A peripheral immune signature of labor induction

Approximately 1 in 4 pregnant women in the United States undergo labor
induction. The onset and establishment of labor, particularly
induced labor, is a complex and dynamic process influenced by multiple
endocrine, inflammatory, and mechanical factors as well as obstetric and
pharmacological interventions. The duration from labor induction to the
onset of active labor remains unpredictable. Moreover, prolonged labor is
associated with severe complications for the mother and her offspring,
most importantly chorioamnionitis, uterine atony, and postpartum
hemorrhage. While maternal immune system adaptations that are critical for
the maintenance of a healthy pregnancy have been previously characterized,
the role of the immune system during the establishment of labor is poorly
understood. Understanding maternal immune adaptations during labor
initiation can have important ramifications for predicting successful
labor induction and labor complications in both induced and spontaneous
types of labor. The aim of this study was to characterize labor-associated
maternal immune system dynamics from labor induction to the start of
active labor. Serial blood samples from fifteen participants were
collected immediately prior to labor induction (baseline) and during the
latent phase until the start of active labor. Using high-dimensional mass
cytometry, a total of 1,059 single-cell immune features were extracted
from each sample. A multivariate machine-learning method was employed to
characterize the dynamic changes of the maternal immune system after labor
induction until the establishment of active labor. A cross-validated
linear sparse regression model (least absolute shrinkage and selection
operator, LASSO) predicted the minutes since induction of labor with high
accuracy (R = 0.86, p = 6.7e-15, RMSE = 277 min). Immune features most
informative for the model included STAT5 signaling in central memory CD8+
T cells and pro-inflammatory STAT3 signaling responses across multiple
adaptive and innate immune cell subsets. Our study reports a peripheral
immune signature of labor induction, and provides important insights into
biological mechanisms that may ultimately predict labor induction
success as well as complications, thereby facilitating clinical
decision-making to improve maternal and fetal well-being.