Cytokine Changes in Maternal Peripheral Blood Correlate With Time-to-Delivery in Pregnancies Complicated by Premature Prelabor Rupture of the Membranes

Abstract

Premature prelabor rupture of the membranes (PPROM) causes one-third of preterm births worldwide and is most likely caused by subclinical intrauterine infection and/or inflammation. We proposed that women with systemic inflammation at the time of PPROM would have shorter latency. Peripheral blood samples were collected from 20 singleton pregnant women with PPROM between 23 ± 1 and 33 ± 6 weeks. The first sample was drawn within 48 hours of admission, followed by weekly blood draws until delivery. Pregnancies complicated with acute chorioamnionitis, preeclampsia, intrauterine growth restriction, obesity, substance abuse, and chronic maternal disease were excluded. Twenty uncomplicated, gestational age-matched pregnancies served as controls. Plasma concentration of 39 cytokines was measured longitudinally using Luminex assays to investigate their value as predictive biomarkers of latency. Women with PPROM exhibited significantly lower plasma concentration of interferon-γ-inducible protein 10-Chemokine (c-x-c motif; IP10/CXCL10), Chemokine (c-x-c motif) Ligand 9 (MIG/CXCL9), Platelet-derived growth factor BB (PDGFbb), and cutaneous T cell-attracting chemokine, also known as CCL27/CCL27 than controls at admission but significantly elevated interleukin (IL)1RA, tumor necrosis factor α, monocyte chemotactic protein-1/CCL2 at delivery compared to admission. Women with PPROM who delivered within 7 days had significantly lower plasma concentration of anti-inflammatory cytokine IL1RA than those with latency periods >7 days. The IL1RA and endotoxin activity in conjunction with clinical parameters results in excellent prediction of latency to delivery (area under the receiver–operating characteristic curve = 0.91). We concluded that higher levels of anti-inflammatory cytokines in women with PPROM were associated with increased latency until delivery, likely due to counterbalancing of proinflammatory load. When used in conjunction with other predictive characteristics of time until delivery, cytokines may further assist clinical decision-making and optimize pregnancy outcomes in women with PPROM.