Vaginal progesterone for preventing preterm birth and adverse perinatal outcomes in twin gestations: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the efficacy of vaginal progesterone for the prevention of preterm birth and adverse perinatal outcomes in twin gestations. DATA SOURCES: MEDLINE, Embase, LILACS, and CINAHL (from their inception to January 31, 2023), Cochrane databases, Google Scholar, bibliographies, and conference proceedings. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials that compared vaginal progesterone to placebo or no treatment in asymptomatic women with a twin gestation. METHODS: The systematic review was conducted according to the Cochrane Handbook for Systematic Reviews of Interventions. The primary outcome was preterm birth <34 weeks of gestation. Secondary outcomes included adverse perinatal outcomes. Pooled relative risks with 95% confidence intervals were calculated. We assessed the risk of bias in each included study, heterogeneity, publication bias, and quality of evidence, and performed subgroup and sensitivity analyses. RESULTS: Eleven studies (3401 women and 6802 fetuses/infants) fulfilled the inclusion criteria. Among all twin gestations, there were no significant differences between the vaginal progesterone and placebo or no treatment groups in the risk of preterm birth <34 weeks (relative risk, 0.99; 95% confidence interval, 0.84-1.17; high-quality evidence), <37 weeks (relative risk, 0.99; 95% confidence interval, 0.92-1.06; high-quality evidence), and <28 weeks (relative risk, 1.00; 95% confidence interval, 0.64-1.55; moderate-quality evidence), and spontaneous preterm birth <34 weeks of gestation (relative risk, 0.97; 95% confidence interval, 0.80-1.18; high-quality evidence). Vaginal progesterone had no significant effect on any of the perinatal outcomes evaluated. Subgroup analyses showed that there was no evidence of a different effect of vaginal progesterone on preterm birth <34 weeks of gestation related to chorionicity, type of conception, history of spontaneous preterm birth, daily dose of vaginal progesterone, and gestational age at initiation of treatment. The frequencies of preterm birth <37, <34, <32, <30, and <28 weeks of gestation and adverse perinatal outcomes did not significantly differ between the vaginal progesterone and placebo or no treatment groups in unselected twin gestations (8 studies; 3274 women and 6548 fetuses/infants). Among twin gestations with a transvaginal sonographic cervical length <30 mm (6 studies; 306 women and 612 fetuses/infants), vaginal progesterone was associated with a significant decrease in the risk of preterm birth occurring at <28 to <32 gestational weeks (relative risks, 0.48-0.65; moderate- to high-quality evidence), neonatal death (relative risk, 0.32; 95% confidence interval, 0.11-0.92; moderate-quality evidence), and birthweight <1500 g (relative risk, 0.60; 95% confidence interval, 0.39-0.88; high-quality evidence). Vaginal progesterone significantly reduced the risk of preterm birth occurring at <28 to <34 gestational weeks (relative risks, 0.41-0.68), composite neonatal morbidity and mortality (relative risk, 0.59; 95% confidence interval, 0.33-0.98), and birthweight <1500 g (relative risk, 0.55; 95% confidence interval, 0.33-0.94) in twin gestations with a transvaginal sonographic cervical length ≤25 mm (6 studies; 95 women and 190 fetuses/infants). The quality of evidence was moderate for all these outcomes. CONCLUSION: Vaginal progesterone does not prevent preterm birth, nor does it improve perinatal outcomes in unselected twin gestations, but it appears to reduce the risk of preterm birth occurring at early gestational ages and of neonatal morbidity and mortality in twin gestations with a sonographic short cervix. However, more evidence is needed before recommending this intervention to this subset of patients.

Placental growth factor testing in the management of late preterm preeclampsia without severe features: a multicenter, randomized, controlled trial.

