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05 November 2024

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06 November 2024

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Abstract
Single umbilical artery (SUA) is considered an ultrasound marker of anomalies. Although it may be present in about 5% of normal gestations, it has been observed to be associated with an increased risk of intrauterine growth retardation, cardiac, genitourinary and gastrointestinal malformations, as well as with the appearance of chromosomal anomalies such as trisomy 21 and 18. Objectives: This study aims to check whether the presence of isolated SUA (ISUA) is related to adverse perinatal outcomes. Methods: This is a descriptive, observational and retrospective study with a total of 1266 gestations were studied (1189 normal gestations and deliveries collected from the registry of the Hospital Univeritario de Salamanca, during the period from January 1st to August 31st, 2023 and 77 cases of ISUA). Results: The presence of ISUA was associated with a lower gestational age (38 vs 39 weeks) and a lower birth weight (3013 vs 3181 g) though not increasing the prematurity rate. No significant differences were found in the increase in malformations, genetic disorders, Apgar test, pH at birth or admissions in the neonatal ICU. Conclusions: The presence of ISUA during gestation is associated with lower gestational age and lower birth weight though this did not result in a higher rate of prematurity or an increase in the number of admissions associated with low birth weight. No significant association was found between the presence of ISUA and genetic disorders or fetal malformations. Neither were worse Apgar test scores or lower pH values found in these newborns.
Keywords: 
Subject: 
Medicine and Pharmacology  -   Obstetrics and Gynaecology

1. Introduction

Prenatal examination of the umbilical cord is an essential part of the ultrasound scan in pregnancy. The presence of a single artery, known as a single umbilical artery (SUA), is considered a risk marker for trisomy and may be associated with fetal malformations in up to 11-30% of cases [1,2,3]. When the single umbilical artery is present in the absence of any other detectable malformation, it is referred to as isolated single umbilical artery (ISUA). The results of the studies published to date are inconsistent: in some of them, the presence of SUA is associated with an increase in preterm birth, intrauterine growth retardation (IUGR) of the fetus and an increase in perinatal morbidity and mortality [2,4,5,6,7,8]. However, these data have not been confirmed in other studies [9,10], resulting in conflicting information when discussing this condition.
The main objective of this study was to analyse the value of the isolated single umbilical artery as a predictor of adverse perinatal outcomes, considering as adverse perinatal outcomes prematurity, low birth weight, low Apgar score, low postnatal pH and the need for NICU admission.

2. Materials and Methods

This is a descriptive, observational and retrospective study with a total of 1189 consecutive singleton gestations attended at the Department of Gynaecology and Obstetrics of the Hospital Universitario de Salamanca, during the period from 1 January to 31 August 2013. These gestations were compared with 77 gestations with ISUA, whose data were collected during the years 2019 to 2023 at the same centre. This study was approved by the Hospital Ethics Committee. All patients were over 18 years of age and signed informed consent for the study. Data were collected in a database created specifically for the study with Microsoft Excel (Microsoft Corporation, Redmond, WA, USA) which was accessible from the outpatient clinic, the delivery room and the hospital ward.
For statistical analysis, SPSS software (IBM SPSS Statistics, version 28) was used. A normality goodness-of-fit test was performed by using the Kolmogorov-Smirnov test, finding that the quantitative variables did not follow a normal distribution, so non-parametric tests were used to analyse the results (chi-square test for qualitative variables and Mann-Whitney U test). The statistical significance level was set at 95 % (p < 0.05).

