Key words nuchal translucency - anatomy scanning - fetal anomalies - first trimester
Introduction
The present recommendation of the DEGUM Section Obstetrics and Gynecology for the
quality requirements of the early fetal ultrasound assessment at 11 – 13+6 weeks of gestation updates the version of 2004 [1 ]. It addresses specialized ultrasonographers (DEGUM Levels II & III). During the
recent years there have been many changes which made an update of the previous version
necessary. In particular the following aspects should be mentioned:
Improvements in the resolution of ultrasound and increasing experience of operators
allow a very detailed examination of the first trimester fetus if conditions are favourable.
Therfore, beyond the measurement of the nuchal translucency, a detailled anatomical
survey and early detection of major or complex anomalies can be achieved.
With the introduction of the Gendiagnostikgesetz (GenDG) in 2009 and the Schwangerschaftskonfliktgesetz
(SchKG) extensive counseling of the pregnant woman has become compulsory [2 ]
[3 ]. Also the directive of the Gendiagnostik-Kommission of the Robert Koch Institute
(GEKO directives of the RKI) on the requirements for the qualification of genetic
counseling and the content and the requirements for the implementation of the antenatal
risk assessment should be considered [4 ]
[5 ]. In Austria the pregnant woman must be counseled by a specialist on the nature,
consequences and significance of the suggested technique (genetische Analyse gem.
§ 68 GTG (Gentechnikgesetz)) if NIPT is done [6 ]. In Switzerland there is an obligation for counselling about the significance and
potential consequences of prenatal examinations for risk assessment [7 ].
The introduction of non-invasive prenatal testing (NIPT) in 2012 based on the examination
of the cell-free fetal DNA (cffDNA) in the maternal blood has as a further screening
test yielded very high detection rates predominantly for trisomy 21, but also for
the trisomies 18 and 13. First trimester ultrasound however can achieve much more
than the risk calculation for chromosomal abnormalities only.
Beyond fetal anomalies, using ultrasound among others, risk factors for the main problems
of pregnancy can be established. This knowledge may lead to the early identification
and therapy of high risk patients thus reducing the risks of the subsequent manifestation
of the disease later in pregnancy and to be able to manage pregnancies individually
according to their risks [8 ].
The DEGUM quality requirements for the ultrasound examination in early pregnancy (4 – 14
wks) are dealt with separately. There, dating of pregnancy based on ultrasound parameters
is described in detail [9 ].
Objectives of the ultrasound examination
There are a number of objectives for the examination in early pregnancy which may
differ according to the problem in question, the history and risk factors. This is
the first detailed ultrasound examination in pregnancy which allows an early assessment
of the fetal anatomy. Thus at this early stage major fetal anomalies can be detected.
Doubting and fear of the future parents can therefore be taken away in particular
when there is a risk of recurrence for a specific anomaly. The present recommendation
describes a structured examination at 11 – 13+6 weeks' of gestation.
Many couples participate in first trimester screening mainly to get a result of the
fetal risk for a chromosomal abnormality. If the risks are high or there is a suspicion
of an anomaly an invasive procedure can be offered to make a diagnosis [9 ]. In case of a major anomaly the patientin can be counseled in a multidisciplinary
team and be supported in the decicion making. If the decision is termination it can
be done early in pregnancy. This may help in avoiding late terminations which have
higher risks for the mother and are felt to be more stressful both for patients, relatives
and medcical personnel.
Prerequisites & technical aspects
Prerequisites & technical aspects
One of the prerequisites to carry out an anomaly scan at 11 – 13+6 weeks of gestation is a profound knowledge in the ultrasound assessment of the fetus.
Expertise can be demonstrated for example in obtaining the DEGUM levels II and III.
Risk assessment for fetal chromosomal defects requires licencing through the Fetal
Medicine Foundation (FMF) of Germany or the United Kingdom. In Germany first trimester
screening is subject to the Gendiagnostikgesetz, therefore, prior to the scan, the
woman must be counseled for the content of the examination and the potential consequences.
It may be useful to let the women confirm the content of the discussion in written
[2 ]
[4 ]
[5 ].
