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Heart 1997;77:68-72 Anatomical and echocardiographic correlates of normal cardiac morphology in the late first trimester fetus Lindsey D Allan, Rosalba Santos, Tomas Pexieder Gestational age offetuses studied Weeks n 5-6 4 6-7 8 7-8 6 8-9 14 9-10 8 10-11 6 11-12 7 Abstract Objectives-To describe the normal car- diac morphology as seen by transvaginal ultrasound imaging in the first trimester fetus and to compare it with the morphol- ogy of the heart as seen by microdissection at the same gestational age. Design-In 53 mothers undergoing early sonography, the fetal heart was examined and the images recorded. The gestational age range was 5-12 weeks of gestation, which represents 21 to 70 days after con- ception. Images were analysed frame by frame and compared with the anatomy of embryos and fetuses at the same gesta- tional ages. Results-After the 9th week of gestation, four cardiac chambers, the aortic origin, and the pulmonary artery could be identi- fied on cross sectional echocardiography in conjunction with colour flow Doppler. At 9 weeks, the apex pointed anteriorly and the right ventricle and pulmonary artery lay to the right of the midline. By the 11th week of gestation, the apex pointed to the left and the pulmonary artery lay to the left of the midline as in the older fetus. Between 9 and 12 weeks' gestation the aorta was larger than the pulmonary artery. These findings were confirmed in the microdissected hearts. Conclusions-The current quality of ultra- sound images obtained using transvaginal transducers in the first trimester fetus allows the study of fetal cardiac anatomy. Some of the later developmental changes can be demonstrated. As technology improves further the details of earlier car- diac morphogenesis may also become visi- ble. (Heart 1997;77:68-72) Keywords: fetus; organogenesis; echocardiography; pre- natal diagnosis Advances in prenatal ultrasound imaging, espe- cially the advent of cross sectional scanning, allowed the echocardiographic features of the normal mid-trimester fetus to be correlated with anatomical sections in 1980.' The study reported in 1980 showed that most of the fea- tures that characterise the normal heart in post- natal life can also be seen in the fetus. However, it also highlighted some of the differences between prenatal and postnatal cardiac find- ings, particularly the more horizontal position of the heart produced by the size of the fetal liver and the equality of the right and left ven- tricular dimensions when imaged in a four chamber projection. In addition, as was expected from our knowledge of fetal physiol- ogy, the patent foramen ovale and the patent arterial ductal connection were visible in every normal fetus. Since 1980 improvements in the resolution of vaginal transducers have led to the study of the conceptus at increasingly early stages of ges- tation. The evaluation of embryological fea- tures such as the appearance of the yolk sac and the physiological hemiation of the midgut can be studied and even used to date the pregnancy accurately.2 Many of the standard echocardio- graphic views can be obtained as early as 11 to 12 weeks of gestation' and the atrioventricular and arterial Doppler flow velocity profiles can be analysed.4 The heart is one of the first organs to develop in the embryo, with cardiac motion seen between 26 and 32 days after conception' (5-6 weeks post-menstrual age), when the crown- rump length is between 5 and 10 mm. The atrioventricular endocardial cushions and atri- oventricular valves develop in post-menstrual weeks 6-7, the outflow tract septum is com- pleted between post-menstrual weeks 7-8, and the interventricular foramen closes between post-menstrual weeks 8 and 9.6 The tricuspid valve is the last cardiac structure to complete its formation at post-menstrual weeks 9-10. We attempted to evaluate the fetal heart during the first trimester of pregnancy to see if any part of cardiac development was currently identifiable by the most modem high resolution transduc- ers. Patients and methods ECHOCARDIOGRAPHIC IMAGES In 53 patients the fetal heart was imaged using an Advanced Technical Laboratories HDI sys- tem with a 5 or a 9 MHz vaginal tranducer. These patients were referred for ultrasound examination to confirm the presence of an intrauterine pregnancy or to establish viability after an episode of vaginal bleeding. The crown-rump length was used to estimate the gestational age, which ranged from 5 to 12 weeks. The gestational ages studied are shown in the table. The long axis view of the fetus was first obtained as in fig 1. The beam was then located at right angles to this section at the level of the heart. A horizontal sweep from the diaphragm to the neck was then recorded as cross sectional images with a colour flow map- ping, in a similar fashion to the scanning method in the older fetus.7 Department of Pediatrics, Babies and Children's Hospital, Columbia- Presbyterian Medical Center, New York, USA L D Allan Department of Obstetrics and Gynecology, Sloane Hospital for Women, Columbia- Presbyterian Medical Center, New York, USA R Santos Institute d'Histologie et d'Embryologie, Universite de Lausanne, Switzerland T Pexieder Correspondence to: Dr L D Allan, Department of Pediatrics, Babies and Children's Hospital, 3959 Broadway, New York, NY 10032, USA. Accepted for publication 23 July 1996 68 on March 25, 2021 by guest. Protected by copyright. http://heart.bmj.com/ Heart: first published as 10.1136/hrt.77.1.68 on 1 January 1997. Downloaded from

