Mid-pregnancy maternal plasma levels of interleukin 2, 6, and 12, tumor necrosis factor-alpha, interferon-gamma, and granulocyte-macrophage colony-stimulating factor and spontaneous preterm delivery

Abstract

Background: Few studies have investigated the relationship between inflammation and spontaneous preterm delivery (sPTD) in women before preterm labour. The authors examine whether mid-pregnancy plasma cytokine levels are associated with sPTD, and whether associations vary by maternal age, body mass index, prior preterm delivery, or gravidity.

Methods: This case-control study was nested within the Danish National Birth Cohort, a cohort of women with 101,042 pregnancies from 1997 to 2002. Included in this study are 61 women delivering at 24-29 weeks, 278 delivering at 30-33 weeks, 334 delivering at 34-36 weeks, and 1,125 delivering at > or =37 weeks. Maternal plasma interleukin (IL)-2, IL-6, tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, and granulocyte-macrophage colony-stimulating factor (GM-CSF) at 25 weeks' gestation were measured using multiplex flow cytometry.

Results: For IL-2, TNF-alpha, and GM-CSF, the proportion of women with levels >75th or >90th percentile did not differ by gestational age at delivery. IFN-gamma >90th percentile was associated with an increased risk of delivering at 30-33 weeks (crude odds ratio (cOR): 1.56; 95% confidence interval (CI): 1.07-2.30), while IFN-gamma >75th percentile and IL-6 >75th percentile were associated with an increased risk of delivering at 34-36 weeks (cOR: 1.32; 95% CI: 1.01-1.73); estimates changed little after adjusting for confounders. There was no effect-measure modification by maternal factors.

Conclusion: Elevated mid-pregnancy plasma IL-2, TNF-alpha, and GM-CSF did not appear to be associated with an increased risk of sPTD, while elevated IFN-gamma and IL-6 levels were weakly associated with moderate and late sPTD. The value of using mid-pregnancy cytokines in predicting spontaneous preterm delivery appears limited.