The scan can be performed transabdominally or vaginally. An advantage of the transabominal
scan is the better visualization of the whole content of the amniotic sac and measurements
are easier to perform. An advantage of the vaginal approach is the better resolution
but the route may be more time consuming. With a retroflexed uterus, bowel interponation,
adipous abdominal walls or the suspicion of anomalies an additional vaginal scan may
be helpful.
A variety of techniques may be included in first trimester screening such as B-mode,
color doppler, pulsed wave dopper and 3 D sonography. At this gestation, the fetus
is at a critical period of its development. Therefore knowledge of the principles
of risk reduction using dopplers is mandatory. In particular the use of pulsed spectral
doppler sonography imposing the highest energetic strain should be particularly considered.
Therefore the use of dopplers should both be subject to an indication and exposure
reduced to a minimum (ALARA = as low as reasonably achievable) [11 ]. The heart rate can also be determined using pulsed wave dopplers on a free loop
of the umbilical cord or can be measured using M-mode. Color doppler applied in early
fetal echocardiography imposed no risks ([Table 1 ]).
Table 1
Technical requirements for ultrasound machines.
abdominal probes (electronic and/or mechanical curved-array or linear probes), broadband
(frequency range 3.0 – 7.5 MHz) and / or transvaginal electronic or mechanical probes,
broadband, high frequency (4.0 – 10.0 MHz)
Nuchal translucency & risk assessment for fetal chromosomal defects
Nuchal translucency & risk assessment for fetal chromosomal defects
Ultrasound will remain the most important technique in assessing the individual risks
for aneuplody despite the increasing use of cffDNA. The measurement of nuchal translucency
(NT) is central as it gives information on chromosomal abnormalities which can not
be detected using cffDNA, genetic syndromes and fetal structural defects [12 ]
[13 ]
[14 ]
[15 ]
[16 ]. Also the chances for intrauterine fetal death and for a healthy live birth can
be assessed [17 ]. The use of cffDNA should only be offered once the woman has been counseled about
the nature, consequences and significance of the test [18 ]
[19 ]. As the accuracy of the fetal NT measurement and risk calculation is depending on
the quality of the examination, the measurement must be done adhering to the guidelines
of the Fetal Medicine Foundation and is subject to annual audit [20 ] ([Table 2 ], [Fig. 1 ]).
Table 2
FMF-Protocol for the measurement of the fetal nuchal translucency (NT) ([Fig. 1 ]).
placing the calipers: measurements should be taken with the inner border of the horizontal
line of the callipers placed ON the line that defines the nuchal translucency thickness
– the crossbar of the calliper should be such that it is hardly visible as it merges
with the white line of the border, not in the nuchal fluid
1 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.
Fig. 1 Fetus at 12+ 6 weeks of gestation with normal nuchal translucency. Note the nasal bone (NB), the
Thalamus (T), the Midbrain (M), the Brain Stem (BS), the Intracranial Translucency
(IT), the Cisterna magna (CM), the Nuchal Translucency (NT) and the Amnion.
Risk assessment for fetal trisomy 21 should be done through combined first trimester
screening (combined test). In addition to the NT, free beta-hCG and PAPP-A must be
measured [13 ]
[14 ]
[20 ]
[21 ]
[22 ]. These parameters should be evaluated simultaneously, not sequentially, together
with maternal age and gestational age through the programs of the FMF. Only the background
risk and the adjusted risk should be communicated respectively. The detection rate
for the combined first trimester screening is about 90 % for a false-positive rate
of 3 – 5 % [21 ]
[23 ]
[24 ]
[25 ]. If the blood for biochemistry is being taken a week or two earlier detection rates
may even be higher.
In dichorionic twins the risk for each fetus is calculated individually. As monochorionic
(MC) twins are always monzygotic only one risk for counseling should be used. This
can be derived from the mean of the two risks calculated individually for each fetus.
The presence of a big difference in the NT of MC twins may suggest the subsequent
development of a twin-to-twin transfusion syndrome [26 ].
