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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5786_Библиотеки_им_академика_М_И_Перельмана.pdf
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graph is called a scattergram and allows a visual analysis of the data. A correlation
is probable if the data are distributed along a line, whereas it is obviously absent in
cases of random dispersion of values. Preliminary mathematical analysis consists
of: producing for each GA a mean value with standard deviations (SD), fitting
a curve to the data passing through the mean of the scattergram, and drawing
the variability around this curve. Curve fitting is done by regression analysis that
allows the prediction of one variable (biometric value) from the other (GA). The
dependent or predicted variable is reported on the x-axis and the independent or
observed variable is represented on the y-axis.
Linear regression analysis
In linear regression analysis it is possible to calculate an unknown biometric variable from the following formula: y = a + xb where a is the value of y at the point
of intersection with the x-axis and b is the slope of the line. Linear regression is
simple to calculate and is appropriate for small samples with a large variability of
the parameter whenever the accuracy of the prediction is not crucial, such as in
the case of preliminary studies.
Curvilinear regression analysis
For fetal biometry curvilinear polynomial regression analysis is more appropriate,
but more data points are needed. Polynomial equations can be of different orders:
first order: a + bx; second order, a + bx + cx2, and third order, a + bx+ cx2 + dx3.
The accuracy of the description of the data increases with the order of the
polynomial equation but for practical reasons, the lowest order that correlates
with the data is usually selected.
Fetal biometry, estimation of gestational age, assessment of fetal growth
The coefficients of correlation
The coefficient of multiple correlation, R, or the coefficient of determination, R2,
indicates the quality of the fit and should be as close as possible to 1. A value of
1 indicates a perfect correlation with all the points in the scattergram located
on the regression line, whereas a value of 0 demonstrates no correlation at all.
Whenever R2 exceeds 0.90 the correlation is good and the most appropriate
curve is the one with the lowest order.
The F test
To discriminate among equations of different order, the F test, which is a variant of the t-test, is needed. This test is employed to verify the hypothesis that the
coefficients (b, c, d …n) of the equations, although very small (since they must be
multiplied by x, x
2
, x3…), are different from 0. A higher order of equation needs
more coefficients but these figures will be helpful, increasing the order of the
equation and complicating it only if significantly different from 0.
PREDICTION OF DATE AND SIZE
The obtained equation cannot be used correctly in two senses because a twodirectional reading is a mathematical mistake. Tables used for dating should be
143
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different from those employed for fetal size assessment. If a biparietal diameter
(BPD) of 50 mm corresponds to a determined GA (fetal dating), the reverse is
not true because 50 mm will not be necessarily the mean BPD value for that GA
(fetal growth assessment). Therefore, a good rule is not to use the same table to
determine GA from a parameter and to assess the normality of this parameter
against GA.14 In growth curves the biometric value is the dependent variable and
GA the independent variable. In dating curves the gestational age is the dependent variable and the biometric value the independent one.
THE CONFIDENCE LIMITS
The dispersion of values around the mean is the SD and is used to describe the
statistical limits of normality. The SD thus measures our degree of uncertainty
concerning the biometric value of a random individual from its population.
A symmetrical distribution favours the use of SD whereas a skewed distribution
suggests the use of percentiles. The interval of variation is also called the confidence limit and is set at the fifth and 95th percentiles (1.66 SD) or at the first and
Ultrasound in obstetrics and gynaecology
99th percentiles (2.38 SD). Two SD include 95% of the population, 2.5% being
above and 2.5% below the normal limits. Using the fifth and 95th percentiles as
reference values, 10% of patients will be outside the normal limits by definition,
without necessarily being affected by pathology.
It is important, for a good predictive value of the equation, that the SD will not
change significantly with variation of the observed value and this can be investigated by the Bartlett or Levene test.
