Prenatal exposure to environmental air pollution and psychosocial stress jointly contribute to the epigenetic regulation of the serotonin transporter gene in newborns.

Antenatal exposures to maternal stress and to particulate matter with an aerodynamic diameter of less than 2.5 µm (PM2.5) have been independently associated with developmental outcomes in early infancy and beyond. Knowledge about their joint impact, biological mechanisms of their effects and timing-effects, is still limited. Both PM2.5 and maternal stress exposure during pregnancy might result in altered patterns of DNA methylation in specific stress-related genes, such as the serotonin transporter gene (SLC6A4 DNAm), that might, in turn, influence infant development across several domains, including bio-behavioral, cognitive and socio-emotional domains. Here, we investigated the independent and interactive influence of variations in antenatal exposures to maternal pandemic-related stress (PRS) and PM2.5 on SLC6A4 DNAm levels in newborns. Mother-infant dyads (N = 307) were enrolled at delivery during the COVID-19 pandemic. Infants' methylation status was assessed in 13 CpG sites within the SLC6A4 gene's region (chr17:28562750-28562958) in buccal cells at birth and women retrospectively report on PRS. PM2.5 exposure throughout the entire gestation and at each gestational trimester was estimated using a spatiotemporal model based on residential address. Among several potentially confounding socio-demographic and health-related factors, infant's sex was significantly associated with infants' SLC6A4 DNAm levels, thus hierarchical regression models were adjusted for infant's sex. Higher levels of SLC6A4 DNAm at 6 CpG sites were found in newborns born to mothers reporting higher levels of antenatal PRS and greater PM2.5 exposure across gestation, while adjusting for infant's sex. These effects were especially evident when exposure to elevated PM2.5 occurred during the second trimester of pregnancy. Several important brain processes (e.g., synaptogenesis and myelination) occur during mid-pregnancy, potentially making the second trimester a sensitive time window for the effects of stress-related exposures. Understanding the interplay between environmental and individual-level stressors has important implications for the improvement of mother-infant health during and after the pandemic.

The effect of executive function on health related quality of life in children with self-limited epilepsy with centrotemporal spikes.

AIM: The current study aims to investigate the effect of Executive Functions (EFs) on Health Related Quality of Life (HRQoL) in a cohort of children with self-limited epilepsy with centrotemporal spikes (SeLECTS) and to identify possible factors that impact HRQoL specifically related to epilepsy-related variables and EFs skills. MATERIAL AND METHOD: The Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL) and The Behavior Rating Inventory of Executive Function (BRIEF-2 and BRIEF-P) were completed by the parents of 129 patients with SeLECTS. Demographic variables and epilepsy-related variables were collected. RESULTS: Our sample performed in the average range across all the subscales and summary scores of the PedsQL and performed in the normal range of the BRIEF questionnaire. We observed that a lower functioning in EFs was associated with lower overall HRQoL scores. We explored the relationship between epilepsy characteristics and scores on the PedsQL. We found that the use of antiseizure medications (ASMs), longer duration of the treatment, and a higher seizure frequency were associated with a lower HRQoL. Moreover, we observed that executive dysfunction was a significant predictor of reduced HRQoL. CONCLUSION: Our results suggest the importance of the identification of patients with SeLECTS with a high level of risk for a poor HRQoL. We may now add executive dysfunction to the list of known risk factors for poor HRQoL in children with SeLECTS, along with such factors as seizure frequency, recent seizures, use of ASMs and longer duration of therapy. The early identification of children with SeLECTS at risk of a poor HRQoL could allow the activation of adequate interventions.

The effects of ketogenic dietary therapies on sleep: A scoping review.

Sleep problems are common in neurological conditions for which ketogenic dietary therapies (KDTs) are recognised as an effective intervention (drug-resistant epilepsy, autism spectrum disorder, and migraine). Given the composite framework of action of ketogenic dietary therapies, the prevalence of sleep disturbance, and the importance of sleep regulation, the present scoping review aimed at identifying and mapping available evidence of the effects of ketogenic dietary therapies on sleep. A comprehensive web-based literature search was performed retrieving publications published to June 2023 using PubMed and Scopus, yielding to 277 records. Twenty papers were finally selected and included in the review. Data were abstracted by independent coders. High variability was identified in study design and sleep outcome evaluation among the selected studies. Several changes in sleep quality and sleep structure under ketogenic dietary therapies were found, namely an improvement of overall sleep quality, improvement in the difficulty falling asleep and nighttime awakenings, improvement in daytime sleepiness and an increase of REM sleep. The relevance and possible physiological explanations of these changes, clinical recommendations, and future directions in the field are discussed.

