Correlation between types of Ventricular Septal Defect and chromosomal abnormalities in Low-Risk Non-Invasive Prenatal Testing: A Retrospective Study

doi:10.21203/rs.3.rs-3213119/v1

Download PDF

Research Article

Correlation between types of Ventricular Septal Defect and chromosomal abnormalities in Low-Risk Non-Invasive Prenatal Testing: A Retrospective Study

https://doi.org/10.21203/rs.3.rs-3213119/v1

This work is licensed under a CC BY 4.0 License

Version 1

posted

You are reading this latest preprint version

Objective

The purpose of this study was to find the association between different types of ventricular septal defect (VSD) and chromosomal abnormalities in the low-risk setting of non-invasive prenatal testing (NIPT), as well as to analyze the prognosis of fetuses with different types of VSD.

Methods

Cases with prenatal diagnosis of fetal VSD by amniocentesis were collected from May 2017 to May 2022 at Tianjin Central Obstetrics and Gynecology Hospital. Patients with high risk of prenatal NIPT, including chromosomal number abnormalities, fragment deletions or duplications, and polymorphisms, were excluded from the study. The data collected included ultrasound classification of VSD, prenatal NIPT results, copy number variations (CNVs) results, and neonatal outcomes.

Results

This study examined 74 cases, consisting of 45 isolated VSDs (8 of which were muscular septal defects and 37 non-muscular septal defects) and 29 non-isolated VSDs (10 associated with intracardiac structural anomalies and 19 with extra-cardiac structural anomalies). The results showed that the prevalence of pathogenic CNV was lower in isolated VSDs than in non-isolated VSDs in a low-risk NIPT condition (χ2 = 9.344, P = 0.002). There was no significant disparity in the incidence of pathogenic CNV between VSDs with intracardiac and extra-cardiac structural anomalies (P = 0.541). Additionally, VSDs associated with intracardiac structural anomalies had the highest rate of surgical intervention.

Conclusions

When NIPT is low-risk, isolated VSD does not raise the likelihood of fetal chromosomal defects. However, when VSD is non-isolated and combined with either intra- or extracardiac structural issues, the possibility of pathogenic CNV is significantly higher, and thus, invasive prenatal diagnosis is suggested. Additionally, it was observed that isolated muscular septal defects usually does not require surgical treatment, which provides a useful foundation for prenatal counseling regarding fetal VSD.

Ventricular septal defect

non-invasive prenatal testing

copy number variation

invasive prenatal diagnosis

Congenital heart disease (CHD) is a widespread birth defect observed worldwide, affecting approximately 3 to 11 cases per 1000 live births. Among the various types of CHD, Ventricular Septal Defect (VSD) stands out as the most prevalent, making up around 35% of neonatal CHD cases. Unfortunately, patients with VSD generally face a lower survival rate compared to the general population[1]. VSD can occur not only in isolation but also as an integral component of other complex anomalies, such as Tetralogy of Fallot, Univentricular Atrioventricular Junction, Transposition of the Great Arteries, Aortic Constriction, or Disruption[2]. It has been reported that 20–40% of VSDs are associated with chromosomal abnormalities. If all prenatal ultrasound findings of VSD are recommended for invasive prenatal diagnosis, which not only increases the risk of fetal miscarriage but also adds to patient anxiety. With the advancement of prenatal screening technology, the approach to prenatal screening has evolved over the last decade. Non-invasive prenatal testing (NIPT) has been used to detect fetal chromosomal abnormalities in pregnant women. Extended NIPT not only significantly enhances the screening efficiency for trisomy 13, 18, and 21 but also enables the detection of specific chromosomal microdeletion/microduplication syndromes. This improved screening capability further enhances clinical efficiency and effectively reduces the occurrence of birth defects. As a result, extended NIPT as a prenatal screening strategy offers a more efficient and less invasive alternative to invasive prenatal diagnosis. It not only minimizes the risk of fetal miscarriage but also reduces patient anxiety, making it a valuable option for ensuring a healthy pregnancy and reducing the incidence of birth defects. However, it is important to note that NIPT is a screening test, not a definitive diagnosis. It has certain false positives and negatives and cannot screen for all microdeletions or microduplications[3]. Moreover, the utility of NIPT in the detection of VSD remains unclear. But NIPT may not detect all chromosomal abnormalities that could be present in fetuses with VSD. Studies have reported that isolated VSDs may not significantly increase the risk of fetal chromosomal abnormalities in cases of low-risk prenatal screening, while the rate of chromosomal abnormalities tends to be higher in non-isolated VSDs[2, 4]. In the context of low-risk prenatal screening, it is suggested that invasive prenatal diagnosis may not be necessary for isolated VSD[2, 4]. Therefore there is still a need to explore the correlation between different subtypes of VSD and fetal chromosomal abnormalities in the Chinese population under the condition of low-risk NIPT. The objective of this study is to investigate the relationship between different types of VSD and fetal chromosomal abnormalities in the setting of low-risk NIPT, aiming to provide a theoretical basis for reducing the need for invasive prenatal diagnosis while ensuring that the underdiagnosis rate remains low.

