Allogenic umbilical cord-derived mesenchymal stromal cells improve motor function in prenatal surgical repair of myelomeningocele: An ovine model study.

OBJECTIVE: To investigate the effects of an adjuvant allogenic umbilical cord mesenchymal stromal cell (UC-MSC) patch applied during fetal surgery on motor and sphincter function in the ovine MMC model. DESIGN: MMC defects were surgically created at 75 days of gestation and repaired 14 days later. POPULATION: Ovine MMC model: fetal lambs. METHODS: We compared lambs that received a UC-MSC patch with a control group of lambs that received an acellular patch. MAIN OUTCOME MEASURES: Clinical neurological assessment was performed at 2 and 24 hours of life and included determination of the Sheep Locomotor Rating scale (SLR), which has been validated in the ovine MMC model. Electrophysical examinations, spine scans and histological analyses were also performed. RESULTS: Of the 13 operated lambs, nine were born alive: five had of these had received a UC-MSC patch and four an acellular patch. At 24 hours of life, lambs in the UC-MSC group had a significantly higher score (14 versus 5, P = 0.04). Amyotrophy was significantly more common in the control group (75% versus 0%, P = 0.02). All the lambs in the control group and none of those in the UC-MSC group were incontinent. No significant differences were observed between the UC-MSC and control groups in terms of the presence of spontaneous EMG activity, nerve conduction or spinal evoked potentials. In the microscopic examination, lambs in the UC-MSC group had less fibrosis between the spinal cord and the dermis (mean thickness, 453 versus 3921 µm, P = 0.03) and around the spinal cord (mean thickness, 47 versus 158 µm, P < 0.001). Examination of the spinal cord in the area of the MMC defect showed a higher large neuron density in the UC-MSC group (14.5 versus 5.6 neurons/mm2, P < 0.001). No tumours were observed. CONCLUSIONS: Fetal repair of MMC using UC-MSC patches improves motor and sphincter function as well as spinal preservation and reduction of fibrosis.

Prenatal diagnosis of isolated bilateral clubfoot: Is amniocentesis indicated?

INTRODUCTION: The aim of this study is to evaluate the benefit of cytogenetic testing by amniocentesis after an ultrasound diagnosis of isolated bilateral talipes equinovarus. MATERIAL AND METHODS: This multicenter observational retrospective study includes all prenatally diagnosed cases of isolated bilateral talipes equinovarus in five fetal medicine centers from 2012 through 2021. Ultrasound data, amniocentesis results, biochemical analyses of amniotic fluid and parental blood samples to test neuromuscular diseases, pregnancy outcomes, and postnatal outcomes were collected for each patient. RESULTS: In all, 214 fetuses with isolated bilateral talipes equinovarus were analyzed. A first-degree family history of talipes equinovarus existed in 9.8% (21/214) of our cohort. Amniocentesis was proposed to 86.0% (184/214) and performed in 70.1% (129/184) of cases. Of the 184 karyotypes performed, two (1.6%) were abnormal (one trisomy 21 and one triple X syndrome). Of the 103 microarrays performed, two (1.9%) revealed a pathogenic copy number variation (one with a de novo 18p deletion and one with a de novo 22q11.2 deletion) (DiGeorge syndrome). Neuromuscular diseases (spinal muscular amyotrophy, myasthenia gravis, and Steinert disease) were tested for in 56 fetuses (27.6%); all were negative. Overall, 97.6% (165/169) of fetuses were live-born, and the diagnosis of isolated bilateral talipes equinovarus was confirmed for 98.6% (139/141). Three medical terminations of pregnancy were performed (for the fetuses diagnosed with Down syndrome, DiGeorge syndrome, and the 18p deletion). Telephone calls (at a mean follow-up age of 4.5 years) were made to all parents to collect medium-term and long-term follow-up information, and 70 (33.0%) families were successfully contacted. Two reported a rare genetic disease diagnosed postnatally (one primary microcephaly and one infantile glycine encephalopathy). Parents did not report any noticeably abnormal psychomotor development among the other children during this data collection. CONCLUSIONS: Despite the low rate of pathogenic chromosomal abnormalities diagnosed prenatally after this ultrasound diagnosis, the risk of chromosomal aberration exceeds the risks of amniocentesis. These data may be helpful in prenatal counseling situations.

Asymptomatic short cervix and threatened preterm labor: A comparative study on perinatal outcomes.

