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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause severe placental lesions leading rapidly to intrauterine fetal death (IUFD). From August 2020 to September 2021, in the pathology department of Toulouse Oncopole, we analyzed 50 placentas from COVID-19-positive unvaccinated mothers. The purpose of our study is to describe the clinicopathological characteristics of these placental damages and to understand the pathophysiology. Ten of them (20%) showed placental lesions with positive immunohistochemistry for SARS-CoV-2 in villous trophoblasts. In five cases (10%), we observed massive placental damage associating trophoblastic necrosis, fibrinous deposits, intervillositis, as well as extensive hemorrhagic changes due to SARS-CoV-2 infection probably responsible of IUFD by functional placental insufficiency. In five other cases, we found similar placental lesions but with a focal distribution that did not lead to IUFD but live birth. These lesions are independent of maternal clinical severity of COVID-19 infection because they occur despite mild maternal symptoms and are therefore difficult to predict. In our cases, they occurred 1-3 weeks after positive SARS-CoV-2 maternal real-time polymerase chain reaction testing and were observed in the 2nd and 3rd trimesters of pregnancies. When these lesions are focal, they do not lead to IUFD and can be involved in intrauterine growth restriction. Our findings, together with recent observations, suggest that future pregnancy guidance should include stricter pandemic precautions such as screening for a wider array of COVID-19 symptoms, enhanced ultrasound monitoring, as well as newborn medical surveillance.

OBJECTIVE To assess the cost-effectiveness of vaginal misoprostol (PGE1; 25 μg) compared with a slow-release dinoprostone (PGE2) pessary (10 μg) for labor induction due to an unfavorable cervix at term. METHODS We used data from an open-label multicenter, randomized non-inferiority trial that recruited women for whom labor was induced for medical reasons. The incremental cost-effectiveness ratio was assessed from the payer's perspective, with the focus on inpatient care costs and using the cesarean deliveries avoided (CDA) rate as the primary analysis and the rate of vaginal delivery within 24 h (VD24) as the secondary analysis. RESULTS Analyses were based on 790 women in each group. Differences between treatment arms were the mean cost per patient of €4410 and €4399, a CDA rate of 80.1% and 77.9% and a VD24 rate of 46.1% and 59.4% for dinoprostone and misoprostol, respectively. Dinoprostone is not cost-effective according to the CDA rate and misoprostol was either a cost-effective or a dominant strategy according to the VD24. CONCLUSION Misoprostol and dinoprostone have equal cost management with mixed efficacy according to the clinical outcome used. Finally, misoprostol may be an attractive option for hospitals as the price is lower and it is easier to use. TRIAL REGISTRATION ClinicalTrials.gov: NCT01765881. URL: https://clinicaltrials.gov/ct2/show/NCT01765881. ClinicalTrialRegistrer.eu: 2011-000933-35. URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2011-000933-35/FR.

Premature placental senescence is a hallmark of pregnancy-related disorders such as intrauterine growth restriction (IUGR) and preeclampsia (PE), two major cause of maternal and neonatal morbidity and mortality. Oxidative stress and lipid peroxidation are involved in the pathogenesis of PE and IUGR, and may play a role in placental aging. In this study, we investigated whether 4-hydroxy-2-nonenal (HNE), a lipid peroxidation-derived aldehyde present in preeclamptic placentas, may contribute to premature senescence in placenta-related complications. Placentas from PE-affected women, exhibited several senescence patterns, such as an increased expression of phosphorylated (serine-139) histone γH2AX, a sensitive marker of double-stranded DNA breaks, the presence of lipofuscin granules, and an accumulation of high molecular weight cross-linked and ubiquitinated proteins. PE placentas showed an accumulation of acetylated proteins consistent with the presence of HNE-adducts on sirtuin 1 (SIRT1). Likewise, oxidative stress and senescence markers together with SIRT1 modification by HNE, were observed in murine placentas from mice treated with lipopolysaccharide during gestation and used as models of IUGR. The addition of HNE and ONE (4-oxo-2-nonenal), to cultured HTR-8/SVneo human trophoblasts activated the senescence-associated- β-galactosidase, and generated an accumulation of acetylated proteins, consistent with a modification of SIRT1 by HNE. Altogether, these data emphasize the role of HNE and lipid peroxidation-derived aldehydes in premature placental senescence in PE and IUGR, and more generally in pathological pregnancies.

Traditional obstetric units are inadequate for the level of monitoring required in pre-eclamptic patients. It remains to be determined which facility and tools should be implemented. The aim of this work was to identify predictive factors of admission to Intensive Care Unit (ICU) admissions for pregnancy-related hypertensive complications.We conducted an observational, retrospective multicenter study (Toulouse, Nantes). Both have a level III maternity unit and an ICU. The selected patients had one or more of the following diagnoses on admission in the ICU or during hospitalization: pre-eclampsia, eclampsia, HELLP syndrome, Acute Fatty Liver of Pregnancy (AFLP), Hemolytic Uremic Syndrome (HUS). SAPS II, SOFA and APACHE II on admission, and a validated nursing workload assessment score: TISS 28, were collected.211 parturient women were included. According to the multivariate analysis: APACHE II and SAPS 2 severity scores15 were significantly higher in the TISS 28 ≥ 20 group. There were also higher rates of uricemia360 mmol/l.To date, there are no reliable and validated predictive factors of severity to guide the transfer of pre-eclamptic patients to an ICU. The combination of an increased APACHE II score and uricemia, as well as a high care workload score that could help with the transfer of high-risk pre-eclamptic patients to a specific care facility. This hypothesis should be tested prospectively. This work could incite reflection on the value of creating obstetric intensive care units, according to the size of the maternity unit.

Résumé Un nouveau coronavirus (SARS-CoV-2) mis en évidence en fin d’année 2019 en Chine se diffuse à travers tous les continents. Le plus souvent à l’origine d’un syndrome infectieux sans gravité, associant à différents degrés des symptômes bénins (fièvre, toux, myalgies, céphalées et éventuels troubles digestifs) le SARS-Covid-2 peut être à l’origine de pathologies pulmonaires graves et parfois de décès. Les données sur les conséquences pendant la grossesse sont limitées. Les premières données chinoises publiées semblent montrer que les symptômes chez la femme enceinte sont les mêmes que ceux de la population générale. mais il y a un risque qu'il y ai plus de formes graves. Il n’y a pas de cas de transmission maternofœtale intra utérine mais des cas de nouveau-nés infectés précocement font penser qu’il pourrait y avoir transmission verticale per-partum ou néonatale. Une prématurité induite et des cas de détresses respiratoires chez les nouveau-nés de mères infectées ont été décrits. La grossesse est connue comme une période plus à risque pour les conséquences des infections respiratoires, comme pour la grippe, il parait donc important de dépister le Covid-19 en présence de symptômes et de surveiller de façon rapprochée les femmes enceintes infectées. Dans ce contexte d’épidémie de SARS-Covid-2, les sociétés savantes de gynécologie-obstétrique, d’infectiologie et de néonatalogie ont proposé un protocole français de prise en charge des cas possibles et avérés de SARS-Covid-2 chez la femme enceinte. Ces propositions peuvent évoluer de façon quotidienne avec l’avancée de l’épidémie et des connaissances chez la femme enceinte.

HELLP syndrome is a rare and severe pregnancy complication which exposes to severe maternal and fetal morbidity. Management of HELLP syndrome occurring before 34 weeks of gestation (WG) is still controversial but conservative management may be beneficial in patients with stable HELLP syndrome. The aim of the study was thus to identify which maternal and fetal prognostic factors could be predictive of HELLP syndrome evolution.From 2003 to 2016, all patients with HELLP syndrome occurring between 26 and 34 WG were retrospectively enrolled. Study population was stratified according to obstetrical management. Patients in whom delivery was initiated within 48 h following diagnosis constituted the active management group. In the expectant management group, pregnancy was prolonged until maternal or fetal follow up indicated delivery.Ninety-nine patients were included in our study. Among them, 61 were managed expectantly. At baseline, the active management group was more likely to suffer from persistent hyperreflexia (While expectant management in HELLP syndrome might be beneficial through its reduction of prematurity, it cannot be conducted in all patients. Identification of baseline parameters predictive of disease evolution is thus of tremendous importance to define which obstetrical approach should be prioritized.

