Publications

Abstract

Objective: To compare different antibiotic prophylaxis administered after preterm premature rupture of membranes to determine whether any were associated with differences in obstetric and/or neonatal outcomes and/or neurodevelopmental outcomes at 2 years of corrected age.

Design: Prospective, nationwide, population-based EPIPAGE-2 cohort study of preterm infants.

Setting: France, 2011.

Sample: We included 492 women with a singleton pregnancy and a diagnosis of preterm premature rupture of membranes at 24-31 weeks. Exclusion criteria were contraindication to expectant management or indication for antibiotic therapy other than preterm premature rupture of membranes. Antibiotic prophylaxis was categorised as amoxicillin (n = 345), macrolide (n = 30), third-generation cephalosporin (n = 45) or any combinations covering Streptococcus agalactiae and >90% of Escherichia coli (n = 72), initiated within 24 hours after preterm premature rupture of membranes.

Methods: Population-averaged robust Poisson models.

Main outcome measures: Survival at discharge without severe neonatal morbidity, 2-year neurodevelopment.

Results: With amoxicillin, macrolide, third-generation cephalosporin and combinations, 78.5%, 83.9%, 93.6% and 86.0% of neonates were discharged alive without severe morbidity. The administration of third-generation cephalosporin or any E. coli-targeting combinations was associated with improved survival without severe morbidity (adjusted risk ratio 1.25 [95% confidence interval 1.08-1.45] and 1.10 [95 % confidence interval 1.01-1.20], respectively) compared with amoxicillin. We evidenced no increase in neonatal sepsis related to third-generation cephalosporin-resistant pathogen.

Conclusion: In preterm premature rupture of membranes at 24-31 weeks, antibiotic prophylaxis based on third-generation cephalosporin may be associated with improved survival without severe neonatal morbidity when compared with amoxicillin, with no evidence of increase in neonatal sepsis related to third-generation cephalosporin-resistant pathogen.

Abstract

The clinical benefits to be expected from intraoperative nociception monitors are currently under investigation. Among these devices, the Analgesia Nociception-Index (ANI) has shown promising results under sevoflurane anesthesia. Our study investigated ANI-guided remifentanil administration under propofol anesthesia. We hypothesized that ANI guidance would result in reduced remifentanil consumption compared with standard management. This prospective, randomized, controlled, single-blinded, bi-centric study included women undergoing elective gynecologic surgery under target-controlled infusion of propofol and remifentanil. Patients were randomly assigned to an ANI or Standard group. In the ANI group, remifentanil target concentration was adjusted by 0.5 ng mL^-1 steps every 5 min according to the ANI value. In the Standard group, remifentanil was managed according to standard practice. Our primary objective was to compare remifentanil consumption between the groups. Our secondary objectives were to compare the quality of anesthesia, postoperative analgesia and the incidence of chronic pain. Eighty patients were included. Remifentanil consumption was lower in the ANI group: 4.4 (3.3; 5.7) vs. 5.8 (4.9; 7.1) µg kg^-1 h^-1 (difference = -1.4 (95% CI, -2.6 to -0.2), p = 0.0026). Propofol consumption was not different between the groups. Postoperative pain scores were low in both groups. There was no difference in morphine consumption 24 h after surgery. The proportion of patients reporting pain 3 months after surgery was 18.8% in the ANI group and 30.8% in the Standard group (difference = -12.0 (95% CI, -32.2 to 9.2)). ANI guidance resulted in lower remifentanil consumption compared with standard practice under propofol anesthesia. There was no difference in short- or long-term postoperative analgesia.

Abstract

Background: The time between symptoms onset and endometriosis diagnosis is usually long. The negative impacts of delayed endometriosis diagnosis can affect patients and health outcomes.

Methods: We conducted a case-control study using clinical symptoms and epidemiological data extracted from a prospective pre-operative patient questionnaire compared between patients with histologically proven endometriosis and patients with no endometriosis at surgical exploration from 2005 to 2018, in a French referral center. We used the beta coefficients of the significant variables introduced in a multiple regression model to devise a score (score 1), evaluated by the area under the curve (or C-index), with three levels, defined by a score between 1 and ≥ 25: (i) highly specific, identifying correctly the patients without the disease; (ii) highly sensitive, identifying the patients with the disease; and (iii) a level maximizing sensitivity and specificity for the best classification of the whole population. To minimize patient self-evaluation of pain, we devised a second score (score 2) with the same method and levels and scores definition, excluding visual analog scale pain scores, except for dysmenorrhea. These scores were validated on an internal and external population.