Sex-dimorphic pathways in the associations between maternal trait anxiety, infant BDNF methylation, and negative emotionality.

Maternal antenatal anxiety is an emerging risk factor for child emotional development. Both sex and epigenetic mechanisms, such as DNA methylation, may contribute to the embedding of maternal distress into emotional outcomes. Here, we investigated sex-dependent patterns in the association between antenatal maternal trait anxiety, methylation of the brain-derived neurotrophic factor gene (BDNF DNAm), and infant negative emotionality (NE). Mother-infant dyads (N = 276) were recruited at delivery. Maternal trait anxiety, as a marker of antenatal chronic stress exposure, was assessed soon after delivery using the Stait-Trait Anxiety Inventory (STAI-Y). Infants' BDNF DNAm at birth was assessed in 11 CpG sites in buccal cells whereas infants' NE was assessed at 3 (N = 225) and 6 months (N = 189) using the Infant Behavior Questionnaire-Revised (IBQ-R). Hierarchical linear analyses showed that higher maternal antenatal anxiety was associated with greater 6-month-olds' NE. Furthermore, maternal antenatal anxiety predicted greater infants' BDNF DNAm in five CpG sites in males but not in females. Higher methylation at these sites was associated with greater 3-to-6-month NE increase, independently of infants' sex. Maternal antenatal anxiety emerged as a risk factor for infant's NE. BDNF DNAm might mediate this effect in males. These results may inform the development of strategies to promote mothers and infants' emotional well-being.

Prenatal maternal stress during the COVID-19 pandemic and infant regulatory capacity at 3 months: A longitudinal study.

The COVID-19 pandemic is a global traumatic experience for citizens, especially during sensitive time windows of heightened plasticity such as pregnancy and neonatal life. Pandemic-related stress experienced by mothers during pregnancy may act as an early risk factor for infants' regulatory capacity development by altering maternal psychosocial well-being (e.g., increased anxiety, reduced social support) and caregiving environment (e.g., greater parenting stress, impaired mother-infant bonding). The aim of the present longitudinal study was to assess the consequences of pandemic-related prenatal stress on infants' regulatory capacity. A sample of 163 mother-infant dyads was enrolled at eight maternity units in northern Italy. They provided complete data about prenatal stress, perceived social support, postnatal anxiety symptoms, parenting stress, mother-infant bonding, and infants' regulatory capacity at 3 months of age. Women who experienced emotional stress and received partial social support during pregnancy reported higher anxious symptoms. Moreover, maternal postnatal anxiety was indirectly linked to the infants' regulatory capacity at 3 months, mediated by parenting stress and mother-infant bonding. Dedicated preventive interventions should be delivered to mothers and should be focused on protecting the mother-infant dyad from the detrimental effects of pandemic-related stress during the COVID-19 healthcare emergency.

Post-partum Women's Anxiety and Parenting Stress: Home-Visiting Protective Effect During the COVID-19 Pandemic.

OBJECTIVES: The COVID-19 pandemic resulted in a particularly adverse and stressful environment for expecting mothers, possibly enhancing feelings of anxiety and parenting stress. The present work assesses mothers' anxiety levels at delivery and parenting stress after 3 months as moderated by home-visiting sessions. METHODS: Women (n = 177) in their second or third trimester of pregnancy during the COVID-19 lockdown were enrolled in northern Italy and split into those who did and did not receive home visits. After 3 months, the association between anxiety at delivery and parenting stress was assessed with bivariate correlations in the whole sample and comparing the two groups. RESULTS: Higher anxiety at birth correlated with greater perceived stress after 3 months. Mothers who received at least one home-visiting session reported lower parenting stress at 3 months than counterparts who did not receive home visits. CONCLUSIONS FOR PRACTICE: The perinatal period is a sensitive time window for mother-infant health, especially during a critical time like the COVID-19 pandemic. We suggest that home-visiting programs could be beneficial during global healthcare emergencies to promote maternal well-being after delivery.

Impact of COVID-19 pandemic in pediatric patients with epilepsy with neuropsychiatric comorbidities: A telemedicine evaluation.