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

International audience; 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

OBJECTIVE To assess, according to chorionicity, the perinatal outcome of twin pregnancy in which vaginal delivery is planned. METHODS JUMODA (JUmeaux MODe d'Accouchement) was a national prospective population-based cohort study of twin pregnancies, delivered in 176 maternity units in France, from February 2014 to March 2015. In this planned secondary analysis, we assessed, according to chorionicity, the perinatal outcome of twin pregnancies, in which vaginal delivery was planned, that delivered at or after 32 weeks of gestation with the first twin in cephalic presentation. In order to select a population with well-recognized indications for planned vaginal delivery, we applied the same exclusion criteria as those in the Twin Birth Study, an international randomized trial. Monochorionic twin pregnancies with twin-to-twin transfusion syndrome or twin anemia-polycythemia sequence were defined as complicated and were excluded. The primary outcome was a composite of intrapartum mortality and neonatal morbidity and mortality. Multivariable logistic regression models were used to control for potential confounders. Subgroup analyses were conducted according to birth order (first or second twin) and gestational age at delivery (

International audience; 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

Preeclampsia (PE) is a multifactorial pregnancy disease, characterized by new-onset gestational hypertension with (or without) proteinuria or end-organ failure, exclusively observed in humans. It is a leading cause of maternal morbidity affecting 3–7% of pregnant women worldwide. PE pathophysiology could result from abnormal placentation due to a defective trophoblastic invasion and an impaired remodeling of uterine spiral arteries, leading to a poor adaptation of utero-placental circulation. This would be associated with hypoxia/reoxygenation phenomena, oxygen gradient fluctuations, altered antioxidant capacity, oxidative stress, and reduced nitric oxide (NO) bioavailability. This results in part from the reaction of NO with the radical anion superoxide (O2•−), which produces peroxynitrite ONOO-, a powerful pro-oxidant and inflammatory agent. Another mechanism is the progressive inhibition of the placental endothelial nitric oxide synthase (eNOS) by oxidative stress, which results in eNOS uncoupling via several events such as a depletion of the eNOS substrate L-arginine due to increased arginase activity, an oxidation of the eNOS cofactor tetrahydrobiopterin (BH4), or eNOS post-translational modifications (for instance by S-glutathionylation). The uncoupling of eNOS triggers a switch of its activity from a NO-producing enzyme to a NADPH oxidase-like system generating O2•−, thereby potentiating ROS production and oxidative stress. Moreover, in PE placentas, eNOS could be post-translationally modified by lipid peroxidation-derived aldehydes such as 4-oxononenal (ONE) a highly bioreactive agent, able to inhibit eNOS activity and NO production. This review summarizes the dysfunction of placental eNOS evoked by oxidative stress and lipid peroxidation products, and the potential consequences on PE pathogenesis., Graphical abstract Image 1, Highlights • Physiological ROS production is enhanced during pregnancy. • eNOS is one of the main target of oxidative stress in PE placenta. • eNOS is S-glutathionylated in PE placentas. • eNOS is modified by lipid oxidation products in PE placentas.

Resume Objectifs Le coronavirus SARS-CoV-2 mis en evidence en fin d’annee 2019 en Chine a atteint tous les continents, avec plus de 28 millions de cas declares dont plus de 920 000 deces au 17/9/2020. Le plus souvent a l’origine d’un syndrome infectieux benin, associant a differents degres des symptomes (fievre, toux, myalgies, cephalees et eventuels troubles digestifs), voire totalement asymptomatique, le SARS-CoV-2 peut etre a l’origine de pathologies pulmonaires graves et parfois de deces. Methode Au vu de l’evolution de l’epidemie, le College national des gynecologues obstetriciens francais a decide de mettre a jours les avis emis precedemment. Pour cela, le meme groupe d’experts, a ete sollicite avec realisation d’une revue de la litterature et prise en compte des avis de la Direction Generale de la Sante, la Haute Autorite de Sante, du Haut Conseil de Sante Publique. Resultats Les donnees pendant la grossesse sont plus nombreuses et plus precises. Les donnees publiees semblent montrer que les symptomes chez les femmes enceintes sont les memes que ceux de la population generale et qu’un sur risque existe chez la femme enceinte particulierement au troisieme trimestre. Un cas de transmission materno-fœtale intra uterine a ete formellement identifie. Une prematurite induite et des cas de detresses respiratoires chez les nouveau-nes de meres infectees ont ete decrits. Conclusion A la lumiere des nouvelles donnees, nous proposons une actualisation des recommandations de prise en charge. Ces propositions peuvent encore evoluer avec l’avancee de la pandemie et de potentielles nouvelles connaissances chez la femme enceinte.

BackgroundPre-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.MethodsElectronic-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.DiscussionThe findings of the ePPOP-ID trial will help design e-health intervention program for obese women in pregnancy.Trial registrationClinicalTrials.govIdentifier:NCT02924636/ October 5th 2016.

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-β4. 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-β4 abundance was confirmed with ELISA. Knockout of thymosin-β4 in zebrafish altered proximal and distal tubule pronephros growth suggesting a possible role of thymosin β4 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. ispartof: KIDNEY INTERNATIONAL vol:99 issue:3 pages:737-749 ispartof: location:United States status: published

Objective To describe the course over time of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in French women from the beginning of the pandemic until mid-April, the risk profile of women with respiratory complications, and short-term pregnancy outcomes. Methods We collected a case series of pregnant women with COVID-19 in a research network of 33 French maternity units between March 1 and April 14, 2020. All cases of SARS-CoV-2 infection confirmed by a positive result on real-time reverse transcriptase polymerase chain reaction tests of a nasal sample and/or diagnosed by a computed tomography chest scan were included and analyzed. The primary outcome measures were COVID-19 requiring oxygen (oxygen therapy or noninvasive ventilation) and critical COVID-19 (requiring invasive mechanical ventilation or extracorporeal membrane oxygenation, ECMO). Demographic data, baseline comorbidities, and pregnancy outcomes were also collected. Results Active cases of COVID-19 increased exponentially during March 1–31, 2020; the numbers fell during April 1–14, after lockdown was imposed on March 17. The shape of the curve of active critical COVID-19 mirrored that of all active cases. By April 14, among the 617 pregnant women with COVID-19, 93 women (15.1 %; 95 %CI 12.3–18.1) had required oxygen therapy and 35 others (5.7 %; 95 %CI 4.0–7.8) had had a critical form of COVID-19. The severity of the disease was associated with age older than 35 years and obesity, as well as preexisting diabetes, previous preeclampsia, and gestational hypertension or preeclampsia. One woman with critical COVID-19 died (0.2 %; 95 %CI 0−0.9). Among the women who gave birth, rates of preterm birth in women with non-severe, oxygen-requiring, and critical COVID-19 were 13/123 (10.6 %), 14/29 (48.3 %), and 23/29 (79.3 %) before 37 weeks and 3/123 (2.4 %), 4/29 (13.8 %), and 14/29 (48.3 %) before 32 weeks, respectively. One neonate (0.5 %; 95 %CI 0.01–2.9) in the critical group died from prematurity. Conclusion COVID-19 can be responsible for significant rates of severe acute, potentially deadly, respiratory distress syndromes. The most vulnerable pregnant women, those with comorbidities, may benefit particularly from prevention measures such as a lockdown.