Findings: Score 1 had a C-index of 0.81 (95% CI [0.79-0.83]). Results for the three score 1 levels were: ≥ 25: specificity of 91% (95% CI [89-93]); < 11: sensitivity of 91% (95% CI [89-93]); ≥ 18: specificity of 75% (95% CI [72-78]) and sensitivity of 73% (95% CI [70-76]). Score 2 had a C-index of 0.75 (95% CI [73-77]). The three levels of score 2 were: ≥ 24: specificity of 82% (95% CI [80-85]); < 7: sensitivity of 92% (95% CI [90-94]); ≥ 17: specificity of 62% (95% CI [58-65]) and sensitivity of 78% (95% CI [75-81]). The two scores were internally and externally validated.

Interpretation: A score based only on a patient questionnaire could allow identification of a population at high risk of endometriosis. This strategy might help referral to specialized radiologists for a non-surgical endometriosis scan.

Abstract

ackground Hygiene measures are recommended to prevent toxoplasmosis during pregnancy, although screening for seroconversion in pregnant women currently are debated and practices vary among countries. Objectives The purpose of this systematic literature review was to assess the effectiveness of hygiene measures during pregnancy to prevent toxoplasmosis infection. Search Strategy We followed the standard MOOSE and PRISMA criteria when conducting this systematic review and reporting the results. Selection criteria A systematic literature search was conducted for studies focused on congenital toxoplasmosis prevention, toxoplasmosis prevention during pregnancy, toxoplasmosis prevention and hygiene measures, which were published between 1970 and August 2020, using the databases of PubMed, Scope Med, EMBASE, and the Cochrane library. Data collection and analysis Our literature search identified 3964 articles, 3757 were excluded after review of title or abstract and 67 studies were considered relevant to the subject. We reviewed risk factors for toxoplasmosis infection during pregnancy and for congenital toxoplasmosis, preventive measures for toxoplasmosis during pregnancy, including: dietary recommendations, pet care measures, environmental measures, knowledge of risk factors and ways to control toxoplasmosis infection, knowledge of risk factors for infection by health professionals, knowledge of primary prevention measures by pregnant women. Conclusion: Hygiene measures are effective and applicable primary prevention to reduce toxoplasmosis and avoid congenital toxoplasmosis and its consequences. Funding No.

Abstract

Context: After 41 weeks, the labor induction term varies according to countries and obstetrical teams. The French recommendations are not to exceed 41 weeks 6 days. However, there are no data on the percentage of nulliparous women with an unfavorable cervix at 41 weeks going into spontaneous labor within five or six days.

Objective: The objective was to establish the rate of spontaneous labor within five days amongst nulliparous women with an unfavorable cervix at 41 weeks, and to identify the maternal and obstetrical factors associated with this spontaneous labor.

Materials and methods: Retrospective study in a University Hospital Maternity between January 1st and December 31st 2017. All nulliparous women with a cephalic fetal presentation and unfavorable cervix at 41 weeks (Bishop ≤ 3) were included. The maximum term for induced labor was set at 41 weeks 5 days. The population was divided into two groups: spontaneous labor and induced labor (induction between 41 weeks and 41 weeks 4 days for medical indications or maternal wish and induction at 41 weeks 5 days for full term). The maternal and obstetrical characteristics of the two groups at 41 weeks were compared as well as the maternal and neonatal outcomes.

Results: The rate of spontaneous labor among the 269 women included was 38.3% (n = 103/269). At 41 weeks, the presence of painful uterine contractions and a Bishop score of 3 were associated with spontaneous labor within five days (p < 0.01). The Bishop score criteria most associated with spontaneous labor were cervical dilation and fetal station. The cesarean delivery rate was 20.4% in the group of women with spontaneous labor versus 41.0% in the group of induced labor (p < 0.01). There were no differences between the two groups in terms of neonatal outcome.

