Threatened preterm labor (TPL) is the most common cause of hospitalization in the second half of pregnancy and entails high costs for health systems. Currently, no reliable labor proximity prediction techniques are available for clinical use. Regular checks by uterine electrohysterogram (EHG) for predicting preterm labor have been widely studied. The aim of the present study was to assess the feasibility of predicting labor with a 7- and 14-day time horizon in TPL women, who may be under tocolytic treatment, using EHG and/or obstetric data. Based on 140 EHG recordings, artificial neural networks were used to develop prediction models. Non-linear EHG parameters were found to be more reliable than linear for differentiating labor in under and over 7/14 days. Using EHG and obstetric data, the <7- and <14-day labor prediction models achieved an AUC in the test group of 87.1 ± 4.3% and 76.2 ± 5.8%, respectively. These results suggest that EHG can be reliable for predicting imminent labor in TPL women, regardless of the tocolytic therapy stage. This paves the way for the development of diagnostic tools to help obstetricians make better decisions on treatments, hospital stays and admitting TPL women, and can therefore reduce costs and improve maternal and fetal wellbeing.
One of the remaining challenges for the scientific-technical community is predicting preterm births, for which electrohysterography (EHG) has emerged as a highly sensitive prediction technique. Sample and fuzzy entropy have been used to characterize EHG signals, although they require optimizing many internal parameters. Both bubble entropy, which only requires one internal parameter, and dispersion entropy, which can detect any changes in frequency and amplitude, have been proposed to characterize biomedical signals. In this work, we attempted to determine the clinical value of these entropy measures for predicting preterm birth by analyzing their discriminatory capacity as an individual feature and their complementarity to other EHG characteristics by developing six prediction models using obstetrical data, linear and non-linear EHG features, and linear discriminant analysis using a genetic algorithm to select the features. Both dispersion and bubble entropy better discriminated between the preterm and term groups than sample, spectral, and fuzzy entropy. Entropy metrics provided complementary information to linear features, and indeed, the improvement in model performance by including other non-linear features was negligible. The best model performance obtained an F1-score of 90.1 ± 2% for testing the dataset. This model can easily be adapted to real-time applications, thereby contributing to the transferability of the EHG technique to clinical practice.
Background:Decidualization of the uterine mucosa drives the maternal adaptation to invasion by the placenta. Appropriate depth of placental invasion is needed to support a healthy pregnancy; shallow invasion is associated with the development of severe preeclampsia (sPE). Maternal contribution to sPE through failed decidualization is an important determinant of placental phenotype. However, the molecular mechanism underlying the in vivo defect linking decidualization to sPE is unknown.Methods:Global RNA sequencing was applied to obtain the transcriptomic profile of endometrial biopsies collected from nonpregnant women who suffer sPE in a previous pregnancy and women who did not develop this condition. Samples were randomized in two cohorts, the training and the test set, to identify the fingerprinting encoding defective decidualization in sPE and its subsequent validation. Gene Ontology enrichment and an interaction network were performed to deepen in pathways impaired by genetic dysregulation in sPE. Finally, the main modulators of decidualization, estrogen receptor 1 (ESR1) and progesterone receptor B (PGR-B), were assessed at the level of gene expression and protein abundance.Results:Here, we discover the footprint encoding this decidualization defect comprising 120 genes—using global gene expression profiling in decidua from women who developed sPE in a previous pregnancy. This signature allowed us to effectively segregate samples into sPE and control groups. ESR1 and PGR were highly interconnected with the dynamic network of the defective decidualization fingerprint. ESR1 and PGR-B gene expression and protein abundance were remarkably disrupted in sPE.Conclusions:Thus, the transcriptomic signature of impaired decidualization implicates dysregulated hormonal signaling in the decidual endometria in women who developed sPE. These findings reveal a potential footprint that could be leveraged for a preconception or early prenatal screening of sPE risk, thus improving prevention and early treatments.Funding:This work has been supported by the grant PI19/01659 (MCIU/AEI/FEDER, UE) from the Spanish Carlos III Institute awarded to TGG. NCM was supported by the PhD program FDGENT/2019/008 from the Spanish Generalitat Valenciana. IMB was supported by the PhD program PRE2019-090770 and funding was provided by the grant RTI2018-094946-B-100 (MCIU/AEI/FEDER, UE) from the Spanish Ministry of Science and Innovation with CS as principal investigator. This research was funded partially by Igenomix S.L.
Electrohysterography (EHG) has emerged as an alternative technique to predict preterm labor, which still remains a challenge for the scientific-technical community. Based on EHG parameters, complex classification algorithms involving non-linear transformation of the input features, which clinicians found difficult to interpret, were generally used to predict preterm labor. We proposed to use genetic algorithm to identify the optimum feature subset to predict preterm labor using simple classification algorithms. A total of 203 parameters from 326 multichannel EHG recordings and obstetric data were used as input features. We designed and validated 3 base classifiers based on k-nearest neighbors, linear discriminant analysis and logistic regression, achieving F1-score of 84.63 ± 2.76%, 89.34 ± 3.5% and 86.87 ± 4.53%, respectively, for incoming new data. The results reveal that temporal, spectral and non-linear EHG parameters computed in different bandwidths from multichannel recordings provide complementary information on preterm labor prediction. We also developed an ensemble classifier that not only outperformed base classifiers but also reduced their variability, achieving an F1-score of 92.04 ± 2.97%, which is comparable with those obtained using complex classifiers. Our results suggest the feasibility of developing a preterm labor prediction system with high generalization capacity using simple easy-to-interpret classification algorithms to assist in transferring the EHG technique to clinical practice.
Ovarian hyperthecosis and ovarian stromal hyperplasia (OSH) are two uncommon non-neoplastic causes of ovarian hyperandrogenism, whose etiology is still unknown. These conditions are characterized by obesity, hyperinsulinemia, acanthosis nigricans, and even virilization, mainly in postmenopausal women. Here we have reported the case of a 67-year-old patient with a diagnosis of OSH, which was resolved after bilateral laparoscopic oophorectomy. In this case report, we have discussed two different conditions posing a diagnostic challenge and requiring a high index of suspicion.
Pharmacological agents are often used to induce labor. Failed inductions are associated with unnecessarily long waits and greater maternal-fetal risks, as well as higher costs. No reliable models are currently able to predict the induction outcome from common obstetric data (area under the ROC curve (AUC) between 0.6 and 0.7). The aim of this study was to design an early success-predictor system by extracting temporal, spectral, and complexity parameters from the uterine electromyogram (electrohysterogram (EHG)). Different types of feature sets were used to design and train artificial neural networks: Set_1: obstetrical features, Set_2: EHG features, and Set_3: EHG+obstetrical features. Predictor systems were built to classify three scenarios: (1) induced women who reached active phase of labor (APL) vs. women who did not achieve APL (non-APL), (2) APL and vaginal delivery vs. APL and cesarean section delivery, and (3) vaginal vs. cesarean delivery. For Scenario 3, we also proposed 2-step predictor systems consisting of the cascading predictor systems from Scenarios 1 and 2. EHG features outperformed traditional obstetrical features in all the scenarios. Little improvement was obtained by combining them (Set_3). The results show that the EHG can potentially be used to predict successful labor induction and outperforms the traditional obstetric features. Clinical use of this prediction system would help to improve maternal-fetal well-being and optimize hospital resources.
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