Mild Hypoxic Ischemic Encephalopathy of Newborn
Conditions
Keywords
mild HIE (Hypoxic Ischemic Encephalopathy), neonatal encephalopathy, brain ischemia, brain hypoxia
Brief summary
To determine effectiveness of therapy to improve neurodevelopmental outcomes in infants with mild HIE. To determine the adverse effects of Therapeutic Hypothermia (TH) in mild HIE on the neonate and his/her family. Determine heterogeneity of the treatment effect across key subgroups obtained in the first 6 hours after birth prior to the decision to initiate therapy.
Detailed description
This study leverages practice variation within and across 15 participating sites to compare the effectiveness of TH versus normothermia for mild HIE on neurodevelopmental outcomes at 2 years of age.After standardizing all aspects of clinical care for mild HIE (except for TH vs. normothermia)we will enroll 460 infants with mild HIE into the longitudinal, observational comparative effectiveness study.The central aim of the comparative longitudinal cohort of mild HIE is (1) to compare the effectiveness of hypothermia to normothermia on neurodevelopmental outcomes at 2 years, (2) determine the adverse effects of TH on the infant and his/her family; and (3) determine the heterogeneity of treatment effects (moderating effect) across mild HIE subgroups as determined by physiological biomarkers obtained during the 6 hours window to initiate hypothermia. The decision to apply TH or normothermia will be entirely determined by practice parameters at each site.
Interventions
PROCEDURENormothermia
Usual care for first 72 hours for neonates with mild encephalopathy maintaining core temperature (36.5°C ± 1 C).
PROCEDUREWhole body therapeutic hypothermia
Whole-body therapeutic hypothermia (33.5°C ± 0.5°C) for 72 hours began by 6 hours of age for neonates with mild encephalopathy per site standard of care practice.
Sponsors
University of California, San Francisco
Children's National Research Institute
Children's Hospital Los Angeles
St. Louis University
Stanford University
University of Utah
University of Pittsburgh Medical Center
Children's Hospital Medical Center, Cincinnati
University College Cork
The Children's Hospital of San Antonio
Harvard University
Washington University School of Medicine
Sharp HealthCare
The Cleveland Clinic
University of Florida Health
Emory University
Nationwide Children's Hospital
Children's Hospital of Orange County
University of Texas Southwestern Medical Center
Study design
Observational model
OTHER
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
36 Weeks to No maximum
Healthy volunteers
No
Inclusion criteria
Infants must meet all 3 inclusion criteria 1. Neonates born at ≥ 36 0/7 weeks 2. Mild Encephalopathy on neonatal neurologic exam within 6 hours after birth: defined as presence of at least 2 signs of mild, moderate, or severe encephalopathy with no more than 2 signs in the moderate or severe category. 3. Perinatal Acidosis based on at least one of the following (A or B): 1. pH ≤ 7.00 in any cord or first infant gas (arterial, venous, or capillary) within ≤ 60 min OR base deficit ≥ 16 in any cord or first infant gas (arterial, venous or capillary) within ≤ 60 min 2. If pH is between 7.01 and 7.15, OR base deficit is between 10 and 15.9 mmol/liter, OR blood gas is not available, an acute perinatal event is an additional criteria required (see below definition) An acute perinatal event is defined by at least one of the following: 1. Apgar score at 10 min ≤ 5 2. Continued need for resuscitation at 10 min (chest compressions, bag mask ventilation, or positive pressure ventilation) 3. Uterine rupture, placental abruption, cord accident (prolapse, rupture, knot or tight nuchal cord) 4. maternal trauma, maternal hemorrhage, or cardiorespiratory arrest 5. fetal exsanguination from either vasa previa or feto-maternal hemorrhage, shoulder dystocia 6. Any evidence suggestive of acute perinatal event. Infants are still eligible for enrollment in the COOLPRIME study if the cord or infant's first blood gas (arterial, venous, or capillary) is obtained \>60 minutes of life.
