Publications

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.

Abstract

Introduction: The « en caul » technique, i.e. delivery with intact membranes, may reduce the risk of obstetric trauma in vaginal breech delivery of extreme preterm infants. We aimed at comparing perinatal mortality and morbidity among extremely preterm breech vaginal deliveries between infants delivered « en caul » and those with « ruptured membranes ».

Material and methods: We performed a fourteen-year retrospective study in a tertiary university center. All vaginal deliveries of singleton breech live infants with an antenatal decision of active resuscitation between 24 weeks and 27⁺⁶ weeks were included. Perinatal outcomes were compared between the « en caul » group, with intact membranes at the onset of pushing efforts and the « ruptured membranes » group, with ruptured membranes at the onset of pushing efforts. The primary outcome was perinatal mortality defined by intrapartum or neonatal death. The secondary outcomes were fetal extraction difficulties, arterial pH and 5 min Apgar score.

Results: We included 52 infants in the « en caul » group and 71 in the « ruptured membranes » group. The perinatal mortality rate did not differ between the two groups (19.2% in the « en caul » group versus 28.2% in the « ruptured membranes » group, p = 0.25). The mean arterial pH at birth was higher in the « en caul » group (7.32 ± 0.1 vs 7.24 ± 0.1, p = 0.001). There were no differences between the groups for fetal extraction difficulties, especially fetal head entrapment (9.6% versus 9.9%).

Conclusion: Even though the « en caul » technique does not seem to decrease the perinatal mortality rate, it remains a simple technique, which could improve neonatal morbidity.

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

Background: Overall and respiratory management of preterm children are constantly evolving, which might have changed both the pathophysiology and neurodevelopmental consequences of bronchopulmonary dysplasia (BPD).

Objectives: The objective of this study is to determine whether the previously shown association between BPD and risk of developmental delay persists.

Methods: The study population was children born before 32 weeks’ gestation from the French prospective cohort EPIPAGE-2. The exposure was BPD assessed at 36 weeks’ postmenstrual age. The main outcome was risk of developmental delay defined by an Age & Stages Questionnaires (ASQ) score below threshold at 24 months’ corrected age.

Results: The analyzed population included 2,706 children. Among those with available ASQ score, 196/1,587 had BPD and 671/1,587 had an ASQ score below threshold. BPD was associated with an ASQ score below threshold (odds ratio 1.52, 95% confidence interval 1.11-2.08; p = 0.008).

Conclusions: BPD was strongly associated with risk of developmental delay.

Abstract

Aim: Birth asphyxia can lead to organ dysfunction, varying from isolated biological acidosis to hypoxic-ischemic encephalopathy (HIE). Pathophysiology of moderate or severe HIE is now well known and guidelines exist regarding the care required in this situation. However, for newborns without moderate or severe HIE, no consensus is available. Our objective was to describe the immediate neonatal consequences and need for care of asphyxiated newborns without moderate or severe HIE.

Methods: Multicentre retrospective study from January 2015 to December 2017 in two academic centres, including neonates ≥37 gestational weeks with pathological foetal acidemia (umbilical arterial pH<7.00 and/or lactate≥10 mmol/L).

Results: Among 18 550 births, 161 (0.9%) had pathological foetal acidemia. 142 (88.0%) were not diagnosed with moderate or severe HIE. Among them, 82 (58.0%) were hospitalised. 13 (9.0%) had respiratory failure and required nutritional support. 100 (70.0%) underwent blood sampling, which showed at least one biological anomaly in 66 (66.0%) of cases.

Conclusion: Newborns born with pathological foetal acidemia without the occurrence of moderate or severe HIE had metabolic disorders and could need organ support. A prospective study describing this vulnerable population would help to establish consensus guidelines for the management of this population.

Abstract

Background: Disparities in neuraxial analgesia use for childbirth by maternal origin have been reported in high-resource countries. We explored the association between maternal immigrant status (characterised separately by geographic continental origin and Human Development Index [HDI] of maternal country of birth) and neuraxial analgesia use. We hypothesised that immigrant women from low-resource countries may have more limited access to neuraxial analgesia than native French women.

Methods: The study population, extracted from the 2016 National Perinatal Survey, a cross-sectional study of a representative sample of births in France, included only women who initially wished to deliver with neuraxial analgesia. We used multivariable multilevel logistic regression to explore the association between immigrant status and both use of neuraxial analgesia and its timely administration.

Results: Among the 6070 women included, 88.1% gave birth with neuraxial analgesia and 15.8% were immigrants. There was no difference in neuraxial analgesia use between native French women and either immigrant women by geographic continental region of origin, or immigrants from countries with low HDI. However, immigrants from countries with very high HDI were more likely to give birth with neuraxial analgesia (adjusted odds ratio [aOR]=2.6; 95% confidence interval (CI), 1.2-5.8; P=0.018) and its timeliness <60 min after admission (aOR=1.8; 95% CI, 1.2-2.7; P=0.005) compared with native French women.

Conclusions: In France, immigrant women from low-resource countries have similar access to labour neuraxial analgesia to native French women. Our results suggest differential neuraxial analgesia use in favour of immigrant women from very high HDI countries compared with native women.

Abstract

Objective: To compare the performance of estimated fetal weight (EFW) charts at the third trimester ultrasound for detecting small- and large-for-gestational age (SGA/LGA) newborns with adverse outcomes.

Design: Nationally representative observational study.

Setting: French maternity units in 2016.

Population: 9940 singleton live births with an ultrasound between 30 and 35 weeks of gestation.

Methods: We compared three prescriptive charts (INTERGROWTH-21st, World Health Organization (WHO), Eunice Kennedy Shriver National Institute of Child Health and Human Development [NICHD]), four descriptive charts (Hadlock, Fetal Medicine Foundation, two French charts) and a French customised growth model (Epopé).

Main outcome measures: SGA and LGA (birthweights <10th and >90th percentiles) associated with adverse outcomes (low Apgar score, delivery-room resuscitation, neonatal unit admission).

Results: 2.1% and 1.1% of infants had SGA and LGA and adverse outcomes, respectively. The sensitivity and specificity for detecting these infants with an EFW <10th and >90th percentile varied from 29-65% and 84-96% for descriptive charts versus 27-60% and 83-96% for prescriptive charts. WHO and French charts were closest to the EFW distribution, yielding a balance between sensitivity and specificity for SGA and LGA births. INTERGROWTH-21st and Epopé had low sensitivity for SGA with high sensitivity for LGA. Areas under the receiving operator characteristics curve ranged from 0.62 to 0.74, showing low to moderate predictive ability, and diagnostic odds ratios varied from 7 to 16.

Conclusion: Marked differences in the performance of descriptive as well as prescriptive EFW charts highlight the importance of evaluating them for their ability to detect high-risk fetuses.

Tweetable abstract: Choice of growth chart strongly affected identification of high-risk fetuses at the third trimester ultrasound.