Original Research

Fetal Cardiac Axis and Congenital Heart Defects in Early Gestation Elena S. Sinkovskaya, MD, PhD, Rabih Chaoui, MD, Katrin Karl, Ludmila Zhuchenko, MD, PhD, and Alfred Z. Abuhamad OBJECTIVE: To investigate the association between cardiac axis and fetal congenital heart defects to demonstrate the potential clinical applicability of cardiac axis measurement for detection of congenital heart defect in early gestation. METHODS: This case–control study was undertaken in three tertiary centers with expertise in fetal imaging in early gestation. Fetal cardiac axis was evaluated between 11 0/7 and 14 6/7 weeks of gestation in 197 fetuses with confirmed congenital heart defects. A control group was selected by matching each fetus with a congenital heart defect with two fetuses in the control group with similar crown-rump length (65 mm) and date of study (62 months). Cardiac axis was measured on the fourchamber view as the angle between the line that traces the long axis of the heart and the line that bisects the thorax in an anteroposterior direction. RESULTS: In the control group, mean cardiac axis was 44.567.4˚. The cardiac axis did not significantly change in early pregnancy. In the congenital heart defect group, 25.9% of fetuses had cardiac axis measurements within normal limits. In 74.1%, the cardiac axis was abnormal including 110 fetuses in the case group with left deviation (cardiac axis .97.5th percentile), 19 fetuses in the case group with right deviation (cardiac axis ,2.5th percentile), and 17 fetuses in the case group with nonidentifiable cardiac axis. The performance of cardiac axis measurement in detection of major congenital heart defect was significantly better than enlarged nuchal

From the Departments of Obstetrics and Gynecology, Eastern Virginia Medical School, Norfolk, Virginia, and Maistrasse, Ludwig-Maximilians-University, Munich, Germany; the Prenatal Diagnosis Center, Berlin, Germany; and the Moscow Regional Research Scientific Institute of Obstetrics and Gynecology, Moscow, Russia. Corresponding author: Elena S. Sinkovskaya, MD, PhD, Department of Obstetrics and Gynecology, 825 Fairfax Avenue, Suite 310, Norfolk, VA 23507; e-mail: [email protected] Financial Disclosure The authors did not report any potential conflicts of interest. © 2015 by The American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved. ISSN: 0029-7844/15

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MD,

Elena Andreeva,

MD, PhD,

translucency, tricuspid regurgitation, or reversed A-wave in ductus venosus used alone or in combination. CONCLUSION: Abnormal cardiac axis is present in twothirds of fetuses with congenital heart defect in early gestation. Adding cardiac axis assessment to the nuchal translucency measurement is helpful in defining a population at risk for fetal congenital heart defect. (Obstet Gynecol 2015;125:453–60) DOI: 10.1097/AOG.0000000000000608

LEVEL OF EVIDENCE: II

C

ongenital heart disease is the most common congenital abnormality in the human fetus and accounts for more than half of the deaths from birth defects in childhood.1 To improve the early prenatal detection of congenital heart disease, several indirect ultrasonographic markers have been proposed for screening between 11 0/7 and 13 6/7 weeks of gestation including increased nuchal translucency, abnormal blood flow in ductus venosus, and tricuspid regurgitation.2–7 High-frequency ultrasound probes along with substantial improvements in signal processing have dramatically increased our ability to visualize the developing fetus during the first trimester of pregnancy, allowing detailed investigation of fetal anatomy and diagnosis of major congenital anomalies in this period.8 Assessment of the transverse view of the fetal chest at the level of the four-chamber view is currently required by the International Society of Ultrasound in Obstetrics and Gynecology practice guidelines for performance of first-trimester fetal ultrasound scan to document the normal position of the heart (levocardia).9 The four-chamber view allows for the assessment of the fetal cardiac axis. Studies were performed to establish normal values and the feasibility of cardiac axis measurement in early gestation using either the transabdominal or transvaginal approach.10,11 It was shown that successful cardiac axis measurement rates increased with increasing gestational age and can be achieved in 80–100% of cases.10,11

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The purpose of this study was to investigate the association between abnormal cardiac axis and fetal congenital heart disease to demonstrate the potential clinical applicability of cardiac axis measurement for detection of congenital heart disease in early gestation.

