We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
ClinicalTrials.gov Menu

Early Intervention in Preterm Infants: Short and Long Term Developmental Outcome After a Parental Training Program

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02983513
Recruitment Status : Active, not recruiting
First Posted : December 6, 2016
Last Update Posted : March 31, 2022
Information provided by (Responsible Party):
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

Brief Summary:
Preterm infants, during their stay in the Neonatal Intensive Care Unit (NICU), face a period of stressful environment, which may negatively impact early brain development and subsequent neurobehavioral outcomes. This study aims to assess the effectiveness of training parents in reducing stressful experiences early in life and in enhancing brain development and long term developmental outcomes.

Condition or disease Intervention/treatment Phase
Premature Birth Behavioral: Early Intervention Not Applicable

Detailed Description:

Very preterm birth is associated with motor, cognitive and behavioral problems.

Micro-structural brain abnormalities, even in the absence of focal lesions, have been documented by neuroimaging studies in preterm infants at term corrected age and later in childhood. These alterations in brain maturation occurring during the neonatal period may be implicated in long-term neurobehavioral disorders later experienced by preterm babies.

However, there is increasing evidence that also negative environmental factors (intensive care, excessive sensory stimulation, paucity of parental contact etc.) can affect later outcomes.

Potential benefits of early dyadic interaction and preterm baby massage in reducing the effects of the NICU stressor environment have been demonstrated. More recently, few studies have investigated visual function in preterm infants focusing on the potential role of early visual interaction to enhance attention and improve later neurodevelopment.

The role of early intervention strategies to improve neurodevelopment has been recently emphasized.

Early intervention programs based on the concept of "individualized care" have proved to be effective in promoting brain maturation and neurodevelopmental outcome. In this context, early interventions as the Mother Infant Transaction Program (MITP) and the Premie Start, both targeting parenting, have the greatest potential to have sustained effects on child development.

In addition, recent studies have shown that exposure to stressful events in the neonatal period can cause epigenetic modifications in children born preterm; in particular alteration of serotonergic tone was observed, associated with methylation of the serotonin transporter gene, which could be implicated in the etiology of behavioral disorders observed in these children. In animal models these epigenetic effects appear to be influenced by maternal care that can epigenetically modulate the offsprings' stress response.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 70 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Supportive Care
Official Title: Early Intervention in Preterm Infants: Effects of a Parental Training Program on Neonatal Brain Development, Visual Functions and Neurobehavioral Outcome
Study Start Date : April 2014
Actual Primary Completion Date : April 2017
Estimated Study Completion Date : February 2023

Arm Intervention/treatment
Experimental: Early Intervention

The early intervention program is delivered during the NICU stay, according to the MITP and Premie Start Protocol, in order to train parents to: recognize signs of infant stress and alert-available behavior to promote mother-infant interaction; adopt principles of graded stimulation; optimize interactions and avoid overwhelming infants through facilitation strategies (for example, engage and support the visual attention of the newborn). The program is held in eight main sessions and one additional post-discharge session.

In addition parents are trained and invited to daily promote preterm baby massage therapy and visual attention according to a detailed protocol.

Behavioral: Early Intervention
No Intervention: Standard Care
Standard Care according to NICU protocols including Kangaroo Mother Care, nesting and minimal handling

Primary Outcome Measures :
  1. Neonatal Visual Assessment Battery to evaluate visual function [ Time Frame: 40 weeks postmenstrual age ]
    Neonatal Visual Function is assessed using the Visual Assessment Battery developed by Ricci et al. The assessment evaluates the following items: Ocular spontaneous motility, ability to fix and follow a target, reaction to colour, visual acuity and visual attention at distance. Each item is scored as normal (score 0) or abnormal (score 1). The global score is then calculated as the sum of all the individual items, as designed by the authors.

  2. Neonatal Behavior [ Time Frame: 2 months corrected age ]
    Neonatal behavior is assessed using the Neonatal Behavior Assessment Scale that evaluates: habituation, social-interactive, motor system, state organization and regulation, autonomic system, reflexes.

