Effects of Early Vocal Contact (EVC) in the Neonatal Intensive Care Unit

Study Overview
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Brief Summary
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Background: Preterm infants are at risk for developing altered trajectories of cognitive, social, and linguistic competences compared to a term population. This is mainly due to medical and environmental factors, as they are exposed to an atypical auditory environment and, simultaneously, to long periods of early separation from their parents. The short-term effects of Early Vocal Contact (EVC) on an infant's early stability have been investigated, but currently, there is limited evidence of its impact on the infant's autonomic nervous system maturation, as indexed by the heart rate variability, as well as on its long-term impact on infant neurodevelopment. This multi-centric study aims to investigate the effects of EVC on a preterm infant's physiology, neurobehaviour, and development. Methods: Eighty stable preterm infants, born at 25 to 32 weeks and 6 days gestational age, without specific abnormalities, will be selected and randomized to either an intervention or a control group. The intervention group will receive EVC: mothers talking and singing to their preterm infants for 10 minutes thrice a week for 2 weeks. Mothers in the control group will be encouraged to spend the same amount of time next to the incubator, observing the infant's behaviour through a standard cluster of indicators. Infants will be assessed at baseline, at the end of the intervention, at term equivalent age, and at 3, 6, 12- and 24-months corrected age, with a battery of physiological, neurobehavioral, and developmental measures. Discussion: Early interventions in the neonatal intensive care unit have shown important effects on the neurodevelopment of preterm infants, lowering the negative long-term effects of an atypical auditory and interactional environment. This study will provide new insights into the mother-infant early contact as protective intervention against the sequelae of prematurity during the sensitive period of development. An early intervention, such as EVC, is intuitive and easy to implement in the daily care of preterm infants. However, its long-term effects on infant neurodevelopment and on maternal sensitivity and stress still need accurate investigations.

Detailed Description
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Aims This study aims to test the effects of EVC on infants born prematurely between 25 and 32 weeks and 6 days GA. The effects on newborns will be assessed at physiological (primary outcome), neurobehavioral, and developmental levels during the intervention, at term equivalent age, and at 12- and 24-months CA. The effect of EVC will also be assessed on maternal stress at hospital discharge and on the mother's presence in the NICU. Design A four-site randomized controlled trial will be conducted to investigate the short- and long-term physiological and neurobehavioral effects of EVC. Participants Eighty preterm infants, born at 25 to 32 weeks and 6 days GA, will be recruited from the four centres (20 per centre). Recruitment will be undertaken in each centre by a trained research assistant (RA), who will review birth records daily. After obtaining permission from the attending physicians of both the mother and the infant, the RA will invite qualifying families to participate in the study and will obtain written informed consent from those enrolling. Infants will be then assigned to the EVC intervention or control group using a randomized design, stratifying infants by gender and GA (see Randomization). Mothers whose infants are assigned to the control group will be asked to spend the same amount of time as that of mothers in the intervention group, observing their infants' spontaneous behaviour, with the subsequent compilation of an observation grid developed ad hoc, according to few indicators drawn from The Neonatal Behavioural Assessment Scale (NBAS).

Official Title
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Effects of Early Vocal Contact (EVC) in the Neonatal Intensive Care Unit: A Multi-centre, Randomized Clinical Trial

Conditions
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Early Intervention, Prematurity

Intervention / Treatment
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* Behavioral: Early Vocal Contact
* Behavioral: Behavioral Observation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: • GA between 25+0 and 32 +6 weeks at birth Apgar score: ≥ 7 at 10 minutes Birth weight: >3th centile and <97th centile Birth cranial circumference: >10th centile Periventricular leukomalacia (PVL) grade 1 Intraventricular haemorrhage (IVH) grade 1-2 Hypoglycaemia Hyponatremia acceptable, provided they are not persistent and severe Hypocalcaemia Exclusion Criteria: • PVL, grade III and IV IVH, grade III and IV Sepsis (vertical and horizontal) Congenital malformations and/or genetic abnormalities Need of respiratory support with high flow/nCPAP Repeated apnoea associated with bradycardia and fall of saturation Hyaline membrane disease Respiratory Distress Syndrome Hyperbilirubinemia, requiring exchange transfusions during hospitalization Lack of informed consent signed by the parents The exclusion criteria for the mothers will be: Presence of depressive symptoms Drug abuse Age ˂18 years

Ages Eligible for Study
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Minimum Age: 25 Weeks
Maximum Age: 33 Weeks