OBJECTIVE: The objective of this study was to evaluate care needs, emotional and behavioral changes, and parental stress indices in a cohort of pediatric patients with epilepsy with neurocognitive and emotional comorbidities at the time of the coronavirus disease 2019 (COVID-19) pandemic. METHODS: This is a prospective observational study involving pediatric patients with epilepsy with neurocognitive and emotional comorbidities. Included patients were admitted to our hospital between August 2019 and February 2020 for epilepsy and neuropsychiatric assessment, and Child Behavior Checklist (CBCL) questionnaires were filled in by parents. Those patients and their families accepted to participate in a phone follow-up visit in April-May 2020 and to refill CBCL and Parenting Stress Index-Short Form (PSI-SF) questionnaires. Descriptive statistics for demographic and clinical data, CBCL questionnaire scores before and during the COVID-19 pandemic, and PSI-SF scores have been computed. Moreover, results of a short phone survey on the psychological burden during COVID lockdown have been reported. RESULTS: This study provides the parental-proxy report of emotional and behavioral profile changes of 23 pediatric patients with epilepsy and neurocognitive and emotional comorbidities during the COVID-19 pandemic. Concerns for therapy monitoring at the time of lockdown emerged in 43% of families, and 30% of patients showed worries for an altered contact with the referring medical team. Patients with neurocognitive comorbidities were more likely to exhibit behavioral problems, especially externalizing problems compared with patients with a diagnosis of anxiety/depression. CONCLUSION: Our data suggest the importance to monitor disease trajectory and behavior and affective symptoms with telehealth strategies to provide effective care to patients and their families.

A systematic review of human paternal oxytocin: Insights into the methodology and what we know so far.

With the consolidation of fathers' engagement in caregiving, understanding the neuroendocrine and hormonal mechanisms underlying fatherhood becomes a relevant topic. Oxytocin (OT) has been linked with maternal bonding and caregiving, but less is known about the role of OT in human fatherhood and paternal caregiving. A systematic review of methods and findings of previous OT research in human fathers was carried. The literature search on PubMed and Scopus yielded 133 records. Twenty-four studies were included and analyzed. Significant variability emerged in OT methodology, including laboratory tasks, assessment methods, and outcome measures. Fathers' OT levels appear to increase after childbirth. OT was significantly correlated with less hostility and with the quality of paternal physical stimulation in play interactions, but not with paternal sensitivity. Fathers' and children's OT levels were significantly correlated in a limited subset of studies, intriguingly suggesting that cross-generational OT regulation may occur during the early years of life. This study highlights relevant issues and limitations of peripheral OT assessment in human subjects, especially in fathers. Although the study of paternal neuroendocrinology appears promising, coping with these issues requires dedicated efforts and methodological suggestions are provided to guide future advances in this field.

The Experience of Child Neuropsychiatry Residents who Volunteered in Italian COVID-19-Designated Hospitals.

OBJECTIVE: During the first months of 2020, the coronavirus disease of 2019 (COVID-19) spread rapidly and soon reached a pandemic level. With the increasing number of hospitalizations, medical and nursing personnel resources were soon inadequate. As a consequence, medical volunteers became a key human resource and young medical residents in any specialty were hired on a voluntary basis to contribute to take care of patients with COVID-19. This study reports on the lived experience of residents in child neuropsychiatry who volunteered in Italian hotspot COVID-19-designated hospitals during the epidemic outbreak. METHODS: A phenomenological, qualitative approach using semi-structured interviews with open-ended questions was used to obtain in-depth narratives of the experience of residents in child neuropsychiatry volunteering in North Italy COVID-19-designated hospitals. All residents (n = 8) participated in the study. Interviews were conducted by an expert researcher trained in qualitative methods. Data analysis was performed by independent coders. RESULTS: Five core themes could be identified from the interviews: acting as mediators on two fronts, facing the shock of COVID-19 reality, capitalizing from specialty education, growing as persons and professionals, and humanizing medical care. CONCLUSIONS: This study is unique in providing an in-depth understanding of the experience of young residents in child neuropsychiatry volunteering in general hospitals during the COVID-19 pandemic in Northern Italy. The findings suggest that this experience may be highly beneficial for both the residents and the hospital quality of care. Insights for an accurate planning of residents' engagement in future healthcare emergencies are provided.

Short report: Siblings of children with neurodevelopmental disorders, a phenomenological perspective on parental perception.