The detection rate may further be increased through the inclusion of the fetal nasal
bone, the ductus venosus or tricuspid valve flow [27 ]
[28 ]
[29 ]
[30 ]. If these additional parameters are to be included in the risk calculation further
certification through the FMF is required [27 ]
[28 ]
[29 ]
[30 ]. If detection rates are to be increased both cffDNA analysis and/or the assessment
of additional ultrasound parameters have to be considered [18 ].
Fetal anomaly scanning at 11 – 13+6 weeks of gestation
Fetal anomaly scanning at 11 – 13+6 weeks of gestation
Standard measurements at 11 – 13+6 weeks of gestation are the crown-rump-length (CRL), the biparietal diameter (BPD)
and nuchal translucency (NT). The head circumference may be used for dating from 14
weeks. Further measurements are optional ([Table 3 ]).
Table 3
Ultrasound first trimester standard biometry and optional parameters.
standard biometry
optional parameters
crown-rump-length (CRL)
biparietal diameter (BPD)
head- and -abdominal circumference (HC, AC), femur length (FL)
nuchal translucency (NT)[1 ]
nasal bone (NB)1
intracranial translucency (IT) / brain stem
fetal heart rate (FHR)
trikuspid flow (TR)1
ductus venosus flow (DV)1
uterine arteries (UA)1
cervical length (Cx)1
1 After counselling and consenting (GenDG) and certification through the FMF: NT, NB,
TR, DV, UA, Cx.
A detailed anatomical survey is done best in the second trimester [31 ]
[32 ], but many anatomical structures can already be identified in the first [33 ]. The visualisation of details is depending on a variety of factors such as the fetal
size (45 – 84 mm), the route (transvaginal vs transabdominal), the maternal habitus,
the resolution of the ultrasound machine and the training of the operator. In many
cases a reliable assessment can be achived today using the transabdominal route. The
following structures can usually be assessed ([Table 4 ]).
Table 4
Ultrasound standard views of the fetal anatomy and optional parameters [42 ]
[43 ]
[44 ]
[45 ].
standard views
optional parameters
skull / brain
bone of the skull, falx cerebri, chorioid plexus
intracranial translucency IT
brain stem
face
profile
eyes, maxillary and mandible, lips
neck
nuchal translucency (NT)[1 ]
nasal bone (NB)1
spine
outline
heart / thorax
position, contour
four chamber view
lungs
outflow tracts (color)
three-vessel-trachea view
tricuspid flow (TR)1
abdomen
stomach
abdominal wall
diaphragm
ductus venosus flow (DV)1
umbilical arteries and urinary bladder
extremities
arms & legs
hands & feet
(femur tibia fibula humerus radius ulna)
urogenital tract
urinary bladder
kidneys
plazenta
chorionicity, amnionicity (multiple gestation), structure
position,
insertion of umbilical cord
uterine arteries1
1 After counselling and consenting (GenDG) and certification through the FMF: NT, NB,
TR, DV, UA, Cx.
Head and Brain
The head and brain can be simultaneously assessed when the BPD is taken [33 ]
[34 ]. In a transverse section the ovoid shape of the fetal head, the intact bone of the
skull and the falx cerebri separating both hemispheres can be demonstrated. Both chorioid
plexus are prominent in early gestation filling almost completely the lateral ventricles
sometimes slightly asymmetrical [34 ]
[45 ]. A median sagittal section of the fetal head is the basis for the measurement of
the NT. But additional structures of the fetal brain in the posterior fossa should
also be considered, such as the fourth ventricle or intracranial translucency (IT)
and the brain stem as they may be helpful in early detection of open spina bifida
[36 ]
[37 ] ([Fig. 1 ]).
Face
The face ist best viewed in a median sagittal plane (profile) and in frontal and/or
transversal views demonstrating the eyes and maxilla and mandible.
Neck and Spine
The standard view to measure NT is a dorsoposterior or dorsoanterior median sagittal
plane of the fetus ([Fig. 1 ]). If the nuchal is increased additional transversal views may be helpful to asses
more details. An increased NT is associated with fetal anomalies [38 ].
The spine can be best viewed in sagittal and transversal planes but many anomalies
may remain undetected at 11 – 13+6 weeks.
