CHAPTER 1 • Guidelines to Fetal Imaging in the First Trimester. First Trimester Ultr

 CHAPTER 1 • Guidelines to Fetal Imaging in the First Trimester

INTRODUCTION

In the late 1980s and early 1990s, ultrasound evaluation of the fetus at less than 16

weeks of gestation was made possible by the advent of high-resolution transvaginal

transducers.1–7 With the introduction of transvaginal ultrasound, several reports

evaluated the feasibility of this approach in the first trimester and demonstrated the

ability to assess normal and abnormal anatomy of the fetal brain, heart, kidneys, and

other organs.1–7 The observation of the relationship between the presence of increased

fluid in the fetal neck region in the first trimester and chromosomal abnormalities

resulted in the establishment of nuchal translucency (NT) as an ultrasound screening tool

for aneuploidy.8–10 Largely through the efforts of Dr. Nicolaides and his coworkers, the

NT measurement was standardized and a first trimester screening strategy program was

established.10–13 Consistency and reliability of NT was ensured through standardization

of measurement and with the establishment of quality assurance programs.14,15 Over the

past two decades, the first trimester NT ultrasound examination has evolved beyond

aneuploidy screening and now includes an evaluation of fetal anatomy in early gestation.

Recently published guidelines reflect this development.16,17 Familiarization with

existing standardization of measurements and with national/international guidelines is an

important step in the performance of the first trimester ultrasound examination. Given

that knowledge in this field is evolving at a rapid pace, we recommend that ultrasound

practitioners stay abreast of the literature on this subject. In this chapter, we present

information on standardization of ultrasound measurements in the first trimester and

report on existing guidelines. It is important to note that with new evidence, guidelines

change over time and the readers are encouraged to refer to the most current version as

reference.

DEFINITION OF TERMS

It is important to understand the various terms that are used in standardization ofultrasound practice. Guidelines, protocols, standards, and policies refer to the

ultrasound examination itself (the NT screening or the first trimester anatomy survey).

Certifications, credentialing, and qualifications refer to the personnel performing the

ultrasound examinations including physicians, sonographers, and allied health

personnel. Accreditation, on the other hand, refers to the ultrasound laboratory/unit

where the examination is performed and thus requires evaluation of the qualifications of

the personnel performing the ultrasound examination, the equipment that is being used

for the ultrasound examination, compliance with existing examination guidelines, and

quality assurance.

The last 20 years have shown that standardizing the approach to NT, nasal bone,

tricuspid regurgitation, and ductus venosus in the first trimester has increased the

reliability and reproducibility of these measurements.13 Recently published guidelines

on first trimester ultrasound incorporate the NT and emphasize the role that the first

trimester ultrasound plays in the assessment of fetal anatomy.16,17 In general, guidelines

are consensus based and reflect on the scientific evidence at the time of guideline

development. Guidelines reduce inappropriate variations in practice and provide a

more rational basis for study referral. Guidelines also, when appropriately developed,

provide a focus for quality control and a need for continuing medical education for the

personnel performing the ultrasound examination. Guidelines may also identify

shortcomings of scientific studies and suggest appropriate research topics on the

subject.

STANDARDIZATION OF MEASUREMENTS

Nuchal Translucency

NT is the sonographic appearance of a collection of fluid under the skin behind the fetal

neck and back in the first trimester of pregnancy.13,14 Appropriate training of

sonographers and physicians, and compliance with established standard ultrasound

techniques, is essential to ensure uniformity of NT measurements among various

operators.13 NT image criteria have been developed for adequate measurements (Fig.

1.1).14,18 Semi-automated methods of measuring NT thickness have also been developed

by several ultrasound manufacturers in order to reduce operator-dependent bias in NT

measurements (Fig. 1.2).19 Table 1.1 summarizes the essential criteria for an adequate

NT measurement. The role of NT in detecting fetal aneuploidies is discussed in Chapter

6.

