HIGHLIGHTS OF THE OBSTETRIC ULTR

Since Ian Donald first introduced ultrasound into obstetric practice in the 1950’s, sonography has become an important diagnostic and investigative tool for clinicians. Improvements in electronic and microchip technology have enabled health care workers to evaluate fetal anatomy and organ function in greater detail which, in turn, results in more accurate diagnosis of fetal diseases and malformations. Concurrently, fetal therapeutic options are also increased as a result of improved understanding and visualization of the fetus. Advancements in ultrasound technology is occurring at an exponential rate, and hence, clinicians need to keep up to date with new developments as well as be familiar with current accepted practices. This three day intensive course was meant to familiarize health care providers, including specialist and trainee obstetricians and gynaecologists, and family practitioners, to three essential uses of obstetric ultrasound, namely: amniocentesis, first trimester screening, and fetal echocardiography with a small note on three and four-dimensional imaging. There were over 60 participants each day. The faculty comprised of four main senior obstetricians and gynaecologists well known in the field of feto-maternal medicine from Kuala Lumpur (Dr. Patrick Chia, Prof. S. Raman), Singapore (Dr. Douglas Ong), and London (Dr. Pranav Pandya). The workshop was held in one of the conference rooms at Saujana Hyatt Regency in Subang, which is surrounded by a golf course with lush green pastures and man-made lakes with a beautiful water fountain.

The amniocentesis workshop on the first day started off with theory behind amniocentesis and how to perform it by Dr. Pranav, followed by how to minimize complications by Prof. Raman. The take home messages from these lectures were:

1) Amniocentesis is used mainly for prenatal diagnosis of karyotypic, genetic, and infective pathologies, but has many other applications in obstetrics, eg. amnioreduction of polyhydramnios, and amnioinfusion of oligohydramnios in helping diagnose renal agenesis.

2) Amniocentesis is safe when done from 15 weeks onwards, but is associated with higher miscarriage rate and fetal anomalies (limb and oromandibular dyplasia) if done before 15 weeks.

5) Adequate training (>100 under supervision), maintenance of skill (>30 per year), and audit of complications and successes will help minimize complications and are accepted recommendations from the Royal College of Obstetricians and Gynaecologists (UK).

6) Couples should be counseled about the nature, risks, and implications of results before the procedure supplemented with reading material in form of a pamphlet.

7) A detailed fetal structural (anomaly) scan is done prior to the procedure to localize placenta, pocket of liquor, cord, and look for any fetal abnormalities.

9) The largest pocket of amniotic fluid is targeted. Approximately 1 ml of amniotic fluid is withdrawn per week of pregnancy (ie. 20mls at 20 weeks) via a 22 gauge spinal needle with or without local anesthesia.

10) After the procedure, the fetal heart is scanned and its normal beating shown to the parents for reassurance.

11) The procedure should be abandoned if an unsuccessful (dry) tap is encountered after 2 attempts, and the patient should be referred to a feto-maternal sub-specialist.

12) The patient is allowed to rest for about 30 – 60 minutes and discharged home when well.

13) Patients are given instructions as to what symptoms to look out for in case of a complication, what to do, who to call, and where to go when problems arise.

14) Choose a good cytogenetics laboratory to send your specimens to. For example, Prof. Raman sends his samples to Singapore General Hospital which can provide a preliminary karyotypic result using Flourescent In-Situ Hybridization (FISH) on quantitative fluorescence polymerase chain reaction (QF-PCR) within 24-48 hours. The formal karyotypic culture result can be obtained within 2-3 weeks.

15) Failed amniocentesis (non-culture) occurs very uncommonly about 0.2% of times.

16) Mosaicism (which means a mismatch between the true fetal karyotype and amniocytes obtained) is also very uncommon about <0.2%.

The afternoon session involved clinical hands-on using a pregnant uterus model. Three such models were brought over by Dr. Pranav each costing £500.00 (MYR$3000.00). The echo-texture of these models simulated a real gestational sac and its contents which allowed us to have good practice. The new ultrasound machines on demonstration were used and gave superb resolution.

Dr. Patrick Chia, Prof. Raman, and Dr. Pranav demonstrating amniocentesis on a model.

