Does phototherapy induce an oxidative stress in preterm neonates?

Of this study was to investigate whether phototherapy leads to oxidative stress in preterm newborns. Lipid peroxidation products as indicated by the thiobarbituric acid reacting substances [TBARS] in blood and urinary 8-Hydroxydeoxyguanosine [8-OHdG] as a protein peroxidation product in urine were assessed before and after exposure to phototherapy. Meanwhile, antioxidant activity in terms of plasma vitamin E and erythrocyte-glutathione peroxidase [GSH-PX] was assessed. The study group enrolled 24 preterm infants with physiological hyperbilirubinemia categorized according to the used modality of phototherapy into single and double phototherapy groups. Their mean gestational age was 31.22 +/- 2.63 weeks, and birth weight was 2.175 +/- 0.86 kg. Blood samples were collected immediately before and after 72 hours of phototherapy. Samples were analyzed for total serum bilirubin [TSB], serum albumin, blood TBARS, plasma vitamin E and erythrocyte-GSH-PX. Urine samples were collected before and after phototherapy for analysis of 8-OHdG. Levels of blood TBARS, Urine 8-OHdG were significantly elevated after phototherapy while plasma vitamin E and erythrocyte GSH-PX did not significantly change. Blood TBARS showed a negative correlation to TSB before phototherapy. The percent increase in serum TBARS or Urine 8-OHdG after phototherapy did not significantly correlate to gestational age or birth weight. Phototherapy induces oxidative stress in preterm neonates with unconjugated hyperbilirubinemia, regardless of their birth weight or gestational age. In face of this stress, antioxidant defense may be inadequate, requiring vitamin E supplementation. No significant photo-oxidant hazard is added in proceeding with double phototherapy in neonates under single phototherapy

Superior mesenteric artery duplex doppler examination as a tool to predict early tolerance to enteral feeding in preterm neonates

The question when to feed a sick preterm neonate remains a clinical challenge. The dominant argument to postpone enteral feeding is the risk of necrotizing entero-colitis [NEC]. Predicting feeding tolerance is still largely dependent on clinical observation. Changes in superior me-senteric artery [SMA] blood flow velocity measured by Duplex Doppler in PT neonates have been shown to occur in response to feeds. The aim of this study was to evaluate whether serial Doppler measurements of SMA blood flow velocity could predict early enteral feeding tolerance in preterm infants. The study included 32 preterm neonates subjected to history taking, clinical evaluation, and determination of cause of prematurity.The need for resuscitation after 5 minutes of birth, the exposure to phototherapy or aminophylline intake were determined. Preterms with clinical signs of suspected or confirmed NEC or PDA were excluded from the study. On the day of start of enteral feeding as decided by the nursery clinician, blood pressure, heart rate and urine output were recorded and SMA Duplex Doppler sonography was performed. Blood flow velocity in SMA was assessed 15 minutes prepr and ial, a test feed was given, then re-evaluated 60 minutes postpr and ial. Values of peak systolic velocity [PSV], end diastolic velocity [EDV], time-averaged mean velocity [TAMV], pulsatility index [PI] and resistive index [RI] were presented. PT neonates were subjected to close clinical follow-up and the duration from test feed to full enteral feeding was estimated for each neonate. Accordingly, survived neonates were grouped into: Group I: neonates who achieved full enteral intake within 7 days, which included 17 preterm neonates and group II: neonates who achieved full enteral intake after 7 days, which included 13 preterm neonates. A significant negative correlation existed between TAMV at 60 min and the number of days needed to achieve full enteral intake. Early feeders showed an adequate hemodynamic response to the test feed as demonstrated by a significant rise of EDV and a significant drop of RI and PI. Late feeders showed poor hemodynamic response as illustrated by non-significant change in all parameters. Late tolerance to enteral feeding and poor postpr and ial hemodynamic response were significantly more frequent among c and idates of resuscitation and neonates exposed to phototherapy. Percentage of postpr and ial drop of RI was more significant in the early as compared to the late tolerance group. Clinical and Doppler predictions of tolerance to enteral feeding in terms of RI% postpr and ial drop were properly matched in two thirds of cases. Tolerance to enteral feeding in preterm neonates can be predicted from postpr and ial hemodynamic response to the initial trophic feed. By Doppler sonographic investigation of the SMA in preterm infants, the percentage of postpr and ial Doppler change at 60 min after the first feed might be a good tool for the clinician in predicting early tolerance to enteral feeding.