Conclusion: Among nulliparous women with an unfavorable cervix at 41 weeks, almost 40 % will have a spontaneous onset of labor within five days. The only factors found to be associated with this onset of labor are the presence of painful uterine contractions and a higher Bishop score at 41 weeks.

Abstract

Objective: To assess the association between early empirical antibiotics and neonatal adverse outcomes in very preterm infants without risk factors for early-onset sepsis (EOS).

Study design: This is a secondary analysis of the EPIPAGE-2 study, a prospective national population-based cohort that included all liveborn infants at 22-31 completed weeks of gestation in France in 2011. Infants at high risk of EOS (ie, born after preterm labor or preterm premature rupture of membranes or from a mother who had clinical chorioamnionitis or had received antibiotics during the last 72 hours) were excluded. Early antibiotic exposure was defined as antibiotic therapy started at day 0 or day 1 of life, irrespective of the duration and type of antibiotics. We compared treated and untreated patients using inverse probability of treatment weighting based on estimated propensity scores.

Results: Among 648 very preterm infants at low risk of EOS, 173 (26.2%) had received early antibiotic treatment. Early antibiotic exposure was not associated with death or late-onset sepsis or necrotizing enterocolitis (OR, 1.04; 95% CI, 0.72-1.50); however, it was associated with higher odds of severe cerebral lesions (OR, 2.71; 95% CI, 1.25-5.86) and moderate-severe bronchopulmonary dysplasia (BPD) (OR, 2.30; 95% CI, 1.21-4.38).

Conclusions: Early empirical antibiotic therapy administrated in very preterm infants at low risk of EOS was associated with a higher risk of severe cerebral lesions and moderate-severe BPD.

Abstract

Objective: To study the cyclic fertilin peptide effects on preimplantation human embryogenesis. Cyclic fertilin peptide reproduces the structure of the binding site of the sperm Fertilin β (also named A Disintegrin and Metalloprotease 2: ADAM2) disintegrin domain. It binds to the oocyte membrane and increases sperm-oocyte fusion index in human and fertilization rate in mouse, providing healthy pups. It also improves human oocyte maturation and chromosome segregation in meiosis I and binds to human embryo blastomeres, suggesting that it has a membrane receptor.

Design: Thawed human embryos at the 3 to 4 cells stage were randomly included in a dose-response study with cyclic fertilin peptide. Inner cell mass (ICM), trophectoderm (TE), and total cell numbers were evaluated in top- and good-quality blastocysts.

Setting: The study was performed in an academic hospital and research laboratory.

Patient(s): Human embryos donated for research. This project was approved by the French « Agence de la Biomédecine. »

Intervention(s): Immunofluorescence and tissue-specific gene expression analysis, using Clariom D microarrays, were performed to study its mechanism of action.

Main outcome measure(s): Cyclic fertilin peptide improves blastocyst formation by almost 20%, the concentration of 1 μM being the lowest most efficient concentration. It significantly increases twice the TE cell number, without modifying the ICM. It increases the in vitro hatching rate from 14% to 45%.

Result(s): Cyclic fertilin peptide stimulates TE growth. In the ICM, it induces transcriptional activation of intracellular protein and vesicle-mediated transport.

Conclusion(s): Cyclic fertilin peptide dramatically improves human embryo development potential. It could be used to supplement culture medium and improve the in vitro human embryo development. Starting supplementation immediately after fertilization, instead of day 2, could significantly upgrade assisted reproductive technology outcome.

Abstract

Background: Placenta accreta spectrum is a life-threatening condition that has increased dramatically in recent decades along with cesarean rates worldwide. Cesarean hysterectomy is widely practiced in women with placenta accreta spectrum; however, the maternal outcomes after cesarean hysterectomy have not been thoroughly compared with the maternal outcomes after alternative approaches, such as conservative management.

Objective: This study aimed to compare the severe maternal outcomes between women with placenta accreta spectrum treated with cesarean hysterectomy and those treated with conservative management (leaving the placenta in situ).

Study design: From a source population of 520,114 deliveries in 176 hospitals (PACCRETA study), we designed an observational cohort of women with placenta accreta spectrum who had either a cesarean hysterectomy or a conservative management (the placenta left in situ) during cesarean delivery. Clinicians prospectively identified women meeting the inclusion criteria and included them at delivery. Data collection started only after the women had received information and agreed to participate in the study in the immediate postpartum period. The primary outcome was the transfusion of >4 units of packed red blood cells within 6 months after delivery. Secondary outcomes were other maternal complications within 6 months. We used propensity score weighting to account for potential indication bias.

