Single umbilical artery

INTRODUCTION — The umbilical cord typically contains two arteries and one vein. Single umbilical artery (SUA) refers to a variation of umbilical cord anatomy in which there is only one umbilical artery. It may be an isolated finding, or associated with aneuploidy or other congenital anomalies.

This topic will discuss issues related to prenatal diagnosis and pregnancy management of SUA. A review of other umbilical cord anomalies can be found separately. (See "Umbilical cord abnormalities: Prenatal diagnosis and management".)

EMBRYOGENESIS — Three mechanisms have been proposed to explain the development of SUA [1]:

●Secondary atresia or atrophy of a previously normal umbilical artery

●Primary agenesis of one of the umbilical arteries

●Persistence of the original single allantoic artery of the body stalk

Approximately 40 percent of umbilical cords with SUA examined microscopically have muscular remnants, which supports secondary atresia or atrophy of a previously normal umbilical artery as the likely mechanism of SUA in these cases [2].

CLASSIFICATION — SUA has been classified into four types based upon the likely developmental etiology [3,4]:

●Type 1 is the most common form of SUA, comprising 98 percent of cases. The umbilical cord contains two patent vessels, an artery of allantoic origin and a vein derived from the left umbilical vein. This type of SUA has been associated with genitourinary anomalies.

●Type 2 accounts for 1.5 percent of cases. The umbilical cord contains two patent vessels, an umbilical artery of vitelline origin arising from the superior mesenteric artery and a vein arising from the left umbilical vein. Severe fetal anomalies, such as caudal regression syndrome and sirenomelia, have been associated with Type 2 SUA.

●Type 3 is rare. The umbilical cord contains three patent vessels, one artery of allantoic origin and two veins. The veins arise from the left umbilical vein and a persistent anomalous right umbilical vein. This form of SUA has been associated with major congenital anomalies, resulting in a poor fetal prognosis.

●Type 4 is extremely rare. It consists of one artery of either vitelline or allantoic origin and a vein derived from the right umbilical vein. The risk of embryonic loss may be increased in these cases.

PREVALENCE AND EPIDEMIOLOGY — The prevalence of SUA depends on characteristics of the population studied:

●At 11 to 14 weeks of gestation before chorionic villus sampling – 5.9 percent [5]

●At 16 to 23 weeks of gestation on prenatal ultrasound in an unselected population – 0.48 percent [6]

●Among fetal deaths, autopsies, or aborted fetuses – 2.13 percent [7]

●Among live born infants – 0.55 percent [7]

SUA has been reported to occur more frequently in pregnancies at the extremes of maternal age [8] and in those from Eastern European; SUA is less frequent among those from Japan and Africa [3]. There are inconsistent data that male fetuses are more often affected than female fetuses [9] and are more likely to have additional malformations [8]. SUA is more common in fetuses with sirenomelia (sacral agenesis with fused lower extremities) [10].

SUA is more common in twin pregnancies (3.9 to 8.8 percent) [8,11-14], with similar prevalence in monochorionic and dichorionic twins [15]. Isolated SUA has been reported on prenatal ultrasound in 1.7 percent of twins at 17 to 22 weeks of gestation [16]. In twins discordant for SUA, the smaller twin is more likely to have the single artery [8,15,17]. SUA is invariably present in acardiac twins [3].

RISK FACTORS — SUA has been associated with maternal smoking, diabetes, hypertension, and seizure disorders [3,12].

CLINICAL PRESENTATION — SUA may be first detected on obstetric ultrasound examination. In view of the perinatal implications of SUA, we routinely examine the umbilical cord for the number of vessels during the second-trimester ultrasound scan. SUA can be detected in the first trimester, but sensitivity and specificity are higher in the second trimester (sensitivity: 57.1 versus 86.6 percent; specificity: 98.9 versus 99.9 percent in one study [18]). Associated fetal and/or placental abnormalities are common. (See 'Assessment for associated abnormalities' below.)

In the second and third trimesters, the AIUM-ACR-ACOG-SMFM-SRU Practice Parameter for the Performance of Standard Diagnostic Obstetric Ultrasound Examinations recommends imaging the umbilical cord as part of a standard prenatal ultrasound examination and evaluating the number of vessels in the cord [19]. However, the ISUOG guidelines for the routine midtrimester fetal ultrasound examination consider examination of the umbilical cord for number of vessels optional [20].