Secondary Outcome Measures :
  1. Brain development [ Time Frame: 40 weeks postmenstrual age ]
    Conventional and advanced MRI

  2. Developmental outcome [ Time Frame: 24 months corrected age ]
    Children development is assessed using the Bayley Scales of Infant and Toddlers (Third edition) - including: cognitive, motor, language, social-emotional and adaptive behavior)

  3. Epigenetic changes [ Time Frame: up to 48 weeks gestational age ]
    epigenetic analysis is performed at birth on a cord blood sample (0.5 ml) and at hospital discharge on a peripheral blood sample (0.5 ml) collected according routine clinical procedures

  4. overall duration of hospitalisation [ Time Frame: up to 48 weeks gestational age ]
    number of days from admission to home discharge from NICU

  5. Weight (in grams) at 40 weeks postmenstrual age [ Time Frame: 40 week gestational age ]
  6. Length(in centimeters) at 40 weeks postmenstrual age [ Time Frame: 40 week gestational age ]
  7. Head circumference (in centimeters) at 40 weeks postmenstrual age [ Time Frame: 40 week gestational age ]
  8. Acquisition of full oral feeding [ Time Frame: up to 48 weeks gestational age ]
    Postmenstrual age at the acquisition of full oral feeding

  9. Feeding with Human milk [ Time Frame: up to 40 weeks gestational age ]
    Feeding with human milk at 40 weeks postmenstrual age (yes or no)

  10. Neurodevelopmental outcome [ Time Frame: 5-6 years of age ]

    Children neurodevelopment is assessed using the Griffiths Development Scales (GMDS).

    Scores range from 50 to 150 General quotient mean 100 SD 12, sub scales mean 100 SD 16 Higher scores mean a better outcome

  11. Behavioral outcome [ Time Frame: 5-6 years of age ]
    Children behavior is assessed using the Child Behavior Checklist. A T score above 70 is considered to be in the clinical range, a T score between 65 an 70 is considered borderline while a T score below 65 is considered normal

  12. Neuromotor outcome [ Time Frame: 5-6 years of age ]

    Children neuromotor is assessed using the Movement Assessment Battery for Children (Movement ABC).

    A score above 67 is considered to be in the normal range, a score between 57 an 67 is considered borderline while a score below 56 is considered pathological

  13. Attention outcome [ Time Frame: 5-6 years of age ]

    Child attention abilities is assessed using the Early Childhood Attention Battery (ECAB).

    Scaled scores range from 1 to 19. Lower scores indicate worst outcome

  14. L1 promoter methylation levels on buccal swab [ Time Frame: 5-6 years of age ]
    epigenetic analysis - L1 promoter methylation (Percent) assessment is performed on a buccal swab collected at follow-up assessment at 5-6 years.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   25 Weeks to 29 Weeks   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Gestational age between 25+0 and 29+6 weeks

Exclusion Criteria:

  • major brain lesions as documented by cranial ultrasound (intraventricular hemorrhage > 2 grade, cystic periventricular leukomalacia)
  • neurosensorial deficits (retinopathy of prematurity > stage 2)
  • genetic syndromes and/or major congenital malformations
  • major neonatal comorbidities

Mothers are selected according to the following inclusion criteria: age over 18 years, good comprehension of Italian language, no obvious cognitive impairments or psychiatric disorders, no drug addiction and no single-parent families.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02983513

Layout table for location information
NICU, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
Milan, Italy, 20122
Sponsors and Collaborators
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Layout table for investigator information
Principal Investigator: Monica Fumagalli, MD Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
ClinicalTrials.gov Identifier: NCT02983513    
Other Study ID Numbers: MITP Preterm
First Posted: December 6, 2016    Key Record Dates
Last Update Posted: March 31, 2022
Last Verified: March 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: individual patient consent would be required according to the EU GDPR and Italian regulations
Keywords provided by Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico:
Early intervention
Brain Development
Additional relevant MeSH terms:
Layout table for MeSH terms
Premature Birth
Obstetric Labor, Premature
Obstetric Labor Complications
Pregnancy Complications