1 Clinical data

This retrospective cohort study was conducted at Tianjin Central Hospital of Obstetrics and Gynecology and included pregnant women who underwent amniocentesis due to fetal VSD between May 2017 and May 2022. Those who were diagnosed with either isolated VSDs or non-isolated VSDs through echocardiography were included in the study, while pregnant women without Non-Invasive Prenatal Testing (NIPT), those at high risk of NIPT, and those with genetic disorders were excluded. The focus of the analysis was on the population undergoing amniocentesis due to fetal VSD under the condition of low-risk NIPT. High-risk NIPT cases, which included chromosomal number abnormalities, segment deletions or duplications, and polymorphisms, were also taken into consideration. To monitor the pregnancy outcomes, phone calls were made and newborns were followed up for at least six months after delivery. Postpartum diagnoses and prognoses were documented, including those that required surgical intervention and those that healed naturally without surgery, either inside or outside the uterus. The data collection and analysis process was illustrated in Fig. 1.

2 The ultrasonic diagnosis criteria and classification of fetal VSD

The transabdominal ultrasound was conducted using the GE Volson E10 color Doppler ultrasound diagnostic instrument, accompanied by the C1-5-D probe of 3.5-5.5MHz frequency. Diagnosis of fetal VSD was determined by the presence of a continuous disruption of the ventricular septum in the parasternal four-chamber view, and enhanced echo at the septal end, which was made visible with the use of color Doppler imaging. This diagnosis was made by cardiac ultrasound experts with more than 5 years of experience in our hospital.

The presence of other cardiac and extracardiac abnormalities on ultrasound examination was used to divide VSD into isolated and non-isolated types. Isolated VSD was further divided into muscle defect and non-muscle defect groups, with the latter including perimembranous and mixed-type defects. Non-isolated VSD included intracardiac and extracardiac structural abnormalities, such as atrioventricular septal defect, coarctation of the aorta, and Fallot's tetralogy. Additionally, extracardiac abnormalities could include Fetal Growth Restriction (FGR), lateral ventricles expansion, double renal pelvis expansion, digestive tract obstruction, hypospadias, and short long bones.

3 Chromosomal examination

Chromosome G banding karyotype analysis and CNV seq based on high-throughput sequencing were conducted at 18–24 weeks of gestation, with Fluorescence in situ hybridization (FISH) and CNV-seq also performed at more than 24 weeks. The results of CNV-seq were classified according to the ACMG2019 guidelines, which included Pathogenic (P), Likely Pathogenic (LP), Uncertain Significance (VUS), Likely Benign (LB), and Benign (B). After a comprehensive analysis of CNV seq and G banding karyotype analysis/FISH, the cases in this study were categorized as non-probable pathogenic (LP) CNV patients, which were divided into pathogenic CNV (P) and nonpathogenic CNV. The latter included CNV of unknown clinical significance and benign CNV. Women and their families could then decide to continue or terminate the pregnancy based on the presence of pathogenic CNV, gestational age, and the severity of fetal structural abnormalities.

4 Statistical analysis

SPSS 24.0 was utilized in data processing. To compare the incidence of pathogenic CNV in various kinds of VSD and the rate of surgical intervention between the groups, χ2 test (with continuous correction or Fisher's test) was employed. A P-value of less than 0.05 showed that the difference was statistically significant.