Matrix metalloproteinase-8 and tissue Inhibitor of metalloprotinases-2 in tracheal aspirates from ventilated preterm neonates with respiratory distress syndrome

Matrix metalloproteinases [MMPs] are a family of endoproteinases that act in remodeling and destruction of extracellular matrix and basement membrane. An imbalance among their inducers, activators and specific inhibitors is believed 10 generate parenchymal destruction in pulmonary inflammatory diseases. In this study the concentrations of MMP-8 and tissue inhibitor of metalloprotinases [TIMP]-2 were assessed in tracheal aspirate fluids [TAFs] obtained from ventilated preterm neonates during the first postnatal week. The aim was to investigate their possible role in acute inflammatory lung injury associating respiratory distress syndrome [RDS], assess their relation to disease severity and their possible contribution to the development of chronic lung disease [CLD].Clinical and radiographic assessments of respiratory distress were attempted for 90 ventilated preterm neonates who were defined in 3 groups. Group A comprised 32 neonates with RDS, group B constituted 28 neonates with bronchopneumonia while group C included 30 ventilated neonates for extrapulmonary disorders. The median values for fraction of inspired oxygen [FiO[2]] and arterial/alveolar O[2] tension ratio [a/A O[2]] during the first 24 hours of ventilation, as measures of initial severity of respiratory distress, were calculated. TAF samples were collected for measurement of MMP-8 and TIMP-2 levels by ELISA with calculation of MMP-8/TIMP-2 ratio. Clinical outcome was determined in terms of evolution to CLD. A significant increase in MMP-8/TIMP-2 ratio was found in group A as compared to groups B and C [p<0.01, respectively]. Meanwhile, no significant change in MMP-8/TIMP-2 ratio was encountered in group B in comparison to group C [p>0.05]. Among neonates with RDS, MMP-8 was positively correlated to FiO[2] [r=0.64, p<0.01] and was inversely related to a/A O[2] [r=-0.72, p<0.01]. Nineteen [59%] of RDS neonates developed CLD and those were found to have significantly higher MMP-8, MMP-8/TIMP-2 ratio and initial FiO[2] and significantly lower initial a/A O[2] ratio as compared to RDS neonates with no CLD [p<0.01, respectively]. MMP-8 at an optimum cut-off value of 188 ng/mL was the best to predict RDS progression to CLD with a positive predictive value [PPV] of 94.1% and an efficacy of 87.5%. An imbalance between tracheal aspirate MMP-8 and TIMP-2 levels during the early postnatal period could play a role in the acute inflammatory lung injury in neonatal RDS. This imbalance is associated with disease severity and probably contributes to subsequent evolution of CLD. It could also be speculated that early assessment of tracheal aspirate MMP-8 in preterm neonates with RDS might help prediction of later CLD development

Neutrophil CD11b expression, soluble tumor necrosis factor receptors and plasma interleukin 6 as markers of early neonatal sepsis

The value of neutrophil CD11b expression, soluble tumor necrosis factor receptors [sTNF-R] 55 and 75 and plasma interleukin-6 [IL-6] in early detection of neonatal infection was studied in 288 neonates. The studied newborns were classified into 4 group: group 0 [not infected], group 1 [possibly infected], group 2a [probably infected, culture-ve] and group 2b [culture +ve infection]. We looked for the optimal cutoff points of these parameters using the receiver operating characteristics [ROC] curve. The neutrophil CD11b expression by flowcytometry [FCM] was >100 median FU in all neonates with confirmed infection, >60 in all but one neonate of those with suspected infection, and <60 FU in non-infected group. A cutoff value of 60 FU or greater a 96% sensitivity, and a negative value of 99%. The sTNF-R 55 levels were significantly higher in the culture +ve group; 2a [median 7ng/ml], 2b [median 12ng/ml], and 1 [median 7ng/ml] than group 0 [median 3.9 ng/ml]. The sensitivity and specificity of a cutoff level of 6 ng/ml were 75% and 69% respectively. Similarly, sTNF-R 75 levels in groups 2a [median 11.2ng/ml], 2b [median 7 ng/ml], and 1 [median 10.6 ng/ml] than group 0 [median 7 ng/ml]. With a cutoff value of 9 ng/ml, sensitivity and specificity were 80% and 67% respectively The median levels of plasma IL-6 in groups 2a, 2b, 1, and 0 were 700 pg/ml, 260 pg/ml, 160 pg/ml, and 0 pg/ml respectively. A cutoff value of 100 pg/ml was 83.3% sensitive and 90.3% specific in diagnosing neonatal infection. For newborns sampled at birth or within the 1st postnatal hour, sensitivity was 100% and specificity 92.3%. This high sensitivity persisted until the 12th hour of life. On the other hand sensitivity of C- reactive protein [CRP] was low initially but improved with progress of infection. It is concluded that neutrophil CD11b is a promising test for ruling out early onset neonatal sepsis. If validated prospectively, such assay may reduce hospital stay and antibiotic use in newborns at risk of sepsis. High plasma IL-6 alone before 12th hour of life, and combined with high CRP thereafter, provides a useful maker for identifying the majority infected neonates. The sTNF-R seem less useful in this context because of their smaller magnitude of variation

