RHOBTB2 was first described as epileptogenic when it presents a missense variant in 2016 and studied more specifically in 2018. It is a gene that causes rare, but potentially severe childhood epileptic encephalopathy. In 2021, research confirmed that heterozygous mutations of RHOBTB2 included other clinical signs besides these encephalopathies. Thus, these infantile epilepsies are mainly associated with highly variable phenotypes, with developmental delay, post-traumatic encephalitis, paroxysmal movement disorders and iconographic brain damage. In this work, after presenting a clinical case, we will recall the role of RhoGTPases on neuronal development. We will then discuss a study which highlighted the neurodevelopmental impact of mutations on the RHOBTB2 gene by carrying out work on Drosophila melanogaster flies. Finally, we will compare the presented clinical case with a literature review.
Le gène RHOBTB2 est décrit pour la première fois comme épileptogène alors qu’il présente un variant faux-sens en 2016, puis est étudié plus précisément en 2018. Il s’agit d’un gène qui est à l’origine d’encéphalopathies épileptiques infantiles rares, mais pouvant être sévères. En 2021, des recherches ont confirmé que les mutations hétérozygotes de RHOBTB2 englobaient d’autres signes cliniques que ces encéphalopathies. Ainsi, ces épilepsies infantiles sont associées, principalement, avec des phénotypes fortement variables, à un retard développemental, à des encéphalites post-traumatiques, à des troubles paroxystiques des mouvements et à des atteintes iconographiques de l’encéphale. Dans ce travail, après avoir présenté un cas clinique, nous rappellerons le rôle des RhoGTPases sur le développement neuronal. Nous discuterons ensuite d’une étude qui a mis en évidence l’impact neurodéveloppemental de mutations sur le gène RHOBTB2 en réalisant des travaux sur des mouches Drosophila melanogaster. Pour terminer, nous mettrons le cas clinique présenté en parallèle avec une revue de la littérature réalisée par rapport à ce gène.

Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are essential fatty acids for the human body. Seafood and microalgae are the most important sources of omega-3 fatty acids. Supplementation with 200 mg/day of DHA during pregnancy and breastfeeding has been suggested for women and infants in countries with low seafood consumption. Maternal concentration of DHA and EPA was associated with concentration in cord blood and breast milk. High concentrations of DHA and EPA were identified at the level of retinal photoreceptors and neuronal cell membranes. It was observed that supplementation with DHA and EPA during pregnancy had beneficial effects on the neurological development of the fetus and infant by improving language, memory, attention, and hand coordination, affecting sleep patterns, and improving visual acuity. Beneficial effects on the development of the infant were also associated with the maternal intake of omega-3 fatty acids during breastfeeding. Supplementation with DHA and EPA may reduce the risk of preterm birth but also of preeclampsia in low-risk pregnancies. Women of childbearing age should have an intake of 250 mg/day of DHA + EPA from their diet or supplements. To reduce the risk of premature birth, pregnant women must additionally receive at least 100-200 mg of DHA every day. It is recommended that supplementation with omega-3 fatty acids starts before 20 weeks of pregnancy. Beneficial effects on the mother have been identified, such as the reduction of postpartum depression symptoms, the decrease of cardiovascular risk, and the anti-inflammatory role.

Developmental delay is a multifaceted condition that can hamper a child\'s ability to attain developmental benchmarks within expected timelines. Vitamin B12 deficiency has been identified as a potentially reversible causative factor and is critical to neurological function, influencing myelination and nerve conduction. Insufficiency during critical developmental stages can lead to motor, cognitive, and language delays. Physiotherapy interventions have been found effective in addressing motor delays associated with both developmental delay and B12 deficiency. Early intervention programs that focus on motor skill development, sensory integration, and adaptive equipment use are among the interventions that physiotherapists provide. Collaboration with multidisciplinary teams allows physiotherapists to manage B12 deficiency effectively and provide rehabilitative strategies aimed at maximizing motor function and overall development for long-term health. Early identification and intervention in children with developmental delays is crucial, especially in cases related to vitamin B12 deficiency. Physiotherapy is a critical aspect of addressing motor delays associated with developmental delay and B12 deficiency. By providing early interventions, physiotherapists can help children attain their full potential and attain developmental milestones. In conclusion, this highlights the significance of early identification and intervention in children with developmental delay, especially those with vitamin B12 deficiency, for optimal long-term health.

