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Volume 6, No. 2, April, 2005
NEUTROPHIL CD11b EXPRESSION, SOLUBLE TUMOR NECROSIS FACTOR RECEPTORS AND PLASMA INTERLEUKIN-6 AS MARKERS OF EARLY NEONATAL SEPSIS
TAHANI A. EL-KERDANI*and FATMA Z. ABDEL-BASSET
Clinical Pathology* and Pediatric Departments, Ain-Shams UniversityABSTRACT
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
Galila M Mokhtar, Fatma Z Abdel- Basset, Dalia F El-Sherif, *Karima M Maher and **Mona M Zaki
Departments of Pediatrics,*Diagnostic Radiology and **Clinical Pathology Ain-Shams University
ABSTRACT
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. Aim: to investigate possible relation of both measurements to the type of the offending risk factor and to the severity of neurologic presentation. Methods: 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. Results: 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.
Key words: cerebral Duplex Doppler, D-Dimer, Plasminogen activator inhibitor, fetal bradycardia, liquor stained meconium, cerebrovascular thrombosis.
IMPAIRED SYSTEMIC FIBRINOLYSIS IN SEVERE NEONATAL RESPIRATORY DISTRESS SYNDROME
Fatma Z. Abdel –Basset *and Tahany El-Kerdany
Departments of Pediatrics* and Clinical Pathology, Ain-Shams University
ABSTRACT
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. Results: 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.
Conclusions: 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.
SPECT VERSUS ULTRASONOGRAPHY CRANIAL IN PERINATAL ASPHYXIA
*Khaled Taman; *Nayera Ismail; And ***Laila Faris
*Institute Of Postgraduate Childhood Studies, And ***Nuclear Medicine Departments. Ain Shams University, Cairo, EGYPT
ABSTRACT
This study was conducted on 25 asphyxiated term neonates with a mean birth weight of 3-49 + 0.53kg. They were admitted to the Neonatal Intensive Care Unit of the Obstetric and Gynecology Department Ain shams University Hospitals in the period from September 2003 to January 2005. All neonates were simultaneously evaluated with cranial sonography and SPECT during the first week of life. The objective of this study was to evaluate degree of brain insult in neonates with perinatal asphyxia using SPECT versus cranial sonography performed approximately at the same time. A second goal was also to correlate the value of SPECT findings detected in perinatal asphyxia with urinary excretion of alpha 1 microglobulin (A1M), which is considered as an early biochemical marker of tubular damage in perinatal asphyxia.
Our results showed that there was abnormal cerebral blood flow detected by SPECT whether focal or diffuse uptake detect in 100% (25cases) of asphyxiated neonates, while abnormal sonography findings were found in 10 out of 25 asphyxiated neonates (40%). The effect of asphyxia on lobe perfusion was different where frontal lobe was the most frequent hypoperfused lobe in 100% of cases and cerebellar region was the least frequent hypoperfused lobe40% of cases. However, there was no statistical significant difference between focal and diffuse SPECT and abnormal cranial sonographic findings (P>0.05). On comparing the three stages of hypoxic-ischemic encephalopathy (HIE) to each other as regards SPECT abnormalities, a statistical significant difference (P<0.01) was found showing more diffuse hypoperfusion with increased severity of HIE. A significant statistical increase was found in cases with diffuse hypoperfusion compared to focal hypoperfusion as regards neurological abnormalities (P<0.05). On the other hand, there was significant statistical increase of urinary alpha-1 microglobulin excretion in asphyxiated cases with diffuse hypoperfusion (53%) than in cases with focal hypoperfusion (47%) (P<0.05). On the other hand, a significant statistical difference was found between cases with focal and diffuse hypoperfusion as regards birth weight, pH, HCO3, pO2 and Apgar score at 5 minutes. The sensitivity of SPECT in detecting cerebral blood flow abnormalities was 100% in comparison to 44% sensitivity in cranial sonography when the neurological assessment was used as the gold standard.We could conclude that SPECT study is more sensitive than cranial sonography as a diagnostic tool to detect brain insult resulting from perinatal asphyxia. Therefore we think that, the potential use of brain SPECT to predict the outcome of mental development and assessment of neurological sequalae especially in cases with perinatal asphyxia is essentially recommended
RETINOPATHY OF PREMATURITY: INCIDENCE AND RISK FACTORS
Ehab Nabil El-Rayes*,Rasha M.Gamal El-Din**
*Research Institute of Ophthalomology.**Pediatric Departement,Faculty of Medicine,Cairo University,Egypt.Abstract:
Improved survival of low birth weight, premature babies have increased the incidence of retinopathy of prematurity (ROP).ROP is a bilateral vasoproliferative retinopathy affecting preterm or low birth weight babies, which sometimes progresses to cause visual impairment or blindness .The purpose of this study is to highlight the magnitude of the problem due to ROP in Egyptian preterm babies and to define risk factors associated with ROP .Subjects and methods: The study was performed at Research Institute of Ophthalmology and different neonatal intencive care units(NICUs) participating in the study during the period from April 2004 to March 2005.The study population included 68 infants ,infants were divided into 2 groups, group I included 43 infants who were reffered for Ophthalmological consultation and group II included 25 infants who were examined during their presence in different neonatal intensive care units. Included were infants with birth weight of less than 1500g or with gestational age of 32 weeks or less, as well as selected infants between 1500g and 2000g who were belived to be at high risk. Multiple variables for ROP positive and ROP negative infants were compared. Data of patients were analyzed retrospectively ,patients were examined by indirect Ophthalmoscopy once, scheduling of follow-up examinations were determined by the findings at the first examination using the international classification of ROP. RESULTS: Of the total infants examined,20 (29.4%) were ROP positive. Statistically significant risk factors included: lower gestational age, lower birth weight, sepsis ,seizures, intraventricular hemorrhage, higher number of days on ventilator, and twin births, There was no correlation between the sex of the infant and the risk of developing ROP. The total number of days on oxygen did not reach statistical significant. CONCLUSION: The present study clearly highlights the magnitude of the problem due to ROP in Egyptian preterm babies. Prematurity and low birth weight remains on the top of the list of risk factors for developing ROP. These risk factors are difficult to control, The most practical recommendation would be proper screening of infants at risk for early detection and treatment.We suggest that indirect Ophthalmoscopy should be performed in all preterm babies weighing = 1500 g, beginning first at 4 weeks postnatal age. Screening should be intensified in the presence of factors like apnea, oxygen administration and septicemia.
FEEDING OF THE PRETERM NEONATE
Review Article
Quoted by: Assist. Prof. Dr. Fatma El-Zahraa Abd El-Basset
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