Vaginal misoprostol versus vaginal dinoprostone for cervical ripening and induction of labour: An individual participant data meta-analysis of randomised controlled trials.

BACKGROUND: Induction of labour (IOL) is common practice and different methods carry different effectiveness and safety profiles. OBJECTIVES: To compare the effectiveness, and maternal and perinatal safety outcomes of IOL with vaginal misoprostol versus vaginal dinoprostone using individual participant data from randomised clinical trials. SEARCH STRATEGY: The following databases were searched from inception to March 2023: CINAHL Plus, ClinicalTrials.gov, Cochrane Pregnancy and Childbirth Group Trial Register, Ovid Embase, Ovid Emcare, Ovid MEDLINE, Scopus and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). SELECTION CRITERIA: Randomised controlled trials (RCTs), with viable singleton gestation, no language restrictions, and all published and unpublished data. DATA COLLECTION AND ANALYSIS: An individual participant data meta-analysis was carried out. MAIN RESULTS: Ten of 52 eligible trials provided individual participant data, of which two were excluded after checking data integrity. The remaining eight trials compared low-dose vaginal misoprostol versus dinoprostone, including 4180 women undergoing IOL, which represents 32.8% of all participants in the published RCTs. Of these, 2077 were assigned to low-dose vaginal misoprostol and 2103 were assigned to vaginal dinoprostone. Compared with vaginal dinoprostone, low-dose vaginal misoprostol had a comparable rate of vaginal birth. Composite adverse perinatal outcomes did not differ between the groups. Compared with vaginal dinoprostone, composite adverse maternal outcomes were significantly lower with low-dose vaginal misoprostol (aOR 0.80, 95% CI 0.65-0.98, P = 0.03, I2 = 0%). CONCLUSIONS: Low-dose vaginal misoprostol and vaginal dinoprostone for IOL are comparable in terms of effectiveness and perinatal safety. However, low-dose vaginal misoprostol is likely to lead to a lower rate of composite adverse maternal outcomes than vaginal dinoprostone.

Growth charts for use at birth and in the neonatal period: Recommendations of the French Neonatal Society.

INTRODUCTION: The use of different growth charts can lead to confusion in discussions between professionals. There are obstetric charts (of fetal growth) and neonatal charts (of measurements at birth and of postnatal growth). These charts can be descriptive (derived from an unselected population) or prescriptive (derived from of a population at low risk and with optimal conditions for growth). OBJECTIVES: (1) To describe available charts for infants at birth and in the neonatal period and compare them, and (2) to recommend one or more charts for use in neonatology in France. METHODS: Bibliographic research was conducted on MEDLINE and completed by the guidelines of professional societies. RESULTS: Antenatal information about fetal growth restriction (FGR) or fetuses identified as small-for-gestational-age using Intrauterine charts must be integrated into the identification of newborns at risk, but the use of Intrauterine charts to evaluate birthweight is not recommended to allow consistency with postnatal charts used in neonatal practice. Z-score variations using the updated Fenton postnatal charts are the most appropriate for the assessment of birthweight and postnatal growth for infants born preterm. These charts are sex-specific, include the three measurements (length, weight, and head circumference) and enable longitudinal follow-up of growth up to 50 weeks of corrected age and are linked to the WHO charts at term. The French Audipog charts, although are individualized, accessible online and can be used in maternity units to evaluate birthweight for term infants, but do not allow the follow-up of postnatal growth, while Fenton charts may be used to evaluate birthweight and postnatal growth in the first month for hospitalized term infants. CONCLUSION: The updated Fenton charts are the neonatal charts that best suit the objectives of pediatricians in France for monitoring the growth of preterm newborns. The use of the Audipog charts at term remains an alternative in maternity wards, while Fenton charts can be used for hospitalized term newborns.

Human papillomavirus testing using HPV APTIMA® assay and an external cellularity control in self-collected samples.

In cervical cancer screening programs, the detection of high-risk human papillomavirus (HR-HPV) is now widely implemented on physician-collected samples and has expanded to include self-collected samples. The use of a cellularity control (CC) is needed to reduce false-negative HPV results. An external mRNA CC for the HPV APTIMA® assay was assessed for its analytical performance and the results were compared with both cervix cytobrush samples taken by physicians and self-collected vaginal samples from 148 women. The performance of the CC was adjusted to control for the presence of cellular mRNA in the ThinPrep® and Multitest® transport media. This CC is user-friendly but implies to perform two independent assays on PANTHER® automate. Self-collected vaginal sampling gives a lower median CC results (13.2 vs. 16.9 min) but a higher risk of negative CC results (3.3 vs. 0%). The usefulness of the CC for the HR-HPV assay may be optimized by the definition of a threshold for a minimum cell number to be tested to increase confidence in HPV-negative results. The systematic use of an RNA CC increases confidence for HPV RNA assays on self-collected vaginal samples.

