Predictive Value Of Th1 And Th2 Cytokines For Pregnancy Outcome In Early Pregnancy Patients With Recurrent Spontaneous Abortion

Background and ObjectiveRecurrent spontaneous abortion(RSA)refers to the loss of pregnancy that occurs two or more times in succession and occurs less than 28 weeks of gestation,and the biochemical pregnancy that occurs continuously should also be included in the management of RSA.RSA is an extremely complex disease involving multiple factors.In addition to the known etiologies,nearly half of the cases still cannot find the exact etiologies,which is called unexplained recurrent spontaneous abortion(URSA).Immunodeficiency at the maternal-fetal interface is likely to be an important cause of URSA.Embryos are semi-homografts to the mother.A successful pregnancy requires a delicate balance between the pro-inflammatory and immune responses at the interface between the mother and the embryo to form the mother’s immune tolerance to the embryo.CD4+T helper cells are an important type of immune cells in the maternal-fetal immune interface,which can be divided into Th1 cells(T Helper 1 cell)and Th2 cells(T Helper 2 cell)according to their cytokine secretion.Th1 cells secrete IL-2,TNF-α and IFN-γ,which have lethal effects.Th2 cells secrete IL-4,IL-6 and IL-10,which can antagonize the action of Th1-type cytokines.Th2 dominance during pregnancy can protect the embryo from the attack of maternal Th1 cytokines and avoid the occurrence of abortion,while the occurrence of adverse pregnancy outcomes may be related to the enhancement of Th1 cytokines.This paper retroactively analyzed the expression of Th1 and Th2 cytokines between RSA early pregnancy patients and normal early pregnancy women,RSA aborted patients and RSA continued pregnancy patients,and explored the relationship between the balance of Th1 and Th2 cytokines,Th1/Th2 cytokines and the early pregnancy outcome of RSA patients.To analyze its predictive value for early pregnancy outcome in patients with RSA,and to identify independent risk factors affecting early pregnancy outcome in patients with RSA.Materials and MethodsCollected from January 2018 to March 2020 in the second affiliated hospital of zhengzhou university recurrent abortion of early pregnancy patients in clinic and the normal early pregnancy women for clinical data,according to include and exclude standards,set included 210 patients with RSA early pregnancy for RSA pregnancy group,included 101 cases of normal pregnancy group early pregnant women as control.Age,gestational age at visit,menstrual cycle,pregnancy outcome,Th1 and Th2 cytokines,and Th1 / Th2 cytokine ratios between the two groups were recorded and analyzed.Pregnancy outcomes of RSA early pregnancy women before 13+6 weeks of gestation were followed up.According to the different pregnancy outcomes,the RSA early pregnancy group was divided into the RSA aborted subgroup and the RSA continued pregnancy subgroup,and the Th1 and Th2 cytokines and Th1 /Th2 cytokine ratios between the two groups were analyzed.The predictive value for early pregnancy outcome in patients with RSA was analyzed,and independent risk factors affecting early pregnancy outcome in patients with RSA were identified.In this study,SPSS 23.0 was used for data sorting and statistical analysis.Receiver operating characteristic(ROC)curve was used to evaluate the predictive value of Th1 and Th2 cytokines and Th1 / Th2 cytokine ratio for early pregnancy outcome of patients with RSA,and to calculate Youden index and optimal cutoff value.The possible risk factors affecting the early pregnancy outcome of RSA patients were analyzed by univariate Logistic regression,and P< 0.1 was considered statistically significant.Then variables with P < 0.1 were included in multivariate Logistic regression analysis to identify independent risk factors affecting the early pregnancy outcome of RSA patients.Results1.There were no significant differences in age [30(28-35)vs 30(28-34)],gestation days [52(45-59)vs 47(41-53)] and menstrual cycle [31(29-34)vs 31(29-34)]between the RSA early pregnancy group and the control group(P>0.05).2.The RSA pregnancy abortion rate higher than contrast pregnancy group[36.7%(76/210)vs 22.7%(23/101)],the difference was statistically significant(χ2= 5.898,P = 0.015 < 0.05).3.Compared with the control group,the expression of Th1 cytokines was significantly higher in the RSA early pregnancy group,and the expression of Th2 cytokines was lower in the RSA early pregnancy group,with statistical significance(P<0.05).4.Compared with the RSA abortion subgroup,the expression of Th1 cytokines was higher and the expression of Th2 cytokines was lower in the RSA abortion subgroup,with statistical significance(P<0.05).5.The Th1 / Th2 cytokine ratio in the RSA abortion subgroup was more inclined to Th1 dominant level than that in the RSA continuing pregnancy subgroup(P<0.05).6.IL-2,TNF-α and IFN-γ had predictive value for pregnancy outcome of patients with early pregnancy RSA(AUC>0.5),while IL-4,IL-6 and IL-10 had no predictive value for pregnancy outcome of patients with early pregnancy RSA(AUC<0.5).7.TNF-α/IL-4,TNF-α/IL-10,IFN-γ/IL-10 had high predictive value for pregnancy outcome of early pregnancy patients with RSA(AUC=0.724,0.803,0.809),and the combined predictive value of the three was higher(AUC=0.895).8.According to univariate analysis,risk factors associated with pregnancy outcome of patients with RSA during early pregnancy: Inclusion of IL-2,TNF-α,IFN-γ,IL-2/IL-4,IL-2/IL-6,IL-2/IL-10,TNF-α/IL-4,TNF-α/IL-6,IFN-γ/IL-4,IFN-γ/IL-10 in multivariate Logistic regression analysis showed that IFN-γ/IL-10 was an independent risk factor affecting pregnancy outcome of early pregnancy patients with RSA(P=0.006,P<0.05).Conclusions1.High expression of Th1 cytokines,low expression of Th2 cytokines and bias of Th1 / Th2 cytokine balance during pregnancy may be related to the occurrence of abortion.2.The value of Th1 and Th2 cytokine levels in predicting pregnancy outcome of early pregnancy patients with RSA is limited,and their use is not recommended.3.The combination of TNF-α/IL-4,TNF-α/IL-10 and IFN-γ/IL-10 has a high value in predicting the pregnancy outcome of early pregnancy patients with RSA.4.IFN-γ/IL-10 is an independent risk factor affecting the pregnancy outcome of patients with RSA during early pregnancy.