3. Results

The general characteristics of the study population are shown in Table 1. During the study period, a total of 1266 pregnancies (1189 with normal cord and 77 with ISUA) that met the inclusion criteria for the study were analysed. The mean gestational age at delivery was 38 weeks. The mean maternal age was 32 years, ranging from 14 to 47 years. Most pregnancies were spontaneous (89.4%). The main mode of delivery was normal vaginal birth (58.3%), followed by caesarean section (24.7%). Induced labour occurred in 45.5% of gestations. Most newborns (95.2%) had no conditions at birth. Urinary tract disease was the most common, accounting for 23.7% of all prenatally diagnosed disorders. The incidence of SUA in the study population was 6.1%. Regarding the reasons for admission to the neonatal unit, prematurity was the most common cause in our setting (46%), followed by respiratory distress, which reached 19%.
The presence of ISUA was associated with both lower gestational age and lower birth weight (Table 2), although this lower gestational age was not associated with an increase in prematurity (38 vs 39 weeks at birth). On the other hand, we found no association between the presence of ISUA and the occurrence of genetic disorders in the newborn, nor an increase in neonatal malformations. No statistically significant association was found between ISUA and poor Apgar scores or low pH. Finally, the presence of ISUA was not associated with an increased number of neonatal admissions or perinatal deaths (Table 2 and Table 3).

4. Discussion

The presence of a single umbilical artery in the fetal umbilical cord has been considered in multiple papers as a marker not only of aneuploidy and genetic disorders, but also of fetal malformations [1,11], low birth weight and neonatal death [2,4,5,7].
In our study population, the presence of a single umbilical artery in the fetus was associated with both lower gestational age and birth weight in a statistically significant manner. Our finding is consistent with the most of published studies; the meta-analysis by Kim et al. [7] revealed that pregnancies with SUA have a three times higher risk of low birth weight compared to singleton pregnancies with a three-vessel cord and these infants have a lower birth weight of about 200 g compared to those with a normal cord. Similarly, Siargkas et al. in a prospective study of 6528 patients found a significant association between the presence of SUA, lower birth weight and gestational age at birth [8]. In their study, these authors state that a fetus with SUA is twice as likely to have both low birth weight and preterm delivery as a fetus with a normal cord. These findings are shared by other researchers. In contrast, Wiegand et al. [12] state that the presence of SUA does not modify the risk of low birth weight or preterm delivery. However, this study was carried out with 273 gestations with SUA, without a control group, and the results were compared with those of the literature. There are three meta-analyses published to date analysing the influence of the single umbilical artery on the risk of preterm birth and birth weight, with discordant results among them. While the studies by Dagklis et al and Kim et al. find an association between the presence of ISUA and these conditions, the study by Voskamp et al. states that such an association cannot be demonstrated [4,7,10].
Our results are consistent with those of those of most published studies: in our study the mean gestational age was one week lower in foetuses with SUA compared to those with a normal cord, and birth weight was almost 10% lower in these newborns.
Another noteworthy aspect of the presence of SUA in the literature is its potential as a marker of genetic alterations or fetal malformations. In our case, the presence of SUA has not been associated with genetic abnormalities, as we have not demonstrated a statistically significant association between the two variables. Nor have we been able to relate the presence of SUA with malformative conditions, as reported in other published studies [1,2,11,13]. Most of the studies that relate the presence of SUA with genetic or malformative abnormalities do not consider SUA as an isolated marker, since affected fetuses usually have more malformations or associated markers [1,3,11]. We have selected patients where SUA was an isolated marker, excluding pregnancies whose fetuses had other malformations or other associated markers, as our intention was to study the influence of SUA as a single marker. Like us, Granese et al, in their results analysing ISUA without association with other markers or malformations, found no association between this marker and higher rates of aneuploidy at gestation [3].
There are few studies that relate the presence of AUU with parameters of well-being in the immediate postpartum period (Apgar test and pH in cord blood). The meta-analysis by Dagklis et al. and the study by Ebbing et al. report an increased risk for fetuses with SUA to have lower values for both pH at birth and Apgar test at 5 minutes, as well as an increased risk of admission to the Neonatal Intensive Care Unit and neonatal death [2,4]. Therefore, these authors concluded that prenatal assessment of SUA is of significant relevance. On the contrary, in our study we did not find these data as we could not demonstrate statistically significant differences in any of these parameters. None of the newborns with SUA required admission to the neonatal unit, and no perinatal deaths were recorded in these infants. This disparity is likely to be related to the kind of gestations included in the study. As previously mentioned, the studies referred included gestations with fetuses with multiple conditions, where SUA was not assessed as an isolated marker, but as part of a syndrome. In our study we have included gestations with isolated SUA, i.e. with the rest of the parameters being normal, so these populations are probably not comparable.

