European Journal of Obstetrics & Gynecology and Reproductive Biology 184 (2015) 8083

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European Journal of Obstetrics & Gynecology and

Reproductive Biology
journal homepage: www.elsevier.com/locate/ejogrb

Isolated single umbilical artery: evaluating the risk of adverse

pregnancy outcome
Mariella Mailath-Pokorny a,*, Katharina Worda a, Maximilian Schmid a,
Stephan Polterauer b, Dieter Bettelheim a
a
b

Medical University of Vienna, Department of Obstetrics and Gynecology, Division of Obstetrics and Feto-maternal Medicine, Austria
Medical University of Vienna, Department of Obstetrics and Gynecology, Division of General Gynecology and Gynecologic Oncology, Austria

A R T I C L E I N F O

A B S T R A C T

Article history:
Received 28 August 2014
Received in revised form 29 October 2014
Accepted 11 November 2014

Objective: To evaluate if isolated single umbilical artery (SUA) diagnosed on second-trimester ultrasound
has an independent risk association with adverse pregnancy outcomes.
Study design: We compared 136 singleton pregnancies with isolated SUA with 500 consecutive singleton
pregnancies with a three-vessel cord (3VC). Pregnancies complicated by chromosomal abnormalities
and other congenital malformations were excluded. The rates of intrauterine growth restriction (IUGR)
dened as birth weight less than the 3rd percentile, small for gestational age (SGA) fetuses, dened as a
birth weight lower than the 10th percentile and the incidence of very preterm deliveries before 34 weeks
of gestation were compared between the two groups. Multivariable logistic regression analysis was
performed to evaluate the risk association between SUA and adverse pregnancy outcomes, while
controlling for potential confounders.
Results: Fetuses with isolated SUA had signicantly lower birth weight (2942.5  783.7 vs.
3243.7  585.6 g, p = 0.002), and were delivered at an earlier gestational age (38.7  3.4 vs.
39.5  2.2 weeks, p < 0.001), when compared to fetuses with a 3VC. Fetuses with isolated SUA were at
higher risk for IUGR (15.4% vs. 1.8%, p < 0.001), SGA (20.6% vs. 4.4%, p < 0.001) and very preterm delivery
(6.6% vs. 1.4%, p = 0.002). Using a multiple logistic regression model, isolated SUA was shown to be an
independent risk factor for IUGR (adjusted OR = 11.3, 95% CI 4.825.6; p < 0.001) and very preterm delivery
(adjusted OR = 5.0, 95% CI 1.813.8; p = 0.002).
Conclusions: The presence of isolated SUA is independently associated with an increased risk for IUGR,
SGA and very preterm delivery.
2014 Elsevier Ireland Ltd. All rights reserved.

Keywords:
Single umbilical artery
Perinatal outcome
IUGR
SGA
Preterm delivery

Introduction
The absence of one umbilical artery, which represents the most
common anatomical abnormality of the umbilical cord, is found in
0.22.0% [14] of deliveries. The pathogenesis of this condition,
known as single umbilical artery (SUA), is uncertain. Aplasia or
atrophy of the missing vessel has been suggested in the etiology
[5]. Fetuses with SUA are considered at increased risk of
chromosomal and structural abnormalities and increased adverse
perinatal outcome, such as perinatal mortality, growth restriction

* Corresponding author at: Medical University of Vienna, Department of

Obstetrics and Gynecology, Waehringer Guertel 18 20, 1090 Vienna, Austria.
Tel.: +43 1 40400 2821; fax: +43 1 40400 2862.
E-mail address: mariella.mailath-pokorny@meduniwien.ac.at
(M. Mailath-Pokorny).
http://dx.doi.org/10.1016/j.ejogrb.2014.11.007
0301-2115/ 2014 Elsevier Ireland Ltd. All rights reserved.

