Abstract
BackgroundWe have previously shown in two independent cohorts that circulating first trimester Macrophage Inhibitory Cytokine-1 (MIC-1) levels are lower in women in early pregnancy who are destined to miscarriage. While promising, the diagnostic performance of measuring MIC-1 alone was not sufficient for it to be a useful predictive test for miscarriage. Besides MIC-1, there are other cytokines, as well as chemokines, involved in facilitating early pregnancy. We reasoned that screening these factors in maternal plasma could uncover other predictive markers of miscarriage.MethodsThis was a nested case control study, of 78 women from a prospective study of 462 attending the Early Pregnancy Assessment Unit in the first trimester (EPAU) with a threatened miscarriage; 34 of these subsequently miscarried (cases) and 44 went on to have a normal delivery (controls) Cytokines IL-1β, IL-6 and IL-10, and the chemokines, CXCL8, CCL2, CCL5, CCL7 and CX3CL1 were measured in plasma from our cohort.ResultsThe cytokines IL-1β, IL-6, IL-10 and the chemokine CXCL8 were not detectable in first trimester plasma. The chemokines CCL2, CCL5, CCL7 and CX3CL1 were detectable in all samples but levels did not vary across 5–12 weeks of gestation among controls. Plasma levels of these chemokines were no different in the miscarriage cohort compared to controls.ConclusionThe chemokines CCL2, CCL5, CCL7 and CX3CL1 were detectable in plasma during the first trimester while IL-1β, IL-6, IL-10 and CXCL8 were not. However, none of the cytokines and chemokines screened were different in maternal plasma in cases or controls. These therefore do not appear to have potential for application as predictive biomarkers of miscarriage.
Highlights
Miscarriage is the most common complication of pregnancy
All women in the ongoing pregnancy cohort progressed to delivery of a live born infant, with most delivering at term
A further clinical application of a predictive test would be to use it as a counseling tool when, potentially, anxious women may be reassured or, alternately, warned they are at risk of a spontaneous miscarriage at a very early stage of pregnancy
Summary
Miscarriage is the most common complication of pregnancy. There are currently no accurate predictive tests and treatments that can prevent spontaneous miscarriage. We have previously postulated that developing an accurate predictive test for miscarriage may open the window for identifying euploid pregnancies that are still viable but destined to miscarry. It follows that conceivably, emerging therapeutics could be targeted at such high risk euploid pregnancies so that some of them may continue to viability, (i.e. rescuing some from miscarriage). We have previously shown in two independent cohorts that circulating first trimester Macrophage Inhibitory Cytokine-1 (MIC-1) levels are lower in women in early pregnancy who are destined to miscarriage. The diagnostic performance of measuring MIC-1 alone was not sufficient for it to be a useful predictive test for miscarriage. We reasoned that screening these factors in maternal plasma could uncover other predictive markers of miscarriage
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