Echocardiographic parameters for evaluating coarctation of the aorta before and after birth: A meta-analysis

doi:10.21203/rs.3.rs-5013947/v1

Objective

To investigate the diagnostic value and correlation strength of echocardiographic parameters in evaluating and predicting fetal coarctation of the aorta (CoA).

Methods

PubMed, Web of Science, GeenMedical, The Cochrane Library, CMB, CNKI, Wanfang, and VIP were searched to obtain all data on the echocardiographic diagnosis of aortic coarctation collected from the database to December 1, 2023. Related literature. The quality of the included literature was evaluated using the QUADAS-2 risk assessment standard provided by Revman 5.3 statistical software. The majority of the parameters were analyzed by the Z-score and the corresponding ratio. The results were analyzed using Stata15.1 software, which combined sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), and negative likelihood ratio (NLR) for the data that were pooled. The diagnostic odds ratio (DOR) and publication bias analysis were performed for all included studies.

Results

A total of 17 studies were included containing a total of 1,373 patients. The mean mitral valve diameter Z score, ascending aorta Z score, ascending aorta diameter, aortic isthmus mean diameter Z score ( Three-vessel tracheal section), and ductus arteriosus/aortic isthmus diameter (P < 0.05) of the fetuses with aortic coarctation were lower compared with those of the normal fetuses (P = 0.007, P = 0.032, P = 0.006, P = 0.011, P = 0.019, respectively). The aortic isthmus/ductus arteriosus (diameter, mm), mean pulmonary valve diameter Z score, right ventricle/left ventricle (diameter), and right ventricle/left ventricle (area) were higher than those noted in normal fetuses (P = 0.455, P = 0.557, P = 0.408, P = 0.522, respectively). The echocardiographic parameter of neonates and infants was the carotid-subclavian artery index. Following combination of the data, the following results were obtained: Sensitivity: 0.90 (95% CI: 0.72–0.97), specificity: 0.97 (95% CI: 0.92–0.99), positive likelihood ratio: 26.7 (95% CI: 10.7–66.5), negative likelihood ratio: 0.10 (95%CI: 0.03–0.32), diagnostic odds ratio: 262 (95% CI: 37-1875), subject area under the operating characteristic curve (AUC): 0.98.

Conclusion

For fetuses at risk, the cardiac parameters of the aforementioned ultrasound signs can be more accurately evaluated and can predict the occurrence of CoA before and after birth.

Coarctation of the aorta

Echocardiography

Prenatal diagnosis

Meta-analysis

Coarctation of the aorta (CoA) is one of the most common congenital heart diseases (CHD), accounting for approximately 7% of all live births with CHD. CoA is one of the main life-threatening cardiovascular diseases in the early neonatal period ^[1]. It usually occurs in the aortic isthmus distal to the left subclavian artery and is associated with aortic arch hypoplasia (63%), left ventricular outflow tract obstruction (40%), bicuspid aortic valve (40%), and ventricular cardiac malformations, such as septal defect (28%) and atrial septal defect (12%). The development of fetal echocardiography has improved the prenatal diagnosis of CoA to a certain extent; however it is difficult to make an accurate diagnosis due to the particularity of the blood circulation in the fetal period, so its high false positive rate remains a major problem. Certain challenging issues have been reported ^[2–3]; specifically, if not diagnosed in the fetal period, the follow-up should be maintained to confirm the diagnosis prior to the closure of the ductus arteriosus in the neonatal period after birth. This provides a good opportunity for treatment and can avoid the deterioration of cardiac function in infancy and later in life. Poor systemic perfusion is a major factor affecting the coarctation of the aorta. In certain cases, concomitant patent ductus arteriosus (PDA) is difficult to diagnose due to hemodynamic effects, which results in the delay of surgery following the closure of the ductus. In children and adults, there may be only mild clinical symptoms, such as upper extremity hypertension, systolic murmur, and/or decreased femoral pulse. In this context, the diagnostic accuracy of prenatal testing and the high sensitivity and specificity of the diagnosis in postnatal infancy are important. Reliable screening and diagnosis of coarctation fetuses and all neonates can reduce CoA morbidity and mortality, which in turn reduces the false-positive diagnosis of CoA and can avoid unnecessary stress and suffering for the family of the newborn ^[4].

