Environmental Enrichment Intervention and Brain Development in Preterm Infants (PRE-ENV)

Eskisehir Osmangazi University

Status: Not yet enrolling

Conditions: Preterm Birth

Treatments: Other: Standard Developmental Care; Behavioral: Environmental Enrichment-Based Intervention

Study type: Interventional

Funder types: Other

Identifiers

NCT07343505

ESOGU-TA-PretermEE-001

TDK-2025-3575 (Other Grant/Funding Number)

Details and patient eligibility

About

This study aims to evaluate the effects of a structured environmental enrichment (EE)-based early developmental intervention on brain, motor, and cognitive outcomes in preterm infants. Infants born before 37 weeks of gestation are at increased risk for alterations in structural and functional brain development, which may be further influenced by the neonatal intensive care environment, including exposure to excessive light, noise, and frequent medical procedures.

The intervention is a prospectively implemented, home-based developmental program structured according to the HEP (Homeostasis-Enrichment-Plasticity) approach, providing enriched sensory-motor experiences, environmental novelty, problem-solving activities, and opportunities for active exploration. The program is delivered through guided parental involvement with support from trained therapists, according to a predefined protocol.

Developmental outcomes will be assessed at baseline and after the intervention period using standardized, non-invasive assessment tools. The intervention does not include any pharmacological treatment or medical device. This study evaluates whether participation in an EE-based early developmental intervention leads to improved neurodevelopmental outcomes in preterm infants.

Full description

The purpose of this study is to investigate the effects of an environmental enrichment (EE)-based early developmental intervention on brain, motor, and cognitive development in preterm infants. Infants born before 37 weeks of gestation are at increased risk for alterations in brain structure and subsequent neurodevelopmental challenges. In addition to biological vulnerability, early sensory experiences and environmental factors may influence developmental trajectories during infancy.

This study will examine developmental outcomes together with brain morphometric measurements and urinary biochemical markers, including brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), Tau, and S100B.

Objectives:

1. To assess urinary biochemical markers, brain morphometry, and motor and cognitive development in preterm infants at corrected 1 month of age.
2. To examine relationships among urinary biochemical markers, brain morphometry, and developmental outcomes at baseline.
3. To compare changes in biochemical, neuroimaging, and developmental outcomes over a 12-week period between infants receiving standard care and those receiving an EE-based intervention.

Study Design:

A total of 28 preterm infants born before 37 weeks of gestation will be enrolled. The study will begin when infants reach corrected 1 month of age. Participants will be allocated into two parallel groups using stratified assignment based on relevant clinical characteristics.

Standard Care Group:

Infants in the standard care group will continue to receive routine medical follow-up and developmental monitoring as provided by their healthcare services. No additional intervention beyond usual care will be introduced as part of the study.

Environmental Enrichment (HEP) Intervention Group:

Infants in the intervention group will receive a structured environmental enrichment-based developmental program guided by a therapist through weekly in-person sessions. The intervention is based on the Homeostasis-Enrichment-Plasticity (HEP) approach and focuses on providing enriched sensory-motor experiences, environmental novelty, problem-solving opportunities, and active exploration appropriate to the infant's corrected age.

Weekly sessions are conducted by a trained therapist and are designed to support infant-environment interaction, promote motor and cognitive engagement, and coach caregivers in implementing developmentally appropriate practices. In addition to the therapist-guided sessions, caregivers are encouraged to integrate the HEP-based practices into their daily routines at home.

All intervention components are non-invasive, behavioral, and developmentally supportive in nature. No pharmacological treatments, invasive procedures, or medical devices are used as part of the intervention.

Procedures:

Urinary biochemical markers: Urine samples will be collected from all infants at baseline (corrected 1 month of age) and after the 12-week intervention period to measure levels of BDNF, NGF, Tau, and S100B. Samples will be stored at -80°C until analysis.

Brain imaging: Cranial ultrasonography obtained as part of routine clinical care will be used for morphometric analysis. No additional imaging procedures will be performed solely for research purposes.

Developmental assessment: Motor development will be assessed using the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) Motor Scale and the Test of Infant Motor Performance (TIMP). Cognitive development will be evaluated using the Bayley-III Cognitive Scale.

Caregiver well-being: Caregivers will complete the Depression Anxiety Stress Scales-21 (DASS-21) to assess caregiver psychological status.

Follow-up and Analysis:

All outcome measures, including urinary biochemical markers, cranial ultrasonography, developmental assessments, and caregiver questionnaires, will be repeated after the 12-week intervention period. Statistical analyses will examine within- and between-group changes over time, as well as associations among biochemical markers, brain morphometry, and developmental outcomes.

Enrollment: 28 estimated patients

Sex: All

Ages: 4 to 7 weeks old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

• Preterm infants born before 37 completed weeks of gestation.
• Corrected age between 4 and 7 weeks at the time of enrollment.
• Medically stable, as confirmed by the attending neonatologist
• Written informed consent obtained from parents or legal guardians.

Exclusion Criteria

• Major congenital anomalies or known genetic syndromes.
• Severe intraventricular hemorrhage (Grade III-IV) or other major neurological impairment.
• Unstable medical conditions that would interfere with safe participation in the study procedures.
• Caregivers unable to attend scheduled study sessions or comply with study-related procedures.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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28 participants in 2 patient groups

Control Group

Active Comparator group

Description:

Infants in this group will receive conventional developmental therapy and routine medical follow-up as provided within standard clinical practice. This approach represents an active comparator and does not include the structured environmental enrichment or the Homeostasis-Enrichment-Plasticity (HEP)-based intervention used in the experimental group. Participants in this group will undergo the same study-related assessments as the intervention group at baseline and after 12 weeks.

Treatment:

Other: Standard Developmental Care

HEP Home-Practice Group:

Experimental group

Description:

A structured environmental enrichment-based developmental intervention delivered over a 12-week period. The program is based on the Homeostasis-Enrichment-Plasticity (HEP) framework and includes age-appropriate sensory-motor activities, environmental novelty, problem-solving opportunities, and active caregiver-infant interaction. The intervention is delivered through weekly therapist-guided sessions, with caregivers encouraged to continue the practices at home as part of daily care.

Treatment:

Behavioral: Environmental Enrichment-Based Intervention