ISSN 1012-8220

Volume 16 July 2002Issue 1

2

CONTENTS

EFSUMB Officers and Committees

Contents

Report from the Past President

Message from the New President

Report from the Past Honorary Secretary

Report from the Honorary Treasurer

Young Investigator Award 2002

16th Euroson Congress 2004, Zagreb, Croatia

Paper from the Education and Professional Standards

Committee

15th Euroson Congress 2003, Copenhagen, Denmark

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3

4

5

6

7

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8-11

12-13

Safety Session at Euroson 2002

EFSUMB Safety Tutorial

Contents of EJU

Report from the Publication Committee

Report from the Newsletter Editor

IBUS Breast Ultrasound Seminar, Warsaw 2002

Industrial Board

Letter from WFUMB

Diary Dates

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15-18

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19

19

20

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EFSUMBEUROPEAN FEDERATION OF SOCIETIES FORULTRASOUND IN MEDICINE AND BIOLOGY

EXECUTIVE BUREAU

President: K Jäger (Switzerland)President Elect: D H Evans (UK)Past-President: M Claudon (France)Honorary Secretary: L Greiner (Germany)Honorary Treasurer: N Juul (Denmark)

ECMUS - EUROPEAN COMMITTEEFOR MEDICAL ULTRASOUND

Chairman: K Salvesen (Norway)Secretary: T Whittingham (UK)Members: P Arbeille (France)

K Marsál (Sweden)

EDUCATION AND PROFESSIONALSTANDARDS COMMITTEE

Chairperson: L Valentin (Sweden)Members: B Cacciatore (Finland)

B J Hackelöer (Germany)D Lindsell ( UK)

PUBLICATION COMMITTEEMembers: J-M de Bray (France)

D W Pilling (UK)W Mann (Germany)

Ex-officio: M Claudon (France)L Greiner (Germany

EFSUMB NEWSLETTEREditor: D W Pilling (UK)

SECRETARIATGeneral Secretary: Gianna Stanford,Carpenters Court, 4a Lewes Road, Bromley, Kent BR1 2RN, UKTel: +44 (0)20 8402 8973Fax: +44 (0)20 8402 9344Email:efsumb@compuserve.comWebsite:http://www.efsumb.org

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REPORT FROM THE PAST PRESIDENT

This is my final message, as President of EFSUMB. Threeyears have passed quickly, and time has now come to makean assessment of our activities.

EFSUMB membership has increased during the last period,with now approximately 14500 members from 25 nationalsocieties. The European Federation has definitivelyestablished itself as the second largest affiliated societywithin the World Federation, after the Asian group. Wesuspended the Turkish Society’s membership following nocommunication over the past two years; however we haveestablished contacts with Yugoslavian and Georgiansocieties.

Three years ago Luigi Bolondi established threecommittees within the Federation which have done a greatjob, and significantly contributed to the life of theFederation. I would like to express my gratitude to allcommittee members for their work and expertise. I suggestthat all our national societies should become increasinglyinvolved in these committees’ activities: the more aNational Society does for the Federation, the more it willbe recognized and honored.

The Education and Professional Standards Committee hasbeen brilliantly chaired by Lil Valentin and Henry Irving.This group has worked hard to prepare a specific session,held during our last meeting in Edinburgh. A veryproductive discussion involved representatives from theEuropean clinical specialties working in the world ofultrasound, including gynecology and obstetrics, radiology,gastroenterology, urology, angiology, and cardiology. Arevised version of the initial draft entitled “Minimumtraining requirements for the practice of medical ultrasoundin Europe” has been completed and will be sent to all thesegroups. EFSUMB acting as an umbrella organisation ishelping to establish commonly accepted guidelines forinitial and continuous education in ultrasound.

The ECMUS, Safety committee, previously named theWatchdog Committee, has been effectively managed byFrancis Duck with review documents regularly publishedin the Newsletter. To emphasize the importance of thisfield for the practice of ultrasound, the decision was madeto organize a plenary session on various aspects of safetyduring the present congress in Warsaw, congregatingexperts from all around the world, including WFUMBSafety Committee. The key points of this session are to becirculated to the European clinical societies, as suggestedin Edinburgh.

Hylton Meire has the difficult task of managing thePublication’s Committee. This has been a tough task,because preparing the biennial Newsletter is a challenge. Thischallenge has been highly successful, and the Newsletter isnow a well-established, effective link between all themembers. However, a major problem has arisen with theEuropean Journal of Ultrasound. This scientific journal,edited by Johann Thijssen and listed two years ago byMedline, has unfortunately not been accepted by ISI, andtherefore did not achieve any impact factor. Despite multipleefforts the newly appointed Editor-in-Chief, Peter Twinning,has had to face a very low flow of manuscripts, thus makingthe situation critical.

Unfortunately, after a recent discussion with the Publisher,Elsevier, the EJU might cease at the end of the year.

We have also opened relation-ships within the industry. Thishas already been rewarding inthe fields of Education andSafety with COCIR, whichregroups at the European level,the main companies providingUS machines. We are willingto further develop this coope-ration with all those involvedin ultrasound, including con-trast agents and recordingmedia companies and create anindustrial board.

Holding Euroson Congresses in conjunction with NationalSociety congress is a new formula, established five years ago.After Tours in 1998 and Berlin in 1999, we had a verysuccessful and a high scientific level congress in Edinburgh in2001. The present meeting in Warsaw is a unique opportunityto reinforce the contribution to the Federation of previouslynamed Eastern countries. This is a major objective for thecoming years, as we together build the European community,step by step. The introduction of the Euro has resulted in adecrease of exchange cost for our budget. However, we haveto review our by-laws to better determine the responsibility ofboth parts, the National Society and EFSUMB in thepreparation and management of joint meetings.

I would like to take this opportunity to express the sincerethanks of EFSUMB to Prof Wieslaw Jakubowski and hiscolleagues for organising such a successful and enjoyablecongress in Warsaw. A full report of this Congress willappear in the next Newsletter.

A positive point was the success of the Euroson Schoolsorganized during the last years in Germany, Italy, UK andespecially in Romania. These Euroson Schools have to bedeveloped, as they also appear to be an effective tool forcontinuous education.

The WFUMB, our World Federation, has decided, after manyrequests from EFSUMB, to improve communication with allthe affiliated societies’ members, and to regularly circulate aNewsletter. We are very happy with this decision, which willresult in clearer information about their activities, which at thepresent time include two new development projects, in Africaand Asia (Bangladesh). These demonstrate to our membersthe value of their indirect financial contribution of 1.5 USD tothe World Federation. The next World meeting will be held inMontreal, Canada, 1-4 June 2003. I hope that many Europeanrepresentatives will be present at this important event. SeveralEuropean lecturers have already been selected. Luigi Bolondiand I have been nominated for the next board election,respectively as President Elect and Vice president.

I would like to warmly thank the ExB of EFSUMB, KurtJäger, David Evans, Niels Juul, Luigi Bolondi, Ioan Sporeaand our General Secretary, Gianna Stanford, for their verypositive action, continuous support and friendship. It has beena real pleasure to work hard with all of you, for the benefit ofthe European Federation, and progress in Ultrasound.

Michel ClaudonPast President EFSUMB

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MESSAGE FROM THE NEW PRESIDENT

With the general assembly held in connection with theEUROSON Congress in Warsaw, a new 3-year cyclecommenced for the EFSUMB. It is indeed both apleasure and a privilege to be able to lead the EFSUMBduring the next three years as its president, and Isincerely appreciate the trust you have extended to me.Professor Michel Claudon (Nancy, France) has assumedthe office of the Past President and the former PastPresident, Professor Luigi Bolondi (Bologna, Italy) nowretires from the Executive Bureau. I would like towarmly thank these gentlemen, both personally and onbehalf of the EFSUMB, for their untiring engagement.Professor David Evans (Leicester, UK) who, to date, hasserved as the Honorary Secretary, has been selected as thePresident Elect, and Professor Lucas Greiner (Wuppertal,Germany) has been chosen as the Honorary Secretary. Weare fortunate in being able to continue to rely on thevaluable collaboration of the Honorary Treasurer, NielsJuul (Roskilde, Denmark). It is extremely gratifying tohave such an outstanding staff at my side and I amconvinced that, together, we will experience a very positiveand constructive time at the EFSUMB. A friendship thatextends beyond professional cooperation and respectcombined with a common goal of achieving optimalcollaboration in their endeavors has always characterizedthe Executive Bureau to date, and should continue to beour leitmotif.

In past years, resourceful and initiative presidents havesteered the Executive Bureau on a very dynamic path.Many good ideas for our continuing course have beeninitiated and should be followed or indeed, their time isripe for implementation. The future of the EFSUMB is thuson solid ground and there is no need for a change in ourorientation. However, responsibilities, duties and problemshave not become smaller and an increasing engagement isrequired on the part of the Executive Bureau. Activeleadership is expected on various fronts in the EuropeanUltrasound arena, and I would like to emphasize a few ofthese below.

EUROSON CongressThe annual EUROSON Congress, held in cooperation witha national society, boasts an ever-increasing popularity andquality. I need only mention the past congresses in Berlin(together with the Dreiländertreffen), Florence (ItalianSociety and World Federation), Edinburgh (BritishSociety) and, recently, Warsaw (Polish UltrasoundSociety) with 1000 - 2000 participants. Even at this stage,we can foretell that the 2003 EUROSON Congress inCopenhagen (in cooperation with the ScandinavianUltrasound Societies) will be a success. The organizershave already assembled a program that has been workedout with a fine eye for detail. The list of the invitedspeakers is impressive, the selected topics are of utmostrelevance and, in addition, a broad spectrum of continuededucation and training courses will be offered.

Success encourages and impels us to offer to our membersEUROSON Congresses that are constantly improving. Theannual congress is, to a certain degree, the central event ofany association, but at the same time, it is also arepresentative beacon that encourages identification with

the association. We wouldtherefore like to bring theEUROSON Congresses up toan even more professionallevel. In the future, aEUROSON Committee willthus revise the statutes and by-laws and, in collaboration withthe Organizing Committee fromthe lcal associations, coordinateboth the administrative and thescientific interests of thecongress. Here it is obvious thatrepresentatives of the industrymust also be included asimportant partners.

In this respect, the EFSUMB Committee for Education andStandardization takes on a special importance. It isexpected that the EFSUMB will play a leading role instandardization questions. Here, as an example, one couldthink of guidelines for contrast media examinations.

National Societies and Member Communication:It was only a few years ago that ultrasound techniques gavethe impression of being a method that was somewhatstagnant. This has now fundamentally changed. Thetechnical advances of the past years open new perspectiveswhose abundant possibility for development can hardly beappreciated at this time. This naturally advances thenational associations and the EFSUMB is most pleasedabout the continually increasing number of members.Typically, ultrasound societies are multidisciplinarygroups. This is, on one hand, a great strength of theEFSUMB and its national associations, however, for someindividual national societies, it can simultaneously becomea weak link. In many European countries, it has beenpossible to promote the interdisciplinary character, andthus to potentiate the political clout of the association.However, in other countries, the activities have been takenover by the specialized professional societies and not by theUltrasound Society. From a strictly professional point of view,this may have a certain advantage, it does, however, weakenthe matters of ultrasound itself. Furthermore, representation bya common and unified voice vis-à-vis third parties, such aspolitical authorities or insurance companies, is lacking.EFSUMB is challenged to give these national societies thenecessary support.

Based on the experiences made in past years, we would like tostrengthen and enhance the communication between theEuropean Federation and the national societies. EFSUMB’sefforts for the society should be communicated to theindividual members, who should clearly be made more awareof these endeavors. The Newsletter is probably the best tool toachieve this. Since the European Journal of Ultrasound has notbeen able to meet expectations, we will have to plan a neworientation for our communication instrument.

Much work awaits us and I eagerly look forward to aproductive and gratifying collaboration with all of you, mycolleagues. The future is now.

Kurt JägerPresident EFSUMB

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REPORT FROM THE PAST HONORARY SECRETARY

It seems amazing that my term of office as HonorarySecretary has flown by so quickly, but this will be mylast secretary’s report. A great deal has been achievedby the Executive Bureau, the Board of Directors, and byour committees during those three years, and it has beena privilege and a pleasure to work with so manycommitted people, and to begin many new friendships.Professor Claudon has summarised many of theachievements of the Federation over this period in hisreport, and so it falls to me simply to provide an updateon the many events that occurred at the recentEUROSON meeting in Warsaw. First and foremost Iwould like to take this opportunity to thank ProfessorJakubowski for organising what was without doubt atremendous meeting, both scientifically and socially,one I am sure will long remain in the memory of allparticipants. Special mention must also go to the rest ofthe team involved in the organisation and particularly toAnna Pajk. Many thanks indeed!

During the course of the meeting we were able to talk tothe organisers of all the EUROSON meetings currentlyin the planning phase, and the Board of Directorsendorsed a new bid for 2006. The 2003 meeting will ofcourse be held in Copenhagen in April, in conjunctionwith the Scandinavian Societies, and plans for thismeeting are well advanced. The 2004 meeting is to beheld in Zagreb in June, and I know that ProfessorDrinković and his team will be working hard over thenext few months to ensure the meeting is a greatsuccess. EUROSON 2005 is to be held in Geneva inJune in conjunction with the Dreiländertreffen, whilst itwas agreed that the 2006 meeting will be held inBologna in conjunction with the Italian Society,probably in October.

As in Edinburgh last year there was a special EFSUMBsession at the meeting, kindly sponsored by COCIR, onthis occasion devoted to ultrasound safety, withspeakers drawn from the USA, Japan, and Australia inaddition to a number of safety experts from Europeancountries. In addition, the EUROSON lecture alsoaddressed the issue of safety, and was given byProfessor Francis Duck from Bath in England. Both thesession and the lecture were of an extremely highstandard and highly entertaining. The YoungInvestigator session was also of a high standard, withentries from Belgium, Denmark, Norway and Poland.The only disappointment was that there were not entriesfrom many more National Societies, and I would like toencourage all eligible young investigators to considersubmitting an entry for forthcoming EUROSONmeetings. The bylaw concerning the Young InvestigatorAward can of course be found on our web-site, but can Iremind you that the selected candidates are offered freeregistration by the congress, have their travel andaccommodation expenses sponsored by their membersociety, and stand to win €1,000 if they are selected aswinner. Not a bad deal! On this occasion the winner ofthe award was Dr J Eiberg from Denmark for hispresentation entitled ‘Ultrasound imaging of

infrainguinal arterial disease has a high inter-observeragreement’. Theabstract of thispaper appearselsewhere in thisnewsletter.

As usual ourvarious committeeswere hard at workduring the meeting,and their reportsappear elsewhere.Two things Iwould particularly like to draw to your attention are theexcellent news that a new draft of the ‘MinimumTraining Requirements for the Practice of MedicalUltrasound in Europe’ was unanimously agreed by theEducation and Professional Standards Committee, andthe very sad news that the European Journal ofUltrasound is to cease publication at the end of the year,although the Publications Committee are activelyconsidering ways in which the journal might be re-launched.

Remaining with EFSUMB committees, the Board ofDirectors have agreed to set up two new committees, one asmall ad-hoc committee to consider ways of strengtheningEUROSON meetings, the second an Industrial Board,where representatives of EFSUMB and the manufacturerscan discuss matters of mutual interest includingforthcoming meetings. Initial exploratory talks in Warsawwith several manufacturers proved very productive andbode well for mutual cooperation in years to come.

