Inflammatory Marker Levels in Preeclampsia versus Normal Pregnancies and Prediction of Preeclampsia Occurrence: A Prospective Mixed Methods Study

Abstract

Introduction: Preeclampsia is an important cause of adverse maternal and perinatal outcomes. However, this condition remains poorly understood, and since the only cure is delivery, prediction and prevention are crucial to prevent preterm birth or maternal compromise. Aim: To determine the levels of acute phase reactants, namely high-sensitivity C-reactive Protein (hsCRP) and fibrinogen, between preeclamptic and non preeclamptic pregnancies. Additionally, the study aims to determine the predictive value of these acute phase reactants for preeclampsia. Materials and Methods: A prospective mixed methods study was conducted in two tertiary hospitals and two specialist hospitals in the Ijebu/Remo axis of Ogun state, Nigeria. Preeclamptic participants were recruited during pregnancy and postpartum and matched with non preeclamptic controls (case-control arm, n=179, comprised of 87 preeclamptics and 92 controls). Additionally, a cohort of non preeclamptic women (n=71) was recruited and biomarker-assayed before 20 weeks gestation, followed-up for the development of preeclampsia. The biomarker assay was performed using the ELISA technique. The Student's t-test was used to compare the mean levels of markers between the studied groups. Categorical data were compared using the Chi-square test. A p-value <0.05 was considered to be statistically significant. Results: The levels of hsCRP were significantly higher in pregnant preeclamptic women (12.71±1.99 mg/L) compared to non preeclamptic women (4.39±3.41 mg/L) (p-value=0.001). Similarly, fibrinogen levels were elevated in preeclamptic women (9.45±1.28 g/L) compared to non preeclamptic women (7.19±1.86 g/L) (p-value =0.001). This trend was also observed among postpartum women, with hsCRP levels of 10.39±2.43 mg/L in preeclamptics compared to 2.53±2.06 mg/L in non preeclamptics (p-value=0.001). The mean fibrinogen level was 8.63±1.91 g/L in preeclamptics compared to 4.09±1.66 g/L in non preeclamptics. Fibrinogen demonstrated a higher specificity (88.9%) and Negative Predictive Value (NPV) of 100% compared to hsCRP (specificity=47.1% and NPV=76.1%). The biomarker levels also correlated significantly with the severity of preeclampsia. For hsCRP, there was a correlation with Systolic Blood Pressure (SBP) (r-value=0.385, p-value=0.001), Diastolic Blood Pressure (DBP) (r-value=0.364, p-value=0.001), and proteinuria (r-value=0.314, p-value=0.001). For fibrinogen, there was a correlation with SBP (r-value=0.252, p-value=0.014), DBP (r-value=0.378, p-value=0.001), and proteinuria (r-value=0.356, p-value=0.001). Conclusion: Although hsCRP and fibrinogen levels were significantly higher and correlated well with the severity of preeclampsia, their use for prediction may be limited. However, fibrinogen appears to have better prospects.