OBJECTIVE: To determine the rate of delivery within 15 days of admission among patients with an asymptomatic short cervix (ASC) compared to those admitted for threatened preterm labor (TPL). MATERIAL AND METHODS: This retrospective study conducted in a tertiary maternity hospital, included patients with a singleton pregnancy admitted with a cervical length of less than 25 mm between 24 and 34 weeks. The population was divided into two groups, patients with ASC (i.e., with no contractions at admission) and patients with TPL. The primary outcome was the delivery rate within 15 days of admission. Secondary outcomes included gestational age at delivery, preterm delivery rate before 37°/7 weeks and before 34°/7 weeks, admission to delivery interval, 5 min Apgar score and transfer to neonatal intensive care unit rate. The characteristics of the two groups and the primary and secondary outcomes were compared between the two groups using univariate analysis. Two subgroup analysis were performed, one restricted to patients with a mildly modified CL (15 ≤ CL < 25 mm), and one excluding patients at high risk of preterm birth. RESULTS: Among the 247 included patients, 136 (55.1 %) had TPL, and 111 (44.9 %) ASC. There were no significant differences in the rate of patient who delivered within 15 days of admission between the groups, 13.2 % in the TPL group vs 8.0 % in the ASC group (p = 0.22). Patients in the TPL group had a significantly higher frequency of delivery before 34 weeks compared to those in the ASC group (19.9 % versus 9.0 %, p = 0.02 This finding persisted in the subgroup analysis excluding patients at high risk of preterm birth (16.5 % in the TPL subgroup vs. 6.9 % in the ASC subgroup, p = 0.04). There were no significant differences in the rates of preterm delivery before 37 weeks, the admission-to-delivery interval, or neonatal outcomes between the two groups or within the subgroup analyses. CONCLUSION: The frequency of delivery within 15 days of admission was not statistically different between patients with an asymptomatic short cervix and those with TPL. Nevertheless, these asymptomatic patients delivered significantly later and less frequently before 34 weeks, with only one in ten requiring corticosteroids.

Maintenance oxytocin in the immediate postpartum period: Frequency, determinants and practices in a tertiary maternity unit.

OBJECTIVE: To prevent post-partum haemorrhage (PPH), national and international guidelines recommend the administration of a prophylactic injection of oxytocin after all vaginal births. Although additional maintenance oxytocin is not recommended in the immediate postpartum, its administration is quite common (30 % of French births in 2021). To assess in a single center, the frequency and determinants associated with the administration of maintenance oxytocin in immediate postpartum. STUDY DESIGN: A retrospective observational single-centre study was conducted in a tertiary-care university centre in Paris (France), with data from April-May 2022. All women who gave birth vaginally at or after 37 weeks, except for those with immediate PPH. Univariate and multivariate analysis were performed to compare determinants between the group receiving maintenance oxytocin and the control group without this intervention. A sensitivity analysis in a population of women at low risk of PPH was performed. Maternal, obstetrical, perinatal and organisational determinants were collected. RESULTS: This study included 584 patients, 278 (47.6 %) of whom received maintenance oxytocin. We observed a significantly higher rate of maintenance oxytocin administration to parous women (OR 1.57, 90 %CI 1.09-2.27) and women with a history of PPH (OR 2.88, 90 %CI 1.08-9.08). Additional maintenance oxytocin was also administered more often when the midwife handling the birth had more than 5 years of practice since completion of training (OR 1.77, 1.24-2.53) or during night-time births (OR 1.47, 90 %CI 1.03-2.10). CONCLUSION: Maintenance oxytocin administration is a frequent practice, performed for almost half the patients in our center. This practice is associated with maternal and obstetric factors, but also with health professionals' individual decisions and practices.

Usefulness of early morphological ultrasound in association with cell-free DNA testing in case of atypical serum markers in first trimester of pregnancy: A retrospective study over 5 years.

BACKGROUND: Early morphologic ultrasound, generally carried out in case of atypical first trimester serum markers (PAPP-A and/or free hCGß <0.30 MoM), has not been re-evaluated since the possibility of performing a cell-free fetal DNA analysis in this indication. Our objective was to evaluate the usefulness of early morphological ultrasound in case of atypical profile of serum markers performed in association with Non-Invasive Prenatal Testing (NIPT). METHODS: This was a single-center retrospective study in a tertiary maternity. Between January 2017 and December 2021, women with an atypical first trimester serum markers and low/intermediate risk for trisomy 21 (<1/50) were included. The clinical data, results of first trimester serum markers, NIPT, early morphological ultrasound and subsequent ultrasounds and other investigations (amniocentesis, pregnancy outcomes) were analyzed. RESULTS: After exclusion of women with high-risk of trisomy 21 and lost to follow-up, 163 women were included. In 72 % of cases (117/163), women had a low risk of trisomy 21, and 39 % (59/163) had an early morphological ultrasound. Early morphological ultrasound was useful to detect severe IUGR leading to the suspicion of triploidy (3/163, 1.8 %). In all other situations, it did not allow earlier management. After analysis of the 3 triploidy cases, a collapsed profile for both serum markers was demonstrated (<0.25 MoM). CONCLUSIONS: Systematic early morphological ultrasound in case of an atypical serum marker profile seems useless considering the performance of NIPT. An ultrasound restricted to women with both markers below 0.25 MoM would allow the early detection of triploidy.