BACKGROUND: Siblings, typically developing brothers and sisters of children with neurodevelopmental disorders (NDD), are at risk for long-term psychosocial difficulties. OBJECTIVE: The present study aims at obtaining an in-depth insight on the lived experience of siblings of children with NDD through their parents' perspective. METHODS: Seven mothers and three fathers who signed up their sibling children (12-15 years) to a peer-support intervention participated in a semi-structured videoconference interview according to the Interpretative Phenomenological Analysis (IPA) qualitative approach. Interviews were conducted by trained personnel and independently coded. RESULTS: Thematic analysis highlighted three core themes and twelve sub-themes: "The complexity of the fraternal relationship" (three sub-themes), "Growing up with diversity" (six sub-themes), and "Me as a sibling" (three sub-themes). CONCLUSIONS: The study provides insight on parents' perception of the lived experience of their sibling children, thus spreading awareness on the everyday difficulties families with a child with NDD may encounter. WHAT THIS PAPER ADDS: The present study contributes to the scarce literature on the lived experience of siblings of children with NDD, and notably it is one of the few qualitative studies on the topic which makes use of an IPA interviewing style. This methodological choice allowed for an in-depth understanding of siblings' strengths and struggles as perceived by their own parents, and of how their brother/sister's condition impacted on their family role, socio-emotional development and personality. Recounting siblings' experiences contributes in spreading awareness on the everyday difficulties siblings and their families face when cohabitating with a child with NDD.

Gaze Orienting in the Social World: An Exploration of the Role Played by Caregiving Vocal and Tactile Behaviors in Infants with Visual Impairment and in Sighted Controls.

Infant attention is a cognitive function that underlines sensory-motor integration processes at the interface between the baby and the surrounding physical and socio-relational environment, mainly with the caregivers. The investigation of the role of non-visual inputs (i.e., vocal and tactile) provided by the caregivers in shaping infants' attention in the context of visual impairment is relevant from both a theoretical and clinical point of view. This study investigated the social attention (i.e., gaze orientation) skills in a group of visually impaired (VI) and age-matched sighted controls (SCs) between 9 and 12 months of age. Moreover, the role of VI severity and maternal vocalizations and touch in shaping the social attention were investigated. Overall, 45 infants and their mothers participated in a video-recorded 4 min interaction procedure, including a play and a still-face episode. The infants' gaze orientation (i.e., mother-directed, object-directed, or unfocused) and the types of maternal vocalizations and touch (i.e., socio-cognitive, affective) were micro-analytically coded. Maternal vocalizations and touch were found to influence gaze orientation differently in VI infants compared SCs. Moreover, the group comparisons during the play episode showed that controls were predominantly oriented to the mothers, while VI infants were less socially oriented. Visual impairment severity did not emerge as linked with social attention. These findings contribute to our understanding of socio-cognitive developmental trajectories in VI infants and highlight the need for tailored interventions to promote optimal outcomes for VI populations.

Sleep effects of Ketogenic diet in pediatric patients with migraine: Preliminary data of a prospective study.

OBJECTIVE/BACKGROUND: Ketogenic dietary therapies' effects on sleep have been poorly investigated up to date. Preliminary results of a prospective study aimed at evaluating possible sleep changes in pediatric patients with migraine treated with classic ketogenic diet are presented. PATIENTS/METHODS: Included patients were aged 14-18 years and had a diagnosis of chronic migraine. A customized classic ketogenic diet was drawn up for all patients and all participants underwent neurological, nutritional and subjective and objective sleep assessment at baseline and after three months of follow-up (standardized sleep questionnaires, polysomnography, actigraphy). RESULTS: The majority of patients reported an improvement in migraine symptoms and quality of life. As far as sleep effects, a possible sleep stabilization was evidenced according to actigraphic data, and polysomnographic data showed a slight increase in total sleep time and sleep efficiency together with a reduction in waking time during night and a trend of NREM stage 1 decrease and REM increase. CONCLUSIONS: Future analyses on a broader population are needed to shed light on the ketogenic dietary therapies' effects on sleep and future research should be devoted to identify influence of possible individual and diet characteristics, and biochemical related changes.

Stability of maternal postnatal bonding between 3 and 6 months: Associations with maternal mental health and infant temperament.

Maternal bonding is key for infant development and well-being. Research to date focused on prenatal bonding experience, with fewer studies looking at the postnatal period. Moreover, evidence suggests significant associations among maternal bonding, maternal mental health, and infant temperament. The joint impact of maternal mental health and infant temperament on maternal postnatal bonding remains unclear, with limited research reporting longitudinal data. Hence, the present study aims (1) to explore the impact of maternal mental health and infant temperament on postnatal bonding at both 3 and 6 months of age, (2) to explore postnatal bonding stability from 3 to 6 months, and (3) to determine which factors are linked with 3-to-6-month changes in bonding. At the infants' 3 months (n = 261) and 6 months of age (n = 217), mothers provided measures of bonding, depressive and anxious symptoms, and infant temperament via validated questionnaires. At 3 months, higher levels of maternal bonding were predicted by lower levels of anxiety and depression in the mothers and by higher infants' regulation scores. At 6 months, lower levels of anxiety and depression predicted higher levels of bonding. Moreover, mothers showing decreases in bonding were characterized by 3-to-6-month increases in depression and anxiety, as well as increased reported difficulties in regulation dimensions of infant temperament. This study highlights the impact of both maternal mental health and infant temperament on maternal postnatal bonding in a longitudinal sample and could offer useful information for early childhood prevention and care.