and preterm labor [2,3,6,7]. Despite these associations, controversy

exists regarding the clinical signicance of SUA as an isolated
nding in a low-risk patient population. Some of the current
literature did not demonstrate an increased risk of IUGR in
anatomically normal fetuses with SUA and the authors suggested
that the remaining artery in SUA fetuses carries twice the blood
volume of an artery in a 3VC [4,8,9]. Other studies reported that the
nding of SUA is associated with increased incidence of fetal
growth restriction, prematurity and perinatal mortality and
recommended serial sonograms for fetal growth and close
obstetric follow-up [3,1013].
While other authors have placed much emphasis on the
association between SUA and aneuploidy or co-existing anomalies
[1,2,57,1012], the aim of our study was to estimate the rates of
adverse pregnancy outcome in a low-risk patient population.
Therefore, we included only fetuses without known chromosomal

M. Mailath-Pokorny et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 184 (2015) 8083

abnormalities and associated major congenital anomalies and

evaluated the risk of intrauterine growth restriction (IUGR), small
for gestational age (SGA) fetuses and the incidence of deliveries
before 34 gestational weeks compared to a control group of
500 fetuses with a three-vessel cord (3VC) using a robust,
prospectively obtained database.

81

entering preterm birth or presence of IUGR as dependent variable

and risk factors as covariates. The statistical software SPSS 18.0 for
Windows (SPSS 18.0, SPSS Inc, Chicago, IL, USA) was used for
statistical analyses. p-Values of <0.05 were considered statistically
signicant.
Results

Materials and methods

This is a retrospective cohort study of consecutive patients,
with a two-vessel umbilical cord, who received second-trimester
ultrasonography at our tertiary referral center between 2004 and
2011 as part of routine antenatal care. Study approval was
obtained from the institutional review board of the Medical
University of Vienna (ECS 1160-2013). Demographic information,
maternal medical and obstetrical history, ultrasonographic ndings, and genetic screening or diagnostic results are entered into a
prospective perinatal database at the time of the ultrasound
examination for all patients seen at our institution. Additionally, all
pregnancy and neonatal outcome information, assessed by a
neonatologist, was entered into this database. A SUA was
diagnosed by visualizing two vessels on a cross section of the
umbilical cord. If necessary, color ow mapping was used to
visualize the umbilical arteries adjacent to the fetal bladder. When
SUA was suspected, a detailed second trimester fetal anomaly scan
was undertaken according to routine clinical practice and the
patients were offered fetal karyotyping. Doppler ow indices of the
uterine and the umbilical artery were performed in all cases at 20
25 weeks of gestation. We measured the Pulsatility Index (PI) of the
umbilical artery in each fetus together with PI ow measurements
and notch evaluation of the uterine arteries was obtained. All
measurements were performed in accordance to the guidelines of
the International Society for Ultrasound in Obstetrics and
Gynecology (ISUOG) (www.isuog.org).
Primary outcomes included the risk of IUGR, small for
gestational age fetuses (SGA), intrauterine fetal death (IUFD)
and very preterm delivery in cases of isolated SUA.
Estimation of fetal weight was calculated by applying the
Hadlock formula using composite measures of fetal biometry
[14]. IUGR was dened as birth weight less than the 3rd percentile
and SGA was dened as a birth weight less than the 10th
percentile. Very preterm delivery was dened as a delivery before
34 gestational weeks and IUFD was dened as fetal death at
20 weeks or more of gestation.
The institutions perinatal database was the used to identify
500 consecutive pregnancies with a 3VC, which were seen during
the same time period at our institutions outpatient clinic. All
baseline characteristics as well as the incidence of the primary
outcomes were compared between patients with and without
isolated SUA. Additionally we controlled for potential confounders
such as obesity, dened as a BMI >30, tobacco use, gestational
diabetes with insulin treatment, hypertension and methadone
abuse. Given the known risk of adverse pregnancy outcome in
fetuses with aneuploidy and severe malformations, all cases with
chromosomal abnormalities and major fetal anomalies were
excluded.
Statistical analysis
In this cohort study we used descriptive statistics for analyses of
patients demographic data. Values are given as mean (standard
deviation [SD]) when normally distributed or as median (range) at
presence of skewed distribution. Students t-test was used to
compare continuous variables, and Chi square test and Fishers
exact test was used to compare categorial variables. For
multivariable analysis a logistic regression model was used

