Archives of Gynecology and Obstetrics

https://doi.org/10.1007/s00404-020-05910-x

MATERNAL-FETAL MEDICINE

10 cases of umbilical cord thrombosis in the third trimester

Ying Zhu1 · Rajluxmee Beejadhursing1 · Yanyan Liu1 

Received: 2 March 2020 / Accepted: 18 November 2020

© Springer-Verlag GmbH Germany, part of Springer Nature 2021

Abstract
Background  Thrombosis of umbilical vessels is a rare occurrence that is difficult to detect during routine antenatal examina-
tions but can lead to poor perinatal outcomes.
Objective  The aim of this study is to examine the association between meaningful clinical manifestations and features
associated with thrombosis of umbilical vessels, and to evaluate optimal management options.
Methods  A retrospective study of umbilical cord thrombi cases enrolled between 2015–2019 was carried out. Data were
analyzed from the medical archives where the diagnosis of all cases was established by histopathology.
Results  Gross examination reported additional cord abnormalities (7/10), including the irregular length of the umbilical
cord, narrowed cord with hyper-coiling, swollen cord with deficiency of Wharton’s jelly, placenta velamentous and umbili-
cal infarction. Pathological examination accounted for 10 cases of umbilical cord thrombosis including umbilical artery
embolism (3/10), umbilical vein thrombi (5/10) and funisitis (2/10). Clinical findings depicted that the chief complaint was
decreased fetal movement companied by nonreactive NST tests (5/10). With the exception of two stillbirths, the remaining
pregnancies (8/10) were terminated by cesarean section. All neonates are alive, including one VLBW and three LBW cases.
Conclusion  We have observed that umbilical structural dysplasia, maternal coagulation disorder, vascular endothelial injury
and elevated blood glucose may lead to the formation of thrombosis. Focus on specific signs during a prenatal ultrasound,
EFM monitoring and counting fetal movements can help in early identification of umbilical cord thrombi. Our results sup-
port the more effective approach of emergency cesarean section during the third trimester.

Keywords  Umbilical cord thrombosis · Third trimester · Perinatal outcomes · Risk factors · Fetal distress

Introduction higher-risk factor for occlusion of the umbilical cord [2]. In

Thrombosis of umbilical cord vessels is a rare occurrence
which is highly associated with perinatal mortality. The inci-
dence of umbilical vein thrombosis manifests more than that
of one or both umbilical arteries, even if adverse outcomes
tend to be more associated with arterial thrombosis [1]. Ana-
tomical cord dysplasia, abnormal length of the umbilical
cord or unusual Wharton jelly morphology may present a
* Yanyan Liu
263600391@qq.com
Ying Zhu
736802127@qq.com
Rajluxmee Beejadhursing
liuxw1810@qq.com
1
Department of Obstetrics and Gynecology, Tongji Hospital,
Tongji Medical College, Huazhong University of Science
and Technology, Wuhan, China
addition, the state of maternal circulation is another signifi-
cant parameter in cases of the placental disease, particularly
when afflicted by complications during pregnancy, such as
gestational diabetes mellitus, hypertensive disorders, or
thrombophilia. These conditions can certainly hinder the
fetal development and its viability by inducing the forma-
tion of blood clots in the umbilical cord, which could cause
intrauterine growth restriction, abnormal umbilical cord
blood flow ratio, newborn thrombotic diseases, and even
perinatal death [3, 4]. However, the etiology and pathogen-
esis of umbilical vascular thrombosis have not yet been fully
comprehended. In this article, we report a series of 10 cases
of umbilical disorders, comprising of umbilical vein throm-
bosis, arterial thrombi and funisitis.