I mentioned at the beginning of my report that this wouldbe my last as Honorary Secretary, as three years haveelapsed since the election of the current ExecutiveBureau (ExB). Our Past President, Luigi Bolondi, leavesthe ExB after nine years, and we must thank him for thevast amount of time and effort that he has put intoEFSUMB over that period. Our President, Michel Claudon,automatically becomes Past President, and our PresidentElect, Kurt Jäger, automatically becomes President. Thisleaves three vacancies on the ExB for President Elect,Honorary Secretary, and Honorary Treasurer. Elections forthese positions took place at our General Assembly, andwere filled by myself, Professor Lucas Greiner fromWuppertal, Germany and Dr Niels Juul from Copenhagen,Denmark (for a second term) respectively. I am of coursedelighted and flattered that the Board of Directors andGeneral Assembly have seen fit to appoint me asPresident Elect.

I would like to finish my report by saying how much I haveenjoyed working with the ExB and Board of Directors overthe past three years and to thank Mrs Stanford for thetremendous work she has done for the Federation, and thesupport she has given me in my capacity as HonorarySecretary.

David H EvansPast Honorary Secretary EFSUMB

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REPORT FROM THE HONORARY TREASURER

My mandate period from1999 to 2002 as HonoraryTreasurer is about toterminate. It has been apleasure for me to work inthe Executive Bureau totake care of the finances,with the assistance of theGeneral Secretary.

The EFSUMB economy isnow stable and solid.After a year with a loss,two years with surplus hasfollowed and furthermore,a positive outcome of the years 2002 and 2003 isexpected. It is therefore not necessary in the comingyears to raise the fee, which still can be kept as low as8€ per member.

As previously mentioned, the WFUMB congress inFirenze in 2000 was also an economical success, andtogether with surplus from successful Euroson Schoolevents in Romania, Germany and in the UK, aconsiderable income has been paid to EFSUMB. TheTreasurer is very grateful for this contribution fromthe organizers of the Euroson Schools.

On this page I have listed the end of year accounts for2001, the budget for 2003 and an updated membershipstatus.

Niels JuulHonorary Treasurer EFSUMB

CountryNumber Of Members

In DatabaseAUSTRIA 813BELGIUM 211BULGARIA 75CROATIA 67CZECH REP 45DENMARK 332FINLAND 270FRANCE 361GERMANY 5007GREECE 100HUNGARY 49ISRAEL 101ITALY 1850NETHERLANDS 49NORWAY 194POLAND 800PORTUGAL 63ROMANIA 247RUSSIA 68SLOVAK REP 40SLOVENIA 108SPAIN 168SWEDEN 96SWITZERLAND 2043UK 2150TOTAL 15307

EFSUMB Trading and profit and loss accountYear ended 31 December 2001 in £sterling

INCOMESubscriptions 65,055Newsletter sponsorship 14,942EurosonSchool/Congresses 11,139Deposit account interest 486Reimbursements 2,176

93,798EXPENDITURESubscription WFUMB 15,034Publishing and mailingcosts of Newsletter 27,734Meeting and Travellingexpenses of allcommittees 17,364Wages 13,256Printing, postage andstationery 619Auditors remuneration 764Loss on exchange 195Office services 6,224Bank charges 486

Depreciation:Plant and machinery 91Fixtures and fitting 234Computer equipment 852

82,853Excess of income overexpenditure 10,945

EFSUMB Budget For The Year 2003(In £sterling)

INCOMEMembership fee 14000 membersbecause of the euro rate againstthe pound sterling

72,000.00

Newsletter sponsorship 6,000.00Bank deposit interests 1,000.00European Journal 0.00EUROSON CONGRESSWarsaw 2002 to be determined 0Copenhagen to be determined 0TOTAL INCOME 79,000.00EXPENDITUREWFUMB 15,000.00Newsletter 24,000.00Meetings, Executive Bureau 8,000.00Meetings, Committees 8,000.00Prizes etc 1000Secretary 14,000.00Printing, postage 2,000.00Accountants 1,000.00Loss on exchanges 2,000.00Office 5,000.00Bank charges 500TOTAL EXPENDITURE 80,500.00BALANCE -1,500.00

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YOUNG INVESTIGATOR AWARD 2002The following papers were accepted for presentation at the Young Investigator Session during the 14th EurosonCongress in Warsaw on 6 July 2002.

• Dr Roland Devlieger - Department of Obstetrics and Gynaecology, University Hospital “Gasthuisberg”, Leuven, BelgiumReducing the risks of ultrasound guided endoscopic fetal surgery: experimental models in sheep and rhesus monkey.

• Dr Jonas Eiberg Dept of Vascular Surgery, Rigshospitalet, Copenhagen, DenmarkUltrasound Imaging of Infrainguinal arterial disease has a high interobserver agreement

• Dr. Johan Axel Lunding, Medical department, Haukeland University Hospital of Bergen, NorwaySymptom perception and gastric response to an increasing gastric water load with and without simultaneous duodenal lipidinfusion in functional dyspepsia patients using 3D ultrasonography.

• Dr Ewa Bialek Wojewódski Szpital Bródnozski Zaklad Diagnostyki Obrazowejul. Kondratowicza 8, 03-242 Warsaw, PolandNew Ultrasound Imaging Methods (tissue Harmonic Imaging, Panoramic Imaging, Three dimensional imaging) in head and neckarea.

The winner was Dr Jonas Eiberg, Dept of Vascular Surgery, Rigshospitalet, Copenhagen, Denmark. The abstract of hispresentation is printed below:

“ULTRASOUND IMAGING OF INFRAINGUINAL ARTERIAL DISEASE HAS AHIGH INTEROBSERVER AGREEMENT”

Objectives: To evaluate the operator dependency ofduplex arterial scanning (DUAS) and contrast arteriography(CA) in chronic lower limb ischaemia.Design: Prospective and blinded study.Material: 26 consecutive patients (13 men and 13 female)with severe claudication (n=6, 23%), rest pain (n=7, 27%)and tissue loss (n=13, 50%).Methods: Two physicians independently performed aDUAS of the entire lower limb, from the groin to the foot.

Arterial segments were diagnosed as insignificantly (< 50%

stenosis) or significantly (> 50% stenosis or occlusion)diseased, alternative inconclusive. CA was performed within24h and was independently described by two radiologists inthe same manner. Within 10 months the arteriograms werereassessed.Results: DUAS interobserver-agreement was good (ic =0.79 (Cl: 0.72-0.86)) and not significantly different (p>0.7)from the CA interobserver-agreement (rc= 0.80 (0.74-0.87)).The intraobserver-agreement between the two CA readingswas 0.84 (0.79-0.90).Conclusion: Arterial duplex scanning is as reliable asarteriography when visualizing severe lower limb ischaemia.

16th EUROSON CONGRESS – 6-9 JUNE 2004 - ZAGREB – CROATIA

Dear Colleagues,

On behalf of The Croatian Society for Ultrasound in Medicine andBiology, I have the great pleasure in inviting all involved andinterested ultrasound societies to Zagreb, the capital of the republic ofCroatia, where we will host the XVIth Congress of the EuropeanFederation of Societies for Ultrasound in Medicine and Biology.

Zagreb, your host city, has developed out of the thousand year oldmedieval market place and ecclesiastical centre of North-westernCroatia. Its geographical position at the cross-roads of trade routes andits turbulent past have made Zagreb an important cultural and scientificcentre, an economic centre, a traffic cross-roads, and the capital ofCroatia.

Come and share with us your recent research achievements, yourclinical experiences, and the pleasure of your company. The localorganizing committee, the University, and the City of Zagreb will behonoured to be able to provide you with Croatian hospitality and lookforward to giving you a warm welcome and a memorable congress.

Kurt Jäger Ivo DrinkovićCongress Co-President EFSUMB Congress Co-President CSUMB

IF YOU WISH TO SUBMIT A PAPER FOR THE YOUNG INVESTIGATOR AWARD SESSION TO BE HELD DURINGTHE 15TH EUROSON CONGRESS IN COPENHAGEN 27-30 APRIL 2003

PLEASE CONTACT YOUR NATIONAL SOCIETY (and see Bylaw no.4 on the EFSUMB website: www.efsumb.org)

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EDUCATION AND PROFESSIONAL STANDARDS COMMITTEEEFSUMB´s Education and Professional StandardsCommittee are trying to collect evidence for how somecommon ultrasound guided invasive procedures should beperformed. In January 2001 we published a document onamniocentesis. Below you will find a document presentingthe evidence with regard to chorionic villus sampling (CVS)in singleton pregnancies. The document has been preparedby Dr Lil Valentin (Malmö, Sweden) and Dr Steen SmidtJensen (Hvidovre, Denmark).

We should highly value any comments you might care to makeon the document. Are you aware of evidence that is not presentedin the document? Have we forgotten to discuss one or moreimportant issues? Do you disagree with one or more statements,and if so, which are your arguments for doing so??Send your comments to EFSUMB´s general secretary, Ms.Gianna Stanford (efsumb@compuserve.com).

Lil ValentinCommittee Chairman

DIAGNOSTIC CHORIONIC VILLUS SAMPLING (CVS) IN SINGLETON PREGNANCIES.

Indications:a) Increased risk of chromosomal abnormalityb) DNA and biochemical analyses for monogenic hereditary diseasesc) Determination of fetal sexd) Paternity testing

CommentsRe a) The individual risk of chromosomal abnormality can becalculated on the basis of maternal age, personal and family history,status of inherited structural chromosomal abnormalities, firsttrimester serum biochemistry, fetal nuchal translucency, and fetalabnormality.

Ad b) Trophoblastic tissue constitutes an excellent basis for DNAanalysis and biochemical analyses in case of a family history ofmonogenetic diseases or carrier status.

Re c) The gender of the fetus can be established in the first trimester.This may be clinically important in case of serious x-linked hereditarydisease, e.g. hemophilia.

Re d) Paternity can be established in the first trimester by comparingmarkers of the chromosomes of the fetus and of those of its possiblefather.The diagnostic potential of CVS is similar to that of amniocentesiswith regard to chromosomal, DNA and biochemical analyses. Adisadvantage of CVS is that screening for neural tube defects andabdominal wall defects by analysis of AFP is not possible.CVS can be performed transabdominally or transcervically guided byultrasound. For the transabdominal approach some operators use afree-hand needle technique, others use a needle guide attached to thetransducer head and a superimposed electronic needle pathway on theultrasound monitor. For the transcervical approach a plastic catheter orforceps are used.The advantages of CVS in the first trimester over standardamniocentesis at 16 gestational weeks is that knowledge of thechromosomal status of the fetus can be obtained much earlier inpregnancy, because sampling can be performed earlier in gestation,and the reporting time is shorter using trophoblastic cells for cultureinstead of amniocytes. Short term culture of trophoblastic cellsreduces reporting time even more but entails poorer chromosomequality (Therkelsen et al. 1988). Screening with fluorescent in situhybridization (FISH) with probes for the most common aneuploidiescan be performed without culture (Quilter et al. 2001). CVS isattractive to the woman because it offers an early solution of heranxiety, and she can avoid a second trimester termination in case of adiseased fetus.Should a fetal abnormality be detected by ultrasound later inpregnancy, a quick chromosomal result is needed for optimalmanagement of the pregnancy. Short term culture of trophoblastictissue with chromosomal analysis, or FISH analyses of villi oramniotic fluid cells may clarify the chromosomal status of the fetuswithin hours/days (Smidt-Jensen et al. 1994; Hitschold et al. 1997;Podobnik et al. 1997).

Contraindicationsa) The amniotic membranes cannot be avoidedb) Pregnancies with increased risk of miscarriagec) Gestational age < 9 completed weeksd) Rh-immunised woman

CommentsRe a) The unintended abortion rate increases extensively if themembranes are entered (Saura et al. 1991; Lilford et al. 1987). Toeliminate possible side effects of a collapse of the membranes and ofneedle lesions, which could seriously damage the first trimester fetus,the membranes must not be entered. In almost all cases themembranes can be avoided even in a posterior placenta. Difficultsampling by the transabdominal approach may be expected when theuterus is retroflexed. Increased transducer pressure and sampling fromthe lateral side of the uterus may solve the problem (Smidt-Jensen etal. 1988)

Re b) If the ultrasound investigation shows haematomas, the presenceof an intrauterine device (IUD), large fibromas, or other uterineabnormalities, or if there is active bleeding, the risk of spontaneousabortion must be considered to be increased and the woman should becounseled accordingly. Although benefit of postponement in case ofactive bleeding has not been documented, most operators wouldpostpone prenatal testing until the time of amniocentesis or at leastuntil bleeding has ceased.

Re c) Because the spontaneous loss of chromosomally abnormal fetuses ishigh early in pregnancy, the loss rate of fetuses with of Down´s syndromeat 10 gestational weeks being nearly 50 %, and that of fetuses with othertrisomies or Turner´s syndrome being even higher (Snijders and Nicolaides1996), it seems reasonable not to perform CVS earlier than at 9 completedweeks (crown rump length 23 mm). Since the early 1990´ies it has beendiscussed, whether CVS is associated with limb reduction defects, inparticular CVS carried out before 9 completed gestational weeks. Fromthree CVS centres clusters of limb reductions and high abortion rates werereported after CVS (Firth et al 1991; Burton et al. 1992; Hsieh et al 1995).In 1992 the World Health Organization, WHO, initiated an internationalregistration of post-CVS limb defects. Reporting to the registry was madeon a voluntary basis, but special efforts were also made to find and includeclusters of limb defects not directly reported to the registry. It wasconcluded that limb reduction might occur in clusters, but that there is noindication of an increased risk of limb reduction defects after CVS,irrespective of when in pregnancy CVS is performed. However, there isvery limited experience with CVS before 9 completed gestational weeksand insufficient knowledge of the effects of performing CVS before thattime. The WHO group recommends no specific sample week as long asCVS is performed after 9 completed gestational weeks (Froster andJackson 1996; Kuliev et al. 1996).

Re d) Because of feto-maternal bleeding after CVS, the risk of Rh-immunization must be taken into account. Aggravation may occur in awoman already immunized (Brambati et al, 1986), but is perhapsunlikely.

