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Volume 4, No. 3, September, 2003
INTERLEUKIN-8 AS A DIAGNOSTIC MARKER OF NEONATAL SEPSIS
Nahla M. Heshmat, Gehan A. Mostafa, Amal Z. Abd El-Halim* and Manal H. Ahmed
Departments of Pediatrics and *Clinical Pathology Ain Shams University, Cairo, Egypt
Abstract
Early diagnosis of sepsis in the neonate is often difficult as symptoms and signs are usually non-specific and there are cases that are clinically suggestive of sepsis with negative blood culture. So we should try to find out diagnostic markers to diagnose neonatal sepsis very early. The aim of this study was to evaluate plasma IL-8 as a predictor of neonatal sepsis to facilitate early diagnosis and initiation of appropriate therapy.
This study comprised 54 full-term neonates divided into 2 groups; group I included 24 neonates with proven sepsis diagnosed clinically and by positive blood culture. Group II included 30 neonates with suspected or possible infection (they had 2 or fewer clinical signs of sepsis ± positive CRP with a high risk factor of infection and negative blood culture). Thirty healthy age and sex matched full-term newborns were studied as controls. After history taking and clinical examination, the following laboratory investigations were performed: complete blood count, CRP (latex agglutination), blood culture and sensitivity and estimation of IL-8 by ELISA technique.
The 30 patients with suspected infection were followed up clinically and CRP as well as blood culture were repeated after 48 hours. Patients who developed sepsis later on as evidenced clinically and by laboratory investigations including positive blood culture were considered as patients with early sepsis at the time of admission.
Plasma IL-8 of neonates with proven sepsis (1794.38±1816.9 pg/ml) or early sepsis (229.16±221.02 pg/ml) was significantly higher than that of the control group (35.53±17.8 pg/ml). IL-8 had a sensitivity of 100% for sepsis (either at its early or late stages) as it was elevated in all patients with proven and early sepsis. The sensitivity of CRP for diagnosing neonatal sepsis before the evolution of overt clinical manifestations was 50% only. In addition, IL-8 had an excellent negative predictive value (100%) for early sepsis. IL-8 was significantly elevated in non-survivor neonates with sepsis when compared to the survivors indicating that high IL-8 values are associated with poor prognosis.
In conclusion, IL-8 is a highly sensitive marker for diagnosing neonatal sepsis at its early stage. Also, it had an excellent negative predictive value (100%), thus it facilitates the exclusion of the infection in high-risk neonates to avoid the unnecessary antibiotic use. In addition, IL-8 is a useful prognostic marker of neonatal sepsis. This highlights the importance of our recommendation of adding IL-8 to the laboratory investigations performed in neonatal sepsis especially in suspected cases.
ENDOTHELIN-1 IN PLASMA AND AIRWAYS OF PRETERMS WITH RESPIRATORY DISTRESS SYNDROMENancy A. Soliman, Nehal M. El-Raggal, I. S. Abu-Seif, Mona F. Youssef* and H. A. Mostafa
Pediatric and *Clinical Pathology Departments, Ain Shams University.Abstract
The objective of the study was to characterize the relationship between endothelin-1 (ET-1) concentration in plasma and airway of the preterm and the severity of respiratory distress syndrome (RDS) in early postnatal period. 44 preterm neonates were enrolled in two groups. Group I comprised 29 preterms with RDS requiring mechanical ventilation. They were further discriminated into 3 subgroups according to severity of RDS (mild, moderate and severe RDS). Group II comprised 15 preterms on mechanical ventilation for repeated attacks of apnea of prematurity, matched for gestational and postnatal age with group I and served a reference group. Laboratory investigations included plain chest radiographs, sepsis work-up to rule out infection, arterial blood gas analyses with calculation of arterial alveolar oxygen ratio (a/A O2). ET-1 concentration was measured in plasma and tracheal aspirates within the first 48 hours of life. Results: Mean plasma ET-1 concentrations were significantly elevated in preterms with moderate and severe RDS as compared to reference preterms (P <0.01 & P <0.001, respectively). Significant negative correlation existed between plasma ET-1 and each of gestational age and 1 and 5 minutes Apgar scores, whereas significant positive correlation existed between plasma ET-1 and each of fraction of inspired oxygen (FiO2), mean airway pressure (MAP) and radiographic grading of severity. On the contrary, mean concentration of ET-1 in tracheal aspirate was significantly lower in preterms with severe RDS as compared to reference preterms (P <0.01). A significant positive correlation was found between tracheal aspirate ET-1 levels and 5 minutes Apgar score, while a significant negative correlation existed between tracheal aspirate ET-1 and MAP. Finally, a significant negative correlation was found between plasma and tracheal aspirate levels of ET-1 (P <0.001) in preterms with RDS, as well as in reference preterms. Conclusion: High plasma ET-1 level is associated with more severe RDS and could be a specific marker for pulmonary endothelial injury that may contribute to the development of elevated pulmonary vascular resistance in this setting. Meanwhile, the association of low ET-1 level in the airway with severe RDS may be attributable to limitation of its stimulant effect on surfactant secretion and/or the development of airway epithelium; hence, rise in airway ET-1 is indicative of improved pulmonary status in the early course of the disease.
