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

Not Applicable
Completed
Conditions
Premature Birth
Interventions
Behavioral: Early Intervention
Registration Number
NCT02983513
Lead Sponsor
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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
70
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Early InterventionEarly InterventionThe 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.
Primary Outcome Measures
NameTimeMethod
Neonatal Visual Assessment Battery to evaluate visual function40 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.

Neonatal Behavior2 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
NameTimeMethod
Epigenetic changesup 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

overall duration of hospitalisationup to 48 weeks gestational age

number of days from admission to home discharge from NICU

Head circumference (in centimeters) at 40 weeks postmenstrual age40 week gestational age
Developmental outcome24 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)

Feeding with Human milkup to 40 weeks gestational age

Feeding with human milk at 40 weeks postmenstrual age (yes or no)

Brain development40 weeks postmenstrual age

Conventional and advanced MRI

Acquisition of full oral feedingup to 48 weeks gestational age

Postmenstrual age at the acquisition of full oral feeding

Neurodevelopmental outcome5-6 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

Weight (in grams) at 40 weeks postmenstrual age40 week gestational age
Length(in centimeters) at 40 weeks postmenstrual age40 week gestational age
Behavioral outcome5-6 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

Attention outcome5-6 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

Neuromotor outcome5-6 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

L1 promoter methylation levels on buccal swab5-6 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.

Trial Locations

Locations (1)

NICU, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico

🇮🇹

Milan, Italy

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