MATERIALS AND METHODS This multicenter case–control study was undertaken at three tertiary centers with expertise in early fetal imaging in the United States, Germany, and the Russian Federation. Permission was obtained from each local institutional review board or independent ethics committee to retrospectively examine the medical records of all pregnant women who presented for first-trimester screening between January 2005 and June 30, 2011. In all three institutions an assessment of fetal basic anatomy including transverse plane of the fetal chest at the level of the four-chamber view was performed routinely in early gestation (11 0/7 and 14 6/7 weeks of gestation) since January 1, 2005, using the same ultrasound protocol. Cases of confirmed fetal congenital heart disease diagnosed prenatally with well-documented four-chamber views between 11 0/7 and 14 6/7 weeks of gestation were identified from the prenatal database in each study center and comprised the study group. Confirmation of congenital heart disease was based on the second- to thirdtrimester fetal, postnatal imaging or autopsy, or all of these. The term “major congenital heart disease” was used to describe cardiac malformations in which surgery or an intervention procedure is usually necessary during the first year of life. Cases of pregnancy terminations, miscarriages, or lost of follow-up at less than 18 weeks of gestation were excluded. A control group was selected from respective center population by matching each case of congenital heart disease with two fetuses in a control group with similar crownrump length (65 mm) and date of study (62 months). Only cases without preexisting risk factors for fetal congenital heart disease with normal ultrasound findings and known uncomplicated pregnancy outcome were included in the control group. One ultrasound image per case demonstrating the four-chamber view in two-dimensional or in two-dimensional+color Doppler was retrieved from the database. Images for study and control groups were selected if the following criteria were met: 1) obtained at gestational age between 11 0/7 and 14 6/7 weeks, 2) vaginal or transabdominal ultrasonography was used, and 3) demonstrated anatomic markers including one complete rib on each side of the fetal lateral chest wall and clear visualization of the cardiac chambers. All images were deidentified before review (contained no personal

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health information). The Information Technology Department of the research center created centerspecific directories on its FTP server designed to facilitate the uploading of images. A research coordinator who was not involved in the assessment of the data coordinated the reception of the images and randomly assigned a number to each image. A linking tool to crossreference the images to the clinical data was created. All images were placed in a standardized position (the spine at the 6 o’clock position and the apex of the heart in the left upper chest). Cardiac axis was measured by one investigator (E.S.S.) as the angle between the line that traces the long axis of the heart and the line that bisects the thorax in an anteroposterior direction (Fig. 1). In patients with isolated major fetal congenital heart disease, other first-trimester ultrasound findings, including nuchal translucency measurement, presence of tricuspid regurgitation, and blood flow in ductus venosus, were recorded. The investigator performing cardiac axis measurements was blinded to the source of the image, the clinical data, and pregnancy outcomes. All ultrasound examinations were performed on Voluson 730 Expert and Voluson E8 ultrasound equipment with transabdominal transducer 4–8 MHz and transvaginal transducer 5–9 MHz or 6–12 MHz.

Left

Right

Spin Cardiac axis=48° Fig. 1. Four-chamber view of the heart of a normal fetus at 12 6/7 weeks of gestation. Measurement of the cardiac axis is demonstrated. Sinkovskaya. Fetal Cardiac Axis and Congenital Heart Defects. Obstet Gynecol 2015.

