Introduction

A single umbilical artery (SUA) is found in 0.2-2.0% of deliveries and occurs three or four times more frequently in twin births versus singletons^1-7. The condition is associated with malformations of all major organ systems and chromosomal defects^1,8. Previous ultrasonographic studies, in the second and third trimesters of pregnancy, reported chromosomal defects in about 10% of fetuses with SUA, most commonly trisomy 18, but in the vast majority of such cases there were other major defects⁹.

In this study, we examine the association between SUA and chromosomal abnormalities in the second trimester of pregnancy and whether it matters which artery is missing.

Methods

This was a prospective study in 2147 consecutively examined singleton pregnancies to determine the incidence of SUA in fetuses undergoing karyotyping by amniocentesis in the second trimester of pregnancy (at 16-22 weeks' gestation).

In all cases there was a prior screening for chromosomal defects by a combination of maternal age, biochemical screening (alfa fetoprotein + human chorionic gonadotropin + unconjugated estriol) and ultrasound. The patients included in this study were those who after counseling elected to have invasive testing.

An oblique transverse section of the lower fetal abdomen, including the umbilicus and the fetal bladder, was first obtained and color flow mapping was then used to visualize the umbilical arteries on either side of the bladder and in continuity with the umbilical cord insertion to the fetus (Figure 1). All the scans were performed transabdominally using 5-MHz transducers (Toshiba Powervision 6000, Toshiba, Tokyo, Japan; GE Voluson 730 Expert, GE Healthcare Technologies, Zipf, Austria). The fetal biparietal diameter (BPD), head circumference (HC), abdomen circumference (AC) and femur length (FL) were also measured and a systematic search was made for the detection of any associated structural abnormalities. Examination of the umbilical arteries was successfully achieved in all cases and its duration was about 1 min.

Statistical analysis was performed using the χ² test, or Fisher's exact test when appropriate.

Results

The median maternal age was 32 (range, 14-47) years, the median gestation was 18 (range, 16-22) weeks. SUA was diagnosed in 102/2147 (4.8%) cases. The fetal karyotype was normal in 2019 pregnancies and abnormal in 128 (6.0%).

The median maternal age was 32 (range, 14-47) years, the median gestation was 18 (range, 16-22) weeks. SUA was diagnosed in 102/2147 (4.8%) cases. The fetal karyotype was normal in 2019 pregnancies and abnormal in 128 (6.0%).

The left umbilical artery was absent in 60/102 (58.8%) fetuses, compared with 42/102 (41,2%) for the right artery.

Chromosomal abnormalities occured in 19/102 (18.6%) fetuses (p<0.0001; OR 4.07; 95% CI 2.3-7.1), with 11/60 (18.3%) (p<0.0001; OR 3.99; 95% CI 1.9-8.2) in those with absence of the left artery and 8/42 (19.0%) (p<0.0001; OR 4.18; 95% CI 1.74-9.7) in those with absence of the right artery. Which artery was missing was not significant.

Associated structural abnormalities occured in 25/102 (24.5%) fetuses, with 14/60 (23.3%) in those with absence of the left artery and 11/42 (26.2%) in those with absence of the right artery. Which artery was missing was not significant.

There were no chromosomal abnormalities in fetuses where a single umbilical artery was an isolated finding. All fetuses with chromosomal abnormalities had associated malformations 19/19 (100%).

In the chromosomally normal group, the incidence of SUA was 4.1% (83/2019 cases). In the group of 83 fetuses with an SUA there were six (7.2%) fetuses with associated structural abnormalities detected in the second trimester scan (including two cardiac anomalies, one renal agenesis, hydronephrosis, cleft lip and palate and diaphragmatic hernia) (Table 1) and this was similar to the 1936 with two arteries, of which 164 fetuses had other defects (8.4%, Fisher 's exact test p=0.6898).

In the chromosomally abnormal group, the incidence of SUA was 14.8% (19/128 cases). There was an SUA in 5/39 (12,8%) with trisomy 21, 8/16 (50%) with trisomy 18, 1/4 (25%) with trisomy 13 and 5/69 (7.2%) with other chromosomal defects (including two Turner's syndrome, two triploidies and one trisomy 16). In the group of 19 fetuses with SUA there were 19 (100%) fetuses with associated structural abnormalities detected in the second trimester scan (Table 2) and this was significantly higher than in the 109 with two arteries, where there were 36 fetuses with other defects (33%, Fisher's exact test p<0.0001).

Discussion

In this study of fetuses in the second trimester of pregnancy (at 16-22 weeks' gestation), the incidence of SUA was 4,8%, which is lower than the reported incidence of 5.9% in the first trimester of pregnancy (at 11-14 weeks' gestation) ⁹, but substantially higher than the reported birth incidence of 0.2-2.0%^1-7. Furthermore, the incidence of chromosomal defects in fetuses with SUA (19%) was considerably lower than 50% reported at 11-14 weeks' gestation⁹, but higher than 8% reported in second- and third-trimester ultrasonographic studies⁹. It is likely that both the observed incidence of SUA and the incidence of associated chromosomal defects are overestimated because our population was preselected for fetal karyotyping by a combination of maternal age, biochemical screening and ultrasound. In the first trimester study (at 11-14 weeks' gestation)⁹ their population was preselected for fetal karyotyping by a combination of maternal age, being on average 37 years, and increased fetal NT, which was above the 95th centile for CRL in 36% of cases¹⁰.

