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180: Cytokine profiling: Variation in immune modulation in adverse versus uncomplicated obstetrical outcomes

      Objective

      To assess if deviations in longitudinally measured cytokines are associated with development of adverse pregnancy outcomes.

      Study Design

      This is a prospective longitudinal study of maternal cytokines over pregnancy. Women ≥17 years old with a singleton gestation at < 15 weeks were enrolled. Peripheral blood was collected at 8-14 (T1), 18-22 (T2), and 28-32 (T3) weeks gestational age. Using Luminex-100 MAP®, 6 cytokines—IL-1β, IFN-γ, IL-4, IL-6, IL-10, and TNF-α—were measured from whole blood incubated in three conditions: unstimulated, PHA-stimulated, and LPS-stimulated. Data were stratified into two groups based upon pregnancy outcomes: “Uncomplicated” (delivered at or beyond 37 weeks) or “Adverse” (defined as a delivery <37 weeks gestational age or BW <2500g). Using Generalized Linear Modeling, we determined the rate of change for each cytokine from T1 to T3. An Interaction term of group with gestational age was used to compare the rates of change by pregnancy outcome. Differences were defined as significant at the 95% level.

      Results

      32 women with Adverse obstetrical outcomes were compared to 11 women with Uncomplicated outcomes. In both Adverse and Uncomplicated groups, TH1 cytokine (IL-1β), pleiotrophic pro-inflammatory cytokine (IL-6), and counter-regulatory cytokine (IL-10) responses decreased over the course of gestation. However, the rates of change in IL-1β, IL-6, and IL-10 were significantly different; see table. For other cytokines, trajectories did not vary significantly between the groups.
      Tabled 1Significantly Different Cytokine Trajectories
      Uncomplicated (β-coefficient)Adverse (β-coefficient)p-value
      IL-1β-PHA−0.035−0.0070.004
      IL-6-control−0.009−0.0510.018
      IL-10-control−0.011−0.0590.045

      Conclusion

      Women with a PTB or LBW newborn demonstrated significant differences in cytokine trajectory over pregnancy. This supports existing data on the importance of immunoregulation in pregnancy.