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Page 1: Heart Anatomical thelate · fetal thorax abovethefour chamberview. The walls ofthepulmonarytrunk couldbe clarlydefined __ whenit lay in this orientation to the ultrasoundbeam. It

Heart 1997;77:68-72

Anatomical and echocardiographic correlates ofnormal cardiac morphology in the late firsttrimester fetus

Lindsey D Allan, Rosalba Santos, Tomas Pexieder

Gestational age offetusesstudied

Weeks n

5-6 46-7 87-8 68-9 149-10 810-11 611-12 7

AbstractObjectives-To describe the normal car-diac morphology as seen by transvaginalultrasound imaging in the first trimesterfetus and to compare it with the morphol-ogy ofthe heart as seen by microdissectionat the same gestational age.Design-In 53 mothers undergoing earlysonography, the fetal heart was examinedand the images recorded. The gestationalage range was 5-12 weeks of gestation,which represents 21 to 70 days after con-

ception. Images were analysed frame byframe and compared with the anatomy ofembryos and fetuses at the same gesta-tional ages.Results-After the 9th week of gestation,four cardiac chambers, the aortic origin,and the pulmonary artery could be identi-fied on cross sectional echocardiographyin conjunction with colour flow Doppler.At 9 weeks, the apex pointed anteriorly andthe right ventricle and pulmonary arterylay to the right of the midline. By the 11thweek of gestation, the apex pointed to theleft and the pulmonary artery lay to the leftof the midline as in the older fetus.Between 9 and 12 weeks' gestation theaorta was larger than the pulmonaryartery. These findings were confirmed inthe microdissected hearts.Conclusions-The current quality ofultra-sound images obtained using transvaginaltransducers in the first trimester fetusallows the study of fetal cardiac anatomy.Some of the later developmental changescan be demonstrated. As technologyimproves further the details of earlier car-

diac morphogenesis may also become visi-ble.

(Heart 1997;77:68-72)

Keywords: fetus; organogenesis; echocardiography; pre-natal diagnosis

Advances in prenatal ultrasound imaging, espe-

cially the advent of cross sectional scanning,allowed the echocardiographic features of thenormal mid-trimester fetus to be correlatedwith anatomical sections in 1980.' The studyreported in 1980 showed that most of the fea-tures that characterise the normal heart in post-natal life can also be seen in the fetus. However,it also highlighted some of the differencesbetween prenatal and postnatal cardiac find-ings, particularly the more horizontal positionof the heart produced by the size of the fetal

liver and the equality of the right and left ven-tricular dimensions when imaged in a fourchamber projection. In addition, as wasexpected from our knowledge of fetal physiol-ogy, the patent foramen ovale and the patentarterial ductal connection were visible in everynormal fetus.

Since 1980 improvements in the resolutionof vaginal transducers have led to the study ofthe conceptus at increasingly early stages of ges-tation. The evaluation of embryological fea-tures such as the appearance of the yolk sac andthe physiological hemiation of the midgut canbe studied and even used to date the pregnancyaccurately.2 Many of the standard echocardio-graphic views can be obtained as early as 11 to12 weeks of gestation' and the atrioventricularand arterial Doppler flow velocity profiles can

be analysed.4The heart is one of the first organs to develop

in the embryo, with cardiac motion seen

between 26 and 32 days after conception' (5-6weeks post-menstrual age), when the crown-

rump length is between 5 and 10 mm. Theatrioventricular endocardial cushions and atri-oventricular valves develop in post-menstrualweeks 6-7, the outflow tract septum is com-

pleted between post-menstrual weeks 7-8, andthe interventricular foramen closes betweenpost-menstrual weeks 8 and 9.6 The tricuspidvalve is the last cardiac structure to complete itsformation at post-menstrual weeks 9-10. Weattempted to evaluate the fetal heart during thefirst trimester of pregnancy to see if any part ofcardiac development was currently identifiableby the most modem high resolution transduc-ers.