Fetal Cardiac Axis and Congenital Heart Defects

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Statistical analysis was performed using the SAS 9.1.3 software. Normal distribution of continuous variables was assessed with the KolmogorovSmirnov test. Continuous variables are reported as mean6standard deviation or median (range) depending on the data distribution. Categorical data were expressed by frequencies and percentages. A P value of ,.05 was considered significant. The effect of fetal crown-rump length and gestational age on the cardiac axis was evaluated using regression analysis. The prevalence of abnormal cardiac axis, enlarged nuchal translucency (above 95th percentile or greater then 3.5 mm), presence of tricuspid regurgitation, and reversed A-wave in ductus venosus waveform was calculated and compared using the x2 test and Fisher exact test.

RESULTS In total, 197 fetuses met the inclusion criteria and comprised the study group. Three hundred ninetyfour fetuses were selected for the control group. The demographic and clinical characteristics of fetuses with congenital heart disease and fetuses in the control group are shown in Table 1. In the study group, preexisting risk factors for fetal cardiac anomalies were found in 29 of 197 (14.7%) patients including personal (4/29) or family history (6/29) of congenital heart disease, pregestational diabetes (8/29), exposure to medication with a possible teratogenic effect (2/29), and use of assisted

reproductive technology for the current pregnancy (9/29). Nearly 40% of the fetuses in the study group had normal karyotype based on prenatal invasive testing or postnatal studies. Chromosomal and extracardiac abnormalities identified in fetuses with congenital heart disease are presented in Figure 2. In total 407 patient charts were reviewed to select 394 patients for the control group. Thirteen cases (3.3%) did not meet the inclusion criteria secondary to poor resolution of the images between 11 0/7 and 11 6/7 weeks of gestation (six cases), presence of fetal anomalies including enlarged nuchal translucency (four cases), and maternal pregestational diabetes (two cases). In the control group, the cardiac axis ranged from 24 to 68° (mean 44.567.4°; 95% confidence interval 29.8–59.2). Cardiac axis did not appear to differ significantly with gestational age (r520.07; P5.19). Using 1.96 standard deviations, range, and mean for in the entire control group, cardiac axis was defined as abnormal when the measurement was found to be above the 97.5th percentile (left deviation) or below the 2.5th percentile (right deviation). In case of an absent or nonvisualized interventicular septum, measurement was impossible to perform and cardiac axis was considered nonidentifiable (Fig. 3). A normal cardiac axis was defined as being at least 30° but less than 60°. The mean cardiac axis in the entire congenital heart disease group of 197 fetuses was 62.0621.7° (range 0–114°). Individual measurements of cardiac

Table 1. Demographic and Other Characteristics of the Study and Control Groups Parameter No. of fetuses in the case group Maternal age (y) Maternal BMI (kg/m2) Gestational age (wk) 11 0/7–11 6/7 12 0/7–12 6/7 13 0/7–13 6/7 14 0/7–14 6/7 No. of fetuses in the pregnancy Singleton Twins*† Triplets† CRL (mm) Type of ultrasound examination Transabdominal Transvaginal

Study Group

Control Group

P

197 32.966.6 (18–47) 30.766.3 (15.6–72)

394 30.165.8 (18–42) 28.465.8 (18.2–68.5)

— .45 .21 1

27 (13.7) 104 (52.8) 60 (30.5) 6 (3.0)

54 (13.7) 208 (52.8) 120 (30.5) 12 (3.0)

187 (95.0) 9 (4.5) 1 (0.5) 62.369.8 (38.8–91.2)

374 (95.0) 18 (4.5) 2 (0.5) 65.269.0 (41.1–85.2)

176 (89.3) 21 (10.7)

360 (91.4) 34 (8.6)

1

.18 .41

BMI, body mass index; CRL, crown-rump length. Data are mean6standard deviation (range) or n (%) unless otherwise specified. * Including eight dichorionic diamniotic and one monochorionic diamniotic sets of twins. † Only one fetus was affected in each set of multiple gestation and included in analysis in study group; it was matched by one fetus with the closest CRL measurement from selected control set of multiple gestation with the same chorionicity and amnionicity.

