crown-chin length in normal and anencephalic fetuses at 10 to 14 weeks' gestation

4
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, ultrasonography The prenatal diagnosis of anencephaly is usually ac- complished in the second trimester by ultrasonographic demonstration of absent calvarian bones and cerebral hemispheres] In the first trimester, however, anence- phalic fetuses usually have the ultrasonographic feature of acrania with an almost normal amount of cerebral tissue but absence of calcified calvarian tissue3 -4 Because of the continuing exposure to amniotic 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 multicenter ultrasonographic screening study, in 26% of 31 anencephalic fetuses the diagnosis was not made at the 10- to 14-week scan. a In the From the Harris Birthright Resem~h Centrejbr Fetal Medicine, King's College Hospital Medical School. Receivedfor 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 anencephalic fetuses than in normal ones, with 27% of them having a CRL <5th percentile) It is likely that this lower CRL measure- ment 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 recognition of this condition. The aims of this study were to establish a normal range for the fetal mentovertical diameter, or crown-chin length (CCL), and to determine whether this measurement is a useful technique in the prenatal detection of anencephaly in the first trimester. Material and methods Pregnant women with live fetuses, who were attending our center for transabdominal ultrasonographic screen- ing for fetal chromosomal defects at 10 to 14 weeks' gestation, 7 were prospectively recruited for this study. After fetal viability was confirmed, a sagittal view of tile 852

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Page 1: Crown-chin length in normal and anencephalic fetuses at 10 to 14 weeks' gestation

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

Page 2: Crown-chin length in normal and anencephalic fetuses at 10 to 14 weeks' gestation

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,

Page 3: Crown-chin length in normal and anencephalic fetuses at 10 to 14 weeks' gestation

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

Page 4: Crown-chin length in normal and anencephalic fetuses at 10 to 14 weeks' gestation

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.

R E F E R E N C E S

1. Nyberg DA, Mack LA. The spine and neural tube defects. In: Nyberg DA, Mahony BS, Pretorius DH, editors. Diagnostic ultrasound of fetal anomalies. Chicago: Year Book, 1990: 146-202.

2. Wilkins-Haug L, Freedman W. Progression of exencephaly to anencephaly in the human fetus--an ultrasound perspec- tive. Prenat Diagn 1991;11:227-33.

3. Granchrow D, Ornoy A. Possible evidence for secondary degeneration of central nervous system in the path•genesis of anencephaly and brain dysraphia. Virchows Arch A [Pathol Anat] 1979;384:285-94.

4. Hendricks SK, Cyr DR, Nyberg DA, Raabe R, Mack LA. Exencephaly--clinical and ultrasonic correlation to anen- cephaly. Obstet Gynecol 1988;72:898-901.

5. Timor-Tritsch IE, Greenebaum E, Monteagudo A, Baxi L. Exencephaly-anencephaly sequence: proof by ultrasound imaging and amniotic fluid cytology. J Matern Fetal Med 1996;5:182-5.

6. Johnson SP, Sebire NJ, Snijders RJM, Tunkel S, Nicolaides KH. Ultrasound screening for anencephaly at 10-14 weeks of gestation. Ultrasound Obstet Gynecol 1997;8:14-6.

7. Pandya PP, Snijders RJM,Johnson SP, Brizot ML, Nicolaides KH. Screening for fetal trisomies by maternal age and fetal nuchal translucency thickness at 10-14 weeks of gestation. BrJ Obstet Gynaecol 1995;102:957-62.

8. Robinson HP. Sonar measurements of fetal crown-rump length as means of assessing maturity in first trimester of pregnancy. BMJ 1973;4:28-31.

9. Goldstein SR. Embryonic ultrasonographic measurements: crown-rump length revisited. AmJ Obstet Gyneco11991;165: 497-501.

10. Daya S. Accuracy of gestational age estimation by means of fetal crown-rump length measurements. Am J Obstet Gy- uecol 1993;168:903-8.

11. O'Rahilly R, Muller F, Meyer DB. The human vertebral column at the end of the embiTonic period proper. I: The column as a whole. J Anat 1980;131:565-75.