PRENATAL DIAGNOSIS, VOL. 6,5 1-6 1 ( 1986)
ANATOMIC CORRELATES OF ULTRASONOGRAPHIC PRENATAL DIAGNOSIS
JOE c. RIJTLEDGE*, ARTHUR G. WEINBERG*?, JAN M. FRIEDMAN?$, MARY JO HARROD$ AND RIGOBERTO SANTOS-RAMOS~
Departments of *Pathology, t Pediatrics, and $Obstetrics and Gynecology, The University of Texas Health Science Center at Dallas. Dallas. Texas 75235, U.S.A.
SUMMARY
In utero sonographic diagnoses from forty-five malformed infants were correlated with their autopsy findings. Fifty-two malformations were diagnosed prenatally in 42 of the patients but 90 additional malformations were not. Nine sonographically diagnosed abnormalities were not confirmed at autopsy. Factors compromising sonographic diagnosis included : limited examinations, small fetal size, timing of examination, oligohydramnios, fetal posi- tion, nature of the malformation and unfamiliarity of the ultrasonographer with specific malformation syndromes. In utero ultrasonography is an invaluable tool of diagnosing con- genital malformations but has limitations.
KEY WORDS Ultrasonography In utero diagnosis Congenital malformations Fetus
INTRODUCTION
LJltrasonographic study is the method of choice for detecting structural anomalies of the fetus. A wide variety of anomalies have been observed: aberrant twinning, dwarfism, neural tube defects, cervical masses, bowel obstruction, congenital tumours, abdominal wall defects and kidney abnormalities (Hill et al., 1983). Prenatal diagnosis has spawned attempts at early intervention, and in utero treat- ment of hydronephrosis, hydrocephalus and hydrops fetalis secondary to cardiac dysrhythmias (Harrison et al., 1981 ; Clewell et al., 1982; Corson et al., 1983) have been attempted with varying success. This type of intervention is contingent upon an accurate diagnosis not only of the primary defect but also associated fetal anomalies. Few studies, however, have critically evaluated the diagnostic accuracy of fetal ultrasonography.
By correlating the anatomic findings at autopsy with the prenatal ultrasono- graphic diagnoses in 45 patients, we sought to discover the accuracy and limitations of this diagnostic modality in a subset of patients.
METHODS
LJltrasonographic reports of prenatal examination were sought on all neonates and second trimester abortuses with multiple malformations coming to autopsy at Park-
Presented in part at National Foundation Birth Defects Symposium, June 1982, Birming- ham, Alabama, and Pediatric Pathology Club, February 1983, Atlanta, Georgia.
Addressee for correspondence : Joe Rutledge, Department of Pathology, Children’s Medi- cal Center, 1935 Amelia, Dallas, Texas 75235, U.S.A.
0 197-3851/86/010051-11$05.50 1Q 1986 by John Wiley & Sons, Ltd.
Received I 0 April 1985 Revised 10 .lul,y 1985
52 J. C. RUTLEDGE ETAL.
land Memorial Hospital and Children’s Medical Center from July, 1980, to July, 1982. Approximately 300 autopsies for malformations and/or genetic disease were performed during this period; 45 of these had had an antecedent ultrasonographic examination. The reports included not only ultrasound examinations performed in our centre but those from outside physicians as well. No restrictions were placed on the type of ultrasound examination necessary for enrolment in the study; hence, some examinations were routine screenings and some were performed under optimal high resolution conditions. To provide a degree of objectivity, only those diagnoses firmly considered and commented on in the ultrasound report were considered.
High resolution ultrasonography done in our centre was performed by one of us (RSR) managing an obstetric ultrasound case load of > 7500 during the study period using Ronhar 7000 (Phillips) with 3.5 Mhz tranducers with static, real-time sector focused and linear array non-focused scanning. He personally performed the study in all patients at Parkland included in the study. The person actually performing the study at outside institutions is not known. In those studies leading to the termination of pregnancy, the findings were reviewed with at least one medi- cal geneticist, the attending obstetrician, and the Chairman of the Obstetrics Department, and a consensus reached. Level 1 examinations were those that could be performed by an obstetrician and would consist of an evaluation of fetal number, placental location, uterus, fetal viability, BPD, femoral length, abdominal width, and the amount of amniotic fluid. Level 2 examinations, seeking congenital malfor- mations, always involved an extensive physical examination with high-resolution equipment and with physician ultrasonographer participation.