If not detected prenatally, then SUA should be identified at birth. Examination of the number of vessels in the umbilical cord is a routine component of cord and placental evaluation. The number of umbilical vessels are best counted by cutting the cord in a relatively uniform region (away from bulges of false knots) at least 5 cm from the placental insertion since the two arteries sometimes fuse near the insertion. (See 'Fused arteries at the insertion site' below.)

Ultrasound findings — Ultrasound examination shows only two vessels in the umbilical cord. Larger studies report the left artery is absent more often than the right (59 versus 41 percent [21]) [1,21,22]. The side (left or right) of the missing artery does not appear to have clinical significance [21-24], with the exception of one study that reported complex fetal anomalies and chromosomal abnormalities occurred exclusively when SUA resulted from the absence of the left umbilical artery [1].

Most umbilical cords have a normal diameter despite SUA, but the cord may be velamentous or have a small diameter [25,26]. In the longitudinal view, the two-vessel cord frequently appears straight and non-coiled, although occasionally the single artery may loop around the vein.

Absence of one umbilical artery in the cord necessarily implies the absence of the corresponding intraabdominal portion of the umbilical artery.

The SUA is larger than normal. In the normal three-vessel cord, blood flow to the placenta is approximately equally distributed through both arteries. In the two-vessel cord, the entire fetoplacental circulation is transported through only one artery, resulting in a compensatory increase of the arterial diameter. The diameter of the single artery usually measures more than 50 percent of the diameter of the vein, resulting in an umbilical vein-to-artery ratio <2 (figure 1) [27,28]. In contrast, the arteries in a three-vessel cord usually measure less than 50 percent of the diameter of the vein, resulting in an umbilical vein-to-artery ratio >2. The compensatory increase in the single artery diameter can be seen as early as the early second trimester [28,29].

High-resolution color Doppler ultrasound may demonstrate differences in the impedance indices in the pelvic circulation of fetuses with SUA [30,31]. The discordant intraluminal blood flow between common iliac arteries is more marked as pregnancy progresses, which may be due to both the decrease in resistance in the placental circulation and the increase in resistance in femoral arteries [30,31].

PRENATAL DIAGNOSIS

Normal three-vessel cord — Examination of the number of umbilical vessels in the umbilical cord can be difficult in the first trimester due to the small size of the vessels. In the second and third trimesters, the three umbilical vessels in a normal umbilical cord (image 1) can be easily visualized in a cross-sectional image of the cord by two-dimensional ultrasound examination. Color flow Doppler imaging of the intra-abdominal portions of the umbilical arteries running alongside the fetal bladder confirms the diagnosis.

Single umbilical artery — Prenatal diagnosis of SUA is based on the following:

●Ultrasound examination showing only two vessels in the umbilical cord (cross section or longitudinally) (image 2) [32]. The larger vessel is the vein and the smaller vessel is the artery [3]. In the transverse plane, the two-vessel cord resembles a "soda can tab" when the amount of Wharton's jelly is adequate.

●Color flow Doppler in the region of the bifurcation of the fetal aorta shows intra-abdominal umbilical vessels on only one side of the fetal bladder, which is pathognomonic of SUA (image 3). This is particularly helpful in the first trimester and can facilitate early diagnosis of SUA (image 4).

Counting the number of cord vessels in a free loop of cord could be difficult in the presence of multiple loops of cord because the vessels are in very close proximity to each other. Counting the number of cord vessels in a hypercoiled cord is also difficult for the same reason (image 5). Color Doppler of intraabdominal vessels, however, can be more informative than standard real-time imaging and can clearly depict a two-vessel cord in a free loop of the umbilical cord, irrespective of the helical coiling pattern.

Differential diagnosis

Fused arteries at the insertion site — A potential diagnostic pitfall is only imaging the cord close to the placental insertion because the umbilical arteries may fuse along a short (<3 cm) segment of cord at this site [33]. This results in an umbilical cord with a short distal (placental) segment with two vessels and a long proximal (fetal) segment with three vessels (image 6) [34,35]. Imaging intra-abdominal vessels on both sides of the bladder excludes the diagnosis of SUA in these cases.

Hypoplasia of one umbilical artery — Hypoplasia of one umbilical artery is a variant of SUA in which both arteries are present, but there is a gross disparity in their size and blood flow. The hypoplastic but functional artery can occasionally be detected prenatally by ultrasound [36-42]. Constriction of the umbilical arteries after delivery makes the diagnosis difficult to document postnatally in spite of routine examination of the umbilical cord. (See "Umbilical cord abnormalities: Prenatal diagnosis and management", section on 'Hypoplasia of one umbilical artery'.)

