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The Journal of Maternal-Fetal & Neonatal Medicine
ISSN: 1476-7058 (Print) 1476-4954 (Online) Journal homepage: http://www.tandfonline.com/loi/ijmf20
Analysis of cystic hygroma diagnosed in the
prenatal period: 5-years’ experience at a tertiary
hospital in Southeastern Turkey
Hüseyin Çağlayan Özcan, Mete Gurol Uğur, Özcan Balat, Seyhun Sucu,
Neslihan Bayramoğlu Tepe, Ebru Öztürk, Özge Kömürcü Karuserci & Tanyeli
Güneyligil Kazaz
To cite this article: Hüseyin Çağlayan Özcan, Mete Gurol Uğur, Özcan Balat, Seyhun Sucu,
Neslihan Bayramoğlu Tepe, Ebru Öztürk, Özge Kömürcü Karuserci & Tanyeli Güneyligil Kazaz
(2017): Analysis of cystic hygroma diagnosed in the prenatal period: 5-years’ experience at a
tertiary hospital in Southeastern Turkey, The Journal of Maternal-Fetal & Neonatal Medicine, DOI:
10.1080/14767058.2017.1418315
To link to this article: https://doi.org/10.1080/14767058.2017.1418315
Accepted author version posted online: 14
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Published online: 27 Dec 2017.
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ORIGINAL ARTICLE
Analysis of cystic hygroma diagnosed in the prenatal period: 5-years’
experience at a tertiary hospital in Southeastern Turkey
H€
useyin C¸a
glayan
€
Ozcan
a
, Mete Gurol U
gur
a
,
€
Ozcan Balat
a
, Seyhun Sucu
a
, Neslihan Bayramo
glu Tepe
a
,
Ebru
€
Ozt€
urk
b
,
€
Ozge K€
om€
urc€
u Karuserci
a
and Tanyeli G€
uneyligil Kazaz
c
a
Department of Obstetrics and Gynecology, School of Medicine, Gaziantep University, Gaziantep, Turkey;
b
Bahceci IVF Clinic, Istanbul,
Turkey;
c
Department of Biostatistics, School of Medicine, Gaziantep University, Gaziantep, Turkey
ABSTRACT
Purpose: Our aim was to evaluate the association of cystic hygroma (CH) with fetal malforma-
tions and also to investigate the outcome of fetuses with CH diagnosed in the prenatal period.
Methods: We divided the CH patients into two main groups as isolated CH or CH associated
with the congenital structural abnormality (CSA) by measuring the thickness of CH and showing
other fetal abnormalities. Pregnancy outcomes were recorded as spontaneous abortion, elective
termination, intrauterine death, live birth, postnatal death, and lost to follow-up.
Results: There were 74 cases of fetal CH including 19 in CSA-CH group and 55 in isolated-CH
group diagnosed between 11 and 21 weeks’gestation. Karyotype analysis of these 28 patients
revealed 18 (64.2%) normal karyotypes. Pregnancy outcomes included 54 elective terminations,
five postnatal deaths, one spontaneous abortion, six live births, four intrauterine deaths, and
four patients were lost to follow-up.
Conclusion: In the presence of any CSA concurrent with CH, prognosis may be considered as
poor and any additional help of fetal karyotyping is questionable. But fetal karyotyping may be
advocated in counseling patients with isolated CH, in which a better prognosis and resolvement
of CH may be expected in case of a normal karyotype.
ARTICLE HISTORY
Received 14 August 2017
Accepted 29 November 2017
KEYWORDS
Congenital structural
abnormality; cystic
hygroma; prenatal diagnosis
Introduction
A neck mass is most commonly originated from cys-
tic hygroma (CH) in the prenatal period [1]. CH typic-
ally develops in the region of the fetal neck as a
congenital abnormality of the vascular lymphatic sys-
tem [2]. The incidence of prenatal CH is one in 200
[3] spontaneous abortions, one in 600–700 low-risk
pregnancies [4], and 0.35% in singleton pregnancies
[5]. There is a growing incidence of CH in the late
first trimester to early second trimester, becoming
less common in the advanced weeks of pregnancy
[6–8]. CH is less common in the second trimester and
rarely resolves before birth [8]. Fetal aneuploidy is
highly associated with abnormal fetal nuchal translu-
cency between 10 and 14 weeks of gestation [9,10].
Congenital structural abnormalities (CSA) and abnor-
mal karyotype contribute to the poor prognosis in
the prenatal period [9]. In the presence of CH, any
additional abnormal finding helps the clinician in
consulting the family for making a decision to ter-
minate the pregnancy or not [11].
