crown-chin length in normal and anencephalic fetuses at 10 to 14 weeks' gestation
TRANSCRIPT
GENERAL OBSTETRICS AND GYNECOLOGY
Fetus-Placenta-Newborn
Crown-chin length in normal 10 to 14 weeks' gestation
and anencephalic fetuses at
Waldo Sepulveda, MD, Nell J. Sebire, MD, Tak Y. Fung, MD, Eleni Pipi, MD, and Kypros H. Nicolaides, MD
London, United Kingdom
OBJECTIVE: Our goal was to establish a reference range for the fetal crown-chin length at 10 to 14 weeks' gestation and to determine its usefulness in the prenatal detection of anencephaly in the first trimester. STUDY DESIGN: Women attending our center for transabdominal ultrasonographic screening at 10 to 14 weeks' gestation were prospectively recruited for this study. The crown-chin length was measured in a sagittal view of the fetal head, which included the fetal profile, from the highest point of the head to the most anterior aspect of the jaw. Nomograms for the crown-chin length and the ratio of the crown-chin length to the crown-rump length according to gestational age were generated. Additionally, the crown- chin length and the ratio of the crown-chin length to crown-rump length were obtained from a subset of 13 anencephalic fetuses and plotted against the reference range. RESULTS: in normal fetuses the crown-chin length increased (Crown-chin length = 65.2 x Gestational age in days - 28.4; r = 0.74%, p <0.0001) and the ratio of the crown-chin length to the crown-rump length decreased (Ratio of crown-chin length to crown-rump length = -17.2 × Gestational age in days + 60.5; r =0.23, p <0.0001) with advancing gestation. In anencephalic fetuses crown-chin length measurements and the ratio of the crown-chin length to the crown-rump length were below the 5th percentile in 77% and 62% of the cases, respectively. The slope of change in the ratio of the crown-chin length to the crown-rump length with gestational age was significantly different in anencephalic fetuses compared with normal fetuses (t = 2.7, p <0.003). CONCLUSION: Measurement of the crown-chin length at 10 to 14 weeks' gestation provides a technique that can assist in the early recognition of anencephaly. (Am J Obstet Gynecol 1997;176:852-5.)
Key words: Crown-chin length, fetal head, anencephaly, first trimester, ul t rasonography
The prenatal diagnosis of anencephaly is usually ac-
compl ished in the second tr imester by ul t rasonographic
demonst ra t ion of absent calvarian bones and cerebral
hemispheres ] In the first trimester, however, anence-
phalic fetuses usually have the ul t rasonographic feature
of acrania with an almost normal amoun t of cerebral
tissue but absence of calcified calvarian tissue3 -4 Because
of the cont inuing exposure to amniot ic fluid, the unpro-
tected brain tissue is progressively rubbed off, leading to
the classic features found in the second trimester. 5
In a first-trimester mul t icenter ul t rasonographic
screening study, in 26% of 31 anencephal ic fetuses the
diagnosis was not made at the 10- to 14-week scan. a In the
From the Harris Birthright Resem~h Centre jbr Fetal Medicine, King's College Hospital Medical School. Received for publication September 23, 1996; revised November 1, 1996; accepted December 12, 1996. Reprints not available from the authors Copyright © 1997 by Mosby-Year Book, Inc. 0002-9378/97 $5.00 + 0 6/1/79845
same study it was also noted that the crown-rump length
(CRL) was significantly lower in anencephal ic fetuses
than in normal ones, with 27% of them having a CRL
< 5 t h p e r c e n t i l e ) It is likely that this lower CRL measure-
men t could be the result of a smaller cerebral size, and in
this sense sagittal measurements of the fetal head could
provide a potentially more useful tool for the early
recogni t ion of this condit ion. The aims of this study were
to establish a normal range for the fetal mentovert ical
diameter , or crown-chin length (CCL), and to de te rmine
whether this measu remen t is a useful t echnique in the
prenatal detect ion of anencephaly in the first trimester.
Mater ia l and m e t h o d s
Pregnant women with live fetuses, who were a t tending
our center for t ransabdominal ul t rasonographic screen-
ing for fetal ch romosomal defects at 10 to 14 weeks'
gestation, 7 were prospectively recrui ted for this study.
Af ter fetal viability was confi rmed, a sagittal view of tile
852
Volume 176, Number 4 Sepulveda et al. 853 Am J Obstet Gynecol
Fig. 1. Ultrasonographic measurements of CCL at 12 weeks' gestation (between calipers), a, Normal fetus; b, anencephalic ferns.
Crown-chin length (mm)
45
40 . . , ~
• | = I
• | • I
30 ~ ' i ; ! I ~ U : , " . / ' / ; ; m • . • = . = =
• • a i I s | • i • . ' : ' 5 : / J ' , t , l x ~ ' , • / /
J • ' I : ~ { : ! i ' " ~ , . . , . ~ ! i - ' ' - - . / " 25 / .. : : .jA5 I .i i - ; ~ .
