Determination of the cytokine levels in fetal pleural effusion and their association with fetal/neonatal findings

Objectives: Few studies have investigated the distribution of multiple cytokines in fetal pleural effusion, and its clinical implications are uncertain. This study aimed to determine cytokine levels in fetal pleural effusion and their clinical role in affected fetuses. Methods: We obtained fetal pleural fluid samples from 18 infants and investigated the profiles of 40 cytokines using multiplex immunoassay. Relationships among cytokines were estimated by Spearman correlation analysis. Possible associations of cytokine levels with fetal adverse outcomes, including perinatal demise and neurodevelopmental impairment, were studied using univariate logistic regression analysis. Results: Several pro-inflammatory cytokines and CCL chemokines were highly correlated with each other. In contrast, CXCL chemokines had relatively weak correlations with other cytokines. The levels of IL-1β, IL-2, and CCL20 were significantly associated with the occurrence of fetal adverse outcomes. Based on our findings, IL-1β had the strongest causal link to adverse outcomes among the cytokines [odds ratio (OR): 19.74; 95% confidence interval (CI): 1.14–341.9; p = 0.040]. Conclusions: Cytokine levels in fetal pleural effusion varied considerably among cases with or without adverse outcomes. These results provide important information for further clarifying the pathophysiology of fetal pleural effusion and a novel clinical implication that could predict the occurrence of adverse outcomes.