If one artery is atrophic rather than hypoplastic, the muscular remnants of the atrophic artery can only be detected by histologic examination of the umbilical cord [2].

POSTDIAGNOSTIC EVALUATION

Assessment for associated abnormalities — A comprehensive sonographic evaluation of the fetus, cord, and placenta should be performed to look for fetal anomalies, especially genitourinary, cardiac, gastrointestinal, musculoskeletal, and central nervous system anomalies [7,8,10,43-47]. Specific but uncommon anomalies that have been reported with SUA include diaphragmatic hernia, exstrophy of cloaca sequence, sirenomelia sequence, and VATER (VACTERL) association (Vertebral anomalies, Anal atresia, Cardiac defects, Tracheoesophageal fistula and/or Esophageal atresia, Renal & Radial anomalies, and Limb defects) [3,45,48].

The sonographic examination should include:

●A detailed fetal anatomic survey. (See "Overview of ultrasound examination in obstetrics and gynecology", section on 'Second- or third-trimester detailed examination'.)

A standard four-chamber view of the heart and views of the great arteries; fetal echocardiography is not necessary if these standard cardiac assessments are normal and the patient has no other indications for fetal echocardiography [43,49,50]. (See "Congenital heart disease: Prenatal screening, diagnosis, and management".)

The number, location, and appearance of the kidneys should be documented, as renal anomalies are common but not usually clinically significant [7,51].

●Assessment of the placenta and umbilical cord. Velamentous insertion, abnormally short cord, placenta previa, true knot, circumvallate placenta, and placental infarcts are more common with SUA [8,12].

In a meta-analysis of 37 studies that evaluated pregnancy complications associated with SUA, the mean incidence of associated anomalies was 66.3 percent in series of fetal deaths, autopsies, or aborted fetuses and 27 percent in series of live born infants, and renal anomalies were most common [7]. In one of the largest studies published after this analysis, both cardiac anomalies and renal anomalies were significantly more common in infants with SUA than in those without SUA (cardiac anomalies 7.1 versus 0.4 percent; renal anomalies 4.8 versus 1.7 percent) [44]. A population study from Norway found a strong association between SUA and gastrointestinal atresia (odds ratio [OR] 25.8, 95% CI 17.0-39.1 for esophageal atresia and OR 20.3, 95% CI 13.4-30.9 for anorectal atresia or stenosis), as well as a 7- to 8-fold increased risk of congenital heart defects and a 2.8 to 4.8-fold increased risk of diaphragmatic hernia, limb reductions, and cleft lip and palate [47].

The risk of congenital anomalies may be higher with SUA due to primary agenesis than to secondary atresia [52].

Fetal genetic studies — The rate of aneuploidy with isolated SUA does not appear to be increased. In a series of 643 fetuses with SUA, 424 fetuses had isolated SUA and none of these fetuses had a chromosomal abnormality [45]. The same authors' review of the literature found 809 cases of isolated SUA of which six (0.7 percent) had an abnormal karyotype (three trisomy 18 and three trisomy 21).

Most experts do not consider isolated SUA a high-risk factor for offering invasive fetal genetic studies [1,42,45,53-55]. However, offering noninvasive conventional serum screening or a cell-free DNA screening test for trisomies 21, 18, and 13 is reasonable. Invasive diagnostic testing (karyotype with microarray) should be offered to patients in whom additional fetal abnormalities are observed (eg, anatomic abnormalities, symmetric growth restriction) or the aneuploidy screening test is positive [56], given the increased risk of fetal genetic abnormalities in each of these settings. Karyotype abnormalities have been reported in as many as 45 percent of fetuses with non-isolated SUA [6,21,45]; autosomal trisomies, particularly trisomy 18, trisomy 13, or triploidy, appear to be the most common abnormalities [45]. This approach minimizes the number of patients who will require an invasive test while potentially detecting aneuploid fetuses misdiagnosed as isolated SUA prenatally [3,57,58].

Studies evaluating the incidence of pathogenic or likely pathogenic copy number variants (CNV) with isolated SUA are limited and conflicting. In one study including 126 fetuses with isolated SUA, the incidence of pathogenic or likely pathogenic CNV was 1.6 percent [59]. By contrast, in another study including 553 fetuses with isolated SUA, the risk for pathogenic or likely pathogenic CNV was 4.7 percent [60]. Additional studies are needed to determine the role of pathogenic or likely pathogenic CNV and the need for invasive testing in those with isolated SUA.