J J : ..,
10 70 72 74 76 78 80 82 84 86 88 90 92 94 96 9 8 1 0 0
G e s t a t i o n (days)
Fig. 2. Scattergram of CCL measurements according to gesta- tional age (CCL = 65.2 × Gestational age in days - 28.4). Lines
represent mean and 95% confidence interval.
CCL/CRL Ratio (%)
50 • , , , . 1 ! , "
• , i ' l l ' " , i ' : •
, . ; " i ! i : " " ' " " •
40 " ' '
30
20 70 72 74 76 78 80 82 84 86 88 90 92 94 96 98100
Gestation (days)
Fig. 3. Scattergram of CCL-to-CRL ratio at 10 to 14 weeks' gestation (CCL-to-CRL ratio = 17.2 × Gestational age in days + 60.5). Lines represent mean and 95% confidence interval.
fetus was o b t a i n e d for CRL a n d n u c h a l t rans lucency
thickness m e a s u r e m e n t s with the use of f rozen images
and e lec t ron ic cal ipers with a 0.1 m m discr imina t ion , v
T h e CCL was o b t a i n e d by m e a s u r i n g the dis tance be-
tween the h ighes t p o i n t of the fetal h e a d a n d the mos t
an t e r i o r aspect of the jaw in the sagittal view, which
i n c l u d e d the fetal prof i le (Fig. 1, a). A similar m e t h o d
was used to ob ta in CRL a n d GCL m e a s u r e m e n t s in a
subset of a n e n c e p h a l i c fetuses (Fig. 1, b). D e m o g r a p h i c
details a n d u l t r a sonograph ic f indings were e n t e r e d in to
a c o m p u t e r database. Gesta t ional age was calculated
f rom the first day of the last mens t rua l per iod. W o m e n
with i r regula r cycles or u n k n o w n dates a n d those with a
d i screpancy of -->7 days be tween dates a n d CRL measure-
men t s were exc luded f rom this study.
T h e re la t ion be tween ges ta t ional age a n d CCL, CRL,
854 Sepulveda et al. April 1997 Am J Obstet Gynecol
Crown-chin length (mm)
45
40
35
30
25
20
15
10 70 72 74 76 78 80 82 84 86 88 90 92 94 96 98100
Gestation (days)
Fig. 4. CCL in 13 anencephalic fetuses. Lines represent normal range.
and CCL-to-CRL ratio was examined with l inear regres-
sion analysis. Compar ison of the slopes between groups
of normal and anencephal ic fetuses was carried out by
g rouped linear regression with covariance analysis. Addi-
tionally, Spearman 's rank correlat ion was used to exam-
ine the degree of association between the CRL and CCL
measurements .
Results
Cross-sectional measurements of the CCL and CRL
were obta ined f rom 400 singleton pregnancies at a
median gestational age of 12 weeks 1 day (range 10 to 14
weeks). The re was a significant correlat ion between the
CCL and the CRL (r = 0.86, 95% conf idence interval
0.84 to 0.89, p <0.0001). The CCL increased (r = 0.74, p
<0.0001) and the CCL-to-CRL ratio decreased (r = 0.23,
p <0.0001) with gestation (Figs. 2 and 3). Table I shows
the 2.5th, 50th, and 97.5th percent i les of the CCL
according to gestational age.
The CCL and the CCL-to-CRL ratio were also mea-
sured in a subset of 13 anencephal ie fetuses. Values were
below the normal range in 77% and 62% of the cases,
respectively. N o n e of the anencephal ic fetuses evaluated
after the twelfth week had measurements within the
normal range (Fig. 4). The slope of change in the
CCL-to-CRL ratio with gestational age was significantly
Table I. Predict ion values of the crown-chin length
according to gestational age
Gestational age 2.5th percentile 50th percentile 97.5th percentile
10 wk 0 days 12.1 17.2 22.3 10 wk 1 days 12.7 17.8 23.0 10 wk 2 days 13.4 18.5 23.6 10 wk 3 day's 14.1 19.2 24.2 10 wk 4 days 14.7 19.8 24.9 10 wk 5 days 15.4 20.5 25.5 10 wk 6 days 16.0 21.1 26.2 11 wk 0 days 16.7 21.8 26.8 11 wk 1 days 17.3 22.4 27.5 11 wk 2 days 18.0 23.1 28.1 11 wk 3 days 18.7 23.7 28.8 11 wk 4 days 19.3 24.4 29.4 11 wk 5 days 20.0 25.0 30.1 11 wk 6 days 20.6 25.7 30.7 12 wk 0 days 21.3 26.3 31.4 12 wk 1 days 21.9 27.0 32.0 12 wk 2 days 22.6 27.6 32.7 12 wk 3 days 23.2 28.3 33.3 12 wk 4 days 23.9 28.9 34.0 12 wk 5 days 24.9 29.6 34.6 12 wk 6 days 25.2 30.2 35.3 13 wk 0 days 25.8 30.9 35.9 13 wk 1 days 26.5 31.5 36.6 13 wk 2 days 27.1 32.2 37.2 13 wk 3 days 27.8 32.8 37.9 13 wk 4 days 28.4 33.5 38.6 13 wk 5 days 29.4 34.1 39.2 13 wk 6 days 29.7 34.8 39.9 14 wk 0 days 30.3 35.4 40.5
different between the groups of normal and anence-
phalic fetuses (t = 2.7, p = 0.003) (Fig. 5).