Complicationsa) Unintended fetal lossb) Feto-maternal bleeding (possibly causing Rhesus iso-

immunization)c) Vaginal bleeding and amniotic fluid leakaged) Maternal cell contamination

CommentsRe a) Several studies compared first trimester CVS, usually performed at 9- 12 gestational weeks, with ‘standard‘ amniocentesis at around 16gestational weeks. A Danish randomised controlled trial comparingtranscervical CVS in the first trimester, transabdominal CVS in the firsttrimester, and amniocentesis at 16 weeks, showed no significant differencein fetal loss rate between transabdominal CVS and amniocentesis (Smidt-Jensen et al.1992). This Danish

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trial is the only one comparing transabdominal CVS in the firsttrimester with ‘standard‘ amniocentesis. Although the Danish trial didnot present absolute risk estimations for each procedure, the resultssuggest that the absolute risk of transabdominal CVS in the firsttrimester may be similar to the 1% (CI 0.3 – 1.5%) absolute riskassociated with amniocentesis at 16 weeks (Tabor et al. 1986a).In a 7-centre non-randomised study comparing transcervical CVS withamniocentesis, the excess fetal loss rate after CVS was about 0.8%(95% confidence interval; CI; -1.3 – 2.9), a statistically non-significant difference (Rhoads et al. 1989). A similar (0.6%)statistically non-significant excess rate of fetal loss after transcervicalCVS was found in the Canadian 11-centre randomised controlled trial(Canadian Coll. 1989). Thirty-one centres in Europe participated inthe MRC randomized controlled trial (MRC Working Party on CVS1991). Each centre chose their own favoured CVS method, 72% of theCVS procedures being performed transcervically. The fetal loss ratewas significantly higher after CVS than after amniocentesis, theexcess loss rate being 4.6% (95% CI 1.6 – 7.5%; p<0.01).There are also randomised trials comparing transabdominal CVS withtranscervical CVS. In the Danish randomised controlled trialmentioned above, the post-procedure spontaneous loss rate wassignificantly higher after transcervical CVS than after transabdominalCVS, 4% more losses (95% CI 2.3 – 5.8%) occurring in thetranscervical group (Smidt-Jensen et al. 1992). One American and oneItalian randomised trial compared the two approaches without findingany statistically significant difference in fetal loss rate (Brambati et al.1991; Jackson et al. 1992), even though the loss rate was slightlyhigher after transcervical CVS. There were major methodologicaldifferences between the three studies, the American and Italian studiesbeing characterised by a high rate of cross-overs, lack of follow-up,and a high degree of patient selection. Differences in the experience ofthe operators may also have contributed to the differences in results.Transcervical CVS was the prevailing method in the US and in Italy atthe time of the studies. Thus, many American and Italian operatorsprobably had greater experience with the transcervical approach,whereas the reverse was the case in Denmark. An excess riskassociated with transcervical CVS was found in a Germanobservational study including more than 16,000 transabdominal andtranscervical procedures (Stengel-Rutkowski 1993).The abortion mechanism associated with CVS is not known.Theoretically, it may be related to feto-maternal bleeding, disturbanceof the feto-maternal barrier, bleeding or haematomas in the placenta,infection, leakage of amniotic fluid, or decompression of the uterus.A "true" picture the fetal loss rate after CVS can only be obtained inrandomised controlled trials performed after some years of routine useof CVS, after the learning curve of the procedure has been passed.However, a randomised trial conducted after a treatment/diagnosticprocedure has become standard practice may provoke controversy(Pocock 1987). The randomised trial on amniocentesis was conductedafter several years of routine use of amniocentesis (Tabor et al.1986a).

Re b) Feto-maternal bleeding occurs during invasive prenatalprocedures. A rise in maternal alpha-feto-protein (AFP) after aninvasive procedure is a result of feto-maternal bleeding (Warren et al.1985; Brambati et al. 1986; Mariona et al. 1986; Knott et al. 1988). At9 weeks the total amount of fetal blood is 5 ml (Brambati et al. 1986).In 18% of women undergoing transabdominal CVS and in 5% ofthose undergoing transcervical CVS, the maternal serum AFP rose bymore than 34 kU/l, which corresponds to 0.1 ml or more of fetal bloodtransfused into the maternal circulation (Smidt-Jensen et al. 1994).There is a positive correlation between the amount of aspirated villiand the increase in maternal serum-AFP after first-trimester CVS(Brambati et al. 1986; Schulman et al. 1990; Smidt-Jensen et al.1994).The clinical importance of the feto-maternal bleeding caused by CVSin the first trimester or by amniocentesis in the second trimester isuncertain. Brambati and coworkers found no association between apost-CVS increase in maternal serum-AFP and fetal loss aftertranscervical CVS performed at 8 - 12 gestational weeks (Brambati etal. 1986). In a Danish study (Smidt-Jensen et al. 1994) the fetal lossrate increased with increasing maternal serum AFP levels aftertransabdominal first-trimester CVS but not after transcervical first-trimester CVS. The risk of Rhesus immunization after amniocentesisat 16 weeks and after first trimester CVS is probably small (Tabor etal. 1986b, Smidt-Jensen et al. 1994). The increase in maternal serum-AFP caused by CVS does not compromise second trimester maternalserum-AFP screening for neural tube defects or abdominal walldefects (Brambati et al. 1986, Smidt-Jensen et al. 1994).

Re c) Spotting and bleeding occur significantly more often aftertranscervical CVS than after transabdominal CVS (spotting: 7.3% vs.3.2%; 19% vs. 4%; bleeding 6% vs. 1.9%; 8.6% vs. 4.7%; 6% vs. 1%;Brambati et al. 1991; Smidt-Jensen et al. 1992; Jackson et al.1991).Because spotting and bleeding occur more often after transcervicalCVS than after transabdominal CVS, at least some of the bleedingepisodes after transcervical CVS are likely to be caused by theprocedure itself, because if they were not, one would expect the sameincidence of spotting and bleeding episodes after both procedures.In one randomised trial, transabdominal and transcervical CVS wereassociated with a similar rate of amniotic fluid leakage (0.6% vs.0.5%, non-significant difference; Smidt-Jensen et al 1992), whereas inanother randomised trial amniotic fluid leakage was significantly morecommon after transcervical CVS (2% vs. < 1%; p < 0.01; Jackson etal. 1992). The significantly higher rate of leakage after transcervicalCVS suggests that at least some of the leakages after transcervicalCVS are caused by the procedure, because if not, one would expectthe same rate of leakage after both procedures.Because there is no randomized trial comparing transabdominal CVSwith a non-invasive procedure, it is impossible to know whether thespotting, bleeding and amniotic fluid leakage seen aftertransabdominal CVS are caused by the procedure, or whether theyoccur with a rate similar to that in the background population. In therandomised trial of Tabor and colleagues (1986a) comparingamniocentesis at 16 weeks with a non-invasive procedure, there was asignificantly higher rate of amniotic fluid leakage in women who hadundergone amniocentesis at 16 weeks (1.7%) than in controls (0.4%)during 6 weeks of follow-up, whereas bleeding occurred equally oftenin the two groups (2.4% vs. 2.6%).

Re d) Contamination with maternal decidua was seen in about 1% ofcultures after transabdominal CVS vs. in 4% after transcervical CVS(Ledbetter et al. 1992; Smidt-Jensen et al.1993). The cytogeneticresults may be compromised by contamination of maternal tissue.Therefore, maternal tissue must be removed before analysis. Maternaltissue contamination would be negligible if cultures were supportedby non-cultured analyses, or if the cultures were screened forconvoluted cells (Hertz et al. 1987).

Precautions to be takena) The transabdominal route is probably preferableb) No sampling before 9 completed weeksc) Use real-time ultrasound guidanced) Use needle guidee) The membranes must be avoidedf) Experienced operatorg) Sterile conditionsh) Remove no more tissue than needed for diagnosisi) Not more than two needle insertionsj) Rhesus prophylaxis?k) 12 to 24 hours of restricted activity after CVS?l) Pre-CVS coagulation status?

CommentsRe a) The transabdominal route is probably safer, it is easier and moresuccessful in sampling than the transcervical route (Brambati et al.1991; Smidt-Jensen et al. 1992; Jackson et al. 1992). One personoperates both the ultrasound transducer and the needles. Moreover, thetransabdominal route might be more acceptable to the woman and toany accompanying persons.

Re b) The optimal time for sampling of villi seems to be between 9and 11 weeks. The ‘placenta‘ is sufficiently large by this time. Thevilli may loosen more easily the earlier in pregnancy the aspiration isperformed. For cultures in the second and third trimesters more villiare needed, laboratory work is more laborious, and the chromosomequality of direct and short term cultures is poorer (Pijpers et al. 1988;Saura et al. 1990; Holzgreve et al. 1990; Cameron et al. 1990; Evanset al 1990; Smidt-Jensen et al. 1993). For these reasons and for thosementioned above (i.e., high background spontaneous loss rate early inpregnancy, and possibly increased risk of limb reduction defects ifCVS is performed very early in pregnancy), it is reasonable to performroutine CVS late in the first trimester but not before 9 completedweeks.

Re c) and d) There are no randomized controlled trials comparingtransabdominal CVS sampling techniques. However, ultrasonic realtime guidance with a needle guide and the needle pathwaysuperimposed on the

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monitor may have advantages over the free hand technique, becausethe needle can be introduced through the skin into the uterus with onequick insertion (Smidt-Jensen et al. 1988; Rodeck 1991). This isprobably associated with less discomfort to the woman than the slowerfreehand needle insertion, which may make the woman move anddistort the needle pathway. Moreover, increased sampling time mightbe associated with increased risk of chorio-amnionitis, and the morefreely movable needle might increase the risk of feto-maternalbleeding (Weiner et al. 1991)

Re e) CVS should be performed as atraumatically as possible. Themembranes should not be punctured. Studies of first trimesteramniocentesis have shown increased abortion risk and a higher risk oftalipes equinovarus after amniotic fluid leakage (Sundberg et al. 1997;CEMAT group 1998; Nicolaides et al. 1994). CVS performed throughthe amniotic cavity increases the risk of miscarriage (Saura et al.1991).

Re f) The individual transabdominal CVS learning curve depends onprevious experience with amniocentesis (Wijnberger et al. 2000).Transabdominal CVS is easier to learn than transcervical CVS. Peaktechnical performance was achieved after the first series of 100 casesof transabdominal aspirations vs. after the first series of 300 cases oftranscervical aspirations (Brambati et al. 1990; Silver et al. 1990;Saura et al. 1991; Chueh et al. 1995; Stranc et al. 1997). Training onvolunteers undergoing abortion or training on an in vitro trainingmodel (Ville et al 1995; Nizard et al. 2002) is recommended beforeperforming diagnostic CVS.

Re g) There are no randomised controlled trials comparing CVSperformed under clean but not sterile conditions with CVS performedunder sterile conditions. Despite lack of scientific evidence, it isprobably safest to perform transabdominal CVS under sterileconditions: sterile washing of the skin (chlorhexedine or iodine),ultrasound scanning through a sterile medium, sterile gloves andsterilization of the transducer and needle guide for at least 5 minutesbetween the procedures (unless a sterile cover is used), and sterileneedle. Needle insertions through the intestines and urinary bladderare almost certainly best avoided.

Re h) More villi are usually required for DNA analyses andbiochemical analyses than for chromosome analysis. Most laboratoriesrequire 10-15 mg of villi for chromosome analysis and 30-50 mg ofvilli for DNA analysis. There is no evidence of any correlationbetween fetal loss and the amount of villi aspirated within these limits(Smidt-Jensen et al. 1992; Smidt-Jensen et al. 1994).

Re i) Using the double needle CVS technique as many insertions withthe aspiration needle as needed can be done through the introductionneedle. If two needle insertions are unsuccessful most operatorspostpone the procedure for one week. This is not evidence based. Fortranscervical CVS multiple insertions increase the complication rate(Wapner et al. 1988; Roads et al. 1989; Wade and Young 1989).

Re j) There is insufficient evidence to recommend or discourageroutine administration of anti-D immunoglobulin after CVS. Thus, inan unpublished randomized controlled trial comprising 370 women(Smidt-Jensen et al.) benefits of administering 50 micrograms of anti-D-immuno-globulin after CVS were not demonstrated. In theory,anti-D immune-globulin could cross the placenta and destroy bloodcells of Rhesus positive fetuses. On the other hand, a very smallvolume of fetal blood may sensitize or immunize a pregnant woman(Brambati et al 1986).

Re k) There are no studies evaluating the effects of post-CVS regimes.Many centers recommend that hard work be avoided until the nextday, and some recommend bed rest. Others recommend the woman torest only in case of pain, spotting, or fluid leakage, and to contact thecenter if the symptoms continue the following day. None of theserecommendations are based on scientific evidence.

Re l) To the best of our knowledge, there are no reports evaluating theneed for routine testing of maternal coagulation status before CVS andclinical experience suggests that this is unnecessary. Women withknown coagulation defects should be managed in consultation with acoagulation specialist.

The needlesThere are no randomized controlled trials comparing transabdominalCVS performed with different types of needles. The outer trocar of thedouble needle usually has an outer diameter of 1.2 mm (18 Gauge),

and the inner aspiration needle usually has an outer diameter of 0.7-–0.8 mm (20 – 21 Gauge) (Smidt-Jensen et al 1984; Lilford et al 1987;Mackenzie et al. 1988; Bovicelli et al. 1988; Copeland et al. 1989;Hibbard et al. 1994). A 19 – 20 Gauge single needle is usually used(Brambati et al. 1991; Jackson et al. 1992).

Preferred Technique of ultrasound guidancea) Transabdominal approachb) Needle guidec) Double needle

CommentsRe a) See above under complications. Three randomized trialscompared transabdominal and transcervical CVS. Complication rateswere similar in two of these (Brambati et al. 1991; Jackson et al.1992), but in the third study a significantly higher fetal loss rate wasfound in the transcervical group (Smidt-Jensen et al. 1992). The threestudies are methodologically different, see above. An excess riskassociated with transcervical CVS was also found in a Germanobservational study including more than 16,000 transabdominal andtranscervical procedures (Stengel-Rutkowski 1993).

Re b) No study compared freehand transabdominal prenatal invasiveprocedures with transabdominal prenatal invasive proceduresperformed using a needle guide. In two of the three randomised trialscomparing transcervical and transabdominal CVS a single needlefreehand technique was used (Brambati et al. 1991; Jackson et al.1992), whereas in the third trial the double needle technique with aneedle guide was used (Smidt-Jensen et al. 1992). The use of a needleguide might be preferable, because when the freehand technique isused, the more freely movable needle might increase the risk of feto-maternal bleeding and chorio-amnionitis (Weiner et al. 1991). Forquick needle insertion a needle guide is mandatory. See also aboveunder Precautions (c and d).

Re c) No trials/studies compared transabdominal CVS performed withdifferent kinds of needles (double vs. single; needles of differentsizes). Aspiration through an outer guide needle using a double needleis likely to cause minimal trauma, because the necessary amount ofvilli can be obtained through one single needle insertion, and vigorousmovement of the inner needle is not necessary. The single needletechnique is probably more traumatic, because the needle is movedvigorously to-and-fro through the abdominal wall and uterus, and if aninadequate amount of villi is obtained, the needle must be insertedagain to obtain more material.

Concluding remarksThere is evidence from randomized controlled trials that the fetal lossrate after transabdominal CVS is similar to that after amniocentesis at16 weeks (Smidt-Jensen et al.1992), but that the loss rate is higherafter transcervical CVS (Can Coll 1989; MRC Working Party on CVS1991, Smidt Jensen et al. 1992). However, success, ease and safetymay be maximized if operators are experienced in bothtransabdominal and transcervical CVS (Jackson et al. 1992).Many of the recommendations above are based on weak evidence, i.e.on results of case-control studies (Rhoads et al. 1989; Stengel-Rutkowski 1993), descriptive studies (Copeland et al. 1989; Bovicelliet al. 1988; Mackenzie et al. 1988), or case reports (Firth et al. 1994;Burton et al. 1992), or on inference from results of studies onamniocentesis or other invasive procedures, or on clinical experience.It goes without saying that because of the relatively low complicationrate after CVS, a huge number of patients would need to be includedin randomized trials evaluating different CVS techniques (e.g.,different types of needles, or freehand technique vs. use of a needleguide) and post-CVS management strategies (e.g., rest vs. norestriction of activities) to obtain reliable and generalizable results.Moreover, certain questions would not be suitable for answering in arandomized trial, e.g., whether the number of needle insertions affectsthe outcome.

