Maternal cytokine profiles in second and early third trimester are not predictive of preterm birth

PLoS One. 2024 Dec 19;19(12):e0311721. doi: 10.1371/journal.pone.0311721. eCollection 2024.

Abstract

Previous studies have investigated whether inflammatory cytokines in maternal circulation are associated with preterm birth. However, many have reported inconsistent results, and few have investigated cytokine trends through gestation, particularly with respect to subtypes of preterm birth. We explored levels of 15 inflammatory cytokines and growth factors in plasma and serum collected in the second (17-23 weeks, timepoint 1 (T1)) and third (28-32 weeks, timepoint 2 (T2)) trimesters with respect to subtypes of preterm birth: spontaneous preterm labour (sPTL), preterm premature rupture of membranes (PPROM), and medically indicated preterm birth (mPTB). The change in TNFα levels over time (T2/T1) significantly classified mPTB from term birth with an AUC of 0.79. While elevated sICAM-1 levels were significantly associated with sPTL, sICAM-1 was not an effective biomarker for prediction. While statistical differences in some biomarkers, such as TNFα and sICAM-1 were found, these are likely not clinically meaningful for prediction. These results did not reveal a relationship between spontaneous labour and circulating maternal inflammatory biomarkers, however, do suggest distinct inflammatory profiles between subtypes of preterm birth.

MeSH terms

  • Adult
  • Biomarkers* / blood
  • Cytokines* / blood
  • Female
  • Fetal Membranes, Premature Rupture / blood
  • Humans
  • Infant, Newborn
  • Intercellular Adhesion Molecule-1 / blood
  • Obstetric Labor, Premature / blood
  • Pregnancy
  • Pregnancy Trimester, Second* / blood
  • Pregnancy Trimester, Third* / blood
  • Premature Birth* / blood
  • Tumor Necrosis Factor-alpha / blood

Substances

  • Cytokines
  • Biomarkers
  • Tumor Necrosis Factor-alpha
  • Intercellular Adhesion Molecule-1

Supplementary concepts

  • Preterm Premature Rupture of the Membranes

Grants and funding

The All Our Families study was funded by an Alberta Innovates Interdisciplinary Team Grant #200700595 and Alberta Children’s Hospital Foundation. Cytokine analysis was funded by CIHR (Project funding #PJT-173295) the funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.