International audience; OBJECTIVE: To assess neonatal morbidity and mortality according to whether cephalic second twins were born after internal version followed by total breech extraction or after instructions to push. We hypothesized that interval version would result in shorter intertwin delivery intervals and lower cesarean delivery rates for the second twin and therefore better neonatal outcomes. METHODS: These planned analyses of the JUMODA (JUmeaux MODe d'Accouchement) cohort, a national prospective population-based study of twin deliveries, examined births of cephalic second twins after vaginal birth of the first twin at or after 32 weeks of gestation. The internal version group of second twins born in breech presentation after obstetric maneuvers was compared with the pushing group, comprising those born in cephalic presentation. The primary outcome was a composite of neonatal morbidity and mortality. Multivariate modified Poisson regression models were used to control for potential confounders. RESULTS: Of 2,256 cephalic second twins, 487 (21.6%) were born in breech presentation after internal version and total breech extraction and 1,769 (78.4%) in cephalic presentation after pushing. Composite neonatal morbidity and mortality was not lower in the internal version (17/487 [3.5%]) compared with the pushing group (38/1,769 [2.1%]; adjusted relative risk [aRR] 1.73 [95% CI 0.98-3.05]), although median [quartile 1-quartile 3] intertwin delivery intervals were shorter (5 [4-8] vs 8 [5-12] minutes, P

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 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

Objective To assess whether chorioamnionitis is associated with cerebral palsy (CP) or death at 2 years' corrected age in infants born before 32 weeks of gestation after spontaneous birth. Study design EPIPAGE-2 is a national, prospective, population-based cohort study of children born preterm in France in 2011; recruitment periods varied by gestational age. This analysis includes infants born alive after preterm labor or preterm premature rupture of membranes from 240/7 to 316/7 weeks of gestation. We compared the outcomes of CP, death at 2 years' corrected age, and “CP or death at age 2” according to the presence of either clinical chorioamnionitis or histologic chorioamnionitis. All percentages were weighted by the duration of the recruitment period. Results Among 2252 infants born alive spontaneously before 32 weeks of gestation, 116 (5.2%) were exposed to clinical chorioamnionitis. Among 1470 with placental examination data available, 639 (43.5%) had histologic chorioamnionitis. In total, 346 infants died before 2 years and 1586 (83.2% of the survivors) were evaluated for CP at age 2 years. CP rates were 11.1% with and 5.0% without clinical chorioamnionitis (P = .03) and 6.1% with and 5.3% without histologic chorioamnionitis (P = .49). After adjustment for confounding factors, CP risk rose with clinical chorioamnionitis (aOR 2.13, 95% CI 1.12-4.05) but not histologic chorioamnionitis (aOR 1.21, 95% 0.75-1.93). Neither form was associated with the composite outcome “CP or death at age 2.” Conclusions Among infants very preterm born spontaneously, the risk of CP at a corrected age of 2 years was associated with exposure to clinical chorioamnionitis but not histologic chorioamnionitis.

International audience; Regulatory measures and public concerns regarding bisphenol A (BPA) have led to its replacement by a variety of alternatives in consumer products. Due to their structural similarity to BPA, these alternatives are under surveillance, however, for potential endocrine disruption. Understanding the materno-fetal transfer of these BPA-related alternatives across the placenta is therefore crucial to assess prenatal exposure risks. The objective of the study was to assess and compare the placental transfer of a set of 15 selected bisphenols (BPs) (BP 4-4, BPA, BPAF, BPAP, 3-3 BPA, BPB, BPBP, BPC, BPE, BPF, BPFL, BPM, BPP, BPS and BPZ) using the ex vivo human placental perfusion model. The UHPLC–MS/MS method for simultaneous quantification of these BPs in perfusion media, within a concentration range of 0.003–5 μM, was able to measure placenta transfer rates as low as 0.6%–4%. Despite their structural similarities, these BPs differed greatly in placental transport efficiency. The placental transfer rates of BP4-4, BPAP, BPE, BPF, 3-3BPA, BPB, BPA were similar to that of antipyrine, indicating that their main transport mechanism was passive diffusion. By contrast, the placental transfer rates of BPFL and BPS were very limited, and intermediate for BPBP, BPZ, BPC, BPM, BPP and BPAF, suggesting weak diffusional permeability and/or that their passage might involve efflux transport. These placental transfer data will be particularly useful for predicting the fetal exposure of this important class of emerging contaminants.

Objective To investigate the association between absent or reversed end-diastolic flow (ARED) on umbilical artery Doppler ultrasound and poor neurological outcome at 2 years of age after very preterm birth associated with suspected fetal growth restriction (FGR) or maternal hypertensive disorders. Methods The study population comprised all very preterm (22–31 completed weeks) singleton pregnancies delivered because of suspected FGR and/or maternal hypertensive disorders that had umbilical artery Doppler and 2-year follow-up available included in EPIPAGE-2, a prospective, nationwide, population-based cohort of preterm births in France in 2011. Univariate and two-level multivariable logistic regression analyses were used to assess the association of ARED in the umbilical artery, as compared with normal or reduced end-diastolic flow, with severe or moderate neuromotor and/or sensory disability and with an Ages and Stages Questionnaire (ASQ) score below a threshold. This was defined as a score more than 2 SD below the mean in any of the five domains, at age 2, adjusting for gestational age at delivery. ASQ is used to identify children at risk of developmental delay requiring reinforced follow-up and further evaluation. Descriptive statistics and bivariate tests were weighted according to the duration of the inclusion periods. Results The analysis included 484 children followed up at 2 years of age, for whom prenatal umbilical artery Doppler ultrasound was available. Among them, 8/484 (1.6%) had severe or moderate neuromotor and/or sensory disability, and 156/342 (45.4%) had an ASQ score below the threshold. Compared with normal or reduced end-diastolic flow in the umbilical artery (n = 305), ARED (n = 179) was associated with severe or moderate neuromotor and/or sensory disability (adjusted odds ratio (OR), 11.3; 95% CI, 1.4–93.2) but not with an ASQ score below the threshold (adjusted OR, 1.2; 95% CI, 0.8–1.9). Conclusion Among children delivered before 32 weeks of gestation due to suspected FGR and/or maternal hypertensive disorder who survived until 2 years of age, prenatal ARED in the umbilical artery was associated with a higher incidence of severe or moderate neuromotor and/or sensory disability. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd. EPIPAGE-2 was funded by the French Institute of Public Health Research/Institute of Public Health and its partners: the French Health Ministry, the National Institute of Health and Medical Research (INSERM), the National Institute of Cancer, and the National Solidarity Fund for Autonomy (CNSA); the National Research Agency through the French EQUIPEX program for investments in the future (reference ANR-11-EQXP-0038); and the PREMUP Foundation.

Preeclampsia (PE) is a leading cause of pregnancy complications, affecting 3-7% of pregnant women worldwide. The pathophysiology of preeclampsia involves a redox imbalance, oxidative stress and a reduced nitric oxide (NO) bioavailability. The molecular and cellular mechanisms leading to the dysfunction of the placental endothelial NO synthase (eNOS) are not clarified. This study was designed to investigate whether aldehydes generated by lipid peroxidation products (LPP), may contribute to placental eNOS dysfunction in PE. The analysis of placentas from PE-affected patients and normal pregnancies, showed a significant increase in protein carbonyl content, indicative of oxidative stress-induced protein modification, as shown by the accumulation of acrolein, 4-hydroxynonenal (HNE), and 4-oxo-2(E)-nonenal (ONE) adducts in PE placentas. In contrast, the levels of these LPP-adducts were low in placentas from normal pregnancies. Immunofluorescence and confocal experiments pointed out a colocalization of eNOS with ONE-Lys adducts, whereas eNOS was not modified in normal placentas. LC-MS/MS analysis of recombinant eNOS preincubated with ONE, allowed to identify several ONE-modified Lys-containing peptides, confirming that eNOS may undergo post-translational modification by LPP. The preincubation of HTR-8/SVneo human trophoblasts (HTR8) with ONE, resulted in ONE-Lys modification of eNOS and a reduced generation of NO. ONE inhibited the migration of HTR8 trophoblasts in the wound closure model, and this was partly restored by the NO donor, NOC-18, which confirmed the important role of NO in the invasive potential of trophoblasts. In conclusion, placental eNOS is modified by ONE in PE placentas, which emphasizes the sensitivity of this protein to oxidative stress in the disturbed redox environment of preeclamptic pregnancies.

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.The aim of this study was to evaluate whether gestational age26 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.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 age26 weeks and SMMM, we used multivariate logistic regression and a propensity score-matching approach.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 age26 weeks vs 376 (14.2%) between 26 and 34 weeks (P .001). Cluster multivariate logistic regression showed significant association of gestational age26 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).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.

