Background and ObjectivesDevelopmental and epileptic encephalopathies (DEEs) with early burst-suppression EEG (EIDEE-BS) are among the most severe neonatal epileptic syndromes, typically presenting in the first months of life with refractory seizures and profound neurodevelopmental impairment. Although variants in the KCNQ2, STXBP1, and SCN2A genes are recognized as major causes, the full genetic spectrum remains uncertain. We aimed to delineate the electroclinical characteristics, genetic etiologies, and long-term outcomes in a large MRI-negative EIDEE-BS cohort.MethodsWe retrospectively analyzed 110 patients with BS EEG enrolled from a database of 1,540 individuals with suspected genetic epilepsies (2008-2023). Clinical, EEG, and genetic data were systematically collected. Patients were stratified into 4 groups: KCNQ2, STXBP1, "other pathogenic variants," and "without a genetic diagnosis." EEG traces were reviewed independently, and outcomes were assessed through long-term follow-up.ResultsPathogenic or likely pathogenic variants were identified in 62.7% of patients and involved 23 genes, including 2 copy number variants. KCNQ2 (n = 24) and STXBP1 (n = 16) accounted for one-third of diagnoses, whereas SCN2A (n = 3) and KCNT1 (n = 2) were less frequent. In KCNQ2 cases, seizures and BS onset occurred earlier than in STXBP1 cases: mean 2 days vs 6 weeks for seizures and 3 days vs 2 months for BS, respectively. A typical BS pattern (bursts longer than suppressions) strongly correlated with KCNQ2 and STXBP1 variants. Novel associations were found with DPM1, GRIN2A, KCNT2, PIGO, PURA, WWOX, and candidate genes (KMT2E, SNAP25, and SYT1). Most variants were de novo heterozygous; however, recessive and X-linked inheritance patterns were also observed. Mortality was high (25%), primarily from status epilepticus and complications of severe disability. Most patients (72.5%) had persistent seizures at follow-up (a mean of 6.5 years), as well as profound intellectual disabilities, irrespective of genotype.DiscussionThis large series highlights the strong monogenic basis of EIDEE-BS. KCNQ2, STXBP1, and SCN2A were the most commonly affected genes. Early EEG features, particularly BS timing and morphology, can help anticipate the underlying genotype and guide precision therapy, including the early use of sodium channel blockers in selected cases. These findings support recent ILAE reclassification efforts and underscore the importance of comprehensive genomic testing for improved diagnosis and counseling.