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Health Services Research
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A four-site randomized controlled trial will be conducted to investigate the short- and long-term physiological and neurobehavioral effects of Early Vocal Contact.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Early Vocal Contact<br>The EVC will take place in the hospital room while infants are in their individual incubators or open cribs. In the intervention group, mothers will be asked to speak and sing to their infants continuously over a 10-min period for each type of intervention (20 min in total). Mothers will be asked to talk in their native language and to sing familiar songs, while observing their infant's reactions. The order of the two vocalizations, speaking and singing, will be reversed in the next intervention. Early Vocal Contact will be performed by mothers three times a week for 2 weeks, more than one hour after afternoon feeding. It will begin when the newborns are in an active sleep state, in calm awake state or in active awake state, but not in deep sleep or crying. Preterm infants will be enrolled from 25+0 to 32+6 weeks of GA, following the established inclusion criteria. | Behavioral: Early Vocal Contact<br>* Mothers will be asked to speak and sing to their infants continuously over a 10-min period for each type of intervention (20 min in total). Mothers will be asked to talk in their native language and to sing familiar songs, while observing their infant's reactions. The order of the two vocalizations, speaking and singing, will be reversed in the next intervention.<br>|
| Active Comparator: Behavioral observation<br>Mothers in the active control group will be encouraged to spend the same amount of time next to the incubator, observing the infant's behaviours through a standard cluster of indicators. | Behavioral: Behavioral Observation<br>* Mothers in the active control group will be encouraged to spend the same amount of time next to the incubator, observing the infant's behaviours through a standard cluster of indicators.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Heart Rate Variability | Heart rate is the number of heartbeats per minute. | Pre intervention (baseline), during the intervention and immediately after the intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in General Movement Assessment | The General Movement quality from video recording will be scored according to the Ferrari optimality score. Two blinded coders will attribute a single final score for each infant at each time point. For each item a description of optimal performance is given and scored with 2 (e.g., cramped components are absent). Less optimal performance is scored with 1 (e.g., cramped components are occasionally present); non-optimal performance is scored with 0 (e.g., cramped components are predominately present). Adding the scores of each item within a category (neck and trunk, upper extremity and lower extremity) plus the score for sequence gives the GM optimality score with a minimum value of 5 and a maximum value of 42, indicating optimal performance. The minimum score (worst performance) is 5. | Pre intervention (baseline) | 
| Change in General Movement Assessment | The General Movement quality from video recording will be scored according to the Ferrari optimality score. Two blinded coders will attribute a single final score for each infant at each time point. For each item a description of optimal performance is given and scored with 2 (e.g., cramped components are absent). Less optimal performance is scored with 1 (e.g., cramped components are occasionally present); non-optimal performance is scored with 0 (e.g., cramped components are predominately present). Adding the scores of each item within a category (neck and trunk, upper extremity and lower extremity) plus the score for sequence gives the GM optimality score with a minimum value of 5 and a maximum value of 42, indicating optimal performance. The minimum score (worst performance) is 5. | After the intervention, at Term Equivalent Age | 
| Change in General Movement Assessment | The General Movement quality from video recording will be scored according to the Ferrari optimality score. Two blinded coders will attribute a single final score for each infant at each time point. For each item a description of optimal performance is given and scored with 2 (e.g., cramped components are absent). Less optimal performance is scored with 1 (e.g., cramped components are occasionally present); non-optimal performance is scored with 0 (e.g., cramped components are predominately present). Adding the scores of each item within a category (neck and trunk, upper extremity and lower extremity) plus the score for sequence gives the GM optimality score with a minimum value of 5 and a maximum value of 42, indicating optimal performance. The minimum score (worst performance) is 5. | At 3 months | 
| The Griffiths Mental Development Scales (GMDS) | The GMDS will be assessed with mean values in 4 subscales (Locomotor, Per-Social, Hear/Speech, Hand/Eye). A composite final Performance score will also be assessed for each participant at each time point. The mean values will be compared between the intervention and control groups. Scores range from 0 to 109, with better results with higher values. | At 6 months corrected age | 
| The Griffiths Mental Development Scales (GMDS) | The GMDS will be assessed with mean values in 4 subscales (Locomotor, Per-Social, Hear/Speech, Hand/Eye). A composite final Performance score will also be assessed for each participant at each time point. The mean values will be compared between the intervention and control groups. Scores range from 0 to 109, with better results with higher values. | At 12 months corrected age | 
| MacArthur-Bates Communicative Development Inventories | Each child, at each time point, will receive a final score for each questionnaire, measured as a discrete numeric value; the mean values will be compared in the intervention and control groups. The minimum score il 0 and the maximum is 429, with higher scores for better performance. | At 12 months (Gestures and Words Form) and 24 months (Words and Sentences Form) corrected age. | 
| MacArthur-Bates Communicative Development Inventories | Each child, at each time point, will receive a final score for each questionnaire, measured as a discrete numeric value; the mean values will be compared in the intervention and control groups. The minimum score il 0 and the maximum is 429, with higher scores for better performance. | At 12 months corrected age | 
| MacArthur-Bates Communicative Development Inventories | Each child, at each time point, will receive a final score for each questionnaire, measured as a discrete numeric value; the mean values will be compared in the intervention and control groups. The minimum score il 0 and the maximum is 429, with higher scores for better performance. | At 24 months corrected age | 
| Parole in Gioco (PinG) test | Linguistic test for assessing lexical comprehension and production for early childhood. The minimum score il 0 and the maximum is 60, with higher scores for better performance. | At 24 months corrected age | 
| Change in Parental Stressor Scale (PSS-NICU) | The PSS-NICU aims at assessing the parental perception of stressors derived from the physical and psycho-social environment of the NICU across three domains: (i) their parental role, (ii) their infant's behaviour and appearance, and (iii) the sights and sounds in the NICU. For each domain, a mean score will be assessed, and a final composite stress score will be calculated from the mean values of the single scores. Each mother, at each time point, will receive a final score for the single questionnaire (range 0-10). The minimum score il 0 and the maximum is 156, with lower scores for better mental health levels. | Pre intervention | 
| Change in Parental Stressor Scale (PSS-NICU) | The PSS-NICU aims at assessing the parental perception of stressors derived from the physical and psycho-social environment of the NICU across three domains: (i) their parental role, (ii) their infant's behaviour and appearance, and (iii) the sights and sounds in the NICU. For each domain, a mean score will be assessed, and a final composite stress score will be calculated from the mean values of the single scores. Each mother, at each time point, will receive a final score for the single questionnaire (range 0-10). The minimum score il 0 and the maximum is 156, with lower scores for better mental health levels. | At hospital discharge | 
| Maternal presence in the NICU | Time that the mothers spend in the NICU (hours) using maternal self-report forms will be filled out after each visit to the NICU | At hospital discharge | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Early Vocal Contact, Neonatal Intensive Care Unite, Preterm Infants