Patients and methodsECHOCARDIOGRAPHIC IMAGESIn 53 patients the fetal heart was imaged usingan Advanced Technical Laboratories HDI sys-tem with a 5 or a 9 MHz vaginal tranducer.These patients were referred for ultrasoundexamination to confirm the presence of an

intrauterine pregnancy or to establish viabilityafter an episode of vaginal bleeding. Thecrown-rump length was used to estimate thegestational age, which ranged from 5 to 12weeks. The gestational ages studied are shownin the table. The long axis view of the fetus wasfirst obtained as in fig 1. The beam was thenlocated at right angles to this section at the levelof the heart. A horizontal sweep from thediaphragm to the neck was then recorded ascross sectional images with a colour flow map-ping, in a similar fashion to the scanningmethod in the older fetus.7

Department ofPediatrics, Babies andChildren's Hospital,Columbia-Presbyterian MedicalCenter, New York,USAL D AllanDepartment ofObstetrics andGynecology, SloaneHospital for Women,Columbia-Presbyterian MedicalCenter, New York,USAR SantosInstitute d'Histologie etd'Embryologie,Universite deLausanne, SwitzerlandT PexiederCorrespondence to:Dr L D Allan, Department ofPediatrics, Babies andChildren's Hospital, 3959Broadway, New York, NY10032, USA.Accepted for publication23 July 1996

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Anatomical and echocardiographic correlates of normal cardiac morphology in the late first trimester fetus

Figure 1 This image was obtained in a fetus with acrown-rump length equivalent to 9 weeks 5 days

"j..........gestational age (54 days post-conception). The fetus isimaged in a longitudinal plane from head to rump. The

........... umbilical vein (UVT) is prominent, passingfrom the cordthrough the liver to below the heart. The descending aortais seen passing down the back in front of the spine andconnecting to the umbilical artery (UA) in the cord. Alarge head vessel is seen. The heart (H) is seen in thethorax just above the diaphragm. The ultrasound beam isthen positioned at right angles to this plane of section tocut through the heart in a transverse plane. The beam isthen swept up and down the thorax to produce the type ofimages seen in fig 2.

Figure 2 (A-F)Sequential transverseplanes of the fetal thorax.T'hese images wereobtained in afetus with acrown-rump lengthequivalent to 9 weeks 2days gestational age (Sidays post-conception).Note the scal bar at theright indicating that thewhole thorax at this stagemeasures about 1 cm andthe pulmonary artery lessthan hfheamillimetre.(A) The heart liesapposi.tethe spine with the apexpointing directlyanteroposteriorly. Theright heart is locatedentirely in the right halfofthe chest. (B) The colourflow map confirmend thiswhen the ventricles werefilled. The arrow indicatesthe interventricular septumat the apex. (C) This is ahorizontal section of thefetal thorax above the fourchamber view. The wallsof the pulmonary trunkcould be clarly defined __when it lay in thisorientation to theultrasound beam. It arosefrom the right ventricleand crossed the midline toconnect to the descendingaorta. (D) The colourflow map confirmned theflow in the pulmonaryartery (seen in blue)crossing the midline. (E)In a horizontal section justabove thefour chamberview andjust below theimage of the pulmonaryartery seen infigGCandD, the ascending aortacould be identified bycolourflow mappingarisingtfrom the leftventricle (coloured red)and coursing righwmardsinitially. Note that thisvessel appears considerablylarger on colourflowmapping than thepulmonary artery seen infigs C and D. (F) Theaorta then curves in frontof the spine toform thearch, seen here in atransverse section. RV,right ventricle; LV, leftventricle; Ao, aorta; PA,pulmonary artery; Aao,ascending aorta.

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Alan, Santos, Pexieder

Figure 3 (A-C) These images were obtained in afetus with a crown-rump length equivalent to 11 weeks 4 days gestational age (67 days post-conception). (A) By this gestational age, the stomach can be usually be identified and used to identify the left side of the fetus. (B) As the image movescraniallyfrom the stomach, the heart can be seen in the left halfof the chest with the interventricular septum at an angle ofabout 40 degrees to the midline,which is characteristic of later pregnancy. (C) The pulmonary trunk and aorta can be seen in the horizontal projection, showing that the pulmonary arteryis now in the left halfof the chest. In this horizontal section of the thorax above the base of the heart, the connection between the pulmonary artery andductus and the transverse aortic arch are seen to be running parallel to each other in the normalfetus. Although the pulmonary trunk is stil smaller thanthe aorta, there is less difference in size than before. ST, stomach; SP, spine; RV, right ventricle; LV, left ventricle; AO, aorta; RVOT, right ventricularoutflow track.