Autopsy permission was sought for all patients with malformations and was obtained in 100 per cent of the pregnancies terminated electively for fetal anatomic defects. Autopsies were performed under the direction of a pediatric pathologist (JCR and AGW) and included necessary ancillary studies, e.g. radiographs and karyotyping. In most cases the external features and internal anatomy were reviewed with a medical geneticist (JMF or MJEH). Approximately 300 autopsies for malformations and genetic disease were performed during this period.
Cases resulting from terminations for prenatally diagnosed chromosomal defects without major sonographically detected malformations (trisomy 21, XXY) were not included. These infants were confirmed at autopsy to be free of major malforma- tions. Infants dying with isolated congenital heart disease were also excluded, as most were referred from outside institutions and did not have a prenatal history of ultrasonographic exam.
An organ-system-by-organ-system correlation between ultrasonographic and autopsy findings was made.
RESULTS
The spectrum of findings in each patient is shown in Table 1. An ultrasound autopsy correlation is noted as a ‘+’ after the anatomic finding; a lack of correlation is designated as a ‘-’. Special cases discussed in detail are noted by an asterisk. Because of the multiple malformations in most patients, the total number of anatomic correlations greatly exceeds the number of patients.
ULTRASONOGRAPHIC DIAGNOSES 53
Abnormal gestations were detected prenatally in two of three cases of arthro- gryposis-one by a lack of fetal movement and the second by the detection of ‘multiple congenital anomalies’ (abnormal positioning being the ultrasound corre- late). A third case was not detected; however, the only ultrasound examination was at 12 weeks gestation, 2 weeks following removal of a simultaneous ectopic pregnancy. It is likely that the contractures and abnormal limb positioning present in this infant were not yet fully developed.
Defects were detected by ultrasound in two of three patients with abnormalities of chromosome 13. While the specific chromosomal defect was not suggested by the ultrasound findings, the major malformations were. Two of the three pregnancies were terminated, one on the basis of the ultrasound data alone. In one case the ultrasound was done to determine gestational age (30 weeks) in a hypertensive mother. Other cases resulting from termination for chromosome defects without major malformations are not included in this survey.
Short limbs were detected in three of five cases of lethal dwarfism, only one of which led to termination of the pregnancy. The case of mesomelic dwarfism was detected early in the study prior to the availability of data on bone growth in preg- nancy (Rutledge el al., 1984). In the two cases in which dwarfism was not diagnosed prenatally, attention seemed to have been focused on the accompanying severe hydrocephalus. In the case of camptomelic dwarfism, the sonographic findings led to a fetogram and a specific prenatal diagnosis. The degree of limb shortening was not a factor in recognizing the presence of dwarfism as two mildly affected patients were diagnosed and the more severely affected dwarfs were missed.
Numerous other skeletal anomalies were present in our population. While two cases of severe kyphoscoliosis were seen, four cases of limb reduction anomalies, two cases of club feet, three cases of radial deformities and five cases of digital anomalies were not. Two false diagnoses of skeletal anomalies were made in infants with normal limbs.
All seven cases of hydrops fetalis and cystic hygroma with edema were diagnosed by ultrasonography. In two early cases, however, the nuchal sonolucencies were erroneously interpreted as neural tube defects. Additional findings not present, but suggested by the ultrasound examination, included diaphragmatic hernia, omphalocele, and ‘multiple congenital anomalies’. The fetal weights ranged from 63 to 1210 g. In none of the cases was a dynamic cardiac examination performed to seek dysfunction.
Abnormalities of the renal system occurred in 14 patients. Detection of poorly functioning abnormal kidneys was hampered by oligohydramnios which was most marked in those with severe renal disease (group 5 , Table 1). Massive renal enlarge- ment was difficult to identify in one case because of a cystically dilated bladder and, in a second case, because of distortion of renal contour. Of the six patients with enlarged kidneys, 75 per cent of those not detected by ultrasound were uni- lateral enlargements rather than bilateral nephromegaly. One case of unilateral enlargement was diagnosed prenatally. Two of the cases of falsely diagnosed renal agenesis were in patients with cloaca1 exstrophy whose anatomy was altered by a short umbilical cord and severe kyphoscoliosis. The renal anatomy could not be defined prenatally in many cases.
