Original ArticleEarly Use of Transcranial Doppler Ultrasonography to Stratify Neonatal Encephalopathy
Introduction
Neonatal therapeutic hypothermia (TH) was designed to improve neurological outcomes in newborns with hypoxic-ischemic encephalopathy (HIE) who sustain a sentinel event and acute asphyxial injury. However, the etiology of HIE is heterogeneous and response to treatment is likely to vary depending on the timing and type of underlying insult.1, 2, 3 At present, clinicians have to rely on a neurological examination done within the six-hour short therapeutic window to identify infants with moderate or severe HIE and initiate TH as per evidence-based published trials.4,5 This limited therapeutic window contrasts with the dynamic evolving nature of the neonatal encephalopathy assessed by the Sarnat score.6 This contrast is the root cause of the conundrum in the management and recognition of mild encephalopathy where a subset of infants are at high risk for brain injury but are not correctly identified in the first day after birth.7, 8, 9, 10 Infants labeled under the broad umbrella of mild HIE in the first six hours after birth can have abnormal outcomes from an antenatal outcome or from progressing after birth to have increasing severity of HIE.11
In addition to the clinical assessment, there is an urgent need for easily obtainable bedside biomarkers to identify in real time those infants who are at the highest risk of disability but are not currently receiving any therapeutic interventions.12,13
Following a perinatal asphyxial insult, there is an initial adaptive vasodilatation with decreased cerebral vascular tone to maintain oxygen delivery to the brain tissue. In profoundly affected infants, an impaired vascular autoregulation occurs with a reperfusion injury leading to abnormal outcomes.14 Transcranial Doppler (TCD) ultrasonography enables continuous, noninvasive, and objective bedside monitoring of the changes in cerebral hemodynamics, including autoregulation. Using this modality, the blood flow velocities can be obtained, and resistance index (RI) can be calculated to reflect the downstream resistance to blood flow in a cerebral vessel. The objectives of this study were to evaluate the resistive indices of the middle cerebral artery (MCA) in infants with perinatal asphyxia to optimally stratify the severity classification within the first 24 hours of life and identify infants with an evolving, worsening encephalopathy.
Section snippets
Eligibility
This prospective cohort study was conducted between April 2018 and November 2019. Neonates were screened for eligibility if born at ≥ 36 weeks and 0 days gestation with birth asphyxia, defined as (1) an abnormal blood gas pH of ≤7.0 or base deficit ≥ 16 mmol/L or (2) an abnormal blood gas with a pH between 7.01 and 7.15 or a base deficit ≥ 10 and an Apgar score of 5 at 10 minutes or positive pressure ventilation for 10 minutes at delivery. Those who fit the biochemical and clinical criteria
Results
A total of 60 infants enrolled in this study, with 23 controls with no encephalopathy, 18 infants with mild HIE, and 19 infants with moderate or severe HIE (Fig 2). There were no differences seen in maternal characteristics, including perinatal complications, but Apgar scores at one and five minutes were significantly lower in infants with moderate and severe HIE (P < 0.01). Those infants were also more likely to receive resuscitation in the delivery room (i.e., positive pressure ventilation,
Discussion
Key findings in this contemporary, prospective study were that Doppler ultrasonography of the MCA is (1) feasible in the first 24 hours after birth, (2) requires little training for the angle insonnation and the replicability of measures among observers, and (3) could be a useful adjunct to indicate the timing and severity of HIE in the first day after birth. Repurposing an old-established modality for use on the first postnatal day allows RIs to be easily measured soon after birth and can
Conclusion
TCD RI can be serially obtained in real-time at the bedside and is a promising adjunct biomarker to indicate the timing and the severity of neonatal HIE. The findings in this article are promising for the reintroduction of Doppler ultrasonography in the neonatal intensive care unit as an invaluable tool in therapeutic decision-making, especially in situations in which the encephalopathy progression is clinically unclear. In the future, studies with larger numbers are needed with correlation to
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Cited by (6)
Does abnormal Doppler on cranial ultrasound predict disability in infants with hypoxic-ischaemic encephalopathy? A systematic review
2022, Developmental Medicine and Child NeurologyCerebral Oxygenation and Metabolism After Hypoxia-Ischemia
2022, Frontiers in Pediatrics
Contributors' Statement: Dr. Natique performed and implemented all study measures and drafted, reviewed, and revised the manuscript. Mr. Das developed MATLAB data extraction algorithm. Ms. Maxey and Ms. Sepulveda worked on data collection instruments, collected data, and performed Doppler US measurements. Mr. Brown performed biostatistical analysis of study data. Dr. Chalak initiated the study concept and design and reviewed and finalized the submitted manuscript. All authors participated in the study and approved the final manuscript as submitted.
Funding: Dr. Lina Chalak is funded by NIH Grant 5R01NS102617-03.
Conflict of Interest: The authors have declared that there is no conflict of interest.
Category of Study: Clinical research.
Consent: Neonates were enrolled to study after parents signed written consent to participate.