Publications

ABSTRACT

Background: The relationship between maternal obesity and childhood cognitive development remains unclear. Prior stu
ies did not adjust for important confounders, and preterm infants are a developmentally distinct group that remains scarcely
examined.
Objectives: To determine whether maternal prepregnancy body mass index (BMI) is associated with offspring intelligence quo-
tient (IQ) up to 5 years and whether this relationship varies with gestational age.
Methods: Data from two French birth cohorts, EDEN (all gestational ages) and EPIPAGE-2 (preterm children born between 24
and 34 weeks of gestation), were used for this study. Maternal prepregnancy weight and height were used to calculate prepreg-
nancy BMI. The Wechsler Preschool and Primary Scale of Intelligence was used to assess child IQ around 5 years. Multivariable
models were adjusted for confounders, including socioeconomic status and paternal BMI.
Results: Analytical cohorts included 1100 children from EDEN and 2629 from EPIPAGE-2. Lower intellectual functioning
(full-scale IQ < 85) was observed in 8.1% of children in EDEN and 19.6% in EPIPAGE-2. The prevalence of maternal obesity was
13.6% (EDEN) and 21.3% (EPIPAGE-2) among children with lower intellectual functioning compared to 8.9% (EDEN) and 12.9%

Abstract

Background : in France, the infant mortality rate had a long period of decline, but it stopped decreasing after 2010 and then rose. Neonatal mortality is a large part of infant mortality. The aim of this study was thus to describe its main changes, by cause of death and gestational age, and the main changes in socio-spatial distribution, from 2001 to 2017.

Methods: for this purpose, we investigated data on neonatal deaths reported in France from 2001 to 2017. Crude, cause-specific and gestational age-specific neonatal mortality rates were computed and an ecological analysis, according to several contextual factors at commune level, was performed using quasi-Poisson regressions.

Results : the average neonatal mortality rate was 2.42 per 1000 live births in France during the study period, showing an increase from 2011 onwards. This increase was mostly related to perinatal conditions and more births at very low gestational age. Gestational age-specific neonatal mortality rates did not increase during the period. The analysis of socio-spatial factors showed increased mortality rates in large cities, deprived areas and cities with higher percentages of migrants.

Conclusion : this study suggests that a shift in the distribution of gestational age at birth toward low gestational ages may have contributed to the rise in neonatal mortality in France. Furthermore, there is notable spatial heterogeneity in neonatal mortality. Nevertheless, this observation poorly explains the specificity of the high level and recent upsurge in infant mortality in France, in contrast to its European counterparts

Abstract

Background: Recent studies have shown growing evidence that brain function is closely synchronised with global physiological parameters. Heart rate is linked to various cognitive processes and a strong correlation between neuronal activity and breathing has been demonstrated. These findings highlight the significance of monitoring these key physiological parameters during neuroimaging as they provide valuable insights into the overall brain function. Today, in neuroimaging, assessing these parameters requires additional cumbersome devices or implanted electrodes. Here we demonstrate that ultrasonic neurofunctional imaging data alone is sufficient to extract these parameters.

Methods: In this work, we performed ultrafast ultrasound imaging in male rodents and human neonates, and we extracted heart and breathing rates from local tissue motion assessed by raw ultrasound data processing. Such « Physio-fUS » automatically selects two specific and optimal brain regions with pulsatile tissue signals to monitor such parameters.

Findings: We validated the correspondence of these periodic signals with heart and breathing rates assessed using gold-standard electrodes in anaesthetised rodents. We extracted heart and breathing rates in sleeping rats and heart rate in rats moving freely in an arena. We also validated Physio-fUS imaging in sleeping human newborns using conventional ECG.

Interpretation: We show the potential of fUS imaging as an integrative tool for simultaneously monitoring physiological parameters during neurofunctional imaging. Beyond the technological improvement, it could enhance our understanding of the link between breathing, heart rate and neurovascular activity in preclinical research and clinical functional ultrasound imaging.

