European journal of medical research · 2025
Cerebrospinal fluid visinin-like protein, glial cell line-derived neurotrophic factor, and cadherin-6 alterations in pregnancy complications.
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Atalmis Hatice Argun, Kulan Pelin, Tekin Sinem, Guler Emine Yilmaz, Guleroglu Filiz Yarsilikal, Cim Numan, Cetin Ali
Аннотация
BACKGROUND: This exploratory study examined cerebrospinal fluid (CSF) biomarker profiles in pregnancy complications, investigating visinin-like protein 1 (VILIP-1), glial cell line-derived neurotrophic factor (GDNF), and cadherin-6 as indicators of potential central nervous system involvement.
METHODS: A prospective cross-sectional analysis enrolled 110 pregnant women undergoing cesarean delivery with spinal anesthesia: healthy pregnancies (n = 55) and complicated pregnancies (n = 55) comprising hypertensive disorders (n = 21), gestational diabetes (n = 14), preterm labor (n = 12), and fetal growth restriction (n = 8). CSF biomarker concentrations were quantified via enzyme-linked immunosorbent assay.
RESULTS: Complicated pregnancies demonstrated elevated VILIP-1 (median 8.46 [IQR 6.94-10.32] vs. 6.12 [IQR 4.87-7.35] ng/mL, p < 0.001) and reduced GDNF (185.4 [IQR 156.2-208.7] vs. 242.7 [IQR 214.3-274.8] pg/mL, p < 0.001) compared to controls. Cadherin-6 exhibited modest reduction (78.2 [IQR 65.4-92.8] vs. 94.5 [IQR 82.6-108.3] ng/mL, p = 0.003). Stratified analysis identified hypertensive disorders as the primary driver of biomarker alterations (VILIP-1: + 58%; GDNF: - 33%). Restricted correlation analysis within the hypertensive subgroup demonstrated robust associations between biomarkers and clinical severity markers. Multivariate logistic regression confirmed VILIP-1 (aOR 2.14, 95% CI 1.43-3.20, p < 0.001) and GDNF (aOR 0.48, 95% CI 0.32-0.72, p < 0.001) as independent predictors.
CONCLUSION: CSF biomarker alterations in complicated pregnancies, predominantly driven by hypertensive disorders, suggest neuroinflammatory activation and compromised neuroprotection. The heterogeneous grouping of pathophysiologically distinct complications constitutes a primary methodological limitation. These preliminary findings necessitate validation through adequately powered, disease-specific investigations before clinical translation.
METHODS: A prospective cross-sectional analysis enrolled 110 pregnant women undergoing cesarean delivery with spinal anesthesia: healthy pregnancies (n = 55) and complicated pregnancies (n = 55) comprising hypertensive disorders (n = 21), gestational diabetes (n = 14), preterm labor (n = 12), and fetal growth restriction (n = 8). CSF biomarker concentrations were quantified via enzyme-linked immunosorbent assay.
RESULTS: Complicated pregnancies demonstrated elevated VILIP-1 (median 8.46 [IQR 6.94-10.32] vs. 6.12 [IQR 4.87-7.35] ng/mL, p < 0.001) and reduced GDNF (185.4 [IQR 156.2-208.7] vs. 242.7 [IQR 214.3-274.8] pg/mL, p < 0.001) compared to controls. Cadherin-6 exhibited modest reduction (78.2 [IQR 65.4-92.8] vs. 94.5 [IQR 82.6-108.3] ng/mL, p = 0.003). Stratified analysis identified hypertensive disorders as the primary driver of biomarker alterations (VILIP-1: + 58%; GDNF: - 33%). Restricted correlation analysis within the hypertensive subgroup demonstrated robust associations between biomarkers and clinical severity markers. Multivariate logistic regression confirmed VILIP-1 (aOR 2.14, 95% CI 1.43-3.20, p < 0.001) and GDNF (aOR 0.48, 95% CI 0.32-0.72, p < 0.001) as independent predictors.
CONCLUSION: CSF biomarker alterations in complicated pregnancies, predominantly driven by hypertensive disorders, suggest neuroinflammatory activation and compromised neuroprotection. The heterogeneous grouping of pathophysiologically distinct complications constitutes a primary methodological limitation. These preliminary findings necessitate validation through adequately powered, disease-specific investigations before clinical translation.