Publications

Abstract

Background: The efficacy of antenatal corticosteroids for neonatal preterm complications wanes beyond 7 days after treatment. The neurodevelopmental effects of longer treatment-to-birth intervals have not been adequately evaluated.

Objective: This study aimed to assess the impact of antenatal corticosteroid timing on survival without moderate or severe neurologic disabilities at 5½ years.

Study design: This was a secondary analysis of the EPIPAGE-2 study, a national population-based cohort (France) that recruited neonates in 2011 and followed them up at 5½ years (results first reported in 2021). Participants were children born alive between 24+0 and 34+6 weeks, with a complete corticosteroid course, delivery >48 hours after the first injection, and neither limitation of care decided before birth nor severe congenital malformation. The study included 2613 children, 2427 of whom were alive at 5½ years; 71.9% (1739/2427) had a neurologic assessment at this age; 1537 had a clinical examination (complete for 1532), and 202 were assessed with a postal questionnaire. Exposure was defined as the interval between the first injection of the last antenatal corticosteroid course and delivery in days, studied in 2 categories (days 3-7 and after day 7), in 4 categories (days 3-7, 8-14, 15-21, and after day 21), and continuously in days. The main outcome was survival at 5½ years without moderate/severe neurologic disabilities, defined as moderate/severe cerebral palsy, or unilateral or bilateral blindness or deafness, or Full-Scale Intelligence Quotient 2 standard deviations below the mean. A multivariate analysis with a generalized estimated equation logistic regression model assessed the statistical association between the main outcomes and the interval from the first corticosteroid injection of the last course to birth. Multivariate analyses were adjusted for potential confounders, defined with a directed acyclic graph: gestational age in days, number of corticosteroid courses, multiple pregnancy, and cause of prematurity in 5 categories. Because neurologic follow-up was complete in only 63.2% of cases (1532/2427), the analyses used imputed data.

Results: Among 2613 children, 186 died between birth and 5½ years. Overall survival was 96.6% (95% confidence interval, 95.9-97.0), and survival without moderate or severe neurologic disabilities was 86.0% (95% confidence interval, 84.7-87.0). Survival without moderate or severe neurologic disabilities was lower after day 7 (85.0%) than during the interval from day 3 to day 7 (87.0%) (adjusted odds ratio, 0.70; 95% confidence interval, 0.54-0.89).

Conclusion: The association of a >7-day interval between antenatal corticosteroid administration and birth with a lower rate of survival without moderate or severe neurologic disabilities among children aged 5½ years emphasizes the importance of better targeting women at risk of preterm delivery to optimize the timing and thus benefits of treatment.

Abstract

Objective: We aimed to study neurodevelopmental outcomes and healthcare utilisation at age 5-6 years in very preterm children with bronchopulmonary dysplasia (BPD).

Design: Prospective and national population-based study.

Setting: All the neonatal units in 25 French regions (21 of the 22 metropolitan regions and 4 overseas regions).

Patients: Children born before 32 weeks’ gestation in 2011.

Interventions: Blind, comprehensive and standardised assessment by trained neuropsychologists and paediatricians at age 5-6 years.

Main outcome measures: Overall neurodevelopmental disabilities, behavioural difficulties, developmental coordination disorders, full-scale IQ, cerebral palsy, social interaction disorders, rehospitalisation in the previous 12 months and detailed developmental support.

Results: Of the 3186 children included, 413 (11.7%) had BPD. The median gestational age of children with BPD was 27 weeks (IQR 26.0-28.0) and without BPD was 30 weeks (28.0-31.0). At age 5-6 years, 3150 children were alive; 1914 (60.8%) had a complete assessment. BPD was strongly associated with mild, moderate and severe overall neurodevelopmental disabilities (OR 1.49, 95% CI 1.05 to 2.20; 2.20, 1.41 to 3.42 and 2.71, 1.67 to 4.40). BPD was associated with developmental coordination disorders, behavioural difficulties, lower IQ score as well as rehospitalisation in the last 12 months and developmental support. The association between BPD and cerebral palsy was statistically significant before adjustment but not in adjusted analyses.

