Serdar Umit Sarici

High‐dose intravenous immunoglobulin therapy in neonatal immune haemolytic jaundice

A controlled study was conducted to assess the role of high‐dose i.v. immunoglobulin (HDIVIG) therapy in neonatal immune haemolytic jaundice. Patients with ABO and/or Rh incompatibilities proved by significant hyperbilirubinaemia (<204mmol 1−1), positive direct antiglobulin test and high reticulocyte count (>10%) were randomly assigned to receive either conventional phototherapy alone or phototherapy with high‐dose i.v. immunoglobulin (1 g kg−1, over 4h) as soon as the diagnosis was established. Exchange transfusions were performed if serum bilirubin concentrations exceeded 290 mmol 1−1 and increased by more than 17 mmol 1−1 per h despite both treatment manoeuvres. Eight of 58 patients in the HDIVIG group required exchange transfusions, whereas it became necessary in 22 of 58 patients in the control group (p < 0.001). The durations of phototherapy and hospitalization in terms of hours were significantly shorter in the HDIVIG group (p < 0.05). No side effects of HDIVIG therapy were observed. In conclusion, HDIVIG therapy in newborns with ABO or Rh haemolytic diseases reduces haemolysis, serum bilirubin levels and the need for blood exchange transfusion, a procedure which has potential complications and carries a risk of mortality.

Treatment of retinopathy of prematurity:a review of conventional and promising new therapeutic options

Retinopathy of prematurity (ROP), a retinal vascular disease of premature infants, continues to be a major cause of preventable childhood blindness all over the world. The incidence of ROP varies among countries, being influenced by the quality of the level of neonatal intensive care. Here, we discuss the potential treatments that are now available or will soon or probably be available for ROP. Although ablation of the avascular retina with laser photocoagulation remains the current gold standard and well established therapy for ROP, some new therapeutic options including angiostatic therapies are being explored based on our knowledge of the pathophysiology of the ROP and complications and efficacy of laser treatment. However, prevention of the development of severe ROP and screening for ROP seem to be the best strategy in avoiding visual impairment caused by ROP in premature infants. New therapeutic interventions including vascular endothelial growth factor antibody administration, gene therapy and supplemental therapies should be supported with evidence-based data for the treatment of ROP.

Double versus single phototherapy in term newborns with significant hyperbilirubinemia

The efficacy of double phototherapy, in the form of conventional phototherapy with special blue light plus fiberoptic phototherapy, was compared with conventional phototherapy consisting of special blue lamps alone in a relatively larger series of term newborns with significant hyperbilirubinemia. During the study period the sum of the average spectral irradiances in the double phototherapy group was significantly higher than that of the single phototherapy group (p < 0.05). Phototherapy was effective in decreasing bilirubin levels in both groups, but the response was greater in the double phototherapy group; the duration of exposure to phototherapy was significantly shorter (31.2 +/- 8.5 vs. 38.98 +/- 14.7 h, p < 0.05), and the overall bilirubin decline rate as mumol/l/h and per cent/h was significantly greater in the double phototherapy group (4.1 +/- 1.37 vs. 3.3 +/- 0.86 mumol/l/h, and 1.29 +/- 0.38 vs. 1.02 +/- 0.44 per cent/h, p < 0.05). In phototherapy treatment of term newborns with significant hyperbilirubinemia, double phototherapy provided more rapid and effective bilirubin reduction than conventional phototherapy alone due to higher spectral irradiance and larger body surface area exposed to phototherapy. The value of double phototherapy in the treatment of newborns with hemolytic hyperbilirubinemia remains to be determined.

Apelin, vaspin, visfatin and adiponectin in large for gestational age infants with insulin resistance

OBJECTIVE To investigate the relation of circulating four adipokines (apelin, vaspin, visfatin, adiponectin) with markers of insulin sensitivity in large for gestational age (LGA) infants. PATIENTS AND METHODS Forty LGA infants (20 LGA born from diabetic mothers and 20 LGA born from non-diabetic mothers) and 34 appropriate for gestational age (AGA) infants were recruited. Hyperinsulinism and insulin resistance was evaluated using the homeostasis model assessment (HOMA-IR), fasting glucose-to-insulin ratio (FGIR), quantitative insulin-sensitivity check index (QUICK-I) from fasting samples. Plasma adiponectin and vaspin levels were determined by radioimmunoassay. Determination of visfatin and apelin levels was performed by enzyme immunoassay. RESULTS HOMA-IR, apelin and visfatin levels (p<0.001, p<0.001, p<0.001, respectively) were significantly elevated and adiponectin levels, FGIR and QUICK-I values. (p<0.001, p<0.001, p<0.05, respectively) were significantly lower in the LGA group. Vaspin levels were higher in the LGA group than AGA neonates without a significance. The LGA infants with diabetic mother had significantly higher visfatin, apelin, HOMA-IR values, fasting insulin levels and significantly lower adiponectin, FGIR, QUICK-I values. Apelin and visfatin were correlated positively, and adiponectin was correlated negatively with birthweight, HOMA-IR values and fasting insulin levels. CONCLUSION Based on the findings of this study, it is too difficult to explain relation between birthweight and these adipocytokines, but findings of high insulin, HOMA-IR, visfatin, apelin and low adiponectin levels in the LGA neonates showed that these adipocytokines can be used as a good predictor for metabolic syndrome.

