Associations of preterm birth with umbilical cord serum inflammatory cytokines interferon-γ, interleukin-12p70, and interleukin-17A

Background Preterm birth is the main cause of neonatal morbidity and death. Infection causing inflammation is known to be one of the risk factors for preterm birth, but the specific associations between the levels of various inflammatory cytokines and preterm birth need further study.

Objective This study aims to investigate the associations between inflammatory cytokine levels in umbilical cord serum and preterm birth.

Methods Based on the birth cohort study conducted at Ma'anshan Maternal and Child Health Hospital from May 2013 to September 2014, a total of 1 433 pairs of mothers and infants were included in the analysis. Umbilical cord blood samples were collected immediately after delivery to detect the concentrations of eight serum inflammatory factors, including interferon-γ (IFN-γ), interleukin (IL)-1β, IL-6, IL-8, IL-10, IL-12p70, IL-17A, and tumor necrosis factor-α (TNF-α). The Mann-Whitney U test was used to analyze the differences in umbilical cord serum inflammatory cytokine concentrations between the preterm group (gestational age < 37 weeks) and the full term group (gestational age 37 to 41 weeks). The participants were divided into low, medium, and high level groups according to tertiles of inflammatory cytokine concentrations. After adjusting for confounding factors, a binary logistic regression model was used to analyze the associations between umbilical cord serum inflammatory cytokine levels and preterm birth.

Results Among the 1 433 newborns, 3.3% (47 cases) were premature infants. The IFN-γ, IL-1β, IL-6, IL-8, IL-10, IL-12p70, IL-17A, and TNF-α concentrations in umbilical cord serum M (P₂₅-P₇₅) were 1.40 (0.97-2.21), 0.46 (0.31-0.64), 1.83 (1.08-2.87), 6.98 (4.58-10.23), 7.25 (5.37-9.30), 0.88 (0.61-1.25), 1.56 (1.02-2.20), and 12.81 (8.68-17.73) ng·L^-1, respectively, and the positive rates were from 94.77% to 100.00%. The median concentrations of IFN-γ, IL-1β, IL-12p70, and IL-17A in umbilical cord serum of the preterm group were higher than those of the full term group (1.99 vs. 1.40, 0.61 vs. 0.46, 1.23 vs. 0.86, and 14.59 vs. 12.81 ng·L^-1) (Ps < 0.01). After adjusting for confounding factors, compared with the corresponding low level group, the OR (95% CI) values of preterm birth in the high level groups of IFN-γ, IL-12p70, and IL-17A in umbilical cord serum were 3.09 (1.39-6.85), 3.76 (1.66-8.53), and 2.43 (1.16-5.08), respectively, and the associations between other inflammatory cytokines and preterm birth were not statistically significant (Ps > 0.05).

Conclusion There are positive correlations between IFN-γ, IL-12p70, and IL-17A levels in umbilical cord serum and preterm birth, that is, higher levels of inflammatory cytokines are related to a higher risk of preterm birth.