oxidative stress and neonatal respirator

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RESPIRATORY DISTRESS DISORDERS IN NEWBORN : By Rana Refaat Ali Mohammed M.Sc. Pediatrics Zagazig university –Egypt 2009 Role of Oxidative Stress and Endothelial Products

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INTORDUCTION

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An increasing number of studies implicate oxidative stress in the development of endothelial dysfunction and the pathogenesis of pulmonary disorders. This oxidative stress has been shown to be associated with alterations in both the ET-1 and NO signaling pathways. Many data, have shown that oxidative stress ET-1 and NO are co-regulated in complex fashion.

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Also the free radicals have been implicated in the pathogenesis of some respiratory disorders in preterm infants. Even through ascorbic acid is an important antioxidant in human plasma, it can act as a pro oxidant in a high concentrations in the presence of metal ions which causes oxidative damage in newborn infant.

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ET-1 is a novel and potent endothelium-derived vasoconstriction peptide present in human plasma. It plays an unknown role in the pathogenesis and progression of important neonatal pulmonary disorders e.g chronic lung disease of prematurity, persistent pulmonary hypertension of the newborn. The ET-1 concentration can be used as a useful tool in differential diagnosis between the different respiratory distress disorders.

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NO is a potent endogenous vasodilator and is involved in cytotoxicity, neuro-transmission and immunological defense mechanisms. Endogenous production of NO is vital for the decrease in pulmonary vascular resistance that normally occurs after birth. The role of NO in the regulation of pulmonary blood flow at birth is established.

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The interaction and relative potency of NO; an endothelium derived relaxing factor and ET-1; an endothelium derived contracting factor, may be important in the transition from fetal to extrauterine life, and in pathogenesis and progression of neonatal pulmonary distress.

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Vitamin C or ascorbate is a powerful anti-oxidant in human plasma, premature infants are born with high levels of plasma ascorbate, which decline soon after birth. Ascorbate can act as either anti-oxidant or a prooxidant depending on its concentration and the presence of metal ions.

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AIM OF THE WORK

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This study aimed To evaluate the physiological significance of ET-1, NO and antioxidant material (ascorbic acid) in neonates with respiratory distress disorders e.g. transient tachypnea of the newborn, meconium aspiration, respiratory distress syndrome. Also to evaluate the role of other risk factors in neonate i.e. preterm, low birth weight and birth stress in the pathogenesis of these vasoactive materials balance and imbalances.

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SUBJECTS AND METHODS

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SUBJECTS AND METHODS

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This work was carried out in the Pediatrics and Biochemistry Departments, Zagazig University Hospitals through November 2004 to July 2006. Thirty newborns with symptoms and signs suggestive of respiratory distress disorders (13 females, 17 males) and 10 healthy newborns taken as a control group were included in the study.

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Patients of the present study were randomly selected from those admitted to NICU with requirement for supplemental oxygen because of respiratory distress. This group included both full term and preterm newborns.

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Newborns were diagnosed as having respiratory distress disorder if they had : Increasing respiratory rate, chest retraction; intercostals, subcostal and xiphoid, Working ala nasi, expiratory grunting, frothing at lips and cyanosis. The degree of respiratory distress was assessed into mild, moderate and severe.

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INCLUSION CRITERIA : Newborns within 24 hours after labour, if there are signs of respiratory distress and if a written or verbal consents were given from parents.

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Both index and control group were subjected to the following : Full history taking including: Maternal history for usage of drugs, materno-fetal complications, maternal chronic diseases, consanguinity, multiple pregnancy, placenta previa, description of labour and any other pervious maternal reproductive problems. Full clinical examination : including birth weight , length, sex, Apgar score, vital signs e.g. pulse rate and temperature. General examination, head and face, chest, cardiac, abdominal, skin, neurologic, limbs and genitalia . Assessment of gestational age using ballered score.

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Routine investigations : Complete blood count (CBC), urine analysis, glucose level, renal function test, liver function test, serum electrolytes and serum calcium. Arterial blood gases and bicarbonate. Plain x-ray chest. Estimation of level of serum nitric oxide using one step technique. Estimation of plasma endothelin-1 level using EIA technique. Estimation of plasma ascorbic acid using electrochemical detection. Investigations : The following investigations were done for all the included participants :

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All routine laboratory investigations as well as serum nitric oxide, plasma ascorbate and x-ray chest were done on the first day of admission while the plasma endothelin-1 were done on first day and one week later.

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RESULTS

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RESULTS

Demographic characteristics of newborns with respiratory distress (group I) versus control (Group II) : 

Demographic characteristics of newborns with respiratory distress (group I) versus control (Group II)

Clinical characteristics of both studied groups : 

Clinical characteristics of both studied groups *NVD = Normal vaginal delivery ** CS = Cesarean section

Clinical diagnosis in newborns with respiratory distress disorders (Group I) : 

Clinical diagnosis in newborns with respiratory distress disorders (Group I)

Mean + SD of plasma levels of ET-1, NO and ascorbic acid in both groups : 

Mean + SD of plasma levels of ET-1, NO and ascorbic acid in both groups

Relation between level of NO and different causes of respiratory distress in group I : 

Relation between level of NO and different causes of respiratory distress in group I TTN= Transient tachypnea of newborn RDS= Respiratory distress syndromePPHN= Persistent pulmonary hypertension MAS= Meconium aspiration syndrome

Relation between level of ET-1 and different causes of respiratory distress in group I : 

Relation between level of ET-1 and different causes of respiratory distress in group I

Relation between level of ascorbic acid and different causes of respiratory distress in group I : 

Relation between level of ascorbic acid and different causes of respiratory distress in group I

Correlation between ET-1, NO and ascorbic acid with some clinical data : 

