Publications

Abstract

Early life gut microbiota-influencing factors may play an important role in programming individuals long-term health and substantial efforts have been devoted into studying the development of the gut microbiota in relation to early life events. This study aimed to examine in a single study, the persistence of associations between 20 factors occurring in the early life and the gut microbiota at 3.5 years of 798 children from two French nationwide birth cohorts, EPIPAGE 2 (very preterm children) and ELFE (late preterm and full-term children). Gut microbiota profiling was assessed using 16S rRNA gene sequencing-based method. Upon thorough adjustment of confounding factors, we demonstrated that gestational age was one of the factors most associated with gut microbiota differences with a noticeable imprint of prematurity at 3.5 years of age. Children born by cesarean section harbored lower richness and diversity and a different overall gut microbiota composition independently of preterm status. Children who had ever received human milk were associated with a Prevotella-driven enterotype (P_type) compared to those who had never received human milk. Living with a sibling was associated with higher diversity. Children with siblings and those attending daycare centers were associated with a P_type enterotype. Maternal factors including the country of birth and preconception maternal body mass index were associated with some microbiota characteristics: children born to overweight or obese mothers showed increased gut microbiota richness. This study reveals that multiple exposures operating from early life imprint the gut microbiota at 3.5 years that is a pivotal age when the gut microbiota acquires many of its adult characteristics.

Abstract

Research question: What are the reproductive outcomes and the prognostic factors of live birth rates in patients with endometriosis referred to oocyte donation after multiple IVF failures?

Design: Observational cohort study including all women with endometriosis-related infertility and two or more failed IVF/intracytoplasmic sperm injection (ICSI) cycles referred to oocyte donation between January 2013 and June 2022. Endometriosis was diagnosed based on published imaging criteria, and was confirmed histologically in women who had a history of surgery for endometriosis. The main outcome measured was the cumulative live birth rate (CLBR). The characteristics of women who had a live birth were compared with those who did not using univariate and multivariate analysis to identify determinant factors of fertility outcome.

Results: Fifty-seven patients underwent 90 oocyte donation cycles after 244 failed autologous IVF cycles. The mean ± SD age of the population was 36.8 ± 3.3 years, with a mean duration of infertility of 3.6 ± 2.2 years, and a mean number of autologous IVF/ICSI cycles of 4.4 ± 2.3 cycles per patient. Three patients (5.3%) had superficial peritoneal endometriosis, two patients (3.5%) had ovarian endometriomas, and 52 patients (91.2%) had deep infiltrating endometriosis, among which 30 patients (57.7%) had bowel lesions. Thirty patients (52.6%) had associated adenomyosis. Overall, CLBR per patient was 36/57 (63.2%). After multivariate analysis, only being nulligravida (P=0.002) remained an independent negative predictive factor of the live birth rate. Previous surgery did not impact reproductive outcomes.

Conclusion: This study suggests that oocyte donation appears to be a viable option to optimize the live birth rate in women with endometriosis-related infertility and recurrent IVF failures.

Abstract

Objective: To evaluate safety of prenatal corticosteroids in pregnancies of women with sickle cell disease.

Methods: A multicenter observational study of patients with sickle cell disease, comparing vaso-occlusive crises (VOC) requiring hospital care between pregnancies with versus without prenatal corticosteroids.

Results: In 40 pregnancies exposed to prenatal corticosteroids, compared with 370 unexposed pregnancies, VOC were not more frequent (62.5% vs 57.9%, P = 0.578) but they were more severe, with more intensive care hospitalizations (25.0% vs 12.9%, P = 0.039), emergency transfusions (44.7% vs 22.7%, P = 0.006), and acute chest syndromes (22.5% vs 8.9%, P = 0.010). These differences persisted after adjustment for severity and type of sickle cell syndrome (for intensive care admission adjusted odds ratio [aOR] 2.73, 95% confidence interval [CI] 1.10-6.79, P = 0.031 and for acute chest syndrome aOR 4.15, 95% CI 1.57-14.4, P = 0.008). VOC occurred on average 1.2 days following steroid administration. When comparing 36 patients receiving corticosteroids for fetal maturation with 58 patients who were hospitalized for obstetrical complications before 34 weeks of pregnancy but that did not receive corticosteroids, VOC incidence was not significantly higher (41.7% vs 31.5%, P = 0.323).

Conclusion: The present study was the first to study the impact of prenatal corticosteroids on sickle cell disease. They were associated with more severe VOC, suggesting that steroids should be avoided in these women.

No abstract available.