The most common CNS abnormality was hydrocephalus as evidenced by ven-
(n
P
Tabl
e 1 a
. Aut
opsy
-Ultr
asou
nd c
orre
latio
n
Gro
up
Prim
ary
diag
nosi
s C
NS
Hea
rt
Ren
al
Lim
bs
1. 2.
3. 4.
5.
6.
7. 8.
9.
10.
II.
Arth
rogr
ypos
is
Arth
rogr
ypos
is
Arth
rogr
ypos
is
Tris
omy
13
Tris
omy
13
Rin
g I3
M
esom
elic
dw
arf
Cam
ptom
etic
dwar
f Sh
ort-r
ib-p
olyd
acty
ly
Ost
eoge
nesi
s impe
rfec
ti C
offin
sins
synd
rom
e H
ydro
ps
Cys
tic hy
grom
a C
ystic
hydr
orna
C
ystic
hygr
oma
Hyd
rops
H
ydro
ps
Ure
thra
l val
ves
Olig
ohyd
ram
nios
tetra
d R
enal
agen
esis
Ren
al ag
enes
is
Cys
tic ab
dom
en
Hyd
roce
phal
us
Hyd
roce
phal
us
Hyd
roce
phal
us
Hyd
roce
phal
us
Hyd
roce
phal
us
Hyd
roce
phal
us
Hyd
roce
phal
us
Hyd
roce
phal
us
Bra
in c
yst
En ce
ph a l o
c oe l e
A
nenc
epha
ly
Ane
ncep
haly
Po
renc
epha
ly
Gas
trosc
hisi
s O
mph
aloc
cle
Gas
trosc
hisi
s C
loac
al ex
stro
phy
Clo
acal
exst
roph
y T
E fi
stul
a H
iata
l her
nia
Con
join
ed-th
orap
agus
C
onjo
ined
-thor
apag
us
Con
ioin
ed-O
mD
haIo
uam
s
Hyd
roce
phal
us
Hol
opro
scnc
epha
ly
Hol
opro
senc
epha
ly
Ence
phal
ococ
le
Hyd
roce
phal
us
Hyd
roce
phal
us
Hyd
roce
phal
us
Hyd
roce
phal
us
-
- + +
R v
en h
ypop
lasi
a -
Mild
L v
cn h
ypop
lasi
a + +
L ve
n hy
popl
asia
+
Mic
rosc
opic
cyst
s
- -
Ren
al h
ypop
lasi
a R
hyd
rone
phro
sis
- H
ypop
lasi
a (2
5% n
orm
al)
Hyd
rone
phro
sis
Post
min
imi
- Sh
onfe
mur
-
Shor
tlim
bs
- Sh
ortli
mbs
+ Sh
ortli
mbs
Sh
ort,
brok
en, b
cnt
Fals
e le
naph
aloc
ocle
?Lim
b an
omal
y -
Fals
e enc
epha
lmoe
le
L hy
dron
ephr
osis
8 cm k
idne
ys
Fals
e ab
sent
kid
neys
Fu
sion
and
dys
plas
ia
Hyp
opla
sia
(50%
nor
mal
) -
R h
ydro
neph
rosi
s
Clu
b fe
et
- Li
mbr
educ
tion
+ Po
lyda
ctyl
y -
Mild
hyd
roap
halu
s
ASD
and VS
D + + + + + +
Tetra
logy
of F
allo
t 7
Hyd
roce
phal
us
Hyd
roce
phal
us
Hyd
roce
phal
us
Hyd
roce
phal
us
Hyd
roce
phal
us
Hyd
roce
phal
us
CMV
hydr
ance
phal
y H
olop
rose
ncep
halu
s C
horo
id p
lexu
s cys
t Fa
lse
brai
n in
tact
Clu
b fo
ot
-
Ren
al ag
enes
is
Fals
e ab
sent
kid
ney
Ren
al a
gene
sis
- R
adia
l hyp
o po
lyda
ctyl
y
- R
adia
l hyp
opla
sia
Fals
e sho
rt li
mbs
Mild
hyd
roce
phal
us
Ence
phal
ocel
e Pe
lvic
mye
loca
le
Pelv
ic m
yelm
ale
Lim
b de
form
ity
Con
tract
ed lo
wer
lim
bs
Con
tract
ed lo
wer
lim
bs
Rad
ial h
ypop
lasi
a
+ - Te
tralo
gy o
f Fal
lot
-
TN
~CU
S
arte
riosu
s I
Fals
e sh
ared
hea
rt Si
ngle
vent
ricle
- Fa
lse a
bsen
t kid
ney
Fals
e abs
ent k
idne
y
- R
hvd
rone
ohro
sis
. .-
,
.