PREGNANCY MANAGEMENT

Monitoring for growth restriction — There is no consensus about sonographic screening for fetal growth restriction since SUA is not strongly associated with this disorder (see 'Small for gestational age and birth weight' below). The authors perform ultrasound examination at 28 and 36 weeks to screen for growth delay, and this has been suggested by others [44]. The available evidence is limited and neither supports nor excludes the value of routine sonographic screening for growth restriction to improve perinatal outcome in these patients [61].

Antepartum fetal monitoring — With isolated SUA and normal fetal growth, fetal testing with nonstress test and/or biophysical profile is generally not recommended [62]. Although increases in fetal, neonatal, and infant death have been reported with isolated SUA, findings have been inconsistent and inconclusive. However, it is reasonable to offer nonstress testing in the setting of maternal anxiety. (See 'Perinatal outcome' below.)

If fetal growth restriction is identified, then standard fetal testing for pregnancies complicated by this condition is performed. (See "Fetal growth restriction: Evaluation".)

Delivery — SUA alone does not affect the timing or route of delivery.

Pediatric care — The pediatric provider should be notified of the prenatal findings, and the neonate should be closely examined at delivery. Opinions differ as to the value of postnatal renal screening of infants with isolated SUA prenatally. (See "Care of the umbilicus and management of umbilical disorders", section on 'Single umbilical artery'.)

Special issues

Cordocentesis — The safety of cordocentesis, when indicated, in fetuses with SUA has been addressed in two studies involving a total of 43 fetuses with SUA and associated structural anomalies undergoing fetal blood sampling for karyotyping [63,64]. No procedure-related complications were reported and no fetal deaths occurred in the two weeks after the procedure. Vasospasm or tamponade of the cord vessels, which can occur during fetal blood sampling, could have more serious consequences in a fetus with SUA [63,64].

First-trimester diagnosis — There is only limited information on the management of SUA diagnosed in the first trimester. If detected at this early gestational age, nuchal translucency and fetal anatomy should be assessed. Increased nuchal translucency or fetal anomalies are markers of an increased risk for aneuploidy [5] and warrant offering genetic testing. (See "Enlarged nuchal translucency and cystic hygroma" and "Prenatal genetic evaluation of the fetus with anomalies or soft markers".)

PREGNANCY OUTCOME — The type and frequency of adverse outcomes in fetuses with SUA depend largely on whether it is isolated or non-isolated [57,65,66]. Studies evaluating the outcome of SUA are often small, retrospective, and subject to several types of bias, thus limiting the reliability of their findings.

Preterm delivery — An increased risk of preterm delivery has been reported by several authors [44,58,66-69]. In a population-based study (194,809 deliveries), infants with isolated SUA were born on average one week earlier than infants without SUA (38.3±3.0 versus 39.3±2.1 weeks, p <0.001) [67]. Earlier delivery has been related to an increased frequency of a variety of pregnancy complications, including preterm prelabor rupture of membranes, placenta previa, abnormalities of amniotic fluid volume, placental abruption, pregnancy-induced hypertension, and maternal medical disorders [14,67,68].

Small for gestational age and birth weight — Isolated SUA may have a small effect on fetal growth and birth weight, but data are inadequate to make a clear conclusion. In a 2013 systematic review and meta-analysis that pooled data from three cohort studies and four case-control studies (n = 928 pregnancies) comparing pregnancy outcomes with isolated SUA versus a three-vessel cord, isolated SUA was associated with trends toward small for gestational age (SGA; odds ratio [OR] 1.6, 95% CI 0.97-2.6) and a small reduction in mean birth weight (51 grams, 95% CI -154.7 to 52.6 g) that were not statistically significant [70]. Studies were eligible for the analysis if they described at least 30 cases of isolated SUA as identified by ultrasound before an average gestational age of 24 completed weeks. A subsequent study of 219 consecutive patients carrying a fetus with an isolated SUA diagnosed in the second trimester reported a significant association with SGA, pregnancy-induced hypertension, and medically indicated preterm birth [68].

In non-isolated SUA, chromosomal and anatomic abnormalities likely have a greater impact on fetal growth than the number of arteries in the umbilical cord.

Perinatal outcome — Increases in fetal, neonatal, and infant death have been reported inconsistently and inconclusively with isolated SUA. In the 2013 systemic review and meta-analysis described above, isolated SUA was associated with a trend toward increased perinatal mortality that was not statistically significant (OR 2.0, 95% CI 0.9-4.2) [70].