14
144
DATING
Accurate dating or estimation of GA is essential in modern obstetrics for many
reasons such as:
interpretation of biochemical tests early and/or later in pregnancy (double
•
test or triple test)
planning prenatal diagnostic procedures (chorion villus biopsy,
•
amniocentesis) and therapy (cerclage, fetal transfusions)
timing of delivery in a high-risk pregnancy
•
prediction of neonatal viability
•
reliable diagnosis of growth abnormality
•
identification of a true postterm pregnancy.
•
Actually, the incidence of fetal growth restriction is as high as 20% when GA is
based on menstrual history and as low as 5% when based on ultrasound-derived
dates. The incidence of postdate pregnancy is 9% using menstrual dates, but only
3% after ultrasound dating.16 Fetal therapies also require an accurate estimate of
the GA. Yet, there is now evidence that ultrasound dating alone is a better predictor of the date of delivery than the LMP within a 14-, 10- or even 7-day margin
of error.
18
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MENSTRUAL, CONCEPTUAL AND GESTATIONAL AGE
The conceptual age is calculated from the assumed time of the ovulation. The
menstrual age is calculated from the best knowledge of the first day of the LMP
in women with regular cycles. The GA, used in the ultrasound-dated pregnancy, is
based on the estimated LMP from the measured ultrasound parameters. The fetal
age is expressed in complete gestational weeks and not current weeks. Likewise,
maternal age is reported in complete years.
ERRORS OF MEASUREMENTS
The technical error of a measurement is relatively constant depending on the
image selection and caliper positioning. The measurement should be taken at
least three times and averaged. Resolution refers to the ability to discriminate
between points in the ultrasound beam. Axial resolution describes differentiation
of target echoes along the path of a single emitting source of ultrasound. The axial
resolution varies directly with the frequency. A 3.5 MHz transducer has an axial
resolution of 0.5–0.6 mm. Lateral resolution is the differentiation of two targets
that are side by side at a given depth. The time dynamic lateral resolution of diagnostic ultrasound is probably less than 1 mm.
The selection of the start and end points for a given measurement has become
more difficult with improved sonographic definition of the anatomy. With modern equipment, not only the bony table of the calvarium but also hair, skin and
subcutaneous tissue can be identified. It is therefore essential that the starting
point of the measurement is set at the calvarium surface and not the scalp surface since the soft tissues of a full-term fetus can easily exceed a thickness of
5–6 mm, producing an overestimation of true BPD greater than 5%.16 The maximum inter- and intraoperator variations for measurements of the long bones
are 3 and 2 mm, respectively6 but in some studies deviations of up to 14% were
found using different probes.
The use of millimetres instead of centimetres is recommended by the international system of units.
14
12
Fetal biometry, estimation of gestational age, assessment of fetal growth
THE ACCURACY OF DATING
Ultrasound measurement of the fetus prior to 20 weeks' gestation is thought to
be accurate to ±7 days and could be beneficial not only in high-risk pregnancies, since nearly half of fetal growth abnormalities are derived from low-risk
patients.
Accuracy of ultrasound dating is inversely related to the fetal age. The rate of
fetal growth is exponential at the beginning of the pregnancy and linear at late
gestation. The influence of individual factors becomes more pronounced as pregnancy advances with a progressive dispersion of biometric values and broadening
of the nomogram. Accordingly, the accuracy of fetal biometry is inversely proportional to the GA for almost every parameter measurable by ultrasound.
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The optimal method for ultrasound dating varies with GA. From 4 to 5 weeks
the gestational sac can be measured, from 6 to 10 weeks the most accurate
parameter is crown–rump length (CRL). From 10 to 20 weeks, the most accurate parameter may be the BPD because of the effect that deflection and variable
position of the fetus have on the CRL. Fetal long bone measurements become
accurate after 14–16 weeks' gestation.
6
In late gestation the accuracy of ultrasound dating is increased by serial
measurements. Such measurements should be spaced out (2–3 weeks) to ensure
that the supposed increase of the biometric value is greater than the measurement error. The slope of fetal growth predicts GA with an accuracy of 7–10 days21
but this method has not been widely accepted in clinical practice.