In total, 209 cases of SUA were identied during the 8-year

study period, giving an incidence of 1.4% in our patient population.
Seven (3.3%) fetuses showed chromosomal abnormalities (Trisomy
21 (n = 1), Trisomy 18 (n = 4), Trisomy 9 (n = 1) and chromosomal
mosaicism (n = 1)). All fetuses with karyotype aberrations showed
other malformations affecting the central nervous system (n = 2),
the heart (n = 4) or the urogenital system (n = 1). Twenty (9.6%)
chromosomally normal fetuses presented with other major
structural anomalies: Ten fetuses showed congenital heart defects
(atrioventricular valve dysplasia (n = 2), Tetralogy of Fallot (n = 3),
double outlet right ventricle (n = 2), ventricular septal defect
(n = 3)). In 10 cases structural malformations affected the
following systems: musculoskeletal (n = 2), gastrointestinal
(n = 1), urogenital (n = 4) and central nervous system (n = 3).
Additionally, 18 (8.3%) twin pregnancies were observed (dichorionic (n = 16); monochornionic (n = 2)). Cases with congenital
malformations, chromosomal anomalies and multiple pregnancies
were excluded from the cohort. Additionally 28 (13.4%) patients
had to be excluded because they were referred from other
hospitals for a second opinion sonogram and data on pregnancy
outcome was missing. In total, 136 fetuses showed single umbilical
artery as an isolated nding and delivered at our center. These
cases were used for analysis. Maternal demographics and
pregnancy characteristics for our population are shown in
Table 1. Twenty-ve (18.4%) women opted for prenatal karyotyping revealing normal test results. The remaining pregnancies
resulted in healthy infants, therefore no additional karyotypes
were obtained in the postnatal period. Patients with fetuses with
isolated SUA were found to have a comparable BMI at the time of
ultrasound examination and similar rates of hypertension,
preeclampsia, gestational diabetes, tobacco use and substance
abuse compared to patients with a 3VC (n = 500).
Patients with isolated SUA delivered earlier than patients
without SUA (38.7  3.4 weeks vs. 39.5  2.2 weeks, mean difference: 0.8 weeks, p = 0.002) and birth weights were signicantly lower
in neonates with SUA (2942.5  783.7 g vs. 3243.7  585.6 g, mean
difference 301.2 g, p < 0.001) compared to the 3VC group. Results of
the univariate analyses are provided in Table 2. The rate of very
preterm delivery before 34 weeks of gestation was increased in
pregnancies with SUA (p = 0.002) even after controlling for BMI >30,
hypertension, preeclampsia, gestational diabetes, cigarette smoking
and methadone abuse (Table 3). Patients with isolated SUA were at
increased risk for IUGR compared to those without SUA (15.4% versus
1.8%; p < 0.001) (Table 2). The association between SUA and IUGR
Table 1
Patients characteristics (n = 636).

Maternal age (years)

Gravidity
Parity
Gestational age at ultrasound (weeks)
BMI > 30
Diabetes
Preeclampsia
Cigarette smoking
Substance use
Fetal sex (female)
BMI, body mass index, SD, standard deviation.

N or mean

% or SD

28.6
2.7
1.1
21.4
84
51
9
173
13
306

6.5
1.6
1.1
4.7
13.2%
8%
1.4%
27.2%
2%
48.1%

M. Mailath-Pokorny et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 184 (2015) 8083

82

Table 2
Characteristics of women diagnosed with isolated single umbilical artery compared
with controls.