1 Analysis of the composition ratio of each type of VSD and the incidence of pathogenic CNV

Table 1 reveals that of the 74 fetuses with VSD, 60.8% (45/74) had isolated VSD (IVSD), while 39.2% (29/74) had non-isolated VSD (NIVSD). Of the isolated cases, 12.2% (9/74) had muscular septal defect (MSD) and 48.6% (36/74) had non-MSD. As for the non-isolated cases, 13.5% (10/74) had VSD combined with intracardiac structural anomalies while 25.7% (19/74) had VSD combined with extracardiac structural anomalies. Regarding the incidence of pathogenic CNV in different types of VSD, no pathogenic CNV was observed in 9 patients with isolated MSD and 36 patients with non-MSD (0/9, 0%; 0/36, 0%). In contrast, among the 10 patients with VSD combined with intracardiac structural abnormalities (ISA), two had pathogenic CNV (2/10, 20%) and five out of 19 patients with VSD combined with extracardiac structural abnormalities(ESA) had pathogenic CNV(5/19, 26.3%). Additionally, non-pathogenic CNV included clinically significant unknown and normal CNV (Table 1).

Table 1

Incidence of pathogenic CNV of different types of VSD
Groups	Total number (n=)	Pathogenic CNV [n (%)]	Nonpathogenic CNV
Groups	Total number (n=)	Pathogenic CNV [n (%)]	unknown Clinical significance (n=)	Not found (n=)	Total [n (%)]
Isolated MSD	9	0(0)	2	7	9(100)
Isolated MSD	36	0(0)	3	33	36(100)
NIVSD combined with ISA	10	2(20)	0	8	8(80)
NIVSD combined with ESA	19	5(26.3)	2	12	14(73.7)

2. Comparison of pathogenic CNV rates among groups

A comparison of the incidence of pathogenic CNV between isolated and non-isolated VSD showed that the incidence was 0% (0/45) in the isolated VSD group and 24.1% (7/29) in the non-isolated VSD group, with a statistically significant difference, χ2 = 9.344, P < 0.05 (Table 2). This difference was statistically significant, indicating that the incidence of pathogenic CNV was significantly lower in the isolated VSD group. Analysis of the non-isolated VSD subgroups revealed that the incidence of pathogenic CNV in combination with ISA was 20% (2/10) in VSD, and 26.3% (5/19) in combination with ESA in VSD. However, no statistically significant difference was seen between the two groups (Table 2). In contrast, none of the isolated VSD subgroups had pathogenic CNV, so no comparison was made. When comparing the non-isolated VSD subgroups, the incidence of pathogenic CNV in combination with ISA was 20% (2/10) in VSD, and 26.3% (5/19) when linked with ESA; the difference in pathogenic CNV was not significant (Table 2). Isolated VSD subgroups did not have pathogenic CNV, hence no comparison was done.

Table 2

Comparison of the incidence of pathogenic CNV in different groups
Groups	Total number (n=)	Pathogenic CNV [n(%)]	Nonpathogenic CNV [n(%)]	χ2	P
IVSD	45	0(0)	45(100)
NIVSD	29	7(24.1)	22(75.9)	9.344	0.002 a
ISA	10	2(20.0)	8(80.0)
ESA	19	5(26.3)	14(73.7)		0.541b

a Continuity chi-square test

b Fish exact probability method

3. Clinical characteristics and pregnancy outcome of pathogenic CNV and CNV of unknown clinical significance

Out of 74 cases, 7 were identified as pathogenic CNV (nos. 1–7). One of these cases was a VSD combined with left subclavian artery vagal and aortic stenosis (no. 1), another was a VSD with membranous aneurysm and left heart enlargement (no. 2), and three were VSD with fetal growth restriction (FGR) with or without amniotic fluid and heart enlargement (nos. 3). All 7 cases were chosen for termination of pregnancy, and the CNV results and VSD phenotype are shown in Table 3. Seven out of the 74 cases had CNV of unknown clinical significance (nos. 8–14), including one VSD with hypospadias (no. 13), one tetralogy of Fallot (no. 14), three isolated nonmuscular defects (nos. 8–10), and two isolated muscular septal defect (nos. 11, 12). All the cases, except for no. 13, opted for termination of the pregnancy, and the outcome was positive in all of them. The CNV results and VSD phenotypes are detailed in Table 4.