13
Vol.:(0123456789)
 Archives of Gynecology and Obstetrics

Materials and methods

d-dimer

IUGR, polyhydramnios Not satisfied 1.84

2.18
Not satisfied 0.57

1.68
1.69
Not satisfied 1.83

1.08
2.97
4.47
1.79
10 cases diagnosed as umbilical thrombi were retrieved for
this study from the acumulative database of 29,594 patients

Not satisfied
Not satisfied
fetal move-
who gave birth between 2015 and 2019 at the Huazhong

NST and
University of Science and Technology, Tongji Hospital. The

ment
incidence of cord vascular thrombosis is about 1 in 3,000

–
–

–
–
deliveries. Venous thrombosis occurs in approximately 50%
of cases alone and arterial thrombosis in 30%.

Ultrasound findings
Intrauterine Growth Restriction (IUGR) is defined as an

Polyhydramnios
estimated fetal weight below the 10th percentile according
to the Hadlock C formula. Low birth weight (LBW) group

IUGR​
IUGR​

IUGR​
IUGR​
is assigned to neonate weight between 1500 and 2499 g, and
very low birth weight (VLBW) group is attributed to infants

–
–
Fetal death, boy
Fetal death, boy
weighing between 500 and 1499 g [5]. Multiple gestations
and chromosomal abnormalities were excluded from the

6–8, boy

7–8, boy

8–9, boy
7–8, boy

4–8, boy
3–5, boy
analysis. Maternal clinical data and neonatal information

8–9, girl

7–9, girl
Neonate
have been recorded and are presented in Table 1.
Gross features of the placenta and cord were noted in all
cases, including particular findings. Placentas and cords

weight
Maternal Comorbidities Birth
underwent standard histopathological techniques consist-

1.51
2.30
1.29

2.74
3.28
3.30

2.08
4.52
(kg)

–
–
ing of fixation in 10% buffered formalin, sectioning and

I type diabetes mellitus

examination of the cut slices. Sections underwent routine

GDM, hypertension,
GDM, hypertension
processing, embedding and staining with H&E. Stained

GDM, thalassemia
hypothyroidism

Still birth history

Hypothyroidism
slides of the placenta’s and cord’s microscopic features

Hypertension
have been reviewed by two experienced pathologists.

GDM
Vein, excessive short, less than 20 cm
Results

Artery, beaded-like, excessive long,

Vein, Chorioamnionitis, edema,
diameter of cord about 2.5 cm

Gestational age ranged between 3­ 1+2–39+6 weeks (mean

­35+4 weeks) and a mean maternal age of 26.5 years (range

Funisitis velamentous,
20–35 years) at parturition. The 10 cases that were enlisted
Vein, placenta accreta

more than 100 cm

comprised of 3 cases of umbilical artery embolism, 5 cases

No. Gest. age (weeks) Age (years) Gravidity Placenta and Cord

Artery, infarction
of umbilical vein thrombi and 2 cases of funisitis which is Vein, infarction
Artery, twist

defined as an inflammatory process involving the umbilical

Vein, twist
Funisitis

cord structures [6]. Their associated clinical features are

detailed in Table 1.
Clinical investigations found that 4 pregnant women
Table 1  Clinical data of umbilical cord thrombi

& Parity

suffered from gestational diabetes mellitus (GDM), two of

G5P1
G8P1
G1P1

G1P1
G1P1
G3P2

G1P1
G4P2
G1P1
G1P1

whom were diagnosed with polyhydramnios (case 1 and

case 8). Furthermore, one mother had a 15-year medical
history of type I diabetes (case 4). 3 patients had ges-
tational hypertension and 1 had stillbirth history. Ultra-
sound detected only one case of excessive coiling. None
35
26
20

29
27
32

24
24
24
24

of the expectant mothers had any known history of blood

coagulation disorders and D-dimer values ranged between
0.57–4.47 μg/ml. Half of our cases were admitted to a
hospital complaining of a reduction in fetal movement and
32 + 6
38 + 1
31 + 2

39 + 5
39 + 6

35 + 5
35 + 3
39 + 3
34 + 3

repetitive unresponsive EFM recordings (Fig. 1) during

39

their routine prenatal check-up.

