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Endothelial nitric oxide (NO) plays a critical role in vascular homeostasis. It regulates the vascular tone, maintains the blood flow, exerts a vasorelaxing effect on smooth muscle cells and inhibits their proliferation. In the endothelium, NO is synthesized by the endothelial NO synthase which is activated by dimerization in the presence of l-arginine (as substrate) and several cofactors including the essential cofactor tetrahydrobiopterin. The NO/eNOS pathway is basically vasculoprotective and antiatherogenic but it may become dysfunctional and proatherogenic under conditions that locally increase the production of reactive oxygen species, leading to tetrahydrobiopterin oxidation, eNOS dysfunction and uncoupling. In these conditions, eNO synthase switches from a NO-producing to superoxide anion-producing enzyme, which potentiates oxidative and nitrosative stress via the generation of peroxynitrite. In redox-perturbed conditions, eNOS dysfunction may also result from post-translational modifications deriving from oxidative stress such as S-glutathionylation or resulting either from the formation of adducts on eNOS by lipid-oxidation-derived aldehydes or from hyperglycemia-induced modifications. In this review, we summarize the mechanisms by which these post-translational modifications alter eNOS activity, and their potential implication in the pathophysiology of vascular diseases.

Aspirin initiated between 11 and 14 weeks of gestation reduces the risk of preterm preeclampsia and other placenta-mediated complications in screen-positive women. Most of these adverse outcomes are associated with maternal vascular malperfusion of the placenta, a disease that begins during the early first trimester. Assuming that aspirin has direct beneficial actions on the developing placenta, tempts clinicians to believe in the maxim that "the earlier the better", however neither the safety nor the effectiveness of aspirin started before 11th week of gestation has been demonstrated. Therefore, outside of research protocols, aspirin should not be started before the 11th week of pregnancy for the prevention of preeclampsia.

Purpose To evaluate women’s choice in the method of labour induction between oral misoprostol, PGE2 pessary and the Foley catheter. To compare women’s satisfaction according to their choice and to identify factors associated with patient satisfaction. Methods We conducted a comparative, prospective cohort study of 520 women who chose their preferred method for labour induction, in a French tertiary hospital, from July 2019 to October 2020. Before and after the delivery, they were asked to argument their choice and to evaluate their satisfaction through the use of questionnaires. The primary outcome was global level of satisfaction. Results Of the 520 women included, 67,5% of women chose oral Misoprostol compared to 21% PGE2 pessary and 11.5% the Foley catheter. Regarding global satisfaction, we found no significant difference between the three groups: 78,4%, 68,8% and 71,2% (p = 0,091) for respectively oral misoprostol, PGE2 pessary and the Foley catheter. Factors that seem to improve women’s satisfaction were nulliparity (OR = 2.03, 95%CI [1.19–3.53]), delivery within 24 hours after the start of induction (OR = 3.46, 95%CI. [2.02–6.14]) and adequate information (OR = 4.21,95%CI [1.86–9.64]). Factors associated with lower satisfaction rates were postpartum hemorrhage (OR = 0.51, 95%CI [0.30–0.88]) and caesarean section (OR = 0.31, 95%CI [0.17–0.54]). Conclusion Women satisfaction rates were not different between the three methods, when chosen by the patients themselves. These finding should encourage caregivers to promote shared decision making when possible.

The aim of this study was to assess perinatal morbidity associated with spatulas or forceps assisted delivery in preterm birth.This is a retrospective cohort study including all women with assisted deliveries on singleton pregnancy in cephalic presentation, before 37 weeks of gestation, in two tertiary care centers. We compared forceps-assisted deliveries with spatula-assisted deliveries. The main outcome was the rate of neonatal birth trauma. Secondary outcomes included other neonatal parameters, maternal outcomes and obstetric anal sphincter injuries.Out of 37 002 deliveries, 59 (0.2 %) preterm assisted deliveries with forceps and 111 (0.3%) preterm spatulas deliveries were included. The rate of neonatal birth trauma was low for both devices, without significant difference (3.4% in Forceps group vs 0.9% in Spatulas group, p = 0.28). The rate of episiotomy was 79.7% after forceps-assisted delivery and 48.6% for spatulas (p 0.001). The rate of obstetric anal sphincter injuries was 1.7% and 2.7% respectively (p = 0,9).The rate of birth trauma was low in both forceps-assisted deliveries and spatula-assisted deliveries and was not significantly different between the two groups.