BIOMETRIC PARAMETERS
GESTATIONAL SAC
The gestational sac can be seen transvaginally as early as 4 weeks’ gestation when
Ultrasound in obstetrics and gynaecology
its greater diameter is 2 mm with corresponding human chorionic gonadotropin
(hCG) levels around 1000 mIU/mL (International Reference Preparation or IRP).
Its mean diameter bears a linear relationship with GA, and increases 1.0–1.2 mm/
day until the appearance of the fetal pole with its heart beat, at a size of 10 mm,
with corresponding hCG levels around 12,000 mIU/mL (IRP).
146
CROWN–RUMP LENGTH
The CRL is the longest length of the embryo or fetus measurable excluding the
limbs and yolk sac.14 The embryo becomes a fetus after 10 gestational weeks
(71 completed days based on the LMP). The accuracy of the CRL in dating the
pregnancy depends on good correlation between this measurement and fetal age
in a period when growth is rapid and minimally influenced by fetal pathology.
The CRL is predictive of fetal age with an error of 3 days (90% confidence limits)
from 7 to 10 weeks and of 5 days from 10 to 14 weeks' gestation. The CRL grows
approximately 10 mm per week from weeks 8 to 12 and a simple rule to obtain
GA is the following: GA (week) = CRL (cm) + 6.5.
14,22
HEAD MEASURES
Fetal head size has been one of the most useful and proven measurements to
determine GA. The BPD is the most widely used measure, with greatest accuracy
between 12 and 22 weeks, declining after this period because of a wider individual variation. The BPD demonstrates linear growth of 3 mm per week from weeks
14 to 28, and 2 mm per week until term.
of a plane defined by the following intracerebral landmarks: the frontal horns of
the lateral ventricle and cavum septum pellucidum anteriorly, the thalami and
third ventricle centrally, and the occipital horns of the cerebral ventricle, cisterna
5,22
The measurement is taken at the level
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venae magnae cerebri and insula posteriorly. The measurement is taken from the
outer table of the proximal skull to the outer table of the distal skull with the cranial bones perpendicular to the ultrasound beam.14 The occipitofrontal diameter
(OFD) is measured in the same plane as the BPD with the calipers placed on the
outer skull table. This parameter can be used to calculate the head circumference
(HC) and the cephalic index (CI). Fetal head shape variations (dolichocephaly,
brachycephaly) and fetal position can affect the diagnostic accuracy of BPD. In
case of an abnormal CI, defined as the ratio of the BPD divided by OFD (normal
0.75–0.85), the HC could be used instead of BPD to avoid this pitfall.22 In fetuses
with premature rupture of the membranes, breech presentation or multiple pregnancy, the BPD is not reliable in assessing true GA.
19,22
HC is either measured at the same level of BPD directly with trace calipers or
indirectly computed by using a formula such as: HC = (BPD + OFD) × 1.57. The
direct method systematically overestimates the calculated HC by less than 1.5%.
HC grows approximately 14 mm per week between 14 and 17 weeks and 5 mm
per week near term.22 Head measurement is a poor screening method for fetal
growth abnormalities since it is generally spared until late, both in symmetrical
growth restriction and microcephaly.
ABDOMINAL SIZE
Fetal biometry, estimation of gestational age, assessment of fetal growth
Abdominal size is assessed by measuring the middle abdominal diameter (MAD)
or the abdominal circumference (AC) (Fig. 9.1) at the level of the stomach and
the bifurcation of the main portal vein into its right and left branches, taking care
to have a section as round as possible, not deformed by the pressure of the probe.
The most accurate AC is the smallest obtained since it more closely approximates
to a perpendicular plane to the spine at the level of the hepatic vein. Similarly to
the calculation of HC, the measurement can be direct (ellipse or trace) or derived
from the transverse abdominal diameter and anteroposterior abdominal diameter
Fig. 9.1 Measurement of the fetal upper abdominal circumference (AC). Reproduced by
permission of B. Verburg.