ReferencesBovicelli L, Rizzo N, Montacuti V, Morandi R, Vullo C, Toffoli C,Venturoli A. Transabdominal chorionic villus sampling: analysis of350 consecutive cases. Prenat Diagn 1988 Sep;8(7):495-500.Brambati, B, Guercilena, S, Boacchi, I, Oldrini, A, Lanzani, A, Piceni,L. Feto-maternal transfusion after chorionic villus sampling: clinicalimplications. Hum Reprod 1986;1:37-34.Brambati B, Lanzani A, Tului L. Transabdominal and transcervicalchorionic villus sampling: efficiency and risk evaluation of 2,411cases. Am J Med Genet 1990;35(2):160-4.

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Brambati, B, Terzian, E, Tognoni, G. Randomised clinical trial oftransabdominal versus transcervical chorionic villus sampling methods.Prenat Diagn 1991;11:285-293.Burton, B, Schulz, CJ and Burd, LI. Limb abnormalities associated withchorionic villus sampling. Obstet Gynecol 1992;79:726-730.Cameron AD, Mathers AM, Wisdom S, Johnstone J, MacKenzie JR,Walker JJ, Imrie SJ, Lowther GW, Connor JM. Second-trimester placentalbiopsy for rapid fetal karyotyping. Am J Obstet Gynecol 1990;163(3):931.Canadian Collaborative CVS-Amniocentesis Clinical Trial Group.Multicentre randomised clinical trial of chorionic villus sampling andamniocentesis Lancet 1989;1:1-6.Chueh JT, Goldberg JD, Wohlferd MM, Golbus MS. Comparison oftranscervical and transabdominal chorionic villus sampling loss rates innine thousand cases from a single center.Am J Obstet Gynecol. 1995;173(4):1277-82.Copeland KL, Carpenter RJ Jr, Fenolio KR, Ledbetter DH Integration ofthe transabdominal technique into an ongoing chorionic villus samplingprogram. Am J Obstet Gynecol 1989;161(5):1289-94.Farrell SA, Summers AM, Dallaire L, Singer J, Johnson JA, Wilson RD.Club foot, an adverse outcome of early amniocentesis: disruption ordeformation? CEMAT Canadian Early and Mid-Trimester AmniocentesisTrial. J Med Genet 1999;36(11):843-6.Firth, HV, Boyd, PA, Chamberlain, P, Mackenzie, IZ, Lindenbaum, RH,Huson, SM. Severe limb abnormalities after chorion villus sampling at56-66 days' gestation. Lancet 1991;337:762-763.Froster, UG, Jackson, L. Limb defects and chorionic villus sampling:results from an international registry, 1992-94. Lancet 1996;347:489.Hertz JM, Jensen PK, Therkelsen AJ. Convoluted cells as a marker formaternal cell contamination in CVS cultures. Clin Genet 1987;31(6):410-2.Hibbard JU, Loy GL, Hibbard MC. Does chorionic villus samplingcompromise fetal umbilical blood flow? Prenat Diagn 1994;14(12):1107.Hitschold T, Berle P. [Transabdominal chorionic villi and placental biopsy:rapid karyotyping in the 1st-3rd trimester of pregnancy] Ultraschall Med1997;18(3):134-8.Hsieh FJ, Shyu MK, Sheu BC, Lin SP, Chen CP, Huang FY. Limb defectsafter chorionic villus sampling. Obstet Gynecol 1995;85:84-8Holzgreve, W, Miny, P, Schloo, R. "Late CVS" international registrycompilation of data from 24 centres. Prenat Diagn 1990;10:159-167.Jackson, LG, Zachary, JM, Fowler, SE, et al. A randomised comparison oftranscervical and transabdominal chorionic villus sampling. N Eng J Med1992;327:594-598.Knott PD, Chan B, Ward RH, Chard T, Grudzinskas JG, Petrou M, ModellB.Changes in circulating alphafetoprotein and human chorionicgonadotrophin following chorionic villus sampling. Eur J Obstet GynecolReprod Biol 1988;27(4):277-81.Kuliev, A, Jackson, L, Froster, U, Brambati, B, Simpson, JL, Verlinsky, Y,Ginsberg, N, Smidt-Jensen, S, Zakut, H. Chorionic villus sampling safetyReport of World Health Organization/EURO meeting in association withthe Seventh International Conference on Early Prenatal Diagnosis ofGenetic Diseases, Tel, Aviv, Israel, May 21, 1994. Am J Obstet Gynecol1996;174:807-811.Ledbetter, DH, Zachary, JM, Simpson, JL, et al. Cytogenetic results fromthe US collaborative study on CVS. Prenat Diagn 1992;12:317-345.Lilford RJ, Linton G, Irving HC, Mason MK. Transabdominal chorionvillus biopsy: 100 consecutive cases. Lancet 1987;20;1(8547):1415-7.Mackenzie WE, Holmes DS, Newton JR. A study comparing transcervicalwith transabdominal chorionic villus sampling (CVS). Br J ObstetGynaecol 1988;95(1):75-8.Mariona FG, Bhatia R, Syner FN, Koppitch F. Chorionic villi samplingchanges maternal serum alpha-fetoprotein. Diagn 1986;6(1):69-73.MRC working party on the evaluation of chorionic villus samplingMedical Research Council European trial of chorion villus sampling.Lancet 1991;337:1491-1499.Nicolaides KH, Brizot ML, Patel F, Snjders R. Comparison of chorionvillus sampling and early amniocentesis for karyotyping in 1,492 singletonpregnancies. Fetal Diagn Ther 1996;11(1):9-15.Nizard J, Duyme M, Ville Y.Teaching ultrasound-guided invasiveprocedures in fetal medicine: learning curves with and without anelectronic guidance system. Ultrasound Obstet Gynecol 2002;19(3):274-7.Pijpers L, Jahoda MG, Reuss A, Wladimiroff JW, Sachs ES.Transabdominal chorionic villus biopsy in second and third trimesters ofpregnancy to determine fetal karyotype. BMJ 1988;1;297(6652):822-3.Pocock, SJ. Clinical trials. Wiley, S & Sons 1987.Podobnik M, Ciglar S, Singer Z, Podobnik-Sarkanji S, Duic Z, Skalak D.Transabdominal chorionic villus sampling in the second and thirdtrimesters of high-risk pregnancies. Prenat Diagn 1997;17(2):125-33.Quilter CR, Holman S, AL-Hammadi RM, Theodorides D, Hastings RJ,Delhanty JD. Aneuploidy screening in direct chorionic villus samples byfluorescence in situ hybridisation: the use of commercial probes in aclinical setting. BJOG 2001;108(2):215-8.

Rhoads GG, Jackson LG, Schlesselman SE, de la Cruz FF, Desnick RJ,Golbus MS, Ledbetter DH, Lubs HA, Mahoney MJ, Pergament E, et al.The safety and efficacy of chorionic villus sampling for early prenataldiagnosis of cytogenetic abnormalities. N Engl J Med 1989;9;320(10):609-17.Rodeck CH, Sheldrake A, Beattie B, Whittle MJ. Maternal serumalphafetoprotein after placental damage in chorionic villus sampling.Lancet 1993;20;341(8843):500Saura R, Longy M, Horovitz J, Grison O, Vergnaud A, Taine L, MaugeyB. Risks of transabdominal chorionic villus sampling before the 12th weekof amenorrhea. Prenat Diagn 1990;10(7):461-7.Saura R, Horovitz J, Grison O, Longy M, Maugey B, Lesesve JF,Vergnaud A, Roux D. Evaluation of the risks of transabdominal chorionicvillus sampling. 600 cases. J Gynecol Obstet Biol Reprod 1991;20(4):496.Schulman, LP, Meyers, CM, Simpson, JL, Andersen, RN, Tolley, EA,Elias, S. Fetomaternal transfusion depends on the amount of villi aspiratedbut not on method of chorionic villus sampling. Am J Obstet Gynecol1990;162:1185-1188.Silver RK, MacGregor SN, Sholl JS, Hobart ED, Waldee JK. Anevaluation of the chorionic villus sampling learning curve. Am J ObstetGynecol 1990;163(3):917-22.Silver RK, MacGregor SN, Hobart ED. Factors associated with multiple-pass procedures during chorionic villus sampling: a video analysis. PrenatDiagn 1992;12(3):183-8.Smidt-Jensen S, Hahnemann N. Transabdominal fine needle biopsy fromchorionic villi in the first trimester. Prenat Diagn 1984;4(3):163.Smidt-Jensen, S, Hahnemann, N. Transabdominal chorionic villi samplingfor fetal diagnosis Technical and obstetrical evaluation of 100 cases. PrenatDiagn 1988;8:7-17.Smidt-Jensen, S, Permin, M, Philip, J, et al. Randomised comparison ofamniocentesis and transabdominal and transcervical chorionic villussampling. Lancet 1992;340:1237-1244.Smidt-Jensen, S, Lind, A-M, Permin, M, Zachary, JM, Lundsteen, C,Philip, J. Cytogenetic analysis of 2928 CVS and 1075 amniocenteses fromrandomised studies. Prenat Diagn 1993;13:723-740.Smidt-Jensen, S, Lundsteen, C, Lind, A-M, Dinesen, K, Philip, J.Transabdominal chorionic villus sampling in the second and third trimes-ters of pregnancy: Chromosome quality, reporting time and feto-maternalbleeding. Prenat Diagn 1993;13:957-969.Smidt-Jensen, S, Philip, J, Zachary, JM, Fowler, SE, Nørgaard-Pedersen,B. Implications of maternal serum alpha-fetoprotein elevation caused bytransabdominal and transcervical CVS. Prenat Diagn 1994;14:35-45.Smidt-Jensen S. Transabdominal chorionic villus sampling Method, safetyand accuracy. Dan Med Bull 1998;45(4):402-11.Snijders RJM, Nicolaides KH. Ultrasound markers for fetal chromosomaldefects. The Parthenon Publishing Group, New York, London, 1996.Stengel-Rutkowski, S. Prenatal diagnostic on chorionic villi. Final reporton the documentation of the investigation within the collaborative study inthe Federal Republic of Germany 1985-1991, München: KinderzentrumMünchen, 1993.Stranc LC, Evans JA, Hamerton JL. Chorionic villus sampling andamniocentesis for prenatal diagnosis. Lancet 1997;8;349(9053):711-4.Sundberg K, Bang J, Smidt-Jensen S, Brocks V, Lundsteen C, Parner J,Keiding N, Philip. Randomised study of risk of fetal loss related to earlyamniocentesis versus chorionic villus sampling. Lancet 1997;350:697-703.Tabor, A, Philip, J, Madsen, M, Bang, J, Obel, EB, Nørgaard-Pedersen, B.Randomised controlled trial of genetic amniocentesis in 4606 low-riskwomen. Lancet 1986a;7:1287-1293.Tabor A, Jerne D, Bock J. Incidence of rhesus immunization after geneticamniocentesis. BMJ (Clin Res Ed) 1986b;293:533-536.Therkelsen, AJ, Jensen, PKA, Hertz, JM, Smidt-Jensen, S, Hahnemann, N.Prenatal diagnosis after transabdominal chorionic villus sampling in thefirst trimester. Prenat Diagn 1988;8:19-31.Wade RV, Young SR. Analysis of fetal loss after transcervical chorionicvillus sampling-a review of 719 patients. Am J Obstet Gynecol1989;161(3):513-8; discussion 518.Wapner RJ, Jackson L. Chorionic villus sampling. Clin Obstet Gynecol1988;31(2):328-44.Warren RC, Butler J, Morsman JM, McKenzie C, Rodeck CH. Doeschorionic villus sampling cause fetomaternal haemorrhage? Lancet1985;23;1(8430):691.Weiner S. Indications, complications, safety, reliability and assessment ofquality of fetal blood. Ultrasound Obstet Gynecol 1991;1(suppl):17.Wijnberger LD, van der Schouw YT, Christiaens GC. Learning inmedicine: chorionic villus sampling. Prenat Diagn 2000;20(3):241-6.Ville Y, Cooper M, Revel A, Frydman R, Nicolaides KH. Development ofa training model for ultrasound-guided invasive procedures in fetalmedicine. Ultrasound Obstet Gynecol. 1995;5(3):180-3.

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DEAR COLLEAGUES AND FRIENDS

We are delighted to invite you to participate in EUROSON 2003, the 15th Congress of the European Federation of Socie-ties for Ultrasound in Medicine and Biology (EFSUMB) and the 1st joint Scandinavian Meeting. The Congress will be heldin Copenhagen, Denmark, from 27 - 30 April 2003.As a participant to the EUROSON 2003 you may take active part in the courses and workshops planned the first day of theCongress, Sunday April 27. The courses and workshops will be held at the Congress Center or at University Hospitals near-by. We also want to set focus on a series of plenary lectures in honour of professor Hans Henrik Holm´s contribution to dia-gnostic and interventional ultrasound. These lectures will take place immediately after the opening on Sunday April 27. Wehave invited 4 internationally well-known experts who will present the latest within US technology, interventional proce-dures and fetal medicine. The following 3 days - Monday April 28 to Wednesday April 30 - are dedicated to a broad sci-entific programme, which also include sonographers sessions and symposia. In addition to a scientific programme com-prising well-known topics such as urogenital US, gastrointestinal US, breast US, head and neck US and paediatric US wealso want to set focus on topics such as surgical and interventional US, musculoskeletal US, vascular US as well as US ingynaecology and obstetrics.The scientific programme will be held as three parallel sessions. Leading experts will provide invited lectures. However, toensure a high scientific standard an active contribution from participants is needed. We therefore invite you to submit anabstract for an oral communication or a poster presentation.We hope that you find the time and the means to come to Wonderful Copenhagen 27-30 April 2003. We will do our best to offer you an unforgettable stay, both from a scientific and a cultural point of view. Please visit our homepagewww.euroson2003.com for updates, registration, abstract submission, scientific programme, and pre-congress courses etc.

Hope to see you in Copenhagen

Michael Bachmann Nielsen Kurt A. Jäger Steen KarstrupCongress President Congress President Chairman of Scientific CommitteeChairman of Local Organising Committee President of EFSUMB

DEADLINE FOR ABSTRACT SUBMISSION: 16 January 2003

DEADLINE FOR THE LOWREGISTRATION FEE:16 January 2003

DEADLINE FOR REGISTRATION FOR PRE-CONGRESS COURSES AND WORKSHOPS:1 April 2003

CONGRESS DATES:27-30 April 2003

WELCOME RECEPTION:Sunday 27 April 2003

CITY HALL RECEPTION:Monday 28 April 2003

CONGRESS DINNER:Tuesday 29 April 2003

2 7 - 3 0 A P R I L 2 0 0 3 · C O P E N H A G E N · W W W. E U R O S O N 2 0 0 3 . C O M

CALL FOR PAPERS

You are kindly invited to submit an abstract describing an original research work that you wish to present at theCongress, either orally or as a poster. All abstracts will be evaluated. Abstracts will be published in the Final Programme & Abstract Book. Deadline for abstractsubmission is 16 January 2003. For further details pleasecheck the webpage or the second announcement avail-able in September.

REGISTRATION

Early registration is before 16 January 2003. There will bea reduced fee for presenting authors, residents 35 years,sonographers, nurses and midwives. Presenting authorsmust register. We will try to keep the registration fees aslow as possible, please check second announcement andthe homepage for details.