Efficacy of early intrauterine balloon tamponade for immediate postpartum hemorrhage after vaginal delivery: a randomized clinical trial.

BACKGROUND: Many questions remain about the appropriate use of intrauterine balloon devices in postpartum hemorrhage after vaginal delivery refractory to first-line uterotonics. Available data suggest that early use of intrauterine balloon tamponade might be beneficial. OBJECTIVE: This study aimed to compare the effect of intrauterine balloon tamponade used in combination with second-line uterotonics vs intrauterine balloon tamponade used after the failure of second-line uterotonic treatment on the rate of severe postpartum hemorrhage in women with postpartum hemorrhage after vaginal delivery refractory to first-line uterotonics. STUDY DESIGN: This multicenter, randomized, controlled, parallel-group, nonblinded trial was conducted at 18 hospitals and enrolled 403 women who had just given birth vaginally at 35 to 42 weeks of gestation. The inclusion criteria were a postpartum hemorrhage refractory to first-line uterotonics (oxytocin) and requiring a second-line uterotonic treatment with sulprostone (E1 prostaglandin). In the study group, the sulprostone infusion was combined with intrauterine tamponade by an ebb balloon performed within 15 minutes of randomization. In the control group, the sulprostone infusion was started alone within 15 minutes of randomization, and if bleeding persisted 30 minutes after the start of sulprostone infusion, intrauterine tamponade using the ebb balloon was performed. In both groups, if the bleeding persisted 30 minutes after the insertion of the balloon, an emergency radiological or surgical invasive procedure was performed. The primary outcome was the proportion of women who either received ≥3 units of packed red blood cells or had a calculated peripartum blood loss of >1000 mL. The prespecified secondary outcomes were the proportions of women who had a calculated blood loss of ≥1500 mL, any transfusion, an invasive procedure and women who were transferred to the intensive care unit. The analysis of the primary outcome with the triangular test was performed sequentially throughout the trial period. RESULTS: At the eighth interim analysis, the independent data monitoring committee concluded that the incidence of the primary outcome did not differ between the 2 groups and stopped inclusions. After 11 women were excluded because they met an exclusion criterion or withdrew their consent, 199 and 193 women remained in the study and control groups, respectively, for the intention-to-treat analysis. The women's baseline characteristics were similar in both groups. Peripartum hematocrit level change, which was needed for the calculation of the primary outcome, was missing for 4 women in the study group and 2 women in the control group. The primary outcome occurred in 131 of 195 women (67.2%) in the study group and 142 of 191 women (74.3%) in the control group (risk ratio, 0.90; 95% confidence interval, 0.79-1.03). The groups did not differ substantially for rates of calculated peripartum blood loss pf ≥1500 mL, any transfusion, invasive procedure, and admission to an intensive care unit. Endometritis occurred in 5 women (2.7%) in the study group and none in the control group (P=.06). CONCLUSION: The early use of intrauterine balloon tamponade did not reduce the incidence of severe postpartum hemorrhage compared with its use after the failure of second-line uterotonic treatment and before recourse to invasive procedures.

Association between marked fetal heart rate variability and neonatal acidosis: A prospective cohort study.

OBJECTIVE: To assess the association between marked variability in fetal heart rate (FHR) and neonatal acidosis. DESIGN: Bicentric prospective cohort study. SETTING: From January 2019 to December 2019, in two French tertiary care maternity units. POPULATION: Women in labour at ≥37 weeks of gestation, with continuous FHR monitoring until delivery and with the availability of umbilical arterial pH. Women with intrauterine fetal death or medical termination, multiple pregnancies, non-cephalic presentation or planned caesarean delivery were excluded. METHODS: The exposure was marked variability in FHR in the 60 minutes before delivery, defined as a variability greater than 25 beats per minute, with a minimum duration of 1 minute. To assess the association between marked variability and neonatal acidosis, we used multivariable modified Poisson regression modelling. We then conducted subgroup analyses according to the US National Institute of Child Health and Human Development (NICHD) category of the associated fetal heart rate. MAIN OUTCOME MEASURES: Neonatal acidosis, defined as an umbilical artery pH of ≤7.10. RESULTS: Among the 4394 women included, 177 (4%) had marked variability in fetal heart rate in the 60 minutes before delivery. Acidosis occurred in 6.0% (265/4394) of the neonates. In the multivariable analysis, marked variability was significantly associated with neonatal acidosis (aRR 2.30, 95% CI 1.53-3.44). In subgroup analyses, the association between marked variability and neonatal acidosis remained significant in NICHD category-I and category-II groups. CONCLUSIONS: Marked variability was associated with a twofold increased risk of neonatal acidosis.