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Cases qualified for the study (n=197)

Abnormal karyotype (n=119) Trisomy 21: 49 Trisomy 18: 31 Trisomy 13: 11 Monosomy X: 10 Triploidy: 3 Deletion 22q11.2: 3 Other: 12

Normal karyotype (n=78)

Congenital heart defect and other abnormality (n=7) Cleft lip or palate: 2 Holoprosencephaly: 1 Dandy-Walker malformation: 1 Omphalocele: 1 Amniotic band syndrome: 1 CHARGE syndrome: 1

Fig. 2. Clinical characteristics of the study group.

Isolated congenital heart defect (n=71) Major congenital heart defect: 58 Minor congenital heart defect: 13

axis in fetuses with congenital heart disease and normal fetuses in the control group are plotted on the reference range for crown-rump length (median, 5th and 95th percentiles), shown in Figure 4. In the congenital heart disease group, 51 of 197 (25.9%) fetuses had cardiac axis measurements within normal limits and ranged from 33 to 59°. In 146 of 197 (74.1%), the cardiac axis was abnormal including 110 cases with

Cardiac axis=72°

A

Cardiac axis=19°

B

C

Fig. 3. Types of cardiac axis abnormalities: Left deviation (A), right deviation (B), and nonidentifiable axis (C). Sinkovskaya. Fetal Cardiac Axis and Congenital Heart Defects. Obstet Gynecol 2015.

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Sinkovskaya. Fetal Cardiac Axis and Congenital Heart Defects. Obstet Gynecol 2015.

left deviation, 19 cases with right deviation, and 17 cases with nonidentifiable cardiac axis (Table 2). The types of cardiac anomalies and their relation to increased nuchal translucency thickness and cardiac axis between 11 0/7 and 14 6/7 weeks of gestation are summarized in Table 3. In fetuses with congenital heart disease, nuchal translucency above 95th percentile, nuchal translucency above 3.5 mm, or abnormal cardiac axis was observed in 51.7%, 43.1%, and 74.1%, respectively. Prevalence of enlarged nuchal translucency and abnormal cardiac axis was similar for septal defects (69.1% compared with 63.2%; P5.59). However, abnormal cardiac axis was found more commonly in conotruncal anomalies (81.6% compared with 30.6%; P,.01) and complex congenital heart disease including univentricular hearts (96.6% compared with 37.9%; P,.01). When the 119 fetuses with chromosomal abnormalities were excluded, in the reminding 78 fetuses, the mean cardiac axis was 61.7620.1° (range 0–97°). Table 4 presents the incidence of enlarged nuchal translucency and abnormal cardiac axis in the subgroup of 78 fetuses with congenital heart disease and normal karyotype. In this subgroup an abnormal cardiac axis was present more commonly than an enlarged nuchal translucency (71.8% compared with 19.2%; P,.01). The incidence of abnormal cardiac axis in the fetuses with normal and abnormal karyotype did not differ significantly (71.8% compared with 75.6%; P5.81). In 58 fetuses with normal karyotype and major isolated congenital heart disease, data regarding presence or absence of tricuspid regurgitation as well as pattern of blood flow in ductus venosus were

Fetal Cardiac Axis and Congenital Heart Defects

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120

100

Cardiac axis (degrees)

80

Fig. 4. Individual measurements of cardiac axis in fetuses with congenital heart defects (triangles) and fetuses in the normal control group (circles) plotted on the reference range for crown-rump length (median, 5th, and 95th percentiles). Sinkovskaya. Fetal Cardiac Axis and Congenital Heart Defects. Obstet Gynecol 2015.

60

40

20

Control group 0

Study group 40

50

60

70

80

90

Crown rump length (mm)

available for review. Prevalence of enlarged nuchal translucency, abnormal cardiac axis, tricuspid regurgitation, and reversed A-wave in ductus venosus in fetuses with isolated major congenital heart disease is shown in Table 5. The estimated performance of cardiac axis measurement in screening for major congenital heart disease was significantly better than enlarged nuchal translucency, tricuspid regurgitation, or reversed A-wave in ductus venosus used alone or in combination.

