Fetal cardiac axis in 1st trimester

Ultrasound Obstet Gynecol 2010; 36: 676–681Published online in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/uog.8814Defining the fetal cardiac axis between 11 + 0 and14 + 6 weeks of gestation: experience with 100 consecutivepregnanciesE. SINKOVSKAYA*, S. HORTON*, E. M. BERKLEY*, J. K. COOPER*, S. INDIKA†and A. ABUHAMAD**Division of Maternal-Fetal Medicine of the Department of Obstetrics & Gynecology and †Epidemiology and Biostatistics Core, EasternVirginia Medical School, Norfolk, VA, USAK E Y W O R D S: cardiac axis; echocardiography; fetal heart; first trimester; heart defectsABSTRACT cardiac malformations, was made possible by the advent of high-resolution transvaginal and transabdominalObjective The purpose of this study was to establish ultrasonography. Furthermore, the growing acceptance ofnormal fetal cardiac axis values during the first and early nuchal translucency (NT) thickness measurements madesecond trimesters of pregnancy. between 11 and 14 weeks’ gestation to assess the riskMethods This was a prospective observational cohort for chromosomal abnormalities led to the identificationstudy in which the fetal cardiac axis was assessed of fetuses at high risk for major congenital heart diseaseduring ultrasound examinations in 100 consecutive (CHD)1 . Detailed evaluation of the fetal heart in early gestation may therefore allow the early detection offetuses between 11 + 0 and 14 + 6 weeks of gestation. CHD2 – 4 .Transabdominal, and, when indicated, transvaginal, Evaluation of the fetal cardiac axis (CAx) is part of theapproaches were used. Intraobserver and interobserver fetal cardiac examination performed in the mid-secondreproducibility were calculated. and third trimesters of pregnancy5 . In this gestational ageResults The cardiac axis ranged from 34.5 to 56.8◦ window, the normal CAx is defined at a 45◦ angle to the(mean (SD) 47.6 ± 5.6◦ ) in 94 fetuses with normal cardiac left of the midline with a range of plus or minus 20◦6 .anatomy. The fetal cardiac axis tended to be significantly Several studies have suggested fetal CAx measurementhigher in fetuses at 11 + 0 to 11 + 6 weeks of gestation as a possible screening tool for CHD, with a reportedthan in fetuses at 12 + 0 to 14 + 6 weeks of gestation. sensitivity of 79.3% and a specificity of 97.6%7 . Left CAxCongenital heart defects were found in six out of 100 deviation is largely associated with cardiac abnormalities,fetuses, four of which had abnormal cardiac axis values especially conotruncal anomalies, which are commonlyat 11 + 0 to 14 + 6 weeks of gestation. difficult to detect from the four-chamber view alone8,9 . It was also demonstrated that an abnormally narrowConclusion Cardiac axis measurement is possible in CAx with a normal cardiac position may occur in casesthe first and early second trimesters of pregnancy. The of cardiac anomalies10 . The specific embryologic eventassessment of cardiac axis at an early gestational age may that results in an abnormal CAx in some fetuses withhelp to identify pregnancies at high risk for congenital cardiac abnormalities is not currently known; however,heart defects. Copyright  2010 ISUOG. Published by an over-rotation of the bulboventricular loop in earlyJohn Wiley & Sons, Ltd. embryogenesis has been proposed as the underlying mechanism6,7 . The aim of this prospective study was to establishINTRODUCTION normal fetal CAx values during the first and early second trimesters of normal pregnancy as well as to determineThe ability to obtain images of the fetal heart, at an if routine assessment of the CAx in early gestation mayearly gestational age, of sufficient clarity to diagnose identify fetuses with CHD.Correspondence to: Dr E. Sinkovskaya, Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, 825 FairfaxAvenue, Suite 310, Norfolk, VA 23507, USA (e-mail: sinkove@evms.edu)Accepted: 18 August 2010Copyright  2010 ISUOG. Published by John Wiley & Sons, Ltd. ORIGINAL PAPER

