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Uog6115.dviUltrasound Obstet Gynecol 2008; 32: 239–242
Published online in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/uog.6115
ISUOG consensus statement: what constitutes a fetal
W. LEE, L. ALLAN, J. S. CARVALHO, R. CHAOUI, J. COPEL, G. DEVORE, K. HECHER,H. MUNOZ, T. NELSON, D. PALADINI and S. YAGEL for the ISUOG Fetal EchocardiographyTask Force K E Y W O R D S: fetal echocardiography; guidelines; heart; pregnancy
2) a definition of what constitutes a fetal echocardiogram;3) a description of imaging modalities for fetal echocar- In 2006 the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) published practice 4) the importance of multidisciplinary collaboration; and guidelines for the sonographic screening of congenital 5) documentation of diagnostic findings and conclusions.
heart disease (CHD) during the second trimester ofpregnancy1. This document described two levels for One of the main goals for a fetal echocardiogram is to screening low-risk fetuses for heart anomalies. Firstly, confirm the presence or absence of cardiac disease. If this a ‘basic’ scan should be performed by analyzing a scan is abnormal, the examiner should characterize these four-chamber view of the fetal heart. Secondly, an abnormalities, develop an accurate differential diagnosis ‘extended-basic’ scan further examines the size and of the most probable defects, and specifically identify relationships of both arterial outflow tracts. The term fetuses that will require immediate medical or surgical ‘fetal echocardiogram’ was also mentioned as a more attention after birth. Special emphasis should be directed detailed sonographic evaluation to be performed by toward fetuses that are likely to have ductal-dependent specialists in the prenatal diagnosis of CHD. Although common indications and imaging techniques were brieflydiscussed, it was thought important to further explain When should a fetal echocardiogram be performed?
how this advanced diagnostic procedure differs from thebasic and extended-basic cardiac screening examinations.
Fetal echocardiography can be performed at any time A Fetal Echocardiography Task Force was subsequently during the second trimester when cardiac anatomical asked to develop a standard description of ‘what details can be satisfactorily visualized. For example, a constitutes a fetal echocardiogram’. Our original goal mother who is at a slightly increased risk for CHD – e.g.
was to develop guidelines for a detailed examination of 2% against a background rate of 0.8% – should be elec- the fetal heart that were based on the literature and tively scheduled for a detailed cardiac scan at some time a consensus opinion of an expert panel. However, we between 18 and 22 weeks’ menstrual age. These include soon realized that this project was quite different from mothers with a family history of CHD, maternal diabetes developing minimum practice guidelines for fetal cardiac or exposure to teratogenic drugs, and fetuses that have screening. There are several imaging modalities that can had an increased nuchal translucency thickness measure- be used to evaluate fetal heart anomalies, ranging from ment. Fetal cardiac abnormalities may occur in association M-mode techniques and color Doppler sonography to with extracardiac anomalies and therefore a detailed car- the use of four-dimensional (4D) ultrasonography with diac scan may be indicated when such anomalies are spatiotemporal image correlation (STIC). Consequently, detected5–7. A mother who is particularly anxious because our original efforts to develop a minimum practice of a family history, perhaps loss of a previous child for guideline for fetal echocardiography evolved into a example, or where the nuchal translucency measurement consensus statement that covers the following topics: is ≥ 3.5 mm, may be offered a scan at or before 14 weeks’gestation, with a follow-up scan at 20–22 weeks8. If a 1) guidance about timing of and indications for fetal fetus is suspected of having CHD at any scan, it should be seen as soon as possible, regardless of menstrual age.
Correspondence to: Dr W. Lee, Division of Fetal Imaging, William Beaumont Hospital, 3601 West Thirteen Mile Road, Royal Oak,Michigan 48073, USA (e-mail: firstname.lastname@example.org) Copyright 2008 ISUOG. Published by John Wiley & Sons, Ltd.
Others have suggested using a fetal echocardiogram as a component of the genetic sonogram, to evaluate fetuses at risk for chromosome abnormalities9,10.
• venous-atrial, atrioventricular and ventriculoarterial Who should be referred for fetal echocardiography?