MICRODISSECTION IMAGESFrontal and left profile photomacrographs ofmicrodissected human embryonic and fetalhearts were selected from the collectiondescribed in detail by Pexieder and Janecek.8Briefly, the embryos and fetuses were fixed byhigh flow/low pressure intraventricular perfu-sion9 with 2% glutaraldehyde and 1% formal-dehyde. After postfixation in 1% osmiumtetroxide, the embryos and fetuses were micro-dissected. Each step of the microdissection ofthe heart was documented by taking macro-photographs using the Wild M400 Photo-makroskop.

ResultsECHOCARDIOGRAPHIC IMAGESThe videotape recorded was examined frame byframe. Images obtained with the 5 MHz provednoticeably coarser than those obtained with the9 MHz transducer. The spine and umbilicalcord were used as landmarks for posterior andanterior orientation respectively. The ultrasoundimages of cardiac morphology were difficult tounderstand in embryological terms betweenpost-menstrual weeks five and nine and will bethe subject of further analysis. After nine post-menstrual weeks, however, careful analysis ofvideotaped material allowed the recognition ofcharacteristic features in the 21 fetuses in thisgroup. At nine weeks the heart lay centrally inthe thorax with the apex almost directly oppositethe spine. The right heart was found in the righthalf of chest and the left heart in the left half ofthe chest (fig 2). The colour flow map enabled

us to confirm the suspected cross sectional find-ings. The pulmonary trunk was readily seenwhen it was located in perpendicular orientationto the ultrasound beam, as it was in the fetusillustrated. This vessel originated in the rightchest and crossed the midline diagonally to jointhe descending aorta slightly to the left and infront of the spine. The ascending aorta couldnot be seen well on cross sectional scanning inthis embryo-fetal position but the colour flowmap showed it clearly. Flow within the aortaarose in the left ventricle and was directed right-wards initially before turning to form the aorticarch in the same manner as is seen in the olderfetus.10 There was in addition a clear discrep-ancy between the aortic and pulmonary size atthis gestational age, with the pulmonary trunksmaller than the aorta-the reverse of the find-ings at 18 weeks' gestation."IBy the 10th week of gestation, the heart ori-

entation was changing to a position more typicalof later pregnancy.'2 The apex had moved to theleft and the pulmonary trunk had become amore left sided structure, running towards thespine and the ductal junction with the descendingaorta. The pulmonary trunk was still smallerthan the aorta.By the 11th week of gestation, the positional

change was complete. In addition, the stomachwas by now identifiable" and could be used toconfirm the interpretation of the left and rightsides of the thorax. In addition the four cham-bers and great arteries were more readily identi-fied (fig 3). By this stage the great arteries werebecoming more equal in size.

These findings were consistent in the 21

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71Anatomical and echocardiographic correlates of normal cardiac morphology in the late first trimesterfetus

Figure 4 (A-F)Macrophotographs ofpartially microdissectedembryonic andfetal hearts.In all views of this figurethe atria have beenremoved. Scale bars =1 mm. (A) Frontal viewat 9 weeks' gestation of themiddle portion the aortawhich shows that it isrunning almost parallel tothe pulmonary trunk.Ramifications of the leftanterior coronary arteryare visible in theinterventricular sulcus. Theapex points directlyanteriorly, with the rightventricle lying in the rightchest. (B) Left lateral viewof the same heart showingthe branching of thepulmonary trunk into thearterial duct and thepulmonary arteries. Theduct joins the descendingaorta at an acute angle. Itsdiameter is less than that ofthe pulmonary trunk. (C)Frontal view at 10 weeks'gestation showing that theascending aorta is nowrunning more in parallelwith the pulmonary trunk.The apex of the heart ispointing more caudallytowards the diaphragm.(D) The left lateral view ofthe same heart shows thewidening of the arterialduct, which is now almostas large as the pulmonarytrunk. This duct is enteringthe descending aorta atalmost a right angle. (E)Frontal view at 12 weeks'gestation showing that areal aortic arch has beenformed and that thepulmonary trunk seems tobe similar in size or largerthan the ascending aorta.(F) In the same heart seenfrom the left the arterialduct has the same diameteras the pulmonary trunk,which is now aligned withthe axis of the rightventricle. The blurred edgesof the right ventricle in figs4E and 4F are caused bythe large size of thespecimen, which is beyondthe focal depth of thePhotomakroskop. ThePhotomakroskop wasfocused on the roots of thegreat arteries. A, aorta; D,arterial duct; LV, leftventricle; PA, pulmonaryartery; PT, pulmonarytrunk; RV, right ventricle.