BACKGROUND: In women with late preterm preeclampsia, the optimal time for delivery remains a controversial topic, because of the fine balance between the maternal benefits from early delivery and the risks for prematurity. It remains challenging to define prognostic markers to identify women at highest risk for complications, in which case a selective, planned delivery may reduce the adverse maternal and perinatal outcomes. OBJECTIVE: This trial aimed to determine whether using an algorithm based on the maternal levels of placental growth factor in women with late preterm preeclampsia to evaluate the best time for delivery reduced the progression to preeclampsia with severe features without increasing the adverse perinatal outcomes. STUDY DESIGN: This parallel-group, open-label, multicenter, randomized controlled trial was conducted at 7 maternity units across Spain. We compared selective planned deliveries based on maternal levels of placental growth factor at admission (revealed group) and expectant management under usual care (concealed group) with individual randomization in singleton pregnancies with late preterm preeclampsia from 34 to 36+6 weeks' gestation. The coprimary maternal outcome was the progression to preeclampsia with severe features. The coprimary neonatal outcome was morbidity at infant hospital discharge with a noninferiority hypothesis (noninferiority margin of 10% difference in incidence). Analyses were conducted according to intention-to-treat. RESULTS: Between January 1, 2016, and December 31, 2019, 178 women were recruited. Of those women, 88 were assigned to the revealed group and 90 were assigned to the concealed group. The data analysis was performed before the completion of the required sample size. The proportion of women with progression to preeclampsia with severe features was significantly lower in the revealed group than in the concealed group (adjusted relative risk, 0.5; 95% confidence interval, 0.33-0.76; P=.001). The proportion of infants with neonatal morbidity was not significantly different between groups (adjusted relative risk, 0.77; 95% confidence interval, 0.39-1.53; P=.45). CONCLUSION: There is evidence to suggest that the use of an algorithm based on placental growth factor levels in women with late preterm preeclampsia leads to a lower rate of progression to preeclampsia with severe features and reduces maternal complications without worsening the neonatal outcomes. This trade-off should be discussed with women with late preterm preeclampsia to allow shared decision making about the timing of delivery.

Preeclampsia: a defect in decidualization is associated with deficiency of Annexin A2.

BACKGROUND: Decidualization defects in the endometrium have been demonstrated at the time of delivery in women with severe preeclampsia and to linger for years, which suggests a maternal contribution to the pathogenesis of this condition. Global transcriptional profiling reveals alterations in gene expression, which includes down-regulation of Annexin A2 in severe preeclampsia patients with decidualization resistance. OBJECTIVE: We investigated the functional role of Annexin A2 deficiency during endometrial decidualization and its potential contribution to shallow trophoblast invasion during implantation and subsequent placentation using in vitro and in vivo modeling. STUDY DESIGN: Annexin A2 gene and protein levels were assessed during in vitro decidualization of human endometrial stromal cells isolated from biopsy specimens that were collected from women with previous severe preeclampsia (n=5) or normal obstetric outcomes (n=5). Next, Annexin A2 was inhibited with small interference RNA in control human endometrial stromal cells that were isolated from endometrial biopsy specimens (n=15) as an in vitro model to analyze decidualization defects at the morphologic level and the secretion of prolactin and insulin-like growth binding protein-1. Annexin A2-inhibited cells were used to evaluate motility and promotion of embryo invasion. Decidualization and placentation defects of Annexin A2 deficiency were confirmed with the use of an Annexin A2-null mouse model. RESULTS: Annexin A2 gene and protein levels were down-regulated during in vitro decidualization of human endometrial stromal cells from women with previous severe preeclampsia compared with control individuals. To assess its role in the endometrial stroma, we inhibited Annexin A2 expression and detected decidualization failure as evidenced by impaired morphologic transformation, which was associated with altered actin polymerization and low prolactin and insulin-like growth binding protein-1 secretions. Functionally, in vitro models demonstrated that Annexin A2 inhibition failed to support embryo invasion. This finding was corroborated by reduced trophoblast spreading through human endometrial stromal cells, lack of motility of these cells, and reduced trophoblast invasion in the presence of conditioned media from Annexin A2-inhibited cells. Extending our discovery to an animal model, we detected that Annexin A2-null mice have a functional deficiency in decidualization and placentation that impairs fetal growth as a feature that is associated with severe preeclampsia. CONCLUSION: Together, in vitro and in vivo results suggest that endometrial defects in Annexin A2 expression impair decidualization of endometrial stromal cells as well as the uterine microenvironment that promotes embryo implantation and placentation. Our findings highlight the maternal contribution to the pathogenesis of severe preeclampsia and suggest that evaluation of Annexin A2 may provide a novel strategy to assess a woman's risk of experiencing this disease and perhaps discover therapeutic interventions to improve decidualization.