Abstract

Background: The exposure to plastic derivatives during human life is deleterious. Infants conceived using ART (IVF or ICSI) have twice as many risks of major birth defects compared to naturally conceived infants. Could plastic ware used during ART trigger defects in the fetal development?

Methods: Three groups of blastocysts were transferred to pseudopregnant mice. One was obtained after IVF and embryo development in plastic ware, the second in glass ware. The third, was obtained in vivo by natural mating. On day 16.5 of pregnancy, females were sacrificed and fetal organs collected for gene expression analysis. Fetal sex was determined by RT-PCR. RNA was extracted from a pool of five placental or brain samples coming from at least two litters from the same group and analyzed by hybridisation onto the mouse Affymetrix 430.2.0 GeneChips, confirmed by RT-qPCR for 22 genes.

Findings: This study highlights a major impact of plastic ware on placental gene expression (1121 significantly deregulated genes), while glassware was much closer to in vivo offspring (only 200 significantly deregulated genes). Gene Ontology indicated that the modified placental genes were mostly involved in stress, inflammation and detoxification. A sex specific analysis revealed in addition a more drastic effect on female than male placentas. In the brains, whatever the comparison, less than 50 genes were found deregulated.

Interpretation: Embryos incubated in plastic ware resulted in pregnancy with massive alterations of placental gene expression profile in concerted biological functions. There were no obvious effects on the brains. Besides other effects, this suggests that plastic ware in ART could be a cause of the increased level of pregnancy disorders observed recurrently in ART pregnancies

Abstract

Screening of retinopathy of prematurity (ROP) was modified in a level-3 neonatal intensive care unit by the introduction of a wide-field retinal imaging. The aim of this study was to evaluate whether retinopathy of prematurity (ROP) diagnosis was improved or not compared to previously used binocular indirect ophthalmoscopy (BIO). This was a retrospective, uncontrolled, quality improvement project. Records of consecutive premature newborns screened for ROP over two 1-year periods were reviewed. Systemic factors potentially influencing the occurrence of ROP were investigated using uni- and multivariable linear regression followed by stepwise forward regression. ROP screening was performed by ophthalmologists using BIO in 2014, and digital wide-field retinal imaging (Panocam™ pro) in 2019. Records of N = 297 patients were analyzed (N = 159 in 2014 and N = 138 in 2019). The proportion of ROP diagnosed at any stage, over the total number of neonates screened, was significantly higher in 2019 (n = 46/138, 33.1%) compared to 2014 (n = 11/159, 6.9%) (p < 0.0001). Most neonates presented with mild forms of ROP during both 1-year periods analyzed. After adjustment for all parameters influencing ROP occurrence, the variables contributing independently to the diagnosis of any stage of ROP were birth weight (p = 0.002), duration of mechanical ventilation (p = 0.028) and wide-field fundus camera-assisted screening (p < 0.001).

Conclusion: After adjusting for many recognized systemic factors influencing the development of ROP, screening by wide-field digital retinal imaging was independently associated with higher ROP detection.

What is known: • No consensus has been reached to replace binocular indirect ophthalmoscopy by retinal imaging for ROP screening. • Diagnostic accuracy and high sensitivity and specificity has been reported for wide-field digital imaging.

What is new: • The introduction of wide-field imaging for ROP screening in at level-3 reference center was independently associated to higher ROP detection.

Abstract

Objectives: The objectives were to describe mortality and causes of death in children with intraventricular hemorrhage (IVH) and to study neurodevelopmental outcomes.

Methods: The study was a secondary analysis of the French national prospective and population-based cohort EPIPAGE-2. Children were recruited in 2011. A standardized assessment was conducted at age 5. Children born before 32 weeks’ gestation and admitted to a NICU were eligible. Exposure was IVH defined by the Papile classification. Main outcomes were mortality, causes of death, and neurodevelopmental outcomes at age 5.

Results: Among the 3468 children included, 578 (16.7%) had grade 1 IVH, 424 (12.2%) grade 2 IVH, and 114 (3.3%) grade 3 IVH; 144 (4.1%) had intraparenchymal hemorrhage (IPH). Mortality was 29.7% (36 of 114) for children with grade 3 IVH and 74.4% (109 of 144) for those with IPH; 67.6% (21 of 31) and 88.7% (86 of 97) of deaths, respectively, were because of withholding and withdrawing of life-sustaining treatment. As compared with no IVH, low-grade IVH was not associated with measured neurodevelopmental disabilities at age 5. High-grade IVH was associated with moderate and severe neurodevelopmental disabilities, reduced full-scale IQ, and cerebral palsy.