Our aim was to evaluate the association of CH with
fetal malformations and also to investigate the out-
come of fetuses with CH diagnosed in the prenatal
period.
Materials and methods
We reviewed our database to identify patients with CH
that are diagnosed and/or referred to our tertiary clinic
between 2012 and 2017. Demographic and clinical
data were retrieved for all patients. Institutional review
board approval was obtained with 303/2017-project
number for this cross-sectional retrospective study. All
patients approved the informed consent. We only
included pregnancies with live fetuses that had sep-
tated CH at the fetal neck in first or second trimester
(between 11 and 21 weeks of gestation). The presence
of molar pregnancy, ectopic pregnancy, acrania, and
encephalocele was considered as exclusion criteria.
The same experienced obstetrician team performed
the ultrasonographic examinations by using Voluson
CONTACT H€
useyin C¸aglayan
€
Ozcan ozcan.caglayan8@hotmail.com Department of Obstetrics and Gynecology, Gaziantep University, Faculty of
Medicine, Sahinbey, Gaziantep, Turkey
ß2017 Informa UK Limited, trading as Taylor & Francis Group
THE JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE, 2017
https://doi.org/10.1080/14767058.2017.1418315
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E6
V
R
(GE Healthcare, Milwaukee, WI); multi-frequency
convex transducer 2.14–6.10 MHz. The diagnosis of
fetal CH depended on increased nuchal translucency
(NT) (equal to or above the 95th percentile for CRL)
with the use of transverse and mid-sagittal sono-
graphic views of the fetal neck (Figures 1 and 2).
Common features of CH included excess nuchal fluid
with one or more septations and intact skull with spi-
nal column [12,13]. We offered routine fetal karyotyp-
ing to all patients via chorionic villi sampling (CVS) at
the first trimester or amniocentesis (AS) at the second
trimester. We divided the CH patients into two main
groups as isolated CH or CH associated with the con-
genital structural abnormality (CSA) by measuring the
Figure 1. Ultrasound image of a septated cystic hygroma which demonstrates the transverse view of the fetal neck.
Figure 2. Ultrasound image of a septated cystic hygroma which demonstrates the mid-sagittal sonographic view of the fetal neck
(asterisk indicates the thickness of fetal cystic hygroma).
2H. C.
€
OZCAN ET AL.
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thickness of CH and showing other fetal abnormalities.
Pregnancy outcomes were recorded as spontaneous
abortion, elective termination, intrauterine death, live
birth, postnatal death, and lost to follow up. The deci-
sion of termination was made due to the consensus
report among three obstetricians after counseling and
approval of the parents. We suggested autopsy to all
patients after abortion, termination of pregnancy or
perinatal death and confirmed the diagnosis after aut-
opsy or pathological examination in all fetuses.
Results
There were 74 cases of fetal CH including 19 in the
CSA-CH group and 55 in the isolated-CH group diag-
nosed between 11 and 21 weeks’gestation. There was
no significant difference regarding maternal age and
gestational age (days) between CSA-CH group and iso-
lated-CH group (28.22 ± 7.37 versus 28.18 ± 7.27 and
102 ± 19.09 versus 96.78 ± 19.31) (p¼.969 and
p¼.128). Cytogenetic studies could not be performed
in 46 patients (62.2%) that refused prenatal karyotyp-
ing. A total of 28 patients underwent karyotyping
including 22 CVS and 6 AS. The karyotyping rate in
the isolated-CH group and the CSA-CH group were
40% (22/55) and 31.5% (6/19), respectively. Karyotype
analysis of these 28 patients revealed 18 (64.2%) nor-
mal karyotypes. Our study demonstrated 10 abnormal
fetal karyotypes (35.7%) including six trisomy 21 cases
(60%), three trisomy 18 cases (30%), and one trisomy
13 cases (10%). Associated abnormalities in the CSA-
CH group were hydrops fetalis, skin edema, polycystic
kidneys, pleural effusion, gastroschisis, intra-abdominal
ascites, cardiac abnormality (hypoplasia of right ven-
tricle), talipes equinovarus, achondroplasia, and rhizo-
melia. Pregnancy outcomes included 54 terminations
(32 terminations with no karyotype available and iso-
lated CH, 13 terminations with normal karyotype and
CSA, five terminations with isolated normal karyotype,
and four terminations with abnormal karyotype), five
postnatal deaths, one spontaneous abortion, six live
births, four intrauterine deaths, and four patients were
lost to follow-up.