Abstract

The European Society for Paediatric Research (ESPR) first developed recommendations for a Neonatology specific European training curriculum in 1998, with updates in 2007 and 2021. The aim of these recommendations was to define a common, European standard of training for national educational programmes for Neonatologists. Following the Union of European Medical Specialists’ (UEMS) framework of European Training Requirements (ETR), and similar to the American Board of Pediatrics (ABP) recommendations, graduates of training programmes conforming to the ETR will be eligible throughout Europe for recognition of equality of training, and with that should be enabled to freedom-of-movement. This concept also accounts for neonatal specialists. We therefore present the pan-European work on the ETR Neonatology in its third iteration (ETR III), summarising the basic requirements for contemporary training programmes, trainers, and training centres in neonatology. We highlight the European School of Neonatology (ESN) as a comprehensive online educational platform which provides the theoretical and practical background to satisfy the ETR-III. Lastly, we introduce the European Board of Neonatal & Child Health Research (EBNCHR) as a committee dedicated to gaining acceptance for the concept of harmonising education and training in Neonatology and recognising Neonatology as a Paediatric subspecialty in every European Union member state. IMPACT: Neonatology currently is not uniformly recognised as a Paediatric subspecialty throughout the 27 European countries. Hence, training in Neonatology formerly followed no commonly agreed standard throughout the European Union (EU). To ensure a minimum standard of care, an agreed minimum standard of training is required. The European Society for Paediatric Research (ESPR) has led on generating an EU-accredited, pan-European Syllabus for Neonatal training in Europe, the European Training Requirements (ETR) in Neonatology (2021). This article presents the ETR Neonatology from commissioning to accreditation and discusses means of how high-grade post-graduate education, aligned with the ETR can be achieved by practitioners.

Abstract

Acute community-acquired pneumonia (CAP) during pregnancy is a frequently encountered and potentially severe condition. CAP incidence and ecology are unchanged during pregnancy as compared with the overall young adult population. Risk factors specifically identified in pregnant women include advanced gestational age, asthma, anemia and repeated courses of corticosteroid therapy for fetal lung maturation. The clinical presentation of CAP is not altered during pregnancy. Key points in the pregnant host encompass: (i) reduced maternal tolerance to hypoxia, due to physiological adaptations during pregnancy; (ii) heightened severity of some infections, notably viral pneumonias such as influenza, varicella or SARS-CoV-2 pneumonia; (iii) potentially deleterious fetal repercussions of infection and maternal hypoxia, with an increased risk of premature delivery and prematurity; (iv) the need for specific attention to the risk of fetal irradiation in the performance of possibly repeated radiological examinations and (v) therapeutic specificities arising from the possible embryo-fetal toxicity of certain anti-infectious agents. CAP prevention is premised on compliance with universal hygiene measures and on vaccination, which guarantees protection against severe forms of pneumonia not only in the mother (Streptococcus pneumoniae, seasonal flu, chickenpox, COVID-19), but also in the child during the first few months of life (whooping cough, RSV

Abstract

By interfering with the normal sequence of mechanisms serving the brain maturation, premature birth and related stress can alter perinatal experiences, with potential long-term consequences on a child’s neurodevelopment. The early characterization of brain functioning and maturational changes is thus of critical interest in premature infants who are at high risk of atypical outcomes and could benefit from early diagnosis and dedicated interventions. Using high-density electroencephalography (HD-EEG), we recorded brain activity in extreme and very preterm infants at the equivalent age of pregnancy term (n = 43), and longitudinally 2 months later (n = 33), compared with full-term born infants (n = 14). We characterized the maturation of brain activity by using a dedicated microstate analysis to quantify the spatio-temporal dynamics of the spontaneous transient network activity while controlling for vigilance states. The comparison of premature and full-term infants first showed slower dynamics as well as altered spatio-temporal properties of brain activity in preterm infants. Maturation of functional networks between term-equivalent age and 2 months later in preterms was linked to the emergence of faster dynamics, manifested in part by shorter duration of microstates, as well as an evolution in the spatial organization of the dominant microstates. The inter-individual differences in the temporal dynamics of brain activity at term-equivalent age were further impacted by sex (with slower microstate dynamics in boys) and by gestational age at birth for some microstate dynamics but not by other considered risk factors. This study highlights the potential of the microstate approach to reveal maturational properties of the emerging brain network activity in premature infants.

