Cluster Analysis of Placental Inflammatory Proteins can Distinguish Preeclampsia from Preterm Labor and Premature Membrane Rupture in Singleton Deliveries Less Than 28 Weeks of Gestation


Jessica M. Faupel-Badger, National Cancer Institute, Cancer Prevention Fellowship Program, 6120 Executive Blvd (EPS), Suite 150E, MSC 7105, Bethesda, MD 20892-7105, USA.


Citation Faupel-Badger JM, Fichorova RN, Allred EN, Hecht JL, Dammann O, Leviton A, McElrath TF. Cluster analysis of placental inflammatory proteins can distinguish preeclampsia from preterm labor and premature membrane rupture in singleton deliveries less than 28 weeks of gestation. Am J Reprod Immunol 2011; 66: 488–494

Problem  Inflammation within the preterm placenta is common and leads to adverse outcomes for premature infants. The risks of complications are different between iatrogenic (e.g. PE) and spontaneous (e.g. PL and membrane rupture) causes of preterm delivery, suggesting different underlying biology contributes to these placental conditions.

Method of study  Thirty preterm singleton placentas from the following groups were analyzed: (i) severe PE, (ii) preterm premature membrane rupture (pPROM), and (iii) PL. Proinflammatory and anti-inflammatory cytokines, adhesion and angiogenic molecules were measured in placental lysates using a multiplex assay. K-means cluster analysis was used to generate patterns of protein level intensity.

Results  Three cluster patterns were apparent. Placentas from PE had high levels of vascular endothelial growth factor (VEGF) combined with low levels of acute inflammatory proteins (IL-1β, IL-18, IL-6, TNF-α), low IL-1 RA, and high transforming growth factor β (TGF-β). PL and pPROM had higher anti-inflammatory IL-1 RA and thrombomodulin combined with lower VEGF, regardless of proinflammatory cytokines and adhesion molecules. Half of the PL and pPROM cases had clusters of heightened inflammatory responses (lower TGF-β clustered with higher intensity of inflammatory mediators).

Conclusion  Discriminating protein patterns were elucidated and may serve as a foundation from which to understand the biologic mechanisms underlying these pregnancy complications.