PRE-CONGRESS COURSES AND WORKSHOPS

Sunday 27 April 2003“IBUS - International Breast Ultrasound Seminar”“Advanced “hands-on” in surgical and interventionalultrasound, including RF tissue ablation”“Workshop in Ultrasonography of Joints”“Workshop in Vascular Ultrasound”“US Technology Update”“The 11 to 14-week scan - Fetal Medicine Foundation(FMF) Course”“Fetal echocardiography”“The role of ultrasound in early pregnancy complications”

CONGRESS VENUE

The Bella Center, which will be the Congress Venue, is amodern Congress and Exhibition facility, less than 10minutes from downtown Copenhagen and the airport.

Odd Helge Gilja (NO), Vicepresident

Lil Valentin (SE), Vicepresident

Bruno Cacciatore (FI), Vicepresident

Christian Nolsøe (DK), Vicepresident

Torben Lorentzen (DK), Treasurer

Peter Myschetzky (DK), Secretary

Bjørn Skjoldbye (DK), Chairman of Exhibition & Sponsorships

Nanna Bang (DK), Chairman of Publications & PR

Anders Nilsson (SE), Chairman of Social Committee

Niels Juul (DK)

Torben Larsen (DK)

Thomas Axelsen (DK), Webmaster

Congress Secretariat, ICS A/S, CopenhagenTel: +45 3946 0500 • Fax: +45 3946 0515E-mail: euroson2003@ics.dk

GENERAL INFORMATIONWELCOME TO COPENHAGEN

ORGANISATION

15 T H E U R O P E A N C O N G R E S S O F U LT R A S O U N DF I R S T J O I N T S C A N D I N AV I A N M E E T I N G

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IMPORTANT DATES

v

2002-186_ICS Nanna Bang 15/07/02 12:40 Side 2

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EUROSON 2002 SAFETY SESSION: 6 JULY 2002: WARSAW

Euroson 2002, held in Warsaw during the first week ofJuly, gave this year a particular emphasis to the safety ofdiagnostic ultrasound. Thanks to the generous financialsupport of COCIR an international group of speakers wereable to come together in Warsaw to share with theCongress delegates their knowledge and experience. Inaddition to European experts, speakers from Australia,USA and Japan also contributed to the sessions. It waspossibly the first time that the chairs of the Japanese,European, Australian, American and WFUMB ultrasoundsafety committees all spoke during a safety session of amedical ultrasound congress.The papers on safety were grouped into two sessions. Inthe first, appropriate ways of managing ultrasound safetywere discussed. Prof Marvin Ziskin, Chairman of theWFUMB Safety Committee, described the activities ofWFUMB in creating recommendations on safety ofdiagnostic ultrasound. He reviewed the many issuesneeding consideration to ensure that the clinical benefits ofusing ultrasound are weighed against any small risks. Heinformed the audience that the WFUMB Safety Committeeis currently compiling information on any risks that may beassociated with the use of gas-body contrast agents. Sixinternational experts meet immediately after EUROSON2002 to discuss a detailed draft report. This report, withconclusions and recommendations, will be circulated to awider group for comment in the next few months, and it isintended to complete the report in time for the nextWFUMB meeting in Montreal in June 2003.The responsibility of industry to design safe ultrasoundsystems was reviewed by Dr Peter Linders (PhilipsMedical). He made it clear that manufacturers were boundby international safety standards of manufacture, but thatthe safe use of ultrasound scanners, and risk/benefitjudgements, were in the hands of clinical users.Classification of equipment was presented by Dr RoyPreston (National Physical Laboratory, UK) as a possiblemeans to assist users to make safety judgements.Publications in Germany and in the UK describe aclassification scheme, within which the lowest class couldbe used with minimal concern for patient safety. Thisapproach has been rejected, at present, by the InternationalElectrotechnical Commission (IEC). It was interesting,nevertheless, to hear from the chairman of the JapaneseUltrasound Society Safety Committee, Dr Natori, whodescribed the difficulties experienced in Japan in creatingcomplete links between the national medical ultrasoundsociety and the national standards committees.Safe management is becoming increasingly important, withthe rapid development of wide range of new techniques.The safety implications of these new techniques werereviewed by Dr Tony Whittingham, secretary of ECMUS.He reminded us that some new techniques may result inreduced exposure, in 3D scanning for instance. Othertechniques may require no net alteration in exposure, whilstyet others may be expected to require higher levels to worksuccessfully. Users should ensure that they are informed aboutthe exposure implications of the introduction of new methods.At the end of the first safety session, the speakers debatedbriefly the question of whether acoustic output should belimited: only the FDA in the USA applies output limits atpresent. Of particular interest from this discussion was theview that the Safety Indices (TI and MI) are, to a large extent,ignored by users as a means for safety management.

Much more emphasis will berequired during training before itmay be assumed that these indicesare the sole means of managingsafety.During the second session, sixspeakers gave detailed reviews ofparticular aspects of safety.Tissue heating in vivo, caused byclinical scanners, is beinginvestigated by a team in the UK,funded by the Department of Health. Some results werepresented by Adam Shaw (NPL), who showed quite goodagreement between predicted and measured heating, at leastfor soft tissues. Temperature rises of a few degrees have beenobserved, with greatest heating close to the transducer, causedby probe self-heating. Professor Lesek Filipczynski (Warsaw)has also been studying tissue heating, but at higher frequenciesin a 33MHz ultrasonic microscope. He reported focaltemperature increases of 3.3 K for 2.25W pulses. Contrastagents present completely concerns for ultrasound safety, andthis rapidly-developing field was presented with great clarityby Prof Diane Dalecki, from Rochester, New York. Drawingon her own experimental results and those of other leadinglaboratories, she identified two major safety issues for contrastuse. These are the potential to cause capillary rupture, and thegeneration of premature ventricular contractions. Furtherstudies are essential to create further understanding of themechanisms and thresholds.The chair of ECMUS, Dr Kjell Salvesen, discussed insome detail new evidence for an association betweenultrasound exposure in utero and a subsequent tendency tobe left-handed. There is consistency between the fourepidemiological studies into this topic. Nevertheless, headvised that causation has yet to be proved, and that theevidence does not alter ECMUS advice allowingultrasound examination during pregnancy for all patients.Dr Stan Barnett, (Sydney, Australia) chair of the ASUMsafety committee, reviewed policies used around the worldon the use of live models at scientific conferences. Hecontrasted the ASUM position, banning all use of livemodels, with that of EFSUMB where the ban extends onlyto exposure of pregnant women, juveniles and the use ofcontrast agents. WFUMB has no policy at present. He pointedout that some countries and disciplines place no bar on livescanning at commercial exhibits, and expressed the view thatsuch practices should not be supported by responsiblesocieties of ultrasound in medicine. The Safety Session wasconcluded with an entertaining overview by Dr JacquesAbramovich (Chicago), who drew many of the themestogether in presenting a practical approach to safetymanagement in the clinic. MI and TI give a practical means tomonitor exposure from which to make risk-benefitjudgements. For all their deficiencies safety indices give, atpresent, the best means available for users to ensure thecontinued safety of their patients.

The EUROSON 2002 Safety Session enabled a wide-rangingdebate of safety issues at the highest level of knowledge andunderstanding. It demonstrated the intimate links betweenclinical users, basic scientists, industry and regulators who,working in co-operation, will ensure that diagnostic ultrasoundremains the safest of imaging modalities.

Francis DuckPast Chairman ECMUS – Safety Committee

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EPIDEMIOLOGY OF DIAGNOSTIC ULTRASOUND EXPOSURE DURING PREGNANCYEFSUMB SAFETY TUTORIAL

Despite many laboratory experiments, which show a lack of adverseeffects from diagnostic ultrasound, it will always be necessary tostudy directly its effect in human populations before any definitivestatements regarding risk can be made. With an increasing number ofepidemiological studies of diagnostic ultrasound, the need to reviewand interpret the results from these studies is evident.

Epidemiological studies may be divided into observational andexperimental studies (see figure 1). The observational studies aresubdivided into descriptive and analytical studies. Descriptive studiesare suitable for generating new hypotheses about associations betweenexposure and disease, whereas analytical studies are designed to testsuch hypotheses. The simplest descriptive study is the cross-sectionalstudy, in which patients are examined only once. In a longitudinalstudy, the patients are followed over time, but the study is stillclassified as hypothesis generating. Analytical studies, on the otherhand, have a prior hypothesis of a possible association betweenexposure and disease. They are subdivided into cohort and case-control studies depending on whether the scientist starts out with theexposure or the disease. In the simplest case-control design, patientsare examined only once, whereas it is necessary to follow patientsover time in a cohort study. The randomised controlled trial isregarded to be the best way to examine possible cause-effectrelationships in human populations. There are, however, manyproblems in medicine that would be impossible or unethical to test in arandomised controlled trial.

This tutorial summarises some of the epidemiological evidence fromstudies on in utero ultrasound and subsequent childhood development.Emphasis is placed on birth weight, childhood malignancies,neurological development, handedness and speech development.

Birth weightThe question of whether ultrasound exposure in utero leads to reducedbirth weight has probably been given more attention than any otherend point. This may be due to the existence of such an effect in someanimal models or possibly because it is relatively quick and easy tomeasure.

Human birth weight data have been reported in many epidemiologicalstudies[1-12], but there is only one study[12], which has created someconcern. Newnham and co-workers did a randomised controlled trialwith 2 834 pregnant women from Western Australia[12]. They offeredhalf of the women continuous wave Doppler ultrasound examinationsfive times in the 3rd trimester. These were compared with controlsthat received one diagnostic imaging ultrasound scan at 18 weeks andotherwise had standard antenatal care. The authors reported astatistically significant increase in the number of babies in the Dopplergroup with a birth weight below the 10th percentile (relative risk 1.35,95% confidence interval 1.09 to 1.67), but the difference in mean birthweight between the groups was only 25 g (not significant). It must beemphasised that this randomised trial tested a formal hypothesis thatfrequent Doppler ultrasound examinations might improve pregnancyoutcome. Additional data analyses performed in the study do not havethe advantages built into a randomised controlled trial. They may,however, be used to generate a new hypothesis, which must then betested in another independent study.

Results from the Australian trial are inconsistent with the availabledata on birth weight from other randomised trials of diagnosticimaging ultrasound[1, 2, 7, 8, 10, 11]. Those studies have beensummarised in a Cochrane review [13] which concludes that there isno statistically significant difference in the proportion of low birthweight children (< 2.5 kg) between ultrasound-screened children andcontrols (odds ratio 0.96, 95% confidence interval 0.82 to 1.12). SinceDoppler ultrasound studies usually imply higher levels of exposurethan diagnostic imaging, the differences between the Australian trialand the other trials may reflect a dose-response relationship. However,the results from the Australian trial should be repeated by a newindependent study before the reported effect of Doppler ultrasound onbirth weight should be regarded as anything more than a chancefinding.

Childhood malignanciesWhen the outcome under study is rare, such as childhood malignancies,any approach other than the case-control design is unsuitable. Fourpublished studies regarding ultrasound and childhood malignancies havebeen well conducted and are of adequate size[14-17]. Results from thesestudies are presented in Table 1. No association between in uteroultrasound exposure and childhood leukemia or solid tumours was found.

Neurological development and dyslexiaIn a cohort study, Stark and co-workers (1984) examined 425 ultrasoundexposed and 381 unexposed children when they were 7 to 12 years old[3].They studied a possible association between ultrasound exposure and 17outcomes that included hearing, vision, cognitive function, behaviour, andneurological examination. They found a significantly greater proportion ofexposed children to be dyslexic, but no association with other outcomes.The difference between groups was possibly a chance finding due tomultiple hypotheses testing, or the result of the general problem with biasand confounding factors in cohort studies. The consensus was, however,that further research was needed, and this is why a follow-up of twoNorwegian randomised controlled trials on routine ultrasound inpregnancy was performed in 1988-90.

The follow-up of the Norwegian trials was designed to look forpossible adverse effects of ultrasound on the fetal brain. The studytested six hypotheses of a possible association between ultrasound anddyslexia, school performance, non-right handedness, deficits inattention, motor control and perception, hearing ability, visual acuityand neurological development. Handedness was assessed because left-handedness is linked to dyslexia and deficits in attention, motorcontrol and perception. Data were collected from a questionnaire tothe parents and records from maternal and child health centers. In thesecond year of primary school, 2 011 children were evaluated by theirteachers with regards to reading aptitude, spelling, arithmetic andoverall performance. A subset of 603 children was tested with specifictests for dyslexia (tests measuring intelligence, reading and spelling).There were no associations between ultrasound and dyslexia, poorschool performance, delayed neurological development, poor vision orhearing[18-20]. In fact, there was a trend towards improvement of allthese outcomes in the ultrasound group, although this was notstatistically significant. The results suggested that it is unlikely thatroutine ultrasound examinations can “cause harm to the developingfetal brain”.

HandednessThere was, however, a statistically significant association betweentwo routine ultrasound examinations at 18 and 32 pregnancy weeksand subsequent non-right handedness among 8-9 year oldchildren[20]. The finding was of borderline statistical significance(odds ratio 1.32, 95% confidence interval 1.02 to 1.71), but thehypothesis was stated in advance and thus it was unlikely to resultfrom multiple hypotheses testing. The association was restricted toboys[21], and it was strengthened when an exploratory analysis onultrasound exposure was performed[20]. The authors emphasised “theneed to replicate the association between ultrasound and non-righthandedness before it is interpreted as more than a chance finding”[20].

In a similar follow-up study from Sweden, 3 265 children (71% of alleligible children from a randomised controlled trial) were followed upthrough a questionnaire sent to their mothers. There were nodifferences between ultrasound exposed and unexposed children withregards to hearing, vision, growth or behavioural disorders[22, 23].Furthermore, there was no statistically significant association betweenone routine ultrasound scanning at 15 weeks and non-right handednessamong all the children at age 8-9 years[24]. However, there was astatistical significant association between ultrasound exposure in uteroand non-right handedness in a separate analysis of the boys (odds ratio1.33, 95% confidence interval 1.02 to 1.74)[24].

The results from the Norwegian and Swedish follow-up studies havebeen analysed together in two review papers[25, 26]. A meta-analysisis also available in a Cochrane review[13]. The metaview fromCochrane is presented as figure 2. Figure 2 demonstrates that almostall the odds ratios (except for handedness) lie to the left of the verticalline.

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the odds ratios (except for handedness) lie to the left of the verticalline. This means that ultrasound screened children are doing betterthan the controls for all outcomes other than handedness. This is notstatistically significant, however, because the 95% confidenceintervals include the value of 1. However, it should be noted that bothspelling at school (odds ratio 0.73, 95% confidence interval 0.53 to1.00) and visual acuity (odds ratio 0.82, 95% confidence interval 0.66to 1.01) were improved among the screened children with“borderline” statistical significance[13]. The metaview from Cochranealso demonstrates that there are no statistically significant differencesbetween screened children and controls with regards to non-righthandedness, left-handedness or ambidexterity (figure 2).

There is a debate in epidemiological literature whether to allow forsubgroup analyses in randomised controlled trials. A gender-specificanalysis of handedness is a subgroup analysis. Subgroup analysesmust always be interpreted with caution, and exploratory analyses willalways be influenced by possible biases and confounding factors. TheCochrane review has chosen not to present any data from a gender-specific subgroup analysis of the trials[13].