Comment
This study demonstrates that CCL measurements can
be obta ined by t ransabdominal ul t rasonography at 10 to
14 weeks' gestation. Because the fetal head is the most
p r o m i n e n t segment of the body dur ing the first trimes-
ter, availability of nomograms for the fetal head size can
be a valuable adjunct for early pregnancy dating. Further-
more, as shown in this series this t echnique is potentially
useful in the early prenatal detect ion of anencephaly.
Ul t rasonographic measu remen t of the nuchal translu-
cency thickness at 10 to 14 Weeks' gestation is the most
effective me thod for screening of fetal chromosomal
defects. 7 Because the nuchal translucency thickness var-
ies with gestational age, 7 accurate dat ing is impor tan t for
reliable calculation of the risks. Since the original de-
scription of the use of static ul t rasound e q u i p m e n t in
1973, first-trimester human pregnancies have tradition-
ally been dated by the CRL. s However, fetal s tretching
movements and changing in the curvature of the early
fetus can affect the variability of the measurement , thus
reducing its accuracy. 9'1° Indeed, data f rom assisted
pregnancies in which there is a conf ident concept ion
date show that discrepancies between gestational age and
CRL measurements increase steadily after the fort ieth
Volume [76, Number 4 Sepulveda et al. 855 ~'Mn J Obstet G)~]ecol
CCL/CRL Ratio (%)
60
50
40
30
20
• = ; i
• • • • • | | • • . • ,
• • ' . ; ; ' : " I ! " . " . . - - - - - - -~_" ' i : , ' " ; ! I ; -" : • ,
• " i a • ; • : = \~ • • -" m " | • "
. .
" " . - : , ; ! . ~ , ' 1 : ; ~" • • ~'L~ m I m-- • | " . • '
.,:<. , :
x
\
7 2 7 4 7 6 7 8 8 0 8 2 8 4 8 6 8 8 9 0 9 2 9 4 9 6 9 8 1 0 0
G e s t a t i o n ( d a y s )
Fig. 5. Scattergram of CCL-to-CRL ratio with gestational age in normal fetuses (small solid squares) and anencephalic fetuses (solid circles) showing corresponding regression lines.
day, which coincides with the deve lopment of the fetal
sp ineJ ~ In this regard, because the CCL i s not inf luenced
by fetal position, rout ine implementa t ion of this tech-
n ique at 10 to l4 weeks' gestation could overcome the
difficulties encoun te red with the CRL when fetal move-
ments are present. Moreover , the adjunctive use of the
CCL could also be useful to conf i rm or reject informa-
tion on gestational age derived f rom the CRL alone.
However, in the cur ren t study it was not possible to
de te rmine whether the CCL is a bet ter predictor of
gestational age than the CRL because the operators were
no t b l inded regarding informat ion on gestational age
and CRL measurements .
The re is growing evidence that anencephaly is the end
stage of a wide spect rum of anomalies affecting the fetal
calvarium, in which progressive destruct ion of cerebral
tissue leads to the classic appearance of anencephaly in the second and third trimesters, s~ Our data provide
additional suppor t for this hypothesis, because CCL
measurements and CCL-to-CRL ratios in anencephal ic
fetuses progressively diverge f rom the normal with ad-
vancing gestation. In the first t r imester u l t rasonographic
findings in anencephal ic fetuses range from the pres-
ence of a normal brain with no ossification of the
calvarium to disorganized cerebral tissue without a cra-
nial vault. It has been suggested that the ul t ras•no-
graphic diagnosis of this lethal abnormali ty is not possi-
ble before 12 weeks, when ossification of the cranial vault
should begin. In a previous ul t rasonographic screening
f rom our group we demons t ra ted that anencephaly can
be confidently de tec ted at the 10- to 14-week scan if signs
of acrania are specifically looked for, 6 including absent
cranial vault, smaller cerebral hemispheres , abnormal
outl ine of the cerebral tissue, and disorganized brain
tissue with cystic areas in the cephalic pole. Frequently,
these ul t rasonographic signs are subtle and not easily
recognizable by the ul t rasonographer . Measurement of
the CCL promotes a focused examinat ion of the fetal
head, facilitating the early recogni t ion of congeni ta l
anomalies affecting the cephalic pole. The detect ion of
abnormal measurements should p r o m p t the ultrasonog-
rapher to under take detailed transvaginal ultrasonogra-
phy or close follow-up to establish the final diagnosis.
The role of CCL measurements in the early recogni t ion
of o ther major brain abnormali t ies requires fur ther
investigation.
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