孕早中期孕妇肠道菌群差异与子痫前期发病关系的研究

Study on the Relationship between Intestinal Microflora Differences and the Incidence of Preeclampsia in Pregnant Women in the Early and Middle Stages of Pregnancy

背景子痫前期病情严重者可进展至子痫并威胁母婴生命安全,而肠道菌群构成变化可能参与子痫前期的发生、发展,但尚无明确证据。目的探讨孕早中期孕妇肠道菌群差异与子痫前期发病的关系。方法选取2019年1月至2021年1月桂林医学院第二附属医院产科招募且符合本研究纳入标准的孕妇455例。将妊娠20周后确诊为子痫前期的孕妇作为子痫前期组(n=32),未发生子痫前期的孕妇作为非子痫前期组(n=423)。收集孕妇的临床资料,并分别留取孕早期(≤12;周)、孕中期(13~27;周)粪便标本进行肠道菌群生物信息学分析,分析其与子痫前期发病的关系。结果子痫前期组和非子痫前期组年龄、孕早期Shannon指数和Simpson指数比较,差异均有统计学意义(P<0.05)。多因素Logistic回归分析结果显示,年龄≥35周岁〔OR=1.894,95%CI(1.432,2.369)〕、孕早期Shannon指数下降〔OR=0.709,95%CI(0.465,0.921)〕、孕早期Simpson指数下降〔OR=0.612,95%CI(0.354,0.893)〕是孕妇发生子痫前期的独立危险因素(P<0.05)。孕早期Shannon指数预测孕妇子痫前期发病的受试者工作特征(ROC)曲线下面积为0.745〔95%CI(0.652,0.838)〕,截断值为6.255,灵敏度为76.58%,特异度为60.00%;孕早期Simpson指数预测孕妇子痫前期发病的ROC曲线下面积为0.724〔95%CI(0.623,0.826)〕,截断值为0.945,灵敏度为62.90%,特异度为60.61%。结论孕早期粪便肠道菌群Shannon指数、Simpson指数降低是孕妇发生子痫前期的独立危险因素,且对子痫前期发病具有早期预测价值。

Background Severe preeclampsia can progress to eclampsia and threaten the life safety of mothers and infants,while intestinal flora composition changes may be involved in the occurrence and development of preeclampsia,but there is no clear evidence.Objective To investigate the relationship between intestinal flora differences and the incidence of preeclampsia in pregnant women in the early and middle stages of pregnancy.Methods A total of 455 pregnant women recruited from the Department of Obstetrics,the Second Affiliated Hospital of Guilin Medical University from January 2019 to January 2021 who met the requirements were selected.Pregnant women diagnosed with preeclampsia after 20 weeks of gestation were classified as preeclampsia group(n=32),and pregnant women without preeclampsia were classified as non-preeclampsia group(n=423).The clinical data of pregnant women were collected,and fecal samples were collected in the early(≤12^(+6)weeks)and middle stages of pregnancy(13~27^(+6)weeks)for bioinformatics analysis of intestinal flora,and the relationship between bioinformatics and the incidence of preeclampsia was analyzed.Results There were statistically significant differences in age,Shannon index and Simpson index in early pregnancy between preeclampsia group and non-preeclampsia group(P<0.05).Logistic regression analysis showed that age≥35 years old〔OR=1.894,95%CI(1.432,2.369)〕,low Shannon index in early pregnancy〔OR=0.709,95%CI(0.465,0.921)〕and low Simpson index in early pregnancy〔OR=0.612,95%CI(0.354,0.893)〕were independent risk factors for preeclampsia(P<0.05).ROC curve showed that the optimal cut-off value and AUC of Shannon index for predicting the incidence of preeclampsia in pregnant women in early pregnancy were 6.255 and 0.745〔95%CI(0.652,0.838)〕,with the corresponding sensitivity and specificity of 76.58%and 60.00%,respectively.The Simpson index in early pregnancy predicted the onset of preeclampsia with the best truncation value of 0.945 and AUC of 0.724〔95%CI(0.623,0.826)〕,and the corresponding sensitivity and specificity were 62.90%and 60.61%,respectively.Conclusion Decreased Shannon index and Simpson index of fecal intestinal flora in early pregnancy in early pregnancy are independent risk factors for the occurrence of preeclampsia in pregnant women,and have early predictive value for the onset of preeclampsia.