Serial plotting of symphysis-fundal height and estimated fetal weight to improve the antenatal detection of infants small for gestational age: A cluster randomised trial.

OBJECTIVE: To assess whether standardised longitudinal reporting of growth monitoring information improves antenatal detection of infants who are small for gestational age (SGA), compared with usual care. DESIGN: Cluster-randomised controlled trial. SETTING: Sixteen French level-3 units in 2018-2019. POPULATION: Singleton pregnancies. METHODS: The intervention consisted of the serial plotting of symphysis-fundal height (SFH) and estimated fetal weight (EFW) measurements on customised growth charts using a software program, compared with standard antenatal care. We estimated relative risks (RR) adjusted for known risk factors for fetal growth restriction (FGR). MAIN OUTCOME MEASURES: The primary outcome was antenatal detection of FGR among SGA births (with birthweights below the tenth centile of French customised curves), defined as the mention of suspected FGR in medical records and either referral ultrasounds for growth monitoring or indicated delivery for FGR. Secondary outcomes were false-positive rates, mode of delivery, perinatal morbidity and mortality, and number of antenatal visits and ultrasounds. RESULTS: In total, seven intervention clusters (n = 4349) and eight control clusters (n = 4943) were analysed, after the exclusion of one intervention centre for a major deviation in protocol. SGA births represented 613 (14.1%) and 626 (12.7%) of all births, respectively. The rates of antenatal detection of FGR among SGA births were 40.0% in the intervention arm versus 37.1% in the control arm (crude RR 1.08, 95% CI 0.87-1.34; adj RR 1.09, 95% CI 0.88-1.35). No benefits of the intervention were detected in the analyses of secondary outcomes. CONCLUSIONS: Serial plotting of SFH and EFW measurements on customised growth charts did not improve the antenatal detection of FGR among SGA births.

Adverse perinatal outcomes associated with prenatal exposure to protease-inhibitor-based versus non-nucleoside reverse transcriptase inhibitor-based antiretroviral combinations in pregnant women with HIV infection: a systematic review and meta-analysis.

BACKGROUND: About 1.3 million pregnant women lived with HIV and were eligible to receive antiretroviral therapy (ART) worldwide in 2021. The World Health Organization recommends protease inhibitors (PI)-based regimen as second or third-line during pregnancy. With remaining pregnant women exposed to PIs, there is still an interest to assess whether this treatment affects perinatal outcomes. Adverse perinatal outcomes after prenatal exposure to PI-based ART remain conflicting: some studies report an increased risk of preterm birth (PTB) and low-birth-weight (LBW), while others do not find these results. We assessed adverse perinatal outcomes associated with prenatal exposure to PI-based compared with non-nucleoside reverse transcriptase (NNRTI)-based ART. METHODS: We performed a systematic review searching PubMed, Reprotox, Clinical Trial Registry (clinicaltrials.gov) and abstracts of HIV conferences between 01/01/2002 and 29/10/2021. We used Oxford and Newcastle-Ottawa scales to assess the methodological quality. Studied perinatal outcomes were spontaneous abortion, stillbirth, congenital abnormalities, PTB (< 37 weeks of gestation), very preterm birth (VPTB, < 32 weeks of gestation), LBW (< 2500 grs), very low-birth-weight (VLBW, < 1500 g), small for gestational age (SGA) and very small for gestational age (VSGA). The association between prenatal exposure to PI-based compared to NNRTI-based ART was measured for each adverse perinatal outcome using random-effect meta-analysis to estimate pooled relative risks (RR) and their corresponding 95% confidence intervals (CI). Pre-specified analyses were stratified according to country income and study quality assessment, and summarized when homogeneous. RESULTS: Out of the 49,171 citations identified, our systematic review included 32 published studies, assessing 45,427 pregnant women. There was no significant association between prenatal exposure to PIs compared to NNRTIs for VPTB, LBW, SGA, stillbirth, and congenital abnormalities. However, it was inconclusive for PTB, and PI-based ART is significantly associated with an increased risk of VSGA (sRR 1.41 [1.08-1.84]; I2 = 0%) compared to NNRTIs. CONCLUSIONS: We did not report any significant association between prenatal exposure to PIs vs NNRTIs-based regimens for most of the adverse perinatal outcomes, except for VSGA significantly increased (+ 41%). The evaluation of antiretroviral exposure on pregnancy outcomes remains crucial to fully assess the benefice-risk balance, when prescribing ART in women of reproductive potential with HIV. PROSPERO NUMBER: CRD42022306896.