147
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(MAD). Due to the irregular shape of the fetal abdomen, the direct method overestimates the indirect one by about 5%; this variation could be relevant in the
assessment of fetal weight.
24
The AC demonstrates linear growth with a mean of 11–12 mm per week
throughout gestation.22 This parameter is the most sensitive in predicting
nutritional problems of the fetus, being influenced by the thickness of the
abdominal wall and by the amount of the hepatic glycogen stores, and it is
used for estimation of fetal weight. For the same reason, the AC should not
be used for calculation of a composite GA after the early second trimester.
Unfortunately, its measurement is affected by the greatest inter- and intraobserver variation, accounting for the widely disparate limits of reference
values reported by different investigators. Actually, fetal position and breathing
movements, probe compression and oligohydramnios could affect the accuracy
of this measurement.
LIMBS
Ultrasound in obstetrics and gynaecology
Femur length (FL) can be measured from 10 weeks onwards and it is reproducible from 15 weeks' gestation to term. It represents fetal linear growth, being
related to crown–heel length at birth.15 It was originally measured to diagnose
limb dwarfism and it is seldom affected by fetal nutritional problems, presentation or oligohydramnios,
14,22
being a good parameter for dating the pregnancy. It is
measured (Fig. 9.2) from the origin to the distal end of the shaft, from the greater
trochanter to the lateral condyle. The femoral head and distal epiphysis are not
included in the measurement and the bone should be perpendicular to the ultrasound beam. The femur grows 3 mm per week from 14 to 27 weeks and 1 mm
per week in the third trimester.22 Reported accuracy for pregnancy dating ranges
from 1 week in the second trimester to 3–4 weeks at term.
22
The humerus, tibia, radius and ulna may be measured in the same way as the
FL, but they are traditionally not used to date the pregnancy. The tibia and fibula
can be differentiated because the fibula is lateral to the tibia. The radius and ulna
22
148
Fig. 9.2 Measurement of the fetal femur length (FL). Reproduced by permission of B.
Verburg.
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can be well differentiated and measured when the arm is in a supine position
because the two bones are lying exactly parallel but in a prone position, the crossing of the two bones requires two different sonar planes to obtain measurements.
The ulna appears longer than the radius proximally but distally both bones end
at the same level.6 The accuracy of measurement of a long bone is affected by
several factors such as the angle of the beam to the long axis of the bone (an angle
close to 90 ° should be obtained) and the type of transducer (linear and convex
probes are better than sector probes).
12
Some researchers have suggested a sort of prenatal ponderal index could be
derived from femur length but most likely this calculation adds little information
to the other commonly used biometric parameters.
14,22
OTHER MEASUREMENTS AND DATING
Binocular distance should be measured as the smallest diameter between the fetal
eyes in a plane including both orbits that must appear symmetrical and equal in
size showing its maximal width.
It may be useful for dating in cases of occiput-posterior position of the fetus,
whenever the measurement of BPD is difficult. This measurement correlates with
GA but its growth is non-linear. Variability in predicting GA is 14 days between
14 and 27 weeks and 24 days between 29 and 40 weeks. Binocular distance is
important in patients at risk for congenital anomalies and syndromes.
The transverse cerebellar diameter (TCD) measured at the level of the suboccipito-bregmatic plane of the head (Fig. 9.3) has a curvilinear relation with GA
and is not much affected by the shape of the head or by growth disturbances.22
Its midpregnancy size in millimetres reflects GA in weeks.
The clavicle has a linear growth throughout the second and third trimesters and
was proposed as a measurement useful for dating, its length in millimetres being
very close to the GA expressed in weeks.
14,22
Having an intramembranous ossification instead of endochondral ossification, the clavicle is different from other long
bones of the body and is not affected by the same disorders.
14,22
Fetal biometry, estimation of gestational age, assessment of fetal growth
Fig. 9.3 Measurement of the fetal transverse cerebellar diameter (TCD). CM, cisterna
magna. Reproduced by permission of B. Verburg.