Serum Secretory phospholipase A2 and Interleukin-1ß for prognosis and mortality prediction in neonatal sepsis
Ismail S Ismail*, Safaa S Imam*, karim Y Shahin**, Ahmed R Youssef *
Pediatric* and Clinical Pathology** Departments Faculty of Medicine Ain Shams University.Abstract
To evaluate the measurement of IL-1ß and sPLA2 for the diagnosis of neonatal sepsis as well as their relation to severity and outcome. The current study was carried out on 40 full term neonates (23 males and 17 females) selected from the Neonatal Intensive Care Unit and the General Nursery of Gynecological and Obstetric Hospital of Ain Shams University. The studied neonates were divided into two groups: Group I: included 25 neonates with neonatal sepsis 15 males and 10 females. Their postnatal age ranged between 3-21days (mean±SD 7.12±4.04 days) they were 14 neonates with early onset sepsis and 11 neonates with late onset sepsis. Group II: included 15 healthy neonates 8 males and 7 females served as control group. Their postnatal age ranged between 3-21 days (mean ±SD 10.6±3.66 days). All neonates underwent full history taking, thorough clinical examination, complete blood count, CRP level, blood culture, measurement of serum IL-1ß, and sPLA2. A second sample was withdrawn after one week from seven cases who were improved clinically, to measure serum CRP, IL-1ß, and sPLA2.The result of this study demonstrated that IL-1ß was significantly higher in the septic group in comparison with the control group (21.10± 9.79 vs. 4.90 ±3.58 pg/ml respectively, P<0.0001) and declined after antibiotic therapy (16.91± 9.3 vs. 9.55± 3.2, P<0.05). No significant difference between early onset sepsis and late onset sepsis neonates was observed in regards IL-1ß, and sPLA2. Also significant elevations in IL-1ß levels in non-survivors than survivors of the septic group were observed (28.37 ±11.93 vs. 18.27 ±7.40pg/ml respectively, P<0.05). Furthermore, secretory PLA2 (sPLA2) was significantly higher in the septic group in comparison with the control group (185.20± 64.42 vs. 63.53±33.52 U/ml respectively, P<0.0001). sPLA2 was significantly lower after antibiotic therapy (164.29± 90.94 vs.57.14± 15.77 U/ml, P<0.05). Higher levels of sPLA2 were observed in non-survivors when compared with survivors of the septic group (243.43± 34.54 vs. 162.56 ± 59.15 U/ml respectively, P<0.001). A positive correlation between the level of IL-1ß and sPLA2 was observed in the septic group (r = 0.78, P<0.0001) and the rate of change of sPLA2 was higher than IL-1ß after antibiotic therapy (61.23% vs. 46.57% respectively). In conclusion, IL-1ß and sPLA2 played a role in pathogenesis of neonatal sepsis. Moreover, their measurements could be used for diagnosis of neonatal sepsis and for prediction of prognosis and mortality.
Cytomegalovirus Load among Egyptian Newborn infants Admitted to the Neonatal Intensive Care Unit: New Perspective
Hamed A. El-Khayat*, Mohamed F. Mostafa*, Nayera I. Attia **, May F. Nassar.* and
Tantawy Amin ***
*Pediatric Department, Faculty of Medicine, Ain Shams University, **Institute of Postgraduate Childhood Studies (Medical department), Ain Shams University and ***NAMRU-3, Virus Isolation Center.
Abstract
Background: CMV transmission is very hazardous to neonates whether due to its severe congenital form or the latent effects of this virus.
Objective: The aim of this study was to assess CMV load among Egyptian newborn infants admitted to the NICU, to clarify the risk factors for CMV transmission and to set clinical criteria for suspicion of this viral infection among such neonates.
Patients and Methods: This cross-sectional prospective study included 260 neonates admitted to the NICU of the Gynecology and Obstetric hospital, Ain Shams University. Each enrolled case was subjected to detailed history taking laying stress on the socioeconomic standard, maternal diseases such as infection, fever, premature rupture of membranes and past history of any abortion, neonatal death or affected newborns. APGAR score at 1 and 5 minutes, their birth weights and skull circumferences were assessed. Thorough clinical examination including assessment of gestational age was done together with regular follow up of the clinical course of the neonates during their NICU admission for a mean postnatal age of 12.35 ± 10.34 days. In addition to the routine laboratory investigations and the sepsis screen, peripheral blood samples and nasopharyngeal secretions were taken from all the studied neonates on their first and fifth day of life for viral isolation using human fibroblasts cell line culture. Indirect Fluorescent Antibody (IFA) test was carried out for the identification of isolated CMV virus.