Oral and periodontal assessment at the first trimester of pregnancy: The PERISCOPE longitudinal study.

INTRODUCTION: Periodontal diseases (gingivitis and periodontitis) are chronic non-communicable inflammatory diseases. The risk of developing gingivitis and periodontitis increases during pregnancy. Also, periodontitis increases the risk of developing adverse pregnancy outcomes such as preterm birth and preeclampsia. Early diagnosis of adverse pregnancy outcomes is essential and periodontitis could be an early sign to take into consideration. MATERIAL AND METHODS: We conducted a longitudinal observational study (PERISCOPE study: CNIL, no. 1 967 084 v 0; CER, no. 01-0416) on 121 pregnant women in the first trimester to determine their oral and periodontal health status. We explored the relations between oral and periodontal health status and sociodemographic and behavior characteristics, as well as their course and outcome of pregnancy. RESULTS: A total of 47.1% of the women had periodontitis, of which only 66.7% presented clinical manifestations associated with the disease such as gingival bleeding. These women had a poorer oral and periodontal health, and a higher body mass index, and more of them developed gestational diabetes during the course of pregnancy. The remaining 33.3% showed only discreet and isolated inflammatory signs and, unless thoroughly examined, would have gone undiagnosed for periodontitis. Interestingly these women were more often primiparous, still active professionally and had had a recent oral examination. CONCLUSIONS: The PERISCOPE study is one of the few studies that reports the oral and periodontal health status of pregnant women in the first trimester. Furthermore, the results highlight the need for early oral and periodontal assessment and treatment, even in the absence of exterior clinical signs, in order to prevent periodontal disease aggravation and also, by reducing low grade systemic inflammation, possibly adverse pregnancy outcomes.

PROMPT: Prospective Meta-analysis for Pessary Trials Study Protocol.

OBJECTIVE: Preterm birth, defined as birth before 37 weeks of gestation, is a leading cause of perinatal and infant mortality throughout the world. Preterm birth is also associated with long-term neurological disabilities and other significant health issues in children. A short cervix in the second trimester has been noted to be one of the strongest predictors of subsequent spontaneous preterm birth in both singleton and multiple pregnancies. Some studies have shown that cervical support in the form of an Arabin pessary lowers the risk of preterm birth in women with a singleton gestation and short cervical length; however, other studies have conflicting results. Our objective was to form an international collaborative of planned or ongoing randomized trials of pessary in singleton and twin gestations with a short cervix. STUDY DESIGN: In November 2014, an international group of investigators, who had initiated or were planning randomized trials of pessary for pregnant people with a short cervix and singleton or twin gestation to prevent preterm birth, formed a collaboration to plan a prospective individual patient data (IPD) meta-analysis of randomized trials (PROspective Meta-analysis of Pessary Trials [PROMPT]). The PROMPT investigators agreed on meta-analysis IPD hypotheses for singletons and twins, eligibility criteria, and a set of core baseline and outcome measures. The primary outcome is a composite of fetal death or preterm delivery before 32 weeks' gestation. Secondary outcomes include maternal and neonatal morbidities. The PROMPT protocol may be viewed as a written agreement among the study investigators who make up the PROMPT consortium (PROSPERO ID# CRD42018067740). RESULTS: Results will be published in phases as the individual participating studies are concluded and published. Results of the first phase of singleton and twin pessary trials are expected to be available in late 2022. Updates are planned as participating trials are completed and published. KEY POINTS: · Short cervical length predicts preterm birth.. · Results of prior cervical pessary trials are mixed.. · Meta-analysis of pessary trials protocol..

Arabin pessary to prevent adverse perinatal outcomes in twin pregnancies with a short cervix: a multicenter randomized controlled trial (PESSARONE).