• size and relationships of the left and right ventricular The detection rate of structural heart anomalies will be higher with fetal echocardiography than with screening examinations. Women with recognized increased risks for fetal cardiac anomalies should be offered a more detailed • atrial septum, atrial chamber size, and foramen ovale scan. Risk factors for fetal cardiac anomalies can be • atrioventricular and semilunar valves categorized as fetal or maternal in origin. Some of the • flow across each heart connection, as seen with Doppler more common indications for fetal echocardiography are summarized in Table 1. Acquired cardiac lesions thatbecome apparent later in life, even those of genetic These anatomical features are usually evaluated using origin such as Marfan’s syndrome and hypertrophic transverse views, although sagittal scanning planes are subaortic stenosis, are not generally detectable by prenatal also used as necessary. However, the specific views are less important as long as the relevant cardiac structures arebeing satisfactorily visualized. Color Doppler ultrasono- What constitutes a fetal echocardiogram during the
graphy is an important component of the fetal echocar- second trimester of pregnancy?
diogram. Although spectral Doppler ultrasonography is Many experienced healthcare professionals, whether they not essential, it can be used to further characterize the are midwives, sonographers, obstetricians, perinatologists nature and severity of suspected flow disturbances15,16.
or radiologists, can evaluate the fetal heart with a high Continuous-wave Doppler sonography is sometimes nec- degree of diagnostic accuracy during an obstetric ultra- essary to quantify very high velocity flow across stenotic sound evaluation. The echocardiogram can be individu- or incompetent valves. Occasionally, advanced techniques alized, depending on the nature of the suspected cardiac may be required to evaluate fetal cardiac function using lesion. As a minimum, it involves a thorough exami- measurements of ventricular ejection fraction, stroke vol- nation of the four-chamber view, both arterial outflow ume, cardiac output, mechanical PR intervals, Tei indices, tracts, three vessels and trachea view, and an assess- and ventricular strain parameters17–20. Volume sonog- ment of pulmonary venous return11–14. The examiner raphy allows a supplemental approach for analyzing should confirm anatomical relationships and functional complex cardiac lesions and may also provide impor- flow characteristics through a systematic analysis of the tant benefits for telemedicine, educational and research Although two-dimensional (2D) measurements of cardiac chambers or vessels are not always required for Table 1 Common indications for fetal echocardiography
fetal echocardiography, they may help to interpret findingswhen compared against expected values. Quantitative measurements can be used to objectively interpret theseverity of some cardiac lesions and as a basis for comparison over time. Measurements can be especially helpful where several different examiners are obtaining cardiac biometry throughout pregnancy. Standardized techniques must be used to maintain appropriate quality control. Some investigators have proposed the use of Z-scores to improve the interpretation of cardiac What type of imaging techniques are used for fetal
Suspected anomalies can be evaluated using several imaging modalities, although the examination can be individualized for specific cardiac anomalies (Table 2).
Real-time gray-scale sonography and complementary Doppler ultrasound techniques (e.g. spectral and color) are often applied. M-mode echocardiography and Doppler ultrasonography are also important tools for theanalysis of fetal cardiac dysrhythmias. Additional results, from three-dimensional (3D) and 4D ultrasonography, Copyright 2008 ISUOG. Published by John Wiley & Sons, Ltd.
Ultrasound Obstet Gynecol 2008; 32: 239–242.
may further increase diagnostic confidence for the disease can be quite different from what is found in a accurate characterization of some complex lesions.
pediatric population. For example, prenatal recognition of The examiner must be completely familiar with the trisomy 18 in a fetus with an inlet ventricular septal defect potential impact of technical factors for acquiring the may dramatically alter management of the pregnancy or best diagnostic heart images within the constraints child after delivery. The rarity of individuals with both of acceptable thermal and mechanical safety indices.
cardiac and extracardiac diagnostic skills supports the Ultrasound signal gain, image magnification, compound need for close teamwork to provide the most precise imaging, and harmonic imaging should be optimized.
fetal prognosis. Only an accurate differential diagnosis Other important factors should also be considered, will lead to appropriate prenatal counseling. For these including menstrual age, maternal body habitus, fetal reasons, we recommend multidisciplinary counseling for movement and position, and ultrasound transducer parents who expect to deliver an infant with heart disease.
frequency. It may be necessary to wait until an optimal This may include collaboration between specialists fetal position is obtained or even to reschedule the patient in pediatric cardiology, maternal fetal medicine, fetal imaging, neonatology, genetics, cardiothoracic surgery, An accurate prenatal diagnosis is extremely important for healthcare professionals who will be counselingparents about the nature, severity, clinical management How should fetal echocardiogram results be
and prognosis of their unborn child. Some aspects of documented?
how to obtain information concerning the entire fetus There is currently no universal legal requirement to doc- may be well beyond the scope of a pediatric cardiologist ument, record and archive a fetal echocardiogram. Both working in isolation from the obstetric imaging specialist.
stored images and a report to the managing/referring The interpretation of some cardiac abnormalities can clinician are highly recommended and are mandatory in be challenging, and minor differences can substantially some jurisdictions. However, we suggest that those pro- alter the surgical approach and clinical prognosis. For viding fetal echocardiography should have the facilities example, abnormal mitral valve attachments can preclude for recording still and moving images of the heart, and the switch operation for transposition of the great these should be available for future reference. Another arteries, a remote or small VSD in a double-outlet alternative is to store volume data sets using 3D and 4D right ventricle can only be treated by a one ventricle repair, or a restrictive atrial septum can change theimmediate postnatal management and prognosis in fetuses Acknowledgments
with hypoplastic left heart syndrome. It should also berecognized that some cardiac lesions will evolve over time This consensus statement was developed under the and may not be apparent until later in pregnancy28.
auspices of the ISUOG Clinical Standards Committee.