10
1
2
3

4
5
6

7
8
9

13
Archives of Gynecology and Obstetrics

Two cases of umbilical cord infarction resulted in fetal
death with the umbilical cords presenting excessive torsion
and slender appearances, respectively for case 9 and case 10.
The remaining 8 cases were terminated by emergency cesar-
ean section and three infants were transferred to the neo-
natal intensive care unit (NICU) due to prematurity which
required respiratory support (cases 3, 7and 8). Fortunately,
the 8 babies are still alive and thriving.
Gross examination of the placenta further revealed that
most cases had other cord complications associated with
enhanced risk of thrombi formation, including long cord
that spanned more than 100 cm (case 6) (Fig. 2a), short
cord measuring less than 20 cm (case 4), narrowed cord
with hyper-coiling (case 5 and case 7), swollen cord with
deficiency of Wharton’s jelly (case 3) and one rare case of
placenta velamentous (Fig. 2b). On pathology, umbilical
vein showed characteristic features of occlusive thrombus
(Fig. 3). Umbilical artery occlusion with thrombus contained
fibrin and hypereosinophilic myocytes (Fig. 4). Another
case displayed perivascular hemorrhage, with necrosis of
the arterial vascular wall, and loss of nuclear detail (Fig. 5).
Discussion
Thrombosis of umbilical vessels is a rare occurrence but
it is insidiously associated with serious consequences. In
pregnancy, the formation of thrombosis in the umbilical ves-
sels is prone to fetal distress, stillbirth and hypoxic-ischemic
encephalopathy. After birth, neonates are likely to develop

Fig. 1  a Electronic fetal heart

rate monitor. An obvious FHR
deceleration (red circle). Two
spots reflect fetal movements
(blue arrow). The bottom
recording displays uterine
activity (black arrow). b Gross
examination shows the umbili-
cal cord thrombosis

Fig. 2  Umbilical cord dysplasia:

a excessive length more than
100 cm; b placenta membrana-
cea

Fig. 3  Thrombosis of umbilical
vein, ×20 magnification (a),
×100 magnification (b)

