PRIME: Prospective Research in Infants With Mild Encephalopathy
Study Details
Study Description
Brief Summary
A multicenter observational pilot study will be conducted to determine the natural history of infants with early diagnosis (≤ 6 hrs of age) of mild neonatal encephalopathy (NE) who are not qualified for therapeutic hypothermia. The intervention includes: neurologic examination by using modified Sarnat score at ≤ 6 hrs of age, 24 hrs and before discharge home, amplitude-integrated electroencephalography (aEEG) at 6 ± 3 hrs of age, brain MRI at before discharge home to 30 days of age and follow-up at 18-22 months of age. Primary outcome is the percentage of mild NE infants with evidence of brain injury defined by the presence of at least 1 abnormality of brain MRI, aEEG or neurologic examination in the neonatal period. Secondary outcome is the percentage of brain MRI, aEEG and neurological exam abnormalities, seizure, length of hospital stay, need of gavage feeds or gastrostomy at discharge home, death and long-term outcome.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Detailed Description
Globally, an estimated 1.8 to 7.7 infants per 1000 live term births suffer from perinatal asphyxia, which remains an important cause of neonatal encephalopathy (NE) and neurodevelopmental impairment. Over the last six years, several randomized control trials have demonstrated that prolonged and moderate therapeutic hypothermia (TH) reduces the rate of death or disability at 18 months of age among infants who survived. In these trials, infants were eligible if there was evidence of perinatal hypoxia-ischemia and a moderate or severe degree of encephalopathy on neurological evaluation performed at ≤ 6 hrs of age. However, it has been recognized that the level of NE may change over time. Preliminary and unpublished observations from our group indicated that some infants who were not classified as moderate or severe NE had neurological abnormalities at discharge or evidence of brain injury on MRI performed during the neonatal period. Unfortunately, precise data on the outcomes of this specific population is not clear. Since TH is not offered to this population, the outcomes of infants that do not qualify for TH based on neurological evaluation performed ≤ 6 hrs of life requires a more precise investigation.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Mild NE Infants with evidence of a perinatal event and NE who do not qualify for therapeutic hypothermia. |
Other: Neurologic examination
Neurologic examination includes: (1) neurologic examination using modify Sarnat score at </= 6 hrs of age, 24 hrs and at discharge home, (2) aEEG at 6 ± 3 hrs of age, (3) Brain MRI before discharge home to 30 days of age.
|
Outcome Measures
Primary Outcome Measures
- Percentage of infants with evidence of neurological dysfunction, brain injury and/or abnormality. [1 month]
Evidence of neurological dysfunction/injury/abnormality will be defined by any of these 3 criteria, as follows: MRI = Brain MRI score of pattern of injury (NICHD-NRN) > 0, aEEG = abnormal background pattern on aEEG (voltage or background pattern) at 6 ± 3 hrs of age. Any abnormality on the neurological at discharge exam.
Secondary Outcome Measures
- Percentage of infants with seizures [Participants will be followed for the duration of hospital stay, an expected average of 3 days]
Development of clinical or electrographic seizures
- Length of hospital stay [Participants will be followed for the duration of hospital stay, an expected average of 3 days]
- Percentage of infants who need gavage feeds or gastrostomy at discharge home [Participants will be followed for the duration of hospital stay, an expected average of 3 days]
- Mortality rate [Participants will be followed for the duration of hospital stay, an expected average of 3 days]
Death during the hospitalization
Other Outcome Measures
- Long-term neurodevelopment [18-22 months of age]
Long-term outcomes (18-22 months of age): Severe disability if there is a Bayley III Cognitive score < 70, severe cerebral palsy (CP), defined by the Gross Motor Function Classification System (GMFCS) grade level 3 to 5, blindness or profound hearing loss. Moderate disability will be defined as the Bayley Cognitive score is 70-84 and either seizures, moderate CP (defined by GMFCS grade level 2) or a hearing deficit requiring amplification to understand commands. Mild disability will be defined by a cognitive score 70-84, or a cognitive score ≥ 85 and either presence of mild or moderate CP (GMFCS grade levels 1 or 2), a seizure disorder or hearing loss with or without amplification. Normal will be defined as Bayley III Cognitive score ≥ 85 without any visual or hearing impairment, or CP.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Infants with birth weight > or = 1800g and gestational age > or = 36 weeks AND
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Admission to neonatal intensive care unit (NICU) for possible hypothermia at < or = 6hr of life
Exclusion Criteria:
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Infants with normal neurological evaluation
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Major congenital abnormalities
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Refusal of informed consent
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Infants who receive passive or active cooling prior to the NICU admission
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Infants that develop seizures or moderate/severe NE within the first 24 hr of life and are initiated on therapeutic hypothermia after 6 hr of life.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Wayne State University | Detroit | Michigan | United States | 48201 |
| 2 | The Ohio Stage University - Nationwide Children's Hospital | Columbus | Ohio | United States | 43205-2664 |
| 3 | Brown University | Providence | Rhode Island | United States | 02905 |
| 4 | University of Texas Southwestern | Dallas | Texas | United States | 75235 |
| 5 | Montreal Children's Hospital | Montreal | Quebec | Canada | H3H 1P3 |
| 6 | Mahidol University - Ramathibodi Hospital | Bangkok | Thailand | 10400 | |
| 7 | Imperial College London | London | United Kingdom | W12 0HS |
Sponsors and Collaborators
- McGill University Health Centre/Research Institute of the McGill University Health Centre
- Brown University
- University of Texas Southwestern Medical Center
- Wayne State University
- Mahidol University
- Ohio State University
- Imperial College London
Investigators
- Principal Investigator: Guilherme Sant'Anna, MD, McGill University
- Principal Investigator: Lina Chalak, MD, University of Texas
- Principal Investigator: Abbot Laptook, MD, Brown University
- Principal Investigator: Seetha Shankaran, MD, Wayne State University
- Principal Investigator: Chatchay Prempunpong, MD, Mahidol University
- Principal Investigator: Sudhin Thayyil, MD, Imperial College London
- Principal Investigator: Pablo Sanchez, MD, Ohio State University
- Study Director: Pablo Sanchez, MD, The Ohio Stage University
- Study Chair: Guilherme Sant'Anna, MD, McGill University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- PRIME01
- 12-108-PED