A

D

F D, -

fetuses aged 9 to 12 weeks gestation. The fourchamber view was identifiable in all thesefetuses, though less easily during the 10th and1 1th week than during the 9th week. Crossoverof two great arteries was identified in three of sixfetuses scanned during the 9th week and in 14 ofthe 15 remaining fetuses. In some cases,repeated frame by frame evaluation of the video-tape was necessary especially if images had beenrecorded with the 5 MHz transducer (six stud-ies). Of the fetuses scanned two were lost to fol-low up and two proceeded to therapeutic

abortion. The remaining 17 resulted in successfulpregnancies with no cardiac abnormality foundat birth by postnatal clinical examination.

MICRODISSECTION IMAGESAt nine postmenstrual weeks, the embryonicheart was in a horizontal position (fig 4B). Theorigin of the pulmonary trunk lay to the right sothat this vessel had to cross the midline (fig4A), joining the descending aorta, via the arter-ial duct, at an acute angle (fig 4B). At this stagediameter of the arterial duct was smaller than

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Allan, Santos, Pexieder

the diameter of the pulmonary trunk.Ramification of the anterior interventricularcoronary artery was already visible.

At 10 postmenstrual weeks the root of thepulmonary trunk had moved closer to the mid-line (fig 4C) and seemed to be slightly smallerthan the ascending aorta. The size of the arterialduct had increased (fig 4D) and the apex of theheart was starting to point caudally.

At 12 postmenstrual weeks the origin of thepulmonary trunk lay slightly on the left of themidline and almost perpendicular to the aorticarch (fig 4E). The diameter of the pulmonarytrunk begain to approximate to that of theascending aorta. At the same time the size ofthe arterial duct had further increased (fig 4F).By comparing figs 4B, 4D, and 4F, we couldfollow the change in orientation of the pul-monary artery, from antero-posterior oblique(fig 4B) to cranio-caudal (fig 4F).

DiscussionThe organogenesis of the heart has always fasci-nated cardiologists. This is partly because of itsintriguing complexity and partly because of itsimportance in the formation of the abnormalheart, particularly those malformations whichinvolve abnormal looping or abnormalities ofconotruncal (outflow tract) septation. Ana-tomical studies of early abortus specimens7 havedetailed the morphological features of the heartas it develops in the first weeks after conception.If the normal characteristics and sequence ofcardiac development could be visualised anddescribed, deviations from this normal patternor delay in cardiac formation might indicate anascent malformation. This may help to iden-tify primary aetiological factors contributing tothe malformation, because they would be actingwhen development was abnormal.

This study was not designed to identify allthe usual normal cardiac connections in earlypregnancy with a view to offering early prenataldiagnosis. Although this may be possible intime, in the first instance the normal features ofthe fetal heart must be understood and not mis-interpreted. For example, if the heart in themid-trimester fetus is in a central position itmay indicate a cardiac malformation.'4 In addi-tion, in later pregnancy a pulmonary trunksmaller than the aorta indicates some degree ofright ventricular outflow tract obstruction.'5 Inthe late embryos and early fetuses we studied,these were normal features of early develop-ment. This was confirmed when we comparedthe echocardiographic findings with anatomicalstudies of the fetal heart at the same gestationalage. In addition, despite experience of over13 000 fetal heart examinations (LA), identifi-cation of cardiac structures was qualitativelydifficult in the smallest fetuses or those inwhom the lower resolution transducer was usedand it required intensive study of recordedmaterial. Therefore, with current ultrasoundequipment at the present time, the technique isnot likely to be useful for clinical diagnosis.Also the study was opportunistic in that imageswere recorded during evaluation of early preg-nancy and not specifically for cardiac examina-

tion. There is no known risk to the early fetusassociated with the use of ultrasound or colourflow mapping. Colour flow mapping is a nor-mal part of this assessment and its use was keptto a minimum in the cardiac analysis.The embryos and fetuses we studied were 5

