Objective: A high ratio of soluble fms‐like tyrosine kinase‐1 (sFlt‐1) to placental growth factor (PlGF) has been linked to pre‐eclampsia (PE). We evaluated the sFlt‐1/PlGF ratio as a predictive marker for early‐onset PE in women at risk of PE.Methods: This prospective, Spanish, multicenter study included pregnant women with a risk factor for PE, including intrauterine growth restriction, PE, eclampsia or hemolysis, elevated liver enzymes and low platelet count syndrome in previous pregnancy, pregestational diabetes or abnormal uterine artery Doppler. The primary objective was to show that the sFlt‐1/PlGF ratio at 20, 24 and 28 weeks' gestation was predictive of early‐onset PE (< 34 + 0 weeks). Serum sFlt‐1 and PlGF were measured at 20, 24 and 28 weeks. Multivariate logistic regression was used to develop a predictive model.Results: A total of 819 women were enrolled, of which 729 were suitable for analysis. Of these, 78 (10.7%) women developed PE (24 early onset and 54 late onset). Median sFlt‐1/PlGF ratio at 20, 24 and 28 weeks was 6.3 (interquartile range (IQR), 4.1–9.3), 4.0 (IQR, 2.6–6.3) and 3.3 (IQR, 2.0–5.9), respectively, for women who did not develop PE (controls); 14.5 (IQR, 5.5–43.7), 18.4 (IQR, 8.2–57.9) and 51.9 (IQR, 11.5–145.6) for women with early‐onset PE; and 6.7 (IQR, 4.6–9.9), 4.7 (IQR, 2.8–7.2) and 6.0 (IQR, 3.8–10.5) for women with late‐onset PE. Compared with early‐onset PE, the sFlt‐1/PlGF ratio was significantly lower in controls (P < 0.001 at each timepoint) and in women with chronic hypertension (P < 0.001 at each timepoint), gestational hypertension (P < 0.001 at each timepoint) and late‐onset PE (P < 0.001 at each timepoint). A prediction model for early‐onset PE was developed, which included the sFlt‐1/PlGF ratio plus mean arterial pressure, being parous and previous PE, with areas under the receiver–operating characteristics curves of 0.86 (95% CI, 0.77–0.95), 0.91 (95% CI, 0.85–0.97) and 0.93 (95% CI, 0.86–0.99) at 20, 24 and 28 weeks, respectively, and was superior to models using the sFlt‐1/PlGF ratio alone or uterine artery mean pulsatility index.Conclusions: The sFlt‐1/PlGF ratio can improve prediction of early‐onset PE for women at risk of this condition. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

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.

Objective: To determine if absence of sub-clinical intra-amniotic inflammation improves the prognosis of rescue cerclage in cases of bulging membranes. Methods: Cohort study with all women with bulging membranes admitted into our hospital between 2009 and 2013. Patients underwent amniocentesis to quantify amniotic glucose, leukocytes, IL-6 and leukocyte esterase levels and for microbiological culture. All patients without intra-amniotic inflammation or sub-clinical chorioamnionitis were proposed a physical examination-indicated cervical cerclage. Those who did not accept were treated with bed rest. Results: We enrolled 31 women. Median gestational age at diagnosis was 23 + 1 (21–25 + 4) weeks. Median interval until delivery was 12 (3–52.5) d. IL-6 had the highest diagnostic accuracy for good prognosis. Patients with IL6 <2.90 ng/ml were diagnosed later in pregnancy and presented a longer interval until delivery (89 versus 4 d), higher gestational age at delivery (35 + 1 versus 23 + 3 weeks) and a lower rate of prematurity (54.5% versus 100%) and perinatal mortality (0% versus 80%) than those with IL-6 ≥2.90 ng/ml. Rescue cerclage and low Il-6 were the best predictors of good outcome. Conclusion: IL-6 levels in amniotic fluid may be of clinical value for individualizing the management of patients with bulging membranes for placement of rescue cerclage.

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.

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.

The management of pregnant women with acute promyelocytic leukemia (APL) is a challenging situation where limited evidence-based information is available. We performed a systematic literature review to analyze the outcomes reported for both mother and fetus when APL is diagnosed during pregnancy. PubMed, Scopus and Web of Science databases were systematically searched to identify studies reporting cases of APL during pregnancy. Sixty-six articles met the eligibility criteria (53 single case reports). Ninety-two patients were eligible for induction therapy, with most them being treated with all-trans retinoic acid alone (32%) or combined with chemotherapy (43%), while the remaining patients received chemotherapy alone. Three patients were treated with arsenic-based regimens after delivery. Overall complete remission rate was 89%, with no statistically significant differences according to the type of induction and gestational age. During the first trimester, women were more likely to experience spontaneous and induced abortion compared to those during the second trimester (88% vs. 30%) (p < 0.0001), while only one patient diagnosed during the third trimester terminated in stillbirth. Twelve of 16 infants with neonatal complications had respiratory distress syndrome. Except two early deaths (Potter’s syndrome and pulmonary hemorrhage), all neonates evolved favorably. This study confirms that gestational age does not affect the results in the mother, but is closely related to fetal viability. Our results may be useful for the process of decision making that requires the involvement of the patient, hematologist, obstetrician and neonatologist.