There were six live-birth isolated CH patients with
normal karyotype that CH resolved spontaneously. In
our database, the length of CH could be measured
only in 31 patients. Twenty-one of 31 fetuses had CH
with 6 mm. These 21 patients were associated with
abnormal karyotype in three (3/6, 50%) patients and
CSA in eight (8/21, 38%) patients. Ten patients with
CH less than 6 mm were also associated with abnormal
karyotypes in two cases (2/6, 33%) and CSA in three
patients (3/10, 30%) and one of these patients had
both these findings concurrently. The features of CH-
CSA patients are summarized in Table 1. The outcomes
of isolated CH patients are documented in Table 2.
Table 1. The outcome of cystic hygroma patients with congenital structural abnormality.
Number of patients Cytogenetic analysis Pregnancy outcome Age (years) Gestational age (days)
2 Trisomy 21 1 Intrauterine death
1 Postnatal death
–Trisomy 18 –
–Trisomy 13 –28.22 ± 7.37
a
102 ± 19.09
a
13 Not available 13 Elective terminations
4 Normal 1 Intrauterine death
1 Postnatal death
2 Elective terminations
a
Mean ± std deviation.
Table 2. The outcome of isolated cystic hygroma patients.
Number of patients Cytogenetic analysis Pregnancy outcome Age (years) Gestational age (days)
4 Trisomy 21 1 Intrauterine death
2 Elective terminations
1 Spontaneous abortion (one of the twins)
3 Trisomy 18 1 Postnatal death
2 Elective terminations
28.18 ± 7.27
a
96.78 ± 19.31
a
1 Trisomy 13 1 Postnatal death
33 Not available 33 Elective terminations
1 Intrauterine death
14 Normal 4 Lost to follow up
6 Live birth
3 Elective terminations
1 Postnatal death
a
Mean ± std deviation.
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Statistical analysis
The normality of distribution of continuous variables
was tested by Shapiro–Wilk test. Mann–Whitney Utest
was used for comparison of two independent groups
of variables with a non-normal distribution. Statistical
analysis was performed with SPSS for Windows version
24.0 (SPSS Inc., Chicago, IL) and a pvalue <.05 was
accepted as statistically significant.
Discussion
In our study, fetal karyotyping could be available only
in 28 of 74 CH patients. Among these 28 patients, we
demonstrated 10 CH patients with an abnormal karyo-
type including two with CSA-CH and eight with iso-
lated CH. Although we offered routine fetal
karyotyping to all patients, majority of the couples (46
patients) refused prenatal karyotyping cytogenetic
studies. The refusal rate of suggested prenatal karyo-
typing in CH patients was quite high (62.2%) and we
think that this rate is highly influenced by religious
motives and social or cultural concerns of the society.
Couples in the CSA-CH group abundantly preferred to
end the pregnancies (79%) but this choice was less
remarkable in the isolated CH group (71%).
The incidence of chromosomal aneuploidies, miscar-
riage, cardiac, lymphatic, skeletal and pulmonary
abnormalities, single-gene defects, familial inheritance,
and a wide range of other congenital syndromes are
highly related to CH [14]. Normal karyotype can be
associated with 22–32% of CH [15]. Different types of
abnormalities are associated with CH in 60% of
patients and there is a growing risk for fetal aneu-
ploidy with the additional number of abnormalities
[15,16]. Our study demonstrated a 64.2% (18/28) rate
normal karyotype in a small subset of 74 patients with
karyotype analysis available. Subgroup analysis showed
that in the CSA-CH group, normal karyotype rate was
66.6% (four of six patients), which is similar with the
isolated CH group (63.6%, 14/22). We think that this
finding, which is in contradictory with the literature,
very surprising. But this finding may also be the result
of a selection bias. Only 40% of the patients agreed to
have karyotyping in the isolated-CH group, whereas
31.5% in the CSA-CH group. This is of clinical signifi-
cance and we suggest that there is an evident need
for further large-scale reports to clarify if there is a dif-
ference in abnormal karyotype between isolated CH
and CSA-CH fetuses. This finding Normal karyotype
rate of CH patients was higher in our study compared
with the literature that may be related to limited num-
ber of available karyotyping. The incidence of
abnormal karyotypes in our series (35.7%) is different
from other reports, varying between 51% and 61%
[17,18]. In our study, trisomy 21 was the most com-
mon chromosomal abnormality consistent with
Malone [19] and Scholl’s finding [20].