Fetal cardiac axis 677METHODSThis study was approved by the Human InvestigationBoard of the Eastern Virginia Medical School (EVMS),and was conducted at EVMS’s Division of Maternal-FetalMedicine ultrasound laboratories. After receiving writ-ten informed consent, a total of 100 consecutive women,≥ 18 years of age and with singleton pregnancies between11 + 0 and 14 + 6 weeks’ gestation, were enrolled in thestudy. Exclusion criteria included maternal obesity (bodymass index (BMI) ≥ 30) and refusal to participate in thestudy. Transabdominal ultrasound was initially performed inall study patients to examine the fetus. The transvaginalapproach was used if visualization of the fetus (because ofits position) was insufficient or if suboptimal transabdom-inal images were obtained. All ultrasound examinationswere performed using Voluson 730 Expert and VolusonE8 ultrasound equipment (GE Healthcare Ultrasound,Zipf, Austria) with a 4–8-MHz transabdominal trans- Figure 1 Cardiac axis measurement in a fetus at 13 + 4 weeks’ducer and a 5–9-MHz transvaginal transducer. gestation. The angle shown in this case is 43◦ (normal). LV, left The ultrasound examination included a crown–rump ventricle; RV, right ventricle; S, spine.length (CRL) measurement of the fetus followed by aNT measurement when requested by the patient. The as frequencies and percentages. A P < 0.05 was consid-CAx was assessed by obtaining an axial view of the fetal ered significant. The Tukey test was applied to examinechest at the level of the four-chamber view with a single the variance of the CAx at different gestational ages. Thefull rib visible on each side and then by measuring the effect of CRL on the CAx was evaluated using regres-CAx as the angle of two lines. The first line started at sion analyses. Repeated-measures ANOVA was usedthe spine posteriorly and ended in mid-chest anteriorly, to assess intraobserver variations. Interobserver repro-bisecting the chest into two equal halves. The second line ducibility was evaluated by calculating the limits oftraced the long axis of the heart and ran through the agreement using the Bland–Altman analysis11 and theinterventricular septum (IVS) (Figure 1). Color or power coefficient of variation (CV). The following formula wasDoppler was occasionally used to confirm the location used to assess the CV: CV (%) = (SD/mean of measure-of the IVS, which then guided the accurate placement of ment (Observer 1; Observer 2)) × 100.the intersecting angle line when the IVS was not clearlyimaged on two-dimensional (2D) ultrasound (Figure 2). Ineach case one of the authors (E.S.) measured the CAx three RESULTStimes. The average of these three measurements was used Demographic characteristics, gestational age and NTto represent the CAx for each participant. In addition, measurements at first presentation of the study patientsthe CAx was also measured by another author (S.H.). are shown in Table 1. Seventy-two patients underwentBoth investigators were blinded to each other’s results. first-trimester screening with NT measurement forIn addition to measurement of the CAx, an evaluation of chromosome abnormalities. Of the 72 fetuses in whichthe fetal heart was performed, which included imaging NT thickness was measured, 2/72 had an NT of ≥ 3.5 mmof the four-chamber view and the outflow tracts. All and both had CHD.patients underwent ultrasound examination during the A transabdominal ultrasound alone was performed insecond and/or third trimesters, which included a targeted 81/100 (81%) of cases, and a combined transabdominalevaluation of fetal anatomy, fetal echocardiography and and transvaginal approach was used in 19/100 (19%) ofCAx measurement. Postnatal follow up was obtained cases.for all patients by reviewing the medical records and by The four-chamber view was visualized in all fetuses intelephone interview. early gestation. In 94 fetuses heart anatomy was normal. The CAx value in this group of normal fetuses rangedStatistical analysis from 34.5 to 56.8◦ (mean (SD) 47.6 ± 5.6◦ ). Based on our results, a CAx of < 35◦ and > 60◦ represents 2 SDStatistical analysis was performed using the SAS 9.1.3 outside our mean measurement and should be consideredsoftware (SAS, Cary, NC, USA). Normal distribu- abnormal. The relationship between CAx and gestationaltion of continuous variables was assessed using the age is shown in Figure 3. The CAx showed a tendency toKolmogorov–Smirnov test. Continuous variables are be significantly higher (levorotation) at a gestational agereported as mean ± SD or as median (range), depending of 11 + 0 to 11 + 6 weeks compared with a gestationalon the data distribution. Categorical data are expressed age of between 12 + 0 and 14 + 6 weeks (Table 2).Copyright  2010 ISUOG. Published by John Wiley & Sons, Ltd. Ultrasound Obstet Gynecol 2010; 36: 676–681.

