Cerebral microhemorrhages in children with congenital heart disease: Prevalence, risk factors, and impact on neurodevelopmental outcomes

Abstract

Background: Infants with complex congenital heart disease (CHD) require life-saving corrective/palliative heart surgery in the first weeks of life. These infants are at risk for brain injury and poor neurodevelopmental outcomes. Cerebral microhemorrhages (CMH) are frequently seen after neonatal bypass heart surgery, but it remains unknown if CMH are a benign finding or constitute injury. Herein, we investigate the risk factors for developing CMH and their clinical significance. Methods: 192 infants with CHD undergoing corrective cardiac surgery with cardiopulmonary bypass (CPB) at a single institution were prospectively evaluated with pre- (n = 183) and/or postoperative (n = 162) brain magnetic resonance imaging (MRI). CMH severity was scored based on total number of microhemorrhages. Antenatal, perioperative, and postoperative candidate risk factors for CMH and neurodevelopmental (ND) outcomes were analyzed. Eighteen-month neurodevelopmental outcomes were assessed using the Bayley-III Scales of Infants and Toddler Development in a subset of patients (n = 82). Linear regression was used to analyze associations between risk factors or ND outcomes and presence/number of CMH. Results: The most common CHD subtypes were hypoplastic left heart syndrome (HLHS) (37%) and transposition of the great arteries (TGA) (33%). Forty-two infants (23%) had CMH present on MRI before surgery and 137 infants (85%) post-surgery. No parameters evaluated were significant risk factors for preoperative CMH. In multivariate analysis, cardiopulmonary bypass (CPB) duration (p < 0.0001), use of extracorporeal membrane oxygenation (ECMO) support (p < 0.0005), postoperative seizure(s) (p < 0.03), and lower birth weight (p < 0.03) were associated with new or worsened CMH postoperatively. Higher CMH number was associated with lower scores on motor (p < 0.03) testing at 18 months. Conclusion: CMH is a common imaging finding in infants with CHD with increased prevalence and severity after CPB and adverse impact on neurodevelopmental outcomes starting at a young age. Longer duration of CPB and need for postoperative ECMO were the most significant risk factors for developing CMH. However, presence of CMH on preoperative scans indicates non-surgical risk factors that are yet to be identified. Neuroprotective strategies to mitigate risk factors for CMH may improve neurodevelopmental outcomes in this vulnerable population.

Competing Interest Statement

The authors have declared no competing interest.

Clinical Trial

N/A

Funding Statement

National Institutes of Health (NIH R01 (NS072338)) Steve and June Wolfson Family Foundation Brian R White is supported by the National Institute of Neurological Disorders and Stroke (K08 NS117897)

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

CHOP IRB 11-008191

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Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

Data Availability

The data that supports the findings of this study are available upon reasonable request from the corresponding author.

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