Publication rate and factors associated with publication of research projects by obstetrics residents in an academic department over 10 years.

OBJECTIVES: To determine the publication rate of mandatory research projects conducted by obstetrics residents and to evaluate the publication-associated factors and reported obstacles. STUDY DESIGN: This retrospective cohort study included all consecutive residents in an academic obstetrics-gynecology department in Paris, France, between 2010 and 2020. All residents were required to conduct a research project. Information about publication was collected by searching PubMed. A closed-ended questions questionnaire was sent to former residents about their characteristics, subsequent professional development, and research project characteristics. Factors associated with publication were identified by univariable and multivariable analysis with logistic regression. RESULTS: During the study period, 156 residents trained in our obstetrics-gynecology department. The overall publication rate was 30.8% (48/156) and the median time to publication 27 months (IQR, 18-37). The resident was first author in 36 (75.0%) publications. Among the 130 (83.3%) residents who completed the questionnaire, 43 (33%) had published their research project. Overall, 74/130 (60.8%) residents used their project for their mandatory medical thesis. Factors associated with publication in univariable analysis were younger age (median), completion of a PhD, planned career in academic medicine, prospective study design, presentation at a conference or congress and use their project for their medical thesis. The only factors associated with publication in the multivariable analysis were planned career in academic medicine (aOR 5.62 95 %CI[1.84-17.19]) and the prospective study design of the research project (aOR 6.1 95 %CI[1.24-29.56]). The main reasons for nonpublication reported by resident were lack of time and failure to complete the project. CONCLUSION: Among the mandatory clinical research projects conducted by obstetrics residents over a decade in our department, 30.8% were published. The main factors associated with publication were planned career in academic medicine and a prospective design of the research project.

[Pelvic exam in gynecology and obstetrics: Guidelines for clinical practice]. / Examen pelvien en gynécologie et obstétrique : recommandations pour la pratique clinique.

OBJECTIVE: To provide guidelines for the pelvic clinical exam in gynecology and obstetrics. MATERIAL AND METHODS: A multidisciplinary experts consensus committee of 45 experts was formed, including representatives of patients' associations and users of the health system. The entire guidelines process was conducted independently of any funding. The authors were advised to follow the rules of the Grading of Recommendations Assessment, Development and Evaluation (GRADE®) system to guide assessment of quality of evidence. The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasized. METHODS: The committee studied 40 questions within 4 fields for symptomatic or asymptomatic women (emergency conditions, gynecological consultation, gynecological diseases, obstetrics, and pregnancy). Each question was formulated in a PICO (Patients, Intervention, Comparison, Outcome) format and the evidence profiles were produced. The literature review and recommendations were made according to the GRADE® methodology. RESULTS: The experts' synthesis work and the application of the GRADE method resulted in 27 recommendations. Among the formalized recommendations, 17 present a strong agreement, 7 a weak agreement and 3 an expert consensus agreement. Thirteen questions resulted in an absence of recommendation due to lack of evidence in the literature. CONCLUSIONS: The need to perform clinical examination in gynecological and obstetrics patients was specified in 27 pre-defined situations based on scientific evidence. More research is required to investigate the benefit in other cases.

Association between hospitals' cesarean delivery rates for breech presentation and their success rates for external cephalic version.

