Pentraxin 3 in maternal circulation: An association with preterm labor and preterm PROM, but not with intra-amniotic infection/inflammation

Abstract

Objective Pentraxin 3 (PTX3) is an acute-phase protein that has an important role in the regulation of the innate immune response. The aim of this study was to determine if maternal plasma PTX3 concentration changes in the presence of intra-amniotic infection and/or inflammation (IAI) in women with preterm labor (PTL) and intact membranes as well as those with preterm prelabor rupture of membranes (preterm PROM). Study design This cross-sectional study included women in the following groups: 1) non-pregnant (n=40); 2) uncomplicated pregnancies in the first (n=22), second (n=22) or third (n=71, including 50 women at term not in labor) trimester; 3) uncomplicated pregnancies at term with spontaneous labor (n=49); 4) PTL and intact membranes who delivered at term (n=49); 5) PTL without IAI who delivered preterm (n=26); 6) PTL with IAI (n=65); 7) preterm PROM without IAI (n=25); and 8) preterm PROM with IAI (n=77). Maternal plasma PTX3 concentrations were determined by ELISA. Results 1) Maternal plasma PTX3 concentrations increased with advancing gestational age (r= 0.62, p<0.001); 2) women at term with spontaneous labor had a higher median plasma PTX3 concentration than those at term not in labor (8.29 ng/mL vs. 5.98 ng/mL, p=0.013); 3) Patients with an episode of PTL, regardless of the presence or absence of IAI and whether these patients delivered preterm or at term, had a higher median plasma PTX3 concentration than normal pregnant women (p<0.001 for all comparisons); 4) Similarly, patients with preterm PROM, with or without IAI had a higher median plasma PTX3 concentration than normal pregnant women (p<0.001 for both comparisons); and 5) Among patients with PTL and those with preterm PROM, IAI was not associated with significant changes in the median maternal plasma PTX3 concentrations. Conclusions The maternal plasma PTX3 concentration increases with advancing gestational age and is significantly elevated during labor at term and in the presence of spontaneous preterm labor or preterm PROM. These findings could not be explained by the presence of IAI, suggesting that the increased PTX3 concentration is part of the physiologic or pathologic activation of the pro-inflammatory response in the maternal circulation during the process of labor at term or preterm.

Characterization of the myometrial transcriptome and biological pathways of spontaneous human labor at term

“…Each of these pathways is central in the deployment of an inflammatory response: cytokine-cytokine receptor interaction, Jak-STAT signaling, the complement and coagulation pathway, NOD-like receptor signaling, systemic lupus erythematosus (specifically the complement C1q complex), and chemokine signaling. Interestingly, components of these pathways have been previously linked to both normal parturition [57, 75, 76, 159, 180, 201, 213, 221, 226–228, 235, 271, 274, 308] and the “Great Obstetrical Syndromes” [32, 33, 64, 79–82, 84, 85, 89, 238, 267, 291, 295, 307, 320], including preterm labor [28, 58, 74, 77, 83, 86–88, 119, 120, 164, 165, 211, 223, 246, 252, 254, 290, 292, 293, 316–319]. Indeed, our group has reported an association between activation of the NALP3 inflammasome and the common pathway of parturition [119].…”

Noninvasive Sampling of the Intrauterine Environment in Women with Preterm Labor and Intact Membranes

“…They found the lowest concentrations in women with infection (based on amniotic fluid culture) or with IAI (based on amniotic fluid IL-6 levels). However, the same group did not find differences in levels of pentraxin-3 in maternal plasma [50] between women exposed and not exposed to this infectious/inflammatory condition. Finally, Park et al [51] suggested maternal serum C-reactive protein as an independent predictor of IAI (based on amniotic fluid matrix metalloproteinase-8 levels).…”

Increased expression of pentraxin 3 in placental tissues from patients with unexplained recurrent pregnancy loss

“…Recent studies indicate that the highest PTX3 levels in plasma occur during labor [13,14,26]. Moreover, significant differences in plasma PTX3 levels were observed between women with differing types of delivery.…”