Decreased nitric oxide (NO) bioavailability plays a critical role in the pathophysiology of preeclampsia (PE). Recent evidence indicates that S-glutathionylation may occur on the endothelial nitric oxide synthase (eNOS), leading to eNOS uncoupling, characterized by a decreased NO production and an increased generation of superoxide anion (O2•–). We hypothesized that eNOS glutathionylation may occur in PE placentas and participate in eNOS dysfunction. The glutathionylation of eNOS was investigated in thirteen PE-affected patients and in nine normal pregnancies. Immunofluorescence, confocal microscopy and western-blot experiments carried out on eNOS immunoprecipitates, revealed a high level of eNOS glutathionylation in PE placentas, mostly reversed by dithiotreitol (DTT), thus indicative of S-glutathionylation. In order to investigate whether eNOS glutathionylation may alter trophoblast migration, an important event occurring during early placentation, cultured HTR-8/SVneo human trophoblasts (HTR8) were exposed either to low pO2 (O2 1%) or to pO2 changes (O2 1–20%), in order to generate oxidative stress. Trophoblasts exposed to low pO2, did not undergo oxidative stress nor eNOS S-glutathionylation, and were able to generate NO and migrate in a wound closure model. In contrast, trophoblasts submitted to low/high pO2 changes, exhibited oxidative stress and a (DTT reversible) S-glutathionylation of eNOS, associated with reduced NO production and migration. The autonomous production of NO seemed necessary for the migratory potential of HTR8, as suggested by the inhibitory effect of eNOS silencing by small interfering RNAs, and the eNOS inhibitor L-NAME, in low pO2 conditions. Finally, the addition of the NO donor, NOC-18 (5 µM), restored in part the migration of HTR8, thereby emphasizing the role of NO in trophoblast homeostasis. In conclusion, the high level of eNOS S-glutathionylation in PE placentas provides new insights in the mechanism of eNOS dysfunction in this disease., Graphical abstract fx1, Highlights • eNOS is S-glutathionylated in preeclamptic placentas. • Oxidative stress evoked by pO2 changes, triggers eNOS S-glutathionylation in HTR8. • pO2 changes alter the invasive potential of HTR8 in the wound closure model. • The NO donor NOC-18 restores the invasive potential of HTR8.

Little is known about neurodevelopment of children exposed to psychotropic drugs during pregnancy. The purpose of this study was to evaluate the effects of prenatal exposure to psychotropic drugs on psychomotor development in children. This observational study used the EFEMERIS database. The database records the drugs prescribed and delivered during pregnancy and the resulting outcomes. Neurodevelopment at nine and 24 months of children born to women exposed to psychotropic drugs (anxiolytics, antidepressants, neuroleptics and anti-epileptics) during the second and/or third trimesters of pregnancy was compared to children who were not exposed to these drugs. Psychomotor development of 493 children (1.5%) exposed to psychotropic drugs during pregnancy was compared to 32 303 unexposed children. Exposure to psychotropic drugs during pregnancy was associated with an increased risk of abnormal motor development at 9 months (OR = 1.3 [1.1-2.2]) and abnormal motor and mental development at 24 months (OR = 4.8 [2.1-11.0] and OR = 2.3 [1.05-4.9]). Increased risk was observed in children born to women exposed to anti-epileptic drugs, neuroleptics or antidepressants during pregnancy. This study found a higher rate of deviation from the normal developmental milestones in children born to women exposed to psychotropic drugs during pregnancy and more particularly antidepressants, neuroleptics and anti-epileptics.

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely used drugs. On June 2008 and February 2009, Dear Doctor Letters (DDLs) were sent by the French Health Authorities (AFSSAPS) to remind practitioners of risks with NSAIDs after the fifth month of pregnancy. The aim of this study was to evaluate the impact of these letters on NSAID prescriptions during late pregnancy. EFEMERIS is a French database that registers drugs prescribed and reimbursed during pregnancy and outcomes between 2004 and 2015. We performed a descriptive study and a 'before-and-after' comparison of NSAID prescriptions between 3 June 2006 and 3 June 2008 ('before group'), and between 1 March 2010 and 1 March 2012 ('after group'). We carried out a Cochran Armitage trend test to check whether the rate of women exposed to NSAIDs varies linearly over time. We identified 948 (4.38%) pregnant women in the 'before group' and 678 (2.73%) in the 'after group' receiving at least one NSAID prescription in late pregnancy (P 0.0001). Between 2006 and 2012, mainly prescriptions for morniflumate/niflumic acid (1.7% vs. 0.9%; P 0.0001), ibuprofen (0.8% vs. 0.6%; P = 0.01) and ketoprofen (0.7% vs. 0.3%; P 0.0001) fell significantly after DDLs. The Cochran Armitage trend test shows that the percentage of women exposed to NSAIDs in late pregnancy decreased significantly during the study period (P 0.0001). This study highlighted a significant decrease in the percentage of women receiving NSAID prescriptions during late pregnancy after DDLs. This decrease is not linked to a specific women's profile or prescriber's medical discipline.

ObjectiveTo estimate the magnitude of the correlation between neonatal outcomes of twins and demonstrate how this information can be used in the design of randomised controlled trials (RCTs) in women with twin pregnancies.DesignSecondary analysis of data from 12 RCTs.SettingObstetric care in multiple countries, 2004-2012.Population or sample4504 twin pairs born to women who participated in RCTs to assess treatments given during pregnancy.MethodsIntraclass correlation coefficients (ICCs) were estimated using log-binomial and linear models.Main outcome measuresPerinatal death, respiratory distress syndrome, bronchopulmonary dysplasia, intraventricular haemorrhage, necrotising enterocolitis, sepsis, neonatal intensive care unit admission, birthweight, low birthweight and two composite measures of adverse neonatal outcome.ResultsICCs for the composite measures of adverse neonatal outcome were all above 0.5, indicating moderate to strong correlation between adverse outcomes of twins. For individual neonatal outcomes, median ICCs across trials ranged from 0.13 to 0.79 depending on the outcome. An example illustrates how ICCs can be used in sample size calculations for RCTs in women with twin pregnancies.ConclusionsThe correlation between neonatal outcomes of twins varies considerably between outcomes and may be lower than expected. Our ICC estimates can be used for designing and analysing RCTs that recruit women with twin pregnancies and for performing meta-analyses that include such RCTs. Researchers are encouraged to report ICCs for neonatal outcomes in twins in their own RCTs.Tweetable abstractCorrelation between neonatal outcomes of twins depends on the outcome and may be lower than expected.Tweetable abstract Correlation between neonatal outcomes of twins depends on the outcome and may be lower than expected.

International audience; The aim of our study was to evaluate the bidirectional transfer of Bisphenol S (BPS) and its main metabolite, BPS Glucuronide (BPSG), using the model of perfused human placenta and to compare the obtained values with those of Bisphenol A (BPA) and BPA Glucuronide. Fourteen placentas at term were perfused in an open dual circuit with deuterated BPS (1 and 5 μM) and non-labelled BPSG (2.5 μM) and a freely diffusing marker antipyrine (800 ng/ml) in the presence of albumin (25 mg/ml). In a second experiment, the potential role of P-glycoprotein in the active efflux of BPS across the placental barrier was studied using the well-established P-glycoprotein inhibitor, PSC833 (2 and 4 μM). Placental transfer of BPS was much lower than that of BPA in both directions. The placental clearance index of BPS in the materno-fetal direction was three times lower than in the opposite direction, strongly suggesting some active efflux transport. However, our results show that P-glycoprotein is not involved in limiting the materno-fetal transfer of BPS. Placental transfer of BPSG in the fetal compartment was almost non-existent indicating that, in the fetal compartment, BPSG originates mainly from feto-placental metabolism. The feto-maternal clearance index for BPSG was 20-fold higher than the materno-fetal index. We conclude that the blood-placental barrier is much more efficient in limiting fetal exposure to BPS than to BPA, indicating that the placenta has a crucial role in protecting the human fetus from BPS exposure.

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

To compare the short- and long-term perineal consequences (at 6 months postpartum) and short-term neonatal consequences of instrumental rotation (IR) to those induced by assisted delivery (AD) in the occiput posterior (OP) position, in case of manual rotation failure. A prospective observational cohort study; tertiary referral hospital including all women presenting with persistent OP position who delivered vaginally after manual rotation failure with attempted IR or AD in OP position from September 2015 to October 2016. Maternal and neonatal outcomes of all attempted IR deliveries were compared with OP operative vaginal deliveries. Main outcomes measured were pelvic floor function at 6 months postpartum including Wexner score for anal incontinence and ICIQ-FLUTS for urinary symptoms. Perineal morbidity comprised severe perineal tears, corresponding to third and fourth degree lacerations. Fetal morbidity parameters comprised low neonatal Apgar scores, acidaemia, major and minor fetal injuries and neonatal intensive care unit admissions. Among 5265 women, 495 presented with persistent OP positions (9.4%) and 111 delivered after manual rotation failure followed by AD delivery: 58 in the IR group and 53 in the AD in OP group. The incidence of anal sphincter injuries was significantly reduced after IR attempt (1.7% vs. 24.5%; p

To assess the value of the prenasal thickness to nasal bone length ratio (PT/NBL) for detecting trisomy 21 (T21) after the first trimester.Two examiners blinded to fetal T21 status retrospectively measured prenasal thickness (PT) and nasal bone length (NBL) of T21 and control fetuses at 15-36 weeks' gestational age on two-dimensional images from all T21-screening ultrasounds from November 2010 to April 2013. ROC curve analysis and its diagnostic values determined the best cut-off value for the ratio. Interobserver reproducibility was assessed.Good quality ultrasound profile images were available for 26 fetuses with T21 compared to 91 normal fetuses. The median PT/NBL ratio was 1.28 for T21 and 0.73 for control fetuses (p0.0001). The PT/NBL ratio performed significantly better (AUC 0.99; 95%CI 0.97-1) than either PT (0.82; 0.73-0.91) or NBL (0.91; 0.85-0.98). The optimal PT/NBL ratio cut-off was 0.98, with a sensitivity of 88.5% [76.2-100%] and a specificity of 100%. Interobserver variability was low.The PT/NBL ratio is a strong marker for detecting T21 in the second and third trimesters, significantly more effective than either indicator alone.

