Altered angiogenic and neuroinflammatory markers in peripartum individuals with and without severe preeclampsia compared to non-pregnant adults
Noora Haghighi1, Mary Claire Tuohy4, Natalie Bello5, Whitney Booker4, Andrea Miltiades2, Ronald Wapner3, Randolph Marshall1, Eliza Miller1
1Neurology, 2Anesthesiology, 3Obstetrics and Gynecology, Columbia University, 4Columbia University, 5Cardiology, Cedars-Sinai
Objective:
To characterize angiogenic and neuroinflammatory cytokine levels in serum and cerebrospinal fluid (CSF) of peripartum individuals with and without preeclampsia.
Background:
Preeclampsia, a hypertensive disorder of pregnancy associated with systemic endothelial dysfunction, carries high risk of neurovascular complications. Preliminary studies suggest maternal blood-brain barrier (BBB) dysfunction in preeclampsia.
Design/Methods:
We analyzed serum from 26 peripartum participants (13 severe preeclampsia, 13 normotensive controls), of whom 13 participants (7 cases, 6 controls) also had CSF available for analysis. ProcartaPlex and ELISA immunoassays were used to quantify angiogenic and neuroinflammatory proteins implicated in BBB dysfunction in serum and separately CSF. We used t-test or Wilcoxon tests to compare levels between participants with and without preeclampsia. We next compared our values to published normative values for healthy non-pregnant adults. We did not correct for multiple comparisons for this exploratory analysis.
Results:
We found no statistically significant difference in serum or CSF levels of angiogenic (VEGF, PlGF, and sFLT1) or neuroinflammatory (CCL5/RANTES, GM-CSF, CXCL10) markers between normotensive peripartum controls and those with severe preeclampsia. Compared to historical non-pregnant controls, serum levels in both cases and controls were lower of VEGF (p<0.005 for both comparisons), CCL5 (p<0.002 for both comparisons), and CXCL10 (p<0.0.002 for both comparisons), and sFLT1 and GM-CSF were higher (p<0.02 for all comparisons). In CSF analyses, the concentration of CXCL10 was significantly lower (p<0.002 for both comparisons) and sFLT1 was significantly higher (p<0.03 for both comparisons), compared with non-pregnant adult reference values.
Conclusions:
In this pilot study, angiogenic and neuroinflammatory profiles in the serum and CSF of peripartum individuals with and without severe preeclampsia were not significantly different. However, when compared with normative values for healthy non-pregnant adults, peripartum individuals demonstrate alterations in factors regulating BBB permeability. Our results suggest that the peripartum state may be associated with changes in BBB regulation, regardless of preeclampsia diagnosis.