Maternal Serum Macrophage Inhibitory Cytokine-1 as a Biomarker for Ectopic Pregnancy in Women with a Pregnancy of Unknown Location

Monika Skubisz, Jeremy Brown, Stephen Tong, Andrew Horne, Tu'uhevaha Kaitu'u-Lino

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output


Ectopic pregnancy (EP) occurs in 1–2% of pregnancies, but is over-represented as a leading cause of maternal death in early pregnancy. It remains a challenge to diagnose early and accurately. Women often present in early pregnancy with a ‘pregnancy of unknown location’ (PUL) and the diagnosis and exclusion of EP is difficult due to a lack of reliable biomarkers. A serum biomarker able to clearly distinguish between EP and other pregnancy outcomes would greatly assist clinicians in diagnosing and safely managing PULs. This study evaluates the ability of maternal serum macrophage inhibitory cytokine-1 (MIC-1) levels to differentiate between EP and other pregnancy outcomes in women with a PUL.


Sera were collected from 120 women with a PUL at first clinical presentation and assayed for MIC-1 by ELISA. Results were classified according to ultimate pregnancy outcome and the discriminatory ability of MIC-1 to diagnose EP was assessed.


Serum MIC-1 levels were lower in women with histologically confirmed (definite) EP (dEP) (median 552 ng/mL; interquartile range (IQR) 414–693 ng/mL) compared to women with definite viable intra-uterine pregnancies (dVIUPs) (722 ng/mL; IQR 412–1122 ng/mL), and higher when compared to women with definite non-viable intra-uterine pregnancies (dNVIUPs) (465 ng/mL; IQR 341–675 ng/mL). MIC-1 levels were significantly higher in women with dEP compared to women whose PULs resolved without medical intervention (srPUL) (401 ng/mL; IQR 315–475 ng/mL) (p<0.003). There were no women with an ectopic pregnancy where serum MIC-1>1000 ng/mL.


Serum MIC-1 levels in PUL were not able to categorically diagnose EP, however, MIC-1 could distinguish women with an EP that required medical intervention and those women whose PULs spontaneously resolved. A single serum MIC-1 measurement also excluded EP at levels above 1000 ng/mL. MIC-1 may play a role in the development of a combined assay of biomarkers for the diagnosis of EP.

Citation: Skubisz MM, Brown JK, Tong S, Kaitu’u-Lino T, Horne AW (2013) Maternal Serum Macrophage Inhibitory Cytokine-1 as a Biomarker for Ectopic Pregnancy in Women with a Pregnancy of Unknown Location. PLoS ONE 8(6): e66339. doi:10.1371/journal.pone.0066339

Editor: Colette Kanellopoulos-Langevin, Institut Jacques Monod - UMR 7592 CNRS - Université Paris Diderot, France

Received: December 3, 2012; Accepted: May 9, 2013; Published: June 18, 2013

Copyright: © 2013 Skubisz et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: The study was supported by the Australian National Health and Medical Research Council (#1008276; #606611) and by the United Kingdom Medical Research Council (MRC G0802808). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: AH holds a United Kingdom patent for a diagnostic biomarker for ectopic pregnancy (# 0712801.0). This does not alter the authors’ adherence to all PLOS ONE policies on sharing data and materials
Original languageEnglish
Article numbere66339
Number of pages5
JournalPLoS ONE
Issue number6
Publication statusPublished - 18 Jun 2013


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