Retinopathy of prematurity: a study of prevalence and risk factors

Retinopathy of prematurity [ROP] is a serious complication of prematurity treatment and can lead to blindness unless recognized and treated early. The objective was to estimate the prevalence of ROP in preterm infants in the Neonatal Intensive Care Unit [NICU], to identify the risk factors which predispose to ROP, and to assess the outcome of these cases. A ROP prospective screening survey was performed enrolling all prematures admitted to the NICU from January 2009 to December 2010, with a gestational age of 32 weeks or less at birth and a birth weight of 1500 g or less. Infants whose gestational age was >32 weeks or birth weight was >1500 g were included if they were exposed to oxygen therapy for more than 7 days. A total of 172 infants [84 males and 88 females] had retinal evaluation by indirect ophthalmoscopy from the fourth postnatal week and followed up periodically. Perinatal risk factors for ROP were assessed using univariate and multivariate analysis. Infants who progressed to stage 3 ROP were given laser therapy. Out of the studied 172 infants, 33 infants [19.2%] developed ROP in one or both eyes; 18 [54.5%] cases stage 1, 9 [27.3%] cases stage 2, and 6 [18.2%] cases stage 3. None of the studied neonates presented ROP at stages 4 or 5. The six cases diagnosed as ROP stage 3 underwent laser ablative therapy. Univariate analysis showed that there was a significant relationship between the occurrence of ROP and gestational age [P = 0.000], sepsis [P = 0.004], oxygen therapy [P = 0.018], and frequency of blood transfusions [P = 0.030]. However, an insignificant relationship was found between the occurrence of ROP and sex, mode of delivery, birth weight, respiratory distress syndrome, patent ductus arteriosus, intraventricular hemorrhage, hypotension, phototherapy, duration of oxygen therapy, mechanical ventilation, and CPAP [all P > 0.05]. Gestational age, sepsis, oxygen therapy, and frequency of blood transfusions remained significant variables after logistic regression analysis. The prevalence of ROP in this study was 19.2%; low gestational age, sepsis, oxygen therapy, and frequent blood transfusions were significant risk factors for ROP. Laser was effective in treatment and decreasing the progression of ROP. As this is a unit-based study, a comprehensive countrywide survey on ROP in Egypt is recommended to determine any regional differences in disease prevalence

Serum levels of matrix metalloproteinase-2 [MMP-2] in children and adolescents with type I diabetes mellitus

Type I diabetes mellitus [T1DM] is an autoimmune disorder of unknown etiology. It has been suggested that matrix metalloproteinases [MMPs] play important roles in the development and complications of autoimmune disorders. Results published on the use of MMPs as markers in relation to diabetic complications are somewhat conflicting. The aim of this study was to estimate serum levels of MMP-2 in children and adolescents with T1DM, compared with levels in age-matched controls, and to correlate the levels of MMP-2 with duration of the disease, and with parameters of both glycemic control and renal function. We measured serum levels of MMP-2 in 60 patients with T1DM, aged 2-18 years, with or without microangiopathic complications and in 20 sex-and age-matched controls using enzyme immunoassay. Serum levels of MMP-2 were significantly higher in the studied patients than in the controls [p=0.000]. Serum levels of MMP-2 in diabetic patients with microangiopathic complications were significantly higher than serum levels of MMP-2 in diabetic patients without microangiopathic complications [p=0.002]. Positive significant correlation between serum level of MMP-2 and disease duration [r=0.715; p=0.000] was noted. On the other hand, no significant correlation was found between serum level of MMP-2 and any of the following parameters: Fasting blood glucose, glycated hemoglobin, blood urea, and serum creatinine [all p>0.05]. In conclusion, Serum MMP-2 levels are elevated in T1DM. Because higher MMP-2 levels were associated with the presence of diabetic complications, we raise the possibility that upregulation of MMP-2 levels might play a role in the pathogenesis of diabetic complications. Measurement of serum MMP-2 is a potentially useful marker in studies of diabetic patients at risk of progression to diabetic complications

Plasma concentration of osteopontin [OPN] in children with systemic lupus erythematosus: relationship with disease activity

