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

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

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

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.

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.

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.

Standard Care according to NICU protocols including Kangaroo Mother Care, nesting and minimal handling

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 behavior is assessed using the Neonatal Behavior Assessment Scale that evaluates: habituation, social-interactive, motor system, state organization and regulation, autonomic system, reflexes.

Children development is assessed using the Bayley Scales of Infant and Toddlers (Third edition) - including: cognitive, motor, language, social-emotional and adaptive behavior)

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

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

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

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

Child attention abilities is assessed using the Early Childhood Attention Battery (ECAB). Scaled scores range from 1 to 19. Lower scores indicate worst outcome

epigenetic analysis - L1 promoter methylation (Percent) assessment is performed on a buccal swab collected at follow-up assessment at 5-6 years.

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.

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