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Measurement of the scapula, sacrum, iliac bone and foot have been shown to
correlate well with GA.
14
Many fetal organs have been measured and related to GA such as kidney, heart,
aortic and pulmonary arteries.
2,10
DATA REPORT
Fetal size is more uniform in early pregnancy than later. Early estimation of the
GA (11/0–13/6 week scan) or at the routine fetal examination (16–18 weeks)
has been shown to be of considerable value.26 Estimation of day of delivery should
not be done later than 22 weeks (BPD 60 mm). The accuracy reduces from
7 days before 16 weeks to 28 days after 28 weeks. If an early scan has been done
and a second scan yields a later estimate than the first one, it is not advisable to
change the original estimate. The delay is most likely a result of growth restriction. The ultrasonographic composite age is used after the first trimester, obtaining measurements of as many parameters as possible, with the exclusion of AC, to
increase the accuracy of estimate. Most authors favour reporting the lower fifth
Ultrasound in obstetrics and gynaecology
and the upper 95th confidence limits on the prediction of each measurement
since this could have legal implications in case of use in management decisions.
In a multiple pregnancy, most authors agree that the tables used for singleton
pregnancies are appropriate for twins, at least in the first and second trimesters.
It is advised to base the assessment of GA on the larger twin. The delay of fetal
growth in a multiple pregnancy becomes apparent between 25 and 36 weeks of
gestation, being more pronounced in triplets compared to twin pregnancies.
13
22
150
FETAL WEIGHT ESTIMATION
Fetal weight estimation may provide the first indication of abnormal fetal growth.
Multiple methods of estimating fetal weight have been developed, ranging from a
single biometric parameter to the combination of multiple parameters. With the
incorporation of multiple parameters, the error is decreased in comparison with
results derived from AC alone.16 However, the accuracy of fetal weight estimation
depends on several theoretical and practical factors including the variability of fetal
volume and density, the technique and skill of the operator, the scanner and the
formula used for calculation. The error is reported to vary from 15%
The smallest theoretical error in estimate is achieved when true volume is known
with certainty as with water displacement or by direct measurement of physical
dimensions and is calculated to be respectively 7.6% and 8.2%. However, when
sonographic measurement of the fetus is applied, the error increases to 16.2%.23
However, the greatest error occurs at the extremes of fetal weight, with LGA
mostly being underestimated and SGA mostly being overestimated, or in the presence of diabetes or oligohydramnios.22 This inaccuracy can be easily explained since
among fetuses with an abnormal growth pattern, variation of density may be even
greater than in the normal population, whereas reduced amniotic fluid can determine deformation of the fetus, increasing the error of sonographic measurements.
9,22
to 21.2%.16
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The clinical utility of fetal weight estimation is still debated since it is quite
reliable in the case of normality, but often unreliable in the case of pathology, just
when legal problems could originate from the association between an ominous
fetal outcome and what is wrongly called a ‘diagnostic error’. Therefore most
authors agree that the accuracy of fetal weight prediction must be used with
caution for management decisions, in particular for fetuses large for gestational
1,17
age.
The use of three-dimensional ultrasonography in the estimation of fetal
weight is under study and was reviewed in 2000.
25
BIOMETRIC RATIOS
Biometric ratios have been proposed to alert the examiner to the possibility of
nutritional or genetic fetal disorders.4 The range is very wide because the increase
of different body parts, throughout pregnancy, is not synchronous.
The HC/AC ratio described by Campbell and Thomas and the FL/AC ratio
(0.20–0.24) are applicable only to asymmetrical fetuses but the wide overlap
between normal and abnormal values limits their clinical value in the diagnosis of
fetal growth disturbances.4 The HC/AC ratio is greater than 1 until 34–36 weeks'
gestation and decreases to 1 or less until delivery.22 The FL/BPD ratio (71–87%) is
used in the case of suspected skeletal dysplasias or head anomalies.14 Thoracic circumference (TC) is measured at the level of the four-chamber view of the heart.