Diagnostic value of resistin and visfatin, in comparison with C-reactive protein, procalcitonin and interleukin-6 in neonatal sepsis

AIM The aim of this study was to evaluate the predictive value of resistin and visfatin in neonatal sepsis, and to compare these adipocytokines with C-reactive protein (CRP), procalcitonin and interleukin 6 (IL-6). DONORS AND METHODS A total of 62 term or near term infants with sepsis proven by positivity of blood culture, and 43 healthy infants were included in this study. RESULTS There were no statistically significant differences between the two groups as regards birthweight and gestational age. White blood cell count (p= 0.039), CRP levels (p=0.01), procalcitonin levels (p=0.01), IL-6 levels (p= 0.01), visfatin levels (p=0.01) and resistin levels (p=0.01) were significantly higher in septic infants. There was a positive correlation between visfatin, resistin and other markers (WBC, CRP, procalcitonin and IL-6). A cut-off value of 10 ng/mL for visfatin, showed 92% sensitivity and 94% specificity, and a cut-off value of 8 ng/mL for resistin showed 93% sensitivity and 95% specificity for neonatal sepsis. CONCLUSION In the light of these results, visfatin and resistin can be used as a diagnostic marker similar to CRP, procalcitonin and IL-6 in neonatal sepsis. Further studies are needed to better understand the role and predictive value of these molecules in neonatal sepsis.

Toll-like receptor levels and caffeine responsiveness in rat pups during perinatal period.

Infants born prematurely are prone to bronchopulmonary dysplasia which is a devastating form of chronic lung disease that develops in very low birth weight infants. Toll-like receptors (TLRs) are pattern recognition receptors that initiate innate immune responses. We tested TLR2, 4, and 9 levels in the lungs of rat pups given caffeine at the first days of postnatal life. Twenty-four rat pups equally divided into three groups. The study group received caffeine immediately after birth for ten days. The levels of TLR9 were found significantly higher in study group than control groups. We conclude that the beneficial and anti-inflammatory effects of caffeine in the lungs of newborn rats may be due to increased TLR9 levels.

Neurodevelopmental status of preterm newborns at infancy, born at a tertiary care center in Turkey.

Our objective was to determine the incidence of early neonatal problems and the neurodevelopmental status and probable risk factors associated with neurodevelopmental abnormality in preterm infants of < or = 32 weeks of gestation. Preterm newborns of < or = 32 weeks of gestation followed at the neonatal intensive care unit of the Department of Pediatrics of Gülhane Military Medical Academy, Ankara, Turkey, were evaluated with a complete neurological examination and the Bayley Scales of Infant Development at a mean age of 25.85 + or - 11.79 months (range, 10 to 42 months). Multivariate logistic regression analyses were performed to determine the probable risk factors associated with neurodevelopmental abnormalities. Regarding the results of the neurological examination in a total of 169 preterms included in the study, 28 (16.6%) and 14 (8.3%) patients were determined to have mild neurological dysfunction or cerebral palsy, respectively. The rate of psychomotor abnormality according to a low Bayley Psychomotor Development Index (PDI) score was 24.8%, and the rate of mental/cognitive abnormality on the basis of a low Bayley Mental Development Index (MDI) score was 25.4%. In the subgroup of infants with < or = 29 weeks of gestational age (n = 55); 22 (40%) patients had an abnormal neurological examination, and 24 (43.6%) and 23 (41.8%) patients had low Bayley PDI and MDI scores, respectively. In the study group, logistic regression analysis revealed the significant predictors of an abnormal neurological examination to be the duration of mechanical ventilation (odds ratio [OR], 1.133; 95% confidence interval [CI], 1.062 to 1.208) and necrotizing enterocolitis (OR, 6.697; 95% CI, 1.776 to 25.252). One of the major conclusions of the present study is the risk of neurodevelopmental sequelae in one of every four preterm infants with <32 weeks of gestation and the need for follow-up in this group. Measures in neonatal care and treatment, such as the use of less traumatic modes of mechanical ventilation with as short duration as possible as well as increasing perinatal/antenatal care, should be taken to overcome these risk factors.

Comparison of the efficacy of conventional special blue light phototherapy and fiberoptic phototherapy in the management of neonatal hyperbilirubinaemia.