In a meta-analysis with a less conservative statistical approach, agender-specific subgroup analysis was done[26]. When boys wereanalysed separately and according to the “intention-to-treat” principle,there was a statistically significant increase of non-right handednessamong the screened boys (odds ratio 1.26, 95% confidence interval1.03 to 1.54)[26]. In an exploratory analysis according to ultrasoundexposure before 19 or 22 weeks of pregnancy, there was a statisticallysignificant increased prevalence of non-right handedness among theexposed children (odds ratio 1.19, 95% confidence interval 1.02 to1.38). When the analysis of exposure was confined to boys only, thedifference between the groups increased (odds ratio 1.34, 95%confidence interval 1.10 to 1.65)[26]. All meta-analyses can give”numbers needed to treat” (NNT). This relationship between treatment(or exposure) and outcome is calculated from the observed riskdifferences. The risk difference (RD) between exposed and non-exposed boys was 0.05 (95% confidence interval 0.01 to 0.08). SinceNNT = 1/RD, it may be estimated that 20 male fetuses need to beexposed to give one non-right handed boy. This corresponds to fiveextra non-right handed boys among one hundred male births[26].

The University Hospital in Malmö was the first medical center inSweden to use ultrasound scans as part of standard antenatal care. In afurther study, males born in Malmö in 1973-78 were compared withmales born during the same time period at other Swedish medicalcenters that had not yet introduced ultrasound[27]. Handedness wasdetermined as part of eligibility testing for military service. Preferredhand was determined by handing a replica rifle to the enrolee, whowas then asked to take up alert position. Only enrolees who shot left-handed were registered as such. Those not registered were either righthanded or not tested. During the introduction phase of routinescreening with ultrasound (1973-75) there was no difference in left-handedness between ultrasound exposed and unexposed (odds ratio1.03, 95% confidence interval 0.91 to 1.17). When ultrasound wasoffered more widely (1976-78), the association with left-handednesswas higher among those exposed to ultrasound compared with thoseunexposed (odds ratio 1.32, 95% confidence interval 1.16 to 1.51).The estimated effect corresponds to three extra left-handers amongone hundred male births[27].

Since the study is a cohort study, there might be bias or confoundingfactors involved in explaining the reported association betweenultrasound and left-handedness. There is no doubt that the roughmethod of assigning ultrasound exposure has misclassified some ofthe people in the study. Misclassification of handedness is alsopossible. However, the authors argue that the misclassification biaswould be of non-differential nature. This means that misclassificationof exposure and outcome are unrelated (enrolees at different centresthroughout Sweden had equal chance of being misclassified as left-handed according to the replica rifle test). This implies that if theassociation between ultrasound and handedness is distorted, it wouldbe larger than what is reported, not smaller.

The authors have controlled for the influence of possible confoundingfactors. The statistical analyses are appropriate and support thereported association between ultrasound and left-handedness.However, there are indications of differences between the populationsof Malmö and the rest of Sweden. Such differences (e.g. race, socialconditions, and sinistrality in the family) can distort the results. This is

a general problem with all cohort studies. One can control for knownconfounding factors, but there is always the possibility that some otherunknown bias or confounding factor can invalidate the study. Thus, acohort design will always give weaker epidemiological evidence of anassociation between exposure and outcome than a randomisedcontrolled trial.

A final conclusion of a possible association between prenatalultrasound and left-handedness among males can not yet be drawn. Ifwe rely on the data presented in the Cochrane review[13], there is nostatistically significant association between prenatal ultrasound andleft-handedness (figure 2). The Cochrane review has decided not topresent any data from a gender-specific subgroup analysis of the trials.If we accept subgroup analyses from randomised controlled trials[26],we find a statistically significant association between prenatalultrasound and left-handedness among males. If we also accept theresults from cohort studies, such as the Swedish one[27], theconclusion must be that three epidemiological studies report a 30%increase in the likelihood of sinistrality among males, and so far noother epidemiological evidence contradicts this association.

The discussion on prenatal ultrasound and left-handedness is complexand is explored in greater detail elsewhere[28]. A statisticalassociation between ultrasound and left-handedness should not lead tothe conclusion that ultrasound causes harm to the developing brain.One of the experts in the field of laterality research has stated:”Laterality research is unfortunately prone to misapplying complexstatistics and producing wrong or uninterpretable findings”[29].Studies on adverse effects on the brain must be based on multipleoutcomes, not on a single parameter like handedness. TheScandinavian randomised controlled trials were based on multipleoutcomes, and the results were reassuring.

Speech developmentIn a case-control study[30], Campbell and co-workers compared 72children with delayed speech of unknown origin with 144 matchedcontrols. The study reported that the odds of suffering from delayedspeech were 2.8 (p = 0.001) times higher among children who wereexposed to ultrasound at least once during pregnancy. In this rathersmall study, the information on ultrasound exposure was not assessedblind, and there is the possibility of misclassification of exposure.Also, the study design of a case-control study makes it impossible torule out other biases, especially related to selection of subjects andmisclassification of information between cases and controls. Thus, theresults from the study should be viewed cautiously.

In the Norwegian randomised follow-up study, assessment of speechdevelopment was done through a parental questionnaire and also fromrecords from maternal and child health centers[31]. According tohealth center records, screened children were not referred to a speechtherapist as often as control children were (odds ratio 0.51, 95%confidence interval 0.31 to 0.85). However, the association betweenultrasound exposure in pregnancy and speech development was notamong the six prior hypotheses in the Norwegian study. Thus, thestatistically significant protective effect of ultrasound exposure mayhave been due to chance. On the other hand, unlike the Canadian case-control study[30], misclassification bias was not likely to beresponsible for this result.

The Swedish follow-up study has also reported on speechdevelopment[22]. In a questionnaire with 52 questions, parents wereasked four questions regarding the speech development of theirchildren. Delayed speech development was reported by 2.9% in thescreened group compared with 2.4% in the control group (odds ratio1.21, 95% confidence interval 0.79 to 1.88).

ConclusionsEpidemiological studies have indicated no association betweendiagnostic ultrasound exposure during pregnancy and childhoodmalignancies. Diagnostic ultrasound imaging does not seem toinfluence birth weight, whereas frequent Doppler ultrasound wasassociated with reduced birth weight in one study. This associationbetween Doppler ultrasound and low birth weight is probably achance finding. The possible associations between ultrasound anddyslexia, and ultrasound and delayed speech development, reported intwo studies, have not been confirmed in two later randomisedcontrolled trials. However, the two randomised controlled trials and arecent cohort study have been unable to rule out a possible association

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between ultrasound and left-handedness among males. Thus, there isstill a need for more research.

Based on scientific evidence of ultrasonically induced biologicaleffects to date, there is no reason to withhold scanning for any clinicalapplication, including the routine clinical scanning of every womanduring pregnancy. Competent personnel who are trained in safetymatters should continue their prudent use of ultrasound.

AcknowledgmentThe figure from the Cochrane Review is reproduced with the kindpermission of Update Software Limited. Cochrane Reviews areregularly updated as new information becomes available and inresponse to comments and criticisms. The reader should consult TheCochrane Library for the latest version of a Cochrane Review.Information on the Cochrane Library can be found at www.update-software.com.

Table 1. Case-control studies of ultrasound exposure during pregnancy and childhood malignancies.

Year of Cases Exposed Controls Exposed

Study Cancer type death/diagn. N % N % OR p-value

Leukemia 1972-81 665 6 665 6 1 nsWilson andWaterhouse1984 Solid

tumours 1972-81 1066 6 1066 6 0.98 ns

Leukemia 1980-83 149 23 298 22 1.12 nsCartwright et al.1984 Other

tumours 1980-83 406 27 812 29 0.86 ns

Leukemia 1986-91 166 36 166 38 0.9 nsShu et al. 1994 Other

tumours 1981-91 476 23 476 27 0.8 nsRESneoplasms 1982-84 212 25 212 25 1.03 nsSorahan

et al. 1995 Solidtumours 1982-84 308 28 308 29 0.94 ns

Figure 1. Classification of epidemiological studies

Figure 2. Metaview from the Cochrane Review of ultrasoundfor fetal assessment in early pregnancy. The Peto odds ratiosare displayed with 95% confidence intervals.

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References1. Bakketeig, L., et al., Randomised controlled trial of ultrasonographic

screening in pregnancy. Lancet, 1984. 2: p. 207-211.2. Eik-Nes, S., et al., Ultrasound screening in pregnancy: a randomised

controlled trial. Lancet, 1984. 2: p. 1347.3. Stark, C., et al., Short and long term risks after exposure to

diagnostic ultrasound in utero. Obstet Gynecol, 1984. 63: p. 194-200.4. Scheidt, P., F. Stanley, and D. Bryla, One-year follow-up of infants

exposed to ultrasound in utero. Am J Obstet Gynecol, 1978. 131: p.743-748.

5. Moore, R., E. Diamond, and R. Cavalieri, The relationship of birthweight and intrauterine diagnostic ultrasound exposure. ObstetGynecol, 1988. 71: p. 513-517.

6. Lyons, E., et al., In utreo exposure to diagnostic ultrasound: A 6-yearfollow-up. Radiology, 1988. 166: p. 687-690.

7. Waldenström, U., et al., Effects of routine one-stage ultrasoundscreening in pregnancy: a randomised controlled trial. Lancet, 1988.2: p. 585-588.

8. Saari-Kemppainen, A., et al., Ultrasound screening and perinatalmortality: controlled trial of systematic one-stage screening inpregnancy. Lancet, 1990. 336: p. 387-391.

9. Davies, J., S. Gallivan, and J. Spencer, Randomised control trial ofDoppler ultrasound screening of placental perfusion duringpregnancy. Lancet, 1992. 340: p. 1299-1303.

10. Ewigman, B., et al., Effect of prenatal ultrasound screening onperinatal outcome. N Engl J Med, 1993. 329: p. 821-827.

11. Geerts, L., E. Brand, and G. Theron, Routine ultrasoundexaminations in South Africa: cost and effect on perinatal outcome -a prospective randomised controlled trial. Br J Obstet Gynecol, 1996.103: p. 501-507.

12. Newnham, J., et al., Effects of frequent ultrasound during pregnancy:a randomised controlled trial. Lancet, 1993. 342: p. 887-891.

13. .Neilson, J., Ultrasound for fetal assessment in early pregnancy(Cochrane Review). 2001, The Cochrane Library: Oxford.

14. Wilson, L.K. and J. Waterhouse, Obstetric ultrasound and childhoodmalignancies. Lancet, 1984. 2: p. 997-999.

15. Sorahan, T., et al., Pregnancy ultrasound and childhood cancer: asecond report from the Oxford Survey of Childhood Cancers. Br JObstet Gynaecol, 1995. 102: p. 831-832.

16. Cartwright, R., et al., Ultrasound examination in pregnancy andchildhood cancer. Lancet, 1984. 2: p. 999-1000.

17. Shu, X., et al., Diagnostic x-ray and ultrasound exposure and risk ofchildhood cancer. Br J Cancer, 1994. 70: p. 531-536.

18. Salvesen, K., et al., Routine ultrasonography in utero and subsequentvision and hearing at primary school age. Ultrasound ObstetGynecol, 1992. 2: p. 243-247.

19. Salvesen, K., et al., Routine ultrasonography in utero and schoolperformance at age 8-9 years. Lancet, 1992. 339: p. 85-89.

20. Salvesen, K., et al., Routine ultrasonography in utero and subsequenthandedness and neurological development. Br Med J, 1993. 307: p.159-164.

21. Salvesen, K., et al., Routine ultrasound scanning in pregnancy -Authors' reply. Br Med J, 1993. 307: p. 1562.

22. Kieler, H., et al., Routine ultrasound screening in pregnancy andaspects of the children's subsequent neurologic development. ObstetGynecol, 1998. 91: p. 750-756.

23. Kieler, H., et al., Routine ultrasound screening in pregnancy and thechildren's subsequent growth, vision and hearing. Br J ObstetGynaecol, 1997. 104: p. 1267-1272.

24. Kieler, H., et al., Routine ultrasound screening in pregnancy and thechildren's subsequent handedness. Early Hum Dev, 1998. 50: p. 233-245.

25. Salvesen, K. and S. Eik-Nes, Ultrasound during pregnancy andbirthweight, childhood malignancies and neurological development.Ultrasound Med Biol, 1999. 25: p. 1025-1031.

26. Salvesen, K. and S. Eik-Nes, Ultrasound during pregnancy andsubsequent childhood non-right handedness: a meta-analysis.Ultrasound Obstet Gynecol, 1999. 13: p. 241-246.

27. Kieler, H., et al., Sinistrality - a side-effect of prenatal sonography: acomparative study of young men. Epidemiology, 2001. 12: p. 618-623.

28. Salvesen, K., Ultrasound and left-handedness: a sinister association?Editorial. Ultrasound Obstet Gynecol, 2002. 19.

29. McManus, I., On the one hand, on the other hand: statistical fallaciesin laterality research. Behav Brain Sci, 1987. 10: p. 282–283.

30. Campbell, J., R. Elford, and R. Brant, Case-control study of prenatalultrasonography exposure in children with delayed speech. Can MedAssoc J, 1993. 149: p. 1435-1440.

31. Salvesen, K., et al., Routine ultrasonography in utero and speechdevelopment. Ultrasound Obstet Gynecol, 1994. 4: p. 101-103.

CONTENTS OF EJUVOLUME 15 - ISSUE 3 2002

Combined carotid and transcranial color coded sonography inacute ischemic stroke.Wada et al.Bronchioloalveolar carcinoma: Sonographic pattern ofpneumonia.Gorg et al.Improved detection of liver metastases with contrast enhancedwideband harmonic imaging :comparison with CT findings.Esteban et alThe efficacy of liver biopsy under ultrasonographic guidance onan outpatient basis.Spezia et al.GPs skills to perform limited goal orientated abdominalultrasound examinations after one month of intensive training.Suramo et al.Grading of Pars Planitis by ultrasound biomicroscopy-echographic and clinical study.Greiner at al.Observer variation in the sonographic measurement of opticnerve sheath diameter in normal adults.Ballantyne et al.Performance testing of medical echo/Doppler equipment .Thijssen and Cuypers.

NEUROSONOLOGY SPECIAL ISSUE

Transcranial Doppler Assessment of Cerebral VasospasmRune AaslidMicroembolus Detection by Transcranial Doppler SonographyRalf DittrichClinical Impact of PFO Diagnostics with TCDG.P. AnzolaClinical Applications of a Non-invasive ICP Monitoring MethodBernhard SchmidtNAIS – Design of a Multicenter Study on Neurosonology in AcuteIschemic StrokeMichael GoertlerSonographic Imaging of the Brain ParenchymaStefanie BehnkeImpact of Contrast Agents in Cerebrovascular DiagnosticsGünter SeidelImpact of the Contrast Agents in Cerebrovascular Diagnostics:Brain Perfusion and Ultrasonic Imaging TechniquesJens EydingUltrasound Enhanced Thrombolysis for Stroke: ClinicalSignificanceAndrei AlexandrovClinical Impact of IMT measurementsTouboulAxial plane – the main domain of the transcranial duplexultrasonography?E BartelsCerebral autoregulation studies in clinical practiceDiehlUltrasound enhanced thrombolysisDaffertshoferTranscranial duplex sonography of the venous systemValdueza / Stolz

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REPORT FROM THE PUBLICATIONSCOMMITTEE

The Committee met during the Warsaw EUROSONCongress in July.