BACKGROUND: The number of twin pregnancies continues to increase worldwide as both the number of pregnancies obtained by medically assisted reproduction and age at first pregnancy keep rising. Preterm delivery is the major complication associated with twin pregnancies. The effectiveness of preventive treatments such as progesterone or cervical cerclage for women with a short cervix is doubtful in twin pregnancies. The effectivity of cervical pessaries in preventing preterm birth and its associated morbidity and mortality is also controversial. OBJECTIVE: We sought to investigate if the Arabin pessary reduces adverse neonatal outcomes in twin pregnancies with a short cervix. STUDY DESIGN: This open-label, multicenter, randomized controlled trial on twin pregnancies with a cervical length of <35 mm compared pessary placement at 16+0 to 24+0 weeks' gestation with standard care alone. The primary endpoint was a composite of adverse neonatal outcomes, namely peripartum or neonatal death or significant neonatal morbidity before hospital discharge, defined as at least 1 of the following complications: bronchopulmonary dysplasia, intraventricular hemorrhage grade III to IV, periventricular leukomalacia, necrotizing enterocolitis grade II or higher, culture-proven sepsis, and retinopathy requiring treatment. A sample size of 308 pregnancies was planned to ensure 80% power to compare the proportions of women with at least 1 infant with an adverse neonatal outcome. The intention-to-treat analysis after multiple imputation of missing data, was supplemented with a secondary analysis that controlled for gestational age and cervical length, both at inclusion. The primary endpoint was also compared between randomization groups in the per-protocol population, which excluded patients with prespecified major protocol violations (mostly cervical cerclage and/or progesterone after inclusion). Secondary endpoints included preterm birth, spontaneous preterm birth, and pessary side effects. RESULTS: In total, 315 women were randomized to either receive a pessary (n=157) or standard management (n=158). Overall, 10.8% (34 women) of participants had a missing value for the primary endpoint, mostly (79%) because of the lack of paternal consent for neonatal data collection. In the intention-to-treat analysis, the adverse neonatal outcome occurred in 16.8% of the pessary group vs in 22.5% of the control group (risk ratio, 0.69; 95% confidence interval, 0.39-1.23; P=.210). The per-protocol analysis did not show any significant difference between groups (risk ratio, 0.78; 95% confidence interval, 0.47-1.28; P=.320). The occurrence of preterm birth or spontaneous preterm birth did not differ significantly between groups. No serious side effects were associated with pessary use. CONCLUSION: Pessary use in our study did not significantly reduce adverse neonatal outcomes in twin pregnancies with a short cervix.

Amniotic fluid peptides predict postnatal kidney survival in developmental kidney disease.

Although a rare disease, bilateral congenital anomalies of the kidney and urinary tract (CAKUT) are the leading cause of end stage kidney disease in children. Ultrasound-based prenatal prediction of postnatal kidney survival in CAKUT pregnancies is far from accurate. To improve prediction, we conducted a prospective multicenter peptidome analysis of amniotic fluid spanning 140 evaluable fetuses with CAKUT. We identified a signature of 98 endogenous amniotic fluid peptides, mainly composed of fragments from extracellular matrix proteins and from the actin binding protein thymosin-ß4. The peptide signature predicted postnatal kidney outcome with an area under the curve of 0.96 in the holdout validation set of patients with CAKUT with definite endpoint data. Additionally, this peptide signature was validated in a geographically independent sub-cohort of 12 patients (area under the curve 1.00) and displayed high specificity in non-CAKUT pregnancies (82 and 94% in 22 healthy fetuses and in 47 fetuses with congenital cytomegalovirus infection respectively). Change in amniotic fluid thymosin-ß4 abundance was confirmed with ELISA. Knockout of thymosin-ß4 in zebrafish altered proximal and distal tubule pronephros growth suggesting a possible role of thymosin ß4 in fetal kidney development. Thus, recognition of the 98-peptide signature in amniotic fluid during diagnostic workup of prenatally detected fetuses with CAKUT can provide a long-sought evidence base for accurate management of the CAKUT disorder that is currently unavailable.

Induction of labor at term with vaginal misoprostol or a prostaglandin E2 pessary: a noninferiority randomized controlled trial.

BACKGROUND: Induction of labor is among the most common procedures for pregnant women. Only a few randomized clinical trials with relatively small samples have compared misoprostol with dinoprostone. Although their efficacy seems similar, their safety profiles have not been adequately evaluated, and economic data are sparse. OBJECTIVE: This study aimed to test the noninferiority of vaginal misoprostol (prostaglandin E1) (25 µg) to a slow-release dinoprostone (prostaglandin E2) pessary (10 µg) for induction of labor with an unfavorable cervix at term. STUDY DESIGN: This was an open-label multicenter randomized noninferiority trial at 4 university hospitals of the Research Group in Obstetrics and Gynecology between 2012 and 2015. We recruited women who underwent induction of labor for medical reasons, those with a Bishop score of ≤5 at ≥36 weeks' gestation, and those with a cephalic-presenting singleton pregnancy with no previous cesarean delivery. Women were randomly allocated to receive either vaginal misoprostol at 4-hour intervals (25 µg) or a 10-mg slow-release dinoprostone pessary. The primary outcome was the total cesarean delivery rate. Noninferiority was defined as a difference in the cesarean delivery rates between the groups of no more than 5%. Secondary outcomes included neonatal and maternal morbidity, vaginal delivery at <24 hours after starting the induction of labor process, and maternal satisfaction. RESULTS: The study included 1674 randomized women. The per-protocol analysis included 790 women in each group. The total cesarean delivery rates were 22.1% (n=175) in the misoprostol group and 19.9% (n=157) in the dinoprostone group, a difference of 2.2% (with an upper-bound 95% confidence limit of 5.6%) (P=.092). Results in the intention-to-treat analysis were similar. Neonatal and maternal morbidity rates were similar between groups. Vaginal delivery within 24 hours was significantly higher in the misoprostol group (59.3% vs 45.7%; P<.001) as was maternal satisfaction, assessed in the postpartum period by a visual analog scale (mean score, 7.1±2.4 vs 5.8±3.1; P<.001). CONCLUSION: The noninferiority of a 25-µg dose of vaginal misoprostol every 4 hours to the dinoprostone pessary for cesarean delivery rates after induction of labor at term could not be demonstrated, although the confidence limit of the difference barely exceeded the noninferiority margin. Nonetheless, given the small difference between these cesarean delivery rates and the similarity of neonatal and maternal morbidity rates in this large study, the clinical risk-to-benefit ratio justifies the use of both drugs.