Defective decidualization during and after severe preeclampsia reveals a possible maternal contribution to the etiology.

In preeclampsia (PE), cytotrophoblast (CTB) invasion of the uterus and spiral arteries is often shallow. Thus, the placenta's role has been a focus. In this study, we tested the hypothesis that decidual defects are an important determinant of the placental phenotype. We isolated human endometrial stromal cells from nonpregnant donors with a previous pregnancy that was complicated by severe PE (sPE). Compared with control cells, they failed to decidualize in vitro as demonstrated by morphological criteria and the analysis of stage-specific antigens (i.e., IGFBP1, PRL). These results were bolstered by global transcriptional profiling data that showed they were transcriptionally inert. Additionally, we used laser microdissection to isolate the decidua from tissue sections of the maternal-fetal interface in sPE. Global transcriptional profiling revealed defects in gene expression. Also, decidual cells from patients with sPE, which dedifferentiated in vitro, failed to redecidualize in culture. Conditioned medium from these cells failed to support CTB invasion. To mimic aspects of the uterine environment in normal pregnancy, we added PRL and IGFBP1, which enhanced invasion. These data suggested that failed decidualization is an important contributor to down-regulated CTB invasion in sPE. Future studies will be aimed at determining whether this discovery has translational potential with regard to assessing a woman's risk of developing this pregnancy complication.

A Comparative Study of Vaginal Labor and Caesarean Section Postpartum Uterine Myoelectrical Activity.

Postpartum hemorrhage (PPH) is one of the major causes of maternal mortality and morbidity worldwide, with uterine atony being the most common origin. Currently there are no obstetrical techniques available for monitoring postpartum uterine dynamics, as tocodynamometry is not able to detect weak uterine contractions. In this study, we explored the feasibility of monitoring postpartum uterine activity by non-invasive electrohysterography (EHG), which has been proven to outperform tocodynamometry in detecting uterine contractions during pregnancy. A comparison was made of the temporal, spectral, and non-linear parameters of postpartum EHG characteristics of vaginal deliveries and elective cesareans. In the vaginal delivery group, EHG obtained a significantly higher amplitude and lower kurtosis of the Hilbert envelope, and spectral content was shifted toward higher frequencies than in the cesarean group. In the non-linear parameters, higher values were found for the fractal dimension and lower values for Lempel-Ziv, sample entropy and spectral entropy in vaginal deliveries suggesting that the postpartum EHG signal is extremely non-linear but more regular and predictable than in a cesarean. The results obtained indicate that postpartum EHG recording could be a helpful tool for earlier detection of uterine atony and contribute to better management of prophylactic uterotonic treatment for PPH prevention.

Maternal and fetal outcomes in pregnant women with acute promyelocytic leukemia.