BACKGROUND:Magnesium sulphate is a common therapy in perinatal care. Its benefits when given to women at risk of preterm birth for fetal neuroprotection (prevention of cerebral palsy for children) were shown in a 2009 Cochrane review. Internationally, use of magnesium sulphate for preterm cerebral palsy prevention is now recommended practice. As new randomised controlled trials (RCTs) and longer-term follow-up of prior RCTs have since been conducted, this review updates the previously published version. OBJECTIVES:To assess the effectiveness and safety of magnesium sulphate as a fetal neuroprotective agent when given to women considered to be at risk of preterm birth. SEARCH METHODS:We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) on 17 March 2023, as well as reference lists of retrieved studies. SELECTION CRITERIA:We included RCTs and cluster-RCTs of women at risk of preterm birth that assessed prenatal magnesium sulphate for fetal neuroprotection compared with placebo or no treatment. All methods of administration (intravenous, intramuscular, and oral) were eligible. We did not include studies where magnesium sulphate was used with the primary aim of preterm labour tocolysis, or the prevention and/or treatment of eclampsia. DATA COLLECTION AND ANALYSIS:Two review authors independently assessed RCTs for inclusion, extracted data, and assessed risk of bias and trustworthiness. Dichotomous data were presented as summary risk ratios (RR) with 95% confidence intervals (CI), and continuous data were presented as mean differences with 95% CI. We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS:We included six RCTs (5917 women and their 6759 fetuses alive at randomisation). All RCTs were conducted in high-income countries. The RCTs compared magnesium sulphate with placebo in women at risk of preterm birth at less than 34 weeks' gestation; however, treatment regimens and inclusion/exclusion criteria varied. Though the RCTs were at an overall low risk of bias, the certainty of evidence ranged from high to very low, due to concerns regarding study limitations, imprecision, and inconsistency. Primary outcomes for infants/children: Up to two years' corrected age, magnesium sulphate compared with placebo reduced cerebral palsy (RR 0.71, 95% CI 0.57 to 0.89; 6 RCTs, 6107 children; number needed to treat for additional beneficial outcome (NNTB) 60, 95% CI 41 to 158) and death or cerebral palsy (RR 0.87, 95% CI 0.77 to 0.98; 6 RCTs, 6481 children; NNTB 56, 95% CI 32 to 363) (both high-certainty evidence). Magnesium sulphate probably resulted in little to no difference in death (fetal, neonatal, or later) (RR 0.96, 95% CI 0.82 to 1.13; 6 RCTs, 6759 children); major neurodevelopmental disability (RR 1.09, 95% CI 0.83 to 1.44; 1 RCT, 987 children); or death or major neurodevelopmental disability (RR 0.95, 95% CI 0.85 to 1.07; 3 RCTs, 4279 children) (all moderate-certainty evidence). At early school age, magnesium sulphate may have resulted in little to no difference in death (fetal, neonatal, or later) (RR 0.82, 95% CI 0.66 to 1.02; 2 RCTs, 1758 children); cerebral palsy (RR 0.99, 95% CI 0.69 to 1.41; 2 RCTs, 1038 children); death or cerebral palsy (RR 0.90, 95% CI 0.67 to 1.20; 1 RCT, 503 children); and death or major neurodevelopmental disability (RR 0.81, 95% CI 0.59 to 1.12; 1 RCT, 503 children) (all low-certainty evidence). Magnesium sulphate may also have resulted in little to no difference in major neurodevelopmental disability, but the evidence is very uncertain (average RR 0.92, 95% CI 0.53 to 1.62; 2 RCTs, 940 children; very low-certainty evidence). Secondary outcomes for infants/children: Magnesium sulphate probably resulted in little to no difference in severe intraventricular haemorrhage (grade 3 or 4) (RR 0.81, 95% CI 0.64 to 1.04; 6 RCTs, 6542 infants; moderate-certainty evidence) and may have resulted in little to no difference in chronic lung disease/bronchopulmonary dysplasia (average RR 0.92, 95% CI 0.77 to 1.10; 5 RCTs, 6689 infants; low-certainty evidence). Primary outcomes for women: Magnesium sulphate may have resulted in little or no difference in severe maternal outcomes potentially related to treatment (death, cardiac arrest, respiratory arrest) (RR 0.32, 95% CI 0.01 to 7.92; 4 RCTs, 5300 women; low-certainty evidence). However, magnesium sulphate probably increased maternal adverse effects severe enough to stop treatment (average RR 3.21, 95% CI 1.88 to 5.48; 3 RCTs, 4736 women; moderate-certainty evidence). Secondary outcomes for women: Magnesium sulphate probably resulted in little to no difference in caesarean section (RR 0.96, 95% CI 0.91 to 1.02; 5 RCTs, 5861 women) and postpartum haemorrhage (RR 0.94, 95% CI 0.80 to 1.09; 2 RCTs, 2495 women) (both moderate-certainty evidence). Breastfeeding at hospital discharge and women's views of treatment were not reported. AUTHORS' CONCLUSIONS:The currently available evidence indicates that magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus, compared with placebo, reduces cerebral palsy, and death or cerebral palsy, in children up to two years' corrected age. Magnesium sulphate may result in little to no difference in outcomes in children at school age. While magnesium sulphate may result in little to no difference in severe maternal outcomes (death, cardiac arrest, respiratory arrest), it probably increases maternal adverse effects severe enough to stop treatment. Further research is needed on the longer-term benefits and harms for children, into adolescence and adulthood. Additional studies to determine variation in effects by characteristics of women treated and magnesium sulphate regimens used, along with the generalisability of findings to low- and middle-income countries, should be considered.

