الفهرس 
Birth asphyxiaOnly 14 pages are availabe for public view
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Abstract
Perinatal asphyxia is the single most important perinatal cause of neurologic morbidity in newborn infants. CK-BB isoenzyme is the only CK isoenzyme present in brain cells, therefore damage to these cells might produce measurable amounts of CK-BB in the serum. In perinatal asphyxia the blood brain barrier becomes more permeable and permits the passage of CK-BB isoenzymes into the blood stream. CK-BB isoenzymes have attracted attention as a possible predictor of the extent of brain damage. An acute hypoxic-ischemic insult initiates a cascade of biochemical events which lead over the course of hours or even days to irreversible neuronal injury. Glutamate is an excitatory amino acid released in excess during hypoxic-ischemic insults leads to over-activity of neurons. Magnesium acts as a glutamate receptor antagonist and increasing the extracellular magnesium concentration may protect the brain from NMDA receptor mediated damage. This study was done for evaluation of the serum levels of CK-BB isoenzyme, on the first day of life, in infants who had suffered perinatal asphyxia as a predictor or a marker of perinatal asphyxia. It is also aimed to study the effect of magnesium sulfate (MgSo4) administration as a protective for brain damage. For this purpose we have 47 newborns, 33 full term who had suffered perinatal asphyxia, 18 of them received MgSo4 in their management, 15 without MgSo4 administration and 14 full term healthy newborns as a controls. To all of the studied neonates, a full and detailed history was taken and a thorough clinical examination was done. Apgar scores was recorded at 1, 5, 10 and 20 minutes, and arterialized capillary blood gases was done on admission. Serum total CK, CK-BB and magnesium were analysed at the 4 - 6 hours of age for both the study and the control groups and at the age of 24 hours only in the neonates who had suffered perinatal asphyxia. Estimation of serum total CK and serum magnesium were done on spectrophotometer (NOVA spec, LKB, Pharmacia) using the specific kit from Randox and Human Laboratories respectively. CK-BB isoenzymes were separated and quantitated on agarose gel electrophoresis using Titan gel CK isoenzyme from Helena Laboratories and scanned on Beckman fluorescence densitometer scan. The study revealed that serum total CK and serum CK-BB isoenzymes, withdrawn between 4 - 6 hours of age were significantly higher in the asphyxiated newborns than the controls. The mean value of serum total CK in the patients group was 1773.3 1575.2 U/L, while that of the control group was 273.7 63.1 U/L. The mean value of serum CK-BB isoenzymes in the patients group, 91.8 62.9 U/L, in the controls, 15.1 3.7 U/L. This difference was statistically significant (p < 0.01). This indicates that serum total CK and serum CK-BB isoenzymes in the newborns who had shown signs of perinatal asphyxia could identify the risk of tissue damage and CK-BB isoenzyme is an indicator of neuronal damage. There was no significant difference detected between the mean value of serum magnesium in the asphyxiated newborns and the controls. The mean serum magnesium level in the asphyxiated newborns was 2.1 0.4 mg/dl while that of the controls was 2.2 0.4 mg/dl. There was no significant difference between the mean blood level of total CK (at 4 - 6 hrs of life) in the asphyxiated newborns who had received MgSo4 (group Ia), 1758.1 1751.3 U/L and those who had not received MgSo4 (group Ib), 1791.5 1395.3 U/L. The mean blood level of CK-BB (at 4 - 6 hrs) in group Ia, 85.9 57.6 U/L, carry no significant difference than that of group Ib, 98.9 73.3 U/L. The first sample (at 4 - 6 hrs) of serum magnesium level in group Ia, 2.2 0.5 mg/dl, was not significantly different from that of group Ib, 2.1 0.4 mg/dl. After infusion of MgSo4 in group Ia, serum magnesium increased significantly from 2.2 0.5 mg/dl to 3.33 0.4 mg/dl. No significant changes in heart rate, pattern of respiration and muscle tone had been observed during and after MgSo4 infusion. No significant difference was detected between group Ia and group Ib in the level of total CK at 24 hrs. However, a significant decrease in the level of CK-BB at 24 hrs was detected in group Ia, 55.4 55.6 U/L when compared to group Ib, 105.0 83.1 U/L (p < 0.05). In the group of patients who had