This study aimed to investigate the impact of early erythropoietin (EPO) administration on the neurodevelopment of newborns, specifically focusing on its effects on hypoxic-ischemic encephalopathy (HIE) and intraventricular hemorrhage (IVH). The primary objective was to determine whether early EPO administration could impact the short-term neurodevelopmental outcomes and provide safety in neonates at risk for neurodevelopmental disorders. Conducted at the \"Louis Turcanu\" Children\'s Emergency Clinical Hospital in Timisoara, Romania, this observational study included 121 neonates receiving EPO and 130 No EPO controls. EPO was administered within the first 48 h of life, with doses of 1000 U/kg that escalated to 2000 U/kg if necessary. Besides observing the occurrence of IVH and HIE, this study measured clinical and biochemical markers, including LDH, blood glucose, urea, creatinine, CPK, CRP, PCT, and erythropoietin levels alongside hematology and coagulation profiles. There were no significant differences in baseline characteristics between the groups. The EPO group showed significant reductions in LDH levels from days 1-3 to 7-10 (695.0 U/L to 442.0 U/L) and the APTT value (54.0 s) compared with the No EPO group (38.0 s). Notably, early EPO administration was associated with a significant decrease in HIE severity (beta coefficient: -0.38, p = 0.001). Additionally, lower gestational ages and hemoglobin levels correlated with increased severity of HIE. By week four, there was a significant reduction in moderate and severe HIE cases in the EPO group compared with controls (p = 0.001). Early administration of EPO in neonates significantly reduced the severity of IVH and HIE, suggesting its potential as a neuroprotective agent in neonatal care.

Nearly 80% of the world\'s population trusts traditional medicine and plant-based drug compounds to improve health, and more than 50% of women who participated in a study have used herbal remedies during pregnancy. Bocconia frutescens L. is a plant native to tropical America, where infusion of its leaves has been widely used for the treatment of several gastrointestinal disorders. We have already shown that orogastric consumption of B. frutescens L. during the organogenesis period at concentrations equivalent to human consumption produces teratogenic effects in rats, but effects on progeny development have not yet been studied. In this study, we aimed to investigate the possible association between the consumption of B. frutescens L. at a dose equivalent to that consumed by humans and the neurological development of rat progeny. Pregnant Wistar rats were administered lyophilized B. frutescens L. extract at 300 mg/kg/day or vehicle via the orogastric route during the organogenesis period (gestation days 7-13). The physical development and sensory and motor maturation of their offspring during lactation were analyzed with a battery of reflex and physical tests. B. frutescens L. produced a significant delay in physical development and sensorimotor maturation, compared to the control group. Proton nuclear magnetic resonance spectroscopy analysis showed signals for both flavonoids and alkaloids in the B. frutescens L. extract. We conclude that the delay in physical and neurological development could be interpreted as alterations in the maturation of some neuronal circuitries induced by B. frutescens L.

Particulate matter of size ≤ 2.5 μm (PM2.5) is a critical environmental threat that considerably contributes to the global disease burden. However, accompanied by the rapid research progress in this field, the existing research on developmental toxicity is still constrained by limited data sources, varying quality, and insufficient in-depth mechanistic analysis. This review includes the currently available epidemiological and laboratory evidence and comprehensively characterizes the adverse effects of PM2.5 on developing individuals in different regions and various pollution sources. In addition, this review explores the effect of PM2.5 exposure to individuals of different ethnicities, genders, and socioeconomic levels on adverse birth outcomes and cardiopulmonary and neurological development. Furthermore, the molecular mechanisms involved in the adverse health effects of PM2.5 primarily encompass transcriptional and translational regulation, oxidative stress, inflammatory response, and epigenetic modulation. The primary findings and novel perspectives regarding the association between public health and PM2.5 were examined, highlighting the need for future studies to explore its sources, composition, and sex-specific effects. Additionally, further research is required to delve deeper into the more intricate underlying mechanisms to effectively prevent or mitigate the harmful effects of air pollution on human health.

Sulfate is an important anion as sulfonation is essential in modulation of several compounds, such as exogens, polysaccharide chains of proteoglycans, cholesterol or cholesterol derivatives and tyrosine residues of several proteins. Sulfonation requires the presence of both the sulfate donor 3\'-phosphoadenosine-5\'-phosphosulfate (PAPS) and a sulfotransferase. Genetic disorders affecting sulfonation, associated with skeletal abnormalities, impaired neurological development and endocrinopathies, demonstrate the importance of sulfate. Yet sulfate is not measured in clinical practice. This review addresses sulfate metabolism and consequences of sulfonation defects, how to measure sulfate and why we should measure sulfate more often.