Objective There are few published data about possible effects of veinotonics in pregnant women. The present study investigates potential adverse drug reactions of veinotonics in pregnancy. Method EFEMERIS is a database including prescribed and dispensed reimbursed drugs during pregnancy (data from Caisse Primaire d’Assurance Maladie) and outcomes (data from Maternal and Infant Protection Service and Antenatal diagnostic Centre). Women who delivered from 1 July 2004 to December 2007 in Haute-Garonne and were registered in the French Health Insurance Service have been included in the EFEMERIS database. We compared pregnancy outcomes and newborn health between women exposed to veinotonics during pregnancy and unexposed women. Results We found that 8998 women (24%) had received at least one prescription for venotonic agents during their pregnancy, corresponding to the period of organogenesis in 1200 cases. We compared data for these women with those for the 27,963 women for whom these drugs were not prescribed during pregnancy. The most widely used veinotonics were hesperidin, diosmin and troxerutin. Pregnancies led to 98.4% versus 93.6% of live births, 0.2% versus 0.2% of postnatal deaths and 1.6% versus 6.4% of pregnancy termination (miscarriage, ectopic pregnancy, medical termination, intrauterine death) in exposed and non-exposed groups, respectively. The risks of pregnancy termination (HR = 0.71 (0.60–0.84)) and prematurity (HR = 0.82 (0.73–0.93)) remained significantly lower in the women exposed to venotonics than in unexposed women. In the group of newborns whose mother had a prescription of veinotonics during organogenesis, 39 out of 1200 (3.4%) had a malformation versus 789 (3.0%) in the control group (ORa = 1.134 (0.873–1.472)). The risk of neonatal diseases was not increased by exposure to venotonic agents in the third trimester (4.9% versus 6.1% for the controls, ORa = 1.07 (0.95–1.20)). Conclusion We found no increased risk of adverse pregnancy outcome among women exposed to veinotonics compared with unexposed pregnant women.

Objectives To investigate the efficacy of antenatal corticosteroid (ACS) therapy on short-term neonatal outcomes in preterm twins, and further document the influence of the ACS-to-delivery interval. Design EPIPAGE-2 is a nationwide observational multicentre prospective cohort study of neonates born between 22 and 34 completed weeks of gestation. Setting All French maternity units, except in a single administrative region, between March and December 2011. Population A total of 750 twin neonates born between 24 and 31 weeks of gestation. Methods Exposure to ACSs was examined in four groups: single complete course, with an ACS administration-to-delivery interval of ≤7 days; single complete course, with an ACS-to-delivery interval of >7 days; repeated courses; or no ACS treatment. Main outcome measures Neonatal outcomes analysed were severe bronchopulmonary dysplasia, periventricular leukomalacia or intraventricular haemorrhage grade III/IV, in-hospital mortality, and a composite indicator of severe outcomes. Results Compared with no ACSs, in multivariable analysis, a single course of ACSs with an administration-to-delivery interval of ≤7 days was significantly associated with a reduced rate of periventricular leukomalacia or intraventricular haemorrhage grade III/IV (aOR 0.2; CI 95% 0.1–0.5), in-hospital mortality (0.3; 0.1–0.6), and the composite indicator (0.1; 0.1–0.3), whereas a single course of ACDs with an administration-to-delivery interval of >7 days did not significantly reduce the frequency of in-hospital mortality (0.7; 0.3–1.8). No significant differences in terms of benefit or risk were found when comparing repeated courses with a single complete course. Conclusion In preterm twins, a single complete course of antenatal corticosteroids was associated with an improvement of severe neurological outcome, whereas reduced in-hospital mortality was seen only when the ACS-to-delivery interval was ≤7 days. Tweetable abstract A single complete course of antenatal steroids reduced severe neurological morbidity in preterm twins (24–31 weeks).

International audience; The number of elective abortions has been stable for several decades. Many factors explain women's choice of abortion in cases of unplanned pregnancies. Early initiation of contraceptive use and a choice of contraceptive choices appropriate to the woman's life are associated with lower rates of unplanned pregnancies. Reversible long-acting contraceptives should be favored as first-line methods for adolescents because of their effectiveness (grade C). Ultrasound scan before an elective abortion must be encouraged but should not be obligatory (professional consensus). As soon as the embryo appears on the ultrasound scan, the date of pregnancy is estimated by measuring the crown-rump length (CRL) or, from 11 weeks on, by measuring the biparietal diameter (BPD) (grade A). Because reliability of these parameters is ±5 days, the abortion may be done if measurements are respectively less than 90 mm for CRL and less than 30 mm for BPD (professional consensus). A medically induced abortion, performed with a dose of 200 mg mifepristone combined with misoprostol, is effective at any gestational age (Level of Evidence (LE) 1). Before 7 weeks, mifepristone should be followed 24-48 h later by misoprostol, administered orally, buccally, sublingually, or even vaginally followed if needed by a further dose of 400 μg after 3 h, to be renewed if needed after 3 h (LE 1, grade A). After 7 weeks, administration of misoprostol by the vaginal, sublingual, or buccal routes is more effective and better tolerated than by the oral route (LE 1). Cervical preparation is recommended for systematic use in surgical abortions (professional consensus). Misoprostol is a first-line agent for cervical preparation at a dose of 400 μg (grade A). Vacuum aspiration is preferable to curettage (grade B). A uterus perforated during surgical aspiration should not routinely be considered to be scarred (professional consensus). An elective abortion is not associated with a higher risk of subsequent infertility or ectopic pregnancy (LE 2). The medical consultation before an elective abortion generally does not affect the decision to end or continue the pregnancy, and most women are sufficiently certain about their choice at this time. Women appear to find the method used most acceptable and to be most satisfied when they were able to choose the method (grade B). Elective abortions are not associated with an increased rate of psychiatric disorders (LE 2). However, women with psychiatric histories are at a higher risk of psychological disorders after the occurrence of an unplanned pregnancy than women with such a history (LE 2). For surgical abortions, combined hormonal contraceptives - oral or transdermal - should be started on the day of the abortion, while the vaginal ring should be inserted 5 days afterwards (grade B). For medical abortions, the vaginal ring should be inserted in the week after mifepristone administration, while the combined contraceptives should begin the same day as the misoprostol or the day after (grade C). Contraceptive implants should be inserted on the same day as a surgical abortion, and may be inserted the day the mifepristone is administered for medical abortions (grade B and C respectively). In case of medical abortion, the implant can be inserted the same day the mifepristone is administered (grade C). Both the copper IUDs and levonorgestrel intrauterine system should be inserted on the day of the surgical abortion (grade A). After medical abortions, an IUD can be inserted in 10 days after mifepristone administration, after ultrasound scan verification of the absence of an intrauterine pregnancy (grade C).