The protein-rich fluid in CH patients is characterized
by fetal hypoproteinemia, generalized edema, and
non-immune hydrops [16]. Lymphatic obstruction can
cause a variety of cardiac defects by compression of
the dilated lymphatic ducts to the aorta as well as the
left atrium [21]. The hydropic fetuses result in death
with a rate of 96.5% [22]. CH may either regress or
progress to generalized edema. Chervenak et al. [6]
found that severe hydrops leads to fetal death, but
some reports showed that hydrops and CH could com-
pletely recover [15,23]. We found in our study that
nine fetuses with hydrops in the CSA-CH group
resulted in either termination or intrauterine/postnatal
death. The prognosis is very poor if CH is associated
with hydrops fetalis [24] that is consistent with our
study. Some of the previous studies recruited pregnan-
cies with both septated and non-septated CH [6,25,26].
We included only the patients with septated CH in our
study in order to rule out other causes of fetal
increased nuchal edema. First-trimester NT scan is
becoming widespread as part of screening for fetal
aneuploidy [27] as well as for fetal structural abnor-
malities [9].
We agreed with previous studies that CH associ-
ated with fetal abnormalities is associated with a
much worse prognosis [12,28–31]. The outcome of
CH in fetuses with a normal karyotype depends on
the presence of any additional defects [30,31].
Spontaneous resolution before 20 weeks can be con-
sidered as a good prognostic indicator. Pregnancy
can be continued if both karyotype and detailed
ultrasonography are normal with a close follow up
[32]. In cases of persisting CH after 20 weeks with
normal karyotype and no associated sonographic
abnormalities, the decision to terminate or to con-
tinue must be discussed with the parents, for the
reason that there is no obvious answer in the litera-
ture [33]. In our study, we observed six live-births
only in isolated CH patients with a normal karyotype
(14 patients). Three out of 14 patients chose to ter-
minate their pregnancies and four of the remaining
11 patients were lost to follow-up. Therefore, the
chance of a live birth is at least 55% in cases with
isolated CH and a normal karyotype. We confirmed
the resolution of CH by recalling the parents after
birth and examining the babies. We believe that if
there is no CSA and abnormal karyotype in the
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prenatal examination, the pregnancy outcome may
be in favor of both for parents and fetus.
As for the structure of CH in euploid fetuses,
Bernstein et al. [34] reported that both the maximum
size and septation of CHs were associated with poor
fetal prognosis [35]. A study of about 1320 fetuses
with a euploid karyotype and increased nuchal translu-
cency in the first trimester reported the worse out-
come in 61.7% of cases with nuchal size larger than
6.5 mm [13]. Patients with normal karyotype and nor-
mal structure, but with non-immune hydrops are can-
didates for intrauterine management. Success depends
on the size of CH, but intrauterine or neonatal death
has a high incidence [36]. In our study, CH patients
with 6 mm resulted in 19 terminations and two intra-
uterine deaths. There was no association between size
of CH (>6mm or <6 mm) and clinical outcomes.
Another interesting finding in our study is that
although there is no significant difference (p¼.557),
patients with a CH >6 mm had less abnormal karyo-
types than patients with a CH <6 mm. Associated CSA
rate was more in patients with a CH >6 mm, as
expected (p¼.657).
There are some limitations of our study. First, 45
patients preferred termination without completing the
entire prenatal examination including CVS, amniocen-
tesis, and detailed sonography. Second, the small
number of CH cases might lower the power of our
study. Third, the lack of data in all patients might lead
to decrease the realization regarding the effect of CH
size on prognosis. Fourth, there was a small subset of
patients with normal karyotype available.
Conclusion
Fetal karyotyping, detailed sonography and documen-
tation in order to provide detailed parental counsel-
ing separately have important priorities in CH
patients due to the presence of high risk for aneu-
ploidy and fetal malformation. In the presence of any
CSA concurrent with CH, the prognosis may be con-
sidered as poor and any additional help of fetal kar-
yotyping is questionable. Fetal karyotyping may be
advocated in counseling patients with isolated CH, in
which a better prognosis and resolvement of CH
may be expected in case of a normal karyotype. But
there are so little results from this group to come to
that conclusion due to the significant number of ter-
mination for isolated defects with and without
karyotyping.
The need for large-scaled multicenter studies is evi-
dent for developing more conclusive data regarding
management of patients with CH.
Acknowledgements
There is no acknowledgement to declare.
Disclosure statement
There is no conflict of interest in our study to declare.
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