Nasal Bones

The nasal bones are hypoplastic or not ossified in the majority of fetuses with trisomy

21 and other aneuploidies in early gestation (Fig. 1.3).13 Typically, one of the two nasal

bones is imaged in a midsagittal plane of the fetus in the first trimester. It is important to

note that the ultrasound assessment of the nasal bone is technically difficult and requiressubstantial expertise for optimal performance.20 The correct assessment of the nasal

bone was shown to improve the performance of combined first trimester screening for

Down syndrome.13 In the normal fetus between the 11th and early 12th week of

gestation, the nasal bone may appear poorly ossified or absent.14 In such cases, it is

recommended to repeat the measurement one week later.14 Table 1.2 summarizes the

essential criteria for an adequate nasal bone assessment in the first trimester.

Ductus Venosus

The ductus venosus is an important vessel in the fetus as it directs highly oxygenated

blood from the umbilical vein, through the foramen ovale and into the systemic arterial

circulation. Doppler waveforms of the ductus venosus primarily reflect right atrial

preload. Abnormalities in the Doppler waveforms of the ductus venosus in the first

trimester have been reported in association with fetal aneuploidies, cardiac defects, and

other adverse pregnancy outcomes.13 Ductus venosus waveforms can be assessed

qualitatively by observing the A-wave component of the Doppler spectrum, which

reflects the atrial kick portion of diastole. Normal ductus venosus Doppler waveforms

show a positive A-wave (Fig. 1.4), whereas the presence of an absent or reversed Awave defines abnormal ductus venosus waveforms. An alternative approach relies on

the quantification of the ductus venosus waveforms by using indices such as the

pulsatility index for veins as a continuous variable.14 We do not recommend routine

assessment of ductus venosus flow in all pregnancies, but rather in pregnancies at

increased risk for congenital heart disease or in pregnancies with an intermediate risk

for aneuploidy.14 Table 1.3 summarizes essential criteria for the adequate assessment of

ductus venosus Doppler waveforms.Figure 1.1: Midsagittal view of a fetus at 13 weeks of gestation showing the

nuchal translucency (NT) thickness measurement according to the

recommended standards as listed in Tables 1.1 and 1.7. The schematic

diagram in the figure shows the correct (C) and incorrect (A, B, D) placement

of the calipers for NT measurements. In this example the NT measurement is

2.2 mm.Figure 1.2: Midsagittal view of a fetus at 12 weeks of gestation showing the

semiautomatic measurement of the nuchal translucency (NT) thickness. In the

semiautomatic approach, the examiner places a box around the region of

interest (dash box) and the software recognizes the largest NT size and places

the calipers accordingly. This approach decreases the subjectivity of the

measurement and increases its accuracy. In this example the NT measurement

is 2.1 mm.

Table 1.1 • Criteria for the Standardized Measurement of Nuchal

Translucency (NT) According to the Fetal Medicine Foundation-United

Kingdom14

Gestational age should be between 11 and 13 +6 weeks.

The fetal crown-rump length should be between 45 and 84 mm.The magnification of the image should be such that the fetal head and

thorax occupy the whole screen.

A midsagittal view of the face should be obtained. This is defined by the

presence of the echogenic tip of the nose and rectangular shape of the

palate anteriorly, the translucent diencephalon in the center, and the nuchal

membrane posteriorly.

The fetus should be in a neutral position, with the head in line with the

spine.

Care must be taken to distinguish between fetal skin and amnion.

The widest part of translucency must always be measured.

Measurements should be taken with the inner border of the horizontal line

of the calipers placed on the line that defines NT thickness

It is important to turn the gain down to avoid the mistake of placing the

caliper on the fuzzy edge of the line.

More than one measurement must be taken and the maximum one that

meets all the above criteria should be recorded in the database.

The semi-automated technique may also be used.

Nuchal cord: Use the mean of NT from above and below the cord

Nicolaides KH. The fetal medicine foundation. Available from:

https://fetalmedicine.org. Accessed March 1, 2017.Figure 1.3: Midsagittal view of a fetus at 13 weeks of gestation showing the

display of the nasal bone according to the recommended standards as shown

in Table 1.2. Yellow calipers measure the nasal bone. Note the presence of

two other echogenic lines, superior to the nasal bone, representing the nasal

skin (short arrow) and the tip of the nose (long arrow).

Table 1.2 • Criteria for the Standardized Measurement of the Nasal Bone

(NB) According to the Fetal Medicine Foundation-United Kingdom14

Gestational age should be between 11 and 13 +6 weeks.

