- Retinol binding protein 4 (RBP4), a specific carrier for retinol in the blood, is a novel adipokine that has been implicated in the pathophysiology of insulin resistance, and its gene expression has been associated with adipose tissue inflammation. Recently, proteomic profiling of amniotic fluid (AF) from women with preterm labor (PTL) revealed over-expression of RBP4 in those who delivered preterm. The aim of this study was to determine whether RBP4 is present in AF, and if its concentrations change with gestational age, in the presence of labor, and intra-amniotic infection/inflammation (IAI) in patients with spontaneous PTL. This cross-sectional study included pregnant women in the following groups: (1) mid-trimester (n = 30); (2) term not in labor (n = 31); (3) term in labor (n = 30); (4) spontaneous PTL without IAI who delivered at term (n = 60); (5) PTL without IAI who delivered preterm (n = 64); and (6) PTL with IAI (n = 56). RBP4 concentrations in AF were determined by ELISA. Non-parametric statistics were used for analyses. (1) RBP4 was detected in all AF samples; (2) among patients with PTL, women with IAI had a higher median AF RBP4 concentration than those without IAI who delivered preterm (1268.9 ng/ml, interquartile range (IQR) 900.3-1970.1 vs. 815.8 ng/ml, IQR 592.4-1098.1; p < 0.001) and at term (828.7 ng/ml, IQR 499.7-1119.6; p < 0.001); (3) the median AF RBP4 concentration was higher in women in the mid-trimester than in those at term not in labor (1861.1 ng/ml, IQR 1486.2-2034.3 vs. 766.1 ng/ml, IQR 608.5-1154.1; p < 0.0001; (4) the median AF RBP4 concentration did not differ significantly between patients with PTL without IAI who delivered preterm and those who delivered at term (p = 0.7); and (5) among women at term, the median AF RBP4 concentrations was not significantly different between those in labor and those not in labor (p = 0.4). RBP4 is a physiologic constituent of the AF. Among patients with PTL, the median AF concentration of immunoreactive RBP4 is elevated in pregnancies complicated by IAI. These results suggest that RBP4 may participate in the host response against IAI.