T-cell immunoglobulin mucin-3 and galectin-9 levels in peripheral blood mononuclear cells predict fetal acidemia in twin pregnancies

The pH in the umbilical artery at delivery provides information on the fetal environment and is related to postnatal outcomes. The ability to predict fetal acidemia at delivery would improve clinical management and neonatal well- being. We hypothesized that an alteration in maternal immunity would accompany placental changes that precede a decrease in pH in the fetal circulation in twin gestations. Peripheral blood mononuclear cells (PBMCs), obtained from 86 women with twin pregnancies, were lysed and assayed for concentrations of T cell immunoglobulin mucin domain 3 (Tim-3) and galectin-9 (gal-9) by ELISA. Tim-3 - gal-9 interaction is a primary mechanism promoting immune suppression. At delivery the pH of arterial cord blood was determined. In eight women (9.3%) the pH in the placental arteries from both twins was < 7.15, indicating fetal acidosis. In the remaining 78 women the arterial pH was ≥ 7.15 in both twins. The median Tim-3 level was 361 pg/ml when arterial pH was < 7.15 and 199 pg/ml when pH was ≥ 7.15 (p = 0.003). Similarly, gal-9 was 31.2 versus 12.4 ng/ml when pH was < 7.15 or ≥ 7.15, respectively (p = 0.001). A Tim-3 concentration > 260 pg/ml predicted arterial pH < 7.15 with a sensitivity of 87.5%, specificity of 79.5% and negative predictive value of 98.4%. A gal-9 level > 18.4 predicted arterial pH < 7.15 with a sensitivity of 100%, specificity of 73.8% and a negative predictive value of 100%. We conclude that elevations in Tim-3 and gal-9 in PBMCs during gestation predict the subsequent occurrence of a pH < 7.15 in the fetal arteries at delivery in twin gestations.