5. Strengths and Limitations

The main strength of this study is that we analysed the influence of SUA as an isolated marker, selecting cases in which this marker was present alone, i.e. without being associated with other conditions, in order to assess its influence without interference from other markers or findings. This is unusual because, as we have seen in the literature, most studies consider the presence of SUA together with several conditions that do not allow the specific influence of this marker to be clearly identified. Furthermore, in the case of neonates, several variables were studied, not only the neonatal admission, which provides a more complete analysis that makes it possible to establish causality or not between the presence of SUA and various neonatal data (fetal pH, low birth weight, Apgar...).
Finally, we would like to point out that there are few studies similar to ours, which makes our study innovative and interesting.
In terms of limitations, we can point out that in our study we were not able to collect data that could have been interesting in the case of a marker related to the umbilical cord and placenta, like the presence of umbilical cord abnormalities (length, placental insertion, etc.) or placental disorders (placenta praevia, placental accretism, placental abruption, etc.).
Regarding the sample size, although it is larger than that of some studies in the literature, it is likely that with an even larger sample we could find a greater number of significant differences in certain parameters. For this reason, we consider it important to continue this study prospectively and record these data for future analysis.

6. Conclusions

Our study outcomes show that the presence of an isolated SUA is associated with lower gestational age and lower birth weight, although it does not increase the prematurity rate.
Also, the presence of SUA as an isolated marker is not associated with a higher number of genetic disorders or malformations, a lower Apgar score at birth, a lower umbilical cord blood pH at birth, the need for admission to the neonatal unit or perinatal death.

Author Contributions

Conceptualization, A.M.C. and M.V.L.A.; methodology, A.M.C. and M.V.L.A.; formal analysis, A.M.C.; data collection: A.M., M.A.C., T.C., E.H.H., P.O., A.V.Y., F.J.G.; investigation, A.M., A.M.C.; data curation, A.M.C., A.M., M.V.L.A.; writing—original draft preparation, A.M.C., A.M., M.V.L.A.; A.M.C.; visualization, M.A.C., T.C., E.H.H., P.O., A.V.Y., F.J.G.; supervision, A.M.C.; project administration, A.M.C.; funding acquisition, A.M.C. All authors have read and agreed to the published version of the manuscript.

Funding

The APC of this paper was funded by University of Salamanca (USAL).

Institutional Review Board Statement

The study was conducted in accordance with the Declaration of Helsinki, and approved by the Institutional Review Board (or Ethics Committee) of Hospital Universitario de Salamanca (protocol code PI 2022 06 323, date of approval: 16/06/2022).

Informed Consent Statement

Informed consent was obtained from all subjects involved in the study.

Data Availability Statement

The data presented in this study are available on request from the corresponding author due to the data protection of the patients involved.

Conflicts of Interest

The authors declare no conflicts of interest.