Tab
le 1 b
~~
~
Gro
up
Pnm
ary
diag
nosi
s C
hest
A
bdom
enlb
ack
Oth
er
Rea
son.
type
, pla
ce. a
ge
I.
2.
3. 4.
5.
6.
7.
8.
9.
10.
II.
Arth
rogr
ypos
ia
Arth
rogr
ypos
is
Arth
rogr
ypos
is
Tris
omy
13
Tris
omy
13
Rin
g I3
M
esom
elic
dwar
f C
ampt
omel
ic dw
arf
Shor
t-nb-
poly
dact
yly
Ost
eoge
nesi
s im
perf
ecti
Cof
fin si
ris sy
ndro
me
Hyd
rops
C
ystic
hygr
oma
Cys
tic hy
drom
a C
ystic
hygr
oma
Hyd
rops
H
ydro
ps
Ure
thra
l val
ves
Olig
ohyd
ram
nios
tetra
d R
enal
agen
esis
R
enal
agen
csis
C
ystic
abdo
men
H
ydro
ceph
alus
H
ydro
ceph
alus
H
ydro
ceph
alus
H
ydro
ceph
alus
H
ydro
ceph
alus
H
ydro
ceph
alus
H
ydro
apha
lus
Hyd
roce
phal
us
Bra
in c
yst
Enap
halo
coel
e A
nenc
epha
ly
Ane
ncep
haly
Po
reno
epha
ly
Gas
trosc
hisi
s O
mph
aloc
ele
Cas
trosc
hisi
s C
loac
al ex
stro
phy
Clo
acal
exst
roph
y TE
fist
ula
Hia
tal h
erni
a C
onjo
ined
-thor
apag
us
Con
join
ed-th
orap
agus
+ L
ilngs
32%
exp
ecte
d + -
Lung
s 58%
exp
ecte
d
+ + Lu
ng h
ypop
lasi
a -
Lung
s 8O
hexp
ecte
d ~
Lung
s 62%
exp
ecte
d +
Lung
s 21%
exp
ecte
d + + + + +
Lungs 44% e
xpec
ted
+ Lu
ng h
ypop
lasi
a +
Lung
s 55%
exp
ecte
d
-
Lung
hyp
opla
sia
i
+ + + Su
nken
ches
t + +
Lung
s 74%
exp
ecte
d +
R Lu
ng 6
6% ex
pect
ed
+ .L
ungs
36%
exp
ecte
d +
Lung
s 54%
exp
ecte
d + + + + - * - - +
Smal
l L h
emith
orax
-
Lung
s 50%
expe
cted
-
Lung
s 24%
exp
ecte
d -
Esop
hage
al at
resi
a +
Lung
s SO%
exp
ecte
d +
2 an o
mph
aloc
oele
-
7 er
n om
phal
ocoe
le
-
Smal
l viii
phal
ocoe
le
-
Dia
phra
gmat
ic h
erni
a
? Om
phal
ocoe
le
-
? D
iaph
ragm
atic
her
nia
-
-
-
Ana
latr
esia
- 5 cm th
orac
. mye
loco
ele
Thor
ac-lu
mb.
mye
loco
ele
- -
-
-
Ana
latr
sia
Rac
hisc
hisi
s
-
Om
phal
ocoe
lc
-
Om
phal
ocoe
le
- N
oeye
s N
o ga
llbla
dder
N
o ga
llbla
dder
~
Smal
l gal
lbla
d, p
olyd
ac.