Objectives Placental growth factor (PlGF) is used for first-trimester preeclampsia screening and could be combined with other biochemical markers for Down syndrome screening. We aim to estimate the predictive value of the combination of pregnancy-associated plasma protein (PAPP-A), free β-human chorionic gonadotropin (free β-hCG), placental growth factor (PlGF) and α-fetoprotein (AFP) with and without nuchal translucency. Methods Singleton pregnancies recruited at 11–14 weeks and followed until delivery. The four maternal markers were measured using Kryptor (ThermoFisher-BRAHMS) and adjusted for gestational age and maternal characteristics. The risk of Down syndrome was calculated using the Fetal Medicine Foundation algorithm and multivariate linear regression analyses in all cases and in 2,200 controls. Receiver-operator characteristic (ROC) curves were used to calculate the detection and false-positive rates. Results Twenty-six (0.2%) cases of Down syndrome were diagnosed among 13,386 participants. The combination of the four biomarkers could have detected 88% (95% CI: 72–97%) of the cases at a false-positive rate of 13% (95% CI: 12–15%). The addition of nuchal translucency would have increased the detection rate to 96% (95% CI: 82–99%) at a false-positive rate of 4% (95% CI: 4–5%) using a 1:300 cut-off and to 100% (95% CI: 89–100%) at a false-positive rate of 6% (95% CI: 5–8%) using a 1:500 cut-off. Conclusions First-trimester screening using biochemical markers allows the identification of approximately 88% of Down syndrome cases for a false-positive rate of 13%. The addition of nuchal translucency raises the detection rate above 95% with a false-positive rate below 5%.

Lower uterine segment (LUS) thickness measurement using transabdominal ultrasound (TA-US), transvaginal ultrasound (TV-US), or the combination of both methods can detect scar defect in women with prior cesarean. We aimed to compare the sensitivity of three approaches.Women with prior cesarean underwent LUS thickness measurement at 34-38 weeks' gestation. Among those who underwent repeat cesarean before labor, we compared the accuracy of TA-US, TV-US, and the thinner of the two measurements (the "combined measurement") for uterine scar dehiscence using the area under the curve (AUC) of receiver operating curves with their 95% confidence intervals (CI). We calculated the sensitivity and specificity of the three approaches using a cut-off of 2.3 mm based on prior literature.We included 747 participants. The mean LUS thickness was greater with TA-US (3.8 ± 1.6 mm) compared with TV-US (3.5 ± 1.9 mm) or the combined measurement (3.2 ± 1.5 mm; P .001). The AUC was 78% (95% CI: 69%-87%), 85% (95% CI: 79%-91%), and 88% (95% CI: 82%-93%), respectively (all with P .001). The AUC difference between TA-US and the combined measurement was not significant (P = .057). A LUS below 2.3 mm would have predicted 9 (45%) of the 20 cases of uterine scar dehiscence using TA-US, 17 (85%) using TV-US, and 18 (90%) using the combined measurement (P .01).The choice of ultrasound approach influences the measurement of the LUS thickness. The combination of the TA-US and TV-US seems to be superior for the detection of uterine dehiscence.

To assess the association between marked variability in fetal heart rate and neonatal acidosis.Bicentric prospective cohort study.From 01/2019 to 12/2019, in two French tertiary care maternity units.Women in labor at or after 37 weeks, with continuous FHR monitoring until delivery and availability of umbilical arterial pH. Women with intrauterine fetal death or medical termination, multiple pregnancies, non-cephalic presentation, or planned cesarean delivery were excluded.The exposure was marked variability in fetal heart rate 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 modeling. We then conducted subgroup analyses according to the NICHD category of the associated fetal heart rate.Neonatal acidosis, defined as an umbilical artery pH ≤ 7.10.Among the 4,394 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 (adjusted relative risk 2.30, 95% confidence interval 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.Marked variability was associated with a two-fold increased risk of neonatal acidosis.

