Low Variability of Blood Pressure Predicts Abnormal Electroencephalogram in Infants with Hypoxic Ischemic Encephalopathy

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Hypoxic-ischemic encephalopathy (HIE) (n=91). Intervention: Composite model of clinical predictors and time- and frequency-domain mean arterial blood pressure (MABP) variability metrics (21-24 hours after birth) vs. Perinatal clinical predictor variables alone (5-minute or 10-minute Apgar score, Sarnat stage, and arterial cord pH). Primary outcome: Moderate-to-severe grade abnormal electroencephalogram (EEG) background pattern or electrographically confirmed seizures at 48 hours (AUC 0.86 vs AUC 0.66-0.68).

Q: What does this research mean for the field?

Combining early time- and frequency-domain arterial blood pressure variability metrics with perinatal clinical predictors substantially improves the prediction of adverse 48-hour EEG outcomes in infants with hypoxic-ischemic encephalopathy. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

Abigail Flower; Daniel Vasiliu; Tianrui Zhu; Robert T. Andris; Maryam Abubakar; Karen D. Fairchild; Santina Zanelli; Julie A. Matsumoto; Amit Mathur; J. B. Delos; Zachary A. Vesoulis

doi:10.1055/s-0040-1715822

August 20, 2020American Journal of PerinatologyOpen Access

Low Variability of Blood Pressure Predicts Abnormal Electroencephalogram in Infants with Hypoxic Ischemic Encephalopathy

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Key result

Adding arterial pressure variability to clinical predictors improves 48-hour EEG outcome prediction in HIE infants.

AUC 0.86 vs AUC 0.66-0.68
n=91

Why the study?

The study aimed to evaluate arterial blood pressure variability as an objective physiologic biomarker for early identification of adverse short-term EEG outcomes in infants with hypoxic-ischemic encephalopathy.

Does adding early time- and frequency-domain mean arterial blood pressure variability metrics to perinatal clinical predictors improve the prediction of abnormal 48-hour EEG background in infants with hypoxic-ischemic encephalopathy?

Key Points

To evaluate arterial blood pressure variability as an objective physiologic biomarker for the early prediction of adverse short-term electroencephalogram outcomes in infants with hypoxic-ischemic encephalopathy.
Multicenter observational study analyzing 91 infants with neonatal encephalopathy diagnosed by modified Sarnat exam, continuous mean arterial blood pressure recorded between 18 and 27 hours after birth, and continuous EEG monitoring for at least 48 hours.
Computed standardized time-domain metrics and power spectral density without interpolation, using multivariate binary logistic regression to evaluate predictive power for moderate-severe EEG abnormalities at 48 hours.
At 48 hours, 58% (53/91) of infants had normal or mildly abnormal EEG backgrounds, 42% (38/91) had moderate or severe EEG backgrounds, and 11% (10/91) died.
Standard clinical predictors (5-minute Apgar score, Sarnat stage, and cord pH) were modestly predictive of 48-hour EEG outcomes, with an AUC of 0.66 to 0.68.
A composite model combining clinical predictors with optimal time- and frequency-domain blood pressure variability metrics substantially improved predictive accuracy, achieving an AUC of 0.86.

Study Design

Type

Cohort (n=91)

Multicenter

Yes

Structured PICO

Does adding early time- and frequency-domain mean arterial blood pressure variability metrics to perinatal clinical predictors improve the prediction of abnormal 48-hour EEG background in infants with hypoxic-ischemic encephalopathy?

P

Population

91 neonates with hypoxic-ischemic encephalopathy undergoing therapeutic hypothermia (mean gestational age 38.4 weeks, 42.9% female) across two US centers, monitored with invasive arterial blood pressure from 18-27 hours of life and continuous EEG for at least 48 hours.

E

Exposure

Composite predictive model incorporating continuous invasive mean arterial blood pressure (MABP) variability metrics between 21 and 24 hours after birth—specifically time-domain (standard deviation of the first difference of MABP) and frequency-domain (total spectral power in the 25-65 mHz band)—combined with perinatal clinical predictors and adjusted for inotrope exposure

C

Comparator

Standard perinatal clinical predictor variables alone (5-minute or 10-minute Apgar score, worst Sarnat stage in first 6 hours, and arterial cord blood pH)

O

Outcome

Unfavorable short-term electroencephalogram (EEG) outcome at 48 hours after birth, defined as moderately abnormal (loss of cyclicity and discontinuous activity) or severely abnormal (burst suppression or isoelectric activity) EEG background pattern, or presence of electrographically confirmed seizuressurrogate

