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

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 >= 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.