However, the high false-positive rate of prenatal diagnosis of coarctation of the aorta is a current challenge. The presence of the aortic arch disease was assessed for the first time with the Z-score, which was estimated using natural logarithms over a two-stage process. Gestational age was divided according to the weeks of gestation. The prediction of the isthmus or ductus was performed by the following parameters: Diameter m ln (gestational age) c and Z score [measured isthmus or duct diameter], and ln [(predicted isthmus or duct diameter)]/root MSE, where m and c are the regressions used to predict the heart size from the gestational age measurements, respectively (the m and c variables corresponded to the slope and intercept of the equation) and MSE was the mean squared error. When scan information from the first trimester was available, the Z-scores were calculated using a genetic algorithm; they could also be calculated from the femoral length. In the present study, the strength of the association between fetal echocardiographic signs and CoA was analyzed and the majority of the parameters were analyzed by the Z-score.

In a neonatal study, Dodge-Khatam et al defined the ratio of the diameter of the distal aortic arch to the distance between the left common carotid artery and the left subclavian artery as the carotid-subclavian artery index. By studying the index and its related parameters, this ratio exhibited optimal diagnostic performance in the majority of the studies and was a relatively simple and repeatable method for the screening and diagnosis of neonatal CoA. In recent literature reports, certain researchers have also used this index to evaluate fetal CoA.

Therefore, the present study integrated the related published research reports so as to perform a meta-analysis. This analysis evaluated the influence and diagnostic accuracy of the related ultrasound parameters prior to and following birth.

1. Search strategy

The English databases searched included the following: PubMed, GeenMedical, Web of Sciences, EMBASE, and Corchrane Library; the Chinese databases included the following: Wanfang Database, VIP Database, China National Knowledge Infrastructure (CNKI), and China Biology Medicine disc (CBM). The search time was limited to the time period from the time of database establishment to December 1, 2023. The language was limited to English and Chinese. Firstly, the searched literature was screened according to the title and the abstracts of each study were read for general inclusion and exclusion. In case the content was relevant, all articles that met the inclusion and exclusion criteria were evaluated. The reviews, case reports, and articles on the animal experimental models were excluded and all relevant clinical studies were included. In order to avoid the omission of relevant literature, a manual literature search was carried out by assessing each study one by one for the relevant references found in the retrieved literature.

The retrieval of the English databases mainly included the following keywords: "aortic coarctation", "coarctation of aorta", "echocardiography", "ultrasound", "diagnosis" for literature retrieval; the retrieval of the Chinese databases mainly included the following keywords: "coarctation of the aorta", "echocardiography", "ultrasound", "prenatal diagnosis", and other.

The combination of the keywords used for the English database literature retrieval was as follows: (by using the Pubmed database as an example, other English databases were slightly adjusted on this basis):

(1)(aortic coarctation);

(2)(aortic coarctation) AND (echocardiography);

(3)(coarctation of aorta) AND (echocardiography);

(4)(aortic coarctation) AND (ultrasound);

(5)(aortic coarctation) AND(echocardiography) AND (prenatal diagnosis);

(6)(aortic coarctation) AND (echocardiography OR ultrasound) AND (prenatal diagnosis);

The combination of the keywords used for document retrieval in the Chinese databases was as follows (by using the CNKI database as an example, other Chinese databases were slightly adjusted on this basis):

(1)All: (coarctation of the aorta);

(2)All: (coarctation of the aorta) * All: (Echocardiography);

(3) All: (coarctation of the aorta) * All: (ultrasound);

(4) All: (coarctation of the aorta) + all: (coarctation of the aorta) * all: (echocardiography) * all: (prenatal diagnosis);

2. Study selection and data extraction

2.1. Inclusion criteria

(1) All relevant domestic and foreign literature studies published and all clinically diagnosed aortic coarctation studies were comprehensively reviewed;(2) Studies related to the diagnosis of coarctation of the aorta by echocardiography, and complete and detailed echocardiographic follow-up data;

(3) Complete original data provided in the literature and four-table data obtained directly or indirectly;

(4) The number of cases in each group in the study was ≥ 10;

(5) The gold standard methods used were surgical procedures, postpartum echocardiography or catheter angiography.

2.2. Exclusion criteria

(1) Review, clinical research case reports, literature reviews, animal experimental studies, and conference abstracts, non-Chinese or English research literature;

(2) Literature studies that were not officially published (only those with abstracts); the research studies with the most complete data were selected for those published repeatedly, and the remaining studies were excluded;

(3) The studies, which did not provide the relevant clinical diagnostic information in the literature, or demonstrated incomplete data and lack of detailed clinical raw data available for the combined calculation of the outcome indicators;

(4) Documents related to the title but irrelevant in content;

(5) The studies for which the full text could not be obtained by various literature sources (email, author correspondence) and for which only the abstract was available.