The management of pregnant women with acute promyelocytic leukemia (APL) is a challenge with limited evidence-based information available. We are reporting a series of 14 consecutive pregnant women with APL who were registered in the PETHEMA Data Centre between 1996 and 2012. APL was diagnosed during early pregnancy in five women, late pregnancy in seven, and two additional patients after delivery in an extremely poor clinical condition (pulmonary and cerebral hemorrhage). Eleven of the 12 patients eligible for induction therapy with all-trans retinoic acid and idarubicin achieved complete remission (CR 92 %) and are still in the first CR. All early pregnancies ended in abortion (four induced and one spontaneous), with four of them achieving CR. Eight of nine women in late pregnancy delivered a healthy infant (six cesarean section and two vaginal delivery). All eight babies developed normally. Our results confirm a high cure rate for pregnant women with APL who received all-trans retinoic acid and idarubicin for induction therapy, and an excellent outcome for babies when the disease is diagnosed during late pregnancy.

The effectiveness of cervical cerclage in twin pregnancies with a mid-trimester short cervix: A retrospective cohort study.

OBJECTIVE: To analyze the effectiveness of cerclage in twin pregnancies with a short cervix. STUDY DESIGN: Retrospective cohort study performed in two University Institutions in Valencia (Spain) with two different protocols for the management of asymptomatic dichorionic diamniotic twin pregnancies with mid-trimester cervical length ≤ 25 mm: treatment with indomethacin, antibiotics and cerclage (cerclage group) (N = 43) versus expectant management (control group) (N = 37). RESULTS: The initial cervical length was similar in both groups but detection of a short cervix was performed earlier in the cerclage group (21.6 vs 24.1 weeks, p < 0.001). Women with cerclage had a greater pregnancy latency (12.5 vs. 7.7 weeks, p < 0.001); higher gestational age at delivery (34.1 vs. 31.8 weeks, p < 0.04); less spontaneous preterm birth (SPB) < 28 weeks (11.6 % vs 37.8 %, p < 0.009); higher birthweight (2145 vs 1733 g, p < 0.001); lower birthweight < 1500 g (12.5 % vs 40.0 %, p < 0.001); less admissions to the neonatal intensive care unit (NICU) (24.1 % vs 43.3 %, p < 0.03); shorter stay at NICU (25.6 vs 49.4 days, p < 0.02); lower respiratory distress requiring mechanical ventilation (14.9 % vs 36.5 %, p < 0.02); fewer patent ductus arteriosus (8.9 % vs 26.9 %, p < 0.008); and lower composite adverse neonatal outcome (26.6 % vs. 44.8 %, p < 0.03). Cerclage and gestational age at diagnosis were the only independent predictors of SPB < 32 and < 28 weeks by multivariate analysis. The cumulative data in the literature show promising beneficial effects of cerclage. CONCLUSION: Our data suggest that cerclage in asymptomatic twin pregnancies with a short cervix may reduce the earliest SPB and may improve neonatal outcome.

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.

Progestogens to prevent preterm birth in twin pregnancies: an individual participant data meta-analysis of randomized trials.

BACKGROUND: Preterm birth is the principal factor contributing to adverse outcomes in multiple pregnancies. Randomized controlled trials of progestogens to prevent preterm birth in twin pregnancies have shown no clear benefits. However, individual studies have not had sufficient power to evaluate potential benefits in women at particular high risk of early delivery (for example, women with a previous preterm birth or short cervix) or to determine adverse effects for rare outcomes such as intrauterine death. METHODS/DESIGN: We propose an individual participant data meta-analysis of high quality randomized, double-blind, placebo-controlled trials of progestogen treatment in women with a twin pregnancy. The primary outcome will be adverse perinatal outcome (a composite measure of perinatal mortality and significant neonatal morbidity). Missing data will be imputed within each original study, before data of the individual studies are pooled. The effects of 17-hydroxyprogesterone caproate or vaginal progesterone treatment in women with twin pregnancies will be estimated by means of a random effects log-binomial model. Analyses will be adjusted for variables used in stratified randomization as appropriate. Pre-specified subgroup analysis will be performed to explore the effect of progestogen treatment in high-risk groups. DISCUSSION: Combining individual patient data from different randomized trials has potential to provide valuable, clinically useful information regarding the benefits and potential harms of progestogens in women with twin pregnancy overall and in relevant subgroups.