The second day was more intensive with six lectures interspersed by live demonstrations on pregnant patients. There was also a drug company sponsored talk on hormonal therapy for menopause. Speakers were Dr. D. Ong on the normal fetus in the first trimester and essentials of gestational age measurement, Dr. Pandya on multi-fetal pregnancies, early detection of structural anomalies, and screening for chromosomal defects in the first trimester, and Dr. P. Chia on ultrasound features in predicting pregnancy loss and the role of 3-D ultrasound in first trimester. Again, take home messages for each lecture are summarized below.

1) Studies have confirmed the usefulness of first trimester ultrasound in confirmation of pregnancy and its viability, detection of multiple gestations, accurate dating of pregnancy with reduction in erroneous preterm or post-term deliveries, assessment of normal chronological development, and assessment for the possibility of an ectopic pregnancy.

2) Fetal cardiac activity is the most important indicator of fetal viability. Other less robust markers are size and volume of the gestational sac, presence and size of yolk sac, and fetal crown-rump length (CRL). However, these markers are useful for dating.

3) Fetal heart activity is seen after 6 weeks on a transvaginal scan and should be present when CRL is > 1cm. Yolk sac should be seen in a gestational sac of > 2 cm diameter. However, yolk sacs can be absent in up of 1/3 of normal pregnancies.

4) The fetus has a steep growth gradient between 5-12 weeks of pregnancy. To estimate weeks of pregnancy with CRL, a useful formula is: Gestational age (weeks) = 6.5 (weeks) + CRL (in cm). For example CRL of 1 cm corresponds to 7.5 weeks.

5) CRL estimation of gestational age is very accurate with a +/- 3 day margin of error.

6) On a transvaginal ultrasound scan (TVS), the gestational sac is visible at 4 weeks, the yolk sac at 5 weeks, fetal heart pulsations at 6 weeks, embryonic movements at 7 weeks, head and limb buds at 8 weeks, physiologic omphalocoele at 8-10 weeks, and umbilical cord insertion at 9 weeks.

1) About 1.2 % of pregnancies are dizygotic twins, and 0.4% are monozygotic. However, multiple pregnancies are on the rise in conjunction with increasing use of assisted conception (eg.In-vitro-fertilization). The perinatal morbidity and mortality of twins is 5 times that of a singleton pregnancy and this risk increases with higher order multiple pregnancies. Cerebral palsy risk in twins is increased by 8 times compared with singletons.

2) Determination of chorionicity (or number of placentas) is essential in the management of multiple pregnancies. Monochorionic twin pregnancies are associated with increased risk of miscarriage, fetal malformations, chromosomal anomalies, and obstetric complications. These can all be assessed by ultrasound.

3) Chorionicity is best detected by ultrasound between 10-14 weeks and the most useful marker is the Lambda or “twin peak” sign for dichorionic twins and the “T” sign for monochorionic ones.

4) In addition to the usual benefits of first trimester screening mentioned in the first lecture, ultrasound can be used for screening and invasive prenatal diagnostic testing for chromosomal disorders eg. Trisomy 21, 13, and 18. This allows counseling of couples on the risks of genetic and structural defects and possible management options, including termination of pregnancy, selective fetocide (not available in Malaysia), or conservative management eg. no fetal heart rate monitoring in labour and no active neonatal resuscitation for Patau’s.

5) The best antenatal screening method for chromosomal anomalies in multiple pregnancy is measurement of the nuchal translucency between 10 and 14 weeks.

6) Amniocentesis is offered to women at high risk of carrying a fetus with chromosomal aberration or when there is an abnormal nuchal translucency result. The overall risk of amniocentesis is similar to singleton pregnancies about 1%.

7) Any prenatal testing should be done at a tertiary center with appropriate expertise. Hence, multiple gestations should be referred early when detected.

1) Per vaginal bleeding in early pregnancy occurs in over 30 % of pregnancies and accounts for over 70% of emergency gynaecology workload. This results in tremendous maternal and paternal anxiety. Ultrasound features allow the clinician to predict fetal viability and prognosis enabling accurate counseling.

2) The best predictor is fetal cardiac activity: fetal bradycardia < 90 beats per minute (bpm) is associated with poor outcome. Similarly, the absence of fetal heart activity when the fetal pole is > 5mm by TVS or > 9 mm by trans-abdominal scan (TAS) is a predictor of poor outcome.