3. Article filtering

Two researchers independently performed literature screening and data extraction. The first step was to browse the retrieved article titles and abstracts. Initially, the relevant literature was screened and following the exclusion of the studies that did not meet the inclusion criteria, 2 independent researchers cross-checked the studies that may have met the inclusion criteria and conducted a careful review of the full texts of the studies. In case of divergent studies and/or difficulty in establishing a consensus, a third researcher was consulted to reach a decision.

A total of 3,495 literature studies were identified through the search and screening method described above. The search results were imported into EndNote X8 software for literature management, and the "Find Duplication" function was used to eliminate duplicate published studies. A total of 3,478 irrelevant studies were excluded (exclusion reasons were non-clinical experimental studies, case reports, or irrelevant articles to the current analysis). The remaining studies that could be included were cross-checked by 2 independent researchers and finally screened according to the established literature inclusion and exclusion criteria. Ultimately, a total of 17 studies that were identified as eligible for quantitative analysis were included in the current meta-analysis (Fig. 1).

The following document databases and number of documents were retrieved: CNKI database (n = 220 articles), Wanfang database (n = 600 articles), VIP database (n = 63 articles), PubMed (n = 1,371), GeenMedical (n = 600 articles) = 462), Web of Science (n = 750), and Cochrane Library (n = 29).

4. Data extraction and literature quality assessment

The data to be extracted for the included literature included the following: (1) Basic information characteristics of the included literature, including the first author of each study, the time of publication, the country (region) where the study was conducted, the type of study, and the sample size of the study; (2) predictive indicators of the study; (3) echocardiographic results and outcome indicators; (4) literature quality evaluation and other related information.

4.1. Data extraction

The extraction of parameters related to fetal echocardiography and the diagnostic test outcome indicators were the following: True positives (TP), false positives (FP), false negatives (FN), true negatives (TN), positive likelihood ratio (PLR), negative Likelihood Ratio (NLR), and Diagnostic Odds Ratio (DOR).

4.2 Literature quality assessment

Two reviewers independently assessed the quality of the included literature through the QUADAS-2 risk assessment tool provided by Revman 5.3. In case of a disagreement, a third reviewer was invited to participate in the discussion to reach an agreement. The criteria included case selection, presence of an evaluation test, gold standard method, case process and progress, and answering "yes", "no", and "unclear" to each part of the question by carefully reading the literature to grasp the baseline characteristics of the included studies and assess the corresponding risk of bias level. The judgment was characterized as "low", "high" and "indeterminate". The risk of bias and quality assessment of the included studies are shown in Fig. 2.

The risk assessment results of the 17 literature studies are shown in Fig. 2. These studies all reached the medium and high quality levels. All the included literature studies contained patients with coarctation of the aorta, all of which were diagnosed as gold standard cases during admission; the testing equipment and specifications were described in detail.

5. Study characteristics

Table 1

General characteristics of the study
Reference	Time	Country	Research design	Guideline	Gestational age (weeks)/age (days/months)	n	CoA, n
Chandni Patel^[4]	2018	US	retrospective	postpartum echocardiography	not specified	57	13
Meaghan^[5]	2016	U.K.	forward- looking	postpartum echocardiography/ Operation	15.0–36.0	62	45
Aray^[6]	2016	US	retrospective	postpartum echocardiography/ Operation	32.8 ± 4.2	40	20
Toole^[7]	2015	US	retrospective	postpartum echocardiography/ Operation	33.9 (30.4–36.0)	62	27
Mărginean^[8]	2015	Romania	forward- looking	postpartum echocardiography/ Operation	36.0 (32.0–39.0)	32	9
Durand^[9]	2015	France	forward- looking	postpartum echocardiography/ Operation	36.0 ± 3	285	41
Sivanandam^[10]	2015	US	retrospective	postpartum echocardiography/ Operation	25.6 (20.0–35.0)	31	11
Sanitra Anuwutnavin^[11]	2015	US	retrospective	postpartum echocardiography/ Operation	26.1 ± 4.6	35	9
Gomez^[12]	2014	Spain	retrospective	postpartum echocardiography/Operation	27.6 ± 6.6	115	52
Slodki^[13]	2009	Poland/ U.S.	retrospective	postpartum echocardiography/ Operation	33.0 ± 3.8	52	12
Matsui^[14]	2008	United Nations	retrospective	postpartum echocardiography/ autopsy	22 (15 + 4–38 + 4)	44	20
Dodge-Khatam^[15]	2005	Switzerland/Germany	retrospective	Operation	baby	86	63
CHun-Wei Lu^[16]	2006	Taiwan	forward- looking	angiography/ Operation	newborn	162	12
Yvan Mivelaz^[17]	2008	Switzerland	retrospective	Operation	Infants < 3 months and > 3 months	92	68
AliA.AlAkhfash^[18]	2013	Saudi Arabia	retrospective	Operation	Infants ≤ 3 months	81	31
Tamara Ilisic^[19]	2015	US	retrospective	Operation	Baby not specified	50	30
David M.Peng^[20]	2015	US	retrospective	Operation	Infants younger than 30 days	87	30