DISCUSSION The transverse plane of the fetal chest at the level of the cardiac four-chamber view is routinely used in screening for congenital heart disease in the second trimester of pregnancy and has been recently

proposed as a potential screening tool in the first trimester.9,12 This view allows evaluation of cardiac axis and position. Cardiac axis is defined as the angle made by the interventricular septum of the heart and the anteroposterior axis of the chest. In normal fetuses, cardiac axis was reported to be approximately 45620° in the second and third trimesters.13 It has been demonstrated that cardiac axis measurement in early gestation is feasible using either the transabdominal or transvaginal approach (or both).10,11 There has been some discrepancy in the reported data on the normal values of the cardiac axis in early gestation. This discrepancy may be explained by the relatively small number of cases in earlier studies, the technical difficulties or limited resolution of cardiac imaging before 12 weeks of gestation, and differences in

Table 2. Cardiac Axis in the Study and Control Groups Study Group Cardiac Axis Normal Left deviation Right deviation Nonidentifiable

All CHDs (N5197) 51 110 19 17

(26)* (55.8)* (9.6)* (8.6)*

CHD With Normal Karyotype (n578) 22 39 5 12

(28.2)* (50)* (6.4)* (15.4)*

Isolated Major CHD With Normal Karyotype (n558) 12 31 3 12

(20.7)* (53.4)* (5.2)* (20.7)*

Control Group (n5394) 383 (97.2) 7 (1.8) 4 (1) 0

CHD, congenital heart defect. Data are n (%). * Significant difference in comparison with the control group; P,.01.

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Table 3. Frequency of Enlarged Nuchal Translucency and Abnormal Cardiac Axis in Fetuses With Congenital Heart Defect, Stratified by Type of Cardiac Anomaly Type of Cardiac Anomaly Septal defects Large VSD Small VSD Multiple VSDs AVC complete AVC partial Conotruncal anomalies TOF CAT D-TGA L-TGA DORV IAA Univentricular hearts HLHS MA with VSD TA Double inlet SV Valvular pathology AS PS Tricuspid dysplasia Ebstein anomaly Mitral stenosis Aortic arch anomalies CoAo RAA Double AoA Combined CHD AVC+TOF AVC+DORV AVC+CAT AVC+L-TGA Heterotaxy Other Total

n

Nuchal Translucency Greater Than the 95th Percentile

Nuchal Translucency Greater Than 3.5 mm

Abnormal CAx

68 23 8 1 34 2 49 33 4 4 1 4 3 29 10 9 3 7 9 1 3 3 1 1 23 17 5 1 19 8 2 1 1 1 6 197

47 (69.1) 16 3 0 27 1 15 (30.6) 13 0 0 0 2 0 11 (37.9) 4 6 0 1 3 (33.3) 1 1 1 0 0 15 (65.2) 14 1 0 11 (57.9) 5 1 0 0 1 4 102 (51.7)

40 (58.8) 16 2 0 22 0 13 (26.5) 12 0 0 0 1 0 8 (27.6) 4 4 0 0 3 (33.3) 1 1 1 0 0 13 (56.5) 12 1 0 8 (42.1) 5 1 0 0 0 2 85 (43.1)

43 (63.2) 14 1 0 26 2 40 (81.6)*† 28 4 1 1 3 3 28 (96.6)*† 9 9 3 7 6 (66.6) 1 1 2 1 1 11 (47.8) 9 1 1 18 (94.7)*† 8 2 1 1 1 5 146 (74.1)*†