3) The presence of normal cardiac activity is associated with a good prognosis in most cases but does not guarantee this.

4) If an embryo (or “fetal pole”) is not visible measurement of mean gestational sac diameter (MSD) and noting its shape can help predict prognosis. A large gestational sac without a yolk sac (MSD> 1cm by TVS or MSD > 2cm by TAS) which is an anembryonic pregnancy (“blighted ovum”), irregular or collapsed sac shape, or presence of an amnion without an embryo are all indicators of a poor outcome.

5) A large yolk sac (> 10 cm) and sub-chorionic haematoma are also associated with increased risk of miscarriage.

6) Where there is a fetal pole, if the difference between MSD and CRL is < 5mm is associated with a 94% miscarriage rate.

1) First trimester ultrasound allows clinicians to confirm fetal viability, assess gestational age, detect multiple pregnancy, diagnose early pregnancy failure, screen for trisomies, and diagnose major defects.

2) The best time for screening is between 11 to 14 gestational weeks when the fetus is well developed because before this, during the embryonic stage, rapid structural development makes it difficult to detect any structural abnormality; also the majority of anomalous fetuses would have naturally aborted by this time, hence reducing unnecessary workload, eg. at 5 weeks the chance of miscarriage is 5% vs. 11 weeks when the risk drops to 2%.

3) Either TVS or TAS can be used, but each has its pros and cons. For such early scanning, TVS offers better resolution and visualization and is the preferred method, although it may not be readily accepted by the patient.

4) The number of organ systems where gross anomalies can be detected is limited.

5) CNS abnormalities: such as spina bifida including acrania, exencephaly, anencephaly (all defects in cranial bone ossification in increasing severity from 11 weeks onwards), lemon sign (scalloped frontal skull), banana sign (caudal displacement of cerebellum), encephalocoele (bony defect in skull with protrusion of brain), ventriculomegaly, and holoprosencephaly (single ventricle with incomplete cleavage of forebrain associated with midline facial abnormalities).

6) First trimester screening for spinal bifida should be limited to women at high risk of having a fetus with this condition, because of low detection rates (17%) when used in screening the general population.

7) Cardiac anomalies: the normal four-chamber view and outflow tracts can be seen after 13 weeks, but a follow up scan at 18 to 20 weeks is needed to confirm abnormalities. Eighty-one percent of fetuses with a congenital heart malformation have an increased nuchal translucency (NT).

8) NT measurements between 11-14 weeks acts not only as a marker for trisomy screening, but also for fetal congenital cardiac defects, and a careful search for these is made via fetal echocardiography at 18-20 weeks.

9) Thoracic lesions such as congenital diaphragmatic hernia and cystic adenomatoid malformation can be detected.

10) Abdominal wall defects: physiologic herniation occurs during 8.5 to 10.5 weeks (CRL<38mm) and never after 11+5 weeks (CRL>45 mm). Both exomphalos and gastroschisis can be detected.

11) Reno-urologic system: kidneys are seen from 9 weeks, but apart from gross anomalies such as polycystic kidneys and megacystis, lesions such as renal agenesis is hard to detect.

12) Facial profile: Cyclops, proboscis, and cleft lip (all associated with trisomy 13) may be seen.

13) Limbs: are seen from 9 weeks and digits of hands and feet are visible from 11 weeks.

14) The advantages of first trimester scan include early reassurance, and if a gross anomaly is found, an early and less traumatic therapeutic abortion can be offered.

15) A routine 18 to 20 week scan is still needed because some anomalies, such as duodenal atresia, present after the first trimester.

Normal (left) and abnormal (right) Nuchal translucency (see“+”) taken on a sagittal view.

1) The role of screening is to provide information to couples. It does not equate to termination of pregnancy. A risk estimate (eg. 1/300 chance of trisomy, etc.) is obtained from screening, and based on this risk, couples can be offered a diagnostic test to confirm.

2) A diagnostic test such as amniocentesis or chorionic villus sampling (CVS) cannot be offered to every pregnant woman because of procedural related risk of miscarriage (around 1% for both).

