First-trimester maternal plasma cytokine levels, pre-pregnancy body mass index, and spontaneous preterm delivery

Objective. To examine associations between first-trimester plasma cytokines and spontaneous preterm delivery (sPTD). Design. A case-control study was nested within the Danish National Birth Cohort, a cohort of women with 101,042 pregnancies from 1997 to 2002 who were recruited during pregnancy and followed prospectively. Sample. Subjects included 107 women delivering singleton infants at 24-29 weeks, 353 at 30-33 weeks, 422 at 34-36 weeks, and 1,372 at 37 weeks. Methods. Maternal plasma interleukin (IL)-2, IL-6, tumor necrosis factor (TNF)-, interferon (IFN)-, and granulocyte-macrophage colony-stimulating factor (GM-CSF) were measured at a median of eight weeks gestation using multiplex flow cytometry. Adjusted odds ratios (ORs) were obtained using polytomous logistic regression. Main outcome measures. sPTD categorized as: 24-29 weeks, 30-33 weeks, 34-36 weeks, and 37 weeks (controls). Results. Elevated TNF- and GM-CSF were associated with an increased risk of delivery at 34-36 weeks. In underweight women, sPTD 34 weeks was associated with elevated (75th percentile) IL-6 (OR=5.62, 95% confidence interval (CI): 1.73, 18.26) and TNF- (OR=3.02, CI: 1.02, 8.91) compared with term delivery. Conversely, among obese women, elevated IL-2 (OR=0.30, CI: 0.11, 0.78) and TNF- (OR=0.15, CI: 0.05, 0.47) were associated with a reduced risk of delivering at 34 weeks. Cytokines were not related to delivery at 34 weeks in normal-weight and overweight women. Conclusions. These findings suggest that the association between first-trimester plasma cytokine levels and sPTD may depend on pre-pregnancy body mass index.