OBJECTIVE To evaluate the delivery rate in the occiput posterior position according to the result of manual rotation performed in the case of persistent occiput posterior position. Secondary objectives were perinatal outcomes. METHODS This was a prospective cohort study conducted in two French tertiary care units. All women with a singleton pregnancy after 37 weeks of gestation with a fetus in persistent occiput posterior position and an attempt of manual rotation were included. The main outcome was the occiput position at delivery. The secondary outcomes were duration of labor, mode of delivery, and perineal tears. Two groups were compared according to the result of manual rotation. RESULTS In total, 460 women were included, with a manual rotation success of 62.4%. The success was significantly associated with a decrease in occiput posterior position at vaginal delivery (1.4% vs 57.2%, P

The idea of using an instrument to assist natural childbirth is not new and it was in the 18th and 19th centuries that the forceps was developed. It is only after the Second World War that the suction cup provides an alternative to instrumental childbirth, but still based on prehension and traction. In 1950, Emile Thierry, in France, presented his spatulas based on the then original principle of propulsion. The diffusion of spatulas is almost non-existent in the Anglo-Saxon world but is not limited to France since its use was real by the Iberians and Latin Americans. There are currently three types of spatula, two of which are French and one Colombian. This review takes up the saga of this instrument for more than 70 years, develops its particularities and describes the present literature.

Accelerated placental senescence is associated with preeclampsia (PE) and other pregnancy complications. It is characterized by an accelerated decline in placental function due to the accumulation of senescence patterns such as telomere shortening, mitochondrial dysfunction, oxidative damages, increased expression of phosphorylated (serine-139) histone γ-H2AX, a sensitive marker of double-stranded DNA breaks, accumulation of cross-linked ubiquitinated proteins and sirtuin inhibition. Among the lipid oxidation products generated by the peroxidation of polyunsaturated fatty acids, aldehydes such as acrolein, 4-hydroxy-2-nonenal, 4-oxo-2-nonenal, are present in the blood and placenta from PE-affected women and could contribute to PE pathogenesis and accelerated placental aging. In this review we summarize the current knowledge on premature placental senescence and the role of oxidative stress and lipid oxidation-derived aldehydes in this process, as well as their links with PE pathogenesis. The interest of developing (or not) new therapeutic strategies targeting lipid peroxidation is discussed, the objective being a better understanding of accelerated placental aging in PE pathophysiology, and the prevention of PE bad outcomes.

To evaluate the obstetrical prognosis of term breech delivery in case of asymmetric pelvis. An observational, comparative, retrospective, bi-centric study of 559 patients who had a computer tomography pelvimetry prior to delivery of a term breech presentation was conducted between August 2013 and August 2019. Patients with an attempted vaginal delivery were divided into two groups: a group of asymmetric pelvis (AP) when the difference between the lengths of both oblique diameters was ≥ 1 cm and a group of symmetric pelvis (SP) when the two oblique diameters differed by

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.

Objectives To estimate the ability of a combination of first-trimester markers to predict preterm preeclampsia in nulliparous women. Methods We conducted a prospective cohort study of nulliparous women with singleton gestations, recruited between 110 and 136 weeks gestation. Data on the following were collected: maternal age; ethnicity; chronic diseases; use of fertility treatment; body mass index; mean arterial blood pressure (MAP); serum levels of pregnancy-associated plasma protein A (PAPP-A), placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), alpha fetoprotein (AFP), free beta human chorionic gonadotropin (s-hCG); and mean uterine artery pulsatility index (UtA-PI). We constructed a proportional hazard model for the prediction of preterm preeclampsia selected based on the Akaike information criterion. A receiver operating characteristic curve was created with the predicted risk from the final model. Our primary outcome was preterm preeclampsia and our secondary outcome was a composite of preeclampsia, small for gestational age, intrauterine death, and preterm birth. Results Among 4659 nulliparous women with singleton gestations, our final model included 4 variables: MAP MoM, log10PlGF MoM, log10AFP MoM and log10UtA-PI MoM. We obtained an area under the curve of 0.84 (95% CI 0.75–0.93) with a detection rate of preterm preeclampsia of 55% (95% CI 37%–73%) and a false-positive rate of 10%. Using a risk cut-off with a false-positive rate of 10%, the positive predictive value for our composite outcome was 33% (95% CI 29%–37%). Conclusions The combination of MAP, maternal serum PlGF and AFP, and UtA-PI are useful to identify nulliparous women at high risk of preterm preeclampsia but also at high risk of other great obstetrical syndromes.