Early cerebral duplex, doppler D-dimer, and plasminogen activator inhibitor - 1 in high risk term neonates

Alterations in the cerebral blood flow in the neonate can be assessed by Duplex Doppler. Stressed neonates may be liable to cerebral thrombosis owing to disturbed procoagulant balance between reactive fibrinolysis and antifibrinolysis. This study assessed some plasma hemostatic markers in correlation with cerebral hemodynamics in a group of stressed FT neonates. To investigate possible relation of both measurements to the type of the offending risk factor and to the severity of neurologic presentation. In this study, plasma level of D-dimer, a marker of fibrin formation and reactive fibrinolysis, and plasminogen activator inhibitor-1 [PAI-1], a marker of anti-fibrinolysis were assessed in 62 FT neonates. Of these, 52 were perinatally distressed, having neurological manifestations in the immediate post-natal period and 10 were healthy FT neonates who served as control. Studied neonates were clinically assessed at birth by Apgar score, resuscitated as required, sampled for ABG and CRP, and subjected to full clinical evaluation. Stressed neonates were categoriesed according to the type of perinatal insult into: One risk factor group; namely perinatal asphyxia [group A] and intrapartum trauma [group B], Two risk factor group; comprising group C, that included the above two risks, groups D and E that included any of the above two risks with superadded early postnatal sepsis. They were eventually classified by neurological criteria according to early postnatal encephalopathy score [ES] into minimum ES and maximum ES groups. Re-sampling followed for ABG and laboratory investigations that included CBC, platelet count, PT, PTT, D-dimer and PAI-1 assay by enzyme linked immunosorbant assay [ELISA]. Within 24 hours of birth, middle cerebral artery blood flow velocity was assessed and resistive index [RI] was measured using Duplex Doppler sonography. The mean values of RI, plasma D dimer and PAI-1 were significantly higher than control in all stressed neonates and in each high risk group. Reduced cerebral blood flow in asphyxiated neonates was mainly aggravated by birth trauma. Traumatised neonates had significantly higher mean plasma D-dimer and PAI-1 as compared to neonates with perinatal asphyxia. Development of postnatal sepsis significantly raised plasma level of PAI-1 in asphyxiated neonates. RI was more predictive of severity of encephalopathy than either hemostatic markers. Cerebral ischemia was significantly associated with instrumental delivery, premature rupture of membranes [PROM] while no significant association existed with either fetal bradycardia, liquor stained meconium, emergency CS, degree of hypoxemia or hypocarbia. A significant positive correlation existed between values of RI and each of plasma levels of D-dimer and PAI-1 in all stressed neonates. Conclusions: On the first day of life, cerebral blood flow is reduced and some plasma prothrombotic markers are elevated in FT neonates subjected to trauma or asphyxia at birth. Cerebral ischemia in severely stressed FT neonates may pave the way to future cerebrovascular thrombosis. It follows that early screening by cerebral Duplex Doppler is crucial for high risk FT neonates especially following exposure to intrapartum trauma

Impaired systemic fibrinolysis in severe neonatal respiratory distress syndrom

The intravascular and intra-alveolar deposition of fibrin in severe neonatal respiratory distress syndrome [RDS] have been attributed to activation of clotting. We questioned whether in face of enhanced clotting, fibrinolysis is sufficient in these neonates. Therefore, we aimed to assess plasminogen activator inhibitor-1 [PAI-1] as a marker of fibrinolysis in plasma of neonates with RDS to investigate its relation to disease severity and the possible prognostic value of its early measurement. The study included 65 neonates, all of them were clinically assessed within 6 hours of birth for inclusion in the study. The study group consisted of 45 preterm neonates, 30 with RDS, and 15 healthy preterm control neonates. The remaining twenty neonates were fullterms; 10 had clinical evidence of infection and 10 were healthy fullterm control neonates. Neonates with RDS were clinically and radiologically evaluated to assign severity and accordingly they were categorized into a severe group and a mild to moderate group. Blood samples were obtained from these neonates while on mechanical ventilation during the first day of life. Fraction of inspiratory oxygen [FiO2] was determined and they were clinically followed up throughout the whole duration of ventilation. Laboratory investigations included CBC, C-reactive protein [CRP], ABG and plasma PAI-1 determination for all neonates as well as a coagulation assay including PT, PTT, fibrinogen and fibrin degradation products [FDPS] done for 18 RDS neonates. Mean plasma concentrations of PAI-1 were significantly elevated in PT neonates with RDS as a whole [P<0.001] and in each subgroup [P<0.01] as compared to control PT neonates. Severe RDS group showed significantly higher PAI-1 in plasma as compared to the mild to moderate group [P<0.001]. A significant positive correlation existed between PAI-1 and FiO2 in all neonates with RDS [P<0.01]. Fibrinogen levels were significantly lower in neonates with severe RDS as compared to the mild to moderate group [P<0.05] and they were negatively correlated to plasma PAI-1 in all studied RDS neonates [P<0.05]. The ratio of FDPs between 5 and 20 to FDPs<5 was 9:1 in the mild to moderate RDS group, compared to 1:1 in the severe group. Plasma levels of PAI-1 in full term neonates with systemic infection were significantly higher as compared to healthy fullterms [P<0.05]. Sepsis was documented in 21.05% of deaths among neonates with RDS. Retrospective tracing of CRP in neonates with RDS who died revealed values that were non-significantly higher than those of survivors [P>0.05]. Meanwhile, Plasma PAI-1 levels in deceased were significantly higher than those of survivors [P<0.001]. PAI-1 cut off value of 58 ng/ml was 60% sensitive and 73.68% specific to predict mortality in RDS. In severe RDS, high PAI-1 impairs systemic fibrinolysis which likely facilitates the deleterious effects of early clotting activation, contributing to disease severity and mortality. Plasma level of PAI-1 within 24 hours of birth, though might be influenced by early infection may be a useful predictor of outcome in neonatal RDS

