Infant, Premature, Diseases
Conditions
Brief summary
The goal of this clinical trial is to learn if the multisensory early oral administration of human milk (M-MILK) intervention helps infants who are born younger than 32 weeks gestational age (very preterm infants). The main question that this clinical trial aims to answer is: Does M-MILK improve stress regulation, support optimal neurodevelopment, and promote competent oral feeding skills in very preterm infants? Researchers will compare M-MILK to the standard of care to see if M-MILK helps very preterm infants. Specifically, researchers will compare the differences in: * Cortisol levels * DNA methylation of the two stress related genes (NR3C1 and HSD11B2) * Neurodevelopment * Oral feeding skills Participants in the M-MILK group will receive standard of care plus M-MILK intervention, which starts on day 3 of life and continues until they begin their oral feeding. M-MILK will be provided by clinical research nurses, during the day shift, up to 4 times a day. Participants in the standard of care group will continue to receive their usual care.
Interventions
OTHERMultisensory early oral administration of human milk
M-MILK is implemented starting on day 3 of life, during the day shift, after every hands-on care, during the beginning of a full gavage feeding, and up to 4 times a day. 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 research nurses or parents.
Sponsors
Loyola University
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Rush University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
23 Weeks to 32 Weeks
Healthy volunteers
No
Inclusion criteria
* Born at ≤ 32 weeks gestational age. * Receiving mother's own milk and/or donor human milk at the time of screening.
Exclusion criteria
* Receiving only formula. * Gastrointestinal defects, i.e., cleft lip or cleft palate. * Congenital cardiac defects requiring surgery. * Necrotizing enterocolitis. * Chromosomal abnormalities.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Oral feeding Skills: EFS assessment total score at PO Initiation | Up to 12 weeks after birth. | We will evaluate oral feeding skills using the Early Feeding Skills Assessment (EFS) at oral feeding (PO) initiation. The EFS provides a summary score for each of the 5 subscale (respiratory regulation, oral-motor functioning, swallowing coordination, engagement, and physiologic stability), as well as a total summary score. Higher EFS summary scores indicate more competent oral feeding skills. |
| Oral Feeding Skills: EFS assessment total score at 36 Weeks PMA | 36 weeks postmenstrual age. | We will evaluate oral feeding skills using the Early Feeding Skills Assessment (EFS) at 36 weeks post-menstrual age (PMA). The EFS provides a summary score for each of the 5 subscale (respiratory regulation, oral-motor functioning, swallowing coordination, engagement, and physiologic stability), as well as a total summary score. Higher EFS summary scores indicate more competent oral feeding skills. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Stress Regulation: Salivary Cortisol at PO Initiation | Up to 12 weeks after birth. | We will evaluate stress regulation, measured by salivary cortisol levels (μg/dL) at oral feeding (PO) initiation. |
| Stress Regulation: Salivary Cortisol at 36 Weeks PMA | At 36 weeks postmenstrual age. | We will evaluate stress regulation, measured by salivary cortisol levels (μg/dL) at 36 weeks PMA. |
| Stress Regulation: Buccal Cell DNAm of NR3C1 Exon 1F Promoter at PO Initiation | Up to 12 weeks after birth. | We will evaluate stress regulation, measured by buccal cell DNA methylation (DNAm) of NR3C1 Exon 1F promoter at oral feeding (PO) initiation. We anticipate to cover 33 CpG sites within the NR3C1 Exon 1F promoter. Methylation percentage (%) will calculated per CpG site (aligning with the human reference genome hg38). |
| Stress Regulation: Buccal Cell DNAm of NR3C1 Exon 1F Promoter at 36 Weeks PMA | At 36 weeks postmenstrual age. | We will evaluate stress regulation, measured by buccal cell DNA methylation (DNAm) of NR3C1 Exon 1F promoter at 36 weeks post-menstrual age (PMA). We anticipate to cover 33 CpG sites within the NR3C1 Exon 1F promoter. Methylation percentage (%) will calculated per CpG site (aligning with the human reference genome hg38). |
| Stress Regulation: Buccal Cell DNAm of HSD11B2 Promoter at PO Initiation | Up to 12 weeks after birth. | We will evaluate stress regulation, measured by buccal cell DNA methylation (DNAm) of HSD11B2 promoter at oral feeding (PO) initiation. We anticipate to cover 30 CpG sites within the HSD11B2 promoter. Methylation percentage (%) will calculated per CpG site (aligning with the human reference genome hg38). |
| Stress Regulation: Buccal Cell DNAm of HSD11B2 Promoter at 36 Weeks PMA | At 36 weeks postmenstrual age. | We will evaluate stress regulation, measured by buccal cell DNA methylation (DNAm) of HSD11B2 promoter at 36 weeks post-menstrual age (PMA). We anticipate to cover 30 CpG sites within the HSD11B2 promoter. Methylation percentage (%) will calculated per CpG site (aligning with the human reference genome hg38). |
| Neurodevelopment: NNNS-II Attention score 36 Weeks PMA | At 36 weeks postmenstrual age. | We will evaluate neurodevelopment using the NeoNatal Neurobehavioral Scale (NNNS-II) at 36 weeks post-menstrual age (PMA). The NNNS-II provides a summary score for each of the 13 domain (attention, handling, self-regulation, habituation, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, quality of movement, and stress/abstinence). High-risk neurodevelopment is characterized by higher scores in handling, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, and stress/abstinence, along with lower score in quality of movement, attention, self-regulation, habituation. Low-risk neurodevelopment is characterized by higher scores in attention, self-regulation, habituation, and quality of movement, along with lower scores in handling, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, and stress/abstinence. |
