Neonatal Hypoxic Ischemic Encephalopathy:Early Diagnosis and Management of Comorbidities

Neonatal Hypoxic Ischemic Encephalopathy Clinical Trial

Official title:

Neonatal Hypoxic Ischemic Encephalopathy:Targeting Early Diagnosis and Management of Associated Comorbidities

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03550612
• Other study ID #: NHIE
• Status: Not yet recruiting
• Start date: February 1, 2019
• Est. completion date: December 2020

Study information

• Verified date: June 2018
• Source: Assiut University
• Contact: Prof.Samia A Mohamed, MD
• Phone: 00201223971326
• Email: samiaatwa[@]gmail.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 100
• Est. completion date: December 2020
• Est. primary completion date: February 1, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 6 Hours

Eligibility

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.

Related Conditions & MeSH terms

• Brain Diseases
• Brain Ischemia
• Hypoxia
• Hypoxia-Ischemia, Brain
• Ischemia
• Neonatal Hypoxic Ischemic Encephalopathy

Intervention

Diagnostic Test:
• magnetic resonant imaging,cranial ultrasound.
Magnetic resonant image performed at term gestation neonate suffer of hypoxic ischemic encephalopathy and its results will be analysed in details and classified according to global score of magnetic resonant image injury.Cranial ultrasound results will be analysed regards (periventricular - interventricular haemorrhage-Ventricular size-basal ganglia, thalamus and cerebellum affection) and Doppler (peak systolic flow velocity-end diastolic peak flow velocity-mean velocity and resistance index).Cerebral bleeding will be diagnosed be cranial ultrasound and confirmed be standard magnetic resonant image in term equivalent age.
• Amplitude integrated electroencephalogram
Amplitude integrated electroencephalogram before and during cooling will be assessed and classified according to Hellstrom Westas et al 2006 and it will be compared with the results of cranial ultrasound and magnetic resonant imaging. Neurodevelopment study at 12 and 14 month age using Bayley ??? score will be compared with the results of cranial ultrasound,magnetic resonant imaging and Amplitude integrated electroencephalogram.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Assiut University

References & Publications (7)

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. — View 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. — View 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. — View 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. — View 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. Review. — View Citation

Pierrat V, Haouari N, Liska A, Thomas D, Subtil D, Truffert P; Groupe d'Etudes en Epidémiologie Périnatale. 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. — View 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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Compare results of cranial ultrasound with Magnetic resonant imaging to improve quality of cranial ultrasound to early diagnosis of hypoxic ischemic encephalopathy	Cranial ultrasound results will be analysed regards (periventricular - interventricular haemorrhage-Ventricular size-basal ganglia, thalamus and cerebellum affection) and Doppler (peak systolic flow velocity-end diastolic peak flow velocity-mean velocity and resistance index).magnetic resonant imaging performed at term gestation results will be analysed in details and classified according to global score of magnetic resonant imaging injury (mild, moderate and severe injury) and compare it with results of cranial ultrasound	3 weeks age.
Secondary	Detect incidence of intracranial haemorrhage in asphyxiated newborn treated by therapeutic hypothermia.	Analysis of perinatal risk factors associated with increase incidence of intracranial hemorrhage.and coagulation limits after that intracranial haemorrhage occurs and transfusion limits decrease incidence of intracranial haemorrhage.	12 month
Secondary	Detection of associated infection in asphyxiated newborn treated by therapeutic hypothermia.	Detection of associated infection that increase seizure activity and make it difficult to control.C-reactive protein and blood culture will be the gold standard to diagnosis associated infection, suspicious sepsis on C-reactive protein = 10 and confirmed by blood culture.	1 month
Secondary	Ability of cranial ultrasound in early diagnosis of intracranial haemorrhage.	By compare results of cranial ultrasound with standard magnetic resonant imaging	1 month age
Secondary	Compare results of diagnostic methods of hypoxic ischemic encephalopathy with neurodevelopmental study of the baby at 12 month	Compare results of magnetic resonant imaging,Cranial ultrasound and amplitude integrated encephalogram in babies with Hypoxic ischemic encephalopathy undergoes therapeutic cooling with neurodevelopmental score at 12 month age.	12 month age