The TC/AC ratio (0.83–0.95) was suggested to predict pulmonary hypoplasia in
cases of early, long-lasting oligohydramnios or skeletal dysplasia.
22
14,22
Fetal biometry, estimation of gestational age, assessment of fetal growth
OTHER PARAMETERS
Soft tissue thickness is related to the amount of adipose tissue and has been investigated as a marker of fetal nutritional problems. In particular, the thigh circumference and the cheek-to-cheek diameter14 measured on the coronal view of the
face at the level of nostrils and lips have been proposed. The overlap between
values belonging to normal fetuses and those with growth disturbances precludes
the use of soft tissue parameters in management decisions.
11,22
EVALUATION OF FETAL GROWTH
DEFINITION
Growth disturbances often represent a progressive disease and sooner or later the
affected fetus is supposed to develop an abnormal biometry. Therefore, the final
result of growth disturbance can often be diagnosed by a single ultrasound examination with increased sensitivity with advancing gestation. This is particularly true
for fetuses with accelerated growth that are commonly delivered at term, whereas
most growth-restricted infants are delivered prematurely. In addition, even in the
absence of available successful treatment modalities, an early diagnosis of growth
restriction is potentially useful to limit fetal and neonatal wastage.
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According to their weight, neonates can be classified at birth as small for GA
(SGA), appropriate for GA (AGA) or large for GA (LGA). Prenatal definitions for
intrauterine growth retardation (IUGR) have varied widely concerning both the
cut-off value (2SD, 2.5th, 3rd, 5th, 6th percentiles) and the parameter considered
(AC, its growth in 2–3 weeks, biometric ratios, abnormal growth rate defined by
means of individual or personal models). Gardosi et al8 adjusted biometric curves,
taking into account physiological factors such as fetal gender, maternal weight and
height, ethnic group, parity and size of previous children. Deter & Harrist5 applied
a mathematical function to fetal measurements between 15 and 26 weeks' gestation to evaluate the growth potential of the individual fetus, using each fetus
as its own control. Both methods have a limited application in current clinical
practice.
The definition of macrosomia is also imprecise and arbitrary as a variable cutoff is considered for weight at birth (4000, 4200, 4500 g) or for population-based
percentile charts (90th, 95th, 97th percentiles). Although defining a pathological
condition using the 10th and 90th percentile cut-off is statistically correct, it may
not be clinically relevant since abnormal perinatal outcome will generally only
Ultrasound in obstetrics and gynaecology
be seen in cases of birthweight below the 3rd percentile or untreated gestational
diabetes. Actually, growth is a dynamic process and a single sonographic measurement of the fetus is not sufficient to diagnose a growth disorder at its very
beginning, when the size of the fetus could be still within normal. On the other
hand, the availability of serial biometric observation is rare and the interobserver
variability (with two errors in the opposite direction) could heavily influence the
slope of the curve. In addition, in cases of overfrequent scanning requested for
high-risk pregnancies, the interobserver variation could even exceed the expected
fetal growth, leading to unwise management decisions.
152
UNSOLVED PROBLEMS
Many unsolved problems still exist about definition and sonographic evaluation
of fetal growth disturbances:
the widely accepted cut-off value of the 10th and 90th percentile decreases
•
the power of follow-up studies by including normal fetuses since by
definition, 10% of normal infants in any population will have birthweights
at or below the 10th percentile or at or above the 90th percentile
different definitions preclude a comparison between studies and meta-
•
analysis
the utilization of GA-independent standards, such as ratio or ponderal
•
index, and of soft tissue thickness has been unsatisfactory
the classification in symmetrical or proportioned and asymmetrical or
•
dysproportioned fetuses does not help to define the aetiology and prognosis
the cardiovascular and central nervous function could actually be more
•
relevant than the size of the baby and its sonographic evaluation could be
a better target to define fetal well-being.