The main item on the agenda was the position of theEuropean Journal of Ultrasound. Unfortunatelymanuscript flow has remained below the level necessaryto ensure the viability of the Journal and the number ofsubscriptions remains insufficient to make the Journalfinancially viable.

The combination of these two factors has lead thepublishers, Elsevier, to decide to cease publication ofthe EJU at the end of 2002. In addition our Editor-in-Chief, Dr Peter Twining, has decided that he can nolonger continue to dedicate his time to a ratherunsuccessful journal.

There will be a special issue of the Journal later thisyear on Neurosonology. This has been prepared underthe editorship of Dr Eva Bartels and promises to beextremely good. We hope that there will be sufficientpapers to fill the remaining issues to complete 2002.

At the end of the year ownership of the journal will bepassed from Elsevier to EFSUMB in order to allowEFSUMB to consider relaunching the journal at sometime in the future. There are three possible forms inwhich the EJU could be relaunched; these are, as asimilar paper journal, as an electronic journal, orincorporated with an existing ultrasound journal. Eachof these is under active consideration. However,whichever route is chosen we will need an enthusiasticand dedicated Editor-in-Chief. Any volunteers?

There were major changes to the membership of thecommittee.

The new committee is:

Michel Claudon, Past President of EFSUMB,ex officio memberLucas Greiner the new Honorary Secretary of EFSUMB,ex officio memberJean-Michel de Bray, continuing memberDavid Pilling, continuing memberW Mann, new member

Dr David Pilling has agreed to take over editorship of theEFSUMB Newsletter, starting with the January 2003 issue.

It has not yet been possible to publish the collected tutorialarticles of ECMUS but the editing of these is almostcomplete and we hope to send them for publication beforethe end of the year.

Hylton B MeirePast Chairman Publication Committee

REPORT FROM THE NEWSLETTER EDITOR

This will be my final issue ofthe Newsletter. I have had theprivilege of compiling andediting the Newsletter for thepast nine years and I wouldlike to welcome Dr DavidPilling as the new editor. Hisfirst issue will be the January2003 issue.

It is my sincere hope that atleast some of you have found the contents of theNewsletter interesting and helpful. It is the prime meansby which the decisions and activities of the committeesof EFSUMB are notified to its members.

The publication and distribution of the Newsletter hasbecome the single most expensive item in the EFSUMBbudget. My only real regret about my time as editor isthat I have not managed to solicit more support fromindustry. However, we did receive great support fromboth ACUSON and ESAOTE during the early years andsubsequently BRACCO have been fantasticallygenerous in their support for the Newsletter. I wouldlike to thank all three of these companies most sincerelyfor their generosity, the Newsletter could not havesurvived without them.

As you will see elsewhere in the Newsletter EFSUMBhas established an Industrial Board to establish andimprove communication between industry andEFSUMB. The first meeting was held in Warsaw and itwas very reassuring to perceive the enthusiasm of theindustrial representatives present for various forms ofsupport for, and collaboration with, EFSUMB. I am surethat this new liaison will be very fruitful for bothindustry and EFSUMB and I hope that it may lead toincreasing and more diverse support from industry forthe Newsletter.

Finally I would like to thank Gianna Stanford, GeneralSecretary of EFSUMB, for her unerring support andassistance with the production of the Newsletter. Eversince her appointment she has progressively improvedand refined the ways in which the Newsletter isproduced and has repeatedly searched out new printersand alternative means of distribution in order to try tocontain the cost. Both EFSUMB and I owe her a greatdebt of gratitude.

I wish EFSUMB and all its members success in thefuture.

Hylton B MeirePast Editor EFSUMB Newsletter

20

IBUS BREAST ULTRASOUND SEMINAR - WARSAW 2002

A one-day "Breast Ultrasound Seminar" was held onJuly 4th, 2002 in Warsaw, Poland under the auspices ofthe 6th Scientific Congress of the Polish UltrasoundSociety and the 14th Congress of the EuropeanFederation of Societies for Ultrasound in Medicine andBiology - Euroson 2002. The programme wascomplimentary for all participants registered at theEuroson 2002 congress, and three hundred fifty sixphysicians from 31 countries participated.

The seminar was arranged by the International BreastUltrasound School (IBUS) as part of a series of teachingprogrammes designed to improve the quality of breastultrasound examinations. Dr Dominique Amy of Francewas the programme director for the Warsaw seminar,and Dr Kazimierz Szopinski the local co-ordinator. Acomprehensive set of lecture notes edited by Dr JackJellins, the Founding President of IBUS, was distributedto all registrants, and consisted of texts covering thelecture topics as well as other teaching materialssupplied by IBUS faculty members.

The seminar consisted of nine presentations covering awide range of subjects including a special emphasis onthe thorough understanding of breast anatomy andpathology, and defining the role of breast ultrasound inrecognizing benign changes and early breast cancers.

Topics included: high resolution ultrasonic imagingprinciples (Dr Jack Jellins, Australia); ultrasonicanatomy and examination techniques (Dr DominiqueAmy, France); ultrasonic differentiation of benign andmalignant lesions (Prof. B Joachim Hackelöer,Germany); mammographic – ultrasonic correlation (DrMichel Teboul, France); assessment of vascularity byultrasound (Prof. Ivan Drinkovic, Croatia); theultrasonic examination of cancers less than one cm

(Dr Dominique Amy, France); ultrasound guided biopsy(Prof. Enzo Durante, Italy); 3D and 4D ultrasound ofthe breast (Prof. Christian Weismann, Austria), and newultrasound techniques (Dr Kazimierz Szopinski,Poland).

The last session in the afternoon took the form ofdemonstrating scanning techniques on a series ofpatients to find breast pathology, and the use ofultrasound guidance to perform a biopsy on a breastphantom. Ultrasonic imaging equipment was providedby B-K Medical, Hitachi Medical Systems and SiemensMedical Systems, and these companies also sponsoredthe production of the lecture notes.

The majority of the participants were from Poland(245), followed by Lithuania (25), Russia (18), Croatia(6), Latvia (6), Switzerland (5), Ukraine (5), Finland(4), Romania (4), Spain (4), Germany (3), Austria (2),Byelorussia (2), Denmark (2), Estonia (2), France (2),Ireland (2), Italy (2), Norway (2), Sweden (2), Turkey(2), USA (2), Australia (1), Azerbaijan (1), Belgium (1),China (1), Greece (1), Israel (1), Portugal (1), SouthAfrica (1), and United Kingdom (1).

The International Breast Ultrasound School would liketo gratefully acknowledge Drs Malgorzata Szopinska,Katarzyna Wojtowicz, Javier Amoros, Camilo Fuster,and Mr Robert Cichecki who were instrumental with theorganization of the IBUS seminar, and in particularProfessor Wieslaw Jakubowski (President of the PolishUltrasound Society) for inviting IBUS to Warsaw sothat Euroson 2002 participants could benefit fromexperts in breast ultrasound.

Kazimierz SzopinskaLocal Organizing Committee.

INDUSTRIAL BOARD

The first meeting of this group was held during theWarsaw Congress in July.

If was agreed that the group would remain informaland that up to 2 members could attend from anyCompany with a bona fide interest in any aspect ofultrasound.

The industrial members present at the first meetingexpressed great enthusiasm for the concept of anIndustrial Board and were keen to co-operate withEFSUMB on a wide range of subjects. These included;standardisation, safety, education, Congresses, EurosonSchools and the establishment of guidelines for variousultrasound related procedures.

Although no firm decisions were made during this firstexploratory meeting many matters were discussed,including the establishment of an 'Industrial Member'category of EFSUMB and the formation of formallinks between EFSUMB and the EC administration inBrussels.

The Board will meet again during the CopenhagenCongress in April 2003. There was general agreementthat the Board was an excellent idea and should lead tobenefits for both EFSUMB and the individualcompanies.

21

LETTER FROM WFUMBHARALD LUTZ – CHAIRMAN COMMITTEE AFRICAN PARTNERSHIP

The purpose of my letter is to inform the members ofthe European Federation about the activities ofWFUMB concerning the project, “AfricanPartnership”.

This committee was created following initialdiscussions a few years before the board meeting inFlorence 2000. The idea is to support the developmentof ultrasound in Africa in cooperation with theMediterranean and African Society for Ultrasound(MASU) and World Health Organization (WHO).

WHO has formed a global steering group for educationand training in diagnostic imaging. Dr. HaraldØstensen, Med. Officer of WHO as Chairman.WFUMB, MASU and the Asian Federation(AFSUMB) are permanent members of this steeringgroup. The common vision of this steering group is tomake safe and reliable diagnostic imaging servicesaccessible to as many as possible. The idea is tosupport especially diagnostic imaging service in lessdeveloped regions of the world. One of these areas is,as you know, the Sub-saharian part of Africa.The present members of the African partnershipcooperation group of WFUMB are Søren Hancke fromDenmark, Hassen Gharbi from Tunisia and ElisabettaBuscarini from Italy, the present secretary of theMASU and me as chairman.

The group coordinates the activities of WFUMB inAfrica in cooperation with MASU. The purpose is topromote and facilitate collaboration on educationbetween societies, institutes and individuals in Africaand in well developed countries.

The idea is to establish so called, “twin partnerships”,according to a proposal of WHO.

The group will work out roles for these twin

partnerships, identify and support centers of excellencein Africa in cooperation with WHO, organize andsupport regional courses and meetings, care forteaching material and establish a system of certificationfor teachers and students.

As a first step, the group visited Kenya and Uganda inautumn last year. In Kenya, the group took part in ameeting in the WHO recognized center of excellence ineducation and training in diagnostic imaging in theKenyatta National Hospital, chaired by Dr. Wambugu.We held discussions there and at other Hospitals aboutthe situation in Kenya, especially the ultrasoundexamination facilities.

In Uganda, the members of the group participated inthe annual meeting of the Uganda Society for theAdvancement of Radiology and Imaging. Theexclusive theme of the meeting was medicalultrasound. I was sponsored by MASU. The membersof the group presented as teachers a number of lecturesat this occasion and had a very interesting discussionwith around 80 engaged participants. At this occasionthe situation in Uganda was discussed again with localauthorities, the chairman of the University andinterested doctors and medical officers.

The next event supported by the WFUMB group willbe an ultrasound course in Tanzania.

With this information I would like to invite everybodywho has special contacts in this area and is interested tocooperate with us to support or to participate in ourefforts for the development of ultrasound in Africa.Please contact myself or other members of the groupand give your proposals and comments for this project.

Prof Dr Med H Lutzemail:herald.th.lutz@t-online.de

22

DIARY DATES

August 4 - 6, 2002World Class Breast Imaging: You Can Provide It, Vancouver, BC,Canada. Contact: Timothy Blackwelder, Loma Linda University Schoolof Medicine, Loma Linda, CA 92350. Tel: 888-207-9105; Fax: 909-558-0330; E-mail: blackt@hscis.net;Website: http://www.worldclassrad.com

August 5 - 7, 2002Introduction to Carotid Duplex/Color Flow Imaging; August 8-9, Introductionto Peripheral Vascular Duplex/Color Flow Imaging. St. Pete Beach, FL.Contact: Gulfcoast Ultrasound Institute, Inc, 4615 Gulf Blvd, Suite 205, St.Pete Beach, FL 33706. Tel: 727-363-4500; Fax: 727-363-0811; E-mail:learn@gcus.com; Website: http://www.gcus.com.

August 7 - 10, 2002Vascular Imaging and Doppler Ultrasound, Philadelphia, PA. Contact:Ultrasound Institute, Thomas Jefferson University, 7th Floor-Main Building,132 South 10th Street, Philadelphia, PA 19107-5244 Tel: 215-955-8533 or888-390-5051; Fax: 215-923-9452; E-mail: JUREI@mail.tju.edu;Website: http://jeffline.tju.edu/ultrasound.

August 10 - 11, 2002Current Trends in Breast Ultrasound and August 11, AIUM AccreditationGetting Started Workshop, New York, NY. Contact: Brenda Kinney,AIUM, 14750 Sweitzer Lane, Suite 100, Laurel, MD 20707-5907. Tel:301-498-4100 or 800-638-5352; Fax: 301-498-4450; E-mail:conv_edu@aium.org; Website: http://www.aium.org

August 31 - September 4, 200212th Annual Musculoskeletal Ultrasound Society Conference, Brussels,Belgium. Contact: AIMS International Belgium, Park Hill,Mommaertslaan 18B, B-1831 Diegem, Belgium. Tel:+ 32 2 722 82 30;Fax: + 32 2 722 8240; E-mail: dflament@aimsbru.be;Website: http://www.musoc.com/index.htm

September 6 - 8, 2002Fetal and Women's Ob/Gyn Imaging Course 2002, Seattle, WA. Contact:David Nyberg, MD, (Sponsored by Fetal and Women's Center andSwedish Medical Center). Tel: 206-386-6300, ext. 40438; Fax: 206-386-6316; E-mail:nyberg@u.washington.edu; Website:http://www.fetalcenter.org.

September 11 - 14, 200215th Congress of the International Perinatal Doppler Society at Prague,Czech Republic. Contact: Congress Secretariat, Guarant Ltd /IPDS,Opletalova 22, 111 00 Praha 1, Czech Republic, Tel: +420-2-84 001 444,Fax: +420-2-84 001 448, E-mail: IPDS@guarant.cz,, website:www.guarant.cz/IPDS2002

September 19 - 22, 200232nd Annual Scientific Meeting of the Australasian Society forUltrasound in Medicine (ASUM). Queensland, Australia. Contact:ASUM, 2/181 High Street, Willoughby NSW 2068. Tel: 61 2 9958 7655;Fax: 61 2 9958 8002; E-mail: asum@asum.com.au;Website: http://www.asum.com.

September 20 - 22, 200231st t Annual Diagnostic Ultrasound in Gynecology and Obstetrics andAbdomen, Baltimore, MD. Contact: Johns Hopkins Medical Institutions,Office of Continuing Medical Education, Turner 20 / 720 Rutland Avenue,Baltimore, MD 21205; Tel: 410-955-5880; Fax: 410-955-0807;E-mail: cmenet@jhmi.edu; Website: http://www.med.jhu.edu/cme.

September 24 - 25, 2002Gynaecological Ultrasound Course, London, United Kingdom. Contact: RoyalCollege of Obstetricians and Gynaecologists, 27 Sussex Place, Regent's Park,London NW1 4RG. Tel: +44 (0)20 7772 6200; Fax: +44 (0)20 7723 0575;Website: http://www.rcog.org.uk.

September 27 – 29, 20023rd Annual Obstetric Ultrasound in the High Risk Patient, Las Vegas, NV.Contact: Institute for Advanced Medical Education, 14 Elm Place, Rye, NY10580. Tel: 914-921-5700; Fax: 914-921-6048; E-mail: info@iame.com;Website: http://www.iame.com.

October 3, 2002IBUS - International Breast Ultrasound Seminar A lecture programme inconjunction with the Gemeinsame Jahrestagung der ÖsterreichischenGesellschaft und der Schweizerischen Gesellschaft für Senologie, Bregenz,Austria. E-mail: info@ibus.org, website: www.ibus.org

October 4 - 6, 2002Advanced Sonography Symposium in Ob/Gyn, Boston, MA. Contact: HarvardMED-CME, PO Box 825, Boston, MA 02117-0825. Tel: 617-384-8600; Fax:617-384-8686; E-mail:hms-cme@hms.harvard.edu;Website: http://www.cme.hms.harvard.edu.

