Early pregnancy biomarker discovery study for spontaneous preterm birth.

(1) OBJECTIVE: discover new candidate biomarkers for spontaneous preterm birth in early pregnancy samples. When fully clinically validated, early pregnancy biomarkers for sPTB give the possibility to intervene or monitor high-risk pregnancies more intensively through, as example, pelvic exams, ultrasound or sonographic cervical length surveillance. (2) STUDY DESIGN: Early pregnancy serum samples of eight spontaneous extreme and very preterm birth cases (<32 weeks of gestational age) without any symptoms of preeclampsia and fetal growth restriction and eight uncomplicated pregnancies were analyzed by liquid chromatography mass spectrometry (LC-MS). Thirteen proteins, which were differentially expressed according to the LC-MS data, were subsequently selected for confirmation by enzyme-linked immunosorbent assay (ELISA). (3) RESULTS: Differential expression of four candidate biomarkers was confirmed by ELISA with decreased early pregnancy levels of gelsolin and fibulin-1 and increased levels of c-reactive protein and complement C5 in the preterm birth group. (4) CONCLUSIONS: The confirmed candidate biomarkers are all to some extent related to inflammatory pathways and/or the complement system. This supports the hypothesis that both play a role in extreme and very preterm birth without any symptoms of preeclampsia and fetal growth restriction. The predictive value of complement C5, c-reactive protein, fibulin-1 and gelsolin should, therefore, be validated in another cohort with early pregnancy samples.