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Intermittent hypoxemia in preterm infants: Glial fibrillary acidic protein as a potential brain injury biomarker
EElie G Abu Jawdeh1, Linda J Van Eldik2, Xiao Xu3
1Department of Pediatrics, UT Southwestern Medical Center, and Children's Medical Center of Dallas, Dallas, TX, United States.
Insights
Intermittent hypoxemia (IH) in preterm infants is linked to brain injury. This study found that urinary glial fibrillary acidic protein (GFAP) levels increase with greater IH exposure, suggesting GFAP is a biomarker for brain injury.
Area of Science:
- Neonatal research
- Biomarker discovery
- Neuroprotection
Background:
- Intermittent hypoxemia (IH) is common in preterm infants and associated with adverse outcomes.
- Previous research linked IH to S100B, a brain injury biomarker.
- This study investigates the relationship between IH and glial fibrillary acidic protein (GFAP), a marker of astrocyte injury.
Purpose of the Study:
- To assess the association between intermittent hypoxemia (IH) metrics and urinary glial fibrillary acidic protein (GFAP) concentrations in preterm infants.
- To determine if GFAP can serve as a noninvasive biomarker for IH-related brain injury in this population.
Main Methods:
- Prospective enrollment of preterm infants (≤32 weeks' gestation).
- Continuous oxygen saturation monitoring and quantification of IH metrics.
- Measurement of urinary GFAP concentrations using an ultrasensitive immunoassay.
- Weighted Spearman correlation analyses to examine associations between IH and GFAP.
Main Results:
- Higher urinary GFAP concentrations correlated with increased IH burden, including duration, frequency, and severity (p <0.001).
- Extremely preterm infants showed associations between GFAP and both short and long IH events.
- Very preterm infants demonstrated associations primarily with longer IH events.
Conclusions:
- Urinary GFAP levels rise with increased intermittent hypoxemia exposure in preterm infants.
- GFAP, along with S100B, may serve as astroglial biomarkers for IH-related brain injury.
- GFAP offers a potential noninvasive tool for early detection of brain injury in vulnerable preterm infants.
Introduction:
Intermittent hypoxemia (IH) frequently occurs in preterm infants and is increasingly linked to adverse outcomes. We previously demonstrated a relationship between IH and S100B, a brain injury biomarker. Here, we assess these relationships with glial fibrillary acidic protein (GFAP), a protein released following astrocyte injury.
Methods:
Infants ≤ 32 weeks' gestation were prospectively enrolled. Oxygen saturation was continuously monitored. IH metrics were quantified using validated algorithms using multiple SpO₂ thresholds. Urine was collected at multiple time points, and GFAP concentrations were measured using an ultrasensitive immunoassay. Infants with severe intraventricular hemorrhage were excluded. Associations between IH metrics and urinary GFAP were examined using weighted Spearman correlation analyses (ρ).
Results:
Twenty-nine infants contributed 71 urine samples with a median of 2.4 samples per infant [IQR 1.0-4.0] collected at a median postnatal age of 36.0 days [IQR 24.0-45.3]. Higher GFAP concentrations were associated with greater IH burden, including greater percent time in hypoxemia (ρ=0.45-0.47), increased IH frequency (ρ=0.42-0.44), longer IH duration (ρ=0.47-0.48), and lower nadir (ρ= -0.42 to -0.44), all p < 0.001. When stratified by gestational age, extremely preterm infants (<28 weeks gestational age) demonstrated strong relationships between GFAP and IH events of both short (<1 min) and longer (≥1 min) duration, whereas very preterm infants (28-31 weeks gestational age) showed significant associations primarily with longer IH events.
Conclusions:
Urinary GFAP levels increase with greater IH exposure in preterm infants. Together with our prior findings for S100B, these results suggest that GFAP represents another astroglial biomarker associated with IH-related brain injury and may provide both mechanistic insight and a noninvasive tool for detecting early brain injury in this vulnerable population.
