Fetal Ventricular Septal Defect Research Articles

Correlation between types of ventricular septal defect and chromosomal abnormalities in low-risk non-invasive prenatal testing.

The aim of this study was to examine whether there is a correlation between different types of ventricular septal defects (VSD) and chromosomal abnormalities in the low-risk setting of non-invasive prenatal testing (NIPT) and to evaluate the prognosis of fetuses with varying types of VSD. Cases of pregnant women who underwent amniocentesis due to fetal VSD were collected by Tianjin Central Hospital of Obstetrics and Gynecology from May 2017 to May 2022. Exclusions were made for those without NIPT, with high-risk NIPT results, genetic disorders, and those lost to follow-up. Data collected included ultrasound classification of VSD, prenatal NIPT results, copy-number variations (CNVs) results, and neonatal outcomes. The prevalence of pathogenic CNVs was investigated in 74 cases of VSDs. Of these cases, 45 were isolated VSDs (9 muscular and 36 non-muscular) and 29 were non-isolated VSDs (10 with intracardiac and 19 with extra-cardiac structural anomalies). The results revealed that the incidence of pathogenic CNVs was lower in isolated VSDs compared to non-isolated VSDs in a low-risk NIPT condition (χ2 = 9.344, P = 0.002). There was no significant difference in the prevalence of pathogenic CNVs between VSDs with intracardiac and extra-cardiac structural anomalies (P = 0.541). Moreover, VSDs associated with intracardiac structural anomalies had the highest rate of surgical intervention. When NIPT is low-risk and VSD is isolated, the likelihood of fetal chromosomal defects is not increased. However, if there are intra- or extra-cardiac structural abnormalities present alongside VSD, the possibility of pathogenic CNV is considerably greater, necessitating invasive prenatal diagnosis. Isolated muscular VSDs usually do not require surgery, which can be used as a basis for prenatal counseling regarding fetal VSD.

Prenatal genetic diagnosis associated with fetal ventricular septal defect: an assessment based on chromosomal microarray analysis and exome sequencing

Objective: In the study, we investigated the genetic etiology of the ventricular septal defect (VSD) and comprehensively evaluated the diagnosis rate of prenatal chromosomal microarray analysis (CMA) and exome sequencing (ES) for VSD to provide evidence for genetic counseling.Methods: We carried out chromosomal microarray analysis (CMA) on 468 fetuses with VSD and exome sequencing (ES) on 51 fetuses.Results: In our cohort, 68 (14.5%) VSD fetuses received a genetic diagnosis, including 61 (13.03%, 61/468) cases with chromosomal abnormalities and seven (13.7%, 7/51) cases with gene sequence variants. The detection rate of total pathogenic and likely pathogenic gene variations in the non-isolated VSD group (61/335, 18.2%, 55 by QF-PCR/karyotype/CMA + 6 by ES) was significantly higher than that in the isolated VSD group (7/133, 5.3%, 6 by QF-PCR/karyotype/CMA + 1 by ES, p = 0.000). The most common copy number variation (CNV) was 22q11.2 microdeletion syndrome. Additionally, we found six previously unreported variants, which expanded the variation spectrum of VSD-related genes.Conclusion: In this study, CNVs and sequence variants were found in 13.03% and 13.7% of cases, respectively. ES can be recommended for fetuses with VSD without chromosome abnormalities and pathogenic CNVs, especially those that are combined with other ultrasound abnormalities.