13

Fig. 4  Thrombosis of the
umbilical artery, hematoxylin
and eosin ×20 magnification
(a); ×100 magnification (b)
Fig. 5  Perivascular hemorrhage around the artery and occlusion with
thrombus is visible in the vein, ×20 magnification
metabolic acidosis, thrombocytopenia, neonatal arterial
thrombosis and cerebral palsy [7]. A retrospective study
reported that up to 10% of 317 spontaneous intrauterine
fetal demise cases were caused by thrombosis of umbilical
cord vessels [2], which entails that such a significant number
should be taken seriously.
According to Virchow’s hypothesis, there are three
key elements that are responsible for thrombosis, namely
hypercoagulability, blood flow stasis and endothelial injury.
Hypercoagulability may be associated with maternal genetic
or acquired factors. In recent years, there have been reports
announcing that some genetic risk factors, responsible for
more than 60% of idiopathic thromboembolic events during
pregnancy [8]. Antithrombin source deeply influences the
expression of protein S and protein C affecting the balance
of anticoagulant material in vascular endothelium providing
a high risk for thrombosis [3, 7]. With respect to non-preg-
nant cohorts, the risk of thrombosis increases from 4 to 5
times in pregnancy [9]. If maternal blood glucose levels are
unstable, the imbalanced expression of endothelial vasodila-
tation factors and shrinkage factors may be induced, which
could evoke disorder of blood coagulation and the eventual
occurrence of blood clots [10]. In our series, 5 out of 10
13
Archives of Gynecology and Obstetrics
pregnant women had elevated blood sugar levels. Positive
identification of risk factors and thrombophilia related indi-
cators are crucial and more importantly, attention should be
prioritized on predisposition and precaution.
Congenital umbilical cord dysplasia such as abnormal
length, umbilical cord stricture or hyper-coiling and defi-
ciency of Wharton’s jelly has been established as risk factors
of the impedance of blood flow velocity because either the
presence of true knots or deposition of collagen can lead to
blood stasis [11–13]. Among the cases presented here, there
are four cases with apparent unusual morphologies of the
umbilical cord, with spindly stricture and little Wharton’s
jelly, leading to mechanical compression and dilated vessels.
In addition, umbilical vein varix is another very rare cord
anomaly associated with occlusion of umbilical vessels. A
recent report describes a case of extra-abdominal umbili-
cal vein varix with an abnormal bean-like dilation of the
umbilical vein which was detected during routine screening
ultrasonography at 23 weeks of gestation. The pathological
examination was coherent with antenatal ultrasonography,
which suggests that fresh thrombi and venous dilatation,
resulting in its occlusion by thrombus formation [14].
As underlined by Avagliano L, the etiology and pathogen-
esis of umbilical vessels thrombosis may be due to endothe-
lial damage caused by intrauterine infections. They were
described as three steps: firstly, fetal inflammatory response
with diapedesis and transmigration of neutrophils across the
vessel walls, followed by neutrophils infiltrating the Whar-
ton jelly in an arc-like distribution, at lastly, encouraging
endothelial activation and vascular smooth muscle lesion,
which ultimately leads to thrombosis [2, 15]. Owing to its
unique anatomy, inflammation begins with the involvement
of phlebitis and is followed by arteritis, then the infiltra-
tion of neutrophils into the Wharton’s jelly [16]. Upon
recent analysis, the thrombosis of the umbilical cord could
be also related to inadvertent umbilical vascular puncture
[17]. Smith et al. described a case of serial intravascular
fetal transfusion complicated by regression of an umbili-
cal artery and occurrence of refractory fetal bradycardia. At
length, thrombosis of the umbilical artery was confirmed
Archives of Gynecology and Obstetrics
by pathology [18]. A similar case was reported character-
izing severe fetal anemia secondary to Rh alloimmuniza-
tion after receiving intrauterine transfusions which led to the
bradycardia. After delivery, intraluminal hematoma of the
umbilical artery was noted. The unique histological change
that was observed was only artery thrombosis where partial
necrosis of the vascular wall was not accompanied by villous
sclerosis [25]. Spasm of the vessel or excessive bleeding
might be induced by inserting the needle into the umbilical
artery [19]. Vasculitis can develop leading to endothelial
damage, inflammatory response and the potential occlusion
of umbilical vessels.
Ultrasound remains the optimal imaging modality which
may provide significant indications in prenatal screening
since it can effectively identify abnormality [14, 20]. A sin-
gle umbilical artery (SUA) is the most common malforma-
tion of the umbilical cord and is regarded as a risk factor for
