Children with neurodevelopmental disabilities (ND) represent an heterogeneous population characterized by a wide range of clinical diagnoses (e.g., cerebral palsy, sensory impairment, psychomotor retardation), which are associated with various deficits that emerge early in the child's life. Although it has been broadly demonstrated that children with ND exhibit several differences in social-emotional skills and emotional-behavioral regulation, the underlying mechanisms that are associated with more or less impaired developmental trajectories remain still partially unexplored. While several studies have investigated the role of biological and environmental factors in the emotional behavioral regulation of typically developing children or children with risk conditions other than ND (e.g., children who are victims of maltreatment), little research has jointly explored the role of methylation, polymorphisms, and environmental experience in the emotional-behavioral regulation of children with ND during the first years of life. The aim of this project is to investigate biological (DNA methylation, polymorphic variants, and proteomics) and environmental (e.g., painful and/or invasive nursing procedures, proximity, and physical contact) factors that might be associated with the emotional behavioral regulation of children with ND.

Background: Children with neurodevelopmental disabilities (ND) are an heterogeneous population characterized by a wide variety of clinical diagnoses, which are associated with different deficits that emerge during infancy and childhood. Although diagnostic framing may vary, several studies observed that children with ND share reduced social-relational skills, characterized by lower interactive and dyadic attention skills and decreased use of interpersonal communication cues. Although it has been broadly demonstrated that children with ND exhibit several differences in social-emotional skills and emotional behavioral regulation, the underlying mechanisms that are associated with more or less impaired trajectories remain partially unexplored.

Primary aim: to explore in a sample of children with ND aged 3 to 24 months the contribution of 1) methylation of candidate genes (e.g., OXTR, SLC6A4, BDNF, and DRD4), 2) polymorphisms in emotional-behavioral regulation, and 3) environmental experience (i.e., adverse experiences and quality of parental behavior) in emotional-behavioral regulation.

Secondary aim: 1) to explore a possible association between proteomics and emotional-behavioral regulation in a sample of children with ND aged between 3 and 24 months; 2) to identify functional and structural patterns of candidate genes associated with emotional behavioral regulation by applying a computational approach. Modules of genes potentially associated with social-emotional development in networks of interaction and spatio-temporal co-expression in the encephalon will also be identified.

Planned Activities:

Methods:the project involves a clinical group of children with ND and their mothers and a control group of typically developing children and their mothers. Because of the nature of the groups, the study is a quasi-experimental research design.

The study involves the following procedures:

• collection of biological material: saliva collection using non-invasive modalities and the Oragene OG575 kit (Genotek DNA) and urine collection using non-invasive modalities.
• administration of questionnaires and diary of proximity: the mother (both for the clinical group and for the control group) will be asked to fill out some questionnaires relating to their mood, habitual behavior and development of the child. It will also be evaluated how much and in what way the mother spends in physical contact (e.g. time spent caressing the baby; time spent holding the baby; time spent when the baby is attached to the mother's breast). This data will be derived through the use of a repurposed version of Raiskila et al.'s "closeness diary" implemented in an electronic format, in the form of an APP (APP: inContatto);
• videotaping the Parent-Child Interaction in a semi-structured context in 5 different phases in accordance with the Still Face paradigm (Tronick et al., 1978): Play, Still#1, Reunion#1, Still#2, Reunion#2.

Interactions will be videotaped for subsequent behavioral coding using various coding tools. The child's emotional-behavioral regulation will be coded using the coding systems: a) Infant and Caregiver Engagement Phase, b) Infant Regulatory Scoring System and Maternal Regulatory Scoring System by Tronik. In addition, infant and maternal behavior will be coded using the Global Rating Scale coding system by Murray and maternal touch behavior using the Maternal Touch Coding System by Provenzi.

Inclusion Criteria:

Children with ND:

• Age between 3 and 24 months (chronologically or corrected in the case of children born preterm);
• mild to moderate developmental delay documented by clinical signs (e.g., symptoms of brain injury on neurological examination or neuroimaging) or by developmental scales (i.e., Griffiths III scales) associated with various diagnoses (e.g., cerebral palsy, prematurity);
• absence of genetic syndromes. The Griffiths III scale will be used to assess the child's overall level of development.

Typical developmental children:

• birth to term;
• age between 3 and 24 months (chronological);
• absence of peri- or postnatal pathology.

Inclusion criteria for mothers (DN and typical development):

• age above 18 years;
• good understanding of the Italian language;
• absence of cognitive difficulties and/or psychiatric disorders;
• no intake of psychotropic medications;
• not part of a single-parent family.

Exclusion Criteria: refer to the inclusion criteria.

Children with ND and their mothers will be recruited through consecutive and convenience sampling at the U.O.C. "Specialistic Rehabilitation - Neuropsychiatric Pathologies of Developmental Age" and the U.O.C. "Functional Rehabilitation" of the Scientific Institute "E. Medea" (Bosisio Parini site). Children with typical development and their mothers will be recruited from nursery schools in the province of Lecco. After viewing an informative letter describing the general research, mothers will be contacted by telephone and invited to participate voluntarily.