Infant Development, Stress
Conditions
Keywords
stress, preterm infants, epigenetics, gut microbiome, parent-infant relationship
Brief summary
The aims of this pilot are to determine the feasibility and acceptability of the Multisensory early oral administration of human milk (M-MILK) intervention, recruitment, retention, and obtain data for sample size estimation. This study will advance nursing science and practice because it will inform our R01 RCT to examine the efficacy of M-MILK to attenuate adverse effects of early life toxic stress in preterm infants.
Interventions
OTHERMultisensory Early Oral Administration of Human Milk (M-MILK)
M-MILK is implemented starting on day 3 of life, after every hands-on care, during the beginning of a full gavage feeding. Infants receive M-MILK in small droplets via a 1-ml syringe. M-MILK will cease upon oral feeding initiation. Infants will receive either mother's own milk or donor's milk based on availability. Infants may receive up to 1 mL of milk each time based on their cues and responses. The 1 mL volume intake is included as part of their oral caloric intake. M-MILK is provided by nurses or parents.
Sponsors
Loyola University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
0 Years to 1 Years
Healthy volunteers
No
Inclusion criteria
* born between 22 to 34 weeks gestational age and receiving mother's own milk and/or donor milk.
Exclusion criteria
* receiving only formula, oral cavity defects, gastrointestinal defects, chromosomal abnormalities, severe cardiac defects that require surgery, or intraventricular hemorrhage grade III or IV
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Early Feeding Skill Assessment Score | At the time of discharge from NICU, which is typically 10 to 16 weeks from birth. | EFS has 22 items (32-50 weeks PMA), summary scores, 5 subscales: respiratory regulation (range 5 - 15), oral-motor functioning (range 4 - 12), swallowing coordination (range 4 - 12), engagement (range 2 - 6), & physiologic stability (range 4 - 12), where higher scores indicate better oral feeding skill development. The total score is the sum of the subscales and ranges from 19-57. |
| Retention | 2 months corrected age | Retention will be described by the number of post-discharge follow-up surveys completed. |
| The Scarf Sign Cluster of the Neurobehavioral Assessment of the Preterm Infants Score | At the time of discharge from NICU, which is typically 10 to 16 weeks from birth. | The Neurobehavioral Assessment of the Preterm Infants (NAPI, 73 items, 32-37 weeks PMA): cluster score for scarf sign ranges from 0-100, where higher scores indicate better neurodevelopmental performance. |
| Variability in the Motor Development & Vigor Cluster of the Neurobehavioral Assessment of the Preterm Infants Score | At the time of discharge from NICU, which is typically 10 to 16 weeks from birth. | The Neurobehavioral Assessment of the Preterm Infants (NAPI, 73 items, 32-37 weeks PMA): cluster score for motor development & vigor ranges from 0-100, where higher scores indicate better neurodevelopmental performance. |
| Popliteal Angle Cluster of the Neurobehavioral Assessment of the Preterm Infants Score | At the time of discharge from NICU, which is typically 10 to 16 weeks from birth. | The Neurobehavioral Assessment of the Preterm Infants (NAPI, 73 items, 32-37 weeks PMA): cluster score for popliteal angle ranges from 0-100, where higher scores indicate better neurodevelopmental performance. |
| Alertness and Orientation Cluster of the Neurobehavioral Assessment of the Preterm Infants Score | At the time of discharge from NICU, which is typically 10 to 16 weeks from birth. | The Neurobehavioral Assessment of the Preterm Infants (NAPI, 73 items, 32-37 weeks PMA): cluster score for alertness and orientation ranges from 0-100, where higher scores indicate better neurodevelopmental performance. |
| Irritability Cluster of the Neurobehavioral Assessment of the Preterm Infants Score | At the time of discharge from NICU, which is typically 10 to 16 weeks from birth. | The Neurobehavioral Assessment of the Preterm Infants (NAPI, 73 items, 32-37 weeks PMA): cluster score for irritability ranges from 0-100, where higher scores indicate better neurodevelopmental performance. |
| Quality of Cry Cluster of the Neurobehavioral Assessment of the Preterm Infants Score | At the time of discharge from NICU, which is typically 10 to 16 weeks from birth. | The Neurobehavioral Assessment of the Preterm Infants (NAPI, 73 items, 32-37 weeks PMA): cluster score for quality of cry ranges from 0-100, where higher scores indicate better neurodevelopmental performance. |
| Percent Sleep Cluster of the Neurobehavioral Assessment of the Preterm Infants Score | At the time of discharge from NICU, which is typically 10 to 16 weeks from birth. | The Neurobehavioral Assessment of the Preterm Infants (NAPI, 73 items, 32-37 weeks PMA): cluster score for percent sleep ranges from 0-100, where higher scores indicate better neurodevelopmental performance. |
