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Completed

NCT Number: NCT02983513

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

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.

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Key information

Age range

25 week–29 week

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

NICU, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico

Milan, 20122, Italy

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Early Intervention

Behavioral

Primary outcomes

  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 outcomes

  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.

Sponsors and collaborators

Lead sponsor

Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

Other

Registry information

Official study title

Early Intervention in Preterm Infants: Effects of a Parental Training Program on Neonatal Brain Development, Visual Functions and Neurobehavioral Outcome

Important dates

Study start
2014
Primary completion
2017
Study completion
2023
First posted
Dec 6, 2016
Registry last updated
Feb 10, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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