孕12~28周血压潜分类增长模型构建及预测子痫前期效能的研究

Association between blood pressure during 12-28 weeks gestation and pre-eclampsia:predictive value of blood pressure trajectories constructed by latent class growth modeling

目的应用潜分类增长模型(latent class growth model,LCGM)纵向分析孕期血压数据,探索妊娠期间血压潜分类轨迹与未来发生子痫前期(preeclampsia,PE)风险之间的联系。方法该研究为前瞻性队列研究,选取2016年11月1日至2018年5月30日在天津市19家社区医院招募的孕早期女性受试者,采集孕28周前5个阶段(即12、16、20、24和28周)的孕检血压数据纳入分析,同时采集孕妇基本信息问卷、体格检查、实验室检查等数据。应用LCGM建立收缩压、舒张压的潜分类轨迹模型;分别以收缩压轨迹、舒张压轨迹作为预测变量,以妊娠28周后至分娩时是否发生PE作为结局变量,进行PE的预测研究。结果共纳入5560例已生产的单胎妊娠孕妇,其中随访期间诊断PE 128例,妊娠期高血压106例。单因素及多因素logistic回归分析显示基线收缩压与舒张压水平越高,PE发生的风险越高。采用LCGM拟合血压动态变化,确定了4条收缩压潜分类轨迹和4条舒张压潜分类轨迹。收缩压潜分类轨迹对应的血压水平越高,PE发生的风险越高;在校正了初检体重指数、是否初产妇、白细胞计数、血红蛋白水平、血小板计数和谷丙转氨酶水平等混杂因素后,收缩压潜分类轨迹4(SBPtraj4)的OR值为4.023(95%CI:2.368~6.835,P<0.001),收缩压潜分类轨迹3(SBPtraj3)的OR值为1.854(95%CI:1.223~2.811,P=0.004);舒张压潜分类轨迹4(DBPtraj4)的OR值为2.527(95%CI:1.534~4.162,P<0.001),舒张压潜分类轨迹2(DBPtraj2)的OR值为2.238(95%CI:1.328~3.772,P=0.002)。受试者工作特征曲线显示基线血压水平联合血压轨迹对PE具有较好的预测能力。结论应用LCGM潜分类增长模型构建孕12~28周的血压潜分类轨迹可对孕28周后PE进行早期预测分析,提示孕期血压潜分类轨迹是一种可用于孕妇PE危险分层的新方法。

Objective To explore the associations between blood pressure trajectories during pregnancy and risk of future pre-eclampsia in a large cohort enrolling pregnant women at gestational age of~12 weeks from community hospitals in Tianjin.Latent class growth modeling(LCGM)was used to model the blood pressure trajectories.Methods This was a large prospective cohort study.The study enrolled pregnant women of~12 weeks of gestation in 19 community hospitals in Tianjin from November 1,2016 to May 30,2018.We obtained related information during 5 antepartum examinations before gestational week 28,i.e.,week 12,week 16,week 20,week 24 and week 28.LCGM was used to model longitudinal systolic(SBP)and diastolic blood pressure(DBP)trajectories.For the association study,the predictors were set as SBP and DBP trajectory membership(built separately),the outcome was defined as the occurrence of preeclampsia after 28 weeks of gestation.Results A total of 5809 cases with known pregnant outcomes were documented.After excluding 249 cases per exclusion criteria,5560 cases with singleton pregnancy were included for final analysis.There were 128 cases preeclampsia and 106 cases gestational hypertension in this cohort.Univariate logistic regression and multivariate logistic regression showed the higher baseline SBP level and DBP level were related with increased risk of preeclampsia.Four distinctive SBP trajectories and DBP trajectories from 12 weeks to 28 weeks of gestation were identified by LCGM.After controlling for potential confounders(baseline BMI,being primipara or not,white blood cell counts,hemoglobin level,platelet counts and alanine aminotransferase level),the OR for SBP latent classification trajectory_4 was 4.023(95%CI:2.368 to 6.835,P<0.001),and the OR for SBP latent classification trajectory_3 was 1.854(95%CI:1.223 to 2.811,P=0.004).Logistic regression showed that:using the DBP latent classification trajectory_1 as the reference group,the OR for DBP latent classification trajectory_4 was 4.100(95%CI:2.571 to 6.538,P<0.001),and 2.632(95%CI:1.570 to 4.414,P<0.001)for DBP latent classification trajectory_2.After controlling for potential confounders(baseline BMI,being primipara or not,white blood cell counts,hemoglobin level,platelet counts and alanine aminotransferase level),the OR for DBP_traj_4 was 2.527(95%CI:1.534 to 4.162,P<0.001),and the OR for DBP_traj_3 was 1.297(95%CI:0.790 to 2.128,P=0.303),and 2.238(95%CI:1.328 to 3.772,P=0.002)for DBP_traj_2.Therefore,BP trajectories from 12 weeks to 28 weeks identified by LCGM served as novel risk factors that independently associated with the occurrence of preeclampsia.Receiver operating characteristic(ROC)curve analysis showed incremental diagnostic performance by combing baseline blood pressure levels with blood pressure trajectories.Conclusion By applying LCGM,we for the first time identified distinctive BP trajectories from gestational week 12 to 28,which can independently predict the development of preeclampsia after 28 weeks of gestation.