| Objective:The incidence of autoimmune diseases(AID)in the population is 7%.The patients with AID are associated with higher risk of adverse pregnancy outcomes(APOs).Disease activity is a risk factor for APOs.A large total of patients are faced with confusion about disease treatment and safety of medication during pregnancy.Therefore,it is very important to use anti-rheumatic drugs correctly during pregnancy.Hydroxychloroquine(HCQ)could control the disease activity and prevent the flare in pregnancy,but its effect on APOs of AID was not clear.The purpose of this study was to evaluate the safety and effectiveness of HCQ on pregnancy outcomes,fetal outcomes and pregnancy complications of patients with AID during pregnancy.Methods:We systematically searched Pubmed,Embase,Web of Science and Cochrane Library for suitable English language literatures and Chinese databases such as Wanfang,CNKI and VIP up to March,2020.These studies compared APOs in HCQ-exposed and HCQ-unexposed patients with AID during the pregnancy.Two researchers independently evaluated the quality of literatures and collected data.Meta-analysis was carried out by using stata12.0 software.Odds ratio(OR)and 95%confidence intervals(CI)of APOs were calculated by using fixed effect model or random effect model.Cochrane Q-test and I~2 test were used to detect the heterogeneity.For the research with significant heterogeneity,subgroup analysis or sensitivity test were used to analyze the source of heterogeneity.Funnel plot and egger test were used to detect the bias.Results:1.In this meta-analysis,13 articles were included.5 articles contained pregnancy outcomes of patients with varied AID and 8 articles studied pregnancy outcomes of pregnant women with systemic lupus erythematosus(SLE)separately.Therefore,we conducted meta-analysises on APOs of women with AID and SLE respectively.There were 2290 patients with AID,including 941 pregnant women using HCQ(HCQ group)and 1349 pregnant women not using HCQ(control group).2.There were no significant differences in the rate of live birth(OR 1.21,95%CI=0.63,2.35,P=0.570),spontaneous abortion(OR 1.24,95%CI=0.69,2.22,P=0.681),premature birth(OR 0.87,95%CI=0.51,1.51,P=0.628),stillbirth(OR 0.81,95%CI=0.49,1.33,P=0.513),congenital malformation(OR 1.17,95%CI=0.65,2.09,P=0.740),and intrauterine growth restriction(OR 0.50,95%CI=0.11,2.28,P=0.371)with AID.There was high heterogeneity in intrauterine growth restriction and premature birth(P=0.000,I~2=79%;P=0.001,I~2=82%).No significant heterogeneity was present among other studies.3.Compared with the control group,the incidence of preterm birth(OR 0.50,95%CI=0.30,0.82,P=0.006),preeclampsia(OR 0.35,95%CI=0.21,0.60,P=0.006)and pregnancy induced hypertension(OR 0.42,95%CI=0.19,0.89,P=0.024)in HCQ group was significantly lower,and the incidence of live birth(OR 1.61,95%CI=0.93,2.78,P=0.087),stillbirth(OR 1.13,95%CI=0.48,2.63,P=0.785),spontaneous abortion(OR 1.18,95%CI=0.42,3.36,P=0.435),congenital malformation(OR 0.45,95%CI=0.10,1.99,P=0.289),intrauterine growth restriction(OR 0.57,95%CI=0.06,5.55,P=0.632)and low birth weight infants(OR 0.78,95%CI 0.44,1.39,P=0.400)with SLE did not increase significantly.There was high heterogeneity in intrauterine growth restriction(P=0.000,I~2=87.8%).No significant heterogeneity was present among other studies.4.Among all outcomes,visual examination of the funnel plots demonstrated no symmetry and P value of Egger's test>0.1.There were no publication biases.Conclusion:The use of HCQ in pregnancy did not increase the risk of adverse pregnancy outcomes in patients with AID.HCQ treatment during pregnancy could reduce the risk of preterm delivery,preeclampsia and pregnancy hypertension in SLE patients. |
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