Prospective Research in Infants With Mild Encephalopathy

NCT ID: NCT01747863

Last Updated: 2025-01-28

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 63 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2012-12-31
• Study Completion Date: 2017-06-30

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.

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 Preliminary and unpublished observations from our group indicated that some infants who were not classified as moderate or severe NE had neurological abnormalities at discharge or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.

Conditions

Hypoxic-Ischemic Encephalopathy; Brain Injury; Neonatal Seizure

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Mild NE

Infants with evidence of a perinatal event and NE who do not qualify for therapeutic hypothermia.

Neurologic examination

Intervention Type: OTHER

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.

Interventions

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.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Infants with birth weight > or = 1800g and gestational age > or = 36 weeks AND
• Admission to neonatal intensive care unit (NICU) for possible hypothermia at < or = 6hr of life

Exclusion Criteria

• Infants with normal neurological evaluation
• Major congenital abnormalities
• Refusal of informed consent
• Infants who receive passive or active cooling prior to the NICU admission
• 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.

• Maximum Eligible Age: 6 Hours
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Brown University

OTHER

Sponsor Role: collaborator

University of Texas Southwestern Medical Center

OTHER

Sponsor Role: collaborator

Wayne State University

OTHER

Sponsor Role: collaborator

Mahidol University

OTHER

Sponsor Role: collaborator

Ohio State University

OTHER

Sponsor Role: collaborator

Imperial College London

OTHER

Sponsor Role: collaborator

McGill University Health Centre/Research Institute of the McGill University Health Centre

OTHER

Sponsor Role: lead

Responsible Party

Guilherme Sant'Anna, MD

Associate Professor of Pediatrics

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Guilherme Sant'Anna, MD

Role: PRINCIPAL_INVESTIGATOR

McGill University

Lina Chalak, MD

Role: PRINCIPAL_INVESTIGATOR

University of Texas

Abbot Laptook, MD

Role: PRINCIPAL_INVESTIGATOR

Brown University

Seetha Shankaran, MD

Role: PRINCIPAL_INVESTIGATOR

Wayne State University

Chatchay Prempunpong, MD

Role: PRINCIPAL_INVESTIGATOR

Mahidol University

Sudhin Thayyil, MD

Role: PRINCIPAL_INVESTIGATOR

Imperial College London

Pablo Sanchez, MD

Role: PRINCIPAL_INVESTIGATOR

Ohio State University

Pablo Sanchez, MD

Role: STUDY_DIRECTOR

The Ohio Stage University

Guilherme Sant'Anna, MD

Role: STUDY_CHAIR

McGill University

Locations

Wayne State University

Detroit, Michigan, United States

The Ohio Stage University - Nationwide Children's Hospital

Columbus, Ohio, United States

Brown University

Providence, Rhode Island, United States

University of Texas Southwestern

Dallas, Texas, United States

Montreal Children's Hospital

Montreal, Quebec, Canada

Mahidol University - Ramathibodi Hospital

Bangkok, , Thailand

Imperial College London

London, , United Kingdom

Countries

United States; Canada; Thailand; United Kingdom

References

Chalak LF, Adams-Huet B, Sant'Anna G. A Total Sarnat Score in Mild Hypoxic-ischemic Encephalopathy Can Detect Infants at Higher Risk of Disability. J Pediatr. 2019 Nov;214:217-221.e1. doi: 10.1016/j.jpeds.2019.06.026. Epub 2019 Jul 10.

Reference Type: DERIVED

PMID: 31301853 (View on PubMed)

Prempunpong C, Chalak LF, Garfinkle J, Shah B, Kalra V, Rollins N, Boyle R, Nguyen KA, Mir I, Pappas A, Montaldo P, Thayyil S, Sanchez PJ, Shankaran S, Laptook AR, Sant'Anna G. Prospective research on infants with mild encephalopathy: the PRIME study. J Perinatol. 2018 Jan;38(1):80-85. doi: 10.1038/jp.2017.164. Epub 2017 Nov 2.

Reference Type: DERIVED

PMID: 29095433 (View on PubMed)

Other Identifiers

12-108-PED

Identifier Type: OTHER

Identifier Source: secondary_id

PRIME01

Identifier Type: -

Identifier Source: org_study_id