Outperformance of interleukin-6 over placental alpha microglobulin-1 in predicting preterm delivery in symptomatic women.

BACKGROUND: Threatened preterm labor is the major cause of hospital admission during the second half of pregnancy. An early diagnosis is crucial for adopting pharmacologic measures to reduce perinatal mortality and morbidity. Current diagnostic criteria are based on symptoms and short cervical length. However, there is a high false-positive rate when using these criteria, which implies overtreatment, causing unnecessary side effects and an avoidable economic burden. OBJECTIVE: This study aimed to compare the use of placental alpha microglobulin-1 and interleukin-6 as vaginal biomarkers combined with cervical length and other maternal characteristics to improve the prediction of preterm delivery in symptomatic women. STUDY DESIGN: A prospective observational study was conducted in women with singleton pregnancies complicated by threatened preterm labor with intact membranes at 24+0 to 34+6 weeks of gestation. A total of 136 women were included in this study. Vaginal fluid was collected with a swab for placental alpha microglobulin-1 determination using the PartoSure test, interleukin-6 was assessed by electrochemiluminescence immunoassay, cervical length was measured by transvaginal ultrasound, and obstetrical variables and newborn details were retrieved from clinical records. These characteristics were used to fit univariate binary logistic regression models to predict time to delivery <7 days, time to delivery <14 days, gestational age at delivery ≤34 weeks, and gestational age at delivery ≤37 weeks, and multivariate binary logistic regression models were fitted with imbalanced and balanced data. Performance of models was assessed by their F2-scores and other metrics, and the association of their variables with a risk or a protective factor was studied. RESULTS: A total of 136 women were recruited, of whom 8 were lost to follow-up and 7 were excluded. Of the remaining 121 patients, 22 had a time to delivery <7 days and 31 had a time to delivery <14 days, and 30 deliveries occurred with a gestational age at delivery ≤34 weeks and 55 with a gestational age at delivery ≤37 weeks. Univariate binary logistic regression models fitted with the log transformation of interleukin-6 showed the greatest F2-scores in most studies, which outperformed those of models fitted with placental alpha microglobulin-1 (log[interleukin-6] vs placental alpha microglobulin-1 in time to delivery <7 days: 0.38 vs 0.30; time to delivery <14 days: 0.58 vs 0.29; gestational age at delivery ≤34 weeks: 0.56 vs 0.29; gestational age at delivery ≤37 weeks: 0.61 vs 0.16). Multivariate logistic regression models fitted with imbalanced data sets outperformed most univariate models (F2-score in time to delivery <7 days: 0.63; time to delivery <14 days: 0.54; gestational age at delivery ≤34 weeks: 0.62; gestational age at delivery ≤37 weeks: 0.73). The performance of prediction of multivariate models was drastically improved when data sets were balanced, and was maximum for time to delivery <7 days (F2-score: 0.88±0.2; positive predictive value: 0.86±0.02; negative predictive value: 0.89±0.03). CONCLUSION: A multivariate assessment including interleukin-6 may lead to more targeted treatment, thus reducing unnecessary hospitalization and avoiding unnecessary maternal-fetal treatment.

GESTACOVID Project: Psychological and Perinatal Effects in Spanish Pregnant Women Subjected to Strict Confinement Due to the COVID-19 Pandemic and Their Evolution during De-Escalation.

The lockdown and de-escalation process following the COVID-19 pandemic led to a period of new normality. This study aimed to assess the confinement impact on the mental health of peripartum women, as their psychological well-being may be particularly vulnerable and thus affect their offspring's development. A cross-sectional epidemiological study was conducted among women who gave birth during strict confinement (G0) and the new normality period (G1), in which a self-administered paper-based questionnaire assessed 15 contextual factors and the General Health Questionnaire-12 (GHQ-12). For each item, it was verified whether the positive screening rate differed in each confinement phase, and a risk factor study was conducted. For G0, significantly higher positive screening and preterm birth rates were observed in the positive screening group. In the case of G1, maternal age (>35 years), decreased physical activity, and normal weight were found to be protective factors against distress. This study underscores the heightened mental health risk for postpartum women during major psychosocial upheavals (war, economic crisis, natural disasters, or pandemics), along with their resilience as the positive screening rate decreases with the new normality. Findings encourage adopting strategies to identify high-risk women and promote effective measures, such as promoting physical activity.

Diagnosis of intraamniotic inflammation by measuring vaginal interleukin-6 in patients with cervical insufficiency: could amniocentesis be avoided?