The magnification of the image should be such that the fetal head and

thorax occupy the whole screen.

A midsagittal view of the face should be obtained. This is defined by the

presence of the echogenic tip of the nose and rectangular shape of the

palate anteriorly, the translucent diencephalon in the center, and the nuchal

membrane posteriorly. Minor deviations from the exact midline plane would

cause non-visualization of the tip of the nose and visibility of the zygomatic

process of the maxilla.The ultrasound transducer should be held parallel to the direction of the

nose and should be gently tilted from side to side to ensure that the NB is

seen separate from the nasal skin.

The echogenicity of the NB should be greater than the skin overlying it. In

this respect, the correct view of the NB should demonstrate three distinct

lines: the first two lines are horizontal and parallel to each other; the top

line represents the skin and the bottom one the NB. A third line represents

the tip of the nose.

When the NB line appears as a thin line, less echogenic than the overlying

skin, it suggests that the NB is not yet ossified, and it is therefore

classified as being absent.

Nicolaides KH. The fetal medicine foundation. Available from:

https://fetalmedicine.org. Accessed March 1, 2017.

Tricuspid Regurgitation

Color and pulsed Doppler of the tricuspid valve can be obtained in the apical fourchamber view of the fetal heart by placing the color Doppler box and the pulsed

Doppler sample volume over the valve at the level of the annulus (Fig. 1.5). Tricuspid

regurgitation in the first trimester is a common finding in fetuses with aneuploidies

(trisomies 21, 18, and 13) and in those with major congenital heart malformations.14

Trivial tricuspid regurgitation, defined by the presence of a small regurgitant jet at the

valve annulus, is a common finding in the first trimester and has been reported in the

majority of normal fetuses.21 Table 1.4 lists essential criteria for defining tricuspid

regurgitation in screening for fetal aneuploidy and congenital heart disease. Tricuspid

regurgitation, as defined in Table 1.4, is found in about 1% of euploid fetuses, in 55%

of fetuses with trisomy 21, and in one-third of fetuses with trisomy 18 and trisomy 13.14

Similar to the ductus venosus, we do not recommend routine assessment of the tricuspid

valve for tricuspid regurgitation in all pregnancies, but rather in pregnancies at

increased risk for congenital heart disease or in pregnancies with an intermediate risk

for aneuploidy.14

PRACTICE GUIDELINES FOR THE PERFORMANCE

OF THE FIRST TRIMESTER OBSTETRIC

ULTRASOUND EXAMINATION

Practice guidelines in ultrasound imaging are created to better define an ultrasound

examination and to provide for more standardization in its indications, approach, and

content. Typically practice guidelines are evidence based and consensus driven. There

are two types of ultrasound examinations in obstetrics—screening or routineexaminations that are offered to all pregnant women irrespective of risk and targeted

examinations that are indication driven and offered to pregnant women with increased

risk. The second trimester morphology ultrasound examination has become a screening

examination in most countries and is offered routinely to all pregnant women. The fetal

echocardiogram, on the other hand, is a targeted ultrasound examination that is offered

to pregnant women at increased risk for congenital heart disease. The first trimester

ultrasound examination is now considered a screening examination in many countries

but is still indication driven in others.22 As more data accumulate on the value of the

first trimester ultrasound in the assessment of fetal malformations, and more expertise

develops in the performance of the examination, the authors believe that the first

trimester ultrasound examination will be routinely offered to all pregnant women where

local resources allow. The role of the first trimester ultrasound is evolving from

pregnancy dating and aneuploidy screening to the first look at fetal anatomy to detect

major malformations. Guidelines for the performance of the first trimester ultrasound

were published recently. In the following sections, we present highlights of existing first

trimester ultrasound guidelines from the International Society of Ultrasound in

Obstetrics and Gynecology (ISUOG), the American Institute of Ultrasound in Medicine

(AIUM), and the German Society of Ultrasound in Medicine (DEGUM).16,17,23Figure 1.4: Parasagittal view of the abdomen and chest in color and pulsed

Doppler of a fetus at 13 weeks of gestation with the pulsed Doppler sample

volume placed at the ductus venosus. Note that the insonation angle is almost

parallel to the direction of blood flow in the ductus venosus (arrow). Criteria for

optimal display of ductus venosus Doppler waveforms are shown in Table 1.3.