BACKGROUND:To assess rates and factors for disability at 3 following hypoxic-ischemic encephalopathy (HIE). METHODS:Newborns more than 34 weeks with HIE Sarnat grades I to III, mostly treated by hypothermia were included in the population-based cohort LyTONEPAL and followed at 3. Mild, moderate, or severe neurodevelopment was defined on motor, sensorial impairment, epilepsy and neurodevelopmental delay. Main measurement was relative risk ratio (aRRR) and 95% CI of disability, adjusted for birth circumstances and neonatal complications, estimated on complete and imputed cases. RESULTS:647 out of 794 newborns survived, and 463 were assessed. Severe, moderate or mild neurodevelopmental impairment was observed in 10.5% (95% CI 7.6-14.1), 11.8% (95% CI 8.7-15.6) and 22.0% (95% CI 17.9-26.6), respectively. Moderate to severe outcome was increased with an abnormal examination at discharge (aRRR=4.22, 95% CI 1.74-10.25) and hypoglycemia (aRR=8.54, 95%CI 1.88-38.73.05) while hypothermia decreased it (aRRR=0.36 95% CI 0.13-0.99). Mild outcome was associated with neonatal infection (aRRR 3.73, 95% CI 1.55-8.98-8.36), while higher gestational age seemed protective (aRRR 0.83, 95% CI 0.69-1.00). CONCLUSION:Four in 10 HIE had neurodevelopmental sequelae, half of which were mild. A more immature brain or exposure to neonatal infection seemed to worsen prognosis, irrespective of disease severity. TRIAL REGISTRATION:Clinical trials registry, NCT02676063, ClinicalTrials.gov. IMPACT:Follow-up at 3 in a 647 children with HIE Sarnat grades I to III, mostly treated by hypothermia showed impairment of motor, sensorial and learning skills in 44.4%, of which 10.5% and 11.8% were moderate and severe respectively. 45.7% of children have at least one rehabilitation treatment, including 26% of children with favorable outcome. Neonatal infection increased the risk of unfavorable evolution, while more advanced gestational age and hypothermia were protective. In addition to clinical or MRI severity, our data suggest to integrate gestational age and neonatal infection into early prognostic assessment, and extending HIE follow-up to school age.

BACKGROUND:Newborn screening enables early detection and treatment of serious genetic conditions before symptom onset. Lysosomal diseases, a group of more than 70 rare inherited metabolic disorders, are increasingly considered for inclusion in NBS owing to advances in pathophysiological understanding and therapy development. Early, pre-symptomatic identification offers a critical window for intervention that can improve neurodevelopmental outcomes and quality of life. METHODS:To evaluate the feasibility of high-throughput, multi-tiered newborn screening for 13 lysosomal diseases, in the LysoNeo pilot study, families of 106,609 newborns were approached between March 2021 and November 2024; 100,212 consented, and 100,000 newborns were successfully screened. Dried blood spots collected shortly after birth underwent a multi-tier screening process combining first-tier biochemical testing, repeat testing of abnormal samples, second-tier reassessment, multidisciplinary review and confirmatory biochemical and molecular investigations for recalled newborns. RESULTS:Among 106,609 families approached, consent is obtained for 100,212 (94.0%), and screening is successfully completed for 100,000 newborns. First-tier screening identifies 75 newborns with abnormal results (screen-positive rate: 0.075%). Following second-tier reassessment and multidisciplinary review, 14 newborns are recalled (recall rate: 0.014%). Eight newborns have concordant biochemical and molecular findings consistent with lysosomal disease (confirmed case rate: 0.008%; Predictive Positive Value among recalled: 57.1% [8/14]; Predictive Positive Value among first-tier positives: 10.6% [8/75]). Two newborns initiate disease-specific therapy and six remain under structured follow-up. CONCLUSION:LysoNeo demonstrates the feasibility of implementing expanded lysosomal diseases newborn screening within a regional healthcare system and provides real-world evidence on screening cascade dynamics and actionability-based governance to inform national policy.