Objective Preeclampsia is associated with a higher maternal blood levels of soluble fms-like tyrosine kinase-1 (sFlt-1) and lower levels of placental growth factor (PlGF) that appear before clinical onset. We aimed to estimate the normal progression of these biomarkers in normal pregnancies and in those affected by preeclampsia. Methods We conducted a case-cohort study including low-risk nulliparous women recruited at 11–13 weeks gestation (cohort) and women with preeclampsia (cases). Maternal blood was collected at different points during pregnancy including at the time of diagnosis of preeclampsia for cases. Maternal serum PlGF and sFlt-1 concentrations and the sFlt-1/PlGF ratio were measured using B•R•A•H•M•S plus KRYPTOR automated assays and were compared between patients in both groups matched for gestational age. Cases were stratified as early- (≤34 weeks), intermediate- (35–37 weeks) and late-onset (>37 weeks) preeclampsia. Results The cohort consisted of 45 women whose results were compared with those of 31 women who developed preeclampsia, diagnosed at a median gestational age of 32 weeks (range 25–38 weeks). We observed that sFlt-1, PlGF and their ratio fluctuated during pregnancy in both groups, with a significant correlation with gestational age after 28 weeks (P Conclusion PlGF, sFlt-1, and their ratio may be useful in the prediction and diagnosis of early- and intermediate-onset preeclampsia but are not useful for late-onset preeclampsia.

To evaluate the risk of spontaneous preterm birth on subsequent pregnancies after second stage cesarean section.This is a retrospective cohort study. Women were included if they had their two consecutive births in Toulouse University Hospital in the study period. The first birth was a singleton livebirth at term (≥37 weeks of gestation), divided in three categories according to the mode of delivery: vaginal delivery (group A), cesarean section before the second stage of labor (group B), cesarean section during the second stage of labor (group C). The subsequent pregnancy was the first subsequent pregnancy, conducted after 16 weeks of gestation. The primary outcome was spontaneous preterm birth in the subsequent pregnancy, defined as delivery before 37 weeks of gestation. Secondary endpoints included preterm rupture of membranes in the subsequent pregnancy.Between 2003 and 2018, 7776 women (84.7%) in group A, 1263 (13.8%) in group B and 143 (1.5%) in group C were included. The adjusted odds ratio of spontaneous preterm birth before 37 weeks of gestation after second stage cesarean section was 2.4 (group C vs group A + B, 95% confidence interval: 1.2-4.8), P = 0.01). The rate of preterm rupture of membranes was also significantly higher in group C (6% vs 2% in group A, P = 0.009, 6% vs 3% in group B, P= 0.05) with OR = 3.0 (group C vs group A + B, 95% CI: 1.55-6.16, P 0.001).History of term second stage of labor cesarean section is an independent risk factor for spontaneous preterm birth and for preterm rupture of membrane in the subsequent pregnancy.

ObjectiveStudies on psychosocial interventions for perinatal mental health and wellbeing are mostly limited to the postpartum period. However, the physiological changes associated with hypertensive disorders in pregnancy predisposes women to severe psychological distress and adverse birth outcomes. This review investigated the effectiveness of psychosocial interventions for hypertensive disorders during pregnancy.MethodsCochrane CENTRAL, Embase, MEDLINE, MIDIRS, CINAHL, PsycINFO, PsycArticles, and Web of Science were searched up to 22nd August 2021. Effect sizes on relevant health outcomes were pooled in a meta-analysis using STATA software.ResultsEight randomised trials involving 460 participants met the inclusion criteria. Included studies adopted several interventions ranging from music, exercise, cognitive behavioural therapy (CBT), spiritual care education and psychoeducation. The pooled effect showed a significant reduction in anxiety (d= −0.35 [−0.58, −0.11], p=0.004) and depression (d= −0.37 [−0.57, −0.17], p=0.0003). Spiritual care education significantly reduced postpartum stress disorder (d= −62.00 [−93.10, −30.90], p= 0.0001). However, CBT showed no effect on gestational stress (d= −2.20 [-4.89, 0.48], p= 0.11).ConclusionThis study provides satisfactory evidence that psychosocial interventions may likely reduce anxiety and depression associated with hypertensive disorders in pregnancy. However, the evidence is very uncertain about its effect on neonatal outcomes.Summary of findings

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.