| Feasibility of Intervention | At the time of discharge from NICU, which is typically 10 to 16 weeks from birth. | The count of participants who receive M-MILK in at least 50% of their scheduled M-MILK administrations. MILK will be considered feasible if M-MILK is implemented by nurses or parents after every hands-on care and during the beginning of a full gavage feeding at least 50% of the time. |
| Acceptability of Intervention | At the time of discharge from NICU, which is typically 10 to 16 weeks from birth. | The percentage of parents who rate the intervention as very positive, slightly positive, or acceptable on a 5-point Likert scale. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Breastfeeding Rate | At the time of discharge from NICU, which is typically 10 to 16 weeks from birth. | The percentage of mothers who report breastfeeding at discharge. |
| Maternal Edinburgh Postnatal Depression Scale Score | At the time of discharge from NICU, which is typically 10 to 16 weeks from birth. | Scores range from 0 to 30, where higher scores indicate greater depressive symptoms |
| Parent Stressor Scale: NICU Score | At the time of discharge from NICU, which is typically 10 to 16 weeks from birth. | Scores range from 1 to 5, where higher scores indicate greater parental stress.. |
| Parent Discharge Readiness Score | At the time of discharge from NICU, which is typically 10 to 16 weeks from birth. | Scores range from 44 to 308, where higher scores indicate more parental readiness for discharge. |
| Breastmilk Pumping Rate | At the time of discharge from NICU, which is typically 10 to 16 weeks from birth. | The percentage of mothers who report breastmilk pumping at discharge. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Variability in Gut Microbial Community Structure and Relative Abundance of SCFA- and Lactate- Producing Bacteria | At the time of discharge from NICU, which is typically 10 to 16 weeks from birth. | Alpha diversity indices will be obtained. Differential abundance individual taxa will be obtained. |
| Variability in DNA Methylation of HSD11B2 Promoter | At the time of discharge from NICU, which is typically 10 to 16 weeks from birth. | The percent DNAm at the HSD11B2 promoters and at each CpG site will be quantified. |
| Variability in DNA Methylation of NR3C1 Promoter | At the time of discharge from NICU, which is typically 10 to 16 weeks from birth. | The percent DNAm at the NR3C1 promoters and at each CpG site will be quantified. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Attention Control Infants in the attention control group will receive standard of care. | 4 |
| M-MILK Infants in the M-MILK group will receive the M-MILK intervention in addition to standard of care. | 10 |
| Total | 14 |
Baseline characteristics
| Characteristic | Attention Control | M-MILK | Total |
|---|---|---|---|
| Age, Continuous | 30.5 weeks | 27 weeks | 27 weeks |
| Birthweight | 1525 grams | 875 grams | 977 grams |
| Intrauterine growth restriction | 0 Participants | 3 Participants | 3 Participants |
| Preterm premature rupture of the membranes | 1 Participants | 7 Participants | 8 Participants |
| Race/Ethnicity, Customized Hispanic | 1 Participants | 3 Participants | 4 Participants |
| Race/Ethnicity, Customized Non-Hispanic Asian | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Non-Hispanic Black | 0 Participants | 4 Participants | 4 Participants |
| Race/Ethnicity, Customized Non-Hispanic White | 2 Participants | 3 Participants | 5 Participants |
| Region of Enrollment United States | 4 participants | 10 participants | 14 participants |
| Sex: Female, Male Female | 1 Participants | 7 Participants | 8 Participants |
| Sex: Female, Male Male | 3 Participants | 3 Participants | 6 Participants |
| Small for gestational age | 0 Participants | 2 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 10 |
| other Total, other adverse events | 0 / 4 | 0 / 10 |
| serious Total, serious adverse events | 0 / 4 | 0 / 10 |
Outcome results
Primary
Acceptability of Intervention
The percentage of parents who rate the intervention as very positive, slightly positive, or acceptable on a 5-point Likert scale.
Time frame: At the time of discharge from NICU, which is typically 10 to 16 weeks from birth.
Population: Reported by the parent in the study exit survey. Only parents in the M-MILK group were asked about the intervention. Two parents did not complete the acceptability survey.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Attention Control | Acceptability of Intervention | 0 Participants |
| M-MILK | Acceptability of Intervention | 5 Participants |
Primary
Alertness and Orientation Cluster of the Neurobehavioral Assessment of the Preterm Infants Score
The Neurobehavioral Assessment of the Preterm Infants (NAPI, 73 items, 32-37 weeks PMA): cluster score for alertness and orientation ranges from 0-100, where higher scores indicate better neurodevelopmental performance.