BACKGROUND AND OBJECTIVES:Developmental and epileptic encephalopathies (DEEs) with early burst-suppression EEG (EIDEE-BS) are among the most severe neonatal epileptic syndromes, typically presenting in the first months of life with refractory seizures and profound neurodevelopmental impairment. Although variants in the KCNQ2, STXBP1, and SCN2A genes are recognized as major causes, the full genetic spectrum remains uncertain. We aimed to delineate the electroclinical characteristics, genetic etiologies, and long-term outcomes in a large MRI-negative EIDEE-BS cohort. METHODS:We retrospectively analyzed 110 patients with BS EEG enrolled from a database of 1,540 individuals with suspected genetic epilepsies (2008-2023). Clinical, EEG, and genetic data were systematically collected. Patients were stratified into 4 groups: KCNQ2, STXBP1, "other pathogenic variants," and "without a genetic diagnosis." EEG traces were reviewed independently, and outcomes were assessed through long-term follow-up. RESULTS:Pathogenic or likely pathogenic variants were identified in 62.7% of patients and involved 23 genes, including 2 copy number variants. KCNQ2 (n = 24) and STXBP1 (n = 16) accounted for one-third of diagnoses, whereas SCN2A (n = 3) and KCNT1 (n = 2) were less frequent. In KCNQ2 cases, seizures and BS onset occurred earlier than in STXBP1 cases: mean 2 days vs 6 weeks for seizures and 3 days vs 2 months for BS, respectively. A typical BS pattern (bursts longer than suppressions) strongly correlated with KCNQ2 and STXBP1 variants. Novel associations were found with DPM1, GRIN2A, KCNT2, PIGO, PURA, WWOX, and candidate genes (KMT2E, SNAP25, and SYT1). Most variants were de novo heterozygous; however, recessive and X-linked inheritance patterns were also observed. Mortality was high (25%), primarily from status epilepticus and complications of severe disability. Most patients (72.5%) had persistent seizures at follow-up (a mean of 6.5 years), as well as profound intellectual disabilities, irrespective of genotype. DISCUSSION:This large series highlights the strong monogenic basis of EIDEE-BS. KCNQ2, STXBP1, and SCN2A were the most commonly affected genes. Early EEG features, particularly BS timing and morphology, can help anticipate the underlying genotype and guide precision therapy, including the early use of sodium channel blockers in selected cases. These findings support recent ILAE reclassification efforts and underscore the importance of comprehensive genomic testing for improved diagnosis and counseling.

Prenatal alcohol exposure (PAE) induces neurodevelopmental damage leading to fetal alcohol spectrum disorders (FASD) by altering both brain and ocular development. Recent data showed that PAE impairs brain cortical and retinal vasculature leading to defective positioning of interneurons. In the retina, PAE disturbs vascular development and the association of calretinin neurons with vessels. The NMDA receptor (NMDAR) is a major target of alcohol in the brain, and both ligand binding to NMDARs and the expression of NMDAR subunits are altered in FASD. Given that NMDAR is also expressed in endothelial cells and that glutamate stimulation of endothelial NMDAR (eNMDAR) regulates cortical interneuron positioning along blood vessels, we hypothesize that eNMDAR is critical for retinal vascular development and mediates PAE-induced defects. Using an in vivo model of FASD and transgenic mice lacking the endothelial GluN1 subunit of the NMDAR, this study aimed to characterize the neurovascular phenotype of the developing retina in mice of either sex. Our findings show that deletion of the eNMDAR reproduces key PAE-like alterations, including impaired progression of the superficial vascular plexus and changes in neuronal density, particularly in cells located closest to the retinal vasculature. Conversely, in eNMDAR knock-out mice, some of the retinal defects typically induced by PAE are prevented. Moreover, eNMDAR deletion led to an increased number of calretinin-positive interneurons contacting vessels and prevented the PAE-induced decrease. Together, these findings demonstrate that eNMDARs contribute to normal retinal neurovascular development and mediate, at least in part, the adverse effects of ethanol exposure in FASD.

