Sleep as a window for evaluating neurodevelopmental outcome: which impact on the brain of preterm infants? A prospective study on prematurity from a biological neuropsychiatry perspective

Background. Newborns and infants spend most of their time sleeping an immature sleep, which allows brain maturation a good neurodevelopment. Preterm birth is associated with abnormal brain development and alterations in later-in-life sleep patterns, carrying a high social burden, even when not accompanied by major neurological damages. Which impact prematurity itself can have on early sleep architecture, which influence it can have on well- known adverse outcomes, and which role brain lesions play in determining sleep patterns in preterm infants are still matter of debate. This exploratory pilot study aimed to describe the distribution of sleep states among very low birth weight (VLBW) infants, and to correlate it with neurobehavioral assessment at 35 weeks of post-menstrual age (PMA), and to observe if these persisted at term equivalent age (TEA) and at 6 months of corrected age (CA). Secondly, it aimed to assess if the presence of a major or minor brain lesion detected at MRI can affect sleep duration, distribution and quality. Methods. 10 VLBW were assessed at 34±2 weeks PMA with a 24-hours video- polysomnographic recording and received a neurobehavioral examination at the moment of the recording and at TEA (with Neonatal Behavior Assessment Scale; Hammersmith Neurological Neonatal Examination, and the neonatal visual battery). They were followed- up at 6 months CA with Griffiths’ Mental Development Scale III edition. Analysis of sleep stages distribution and spectra was conducted. Results. Total sleep time and total amount of transitional sleep (TS) significantly positively correlated with neurological, and neurobehavioral assessment at 34 weeks PMA, at TEA and with neurodevelopment at 6 months CA, while Sleep Onset Active Sleep (SOAS) had a negative association. Infants carrying severe-moderate brain lesions showed lower Total Sleep time (66.9% ± 7.39 vs 72.2% ± 3.52, p = 0.047) accompanied by a higher prevalence of SOAS (23.9% ± 10.2 vs 12.26% ± 5.5 p = 0.048), and showed a gradient for higher power of posterior slow activity (slow δ and δ) during SOAS from the posterior cerebral regions. Conclusions. Understanding sleep mechanism among preterm infants might provide future therapeutic/management strategies, which need to encompass sleep care. Further analyses with larger samples and more complex methods are claimed

Psychological Impact of the Very Early Beginning of the COVID-19 Outbreak in Healthcare Workers: A Bayesian Study on the Italian and Swiss Perspectives

Background: We investigated the COVID19-related psychological impact on healthcare workers in Italy and in Italian-speaking regions of Switzerland, three weeks after its outbreak. All professional groups of public hospitals in Italy and Switzerland were asked to complete a 38 questions online survey investigating demographic, marital and working status, presence of stress symptoms and need for psychological support. Results: Within 38 h a total of 3,038 responses were collected. The subgroup analysis identified specific categories at risk according to age, type of work and region of origin. Critical care workers, in particular females, reported an increased number of working hours, decline in confidence in the future, presence of stress symptoms and need for psychological support. Respondents reporting stress symptoms and those with children declared a higher need for psychological support. Conclusions: The large number of participants in such a short time indicates for a high interest on topic among health-care workers. The COVID19 outbreak has been experienced as a repeated trauma for many health-care professionals, especially among female nurses' categories. Early evidence of the need of implementating short and long-term measures to mitigate impact of the emotional burden of COVID-19 pandemic are still relevant

Psychological Impact of a Pandemic Widespread in Healthcare Workers: The Italian and Swiss Perspective Early After of {CoVid}-19 Outbreak

Background. We investigated the COVID19-related psychological impact in healthcare workers three weeks after its onset in Italy and in Italian-speaking regions of Switzerland. All professional groups of public hospitals in Italy and Switzerland were asked to complete a 38 questions online survey investigating demographic, marital and working status, presence of stress symptoms and need for psychological support. Results. Within 38 hours a total of 3,038 responses were collected. The subgroup analysis identified specific categories at risk according to age, type of work and region of origin. Critical care workers, in particular females, reported an increased number of working hours, decline in confidence in the future, presence of stress symptoms and need for psychological support. People reporting stress symptoms and those with children declared a higher need for psychological support. Conclusions. The large number of participants in such a short time advocates for a high interest on topic among hospital workers. The COVID19 outbreak could have been and still be a repeated trauma for many health professionals, with risk of future psychiatric sequelae. It is of outstanding importance to implement short and long-term measures to mitigate impact of the emotional burden of this pandemic while at the same time dealing with its clinical challenges

