Emotional Regulation in Children With ND: the Role of Genomic Variation, Proteomic Patterns, and Early Experience
Emotional-behavioral Regulation in Children With Neurodevelopmental Disabilities: an Exploratory Investigation of the Role of Genomic Variation, Proteomic Patterns, and Quality of Early Experience
1 other identifier
observational
248
1 country
1
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for all trials
Started Apr 2021
Typical duration for all trials
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
April 7, 2021
CompletedFirst Submitted
Initial submission to the registry
July 30, 2021
CompletedFirst Posted
Study publicly available on registry
August 13, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 30, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
December 31, 2023
CompletedOctober 18, 2023
October 1, 2023
2.6 years
July 30, 2021
October 17, 2023
Conditions
Outcome Measures
Primary Outcomes (2)
Infant DNA methylation status
The DNA methylation status (i.e. percentage) of candidate genes (e.g., OXTR, SLC6A4, BDNF, and DRD4) will be assessed from salivary samples obtained from infants.
1 day , at the recruitment
Infant behavioral regulation
The infant behavioral regulation (i.e., negative emotionality) will be coded micro-analitically (i.e., second-by-second) from videotapes of mother-infant interactions.
1 day , at the recruitment
Secondary Outcomes (1)
Infant proteomic patterns
1 day , at the recruitment
Study Arms (2)
children with ND
children with neurodevelopmental disabilities (ND) age between 3 and 24 months (chronologically or corrected in the case of children born preterm).
Typical developed children (TD)
children with typical development age between 3 and 24 months (chronological).
Interventions
Genomic DNA will be extracted from 0.4 ml aliquots of each saliva sample using the kit manufacturer's suggested protocol, quantified with Qubit 2.0 (Invitrogen), and stored at -20°C. Aliquots of 250 ng of each DNA will be edited for methylation analysis with the EZ DNA Methylation Lightning kit (Zymo Research). Amplification of samples and their preparation for NGS sequencing will be performed as described. Samples will be sequenced on NextSeq 500 (Illumina). Individual processed sequences (PE reads) will be independently aligned to reference sequences using a parallel Smith-Waterman algorithm. Only reads that consistently align to the same reference sequence will be retained. At each CpG site in each analyzed sequence, the frequencies of the four bases will be evaluated and tabulated.
Urine samples are collected using non-invasive methods and are prepared according to a procedure preparatory to quantitative recovery of exosomes: once thawed and centrifuged at 17,000 x g for 10 min at 4°C, the recovered supernatants are separated and centrifuged at 200,000 x g for 1 hr at 4°C. Exosome pellets are separated, washed repeatedly and resuspended in buffer (NH4HCO3, 0.1 mM ph=7.8). Protein concentration is estimated with the SPNTM Protein Assay kit and each sample (50 ± 0.5 μg protein) is digested with trypsin using a 1:50 (w/w) enzyme/substrate ratio at 37 °C over night (o/w). A second tryptic digestion is performed with an enzyme:substrate ratio of 1:100 (w/w) for 4h. Digested samples, centrifuged at 13,000 × g for 10 min, are purified and concentrated using PepClean C-18 columns. The samples obtained are analyzed by reversed-phase liquid chromatography coupled to high-resolution mass spectrometry.
During an observational session, a short video recording of the mother-child interaction of approximately 10 minutes will be made in a semi-structured setting to assess the child's emotional regulation and social behavior. The interaction will be structured in 5 different phases according to the Still Face paradigm (Tronick et al., 1978): Play, Still#1, Reunion#1, Still#2, Reunion#2. Play: Mothers will be invited to interact with their babies for 10 minutes; Still: mothers will be asked to remain still while maintaining an unresponsive expressionless face and not to smile, touch, or talk to the child for 2 minutes (Still#1: 2 minutes; Still#2: 2 minutes); Reunion: mothers will be asked to resume the play activity with their own for an additional 2 minutes (Reunion#1: 2 minutes; Reunion#2: 2 minutes).
Eligibility 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.
You may qualify if:
- 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.
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
IRCCS E. Medea
Bosisio Parini, Lecco, 23842, Italy
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- observational
- Observational Model
- CASE CONTROL
- Time Perspective
- CROSS SECTIONAL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 30, 2021
First Posted
August 13, 2021
Study Start
April 7, 2021
Primary Completion
November 30, 2023
Study Completion
December 31, 2023
Last Updated
October 18, 2023
Record last verified: 2023-10