Timing of Delivery for Twins With Growth Discordance and Growth Restriction: An Individual Participant Data Meta-analysis.

OBJECTIVE: First, to evaluate the risks of stillbirth and neonatal death by gestational age in twin pregnancies with different levels of growth discordance and in relation to small for gestational age (SGA), and on this basis to establish optimal gestational ages for delivery. Second, to compare these optimal gestational ages with previously established optimal delivery timing for twin pregnancies not complicated by fetal growth restriction, which, in a previous individual patient meta-analysis, was calculated at 37 0/7 weeks of gestation for dichorionic pregnancies and 36 0/7 weeks for monochorionic pregnancies. DATA SOURCES: A search of MEDLINE, EMBASE, ClinicalTrials.gov, and Ovid between 2015 and 2018 was performed of cohort studies reporting risks of stillbirth and neonatal death in twin pregnancies from 32 to 41 weeks of gestation. Studies from a previous meta-analysis using a similar search strategy (from inception to 2015) were combined. Women with monoamniotic twin pregnancies were excluded. METHODS OF STUDY SELECTION: Overall, of 57 eligible studies, 20 cohort studies that contributed original data reporting on 7,474 dichorionic and 2,281 monochorionic twin pairs. TABULATION, INTEGRATION, AND RESULTS: We performed an individual participant data meta-analysis to calculate the risk of perinatal death (risk difference between prospective stillbirth and neonatal death) per gestational week. Analyses were stratified by chorionicity, levels of growth discordance, and presence of SGA in one or both twins. For both dichorionic and monochorionic twins, the absolute risks of stillbirth and neonatal death were higher when one or both twins were SGA and increased with greater levels of growth discordance. Regardless of level of growth discordance and birth weight, perinatal risk balanced between 36 0/7-6/7 and 37 0/7-6/7 weeks of gestation in both dichorionic and monochorionic twin pregnancies, with likely higher risk of stillbirth than neonatal death from 37 0/7-6/7 weeks onward. CONCLUSION: Growth discordance or SGA is associated with higher absolute risks of stillbirth and neonatal death. However, balancing these two risks, we did not find evidence that the optimal timing of delivery is changed by the presence of growth disorders alone. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42018090866.

Phosphorylated insulin-like growth factor binding protein-1 and cervical measurement in women with threatening preterm birth.

OBJECTIVE: To assess the efficacy of the cervical phosphorylated insulin-like growth factor binding protein-1 (pIGFBP-1) in combination with cervical length measurement for the prediction of preterm delivery. DESIGN: Observational prospective study. SETTING: University Hospital, Spain. SAMPLE: A total of 276 women between 24 and 34 weeks gestational age complaining of uterine contractions and intact membranes. METHODS: Transvaginal scan to assess cervical length and cervical swabs for pIGFBP-1 detection. MAIN OUTCOME MEASURES: Prevalence of preterm delivery within 48 hours and 7 days, delivery at < 32, < 34 weeks, admission-to-delivery interval by cervical length and the presence of pIGFBP-1. Results. The prevalence of preterm delivery at < 34 weeks was 14.1% (39/276) and 7.6% (21/276) at < 32 weeks. Cervical pIGFBP-1 was positive in 38.7% (107/276), whereas cervical length < 15 mm was present in 7.2% (20/276) and was > 30 mm for 64.8% (179/276) of the women. The presence of a positive pIGFBP-1 appeared useful for prediction of delivery before 32 (likelihood ratio (LR) = 2.21, confidence interval (CI): 1.63-3.00) and 34 weeks (LR = 1.76, CI: 1.25-2.41), respectively. Receiver operating characteristic curves were significant for cervical length and pIGFBP-1 for prediction of delivery at < 34 weeks, < 32 weeks, < 48 hours and < 7 days. Combining pIGFBP-1 and cervical length had a median interval that was shorter when both were positive as compared to only one positive or both negative, but the CIs overlapped. CONCLUSIONS: Both cervical length measurement and pIGFBP-1 are useful for prediction of spontaneous preterm delivery. A pIGFBP-1 positive result associated with cervical length does not improve preterm delivery prediction rates.