Evaluation of the Prognostic Value of the sFlt-1/PlGF Ratio in Early-Onset Preeclampsia.

OBJECTIVE: Increased expression of soluble fms-like tyrosine kinase 1 (sFlt-1), associated with a decrease in placental growth factor (PlGF), plays a key role in the pathogenesis of preeclampsia (PE). We evaluated the prognostic value of the sFlt-1/PlGF ratio for the onset of adverse maternofetal outcomes (AMFO) in case of early-onset PE with attempted expectant management. STUDY DESIGN: From October 2016 through November 2018, all singleton pregnancies complicated by early-onset PE (before 34 weeks of gestation) were included in a cohort study. The plasma levels of sFlt-1 and PlGF were blindly measured on admission. For the statistical analysis, we performed a bivariate analysis, a comparison of the receiving operating characteristic curves and a survival analysis estimated by the Kaplan-Meier method. RESULTS: Among 109 early PE, AMFO occurred in 87 pregnancies (79.8%), mainly hemolysis, elevated liver enzymes, and low platelet count syndrome and severe fetal heart rate abnormalities requiring urgent delivery. The area under the curve (AUC) of sFlt-1/PlGF ratio was 0.82 (95% confidence interval [CI]: 0.73-0.88) for the risk of AMFO and the difference between the AUCs was significant for each separate standard parameter (p = 0.018 for initial diastolic blood pressure, p = 0.013 for alanine aminotransferase, p < 0.001 for uric acid). Pregnancies were best classified by a cutoff ratio of 293, with a sensitivity of 95% and a specificity of 50%. With a ratio value less than 293, no pregnancy was complicated or had been stopped during the first 5 days. A ratio more than 293 was associated with an increased risk of AMFO onset (hazard ratio [HR]: 3.61; 95% CI: 2.13-6.10; p < 0.001) and had a significant association with the length of time between the diagnosis of PE and delivery (HR: 2.49; 95% CI: 1.56-3.96; p < 0.001). CONCLUSION: The sFlt-1/PlGF ratio is an additional tool in the prediction of AMFO in proven early-onset PE, which is likely to improve care by anticipating severe complications. KEY POINTS: · The sFlt-1/PlGF ratio is associated with AMFO.. · It is an additional tool for physician.. · We proposed a 293 cutoff value for the ratio..

Aspirin for prevention of preeclampsia and fetal growth restriction.

For the past decades, growing attention has been given to aspirin use during pregnancy. It favors placentation by its proangiogenic, antithrombotic, and anti-inflammatory effects. Therefore, low doses of aspirin are prescribed in the prevention of placenta-mediated complications, mainly preeclampsia and fetal growth restriction. However, questions regarding its clinical application are still debated. Aspirin is effective in preventing preeclampsia in a high-risk population. Most guidelines recommend that risk stratification should rely on medical history. Nevertheless, screening performances dramatically improve if biochemical and biophysical markers are included. Concerning the appropriate timing and dose, latest studies suggest aspirin should be started before 16 weeks of pregnancy and at a daily dose of 100 mg or more. Further studies are needed to improve the identification of patients likely to benefit from prophylactic aspirin. Besides, the role of aspirin in the prevention of fetal growth restriction is still questioned.

Risk factors for failed induction of labor among pregnant women with Class III obesity.