OBJECTIVE: To examine infant outcomes at 3 years of age in monochorionic twin pregnancies with Type-II or -III selective fetal growth restriction (sFGR) and isolated oligohydramnios who underwent fetoscopic laser photocoagulation (FLP).
METHODS: This multicenter prospective cohort study included monochorionic diamniotic twins that underwent FLP for sFGR between 16 and 25 weeks\' gestation. The indication for performing FLP was Type-II or -III sFGR with oligohydramnios of the growth-restricted (FGR) twin in which the maximum vertical pocket of amniotic fluid was ≤ 2 cm. This was done in the absence of a typical diagnosis of twin-twin transfusion syndrome. The primary outcome was intact survival rate of both infants at the corrected gestational age of 40 weeks and at 3 years of age. Intact survival at the corrected age of 40 weeks was defined as survival without Grade-III or -IV intraventricular hemorrhage or cystic periventricular leukomalacia. Intact survival at 3 years of age was defined as survival without neurodevelopmental morbidity, which included cerebral palsy, neurodevelopmental impairment with a total developmental quotient of < 70, bilateral deafness or bilateral blindness.
RESULTS: Among 45 patients with sFGR, 30 (66.7%) were classified as having Type-II and 15 (33.3%) as Type-III sFGR. The prevalence of intact survival at the corrected age of 40 weeks was 51.1% (n = 23) in FGR twins and 95.5% (n = 42) in larger twins. The prevalence of intact survival at 3 years of age was 46.7% (n = 21) in FGR twins and 86.4% (n = 38) in larger twins. There was one case of miscarriage. Among the 24 FGR twins who were not classified as having intact survival at 3 years of age, 22 (91.7%) cases suffered fetal or infant demise (other than miscarriage), and there was one case of neurodevelopmental impairment. All larger twins who were not diagnosed with intact survival at 3 years of age (n = 6 (13.6%)) had neurological morbidity.
CONCLUSIONS: FGR twins and their larger cotwins, when subjected to FLP owing to sFGR coupled with umbilical artery Doppler abnormalities and isolated oligohydramnios, exhibit low rates of neurological morbidity and low mortality, respectively. Therefore, FLP for Type-II or -III sFGR with oligohydramnios may be a feasible management option and one that is preferable to expectant management. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Accumulation of bilirubin above normal levels is considered a neurological risk factor for both premature and full-term newborns. This systematic review aimed to determine the effect of neonatal hyperbilirubinemia on neurodevelopment in preterm and full-term newborns.
PubMed, EMBASE, Cochrane Library, CINAHL, PsycINFO, Scopus and Lilacs databases were searched for articles published until 1 June 2022. The quality of cohort and case-control studies was assessed with the Newcastle-Ottawa Scale, and the MINCir scale was used to evaluate the methodological quality of therapy studies or the therapeutic procedures. Premature neonates without neurological conditions and those born at term with hyperbilirubinemia as the sole risk factor were included. Studies reporting one or more neurodevelopmental outcomes were included with an inter-group comparison of a hyperbilirubinemia group versus a non-hyperbilirubinemia or non-pathological hyperbilirubinemia group. The main outcomes were auditory function, visual function, cognitive function, motor function, behavior, global development and neurological risk.
The search identified 951 studies, 19 of which (n = 2210 newborns) were finally included. Fifteen of the cohort and case-control studies presented low risk of bias, and six studies showed high methodological quality. Within the preterm population, hyperbilirubinemia as the sole risk factor was not shown to affect neurodevelopment. Auditory, neurological and motor development alterations were found in the population of full-term newborns with hyperbilirubinemia, which were more evident during the first year of life.
Elevated bilirubin levels may be a trigger for the onset of neurodevelopmental disorders in full-term infants during the first year of life. More studies are warranted in the preterm population with hyperbilirubinemia to draw conclusions about its impact on their neurodevelopment.

OBJECTIVE: To investigate the impact of the environmental layout of the neonatal intensive care unit (NICU) on clinical outcomes and neurological development in very/extremely preterm infants.
METHODS: A total of 304 very/extremely preterm infants admitted to Children\'s Hospital of Chongqing Medical University between January 2021 and June 2022 within 24 hours after birth were included in this retrospective cohort study. Based on different environmental layouts in the NICU, the infants were divided into two groups: centralized layout group (n=157) and decentralized layout group (n=147). The clinical outcomes and Test of Infant Motor Performance (TIMP) scores at corrected gestational age between 34 to 51+6 weeks were compared between the two groups.
RESULTS: The decentralized layout group had lower incidence rates of bronchopulmonary dysplasia (44.9% vs 62.4%, P<0.05) and intracranial hemorrhage (17.7% vs 28.0%, P<0.05) than the centralized layout group. The cure rate was higher in the decentralized layout group compared to the centralized layout group (68.7% vs 56.7%, P<0.05). The decentralized layout group had higher TIMP scores than the centralized layout group at corrected gestational age between 34 to 51+6 weeks (P<0.05).
CONCLUSIONS: The decentralized layout of the NICU exhibits positive effects on the clinical outcomes and early neurological development compared to the centralized layout in very/extremely preterm infants.
目的: 探讨新生儿重症监护室（neonatal intensive care unit，NICU）环境布局对极/超早产儿临床结局及神经发育的影响。方法: 选取重庆医科大学附属儿童医院2021年1月—2022年6月收治、生后24 h内入院的304例极/超早产儿为研究对象。采用回顾性队列研究方法，根据NICU不同环境布局将患儿分为两组，即集中式布局组（157例）和分散式布局组（147例），比较两组患儿临床结局和校正胎龄34~51+6周时婴儿运动表现测试评分结果。结果: 分散式布局组支气管肺发育不良（44.9% vs 62.4%）和颅内出血（17.7% vs 28.0%）的发生率低于集中式布局组（均P<0.05）；分散式布局组治愈率高于集中式布局组（68.7% vs 56.7%，P<0.05）。在校正胎龄34~51+6周时，分散式布局组婴儿运动表现测试评分高于集中式布局组（P<0.05）。结论: NICU分散式环境布局较集中式布局在极/超早产儿临床结局及早期神经发育方面显示出积极的影响。.