Amniotic fluid sTREM-1 in normal pregnancy, spontaneous parturition at term and preterm, and intra-amniotic infection/inflammation.
OBJECTIVE
Intra-amniotic infection/inflammation (IAI) is one of the most important mechanisms of disease in preterm birth. Triggering receptor expressed on myeloid cells (TREM)- 1 is a transmembrane glycoprotein expressed by neutrophils, macrophages and mature monocytes. TREM-1 is upregulated in biological fluids and tissues infected by Gram (+) and Gram (-) bacteria and fungi, amplifies the production of pro-inflammatory cytokines and chemokines, and its soluble form (sTREM-1) is released in the presence of infection. The aim of this study was to determine the effect of gestational age, parturition (term and preterm) and IAI in the amniotic fluid (AF) concentrations of sTREM-1.


METHODS
This cross-sectional study included 434 patients in the following groups: (1) mid-trimester of pregnancy (14-18 weeks, n = 38); (2) normal pregnant women at term with (n = 39) and without (n = 39) labor; (3) patients with spontaneous preterm labor (PTL) and intact membranes classified into: (a) PTL who delivered at term (n = 99); (b) PTL who delivered preterm (<37 weeks gestation) without IAI (n = 80); and (c) PTL with IAI (n = 59); and (4) women with preterm prelabor rupture of membranes (PROM) with (n = 40) and without (n = 40) IAI. The AF concentration of sTREM-1 was determined by enzyme-linked immunoassay. Non-parametric statistics were used for analyses.


RESULTS
(1) sTREM-1 was detected in all the AF samples; (2) the median AF sTREM-1 concentration at term was higher than in the mid-trimester (4277.6 pg/ml vs. 1140.4 pg/ml; p < 0.001); (3) among patients with PTL, the median AF sTREM-1 concentration was higher in patients with IAI than in those without IAI (6154.4 pg/ml vs. 3282.8 pg/ml; p < 0.001) and those with PTL who delivered at term (6154.4 pg/ml vs. 2794 pg/ml; p < 0.001); (4) patients with preterm PROM with IAI had a higher median AF sTREM-1 concentration than those without IAI (7893.1 pg/ml vs. 3386.6 pg/ml; p < 0.001); (5) no differences were observed in the median AF sTREM-1 concentration between patients with spontaneous labor at term and those at term not in labor (4712.4 pg/ml vs. 4277.6 pg/ml; respectively p = 0.4); and 6) an AF sTREM-1 concentration >or=6416 pg/ml (derived from a ROC curve) had a sensitivity of 72% and a specificity of 89% for the diagnosis of intra-amniotic infection.


CONCLUSIONS
sTREM-1 is a physiologic constituent of the AF, and its concentration: (1) is significantly elevated in the presence of IAI; (2) increases with advancing gestation; and (3) does not change in the presence of spontaneous labor at term. We propose that sTREM-1 play a role in the innate immune response against intra-amniotic infection.
Kusanovic
Juan Pedro
JP
Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, Maryland, USA. jkusanov@med.wayne.edu
Romero
Roberto
R
Chaiworapongsa
Tinnakorn
T
Mittal
Pooja
P
Mazaki-Tovi
Shali
S
Vaisbuch
Edi
E
Erez
Offer
O
Gotsch
Francesca
F
Than
Nandor Gabor
NG
Edwin
Sam S
SS
Pacora
Percy
P
Jodicke
Cristiano
C
Yeo
Lami
L
Hassan
Sonia S
SS
D000328:Adult; D000649:Amniocentesis; D000653:Amniotic Fluid / Q000737:chemistry*; D002821:Chorioamnionitis / Q000175:diagnosis / Q000276:immunology / Q000378:metabolism*; D003430:Cross-Sectional Studies; D005260:Female; D005322:Premature Rupture of Fetal Membranes / Q000378:metabolism; D005865:Gestational Age; D006801:Humans; D008562:Membrane Glycoproteins / Q000032:analysis* / Q000276:immunology; D036801:Parturition / Q000378:metabolism*; D011247:Pregnancy; D047928:Premature Birth / Q000378:metabolism*; D012372:ROC Curve; D011971:Receptors, Immunologic / Q000032:analysis* / Q000276:immunology; D012680:Sensitivity and Specificity; D000073871:Triggering Receptor Expressed on Myeloid Cells-1
D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; C408842:TREM1 protein, human; D000073871:Triggering Receptor Expressed on Myeloid Cells-1