Table 2

Ultrasound parameters included in the assessment of the literature
Reference	Time	Ultrasound signs
Chandni Patel^[4]	2018	Carotid subclavian index, descending isthmus index, and distal transverse arch index of carotid artery
Meaghan^[5]	2016	Ao/PA, LV/RV, AAo-Z score, AoI-Z score, AoI/AD, persistence of diastolic flow in the posterior scaffold of the descending aorta and isthmus
Aray^[6]	2016	AoI d-Z score, RV/LV (d, mm), TV/LV, DA/AoI, MPA/AoI, LCSA, Aao/Dao, TAo-Dao
Toole^[7]	2015	TV-Z score, MV-Z score, PV-Z score, AoV-Z score, AAo-Z score, TAo-Z score, AoI -Z score, AoV/PV, RV/LV, AoI/DA, MV/TV, PLSVC, isthmus duct angle, AoI-PSV, AoI-PI
Mărginean^[8]	2015	AoI-Z score, AAo-Z score, AD/AoI, PA/Ao, Ao, AoI, RV/LV, PLSVC, BAV, VSD
Durand^[9]	2015	Ventricle and great vessel disproportion, AoV-Z score(FL and GA), AoV, PSLVC, VSD, MV, AoV, hypoplasia and angle of AoA
Sivanandam^[10]	2015	CSI, AoI-Z score, MV-Z score, AoV-Z score
Sanitra Anuwutnavin^[11]	2015	MV-Z score, AAo-Z score, TAo-Z score, AoV-Z score, PAV-Z score, AoI-Z score, PLSVC, VSD
Gomez^[12]	2014	TV-Z score, MV -Z score, TV/MV, PV, AoV-Z score, MPA -Z score, AAo-Z score, AoI-Z score, AoI/AD
Slodki^[13]	2009	AAo, PA, PAd, PA/AoA
Matsui^[14]	2008	vascular imbalance, PLSVC, VSD, BAV, bracket, AoI-Z score, AoI/AD
Dodge-Khatam^[15]	2005	carotid subclavian index
CHun-Wei Lu^[16]	2006	PA, AAo, DAo, AoI/AAo, AoI/DAo, transverse arch distal to left common carotid artery, the isthmus was immediately adjacent to the origin of the left subclavian artery
Yvan Mivelaz^[17]	2008	Carotid subclavian artery index (CSA index) and isthmus descending aorta ratio (I/D ratio)
AliA. AlAkhfash^[18]	2013	carotid subclavian index, isthmus/ascending aorta ratio and distal transverse arch/ascending aorta ratio
Tamara Ilisic^[19]	2015	Carotid artery-subclavian index, ratio of ascending aorta diameter to distance between LZKA and LPA, ratio of PTL diameter to distance between LZKA and LPA
David M.Peng^[20]	2015	PDA, carotid subclavian index

6. Echocardiographic parameters and measurement methods

The mitral and tricuspid valves were measured in four-chamber views; the right and left ventricle dimensions (length, diameter, area, and volume) at end-systole, and end-diastole and the outflow tract measurements were converted to pregnancy-associated parameters using previously published sectoral data. The age-adjusted Z value and the diameter of the aortic valve were measured at the fetal long-axis angle, whereas the pulmonary valve was measured in the oblique short-axis or oblique transverse section of the fetal chest, and the aortopulmonary artery and its branches were measured in the longitudinal section. The distal transverse aortic arch diameter and the ductus arteriosus were measured in the sagittal plane. The maximum diameters of the ascending aorta, descending aorta, aortic arch, and aortic isthmus were measured in the three-vessel tracheal plane. The ductus arteriosus and the main pulmonary artery were measured in the three-vessel plane. The largest diameters of the ascending aorta, proximal transverse arch, distal transverse arch, aortic arch, and isthmus, and the distance between the left common carotid and left subclavian arteries were measured in the parasternal and/or high parasternal segment.

7.Ethics Approval declaration:

In accordance with the Declaration of Helsinki,Hospital ethics and scientific approval was obtained for this study and additional informed consent were obtained from all patients.the name of the Approval Committee is Medical Ethics Committee of the First Affiliated Hospital of Xinjiang Medical University,Ethical Approval Number:K202409-08.

