妊娠期高血压疾病评估中孕早期PAPP-A、PLGF、Fibulin-3、Ang-2、Hcy的应用价值及其与病情程度的关系OA

Objective To analyze application values of pregnancy-associated plasma protein A(PAPP-A),placental growth factor(PLGF),extracellular matrix protein-3(also called Fibulin-3),angiopoietin-2(Ang-2),homocysteine(Hcy)in the first trimester of pregnancy in assessment of hypertensive disorders complicating pregnancy(HDCP)and their relationships with severity of the disease.Methods In nested case-control study design,371 singleton pregnant women who received regular prenatal examination and early pregnancy screening in the first trimester of pregnancy in our hospital from January 2022 to March 2024 were selected.According to pregnancy outcome and follow-up result,186 pregnant women with HDCP(185 pregnant women ultimately included)were assigned to Group A,and they were further divided into gestational hypertension group(group Ⅰ,n=98),mild preeclampsia group(group Ⅱ,n=58)and severe preeclampsia group(group Ⅲ,n=29).Other185 pregnant women with normal blood pressure during whole pregnancy and without pregnancy-related complications were included in Group B(control group).Clinical data,serum levels of PAPP-A,PLGF,Fibulin-3,Ang-2 and Hcy in early pregnancy of the pregnant women were compared between the Group A and the Group B.The variables with significant differences in univariate analysis were incorporated as independent variables into multivariate Logistic regression analysis.Spearman correlation analysis was applied to analyze relationships between these indexes and severity of HDCP.Receiver operating characteristic(ROC)curve was used to analyze predictive values of PAPP-A,PLGF,Fibulin-3,Ang-2 and Hcy in early pregnancy for severity of HDCP.Results The serum levels of PAPP-A,PLGF,Ang-2 and Fibulin-3 in early pregnancy of the pregnant women in the Group A were significantly lower than those in the Group B,while serum Hcy level was higher than that in the Group B(t=76.764,46.205,34.508,26.412 and 62.255 respectively,all P<0.05).In the Group A,the serum levels of PAPP-A,PLGF,Fibulin-3 and Ang-2 in early pregnancy of the pregnant women in the group Ⅲ were lower than those in the group Ⅱ,and those in the group Ⅱ were lower than those in the group Ⅰ in turn;while,the serum Hcy level of the pregnant women in the group Ⅲ was higher than that in the group Ⅱ,and that in the group Ⅱ was higher than that in the group Ⅰ in turn(F=39.112,66.799,125.093,160.015 and 91.540 respectively,all P<0.05).There was a statistically significant difference in overall incidence of adverse pregnancy outcomes among the group Ⅲ,the group Ⅱ,the group Ⅰand the Group B(χ2=40.106,P<0.001).The serum Hcy level was positively correlated with severity of HDCP(r=0.735,P<0.05),whereas the serum levels of PAPP-A,PLGF,Fibulin-3 and Ang-2 were negatively correlated with severity of HDCP(r=-0.713,-0.782,-0.621 and-0.744 respectively,all P<0.05).Multivariable Logistic regression analysis showed that elevated serum Hcy level(OR=1.399,95%CI:1.146-1.709)was a risk factor for HDCP,while elevated serum levels of PAPP-A(OR=0.427,95%CI:0.221-0.824),PLGF(OR=0.536,95%CI:0.330-0.869),Fibulin-3(OR=0.487,95%CI:0.277-0.857),and Ang-2(OR=0.605,95%CI:0.422-0.868)were the protective factors(all P<0.05).ROC curve analysis showed that combination of serum PAPP-A,PLGF,Fibulin-3,Ang-2 and Hcy in early pregnancy yielded the highest area under the curve(AUC)(AUC=0.880,95%CI:0.842-0.911,P<0.05),with a sensitivity of 88.65%and a specificity of 78.38%respectively.Conclusion The serum levels of PAPP-A,PLGF,Fibulin-3,Ang-2 and Hcy in early pregnancy are closely related to occurrence and severity of HDCP.The combined detection of these five indexes could significantly improve early prediction efficiency for the disease,help identify those HDCP high-risk populations,and improve maternal and neonatal outcomes.