Results: The present study revealed positive viral culture in 49 cases, 13 of which were confirmed CMV by IFA. Ten of the CMV positive cases were detected in the first day sample (prenatally acquired) and the other three were detected in the fifth day sample which denotes either perinatal or community acquired infection. In all, 84.6% of the CMV positive cases were delivered prematurely and 61.54% were IDM. Clinical examination showed that 53.9% of them had MCA, 53.9% had jaundice, 46.2% had rash and 38.5% had enlarged lymph nodes, 30.8% were hypothermic, 23.1% had poor peripheral perfusion, 7.7% were pale and 7.7% were cyanosed. Systemic examination revealed that 46.2% had HSM and 23.1% had abdominal distension. As regards the neurological manifestations, 30.8% had hyporeflexia while 15.4% had hyperreflexia, 38.5% were hypotonic while 15.4% were hypertonic and 15.4% suffered from tonic convulsions. A cardiac murmur was heard in 15.4% and inguinal hernia was detected in 7.7%. In conclusion, CMV acquisition especially the congenital form represents a significant problem among newborn Egyptian infants who may be asymptomatic or present with various manifestations ranging from mild to fatal illness. Thus increasing awareness of this viral infection, its ways of transmission, risk factors for neonatal acquisition and its mode of presentation are mandatory to prevent its neonatal as well as the delayed hazards.
NEONATAL NEUTROPENIA ASSOCIATED WITH PREGNANCY INDUCED HYPERTENSION AND CORD BLOOD GRANULOCYTE COLONY STIMULATING FACTOR
FATMA Z. ABD EL-BASSET, ADHAM M. HEGAZY , SAFAA S. IMAM, NAYERA I. ATTIA**, and MONA F. YOUSSIF*
Departments of Pediatrics , *Clinical Pathology , Faculty of Medicine, Ain Shams University and **Medical department , Institute of Postgraduate Childhood Studies, Ain Shams University
Abstract
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 neutropenia (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 x109/ L) was observed in 35% of infants born to mothers with PIH being moderate to severe (ANC < 1x109/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 and36 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 109/L) . Conclusion: 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 candidates for recombinant human G-CSF (rh G-CSF) threrapy.
IMMUNOGENICITY OF TWO SCHEDULES OF HEPATITIS B VACCINE: EFFECT OF BIRTH WEIGHT AND GESTATIONAL AGE
Nancy A. Soliman, Ehab K. Emam, *Ghada F. El-Dory and **Dina A. Fouad
From Pediatric department, *The high institute of postgraduate childhood study and **Clinical pathology department, Ain Shams University
Abstract
Introduction and aim of the work: Hepatitis B is a global problem causing both acute disease and delayed morbidity. The optimal time to initiate hepatitis B vaccination in low birth weight infants has not been determined. The aim of this work was to study the immune response of low birth weight infants whether full-term or prematures with two different schedules of hepatitis B vaccine, in order to optimize the time of hepatitis B vaccination of these infants. Subjects and methods: This study was conducted on 74 infants. They were 54 low birth weight (LBW) infants with birth weights<2.5 kg and 20 full-term healthy infants with birth weight appropriate for gestational age (AGA) who were served as controls. The 74 infants were followed up from birth at 3-months intervals and completed the follow-up period at the age of 12 months. According to the hepatitis B vaccination schedule given, the studied infants were divided into two groups; group I comprised 38 infants who received hepatitis B vaccine at the 2nd, 4th and 6th months of age (1st schedule) and group II comprised 36 infants who received the vaccine at birth, 1st and 6th months of age (2nd schedule). Considering the birth weight and gestational age, infants of each group were further subdivided into subgroup A which included full-term LBW infants (IA&IIA), subgroup B which included preterm infants (IB&IIB) and subgroup C which included full-term AGA infants ???C&IIC???All mothers were subjected to full medical history taking, assessment of socio-economic class as well as assessment of gestational age and anthropometric measures of their infants. Quantitative measurement of anti-HBsAg levels using ELISA technique was done at birth then at the 3rd, 6th, 9th and 12th months of age. Results: The mean levels of anti-HBsAg titre were significantly lower at all ages among LBW infants of groups I and II compared to those of subgroups IC (full-term AGA of group I) and IIC (full-term AGA of group II) respectively. Meanwhile, the mean levels of the titre were significantly higher at the 6th and 9th months and significantly lower at the 3rd month of age in LBW infants of group I than those of group II, while no significant difference between both groups was found at the 12th month of age. Regarding infants receiving the 1st schedule, the mean levels of anti-HBsAg titre were significantly higher at the 3rd and 