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. 2011 May;204(5):391.e1-8.
doi: 10.1016/j.ajog.2010.09.021. Epub 2010 Nov 11.

Proteomic identification of serum peptides predicting subsequent spontaneous preterm birth

M Sean Esplin  1 , Karen Merrell, Robert Goldenberg, Yinglei Lai, Jay D Iams, Brian Mercer, Catherine Y Spong, Menachem Miodovnik, Hygriv N Simhan, Peter van Dorsten, Mitchell Dombrowski; Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network
Collaborators, Affiliations

Proteomic identification of serum peptides predicting subsequent spontaneous preterm birth

M Sean Esplin et al. Am J Obstet Gynecol. 2011 May.

Abstract

Objective: We sought to identify serum markers of subsequent spontaneous preterm birth (SPTB) in asymptomatic women prior to labor.

Study design: Serum proteomics was applied to sera from 80 pregnant women sampled at 24 weeks and an additional 80 pregnant women sampled at 28 weeks. Half had uncomplicated pregnancies and half had SPTB.

Results: Three specific peptides arising from inter-alpha-trypsin inhibitor heavy chain 4 protein were significantly reduced in women at 24 and 28 weeks having subsequent SPTB. The most discriminating peptide had a sensitivity of 65.0% and specificity of 82.5%; odds ratio, 8.8; and 95% confidence interval, 3.1-24.8. A combination of the 3 new biomarkers and 6 previously studied biomarkers increased sensitivity to 86.5%, with a specificity of 80.6% at 28 weeks.

Conclusion: Three novel serum markers of SPTB have been identified using serum proteomics. Using a combination of these new markers with additional markers, women at risk of SPTB can be identified weeks prior to SPTB.

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Figures

Figure 1
Figure 1
Representative mass spectra from 8 women with later PTB (red) and 8 women with term deliveries (blue). The multiplets centered at 677 m/z represents an example of a peptide marker.
Figure 2
Figure 2
A ROC curves demonstrating the predictive capability of 3 peptide markers to predict subsequent SPTB after sampling at 24 and 28 weeks. Area under the curve and 95% confidence intervals are also included for each marker at each visit. B ROC curve demonstrating the predictive capability of the combination of 9 predictors including peak 677, peak 857, peak 860, corticotrophin releasing factor, defensin, ferritin, lactoferrin, thrombin antithrombin complex, and tumor necrosis factor – receptor type 1 to predict subsequent SPTB after sampling at 28 weeks. Area under the curve and 95% confidence intervals are also reported. C. Normalized biomarker abundance was calculated for all individuals at 28 weeks. The graph shows biomarker (m/z 677) abundance in the sera of women having a subsequent SPTB or term delivery. Sixty five percent (26/40) of the women with subsequent SPTB had a value below the threshold whereas only 17.5 (7/40) percent of women with a term delivery had a value below the same threshold.
Figure 3
Figure 3
A representative plot of one biomarker’s normalized abundance (m/z 857) as a function of time to delivery (days). The correlation was statistically significant (R=0.11, p=0.001).
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