Conclusions: Rates of neurodevelopmental disabilities at age 5 did not differ between children without IVH and those with low-grade IVH. For high-grade IVH, mortality rate was high, mostly because of withholding and withdrawal of life-sustaining treatment, and we found a strong association with overall neurodevelopmental disabilities in survivors.

Abstract

Although the 2022 Monkeypox virus epidemic mostly affects males, particularly men having sex with men, transmission to women may also occur. In case of MPXV infection in pregnancy, transmission to the fetus can result in very severe disease. Thus, caregivers should be aware of the measures to be taken according to the available evidence, in case of exposure or in case of symptoms particularly skin rash compatible with this diagnosis in a pregnant woman. Pregnant women should have access to vaccination, vaccinia immunoglobulin or antiviral medications as required.

Abstract

Introduction: Nicotinamide nucleotide transhydrogenase (NNT) gene deficiency has recently been shown to be involved in Primary Adrenal Insufficiency (PAI). NNT encodes an inner mitochondrial membrane protein that produces large amounts of NADPH. NADPH is used in several biosynthesis pathways and the oxidoreduction of free radicals by the glutathione and thioredoxin systems in mitochondria. Patients with PAI due to NNT deficiency may also exhibit extra-adrenal manifestations, usually including gonadal impairment.

Case report: We present the case of a 35-year-old patient referred to our center for primary infertility with non-obstructive azoospermia, in a context of PAI and obesity. PAI genetic exploration carried out at the age of thirty revealed NNT deficiency due to the presence of two deleterious mutations (one on each allele) in the NNT gene. Scrotal ultrasound revealed a right Testicular Adrenal Rest Tumor (TART). Intensification of glucocorticoid therapy over the course of 8 months failed to reduce the TART volume or improve sperm production and endocrine function. No spermatozoa were found after surgical exploration of both testes, and subsequent histopathological analysis revealed bilateral Sertoli cell-only syndrome. A retrospective review of the hypothalamic-pituitary-gonadic axis hormonal assessment over 20 years showed progressive impairment of testicular function, accelerated during adulthood, leading to hypergonadotropic hypogonadism and non-obstructive azoospermia when the patient reached his thirties, while the PAI remained controlled over the same period.

Conclusion: This case report provides, for the first time, direct evidence of complete germ line loss in an azoospermic man with NNT deficiency. Additional data further support the hypothesis of a determinant role of oxidative cellular damage due to reactive oxygen species (ROS) imbalance in the severe gonadal impairment observed in this NNT-deficient patient. Early and regular evaluation of gonadal function should be performed in patients with PAI, especially with NNT deficiency, as soon as the patients reach puberty. Fertility preservation options should then be provided in early adulthood for these patients.

Abstract

Introduction: The global sequence of the pathogenesis of preterm labor remains unclear. This study aimed to compare amniotic fluid concentrations of extracellular matrix-related proteins (procollagen, osteopontin and IL-33), and of cytokines (IL-19, IL-6, IL-20, TNFα, TGFβ, and IL-1β) in asymptomatic women with and without subsequent spontaneous preterm delivery.

Material and methods: We used amniotic fluid samples of singleton pregnancy, collected by amniocentesis between 16 and 20 weeks’ gestation, without stigmata of infection (i.e., all amniotic fluid samples were tested with broad-range 16 S rDNA PCR to distinguish samples with evidence of past bacterial infection from sterile ones), during a randomized, double-blind, placebo-controlled trial to perform a nested case-control laboratory study. Cases were women with a spontaneous delivery before 37 weeks of gestation (preterm group). Controls were women who gave birth at or after 39 weeks (full term group). Amniotic fluid concentrations of the extracellular matrix-related proteins and cytokines measured by immunoassays were compared for two study groups.

Clinicaltrials: gov: NCT00718705.

Results: Between July 2008 and July 2011, in 12 maternal-fetal medicine centers in France, 166 women with available PCR-negative amniotic fluid samples were retained for the analysis. Concentrations of procollagen, osteopontin, IL-19, IL-6, IL-20, IL-33, TNFα, TGFβ, and IL-1β were compared between the 37 who gave birth preterm and the 129 women with full-term delivery. Amniotic fluid levels of procollagen, osteopontin, IL-19, IL-33, and TNFα were significantly higher in the preterm than the full-term group. IL-6, IL-20, TGFβ, and IL-1β levels did not differ between the groups.

Conclusions: In amniotic fluid 16 S rDNA PCR negative samples obtained during second-trimester amniocentesis, extracellular matrix-related protein concentrations (procollagen, osteopontin and IL-33), together with IL-19 and TNFα, were observed higher at this time in cases of later spontaneous preterm birth.