Maternal cell-free messenger RNA in twin pregnancies: the effects of chorionicity and severe twin to twin transfusion syndrome (TTTS).

Abstract

OBJECTIVE:

To investigate the effects of chorionicity and severe twin to twin transfusion (TTTS) on maternal circulating cell-free messenger RNA (cf-mRNA).

DESIGN:

Prospective cohort study.

SETTING:

A UK tertiary referral Fetal Medicine Center.

POPULATION:

All monochorionic (MC) twins complicated by severe TTTS (n= 23) and a cohort of uncomplicated dichorionic (DC) (n= 10) and MC (n= 7) pregnancies, between October 2006 and December 2007.

METHODS:

Maternal cf-mRNA encoding glyceraldehyde 3-phosphate dehydrogenase (GAPDH), vascular endothelial growth factor receptor 1(VEGFR-1(Flt-1)), vascular endothelial growth factor A (VEGF-A), Endoglin, placental growth factor (PlGF), tyrosine kinase with immunoglobulin-like and EGF-like domains 1 (Tie-1), angiopoietin 1 (Ang-1) and angiopoietin 2 (Ang-2) were measured by a quantitative two-step real-time PCR assay after extraction from maternal plasma.

RESULTS:

The amounts of cf-mRNA detectable are reported for uncomplicated DC, MC and TTTS pregnancies, respectively: GAPDH - 80, 100 and 96%; VEGFR-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 a significant difference was 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 ultrasound screening.

• Authors: Caroline E Fox, Akihiko Sekizawa, Samantha J Pretlove, Ben C Chan, Takashi Okai, Mark D Kilby
• Journal: Acta obstetricia et gynecologica Scandinavica (Acta Obstet Gynecol Scand) Vol. 91 Issue 10 Pg. 1206-11 (Oct 2012) ISSN: 1600-0412 [Electronic] United States
• PMID: 22862673 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2012 The Authors Acta Obstetricia et Gynecologica Scandinavica© 2012 Nordic Federation of Societies of Obstetrics and Gynecology.

Chemical References

• Angiopoietin-2
• Antigens, CD
• Biomarkers
• ENG protein, human
• Endoglin
• RNA, Messenger
• Receptors, Cell Surface
• VEGFA protein, human
• Vascular Endothelial Growth Factor A

Topics

• Adult
• Angiopoietin-2 (blood)
• Antigens, CD (blood)
• Biomarkers (blood)
• Case-Control Studies
• Cell-Free System
• Chorion
• Cohort Studies
• Endoglin
• Female
• Fetofetal Transfusion (blood, diagnosis, genetics)
• Humans
• Infant, Newborn
• Pregnancy
• Prospective Studies
• RNA, Messenger (blood)
• Real-Time Polymerase Chain Reaction
• Receptors, Cell Surface (blood)
• Severity of Illness Index
• Twins, Monozygotic
• Vascular Endothelial Growth Factor A (blood)