BACKGROUND: Cervical insufficiency is a recurrent, passive, and painless dilation of the cervix in the second trimester. The etiology is unclear, but there may be an association with subclinical intraamniotic infection. Interleukin-6 (IL-6) production in the amniotic cavity is induced by bacterial invasion, it is the major proinflammatory cytokine released in response to infection. Although the gold standard method to measure it is through an amniocentesis, the procedure constitutes an invasive technique with several associated risks. The objective of this study is to determine if there is a correlation between intraamniotic and vaginal IL-6 in patients with cervical insufficiency and bulging membranes during the second trimester of pregnancy, in order to avoid an amniocentesis before the rescue cerclage. METHODS: A cohort study was performed in which all patients with cervical insufficiency and bulging membranes admitted into our tertiary hospital between 2019 and 2020 were included, and a control group of asymptomatic women in the second trimester of gestation where studied at the same time. Patients with bulging membranes underwent an amniocentesis to quantify amniotic IL-6, and a sample of vaginal fluid for vaginal IL-6 determination was obtained from both the study and the control group. RESULTS: A total of 20 women were included in each group. Median gestational age at diagnosis was 22 weeks in patients with bulging membranes, and 21 weeks in the control group. Vaginal IL-6 in control group (10.875 pg/mL) is much lower than the study group one (1308.77 pg/ml). In patients with bulging membranes, vaginal IL-6 expression was lower in the vagina than in the amniotic cavity [average IL-6 in the amniotic cavity 26890.07 pg/mL, vs 1308.77 pg/mL in the vagina (p < .01)]. Through a Spearman coefficient correlation rank [rho = 0.709 (p < .001)], there is a positive correlation between amniotic and vaginal IL-6 values. The best value of this correlation was calculated with the ROC curve, being the area under the curve 0.929 (CI 95% 0.721-0.995), and the cutoff of point less than 61.4 pg/ml (sensitivity 83.33%; specificity 92.86%). Patients with vaginal IL-6 < 61.4 pg/ml associated a longer latency time between diagnosis and delivery, a higher neonatal weight and a lower perinatal mortality. Rescue cerclage in vaginal IL-6 < 61.4 pg/ml was the best predictor of good pregnancy outcome. CONCLUSION: There is a correlation between intraamniotic and vaginal IL-6 in patients with cervical insufficiency and bulging membranes during the second trimester of pregnancy. However, further studies are needed in order to considerate the avoidance of an amniocentesis before an emergency cerclage.

GESTACOVID project: psychological and perinatal effects in Spanish pregnant women subjected to confinement due to the COVID-19 pandemic.

INTRODUCTION: COVID-19 was declared a pandemic and confinement with movement restriction measures were applied in Spain. Postnatal mental disorders are common but frequently undiagnosed, being a risk period to develop anxiety and depression symptoms. The aim of this study is to evaluate the impact of confinement as depressive and anxiety symptoms in pregnant women (PrW) and puerperal women (PuW) mental health, as well as obstetric and perinatal outcomes during this period. MATERIALS AND METHODS: The self-administered survey consists of a total of 28 questions, the first 16 providing contextual information and the following ones corresponding to the GHQ-12 that has been evaluated in a binomial form. A logistic regression model has been used to assess whether the contextual variables acted as a protective or risk factor and its fitting has been represented by a receiver operating curve. RESULTS: Of the 754 PrW interviewed, 58.22% were screened positive. Confinement time for these was 54.93 ± 9.75 days. The risk factors that were identified after the refinement have been to have a worse general state of health, to be sadder and to be more nervous. Among the protectors have been found to have a higher Apgar 10 score and induction of labor. The area under the adjusted regression adjustment curve was 0.8056. CONCLUSIONS: Our results show a high prevalence of depression and anxiety symptoms with strict confinement measures. PrW and PuW must be considered a risk group to develop mental health disorders during disruption circumstances. Using a mental health screening tool could help to identify a group of patients with more risk and to carry out a careful monitoring to allow adequate management.

Optimization of Imminent Labor Prediction Systems in Women with Threatened Preterm Labor Based on Electrohysterography.

Preterm birth is the leading cause of death in newborns and the survivors are prone to health complications. Threatened preterm labor (TPL) is the most common cause of hospitalization in the second half of pregnancy. The current methods used in clinical practice to diagnose preterm labor, the Bishop score or cervical length, have high negative predictive values but not positive ones. In this work we analyzed the performance of computationally efficient classification algorithms, based on electrohysterographic recordings (EHG), such as random forest (RF), extreme learning machine (ELM) and K-nearest neighbors (KNN) for imminent labor (<7 days) prediction in women with TPL, using the 50th or 10th-90th percentiles of temporal, spectral and nonlinear EHG parameters with and without obstetric data inputs. Two criteria were assessed for the classifier design: F1-score and sensitivity. RFF1_2 and ELMF1_2 provided the highest F1-score values in the validation dataset, (88.17 ± 8.34% and 90.2 ± 4.43%) with the 50th percentile of EHG and obstetric inputs. ELMF1_2 outperformed RFF1_2 in sensitivity, being similar to those of ELMSens (sensitivity optimization). The 10th-90th percentiles did not provide a significant improvement over the 50th percentile. KNN performance was highly sensitive to the input dataset, with a high generalization capability.

Robust Characterization of the Uterine Myoelectrical Activity in Different Obstetric Scenarios.

Electrohysterography (EHG) has been shown to provide relevant information on uterine activity and could be used for predicting preterm labor and identifying other maternal fetal risks. The extraction of high-quality robust features is a key factor in achieving satisfactory prediction systems from EHG. Temporal, spectral, and non-linear EHG parameters have been computed to characterize EHG signals, sometimes obtaining controversial results, especially for non-linear parameters. The goal of this work was to assess the performance of EHG parameters in identifying those robust enough for uterine electrophysiological characterization. EHG signals were picked up in different obstetric scenarios: antepartum, including women who delivered on term, labor, and post-partum. The results revealed that the 10th and 90th percentiles, for parameters with falling and rising trends as labor approaches, respectively, differentiate between these obstetric scenarios better than median analysis window values. Root-mean-square amplitude, spectral decile 3, and spectral moment ratio showed consistent tendencies for the different obstetric scenarios as well as non-linear parameters: Lempel-Ziv, sample entropy, spectral entropy, and SD1/SD2 when computed in the fast wave high bandwidth. These findings would make it possible to extract high quality and robust EHG features to improve computer-aided assessment tools for pregnancy, labor, and postpartum progress and identify maternal fetal risks.