International audience; Background: There are conflicting results regarding tocolysis in cases of preterm premature rupture of membranes. Delaying delivery may reduce neonatal morbidity because of prematurity and allow for prenatal corticosteroids and, if necessary, in utero transfer. However, that may increase the risks of maternofetal infection and its adverse consequences.Objective: The objective of the study was to investigate whether tocolytic therapy in cases of preterm premature rupture of membranes is associated with improved neonatal or obstetric outcomes.Study Design: Etude Epidémiologique sur les Petits Ages Gestationnels 2 is a French national prospective, population-based cohort study of preterm births that occurred in 546 maternity units in 2011. Inclusion criteria in this analysis were women with preterm premature rupture of membranes at 24–32 weeks’ gestation and singleton gestations. Outcomes were survival to discharge without severe morbidity, latency prolonged by ≥48 hours and histological chorioamnionitis. Uterine contractions at admission, individual and obstetric characteristics, and neonatal outcomes were compared by tocolytic treatment or not. Propensity scores and inverse probability of treatment weighting for each woman were used to minimize indication bias in estimating the association of tocolytic therapy with outcomes.Results: The study population consisted of 803 women; 596 (73.4%) received tocolysis. Women with and without tocolysis did not differ in neonatal survival without severe morbidity (86.7% vs 83.9%, P = .39), latency prolonged by ≥48 hours (75.1% vs 77.4%, P = .59), or histological chorioamnionitis (50.0% vs 47.6%, P = .73). After applying propensity scores and assigning inverse probability of treatment weighting, tocolysis was not associated with improved survival without severe morbidity as compared with no tocolysis (odds ratio, 1.01 [95% confidence interval, 0.94–1.09], latency prolonged by ≥48 hours (1.03 [95% confidence interval, 0.95–1.11]), or histological chorioamnionitis (1.03 [95% confidence interval, 0.92–1.17]). There was no association between the initial tocolytic drug used (oxytocin receptor antagonists or calcium-channel blockers vs no tocolysis) and the 3 outcomes. Sensitivity analyses of women with preterm premature rupture of membranes at 26–31 weeks’ gestation, women who delivered at least 12 hours after rupture of membranes, women with direct admission after the rupture of membranes and the presence or absence of contractions gave similar results.Conclusion: Tocolysis in cases of preterm premature rupture of membranes is not associated with improved obstetric or neonatal outcomes; its clinical benefit remains unproven.

Introduction Total abnormal pulmonary venous return is a heart defect often missed prenatally, yet at birth, it is a surgical emergency. Antenatal detection could be improved by sonographic visualization of the anastomosis of 2 pulmonary veins in a sinus into the left atrium. The objective of this study is to evaluate the feasibility of this screening method. Method Prospective observational study. Five operators selected one representative image taken during morphological ultrasound screening. Anonymized images were later assessed for quality by an expert. Both the operator and the expert were asked to rate the picture and collect clinical data. Feasibility corresponded to the percentage of images judged satisfactory by the expert; reliability corresponded to the percentage judged satisfactory by both the expert and the sonographer. Results A total of 192 patients were included. Feasibility was 73% (95% confidence interval, 67.1%-79.7%) and reliability was 81.4% (95% confidence interval, 75.9%-86.9%). There was no learning curve. Conclusion This study confirms that visualization of the 2 pulmonary veins in a sinus into the left atrium at midtrimester screening is simple and reproducible. The next stage is to evaluate the sensitivity and specificity as a screening test of total abnormal pulmonary venous return and whether that would improve morbidity and mortality.

Objective To assess the impact of latency duration on survival, survival without severe morbidity, and early-onset sepsis in infants born after preterm premature rupture of membranes (PPROM) at 24-32 weeks' gestation. Study design This study was based on the prospective national population-based Etude Epidemiologique sur les Petits Ages Gestationnels 2 cohort of preterm births and included 702 singletons delivered in France after PPROM at 24-32 weeks' gestation. Latency duration was defined as the time from spontaneous rupture of membranes to delivery, divided into 4 periods (12 hours to 2 days [reference], 3-7 days, 8-14 days, and >14 days). Multivariable logistic regression was used to assess the relationship between latency duration and survival, survival without severe morbidity at discharge, or early-onset sepsis. Results Latency duration ranged from 12 hours to 2 days (18%), 3-7 days (38%), 8-14 days (24%), and >14 days (20%). Rates of survival, survival without severe morbidity, and early-onset sepsis were 93.5% (95% CI 91.894.8), 85.4% (82.4-87.9), and 3.4% (2.0-5.7), respectively. A crude association found between prolonged latency duration and improved survival disappeared on adjusting for gestational age at birth (aOR 1.0 [reference], 1.6 [95% CI 0.8-3.2], 1.2 [0.5-2.9], and 1.0 [0.3-3.2] for latency durations from 12 hours to 2 days, 3-7 days, 8-14 days, and >14 days, respectively). Prolonged latency duration was not associated with survival without severe morbidity or early-onset sepsis. Conclusion For a given gestational age at birth, prolonged latency duration after PPROM does not worsen neonatal prognosis.

International audience; OBJECTIVE: To evaluate the association between the planned mode of delivery and neonatal mortality and morbidity in an unselected population of women with twin pregnancies. METHODS: The JUmeaux MODe d'Accouchement (JUMODA) study was a national prospective population-based cohort study. All women with twin pregnancies and their neonates born at or after 32 weeks of gestation with a cephalic first twin were recruited in 176 maternity units in France from February 2014 to March 2015. The primary outcome was a composite of intrapartum mortality and neonatal mortality and morbidity. Comparisons were performed according to the planned mode of delivery, planned cesarean or planned vaginal delivery. The primary analysis to control for potential indication bias used propensity score matching. Subgroup analyses were conducted, one according to gestational age at delivery and one after exclusion of high-risk pregnancies. RESULTS: Among 5,915 women enrolled in the study, 1,454 (24.6%) had planned cesarean and 4,461 (75.4%) planned vaginal deliveries, of whom 3,583 (80.3%) delivered both twins vaginally. In the overall population, composite neonatal mortality and morbidity was increased in the planned cesarean compared with the planned vaginal delivery group (5.2% compared with 2.2%; odds ratio [OR] 2.38, 95% confidence interval [CI] 1.86–3.05). After matching, neonates born after planned cesarean compared with planned vaginal delivery had higher composite neonatal mortality and morbidity rates (5.3% compared with 3.0%; OR 1.85, 95% confidence interval 1.29–2.67). Differences in composite mortality and morbidity rates applied to neonates born before but not after 37 weeks of gestation. Multivariate and subgroup analyses after exclusion of high-risk pregnancies found similar trends.CONCLUSION: Planned vaginal delivery for twin pregnancies with a cephalic first twin at or after 32 weeks of gestation was associated with low composite neonatal mortality and morbidity. Moreover, planned cesarean compared with planned vaginal delivery before 37 weeks of gestation might be associated with increased composite neonatal mortality and morbidity.

Objective: To determine whether cervical shortening between 22 and 27 weeks predicts spontaneous preterm delivery before 34 weeks better than a single cervical length (CL) measurement at 22 or 27 weeks in asymptomatic twins.Prospective 13-center study over a 2-year-period. CL was measured in 120 asymptomatic twin pregnancies. The area under the ROC curve was calculated for each parameter and the cutoff point providing the best diagnostic performance, sensitivity and specificity for predicting spontaneous delivery34 weeks was defined too.About 13/116 women gave birth before 34 weeks. The three ROC curves differed significantly at the 0.05 level. The best cutoff points were CL≤35 mm at 22 weeks, CL≤25 mm at 27 weeks and cervical shortening≥20%. For equal sensitivity values for each, specificity for CL≤25 mm at 27 weeks was 87.5%, significantly better.The performance of cervical shortening for the prediction of preterm delivery of asymptomatic twins before 34 weeks does not differ from that of CL measurements at 22 or 27 weeks. The modest predictive value of CL at 22 weeks and of cervical shortening is an argument against recommending routine CL measurements.

Objective To evaluate the risk of adverse pregnancy outcomes following A/H1N1 vaccination in pregnant women. Methods This observational cohort study compared vaccinated and non-vaccinated pregnant women in EFEMERIS, a French prescription database including pregnant women. Women who ended their pregnancy in South Western France between October 21, 2009 and November 30, 2010 (the period of the French vaccination campaign) were included. Two non-vaccinated women were individually matched to each vaccinated woman by month and year of pregnancy onset. Conditional logistic regression and Cox proportional hazards regression were used to evaluate associations between each outcome (all-cause pregnancy loss, preterm delivery, small for gestational age (SGA) and neonatal pathology) and A/H1N1 vaccination during pregnancy. Results 1645 women of the 12,120 (13.6%) in the database who were administered A/H1N1 vaccine during pregnancy were compared to 3290 non-vaccinated women. Most were vaccinated in December 2009 (61%) with a non-adjuvanted vaccine (93%). The risks of pregnancy loss (adjusted HR = 0.56; 95% CI = 0.31–1.01), of preterm birth (adjusted HR = 0.82; 95% CI = 0.64–1.06), and of neonatal pathology (adjusted OR = 0.70; 95% CI = 0.49–1.02) did not differ between the vaccinated and the non-vaccinated groups. The rate of SGA was lower in the vaccinated group than in the non-vaccinated group (0.5% vs. 1.4%; adjusted OR = 0.36; 95% CI = 0.17–0.78). Conclusion There was no significant association between adverse pregnancy outcomes and vaccination with a non-adjuvanted A/H1N1 vaccine during pregnancy.