INTRODUCTION: Success rates of external cephalic version (ECV) are heterogenous in the published literature. Some individual factors are already known to be associated with ECV success but probably do not fully explain the differences. The objective of this review is to assess the association between hospitals' cesarean delivery rates for breech presentations after ECV failure and their ECV success rates. MATERIAL AND METHODS: We performed a review of the literature using the Medline and Cochrane Library computer databases and by searching on clinicaltrials.gov, from 1985 through 2020. This analysis included all studies reporting ECV success rates and cesarean delivery rates for breech presentations. The prognostic factors for successful ECV, such as rates of nulliparity, gestational age at ECV, BMI, and tocolysis use, were also collected and analyzed. Median ECV success rates from the included studies were compared according to these factors. The cesarean rate for persistent breech presentation after ECV failure reported in these studies was considered a proxy indicator of the unit's policy for breech presentations. The correlation between ECV success rates and cesarean delivery rates was analyzed and is presented as a scatter plot. RESULTS: This analysis included 22 studies reporting rates of both successful ECV and cesarean deliveries for persistent breech presentation after ECV failure. The ECV success rates ranged from 16.3% to 82.5% with a median of 48.8% (interquartile range: 36.9-62.9). The median ECV success rate was higher in the studies that used tocolysis than in those that did not (51.3% versus 22.0%, P = .001) and in the studies with the highest cesarean rates for breech presentations than in those with the lowest cesarean rates (57.9% versus 36.2%, P = .006). The ECV success rates were significantly correlated with cesarean delivery rates for persistent breech presentations (R = 0.67; P = .001). CONCLUSION: The likelihood of successful ECV appears higher in hospitals with policies that generally result in cesarean delivery for persistent breech presentation.

Biodistribution of allogenic umbilical cord-derived mesenchymal stromal cells after fetal repair of myelomeningocele in an ovine model.

BACKGROUND: Myelomeningocele (MMC) is a spinal cord congenital defect that leads to paraplegia, sphincter disorders and potential neurocognitive disabilities. Prenatal surgery of MMC provides a significant benefit compared to surgery at birth. Mesenchymal stromal cell (MSC) therapy as an adjuvant treatment for prenatal surgery showed promising results in animal experiments which could be considered for clinical use in human fetuses. Despite numerous reassuring studies on the safety of MSCs administration in humans, no study focused on MSCs biodistribution after a local MSCs graft on the fetal spinal cord. AIM: The purpose of our study was to assess the biodistribution of umbilical cord-derived mesenchymal stromal cells (UC-MSCs) at birth in lambs who had a prenatal myelomeningocele repair using a fibrin patch seeded with allogenic UC-MSCs. METHODS: After isolation, UC-MSCs were tagged using a green fluorescent protein (GFP)-containing lentiviral vector. MMC defects were surgically created at 75 days of gestation and repaired 15 days later using UC-MSCs patch. Lambs were delivered at 142 days and sacrificed. DNA extraction was performed among biopsies of the different organs and q-PCR analysis was used to detect the expression of GFP (GFP DNA coding sequence). RESULTS: In our 6 surviving lambs grafted with UC-MSCs, GFP lentivirus genomic DNA was not detected in the organs. CONCLUSION: These reassuring data will support translational application in humans, especially since the first human clinical trial using mesenchymal stromal cells for in-utero treatment of MMC started recently in U.S.A.

Ultrasound findings in Pseudoamniotic band syndrome after fetoscopic surgery: Antenatal description of three cases and review of literature.

INTRODUCTION: Pseudoamniotic Bands Syndrome (PABS) was described as iatrogenic complication from in utero procedure as fetoscopy. OBJECTIVE: The aim of our study was to identify the ultrasound findings in PABS diagnosed prenatally METHODS: First, we reported cases of PABS following fetoscopic surgery that were diagnosed prenatally in our institution. We collected all ultrasound data with fetal and neonatal issues. Then, a literature review was conducted by searching the Medline and Cochrane Library computer databases until 2020 to find publications that involve PABS diagnosed prenatally or postnatally. The following keywords were selected and combined: "pseudoamniotic bands syndrome", "fetoscopy", "fetal surgery". RESULTS: We collected three cases of PABS diagnosed prenatally in our center following fetoscopic procedures for complicated monochorionic pregnancies. Among these cases, we reported the following ultrasound findings: floating membrane, amniotic bands, striction of limbs, perilesional edema, reduced member size and anomalies of Doppler flow. Including our cases, we reported 23 published PABS of which eight (35%) were prenatally diagnosed. When it was diagnosed, mean GA at PABS diagnosis was 23 weeks (mean interval from fetoscopic to diagnosis was 4 weeks). Three fetoscopic release of amniotic bands were described. The principal parts affected were the limbs, more particularly the extremities. CONCLUSION: PABS was accessible to an antenatal diagnosis, as well as ABS. Although it is a rare complication of fetoscopic surgery, ultrasound examinations after procedure should focus on PABS signs to improve prognosis of the neonates.

Renal colic with ureterohydronephrosis due to menstrual cup.