Table 3

Clinical data and pregnancy outcome of 7 fetuses with pathogenic CNV
Groups	Number	Clinical phenotypes	Results of CNV	Pregnancy outcome
VSD combined with ISA	1	Left subclavian artery vagus, aortic stenosis	1.25Mb missing at 9q34.3	Induced labor
VSD combined with ISA	2	Ventricular defect with membranous tumor, left heart enlargement	8.0Mb missing at 18p11.32p11.23	Induced labor
VSD combined with ESA	3	FGR、excessive amniotic fluid	2 repeats of 9.6 Mb fragment at 15q11.2q13.3	Induced labor
	4	FGR、cardiomegaly	12.7 Mb fragment missing at 14q32.12q32.33 segment	Induced labor
	5	Widening of the lateral ventricles	5.35 Mb missing at 15q26.2- 15q26.3, along with a 14.2 Mb repeat at 8q24.22-8q24.3	Induced labor
	6	FGR	47XN + 9[64%]/46XN[36%]	Induced labor
	7	Bilateral renal pelvic dilatation	8.95 Mb chimeric repeat at 22q11.1q11.23 with a chimeric ratio of 67%	Induced labor

Table 4

Clinical data and pregnancy outcome of 7 fetuses with CNV of unknown clinical significance
Groups	Number	Clinical phenotypes	Results of CNV	Pregnancy outcome
IVSD	8	Non-muscular VSD	1.3Mb repeat at 8q21.13 segment	Full-term labor
	9	Non-muscular VSD	1.25Mb repeat at 2q14.3 region	Full-term labor
	10	Non-muscular VSD	700Kb missing at 3p24.3-3p24.3	Full-term labor
	11	Muscular VSD	306.4Kb missing at 4q22.1 region	Full-term labor
	12	Muscular VSD	1.45 Mb repeats at 2p12 region	Full-term labor
NIVSD	13	VSD with hypospadias	450kb repeat at Xp11.22 region	Induced labor
	14	Tetralogy of Fallot	541.1Kb fragment repeat at 17p13.3 region	Full-term labor

4. Comparison the rate of surgical interventions for in neonates with various forms of VSD

Out of the 67 cases of non-pathogenic CNV, 7 opted to induce labor for personal reasons, 1 passed away due to metabolic disease after delivery, and the remaining 59 neonates were born without complications and survived. The details of these cases are presented in Table 5. Excluding induction of labor and death, the rate of surgical intervention for newborns or infants with isolated MSD was 0% (0/9), while the rate of surgery for newborns or infants with isolated non-MSD was 20% (7/35). The surgery rate for newborns or infants with VSD combined with ISA was significantly higher than that of newborns or infants with VSD combined with ESA (83.3% vs 11.1%, P < 0.05). However, there was no significant difference in the surgery rate between the isolated MSD group and the isolated MSD group (Table 5).

Table 5

Surgical interventions in 59 neonates with normal and surviving CNVs
Groups	Neonatal outcome		Non-surgical interventions			Surgical interventions [n (%)]	χ2	P
Groups	Normal (n)	Termination of pregnancy (n)	Natural closure [n (%)]	Observation [n (%)]	Total [n (%)]	Surgical interventions [n (%)]	χ2	P
MSD (n = 9)	9	0	5(55.6)	4(44.4)	9(100)	0(0)
Non-MSD (n = 36)	35	1#	2(5.6)	26(72.2)	28(80)	7(20)	0.907	0.341a
NIVSD combined with ISA (n = 8)	6	2	0(0)	1(16.7)	1(16.7)	5(83.3)		0.002b
NIVSD combined with ESA n = 14	9	5	3(33.3)	5(55.6)	8(88.9)	1(11.1)		0.5c

#: death after birth due to metabolic disease

a Isolated MSD vs isolated Non-MSD, continuity chi-square test

b Isolated MSD vs non-isolated VSD combined with ISA, Fish's exact probability method

c Isolated MSD vs non-isolated VSD combined with ESA, Fish exact probability method

NIPT is a widely accepted prenatal screening method, which is able to identify microdeletions and microduplications of certain chromosomes over 3Mb[5]. Research in recent years has revealed a strong connection between VSD and chromosomal abnormalities, particularly trisomies of 21, 18, and 13, as well as sex chromosome abnormalities[6]. However, there was no mention of the prenatal chromosomal serological screening or NIPT results of these pregnant women. In this research, all seven cases of pathogenic CNV had chromosomal deletions or duplications with fragment sizes ranging from 1.25 Mb to 14.2 Mb, but NIPT screening failed to identify them. The reason for this could be attributed to the limitations of NIPT, such as its targeted random quantitative sequencing of cffDNA in maternal plasma, which may not cover all chromosome fragments. Additionally, the location of the chromosome deletions or repetitive fragments may also affect the results of the detection. Other factors that may affect the results include false positive rate, fetal free DNA concentration, and sequencing depth[7]. Despite the fact that some pregnant women with invasive prenatal testing of fetal VSD may be screening high-risk population, many studies have not included the prenatal chromosome serological screening or NIPT results of these women. Consequently, it can be concluded that the proportion of fetal ventricular septal defect with chromosomal abnormalities is high. Therefore, it is unclear whether the prenatal testing of these pregnant women is due to the high risk of combined screening of fetal VSD or just because of fetal VSD. In this study, we mainly analyzed the relationship between different types of VSD fetuses, chromosomes, and prognosis under the condition of low-risk NIPT.