Time frame: At the time of discharge from NICU, which is typically 10 to 16 weeks from birth.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Attention Control | Alertness and Orientation Cluster of the Neurobehavioral Assessment of the Preterm Infants Score | 41.3 score on a scale |
| M-MILK | Alertness and Orientation Cluster of the Neurobehavioral Assessment of the Preterm Infants Score | 82.5 score on a scale |
Primary
Early Feeding Skill Assessment Score
EFS has 22 items (32-50 weeks PMA), summary scores, 5 subscales: respiratory regulation (range 5 - 15), oral-motor functioning (range 4 - 12), swallowing coordination (range 4 - 12), engagement (range 2 - 6), & physiologic stability (range 4 - 12), where higher scores indicate better oral feeding skill development. The total score is the sum of the subscales and ranges from 19-57.
Time frame: At the time of discharge from NICU, which is typically 10 to 16 weeks from birth.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Attention Control | Early Feeding Skill Assessment Score | 47.3 score on a scale | Standard Deviation 3.9 |
| M-MILK | Early Feeding Skill Assessment Score | 49.6 score on a scale | Standard Deviation 5.3 |
Primary
Feasibility of Intervention
The count of participants who receive M-MILK in at least 50% of their scheduled M-MILK administrations. MILK will be considered feasible if M-MILK is implemented by nurses or parents after every hands-on care and during the beginning of a full gavage feeding at least 50% of the time.
Time frame: At the time of discharge from NICU, which is typically 10 to 16 weeks from birth.
Population: Only the intervention arm is assessed for feasibility.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Attention Control | Feasibility of Intervention | 0 Participants |
| M-MILK | Feasibility of Intervention | 7 Participants |
Primary
Irritability Cluster of the Neurobehavioral Assessment of the Preterm Infants Score
The Neurobehavioral Assessment of the Preterm Infants (NAPI, 73 items, 32-37 weeks PMA): cluster score for irritability ranges from 0-100, where higher scores indicate better neurodevelopmental performance.
Time frame: At the time of discharge from NICU, which is typically 10 to 16 weeks from birth.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Attention Control | Irritability Cluster of the Neurobehavioral Assessment of the Preterm Infants Score | 33.4 score on a scale |
| M-MILK | Irritability Cluster of the Neurobehavioral Assessment of the Preterm Infants Score | 33.4 score on a scale |
Primary
Percent Sleep Cluster of the Neurobehavioral Assessment of the Preterm Infants Score
The Neurobehavioral Assessment of the Preterm Infants (NAPI, 73 items, 32-37 weeks PMA): cluster score for percent sleep ranges from 0-100, where higher scores indicate better neurodevelopmental performance.
Time frame: At the time of discharge from NICU, which is typically 10 to 16 weeks from birth.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Attention Control | Percent Sleep Cluster of the Neurobehavioral Assessment of the Preterm Infants Score | 14.3 score on a scale |
| M-MILK | Percent Sleep Cluster of the Neurobehavioral Assessment of the Preterm Infants Score | 14.3 score on a scale |
Primary
Popliteal Angle Cluster of the Neurobehavioral Assessment of the Preterm Infants Score
The Neurobehavioral Assessment of the Preterm Infants (NAPI, 73 items, 32-37 weeks PMA): cluster score for popliteal angle ranges from 0-100, where higher scores indicate better neurodevelopmental performance.
Time frame: At the time of discharge from NICU, which is typically 10 to 16 weeks from birth.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Attention Control | Popliteal Angle Cluster of the Neurobehavioral Assessment of the Preterm Infants Score | 16.7 score on a scale |
| M-MILK | Popliteal Angle Cluster of the Neurobehavioral Assessment of the Preterm Infants Score | 66.7 score on a scale |
Primary
Quality of Cry Cluster of the Neurobehavioral Assessment of the Preterm Infants Score
The Neurobehavioral Assessment of the Preterm Infants (NAPI, 73 items, 32-37 weeks PMA): cluster score for quality of cry ranges from 0-100, where higher scores indicate better neurodevelopmental performance.
Time frame: At the time of discharge from NICU, which is typically 10 to 16 weeks from birth.
Population: Cry quality is only measured if the infant was crying during the assessment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Attention Control | Quality of Cry Cluster of the Neurobehavioral Assessment of the Preterm Infants Score | 0 score on a scale |
| M-MILK | Quality of Cry Cluster of the Neurobehavioral Assessment of the Preterm Infants Score | 25 score on a scale |
Primary
Retention
Retention will be described by the number of post-discharge follow-up surveys completed.