We report a rare case of ureterohydronephrosis due to an improperly positioned menstrual cup.

Term prelabor rupture of membranes: Foley catheter versus dinoprostone as ripening agent.

INTRODUCTION: Term prelabor rupture of membranes (TPROM) occurs in approximately 8 % of pregnancies. This condition regularly requires medical intervention such as induction of labor. The actual data concerning cervical ripening in case of TPROM does not favor any of the available techniques. This is the first study comparing dinoprostone versus Foley catheter for cervical ripening in TPROM. MATERIALS AND METHODS: We conducted a retrospective before-after study. We enrolled all the patients with confirmed TPROM after 37 weeks of gestation (WG) who required cervical ripening. Women were included if they had a singleton fetus in cephalic presentation, with unfavorable cervix (Bishop ≤ 6). Patients were excluded if they had a previous uterine surgery, a multiple pregnancy, contraindication to vaginal delivery, spontaneous labor or favorable cervix (Bishop > 6). During the first period (2015), the protocol of cervical ripening involved dinoprostone (prostaglandins E2) by vaginal administration (vaginal gel or pessary). During the second period (2016-2017), the protocol of cervical ripening involved Foley catheter (FC). The primary outcome was the rate of cesarean section. RESULTS: Two hundred and thirty-eight patients were included for the analysis: 131 in the first period (dinoprostone group) and 107 in the second period (foley catheter group). There was no significant difference between the two groups regarding the mode of delivery (cesarean section: 206 % vs 13 %, p = 016). Concerning tolerance, the were no difference in the rates of postpartum hemorrhage, maternal per-partum fever and endometrisis. Neonatal outcomes were similar between the two groups. The induction to delivery interval was lower with dinoprostone (20,3 h versus 26,0 h, p = 0001). The mean duration of labor was also significantly different (6,9 h for dinoprostone group versus 8,7 h for FC group, p = 001). CONCLUSION: Cervical ripening in case of TPROM after 37 W G with Foley catheter seems to be a safe technique with similar outcomes to prostaglandins regarding the mode of delivery.

Reduced fetal movement during pregnancy: Is the Kleihauer-Betke test really useful?

INTRODUCTION: Reduced fetal movement (rFM) is a frequent cause of consultation during the pregnancy and can reveal feto-maternal hemorrhage (FMH) that is sometimes responsible of severe fetal anemia. Our primary objective was to evaluate the contribution of the KBT in case of rFM. Our secondary objective was to compare it with ultrasound examination including peak systolic velocity of the middle cerebral artery (MCA-PSV) to predict neonatal anemia. MATERIALS AND METHODS: We conducted a retrospective study from January 2016 to December 2017 at Armand-Trousseau Hospital in Paris. We analyzed all patients consulting for rFM from 18 to 41 weeks of gestation. We compared the performance of KBT and MCA-PSV to predict neonatal anemia (Hemoglobin at birth under 13.5 g/dL) and severe neonatal anemia (Hb < 10 g/dL). RESULTS: Among the 338 patients, 327 KBT (96.7%) were performed. KBT was found positive in three cases (0.9%). Only one neonate (0.3%) presented with severe anemia requiring a postnatal transfusion. MCA-PSV was performed in 166 cases (49.1%). KBT and MCA-PSV were significantly correlated with neonatal hemoglobin at birth. KBT was better than MCA-PSV to predict neonatal anemia, while MCA-PSV was better than KBT to predict moderate to severe anemia. The KBT and MCA-PSV Doppler had excellent sensitivity and predictive negative values (100%), but they had poor predictive positive values for severe neonatal anemia. CONCLUSION: In case of decreased fetal movement, we suggest performing fetal cerebral Doppler. MCA-PSV could suffice in first approach. KBT may be performed if there is suspicion of fetal anemia in order to confirm FMH.

Fetal diagnosis of right cardiac ventricular aneurysms: A report of three cases.

Congenital ventricular aneurysms and diverticula are rare congenital heart diseases, currently accessible to prenatal diagnosis. Information on the natural course of ventricular aneurysm or diverticulum detected during fetal life is limited as there are only few case reports and case series enumerating the defect. We aimed to describe through three cases, the prenatal features and clinical outcomes of fetal cardiac aneurysms. The first one was diagnosed during the second trimester and spontaneous evolution was favorable. The two others were diagnosed in the first trimester with a large and early pericardial effusion. For one, the parents opted for termination of pregnancy at 15 weeks of gestation and the other showed a spontaneous regression of the effusion and no hemodynamic compromise.