Aberrant right subclavian artery in fetuses with Down syndrome: a systematic review and meta-analysis

Ultrasound Obstet Gynecol. 2015 Sep;46(3):266-76. doi: 10.1002/uog.14774. Epub 2015 Aug 6.

Abstract

Objectives: The primary objective was to estimate the prevalence of aberrant right subclavian artery (ARSA) in fetuses with Down syndrome. Secondary objectives were to assess the prevalence of ARSA in euploid fetuses, the feasibility of ultrasound evaluation of the right subclavian artery (RSA) in the first and second trimesters of pregnancy, the performance of ARSA in screening for trisomy 21 and its association with other abnormalities.

Methods: Web-based databases (PubMed, EMBASE and MEDLINE) were searched up to July 2014. The STROBE, PRISMA and QUIPS instruments were used to assess all included studies and for reporting of methodology, results and conclusions. Original studies that reported prenatal ultrasound evaluation of ARSA, assessment of its prevalence in Down-syndrome and euploid fetuses, feasibility of ultrasound evaluation of the RSA in the first and second trimesters of pregnancy and correlation of ARSA with other abnormalities were included, excluding duplications and case reports. Collected data were summarized to estimate prevalence and feasibility. A meta-analysis was performed pooling the study-specific positive and negative likelihood ratios (LR+ and LR-), detection rates and false-positive rates for trisomy 21.

Results: Prevalence of ARSA in Down-syndrome fetuses was 23.6% (95% CI, 19.4-27.9%), whereas in euploid fetuses it was 1.02% (95% CI, 0.86-1.10%). Ultrasound evaluation of the RSA course and origin in the first and second trimesters of pregnancy was feasible in 85% and 98% of cases (first and second trimester, respectively) and it was directly related to sonographic experience and fetal crown-rump length and inversely related to maternal body mass index. In more than 20% of fetuses with ARSA there was an association with other abnormalities but ARSA seemed to be an independent marker of trisomy 21. The meta-analysis showed that ARSA is a significant risk factor for Down syndrome (pooled LR+ = 26.93, 95% CI, 19.36-37.47, P for effect < 0.001, P for Q = 0.3, I(2) = 17.3%), whereas normal RSA is a significant protective marker (pooled LR- = 0.71, 95% CI, 0.51-0.99, P for effect = 0.043, P for Q = 0.9, I(2) = 0%).

Conclusions: ARSA appears to be a clinically useful prenatal ultrasound marker of Down syndrome. Additional testing when ARSA is diagnosed should involve evaluation of all risk factors by applying a mathematical model. There is insufficient evidence to recommend fetal karyotyping in cases with isolated ARSA. If the background risk is higher or additional markers are present, full fetal karyotyping is advisable, including analysis for 22q11 microdeletion.

Keywords: Down syndrome; aberrant right subclavian artery; aortic arch; fetal echocardiography; prenatal diagnosis; trisomy 21; ultrasound.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Aneurysm / diagnostic imaging
  • Aneurysm / epidemiology*
  • Cardiovascular Abnormalities / diagnostic imaging
  • Cardiovascular Abnormalities / epidemiology*
  • Deglutition Disorders / diagnostic imaging
  • Deglutition Disorders / epidemiology*
  • Down Syndrome / diagnostic imaging*
  • Female
  • Humans
  • Models, Statistical
  • Pregnancy
  • Pregnancy Trimester, First
  • Pregnancy Trimester, Second
  • Prevalence
  • Subclavian Artery / abnormalities*
  • Subclavian Artery / diagnostic imaging
  • Ultrasonography, Prenatal*

Supplementary concepts

  • Aberrant subclavian artery