A represents the atrial contraction phase of the cardiac cycle in the Doppler

waveform.

Table 1.3 • Criteria for the Standardized Measurement of the Ductus

Venosus (DV) flow According to the Fetal Medicine Foundation-United

Kingdom14Gestational age should be between 11 and 13 +6 weeks.

The examination should be undertaken during fetal quiescence

The magnification of the image should be such that the fetal head and

thorax occupy the whole screen.

A right ventral midsagittal view of the fetal trunk should be obtained and

color flow mapping should be undertaken to demonstrate the umbilical vein,

DV, and fetal heart.

The pulsed Doppler sample volume should be small (0.5–1.0 mm) to avoid

contamination from the adjacent veins, and it should be placed in the

yellowish aliasing area.

The insonation angle should be less than 30 degrees.

The filter should be set at a low frequency (50–70 Hz) so that the A-wave

is not obscured.

The sweep speed should be high (2–3 cm/s) so that the waveforms are

spread allowing better assessment of the A-wave.

The DV PIV is measured by the machine, after manual tracing of the

outline of the waveform.

Nicolaides KH. The fetal medicine foundation. Available from:

https://fetalmedicine.org. Accessed March 1, 2017.

PIV, pulsatility index for veins.Figure 1.5: Axial plane of the fetal chest in a fetus at 13 weeks of gestation

showing placement of the pulsed Doppler sample volume for tricuspid Doppler

flow assessment. Note that the sample volume is placed over the valve to cover

inflow and regurgitation when present. In this example, there is no tricuspid

regurgitation in systole (double arrow) and the Doppler spectrum is normal with

E corresponding to early diastole and A corresponding to the atrial kick portion

of diastole. Criteria for pulsed Doppler of the tricuspid valve are shown in Table

1.4. RV, right ventricle.

First Trimester Ultrasound—Guidelines from the International

Society of Ultrasound in Obstetrics & Gynecology

The ISUOG published in 2013 the practice guidelines for the performance of the firsttrimester ultrasound scan.16 These guidelines are comprehensive and discuss the early

dating scan before 11 weeks of gestation, the aneuploidy screening with NT

measurement, and the anatomic survey.16

Table 1.4 • Criteria for the Standardized Measurement of the Tricuspid

Flow According to the Fetal Medicine Foundation-United Kingdom14

Gestational age should be between 11 and 13 +6 weeks.

The magnification of the image should be such that the fetal thorax

occupies most of the image.

An apical four-chamber view of the fetal heart should be obtained.

A pulsed-wave Doppler sample volume of 2.0 to 3.0 mm should be

positioned across the tricuspid valve so that the angle to the direction of

flow is less than 30 degrees from the direction of the interventricular

septum.

Tricuspid regurgitation is diagnosed if it is found during at least half of the

systole and with a velocity of over 60 cm/s, because aortic or pulmonary

arterial blood flow at this gestation can produce a maximum velocity of 50

cm/s.

The sweep speed should be high (2–3 cm/s) so that the waveforms are

widely spread for better assessment.

The tricuspid valve could be insufficient in one or more of its three cusps,

and therefore the sample volume should be placed across the valve at

least three times, in an attempt to interrogate the complete valve.

Nicolaides KH. The fetal medicine foundation. Available from:

https://fetalmedicine.org. Accessed March 1, 2017.

Purpose of the First Trimester Ultrasound Scan

ISUOG guidelines describe the purpose of the first trimester ultrasound examination as

follows:

In early pregnancy, it is important to confirm viability, establish gestational age

accurately, determine the number of fetuses and, in the presence of a multiple

pregnancy, assess chorionicity and amnionicity. Towards the end of the first

trimester, the scan also offers an opportunity to detect gross fetal abnormalities

and, in health systems that offer first-trimester aneuploidy screening, measure the

nuchal translucency thickness (NT).

The guidelines also discuss the ultrasound equipment to be used (summarized in Table

1.5).Biometry

The minimal required biometric measurements according to ISUOG include the crownrump length, the biparietal diameter, or head circumference. Other measurements can

also be performed including the abdominal circumference (AC), the femur length (FL),

or others. Nomograms in the first trimester are currently available for most of the

biometric measurements that can be performed in the second trimester. ISUOG

guidelines state that there is no reason to measure the AC or FL as part of the routine

first trimester scan.16 The role of biometry and dating in the first trimester is discussed

in more detail in Chapter 4.