mm to 55 mm long. The fetal heart is known tobe very prominent anteriorly and to occupymost of the fetal chest in the smallest fetuses.This has been documented in both anatomicalstudies and by transvaginal scanning.'6 17 Thecardiac images which we were able to interpretwith confidence, and have described here, wereobtained in fetuses over 20 mm long. Thedevelopmental changes that involve the forma-tion and fusion of the endocardial cushions,conotruncal septation, and closure of the inter-ventricular foramen occur before this time,when the embryo is between 5 and 20 mmlong. However, the cardiac anatomy of thesmaller fetuses and embryos proved difficult toidentify and will require further study and prob-ably higher resolution transducers to interpret.

CONCLUSIONThe most recently developed high resolutiontransvaginal transducers allow visualisation ofthe later developmental changes in cardiacmorphology. The interpretation of these find-ings can be confirmed by study of microdis-sected embryos and early fetuses.

1 Allan LD, Tynan MJ, Campbell S, Wilkinson J, AndersonRH. Echocardiographic and anatomical correlates in thefetus. BrHeartJ 1980;44:444-51.

2 Warren WB, Timor-Tritsch I, Peisner DB, Raju S, RosenMG. Dating the early pregnancy by sequential appearanceof embryonic structures. Am Jf Obstet Gynecol 1989;161:747-53.

3 Dolkart LA, Reimers FI. Transvaginal fetal echocardiogra-phy in early pregnancy: normative data. Am Jf ObstetGynecol 1991;165:688-91.

4 Wladimiroff JW, Huisman TW, Stewart PA. Fetal cardiacflow velocities in the late first trimester of pregnancy: atransvaginal study. JAm Coll Cardiol 1991;17:1357-9.

5 Howe RS, Isaacson KJ, Albert JL, Coutifaris CB. Embryonicheart rate in human pregnancy. J Ultrasound Med 1991;10:367-71.

6 McBride RE, Moore GW, Hutchins GM. Development ofthe outflow tract and closure of the intervenricular septumin the normal human heart. AmJAnat 1981;160:309-31.

7 Allan LD. Normal views of the great arteries. In: Fetal heartscanning. New York: Churchill Livingstone,1995.

8 Pexieder T, Janecek P. Organogenesis of the human embry-onic and early fetal heart as studied by microdissection andSEM. In: Nora JJ, Takao A, eds. Congenital heart disease:causes and processes. Mount Kisco, NY: Futura, 1984;401-21.

9 Moscoso G, Pexieder T. Variations in microscopic anatomyand ultrastructure ofhuman embryonic hearts subjected tothree different modes of fixation. Path Res Practice 1990;186:768-74.

10 Sharland GK, Chita SK, Allan LD. The use of colourDoppler in fetal echocardiography. Int J Cardiol 1990:28:229-36.

11 Allan LD. Manual offeud echocardiography. Lancaster: MTPPress, 1986.

12 Smith RS, Comstock CC, Kirk JS, Lee W. Ultrasound leftcardiac axis deviation a marker for fetal anornalities.Obstet Gynecol 1994;85:187-91.

13 Blaas HG, Eik-Nes SH, Kiserud T, Hellevik LR. Earlydevelopment of the abdominal wall stomach and heartfrom 7-12 weeks of gestation: a longitudinal ultrasoundstudy. Ultrasound Obstet Gynecol 1995;6:240-50.

14 Allan LD, Lockart S. Intrathoracic position in the fetus.Ultrasound Obstet Gynecol 1993;3:93-6.

15 Hornberger LK, Sanders SP, Sahn DJ, Rice MJ, Spevak PJ,Benacerraf BR, et al. In utero pulmonary artery and aorticgrowth and potential for progression ofpulmonary outflowtract obstruction in tetralogy of Fallot. J Am Coil Cardiol1995;25:739-45.

16 Zimmer EZ, Chao CR, Santos R. Amniotic sac, fetal heartarea, fetal curvature, and other morphometrics using firsttrimester vaginal ultrasonography and color Doppler imag-ing. I Ultrasound Med 1994;13:685-90.

17 Bronshtein M, Siegler E, Eshcoli Z, Zimmer EZ.Transvaginal ultrasound measurements of the fetal heartat 11 to 17 weeks gestation. AmJ Perinatol 1992;9:38-42.

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