Risk factor analysis for adverse prognosis of the fetal ventricular septal defect (VSD)

BackgroundVentricular septal defect (VSD) is the most common subtype of congenital heart disease. In the present study, we aimed to determine whether chromosome aberration was associated with the occurrence of VSD and evaluate the association of VSD size, location and chromosome aberration with adverse outcomes in the Chinese fetuses.MethodsFetuses with VSD and comprehensive follow-up data were included and evaluated retrospectively. Medical records were used to collect epidemiological data and foetal outcomes. For VSD fetuses, conventional karyotype and microarray analysis were conducted. After adjusting confounding factors by using multivariable logistic regression analyses, the association between chromosome variations and VSD occurrence was explored. The association between defect size, location and chromosome aberrations and adverse foetal outcomes was also investigated.ResultsChromosome aberration was the risk factor for VSD occurrence, raising 6.5-fold chance of developing VSD. Chromosome aberration, peri-membranous site and large defect size of VSD were significant risk factors of adverse fetal outcome. Chromosome aberrations, including pathogenic copy number variations (CNVs) and variations of uncertain significance (VUS), were both risk factors, increasing the risk of the adverse fetal outcome by 55.9 times and 6.7 times, respectively. The peri-membranous site would increase 5.3-fold risk and defects larger than 5 mm would increase the 7.1-fold risk for poor fetal outcome.ConclusionsThe current investigation revealed that chromosomal abnormalities, large defects, and the peri-membranous site were all risk factors for poor fetal outcomes. Our study also indicated that chromosome aberration was one of risk factors for the VSD occurrence.

Circulating microRNA: Myocardium-derived prenatal biomarker of ventricular septal defects.

Background: Recently, circulating microRNAs (miRNAs) from maternal blood and amniotic fluid have been used as biomarkers for ventricular septal defect (VSD) diagnosis. However, whether circulating miRNAs are associated with fetal myocardium remains unknown. Methods: Dimethadione (DMO) induced a VSD rat model. The miRNA expression profiles of the myocardium, amniotic fluid and maternal serum were analyzed. Differentially expressed microRNAs (DE-microRNAs) were verified by qRT–PCR. The target gene of miR-1-3p was confirmed by dual luciferase reporter assays. Expression of amniotic fluid-derived DE-microRNAs was verified in clinical samples. Results: MiRNAs were differentially expressed in VSD fetal rats and might be involved in cardiomyocyte differentiation and apoptosis. MiR-1-3p, miR-1b and miR-293-5p were downregulated in the myocardium and upregulated in amniotic fluid/maternal serum. The expression of amniotic fluid-derived DE-microRNAs (miR-1-3p, miR-206 and miR-184) was verified in clinical samples. Dual luciferase reporter assays confirmed that miR-1-3p directly targeted SLC8A1/NCX1. Conclusion: MiR-1-3p, miR-1b and miR-293-5p are downregulated in VSD myocardium and upregulated in circulation and may be released into circulation by cardiomyocytes. MiR-1-3p targets SLC8A1/NCX1 and participates in myocardial apoptosis. MiR-1-3p upregulation in circulation is a direct and powerful indicator of fetal VSD and is expected to serve as a prenatal VSD diagnostic marker.

Maternal serum CFHR4 protein as a potential non-invasive marker of ventricular septal defects in offspring: evidence from a comparative proteomics study

BackgroundDespite advances in diagnosis of congenital heart defects, there is no non-invasive biomarker clinically available for the early detection of fetal ventricular septal defects (VSD).MethodsThis study was to profile differentially expressed proteins (DEP) in the first trimester maternal plasma samples that were collected in the 12th–14th week of gestation and identify potential biomarkers for VSD. Maternal plasma samples of ten case–control pairs of women (who had given birth to an isolated VSD infant or not) were selected from a birth cohort biospecimen bank for identifying DEPs by using high-performance liquid chromatography-tandem mass spectrometry-based comparative proteomics.ResultsThere were 35 proteins with significantly different levels between cases and controls, including 9 upregulated and 26 downregulated proteins. With Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway enrichment, and protein–protein interaction analyses, most of the DEPs were clustered in pathways related to B cell-mediated immune responses, complement activation, and phagocytosis. Three DEPs were validated using enzyme-linked immunosorbent assay in another set of samples consisting of 31 cases and 33 controls. And CFHR4, a key regulator in complement cascades, was found to be significantly upregulated in cases as compared to controls.ConclusionsSubsequent logistic regression and receiver operating characteristic analysis suggested maternal serum CFHR4 as a promising biomarker of fetal VSD. Further studies are warranted to verify the findings.

