Antibody Microarray Analysis of Plasma Proteins for the Prediction of Histologic Chorioamnionitis in Women With Preterm
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Reproductive Sciences 1-9 ª The Author(s) 2019 Article reuse guidelines: sagepub.com/journals-permissions DOI: 10.1177/1933719119828043 journals.sagepub.com/home/rsx
Jeong Woo Park, MD, PhD1, Kyo Hoon Park, MD, PhD1 , Ji Eun Lee, PhD2, Yu Mi Kim, PhD1, Se Jin Lee, MD1, and Dong Huey Cheon, MS2,3
Abstract We aimed to identify maternal blood biomarkers predictive of histologic chorioamnionitis (HCA) in the plasma of women with preterm premature rupture of membranes (PPROM) and to determine whether the combination of these biomarkers with conventional clinical variables can improve the prediction of HCA. This retrospective cohort study included 82 consecutive women with PPROM (23-34 gestational weeks) who delivered within 96 hours of blood sampling. A membrane-based human antibody microarray was used to analyze the plasma proteome. The validation of 5 candidate biomarkers of interest was performed by enzyme-linked immunosorbent assay (ELISA) in the final cohort (n ¼ 82). Serum C-reactive protein (CRP) levels were measured at sampling. Seventy-nine molecules studied exhibited intergroup differences. Validation by ELISA confirmed higher levels of plasma matrix metalloproteinase-9 (MMP-9), interleukin-6 (IL-6), S100 A8/A9, and insulin-like growth factor-binding protein 1 (IGFBP-1), but not tissue inhibitor of metalloproteinase 1 (TIMP-1), in women with HCA than in women without HCA. Using a stepwise regression analysis, a combined prediction model was developed, which included the plasma MMP-9, serum CRP levels, and gestational age (area under the curve [AUC], 0.932). The AUC for this model was significantly greater than that for any single variable included in the predictive model. Protein–antibody microarray technology can be useful in identifying plasma-based predictors for HCA. This study suggests that plasma MMP-9, IL-6, IGFBP-1, and S100 A8/A9 are important noninvasive predictors for HCA in women with PPROM and that the best predictive model, which combined these biomarkers with conventional clinical factors, can significantly improve the predictability for HCA. Keywords antibody microarray, biomarkers, histologic chorioamnionitis, plasma, preterm premature rupture of membranes
Introduction Preterm premature rupture of the membranes (PPROM), occurring approximately in one-third of all preterm births, is most strongly associated with the presence of inflammation within the placenta, which is often clinically silent. Importantly, several studies have suggested that histologic chorioamnionitis (HCA) confers additional risks for adverse maternal and neonatal outcomes, including earlier gestational age at delivery, neonatal sepsis, neurologic morbidity, hearing impairment, and death.1-5 Therefore, a more accurate and early prenatal identification of subclinical HCA using a noninvasive test is needed to allow decisions to be made regarding treatment strategies and counseling of patients with PPROM. Traditionally, investigators have considered inflammatory biomarkers in amniotic fluid (AF) as useful predictors of subcl
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