| Neurodevelopment: NNNS-II Handling score 36 Weeks PMA | At 36 weeks postmenstrual age. | We will evaluate neurodevelopment using the NeoNatal Neurobehavioral Scale (NNNS-II) at 36 weeks post-menstrual age (PMA). The NNNS-II provides a summary score for each of the 13 domain (attention, handling, self-regulation, habituation, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, quality of movement, and stress/abstinence). High-risk neurodevelopment is characterized by higher scores in handling, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, and stress/abstinence, along with lower score in quality of movement, attention, self-regulation, habituation. Low-risk neurodevelopment is characterized by higher scores in attention, self-regulation, habituation, and quality of movement, along with lower scores in handling, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, and stress/abstinence. |
| Neurodevelopment: NNNS-II Self-Regulation 36 Weeks PMA | At 36 weeks postmenstrual age. | We will evaluate neurodevelopment using the NeoNatal Neurobehavioral Scale (NNNS-II) at 36 weeks post-menstrual age (PMA). The NNNS-II provides a summary score for each of the 13 domain (attention, handling, self-regulation, habituation, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, quality of movement, and stress/abstinence). High-risk neurodevelopment is characterized by higher scores in handling, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, and stress/abstinence, along with lower score in quality of movement, attention, self-regulation, habituation. Low-risk neurodevelopment is characterized by higher scores in attention, self-regulation, habituation, and quality of movement, along with lower scores in handling, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, and stress/abstinence. |
| Neurodevelopment: NNNS-II Habituation score 36 Weeks PMA | At 36 weeks postmenstrual age. | We will evaluate neurodevelopment using the NeoNatal Neurobehavioral Scale (NNNS-II) at 36 weeks post-menstrual age (PMA). The NNNS-II provides a summary score for each of the 13 domain (attention, handling, self-regulation, habituation, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, quality of movement, and stress/abstinence). High-risk neurodevelopment is characterized by higher scores in handling, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, and stress/abstinence, along with lower score in quality of movement, attention, self-regulation, habituation. Low-risk neurodevelopment is characterized by higher scores in attention, self-regulation, habituation, and quality of movement, along with lower scores in handling, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, and stress/abstinence. |
| Neurodevelopment: NNNS-II Arousal score 36 Weeks PMA | At 36 weeks postmenstrual age. | We will evaluate neurodevelopment using the NeoNatal Neurobehavioral Scale (NNNS-II) at 36 weeks post-menstrual age (PMA). The NNNS-II provides a summary score for each of the 13 domain (attention, handling, self-regulation, habituation, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, quality of movement, and stress/abstinence). High-risk neurodevelopment is characterized by higher scores in handling, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, and stress/abstinence, along with lower score in quality of movement, attention, self-regulation, habituation. Low-risk neurodevelopment is characterized by higher scores in attention, self-regulation, habituation, and quality of movement, along with lower scores in handling, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, and stress/abstinence. |
| Neurodevelopment: NNNS-II Excitability score 36 Weeks PMA | At 36 weeks postmenstrual age. | We will evaluate neurodevelopment using the NeoNatal Neurobehavioral Scale (NNNS-II) at 36 weeks post-menstrual age (PMA). The NNNS-II provides a summary score for each of the 13 domain (attention, handling, self-regulation, habituation, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, quality of movement, and stress/abstinence). High-risk neurodevelopment is characterized by higher scores in handling, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, and stress/abstinence, along with lower score in quality of movement, attention, self-regulation, habituation. Low-risk neurodevelopment is characterized by higher scores in attention, self-regulation, habituation, and quality of movement, along with lower scores in handling, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, and stress/abstinence. |
| Neurodevelopment: NNNS-II Lethargy score 36 Weeks PMA | At 36 weeks postmenstrual age. | We will evaluate neurodevelopment using the NeoNatal Neurobehavioral Scale (NNNS-II) at 36 weeks post-menstrual age (PMA). The NNNS-II provides a summary score for each of the 13 domain (attention, handling, self-regulation, habituation, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, quality of movement, and stress/abstinence). High-risk neurodevelopment is characterized by higher scores in handling, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, and stress/abstinence, along with lower score in quality of movement, attention, self-regulation, habituation. Low-risk neurodevelopment is characterized by higher scores in attention, self-regulation, habituation, and quality of movement, along with lower scores in handling, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, and stress/abstinence. |