Exclusion criteria
1. Gestational age at birth \< 36 0/7 weeks 2. Birth weight \< 1800gm 3. Head circumference \<30cm 4. Congenital or chromosomal anomaly associated with abnormal neurodevelopment or death 5. Moderate or Severe HIE of 3 or more moderate or severe abnormalities on COOLPRIME Sarnat exam within 6 hours of life 6. Any seizures within first six hours of life 7. Redirection of care is being considered
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Effectiveness of normothermia in infants as measured by Composite Bayley IV score | 22-26 months of age. | Effectiveness of normothermia in infants is measured by Composite Bayley IV score scale, which is. an extensive formal developmental assessment tool for diagnosing developmental delays in early childhood. Possible scores range from 55- 120 where lower scores indicate worse outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adverse events SAE | Discharge (approximately 7 days) | Safety will be measured by the presence or absence of a serious adverse event (SAE) at discharge. |
| Parent-Infant stress and bonding as measured by MIBS | 3-4 months | Parent-Infant stress and bonding is measured by Mother-to-infant bonding (MIBS) scale, which is a validated questionnaire with good psychometric properties that assesses the mother's feelings towards infant (bondedness) from birth to 4 months. Possible scores range from 0-3, where 0 indicates not at all and 3, very much. |
| Parent-Infant stress and bonding as measured by IBQR | 3-4 months | Parent-Infant stress and bonding is measured by Infant Behavior Questionnaire-Revised (IBQR) which measures differences in reactivity and regulation, and the structure of infant temperament and its relation to parental family functioning. Item scores were summed according to IBQR scoring rules to create scores on the 14 scales, with higher scores indicating greater levels of that temperament dimension. |
| Parent-Infant stress and bonding as measured by PSI | 3-4 months | Parent-Infant stress and bonding is measured by Parenting Stress Index (PSI) which is an abbreviated version of the full-length test with 36 items in three domains (Parental Distress, Parent-Child Dysfunctional Interaction, and Difficult Child) that combine to form a Total Stress scale, which helps identify families that are most in need of support services. In general, items are scored using the following 5-point scale: 1) SA (Strongly Agree), 2) A (Agree), 3) NS (Not Sure), 4) D (Disagree), 5) SD (Strongly Disagree). Responses to both the overall stress score and the three subscales are summed to generate representative scores, resulting the total stress score, perceptions of child behavioral problems, parenting distress, and parent-child dysfunctional interactions. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Infant neurological integrity as measured with HNNE | Discharge | Infant neurological integrity is measured with HNNE (Hammersmith Neonatal Neurological Exams), which is used to assess tone, spontaneous movements, reflexes, and visual and auditory attention allowing for a continuum of assessment from birth to 2 years. The maximum score for any one item is a score of 3 and the minimum is a score of 0. A subscore can be given for each section and the overall global score can be calculated by summing up all 26 items (range: 0-78), with higher scores indicating better neurological performance. The maximum global score is 78. |
| IBQ-R | 9-12months | Infant Behavior Questionnaire Revised (very short) |
| Infant neurological integrity as measured with HINE | 3 - 4 months | Infant neurological integrity is measured with HINE (Hammersmith Infant Neurological Exams), which is used to assess tone, spontaneous movements, reflexes, and visual and auditory attention allowing for a continuum of assessment from birth to 2 years. The maximum score for any one item is a score of 3 and the minimum is a score of 0. A subscore can be given for each section and the overall global score can be calculated by summing up all 26 items (range: 0-78), with higher scores indicating better neurological performance. The maximum global score is 78. |
| Behavioral tendency CBCL | 22-26 months of age. | The Child Behavior Checklist-parent report (CBCL) will provide a profile of behavior and social functioning validated in relation to age and gender. |
| Composite PARCA-R | 22-26 months of age. | The Parent Report of Children's Abilities-Revised (PARCA-R) is used against the Mental Development Index of the Bayley Scales. |
| IFS-R | 9-12 months | Impact on Family Scale - Revised |
Countries
United States
Contacts
Primary ContactLina Chalak, MD
Backup ContactPollieanna Sepulveda, MSN, RN
Outcome results
None listed