CAx, cardiac axis; VSD, ventricular septal defect; AVC, atrioventricular canal defect; TOF, tetralogy of Fallot; CAT, common arterial trunk; D-TGA, dextrotransposition of the great arteries; L-TGA, congenitally corrected transposition of the great arteries; DORV, double outlet right ventricle; IAA, interrupted aortic arch; HLHS, hypoplastic left heart syndrome; MA, mitral atresia; TA, tricuspid atresia; SV, single ventricle; AS, aortic stenosis, PS, pulmonary stenosis; CoAo, coarctation of the aorta; RAA, right atrial appendage; AoA, aortic arch, CHD, congenital heard defect. Data are n (%) or n. * Significant difference in comparison with nuchal translucency greater than the 95th percentile; P,.01. † Significant difference in comparison with nuchal translucency greater than 3.5-mm; P,.01.

grouping of patients by gestational age. In the present study, reference values of the cardiac axis between 11 0/7 and 14 6/7 weeks of gestation were determined using a large cohort of normal fetuses. We have demonstrated that mean values of the cardiac axis did not change significantly between 11 0/7 and 14 6/7 weeks of gestation; however, the highest variation of the cardiac axis measurements was noted at 11 0/7–11 6/7 weeks of gestation. Our results of cardiac axis measurement in early gestation were similar to those

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reported in the middle of the second and third trimesters.14–16 This observation supports the earlier proposed theory that fetal cardiac axis establishes its position by the 12th week of gestation and remains unchanged during pregnancy.17,18 Studies performed in the second and third trimesters have differed slightly with regard to the definition of an abnormal cardiac axis. The very first study by Comstock13 suggested an abnormal cardiac axis as greater than 65° or less than 25°. Another study

Fetal Cardiac Axis and Congenital Heart Defects

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Table 4. Frequency of Enlarged Nuchal Translucency and Abnormal Cardiac Axis in Fetuses With Congenital Heart Defects and Normal Karyotype (n578) Type of Cardiac Anomaly

n

Septal defects Conotruncal anomalies Univentricular hearts Valvular pathology Combined CHD Aortic arch anomalies Total

13 30 13 6 7 9 78

Nuchal Translucency Greater Than the 95th Percentile 4 3 1 1 3 3 15

Nuchal Translucency Greater Than 3.5 mm

(30.8) (10.0) (7.7) (16.7) (42.9) (33.3) (19.2)

2 2 0 1 1 2 8

Abnormal CAx

(15.4) (6.7) (0) (16.7) (14.3) (22.2) (10.3)

7 23 13 3 7 3 56

(53.8)*† (76.7)*† (100)*† (50)*† (100)*† (33.3) (71.8)*†

CHD, congenital heart defect. Data are n (%). * Significant difference in comparison with nuchal translucency greater than the 95th percentile; P,.01. † Significant difference in comparison with nuchal translucency greater than 3.5-mm; P,.01.

considered a small cardiac axis as less than 28° and cardiac axis greater than 59°, consistent with left axis deviation.14 Similar criteria were used to define abnormal axis in small series of 10 fetuses diagnosed with congenital heart disease between 12 and 15 weeks of gestation.11 In our study, we defined normal cardiac axis as at least 30° but less than 60°. In addition, three types of cardiac axis abnormalities were suggested including left axis deviation, right axis deviation, and nonidentifiable cardiac axis. The findings of this study demonstrated that between 11 0/7 and 14 6/7 weeks of gestation, abnormal cardiac axis is present in 74% of fetuses with congenital cardiac anomalies. Our results are in agreement with the findings of a previous study, in which the sensitivity of the abnormal cardiac axis in congenital heart disease between 16 and 40 weeks of

gestation was found to be 75%.14 Cardiac anomalies occurred in fetuses with small and large cardiac axes. However, left deviation of the cardiac axis in fetuses with congenital heart disease is the most common and in our study was found in 55.8% cases. Similar results were previously reported by in the second trimester.15 Defining left axis deviation as greater than 57° allowed the detection of congenital heart disease in 44% of fetuses between 17 and 40 weeks of gestation.15 Incidence of abnormal cardiac axis has been reported to be dependent on type of congenital heart disease.15 Our results demonstrated that an abnormal cardiac axis is more likely to be found in fetuses with conotruncal anomalies and complex congenital heart disease including univentricular hearts. Assessment of the cardiac axis can be particularly helpful in early detection