INTRODUCTION: Our aim was to identify risk factors for failed induction in morbidly obese patients undergoing the induction of labor at term. MATERIAL AND METHODS: This was a retrospective multicenter study on a cohort of 235 patients with a body mass index greater than 40 kg/m2 and giving birth to a singleton in cephalic presentation, who had an induction of labor from 38 weeks of amenorrhea. Scheduled cesareans and spontaneous vaginal deliveries were excluded. Maternal, peri-partum and neonatal characteristics were analyzed according to the delivery route. RESULTS: In all, 235 patients were included. Of these, 62.5% patients delivered vaginally and 37.5% by cesarean section. The frequency of nulliparity was greater in patients who had a cesarean section (56 [interquartile range, IQR, 38.1] vs 56 [IQR 63.6], P < .001). In multivariate analysis, nulliparity (odds ratio [OR] 2.81, 95% confidence interval [CI] 1.58-4.97], P < .001), low Bishop's score (OR .794, 95% CI .70-.90, P < .001) and weight gain (OR 1.04, 95% CI 1.01-1.08, P = .033) were independent risk factors for failed induction. Umbilical cord pH at birth lower than 7 (0 vs 7 [IQR 8.0], P < .001) and lower than 7.20 (36 [IQR 24.5] vs 35 [IQR 39.8], P = .014) as well as the Apgar at 1 minute (14 [IQR 9.5] vs 17 [IQR 19.3], P = .032) was significantly higher in infants born by cesarean section. CONCLUSIONS: In this cohort, 63% of women with Class III obesity had successful inductions of labor; risk factors for failed induction include nulliparity and unfavorable Bishop score.

Rationale and design of ePPOP-ID: a multicenter randomized controlled trial using an electronic-personalized program for obesity in pregnancy to improve delivery.

BACKGROUND: Pre-pregnancy obesity and excessive gestational weight gain (GWG) are established risk factors for adverse pregnancy, delivery and birth outcomes. Pregnancy is an ideal moment for nutritional interventions in order to establish healthier lifestyle behaviors in women at high risk of obstetric and neonatal complications. METHODS: Electronic-Personalized Program for Obesity during Pregnancy to Improve Delivery (ePPOP-ID) is an open multicenter randomized controlled trial which will assess the efficacy of an e-health web-based platform offering a personalized lifestyle program to obese pregnant women in order to reduce the rate of labor procedures and delivery interventions in comparison to standard care. A total of 860 eligible pregnant women will be recruited in 18 centers in France between 12 and 22 weeks of gestation, randomized into the intervention or the control arm and followed until 10 weeks of postpartum. The intervention is based on nutrition, eating behavior, physical activity, motivation and well-being advices in which personalization is central, as well as the use of a mobile/tablet application. Inputs includes data from the medical record of participants (medical history, anthropometric data), from the web platform (questionnaires on dietary habits, eating behavior, physical activity and motivation in both groups), and adherence to the program (time of connection for the intervention group only). Data are collected at inclusion, 32 weeks, delivery and 10 weeks postpartum. As primary outcome, we will use a composite endpoint score of obstetrical interventions during labor and delivery, defined as caesarean section and instrumental delivery (forceps and vacuum extractor). Secondary outcomes will consist of data routinely collected as part of usual antenatal and perinatal care, such as GWG, hypertension, preeclampsia, as well as fetal and neonatal outcomes including premature birth, gestational age at birth, birth weight, macrosomia, Apgar score, arterial umbilical cord pH, neonatal traumatism, hyperbilirubinemia, respiratory distress syndrome, transfer in neonatal intensive care unit, and neonatal adiposity. Post-natal outcomes will be duration of breastfeeding, maternal weight retention and child weight at postnatal visit. DISCUSSION: The findings of the ePPOP-ID trial will help design e-health intervention program for obese women in pregnancy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02924636 / October 5th 2016.

Association between gestational age and severe maternal morbidity and mortality of preterm cesarean delivery: a population-based cohort study.