Correlation between ET-1, NO and ascorbic acid with some clinical data

Correlation between the weightand ascorbic acid level in group I : 

Correlation between the weightand ascorbic acid level in group I

Correlation between the gestational ageand ET-1 level in group I : 

Correlation between the gestational ageand ET-1 level in group I

Correlation between the gestational ageand ascorbic acid in group I : 

Correlation between the gestational ageand ascorbic acid in group I

Correlation between both ET-1, NO and ascorbic acid with Apgar score at 5 minutes : 

Correlation between both ET-1, NO and ascorbic acid with Apgar score at 5 minutes

Relation between mode of delivery and ET-1, NO and ascorbic acid in group I : 

Relation between mode of delivery and ET-1, NO and ascorbic acid in group I

Relation between gestational age and level of ET-1, NO and ascorbic acid in group I : 

Relation between gestational age and level of ET-1, NO and ascorbic acid in group I

Relation between gestational age and level of ET-1, NO and ascorbic acid in group II : 

Relation between gestational age and level of ET-1, NO and ascorbic acid in group II

Correlation matrix between level of ET-1, NO and ascorbic acid : 

Correlation matrix between level of ET-1, NO and ascorbic acid

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Correlation matrix between levelof ET-1 day 1 and day 7

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Correlation matrix between levelof ET-1 day 1 and NO

Relation between the degrees of respiratory distress and ET-1, NO and ascorbic acid : 

Relation between the degrees of respiratory distress and ET-1, NO and ascorbic acid

Relation between mean + standard deviation of NO, ET-1 and ascorbic acid levels and outcome in both groups : 

Relation between mean + standard deviation of NO, ET-1 and ascorbic acid levels and outcome in both groups

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SUMMARY

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SUMMARY

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In the present study, the diseases causing respiratory distress in the early neonatal period were evaluated, RDS was the most frequent, followed by TTN, then MAS, and lastly PPHN.

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ET-1 levels in the present study were significantly higher in newborn infants with respiratory distress disorders compared to control group. The highest concentration of ET-1 level were observed in newborns of PPHN group, more than those with RDS and TTN. The increased circulating ET-1 level was not significantly correlated with the severity of respiratory distress.

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There was no significant correlation between the mode of delivery and level of ET-1 in patients with respiratory distress on the first day and 7th day of life. ET-1was a significantly higher in preterm newborns in comparison to full term infants with respiratory distress disorders.

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The present study also observed a significant decline of ET-1 from the first day of life to the 7th day of life in newborns of respiratory distress group. Also a significant correlation between neonatal ET-1 level and some illness severity signs e.g. Apgar score and degree of hypoxia i.e. blood gases. Plasma ET-1 concentrations may have a good indicator of the prognosis in the first day of life after birth, because it was a significantly different between survivors and dead newborns infants, in whom the ET-1 concentration were higher in the first day of life.

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NO levels, in the present study were not significantly correlated with the degree of respiratory distress. However, Apgar score and arterial blood gases were highly significantly related to level of NO. There is no statistically significant correlation between prematurity and level of serum nitric oxide in newborn with respiratory distress.

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The lowest level of NO was observed in newborns of primary diagnosis of MAS followed by those with TTN. The highest levels were reported in those with primary diagnosis of RDS and PPHN. No significant correlation between the changes in NO levels and mortality in newborn infants with respiratory distress disorders was observed.

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Vitamin C or ascorbate was significantly higher in our group of newborns with respiratory distress compared to the control group. The level of ascorbic acid had highly significant negative correlation with the birth weight and gestational age. Also, significant correlation was observed between the ascorbic acid levels and the Apgar score. There was no significant correlation between the changes of ascorbic acid level and the degree of respiratory distress.

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Also the level of ascorbic acid was much higher in newborns with severe to advanced degree of respiratory distress compared to the newborns with mild to moderate degree of respiratory distress. The highest levels of ascorbic acid were observed in newborns with primary diagnosis of RDS, followed by those with MAS. There was no significant correlation was observed between the levels of ascorbic acid and outcome in newborn infants with respiratory distress disorder.

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On studying the correlation matrix between ET-1, NO and ascorbic acid there were a highly significant negative correlation between the elevation of ET-1 levels on the first day of life and the decrease in level of NO. Non significant correlations were observed between the elevated ET-1 levels and the increase in plasma ascorbic acid levels. On the 7th day of life the level of ET-1.

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A significant negative correlation with NO level and non significant correlation with level of ascorbic acid. Non significant correlation was seen between the changes in NO levels and ascorbic acid. No significant correlation between levels of both ET-1, NO and ascorbic acid were observed.

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CONCLUSION Its speculated that plasma ET-1, NO and ascorbic acid may be specific markers for pulmonary endothelium injury in newborns with respiratory distress disorders of different etiologies. Plasma ET-1 concentrations may have a good indicator of the prognosis in the first day of life after birth. No significant correlation between levels of both ET-1, NO and Ascorbic acid were observed.

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Although ascorbic acid is an important antioxidant in humans, it can act as a prooxidant in high concentration which in the presence of metal ions causes oxidative damage in newborn infants. Other risk factors like, mode of delivery and gestational age, may affect the course of respiratory distress in newborns.

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RECOMMENDATION A wider group of patients and more detailed study is required to determine the border line value of ET-1, may be useful in determining the prognosis and clinical recovery later on in newborns with respiratory distress disorders . New researches to evaluate the role of ET-1, NO and Ascorbic acid, in each etiological item and different risk factors separately Plasma ET-1 concentrations may used as indicator of the prognosis in the first day of life after birth. The routine usage of vitamin C in neonatal period should be restricted.

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THANK YOU