UOG Journal Club: December 2013Relationship 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)

• 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

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

• 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

Methods: Literature search, study selection, data collection and quality assessment

ResultsRecords identifiedthrough PubMed

(n = 441)

Duplicates removed(n=231)

Screening title / abstract(n = 449)

Cohort studies(n = 3)

Full-text articles assessed for eligibility(n = 66)

Studies included in quantitative (& qualitative) synthesis(n = 7)

Records identifiedthrough Embase

(n = 239)

Records identifiedthrough Cochrane

(n = 0)

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)

Case–control studies(n = 4)

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)

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)

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).

• 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)

Results: Perinatal mortality

• 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 meta-analysis

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

Results: Aneuploidy

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

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

Future perspectives

• Large-scale, prospective cohort studies are needed to reach definitive conclusions on the appropriate work-up in iSUA pregnancies

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?

Relationship of isolated single umbilical artery to fetal growth, aneuploidy and perinatal mortality: systematic review with meta-analysis

Voskamp et al., UOG 2013