Heart and Thorax
The heart, lungs and thorax can best be viewed at the level of the four chamber view.
The heart rate may be taken. A B-mode may be used to assess the heart, but color doppler
facilitates the investigation and increases the accuracy. The four chamber view and
the three vessel trachea view should be demonstrated thus enabling the detection of
a number of anomalies.
The measurement of the NT, of the flow across the tricuspid valve and in the Ductus
venosus is an indirect method of screening for cardiac defects [39 ].
Abdomen
Sagittal and transversal views are among important planes to assess the anterior abdominal
wall and internal abdominal organs. The following landmarks should be looked at: stomach,
urinary bladder and intact abdominal wall. Using color doppler the umbilical arteries
around the urinary bladder can be visualized [40 ]. A clear depiction of the kindneys is not always possible at this gestation. A physiological
omphalocele may be noted from 9 and 11 weeks.
Extremities
The extremities can usually be clearly demonstrated. The presence of three segments
on each extremity should be looked at. In selected cases such as with an increased
recurrence risk it may be important to look at individual fingers and toes which may
be easier transvaginally.
Placenta and amniotic fluid
The site and morphology of the placenta should be looked at. In multiple gestation
pregnancies chorionicity and amnionicity should be documented. The diagnosis of placenta
praevia or an abnormal placentation should be made at a later stage of pregancy. The
insertion of the cord at the placenta is often feasible. Amniotic fluid is usually
normal in early pregnancy.
Limitations in assessing fetal anatomy at the first trimester scan
In experienced hands a number of major anomalies can be detected through a systematic
scan. However there are limitations to the method as the anatomy is at an early stage
of development [41 ]. The patient should be informed about the limitations and 2nd trimester screening for anomalies should be recommended [32 ].
Management of abnormal or suspicious findings
Management of abnormal or suspicious findings
The findings of an abnormality or an increased risk of a chromosomal defect should
prompt an invasive procedure. Chorionic villus sampling (CVS) is the standard technique
as it gives results within a day. In that case, cffDNA analysis is not indicated as
only a limited spectrum of aneuploidies can be detected and the test has no diagnostic
reliability.
In the case of an intermediate risk further assessment involving additional ultrasound
markers such as the nasal bone and tricuspid and ductal flows can be carried out.
In that group more detailed ultrasound assessment may be replaced by a cffDNA test.
In fetuses with abnormal anatomy but normal karyotype using conventional cytogenetics,
parents should be counselled about the possibility of CGH-Array-Analysis. If the NT
is > 95. centile the association with genetic syndromes and structural anomalies such
as a cardiac defect should be considered. In those cases anomaly scanning at 16 and
20 weeks including fetal echocardiography may be useful. Genetic counselling may help
identifying familiar single gene disorders which may be amenable for sequencing in
the present pregnancy.
In the case of low free beta hCG and PAPP-A (< 0.41 MoM) serial follow-up scans to
monitor for intrauterine growth restriction (IUGR), pre-eclampsia (PET) and for imminent
intrauterine fetal death [46 ] is advisable.
The significance of early diagnosed fetal anomalies is in some cases difficult to
predict as there may be spontaneous resolution or worsening of the condition. The
prognosis may become more clear at serial scans. A second opinion and an interdisciplinary
approach should be encouraged.
Future prospects
Ultrasound is the basis of first trimester screening at 11 – 13+6 weeks of gestation including the structural and hemodynamical examination of the
fetus and mother in combination with assessment of the background risks and biochemical
and biophysical factors [7 ].
Research focuses at present on the development and advancement of risk algorithms
for chromosomal abnormalities, for intrauterine fetal death / stillbirth, intrauterine
growth restriction and pre-eclampsia, for preterm birth and for macrosomia and diabetes
mellitus [47 ]
[48 ]
[49 ]
[50 ]
[51 ]
[52 ] and on the integration of rapidly evolving molecular techniques.
For the risk assessment algorithms may be used which can publicly be accessed or are
subject of certification (https://fetalmedicine.org/pyramid-of-care).
For individual diseases there is already an early intervention, a potential reduction
of maternal and fetal morbidity and mortality is currently under intensive investigation.