Results: Here, 86 women had conservative management and 62 women had cesarean hysterectomy for placenta accreta spectrum during cesarean delivery. The primary outcome occurred in 14 of 86 women in the conservative management group (16.3%) and 36 of 61 (59.0%) in the cesarean hysterectomy group (risk ratio in propensity score weighted model, 0.29; 95% confidence interval, 0.19-0.45). The rates of hysterectomy, total estimated blood loss exceeding 3000 mL, any blood product transfusion, adjacent organ injury, and nonpostpartum hemorrhage-related severe maternal morbidity were lower with conservative management than with cesarean hysterectomy (all adjusted, P≤.02); but, the rates of arterial embolization, endometritis, and readmission within 6 months of discharge were higher with conservative management than with cesarean hysterectomy.

Conclusion: Among women with placenta accreta spectrum who underwent cesarean delivery, conservative management was associated with a lower risk of transfusion of >4 units of packed red blood cells within 6 months than cesarean hysterectomy.

Abstract

Context: Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disease caused by mutations in the tumor suppressor gene MEN1. The uncertainty of pathogenicity of MEN1 variants complexifies the selection of the patients likely to benefit from specific care.

Objective: MEN1-mutated patients should be offered tailored tumor screening and genetic counselling. We present a patient with hyperparathyroidism for whom genetic analysis identified a variant of uncertain significance in the MEN1 gene (NM_130799.2): c.654G>T p.(Arg218=). Additional functional genetic tests were performed to classify the variant as pathogenic and allowed prenatal testing.

Design: Targeted next generation sequencing identified a synonymous variant in the MEN1 gene in a 26-year-old male with symptomatic primary hyperparathyroidism. In silico and in vitro genetic tests were performed to assess variant pathogenicity.

Results: Genetic testing of the proband’s unaffected parents showed the variant occurred de novo. Transcript study showed a splicing defect leading to an in-frame deletion. The classification of the MEN1 variant as pathogenic confirmed the diagnosis of MEN1 and recommended an adapted medical care and follow-up. Pathogenic classification also allowed to propose a genetic counselling to the proband and his wife. Non-invasive prenatal diagnosis was performed with a personalized medicine-based protocol by detection of the paternally inherited variant in maternal plasmatic cell free DNA, using digital PCR.

Conclusion: We showed that functional genetic analysis can help to assess the pathogenicity of a MEN1 variant with crucial consequences for medical care and genetic counselling decisions.

Abstract

Objective: The number of cesarean deliveries on maternal request (CDMR) is unknown in France. We aimed to evaluate the rate of obstetricians willing to perform a CDMR in 2020 in Paris and to compare OB/GYN seniors’ and residents’ points of view about CDMR using six hypothetical clinical scenarios.

Study design: A survey was conducted between January to March 2020 with an anonymous self-administrated questionnaire sent by email to OB/GYN seniors working in 16 public and private maternity units and residents of Paris. Questionnaire was based on previous peer-reviewed literature. Socio professional characteristics were collected. OB/GYN seniors were asked if they agree to perform a CDMR and have already done one. OB/GYN seniors’ and residents’ points of view on six hypothetical clinical scenarios (CDMR, scarred uterus, breech presentation, multiple pregnancy, history of perineal tears or stillbirth) were compared.

Results: Eighty-three OB/GYN seniors and one hundred and fifteen residents answered to our questionnaire. Twenty-three (27,7%) OB/GYN seniors were ready to perform a CDMR, mostly because they think that mode of delivery is a woman’s choice. Physicians working in a private maternity unit or having an exclusive private practice were significantly more willing to perform a cesarean delivery on maternal request. No differences were found between the OB/GYN seniors’ and residents’ point of view on the six hypothetical clinical scenarios. A third of OB/GYN seniors and residents reported having done at least one CDMR during their career or during their residency.

Conclusion: One out of four OB/GYN senior interviewed is ready to perform a CDMR in Paris in 2020. OB/GYN seniors and residents share the same point of view concerning CDMR.