Preeclampsia (PE), affects up to 8% of pregnancies worldwide. The disease has a multiorgan impact and contributes significantly to the burden of maternal morbidity. PE often causes growth restriction in the developing child and alters oxygenation and nutrient transfer, often precipitating pre-term delivery. Cerebral complications of PE, including eclampsia, cerebral edema and stroke are the leading cause of maternal morbidity and mortality. The long-term consequences of PE and associated complications can include increased risk for lesions, stroke, seizure disorders and dementia.
Magnesium sulfate is often prescribed as a treatment strategy for eclampsia. While the mechanism of action is unclear, animal models suggest it may reduce neuroinflammation and improve blood-brain-barrier (BBB) function.
In our latest blog article, in recognition of World Preeclampsia Day 2024, we would like to highlight the pioneering work of Catherine Cluver and Lina Bergman’s research group in Cape Town, South Africa. Lina and Cathy have been profiling women with PE at risk of neuronal complications, providing landmark data on how PE may have neuroinflammatory consequences including disruption of the BBB. Their work provides key insights, in a highly understudied group of patients, on relevant predictive biomarkers and neurologically-based treatment interventions in at-risk patients.
Their first paper on the topic, published in Cells in 2021, included participants from the South African Preeclampsia Obstetric Adverse Events (PROVE) biobank. Women diagnosed with PE and normotensive controls were enrolled in the biobank at admission to Tygerberg Hospital, the largest referral hospital in the Western Cape of South Africa. In 2018, there were 34,422 deliveries in the referral area, with 8,067 referred to Tygerberg Hospital as high risk. The study excluded women with known neurological and cardiac disease. Key to gaining valuable data, was careful and considered sample collection. The study collected blood samples the day before delivery, at delivery and one, two, three and four days postpartum. Critically, cerebrospinal fluid (CSF) was collected at the time of spinal anaesthesia at delivery. Collection and analysis of CSF in these women differentiates this study and permits biomarker discovery in a scarce and highly relevant matrix in the context of neuroinflammatory complications in PE.
Pro-inflammatory cytokines (IL-1β, IL-6, IL-8 and TNF-α) were measured in CSF. The CSF/plasma albumin ratio served as an indicator of BBB integrity. There were no other neurological complications such as stroke and all women with eclampsia and PE were treated with magnesium sulfate until after delivery. Interestingly, women with eclampsia showed significantly increased CSF levels of IL-6, IL-8 and TNF-α when compared to normotensive and PE women. Women with PE had significantly higher levels of IL-6 and IL-8 compared to normotensive controls. Additionally, both eclamptic and preeclamptic women had elevated CSF/plasma albumin ratios, demonstrating disruption of the BBB. All of the eclamptic women had an albumin quotient above the corresponding reference value, demonstrating the severity of BBB disruption.
The clinical implications of these findings are severe. Disruption of the BBB and neuroinflammation have been linked to long-term neurological outcomes including neurodegenerative disease and loss of cognitive function. Understanding predictive biomarkers that may stratify those patients at risk are crucial in managing treatment for these women. It is important that larger studies be conducted to confirm these findings but also broaden the biomarker net, including additional markers related to neuronal function. Data from these studies can help educate clinicians on appropriate treatments to reduce neuroinflammation and restore BBB integrity, improving the long-term outlook for patients.
New technologies like Olink, may provide even greater insight into novel biomarkers in these women. Using only a single microliter of sample matrix, this technology is uniquely suited for biomarker discovery in situations where samples are very limited. As research into neurological complications of PE continues to grow, Synexa is proud to support research into this field, providing insights and analysis to broaden our knowledge base for improving the quality of human health.
Key reference:
- Â Â Â Bergman et al. Cells. 2021 Nov 5;10(11):3045
