Purpose: IL-33 is associated with invasion, proliferation, and metastasis of various cancers. The trophoblastic cells of placenta previa accreta (PPA) invade into the myometrium in a similar way to the invasion of cancers. We studied the role of IL-33 in PPA and also aimed to investigate its relation with adverse maternal outcome in this placental disorder.
Methods: A total of 87 pregnant patients were enrolled in this prospective case-control study [27 with PPA, 30 with placenta previa totalis (PPT; nonadherent placenta previa), and 30 controls]. IL-33 and IL-6 levels were studied in maternal serum at late preterm gestation weeks. Multiple logistic regression analyses analyzed the risk factors which are associated with PPA and adverse maternal outcomes. Adjusted odds ratios and 95% confidence intervals were also calculated. Enzyme-linked immunosorbent assay (ELISA) method was used to determine maternal serum IL-33 and IL-6 levels.
Results: Serum IL-33 levels were significantly higher in PPA patients when compared with both nonadherent PPT and the control groups (p = .011, p = .010). Serum IL-6 and neutrophil/lymphocyte ratio levels were significantly higher than the control group's (p = .045, p = .028). IL-33 levels and history of previous cesarean section were found to be significantly associated with PPA (OR: 1.039, 95% CI: 1.004-1.075; p = .030 and OR: 0.067, 95% CI: 0.014-0.309, p = .001, respectively). Serum IL-33 levels were positively correlated with previous cesarean section history in PPA. Increased maternal serum IL-33 levels were found to be independently associated with a cesarean hysterectomy and massive transfusion in PPA patients (OR: 1.098, 95% CI: 0.998-1.207; p = .049 and OR: 1.162 95% CI: 1.010-1.337; p = .036).
Conclusion: Increased levels of maternal serum IL-33 and history of previous cesarean section were found to be significantly associated with PPA, and also increased maternal serum IL-33 levels were related to cesarean hysterectomy and massive blood transfusion in PPA. We suggest that IL-33 may have a role in abnormal placental invasion.
Keywords: Cesarean hysterectomy; interleukin 33; interleukin 6; massive blood transfusion; nonadherent placenta previa totalis; placenta previa accreta.