(984) Discordance between inflammatory cervicovaginal cytokine profiles and clinical outcomes among individuals with asymptomatic short cervix

In a prior analysis of the TOPS RCT of pessary vs. usual care in singleton pregnancies with a short CL (≤20 mm) and no prior PTB, we developed a composite pro-inflammatory cytokine score from 12 cervicovaginal fluid (CVF) cytokines obtained at enrollment [median 21.8 (IQR 21.4, 22.4) weeks]. Higher scores indicate higher inflammation and associated eventual PTB and maternal & neonatal infections. As all participants were asymptomatic, the cytokine score reflects subclinical inflammation. We sought to identify factors associated with clinical outcome-cytokine score discordance (e.g., good outcomes despite high cytokine scores or poor outcomes despite low cytokine scores).


Study Design:

Secondary analysis of TOPS; we included those with low (quartile 1) or high (quartile 4) CVF cytokine scores. The primary outcome was outcome-score discordance, defined as PTB < 35 weeks ± maternal (chorioamnionitis) or neonatal (sepsis ± pneumonia) infections contrary to cytokine score expectations. We evaluated patient and clinical factors associated with outcome-score discordance using logistic regression.


Results:
Of 531/544 RCT participants with a cytokine score, 226 met inclusion criteria; 121 had high scores (of whom 47% had unexpectedly good outcomes); 105 had low scores (of whom 24% had unexpectedly poor outcomes). Randomization CL and antenatal bleeding were associated with clinical outcome-cytokine score discordance in both those with low and high cytokine scores. Pessary use was associated with lower odds of unexpectedly good outcomes in the high cytokine score group but not with poor outcomes in the low cytokine score group.

Conclusion:

Quantification of mid-pregnancy subclinical inflammation by CVF cytokines does not fully explain PTB ± maternal or neonatal infections among individuals with an asymptomatic short CL. The value of adding clinical factors such as vaginal bleeding and the extent of cervical length shortening differs by extent of mid-pregnancy CVF subclinical inflammation, highlighting the complexity of PTB pathophysiology and emphasizing the importance of integrating clinical and biologic data.