| Neurodevelopment: NNNS-II Hypertonicity score 36 Weeks PMA | At 36 weeks postmenstrual age. | We will evaluate neurodevelopment using the NeoNatal Neurobehavioral Scale (NNNS-II) at 36 weeks post-menstrual age (PMA). The NNNS-II provides a summary score for each of the 13 domain (attention, handling, self-regulation, habituation, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, quality of movement, and stress/abstinence). High-risk neurodevelopment is characterized by higher scores in handling, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, and stress/abstinence, along with lower score in quality of movement, attention, self-regulation, habituation. Low-risk neurodevelopment is characterized by higher scores in attention, self-regulation, habituation, and quality of movement, along with lower scores in handling, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, and stress/abstinence. |
| Neurodevelopment: NNNS-II Hypotonicity score 36 Weeks PMA | At 36 weeks postmenstrual age. | We will evaluate neurodevelopment using the NeoNatal Neurobehavioral Scale (NNNS-II) at 36 weeks post-menstrual age (PMA). The NNNS-II provides a summary score for each of the 13 domain (attention, handling, self-regulation, habituation, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, quality of movement, and stress/abstinence). High-risk neurodevelopment is characterized by higher scores in handling, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, and stress/abstinence, along with lower score in quality of movement, attention, self-regulation, habituation. Low-risk neurodevelopment is characterized by higher scores in attention, self-regulation, habituation, and quality of movement, along with lower scores in handling, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, and stress/abstinence. |
| Neurodevelopment: NNNS-II Nonoptimal Reflexes score 36 Weeks PMA | At 36 weeks postmenstrual age. | We will evaluate neurodevelopment using the NeoNatal Neurobehavioral Scale (NNNS-II) at 36 weeks post-menstrual age (PMA). The NNNS-II provides a summary score for each of the 13 domain (attention, handling, self-regulation, habituation, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, quality of movement, and stress/abstinence). High-risk neurodevelopment is characterized by higher scores in handling, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, and stress/abstinence, along with lower score in quality of movement, attention, self-regulation, habituation. Low-risk neurodevelopment is characterized by higher scores in attention, self-regulation, habituation, and quality of movement, along with lower scores in handling, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, and stress/abstinence. |
| Neurodevelopment: NNNS-II Asymmetric Reflexes score 36 Weeks PMA | At 36 weeks postmenstrual age. | We will evaluate neurodevelopment using the NeoNatal Neurobehavioral Scale (NNNS-II) at 36 weeks post-menstrual age (PMA). The NNNS-II provides a summary score for each of the 13 domain (attention, handling, self-regulation, habituation, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, quality of movement, and stress/abstinence). High-risk neurodevelopment is characterized by higher scores in handling, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, and stress/abstinence, along with lower score in quality of movement, attention, self-regulation, habituation. Low-risk neurodevelopment is characterized by higher scores in attention, self-regulation, habituation, and quality of movement, along with lower scores in handling, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, and stress/abstinence. |
| Neurodevelopment: NNNS-II Quality of Movement score 36 Weeks PMA | At 36 weeks postmenstrual age. | We will evaluate neurodevelopment using the NeoNatal Neurobehavioral Scale (NNNS-II) at 36 weeks post-menstrual age (PMA). The NNNS-II provides a summary score for each of the 13 domain (attention, handling, self-regulation, habituation, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, quality of movement, and stress/abstinence). High-risk neurodevelopment is characterized by higher scores in handling, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, and stress/abstinence, along with lower score in quality of movement, attention, self-regulation, habituation. Low-risk neurodevelopment is characterized by higher scores in attention, self-regulation, habituation, and quality of movement, along with lower scores in handling, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, and stress/abstinence. |
| Neurodevelopment: NNNS-II Stress/Abstinence score 36 Weeks PMA | At 36 weeks postmenstrual age. | We will evaluate neurodevelopment using the NeoNatal Neurobehavioral Scale (NNNS-II) at 36 weeks post-menstrual age (PMA). The NNNS-II provides a summary score for each of the 13 domain (attention, handling, self-regulation, habituation, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, quality of movement, and stress/abstinence). High-risk neurodevelopment is characterized by higher scores in handling, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, and stress/abstinence, along with lower score in quality of movement, attention, self-regulation, habituation. Low-risk neurodevelopment is characterized by higher scores in attention, self-regulation, habituation, and quality of movement, along with lower scores in handling, arousal, excitability, lethargy, hypertonicity, hypotonicity, nonoptimal reflexes, asymmetric reflexes, and stress/abstinence. |
Countries
United States
Contacts
CONTACTThao Griffith, PhD
CONTACTCara Joyce, PhD
PRINCIPAL_INVESTIGATORThao Griffith, PhD
Loyola University Chicago
Outcome results
None listed