3) Screening should ideally be offered to all pregnant women on an “opt in” basis; that is, it should be done after adequate informed consent is obtained.

4) Ideally, screening tests should be cheap, safe, easy to implement, and available in early pregnancy, and have high detection and low false positive rates. However, none of the currently available tests satisfy all these criteria.

6) Screening modalities all require accurate dating by ultrasound and includes (for a 5% false positive rate):

c) First trimester maternal serum biochemistry (double, triple, or quadruple tests (AFP, BHCG, uE3, pregnancy associated plasma protein-A [PAPP-A]) with 60-70% detection rate when used with age),

d) Combined first trimester screening(age + NT + free BHCG + PAPP-A giving 90% detection rates),

e) Second trimester serum biochemistry (AFP, BHCG, uE3, Inhibin-A—gives 60-70% detection when used with age),

f) Integrated screening which combines first trimester combined screening with second trimester triple or quadruple serum biochemistry (age + NT + PAPP-A + 16 to 20 week AFP + BHCG + uE3 + Inhibin-A—gives a 94% detection rate in one series), and a

h) 20 week anomaly scan to look for “soft” markers and structural defects associated with aneuploidy.

7) The combined first trimester screening using age, NT, and serum biochemistry is preferred to the integrated screening which combines first with second trimester biochemistry along with age and NT measurements. The former offers a single visit and early results whereas the latter requires several visits and delayed results which may lead to maternal anxiety.

8) Soft markers on their own may or may not represent aneuploidy, but the presence of one soft marker should prompt a detailed search for others. These also need to be interpreted in the context of the woman’s prior risk. Karyotyping should be offered when > 2 soft markers are found.

9) Maternal age combined with NT measurements at 11-14 weeks is the best method of screening for aneuploidy for multiple gestations.

10) The screening method of choice is combined first trimester or integrated screening and 20 week scan.

13) Ultrasound assessment of nasal bone hypoplasia or Doppler studies of Ductus Venosus for chromosomal anomaly screening require further research evaluation.

1) Yet to be accepted widely by obstetricians and gynaecologists, the 3D ultrasound has been reported in small case series to be better than 2D in certain aspects: scanning time is reduced which may limit time of exposure to the fetus, data can be stored and analyzed in x, y, and z planes (so called multi-planar or orthogonal views) at a later time, and allows better assessment and visualization of fetal facial and some structural anomalies in the first trimester.

2) The main application for now is the establishment of early bonding with the fetus. However, further research will be required to determine its role in obstetrics.

Live demonstrations of nuchal translucency measurements, first trimester fetal anomaly screening, and 3D ultrasound were carried out with 3 pregnant women in the late first and early second trimesters.

On the last day of this intensive three day course, there were four lectures and one round table discussion interspersed by live demonstrations of fetal echocardiography. There was also a drug talk on the benefits of the ultra-low dose oral contraceptive pill. Lectures included: an introduction to ultrasound of the fetal heart and use of colour imaging and Doppler in the assessment of the fetal heart by Dr. Pranav, the four chamber view and anomalies by Dr. D. Ong, and the outflow tracts and anomalies by Prof. Raman.

A round table discussion on two cases of congenital cardiac anomaly included three additional consultants: Dr. TP Baskaran (feto-maternal medicine expert from HKL), Dr. Haifa Abdul Latif (Paediatric Cardiologist from IJN), and Dr. Hamdan Leman (Paediatric cardiothoracic surgeon from HKL). The lectures and the round table discussion are summarized below.

1) Congenital cardiac disease is the most common congenital abnormality with a prevalence of 4/1000 live births and responsible for around 8% of fetal, 20% of neonatal, and 50% of infant deaths.

2) Maternal risk factors include: diabetes mellitus, exposure to valproic acid or rubella in first trimester, positive family history (if father affected, 2% risk; if mother affected 10% risk; if 1 affected sibling, 2% recurrence, rising to 10% if 2 siblings were affected), auto-antibodies—anti-Ro and/ or anti-La, and genetic disorders( eg. Noonan’s, Marfan, DiGeorge) all of which increase the risk of fetal cardiac anomaly. Fetal risk factors include: suspicious cardiac findings on scan, fetal hydrops, extracardiac anomalies, and arrhythmias. Only 5% of fetuses with congenital cardiac disease have risk factors.