received MgSo4, no statistically significant difference was detected in the level of total CK at 24 hrs, 1933.7 2045.7 U/L compared to that obtained at 4 - 6 hrs, (1758.1 1751.3 U/L) (p > 0.05). While CK-BB at 24 hrs, (55.4 55.6 U/L) was significantly lower than that of 4 - 6 hrs, (85.9 57.6 U/L) (p < 0.01). In patients who had not received MgSo4 a statistically significant increase of the total CK at 24 hrs, (2224.3 1982.0 U/L), was observed when compared to its level at 4 - 6 hrs, (1791.5 1395.3 U/L) (p < 0.05). CK-BB was also higher in 24 hrs samples (105 83.1 U/L) than that of 4 - 6 hrs samples (98.9 73.3 U/L) but the difference was not statistically significant (p > 0.05). As regards HIE staging, out of the 33 diseased newborns, 6 cases were diagnosed as stage I HIE, 13 cases as stage II HIE and 14 cases as stage III HIE. Twenty-two of those 33 patients (66.7%) survived and 11 (33.3%) died. The death rate was higher among stage III HIE [10 (71.43%) out of 14 cases]. The Apgar scores at 1, 5, 10 and 20 min were significantly lower in the patients with severe HIE (stage III) than those of stage II or stage I HIE. There was no significant difference between the patients in stage I and II HIE as regard the Apgar score. The patients of stage III HIE had significantly lower blood pH than the patients of stage II or stage I HIE. The lower blood pH with lower Apgar score at 1, 5, 10 and 20 min reflect the severity of perinatal hypoxia and the severity of HIE. There was no significant difference in serum total CK in relation to the severity of HIE stages, while serum CK-BB isoenzyme was significantly higher in the patients of stage III than those of stage II or stage I HIE (p < 0.01). In group Ia, the mean value of CK-BB at 24 hrs was significantly lower than that of 4 - 6 hrs in stage II HIE, while in stage III, it was also lower but the difference was not statistically significant (p > 0.05). This decrease in the level of CK-BB in the patients who had received MgSo4 can be attributed to the administration of such a small dose of MgSo4. where it might cause a slight cerebral protection. There was insignificant negative correlations between serum magnesium level at 24 hours of life and serum total CK as well as serum CK-BB isoenzymes (p > 0.05). There was a significant negative correlation between the Apgar score at 1, 5, 10 and 20 min and the levels of serum total CK as well as serum CK-BB isoenzymes. But there was insignificant correlation between Apgar score and serum magnesium level (first sample). The remarkably increased concentration of serum CK-BB isoenzymes in severe HIE can be used as a marker of the extent of brain damage. It also enabled us to demonstrate the possible value of the extended Apgar scores and HIE classification system in the clinical evaluation of brain damage in the asphyxiated newborn infants. A significantly positive correlation was observed between the Apgar scores and blood pH. The significantly negative correlation observed between serum CK-BB isoenzymes and Apgar score at 1, 5, 10, 20 min and blood pH, indicate that the elevation of CK-BB early after birth is a good indicator of brain injury in the newborns who had suffered perinatal asphyxia. The non-survivors had significantly lower Apgar score at 1, 5, 10, and 20 min, as well as blood pH compared to the survived patients. Also, the non-survivors had significantly higher levels of serum total CK and CK-BB isoenzymes than the survivors, at the 4 - 6 hours samples. We can consider that CK-BB isoenzyme in the first day of life is a useful predictor of neonatal death due to brain damage. Finally, the outcome of patients with perinatal asphyxia was better in the patients who had received MgSo4 (22.2% died) than those who not (46.7% died). So, we would like to make the following recommendations: 1. It is recommended for CK-BB assay to be done routinely in the first 6 hours after birth in the newborns suffering from neonatal asphyxia, before its activity starts to decrease, for the prognostic significance it possesses. 2. Follow up of the CK and CK-BB levels beyond the first day of life at least for the first week of life, in order to evaluate the effect of therapy and improvement or deterioration on CK and CK-BB levels. 3. Due to the relative small number of patients included in this study, we recommend re-evaluation of the effect of magnesium as a protection of brain damage.