Neonatal neutrpenia associated with pregnancy induced hypertension and cord blood granulocyte colony stimulating factor

Neutropenia is frequently observed in neonates born to mothers with pregnancy induced hypertension [PIH]. Though transient, it may be a leading cause of early neonatal sepsis. Hence, prophylactic exogenous hematopoietic factors are currently tried. However. Causes of this neonatal neutronenia [NN] and its relation to the endogenous production of these factors are still obscure, therefore we aimed to study granulocyte colony stimulating factor [G-CSF] among other determinants of NN in this population. The present study included 92 neonates; 52 born to normotensive mothers and 40 neonates with maternal PIH. Gestational age [GA] and birth weight [BW] were assessed with clinical evaluation of all studied neonates at birth and after 72 hours to rule out infection. Cord blood absolute neutrophil count [ANC] and levels Of G-CSF [as measured by ELISA] were studied. Neonates born to mothers with PIH had significantly [P<0.05] lower ANC than control newborns. ANC was significantly [P<0.01] lower in neonates with GA <32 weeks as compared to those >32 weeks. Values of ANC were significantly positively correlated with BW [P<0.05]. Neonatal neutropenia [ANC <1.5 x 10[9]/ L] was observed in 35% of infants born to mothers with PIH being moderate to severe [ANC< 1x10[9] / L] in 25%. Of these neonates with moderate to severe NN, 90% were of low BW and 60% were preterms of GA less than 32 weeks. Mean value of cord blood G-CSF [126.3 +/- 99.6 pg/L] was significantly [P<0.001] lower in all babies of mothers with PIH than control [283.9 +/- 221.7 pg/L]. A significant positive correlation was noted between ANC and G-CSF [P<0.05] in FT neonates. Neonates whose GA<32 weeks showed significantly increased frequency of moderate to severe neutropenia [66.7%] compared to other GA groups [13.3% and 12.5% in those born after 37 weeks and those born between 33 and 36 weeks, respectively] [p<0.05]. The least reported mean cord blood G-CSF in this study [79.3 +/- 31.14 pg /L] was encountered in neonates whose GA<32 weeks and who exhibited NN that approached severity [mean ANC: 0.59 +/- 0.21 x 10 [9]/L]. Early neutropenia may be noted in neonates born to mothers with PIH. It may be related to reduced serum G-CSF especially in LBW and in those with increased degree of prematurity. This population may be suitable c and idates for recombinant human G-CSF [rh G-CSF] therapy

Value of abdominal ultrasonography and doppler in assessment of portal hypertension in children

This study was carried out to find a relation between ultrasonographic and Doppler findings of portal hypertension and grading of Esophageal varices as detected by upper GIT endoscopy. 24 children suffering from portal hypertension were subjected to full clinical examination laboratory investigations, liver biopsy, upper GIT endoscopy and abdominal US. Their ultrasonographic and Doppler data were compared to those of a control group consisting of 20 healthy children of matched age and sex. According to endoscopic grading of OV, patients were divided into two groups, mild and severe. The severe group was again subdivided into bleeders and non-bleeders for further analysis. Ultrasonographic parameters as MPV-d, sp-MPV, sp-RPV, sp-LPV, SV-d, long axis of the spleen and omental thickness were all significantly different from those of controls. Among patients of the severe group, bleeders were significantly different from non-bleeders as regards SV- d, OT and sp-splenorenal. To predict severity and onset of bleeding of OV in patients with PH, a score was developed. Accordingly, patients having scores above seven are at risk of hematemesis and might be considered for prophylactic regimens