Investigation of the relationship between cord clamping time and risk of hyperbilirubinemia.

BACKGROUND: Although the relationship between umbilical cord clamping time and various parameters such as hemoglobin (Hb) levels, iron deficiency, and risk of neonatal jaundice has previously been studied, to the best of our knowleadge there have been no studies investigating the relationship between cord clamping time and the risk of significant hyperbilirubinemia. We aimed to investigate the relationship between the time of umbilical cord clamping and transcutaneous bilirubin (TcB) measurements made on various postnatal hours, Hb and serum total bilirubin (STB) levels measured on postnatal 4th day, and the risk of development of significant hyperbilirubinemia requiring phototherapy treatment. METHODS: Eligible newborns were divided into two groups on the basis of the time of cord clamping: those clamped late (60 seconds or more; Group I) and those clamped early (less than 60 seconds; Group II). Groups were compared with respect to the parameters of cord Hb, postnatal TcB measurements at 6th, 48th, 96th and 168th hours, and 96th hour Hb, STB and direct bilirubin levels. RESULTS: TcB levels at the 96th and 168th hour were significantly higher in Group I when compared to Group II (p < 0.001 and p < 0.001, respectively). The 96th hour STB level was significantly higher in Group I when compared to Group II (p < 0.001). The need of phototherapy requirement was higher in Group I when compared to Group II (p=0.001). Increase in cord blood Hb for each 1 gr/dl caused a 3.94-fold increased risk in the requirement of phototherapy treatment. Cord clamping time showed statistically significant positive correlations with both cord blood and 96th hour venous Hb levels, with both 96th hour and 168th hour TcB levels, and with 96th hour STB levels. CONCLUSIONS: Newborns whose cords are clamped late should be followed up closely with respect to high postnatal bilirubin levels and other risks associated with significant hyperbilirubinemia requiring phototherapy treatment.

Hyperbilirubinemia due to minor blood group (anti-E) incompatibility in a newborn: a case report.

In addition to Rh and ABO incompatibilities subgroup incompatibilities may rarely play a role among the causes of hemolytic anemia and indirect hyperbilirubinemia in newborns. The most common minor blood group antigens that cause blood incompatibility between the mother and baby are C, c, E, e, Kell, Duffy, Diego, Kidd and MNSs antigens. In this article, a newborn in whom hyperbilirubinemia due to anti-E minor blood group incompatibility developed and was treated with phototherapy succesfully is presented and minor blood group incompatibilities due to anti-E are reviewed.

Association Between Early Idiopathic Neonatal Jaundice and Urinary Tract Infections.

BACKGROUND AND PURPOSE: Etiologic role, incidence, demographic, and response-to-treatment characteristics of urinary tract infection (UTI) among neonates, its relationship with significant neonatal hyperbilirubinemia, and abnormalities of the urinary system were studied in a prospective investigation in early (⩽10 days) idiopathic neonatal jaundice in which all other etiologic factors of neonatal hyperbilirubinemia were ruled out. PATIENTS AND METHODS: Urine samples for microscopic and bacteriologic examination were obtained with bladder catheterization from 155 newborns with early neonatal jaundice. Newborns with a negative urine culture and with a positive urine culture were defined as group I and group II, respectively, and the 2 groups were compared with each other. RESULTS: The incidence of UTI in whole of the study group was 16.7%. Serum total and direct bilirubin levels were statistically significantly higher in group II when compared with group I (P = .005 and P = .001, respectively). Decrease in serum total bilirubin level at the 24th hour of phototherapy was statistically significantly higher in group I compared with group II (P = .022). CONCLUSIONS: Urinary tract infection should be investigated in the etiologic evaluation of newborns with significant hyperbilirubinemia. The possibility of UTI should be considered in jaundiced newborns who do not respond to phototherapy well or have a prolonged duration of phototherapy treatment.

NMR-Based Screening for Inborn Errors of Metabolism: Initial Results from a Study on Turkish Neonates.