BACKGROUND: Cesarean delivery rates at extreme prematurity have regularly increased over the past years, and few previous studies have investigated severe maternal morbidity associated with extreme preterm cesarean delivery. OBJECTIVE: The aim of this study was to evaluate whether gestational age <26 weeks of gestation (weeks) was associated with severe maternal morbidity and mortality (SMMM) of preterm cesarean deliveries in comparison with cesarean deliveries between 26 and 34 weeks. MATERIALS AND METHODS: The Etude Epidémiologique sur les petits âges gestationnels (EPIPAGE) 2 is a national prospective population-based cohort study of preterm births in 2011. We included mothers with cesarean deliveries between 22 and 34 weeks, excluding those who had a cesarean delivery for the second twin only and those with pregnancy terminations. SMMM was analyzed as a composite endpoint defined as the occurrence of at least 1 of the following complications: severe postpartum hemorrhage defined by the use of a blood transfusion, intensive care unit admission, or death. To assess the association of gestational age <26 weeks and SMMM, we used multivariate logistic regression and a propensity score-matching approach. RESULTS: Among 2525 women having preterm cesarean deliveries, 116 before 26 weeks and 2409 between 26 and 34 weeks, 407 (14.4%) presented with SMMM. The SMMM occurred in 31 mothers (26.7%) who were at gestational age <26 weeks vs 376 (14.2%) between 26 and 34 weeks (P < .001). Cluster multivariate logistic regression showed significant association of gestational age <26 weeks and SMMM (adjusted odds ratio [aOR], 2.50; 95% confidence interval [CI], 1.42-4.40) and propensity score-matching analysis was consistent with these results (aOR, 2.27; 95% CI, 1.31-3.93). CONCLUSION: Obstetricians should know about the higher SMMM associated with cesarean deliveries before 26 weeks, integrate this knowledge into decisions regarding cesarean delivery, and be prepared to manage the associated complications.

Fetal electrocardiography ST-segment analysis for intrapartum monitoring: a critical appraisal of conflicting evidence and a way forward.

BACKGROUND: In the past century, some areas of obstetric including intrapartum care have been slow to benefit from the dramatic advances in technology and medical care. Although fetal heart rate monitoring (cardiotocography) became available a half century ago, its interpretation often differs between institutions and countries, its diagnostic accuracy needs improvement, and a technology to help reduce the unnecessary obstetric interventions that have accompanied the cardiotocography is urgently needed. STUDY DESIGN: During the second half of the 20th century, key findings in animal experiments captured the close relationship between myocardial glycogenolysis, myocardial workload, and ST changes, thus demonstrating that ST waveform analysis of the fetal electrocardiogram can provide information on oxygenation of the fetal myocardium and establishing the physiological basis for the use of electrocardiogram in intrapartum fetal surveillance. RESULTS: Six randomized controlled trials, 10 meta-analyses, and more than 20 observational studies have evaluated the technology developed based on this principle. Nonetheless, despite this intensive assessment, differences in study protocols, inclusion criteria, enrollment rates, clinical guidelines, use of fetal blood sampling, and definitions of key outcome parameters, as well as inconsistencies in randomized controlled trial data handling and statistical methodology, have made this voluminous evidence difficult to interpret. Enormous resources spent on randomized controlled trials have failed to guarantee the generalizability of their results to other settings or their ability to reflect everyday clinical practice. CONCLUSION: The latest meta-analysis used revised data from primary randomized controlled trials and data from the largest randomized controlled trials from the United States to demonstrate a significant reduction of metabolic acidosis rates by 36% (odds ratio, 0.64; 95% confidence interval, 0.46-0.88) and operative vaginal delivery rates by 8% (relative risk, 0.92; 95% confidence interval, 0.86-0.99), compared with cardiotocography alone.

Health-related quality of life during pregnancy: A repeated measures study of changes from the first trimester to birth.

INTRODUCTION: The objective was to evaluate the quality of life of pregnant women with a full-term birth from the first trimester to the 9th month using the EQ5D-3L questionnaire, comparing physiological, simple pathological, or complex pathological pregnancies. MATERIAL AND METHODS: A prospective cohort of 500 pregnant women over the age of 18 was monitored between 2015 and 2017 at the Toulouse University Hospital (France). The data were collected monthly with an online report. Given that the decrease in quality of life was not linear during pregnancy, unadjusted and adjusted piecewise linear regression models were performed, considering 3 periods of time during pregnancy: 3-4, 4-8, and 8-9 months. The 5 dimensions of the EQ5D-Index and perceived health status were also analyzed. RESULTS: In total, 1847 questionnaires were collected. Between the 4th and 8th months, the quality of life was lower for pathological pregnancies (P < 0.001) than for physiological ones and decreased over time for each type of pregnancy (physiological: -0.08 points per month, P < 0.001; simple pathological: -0.12 points per month, P < 0.001; complex pathological: -0.11 points per month, P < 0.001). Interestingly, the perceived health status was lower at the 9th month than at the 3rd month of pregnancy, for physiological pregnancies (mean difference = -10.5 points, P < 0.001), pathological pregnancies (mean difference = -10.0 points, P < 0.002), and for complex pathological pregnancies (mean difference = -7.8 points, P = 0.058). CONCLUSIONS: In our population, the quality of life decreased between the 4th and 8th months, and decreased to a greater degree in a pathological pregnancy.

Correction to: Safety considerations regarding Methotrexate of label use in tubal ectopic pregnancy.

In the original article publication, the authors given name and family name were interchanged.