October 23, 2002IBUS - International Breast Ultrasound Seminar, A lecture and workshopprogramme in conjunction with the 26. Dreiländertreffen SGUM - DEGUM -ÖGUM,Basel, Switzerland.E-mail: info@ibus.org, website: www.ibus.org

October 25 - 27, 20022nd Annual Meeting and Postgraduate Course of the Society of Radiologistsin Ultrasound (SRU), San Francisco, CA. Contact: SRU, 44211 SlatestoneCourt, Leesburg, VA 20176-5109. Tel: 703-858-9210; Fax: 703-729-4839;E-mail: info@sru.org; Website: http://www.sru.org.

October 30, 2002IBUS - Breast Ultrasound Seminar, A lecture programme in conjunction withthe Lynn Sage, Breast Imaging Symposium, Chicago, USA.E-mail: info@ibus.org, Website: www.ibus.org

November 1-5, 200212th World Congress on Ultrasound in Obstetrics and Gynecology. NewYork,USA. Tel: +44 20 8725 2505, Fax: +44 20 8725 0212

December 1 – 6, 200288th Annual Meeting of the Radiological Society of North America, (RSNA)at Chicago, USA. Contact: Steven T Drew, Executive Director, 820 JorieBoulevard, Oak Brook, IL 60523-2251, USA.Tel: +1 630 571 2670,Fax: +1 630 571 7837

December 11 -13, 200234th BMUS Annual Scientific Meeting at the Manchester InternationalConference Centre. Contact:BMUS office, 36 Portland Place, LondonW1BLS. Tel:+44 (0)20 7636 3714, Fax: +44 (0)20 7323 7323,E-mail:secretariat@bmus.org

March 20 - 23, 2003Ob/Gyn Ultrasound and Radiology Conference, Paradise Island, Bahamas.Contact: Ulla Buchner-Howard, UBH International, 501 Fifth Avenue, Suite1701, New York, NY 10017. Tel: 646-227-1850; Fax: 646-227-1849;E-mail: ubuchner@ubhinternational.com.

March 26 - 29, 2003Ultrasound/Women's Imaging, Boston, MA. Contact: Danielle PokorskiKlette, Director of Continuing Medical Education, Brigham and Women's Hospital,Department of Radiology, PO Box 470617, Boston, MA 02447-0617. Tel: 617-525-3310; Fax: 617-525-3320; E-mail: dpokorski@partners.org;Website: http://www.radcme.harvard.edu

April 27 – 30, 2003EUROSON 2003, 15th Congress of the European Federation of Societiesfor Ultrasound in Medicine and Biology, First Joint ScandinavianMeeting, Copenhagen, Denmark. Contact: Congress Secretariat :ICS, PO Box 41, Strandvejen 171, DK-2900 Hellerup, Denmark.Tel: +45 3946 0500, Fax: +45 3946 0515, E-mail:euroson2003@ics.dk.Website:www.euroson2003.com

April 27, 2003IBUS - International Breast Ultrasound Seminar, A lecture and workshopprogramme in conjunction with EUROSON 2003, Copenhagen,Denmark. E-mail: info@ibus.org, website: www.ibus.org

June 1 - 4, 2003AIUM hosting World Federation for Ultrasound in Medicine and Biology(WFUMB), Montreal, Canada. Contact: The American Institute ofUltrasound in Medicine (AIUM), 14750 Sweitzer Lane, Suite 100,Laurel, MD 20707-5906. Tel: 301-498-4100 or 800-638-5352; Fax: 301-498-4450; E-mail: conv_edu@aium.org; Website: http://www.aium.org.

June 5 - 7, 2003IBUS - International Breast Imaging Update. A lecture and workshopprogramme in conjunction with the Radiological Society of Finland,Naantali Spa, Finland. E-mail: finland@ibus.org, website: www.ibus.org

September 4 - 7, 200333rd Annual Scientific Meeting of the Australasian Society forUltrasound in Medicine (ASUM). Perth, Western Australia. Contact:ASUM, 2/181 High Street, Willoughby NSW 2068. Tel: 61 2 9958 7655;Fax: 61 2 9958 8002; E-mail: asum@asum.com.au;Website: http://www.asum.com.

November 30 – December 5, 200389th Annual Meeting of the Radiological Society of North America(RSNA) at Chicago, USA. Contact: Steven T Drew, Executive Director,820 Jorie Boulevard, Oak Brook, IL 60523-2251, USA.Tel: +1 630 571 2670, Fax: +1 630 571 7837

June 6 - 9, 2004EUROSON 2004, 16th EFSUMB Congress, Zagreb, Croatia inconjunction with CSUMB. Contact EFSUMB Secretariat: CarpentersCourt, 4a Lewes Road, Bromley, Kent BR1 2RN, UK. Tel: +44 (0)20 84028973, Fax: +44 (0)20 8402 9344, E-mail:efsumb@compuserve.comWebsite:http://www.efsumb.org

June 26 - 29, 2005EUROSON 2005, 17th EFSUMB Congress: Geneva, Switzerland, inconjunction with the Dreiländertreffen at the Palexpo GenevaContact: Dr S Tercanli, Delegate SGUM, Universitäts-Frauenklinik/,Kantonsspital, CH 4031 BASEL SWITZERLAND, Tel: +61 325 90 46,Fax: +61 3259241, E-mail:stercanl@uhbs.ch

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Changing the Role of

Ultrasound

1.1) Name of the medicinal productSonoVue®, 8 microlitres / ml, powder and solvent fordispersion for injection

1.2) Qualitative and quantitative compositionSulphur hexafluoride microbubbles 8µl per mlOn reconstitution as directed, 1 ml of the resultingdispersion contains 8 µl sulphur hexafluoride in themicrobubbles, equivalent to 45 µg.For excipients, see 4.1.6.1

1.3) Pharmaceutical formPowder and solvent for dispersion for injection

1.4) Clinical particulars

1.4.1) Therapeutic indicationsThis medicinal product is for diagnostic use only.

SonoVue® is for use with ultrasound imaging to enhancethe echogenicity of the blood, which results in an improvedsignal to noise ratio.SonoVue® should only be used in patients where studywithout contrast enhancement is inconclusive.EchocardiographySonoVue® is a transpulmonary echocardiographic contrastagent for use in patients with suspected or establishedcardiovascular disease to provide opacification of cardiacchambers and enhance left ventricular endocardialborder delineation.Doppler of macrovasculatureSonoVue® increases the accuracy in detection or exclusionof abnormalities in cerebral arteries and extracranialcarotid or peripheral arteries by improving the Dopplersignal to noise ratio.SonoVue® increases the quality of the Doppler flow imageand the duration of clinically-useful signal enhancementin portal vein assessment.Doppler of microvasculatureSonoVue® improves display of the vascularity of liver andbreast lesions during Doppler sonography, leading tomore specific lesion characterisation.

1.4.2) Posology and method of administrationThis product should only be used by physiciansexperienced in diagnostic ultrasound imaging.The microbubble dispersion is prepared before use byinjecting through the septum 5 ml of sodium chloride0.9%w/v solution for injection to the contents of the vial.The vial is then shaken vigorously for a few seconds untilthe lyophilisate is completely dissolved. The desired volumeof the dispersion can be drawn into a syringe any timeup to six hours after reconstitution. Just before drawinginto the syringe, the vial should be agitated to re-suspendthe microbubbles. SonoVue® should be administeredimmediately after drawing into the syringe by injectioninto a peripheral vein. Every injection should be followedby a flush with 5 ml of sodium chloride 0.9%w/v solutionfor injection.The recommended doses of SonoVue® are:B-mode imaging of cardiac chambers, at rest or withstress: 2 ml.Vascular Doppler imaging: 2.4 ml.During a single examination, a second injection of therecommended dose can be made when deemednecessary by the physician.Elderly PatientsThe dosage recommendations also apply to elderlypatients.Paediatric PatientsThe safety and effectiveness of SonoVue® in patientsunder 18 years old has not been established and theproduct should not be used in these patients.

1.4.3) ContraindicationsSonoVue® should not be administered to patients withknown hypersensitivity to sulphur hexafluoride or to anyof the components of SonoVue®.SonoVue® is contraindicated for use in patients known tohave right-to-left shunts, severe pulmonary hypertension(Pulmonary artery pressure >90 mmHg), uncontrolledsystemic hypertension, and in patients with adult respiratorydistress syndrome.The safety and efficacy of SonoVue® have not beenestablished in pregnant and lactating women therefore,SonoVue® should not be administered during pregnancyand lactation (see Section 4.1.4.6)

1.4.4) Special warnings and special precautions for useECG and blood pressure monitoring should be performed

during SonoVue®-enhanced echocardiography with apharmacological stress (e.g. with dobutamine). ECGmonitoring should be performed in high-risk patients asclinically indicated.Caution is advised when SonoVue® is administered topatients with severe heart failure (NYHA class IV) or topatients with clinically significant pulmonary disease,including severe chronic obstructive pulmonary disease.Numbers of patients with the following conditions whowere exposed to SonoVue® in the clinical trials werelimited, and therefore, caution is advisable whenadministering the product to patients with: seriousarrhythmias, recent myocardial infarction, with ongoingand/or unstable angina, acute endocarditis, prosteticvalves, acute systemic inflammation and/or sepsis,hyperactive coagulation states and/or recentthromboembolism, and end-stage renal or hepaticdisease.SonoVue® is not suitable for use in ventilated patients,and those with unstable neurological diseases.

1.4.5) Interaction with other medicinal products and otherforms of interactionNo specific interaction studies have been performed.There was no apparent relationship with respect tooccurrence of adverse events in the clinical studies forpatients receiving various categories of the most commonconcomitant medications.

1.4.6) Pregnancy and lactationNo clinical data on exposed pregnancies are available.Animal studies do not indicate harmful effects with respectto pregnancy, embryonal/foetal development, parturitionor postnatal development (see section 4.1.5.3 Preclinicalsafety data). Caution should be exercised whenprescribing to pregnant women. It is not known if sulphurhexafluoride is excreted in human milk. Therefore, cautionshould be exercised when SonoVue® is administered tobreast-feeding women.

1.4.7) Effects on ability to drive and use machinesOn the basis of the pharmacokinetic andpharmacodynamic profiles, no or negligibile influence isexpected with the use of SonoVue® on the ability to driveor use machines.

1.4.8) Undesirable effectsThe undesirable effects reported with SonoVue® were, ingeneral, non-serious, transient and resolved spontaneouslywithout residual effects.The most commonly reported adverse reactions areheadache and altered sensation at the injection site,both occurring in approximately 2% of patients.The adverse reactions observed in more than 1400 adultpatients in clinical trials are:Common Reactions (>1%)Body as a whole:headache, altered sensation at the injection site,Digestive system: nauseaNervous System: flushing, paraesthesiaSpecial Senses: taste perversion.Less Common Reactions (<1%)Body as a whole:chest pain, asthenia, abdominal pain,back pain, non-specific painRespiratory system: respiratory disorder, pharyngitis, sinusitisSkin and appendages: pruritus, rashSpecial senses: abnormal visionNervous system: dry mouth, dizziness, personality disorder,insomnia, nervousnessMetabolic and nutritional: hyperglycaemia, peripheraloedemaHaemic and Lymphatic organ system: ecchymosisOne case of sensory-motor paresis was reported.There were isolated changes reported in ECGcomponents, blood pressure and in some laboratoryparameters measured, but these were not deemed tobe of clinical significance.

1.4.9) OverdoseSince there have been no cases of overdose reportedto date, neither signs nor symptoms of overdosage havebeen identified. In a Phase I study doses up to 56 ml ofSonoVue® were administered to normal volunteers withoutserious adverse events being reported. In the event ofoverdosage occurring, the patient should be observedand treated symptomatically.1.5) Pharmacological properties1.5.1) Pharmacodynamic propertiesPharmacotherapeutic group: Ultrasound contrast media ATC code VO8DA.

The addition of sodium chloride 0.9%w/v solution forinjection to the lyophilised powder followed by vigorousshaking results in the production of the microbubbles ofsulphur hexafluoride. The microbubbles have a meandiameter of about 2.5µm, with 90% having a diameterless than 6µm and 99% having a diameter less than 11µm.Each millilitre of SonoVue® contains 8µl of the microbubbles. The interface between the sulphur hexafluoride bubbleand the aqueous medium acts as a reflector of theultrasound beam thus enhancing blood echogenicityand increasing contrast between the blood and thesurrounding tissues.The intensity of the reflected signal is dependent onconcentration of the microbubbles and frequency ofthe ultrasound beam. At the proposed clinical doses,SonoVue® has been shown to provide marked increasein signal intensity of more than 2 minutes for B-modeimaging in echocardiography and of 3 to 8 minutes forDoppler imaging of the macrovasculature andmicrovasculature.Sulphur hexafluoride is an inert, innocuous gas, poorlysoluble in aqueous solutions. There are literature reportsof the use of the gas in the study of respiratory physiologyand in pneumatic retinopexy.

1.5.2) Pharmacokinetic propertiesThe total amount of sulphur hexafluoride administered ina clinical dose is extremely small, (in a 2 ml dose themicrobubbles contain 16 µl of gas). The sulphurhexafluoride dissolves in the blood and is subsequentlyexhaled.After a single intravenous injection of 0.03 or 0.3 ml ofSonoVue®/kg (approximately 1 and 10 times the maximumclinical dose) to human volunteers, the sulphurhexafluoride was cleared rapidly. The mean terminal half-life was 12 minutes (range 2 to 33 minutes). More than80% of the administered sulphur hexafluoride wasrecovered in exhaled air within 2 minutes after injectionand almost 100% after 15 minutes.In patients with diffuse interstitial pulmonary fibrosis, thepercent of dose recovered in expired air averaged 100%and the terminal half-life was similar to that measured inhealthy volunteers.

1.5.3) Preclinical safety dataPreclinical data reveal no special hazard for humansbased on conventional studies of safety pharmacology,genotoxicity and toxicity to reproduction. Caecal lesionsobserved in some repeat- dose studies with rats, but notin monkeys, are not relevant for humans under normalconditions of administration.

1.6) Pharmaceutical particulars1.6.1) List of excipientsPowder:Macrogol 4000DistearoylphosphatidylcholineDipalmitoylphosphatidylglycerol SodiumPalmitic acidSolvent: Sodium chloride 0.9% w/v solution for injection

1.6.2) IncompatibilitiesSonoVue® should not be admixed with any othermedicinal product except the solvent provided.

1.6.3) Shelf life2 yearsOnce reconstituted, chemical and physical stability hasbeen demonstrated for 6 hours. From a microbiologicalpoint of view, the product should be used immediately.If not used immediately, in use storage times andconditions prior to use are the responsibility of the user.

1.6.4) Special precautions for storageNo special precautions for storage.

1.6.5) Nature and contents of containerPresentation 01(with integral Bio-Set transfer system) -25mg of dry, lyophilised powder in an atmosphere of sulphurhexafluoride in a colourless Type I glass vial, withelastomeric closure and integral transfer system.Type I glass pre-filled syringe containing 5 ml sodiumchloride 0.9%w/v solution for injection.Presentation 02 (with separate MiniSpike transfer system):-25 mg of dry, lyophilised powder in an atmosphere ofsulphur hexafluoride in a colourlessType I glass vial, with elastomeric closure.Separate transfer system.Type I glass pre-filled syringe containing 5 ml sodiumchloride 0.9%w/v solution for injection.

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