8. Statistical analysis

The literature data management software Stata 15.1 (Stata Corporation, USA) was used to analyze the data of the included literature and the I² test was used to assess the heterogeneity of the included literature. The heterogeneity was assessed by the I² value. I² ≥ 50% was considered to be heterogeneous between studies. Among them, the I² value of 0%, 25%, 50%, and 75% corresponded to no, low, medium, and high heterogeneity. In the presence of heterogeneity noted in the included studies, a random effects model was used for data analysis. When heterogeneity was detected, a fixed-effects model was used for analysis and a subgroup analysis was performed on the included studies. If the heterogeneity of a subgroup was significantly reduced, the different factors of this subgroup may be the source of this heterogeneity. Finally, the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and their 95% confidence intervals were estimated. The publication bias of this meta-analysis study was assessed by the Egger's regression test, and the corresponding funnel plot was plotted.

1. Basic characteristics and quality evaluation of the included studies

According to the inclusion and exclusion criteria and the literature quality control requirements, a total of 17 literature studies were finally included in the present study. The flow chart and results of the literature screening are shown in Fig. 1. A total of 1,373 cases were included in the 17 included studies. The overall quality of the included studies was estimated to be of medium and low risk, indicating that the quality of each study was high.

2. Meta-Analysis Results

Table 3

Comparison of echocardiographic parameters of different fetal heart structures based on the results of the diagnosis of coarctation of the aorta by meta-analysis
Ultrasound parameters	Number of total sample	Number of cases/normal	95%CI	P	I²
Mitral valve Z score	4(243)	99/144	-0.39(-2.39,1.60)	0.007	75.2
Tricuspid Z-score	2(177)	79/98	0.40(0.09,0.71)	0.046	0
Aortic valve Z score	5(445)	175/270	-1.08(-1.44,-0.73)	0.150	40.7
Ascending aorta Z-score	4(274)	133/141	-1.10(-1.61,-0.60)	0.032	66.0
diameter of ascending aorta, mm	2(84)	21/63	-0.78(-2.86,1.31)	0.006	87.1
Aortic isthmus Z score	5(248)	128/120	-1.39(-1.93,-0.85)	0.072	57.1
Aortic isthmus Z score	4(240)	117/123	-1.56(-2.19,-0.94)	0.011	72.9
Aortic isthmus diameter, mm	2(84)	21/63	-0.99(-1.21,-0.77)	<0.001	0
Pulmonary valve Z score	2(177)	79/98	0.73(0.32,1.13)	0.557	0
Ventricle/Left Ventricle (Diameter, mm)	2(72)	29/43	0.22(0.04,0.40)	0.408	0
Right ventricle/left ventricle (area, mm²)	2(102)	47/55	0.25(-0.01,0.51)	0.522	0
Pulmonary artery/ascending aorta (diameter, mm)	3(199)	73/126	0.31(-0.07,0.69)	<0.001	90.6
Aortic isthmus/ductus arteriosus (diameter, mm)	3(223)	108/115	-0.13(-0.19,-0.08)	0.455	0
ductus arteriosus/aortic isthmus	2(70)	28/42	0.24(-0.17,0.65)	0.019	81.7
Note: From the aforementioned results it can be concluded that certain parameters demonstrated significant differences in fetuses with CoA notably in the left inflow (mean MV diameter Z score) and outflow tract (AAo-Z score, AAo diameter, AoI-Z score, AoI diameter, and AD/AoI ratio) compared with those noted in normal fetuses.

3. Sensitivity analysis and publication bias

The funnel plot was used to determine whether a potential publication bias was present in the meta-analysis. If the funnel plot was asymmetrically distributed, the Begg rank correlation method and Egger's regression test were used to further assess the publication bias of the present study. P < 0.05 was considered to indicate potential publication bias, whereas P > 0.05, indicated no publication bias. The Egger's test was used to calculate the mitral valve Z-score, aortic valve Z-score, ascending aorta Z-score, aortic isthmus Z-score (three-vessel tracheal view), main pulmonary artery/ascending aorta ratio, and aortic isthmus/ductus arterial diameter ratio. The P values obtained by the test were P = 0.547, P = 0.767, P = 0.784, P = 0.207, P = 0.994, and P = 0.697, indicating no evidence of publication bias among the included studies. The publication bias funnel plots are shown in Fig. 5A, 5B, 5C, 5D, 5E, and 5F, respectively.