Acute Promyelocytic Leukemia during Pregnancy: A Systematic Review of the Literature.

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.

Influence of highly active antiretroviral treatment (HAART) on risk factors for vertical HIV transmission.

OBJECTIVE: To analyze the influence of highly active antiretroviral treatment (HAART) on risk factors for perinatal transmission of human immunodeficiency virus (HIV). DESIGN: A prospective cohort study was performed between HIV pregnant women under HAART therapy and without treatment. SETTING: The maternity hospital 'La Fe' in Valencia, Spain. POPULATION OR SAMPLE: Five hundred HIV-positive pregnant women. METHOD: Known maternal and obstetrical perinatal risk factors were analyzed by univariate and multivariate methods (logistic regression). The influence of HAART on the risk factors was evaluated independently to determine whether there was a modulation in perinatal HIV transmission. MAIN OUTCOME MEASURES: Known perinatal risk factors were found not to have any significant influence on perinatal HIV transmission in women under HAART therapy. RESULTS: Vertical transmission risk decreased significantly from 18.2% without treatment to 8.6% with mono/dual therapy and 0.6% with HAART. A CD4+ cell count below 500 cell/microl, intrapartum use of invasive procedures, rupture of membranes >six hours, labor length >five hours, and birthweight were the significant risk factors associated to vertical HIV transmission and elective cesarean section. Antiretroviral treatment administered during delivery was a protective factor in HIV pregnant women before HAART therapy. CONCLUSIONS: HAART therapy reduces the influence of the perinatal risk factors on vertical HIV transmission.

Characteristics of umbilical cord blood units collected from preterm deliveries.

BACKGROUND: Umbilical cord blood (UCB) banking is a well-established activity supporting the increasing number of UCB transplantations in haematological diseases. Our aim was to analyse the UCB characteristics of UCB units from preterm deliveries and compare them to full-term deliveries. MATERIAL AND METHODS: A prospective study in 194 preterm deliveries occurring at the La Fe University Hospital in Valencia was performed. Patients between 25 and 37 weeks of gestation were included. Those cases were compared to a full-term deliveries control group. RESULTS: The cases were grouped according to the gestational age: between 25 and 33 weeks (group 1), between 34 and 37 weeks (group 2) and between 38 and 42 weeks (group 3). Among obstetric variables, only arterial pH and maternal age variables were similar for all the groups. Higher CD34(+) cell counts were observed in the group 2, while the clonogenic efficiency was higher for the most preterm deliveries. DISCUSSION: UCB from deliveries of at least 34 weeks of gestation contain sufficient hematopoietic stem cell content for unrelated banking and transplantation, even containing higher CD34(+) cell content than UCB units from full-term deliveries. However, UCB from deliveries of less than 33 weeks' gestation contain only sufficient progenitors for children under 20 kg.

Comparison of labour induction with misoprostol and dinoprostone and characterization of uterine response based on electrohysterogram.

OBJECTIVE: The objective of this study is to compare the uterine activity response between women administered dinoprostone (prostaglandin E2) and misoprostol (prostaglandin E1) for induction of labour (IOL) by analysing not only the traditional obstetric data but also the parameters extracted from uterine electrohysterogram (EHG). METHODS: Two cohorts were defined: misoprostol (25-µg vaginal tablets; 251 women) and dinoprostone cohort (10 mg vaginal inserts; 249 women). All the mothers were induced by a medical indication of a Bishop Score < = 6. RESULTS: The misoprostol cohort was associated with a shorter time to achieve active labour (p = .017) and vaginal delivery (p = .009) and with a higher percentage of vaginal delivery in less than 24 h in mothers with a very unfavourable cervix score (risk ratio (RR): 1.41, IC95% 1.17-1.69, p = .002). Successful inductions with misoprostol showed EHG parameter values significantly higher than basal state for amplitude and pseudo Montevideo units (PMU) 60' after drug administration, while spectral parameters significantly increased after 150'. This response was not observed in failed inductions. In the successful dinoprostone group, the duration and number of contractions increased significantly after 120', PMU did so after 180', and no significant differences were found for spectral parameters, possibly due to the slower pharmacokinetics of this drug. CONCLUSION: Successful inductions of labour by misoprostol are associated with earlier effective contractions than in labours induced by dinoprostone.

