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  • Despite the significant associations between TNF and TRAIL

    2020-11-16

    Despite the significant associations between TNF-α and TRAIL in our results, the use of a single top cytokine in predicting sPTB is limited, and the previous study using the specific candidate cytokines failed to accurately predict the risk for sPTB in asymptomatic women, with AUC ranged from 0.48 to 0.54 for IL-2, IL-6, TNF-α, GM-CSF, and IFN-g [35]. The differences in study design and statistical analyses can explain, to some extent, the discrepancy in results. The major cause was that the single cytokine failed to accurately predict sPTB. Although the unique biomarker such as fetal fibronectin has an overall accuracy in identifying the risk for sPTB, the systematic review suggested that further researches in different subset of women (symptomatic or asymptomatic) and at different gestational age are required to determine whether the combination of biomarkers can improve the prediction of sPTB [36]. In our study, introducing multiple cytokines to the predictive models considerably improved the predictive ability for sPTB than single risk factors such as TNF-α or TRAIL selected by conditional logistic regression. Cytokines with diverse functions operate in a complex, tightly regulated network, which control the Ticarcillin sodium function. In addition, multiple cytokines network can accurately predict the risk for sPTB than the single cytokine. As sPTB is a physiologically heterogeneous syndrome, it is linked to several molecular inflammatory mechanisms, which include cytokines and contraction-associated proteins [37]. Even with the relatively small sample size of the BMI categories, some interesting associations between multiple cytokines and maternal BMI were observed. Obvious differences were found in the effect of cytokine levels on sPTB depending on the level of pre-pregnancy BMI. AUC performance was better in the overweight women than in the normal and underweight women. Physiologically, pro-inflammatory cytokines such as TNF-α levels positively correlate with BMI [38], [39]. Jelliffe-Pawlowski et al. found that combined elevated TNF-α and hyperlipidemia result in early PTB, suggesting the potential role of obesity [40]. Although few studies have investigated the relationship between BMI, serum cytokines, and sPTB [41], the effect of BMI on cytokine levels could partially explain the improved predictive ability with BMI stratification. Our findings indicate that selected multiple cytokines are a useful marker for the detection of sPTB in overweight pregnant women. For the early prediction of sPTB in asymptomatic pregnant women, we investigated multiple cytokine patterns stratified on gestational age at sample collection with early, second, and third trimesters. Consequently, the AUC improved for the samples collected in the first trimester than those in second and third trimesters. Interestingly, we found that certain cytokines presented an inverse association in two models: for first trimester, IL-8 was negatively associated with sPTB, whereas for second and third trimesters, it was positively associated with sPTB. It suggested that the effect of certain cytokines dynamically changes during pregnancy. To date, only a few studies have investigated the longitudinal changes in the peripheral cytokines of sPTB during pregnancy [42]. Moreover, our findings were consistent with the previous studies. Both preterm and term labor have a “common pathway” of labor: increased uterine contraction, cervical dilatation, and chorioamniotic membranes rupture [43]. The switch of the myometrium from a quiescent to a contractile status is accompanied by the shift of the signal from anti-inflammatory to pro-inflammatory pathways, which include cytokines [37]. The next step involves the investigation of the upstream factors that cause the shift. We have also focused on the relationship between preterm birth and gestational age, and found that the markers are more predictive of preterm birth before 34 weeks’ gestation (marked by considerable neonatal morbidity) than the subsets preterm birth after 34 weeks’ gestation. Therefore, the multiple cytokines may be a useful biomarker to identify asymptomatic pregnant women at risk of more extreme sPTB, and also to determine whether further screening and clinical intervention are required.