Osteopontin [OPN] is an important bone matrix mediator found to have key roles in inflammation and immunity. OPN is a cytokine which can play a number of roles in promoting activation of T lymphocyte, regulating balance between T-helper 1 and T-helper 2, participating in cell-induced immunologic response and stimulating B lymphocyte to express multi-clone antibodies. Overexpression of OPN has been associated with the development of the autoimmune/lymphoproliferative syndrome. The aim of our present study was to analyze the possible correlation between the plasma concentration of OPN and disease activity in children with Systemic Lupus Erythematosus [SLE]. We also investigated the correlation between plasma IL-18 and OPN concentrations to further confirm the association of OPN with disease activity. We measured the plasma concentration of OPN, and the plasma proinflammatory IL-18 concentration in 40 SLE patients with or without renal disease [RSLE group and SLE group, respectively] and in 30 sex-and age-matched controls using enzyme immunoassay. Plasma OPN concentrations were significantly higher in RSLE and SLE patients than in the controls [p=0.000 and p=0.002]. Increase in OPN concentration correlated positively and significantly with SLE disease activity index in all SLE patients [r=0.34; p=0.04]. In RSLE patients, plasma OPN concentration showed a significant positive correlation with proinflammatory cytokine IL-18 concentration [r=0.48; p=0.004]. In conclusion, The above results suggest that the production of OPN is associated with the inflammatory process and SLE development, and may serve as a potential disease marker of SLE

Plasma-free carnitine levels in preterm infants with respiratory distress syndrome

Antenatal carnitine administration has been shown to induce fetal lung maturity by increasing pulmonary surfactant in animal and human studies. In this study, the aim was to investigate the status of carnitine in maternal and neonatal plasma of preterm infants with respiratory distress syndrome [RDS] in the first hours of life. We also aimed to characterize the carnitine status in these neonates with respect to sex, gestational age, birth weight, mode of delivery, and antenatal corticosteroid administration. Maternal plasma-free carnitine levels were determined before delivery and neonatal plasma-free carnitine levels were determined within 2 h of birth in preterm infants

Serum levels of ghrelin, tumor necrosis factor-A [TNF- A], and lnterleukin-6 [IL-6] in infants and children with congenital heart disease

Ghrelin increases food intake, body weight, and growth hormone secretion. The cause of growth retardation in congenital heart disease [CHD] is multifactorial. The aim of this study was to estimate serum levels of ghrelin, tumor necrosis factor-a [TNF-alpha], and interleukin-6 [IL-6] ih infants and children with CHD, compared with levels in age-matched controls, and to correlate the levels ofghrelin with TNF- alpha, and IL-6. We measured serum ghrelin, TNF- alpha and IL 6 levels using ELISA in 60 patients with CHD [40 acyanotic and 20 cyanotic] and in 20 control subjects. Our results showed that patients with CHD, whether compiled in one group or classified into acyanotic and cyanotic, had significantly higher serum ghrelin TNF- alpha, and IL-6 than controls [p = 0.000]. Serum levels of ghrelin and TNF- alpha in the acyanotic patients were significantly higher than in the cyanotic patients [p = 0.000]. On the other hand, there was no significant difference in serum levels of IL-6 between the acyanotic and the cyanotic patients [p = 0.126]. In acyanotic and cyanotic patients with CHD, there was a positive correlation between ghrelin and TNF- alpha [r = 0.424; p = 0.006 and r = 0.577; p = 0.008, resp.]. Ghrelin levels were not correlated with IL-6 in the acyanotic and cyanotic patients with CHD [r = -0.211; p = 0.216 and r = -0.341; p = 0.08, resp.]. Serum ghrelin, TNF- alpha, and IL-6 levels are elevated in patients with CHD whether acyanotic or cyanotic. Increased ghrelin levels represent malnutrition and growth retardation in these patients. The relation of ghrelin with TNF- alpha may be explained by the possible effect of chronic congestive heart failure and chronic shunt hypoxemia

Expired breath hydrogen peroxide as a marker of acute airway inflammation in children with asthma

Airway inflammation is an important factor in the development and progression of asthma. Activation of inflammatory cells induces a respiratory burst resulting in the production of reactive oxygen species, such as hydrogen peroxide [H[2]O[2]]. The aim of this study was to measure the levels of H[2]O[2] in expired breath condensate in asthmatic children, compared with levels in age-matched controls and to outline its relation to asthmatic triggers, asthma severity, treatment modalities, pulmonary function tests, and total and differential white cell count. Forty asthmatic and 20 healthy children were studied. Their ages ranged from 6-18 years. Expired H[2]O[2] was measured using a colorimetric assay. In asthmatic children, there was a significant elevation of the mean H[2]O[2], level compared to values in controls [p=0.003]. Asthmatic triggers [e.g.: bad housing1 passive smoking, upper respiratory tract infection] showed non significant relation to the mean value of H[2]O[2] level in expired air of asthmatic children. Bad housing showed significant relation to number of acute asthmatic attacks [p=0.03]. There was no significant difference between moderate and severe asthma regarding H[2]O[2] levels [p=0.424] Similarly, there was no significant difference between asthmatic patients whether they received inhaled steroids or not regarding H[2]O[2] levels [p=0.875]. Basal spirometric pulmonary function tests, showed no significant correlation to the level of H[2]O[2]. Correlations of H[2]O[2] level in expired air of asthmatic children with total leukocytic counts [r=0.024; p=0.899], eosinophilic counts [r=0.092; p=0.630] and neutrophilic counts [r=0.021; p=0.910] were all non significant. We conclude that expired H[2]O[2] is significantly elevated in asthmatic patients. Measurement of expired H[2]O[2], may be useful to assess airway inflammation and oxidative stress in asthmatic patients