References

  1. Yu, J.; Wu, Q.; Kong, F.; Ning, Y. Diagnosis of Single Umbilical Artery and Risk of Foetal Congenital Malformations by Prenatal Ultrasound: A Retrospective Study. BMC Pregnancy and Childbirth 2024, 24. [Google Scholar] [CrossRef] [PubMed]
  2. Ebbing, C.; Kessler, J.; Moster, D.; Rasmussen, S. Single Umbilical Artery and Risk of Congenital Malformation: Population-Based Study in Norway. Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology 2020, 55, 510–515. [Google Scholar] [CrossRef]
  3. Granese, R.; Coco, C.; Jeanty, P. The Value of Single Umbilical Artery in the Prediction of Fetal Aneuploidy: Findings in 12,672 Pregnant Women. Ultrasound Quarterly 2007, 23, 117–121. [Google Scholar] [CrossRef] [PubMed]
  4. Dagklis, T.; Siargkas, A.; Apostolopoulou, A.; Tsakiridis, I.; Mamopoulos, A.; Athanasiadis, A.; Sotiriadis, A. Adverse Perinatal Outcomes Following the Prenatal Diagnosis of Isolated Single Umbilical Artery in Singleton Pregnancies: A Systematic Review and Meta-Analysis. Journal of perinatal medicine 2021, 50, 244–252. [Google Scholar] [CrossRef] [PubMed]
  5. Rechnagel, A.-S.A.; Jørgensen, F.S.; Ekelund, C.K.; Zingenberg, H.; Petersen, O.B.; Pihl, K. Risk of Adverse Pregnancy Outcome in Isolated Single Umbilical Artery Diagnosed at the Mid-Trimester Anomaly Scan: A Large Danish Retrospective Cohort Study. The Journal of Maternal-Fetal & Neonatal Medicine 2023, 36. [Google Scholar] [CrossRef]
  6. Horton, A.; Barroilhet, L.; Wolfe, H. Perinatal Outcomes in Isolated Single Umbilical Artery. American Journal of Perinatology 2010, 27, 321–324. [Google Scholar] [CrossRef] [PubMed]
  7. Kim, H.J.; Kim, J.-H.; Chay, D.B.; Park, J.H.; Kim, M.-A. Association of Isolated Single Umbilical Artery with Perinatal Outcomes: Systemic Review and Meta-Analysis. Obstetrics & gynecology science 2017, 60, 266–273. [Google Scholar] [CrossRef]
  8. Siargkas, A.; Giouleka, S.; Tsakiridis, I.; Mamopoulos, A.; Kalogiannidis, I.; Athanasiadis, A.; Dagklis, T. Prenatal Diagnosis of Isolated Single Umbilical Artery: Incidence, Risk Factors and Impact on Pregnancy Outcomes. Medicina (Lithuania) 2023, 59. [Google Scholar] [CrossRef] [PubMed]
  9. Shen, N.; Zhang, W.; Li, G. Impact of Isolated Single Umbilical Artery on Pregnancy Outcome and Delivery in Full-Term Births. Journal of Obstetrics and Gynaecology Research 2016, 42, 399–403. [Google Scholar] [CrossRef] [PubMed]
  10. Voskamp, B.J.; Fleurke-Rozema, H.; Oude-Rengerink, K.; Snijders, R.J.M.; Bilardo, C.M.; Mol, B.W.J.; Pajkrt, E. Relationship of Isolated Single Umbilical Artery to Fetal Growth, Aneuploidy and Perinatal Mortality: Systematic Review and Meta-Analysis. Ultrasound in Obstetrics and Gynecology 2013, 42, 622–628. [Google Scholar] [CrossRef] [PubMed]
  11. Li, T. gang; Wang, G.; Xie, F.; Yao, J. min; Yang, L.; Wang, M. lin; Wang, J.; Xing, L.; Nie, F. Prenatal Diagnosis of Single Umbilical Artery and Postpartum Outcome. European journal of obstetrics, gynecology, and reproductive biology 2020, 254, 6–10. [Google Scholar] [CrossRef] [PubMed]
  12. Wiegand, S.; McKenna, D.S.; Croom, C.; Ventolini, G.; Sonek, J.D.; Neiger, R. Serial Sonographic Growth Assessment in Pregnancies Complicated by an Isolated Single Umbilical Artery. American journal of perinatology 2008, 25, 149–152. [Google Scholar] [CrossRef] [PubMed]
  13. Granese, R.; Coco, C.; Jeanty, P. P01.02: Single Umbilical Artery in 12,672 Unselected Patients, Value for Prediction of Fetal Aneuploidies. Ultrasound in Obstetrics & Gynecology 2006, 28, 512–512. [Google Scholar] [CrossRef]
Table 1. Baseline features of the population in the study.