Neuroplacentology is an emerging field of research supporting that the placenta actively contributes to the fetal brain development through the release of bioactive molecules. Recent angiogenesis-focused data showed that prenatal alcohol exposure (PAE) disrupts inter-organ gene expression between the placenta and fetal cortex. The present study aimed to perform the first comprehensive and untargeted analysis of a murine placenta-cortex transcriptomic database of PAE. Gene lists from a recently NCBI-deposited PAE Placenta-Cortex transcriptomic database were analyzed using g:Profiler for unbiased functional profiling querying Gene Ontology, KEGG, and Reactome databases. Genes intersecting with cell-cell communication terms were submitted to STRING and ShinyGO analyses to identify enriched protein-protein interactions and pathways. Several ligand or receptor candidates were then validated by Western blot. g:Profiler revealed 21 enriched GO functional maps, seven KEGG pathways, and six Reactome pathways, of which 11 were related to cell-to-cell communication. STRING analysis exhibited substantial protein-protein interaction enrichments supporting that proteins belonging to the functional maps and pathways are biologically connected. Notably, 38 ligands or receptors from endocrine families including angiotensinogen, leptin, somatostatin, or PACAP were identified. Western blot analysis of protein candidates showed different validation patterns. In particular, the PACAP receptor family confirmed transcriptomic findings and revealed sex-dependent PAE-impacted expression profiles. The present study indicates that PAE is associated with alterations in the transcriptomic placenta-cortex expression profile, including changes in the expression ratios of several ligands and/or receptors implicated in key physiological pathways such as energy balance, vascular development, and neurogenesis. These transcriptomic associations suggest that altered placenta-fetal brain signaling at the gene expression level may be involved in alcohol-induced neurodevelopmental disorders, highlighting the need for future functional validation studies.

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder caused by SMN1 gene variants, leading to the degeneration of anterior horn cells in the spinal cord. It is a disabling disease with varying severity. Nusinersen, the first approved in France, has dramatically transformed SMA management. However, the significant variability in patient response and disease progression highlights a critical need for objective, measurable indicators. This study aims to identify biomarkers in cerebrospinal fluid (CSF) and plasma associated with the clinical status of treatment-naive patients and their disease progression during therapy. We performed targeted metabolomics and proteomics analyses on plasma and CSF samples from SMA patients before and after six months of treatment, along with controls. The differential analysis was carried out to discover the SMA biomarkers. We found that levels of acylcarnitines, biogenic amines, and neurology-related proteins were mainly elevated, while glycerophospholipids primarily decreased in SMA plasma samples compared to controls. The biomarkers showed good performance in distinguishing SMA from controls with plasma AUCs >0.9. NEFH and creatinine were among the most prominent biomarkers for SMA diagnosis. Besides, 26 neurology-related proteins were found to be altered in patient CSF compared to controls. Furthermore, 11 potential proteins were identified to distinguish patients with 2 copies of SMN2 from those with 3 or 4 copies using plasma. By unveiling specific biomarkers, this study offers valuable insights for accurate disease diagnosis and monitoring treatment effectiveness. This enables personalized SMA management and accelerates the development of targeted therapies.

INTRODUCTION:Dystextia refers to a kind of aphasia. It is the inability or the difficulty to text with a mobile phone. It has been described 15 years ago in central neurologic pathologies like stroke, migraine with aura, neurologic tumor disease. CASE PRESENTATION:We report the case of a 15-year-old boy who presented a febrile dystextia with acute insular lobes lesions in MRI. Human Simplex Virus 1 and lymphocytosis were present in the CSF and intravenous treatment with aciclovir has been initiated. Clinical signs were completely reversible. DISCUSSION:This case enhances the importance of emerging symptoms related to the common use of 21st century technology-such as smartphones-especially among younger patients. It also corroborates the association between the insular lobe and dystextia. CONCLUSION:This is the first report of herpetic meningoencephalitis revealed through febrile dystextia in a child.

La protection du développement et de la maturation du cerveau de l’enfant né prématuré reste une priorité pour les néonatalogistes et les obstétriciens compte tenu du risque élevé de troubles du neurodéveloppement/troubles du spectre autistique retentissant sur la qualité de vie et limitant le fonctionnement, les apprentissages scolaires et l’intégration dans la vie sociale et culturelle des enfants et des familles. L’administration anténatale de sulfate de magnésium est recommandée par l’OMS et la plupart des sociétés savantes internationales. Les essais randomisés et les méta-analyses les plus récentes de 2024 et 2025 confirment que le sulfate de magnésium réduit le risque de paralysie cérébrale de 30 % à 2 ans avec un fort niveau de preuve, et le risque d’hémorragies intracrâniennes en période néonatale avec un niveau de preuve modéré. Aucune différence significative n’est observée dans le taux d’effets secondaires délétères sévères chez la mère comme chez le nouveau-né. L’optimisation des méthodes d’administration est désormais un défi majeur, l’objectif étant d’atteindre un taux d’administration anténatale de plus de 90 % chez les patientes éligibles. D’autres études sont nécessaires pour déterminer la dose optimale, le moment de l’administration, la pertinence et la durée de la dose d’entretien, la voie d’administration et, enfin, le résultat à long terme des enfants exposés au MgSO4 pendant la période prénatale.