Maternal serum-derived exosomal lactoferrin as a marker in detecting and predicting ventricular septal defect in fetuses.

Among different types of congenital heart diseases, ventricular septal defect is the most frequently diagnosed type and is frequently missed in early prenatal screening programs. Herein, we explored the role of maternal serum-derived exosomes in detecting and predicting ventricular septal defect in fetuses in the early stage of pregnancy. A total of 104 pregnant women consisting of 52 ventricular septal defect cases and 52 healthy controls were recruited. TMT/iTRAQ proteomic analysis uncovered 15 maternal serum exosomal proteins, which showed differential expression between ventricular septal defect and control groups. Among these, four down-regulated proteins, lactoferrin, SBSN, DCD, and MBD3, were validated by Western blot. The protein lactoferrin was additionally verified by ELISA which was able to distinguish ventricular septal defects from controls with area under the ROC curve (AUC) 0.804 (p < 0.001). Our findings reveal that lactoferrin in maternal serum-derived exosomes may be a potential biomarker for non-invasive prenatal diagnosis of fetal ventricular septal defects.

Construction of the amniotic fluid-derived exosomal ceRNA network associated with ventricular septal defect

Ventricular septal defect (VSD) is the most frequent congenital cardiac malformations. Amniotic fluid (AF) contains a higher abundance of biological compounds that could reflect fetal health information. The aims of our study were to construct a competitive endogenous RNA (ceRNA) network based on AF-derived exosomal ncRNAs. We conducted whole transcriptome profiling in six pairs of AF-derived exosomes from VSD fetuses and matched healthy controls. A total of 1252 differentially expressed (DE) mRNAs, 256 DE-miRNAs and 1090 DE-lncRNAs were found to be significantly altered in the VSD group. We constructed a ceRNA regulatory network including 46 mRNAs, 11 miRNAs and 47 lncRNAs. The expression level of 6 hub RNAs were validated using qRT-PCR. In conclusion, AF-derived exosomal VSD-related ceRNAs provide a basis for a better understanding of the role of ncRNAs in the pathogenesis and mechanisms of VSD, which may lead to the discovery of potential diagnostic biomarkers for fetal VSD.

Maternal Circulating Exosomal miRNAs as Non-invasive Biomarkers for the Prediction of Fetal Ventricular Septal Defect.

Objective: This study aimed to identify maternal circulating exosomal miRNAs as potential non-invasive biomarkers for the early detection of fetal ventricular septal defects (VSDs).Methods: In total, 182 pregnant women, comprising 91 VSD cases and 91 matched controls, were included in this study. Exosomes were isolated; dysregulated exosomal miRNAs were profiled using next-generation sequencing. Differential abundance of miRNAs was verified using quantitative real-time polymerase chain reaction (qRT-PCR). Diagnostic accuracy was evaluated by constructing receiver operating characteristic (ROC) curves.Results: In total, 77 serum exosomal miRNAs were found to be differentially expressed in the VSD group compared to their expression in the control group. Among these, five downregulated exosomal miRNAs were validated using qRT-PCR. hsa-miR-146a-5p was identified to be capable of distinguishing VSD cases from controls (area under the ROC curve [AUC]: 0.997; p < 1.00E-05).Conclusion: Circulating exosomal miRNAs, particularly hsa-miR-146a-5p, may be predictive biomarkers for the non-invasive prenatal diagnosis of fetal VSDs.