Any cardiac abnormality must be interpreted in the Chair: Dr W. Lee, Division of Fetal Imaging, William context of the entire fetus and there should be a Beaumont Hospital, Royal Oak, Michigan, USA.
careful search for possible associations with extracardiac Appreciation is particularly extended to specialty abnormalities. The clinical significance of fetal cardiac consultants on the Fetal Echocardiography Task Force Table 2 General recommendations for fetal echocardiography
Laterality, situs, cardiac connections, other anomalies Cardiac rhythm (M-mode or spectral Doppler) Normal rhythm on two-dimensional ultrasonography Abnormal rhythm on two-dimensional ultrasonography Cardiac function (e.g. M-mode or Doppler) Normal function on two-dimensional ultrasonography Abnormal function on two-dimensional ultrasonography Three- and four-dimensional ultrasonography Copyright 2008 ISUOG. Published by John Wiley & Sons, Ltd.
Ultrasound Obstet Gynecol 2008; 32: 239–242.
an unselected Chilean population. Ultrasound Obstet Gynecol Dr W. Lee (Task Force Chair) Department of Obstetrics 2007; 30: 946–951.
and Gynecology, Division of Fetal Imaging, William 11. Yagel S, Cohen SM, Achiron R. Examination of the fetal heart by five short axis views: A proposed screening method for Beaumont Hospital, Royal Oak, Michigan, USA.
comprehensive cardiac evaluation. Ultrasound Obstet Gynecol Dr L. Allan, Harris Birthright Research Centre, King’s 2001; 17: 367–369.
12. Yagel S, Arbel R, Anteby EY, Raveh D, Achiron R. The three Dr J. S. Carvalho, Brompton Fetal Cardiology, Royal vessels and trachea view (3VT) in fetal cardiac scanning.
Brompton Hospital; Fetal Medicine Unit, St George’s Ultrasound Obstet Gynecol 2002; 20: 340–345.
13. Vi ˜nals F, Heredia F, Giuliano A. The role of the three vessels and trachea view (3VT) in the diagnosis of congenital heart Prof. R. Chaoui, Center for Prenatal Diagnosis and defects. Ultrasound Obstet Gynecol 2003; 22: 358–367.
14. Carvalho JS, Ho SY, Shinebourne EA. Sequential segmental Dr J. Copel, Yale School of Medicine, New Haven, analysis in complex fetal cardiac abnormalities: a logical approach to diagnosis. Ultrasound Obstet Gynecol 2005; 26:
Dr G. R. DeVore, Fetal Diagnostic Center of Pasadena, 15. DeVore GR, Horenstein J, Siassi B, Platt LD. Fetal echocardio- graphy. VII. Doppler color flow mapping: a new technique for Prof. K. Hecher, University of Hamburg-Eppendorf the diagnosis of congenital heart disease. Obstet Gynecol 1987; 156: 1054–1064.
Dr H. Munoz, Universidad de Chile, Clinica Alemana, 16. Chiba Y, Kanzaki T, Kobayashi H, Murakami M, Yutani C.
Evaluation of fetal structural heart disease using color flow mapping. Ultrasound Med Biol 1990; 16: 221–229.
Dr T. Nelson, Department of Radiology, University of 17. DeVore GR. Assessing fetal cardiac ventricular function. Semin Fetal Neonatal Med 2005; 10: 515–541.
Prof. D. Paladini, Fetal Cardiology Unit, Department 18. Tsutsumi T, Ishii M, Eto G, Hota M, Kato H. Serial evaluation for myocardial performance in fetuses and neonates using a new of Obstetrics and Gynecology, University Federico II of Doppler index. Pediatr Int 1999; 41: 722–727.
19. Di Salvo G, Russo MG, Paladini D, Pacileo G, Felicetti M, Prof. S. Yagel, Hadassah Hebrew University Medical Ricci C, Cardaropoli D, Palma M, Caso P, Calabro R. Quantifi- cation of regional left and right ventricular longitudinal function
in 75 normal fetuses using ultrasound-based strain rate and
strain imaging. Ultrasound Med Biol 2005; 31: 1159–1162.
20. Larsen LU, Petersen OB, Norrild K, Sorensen K, Uldbjerg N, Sloth E. Strain rate derived for color Doppler myocardial 1. International Society of Ultrasound in Obstetrics and Gyne- imaging for assessment of fetal cardiac function. Ultrasound cology. Cardiac screening guidelines of the fetus: guidelines Obstet Gynecol 2006; 27: 210–213.
for performing the ‘basic’ and ‘extended basic’ cardiac scan.
