Association of neonatal inflammatory markers and perinatal stroke subtypes

Abstract

Objective:To examine the relationship between neonatal inflammatory cytokines and perinatal stroke, using a systems biology approach analyzing serum and bloodspot cytokines from 47 patients.Methods:This was a population-based, controlled cohort study with prospective and retrospective case ascertainment. Participants were recruited through the Alberta Perinatal Stroke Project (APSP). Stroke was classified as neonatal arterial ischemic stroke (NAIS), arterial presumed perinatal ischemic stroke (APPIS), or periventricular infarction (PVI). Biosamples were stored bloodspots (retrospective) and acute serum (prospective). Controls had comparable gestational and maternal ages. Sixty-five cytokines were measured (Luminex). Hierarchical clustering analysis was performed to create heat maps. Fisher’s linear discriminant analysis was used to create projection models to determine discriminatory boundaries between stroke types and controls.Results:A total of 197 participants were analyzed (27 NAIS, 8 APPIS, 12 PVI, 150 controls). Cytokines were quantifiable with quality control measures satisfied (standards testing, decay analysis). Linear discriminant analysis had high accuracy in using cytokine profiles to separate groups. Profiles in PVI and controls were similar. NAIS separation was accurate (sensitivity 77%, specificity 97%). APPIS mapping was also distinguishable from NAIS (sensitivity 86%, specificity 99%). Classification tree analysis generated similar diagnostic accuracy.Interpretation:Unique inflammatory biomarker signatures are associated with specific perinatal stroke diseases. Findings support an acquired pathophysiology and suggest the possibility that at-risk pregnancies might be identified to develop prevention strategies.Classification of Evidence:This study provides Class III evidence that differences in acute neonatal serum cytokine profiles can discriminate between patients with specific perinatal stroke diseases and controls.

Advances in the research of nano delivery systems in ischemic stroke

“…According to the location of infarction, it can be divided into total anterior circulation infarction, partial anterior circulation infarction, posterior circulation infarction and lacunar infarction (Jolugbo and Ariëns, 2021). In addition, there is a special type of cerebral infarction, perinatal neonatal stroke, which is mainly manifested as focal nerve damage in the early stage of brain development, including neonatal arterial ischemic stroke, cerebral sinus venous thrombosis and neonatal hemorrhagic stroke (Mineyko et al, 2020). Ischemic stroke has no specific early symptoms, which vary according to the infarct site, size, blocked blood vessels and other reasons.…”

Placental pathologic lesions associated with stroke in term neonates

“…This will require creative utilization of what we already know as well as development of new technologies. Recent studies have focused on identifying inflammatory biomarker signatures in patients at-risk for perinatal stroke ( 41 ), which may improve the ability to detect perinatal stroke early and allow initiation of supportive therapies sooner. Some experts have recommended more widespread use of neuroimaging in neonates with risk factors for stroke ( 42 ), but clear algorithms are still lacking to define which neonates are at highest risk.…”

“…Similarly, nearly half of the cohort did not have placental pathologic examination performed, which underscores the selection bias involved in placentas sent for pathology, although our center has a culture of commonly sending placentas to pathology for any indication related to maternal or fetal pregnancy or peripartum risk factors such as pregnancy complications (e.g. maternal studies have focused on identifying inflammatory biomarker signatures in patients at-risk for perinatal stroke (41), which may improve the ability to detect perinatal stroke early and allow initiation of supportive therapies sooner. Some experts have recommended more widespread use of neuroimaging in neonates with risk factors for stroke (42), but clear algorithms are still lacking to define which neonates are at highest risk.…”

Development and Validation of a Prediction Model for Perinatal Arterial Ischemic Stroke in Term Neonates

“…Unique inflammatory biomarkers collected from acute blood samples from neonates have also been associated with PAIS. 52 Application of our clinical prediction model could be used in combination with such biomarkers within the first 48 hours of life to further enhance early identification.…”