Reports show that among the population who had undergone trisomy screening tests, early ultrasound evaluation, and NIPT screening, 8 cases of pathogenic CNV were found in 568 fetuses with isolated VSD. The incidence of fetal carriers of pathogenic CNV was not significantly different from the rate of the general pregnant woman population, which is approximately 1.6–1.7%[8]. Research conducted in pregnancies with low comprehensive risk assessment in early pregnancy and isolated VSD detected before delivery showed that the incidence of chromosomal abnormalities was 0.7%, which was lower than the incidence of chromosomal abnormalities in the general pregnant woman population [9]. It has also been reported that isolated muscular septal defect may be a benign variation[6]. Our research found that under the context of low-risk NIPT, 45 fetuses with isolated ventricular septal defect had no pathogenic CNVs, indicating that the defect may be a benign variation. Conversely, non-isolated VSD had a chromosomal abnormality rate of 14.6%[8]. In addition, the incidence of non-isolated VSD pathogenic CNV was significantly higher than that of isolated VSD, with a ratio of 24.1–0%, especially when combined with ESA. The incidence of its pathogenic CNV was 26.3%, which was slightly lower than the incidence of 40% chromosomal abnormalities of VSD with extracardiac abnormalities reported by Alan et al. The occurrence of non-isolated VSD-causing CNV was notably higher than that of isolated VSD, with a ratio of 24.1–0%, especially when combined with extra-cardiac structural issues. The rate of its pathogenic CNV was 26.3%, which was slightly lower than the 40% chromosomal anomalies of VSD with extra-cardiac issues reported by Alan et al.[10]. The exclusion of high-risk VSD of NIPT in the case data may mean that invasive prenatal diagnosis was not needed for fetuses with isolated VSD when NIPT was at low risk. On the other hand, for those with non-isolated VSD, even if NIPT was at low risk, it is highly recommended to carry out invasive prenatal diagnosis, especially if combined with ESA, in order to prevent any missed diagnosis and possible adverse pregnancy outcomes.

Interestingly, when analyzing the malformation characteristics of pathogenic CNV, we found that 5 of the 7 cases of pathogenic CNV were VSD with extra-cardiac structural issues, and three of them had FGR. It is not clear yet if the link between VSD and FGR is due to hemodynamic changes or changes in the placenta-heart axis during the early stages of embryonic development[11]. It is possible that VSD is more prone to merging with FGR, and more case studies are needed to understand this connection [12]. Therefore, it is suggested that pregnant women with non-isolated VSD, especially when combined with FGR, should go for an invasive prenatal diagnosis and CNV examination.

According to reports, the number of isolated ventricular septal muscle defects and isolated perimembranous VSD that closed spontaneously in fetuses was 31/64 and 3/11, respectively. At 2 years old, the rate of spontaneous closure was 92.2% and 45.5%, respectively[13]. Usually, isolated ventricular septal muscle defects close in pregnancy or during the first two years of life, but isolated perimembranous VSD may necessitate intervention after birth[4]. In this study, all cases were tracked for at least 6 months postnatally. The follow-up results showed that the natural closure rate for isolated muscle defects was 55.6%, while that for non-muscle defects was 5.6%, which was in line with our study. Thus, isolated ventricular septal muscle defects have the highest rate of natural healing and usually do not need surgical treatment, whereas isolated non-muscle defects should be thoroughly evaluated. It has been reported that a defect of ≥ 4 mm is an independent predictor of non-spontaneous closure of perimembranous VSD[14]. In this study, the average size of isolated muscle defects was 2.18 mm, with a maximum of 3.5 mm, and no surgical intervention was performed. On the other hand, the average size of non-muscular defects was 3.07 mm, with 8 cases having a size of more than 4 mm and a 20% surgical intervention rate. It is possible that the size of the defect could be one of the reasons why the natural healing rate of non-muscular defects was lower than that of muscular defects, although no significant data was found (data not shown). It appears that patients with non-isolated VSD have a higher rate of pathogenic CNVs, and most people opt for induced labor. After eliminating chromosomal issues, the surgical intervention rate for VSD combined with ISA was 83.3%, while for VSD combined with ESA, the rate was 11.1%. This suggests that the prognosis of VSD patients with chromosomal abnormalities combined with ESA may be better than that of isolated non-muscular defects and VSD combined with ISA. Despite the small sample size, larger studies are still needed to further analyze the issue. A study showed that 45.4% of VSD closed in the womb, 30.9% closed in the first year of life, and those with a defect larger than 3mm did not close spontaneously[15]. The average size of VSD in the operative and the non-operative groups was 3.89mm and 2.87mm, respectively (data not shown). Although no significant difference was found, it is still important to take into consideration the size of the defect for better patient care.