4. Meta-analysis of postpartum echocardiographic parameters

Table 4

Summary of parameters and effects of postpartum echocardiography
Methods	SEN(95%CI)	SPE(95%CI)	PLR(95%CI)	NLR(95%CI)	DOR(95%CI)	AUC
carotid subclavian index	0.90 (0.72–0.97)	0.97 (0.92–0.99)	26.7 (10.7–66.5)	0.1 (0.03–0.32)	262 (37-1875)	0.98

In the meta-analysis of the postpartum echocardiographic parameters, the parameter indicators could be combined with the data; the combined sensitivity, specificity, diagnostic odds ratio, and AUC of SROC were 0.90, 0.97, 262, and 0.98, respectively; in the diagnostic test, the AUC of SROC was 0.98, indicating that the carotid artery-subclavian index (CSAi) exhibited an optimal diagnostic effect in the prediction and evaluation of aortic coarctation, with high sensitivity and specificity.

5. Analysis of publication bias for cardiogram parameters included in the postpartum studies

The potential publication bias corresponding to the meta-analysis of the included postpartum studies was detected by a funnel plot. If P < 0.05, a potential publication bias was considered; The Deek funnel plot indicated that P = 0.23 > 0.05, suggesting that the difference was not statistically significant and that no publication bias was present in the included studies.

The main purpose of this systematic review was to determine the practical value of echocardiography in prenatal and postnatal diagnosis of CoA. The accurate diagnosis of CoA in prenatal examinations remains a major challenge ^[21–22]. Prenatal diagnosis of CoA can reduce neonatal morbidity and improve survival. In addition, the reduction of the false-positive diagnosis of CoA can avoid unnecessary stress and distress for the neonatal family ^[23]. Severe CoA has been reported as early as 14 to 16 weeks of gestation ^[24]. However, the fetal heart may also be normal in the first and second trimesters. CoA develops in the third trimester, and the possibility of progression from the normal aortic arch to the aortic arch hypoplasia and CoA during fetal life has been previously reported ^[25]. In addition, certain children with CoA are considered to have a normal aortic arch during their fetal development and CoA manifests postpartum or even in adulthood. Based on the 3-vessel view, Yoo et al., and Yagel et al. originally proposed the value of analyzing the 3-vessel and trachea views ^[26]. Viñals et al. proposed the analysis of the fetal mediastinum and 3-vessel for the possible detection of CoA ^[27].

Pasquini et al. published a Z-score of the aortic arch and duct to assess the aortic arch disease ^[28]. Matsui et al. demonstrated that the Z-scores of the aortic arch and ducts in the 3-vessel sections (particularly obtained continuously over time) could be used to detect cases of fetal coarctation of the aorta and differentiate between false-positive and true-positive cases. In the present study, the main 3-vessel trachea section of the arterial isthmus and the ratio of the ductus arteriosus to the aortic isthmus could be used to evaluate the fetuses with CoA.

However, since fetal CoA is a dynamic process, the sole observation of the shape and diameter of the aortic arch exhibits certain limitations and should be combined with the Z-scores of other ultrasound signs, which are calculated according to the gestational age or femoral length ^{[ 29]}. Aray et al., Tool et al., and Mărginean et al. built a good prediction model, which improved the sensitivity and specificity of prenatal prediction of CoA fetuses. With the popularization of prenatal ultrasonography and the development of specific instruments, fetal CoA varies by gestational age (GA) at diagnosis ^[30]. Gómez et al. proposed a GA-specific scoring system (with no more than two parameters) consisting of three size-based cardiac parameters and gestational age at diagnosis (GA), which aided the optimal diagnosis of CoA, providing a clearer distinction between healthy fetuses and fetuses with CoA even beyond 28 weeks of gestation.

Prompt diagnosis of CoA that is missed on prenatal ultrasonography or develops dynamically during neonatal life and infancy is also critical, since CoA in the neonatal period often presents with severe heart failure and shock symptoms. In the presence of widespread PDA, the diagnosis of neonatal CoA is difficult. A step-by-step diagnostic approach was proposed by Romaciotti and Chin first in 1993 by measuring the diameter of the isthmus and Doppler flow maps of the isthmus and duct ^[31]. However, this approach contains various disadvantages. In certain neonates with CoA, both the ascending and descending aortas exhibit higher pressure than that noted in the pulmonary arteries. The blood flow to the PDA exhibits a continuous left-to-right shunt during both systole and diastole ^[32]. Various studies have shown that the diameters of the ascending and descending aortas in children with CoA are comparable to those noted in the control group; however, the diameter of the transverse arch is significantly smaller and the distances between the origins of the great vessels and the distal aortic arch in the coarctation patients are longer than those noted in the control group. The distance between the left common carotid artery and the left subclavian artery, or the carotid-subclavian artery index (CSAi) as defined by Khatam et al., was significantly lower than that of the control group. In the majority of the studies, the sensitivity and specificity of the aortic coarctation were optimal at a cut-off point of 1.5. The specificity can accurately predict neonatal aortic coarctation.