6th months of age in infants of subgroup IA (full-term LBW of group I) than those of subgroup IB (prematures of group I), while no significant differences between the 2 subgroups were found at the 9th and 12th months of age. Meanwhile, the mean levels of anti-HBsAg titre were significantly lower in subgroup IA infants compared to those of subgroup IC at the 6th and 9th months of age and in infants of subgroup IB compared to those of subgroup IC at all ages. Regarding infants receiving the 2nd schedule, the mean levels of anti-HBsAg titre were significantly higher in subgroup IIA infants (full-term LBW of group II) than those of subgroup IIB (prematures of group II) at all ages and significantly lower in subgroup IIA infants compared to those of subgroup IIC (full-term AGA of group II) at the 6th, 9th and 12th months of age and in infants of subgroup IIB compared to those of subgroup IIC at all ages. Comparing the two schedules, the mean levels of the titre were significantly higher in subgroups IIA, IIB and IIC infants compared to those of subgroups IA, IB and IC respectively at the 3rd month of age and in infants of subgroup IB compared to those of subgroup IIB at the 6th, 9th and 12th months of age. However, there were no significant differences regarding the mean titre in subgroups IA and IC infants compared to those of subgroups IIA and IIC respectively at the 6th, 9th and 12th months of age. Conclusion and Recommendations: We can come to the conclusion that the immune response to the different schedules of hepatitis B vaccine is lower in LBW as well as preterm infants. Further, the immune response of LBW infants to Hepatitis B vaccine given at birth, 1st and 6th months of life was higher at the 3rd month of age, while, at 6th and 9th months of age, the response to the vaccine was better in infants who received the 2nd, 4th and 6th months’ schedule. However, by the end of the 1st year both schedules gave similar seroprotection regardless the gestational age and birth weight. Hence, in case there is no risk of perinatal transmission, it is recommended to delay the 1st dose of hepatitis B vaccine in LBW infants especially prematures till the age of 2 months and/or till the weight is 2.5 kg.
SERUM VITAMIN B12 IN NEURAL TUBE DEFECTS: A FACTOR BEHIND FOLATE DEFICIENCY
Sahar M.A Hassanein*, Hanan M El-Shkankiry*, Mona M. Zaki**, Hazem A. Kassem***, Lobna M. Saber**** and Ranya M. N. Abd El-Raouf*.
Departments of Pediatrics*, Clinical Pathology**, Neurosurgery***, Faculty of Medicine, Ain Shams University; Department of Biochemistry****, Faculty of Medicine, Al-Azhar University, Cairo, Egypt.
Abstract
Background: Neural tube defects (NTDs) are the most common congenital anomalies of the central nervous system, resulting from failure of the neural tube to close between 3rd-4th week of gestation. NTDs result from multiple intrinsic and extrinsic factors including maternal folate. Although clear evidence exists on preventability of a large proportion of neural tube defects by periconceptional folic acid intake, however the exact cause of this deficiency is not established.
Hence, the purpose of this study was to determine possible risk factors for the occurrence of NTDs. The relation between maternal serum folate and vitamin B12 and their infant’s levels.
Patients and methods: Clinical history and examination, and serum folic acid and vitamin B12 concentrations (by Radioimmunoassay) were assessed for 20 neonates with neural tube defects (36-39 week of gestation, 11 females and 9 males) and their mothers. They were compared to 20 healthy neonates and their mothers as the control group.
Results: Infants with NTDs have significantly lower serum levels of folic acid and vitamin B12, compared to healthy infants (p = 0.02 and p = 0.001) respectively. Serum level of vit B12 was significantly lower in mothers of infants with NTDs than mothers of healthy infants (p = 0.01), but there was no significant difference between serum level of folic acid in mothers of infants with NTDs and mothers of healthy infants. There was no significant difference between males and females as regards serum levels of both folic acid and vit B12. Positive correlation was found between gestational age and serum level of folic acid (p = 0.01). Also, statistically significant positive correlation was found between serum level of vitamin B12 of infants with NTDs and their mothers (p = 0.031). There was significant correlation between serum level of folic acid and serum level of vitamin B12 in mothers of healthy infants (p < 0.05).
The study demonstrated that not only folate is deficient in infants with neural tube defects, but vitamin B12 is also deficent in them and their respective mothers. This finding focuses light on the pivotal role vit.B12 deficiency as a corner stone of folate deficiency. So deficiency of vitamin B12 rather than folic acid during pregnancy might play a role in the genesis of neural tube defects.
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