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Maternal cell-free messenger rna in twin pregnancies: the effects of chorionicity and severe twin to twin transfusion syndrome (TTTS)
  1. C E Fox1,2,
  2. A Sekizawa3,
  3. S J Pretlove1,
  4. B C Chan1,
  5. T Okai3,
  6. M D Kilby1,2
  1. 1Birmingham Women's Foundation Trust, Birmingham, UK
  2. 2University of Birmingham, Birmingham, UK
  3. 3Showa University School of Medicine, Tokyo, Japan


Objective To investigate the effects of chorionicity in uncomplicated twin pregnancies on maternal circulating cell-free messenger RNA(cf-mRNA) and the effects of severe TTTS.

Methods A prospective cohort of MC twins complicated by severe TTTS (n=23) were studied, between October 2006 and December 2007. A cohort of uncomplicated DC (n=10) and MC (n=7) pregnancies were studied for comparison. Maternal cf-mRNA encoding GAPDH, sVEGFR-1, VEGF-A, Endoglin, PlGF, Tie-1, Ang-1 and Ang-2 were measured by a quantitative 1-step real-time PCR assay after extraction from maternal plasma(stored at −80°C).

Results The overall survival of this TTTS cohort was 69.6% livebirths (32/46) with ≤one survivor in 87% (20/23). The amounts of cf-mRNA detectable are reported for uncomplicated DC, MC and TTTS pregnancies respectively: GAPDH–80%,100% and 96%; sVEGFR-1–10%,0% and 26%; VEGF-A- 80%,71% and 96%; Endoglin–70%,71% and 91%; PlGF–70%,57%, 26%; Tie-1 0%,43%, 0%; Ang–1 71%,50% and 60% and Ang–2 83%,50% and 89%. There was a significant difference in VEGF-A(medians DC−337.3, MC–390.8, TTTS–618.6 copies/ml plasma p=0.024), Endoglin(medians DC-14.49, MC-1171, TTTS–2896 copies/ml plasma p=0.027) and Ang-2(medians DC-13.66, MC-8.49, TTTS 44.80 copies/ml plasma p=0.007).

Conclusion Maternal cf-mRNA could be reliably detected for GAPDH, PlGF, VEGF-A, Endoglin, Ang-1 and Ang-2 in twin pregnancies and significant difference demonstrated in VEGF-A, Endoglin and Ang-2 between uncomplicated twins and MC twin pregnancies complicated by TTTS. If such alterations in maternal cf-mRNA precede the onset of clinically apparent disease, this may be used as an adjuvant blood test to complement first trimester ultrasound screening.

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