-
Poly
dact
yly
Shor
t um
bilic
al co
rd
-
Abs
ent f
inge
r
? R
achi
schi
sis
Big
blad
der
-
Hyd
rops
Aqu
educ
tal f
ork
Lary
ngea
l atre
sia
Hep
a tos
pkno
meg
aly
-
-
-
Abs
ent R
eyc
Plac
enta
l cys
t
+ K
ypho
scol
iosi
s +
Kyp
hosc
olio
sis
Dia
phra
gm O
K
Tric
uspi
d at
resi
a
Dat
es
? Feta
l sta
tus
Siz
tdat
e -
Mat
erna
l age
-
Siz
tdat
e -
Prio
r ano
mal
y -
Poly
hydr
amni
os
Feta
l dem
ise
-
Feta
ldem
ise
- R
apid
gro
wth
? ? ? ? Fe
tal d
emis
e 1
+ A
ge
Size
Sm
all s
ize
+ Si
ze
Size
D
iabe
tes
Size
4ate
X
-ray
in la
bour
B
leed
ing
- G
esta
Lage
D
iabe
tes
-
Feta
ldem
ise
-
Feta
ldem
ise
?Ano
mal
ies
Perim
etry
Po
lyhy
dram
nios
Po
lyhy
dram
nios
1
+ A
-fet
opro
tein
Fe
tal d
emis
e B
leed
ing
+?
+
IUG
R
+?
Fe
tal d
emis
e
- In
tere
st
2.P
.74
2,P,
19
Z.P.
12
2.P.30
Z,
P,21
2.
0.31
2,P,
36
2,P.
28
2.P.38
1,
0,21
2.P
.34
2,P.
I7
2.P.16
2,P,
32
2.P.
18
2.P.20
I.P
.16
2,P,
I8
Z.P.
18
2,P,
30
I.P,2
1 2.0
.26
2.P.31
+
X-r
ay in
labo
ur
I.P,2
4 C
onjo
ined
-om
phal
opag
us
- Lu
ngs 2
6% e
xpec
ted
-
Om
phal
ocoe
le
+ Ex
stro
pby
of b
ladd
er
-?
1,
P.lS
I
h
-. + -
1ndi
cale
s ul
tras
ound
conf
irm
atio
n: ~
--tn
dica
tcs l
ack
of u
ltras
ound
dia
gnos
is: T
hox
wlh
' are
clar
ified
m tc
xl.
?-In
dw.a
tn
the
ultr
asou
nd di
agno
sis w
as q
untm
ablc
: fal
r 8n
dica
te a
n u
ltras
ound
diag
nost
s not
mnf
vmed
at a
utop
sy. U
nder
Rca
son.
TY
PC
. ma=
. th
e ind
ratio
n. ca
tego
ry of
ultr
asou
nd (le
vel I
=rou
tine.
lew
l2 =h
igh
sol
utio
n): l
ocat
ion
whe
E u
ltras
ound
w
as p
erfo
rmed
. P=
Park
land
Mm
ond
Hor
piIa
l;O=o
lrta
de i
nalii
utm
n);
and
wte
sion
agc.
wl
56 J. C. RUTLEDGE ETAL.
tricular enlargement with cortical thinning. Ventricular enlargement was found at autopsy in 16 cases-14 cases due to hydrocephalus and two due to holoprosen- cephaly. One of the latter was correctly distinguished from simple hydrocephalus prenatally. One case diagnosed as hydrocephalus by ultrasound was actually hydra- nencephaly due to cytomegalovirus. One case of holoprosencephaly (not included in the 16 cases with hydrocephaly) did not exhibit ventricular enlargement. A uni- lateral cystic mass was thought to represent porencephaly on the basis of serial sonographic studies, but only mild ventricular dilation was found at autopsy. The three cases of hydrocephalus not detected in utero were mild; and, in one, the ultrasound was performed at 12 weeks gestation. In another case, serial sonograms failed to detect hydrocephalus until 24 weeks gestational age after negative examination at 8 and 16 weeks. In one infant with holoprosencephaly and renal agenesis, the ventricular dilation was not seen at 27 weeks gestation but was seen immediately prior to delivery. Of therapeutic importance is the observation that ventriculomegaly identified in 16 patients was an isolated abnormality in only three cases. Many of these cases are discussed elsewhere in more detail (Harrod et al. 1984). In four patients with other major anomalies, hydrocephalus was the only abnormality detected prenatally.
