Prediction of spontaneous preterm delivery in women with threatened preterm labour: a prospective cohort study of multiple proteins in maternal serum

Abstract

Sir, I was interested to read the paper by Tsiartas and colleagues 1 published in the June 2012 issue of BJOG. The authors reported the prediction of preterm labour by building a model using a cohort data set. As the authors point out in their conclusion, such a model needs to be tested in a new cohort in order to confirm its predictive ability. Why did the authors not divide their cohort into two and develop the model on one half and test it on the other? Or use other methods such as bootstrapping to test the reliability of their model?They have reported a sensitivity of 74%, a specificity of 87%, a positive predictive value (PPV) of 76%, a negative predictive value (NPV) of 86%, a likelihood ratio of 5.8 and an area under the receiver operating characteristic (AUC) curve of 0.88, concluding that serum proteins and cervical length constituted the best prediction model for the mentioned outcome. 1 Sensitivity, specificity, PPV, NPV, positive likelihood ratio (true positive/false negative) and negative likelihood ratio (false positive/true negative), as well as odds ratio (true results/false results, preferably with a value of more than 50), are among the tests to evaluate the validity (i.e. accuracy) of a single test compared with a gold standard. [2][3][4] Considering the range of values for the positive likelihood ratio (LR + = 1-infinity) and negative likelihood ratio (LR ) = 0-1), knowing that both LR + and LR ) equal 1 is the worst situation for the test. An LR + of 5.8 says nothing about the predictive value, because this should be compared with another LR + . Moreover, considering the range of possible LR + values, an LR + of 5.8 seems unimpressive. In such a situation, it is better to at least report the LR ) as well. 2,4 The area under the ROC curve is usually reported for diagnostic rather prognostic values of a model. The ROC for models may be comparable with LR + for a test because both of them actually use sensitivity and 1 -specificity; however, in LR + they are divided, and in the ROC we should plot sensitivity to 1 -specificity. 4 Prediction of spontaneous preterm delivery in women with threatened preterm labour: a prospective cohort study of multiple proteins in maternal serum Authors' ReplySir, First, we would like to thank Dr Sabour 1 for his interest in our paper. 2 He has raised important questions regarding the data analyses, which we appreciate taking the opportunity to clarify. We agree, and have pointed out in our Conclusions, that the predictive model needs to be validated in a new cohort in order to confirm its predictive ability. When we performed the analyses, we decided not to divide our data set into two parts to develop the model in one half and test it in the other. This division would have resulted in a substantial reduction of the predictive power of this study, with its limited number of patients. Our results must thus be replicated in another cohort.

Prediction of spontaneous preterm birth in women with cervical insufficiency: Comprehensive analysis of multiple proteins in amniotic fluid

“…In addition, the current study demonstrates that combining multiple biomarkers, especially with clinical data, can improve the accuracy of risk prediction for preterm birth, and these combinations are more accurate than using each of these biomarkers alone. These findings are in agreement with the results of previous studies in the setting of preterm labor and intact membranes . These observations may be attributed to the fact that preterm parturition is associated with the upregulation of various chemokines and MMPs, as well as traditional proinflammatory cytokines; thus, the evaluation of multiple biomarkers in AF can more precisely represent this inflammatory process in vivo , as well as the fact that spontaneous preterm birth has a multifactorial etiology …”

“…Specifically, in terms of reflecting intra‐amniotic infection and/or inflammation, interleukin (IL)‐6 and matrix metalloproteinase (MMP)‐8 in amniotic fluid (AF) have been suggested as surrogate biomarkers for the prediction of preterm birth in women with cervical insufficiency . Importantly, a recent study aimed at predicting preterm birth in women with preterm labor and intact membranes demonstrated that the combined use of multiple biomarkers in AF, cervical fluid and maternal blood, and clinical factors substantially improved diagnostic efficiency and had better predictive accuracy than any of the biomarkers alone . This observation is not surprising given that the evaluation of multiple biomarkers representing several distinct biological pathways may provide additional information about the biological status of the disease, as well as additional prognostic information.…”

Inflammatory Proteins in the Amniotic Fluid, Plasma, and Cervicovaginal Fluid for the Prediction of Intra-Amniotic Infection/Inflammation and Imminent Preterm Birth in Preterm Labor

“…Therefore, several recent studies have focused on predictors of these outcomes by utilizing noninvasively collected samples (i.e., cervicovaginal fluid [CVF] or maternal serum). [9][10][11][12][13][14] However, most studies have not yet found reliable biomarkers in either the CVF or maternal blood compartment alone, which have high sensitivity and specificity comparable with those of AF sampling-based tests. Moreover, to date, there is little information regarding whether cytokine/ chemokine expression in both the CVF and maternal blood compartment is influenced by immune-inflammatory responses elicited by microbes in the AF compartment.…”

“…These five analytes were selected on the basis of previous findings that their levels were altered in the AF, serum, and CVF in women with PTL in relation to MIAC, IAI, and imminent SPTD. [11][12][13][14]17 We aimed to assess the correlations among multiple cytokine/chemokine levels in AF, CVF, and maternal plasma in women with PTL, and to develop models using these protein levels in CVF and plasma along with widely used noninvasive parameters that have better accuracy for predicting IAI and imminent SPTD ( 48 hours).…”

Combined insulin‐like growth factor binding protein‐1/interleukin‐6 (Premaquick) versus fetal fibronectin for predicting preterm delivery among women with preterm contractions

“…It can lead to preterm delivery, which has high neonatal morbidity and mortality . The resulting preterm delivery can also be a substantial cause of emotional and financial stress to parents and society …”