21. DeVore GR, Falkensammer P, Sklansky MS, Platt LD. Spatio- Ultrasound Obstet Gynecol 2006; 27: 107–113.
temporal image correlation (STIC): a new technology for 2. Berning RA, Silverman NH, Villegas M, Sahn DJ, Martin GR, evaluation of the fetal heart. Ultrasound Obstet Gynecol 2003; Rice MJ. Reversed shunting across the ductus arteriosus or atrial 22: 380–387.
septum in utero heralds severe congenital heart disease. J Am 22. Gon¸calves LF, Lee W, Chaiworapongsa T, Espinoza J, Coll Cardiol 1996; 27: 481–486.
Schoen JL, Falkensammer P, Treadwell M, Romero R. Four- 3. Vi ˜nals F, Tapia J, Giuliano A. Prenatal detection of ductal- dimensional ultrasongraphy of the fetal heart with spatiotem- dependent congenital heart disease: how can things be made poral image correlation. Am J Obstet Gynecol 2003; 189:
easier? Ultrasound Obstet Gynecol 2002; 19: 246–249.
23. Chaoui R, Hoffman J, Heling KS. Three-dimensional (3D) and Kachaner J, Sidi D. Detection of transposition of the great 4D color Doppler fetal echocardiography using spatio-temporal arteries in fetuses reduces neonatal morbidity and mortality.
image correlation (STIC). Ultrasound Obstet Gynecol 2004; Circulation 1999; 99: 916–918.
5. Bromley B, Estroff JA, Sanders SP, Parad R, Roberts D, Frigo- 24. Volpe P, Campobasso G, DeRobertis V, DiPaolo S, Caruso G, letto FD Jr, Benacerraf BR. Fetal echocardiography: accuracy Stanziano A, Volpe N, Gentile M. Two- and four-dimensional and limitations in a population at high and low risk for heart echocardiography with B-flow imaging and spatiotemporal defects. Am J Obstet Gynecol 1992; 166: 1473–1481.
image correlation in prenatal diagnosis of isolated total 6. Copel JA, Pilu G, Kleinman CS. Congenital heart disease anomalous pulmonary venous connection. Ultrasound Obstet and extracardiac anomalies: associations and indications for Gynecol 2007; 30: 830–837.
fetal echocardiography. Am J Obstet Gynecol 1986; 154:
Nido PJ, Jenkins KJ, Lock JE, Tworetzsky W. Fetal tricuspid 7. Paladini D, Calabro R, Palmieri S, D’Andrea T. Prenatal diag- valve size and growth as predictors of outcome in pulmonary nosis of congenital heart disease and fetal karyotyping. Obstet atresia with intact ventricular septum. Pediatrics 2006; 118:
Gynecol 1993; 81: 679–682.
8. Carvalho JS, Moscoso G, Tekay A, Campbell S, Thila- 26. Schneider C, McCrindle BW, Carvalho JS, Hornberger LK, ganathan B, Shinebourne EA. Clinical impact of first and early McCarthy KP, Daubeney PE. Development of Z-scores for fetal second trimester fetal echocardiography on high-risk pregnan- cardiac dimensions from echocardiography. Ultrasound Obstet cies. Heart 2004; 90: 921–926.
Gynecol 2005; 26: 599–605.
9. DeVore GR. The genetic sonogram: its use in the detection of 27. Devore GR. The use of Z-scores in the analysis of fetal cardiac chromosomal abnormalities in fetuses of women of advanced dimensions. Ultrasound Obstet Gynecol 2005; 26: 596–598.
maternal age. Prenat Diagn 2001; 21: 40–45.
28. Yagel S, Weissman A, Rotstein Z, Manor M, Hegesh J, 10. Parra-Cordero M, Quiroz L, Rencoret G, Pedraza D, Mu ˜noz H, Anteby E, Lipitz S, Achiron R. Congenital heart defects: natural Soto-Chac ´on E, Miranda-Mendoza I. Screening for trisomy 21 course and in utero development. Circulation 1997; 96:
during the routine second-trimester ultrasound examination in Copyright 2008 ISUOG. Published by John Wiley & Sons, Ltd.
Ultrasound Obstet Gynecol 2008; 32: 239–242.
ARTICLE IN PRESS Emergence of ﬂuoroquinolone-resistant Streptococcus pneumoniae in Lebanon: A report of three cases Mazen R. Naba , George F. Araj , Tania A. Baban , Zuhayr A. Tabbarah , Ghassan N. Awar , Souha S. Kanj a Division of Infectious Diseases, Department of Internal Medicine, American University of BeirutMedical Center, Beirut, Lebanon b Department of Path