exhibit structural brain abnormalities from birth. Magnetic resonance imaging performed preoperatively demonstrates microcephaly, reduced gyrus folding, and loss of white and gray matter volume2,3, compared with age-matched healthy controls. The white matter injury, phenotypically similar to periventricular leukomalacia, occurs in watershed areas of the developing brain and particularly affects developing oligodendrocytes, critical glial cells responsible for neuronal connections.3

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    1

    Dr Licht is supported by grants from the NINDS, United States (R01NS72338 and RO1NS060653) and NICHD, United States (U01 HD087180-01) support from the June and Steve Wolfson Family Foundation.

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