Assisted reproductive technology and breastfeeding outcomes: a case-control study

Objective: To determine if breastfeeding outcomes differ between mothers who conceived spontaneously compared with those who conceived with assisted reproductive technology (ART). Design: Matched case-control study. Setting: Teaching hospital. Patient(s): Ninety-four women having a singleton baby conceived with ART, matched by maternal age, parity, mode of delivery, and gestational age to controls who conceived spontaneously. Intervention(s): Cases and controls were interviewed using a standardized, structured questionnaire, to obtain information on lactation. Exposure to maternity care practices contributing to breastfeeding success was investigated. Main Outcome Measure(s): Initiation, exclusivity, and continuation of breastfeeding. Result(s): Cases were as likely as controls to initiate breastfeeding (89.4% vs. 90.4%), but by 6 weeks postpartum, a greater proportion of mothers who conceived through ART has ceased breastfeeding (20.2% vs. 5.3%). The percentage of mothers who exclusively breastfed their child for 6 months was similar among the 2 groups. On univariate conditional logistic regression, a history of using ART was the only predictor of early breastfeeding cessation (odds ratio = 65.3 [95% confidence interval: 1.5-2889.3]). Conclusion(s): Women who have conceived with ART should be regarded as being at higher risk for early breastfeeding cessation. This study serves as a first step in the investigation of potential modifiable factors that contribute to breastfeeding failure among women who give birth after using ART, and may help in efforts to customize breastfeeding support strategies

Clinical and Molecular Characterization of Two Patients with CNTN6 Copy Number Variations

Submicroscopic chromosomal alterations usually involve different protein-coding genes and regulatory elements that are responsible for rare contiguous gene disorders, which complicate the understanding of genotype-phenotype correlations. Chromosome band 3p26.3 contains 3 genes encoding neuronal cell adhesion molecules: CHL1, CNTN6, and CNTN4. We describe 2 boys aged 8 years and 11 years mainly affected by intellectual disability and autism spectrum disorder, who harbor a paternally inherited 3p26.3 microdeletion and a 3p26.3 microduplication, respectively. Both anomalies involved only the CNTN6 gene, which encodes contactin 6, a member of the contactin family (MIM 607220). Contactins show pronounced brain expression and function. Interestingly, phenotypes in reciprocal microdeletions and microduplications of CNTN6 are very similar. In conclusion, our data, added to those reported in the literature, are particularly significant for understanding the pathogenic effect of single gene dosage alterations. As for other recurrent syndromes with variable phenotype, these findings are challenging in genetic counselling because of an evident variable penetrance

Stress symptoms and Coronavirus disease 2019 (COVID-19): a comparative study between Attention Deficit Hyperactivity Disorder and typically developing children and adolescents

BACKGROUND: Coronavirus disease 2019 (COVID-19) related confinement severely impacted people wellbeing. Many studies focused on general population, although it is reasonable to expect that patients with neurodevelopmental disorders might have been at higher risk. Children/adolescents with Attention Deficit/Hyperactivity Disorder (ADHD) might be potentially more vulnerable, due to their intolerance to forced restrictions that limit stimulating experiences, to obligation to follow instructions and to acceptation of imposed rules We aimed to compare stress-related behavioral changes of the first COVD-19 related confinement among 6-18 years old ADHD and typically developing subjects. METHODS: Two parent-proxy online surveys have been employed, shared via social media. Symptoms of acute stress related to the pandemic and a question about family members/households\u2019 COVID-19 positivity have been listed in 8 yes/no items. Chi-squared tests were applied. RESULTS: Final sample consisted of 1078 typically developing subjects and 979 ADHD. Exaggerated startle response, difficulties in waking-up, angry mood as well as COVID-19 related fears were more prevalent among ADHD vs. typically developing subjects. typically developing subjects showed higher prevalence of research for information about COVID-19 and worries about death. CONCLUSIONS: In conclusion, the COVID-19 experience significantly impacted children and adolescents with ADHD to a great extent, similarly to typically developing subjects. ADHD showed more anxious-phobic responses, while typically developing subjects demonstrate more depressive attitudes. Differences in stress symptoms profiles between ADHD and T typically developing subjects warrant to develop distinct strategies of therapeutic interviews

1p31.1 microdeletion including only NEGR1 gene in two patients.