Other methods of cigarette consumption include a variety of electronic products, as well as heated tobacco, snus and shisha. The questions in this chapter are: what other methods of consumption are used during pregnancy (either electronic or containing tobacco) and what is their prevalence? What is their benefit/risk balance? Can their use during pregnancy be proposed? Although the fetus is not exposed to the combustible toxins of tobacco, e-cigarette products may contain nicotine, which maintains the exposure of the fetus. Further research is needed on the other components of the electronic cigarette, such as flavorings and propylene glycol and/or glycerol, in order to assess the benefit/risk balance. In addition, some solvents contain ethanol. In the current state of knowledge, the precautionary principle should be respected and not recommend the initiation or continuation of the electronic cigarette during pregnancy (professional agreement). For smoking cessation or electronic cigarette cessation, it is recommended to provide the same advice and to use methods that have already been evaluated (professional agreement). For the JUUL, there are currently no data on obstetrical outcome when used. The use of shisha during pregnancy is associated with decreased fetal growth. It is recommended not to use shisha during pregnancy (GradeC). There are currently no data on the use of heated tobacco and obstetrical outcome.

Objective This study was aimed to estimate the value of transabdominal (TA) ultrasound measurement of cervical length (CL), as an alternative of transvaginal (TV) ultrasound, for universal screening of short cervix in the midtrimester. Study Design We conducted a prospective cohort study of nulliparous women with singleton pregnancy at 20 to 24 weeks of gestation. All participants underwent TA ultrasound followed by TV ultrasound with acquisitions of images and videos of the uterine cervix. A second sonographer, blinded to the participants' data and pregnancy outcomes, measured the CL using TA and TV images and videos. Pearson's correlation test and receiver operating characteristic (ROC) curve analyses were performed. Results A total of 805 participants were recruited, including 780 (97%) where TA CL measurement was feasible. We observed a strong correlation of CL between TA and TV (correlation coefficient: 0.57; p Conclusion Universal short cervix screening in nulliparous women could be performed using TA ultrasound, which could allow the avoidance of TV ultrasound in more than three quarter of women. In low-risk population, TV ultrasound could be reserved to women with TA CL Key Points

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.

This study aimed to estimate the impact of third-trimester ultrasound with measurement of the lower uterine segment thickness (LUST) and estimation of fetal weight (EFW) on maternal and perinatal morbidity among women with a prior cesarean delivery.We performed a secondary analysis of the QUARISMA trial, including women who delivered at term after one prior cesarean delivery in tertiary care centres. Major and minor maternal and perinatal morbidities were compared between centres that had introduced LUST and EFW measurements into routine practice and those that had not, using generalised estimating equations and adjusted odds ratios (aOR). In a secondary analysis, we compared women who underwent a trial of labour with and without LUST and EFW measurements.We observed a significant reduction in major perinatal morbidity (aOR 0.52; 95% CI 0.28-0.96, P = 0.04), minor perinatal morbidity (aOR 0.49; 95% CI 0.25-0.96, P = 0.04), and minor maternal morbidity (aOR 0.56; 95% CI 0.34- 0.94, P = 0.03) but no significant difference in major maternal morbidity (aOR 0.40; 95% CI 0.04-3.69, P = 0.42) in the 2 centres that had introduced third-trimester ultrasound with EFW and LUST measurements (1458 women), compared with the 4 centres (1247 women) that had not. Among women who underwent a trial of labour, we observed a reduction in major perinatal morbidity (aOR 0.25; 95% CI 0.11-0.54, P0.001) and a lower rate of uterine rupture (0% vs. 0.3%, P = 0.045) with LUST and EFW measurements.Third-trimester ultrasound with EFW and LUST measurement is associated with a significant reduction in major perinatal morbidity in women with a prior cesarean delivery.

Objective: To evaluate women’s choice in the method of labour induction between oral misoprostol, PGE2 pessary and the Foley catheter. To compare women’s satisfaction according to their choice and to identify factors associated with patient satisfaction. Design: Prospective cohort study. Setting: Tertiary hospital in Toulouse, France, from July 2019 to October 2020. Population: All women admitted for labour induction at term, by either oral misoprostol, PGE2 pessary or Foley catheter. Methods: Women chose their preferred method. Before and after the delivery, they were asked to argument their choice and to evaluate their satisfaction through the use of questionnaires. Main outcome measures: Global level of satisfaction. Results: Of the 520 women included, 67,5% of women chose oral Misoprostol compared to 21% PGE2 pessary and 11.5% the Foley catheter. Regarding global satisfaction, we found no significant difference between the three groups: 78,4%, 68,8% and 71,2% (p=0,091) for respectively oral misoprostol, PGE2 pessary and Foley catheter. Factors that seem to improve women’s satisfaction were nulliparity (OR = 2.03, 95%CI [1.19 - 3.53]), delivery within 24 hours after the start of induction (OR = 3.46, 95%CI. [2.02 - 6.14]) and adequate information (OR = 4.21,95%CI [1.86 - 9.64]). Factors associated with lower satisfaction rates were postpartum hemorrhage (OR = 0.51, 95%CI [0.30 - 0.88]) and caesarean section (OR = 0.31, 95%CI [0.17 - 0.54]). Conclusion: Women satisfaction rates were not different between the three methods, when chosen by the patients themselves. These finding should encourage caregivers to promote shared decision making when possible.

