Altmetric

Novel circulating placental markers prokineticin-1, soluble fms-like tyrosine kinase-1, soluble endoglin and placental growth factor and risk of late miscarriage

File Description SizeFormat 
HUMREP-16-0367.R2-edit-HFS.docxAccepted version59.6 kBMicrosoft WordView/Open
Supplementary-Data-edit-HFS.docxAccepted version17.74 kBMicrosoft WordView/Open
Tables-edit-HFS.docxAccepted version26.54 kBMicrosoft WordView/Open
160222 Preg paper.pptxAccepted version3.74 MBUnknownView/Open
Title: Novel circulating placental markers prokineticin-1, soluble fms-like tyrosine kinase-1, soluble endoglin and placental growth factor and risk of late miscarriage
Authors: Jayasena, C
Abbara, A
Comninos, A
Narayanaswamy
Gonzalez, J
Izzi-engbeaya, C
Oldham, J
Lee, T
Sarang, Z
Malik, Z
Dhanjal, MK
Williamson, C
Regan, L
Bloom, S
Dhillo, W
Item Type: Journal Article
Abstract: STUDY QUESTION Are novel circulating placental markers prokineticin-1 (PK-1), soluble fms-like tyrosine kinase-1 (sFlt-1), soluble endoglin (sEng) and placental growth factor (PlGF) associated with late miscarriage in asymptomatic first trimester pregnant women? SUMMARY ANSWER Increased serum sFlt-1 or PlGF, but not sEng or PK-1, were significantly associated with reduced miscarriage risk after adjustment for age, BMI, gestational age, smoking and blood pressure. WHAT IS KNOWN ALREADY Abnormal placental development is observed in two-thirds of miscarriages. Identifying women at high risk of late miscarriage could help diagnose potentially treatable causes of miscarriage such as infection, thrombosis or immunological disease. Recently, the circulating placental markers PK-1, sFlt-1, sEng and PlGF have been identified; however, it is not known if circulating levels of these markers are associated with late miscarriage. STUDY DESIGN, SIZE, DURATION A single-centre observational cohort study with prospectively collected data was carried out at a tertiary care centre 2010–2012, in 993 asymptomatic pregnant women. Plasma PK-1, and serum sEng, sFlt-1 and PlGF were measured once in each patient during the antenatal booking visit, and pregnancy outcome was monitored prospectively. Less than 1% of patients were lost to follow-up. Multiples of median (MOM) levels were calculated to adjust for gestational age. PARTICIPANTS/MATERIALS, SETTING, METHODS Nine-hundred and ninety-three asymptomatic pregnant women attending antenatal clinic for a routine booking antenatal appointment were recruited to the study, of whom 12 were lost to follow-up and excluded from analysis. Of the cohort, 50 of the remaining 981 women suffered late miscarriage. MAIN RESULTS AND THE ROLE OF CHANCE Gestation-adjusted sEng, sFlt-1 and PlGF levels were 11% (P < 0.01), 36% (P < 0.001) and 30% (P < 0.001), respectively, lower in women who later suffered miscarriage compared with unaffected pregnancies, while PK-1 did not differ significantly. Logistic regression modelling suggested that increased sFlt-1 (odds ratio (OR) 0.15 95% confidence interval [0.08–0.26], P = 0.0001) and PlGF (OR 0.02 [0.01–0.05], P = 0.0001), but not sEng, were associated with reduced miscarriage risk after adjustment for age, BMI, gestational age, smoking and blood pressure. The combination of sFlt-1 and PlGF did not improve the diagnostic accuracy beyond the use of sFlt-1. LIMITATIONS, REASONS FOR CAUTION First trimester levels of sFlt-1 and PlGF, but not sEng or PK-1, were associated with late miscarriage risk in asymptomatic women. However, a new prospective study is now required to investigate the utility of these markers to predict early (<10 weeks) and late miscarriage, as well as to predict other complications of pregnancy. WIDER IMPLICATIONS OF THE FINDINGS Our data suggest that circulating sFlt-1 and PlGF, but not sEng or PK-1, are independently associated with late miscarriage risk in asymptomatic pregnant women attending their antenatal visit. Therefore, sFlt-1 and PlGF may represent novel markers of placental viability. These data further our understanding of placental function, and have important potential implications for utilizing novel hormonal markers to detect adverse clinical outcomes during pregnancy.
Issue Date: 22-Sep-2016
Date of Acceptance: 11-Aug-2016
URI: http://hdl.handle.net/10044/1/39007
DOI: https://dx.doi.org/10.1093/humrep/dew225
ISSN: 0268-1161
Publisher: Oxford University Press
Start Page: 2681
End Page: 2688
Journal / Book Title: Human Reproduction
Volume: 31
Issue: 12
Copyright Statement: © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. This is a pre-copyedited, author-produced PDF of an article accepted for publication in Human Reproduction following peer review. The version of record C.N. Jayasena, A. Abbara, A.N. Comninos, S. Narayanaswamy, J. Gonzalez Maffe, C. Izzi-Engbeaya, J. Oldham, T.T.M. Lee, Z. Sarang, Z. Malik, M.K. Dhanjal, C. Williamson, L. Regan, S.R. Bloom, and W.S. Dhillo Novel circulating placental markers prokineticin-1, soluble fms-like tyrosine kinase-1, soluble endoglin and placental growth factor and association with late miscarriage Hum. Reprod. first published online September 22, 2016 is available online at: http://humrep.oxfordjournals.org/citmgr?gca=humrep%3Bdew225v1
Sponsor/Funder: National Institute for Health Research
Imperial College Trust
Funder's Grant Number: CDF-2009-02-05
P44488
Keywords: miscarriage
placental markers
pregnancy
prokineticin-1
soluble endoglin and placental growth factor
soluble fms-like tyrosine kinase-1
Obstetrics & Reproductive Medicine
16 Studies In Human Society
11 Medical And Health Sciences
Publication Status: Published
Appears in Collections:Division of Surgery
Department of Medicine
Faculty of Medicine



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Creative Commonsx