CSAi is a relatively simple and reproducible indicator for neonatal CoA detection with high sensitivity and specificity. Nevertheless, it should not be used alone, but should be combined with other supporting clinical and imaging data to finally decide whether surgical intervention is required. The recording of the echocardiography is largely dependent on the examiner's technique, experience, and the degree of understanding of the vascular anatomy. Due to the limited sample size of the included studies, there may also be certain differences and limitations in the reports of each study.

The present study contains several limitations. All of the studies included were derived from electronic searches; since the search scope could be expanded, the negative results reported in other literature studies may affect the diagnostic value of the current study; most of the included literature studies were retrospective studies and some of them did not follow a blinded study design. In view of the aforementioned limitations, it is recommended that future research reports should follow the STARD standard as much as possible to improve the quality of the diagnostic test reporting for clinical decision-making. This will lead to the generation of more accurate analysis results.

Funding/Support:This work was not funded.

Author Contribution

Chen Yuan and Ayijibaike Maimaitituergan conceived and designed the manuscript, Chen Yuan 、Yuming Mu and Lina Guan wrote the manuscript. Ayijibaike Maimaitituergan participated in the data collection, analysis of data, and preparation of the manuscript. All authors read and approved the final manuscript.

Michelle K ,Barbara B, Angela L, et al. Narrative analysis of adults with complex congenital heart disease: Childhood experiences and their lifelong reverberations[J]. Congenital Heart Disease, 2018.
Garne E, Stoll C, Clementi M, Euroscan group. Evaluation of prenatal diagnosis of congenital heart diseases by ultrasound: experience from 20 European registries. Ultrasound Obstet Gynecol 2001;17:386–91.
Galindo A, Herráiz I, Escribano D, et al. Prenatal detection of congenital heart defects: a survey on clinical practice in Spain. Fetal Diagn Ther 2011;29:287–95.
Patel C , Weeks B , Copel J , et al. Fetal Echocardiographic Measures to Improve the Prenatal Diagnosis of Coarctation of the Aorta[J]. Pediatric Cardiology, 2018(2).
Vigneswaran T V , Zidere V , Chivers S , et al. Impact of prospective measurement of outflow tracts in prediction of coarctation of the aorta[J]. Ultrasound in Obstetrics And Gynecology, 2020, 56(6):850-856.
Arya B, Bhat A, Vernon M, Conwell J, Lewin M. Utility of novel fetal echocardiographic morphometric measures of the aortic arch in the diagnosis of neonatal coarctation of the aorta. Prenat Diagn. 2016;36:127–134.
Toole BJ, Schlosser B, McCracken CE, Stauffer N, Border WL, Sachdeva R. Importance of relationship between ductus and isthmus in fetal diagnosis of coarctation of aorta. Echocardiography. 2016;33:771–777.
Mărginean C, Mărginean CO, Muntean I, Togănel R, Voidăzan S, Gozar L. The role of ventricular disproportion, aortic,and ductal isthmus ultrasound measurements for the diagnosis of fetal aortic coarctation, in the third trimester of pregnancy. Med Ultrason. 2015;17:475–481.
Durand I, Deverriere G, Thill C, Lety AS, Parrod C, David N, Barre E, Hazelzet T. Prenatal detection of coarctation of the aorta in a non-selected population: a prospective analysis of 10 years of experience. Pediatr Cardiol. 2015;36:1248–1254.
Sivanandam S, Nyholm J, Wey A, Bass JL. Right ventricular enlargement in utero: is it coarctation? Pediatr Cardiol. 2015;36:1376– 1381.
AnuwutnavinSanitra,SatouGary,ChangRueyKang,DeVoreGreggoryR,AbuelAshley,SklanskyMark.PrenatalSonographicPredictorsofNeonatalCoarctationoftheAorta.[J].Journalofultrasoundinmedicine:officialjournaloftheAmericanInstituteofUltrasoundinMedicine,2016,3511.
Gómez-Montes E, Herraiz I, Gómez-Arriaga PI, Escribano D, Mendoza A, Galindo A. Gestational age-specific scoring systems for the prediction of coarctation of the aorta. Prenat Diagn. 2014;34:1198–1206.
Slodki M, Rychik J, Moszura T, Janiak K, Respondek-Liberska M. Measurement of the great vessels in the mediastinum could help distinguish true from false-positive coarctation of the aorta in the third trimester. J Ultrasound Med. 2009;28:1313–1317.