Plasma interleukin-11 levels in thrombocytopenic and non-thrombocytopenic neonates

Thrombocytopenia is common in sick neonates, and affected neonates have adverse outcomes compared with those without thrombocytopenia. As impaired platelet production underlies many neonatal thrombocytopenias, affected neonates are potential candidates for hemopoietic growth factor therapy. The thrombopoietic cytokine recombinant human IL-11, which stimulates megakaryocytopoiesis and increases platelet counts after chemotherapy, is already licensed for clinical use. However, little is known about IL-11 in neonates. We therefore measured plasma IL-11 by ELISA in healthy term neonates, stable preterm neonates with or without thrombocytopenia, and preterm neonates with sepsis or necrotizing enterocolitis [NEC] with or without thrombocytopenia. At birth IL-11 was undertetable [<10pg/ml] in healthy term neonates [n = 15] and 21 of 25 [84%] stable preterm neonates. Three stable preterm neonates had detectable plasma IL-11[mean, 11.23 +/- 0.64 pg/ml], all three were born after pregnancies complicated by prolonged rupture of membranes or chorioamnionitis, the remaining neonate[IL-11, 15 pg/ml] being one of seven with early onset thrombocytopenia [presented by 72 h of age]. IL-11 was also measured in 50 preterm neonates with suspected sepsis or NEC. In 20 of 50, sepsis or NEC was unconfirmed and IL-11 was undetectable, in contrast, 14 of 30 with proven sepsis or NEC had elevated IL-11 [mean, 25.41 +/- 21.3; range, 11.3-93 pg/ml] [p = 0.0003]. Of the 30 neonates with proven sepsis or NEC, 19 developed thrombocytopenia: nine of 19 [47.4%] had detectable IL-11 and 10 of 19 [52.6%] did not [p = 0.746]. Although the role of IL-11 in platelet production in neonates remains unclear, these data suggest that IL-11 is involved in the endogenous cytokine response to sepsis or NEC in preterm neonates. Further studies of IL-11 in neonates are warranted to assess its role both in platelet production and in mediation of the endogenous inflammatory response

S100B protein levels in cord blood: a study in normal and growth-retarded fetuses

Follow-up studies have shown that the vast majority of neurological abnormalities present during childhood can have a prenatal or perinatal origin. It is relevant, therefore, to investigate the timing of adverse insults in the search for measures of prevention. However, such knowledge is still incomplete and subject to debate. Until recently, clinical-laboratory assessment was based essentially on biochemical aspecific parameters, ultrasound and Doppler patterns, and the determination of blood pH and gases. However, the measurement of brain constituents may offer a direct indicator of cell damage in the nervous system. The S100 B protein, a calcium-binding protein highly concentrated in the nervous system, appears to meet the criteria required of such a marker in prenatal and perinatal medicine for its reproducible, simple and sensible measurements. The aim of this study was to determine whether S100B protein could be helpful in the detection of brain distress in intrauterine growth-retarded [IUGR] fetuses, we studied, by a case-control study, the correlation between S100B protein and the degree of fetoplacental blood flow impairment. Maternal and umbilical blood samples were collected at delivery from IUGR pregnancies with normal [n=10] or abnormal [n=10] umbilical artery Doppler findings and from 20 uncomplicated pregnancies. S1020B protein levels were measured by means of a specific RIA and flow velocimetry waveforms were recorded from uterine, umbilical, and fetal middle cerebral arteries. The results showed that maternal plasma S100B protein levels were under the limit of detection in both IUGR and control groups. In contrast, fetal S100B protein levels in umbilical plasma were significantly higher [p=0.04] in IUGR patients [123.5 +/- 69.7 fmol/mL] compared to the controls [52.4 +/- 20.2 fmol/mL]. IUGR fetuses with redistribution of blood flow showed the higher concentration of the protein [164.8 +/- 54.9 fmol/mL]. Fetal S100B protein levels correlated negatively with middle cerebral artery pulsatility index [r=-0.528; p=0.02], and positively with umbilical artery pulsatility index to middle cerebral artery pulsatility index ratio [r = 0.489; p=0.03]. In the control group, a negative significant correlation between S100B protein and gestational age was found [r= 0.76; p=0.01]. Circulating S100B protein is increased in IUGR fetuses and correlates with cerebral hemodynamics, suggesting that it may represent an index of cerebral cell damage in the perinatal period

Brain-derived neurotrophic factor [BDNF], and neurotrophin 3 [NT3] levels in newborn cord sera