Absence of the skull was noted,in both infants with anencephaly, but in another patient, total rachischisis was missed. A 3.9 x 2.5 cm porencephalic cyst was diag- nosed and prompted the termination at 23 weeks gestation in one patient, but the autopsy revealed only a 1 cm choroid plexus cyst lying in a slightly dilated occipital horn. The three occurrences of occipital encephaloceles were diagnosed, but, in one, the internal structure of the brain was said to appear normal when, in fact, it was severely disarranged. Only one of five spinal neural tube defects were seen by ultrasonography ; two of those not seen were pelvic myelomeningoceles in severely deformed infants with cloaca1 extrophy. Twenty-seven major CNS malfor- mations were present in 24 patients and 20 were detected prenatally. In four addi- tional cases, the exact anatomic diagnosis differed from that predicted by ultrasonography .
The major gastrointestinal malformation seen at autopsy in twelve patients was an abdominal wall defect. One of two cases of gastroschisis, one of three cases of bladder exstrophy, and four of seven cases of omphalocele were diagnosed prenatally. In all three cases with bladder exstrophy, the associated omphalocele was seen. The defects were variably sized and the smallest omphalocele (2 cm) was not seen. An omphalocele thought to be present in one case was not. Other gastroin- testinal malformations included an undetected esophageal atresia with TE fistula, two undetected cases of anal atresia, one undetected diaphragmatic hernia and one lethal hiatal hernia seen ultrasonographically as a thoracic mass with intact diaphragm. During the study period we also autopsied seven patients with diaphragmatic hernia who had not been evaluated by sonography prenatally. Only two of these patients had other malformations.
The heart was not studied prenatally in great detail in most of our patients. Thus, it is not surprising that most of the cardiac malformations escaped detection. Right ventricular hypoplasia was the only one of ten cardiac lesions seen. The most clini- cally important discrepancy involved the ultrasonographic delineation of the heart in conjoined twins. In 24-week gestation thoracopagus twins, what was thought
ULTRASONOGRAPHIC DIAGNOSES 57
to be one heart, was actually two hearts with a slender connection at the atria. One heart exhibited tricuspid atresia. Ultrasonography during labour in 3 1 -week cephalothoracopagus twins demonstrated two separate hearts but not the uni- ventricular anatomy of one. An omphalocele was detected in a third set of conjoined twins, but the nature of the twinning was not noted at an outside hospital.
In utero anatomic delineation of lung size was not accomplished in our study. Table 1 demonstrates the common occurrence of pulmonary hypoplasia in many malformed infants. Indeed, 18 patients had lungs small enough to cause pulmonary compromise.
A variety of other malformations, perhaps less important than those noted above, were also seen at autopsy. Sonography did not identify agenesis of the gall- bladder in two patients or hypoplasia of the gallbladder in two others. Occurrences of bilateral and unilateral absence of the eyes were not detected, but surface mor- phology of the face was not routinely sought during these in utero examinations.
In general, prenatal ultrasonography established that the fetus was anatomically abnormal in all but four cases. It failed in 13 cases to define the exact nature of the most important malformation and failed in many to detect malformations in other organ systems.
DISCUSSION
Because of the rapid development of new technologies applicable to diagnostic medicine, clinical decisions are sometimes based on data derived from a new modality prior to the full appreciation of its limitations. Although the sex and size of fetuses have been predicted routinely by ultrasound for years, only recently have reports of the accuracy of such studies been published (Eden etal. , 1983; Gruenewuld et al., 1984; Birnholz, 1983). Our study has demonstrated some of the capabilities and the limitations of prenatal sonographic diagnosis in a referral practice. Awareness of the limitations of prenatal ultrasonography is important in making clinical decisions concerning the pregnancy.