678 Sinkovskaya et al.Figure 2 Assessment of the cardiac axis using high-definition power Doppler in a normal fetus at 12 + 6 weeks’ gestation. (a) Right and leftventricles are colored bright red and separated by a dark line, which represents the interventricular septum (arrows). (b) Cardiac axismeasurement is shown. LV, left ventricle; RV, right ventricle; S, spine.Table 1 Demographics, gestational age and nuchal translucency(NT) measurements at first presentation (n = 100) 55Parameter Value 50Maternal age (years) 31.1 ± 6.4Race CAx (°) Caucasian 59 45 African–American 31 Asian 8 Hispanic 2 40Gravidity 3 (1–13)Parity 1 (0–4)Body mass index (kg/m2 ) 24.2 ± 3.5 35Gestational age (weeks) 11 + 0 to 11 + 6 18 12 + 0 to 12 + 6 40 40 50 60 70 80 90 13 + 0 to 13 + 6 26 CRL (mm) 14 + 0 to 14 + 6 16NT* (mm) 1.5 (0.9–4.6) Figure 3 Scatter plot presenting cardiac axis (CAx) measurement plotted against crown–rump length (CRL). Individual values forValues given as mean ± SD, median (range) or %. *n = 72. the CAx of normal fetuses and the reference range (mean, 5th and 95th centiles) are shown. Repeated-measures ANOVA showed no significantdifferences in the three separate measurements of CAxmade by the same observer (P = 0.3). Figure 4 presents tetralogy of Fallot and atrioventricular septal defect.a Bland–Altman plot of interobserver reproducibility. All fetuses had abnormal CAx measurements. In threeThe mean difference in CAx measurements performed by of these cases left deviation of the CAx (74, 97 andObserver 1 (E.S.) and Observer 2 (S.H.) was close to zero, 68◦ ) was noted, and one fetus had mesocardia withand no significant difference was obtained. Based on the the CAx = 0◦ (Table 3). Figures 5 and 6 show CAxCV, the interobserver variation for CAx measurements measurements in two fetuses with left axis deviationswas 2.8%. in early gestation (12 + 2 and 13 weeks, respectively). In CHDs were diagnosed prenatally in six out of 100 addition, two fetuses were first diagnosed with CHDsfetuses and were confirmed postnatally or by autopsy. In during fetal echocardiography in the second and thirdfour cases the CHDs were found during the initial scan trimesters of pregnancy. In these two fetuses, CAxat the first trimester and included heterotaxy syndrome measurements in the first trimester were within the normalwith complex CHD, hypoplastic left heart syndrome, range.Copyright  2010 ISUOG. Published by John Wiley & Sons, Ltd. Ultrasound Obstet Gynecol 2010; 36: 676–681.

