Clinical trial NCT02983513: Early Intervention in Preterm Infants: Short and Long Term Developmental Outcome After a Parental Training Program
Official title: Early Intervention in Preterm Infants: Effects of a Parental Training Program on Neonatal Brain Development, Visual Functions and Neurobehavioral Outcome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Premature Birth
Keywords: Early intervention
Brain Development
Neurodevelopment
Lead sponsor: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Sponsor class: OTHER
First posted: 2016-12-06
Enrollment: 70
Sex: ALL
Minimum age (years): 25
Maximum age (years): 29
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Neonatal Visual Assessment Battery to evaluate visual function
timeFrame: 40 weeks postmenstrual age
measure: Neonatal Behavior
timeFrame: 2 months corrected age
Secondary outcomes:
measure: Brain development
timeFrame: 40 weeks postmenstrual age
measure: Developmental outcome
timeFrame: 24 months corrected age
measure: Epigenetic changes
timeFrame: up to 48 weeks gestational age
measure: overall duration of hospitalisation
timeFrame: up to 48 weeks gestational age
measure: Weight (in grams) at 40 weeks postmenstrual age
timeFrame: 40 week gestational age
measure: Length(in centimeters) at 40 weeks postmenstrual age
timeFrame: 40 week gestational age
measure: Head circumference (in centimeters) at 40 weeks postmenstrual age
timeFrame: 40 week gestational age
measure: Acquisition of full oral feeding
timeFrame: up to 48 weeks gestational age
measure: Feeding with Human milk
timeFrame: up to 40 weeks gestational age
measure: Neurodevelopmental outcome
timeFrame: 5-6 years of age
measure: Behavioral outcome
timeFrame: 5-6 years of age
measure: Neuromotor outcome
timeFrame: 5-6 years of age
measure: Attention outcome
timeFrame: 5-6 years of age
measure: L1 promoter methylation levels on buccal swab
timeFrame: 5-6 years of age
Other outcomes:
Locations:
city: Milan
country: Italy
facility: NICU, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
Study officials:
affiliation: Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
name: Monica Fumagalli, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Newnham CA, Milgrom J, Skouteris H. Effectiveness of a modified Mother-Infant Transaction Program on outcomes for preterm infants from 3 to 24 months of age. Infant Behav Dev. 2009 Jan;32(1):17-26. doi: 10.1016/j.infbeh.2008.09.004. Epub 2008 Nov 20.
citation: Provenzi L, Fumagalli M, Sirgiovanni I, Giorda R, Pozzoli U, Morandi F, Beri S, Menozzi G, Mosca F, Borgatti R, Montirosso R. Pain-related stress during the Neonatal Intensive Care Unit stay and SLC6A4 methylation in very preterm infants. Front Behav Neurosci. 2015 Apr 21;9:99. doi: 10.3389/fnbeh.2015.00099. eCollection 2015.
citation: Guzzetta A, D'Acunto MG, Carotenuto M, Berardi N, Bancale A, Biagioni E, Boldrini A, Ghirri P, Maffei L, Cioni G. The effects of preterm infant massage on brain electrical activity. Dev Med Child Neurol. 2011 Sep;53 Suppl 4:46-51. doi: 10.1111/j.1469-8749.2011.04065.x.
citation: Ricci D, Cesarini L, Romeo DM, Gallini F, Serrao F, Groppo M, De Carli A, Cota F, Lepore D, Molle F, Ratiglia R, De Carolis MP, Mosca F, Romagnoli C, Guzzetta F, Cowan F, Ramenghi LA, Mercuri E. Visual function at 35 and 40 weeks' postmenstrual age in low-risk preterm infants. Pediatrics. 2008 Dec;122(6):e1193-8. doi: 10.1542/peds.2008-1888.
citation: Ricci D, Romeo DM, Serrao F, Cesarini L, Gallini F, Cota F, Leone D, Zuppa AA, Romagnoli C, Cowan F, Mercuri E. Application of a neonatal assessment of visual function in a population of low risk full-term newborn. Early Hum Dev. 2008 Apr;84(4):277-80. doi: 10.1016/j.earlhumdev.2007.10.002. Epub 2007 Nov 8.
citation: Fontana C, Marasca F, Provitera L, Mancinelli S, Pesenti N, Sinha S, Passera S, Abrignani S, Mosca F, Lodato S, Bodega B, Fumagalli M. Early maternal care restores LINE-1 methylation and enhances neurodevelopment in preterm infants. BMC Med. 2021 Feb 5;19(1):42. doi: 10.1186/s12916-020-01896-0.
citation: Fontana C, De Carli A, Ricci D, Dessimone F, Passera S, Pesenti N, Bonzini M, Bassi L, Squarcina L, Cinnante C, Mosca F, Fumagalli M. Effects of Early Intervention on Visual Function in Preterm Infants: A Randomized Controlled Trial. Front Pediatr. 2020 Jun 4;8:291. doi: 10.3389/fped.2020.00291. eCollection 2020.