Chromosomal abnormalities and copy number variations in fetal ventricular septal defects

BackgroundThis study aimed to evaluate the applicability of chromosomal microarray analysis (CMA), rather than traditional chromosome analysis, in prenatal diagnosis of ventricular septal defects (VSDs) for superior prenatal genetic counseling and to reveal a potential correlation between submicroscopic chromosomal aberrations and VSDs.ResultsAmong the 151 VSD cases, 79 (52.3%) had isolated defects and 72 (47.7%) had additional ultrasound anomalies. Karyotype analysis identified 16 chromosomal abnormalities. Besides the 14 cases of chromosome abnormalities consistent with karyotype analysis, CMA identified an additional 20 cases (13.2%) of abnormal copy number variations (CNVs), of which 13 were pathogenetic CNVs, 5 were variations of uncertain clinical significance (VOUS) and 2 were benign CNVs. The detection rate of pathogenic CNVs in non-isolated-VSDs was significantly higher than that in isolated-VSDs (36.1% (26/72) vs. 1.3% (1/79), p = 0.001). We also found that CMA results indicating pathogenic abnormalities affected the rate of pregnancy termination.ConclusionsThis study showed that CMA combined with cytogenetic analysis is particularly effective in identifying CNVs in fetuses with VSDs and can have an effect on obstetrical outcomes. The elucidation of the etiology of VSDs suggested that gene mutations or other factors may be implicated.

P18.09: Differential diagnosis of fetal large ventricular septal defect and tetralogy of Fallot based on big data analysis

P18.09: Differential diagnosis of fetal large ventricular septal defect and tetralogy of Fallot based on big data analysis

Statin exposure during first trimester of pregnancy is associated with fetal ventricular septal defect

BackgroundA growing number of young women are exposed to statins during their first trimester of pregnancy. The goal of this study is to examine if first trimester statin exposure is associated with an increase in risk of fetal congenital cardiac anomalies. MethodsIn a cohort of 379,238 pregnancies, we examined the risk of fetal congenital cardiac anomalies in association with maternal exposure to statin therapy during the first trimester of pregnancy using logistic regression models and propensity score matching methods. Results280 women were exposed to statins. Congenital cardiac anomalies were present in 14 (5.0%) of pregnancies exposed to statin and 5282 (1.4%) of non-exposed pregnancies. First-trimester statin exposure was associated with an increased risk of ventricular septal defect (adjusted odds ratio [OR] 3.3, 95% confidence interval [CI]l 1.8–6.0, p < 0.001). This association was confirmed in an analysis using a propensity score-matched cohort (OR 4.7, 95% CI 2.0–10.8, p < 0.001). ConclusionsExposure to statins during the first trimester of pregnancy is associated with fetal ventricular septal defect.

Characteristics of Isolated Ventricular Septal Defects Less Likely to Close In Utero.

To determine the characteristics of fetal ventricular septal defects (VSDs) that will be less likely to close prenatally. In this 4-year retrospective cohort study, 148 fetuses had a diagnosis of a VSD during a comprehensive fetal anatomy survey. The VSD diagnosis was confirmed by color and pulsed wave Doppler studies. These fetuses were followed monthly until their birth. They had postnatal echocardiography performed within 1 month of age to assess the persistence of a VSD. Fisher exact, Wilcoxon rank sum, and log rank tests and bivariate and multivariate logistic regressions were used to examine the association of each individual variable with prenatal VSD closure. One hundred twenty-five of 148 fetuses (84%) had prenatal VSD closure at a mean gestational age ± SD of 26.9 ± 4.5 weeks. Fetuses with a persistent VSD more frequently had other cardiac defects than the closed VSD group (12 of 23 versus 5 of 125; P < .001). Fetuses having a persistent VSD more frequently had an abnormal karyotype (9 of 23 versus 5 of 125; P < .001). The persistent VSDs were larger in their initial size (5.9 ± 8.4 mm versus 2.7 ± 0.8 mm; P = .002) and in their maximal prenatal size (6.0 ± 9.1 mm versus 2.9 ± 0.9 mm; P < .001). The presence of associated cardiac defects (adjusted odds ratio = 0.071; P = .031) and an abnormal karyotype (adjusted odds ratio = 0.058; P = .021) were significantly associated with a lower likelihood of prenatal VSD closure. All VSDs with a maximal size of 2 mm or less closed prenatally. Fetuses with a complex cardiac defect or an abnormal karyotype were less likely to have prenatal VSD closure.