Fetal cardiac axis 679Table 2 Cardiac axis (CAx) measurements in fetuses with normalheart anatomy 3 +2SD CAx (◦ ) Difference in CAx (°)GA (weeks) n Mean ± SD 95% CI 111 + 0 to 11 + 6* 17 52.0 ± 2.9 46.2–57.8 Mean12 + 0 to 12 + 6 38 47.3 ± 2.4 42.4–52.213 + 0 to 13 + 6 24 48.8 ± 3.0 39.9–51.814 + 0 to 14 + 6 15 45.6 ± 5.0 35.6–55.7 −1*Multiple comparison using the Tukey test showed a significant −2SD(P < 0.05) difference between the 11 + 0 to 11 + 6 group comparedwith the three other groups (i.e. between 12 + 0 and 14 + 6 weeks’ −3gestation). GA, gestational age. 30 40 50 60 Mean CAx (°)DISCUSSION Figure 4 Bland–Altman plot of interobserver variation (mean ± SD, 0.4 ± 1.1) in measurements of the fetal cardiac axis (CAx).CHD is the most common congenital abnormality in thehuman fetus, and it accounts for more than half of thedeaths from congenital abnormalities in childhood12 . Sev- NT is associated with cardiac anomalies. Recently-eral risk factors for CHD, including maternal and fetal published data show that, in comparison to other views,factors, have been reported13 . Most neonates born with the four-chamber view has the highest visualization rate atCHD, however, have no preidentified risk factors14 . In each gestational age and can be obtained in 85–100% offact, of all pregnancies referred for fetal echocardio- first-trimester ultrasound examinations17,18 . Based on ourgraphy, the highest rate of CHD (50%) is found in experience, a combined transabdominal and transvaginalpregnancies with a suspected CHD on a routine ultra- approach allows visualization of the four-chamber viewsound examination15 . in all cases between 11 + 0 and 14 + 6 weeks of gestation. The four-chamber view of the heart is included in the The normal CAx does not change significantly betweenbasic obstetric ultrasound examination and has been pro- 16 and 40 weeks of gestation and lies at a 45◦ angle to theposed as a screen for CHD in the second trimester of left of the midline6 . The present study shows the CAx topregnancy5 . Specialized ultrasound skills are not required be significantly higher at 11 + 0 to 11 + 6 weeks of gesta-because the heart is easily imaged in a transverse view of tion than later in pregnancy. The reason for a levorotatedthe fetal chest. Detection of an abnormal four-chamber CAx in early gestation is currently unclear.view, axis or position of the fetal heart should be con- Defining left axis deviation as > 75◦ , one study notedsidered as an indication for fetal echocardiography in the fetal anomalies in 76% of fetuses9 in the second trimester.second trimester7,16 . In left CAx deviation, tetralogy of Fallot, coarctation of In recent years, fetal heart evaluation has become the aorta and Ebstein anomaly are the most commonfeasible in the first and early second trimesters of cardiac lesions, whereas double-outlet right ventricle,pregnancy because of improvements in the resolution of atrioventricular septal defect and common atrium are thetransvaginal and transabdominal probes. Measurement of most common cardiac lesions in right axis deviation8,10,19 .NT is offered routinely in many countries and thickened Our findings in early gestation were similar. ThreeTable 3 Cardiac axis (CAx) values in six fetuses diagnosed with congenital heart defect (CHD) First-trimester scan CAx at CAx NT second/third-trimesterCase (◦ ) (mm) scan (◦ ) GA at diagnosis (weeks) Type of congenital heart defect1 74 2.2 67 12 + 2 Tetralogy of Fallot2 97 3.7 92 12 + 6 Hypoplastic left heart syndrome3 68 4.6 79 13 + 0 AVSD, dominant RV4 0 1.3 2 13 + 6 Heterotaxy syndrome, mesocardia, complex CHD (AVSD, common atrium, infracardiac TAPVC to the portal vein)5 44 1.1 45 23 + 4 Muscular VSD6 48 NM 68 33 + 2 Coarctation of the aorta, small VSDAVSD, atrioventricular septal defect; GA, gestational age; NM, not measured; RV, right ventricle; TAPVC, total anomalous pulmonaryvenous connection; VSD, ventricular septal defect.Copyright  2010 ISUOG. Published by John Wiley & Sons, Ltd. Ultrasound Obstet Gynecol 2010; 36: 676–681.