Approximately 1 in 400 neonates in Turkey is affected by inherited metabolic diseases. This high prevalence is at least in part due to consanguineous marriages. Standard screening in Turkey now covers only three metabolic diseases (phenylketonuria, congenital hypothyroidism, and biotinidase deficiency). Once symptoms have developed, tandem-MS can be used, although this currently covers only up to 40 metabolites. NMR potentially offers a rapid and versatile alternative.We conducted a multi-center clinical study in 14 clinical centers in Turkey. Urine samples from 989 neonates were collected and investigated by using NMR spectroscopy in two different laboratories. The primary objective of the present study was to explore the range of variation of concentration and chemical shifts of specific metabolites without clinically relevant findings that can be detected in the urine of Turkish neonates. The secondary objective was the integration of the results from a healthy reference population of neonates into an NMR database, for routine and completely automatic screening of congenital metabolic diseases.Both targeted and untargeted analyses were performed on the data. Targeted analysis was aimed at 65 metabolites. Limits of detection and quantitation were determined by generating urine spectra, in which known concentrations of the analytes were added electronically as well as by real spiking. Untargeted analysis involved analysis of the whole spectrum for abnormal features, using statistical procedures, including principal component analysis. Outliers were eliminated by model building. Untargeted analysis was used to detect known and unknown compounds and jaundice, proteinuria, and acidemia. The results will be used to establish a database to detect pathological concentration ranges and for routine screening.

Relationship between neonatal adrenomedullin and bilirubin levels.

INTRODUCTION: Oxidative stress and inflammation are the basic molecular mechanisms in bilirubin neurotoxicity. We aimed to investigate the relationship between serum bilirubin and an antioxidant, anti-inflammatory and neuroprotective peptid, adrenomedullin (AM) levels. METHODS: The correlation between serum bilirubin and AM levels was investigated in a total of 87 newborns. Newborns were further divided into two groups according to the serum bilirubin levels. Group I (with significant hyperbilirubinemia) and Group II (without significant hyperbilirubinemia) were compared with respect to demographic, anthropometric and biochemical parameters including serum AM levels. RESULTS: In the correlation analysis, a significant positive correlation was detected between serum indirect bilirubin and AM levels in 87 newborns (p < 0.001, r = 0.945). In demographic, anthropometric and biochemical comparison of the two study groups, serum indirect bilirubin levels were 21.53 ± 3.59 and 9.37 ± 4.87 mg/dl in Groups I and II, respectively (p < 0.001), and serum AM levels were 1.45 ± 0.06 and 1.28 ± 0.07 ng/ml in Groups I and II, respectively (p < 0.001) CONCLUSION: AM probably plays a significant role in adverse effects and neuronal injury steps of significant hyperbilirubinemia. In parallel with the results of this study the role, effects and physiopathological basis of AM in neonatal hyperbilirubinemia should be established especially with further animal studies. Results of this study may be used in establishing reference values for AM as there are very limited number of studies in newborns.

Investigation into the relationship between cord blood adiponectin levels and aortic intima media thickness in healthy, term neonates.

INTRODUCTION: Adiponectin has important anti-inflammatory and anti-atherogenic effects. Although adiponectin and atherosclerosis correlate inversely in children and adults, we have little information regarding this relationship in neonates. METHODS: We measured cord blood adiponectin levels and abdominal aortic intima media thickness (aIMT) in 80 healthy, term neonates and investigated the relationship between adiponectin and total cholesterol (TC), LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C), and triglyceride, and their relationships to infant anthropometry and gender. RESULTS: Mean birth weight, length, head circumference and aIMT values for male neonates were statistically significantly higher than those for female neonates. Adiponectin levels were not significantly different with respect to gender. In correlation analysis, the mean adiponectin level correlated positively with TC, HDL-C and LDL-C levels and birth weight, length and head circumference. There was no significant correlation between aIMT and any other parameters. CONCLUSION: The cord blood adiponectin and aIMT values reported here for the first time, represent reference values in the early neonatal period. The positive correlations between adiponectin levels and birth weight, length and head circumference, and TC, HDL-C and LDL-C indicate that further studies are required to demonstrate the exact relationship and clinical importance of adiponectin metabolism during the neonatal period.

Risk factor analysis for long-term unfavorable ocular outcomes in children treated for retinopathy of prematurity.

The aim in this study was to report long-term ocular outcomes of neonates treated for retinopathy of prematurity (ROP) and potential risk factors for unfavorable ocular outcomes. The study consisted of neonates treated for ROP between March 1999 and November 2009. Data relating baseline characteristics and late structural, functional and refractive ocular outcomes were recorded. The association between the unfavorable ocular outcomes and ROP-related risk factors was evaluated by regression analysis. Forty-eight children were included for assessment. Average chronological age at the time of followup was 3.11±0.73 years. The rates of unfavorable structural and functional outcomes were 12% and 15.3%, respectively. Ocular deviation was common (27.1%), and mostly esotropic (12/13). A clear myopic tendency was observed (51.2%), and the mean spherical equivalent per eye was -0.72±2.9 diopters. Regression analyses for unfavorable ocular outcomes revealed intraventricular hemorrhage as a core independent risk factor. In conclusion, ROP treatment has shown promising results in both structure and function. Because of the high risk of developing an unfavorable outcome, a more intense follow-up is required in neonates with a history of intraventricular hemorrhage in the neonatal period. Further studies from other centers are needed to develop a national database, which may validate this observation.