Clinical application of SNP array analysis in fetuses with ventricular septal defects and normal karyotypes.

The present study aims to evaluate the utility of high-resolution single-nucleotide polymorphism (SNP) arrays in fetuses with ventricular septal defects (VSDs) with or without other structural anomalies but with normal karyotypes and to investigate the outcomes of cases of prenatal VSDs via clinical follow-up. We analyzed 144 fetuses with VSDs and normal karyotypes using Affymetrix CytoScan HD arrays and the analyses were carried out a year after birth. Clinically significant CNVs were detected in 12 fetuses (8.3%). The most common pathogenic CNV was a 22q11.2 deletion with a detection rate of 2.8% (4/144). Well-known microdeletion or microduplication syndromes, including Smith-Magenis, Miller-Dieker, 9q subtelomeric deletion, 1p36 microdeletion, 1q21.1 microduplication, and terminal 4q deletion syndrome, were identified in six cases. Three regions of chromosomal imbalance were also identified: microduplication at 12q24.32q24.33, microdeletion at 16p13.13p13.12 and microdeletion at Xp21.1. The genes TBX1, SKI, GJA5, EHMT1, NOTCH1 were identified as established genes and LZTR1, PRDM26, YWHAE, FAT1, AKAP10, ERCC4, and ULK1 were identified as potential candidate genes of fetal VSDs. There was no significant difference in pathogenic CNVs between isolated VSDs and VSDs with additional structural abnormalities. Ninety-five (74.8%) pregnant women with fetuses with benign CNVs chose to continue the pregnancy and had a favorable prognosis, while nine (75%) pregnant women with fetuses with pathogenic CNVs chose to terminate the pregnancy. High-resolution SNP arrays are valuable tools for identifying submicroscopic chromosomal abnormalities in the prenatal diagnosis of VSDs. An excellent outcome can be expected for VSD fetuses that are negative for chromosomal anomalies and other severe anatomic abnormalities.

OP09.10: The value of echocardiography in the diagnosis and postnatal outcome of fetal pure ventricular septal defect

OP09.10: The value of echocardiography in the diagnosis and postnatal outcome of fetal pure ventricular septal defect

Parental Genetic Variants, MTHFR 677C&gt;T and MTRR 66A&gt;G, Associated Differently with Fetal Congenital Heart Defect

Background Congenital heart defect (CHD) is one of the most common birth defects in the world. The methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) genes are two of the most important candidate genes for fetal CHD. However, the correlations between the two genes and fetal CHD were inconsistent in various reports. Therefore, this study is aimed to evaluate the parental effects of the two genes on fetal CHD via three genetic polymorphisms, MTHFR 677C>T (rs1801133), MTHFR 1298 A>C (rs1801131), and MTRR 66A>G (rs1801394). Methods Parents with pregnancy history of fetal CHD were divided into two subgroups: ventricular septal defect (VSD) (21) and non-VSD groups (78). VSD, non-VSD, and 114 control parents (controls) were analyzed in this study. Genotyping of these genetic polymorphisms was done by sequencing. Results The MTHFR 677C>T polymorphism of either mothers or fathers was independently associated with fetal non-VSD (P < 0.05) but not VSD, while the MTRR 66A>G polymorphism was independently associated with fetal VSD (P < 0.05) but not non-VSD. No significance was found for MTHFR 1298A>C polymorphism. Conclusion In either maternal or paternal group, the MTHFR 677C>T polymorphism was independently related to fetal non-VSD, while the MTRR 66A>G polymorphism was independently related to fetal VSD.

Prediction of spontaneous closure of isolated ventricular septal defects in utero and postnatal life.

