Maternal And Perinatal Outcomes Of Low-dose Aspirin Plus Low-molecular-weight Heparin Therapy On Antiphospholipid Antibody-positive Pregnant Women With Chronic Hypertension

Objectives: Hypertensive disorder complicating pregnancy is one of the important factors for adverse outcomes of pregnant women and newborns.According to the 2015 Chinese guidelines for the diagnosis and treatment of hypertensive disorders complicating pregnancy,it is recommended that pregnant patients with hypertension disorder should be tested for antibodies related to autoimmune diseases in qualified medical institutions,and pregnant women with high risk factors for preeclampsia should be advised to take low-dose aspirin to prevent the occurrence of preeclampsia.At present,LDA or LDA combined with LMWH has become a part of the comprehensive treatment of pregnant patients with chronic hypertension.However,there are no studies on the treatment outcomes of aspirin or aspirin plus low-molecular-weight heparin in pregnant women with positive a PL and chronic hypertension.The aim of this study is to investigate the effect of LDA combined with LMWH on the pregnancy outcome of a PL positive pregnancy complicated with chronic hypertension.Methods: This study was performed at The First Affiliated Hospital of Dalian Medical University from January 2018 to December 2022.Pregnant women diagnosed chronic hypertension complicating pregnancy and positive a PL(lupus anticoagulant,anticardiolipin antibody,anti-β2-glycoprotein 1 antibody)were recruited and divided into untreated group(no LDA and LWMH)and treated group.The treated group including LDA group(low-dose aspirin)and LDA+LMWH group(low-dose aspirin & low molecular weight heparin group)according to whether they use LDA and/or LMWH.Pregnancy outcomes were analysed in three group.117 patients were considered in this study,including 53 in untreated group,23 people in LDA group and 41 in LDA+LMWH group.First,we analysed baseline data from three groups,including age,BMI,preconception blood pressure classification,preconception comorbidities(autoimmune diseases such as APS,systemic lupus erythematosus and connective tissue disease,diabetes,obesity and hypothyroidism).The outcome measures included preeclampsia,severe preeclampsia,early-onset severe preeclampsia,eclampsia,HELLP syndrome,placental abruption,foetal growth restriction,term low birth weight,fetal distress,neonatal asphyxia,oligohydramnios,premature rupture of membranes,gestational age of delivery,neonatal birth weight,fetal loss rate(including first trimester miscarriage rate,fetal death in utero rate,second trimester pregnancy induction rate),live birth rate,preterm birth rate and term birth rate.Results: Firstly,we compared the baseline data between three groups,and we found no statistically significant difference in baseline data between groups.Then we compared outcomes across groups.We found that compared with the untreated group,the fetal loss rate in LDA group(45.28% vs 17.39%,p=0.02)and LDA+LMWH group(45.28% vs7.32%,p<0.01)decreased.Compared with the untreated group,the live birth rate(54.72%vs 82.61%,p=0.02)and term delivery rate(16.98% vs 43.48%,p=0.01)were increased in the LDA group,and the live birth rate(54.72% vs 92.68%,p<0.01)and term delivery rate(16.98% vs 58.54%,p<0.01)were increased in the LDA+LMWH group.However,when compared with the LDA group,there were no significant differences in fetal loss rate(17.39% vs 7.32%,p=0.38),live birth rate(82.61% vs 92.68%,p=0.22)and term delivery rate(43.48% vs 58.54%,p=0.25)between the LMWH group.Compared with the untreated group,the incidence of severe preeclampsia in the LDA group(58.49% vs30.44%,p=0.03)and the LDA+LMWH group(58.49% vs 36.59%,p=0.04)had a statistically significant reduction.However,when compared with the LDA group,there were no significant differences in the incidence of severe preeclampsia(30.44% vs36.59%,p=0.62).Compared with the untreated group,the incidence of severe preeclampsia before 34 weeks(49.06% vs 24.39%,p=0.015)and HELLP syndrome(18.87% vs 2.44%,p=0.01)in pregnant women in the LDA+LMWH group decreased and were statistically different.Compared with the untreated group,the incidence of severe preeclampsia before 34 weeks(49.06% vs 26.09%,p=0.06)and HELLP syndrome(18.87%vs 2.44%,p=0.09)in the LDA group had no statistically significant difference in LD group.Compared with the untreated group,there was no significant difference in the incidence of early-onset severe preeclampsia between the LDA group and the LDA+LMWH group(37.74% vs 21.74% vs 17.07%,p=0.07).Conclusion: In a PL-positive pregnant women with chronic hypertension,both LDA or LDA in combination with LWMH can reduce fetal loss and increase live birth and term delivery rates.However,the use of LDA combined with LMWH can reduce the incidence of severe preeclampsia before 34 weeks and HELLP syndrome in a PL-positive pregnancy with chronic hypertension,suggesting that in patients with a PL-positive pregnancy with chronic hypertension,LDA alone is not enough for avoiding the severe preeclampsia before 34 weeks and HELLP syndrome.It is recommended that a PL should be screened in pregnant patients with chronic hypertension,once abnormal a PL results are found,LDA and LMWH should be added promptly.