Clinical trial NCT03550612: Neonatal Hypoxic Ischemic Encephalopathy:Early Diagnosis and Management of Comorbidities
Official title: Neonatal Hypoxic Ischemic Encephalopathy:Targeting Early Diagnosis and Management of Associated Comorbidities
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Neonatal Hypoxic Ischemic Encephalopathy
Lead sponsor: Assiut University
Sponsor class: OTHER
First posted: 2018-06-08
Enrollment: 100
Sex: ALL
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: all neonates with hypoxic ischemic encephalopathy treated by therapeutic hypothermia 6 hours after birth in period between January 2010 to December 2015.One hundred cases will be included in the study as fifteen to twenty case of HIE admitted for therapeutic hypothermia treatment at the hospital every year.

Brief summary: Perinatal asphyxia is common cause of acquired neonatal brain injury in neonates associated with hypoxic-ischemic encephalopathy, leading to long-term neurologic complication or death. In 2000, the neonatal mortality rate in Egypt was found to be 25 per 1000 live birth. In this survey, hypoxic ischemic encephalopathy accounts for 18% of neonatal mortality and is the second most common cause of neonatal death.

Detailed description: Cerebral palsy as complication of hypoxic ischemic encephalopathy is common problem in Egypt.cerebral palsy is associated with many problems (cognitive disability-epilepsy-visual and hearing problems) that make great economic burden on their family and health care system. In 2010, the prevalence of cerebral palsy in El-Kharga District new valley described 2.04 cases of cerebral palsy every 1000 child.hypoxic ischemic encephalopathy was the second most common cause of cerebral palsy with prematurity the most common. 70.5% of children with cerebral palsy had severe mental retardation and 52% suffer from active epilepsy. An observational study on 224 cerebral palsy case from Tanta University found that 80.8% of patients with cerebral palsy had cognitive disorder, 36% had epilepsy, 25% loss of vision and 16% hearing problems. This health conditions provide a significant financial burden on the health system in Egypt.

There are two problems regard dealing with cases of hypoxic ischemic encephalopathy in Egypt, First one is early diagnosis and second is description of its severity. Assessment of the severity of cerebral injury and neurological outcome in infants with hypoxic ischemic encephalopathy is important for prognosis and stratifying the clinical management. Neurophysiological tests, including amplitude-integrated electroencephalogram , biochemical markers, and neuroimaging like (Trans cranial ultrasound - Magnetic resonance imaging) have been used to assess prognosis and predict long-term outcome. In our neonatal unit investigators perform routine cranial ultrasound to all cases of hypoxic ischemic encephalopathy.Cranial ultrasound is cheap, available, and easily performed bedside examination. However cranial ultrasound is limited in specificity and sensitivity in diagnosis of Hypoxic ischemic encephalopathy and prediction of prognosis.

Magnetic resonant imaging might provide the best information on structural brain lesions associated with long-term neurological impairment but is not available for immediate diagnostics on neonatal unit. Amplitude integrated electroencephalography is unfortunately not routinely performed in Egyptian neonatal units. It might improve early detection of Hypoxic ischemic encephalopathy and risk stratification accordingly.

Cerebral bleeding and infection are commonly described comorbidities in Hypoxic ischemic encephalopathy associated with the poor prognosis. Coagulopathy is common problem in asphyxiated infants. It is associated with asphyxia and therapeutic hypothermia (standardized treatment of hypoxia). Coagulopathy can cause bleeding in serious organs like brain that make the prognosis of Hypoxia bad and control of seizure difficult.

Eligibility criteria: Inclusion Criteria:

* \>36 weeks gestational age babies undergoes therapeutic hypothermia within 6 hours after birth after fulfilling the cooling criteria:
* Apgar score ≤ 5 at 10 minutes after birth.
* Need resuscitation 10 minutes after birth.
* Acidosis PH≤7 at 60 minutes.
* Base deficit ≥16 mmoL ∕ L at 60 minutes.

Exclusion Criteria:

* Birth weight ≤1.8kg.
* Congenital and genetic conditions affect neurodevelopment.

Primary outcomes:
measure: Compare results of cranial ultrasound with Magnetic resonant imaging to improve quality of cranial ultrasound to early diagnosis of hypoxic ischemic encephalopathy
timeFrame: 3 weeks age.
Secondary outcomes:
measure: Detect incidence of intracranial haemorrhage in asphyxiated newborn treated by therapeutic hypothermia.
timeFrame: 12 month
measure: Detection of associated infection in asphyxiated newborn treated by therapeutic hypothermia.
timeFrame: 1 month
measure: Ability of cranial ultrasound in early diagnosis of intracranial haemorrhage.
timeFrame: 1 month age
measure: Compare results of diagnostic methods of hypoxic ischemic encephalopathy with neurodevelopmental study of the baby at 12 month
timeFrame: 12 month age
Other outcomes:
Locations:
Study officials:
References:
citation: Pierrat V, Haouari N, Liska A, Thomas D, Subtil D, Truffert P; Groupe d'Etudes en Epidemiologie Perinatale. Prevalence, causes, and outcome at 2 years of age of newborn encephalopathy: population based study. Arch Dis Child Fetal Neonatal Ed. 2005 May;90(3):F257-61. doi: 10.1136/adc.2003.047985.
citation: Campbell O, Gipson R, el-Mohandes A, Issa AH, Matta N, Mansour E, Mohsen L. The Egypt National Perinatal/Neonatal Mortality Study 2000. J Perinatol. 2004 May;24(5):284-9. doi: 10.1038/sj.jp.7211084.
citation: El-Tallawy HN, Farghaly WM, Shehata GA, Metwally NA, Rageh TA, Abo-Elfetoh N. Epidemiology of cerebral palsy in El-Kharga District-New Valley (Egypt). Brain Dev. 2011 May;33(5):406-11. doi: 10.1016/j.braindev.2010.07.011. Epub 2010 Aug 24.
citation: Merchant N, Azzopardi D. Early predictors of outcome in infants treated with hypothermia for hypoxic-ischaemic encephalopathy. Dev Med Child Neurol. 2015 Apr;57 Suppl 3:8-16. doi: 10.1111/dmcn.12726.
citation: Forman KR, Diab Y, Wong EC, Baumgart S, Luban NL, Massaro AN. Coagulopathy in newborns with hypoxic ischemic encephalopathy (HIE) treated with therapeutic hypothermia: a retrospective case-control study. BMC Pediatr. 2014 Nov 3;14:277. doi: 10.1186/1471-2431-14-277.
citation: Bednarek N, Mathur A, Inder T, Wilkinson J, Neil J, Shimony J. Impact of therapeutic hypothermia on MRI diffusion changes in neonatal encephalopathy. Neurology. 2012 May 1;78(18):1420-7. doi: 10.1212/WNL.0b013e318253d589. Epub 2012 Apr 18.
citation: Tao JD, Mathur AM. Using amplitude-integrated EEG in neonatal intensive care. J Perinatol. 2010 Oct;30 Suppl:S73-81. doi: 10.1038/jp.2010.93.