The efficacy and usefulness of two types of phototherapy differing in the source, wavelength and irradiance of the light, conventional phototherapy consisting of special blue light and fiberoptic phototherapy, were compared in a relatively larger series of term newborns with non‐haemolytic and more significant hyperbilirubinaemia than those in previous studies. In total, 108 newborns were allocated sequentially to receive either conventional phototherapy consisting of five special blue lamps or fiberoptic phototherapy. The average spectral irradiance measured at the skin surface level of newborns during the study period was significantly greater in the conventional phototherapy group. The special blue lamp of the conventional phototherapy unit had an emission spectrum almost identical to the bilirubin absorption spectrum, whereas the tungsten‐halogen lamp of the fiberoptic phototherapy had a broad emission through the blue and green wavelengths (mainly in the green spectrum). Phototherapy was more effective in the conventional phototherapy group; the duration of exposure to phototherapy (h) was significantly shorter, and the overall bilirubin decline rate (as μmol/l/h and %/h) was significantly greater in the conventional phototherapy group. According to the nursing personnel, fiberoptic phototherapy was more comfortable than the conventional phototherapy frame because of the easier accessibility and handling of the infants during phototherapy. They complained of giddiness, nausea, glare, temporary blurring of vision and difficulty in detecting the skin colour changes of newborns with the blue light of the conventional phototherapy unit. Conventional phototherapy consisting of special blue fluorescent lamps with approximately twofold higher irradiance and an emission spectrum almost identical to the bilirubin absorption spectrum is preferable to fiberoptic phototherapy in the standard treatment of term newborns with non‐haemolytic hyperbilirubinaemia.

An Analysis of Neonatal Risk Factors Associated With the Development of Ophthalmologic Problems at Infancy and Early Childhood: A Study of Premature Infants Born at or Before 32 Weeks of Gestation

BACKGROUND To determine the frequency of ophthalmologic problems and the risk factors that affect the occurrence of these problems in premature newborns with a gestational age of 32 weeks or less. METHODS Premature newborns observed at a neonatal intensive care unit between January 2002 and March 2006 were included. A control visit including an ophthalmologic examination was performed at 10 months of age or later. Primary ocular morbidities were studied, and the association between these parameters and prenatal, perinatal, and neonatal characteristics were evaluated. RESULTS A total of 169 premature newborns were included in the study, and they were examined at a mean age of 25.85 ± 11.79 months (range: 10 to 42 months). There was complete vision loss (blindness) in 1 (0.6%) case, strabismus in 15 (8.9%) cases, and refractive errors in 10 (5.9%) cases. Twenty (77%) cases with any abnormality and 50 (35%) cases with a normal examination at follow-up had a history of retinopathy of prematurity (ROP) at any stage during the neonatal period (P = .001). Short gestational age (P = .018), low birth weight (P = .002), and the presence of ROP requiring retinal surgery during the neonatal period (P = .007) were determined to be significant risk factors for the development of vision loss, strabismus, and refractive errors. CONCLUSION Neonates with a gestational age of 32 weeks or less, especially those younger than 30 weeks, should not only be screened for ROP in the neonatal period, but should also have regular follow-up examinations to check for the development of other ophthalmologic problems during infancy and early childhood.

Protective Effects of Valproic Acid, a Histone Deacetylase Inhibitor, against Hyperoxic Lung Injury in a Neonatal Rat Model

Objective Histone acetylation and deacetylation may play a role in the pathogenesis of inflammatory lung diseases. We evaluated the preventive effect of valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, on neonatal hyperoxic lung injury. Methods Forty newborn rat pups were randomized in normoxia, normoxia+VPA, hyperoxia and hyperoxia+VPA groups. Pups in the normoxia and normoxia+VPA groups were kept in room air and received daily saline and VPA (30 mg/kg) injections, respectively, while those in hyperoxia and hyperoxia+VPA groups were exposed to 95% O2 and received daily saline and VPA (30 mg/kg) injections for 10 days, respectively. Growth, histopathological, biochemical and molecular biological indicators of lung injury, apoptosis, inflammation, fibrosis and histone acetylation were evaluated. Results VPA treatment during hyperoxia significantly improved weight gain, histopathologic grade, radial alveolar count and lamellar body membrane protein expression, while it decreased number of TUNEL(+) cells and active Caspase-3 expression. Expressions of TGFβ3 and phospho-SMAD2 proteins and levels of tissue proinflammatory cytokines as well as lipid peroxidation biomarkers were reduced, while anti-oxidative enzyme activities were enhanced by VPA treatment. VPA administration also reduced HDAC activity while increasing acetylated H3 and H4 protein expressions. Conclusions The present study shows for the first time that VPA treatment ameliorates lung damage in a neonatal rat model of hyperoxic lung injury. The preventive effect of VPA involves HDAC inhibition.