Conclusions: BPD was strongly and independently associated with many neurodevelopmental disabilities. Improving medical and neurodevelopmental management of BPD in very preterm children should be a priority to reduce its long-term consequences.

No abstract available.

Abstract

Aim: Neonatologists are exposed to ethical issues and unplanned emergencies that require 24-h in-house coverage. These elements may affect quality of life at work, which we surveyed.

Methods: This was a self-administered, voluntary and anonymous cross-sectional survey of French neonatologists. An online questionnaire was sent to members of the French Society of Neonatology from June to October 2022.

Results: Of approximately 1500 possible responses, 721 were analysed, with a response rate of 48%. Respondents were mostly women (77%), aged 35-50 years (50%), and hospital practitioners (63%). Reported weekly working time was over 50 h for 80%. Among the 650 neonatologists with on-call duty, 47% worked ≥5 shifts per month. For 80% of practitioners, on-call duty was perceived to have a negative impact on personal life; 49% indicated having sleep disorders. The mean satisfaction score at work was 5.7 ± 1.7 on a scale of 0-10. The main reasons for dissatisfaction were excessive working hours and insufficient remuneration for on-call duty.

Conclusion: This first evaluation of the quality of life at work of French neonatologists showed high workload. The working conditions and specificities of NICU activity may have significant consequences for their mental health.

Abstract

The vaginal microbiota refers to the microorganisms that reside in the vagina. These microorganisms contribute significantly to a woman’s reproductive and general health. A healthy vaginal microbiota is typically a low-diversity environment with a predominance of lactic acid-producing Lactobacillus species. Factors such as antibiotic use, sexual activity, and hormonal changes can disrupt the balance of the vaginal microbiota, leading to conditions such as bacterial vaginosis. The composition of the vaginal microbiota changes and takes on added importance during pregnancy, serving as a barrier against infection for both mother and fetus. Despite the importance of the microorganisms that colonize the vagina, details of how changes in composition and diversity can impact pregnancy outcomes is poorly understood. This is especially true for woman with a high prevalence of Gardnerella vaginalis. Here we report on a diverse cohort of 749 women, enrolled in the InSPIRe cohort, during their final trimester of pregnancy. We show that Lactobacilli, including L. crispatus are important in maintaining low diversity, and that depletion in this critical community is linked with preterm delivery. We further demonstrate that it is overall diversity of the vaginal microbiota, not specific species, which provides the best indicator of risk.

Abstract

Primary infection during pregnancy by the protozoan Toxoplasma gondii can be worrisome because transmission to the fetus may lead to congenital toxoplasmosis (CT). Neonatal diagnosis is usually performed by serological profile comparison of the mother and newborn. As previously reported in 2012 by C. L’Ollivier et al., three IgM bands at 75, 90 and 100 kDa called the “IgM triplet” has caught our attention and seems to be pathognomonic of CT. This retrospective multicenter study involved nine reference laboratories included in the French National Reference Center for Toxoplasmosis network and concerned determining the specificity and sensitivity of this IgM triplet. On this basis, we were able to propose a new read of the comparison of IgG and IgM immunoblot profiles of mother and infant to increase the sensitivity of this diagnostic marker. The effect of the trimester of pregnancy at the time of infection, but also of maternal treatment with pyrimethamine/sulfadiazine/folinic acid on the presence of this IgM triplet in the infant, could be studied. The presence of the triplet appears pathognomonic for the diagnosis of CT, and it increased the sensitivity of the immunoblot assay from 55.04% to 72.48%. As a result, it would be wise to enhance conventional immunoblot reading by adding the presence of the three IgM bands in the infant pattern for neonatal diagnosis of CT.

Abstract

We report nine severe neonatal infections caused by a new variant of echovirus 11. All were male, eight were twins. At illness onset, they were 3-5 days-old and had severe sepsis and liver failure. This new variant, detected in France since April 2022, is still circulating and has caused more fatal neonatal enterovirus infections in 2022 and 2023 (8/496; 1.6%, seven associated with echovirus 11) compared with 2016 to 2021 (7/1,774; 0.4%). National and international alerts are warranted.

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.