Matsui H, Mellander M, Roughton M, Jicinska H, Gardiner HM. Morphological and physiological predictors of fetal aortic coarctation. Circulation. 2008;118:1793–1801.
Dodge-Khatami Ali,Ott Stephanie,Di Bernardo Stefano,Berger Felix.Carotid-subclavian artery index: new echocardiographic index to detect coarctation in neonates and infants.[J].The Annals of thoracic surgery,2005,805.
Lu Chun-Wei,Wang Jou-Kou,Chang Chung-I,Lin Ming-Tai,Wu En-Ting,Lue Hung-Chi,Chen Yih-Sharng,Chiu In-Su,Wu Mei-Hwan.Noninvasive diagnosis of aortic coarctation in neonates with patent ductus arteriosus.[J].The Journal of pediatrics,2006,1482.
Mivelaz Yvan,Di Bernardo Stefano,Meijboom Erik Jan,Sekarski Nicole.Validation of two echocardiographic indexes to improve the diagnosis of complex coarctations.[J].European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery,2008,345.
Al Akhfash Ali A,Almesned Abdulrahman A,Al Harbi Badr F,Al Ghamdi Abdullah,Hasson Maan,Al Habshan Fahad M.Two-dimensional echocardiographic predictors of coarctation of the aorta.[J].Cardiology in the young,2015,251.
Peng David M,Punn Rajesh,Maeda Katsuhide,Selamet Tierney Elif Seda.Diagnosing Neonatal Aortic Coarctation in the Setting of Patent Ductus Arteriosus.[J].The Annals of thoracic surgery,2016,1013.
Franklin O, Burch M, Manning N, Sleeman K, Gould S, Archer N. Prenatal diagnosis of coarctation of the aorta improves survival and reduces morbidity. Heart 2002; 87:67–69.
Allan LD, Crawford DC, Anderson RH, Tynan M. Spectrum of congenital heart disease detected echocardiographically in prenatal life. Br Heart J 1985; 54:523–526.
Allan LD, Crawford DC, Tynan M. Evolution of coarctation of the aorta in intrauterine life. Br Heart J 1984; 52: 471–473.
Bronshtein M, Zimmer EZ. Sonographic diagnosis of fetal coarctation of the aorta at 14–16 weeks’ gestation. Ultrasound Obstet Gynecol 1998; 11:254–257.
Sharland GK, Chan KY, Allan LD. Coarctation of the aorta: difficulties in prenatal diagnosis. Br Heart J 1994; 71:70– 75.
Yoo, SJ, Lee YH, Kim ES, et al. Three-vessel view of the fetal upper mediastinum: an easy means of detecting abnormalities of the ventricular outflow tracts and great arteries during obstetric screening. Ultrasound Obstet Gynecol 1997; 9:173–183.
Viñals F, Heredia F, Giuliano A. The role of the three vessels and trachea view (3VT) in the diagnosis of congenital heart defects. Ultrasound Obstet Gynecol 2003; 22:358–367.
Pasquini L, Mellander M, Seale A, Matsui H, Roughton M, Ho SY, Gardiner HM. Z-scores of the fetal aortic isthmus and duct: an aid to assessing arch hypoplasia. Ultrasound Obstet Gynecol. 2007;29: 628 – 633.
Pasquini L, Mellander M, Seale A, et al. Z-scores of the fetal aortic isthmus and duct: an aid to assessing arch hypoplasia. Ultrasound Obstet Gynecol 2007;29:628–33.
Gómez-Montes E, Herráiz I, Mendoza A, et al. Prediction of coarctation of the aorta in the second half of pregnancy. Ultrasound Obstet Gynecol 2013;41:298–305.
]Ramaciotti C, Chin AJ. Noninvasive diagnosis of coarctation of the aorta in the presence of a patent ductus arteriosus. Am Heart J 1993;125:179-85.
Cheng CF, Wu MH, Wang JK. Ductus-dependent aortic coarctation with a left-to right shunt through the ductus. Int J Cardiol 1995;49:209-13.

No competing interests reported.

Echocardiographic parameters for evaluating coarctation of the aorta before and after birth: A meta-analysis

Status:

Version 1

Abstract

Objective

Methods

Results

Conclusion

Figures

Introduction

Method

1. Search strategy

2. Study selection and data extraction

2.1. Inclusion criteria

2.2. Exclusion criteria

3. Article filtering

4. Data extraction and literature quality assessment

4.1. Data extraction

4.2 Literature quality assessment

5. Study characteristics

6. Echocardiographic parameters and measurement methods

8. Statistical analysis

Results

1. Basic characteristics and quality evaluation of the included studies

2. Meta-Analysis Results

3. Sensitivity analysis and publication bias

4. Meta-analysis of postpartum echocardiographic parameters

5. Analysis of publication bias for cardiogram parameters included in the postpartum studies

Discussion

Declarations

Author Contribution

References

Additional Declarations

Supplementary Files

Status:

Version 1