680 Sinkovskaya et al. Isolated ventricular septal defect did not affect the CAx significantly. The interobserver reproducibility for measuring the CAx in our study was similar to that previously reported by Crane et al.7 in fetuses in the second and third trimesters (CV: 2.8% vs. 3%). Intraobserver agreement in measurement of the CAx was also noted in our study. Currently there are no approved indications for patient referral for early fetal echocardiography. Based upon our experience and that of others, an enlarged NT, the presence of a major extracardiac malformation, the presence of reversed flow in the ductus venosus and the detection of tricuspid and/or mitral regurgitation or an abnormal CAx can be considered indications for early fetal echocardiography20 – 22 . Limitations of the study Maternal body habitus and in utero fetal position play a critical role in the image obtained during the ultrasoundFigure 5 Cardiac axis measurement in a fetus with tetralogy ofFallot at 12 + 2 weeks’ gestation. The angle shown in this case is examination in early pregnancy. The ability to perform an74◦ (left axis deviation). RV, right ventricle; S, spine. evaluation of the fetal CAx in difficult-to-image patients (BMI > 30) is challenging and remains to be determined. To our knowledge this is the first study to evaluate prospectively the CAx during the first and early second trimesters of pregnancy. The value of the CAx in early gestations for the prenatal diagnosis of CHD remains to be established in larger studies. However, our initial results are promising. In this study, we demonstrated the feasibility of CAx assessment in the first and early second trimesters of pregnancy and its potential clinical applica- bility. Further prospective studies in a clinical setting are needed to confirm the value of CAx measurement as a screening test for CHD in early gestation. REFERENCES 1. Johnson B, Simpson LL. Screening for congenital heart disease: a move toward earlier echocardiography. Am J Perinatol 2007; 24: 449–456. 2. Smrcek JM, Berg C, Geipel A, Fimmers R, Axt-Fiedner R, Diedrich K, Gembruch U. Detection rate of early fetal echocardiography and in utero development of congenital heart defects. J Ultrasound Med 2006; 25: 187–196.Figure 6 Cardiac axis measurement in a fetus with an unbalanced 3. Huggon IC, Ghi T, Cook AC, Zosmer N, Allan LD, Nico-atrioventricular septal defect at 13 + 0 weeks’ gestation. Left axis laides KN. Fetal cardiac abnormalities identified prior todeviation, with an angle of 68◦ , is present. RV, right ventricle; 14 weeks gestation. Ultrasound Obstet Gynecol 2002; 20:S, spine. 22–29. 4. Haak MC, van Vugt JM. Echocardiography in early pregnancy: review of literature. J Ultrasound Med 2003; 22: 271–280.fetuses with left axis deviations had hypoplastic left 5. Cardiac screening examination of the fetus: guidelines forheart syndrome, tetralogy of Fallot and unbalanced performing the ‘basic’ and ‘extended basic’ cardiac scan. Ultrasound Obstet Gynecol 2006; 27: 107–113.atrioventricular septal defect in our small series. Right 6. Comstock CH. Normal fetal heart axis and position. Obstetdeviation of CAx was found in the fetus with heterotaxy Gynecol 1987; 70: 255.syndrome. Of note, two of four fetuses in our study which 7. Crane JM, Ash K, Fink N, Desjardins C. Abnormal fetal cardiachad CAx deviation in the first trimester and CHD had axis in the detection of intrathoracic anomalies and congenitala normal NT measurement and thus CHD could have heart disease. Ultrasound Obstet Gynecol 1997; 10: 90–93. 8. Shipp TD, Bromley B, Hornberger LK, Nadel A, Benacer-escaped detection by NT screening alone. In one case of raf BR. Levorotation of the fetal cardiac axis: a clue for thecoarctation of the aorta in our series, CAx was normal in presence of congenital heart disease. Obstet Gynecol 1995; 85:the first trimester and left deviated in the third trimester. 97–102.Copyright  2010 ISUOG. Published by John Wiley & Sons, Ltd. Ultrasound Obstet Gynecol 2010; 36: 676–681.

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Fetal cardiac axis in 1st trimester

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