Main Result

Effect estimate: AUC 0.86 vs AUC 0.66-0.68

Limitations

Analytic methods used are best suited to linear systems with stationary statistical properties, whereas non-linear effects may be present
Primary outcome was 48-hour EEG background rather than long-term neurodevelopmental follow-up
Relatively small sample size from two centers requiring external validation across centers with differing clinical practices
Preliminary pilot analysis not yet sufficiently validated for routine clinical use
Analytic methods assume linear systems with stationary statistical properties and may not capture non-linear physiological effects
Primary outcome was short-term 48-hour EEG background rather than long-term neurodevelopmental outcome
Modest sample size (n=91) across two centers, requiring validation in larger multicenter cohorts
Preliminary pilot analysis not yet validated for routine clinical application

Implication

Early time- and frequency-domain arterial blood pressure variability metrics measured at 21-24 hours of life substantially improve the prediction of 48-hour adverse EEG outcomes over standard perinatal clinical variables in neonates with hypoxic-ischemic encephalopathy.

Abstract

OBJECTIVE: This study aimed to evaluate the role of an objective physiologic biomarker, arterial blood pressure variability, for the early identification of adverse short-term electroencephalogram (EEG) outcomes in infants with hypoxic-ischemic encephalopathy (HIE). STUDY DESIGN: In this multicenter observational study, we analyzed blood pressure of infants meeting these criteria: (1) neonatal encephalopathy determined by modified Sarnat exam, (2) continuous mean arterial blood pressure (MABP) data between 18 and 27 hours after birth, and (3) continuous EEG performed for at least 48 hours. Adverse outcome was defined as moderate-severe grade EEG at 48 hours. Standardized signal preprocessing was used; the power spectral density was computed without interpolation. Multivariate binary logistic regression was used to identify which MABP time and frequency domain metrics provided improved predictive power for adverse outcomes compared with standard clinical predictors (5-minute Apgar score and cord pH) using receiver operator characteristic analysis. RESULTS: Ninety-one infants met inclusion criteria. The mean gestational age was 38.4 ± 1.8 weeks, the mean birth weight was 3,260 ± 591 g, 52/91 (57%) of infants were males, the mean cord pH was 6.95 ± 0.21, and 10/91 (11%) of infants died. At 48 hours, 58% of infants had normal or mildly abnormal EEG background and 42% had moderate or severe EEG backgrounds. Clinical predictor variables (10-minute Apgar score, Sarnat stage, and cord pH) were modestly predictive of 48 hours EEG outcome with area under curve (AUC) of 0.66 to 0.68. A composite model of clinical and optimal time- and frequency-domain blood pressure variability had a substantially improved AUC of 0.86. CONCLUSION: Time- and frequency-domain blood pressure variability biomarkers offer a substantial improvement in prediction of later adverse EEG outcomes over perinatal clinical variables in a two-center cohort of infants with HIE. KEY POINTS: · Early outcome prediction in HIE is suboptimal.. · Patterns in blood pressure physiology may be predictive of short-term outcomes.. · Early time- and frequency-domain measures of blood pressure variability predict short-term EEG outcomes in HIE infants better than perinatal factors alone..

Discussion

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Cite This Study

Flower et al. (2020) conducted a cohort in Hypoxic-ischemic encephalopathy (HIE) (n=91). Composite model of clinical predictors and time- and frequency-domain mean arterial blood pressure (MABP) variability metrics (21-24 hours after birth) vs. Perinatal clinical predictor variables alone (5-minute or 10-minute Apgar score, Sarnat stage, and arterial cord pH) was evaluated on Moderate-to-severe grade abnormal electroencephalogram (EEG) background pattern or electrographically confirmed seizures at 48 hours (AUC 0.86 vs AUC 0.66-0.68). Time- and frequency-domain mean arterial blood pressure variability combined with clinical predictors improved prediction of 48-hour adverse EEG outcomes in HIE infants (AUC 0.86 vs 0.66-0.68).

synapsesocial.com/papers/6a7db736603f5e16dd33a0cf https://doi.org/10.1055/s-0040-1715822

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Low Variability of Blood Pressure Predicts Abnormal Electroencephalogram in Infants with Hypoxic Ischemic Encephalopathy

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

Low Variability of Blood Pressure Predicts Abnormal Electroencephalogram in Infants with Hypoxic Ischemic Encephalopathy

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

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