3) Around 95% of cases of congenital heart disease are found in the normal low-risk population; hence, screening is essential. This is done using standard four chamber and outflow tract views done at a routine 20 week scan.

4) It is important to understand the physiology of fetal circulation in order to appreciate scan findings and detect deviations from the norm. Basically it is a parallel arrangement of ventricular pumps, with mixing of venous return, high impedance and low flow in the pulmonary circulation, and presence of shunts including foramen ovale, ductus arteriosus, and ductus venosus.

5) A high nuchal translucency > 99^th centile is associated with an increased risk of cardiac malformation. This risk increases with increasing NT measurements eg. 2.5% if NT 2.5-3.4 mm, and 7% if NT > 3.5 mm.

6) The presence of a congenital cardiac lesion should prompt a search for other extracardiac defects (eg. exomphalos) and karyotyping should be offered because as much as a third of these fetuses have aneuploidy.

7) Apart from structural anomalies, disturbances in cardiac rhythm in the form of arrhythmias may lead to fetal cardiac failure, hydrops, and demise. This is best assessed by M-mode (spectral) Doppler ultrasound.

8) Detection rates by general obstetric practitioners using standard four chamber and outflow tract views with the 20 week scan is about 40 to 60% whereas with scanning done by expert cardiac sonographers the detection rate may increase to 80-100%. Hence, fetuses suspected at high risk of having a cardiac anomaly should be referred to a specialist center with expertise in fetal echocardiography.

9) The advantages of prenatal diagnosis of congenital heart disease is that early detection can allow counseling for further management options and referral to tertiary centers with paediatric cardiology services. Small case reports have shown an improved overall neonatal survival as a result of prenatal discovery of subtle and repairable anomalies as well as more severe ones such as transposition of the great arteries.

10) An autopsy should be offered to fetuses or neonates who succumb to suspected cardiac abnormalities.

11) In conclusion: at 11-14 weeks, situs, NT, fetal heart rate, and 4-chamber view should be checked and referral made if an abnormality is detected; otherwise, follow this up with the usual 20 week scan.

1) The 4 chamber view allows assessment of atrial and ventricular size (cardiomegaly) and function (arrhythmias and impaired contractility). It also allows evaluation of the cardiac valves and intracardiac septae.

2) There are 2 ultrasonic views when assessing the 4 chambers: apical and orthogonal (perpendicular to the long axis of the heart).

4) Step 1: Note situs: ensure that the heart is in and pointing to the left side of chest; next note cardiac size which should be 1/3 that of the thorax; then assess rate and rhythm remembering that normal fetal heart rate is between 120 and 160 bpm; finally use M-mode to assess rhythm to look for atrio-ventricular (AV) concordance (ie. is there 1 systole followed by 1 diastole?).

5) Step 2: Note the 4 chambers—at the correct plane a line drawn anteroposteriorly from the sternum in front to the spine at back will traverse through the right ventricle in front and the left atrium at the back; are the 2 atria and 2 ventricles of equal size?—the right ventricle is rougher at the apex due to the moderator band, whereas the left ventricle has a smooth internal surface; the foramen ovale valve flaps into the left atrium; next assess the septae or interventricular septum—use color Doppler for this; Next note the valves: the mitral and tricuspid valves together with the interventricular septum make up an “off-set” cross with the triscupid valve situated closer to the apex than the mitral; also the valves should flap into their respective ventricles; next note the 3 vessel or outflow tract view: done by moving the ultrasound probe cranially from the 4 chamber view. Note that from top downwards on the screen: a large caliber pulmonary artery is followed by a medium caliber aortic arch, and finally by a small caliber superior vena cava. Occasionally, the trachea can be seen situated beside the aortic arch.

6) Next note the right ventricular (RVOT) and left ventricular (LVOT) outflow tracts individually; the RVOT is best viewed via the 4 chamber and short basal axis view which is a position slightly cephalad from the 4 chamber view but not as cephalad as the 3 vessel view; the LVOT is best viewed via the 4 chamber and long axis views which is a sagittal view of the aortic arch and descending aorta.

