A protein microarray analysis of amniotic fluid proteins for the prediction of spontaneous preterm delivery in women with preterm premature rupture of membranes at 23 to 30 weeks of gestation

• Published in: PloS one 2020-12, Vol.15 (12), p.e0244720-e0244720
• Main Authors: Kim, Hyeon Ji, Park, Kyo Hoon, Kim, Yu Mi, Joo, Eunwook, Ahn, Kwanghee, Shin, Sue
• Format: Article
• Language: English
• Subjects: Adult; Amniocentesis; Amniotic fluid; Amniotic Fluid - metabolism; Antibodies; Antibody microarrays; Biology and Life Sciences; Biomarkers; Biomarkers - metabolism; Case-Control Studies; Complications and side effects; Cytokines; Endostatin; Etiology; fas Receptor - metabolism; Female; Fetal alcohol syndrome; Fetal Membranes, Premature Rupture - metabolism; Gelatinase B; Gestation; Gestational age; Gynecology; Health aspects; Health risks; Humans; Infant, Newborn; Inflammation; Inflammatory response; Interleukin 8; Interleukin-8 - metabolism; Laboratories; Lipocalin; Matrix Metalloproteinase 9 - metabolism; Medical schools; Medicine; Medicine and Health Sciences; Membranes; Methods; Obstetric Labor, Premature - metabolism; Obstetrics; Pregnancy; Premature birth; Premature Birth - diagnosis; Premature Birth - metabolism; Premature rupture of membranes; Prognosis; Protein Array Analysis; Protein arrays; Protein microarrays; Proteins; Quartiles; Research and Analysis Methods; Retrospective Studies; Risk factors; Rupture; Rupturing; Sampling; Women
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0244720

We sought to identify novel biomarkers in the amniotic fluid (AF) related to imminent spontaneous preterm delivery (SPTD) (≤ 14 days after sampling) in women with early preterm premature rupture of membranes (PPROM), using a protein microarray. This was a retrospective cohort study of a total of 88 singleton pregnant women with PPROM (23+0 to 30+6 weeks) who underwent amniocentesis. A nested case-control study for biomarker discovery was conducted using pooled AF samples from controls (non-imminent delivery, n = 15) and cases (imminent SPTD, n = 15), which were analyzed using an antibody microarray. Quantitative validation of four candidate proteins was performed, using ELISA, in the total cohort (n = 88). IL-8, MMP-9, and Fas levels were additionally measured for the comparison and to examine association of SPTD with the etiologic factors of PPROM. Of all the proteins studied in the protein microarray, four showed significant intergroup differences. Analyses of the total cohort by ELISA confirmed the significantly elevated concentrations of AF lipocalin-2, MMP-9, and S100 A8/A9, but not of endostatin and Fas, in women who delivered within 14 days of sampling. For inflammatory proteins showing a significant association, the odds of SPTD within 14 days increased significantly with an increase in baseline AF levels of the proteins (P for trend