Early Parenting Intervention: Bio-behavioral Outcomes in Infants With Neurodevelopmental Disabilities (EPI-BOND)

Clinical Trial of an Early Parenting Empowerment Intervention to Promote Socioemotional Development in Infants With Developmental Disabilities: Parent and Infant Behavioral, Neuroendocrine and Epigenetics Outcomes

Infants with developmental disabilities present a high risk of behavioral and socio-emotional problems. Their parents are themselves at risk of developing emotional and affective disorders which can impact the quality of the interaction with the infant. Early parenting empowerment focused on parent-infant interaction are beneficial in supporting infants development and parental adjustment. By using a multi-layer approach to outcomes assessment (i.e., behavioral, neuroendocrine and epigenetic outcomes), the present longitudinal, multi-center, change-promoting clinical trial is aimed at assessing the effectiveness of an early parenting empowerment intervention based on video-feedback technique to support maternal responsiveness and the socio-emotional development of infants with developmental disabilities.

Study Overview

• Status: Completed
• Conditions: Parent-Child Relations; Developmental Disability; Early Intervention; Epigenomics
• Intervention / Treatment: Behavioral: Video-Feedback Intervention; Other: Phone-Call Intervention

Detailed Description

RATIONALE: Infants with developmental disabilities (e.g., cerebral palsy and genetic syndrome) present a high risk of behavioral and socio-emotional problems. Their parents are themselves at risk of developing emotional and affective disorders which can impact the quality of the interaction with the infant. Typical development research is highlighting the potentials of biological markers of less-than-optimal mother-infant interaction, such as altered neuroendocrine regulation (i.e., cortisol and oxytocin). Increased infants' salivary cortisol reactivity has been found in response to experimental suspension of maternal responsiveness (Still-Face paradigm, SFP). On the other hand, oxytocin administration to mothers increases responsiveness to infants socio-emotional signals and oxytocin has also been associated with socioemotional stress regulation in humans. Interestingly, previous research suggests that the epigenetic regulation of specific genes (i.e., SLC6A4, NR3C1, BDNF, OXTR) transcription might be affected by alterations of maternal caregiving behavior. Nonetheless, to the best of our knowledge, to date there is no investigation of the epigenetic vestiges of the effects of an early parenting intervention (i.e., video-feedback) on the behavioral outcomes of infants with developmental disabilities.

SPECIFIC AIM 1: To assess the effectiveness of the video-feedback intervention to enhance the socio-emotional behavior of infants with developmental disabilities.

EXPERIMENTAL DESIGN AIM 1: The present research project will include two groups (Video-Feedback Group, VFG; Phone-Call Group, PCG) and four phases: T0, baseline assessment; T1, post-intervention assessment ; T2, follow-up#1 (3 months after the intervention); T3, follow-up#2 (6 months after the intervention). All infants and their mothers will be enrolled at three Child Neuropsychiatric Units in Lombardia Region (OU1, Scientific Institute IRCCS E. Medea; OU2, Fondazione Istituto Neurologico Casimiro Mondino, Pavia, Italy; OU3, Università degli Studi, Brescia, Italy). At each phase, mother-infant interactions will be videotaped during SFP. The VFG dyads will participate to a 6-session videofeedback intervention The aim of the video-feedback intervention is to support maternal sensitivity to the infants' behaviors focusing on different aspects of mother-infant interactions. PCG mothers will be contacted by telephone weekly for 6 weeks, and will be asked for information on their infants' development. No advice about sensitive parenting will be given to the control PCG mothers during these conversations. In each of the three Units, the intervention will be conducted by psychologists/developmental neuropsychiatrists trained on the video-feedback intervention. Infant behavior regulation will be observationally assessed at each of the four phases of the research project.

SPECIFIC AIM 2: To examine the effects of the intervention on maternal responsiveness.

EXPERIMENTAL DESIGN AIM 2: Paralleling infants' behavioral assessment, maternal responsiveness will be assessed at each project phase by means of video-tapes. Additionally, maternal reports of emotional and affective states, including depressive and anxious symptoms and stress perception in taking care of the infant, will be obtained and controlled for. The rate of change over the phases of the project in maternal self-reported emotional states, feelings of attachment and coded sensitivity will concur in defining the efficacy of the intervention in the VFG subjects against the PCG counterparts.

SPECIFIC AIM 3: To investigate the immediate and follow-up pre/post intervention variations in the neuroendocrine functioning (i.e., salivary cortisol and oxytocin) and in the DNA methylation of specific genes associated with infants' behavioral regulation such as: NR3C1, BDNF, SLC6A4, OXTR.

EXPERIMENTAL DESIGN AIM 3: Salivary samples will be collected from the infant at each phase before and after the SFP interaction. For what pertains neuroendocrine markers (i.e., salivary cortisol and oxytocin) saliva will be collected from the infants (and mothers) using an oral cotton swab and it will be collected in eppendorf, centrifuged and conserved according to kit producer guidelines. Samples will be obtained before (1 sample) and after (3 samples: +10, +20, and +30 minutes) the SFP procedure. Due to circadian rhythm of the neuroendocrine systems, all the interactions will occur in the morning, between 9.00 and 12.00 AM. For what pertains the epigenetic profiling, saliva will be collected once per phase. DNA methylation will be assessed at the different CpG sites within the promoter regions of specific target genes (NR3C1, SLC6A4, BDNF, OXTR) previously associated with infants' behavioral development. The rate of change in neuroendocrine concentrations of cortisol and oxytocin as well as the alterations in global and site-specific DNA methylation of the selected genes will be used as independent biomarkers of the effects of the video-feedback intervention.