In our study, the incidence of SUA in the chromosomally abnormal group was almost four times higher than in the chromosomally normal group, but we have not found any chromosomal alteration in fetuses with isolated SUA and all chromosomally abnormal fetuses with SUA had associated malformations detected in the second trimester scan.

As is known, the umbilical cord normally contains one vein and two arteries. The development of the vasculature of the cord begins at the end of the third week of gestation. Apart from the two arteries and the vein, the cord also contains the vitelline duct and its vessels (vitelline artery and vein), the latter normally regressing at the end of the third month.

There are three teories regarding the pathogenic mechanism resulting in SUA: 1) primary agenesis of one umbilical artery; 2) secondary atrophy or atresia of a previously normal umbilical artery; and 3) persistence of the original allantoic artery of the body stalk^1,8,11. It is belived that atrophy is the most frequent mechanism. When both umbilical arteries close and the vitelline artery persists, it has been classified as an SUA type II and corresponds with approximately 1.4% of SUA cases. This type is normally associated with sirenomelia or caudal regression syndrome⁸. It is thought that the cause is insufficient irrigation of the terminal portion of the embryo, and depending on the stage of development at which this occurs, it will produce different clinical sypmtoms, so that if it occurs later, the result may be a fetus with no malformations¹². Hypoplasia of one of the two umbilical arteries is much less frequent, affecting 0.03% of pregnancies, and is associated with intrauterine growth retardation (IUGR), maternal diabetes, polyhydramnios, and congenital cardiopathy, described in a case of trisomy 18. This hypoplasia probably represents an incomplete form of SUA¹³.

It is not clear why SUA is linked to other fetal anomalies, and although there is no unique malformative pattern, the most frequent anomalies are genitourinary, followed by cardiovascular malformations, whilst gastrointestinal malformations are the least frequent⁵. We have found these same data in our cases. In the study of Gornall et al.⁵, the diagnosis of congenital anomaly was almost seven times greater in the case group than in the control group. In this study, 20% of the fetuses with SUA had an added congenital anomaly. In our study, 25% of fetuses with SUA had associated structural abnormalities detected by ultrasound and it was more than three times greater than in the group of fetuses with two umbilical arteries.

Similar to the results of Abuhamad et al.¹⁴ (n = 77 cases) and Geipel et al.¹⁵ (n = 102 cases), but in contrast to the studies by Blazer et al.¹⁶ (n = 46 cases) and Fukada et al.¹⁷ (n = 10 cases), which observed no differences in the distribution of the missing side, we found the absence of the left side (58.8%) was more frequent than the right (41.2%). Absent left umbilical artery was more common in fetuses of both groups: chromosomally normal (59%) and chromosomally abnormal (58%). Our results suggest that the left umbilical artery is more commonly absent than the right artery in fetuses with single umbilical artery. We could not find an explanation for this difference. It is interesting to note that the right umbilical artery is usually larger than the lef¹⁸. This asymetry in size between the two umbilical arteries may play a role in the pathogenesis of single umbilical artery by favoring one side over the other.

Because SUA may be associated with other fetal malformations, karyotype anomalies, intrauterine growth retardation (IUGR), preterm birth, and low birth weight, the routine study of the umbilical cord is interesting. The diagnostic attitude on finding an SUA may be controversial. All authors agree that if an SUA is found, a detailed ultrasound must be carried out by an ultrasound specialist, in order to detect other associated fetal anomalies^8,9,19. Some authors recommend adding a fetal echocardiography to the ultrasound exploration if an SUA is found as an isloated finding^6,8,14,20,21. If subsequent explorations are normal, antenatal fetal growth and wellbeing controls should be carried out, considering it as a pregnancy at risk until birth⁷.

The presence of an SUA as an isolated finding, in studies on the general population, is linked to a poor perinatal result, when compared with fetuses with two arteries. They tend to be of low weight, premature and twice as often below the 10th percentile in weight; likewise, a cesarean section is more frequent. Perinatal mortality is greater, six times greater for fetuses with SUA and without associated malformations⁵.

It is not clear why fetuses with SUA achieve poorer perinatal results, even without associated malformations. It has been demonstrated that these cords have a lower number of spirals¹⁸ and a lesser quantity of Wharton jelly, which make them less resistant in situations of stress, such as birth or compression of the umbilical cord, and may act in synergy with other unfavorable circumstances²².

In our study, all chromosomally abnormal fetuses with an SUA had other abnormalities that were detectable by ultrasound. The aneuploidies most frequently found were trisomy 18, 13 and 21, although it was found in others such as triploidy, 45,X0 and trisomy 16. We have not found any chromosomal alteration in fetuses with isolated SUA and all chromosomally abnormal fetuses with SUA had associated malformations detected in the second trimester scan. Our results show that the systematic scanning with Doppler for the number of umbilical arteries in the 20th week of pregnancy is probably a good diagnostic method. The finding of an SUA should alert the ultrasonographer to search for associated malformations and markers of chromosomal defects, such as overlapping fingers, facial cleft, cardiac anomalies, spina bifida and many other abnormalities that are detectable at the 16-22 week scan. In cases of apparently isolated SUA, there is no indication for fetal karyotyping because in this group there is no evidence of increased risk of chromosomal defects and which artery is missing is not significant.

Acknowledgments

This study was supported by the Medical Faculty of Palacký University Olomouc "Safety of Ultrasound in Medicine".

References

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