Uterine electromyography for discrimination of labor imminence in women with threatened preterm labor under tocolytic treatment.

As one of the main aims of obstetrics is to be able to detect imminent delivery in patients with threatened preterm labor, the techniques currently used in clinical practice have serious limitations in this respect. The electrohysterogram (EHG) has now emerged as an alternative technique, providing relevant information about labor onset when recorded in controlled checkups without administration of tocolytic drugs. The studies published to date mainly focus on EHG-burst analysis and, to a lesser extent, on whole EHG window analysis. The study described here assessed the ability of EHG signals to discriminate imminent labor (< 7 days) in women with threatened preterm labor undergoing tocolytic therapy, using both EHG-burst and whole EHG window analyses, by calculating temporal, spectral, and non-linear parameters. Only two non-linear EHG-burst parameters and four whole EHG window analysis parameters were able to distinguish the women who delivered < 7 days from the others, showing that EHG can provide relevant information on the approach of labor, even in women with threatened preterm labor under the effects of tocolytic therapy. The whole EHG window outperformed the EHG-burst analysis and is seen as a step forward in the development of real-time EHG systems able to predict imminent labor in clinical praxis. Graphical abstract The ability of EHG recordings to predict imminent labor (< 7 days) was analyzed in preterm threatened patients undergoing tocolytic therapies by means of EHG-burst and whole EHG window analysis. The non-linear features were found to have better performance than the temporal and spectral parameters in separating women who delivered in less than 7 days from those who did not.

Electrohysterographic characterization of the uterine myoelectrical response to labor induction drugs.

Labor induction is a common practice to promote uterine contractions and labor onset. Uterine electrohysterogram (EHG) has proved its suitability for characterizing the uterus electrophysiological condition in women with spontaneous labor. The aim of this study was to characterize and compare uterine myoelectrical activity during the first 4 h in response to labor induction drugs, Misoprostol (G1) and Dinoprostone (G2), by analyzing the differences between women who achieved active phase of labor and those who did not (successful and failed inductions). A set of temporal, spectral and complexity parameters were computed from the EHG-bursts. As for successful inductions, statistical significant and sustained increases with respect to basal period were obtained for EHG amplitude, mean frequency, uterine activity index (UAI) and Teager, after 60' for the G1 group; duration, amplitude, number of contractions and UAI for the G2 group, after 120'. Moreover, Teager showed statistical significant and sustained differences between successful and failed inductions (1.43 ±â€¯1.45 µV2.Hz2.105 vs. 0.40 ±â€¯0.26 µV2.Hz2.105 after 240') for the G1 group, but not in the G2 group, probably due to the slower pharmacokinetics of this drug. These results revealed that EHG could be useful for successful induction prediction in the early stages of induction, especially when using Misoprostol.

Prediction of labor onset type: Spontaneous vs induced; role of electrohysterography?

