Second trimester cytokine profiles associated with gestational diabetes and hypertensive disorders of pregnancy

Abstract

Healthy pregnancy requires a coordinated immune response, yet complications can arise, putting both the mother’s and child’s health at risk. Hypertensive disorders of pregnancy (HDP) and gestational diabetes mellitus (GDM) are pregnancy-related complications that account for most maternal morbidity and mortality. Cytokines are proteins released as part of the immune response to disease or infection and regulate inflammation. Certain pregnancy complications cause localized and systemic inflammation; however, cytokine profiles specific to such complications are not well understood. This study aims to examine associations between pregnancy complications of HDP and GDM and cytokine profiles in the second trimester of pregnancy. Data was obtained from the All Our Families birth cohort in Calgary, Alberta, Canada. The cohort collected questionnaires at the time of participant enrollment and maternal blood samples at 17–23 weeks gestation. Cases of HDP (n = 27) and GDM (n = 31) were matched to controls on BMI, maternal age, and smoking status in the preconception period at a 1:3 ratio. Cytokine levels were measured in blood samples using Luminex xMAP technology using a panel of 42 cytokines. Using R software, a Classification and Regression Tree (CART) analysis was conducted to identify cytokine profiles and levels associated with each complication. Four cytokines were identified in the HDP CART (in descending order of importance): Monocyte Chemoattractant Protein-1 (cut-off: <480pg/mL), Macrophage Inflammatory Protein-1β (cut-off: ≥26pg/mL), Eotaxin (cut-off: <27/≥27&<36/≥36pg/mL), and Soluble Cluster of Differentiation 40 Ligand (cut-off: <1342pg/mL). Six cytokine levels were identified in the GDM CART: Interleukin-1 Receptor Antagonist (IL-1Ra; cut-off: <25pg/mL), Interleukin-5 (cut-off: ≥0.4pg/mL), Interferon-γ (cut-off: <4.9pg/mL), IL-1Ra (cut-off: ≥111pg/mL), Eotaxin (cut-off: ≥21pg/mL), and Interleukin-18 (cut-off: ≥155pg/mL). By examining the complex inter-relationships between cytokines, findings of cytokine profiles guide further research in identifying biomarkers of pregnancy complications relevant to the design of the future management or prevention of these conditions.