Perinatal asphyxia (PA) remains a common cause of neonatal death and long-term disability, with an incidence of 20 per 1000 live births. Even mild PA, without significant neurological distress at birth, is linked to neurodevelopmental disorders. Premature babies are at high risk for both PA and long-term neurobehavioral deficits. The use of peripherally inserted central venous catheters in neonatal intensive care units has reduced mortality and morbidity in preterms. Given their prevalent use and associated complications, such as thrombosis, the present study aimed to investigate the effects of hypoxia associated with the ligation of the external jugular vein (JH model) in 5-day-old mice, whose central nervous system development shares similarities with that of human preterms. Diffuse white matter (WM) injury is associated with later neurodisabilities following very premature birth before 32 weeks of gestation. The present study aimed to investigate whether the murine JH model replicates a key phenotype of non-cystic WM injury, namely permanent hypomyelination and sensorimotor deficits. The second aim was to determine whether sodium phenylbutyrate (PBA), which is already prescribed in neonates for another indication, could prevent these disabilities. JH induced lasting dysmyelination in males, not prevented by PBA, contrary to the discrete JH-induced neurobehavioral deficits observed in both sexes in the short and long term.

BackgroundSphingolipidoses are rare inherited metabolic diseases belonging to lysosomal diseases. Early and accurate diagnosis is crucial for effective management and treatment. In this study, we aimed to develop a robust method to accelerate the diagnosis of these sphingolipidoses using dried blood spots and plasma.MethodWe employed high-resolution mass spectrometry coupled with liquid chromatography (LC-HRMS) to analyze 6 lysosphingolipids (GlcSph/Psychosine, LysoGb3, LysoSM, LysoSM509, LysoGM1, and LysoGM2) on dried blood spots and plasma samples. The method was used to measure the lysosphingolipid levels in a group of 30 control subjects and 204 samples from patients with sphingolipidoses (61 dB and 143 plasma) including Fabry, Gaucher, GM2 Gangliodosis, Niemann-Pick type A/B, and Niemann-Pick type C.ResultsThe developed multiplex LC-HRMS method demonstrated linearity, precision, and quantification performances particularly for GlcSph/Psychosine and LysoGb3 on samples including controls and patients with sphingolipidoses. LysoSM showed recovery variability, wherease LysoGM1 and LysoGM2 showed higher matrix effect.ConclusionOur study presents a high-resolution mass spectrometry method along with the established cutoff values, providing a valuable tool for targeted screening, accurate diagnosis, and monitoring sphingolipidoses. Furthermore, DBS showed reliable results that lay the path to a broader adoption for screening these diseases.

During cortical development, oligodendrocyte precursor (OPC) attachment and detachment to microvessels play a crucial role in their positioning and differentiation. In the developing brain, endothelial cells are regionally diverse, and previous studies showed a peak in cortical endothelial NMDA receptor (eNMDAR) expression during perinatal life, coinciding with OPC migration along microvessels. This raises the hypothesis that eNMDAR might influence the fate of vessel-associated OPC. In this study, a Grin1lox/lox/VeCadCre mouse model was used to investigate in females and males the effects of endothelial GluN1 invalidation (eNMDAR-/-) on (1) positioning and differentiation of cortical oligodendrocytes and myelination, (2) OPC/microvessel association and endothelial MMP9-like activity, and (3) motor activity. Results showed that, from postnatal days (P) 2 to P15, PDGFRα expression was increased in eNMDAR-/- mice and returned to wild-type levels by P45. CNPase and MBP expression was reduced at P15 and remained low in adult eNMDAR-/- mice. Histological analysis revealed no change in OPC-microvessel association, but positioning was altered with increased density in layers VI and V at P15. Myelination was impaired, as evidenced by thinner corpus callosum, reduced myelin sheath thickness, and higher g-ratio. Axonal mitochondria density was significantly increased. Functional tests revealed that glutamate could not stimulate endothelial MMP9-like activity in eNMDAR-/- mice. Molecular, histological and functional changes were linked to sensorimotor disabilities. At P45, despite the absence of observable myelination defects, locomotor impairments persisted, suggesting that early OPC differentiation disruption contributes to lasting motor dysfunction. These findings offer new insights into OPC vulnerability in human preterm infants.