BACKGROUND AND OBJECTIVE: Induction of labor (IOL) is a medical procedure used to initiate uterine contractions to achieve delivery. IOL entails medical risks and has a significant impact on both the mother's and newborn's well-being. The assistance provided by an automatic system to help distinguish patients that will achieve labor spontaneously from those that will need late-term IOL would help clinicians and mothers to take an informed decision about prolonging pregnancy. With this aim, we developed and evaluated predictive models using not only traditional obstetrical data but also electrophysiological parameters derived from the electrohysterogram (EHG). METHODS: EHG recordings were made on singleton term pregnancies. A set of 10 temporal and spectral parameters was calculated to characterize EHG bursts and a further set of 6 common obstetrical parameters was also considered in the predictive models design. Different models were implemented based on single layer Support Vector Machines (SVM) and with aggregation of majority voting of SVM (double layer), to distinguish between the two groups: term spontaneous labor (≤41 weeks of gestation) and IOL late-term labor. The areas under the curve (AUC) of the models were compared. RESULTS: The obstetrical and EHG parameters of the two groups did not show statistically significant differences. The best results of non-contextualized single input parameter SVM models were achieved by the Bishop Score (AUC= 0.65) and GA at recording time (AUC= 0.68) obstetrical parameters. The EHG parameter median frequency, when contextualized with the two obstetrical parameters improved these results, reaching AUC= 0.76. Multiple input SVM obtained AUC= 0.70 for all EHG parameters. Aggregation of majority voting of SVM models using contextualized EHG parameters achieved the best result AUC= 0.93. CONCLUSIONS: Measuring the electrophysiological uterine condition by means of electrohysterographic recordings yielded a promising clinical decision support system for distinguishing patients that will spontaneously achieve active labor before the end of full term from those who will require late term IOL. The importance of considering these EHG measurements in the patient's individual context was also shown by combining EHG parameters with obstetrical parameters. Clinicians considering elective labor induction would benefit from this technique.

Prospective risk of stillbirth and neonatal complications in twin pregnancies: systematic review and meta-analysis.

OBJECTIVE: To determine the risks of stillbirth and neonatal complications by gestational age in uncomplicated monochorionic and dichorionic twin pregnancies. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Medline, Embase, and Cochrane databases (until December 2015). REVIEW METHODS: Databases were searched without language restrictions for studies of women with uncomplicated twin pregnancies that reported rates of stillbirth and neonatal outcomes at various gestational ages. Pregnancies with unclear chorionicity, monoamnionicity, and twin to twin transfusion syndrome were excluded. Meta-analyses of observational studies and cohorts nested within randomised studies were undertaken. Prospective risk of stillbirth was computed for each study at a given week of gestation and compared with the risk of neonatal death among deliveries in the same week. Gestational age specific differences in risk were estimated for stillbirths and neonatal deaths in monochorionic and dichorionic twin pregnancies after 34 weeks' gestation. RESULTS: 32 studies (29 685 dichorionic, 5486 monochorionic pregnancies) were included. In dichorionic twin pregnancies beyond 34 weeks (15 studies, 17 830 pregnancies), the prospective weekly risk of stillbirths from expectant management and the risk of neonatal death from delivery were balanced at 37 weeks' gestation (risk difference 1.2/1000, 95% confidence interval -1.3 to 3.6; I(2)=0%). Delay in delivery by a week (to 38 weeks) led to an additional 8.8 perinatal deaths per 1000 pregnancies (95% confidence interval 3.6 to 14.0/1000; I(2)=0%) compared with the previous week. In monochorionic pregnancies beyond 34 weeks (13 studies, 2149 pregnancies), there was a trend towards an increase in stillbirths compared with neonatal deaths after 36 weeks, with an additional 2.5 per 1000 perinatal deaths, which was not significant (-12.4 to 17.4/1000; I(2)=0%). The rates of neonatal morbidity showed a consistent reduction with increasing gestational age in monochorionic and dichorionic pregnancies, and admission to the neonatal intensive care unit was the commonest neonatal complication. The actual risk of stillbirth near term might be higher than reported estimates because of the policy of planned delivery in twin pregnancies. CONCLUSIONS: To minimise perinatal deaths, in uncomplicated dichorionic twin pregnancies delivery should be considered at 37 weeks' gestation; in monochorionic pregnancies delivery should be considered at 36 weeks. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42014007538.