Gestational age
at delivery (weeks)
Preterm birth
before 34 weeks
Birth weight (g)
IUGR
Birth weight
<10th percentile
BMI > 30
Diabetes
Hypertension
Preeclampsia
Cigarette smoking
Methadon use

Single umbilical
artery (n = 136)

Controls
(n = 500)

N or
mean

N or
mean

% or SD
3.4

38.7

2942.5
21
28

783.7
15.4%
20.6%

17
12
6
1
30
5

12.5%
8.8%
4.4%
0.7%
22.0%
3.7%

7
3243.7
9
22

p-Value

% or SD

39.5

6.6%

Odds
ratio

2.2

N/A

0.002b

1.4%

5.0

0.002a

585.6
1.8%
4.4%

67
39
27
8
143
8

13.4%
7.8%
5.4%
1.6%
28.6%
1.6%

N/A
10.0
5.6

<0.001b
<0.001a
<0.001a

0.9
1.1
0.8
0.5
0.7
2.3

0.89a
0.72a
0.82a
0.69a
0.16a
0.17a

Chi-square test.
Students t-test.
SD, standard deviation; IUGR, intrauterine growth restriction; BMI, body mass
index.
b

Table 3
Multivariate logistic regression model.
Risk of preterm birth

Risk of IUGR

Variables

OR

95% CI

p-Value

OR

95% CI

p-Value

SUA
BMI > 30
Diabetes
Hypertension
Cigarette smoking

5.00
0.43
0.70
3.35
0.75

1.813.8
0.053.5
0.095.7
0.716.4
0.22.7

0.002
0.43
0.74
0.14
0.66

11.13
2.02
0.00
4.56
1.11

4.825.6
0.75.6
0.00N.A.
1.316.4
0.52.7

<0.001
0.17
0.99
0.02
0.82

IUGR, intrauterine growth restriction; OR, Odds ratio; 95% CI, 95% condence
interval; SUA, single umbilical artery; BMI, body mass index; NA, not available.

(adjusted OR 5.0, 95% CI 1.813.8, p = 0.002) remained statistically

signicant even after controlling for potential confounders (Table 3).
Patients with isolated SUA were also at increased risk for SGA
compared to those without (20.6% versus 4.4%; p < 0.001) (Table 2).
In 4 (1.8%) cases of IUGR fetuses and in 5 (2.3%) cases of appropriate
for gestational age fetuses notching in the uterine arteries was
observed. No patient developed preeclampsia. Doppler velocimetry
measurements of the umbilical artery showed pathological results in
3 (1.4%) cases. Of these, 2 fetuses had an IUGR.
Of the 136 cases of isolated SUA, 75 (55.1%) neonates were
delivered vaginally and 62 (45.6%) neonates were delivered by
cesarean section (primary cesarean section (n = 51); secondary
cesarean section (n = 11)). Of the 11 cases of secondary cesarean
section, 6 (6/136; 4.4%) neonates were delivered by an emergency
cesarean section due to fetal distress. In the SUA cohort in total
9 patients were delivered before 34 weeks. Of these, 3 patients
were delivered vaginally and 6 by cesarean section. Indications for
the very preterm deliveries were premature rupture of membrane
(n = 6), spontaneous preterm labor (n = 2) and IUGR with fetal
distress (n = 1), respectively. In the control group we observed a
vaginal delivery rate of 70.8%. 29.2% were delivered by cesarean
section, with a 2.7% cesarean section rate due to fetal distress. No
case of IUFD or neonatal mortality was observed in the study
population.
Comment
The aim of this study was to estimate the risk of IUGR, SGA and
very preterm birth, associated with the nding of isolated SUA on