This study has some restrictions. Primarily, the sample size is not large as it is a single center study. Secondly, the follow-up data of newborns was obtained by telephone follow-up which may have some discrepancies; the decision of whether to perform a surgical intervention is based on certain human factors. To sum up, this article mainly focused on the incidence of distinct types of VSD chromosomal abnormalities under the condition of low-risk NIPT and the surgical intervention of newborns or infants. Results showed that if NIPT screening was low risk, isolated VSD did not raise the risk of fetal chromosomal abnormalities, so invasive prenatal diagnosis may not be necessary. However, for patients with non-isolated VSD, it is recommended to have an invasive prenatal diagnosis, particularly when combined with ESA, to prevent missed diagnosis and negative pregnancy outcomes. It is important to note that when VSD is complicated with FGR, invasive prenatal diagnosis is recommended. In addition, isolated ventricular septal muscle defects often heal without the need for surgery. However, a thorough evaluation should be conducted for isolated non-MSD and VSD that are accompanied by ESA. Patients with VSD combined with ISA usually require surgical intervention. Going forward, more attention should be paid to the size and type of VSD when conducting research and providing clinical advice, in order to better determine whether spontaneous closure or surgical intervention is necessary. This study provides a theoretical basis for the relationship between different types of VSD and chromosomes under the condition of low-risk NIPT, thus aiding prenatal consultation for VSD patients.

Ethics approval and consent to participate

The studies involving human participants were reviewed and approved by Human Research Ethics Committee of Tianjin Central Hospital of Obstetrics and Gynecology. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. All participants signed a written informed consent form prior to their participation in this study.

Consent for publication

Not Applicable

Availability of data and materials

The datasets generated and/or analysed during the current study are available in the [Science Data Bank] repository, [https://www.scidb.cn/en], the data named “Correlation between types of Ventricular Septal Defect and chromosomal abnormalities in Low-Risk Non-Invasive Prenatal Testing”.

Competing interests

All authors declare that they have no conflict of interest.

Fundings

National Key Specialties and Diseases Cohort Project (GJZDZKZBDL2022-04); National Natural Science Foundation of China (82001579); Tianjin Health Research Project (TJWJ2021QN053, TJSQNYXXR-D2-077); Natural Science Foundation of Tianjin (21JCQNJC00040).

Authors' contributions

Xiaomin Zhao: the acquisition, analysis, or interpretation of data for the work; Yongmei Shen: Drafting the work or revising it critically for important intellectual content; Dexuan Kong and Liying Yao: Ultrasonography; Shanshan Li and Wen Li: Writing-review and editing; Ying Chang: Substantial contributions to the conception or design of the work and final approval of the version to be published.

Acknowledgements

We gratefully acknowledge the Prenatal Diagnosis Center and Ultrasound Center of Tianjin Central Hospital of Obstetrics and Gynecology in supporting this collaborative research.