Time frame: 2 months corrected age
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Attention Control | Retention | 4 Participants |
| M-MILK | Retention | 7 Participants |
Primary
The Scarf Sign Cluster of the Neurobehavioral Assessment of the Preterm Infants Score
The Neurobehavioral Assessment of the Preterm Infants (NAPI, 73 items, 32-37 weeks PMA): cluster score for scarf sign ranges from 0-100, where higher scores indicate better neurodevelopmental performance.
Time frame: At the time of discharge from NICU, which is typically 10 to 16 weeks from birth.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Attention Control | The Scarf Sign Cluster of the Neurobehavioral Assessment of the Preterm Infants Score | 66.7 score on a scale |
| M-MILK | The Scarf Sign Cluster of the Neurobehavioral Assessment of the Preterm Infants Score | 66.7 score on a scale |
Primary
Variability in the Motor Development & Vigor Cluster of the Neurobehavioral Assessment of the Preterm Infants Score
The Neurobehavioral Assessment of the Preterm Infants (NAPI, 73 items, 32-37 weeks PMA): cluster score for motor development & vigor ranges from 0-100, where higher scores indicate better neurodevelopmental performance.
Time frame: At the time of discharge from NICU, which is typically 10 to 16 weeks from birth.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Attention Control | Variability in the Motor Development & Vigor Cluster of the Neurobehavioral Assessment of the Preterm Infants Score | 53.1 score on a scale |
| M-MILK | Variability in the Motor Development & Vigor Cluster of the Neurobehavioral Assessment of the Preterm Infants Score | 60.9 score on a scale |
Secondary
Breastfeeding Rate
The percentage of mothers who report breastfeeding at discharge.
Time frame: At the time of discharge from NICU, which is typically 10 to 16 weeks from birth.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Attention Control | Breastfeeding Rate | 0 Participants |
| M-MILK | Breastfeeding Rate | 1 Participants |
Secondary
Breastmilk Pumping Rate
The percentage of mothers who report breastmilk pumping at discharge.
Time frame: At the time of discharge from NICU, which is typically 10 to 16 weeks from birth.
Population: Two parents in the M-MILK group did not report this data at discharge.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Attention Control | Breastmilk Pumping Rate | 1 Participants |
| M-MILK | Breastmilk Pumping Rate | 5 Participants |
Secondary
Maternal Edinburgh Postnatal Depression Scale Score
Scores range from 0 to 30, where higher scores indicate greater depressive symptoms
Time frame: At the time of discharge from NICU, which is typically 10 to 16 weeks from birth.
Population: Two parents in the M-MILK group did not complete this survey.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Attention Control | Maternal Edinburgh Postnatal Depression Scale Score | 3.8 score on a scale | Standard Deviation 4.5 |
| M-MILK | Maternal Edinburgh Postnatal Depression Scale Score | 4.8 score on a scale | Standard Deviation 4.9 |
Secondary
Parent Discharge Readiness Score
Scores range from 44 to 308, where higher scores indicate more parental readiness for discharge.
Time frame: At the time of discharge from NICU, which is typically 10 to 16 weeks from birth.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Attention Control | Parent Discharge Readiness Score | 231.0 score on a scale |
| M-MILK | Parent Discharge Readiness Score | 211.0 score on a scale |
Secondary
Parent Stressor Scale: NICU Score
Scores range from 1 to 5, where higher scores indicate greater parental stress..
Time frame: At the time of discharge from NICU, which is typically 10 to 16 weeks from birth.
Population: Two parents in the M-MILK group did not complete this survey.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Attention Control | Parent Stressor Scale: NICU Score | 2.4 score on a scale | Standard Deviation 1.2 |
| M-MILK | Parent Stressor Scale: NICU Score | 2.3 score on a scale | Standard Deviation 1 |
Other Pre-specified
Variability in DNA Methylation of HSD11B2 Promoter
The percent DNAm at the HSD11B2 promoters and at each CpG site will be quantified.
Time frame: At the time of discharge from NICU, which is typically 10 to 16 weeks from birth.
Other Pre-specified
Variability in DNA Methylation of NR3C1 Promoter
The percent DNAm at the NR3C1 promoters and at each CpG site will be quantified.
Time frame: At the time of discharge from NICU, which is typically 10 to 16 weeks from birth.
Other Pre-specified
Variability in Gut Microbial Community Structure and Relative Abundance of SCFA- and Lactate- Producing Bacteria
Alpha diversity indices will be obtained. Differential abundance individual taxa will be obtained.
Time frame: At the time of discharge from NICU, which is typically 10 to 16 weeks from birth.