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.

Elevated methylation of the vault RNA2-1 promoter in maternal blood is associated with preterm birth

“…pPROM is the rupture of the membrane before the onset of labor before 37 weeks of gestation and accounts for one-third of all PTBs [ 37 ]. High levels of pro-inflammatory cytokines such as interleukin (IL)1RA, IL-1β, IL-6, tumor necrosis factor α (TNF- α), monocyte chemotactic protein-1 have been reported in the plasma of pregnant women with pPROM [ 38 ]. In a previous investigation of ours, cytokine levels in the vaginal fluid were higher among pregnant women who delivered preterm with pPROM and PTL compared to women with term deliveries [ 4 ].…”

Specific inflammatory profile in each pregnancy complication: A comparative study

“…We observed in PTB increased CXCL9 levels, a chemokine known for attracting Th1 lymphocytes to an inflamed site, 35 which is in contrast to another recent work. 36 In the latter study, the PTB group included solely women with preterm premature rupture of membranes (PPROM) as oppose to our cohort in which only 46%…”

Phthalate Exposure and Long-Term Epigenomic Consequences: A Review

“…There were also reports of DEHP-induced interleukin-1 secretion in mononuclear cells and in babies born to mothers who suffered from prenatal infection and inflammation (Calo et al, 1993;De Felice et al, 1999, 2002Yang et al, 2000). Case-control studies to study preterm birth in pregnant women revealed that increased levels of ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin Motifs) family-ADAMTS4, ADAMTS5 and proinflammatory cytokines like interleukin (IL)-6, and tumor necrosis factor-α (TNF-α) in mid-trimester amniotic fluid associated with spontaneous preterm delivery (Ronzoni et al, 2018;Melekoglu et al, 2019). These data suggest that the toxicity of periconception phthalate exposure and phthalates' capacity to disrupt pregnancy and birth via endocrine and inflammatory pathways impact development and health across the lifespan.…”