Objective The study aimed to estimate the predictive value of midtrimester cervical length (CL) and the optimal cut-off of CL that should be applied with asymptomatic nulliparous women for the prediction of spontaneous preterm birth (sPTB). Study Design This is a prospective cohort study of asymptomatic nulliparous women with a singleton gestation. Participants underwent CL measurement by transvaginal ultrasound between 20 and 24 weeks of gestation. The participants and their health care providers remained blinded to the results of CL measurement. The primary outcomes were sPTB before 35 weeks and sPTB before 37 weeks. Receiver operating characteristics (ROC) curve analyses were performed. Analyses were repeated by using multiples of median (MoM) of CL adjusted for gestational age. Results Of 796 participants, the mean midtrimester CL was 40 ± 6 mm with a 1st, 5th, and 10th percentile of 25, 29, and 32 mm, respectively. ROC curve analyses suggest that a cut-off of 30 mm was the optimal CL to predict sPTB before 35 weeks (area under the ROC curve [AUC]: 0.70, 95% confidence interval [CI]: 0.56–0.85) and before 37 weeks (AUC: 0.70, 95% CI: 0.59–0.80). Midtrimester CL Conclusion A midtrimester CL cut-off of 30 mm (instead of 25 mm), or CL less than 0.75 MoM, should be used to identify nulliparous women at high risk of sPTB. Key Points

Objective Daily aspirin, started in the first trimester of pregnancy, is commonly used for the prevention of preeclampsia and fetal growth restriction in multiple gestation. However, the optimal dose remains controversial and the evidence for the use of aspirin in multiple pregnancies is scarce. We aimed to estimate the impact of 80 mg of aspirin in twin pregnancies. Study Design We performed a pilot double-blind randomized trial of women with twin pregnancies recruited between 8 and 14 weeks of gestation. Fifty participants (25 in each group) were randomized to 80 mg of aspirin daily at bedtime or a placebo from randomization until 36 weeks of gestation. Primary and secondary outcomes included the birth weight of live infants, preeclampsia, and aspirin responsiveness evaluated by a platelet aggregation test (platelet function assay [PFA]-100). Results All participants were followed until birth, including 48 and 47 live newborns in the aspirin and the placebo groups, respectively. The mean birth weight difference between the aspirin (2,385 ± 529 g) and placebo (2,224 ± 706 g) groups was of 179 g (95% confidence interval [CI]: −172–531 g, p = 0.32). We observed two (8%) cases of preeclampsia in the aspirin group and no case with placebo (p = 0.49). Most importantly,16 of 24 participants who received aspirin (67%; 95% CI: 45–84%) had a normal PFA-100 test at 22 to 23 weeks, including the two cases of preeclampsia, suggesting that the majority of the participants were nonresponsive to 80 mg of aspirin. Conclusion Our results suggest that the majority of women with twin pregnancies showed a lack of response to a daily dose of 80 mg of aspirin according to the PFA-100 test, compared with the expected 29% of nonresponsiveness in singleton pregnancies. A daily dose of 80 mg of aspirin is likely to be insufficient for the prevention of preeclampsia and other placenta-mediated complications in twin pregnancies. Key Points

