UOG Journal Club: December 2013 Relationship of isolated single umbilical artery to fetal growth, aneuploidy and perinatal mortality: systematic review with meta-analysis B.J. Voskamp, H. Fleurke-Rozema, K.O. Rengerink, R.J.M. Snijders, C.M. Bilardo, B.W.J. Mol and E. Pajkrt Link to free access article: http://onlinelibrary.wiley.com/doi/10.1002/uog.12541/abstract

1. UOG Journal Club: December 2013
Relationship of isolated single umbilical artery to
fetal growth, aneuploidy and perinatal mortality:
systematic review with meta-analysis
B.J. Voskamp, H. Fleurke-Rozema, K.O. Rengerink, R.J.M.
Snijders, C.M. Bilardo, B.W.J. Mol and E. Pajkrt
Volume 42, Issue 6, Date: December 2013, pages 622-628
Journal Club slides prepared by Dr Aly Youssef
(UOG Editor for Trainees)

2. •
Single umbilical artery (SUA) is seen in 0.5% at the time of 2nd
trimester scan
•
Approximately 33% of fetuses with an SUA have additional
structural anomalies and 10% of these are affected with
aneuploidy
•
In approximately 65% of cases, SUA appears to be an isolated
finding (iSUA)
•
In iSUA cases, however, aneuploidy or small for gestational age
(SGA) fetuses may become apparent later on in pregnancy or at
birth. The reported rate with which this occurs varies. As a result
there is still no consensus regarding the extent of work-up
required

3. Relationship of isolated single umbilical artery to fetal growth, aneuploidy
and perinatal mortality: systematic review with meta-analysis
Voskamp et al., UOG 2013
The aim of this systematic review and meta-analysis
was to assess whether there are sufficient data
available to decide upon the appropriate work-up
and management of pregnancies with iSUA
diagnosed at midtrimester scan

4. Methods: Literature search, study selection, data collection and
quality assessment
•
•
•
•
•
•
Medline (from 1948), EMBASE (from 1980) and Cochrane (until
December 2012) were searched to identify papers reporting on SUA
Studies were considered eligible if they described at least 30 cases of
apparent iSUA at ultrasound performed < 24 weeks of gestation
SUA was considered isolated if researchers reported that there were no
additional structural anomalies, SGA or polyhydramnios at time of scan
Odds ratios with 95% CIs for the occurrence of SGA, perinatal mortality
and for aneuploidy in iSUA versus normal fetuses were calculated
The mean birth weight difference (in g) with 95% CI between SUA and
normal fetuses was calculated
Funnel plots were made to check for publication bias and the
heterogeneity of results across the studies was tested using the I² test

5. Records identified
through PubMed
(n = 441)
Records identified
through Embase
(n = 239)
Results
Records identified
through Cochrane
(n = 0)
Duplicates removed
(n=231)
Screening title / abstract
(n = 449)
Records excluded (n = 383)
Case reports (n = 96)
Cohort is disease or condition associated with SUA (n = 86)
Article on etiology, embryology, Doppler, placenta (n = 21)
Article not on SUA (n = 67)
Review/opinion article (n = 17)
Article on visualization or detection of SUA (n = 16)
Article appeared before 1975 (n = 40)
Only twin gestation or case report twin (n = 10)
Animal study (n = 15)
Other (n = 15)
Full-text articles assessed for eligibility
(n = 66)
Studies included in quantitative (& qualitative) synthesis
(n = 7)
Cohort studies
(n = 3)
Full-text articles excluded (n = 59)
Case series (n = 27)
No discrimination between isolated SUA
and non-isolated SUA (n = 16)
No information on prenatally diagnosed SUA, cohort based
on postnatal data only (n = 10)
No numbers on SUA outcome of interest (n = 5)
Article on aneuploidy in selected population (n = 1)
Case–control studies
(n = 4)

6. Results: Small-for-gestational age
• Four case–control studies reported SGA
• No statistically significant association
between iSUA and SGA at birth (OR 1.59,
95% CI, 0.97–2.60, P=0.06)

7. Results: Birth weight
• Three case–control studies reported birth weight
• Fetuses with iSUA did not have significantly lower
birth weights than normal fetuses (mean 3154g vs
3176g; 95% CI, –154.7 to 52.6; p=0.33).

8. Results: Perinatal mortality
• One cohort study and three case–control studies
reported perinatal mortality
• No statistically significant association between
iSUA and perinatal mortality (OR 1.98; 95% CI,
0.94–4.17; P=0.07)

9. Results: Aneuploidy
• The prevalence of aneuploidy in the apparent iSUA group was
reported in 3 studies:
1. Predanic et al. had no cases of aneuploidy among cases and
controls, thus its results could not be weighted in the metaanalysis
2. Lubusky et al. had no cases of aneuploidy among 77 fetuses
with an SUA while the aneuploidy rate in the controls was
5.3%
3. Granese et al.: The aneuploidy rate was 2.6% among 39 SUA
cases and 0.14% among controls
• In view of these contradictory results, these data could not be
pooled and no firm conclusions could be drawn on the
association between iSUA and aneuploidy

10. Discussion
• This meta-analysis did not show a statistically significant
difference in birth weight, incidence of SGA, and perinatal
mortality between iSUA and normal
• Based on this systematic review no firm conclusions can
be drawn on the association between iSUA and aneuploidy.
• However, well designed and properly powered studies are
lacking
• At present, targeted growth assessment after diagnosis of
iSUA should not be routine practice

11. Future perspectives
• Large-scale, prospective cohort studies are needed to reach
definitive conclusions on the appropriate work-up in iSUA
pregnancies
Limitations
• Study populations differed with regard to a priori risk of
anomalies
• Postnatal confirmation of SUA was described in only (4/7) of
studies
• All included studies were too small to either show or refute a
difference in the occurrence of aneuploidy

12. Relationship of isolated single umbilical artery to fetal growth, aneuploidy
and perinatal mortality: systematic review with meta-analysis
Voskamp et al., UOG 2013
Discussion points
• How can the results of this meta-analysis be applied in clinical
practice?
• Should women with iSUA at midtrimester scan be offered fetal
karyotyping?
• Should women with iSUA be offered regular fetal growth scans in
the third trimester?
• Is there a role for induction of labor at term in women with iSUA?