Summary Background Foetal echocardiography has been used to diagnose congenital heart disease. However, conventional echocardiography can only display two-dimensional (2D) structural images of the intricate three-dimensional (3D) foetal heart. Aim The purpose of this study was to report the first use of a new transabdominal xMATRIX array transducer and to describe its ability to perform all 3D modalities: intelligent spatiotemporal image correlation (iSTIC) acquisition, xPlane imaging and 3D surface imaging. Methods Eighty foetuses without congenital heart disease were included consecutively, with a gestational age between 20 and 37 weeks. 2D and 3D scans were performed with a transabdominal xMATRIX array transducer. Cardiac-STIC volume datasets were acquired and postprocessed with new automatic software (the ‘Fetal Heart Navigator’). Results A total of 224 iSTIC acquisitions were performed (mean time for each, 2 seconds). Only 78 iSTIC acquisitions (35%) were able to detect the ductal arch automatically. ‘Fetal Heart Navigator’ feasibility varied according to foetal position, including the descending aorta. Live xPlane imaging had excellent feasibility regardless of foetal position; using rotation, lateral and vertical tilts, all cardiac structures were identified from a unique reference plane. Live 3D surface imaging had variable feasibility depending on the target structure. Only 10% of the volume dataset offered comprehensive imaging of intracardiac views. Conclusion The new xMATRIX transabdominal transducer allows a multimodality approach to the foetal heart. Further studies that include foetuses with cardiac malformations are required.

To compare the maternal and neonatal outcomes associated with Instrumental Rotation (IR) to operative vaginal delivery in occiput posterior (OP) position with Thierry's spatulas (TS), in the setting of failed manual rotation (MR).We led a prospective observational cohort study in a tertiary referral hospital in Toulouse, France. All women presenting in labor with persistent OP position at full cervical dilatation and who delivered vaginally after failed MR and with IR or OP assisted delivery were included from January 2014 to December 2015. The main outcomes measured were maternal morbidity parameters including episiotomy rate, incidence and severity of perineal lacerations, perineal hematomas and postpartum hemorrhage. Severe perineal tears corresponded to third and fourth degree lacerations. Fetal morbidity outcomes comprised neonatal Apgar scores, acidemia, fetal injuries, birth trauma and neonatal intensive care unit admissions.Among 9762 women, 910 (9.3%) presented with persistent OP position at full cervical dilatation and 222 deliveries were enrolled. Of 111 attempted IR, 97 were successful (87.4%). The incidence of anal sphincter injuries was significantly reduced after IR attempt (1.8% vs. 12.6%; p 0.002). Both groups were similar regarding most fetal outcomes and no birth trauma occurred in our study population. In a multivariable logistic regression analysis, OP operative delivery was a significant risk factor of severe perineal lacerations (OR = 9.5; 95% CI: 2.05-44.05).Our results support the use of IR in order to reduce perineal morbidity associated with OP assisted delivery, in the setting of a failed manual rotation.

The duration of pregnancy varies between 40(+0) and 41(+3) weeks. Conventionally, and essentially arbitrarily, a pregnancy is considered to be "prolonged" after 41(+0) weeks, but the infant is not considered "post-term" until 42(+0) weeks (Professional consensus). A term birth thus occurs during the period from 37(+0) to 41(+6) weeks. In France, prolonged pregnancies (≥41(+0)weeks) involve 15-20% of pregnant women, and post-term pregnancies (≥42(+0) weeks) approximately 1%. The frequency of post-term pregnancies is very heterogeneous: in Europe and the United States, it ranges from 0.5% to 10% according to country. In prolonged pregnancies, the cesarean section rate-especially the emergency cesarean rate-is multiplied by approximately 1.5 (grade B). From 37(0-6) to 43(0-6) weeks, the risk of perinatal mortality increases regularly, from 0.7‰ to 5.8‰. Meconium aspiration syndrome is responsible for substantial morbidity and mortality, and its incidence increases regularly between 38(+0) and 42(+6) weeks, from 0.24‰ to 1.42‰ (grade B). Similarly, the risks of neonatal acidosis (grade B), 5-min Apgar scores less than 7 (grade B) and admissions to neonatal intensive care (grade B) increase progressively between 38(+0) and 42(+6) weeks. These risks appear to double for post-term growth-restricted newborns (grade C). Ultrasound dating of the pregnancy makes it possible to reduce the risk that it will be incorrectly considered prolonged and that labor will therefore be induced unnecessarily. To harmonize practices, if the crown-rump length (CRL) is correctly measured (this measurement should be taken between 11(+0) and 13(+6) weeks, when CRL should measure from 45 to 84mm), ultrasound dating based on it should be used to determine the official date pregnancy began, regardless of its difference from the date assumed by the patient or estimated based on the date of the last menstrual period. This rule does not apply to pregnancies by IVF, for which the date pregnancy began is defined by the date of oocyte retrieval (Professional consensus). From 37(0-6) to 43(0-6) weeks, the risk of perinatal mortality increases regularly and there is no threshold at which a clear increase in perinatal mortality becomes visible. Fetal monitoring by cardiotocography (CTG) that begins at 41(+0) weeks would cover approximately 20% of women and reduce perinatal morbidity compared with monitoring that begins at 42(+0) weeks (grade C). The frequency recommended for this monitoring ranges between two and three times a week (Professional consensus). For ultrasonography assessment, measurement of the largest fluid pocket is recommended, because measurement of the amniotic fluid index (that is, the sum of the four quadrants) is accompanied by more diagnoses of oligohydramnios, inductions of labor, and cesareans for fetal distress without any improvement in neonatal prognosis (grade A). The practice of assessing the Manning biophysical score increases the number of diagnoses of oligohydramnios and fetal heart rage (FHR) abnormalities and generates an increase in the rates of inductions and cesareans without improving neonatal prognosis. The use of this biophysical score in monitoring prolonged pregnancies is therefore not recommended (grade B). In the absence of a specific disorder, induction of labor can be proposed in patients between 41(+0) and 42(+6) weeks (grade B). Nonetheless, the choice of prolongation beyond above 42(+0) weeks appears to involve an increase in fetal risk, which must be explained to the patient and balanced against the potential disadvantages of induction (Professional consensus). Stripping the membranes can reduce the duration of pregnancy by increasing the number of patients going into labor spontaneously during the week afterward (grade B). Compared to an expectant approach, it does not increase the cesarean section rate (grade A). It reduces recourse to induction by 41% at 41(+0) weeks and by 72% at 42(+0) weeks (grade B), without increasing the risk of either membrane rupture or maternal or neonatal infection (grade B). Used as a tampon or vaginal gel, prostaglandins E2 (PGE2) are an effective method of inducing labor (grade A). They can be used to induce labor successfully, regardless of cervical ripeness (grade A). If misoprostol is chosen, the lowest dose is to be preferred, starting with a vaginal dose of 25μg every 3-6h (grade A). For misoprostol, more powerful studies remain necessary for better defining the doses, routes of administration, tolerance and indications. Misoprostol at any dose is contraindicated in women with uterine scars (grade B). Placement of an intracervical Foley catheter is an effective mechanical means of inducing labor, with less uterine hyperstimulation than prostaglandins and no increase in the cesarean section rate (grade A). Nonetheless, as the risk of infection might be increased, this technique requires more robust evaluation before entering general practice (grade B). In cases of meconium-stained amniotic fluid, pharyngeal aspiration before delivery of the shoulders is not recommended (grade A). The team managing a post-term newborn with meconium-stained amniotic fluid at birth must know how to perform intubation and, if the intubation is not helpful, endotracheal aspiration (grade C) and ventilation with a mask. Routine endotracheal intubation of a vigorous newborn is not recommended (grade A).