Abstract

Preeclampsia (PE) is the most threatening pathology of human pregnancy. Placenta from PE patients releases harmful factors that contribute to the exacerbation of the disease. Among these factors is the prokineticin1 (PROK1) and its receptor, PROKR2 that we identified as a mediators of PE. Here we tested the effects of PKRA, an antagonist of PROKR2, on the attenuation of PE symptoms. We used the genetic PE mouse model, STOX1 that overexpresses Stox1 gene in a heterozygosis manner in the placenta. This model allowed exploiting two genotypes of the offspring, those that overexpress the Stox1 gene, and the WT that grow in a PE environment (STE). We characterised the effect PKRA (1 μM) on the attenuation of PE symptoms and compared its effects on STOX1 and STE placentas. We also used STOX1 overexpressing trophoblast cells to decipher the PROK1-underlying mechanism. We demonstrated that (i) antagonisation of PROKR2 attenuated PE-mediated hypertension and proteinuria, (ii) STE placentas and foetuses exhibited better outcomes in response to PKRA, (iii) the secretome of STOX1-trophoblasts impacted the integrity of the fetal vasculature that was attenuated by PKRA treatment. This study demonstrates the direct involvement of the PROK1 in PE and identifies PKRA as a promising therapy for PE.

No abstract available

Abstract

Retinopathy of prematurity (ROP, ORPHA: 90050) is the main cause of visual impairment in preterm infants and the leading preventable cause of childhood blindness in high- and middle-income countries. However, severe stages of the disease remain rare. While screening recommendations for the disease are well-established in France, management of ROP requiring treatment is less standardized, especially since new therapeutic options have been approval on this indication. The management of preterm infants requiring treatment for ROP is complex and involves a multidisciplinary team, including pediatric ophthalmologists, vitreoretinal surgeons, neonatologists, pediatric anesthetists, nurses, and orthoptists, within an adapted structure for premature infants care. There is a genuine need to unify national practices, with a strong demand from physicians involved in ROP care along the country. The objective of this National Diagnostic and Care Protocol (PNDS) is to provide guidelines for diagnostic and management for ROP, and to optimize and harmonize the management of this disease across the country. The main treatment indications, the different treatment modalities including laser photocoagulation, anti-VEGF injections, and vitreoretinal surgery as well as follow-up calendar, are reviewed to establish the best practice recommendations on ROP.

Abstract

Infants born very preterm (below 28 weeks of gestation) are at high risk of developing neurodevelopmental disorders, such as intellectual deficiency, autism spectrum disorders, and attention deficit. Preterm birth often occurs in the context of perinatal systemic inflammation due to chorioamnionitis and postnatal sepsis. In addition, C-section is often performed for very preterm neonates to avoid hypoxia during a vaginal delivery. We have developed and characterized a mouse model based on intraperitoneal injections of IL-1β between postnatal days one and five to reproduce perinatal systemic inflammation. This model replicates several neuropathological, brain imaging, and behavioral deficits observed in preterm infants. We hypothesized that C-sections could synergize with systemic inflammation to induce more severe brain abnormalities. We observed that C-sections significantly exacerbated the deleterious effects of IL-1β on reduced gut microbial diversity, increased levels of circulating peptidoglycans, abnormal microglia/macrophage reactivity, impaired myelination, and reduced functional connectivity in the brain relative to vaginal delivery plus intraperitoneal saline. These data demonstrate the deleterious synergistic effects of C-section and neonatal systemic inflammation on brain maldevelopment and malfunction, two conditions frequently observed in very preterm infants, who are at high risk of developing neurodevelopmental disorders.