Table 1. Baseline features of the population in the study.
Characteristic Media Median SD Minimum Maximum
Gestational age (weeks) 38 39 2,6 12 42
Newborn weight (g) 3171 3185 483,7 795 4880
pH 7,26 7,3 0,08 6,90 7,50
Maternal weight (Kg) 68 64 19,2 40,0 180,0
Maternal BMI (Kg/m2) 25 24 5,7 16,0 54,0
Maternal age (years) 32 33,2 5,8 14 47
Characteristic Category N %
Prenatal condition
(n=1266) 		No observed condition 1207 95,9
Urinary Tract Disease 14 1,1
Hydrops 4 0,3
Increased NT- Cystic hygroma 9 0,7
CNS disease 5 0,4
Congenital heart disease 6 0,5
Congenital diaphragmatic hernia 2 0,2
Bilateral clubfoot 4 0,3
Abdominal disease 7 0,6
Other 8 0,7
Smoking habit
(n=1266) 		No 1070 15.5
Yes 196 84.5
Pregnancy
(n=1266) 		Spontaneous 1131 89,4
IVF 112 8,8
Artificial insemination 23 1,8
Genetic disorder
(n=1266) 		No genetic disorder 1247 98,5
Trisomy 21 11 0,9
Trisomy 18 3 0,2
Pallister Killian syndrome 1 0,1
Turner syndrome 3 0,2
Trisomy 13 1 0,1
Labour induction (n=1266) No 690 54,5
Yes 576 45,5
Delivery
(n=1266) 		Vaginal birth 739 58,3
Caesarean section 312 24,7
Vacuum/forceps assisted vaginal birth 195 15,4
Termination of pregnancy 17 1,4
Spontaneous miscarriage 3 0,2
Fetal gender
(n= 1266) 		Male 652 51,5
Female 614 48,5
APGAR 1st minute
(n=1266) 		Severe ventilatory depression (0-3 points) 45 3,5
Moderate ventilatory depression (4-6 points) 42 3,3
Satisfactory status (7-10 points) 1179 93,2
APGAR 5th minute
(n=1266) 		Severe ventilatory depression (0-3 points) 30 2,3
Moderate ventilatory depression (4-6 points) 12 0,9
Satisfactory status (7-10 points) 1224 96,8
Newborn death
(n= 1266) 		No 1259 99,4
Yes 7 0,6
Hospital admission (n=1266) No 1229 97,1
Yes 37 2,9
Reason for hospital admission (n=37) Prematurity 17 46,0
Respiratory distress 7 19,0
Jaundice 4 10,6
Meconium aspiration 2 5,4
Other 7 19,0
Table 2. Association of ISUA with the presence of genetic disorder, prenatally detected conditions, Apgar test, need for admission to NICU and perinatal death.
Table 2. Association of ISUA with the presence of genetic disorder, prenatally detected conditions, Apgar test, need for admission to NICU and perinatal death.
ISUA NO ISUA p
Genetic disorder
 No genetic disorder 77 1170 0,946
Trisomy 21 0 11
Trisomy 18 0 3
Pallister Killian syndrome 0 1
Turner syndrome 0 3
Trisomy 13 0 1
Prenatal condition
 No observed condition 77 1130 0,943
Urinary Tract Disease 0 14
Hydrops 0 4
Increased NT- Cystic hygroma 0 9
CNS disease 0 5
Congenital heart disease 0 6
Congenital diaphragmatic hernia 0 2
Bilateral clubfoot 0 4
Abdominal disease 0 7
Other 0 8
APGAR 1st minute
 Severe ventilatory depression (0-3 points) 3 42 0,927
Moderate ventilatory depression (4-6 points) 3 39
Satisfactory status (7-10 points) 71 1108
APGAR 5th minute Severe ventilatory depression (0-3 points) 3 27 0,707
Moderate ventilatory depression (4-6 points) 2 10
Satisfactory status (7-10 points) 72 1152
Hospital admission No 77 1152 0,116
Yes 0 37
Newborn death No 77 1182 0,503
Yes 0 7
Table 3. - Association of ISUA with gestational age at birth, birth weight and immediate postnatal pH.
Table 3. - Association of ISUA with gestational age at birth, birth weight and immediate postnatal pH.
ISUA NO ISUA p
Media SD Media SD
Gestational age (weeks) 38 4,4 39 2,4 0,04
Newborn weight (g) 3013,24 507,290 3181,07 480,771 <0,001
pH 7,25 0,092 7,26 0,085 0,413
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Copyright: This open access article is published under a Creative Commons CC BY 4.0 license, which permit the free download, distribution, and reuse, provided that the author and preprint are cited in any reuse.
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