The CPS Workers' Child Removal Decision in Cases of Domestic and Witnessed Violence.

This study aimed to explore maternal and paternal risks and protective factors that may influence the Child Protection Service (CPS) workers' child removal decision in case of domestic and witnessed violence. In all, 218 case reports of Italian CPSs were retrospectively analyzed through the Protocol of Risk and Protective Factors. The sample was then split up into two groups on the basis of the CPS professionals' placement decision after the investigation (child removal decision versus parents support and monitoring intervention). Two statistical approaches were used to identify the patterns of risk and protective factors associated with maternal and paternal assessments: logistic regression models and decision tree analysis. Results showed that mothers who are victims of Intimate Partner Violence experienced the child removal in about half of the cases, while fathers showed a higher removal rate. Differences emerged between mothers' and fathers' risk profiles, suggesting that workers attributed a different weight to some factors depending on whether they concerned the mother or the father. Only the proximal risk factor poor empathy skills was significant for both mothers and fathers. For the mothers' group, one of the most important factors was the presence of direct forms of child maltreatment in addition to witnessed violence, while for fathers' group the drug abuse emerged a crucial relevant proximal risk factor.

Case report: KETOLAND the psychoeducation program for ketogenic diet.

Glucose transporter type 1 deficiency syndrome (GLUT1DS) is a rare neurological disorder characterized by a wide spectrum of symptoms: epilepsy, movement disorders and neurocognitive impairment. The gold standard treatment for GLUT1DS are ketogenic dietary therapies (KDTs), specifically classical ketogenic diet (CKD). Despite the benefits, CKD often represents a challenge for patients and their families since meal preparation is extremely demanding and deviates a lot from normal diet. To assure an optimal compliance to CKD a psychological support for parents and patients with GLUT1DS is highly recommended. Specifically, a psychoeducational intervention that ameliorates the knowledge about the illness and its therapy improves treatment' s adherence and efficacy. The aim of this case report is to investigate the effectiveness of a psychoeducational program, partially implemented through telepsychology, based on the theoretical model of Cognitive Behavioral Play Therapy (CBPT) to support KDT knowledge and adherence in a patient with GLUT1DS who presented a worsening of her clinical picture due to a sparse knowledge of KDTs principles which determined a low adherence. Thus, with this case report we propose a model of intervention with psychoeducation in a patient with a complex chronic disease.

Validation of an Italian Questionnaire of Adherence to the Ketogenic Dietary Therapies: iKetoCheck.

Ketogenic dietary therapies (KDTs) are an effective and safe non-pharmacological treatment for drug-resistant epilepsy, but adherence can be challenging for both patients and caregivers. In Europe, there are no adequate tools to measure it other than monitoring ketosis. This study aimed to adapt and validate the Brazilian adherence questionnaire, Keto-check, into the Italian version: iKetoCheck. Using the Delphi technique, 12 judges validated the contents through agreement rates and the Content Validity Index (CVI). The iKetocheck was self-completed electronically by 61 drug-resistant epilepsy or GLUT1 deficiency patients within an interval of 15 days to measure its reproducibility. The test-retest reliability was evaluated using Pearson's correlation and relative significance test. Exploratory and confirmatory factorial analyses were made using Factor software version 12.03.02. The final tool, iKetoCheck, consists of 10 questions with 5-point Likert scale answers. It evaluates various aspects such as informing caregivers about the diet, organization of meals, measurement of ketosis, weighing food consumed, diet negligence, use of carbohydrate-free medications, attending follow-up visits, reading food labels, consulting an expert for dietary concerns, and cooking at home. The factorial analysis resulted in three factors: "attention," "organization," and "precision," with satisfactory results for indices in exploratory and confirmatory analyses. Although higher mean values of ketonemia measurement were observed in patients with a higher adherence score, these values were not statistically significant (p = 0.284). In conclusion, despite the small sample size, iKetoCheck is a valid tool for evaluating KDTs' adherence in Italian drug-resistant epilepsy or GLUT1 deficiency patients. It can provide valuable information to improve patient management and optimize the effectiveness of KDTs.