Neuronal growth regulator 1 (NEGR1), a member of the immunoglobulin superfamily cell adhesion molecule subgroup IgLON, has been involved in neuronal growth and connectivity. Genetic variants, in or near the NEGR1 locus, have been associated with obesity and, more recently, with learning difficulties, intellectual disability, and psychiatric disorders. Here, we described the only second report of NEGR1 gene disruption in 1p31.1 microdeletion in two patients. Patient 1 is a 14-year-old female with neurological and psychiatric features present also in her family. Patient 2 is a 5-month-old infant showing global hypotonia as unique neurological features till now. This patient also carries 7p22.1 duplication, of paternal origin, that could be responsible for some malformations present in the child. We hypothesize a role of NEGR1 in producing the phenotype of our patients and compare them with other cases previously reported in the literature and DECIPHER database to better identify a possible genotype-phenotype correlation

The effects of mild germinal matrix-intraventricular haemorrhage on the developmental white matter microstructure of preterm neonates: a DTI study

Objectives: To evaluate white matter (WM) microstructural changes in preterm neonates (PN) with mild germinal matrix-intraventricular haemorrhage (mGMH-IVH) (grades I and II) and no other associated MRI abnormalities, and correlate them with gestational age (GA) and neurodevelopmental outcome. Methods: Tract-based spatial-statistics (TBSS) was performed on DTI of 103 patients studied at term-equivalent age, to compare diffusional parameters (fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), axial diffusivity (AD)) between mGMH-IVH neonates (24/103) and controls matched by GA at birth and sex. The relationship between DTI abnormalities, GA and neurodevelopmental outcome assessed with Griffiths\u2019 Developmental Scale-Revised:0-2 was explored using TBSS and Spearman-correlation analysis (p <.05). Results: Affected neonates had lower FA, higher RD and MD of the corpus callosum, limbic pathways and cerebellar tracts. Extremely preterm neonates (GA < 29 weeks) presented more severe microstructural impairment (higher RD and MD) in periventricular regions. Neonates of GA 65 29 weeks had milder WM alterations (lower FA), also in subcortical WM. DTI abnormalities were associated with poorer locomotor, eye-hand coordination and performance outcomes at 24 months. Conclusions: WM microstructural changes occur in PN with mGMH-IVH with a GA-dependent selective vulnerability of WM regions, and correlate with adverse neurodevelopmental outcome at 24 months. Key Points: \u2022 DTI-TBSS analysis identifies WM microstructural changes in preterm neonates with mGMH-IVH. \u2022 Extremely preterm neonates with mGMH-IVH presented more severe impairment of WM microstructure. \u2022 Extremely preterm neonates with mGMH-IVH presented microstructural impairment of periventricular WM. \u2022 mGMH-IVH affects subcortical WM in preterm neonates with gestational age 65 29 weeks. \u2022 WM microstructural alterations are related to neurodevelopmental impairments at 24 months

Photoparoxysmal response in ADCK3 autosomal recessive ataxia: a case report and literature review

Mutations in AarF domain-containing kinase 3 (ADCK3) are responsible for the most frequent form of hereditary coenzyme Q10 (CoQ10) deficiency (Q10 deficiency-4), which is mainly associated with autosomal recessive cerebellar ataxia type 2 (ARCA2). Clinical presentation is characterized by a variable degree of cerebellar atrophy and a broad spectrum of associated symptoms, including muscular involvement, movement disorders, neurosensory loss, cognitive impairment, psychiatric symptoms and epilepsy. In this report, we describe, for the first time, a case of photoparoxysmal response in a female patient with a mutation in ADCK3. Disease onset occurred in early childhood with gait ataxia, and mild-to-moderate degeneration. Seizures appeared at eight years and six months, occurring only during sleep. Photoparoxysmal response was observed at 14 years, almost concomitant with the genetic diagnosis (c.901C>T;c.589-3C>G) and the start of CoQ10 oral supplementation. A year later, disease progression slowed down, and photosensitivity was attenuated. A review of the literature is provided focusing on epileptic features of ADCK3-related disease as well as the physiopathology of photoparoxysmal response and supposed cerebellar involvement in photosensitivity. Moreover, the potential role of CoQ10 oral supplementation is discussed. Prospective studies on larger populations are needed to further understand these data