Table 5. Frequency of Enlarged Nuchal Translucency, Reversed A-Wave in Ductus Venosus, Presence of Tricuspid Regurgitation, and Abnormal Cardiac Axis in Fetuses With Isolated Major Congenital Heart Defects (n558) Type of Cardiac Anomaly Septal defects Conotruncal anomalies Univentricular hearts Valvular pathology Aortic arch anomalies Combined CHD Total

TR

Combined (Nuchal Translucency or DV or TR)

Abnormal CAx

3 1

3 2

3 2

5 18

1

0

0

1

10

4

1

1

2

2

3

5

2

1

0

3

4

6 58

2 10 (17.2)*

0 6 (10.3)*

1 8 (13.8)*

3 14 (24)*

6 46 (79.3)

n

Nuchal Translucency Greater Than the 95th Percentile

Reverse A-Wave in DV

6 25

3 1

12

DV, ductus venosus; TR, tricuspid regurgitation; CAx, cardiac axis; CHD, congenital heart defect. Data are n or n (%). * Significant difference in comparison with CAx; P,.01.

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of conotruncual anomalies such as Tetralogy of Fallot and common arterial trunk, because these are commonly characterized by a normal four-chamber view. In the last 15 years, several ultrasonographic markers including increased nuchal translucency, abnormal flow in the ductus venosus, and tricuspid regurgitation have been proposed for cardiac screening between 11 0/7 and 13 6/7 weeks of gestation. In addition, diagnostic algorithms using different combinations of these markers were developed to estimate patient-specific risk for major congenital heart disease, allowing a detection rate of cardiac anomalies up to 54%.6 An important observation of this study is that in contrast to nuchal translucency, cardiac axis performs equally well in detecting congenital heart disease in fetuses with normal and abnormal karyotype. Furthermore, performance of cardiac axis measurement in detection of major congenital heart disease in fetuses with normal karyotype seems to be significantly better than enlarged nuchal translucency, tricuspid regurgitation, or reversed A-wave in ductus venosus used alone or in combination. This observation, however, should be further substantiated in a larger population-based study. There are several limitations to this study that should be mentioned. First, measurement of the cardiac axis was performed retrospectively. We do not believe that this has a significant effect on the results, because standard four-chamber planes for cardiac axis assessment were retrieved from prospectively collected imaging databases. Second, a case– control study design did not allow estimating diagnostic value of the cardiac axis measurement for the general population. Despite the fact that all cardiac axis measurements were performed by one observer, we do not feel that the accuracy of the results was affected. Excellent interobserver and intraobserver reproducibility of cardiac axis measurement between 11 0/7 and 14 6/7 weeks of gestation was previously reported by our group.10 Finally, every effort was made to keep the observer blinded to the diagnosis; however, evident abnormal appearance of the fourchamber view in certain congenital heart diseases could have contributed to potential bias. This study validates the potential clinical applicability of the cardiac axis measurement as a screening tool for cardiac anomalies in late first and early second trimester of pregnancy. The findings of the study demonstrated that addition of cardiac axis assessment to the nuchal translucency measurement is helpful in defining a population at risk for fetal congenital heart disease. Identification of abnormal cardiac axis during routine ultrasound evaluation in early gestation should be considered an indication for fetal echocardiogram.

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Fetal Cardiac Axis and Congenital Heart Defects

OBSTETRICS & GYNECOLOGY

Copyright ª by The American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.

Fetal cardiac axis and congenital heart defects in early gestation.

To investigate the association between cardiac axis and fetal congenital heart defects to demonstrate the potential clinical applicability of cardiac ...
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