7) By following this routine, the majority of cardiac anomalies may be detected: septal defects (eg. ASD, VSD, AVSD), ventricular anomalies (eg. hypoplastic left or right heart, cardiomegaly), valvular lesions (eg. mitral, tricuspid, aortic, or pulmonary atresia or stenosis, tetralogy of Fallot), great vessels aberrations (eg. transpostition of the great arteries, overriding aorta or pulmonary artery), cardiac tumours, and arrhythmias (eg. congenital heart block, supraventricular tachyarrhythmias).

Ultrasound views of left ventricular (left) and right ventricular (right) outflow tract.

Use of color and spectral Doppler imaging in the assessment of the fetal heart:

1) Color Doppler and pulsed (or power) Doppler are used to assess direction of blood flow in a vessel, or across valves and septal defects. Color is used for general assessment while power is used for local assessment of flow in a vessel or across a valve. Spectral Doppler assesses the velocity flow waveforms of blood traversing such structures or defects. Both modalities compliment each other and greatly improve diagnostic accuracy of standard 4 chamber and outflow tract views described above.

2) Examples of abnormalities assessed by these techniques include ventricular and atria septal defects, valvular regurgitation with myocardial dysfunction, hypoplastic ventricle, and outlet diseases.

Spectral (color) Doppler scan of blood flow across normal mitral and tricuspid valves during diastole (left). Picture on the right is hypoplastic right heart syndrome with minimal right ventricular filling and compensatory overfilling of left ventricle.

1) Case 1: was a case of hydrops fetalis with cardiomegaly and pericardial effusion detected by ultrasound at 30 weeks. M-mode (spectral) Fetal echocardiogram revealed a heart rate of > 180 bpm which is supraventricular tachycardia (SVT). SVT is an uncommon condition potentially lethal, but amenable to digoxin treatment with an overall good outcome. The principles of management is to give corticosteroids to enhance fetal lung maturity and maternal digoxin (0.25mg/d initially) to control the arrhythmia after ensuring normal potassium levels. Most respond to this with spontaneous resolution of hydrops, but if not, second-line agents such as flecainide or amiodarone can be given to the pregnant woman. Third-line treatment in refractory cases is difficult but intra-umbilical arterial administration of adenosine via cordocentesis may be tried. It is best to avoid preterm delivery in a hydropic fetus. Postnatally, most SVT’s would resolve spontaneously, and referral to a paediatric cardiologist is needed for the few who do not.

2) Case 2: was a case of a Down syndrome fetus with an atrio-ventricular septal defect and hypoplastic left heart syndrome (whenever an AVSD is seen, there is a 30% risk of Down syndrome). AVSD is easily treatable by postnatal surgery when the baby is about 5-8Kg and is associated with a good prognosis in fetuses with normal karyotype. This is not the case when AVSD is associated with Down syndrome. Hypoplastic left heart syndrome is also associated with a poor prognosis. Hence the take home message here is that fetuses with a congenital cardiac anomaly should be subjected to karyotyping.

This live demonstrations involved 4 patients in the second trimester between 16 to 20 weeks who volunteered to be scanned for the course. Standard two dimensional echocardiography using 4-chamber and outlet views, color, pulsed, and spectral Doppler scans were demonstrated.

Dr. Pranav demonstrating fetal echo on a live patient for workshop participants.

The ultrasound course was both informative and entertaining. Most of the information listed above are contained in the core textbook which was provided by the workshop and is listed in the main reference. (Those wishing to purchase a copy of this book can email a request to: muse_uss@yahoo.com).

Chia P, Tan CK, Raman S. In: Perspectives in fetal medicine: amniocentesis, first trimester scan, fetal echocardiography. Chia P, Tan CK, Raman S., eds. Medical Ultrasound Educators course manual. Kuala Lumpur: Discern Publishing House. 2002.

[a] The workshop was held on July 18-20^th, 2003, in Saujana Hyatt, Subang, Selangor, Malaysia. It was organized by Medical Ultrasound Educators (MUSE) in collaboration with the Department of Obstetrics and Gynaecology, University College Hospital, London, UK.

[b] Dept. of Obstetrics and Gynaecology, Kulliyyah of Medicine, IIUM, Kuantan campus.

Sponsored by Faculty of Medicine, IIUM, Kuantan, Pahang DM, Malaysia.