Table 1.5 • Requirements for the Ultrasound Equipment in First Trimester

Scanning According to the International Society of Ultrasound in Obstetrics

and Gynecology (ISUOG)16

Real-time, gray-scale, two-dimensional (2D) ultrasound

Transabdominal and transvaginal ultrasound transducers

Adjustable acoustic power output controls with output display standards

Freeze frame and zoom capabilities

Electronic calipers

Capacity to print/store images

Regular maintenance and servicing

Salomon LJ, Alfirevic Z, Bilardo CM, et al. ISUOG practice guidelines:

performance of first-trimester fetal ultrasound scan. Ultrasound Obstet

Gynecol. 2013;41:102–113.

Nuchal Translucency

ISUOG guidelines state the following regarding NT measurement in the first trimester:

A reliable and reproducible measurement of NT requires appropriate training. A

rigorous audit of operator performance and constructive feedback from assessors

has been established in many countries and should be considered essential for all

practitioners who participate in NT-based screening programs. However, even in

the absence of NT-based screening programs, qualitative evaluation of the nuchal

region of any fetus is recommended and, if it appears thickened, expert referral

should be considered.16

Assessment of Fetal Anatomy

ISUOG guidelines emphasize the importance of the early anatomic survey and present

the pros and cons of the first trimester ultrasound for fetal anatomy assessment. ISUOG

guidelines also state that advantages of the early anatomy scan include early detectionand exclusion of many major anomalies, early reassurance to at-risk mothers, earlier

genetic diagnosis, and easier pregnancy termination if appropriate.16 The limitations of

early anatomic assessment are also discussed in the ISUOG guidelines and include the

need for trained and experienced personnel, uncertain cost/benefit ratio, and the need

for a second trimester ultrasound, as some anomalies develop later on in pregnancy and

cannot be excluded early in gestation. Table 1.6 lists the fetal anatomic areas and

organs that can be assessed in the first trimester.

Table 1.6 • Suggested Anatomic Assessment at Time of 11 to 13 + 6-

week Scan According to the International Society of Ultrasound in

Obstetrics and Gynecology (ISUOG)16

Anatomic Region What to Look for

Head Present, cranial bones, midline falx, choroid plexus

fill ventricles

Neck

Normal appearance, nuchal translucency thickness

(if accepted after informed consent and

trained/certified operator available)a

Face Eyes with lensa, nasal bonea, normal

profile/mandiblea, intact lipsa

Spine Vertebrae (longitudinal and axial)a, intact overlying

skina

Chest Symmetrical lung fields, no effusions or masses

Heart Cardiac regular activity, four symmetrical

chambersa

Abdomen Stomach present in left upper quadrant, bladdera,

kidneysa

Abdominal wall Normal cord insertion, no umbilical defects

Extremities Four limbs each with three segments, hands and

feet with normal orientationa

Placenta cord Size and texture

Cord Three-vessel corda

aOptional structures

Salomon LJ, Alfirevic Z, Bilardo CM, et al. ISUOG practice guidelines:performance of first-trimester fetal ultrasound scan. Ultrasound Obstet

Gynecol. 2013;41:102–113.

First Trimester Ultrasound—Guidelines from the American

Institute of Ultrasound in Medicine

As of the date of this writing, the AIUM does not have specific guidelines dedicated for

ultrasound in the first trimester. Ultrasound in the first trimester is discussed however in

the document on the Practice Parameter for the Performance of Obstetric Ultrasound

Examinations which is currently (2017) being revised.23 In this document the AIUM

states the following:

A standard obstetric sonogram in the first trimester includes evaluation of the

presence, size, location, and number of gestational sac(s). The gestational sac is

examined for the presence of a yolk sac and embryo/fetus. When an embryo/fetus

is detected, it should be measured and cardiac activity recorded by a 2-

dimensional video clip or M-mode imaging. Use of spectral Doppler imaging is

discouraged. The uterus, cervix, adnexa, and cul-de-sac region should be

examined.23

Table 1.7 • Parameters for Nuchal Translucency (NT) Measurements

According to Nuchal Translucency Quality Review and the American

Institute of Ultrasound in Medicine15

The margins of the NT edges must be clear enough for proper placement

of the calipers

The fetus must be in the midsagittal plane

The image must be magnified so that it is filled by the fetal head, neck, and

upper thorax

The fetal neck must be in a neutral position, not flexed, and not

hyperextended

The amnion must be seen as separate from the NT line

The “+” calipers on the ultrasound must be used to perform the NT

measurement

Electronic calipers must be placed on the inner borders of the nuchal line

space with none of the horizontal crossbar itself protruding into the space

The calipers must be placed perpendicular to the long axis of the fetus

The measurement must be obtained at the widest space of the NT

Cuckle H, Platt LD, Thornburg LL, et al. Nuchal Translucency QualityReview (NTQR) program: first one and half million results. Ultrasound

Obstet Gynecol. 2015;45:199–204.

The document also reports on NT screening as performed for individual risk assessment

for aneuploidy. The NT prerequisites as listed by the AIUM are shown in Table 1.7.

The AIUM document does not currently provide any details on the assessment of fetal

anatomy in the first trimester. Based upon the existing practice parameter for obstetric

ultrasound examination, the AIUM recommends that the first trimester ultrasound

currently remains indication driven and not routinely offered to all low-risk

pregnancies.23

First Trimester Ultrasound—Guidelines from the German

Society of Ultrasound in Medicine

The DEGUM published in 2016 an update of the guidelines of the first trimester

ultrasound scan, dedicated to ultrasound specialists.17 Prerequisites for the NT

measurements are not only technical as recommended by the Fetal Medicine Foundation,

but include the process of informed consent and patient counseling according to existing

genetic laws.17 The document emphasizes the role of an early anatomic survey

performed by a specialist as an integral part of the first trimester ultrasound, especially

in the era of the noninvasive prenatal testing (see Chapter 6). The minimum anatomic

requirements in the first trimester for the assessment of the fetus are summarized in

Table 1.8 and are slightly different from those listed in the ISUOG guidelines.

CONCLUSIONS

The first trimester ultrasound has evolved over the years to become an integral part of

obstetric scanning in many modalities around the world. Beyond the confirmation of an

intrauterine location of a gestational sac, viability of an embryo or a fetus, accurate

pregnancy dating, determination of placental chorionicity in multiple pregnancies, the

first trimester ultrasound has evolved to become a comprehensive early anatomic survey

when performed by experienced personnel. This book presents the collective

experience in the first trimester ultrasound examination in two prenatal diagnosis

centers. Our experience is also supported by studies and case reports from the

literature. Following chapters in this book present various topics related to the first

trimester ultrasound examination to include bioeffects of ultrasound, fetal biometry,

aneuploidy screening, image optimization, multiple pregnancies, and detailed

assessment of the normal and abnormal anatomy of various fetal organ systems.

Table 1.8 • Ultrasound Standard Views of the Fetal Anatomy and Optional

Parameters According to the German Society of Ultrasound in Medicine

Guidelines (DEGUM)171.

2.

3.

4.

Standard Views Optional Parameters

Skull/brain Bone of the skull, falx cerebri,

choroid plexus

Intracranial translucency,

brainstem

Face Profile Eyes, maxillary and mandible,

lips

Neck Nuchal translucency (NT)a Nasal bone (NB)a

Spine Outline

Heart/thorax Position, contour, fourchamber view, lungs

Outflow tracts (color), threevessel trachea view, tricuspid

flow (TR)a

Abdomen Stomach, abdominal wall

Diaphragm, DV flowa,

umbilical arteries, and urinary

bladder

Extremities Arms, legs Hands and feet (femur, tibia,

fibula, humerus, radius, ulna)

Urogenital

tract Urinary bladder Kidneys

Placenta Chorionicity, amnionicity

(multiple gestation), structure

Position, insertion of umbilical

cord, uterine arteriesa

aAfter counseling and consenting according to German law on genetics and

certification through the Fetal Medicine Foundation (FMF).

Kaisenberg von C, Chaoui R, Häusler M, et al. Quality Requirements for

the early Fetal Ultrasound Assessment at 11-13+6 Weeks of G