During embryonal development, neuronal death occurs only by apoptosis and not by necrosis. Apoptotic neuronal loss may be responsible for altered brain development associated with prematurity and perinatal insults. Neurotrophic factors such as brian-derived neurotrophic factor [BDNF], and neurotrophin 3 [NT3] play crucial roles in protecting neurons form entering or progressing along an apoptotic pathway. The aim of this work was to measure BDNF and NT3 level at different gestational ages in human umbilical cord blood. In addition, we searched for differences in BDNF and NT3 levels in the presence or absence of factors that may affect intrauterine conditions and thus neurodevelopmental outcome. We collected 80 samples of cord blood and categorized them accordingly into three gestational age groups: group 1 [24-30 weeks], group 2 [31-36 weeks], and group 3 [37-42 weeks]. BDNF and NT3 levels were determined by ELISA. The BDNF levels were 798.3 +/- 492.5, 1401 +/- 650.8, and 2236.6 +/- 376.8 pg/ml in group 1, group 2, and group 3, respectively, with a significant difference between the 3 groups [p=0.0001]. In contrast, NT3 levels did not show significant change across gestational ages [p=0.2]. NT3 levels also did not correlate with BDNF levels across gestational ages [r=0.23; p=0.27]. The presence of premature rupture of membranes, chorioamnionitis, pregnancy-induced hypertension, or small for gestational age did not alter either BDNF or NT3 levels significantly. BDNF and NT3 levels were significantly higher in samples from subjects whose mothers received two doses of antenatal steroids compared with those who received only one dose of steroids, and those with no antenatal steroids[p=0.001, and p=0.04]. Cord blood levels of BDNF may reflect the degree of neutral maturity in premature infants. Increased BDNF and NT3 levels may also mediate improved neurodevelopment outcome in infants who received antenatal steroids

Hemostatic changes and autoantibody formation in otherwise healthy children with acute varicella infection

In this study, blood samples were obtained from 20 children with varicella without thrombosis during acute varicella infection. The study included as well 20 healthy controls. Coagulation tests included determination of the prothrombin time, activated partial thromboplastin time, thrombin time, prothrombin fragment 1+2 and free protein S. Blood was assayed also for the D-dimer, antibody binding to protein S, lupus anticoagulant, antiphospholipid antibody and anticardiolipin antibody. The results revealed that the mean free protein S concentration in children with acute varicella was significantly decreased compared to the controls. Thrombin time, D- dimer and prothrombin fragment 1+2 were significantly increased in children with acute varicella compared to that of the controls. There was a significantly increased prevalence of lupus anticoagulant, antiphospholipid antibody, anticardiolipin antibody and antibody binding to protein S in children with acute varicella. Elevated protein S IgG antibody in children with acute varicella showed statistically significant negative correlation with free protein S and positive correlation with prothrombin fragment 1+2. Plasma concentrations of free protein S were reduced and plasma levels of D- dimer and prothrombin fragment 1+2 were elevated in otherwise healthy children with acute varicella infection. Also, these children showed increased prevalence of lupus anticoagulant, antiphospholipid antibody and anticardiolipin antibody

Polarographic studies on mixed Ligand complexes of cadmium-1-methyl imidazolemalonate system

The overall formation constants of the mixed ligand complexes of 1-methylimidazole [l-Melm] and malonate [Mal] with cadmium [II] have been studied polarographically at constant ionic strength, micro = 2. 0, [NaNO3] and pH 8 at 25 +/- 0.1 degree. The reduction of the complexes at a DME, is reversible and diffusion controlled. The constants for three mixed complexes of Cd[II] are log Beta11 = 4.0 for [Cd[l-Melm] [Mal]], log Beta12 = 4.4 for [Cd[l-Melm] [Mal]2] and log Beta21 =5.9 for [Cd[l-Melm]2 [Mal]]. The equilibrium constant values of the tendency of a ligand to add to a complex and to substitute another ligand were compared

Polarographic study of mixed ligand complexes; cadmium-1methyl-imidazole-tartrate system

The composition and complexation constants of the Cd[II] complexes in solution containing mixtures of 1-methylimidazole [l-Melm] and tartrate [Tart] ion have been studied polarographically at constant ionic strength, micro= 2.0 [NaNO[3]] and pH 8 at 25 +/- 0.1 degree. The reduction of the complexes at a D.M.E. is reversible and diffusion-controlled. The mixed complexes formed with 1-methylimidazole and tartrats are [Cd[l-Melm] [Tart]]; [Cd[1 -Melm] [Tart[2]]-; [Cd[l-Melm [2] [Tarf[2]][2] and [Cd[1-Melm][3] [Tart]] with overall stability constants of log Beta 11 = 4.5. log Beta 12 = 4.4. log Beta 22 = 6.0 and log Beta21= 6.0. respectively. The equilibrium constant values of the tendency of a ligand to add lo a complex and to substitute another ligand was compared