The up-dated literature, notably the 2024 Cochrane review, and meta-analysis with individual data, as well as the identified socio-economic benefits, confirms that the administration of magnesium sulfate is recommended in women at risk of imminent preterm delivery before 32 weeks of gestation. In preterm infants, this intervention significantly reduces the risk of neonatal intracranial haemorrhage (moderate level of evidence), which is associated with an increased risk of subsequent neurodisabilities, as well as a very significant reduction in the risk of subsequent cerebral palsy in children (strong level of evidence). No effect on fetal, neonatal or infant mortality rates was observed. Given the still high rates of CP in the subgroup of children born between 30 and 32 or even 32-34 SA, and the absence of severe adverse events in both mother and child, it could be proposed to administer MgSO4 up to 34 SA (expert opinion). Magnesium sulfate is currently the only pharmacological molecule with a proven neuroprotective effect in preterm infants. It represents one of the means available to us to modulate the neurodevelopmental trajectory of the child, in particular the development of neuromotor skills. Optimization of administration methods is now a major challenge, with the aim of achieving an antenatal administration rate of over 90% in eligible patients. Further studies are needed to determine the optimal dosage, the timing of administration, the appropriateness and duration of the maintenance dose, the route of administration and, finally, the long-term outcome of children exposed to MgSO4 in the antenatal period.

Background and objectives: Neurosurgical intervention on the newborn’s developing brain is a risk factor for neurodevelopmental disorders (NDDs). These patients necessarily require regular, coordinated follow-up. The ventricular subgaleal shunt (VSGS) technique has been used since 2013 at Rouen University Hospital. Like any change in practice, this technique must be evaluated. In this paper, we describe the population of patients with hydrocephalus treated by VSGS, the complications associated with the procedure, and the outcome of these patients at two and six years old. Methods: This study was an observational, descriptive, retrospective, single-center study. Children included were those less than three months old with hydrocephalus treated by VSGS at Rouen University Hospital from January 2013 to December 2023. Data were anonymized and collected using EDSaN software. A descriptive analysis was performed. Results: Thirty-two patients were included in our study. Of these, 22 (69%) were born prematurely; 16 (50%) of these 22 had postnatal intraventricular hemorrhage (IVH) requiring treatment with VSGS. A total of three patients (13.6%) died within the first year of life; twenty-four patients (75%) required definitive shunting. Twenty-two patients were over 2 years old in our study. Only 10 of them acquired the ability to walk (45%). Cerebral palsy was present in 10 (45%) patients. Fifteen patients were over 6 years old; thirteen (87%) attended school, but six (40%) had special needs (the need of an assistant, or part-time schedule). In our study, only 24 patients (82%) were followed by a pediatrician trained in neurodevelopment at Rouen University Hospital, and 27 (93%) were followed by a neurosurgeon. Conclusions: This study describes all patients with hydrocephalus treated by VSGS at Rouen University Hospital between January 2013 and December 2023, as well as their complications and their neurological outcomes. The follow-up of these children at risk of NDDs is essential.

Introduction Developmental care delivered during the hospitalization of preterm newborn is now considered as gold standard practice. Healthcare professionals at the University Hospital of Rouen have been trained in developmental care based on André Bullinger's approach, using sensorimotor behavior observation grids to assess preterm infants. While compelling, this approach have been studied less extensively than the NIDCAP program. Being part of a larger effort to promote Bullinger's approach, this first study aims to evaluate the feasibility of using these grids. Materials and methods This is a monocentric, observational cohort study conducted at the University Hospital of Rouen. All preterm neonates born before 33 weeks of gestational age (GA) and admitted between January 1, 2019, and December 31, 2023, were included. Bullinger's observation grid was proposed in the newborn's digital health record and should be filled weekly. Results A total of 979 preterm infants under 33 weeks of GA were included. Sixty-one percent of the included preterm infants were observed during their hospitalization. Preterm infants between 28 and 30 weeks of GA received significantly more observations per week, with 0.44 observations per week on average. Mean observations recorded significantly increased, reaching a peak in 2021. Conclusion The use of sensorimotor observation is feasible. Therefore, it is essential to encourage evaluation of the impact of André Bullinger's sensorimotor approach on the child.