Eckerström F, Nyboe C, Maagaard M, Redington A, Hjortdal VE: Survival of patients with congenital ventricular septal defect. Eur Heart J 2023, 44(1):54-61.
Cheng K, Zhou H, Fu F, Lei T, Li F, Huang R, Wang Y, Yang X, Li R, Li D et al: Should prenatal chromosomal microarray analysis be offered for isolated ventricular septal defect? A single-center retrospective study from China. Front Cardiovasc Med 2022, 9:988438.
Chen Y, Lu L, Zhang Y, Wang F, Ni Y, Wang Q, Ying C: Clinical application of expanded noninvasive prenatal testing for fetal chromosome abnormalities in a cohort of 39,580 pregnancies. American Journal of Medical Genetics Part A 2022, 188(5):1426-1434.
Raucher Sternfeld A, Sheffy A, Tamir A, Mizrachi Y, Assa S, Shohat M, Berger R, Lev D, Gindes L: Isolated ventricular septal defects demonstrated by fetal echocardiography: prenatal course and postnatal outcome. J Matern Fetal Neona 2022, 35(1):129-133.
Hyblova M, Harsanyova M, Nikulenkov-Grochova D, Kadlecova J, Kucharik M, Budis J, Minarik G: Validation of Copy Number Variants Detection from Pregnant Plasma Using Low-Pass Whole-Genome Sequencing in Noninvasive Prenatal Testing-Like Settings. Diagnostics (Basel) 2020, 10(8):569.
Vedel C, Rode L, Jørgensen FS, Petersen OB, Sundberg K, Tabor A, Ekelund CK: Prenatally detected isolated ventricular septum defects and the association with chromosomal aberrations-A nationwide register-based study from Denmark. Prenatal Diagn 2021, 41(3):347-353.
Liu W, Yang J, Zhang J, Lu J, Chen Y, Zhu H, Xiang J, Wang Y, Wang M, Wang J et al: Consensus on technological standards for non-invasive prenatal screening of pathogenic copy number variations by high-throughput sequencing of maternal plasma cell-free DNA. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2021, 38(7):613-619.
Maya I, Singer A, Yonath H, Reches A, Rienstein S, Zeligson S, Ben Shachar S, Sagi-Dain L: What have we learned from 691 prenatal chromosomal microarrays for ventricular septal defects? Acta Obstet Gynecol Scand 2020, 99(6):757-764.
Vedel C, Rode L, Jørgensen FS, Petersen OB, Sundberg K, Tabor A, Ekelund CK: Prenatally detected isolated ventricular septum defects and the association with chromosomal aberrations-A nationwide register-based study from Denmark. Prenatal Diagn 2021, 41(3):347-353.
Allan LD, Sharland GK, Milburn A, Lockhart SM, Groves AM, Anderson RH, Cook AC, Fagg NL: Prospective diagnosis of 1,006 consecutive cases of congenital heart disease in the fetus. J Am Coll Cardiol 1994, 23(6):1452-1458.
Smith M, Nicoll A: Perinatal outcomes following mid trimester detection of isolated short foetal femur length. J Obstet Gynaecol 2018, 38(5):727.
Ghanchi A, Derridj N, Bonnet D, Bertille N, Salomon LJ, Khoshnood B: Children Born with Congenital Heart Defects and Growth Restriction at Birth: A Systematic Review and Meta-Analysis. Int J Env Res Public Health 2020, 17(9):3056.
Raucher Sternfeld A, Sheffy A, Tamir A, Mizrachi Y, Assa S, Shohat M, Berger R, Lev D, Gindes L: Isolated ventricular septal defects demonstrated by fetal echocardiography: prenatal course and postnatal outcome. J Matern Fetal Neonatal Med 2022, 35(1):129-133.
Zhao Q-M, Niu C, Liu F, Wu L, Ma X-J, Huang G-Y: Spontaneous Closure Rates of Ventricular Septal Defects (6,750 Consecutive Neonates). The American Journal of Cardiology 2019, 124(4):613-617.
Gordin Kopylov L, Dekel N, Maymon R, Feldman N, Zimmerman A, Hadas D, Melcer Y, Svirsky R: Prenatally diagnosed isolated perimembranous ventricular septal defect: Genetic and clinical implications. Prenatal Diagn 2022, 42(4):461-468.

No competing interests reported.

Download PDF

Version 1

posted

You are reading this latest preprint version

Correlation between types of Ventricular Septal Defect and chromosomal abnormalities in Low-Risk Non-Invasive Prenatal Testing: A Retrospective Study

Status:

Version 1

Abstract

Objective

Methods

Results

Conclusions

Figures

INTRODUCTION

Materials and Methods

RESULTS

2. Comparison of pathogenic CNV rates among groups

3. Clinical characteristics and pregnancy outcome of pathogenic CNV and CNV of unknown clinical significance

4. Comparison the rate of surgical interventions for in neonates with various forms of VSD

DISCUSSION

Declarations

References

Additional Declarations

Status:

Version 1