BACKGROUND: Intrapartum intravenous zidovudine (ZDV) prophylaxis is a long-standing component of prevention of mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) in high-resource countries. In some recent guidelines, intravenous ZDV is no longer systematically recommended for mothers receiving combination antiretroviral therapy (cART) with low viral load. We evaluated the impact of intravenous ZDV according to viral load and obstetrical conditions. METHODS: All HIV-1-infected women delivering between 1 January 1997 and 31 December 2010 in the French Perinatal Cohort (ANRS-EPF) were analyzed if they received ART during pregnancy and did not breastfeed. We identified maternal and obstetrical characteristics related to lack of intravenous ZDV and compared its association with MTCT rate and other infant parameters, according to various risk factors. RESULTS: Intravenous ZDV was used in 95.2% of the 11 538 deliveries. Older age, multiparity, and preterm and vaginal delivery were associated with lack of intravenous ZDV (n = 554). In women who delivered with viral load ≥1000 copies/mL, the overall MTCT rate was higher without than with intravenous ZDV (7.5% vs 2.9%; P = .01); however, there was no such difference when the neonate received postnatal intensification therapy. Among them, 77% of women who had viral load

Introduction The objective of this study was to compare neonatal respiratory morbidity and rate of emergency caesarean section between elective caesarean sections at 38 gestational weeks following a course of corticosteroids and planned caesarean sections at 39 gestational weeks. Material and methods This was a multicentre randomised controlled trial. The study was conducted between 2007 and 2013 in level 2 and 3 maternity units in France. A total of 208 women with an indication for elective caesarean section were enrolled and 200 analysed in per-protocol analysis. Women were randomised to either elective caesarean section at 38 gestational weeks after a course of corticosteroids (trial group) or elective caesarean section at 39 weeks (control group). The primary outcome was the rate of admission to the neonatal intensive care unit for respiratory distress. Results Two (2.1%) newborn in the tested group were admitted because of respiratory distress versus four (3.8%) in the control group. The relative risk was 0.54 in favour of the corticosteroid group (95% CI: 0.10; 2.86). There were fewer emergency caesareans in the trial group than in the control group: 12 (12.69%) versus 28 (26.67%), p = 0.01. Conclusions Our study suggests that planning caesarean sections at 38 gestational weeks after a course of corticosteroids would enable a significant reduction in the number of emergency caesareans without increasing the risk of neonatal respiratory distress. Limitations of this study include difficulties in patient recruitment and the small number of subjects.

Background: Several studies have investigated the efficacy of moxibustion with or without acupuncture for fetal version, but the results are discordant. Meta-analyses pointed out the need for robust, methodologically sound, randomized controlled trials. Objective: The objective of this study was to assess the effectiveness of acupuncture with fire needling on acupoint BL67 for version of breech presentation. Study design: This was a randomized, sham-controlled, single-blinded trial, which took place in Strasbourg teaching maternity hospital, France. A total of 259 patients between 32 and 34 weeks of gestation have been randomized and analyzed. Patients were randomized to either acupuncture with fire needling or sham group, and were analyzed in their initial allocation group. Statistical analysis was conducted using Bayesian methods, in univariate analysis and in multivariate analysis after adjustment on parity. Results: The primary outcome was the rate of cephalic presentations at ultrasound examination performed between 35 and 36 weeks of gestation. A total of 49 (37.7%) fetuses were in cephalic presentation in the acupuncture group, versus 37 (28.7%) in the sham group: RR 1.34 [0.93-1.89], Pr RR>1=94.3%. After adjustment on parity, the acupuncture did not increase the rate of fetal cephalic version: OR 1.47 [0.84-2.42], Pr OR>1=90.3%. Conclusions: Our study suggests that acupuncture with fire needling on acupoint BL67 does not promote fetal cephalic version. Further studies might investigate effectiveness of other protocols of acupuncture. Randomization should be stratified for nulliparous and parous patients. Keywords: Acupuncture; Breech presentation; Fire needling; Version.

International audience; Postpartum haemorrhage (PPH) is defined as blood loss ≥500mL after delivery and severe PPH as blood loss ≥1000mL, regardless of the route of delivery (professional consensus). The preventive administration of uterotonic agents just after delivery is effective in reducing the incidence of PPH and its systematic use is recommended, regardless of the route of delivery (Grade A). Oxytocin is the first-line prophylactic drug, regardless of the route of delivery (Grade A); a slowly dose of 5 or 10 IU can be administered (Grade A) either IV or IM (professional consensus). After vaginal delivery, routine cord drainage (Grade B), controlled cord traction (Grade A), uterine massage (Grade A), and routine bladder voiding (professional consensus) are not systematically recommended for PPH prevention. After caesarean delivery, placental delivery by controlled cord traction is recommended (grade B). The routine use of a collector bag to assess postpartum blood loss at vaginal delivery is not systematically recommended (Grade B), since the incidence of severe PPH is not affected by this intervention. In cases of overt PPH after vaginal delivery, placement of a blood collection bag is recommended (professional consensus). The initial treatment of PPH consists in a manual uterine examination, together with antibiotic prophylaxis, careful visual assessment of the lower genital tract, a uterine massage, and the administration of 5-10 IU oxytocin injected slowly IV or IM, followed by a maintenance infusion not to exceed a cumulative dose of 40IU (professional consensus). If oxytocin fails to control the bleeding, the administration of sulprostone is recommended within 30minutes of the PPH diagnosis (Grade C). Intrauterine balloon tamponade can be performed if sulprostone fails and before recourse to either surgery or interventional radiology (professional consensus). Fluid resuscitation is recommended for PPH persistent after first line uterotonics, or if clinical signs of severity (Grade B). The objective of RBC transfusion is to maintain a haemoglobin concentration (Hb) >8g/dL. During active haemorrhaging, it is desirable to maintain a fibrinogen level ≥2g/L (professional consensus). RBC, fibrinogen and fresh frozen plasma (FFP) may be administered without awaiting laboratory results (professional consensus). Tranexamic acid may be used at a dose of 1 g, renewable once if ineffective the first time in the treatment of PPH when bleeding persists after sulprostone administration (professional consensus), even though its clinical value has not yet been demonstrated in obstetric settings. It is recommended to prevent and treat hypothermia in women with PPH by warming infusion solutions and blood products and by active skin warming (Grade C). Oxygen administration is recommended in women with severe PPH (professional consensus). If PPH is not controlled by pharmacological treatments and possibly intra-uterine balloon, invasive treatments by arterial embolization or surgery are recommended (Grade C). No technique for conservative surgery is favoured over any other (professional consensus). Hospital-to-hospital transfer of a woman with a PPH for embolization is possible once hemoperitoneum is ruled out and if the patient's hemodynamic condition so allows (professional consensus).

OBJECTIVES: The prenatal finding of a cystic suprarenal mass (CSM) presents a wide differential diagnosis. The aim of this study was to present the natural course and outcome of antenatally diagnosed CSMs. METHODS: We reviewed the medical records of patients with prenatally detected CSMs that were assessed between January 1998 and December 2011. Retrospective data collection included the age at the time of diagnosis, the size of the mass, and the sonographic evolution of the mass. Surgical treatment was indicated in cases of malignant tumors and symptoms or when size increased. RESULTS: The observation period ranged from 1 month to 10 years. The data of 21 patients were analyzed. The median length of follow-up was 32 months (ranging from 2 to 131 months). A total of 13 masses were detected on the left side and 8 on the right side. In 13 patients, the lesions disappeared after a median of 7 months (ranging from 0 to 37 months). Surgery was performed in two neonates: one for a teratoma at 10 days postpartum, and one for a neuroblastoma at 17 days postpartum. Six patients had an extralobar pulmonary sequestration (ELPS), and in four patients, surgical resection was performed at an average of 9.2 months (ranging from 1 to 20 months) postpartum, because of an infection or increase in ELPS size. Histological examination confirmed the pulmonary sequestration. An association with congenital cystic adenomatoid malformation (CCAM) was found in one patient, and ectopic pancreatic tissue was discovered in another patient. Two patients conservatively managed remain under observation. CONCLUSIONS: During the neonatal period, the accurate assessment of CSMs is necessary to exclude the presence of malignant tumors. Most patients can be conservatively managed, with close follow-up, including radiological assessment. If the mass persists after 1 year of age, ELPS should be considered as a probable diagnosis, and minimally invasive laparoscopic surgery can be performed, as it provides both definitive diagnosis and treatment.