Background Very preterm children are at greater risk of academic difficulties (AD). Some of them start school a year earlier than anticipated during pregnancy due to being born preterm. The aim of this study was to analyze the relationship between neurodevelopment, school-entry age, and AD at age seven. Method AD were assessed at age seven in children born before 33 weeks of gestation between January 1st, 2007 and December 31, 2014 and enrolled in LIFT cohort. To analyze the relationship between school-entry age and AD, we used generalized equations with adjustment for perinatal, socio-economic factors, and neurodevelopment assessed by Age Stages Questionnaire (ASQ) at 5 years. Moreover, we used Global Scholar Adaptation (GSA) score to evaluate the school adaptation. Results 2599 children were in routine schooling. Entering school a year earlier was observed in 597 (23.0 %). AD was known for 1943/2599 (74.8 %). Starting school a year earlier was associated with an increased rate of AD: 35.4 % in the exposed group versus 20.2 % in the non-exposed group, with a relative risk of 1.76 (95 % CI: 1.48; 2.08). Both starting school a year earlier and ASQ at 5 years old were independently associated with the GSA score at age 7: standardized β = -0.15 (95 % CI:-0.10;-0.20) and 0.40 (95 % CI: 0.35; 0.45) respectively. Conclusion Starting school a year earlier than anticipated during pregnancy was associated with an increased rate of AD at age 7 in children born very preterm, independently of their neurodevelopment at age 5 assessed by ASQ. Basing school entry age on corrected age seems appropriate to mitigate this risk.

BACKGROUND:Children born preterm face higher risks of neurodevelopmental difficulties that, with social vulnerabilities, may impair school performance. We described and assessed determinants of receiving school support in preterm-born children in France. METHODS:We used data from the prospective population-based cohort of births before 35 weeks' gestation in France, EPIPAGE-2, to estimate crude rates and adjusted relative risks (using multivariable, mixed-effects generalized linear models) of receiving school support at age five, by children's neurodevelopment at five, sociodemographic characteristics, and region. RESULTS:Out of 3,007 children, 99% attended mainstream school at age five, of whom 9% received school support. Support was more often received by boys (11%; aRR = 1.37) than girls (6%), children born at 24-27 weeks' gestation (21%; aRR = 2.78 compared to 32-34 weeks), and children with moderate or severe neurodevelopmental impairments (MSNDI: cerebral palsy, cognitive impairment, visual impairment or blindness, and/or hearing impairment or deafness) (39%; aRR = 17.25 compared to none). Receiving support was not associated with sociodemographic characteristics, after adjusting for covariates. CONCLUSIONS:Neurodevelopmental impairment is a key determinant for receiving school support. However, 9% of the cohort and under 40% of children with MSNDI were receiving support, raising questions on whether unmet needs for school support exist in France. IMPACT:This study provides an overview of school support received at age five by children born before 35 weeks' gestation in France, and associated determinants Less than 10% of the total cohort and 40% of children with a moderate or severe neurodevelopmental impairment were receiving school support Cognitive and neurodevelopmental impairments were key determinants for receiving school support, but sociodemographic characteristics were not Our results raise questions about whether unmet needs for school support exist, calling for further research on the support available in schools, decision-making processes for allocating them, and the psychosocial and academic consequences of their provision on children.

Neuromuscular disorders encompass a spectrum of conditions characterized by primary lesions within the peripheral nervous system, which include the anterior horn cell, peripheral nerve, neuromuscular junction, and muscle. In pediatrics, most of these disorders are linked to genetic causes. Despite the considerable progress, the diagnosis of these disorders remains a challenging due to wide clinical presentation, disease heterogeneity and rarity. It is noteworthy that certain neuromuscular disorders, once deemed untreatable, can now be effectively managed through novel therapies. Biomarkers emerge as indispensable tools, serving as objective measures that not only refine diagnostic accuracy but also provide guidance for therapeutic decision-making and the ongoing monitoring of long-term outcomes. Herein a comprehensive review of biomarkers in neuromuscular disorders is provided. We highlight the role of omics-based technologies that further characterize neuromuscular pathophysiology as well as identify potential therapeutic targets to guide treatment strategies.