BackgroundVentricular septal defect (VSD) is a highly prevalent fetal congenital heart defect, which can become spontaneously closed during infancy. The current study aims to characterize fetal VSDs that were subsequently spontaneously closed in the first 2 years of life in eastern China.MethodsBetween January 2011 and December 2013, 257 fetal patients diagnosed with isolated VSD by fetal echocardiography at Nanjing Maternity and Child Health Care Hospital, China, were enrolled in the study. Subjects were divided into three groups: group 1 = persistent VSD; group 2 = closed after birth; group 3 = closed during gestation. Fetal echocardiography data, physical features at birth and follow-up outcomes for 2 years were compared to identify factors contributing to spontaneous closure (SC) of VSD. A predictive formula was applied to patients admitted to hospital in the first quarter of 2014 (n = 23) for validation.ResultsSC occurred in 42.8% patients. Birth weight (3.095 ± 0.774, 3.174 ± 0.535, 3.499 ± 0.532 kg in groups 1, 2 and 3, respectively) and defect diameter (3.422 ± 0.972, 2.426 ± 0.599, 2.292 ± 0.479 mm, in groups 1, 2 and 3, respectively) showed statistically significant differences between the three groups (P = 0.004 and P = 0.000, respectively). Receiver operating characteristic (ROC) curves identified cut-off value for the defect diameter as 2.55 mm, and logistic regression analysis identified the SC probability = (1 + exp -[-2.151 − 0.716*birth weight + 1.393*diameter])-1. Results indicated that male fetuses, full-term birth, muscular VSD, and defects without blood flow crossing the septum, have higher incidence of SC.ConclusionsThe major determinants of SC of isolated VSD are birth weight and diameter of the defect. In addition, VSD location may also affect the SC incidence.

The role of microRNA-155, microRNA-222 and mitogen-activated protein kinase signaling pathway in ventricular septal defect

Objective To explore the expression and clinical significance of microRNA(miR)-155 and miR-222 in plasma of patients with ventricular septal defect(VSD), and to analyze the possible mechanism. Methods A total of 20 children with VSD who received treatment at the Department of Cardiovascular Surgery from August 2012 to June 2013 were enrolled (the VSD group) and 15 patients with fracture (the control group). The plasma miR-155 and miR-222 expression levels were measured by real-time quantitative reverse transcription-polymerase chain reaction (RT-qPCR). The potential target genes of miR-155 and miR-222 were predicted by using 3 currently available prediction programs, including TargetScan, mirbase and Miranda, and the signaling pathway of miRNA was predicted by Pathway-express analysis. Results Compared with the control group, the expression levels of miR-155(P=0.033) and miR-222(P<0.001) in the VSD group decreased significantly; miR-155 and miR-222 predicted target genes included 74 and 50, respectively.The Pathway-express analysis indicated that 7 signaling pathways played important roles in the occurrence of fetal VSD, including signaling pathways for heart development, such as: mitogen-activated protein kinase(MAPK) signaling pathway. Conclusions The expression levels of plasma miR-155 and miR-222 in VSD were significantly decreased.The target genes were related to signaling pathways for heart deve-lopment (MAPK signaling pathway), which indicates that miR-155 and miR-222 may be involved in the pathological process of VSD, and may serve as an independent evaluation indicator for the diagnosis of VSD. Key words: microRNA; Ventricular septal defect; Mitogen-activated protein kinase signaling pathway

A novel mutated sequence in the T-box transcription factor-5 (TBX-5) gene (c.241A>T) in Holt-Oram syndrome.

We report a case of a 31-year-old pregnant woman who was admitted to our perinatology outpatient clinic because of a fetal ventricular septal defect and limb reduction in the upper extremities of fetus revealed by ultrasonographic investigation diagnosed in the 16(th) week of gestation. First child of the family was diagnosed with Holt-Oram syndrome who had atrial septal defect and upper limb anomalies, whereas the father was documented to have arrhythmia and shortening of upper limbs. The pregnancy was terminated in the 16(th) week of gestation with the consent of the family. We performed mutation analysis in T-box transcription factor-5 (TBX5) gene coding exons, including exon/intron boundaries from peripheral blood or skin fibroblasts. The sequence analysis revealed c.241 adenine (A)>thymine (T) [p. arginine (Arg) 81 Tryptophan (Trp)] alteration in exon-3 of the TBX5 gene in affected family members and fetus. This is a novel mutation causing Holt-Oram syndrome.