Uncontrolled case series have noted an increased frequency of various adverse outcomes in fetuses with isolated SUA (eg, neonatal intensive care unit admission, nonreassuring fetal heart rate leading to cesarean delivery, SGA, perinatal death) [58,67,71]. A reduction of Wharton's jelly and abnormal cord twist have been observed in cords with SUA, which might account, in part, for the adverse outcomes observed in some studies [72,73].

In non-isolated SUA, perinatal morbidity and mortality are increased and depend on the underlying chromosomal and anatomic anomalies.

Long-term outcome in offspring — Studies have generally reported that long-term physical and neurologic development of children with isolated SUA is similar to that in unaffected children [57,65,74].

In non-isolated SUA, long-term outcomes depend on the underlying chromosomal and anatomic anomalies.

RECURRENCE — In the only study addressing the recurrence of SUA in the following pregnancy, isolated SUA in the first pregnancy doubled the odds of having SUA in the second pregnancy, while SUA with associated malformations in the first pregnancy quadrupled the odds of SUA in the second pregnancy [47].

SUMMARY AND RECOMMENDATIONS

●Clinical significance – Single umbilical artery (SUA) refers to a variation of umbilical cord anatomy in which there is only one umbilical artery (figure 1). It may be an isolated finding or associated with fetal abnormalities. The left artery is absent more often than the right; however, the side (left or right) of the missing artery does not appear to have clinical significance. (See 'Embryogenesis' above and 'Ultrasound findings' above.)

●Prevalence – SUA occurs in approximately 0.5 percent of unselected pregnancies undergoing second-trimester ultrasound examination but is more common in twins and in fetal deaths, autopsies, and aborted fetuses. (See 'Prevalence and epidemiology' above.)

●Prenatal diagnosis – Prenatal diagnosis is based on the following (see 'Prenatal diagnosis' above):

•Ultrasound examination showing only two vessels in the umbilical cord (cross section or longitudinally) (image 2).

•Color flow Doppler in the region of the bifurcation of the fetal aorta showing intra-abdominal umbilical arteries on only one side of the fetal bladder (image 3).

●Differential diagnosis – A potential diagnostic pitfall is only imaging the cord close to the placental insertion, where a short segment may contain only two vessels while the remainder of the cord contains three vessels (image 6). (See 'Fused arteries at the insertion site' above.)

●Postdiagnostic evaluation

•A comprehensive sonographic evaluation of the fetus, cord, and placenta should be performed to look for other anomalies, especially genitourinary, cardiac, gastrointestinal, and central nervous system anomalies. Fetal echocardiography is not necessary if a standard four-chamber view of the heart and views of the great arteries are normal and the patient has no other indications for fetal echocardiography. (See 'Assessment for associated abnormalities' above.)

•For pregnancies with isolated SUA, screening for trisomy 21, 13, or 18 by conventional serum screening or cell-free fetal DNA screening is a reasonable first-line approach. Invasive testing with microarray should be offered to patients who have pregnancies with non-isolated SUA or who screen positive. (See 'Fetal genetic studies' above.)

●Pregnancy management

•The authors perform ultrasound examinations at 28 and 36 weeks to screen for growth delay, given the possibly increased risk of this complication in SUA. However, there is no evidence that routine sonographic screening for growth restriction improves perinatal outcome in isolated SUA, and not performing serial ultrasound examinations or performing a single screening examination at 32 weeks is also reasonable. (See 'Small for gestational age and birth weight' above.)

•With isolated SUA and normal fetal growth, fetal testing with nonstress test and/or biophysical profile is generally not recommended; nonstress testing may be reasonable in the setting of maternal anxiety. (See 'Antepartum fetal monitoring' above.)

•SUA alone does not affect the timing or route of delivery. The pediatric provider should be notified of the prenatal findings. (See 'Delivery' above.)

●Outcomes

•Isolated SUA may have a small effect on fetal growth and birth weight, but data are inadequate to make a clear conclusion. In non-isolated SUA, chromosomal and anatomic abnormalities likely have a greater impact on fetal growth than the absence of one artery in the umbilical cord. (See 'Small for gestational age and birth weight' above.)

•Increases in fetal, neonatal, and infant death have been reported with isolated SUA, but findings have been inconsistent and inconclusive. In non-isolated SUA, perinatal morbidity and mortality are increased and depend on the underlying chromosomal and anatomic anomalies. (See 'Perinatal outcome' above.)

●Recurrence – There appears to be an increased risk of recurrent SUA in the subsequent pregnancy. (See 'Recurrence' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Martin Gimovsky, MD, who contributed to an earlier version of this topic review.