If an anatomic lesion is detected, what are the chances that the defect will ultimately prove to be what the ultrasonographer has predicted? The report of two pregnancies terminated, perhaps unnecessarily, because of ultrasound data highlights the occasional non-specificity of the technique (Corson et al., 1983). In one case, an enlarging sonolucent nuchal mass demonstrated in utero was likely localized placental edema from a resolving hematoma. All of our patients with ultrasonographic nuchal masses had lesions at autopsy, and the major discrepancy was the interpretation of two cystic hygromas as encephaloceles: The implications of these two diagnoses differ, although the ultimate outcome of fetuses with cystic hygromas detected early in pregnancy is grave as reflected by the fact that in one study all eight cases in non-terminated pregnancies died in utero (Cherrenak et al., 1983). The finding of non-specific fetal abdominal calcifications was a factor in the termination of one pregnancy (Corson et al., 1983). Another minor anatomic anomaly had the same result in our patient 31 in whom a brain cyst diagnosed in ulero was actually a small cyst of the choroid plexus. Transient choroid plexus cysts have been detected between 16 and 26 weeks gestation in five patients
58 J. C . RUTLEDGE ETAL.
(Campbell and Pearce, 1983). Follow-up of these patients revealed no neurological defects. The termination of pregnancy for such a lesion is unwarranted.
The inability of ultrasonography to delineate the exact anatomy of all lesions is to be anticipated but is often not considered in making prenatal diagnosis. Moreover, our study demonstrates that some lesions thought to have been present in ufero have no correlate at autopsy. The false diagnosis of renal agenesis is but one example. Discrepancies of this nature are of paramount importance when preg- nancy termination is considered. The false positive rate is likely to vary from institu- tion to institution as demonstrated by only six false positive diagnoses in 244 correctly diagnosed anomalies in another series (Campbell and Pearce, 1983).
Although a wide variety of disorders have been diagnosed by prenatal ultrasonography, the sensitivity of the technique has not been examined by most authors. In a retrospective survey of 51 fetuses (varied gestational ages) studied from a referral population, five had more than one malformation diagnosed prenatally while postnatal studies revealed multiple anomalies in 24 of the babies (Horger and Pai, 1983). Among malformations not seen by ultrasound in that series were meningomyeloceles, polycystic kidneys, gastroschisis, encephalocele, sirenomelia, imperforate anus, cleft palates and congenital heart disease. Ultrasonographic and radiographic examinations failed to detect heterozygous achondroplasia in early pregnancy in two cases (Hall et al., 1979). In the British series of 1718 women at high risk for having an abnormal fetus, the following were not detected: six of 79 patients with open spina bifida, one of 14 with encephalocele, one case of sacral agenesis, one of 18 with omphalocele, one of five with gastro- schisis, one of three with duodenal atresia, one of five with renal agenesis, both cases of renal dysplasia, one of two cases of ostium primum defects and the one case with VSD (Campbell and Pearce; 1983). Our series, in which all patients had complete autopsy examinations, demonstrated numerous anatomic defects which escaped detection by ultrasound. Many of the same lesions not detected in the Horger study were missed in ours, but our series also includes cases in which the following sonographically detectable anomalies were not identified prenatally: hydrocephalus, hydronephrosis, renal agenesis, dwarfism, limb reduction anomalies, diaphragmatic hernia, exstrophy of the bladder, absent eyes, absent gall- bladder and pulmonary hypoplasia. Our study, furthermore, demonstrated the common occurrence of pulmonary hypoplasia in the patients involved and dictates the necessity of improving our diagnostic acumen in examining chest. Because this is an autopsy-based series, the majority of our patients had severe malformations. One might predict that the sensitivity of ultrasound could be even lower if patients with fewer lethal defects were included. While the detection of minor anomalies is of less therapeutic import, identification of all the malformations present may aid in reaching an overall diagnosis and prognosis for the fetus.
