Factors Influencing The Spontaneous Closure Of Fetal Ventricular Septal Defect:A Retrospective Nested Case-control Study

ObjectiveTo investigate the influencing factors of spontaneous closure of fetal ventricular septal defect from the prenatal period to the first year of postnatal life,which provides a theoretical basis for clinicians to make clinical decisions.MethodsA retrospective nested case-control study was conducted in 388 fetuses diagnosed with isolated ventricular septal defect by fetal cardiac ultrasound in Guangdong Maternal and Child Health Hospital from January 1,2019 to December31,2021.We followed up the changes of fetal VSD from pregnancy to 1 year after birth.The subjects were divided into prenatal cohort and postpartum cohort according to the conditions of childbirth,and the two groups were further divided into observation group and control group according to whether spontaneous closure of VSD occurred.In the prenatal cohort,according to the principle of individual matching based on the matching condition of pregnant women’s height and progestational weight with a ratio of 1:4,41 patients with spontaneous closure of fetal VSD in utero were selected as the observation group,and 164 patients without spontaneous closure in utero were randomly selected as the control group,a total of205 patients were included in the study.In the postpartum cohort,the subjects of spontaneous closure of fetal VSD in utero were excluded,according to the principle of individual matching based on the matching condition of gestational age with a ratio of 1:1,131 children with spontaneous closure of VSD within 1 year after birth were selected as the observation group,and 131 children without spontaneous closure of VSD were randomly selected as the control group,a total of 262 patients were included in the study.We investigated the factors influencing the spontaneous closure of fetal VSD in two groups respectively,and analyzed the subgroups of VSD to understand the natural outcomes of perimembranous and muscular VSD.Results1.The pregnancy follow-up information of prenatal cohort1.1 Statistical description of general information: The average age of pregnant women was 29.20±4.58 years old,and 11.7% were 35 years old or above.The average progestational BMI of pregnant women was 19.99±1.95 kg/m2.Firsttime pregnant women accounted for 42.0%.The average gestational age of fetal VSD at first diagnosis was 26.04±3.24 weeks,the average defect diameter was2.33±0.67 mm,and the average ratio of defect diameter to aortic root diameter(DVSD/DAR)was 0.507±0.155.The perimembranous VSD accounted for 63.9% of the clinical classification of VSD.Medium VSD accounted for 71.7% of the VSD size.1.2 Analysis of influencing factors of spontaneous closure of fetal VSD: The results of univariate analysis showed that gestational week at first diagnosis,defect diameter at first diagnosis,the ratio of defect diameter to aortic root diameter(DVSD/DAR),clinical classification of VSD and size classification of VSD were influencing factors of spontaneous closure of fetal VSD in prenatal period.Multivariate COX regression analysis showed that clinical classification and size classification of VSD were independent factors affecting spontaneous closure of fetal VSD in prenatal period.Compared with perimembranous VSD,muscular VSD had a statistically significant effect on spontaneous closure of fetal VSD in prenatal period(HR=2.101,95%CI 1.080-4.085).Compared with large VSD,medium VSD and small VSD had statistically significant effects on spontaneous closure of fetal VSD in prenatal period(HR=3.037,95%CI 1.632-5.650).1.3 ROC curve analysis of spontaneous closure of fetal VSD: The area under ROC curve(AUC)of the model of initial diagnosis of defect was 0.744(95%CI0.6677-0.822),and the optimal thresholds was 2.35 mm.The area under ROC curve(AUC)of the model of the ratio of defect diameter to aortic root diameter(DVSD/DAR)was 0.653(95%CI 0.559-0.747),and the optimal thresholds was0.340.The AUC of the model of the initial diagnosis of defect was larger than that of the model of DVSD/DAR with statistical significance(P<0.05),suggesting that the diagnostic efficacy of the model of the initial diagnosis of defect in predicting spontaneous closure of fetal VSD in prenatal period is better than that of the model of DVSD/DAR.2.The 1 year follow-up information of postpartum cohort2.1 Statistical description of general information: The average age of pregnant women was 29.58±4.78 years old,and 15.6% were 35 years old and above.The average defect diameter of VSD at first diagnosis after birth was 3.10±1.18 mm,the average ratio of defect diameter to aortic root diameter(DVSD/DAR)was0.410±0.175.The perimembranous VSD accounted for 67.6% of the clinical classification of VSD.The main VSD size types were medium and small VSD,accounting for 47.3% and 41.2%.The average gestational age of the fetus was 39 weeks and the average birth weight was 3.17±0.42 kg.2.2 Analysis of influencing factors of spontaneous closure of VSD during the first postpartum year: The results of univariate analysis showed that clinical classification of VSD,the initial diagnosis of defect diameter at postpartum,the ratio of defect diameter to aortic root diameter(DVSD/DAR),size classification of VSD and fetal birth weight were the factors affecting the spontaneous closure of VSD during the first postpartum year.Multivariate COX regression analysis showed that fetal birth weight,clinical classification of VSD and size classification of VSD were independent factors affecting the spontaneous closure of fetal VSD.Fetal birth weight was the promoting factor of spontaneous closure of VSD(HR=2.294,95%CI1.439-3.658).Compared with perimembranous VSD,muscular VSD had a statistically significant effect on spontaneous closure of VSD after birth(HR=2.512,95%CI 1.654-3.815).Compared with large VSD,medium VSD and small VSD had statistically significant effects on the spontaneous closure of VSD after birth(HR=2.990,95%CI 2.025-4.414).2.3 ROC curve analysis of spontaneous closure of VSD during the first postpartum year: The area under ROC curve(AUC)of the model of defect diameter with initial diagnosis after birth was 0.826(95%CI 0.776-0.875),and the optimal threshold was 3.150 mm.The area under ROC curve(AUC)of the model of the ratio of defect diameter to aortic root diameter(DVSD/DAR)was 0.878(95%CI0.836-0.919),and the optimal threshold was 0.367.The area under ROC curve(AUC)of the model of fetal birth weight was 0.705(95%CI 0.640-0.770),and the optimal threshold was 3.145 kg.The AUC of the model of DVSD/DAR was larger than that of the model of the defect diameter with initial diagnosis after birth with statistical significance(P<0.05),suggesting that the diagnostic efficacy of DVSD/DAR in predicting the spontaneous closure of VSD after birth was better than that of the defect diameter with initial diagnosis after birth.3.Subgroup analysis of natural outcomes of fetal VSD: The natural outcomes of fetal VSD included spontaneous closure in utero,spontaneous closure at postpartum,reduction,unchanged or enlargement,and surgical closure of the defect,among which spontaneous closure and reduction of the defect were good outcomes,while enlargement or surgical closure of the defect after birth were bad outcomes.The muscular VSD was more likely to have a good outcome of spontaneous closure(P<0.001),while the perimembranous VSD was more likely to have a good outcome of reductive defect and a bad outcome of unchanged or enlarged defect and surgical closure of defect(P<0.001).Conclusions1.The size of VSD,clinical classification of VSD and fetal birth weight were independent factors affecting the spontaneous closure of fetal VSD,but there was no significant relationship between maternal factors such as maternal age,progestational BMI and pregnancy history.The spontaneous closure rate of small VSD and medium VSD with small defect diameter was higher.The time of spontaneous closure of muscular VSD was earlier and the probability was higher.The higher the birth weight of the fetus,the greater the probability of spontaneous closure of VSD after birth.2.In the prenatal period,the defect diameter at first diagnosis had the higher diagnostic efficacy in predicting the spontaneous closure of fetal VSD.In the postpartum period,DVSD/DAR had the higher diagnostic efficacy in predicting the spontaneous closure of VSD after birth.