second-trimester ultrasound using a robust, prospectively

obtained database. Using a large retrospective cohort of patients,
our study demonstrates that the nding of isolated SUA on secondtrimester ultrasound is associated with an increased risk for IUGR,
SGA fetuses and very preterm birth. The incidence of these adverse
pregnancy outcomes was signicantly higher than in the 3VC
group, even after controlling for potential confounders affecting
adverse pregnancy outcome. Using multivariate analysis, we
observed a 5-fold risk for very preterm delivery and a 11-fold
risk of IUGR compared to a 3VC control group. Our ndings are in
accordance with previous reports of Khalil [10], Gornall et al. [11],
Rinehart et al. [12] and Hua et al. [3], who demonstrated that the
presence of an isolated SUA was associated with a poorer perinatal
outcome as compared with a 3VC cohort. The authors reported
IUGR rates between 20% and 50%, respectively [3,11,12]. The
higher prevalence of IUGR or SGA neonates has been related to a
possible reduction in cytoplasmatic mass caused by malnutrition,
rather than the total cell reduction that is usually seen in
malformed fetuses with an early IUGR [13]. The incidence of IUGR
in our cohort (15.4%) was lower than the rates previously reported,
which may be due to the low-risk nature of our patient population,
including only fetuses without congenital malformations or known
chromosomal anomalies. Other researchers did not nd an
increased risk of IUGR in SUA pregnancies. Three recent case
control studies showed no signicant difference in neonatal
outcome when SUA is found without other congenital anomalies
and the authors suggested that routine serial ultrasound for fetal
growth is not warranted in the presence of isolated SUA
[4,8,9]. However, the study of Predanic et al. has only limited
power since 57 of 141 pregnancies were excluded because the
diagnosis of SUA was not veried after delivery [4]. The study of
Wiegand and co-workers [9] lacks data about birth weight and
newborn examination and the article of Bombrys et al. [8] has been
criticized for demographic differences between the comparison
cohorts [3]. One might argue that the incidence of prematurity and
lower birth weight found in the SUA cohort could be inuenced by
iatrogenic preterm deliveries. As our data could show none of the
very preterm deliveries in the SUA cohort was iatrogenic due to
isolated SUA. All cases had additional underlying indications for
vaginal delivery or cesarean section such as PROM, breech
presentation and/or preterm labor.
The presence of an isolated SUA has also been associated with
increased rates of perinatal mortality [15]. In our study population,
no case of IUFD or perinatal mortality has been observed. The rate
of secondary cesarean section deliveries was 8.1% with a rate of
4.4% emergency cesarean section deliveries due to fetal distress,
which is lower than the 19% reported by Gornall et al. [11]. The
higher rate, as reported by Gornall et al. may be explained by the
studys heterogenous patient population, including a composite of
fetuses with congenital anomalies and multiple pregnancies.
Doppler ow measurements in isolated SUA did not predict
adverse neonatal outcome, since 21 fetuses developed IUGR and
pathologic Doppler values of uterine and umbilical artery were
only observed in 4 and 2 cases, respectively. These ndings are
consistent with previously published data, where Doppler ow
indices were within normal ranges [16,17], in cases of isolated and
non-isolated SUA. Other authors however describe abnormal
umbilical artery Dopplers in up to 30% of fetuses [18], showing a
higher amount of growth restriction, complex malformations, or
chromosomal abnormalities in these cases.
Strengths of this study include our prospectively maintained
perinatal database from which robust clinical data including
obstetrical history, maternal demographic data, pregnancy outcome and neonatal outcome data was extracted. Our large sample
size of isolated SUA allowed us to estimate the relationship
between isolated SUA and multiple outcomes of interest.

M. Mailath-Pokorny et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 184 (2015) 8083

Limitations of our study include its retrospective study design and

the fact that not all patients in the cohort underwent invasive
aneuploidy testing. However, none of the neonates with isolated
SUA had any dysmorphic features on postnatal examination by a
neonatologist. Therefore, cytogenetic studies to exclude aneuploidy were not warranted. Additionally we do not have a histopathologic conrmation of SUA and as previously reported, even in
expert hands, the false positive diagnosis of a two-vessel cord may
be made [19,20]. However, a recent study by Lamberti et al. [21],
who compared the ultrasound diagnosis of a two-vessel cord with
postnatal histopathology, reported a sensitivity and specicity of
86% and 99%, respectively for the ultrasound diagnosis of SUA in
the second trimester.
Conclusion
In conclusion, our study demonstrates that nding of isolated
SUA is associated with an increased risk for IUGR, SGA and very
preterm birth. Using multivariate analysis, we observed that the
association between isolated SUA and adverse pregnancy outcome
persists even when other risk factors are excluded from the
analysis. The information gained from this study may be useful for
patient counseling and may also provide important information for
developing appropriate antenatal management strategies.
Acknowledgements
We state that there are no nancial or other relationships that
might lead to a conict of interest.
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