To estimate the role of first-trimester uterine artery pulsatility index (UtA-PI) for the prediction of small-for-gestational age (SGA).We conducted a prospective cohort study of nulliparous women with singleton pregnancy (Great Obstetrical Syndromes study). UtA-PI was performed at 11 + 0 to 13 + 6 weeks and was reported in multiple of median (MoM). SGA was defined as birth weight below the 10th percentile and stratified as term or preterm SGA. Receiver operating characteristic curves analyses with their area under the curve (AUC) were used to estimate the predictive values of UtA-PI, alone and UtA-PI combined with maternal characteristics. We computed the detection rate and false-positive rate (FPR) of the SOGC SGA screening guidelines in our population.Of 4610 participants, SGA was identified in 486 pregnancies (10.3%), including 15 (0.3%) associated with preterm delivery. Compared with unaffected pregnancies, the mean log UtA-PI was significantly higher in term SGA and preterm SGA. The difference between preterm SGA and unaffected pregnancies remains significant after exclusion of SGA without preeclampsia. First-trimester UtA-PI was more predictive of preterm (AUC: 0.89) than term (AUC: 0.60) SGA (P 0.01). Combined with maternal characteristics, UtA-PI could have predicted 64% of preterm and 20% of term SGA (10% FPR). The SOGC guidelines criteria for early screening of SGA had a detection rate of 21% for a FPR of 21%.First-trimester UtA-PI can be used to predict SGA, but mainly preterm SGA. The current SOGC guidelines criteria for SGA screening are not efficient in nulliparous women.

Resume Objectif L’objectif de ce travail est de fournir des recommandations pour la pratique clinique concernant la contraception intra-uterine. Methodes Une revue exhaustive de la litterature a ete effectuee a l’aide des moteurs de recherche Pubmed et Cochrane database. Les recommandations recentes sur le sujet, en langue francaise et anglaise, ont egalement ete considerees. Resultats La contraception intra-uterine peut etre proposee dans de nombreuses situations, y compris chez les nullipares, les adolescentes, les patientes vivant avec le VIH avant le stade SIDA (Grade B) et les femmes presentant un antecedent de grossesse extra-uterine (GEU) (Grade C). Il est recommande de ne pas modifier le schema de depistage du cancer du col chez les utilisatrices de dispositif intra-uterin (DIU) (Grade B). Seuls le toucher vaginal avec examen bimanuel et l’inspection cervicale sont formellement recommandes avant la pose d’un DIU (Grade B). Un depistage systematique des infections sexuellement transmises n’est pas recommande (Grade B). Ce depistage est effectue idealement le jour de la prescription du DIU mais peut etre realise le jour de la pose si la patiente est asymptomatique (Grade B). Le DIU peut etre pose a n’importe quel moment du cycle (Grade B). Il n’est pas recommande de realiser une antibioprophylaxie ou une premedication systematique lors de l’insertion (Grade A). Une visite de suivi peut etre proposee dans les semaines suivant la pose (AP). Il n’est pas recommande de realiser une echographie de controle systematique si la patiente est asymptomatique, que l’insertion du dispositif s’est deroulee sans difficulte et qu’a l’examen les fils sont vus et de longueur attendue (Grade B). Quel que soit le type de DIU, les metrorragies persistantes ou associees a des douleurs pelviennes doivent motiver des explorations complementaires a la recherche d’une complication (AP). Devant une suspicion de perforation uterine, des examens complementaires doivent etre realises pour localiser le DIU (AP). L’abord laparoscopique est la voie a privilegier pour le retrait des DIU en situation abdominale (AP). En cas de grossesse sur DIU, il convient en premier lieu d’eliminer une GEU (Grade B). En presence d’une grossesse intra-uterine evolutive et desiree, il est recommande de retirer le DIU si les fils sont accessibles (Grade C). La presence d’organismes Actinomyces-like au frottis cervico-vaginal chez une patiente asymptomatique ne doit pas motiver d’exploration complementaire, de retrait anticipe ou de traitement anibiotique (Grade B). Il n’est pas recommande de retirer d’emblee le DIU en cas de survenue d’une infection sexuellement transmise ou d’une infection genitale haute (Grade B). En l’absence d’evolution favorable a 48–72 h de l’institution du traitement, le retrait du dispositif doit etre discute (Grade B). Conclusion La contraception intra-uterine constitue un moyen contraceptif de longue duree d’action efficace avec un taux de continuation elevee qui s’accompagne d’un risque faible de complications. Elle peut donc etre proposee a un tres grand nombre de patientes, independamment de la parite.

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.

INTRODUCTION: Preeclampsia (PE), but mainly preterm PE, is associated with deep placentation disorders. We aimed to compare placental pathologies in pregnancies affected by term and preterm PE comp...