SIGNIFICANCE AND INNOVATION: First, the study has the potential to bring new evidence in the clinical practices promoting an early intervention for mothers of infants with developmental disabilities. Second, the multi-center nature of this clinical trial will provide a common early intervention program in the Italian context, with potential indirect implication for healthcare costs optimization. Indeed, it has been shown that interventions starting earlier in childhood may be more effective and efficient than those provided in a later period of life. Consistently, the project will be conducted during the first year of life of infants with the potential to permanently alter infants' development trajectories and to yield a significant economic return for the healthcare system. Finally, examining the epigenetic variations related to early parenting intervention the project introduces an innovative approach to early intervention research for families of infants with developmental disabilities.

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Livio Provenzi, PhD; Phone Number: +39-031-877464; Email: livio.provenzi@lanostrafamiglia.it

Study Locations

• Italy
  • Brescia, Italy, 25123
    • Università degli Studi di Brescia
  • Pavia, Italy, 27100
    • Fondazione Istituto Neurologico Casimiro Mondino
  • Lecco
    • Bosisio Parini, Lecco, Italy, 23842
      • IRCCS E. Medea

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 months to 1 year (Child)
• Accepts Healthy Volunteers: No

Description

ELIGIBILITY CRITERIA FOR INFANTS

Inclusion Criteria:

• Infants with equivalent age range 3-to-18-months
• Mild to moderate psychomotor delay

Exclusion Criteria:

• Presence of severe sensorial (auditory, visual) deficits
• Genetic syndrome with known functional implications for the epigenetic regulation of target genes

ELIGIBILITY CRITERIA FOR MOTHERS

Inclusion Criteria:

• Mastery of Italian language
• Age > 18 years
• Living with the father of the infant

Exclusion Criteria:

• Documented mental disorder
• Documented disability

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Video-Feedback Group (VFG); Dyads of mothers and their infant with developmental disability who are exposed to the video-feedback intervention focused on different domains of mother-infant quality of interaction (number of sessions: 6).	Behavioral: Video-Feedback Intervention; Mothers and infants of the VFG arm will participate to a 6-session video-feedback intervention structured as follows: 4 sessions of video-review discussions with a trained clinician + 2 sessions of integrative intervention aimed at translating into practical caregiving the insights developed during the video-review discussions.
Sham Comparator: Phone-Call Group (PCG); Dyads of mothers and their infant with developmental disability who are not exposed to the video-feedback intervention, instead they receive phone calls focused on obtaining descriptions of different domains of infant behavioral development (number of sessions: 6)	Other: Phone-Call Intervention; Mothers of the PCG arm will participate in 6-session of telephone call during which a trained collaborator will ask details on different domains of infants behavioral development.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in maternal sensitivity	Coded micro-analitically from videotapes of mother-infant interactions.	Through study completion: at intervention start (Baseline, T0), 2 months after intervention start (post-intervention, T1), 3 months after intervention end (follow-up, T2), and 6 months after intervention end (follow-up, T3)
Change in infant behavioral regulation	Coded micro-analitically from videotapes of mother-infant interactions.	Through study completion: at intervention start (Baseline, T0), 2 months after intervention start (post-intervention, T1), 3 months after intervention end (follow-up, T2), and 6 months after intervention end (follow-up, T3)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in hormones salivary concentrations	Salivary cortisol and oxytocin obtained from infants by trained collaborators.	Through study completion: at intervention start (Baseline, T0), 2 months after intervention start (post-intervention, T1), 3 months after intervention end (follow-up, T2), and 6 months after intervention end (follow-up, T3)
Change in DNA methylation status	The methylation status of target genes (e.g., NR3C1, SLC6A4, BDNF, OXTR) will be assessed from salivary samples obtained from infants.	Through study completion: at intervention start (Baseline, T0), 2 months after intervention start (post-intervention, T1), 3 months after intervention end (follow-up, T2), and 6 months after intervention end (follow-up, T3)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility and acceptability	Mothers included in the two arms will rate feasibility and acceptability of the respective intervention received.	Through study completion, 2 months after intervention start (post-intervention, T1)

Collaborators and Investigators

• Sponsor: IRCCS Eugenio Medea
• Collaborators: Università degli Studi di Brescia; Fondazione Istituto Neurologico Casimiro Mondino
• Investigators: Principal Investigator: Rosario Montirosso, PsyD, IRCCS E. Medea

Publications and helpful links

General Publications

• Montirosso R, Rosa E, Giorda R, Fazzi E, Orcesi S, Cavallini A, Provenzi L; Early Intervention Study Group. Early Parenting Intervention - Biobehavioral Outcomes in infants with Neurodevelopmental Disabilities (EPI-BOND): study protocol for an Italian multicentre randomised controlled trial. BMJ Open. 2020 Jul 21;10(7):e035249. doi: 10.1136/bmjopen-2019-035249.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2019
• Primary Completion (Actual): February 5, 2023
• Study Completion (Actual): April 5, 2023

Study Registration Dates

• First Submitted: February 19, 2019
• First Submitted That Met QC Criteria: February 22, 2019
• First Posted (Actual): February 25, 2019

Study Record Updates

• Last Update Posted (Actual): October 18, 2023
• Last Update Submitted That Met QC Criteria: October 17, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Early intervention; Cerebral palsy; DNA methylation; Neuroendocrine regulation; Epigenetic regulation; Video-feedback intervention; Developmental disability; Genetic syndromes; Parent-infant interaction
• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Developmental Disabilities
• Other Study ID Numbers: RF-2016-02361884

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No