perinatal mortality [21]. Lutfallah reported a 30-year-old
woman with umbilical artery thrombosis at 33 weeks’ gesta-
tion, who was diagnosed by ultrasound, with a single right
umbilical artery while the other umbilical cord carried a
hyperechoic segment. During the third trimester, the freshly-
formed thrombosis exhibited no obvious abnormalities in
umbilical cord blood flow, amniotic fluid volume and fetal
development [22]. However, sudden fetal death could still
occur without any foretelling signals. In our case, ultrasound
could not be so sensitive owing to the fact that there were
two cases of polyhydramnios and one case of umbilical cord
over spiral have been revealed. In our opinion, more atten-
tion should be paid to clinical symptoms, for example, the
most common complaint was decreased fetal movement and
abnormal electronic fetal heart rate monitoring. We should
be wary of the possibility of umbilical cord thrombosis
and conduct ultrasound examination seriously when we
encounter presentations of fetal distress. Chronic thrombosis
development has a relatively longer duration and adversely
impacts on the maternal–fetal interface, which might lead
to intrauterine growth restriction [23], fetal distress and
Doppler parameters anomalies. A series of seven umbili-
cal artery thrombosis cases have been presented by Shilling
et al. where included three out of seven fetuses exhibited
IUGR and all cases had testimonies of placental hypoperfu-
sion [24]. Sato reviewed 11 cases where all had occlusions
by thrombi of the umbilical cord, leading to 3 instances of
intrauterine growth restriction [25]. Likewise, three neonates
from our study were delivered as low birth weight infant and
one as VLBW. In similar situations, a prenatal ultrasound
examination should pay particular attention to the umbili-
cal cord. Above all, closer scrutiny should be paid and the
expertise of a senior ultrasound physician may be preferred
when a suspicious case be reported [26].
Considering the adverse outcomes, an urgent cesarean
section surgery is recommended following dexamethasone
regimen to promote fetal lung maturity. In our research, a
primiparous woman at 31 weeks and 2 days of gestation
whose initial complaint was a significant reduction of fetal
movements was referred following repeated unsatisfactory
EFM monitoring. After surgery, umbilical cord thrombosis
was confirmed by pathological diagnosis. Meanwhile, the
newborn was transferred to the neonatal intensive care unit
(NICU) for observation which lasted one week. So far, both
the mother and child have smoothly recovered. Intensive
monitoring of clinical parameters, especially focusing on
ultrasound indices, fetal movement, electronic fetal heart
monitoring, coagulation-related changes are necessary for
expectant management. However, the latter’s duration is
still uncertain, and a larger sample study is needed to assess
its effectiveness and to identify ways to prolong gestation.
Many studies believe that cesarean section should be per-
formed without delay [22, 27]. In the case of preterm birth,
antenatal corticosteroid therapy should be given high pri-
ority in cases with an increased likelihood of generating
umbilical cord clots. Moreover, since the prematurity of the
neonate is often unavoidable, measures should be taken to
ensure transfer and care in NICU equipped with a supportive
environment for extremely and very preterm babies.
Nevertheless, this study has several limitations. First, only
ten pregnant women with thrombosis of umbilical cord were
included in the analyses. A large sample and comparative
studies should be analyzed to get a more comprehensive
understanding of umbilical vessel thrombi. Second, all the
reported cases were in the third trimester, so the effects of
thrombosis on the fetus in the first or second trimester is
unknown. Third, the long-term follow-up of neonates is
inadequate. Thus, we could not evaluate survival rates and
long-term implications of babies born with umbilical cord
thrombosis. However, the data in this study permit a general
assessment of the clinical characteristics and perinatal out-
comes of umbilical cord thrombosis.
Conclusion
Thrombosis of umbilical vessels is a rare occurrence and
cannot be easily diagnosed during the antenatal examination.
Congenital umbilical cord dysplasia, maternal abnormal
blood glucose, endothelial infections and intrauterine trans-
fusion could be likely etiologies. While ultrasound remains
the most reliable imaging diagnostic tool, we believe that
complaints of unusual fetal movement, evidence from non-
stress test and gestational age should also be taken into
consideration. Theoretically, delivery could be delayed as
long as ultrasonographic scans and fetal monitoring are
stable while being kept under close surveillance. Owing to
the adverse outcomes related to umbilical thrombosis, our
findings recommend that the more effective approach is to
13