Prospective study on the isolated ventricular septal defect in fetus

Congenital heart defect is one of the most common birth defects. The isolated ventricular septal defect (VSD) has higher morbidity, and spontaneous closure may occur. Previously many studies about the prognosis of ventricular septal defect in childhood were conducted; in contrast, few studies on evolution and prognosis of ventricular septal defect from fetus to postnatal life have been available. This research aimed to determine the evolution of isolated ventricular septal defect during the period of fetus and postnatal life, and analyze the association between the diameter or location of VSD and the spontaneous closure of VSD. All pregnant women seen at the prenatal diagnosis center of the West China Second Hospital were recruited. From June 2011 to June 2014, these participants underwent the fetal 2-dimensional and color Doppler echocardiographic examinations, and the fetuses with isolated VSD were included in the study, and those with other malformations or abnormal chromosome were excluded. This study was a prospective and longitudinal research. These fetuses were followed-up until the VSD closed spontaneously, or were surgically repaired or percutaneously closed. Outcomes of all the cases were recorded. There were 234 fetuses with isolated VSD who were recruited in our research cohort. Twelve of 234 lost to follow-up, 5 of 234 were still in uterus. Totally 217 fetuses were followed up. One hundred eighty-nine of 217 (87.1%) cases were delivered. The pregnancies were terminated in 28 of 217 (12.9%) cases. Ten cases died after birth. Of the 179 delivered cases, the rate of VSD spontaneous closure was 45.2% (81/179), the VSD of 49 cases (27.4%, 49/179) spontaneously closed in uterus. The VSD of 17.9% (32/179) cases spontaneously closed after birth and those of 75% (24/32) cases closed in the first year of life. Furthermore, these participants were divided into 3 groups according to the diameter of VSD in fetus. There were 87 cases in ≤ 2.0 mm group, 51 spontaneously closed (59%, 51/87) and 30 of 84 spontaneously closed (36%, 30/84) in 2.1-5.0 mm group. There were no spontaneous closure in > 5.0 mm group. There was a significant difference in spontaneous closure rate between the 3 groups (χ(2) = 15.200, P = 0.001). Nevertheless, these participants were divided into 2 groups according to the location of VSD in fetus (perimembrane VSD (P-VSD) group and muscular VSD (M-VSD) group). There were 152 cases in P-VSD group, 69 spontaneously closed (45.4%, 69/152) and 12 of 27 spontaneously closed (44%, 12/27) in M-VSD group. There was no significant difference in spontaneous closure between P-VSD and M-VSD (χ(2) = 0.008, P = 0.950). There was a high spontaneous closure rate of VSD in the period of late pregnancy. The most of postnatal VSD were spontaneously closed within one year of age. The spontaneous closure rates of fetal VSD with different diameter were different. The spontaneous closure rate of VSD with smaller diameter was higher.

Prenatal Isolated Ventricular Septal Defect May Not Be Associated with Trisomy 21.

The aim of this study was to examine if isolated fetal ventricular septal defect (VSD) is associated with trisomy 21. One hundred twenty six cases with prenatal VSD diagnosed by a pediatric cardiologist were reviewed. Cases with known risk factors for congenital heart disease, the presence of other major anomalies, soft signs for trisomy 21 or a positive screen test for trisomy 21 were excluded. Ninety two cases formed the study group. None of the cases in the study group had trisomy 21. The upper limit of prevalence for trisomy 21 in isolated VSD is 3%. When prenatal VSD is not associated with other major anomalies, soft markers for trisomy 21 or a positive nuchal translucency or biochemical screen, a decision whether to perform genetic amniocentesis should be individualized. The currently unknown association between isolated VSD and microdeletions and microduplications should be considered when discussing this option.