Several severe malformations were undetected in utero because of the suboptimal timing of the examination. An ultrasound examination in patient 3 was done prior to the actual development of hydrocephalus and the patient did not return for a follow-up exam. The dynamic development of anomalies must be correlated with the stage of examination. Some patients had ultrasonography performed while already in labour and with suboptimal equipment. Though examinations under compromised circumstances are less than desirable, it nevertheless reflects the
ULTRASONOGRAPHIC DIAGNOSES 59
reality of situations encountered in routine patient care. While information gathered during labour may be too late to allow in utero intervention, such data can alert the delivery room staff to the impending birth of a child who may need prompt pediatric and/or surgical care.
Several anatomic areas were not examined in detail (e.g. hands, heart, palate, eye, gallbladder) during the prenatal examination, which precluded detection of significant defects of those organ systems. The table outlines the abnormalities not seen. In several cases, the sonographic examination was directed to the question of fetal viability; and, hence, only malformations discovered incidentally were diag- nosed. The increased incidence of malformations associated with hydrocephalus is noted not only in our study, but also in the 30 patients with fetal hydrocephalus reported by Williamson et al. (1984). In that study, hydrocephalus was an isolated defect in only 15 per cent of the patients. When malformations are sought, the examination of all organ systems appears to be mandatory to arrive at the complete prenatal diagnosis.
Several malformations were below the resolution of the technology employed. One example is mild hydronephrosis in an infant studied early in gestation. Others include the esophageal atresia, mild facial dysmorphisms, and status of the cerebral aqueduct. Such small lesions, however, may be of little clinical consequence and, in the absence of major malformations, may lead to inappropriate physician and parental anxiety.
Severely deranged anatomy handicaps the in utero examination as illustrated (Figure 1). When major landmarks are missing or have altered orientation, identifi- cation and measurement of important structures may be very difficult. Conjoined
Figure 1
60 J . C. RUTLEDGE ETAL.
twins present a special problem as demonstrated by the inability to clearly delineate cardiac anatomy in our series. Nevertheless, determination of the anatomy in such patients is essential to plan surgical therapy.
The accurate interpretation of sonographic changes is pivotal in the diagnosis of fetal malformations ; a single feature may represent several different malforma- tions, as exemplified by the cystic nuchal mass. Correct or a guarded interpretation depends on a detailed knowledge of the spectrum of congenital malformations that may occur. Involvement in the process by those who have experience in clinical dysmorphology contributes to a refined interpretation and enhanced clinical decision-making.
While demonstrating the limitations of ultrasonographic prenatal diagnosis, some featues of our study preclude extrapolation to the entire population of infants undergoing prenatal diagnosis. We have studied a subset of patients having in utero ultrasonography-those who subsequently came to autopsy. To assess sensitivity, specificity and predictive value for the entire population of infants studied sonographically, prospective, postnatal invasive studies would be necessary to con- firm negative findings and clinically silent positive findings. As demonstrated by the differences in depth of studies performed on our patients prenatally, not all fetuses in our referral area obtained examination under perfect, identical condi- tions. These circumstances reflect the limitations imposed on those who must sub- sequently make recommendations to the parents. The clinician involved in prenatal diagnosis must understand the potential shortcomings of diagnostic studies per- formed by referring physicians to provide him information.
Our study examines the correlation between the sonographic and anatomic find- ings system by system. In many patients, with one major lethal anomaly, the finding of less severe malformations may be inconsequential to medical decision-making. Hence, not all of our reported imaging-anatomic discrepancies would have the same clinical impact.
In utero ultrasonography is a powerful tool for the detection and delineation of birth defects. Optimum examination by experienced physicians is capable of diagnosing many major malformations. However, the certainty of the findings is not always high enough to permit unequivocal recommendations regarding management of the pregnancy to be made. Critical correlations between prenatal examinations and detailed postnatal investigations are likely to improve the diag- nostic value of ultrasonography and should be an integral part of any programme which provides prenatal diagnosis by high resolution ultrasonography. Manage- ment decisions should not be made solely on the basis of interpretations of fetal anomalies made during routine screening sonography examinations. Thorough autopsy examinations provide the feedback necessary to evaluate the ultrasono- graphic data.
ACKNOWLEDGEMENTS
The authors thank Margaret Hardesty for preparation of the manuscript.
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