perform an emergency cesarean section for cases in the third
trimester.
Author contributions  YZ recruited the patients and drafted the article,
RB and YL critically revised the manuscript. Three authors have read
and approved the final manuscript.
Compliance with ethical standards  15. Redline RW (2006) Inflammatory responses in the placenta and
Conflict of interest  The authors report no conflicts of interest.
Ethical approval  The retrospective study was approved by the ethics
committee on human research at Tongji Hospital of Tongji Medical
College of Huazhong University of Science and Technology, Wuhan,
China.
References
1. Heifetz SA (1988) Thrombosis of the umbilical cord: analysis of
52 cases and literature review. Pediatr Pathol 8(1):37–54
2. Avagliano L et al (2010) Thrombosis of the umbilical vessels
revisited. An observational study of 317 consecutive autopsies at
a single institution. Hum Pathol 41(7):971–979
3. Alhousseini A et al (2018) Umbilical artery thrombosis with
associated acute and severe fetal growth restriction and transient
severe protein s deficiency: report of a case with prenatal ultra-
sound diagnosis allowing for timely intervention and good out-
come. Case Rep Obstet Gynecol 2018:6324362
4. Oliveira GH et al (2016) Intrauterine thrombosis of umbilical
artery—case report. Sao Paulo Med J 134(4):355–358
5. Starnberg J et al (2018) Lower cognitive test scores at age 7
in children born with marginally low birth weight. Pediatr Res
83(6):1129–1135
6. Kim CJ et al (2015) Acute chorioamnionitis and funisitis: defini-
tion, pathologic features, and clinical significance. Am J Obstet
Gynecol 213(4 Suppl):S29-52
7. Valero PM, Blazquez DG (2014) Aortic thrombosis in a newborn.
Arch Argent Pediatr 112(6):262–265
8. Trasca LF et  al (2019) Therapeutic implications of inherited
thrombophilia in pregnancy. Am J Ther 26(3):e364–e374
9. Konkle BA (2015) Diagnosis and management of thrombosis in
pregnancy. Birth Defects Res C Embryo Today 105(3):185–189
10. Fritz MA, Christopher CR (1981) Umbilical vein thrombosis and
maternal diabetes mellitus. J Reprod Med 26(6):320–324
11. Peng HQ et al (2006) Umbilical cord stricture and overcoiling are
common causes of fetal demise. Pediatr Dev Pathol 9(1):14–19
13
Archives of Gynecology and Obstetrics
12. Trevisanuto D et al (2007) Overcoiling of the umbilical cord. J
Pediatr 150(1):112
13. Devlieger H et al (1983) Thrombosis of the right umbilical artery,
presumably related to the shortness of the umbilical cord: an unu-
sual cause of fetal distress. Eur J Obstet Gynecol Reprod Biol
16(2):123–127
14. Matsumoto Y et al (2019) A case report of umbilical vein varix
with thrombosis: prenatal ultrasonographic diagnosis and manage-
ment. Case Rep Obstet Gynecol 2019:7154560
umbilical cord. Semin Fetal Neonatal Med 11(5):296–301
16. Kim CJ et al (2001) Histo-topographic distribution of acute inflam-
mation of the human umbilical cord. Pathol Int 51(11):861–865
17. Donepudi RV, Moise KJ Jr (2019) Intrauterine transfusion com-
plicated by umbilical artery thrombosis. Case Rep Obstet Gynecol
2019:5952326
18. Smith JF Jr et al (1999) Umbilical artery regression: a rare com-
plication of intravascular fetal transfusion. Obstet Gynecol 93(5
Pt 2):828–829
19. Van Kamp IL et al (2005) Complications of intrauterine intravas-
cular transfusion for fetal anemia due to maternal red-cell alloim-
munization. Am J Obstet Gynecol 192(1):171–177
20. Hasegawa J et  al (2009) Ultrasound diagnosis and manage-
ment of umbilical cord abnormalities. Taiwan J Obstet Gynecol
48(1):23–27
21. Burshtein S et al (2011) Is single umbilical artery an independ-
ent risk factor for perinatal mortality? Arch Gynecol Obstet
283(2):191–194
22. Lutfallah F et al (2018) A case of umbilical artery thrombosis in
the third trimester of pregnancy. Am J Case Rep 19:72–75
23. Klaritsch P et al (2008) Spontaneous intrauterine umbilical artery
thrombosis leading to severe fetal growth restriction. Placenta
29(4):374–377
24. Shilling C et al (2014) Umbilical artery thrombosis is a rare but
clinically important finding: a series of 7 cases with clinical out-
comes. Pediatr Dev Pathol 17(2):89–93
25. Sato Y, Benirschke K (2006) Umbilical arterial thrombosis with
vascular wall necrosis: clinicopathologic findings of 11 cases.
Placenta 27(6–7):715–718
26. Cook V et al (1995) Umbilical artery occlusion and fetoplacental
thromboembolism. Obstet Gynecol 85(5 Pt 2):870–872
27. Dussaux C et al (2014) Umbilical vein thrombosis: to deliver
or not to deliver at the time of diagnosis? Clin Case Rep
2(6):271–273
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