Cytidine 5'-diphosphocholine ameliorates hyperoxic lung injury in a neonatal rat model.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is an important cause of morbidity. The aim of this study was to evaluate the preventive effect of cytidine 5'-diphosphocholine (CDP-choline) treatment on hyperoxic lung injury in a neonatal rat model. METHODS: A total of 30 newborn pups were divided into control, hyperoxia, and hyperoxia + CDP-choline groups. After birth, pups in the control group were kept in room air and received saline injections, whereas those in hyperoxia and hyperoxia + CDP-choline groups were exposed to 95% O2 and received daily injections of saline and CDP-choline throughout postnatal day 10, respectively. Histopathological scoring, radial alveolar count, lamellar body membrane protein expression, fibrosis, proinflammatory cytokine levels, lung tissue and bronchoalveolar lavage (BAL) fluid phospholipid content, and apoptosis were evaluated. RESULTS: Hyperoxia-induced severe lung damage was reduced significantly by CDP-choline treatment. Radial alveolar count and lamellar body membrane protein expression were significantly recovered, and the number of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling-positive cells, active caspase-3 expression, and tissue proinflammatory cytokine levels were decreased by CDP-choline administration. Lung tissue and BAL phospholipid contents showed significant increases after CDP-choline administration. CONCLUSION: These data show that CDP-choline ameliorates hyperoxic lung injury in a neonatal rat model. It may therefore be suggested that CDP-choline may be a novel therapeutic option for the prevention of BPD.

Evaluation of melatonin and prostaglandin E1 combination on necrotizing enterocolitis model in neonatal rats.

BACKGROUND: Necrotizing enterocolitis (NEC) is one of the most common gastrointestinal emergencies in newborn infants but up to now there is no completely effective treatment for it. OBJECTIVE: In order to show that a combination of melatonin and prostaglandins may be useful to save lives, we use newborn rat as a model of necrotizing enterocolitis to test the hypothesis of using the combination therapy might have more potential effect on mucosal cytoprotection and healing. PATIENTS AND METHODS: A total of 60 newborn pups from 5 time-mated Sprague-Dawley pregnant rats were divided equally into 5 groups as follows: NEC (subjected to NEC), NEC+Melatonin, NEC+Prostaglandin, NEC+Prostaglandin+Melatonin and control. These animals were fed with hyperosmolar formula 3 times daily and subjected to 100% CO2 inhalation for 10 min, +4°C cold exposure for 5 min, and 97% O2 for 5 min twice daily to induce NEC. This procedure was applied to the pups for 3 days. RESULTS: The macroscopic scoring, intestinal injury scoring and apoptosis index scoring were all found to be significantly lower in NEC+Prostaglandin+Melatonin group compared with NEC group. Anti-oxidant enzyme activities were significantly higher, whereas lipid peroxidation was significantly lower in NEC+Prostaglandin+Melatonin group compared with NEC group. CONCLUSION: This combination therapy showed cytoprotective and healing effects on mucosa in the intestinal tissue of rat pups in necrotizing enterocolitis model. Therefore, this therapy might also show benefit in preterm infants with NEC. After confirmation of this data by other clinical and experimental studies, it may be a novel therapeutic option for the prevention of NEC in preterm infants.

Efectos protectores del aceite de Nigella sativa en la lesión pulmonar inducida por hiperoxia / Protective Effects of Nigella sativa Oil in Hyperoxia-Induced Lung Injury

Antecedentes: Se cree que la lesión pulmonar inducida por el oxígeno conduce al desarrollo de una displasia broncopulmonar en los recién nacidos prematuros. Hemos evaluado los efectos favorables del aceite de Nigella sativa (NSO) en ratas con lesión pulmonar inducida por hiperoxia. Métodos: Se utilizaron 30 ratas Sprague-Dawley recién nacidas a las que se dividió aleatoriamente en 3 grupos para aplicarles hiperoxia (O2 al 95%), hiperoxia+NSO o el grupo de control (O2 al 21%). A las crías del grupo de hiperoxia+NSO se les administró NSO a una dosis de 4ml/kg al día por vía intraperitoneal durante el periodo de estudio. Se realizó una evaluación histopatológica, inmunoquímica y bioquímica (superóxido dismutasa [SOD], glutatión peroxidasa [GSH-Px], malonilaldehído [MDA] y mieloperoxidasa [MPO]). Resultados: En la evaluación histopatológica e inmunoquímica, la gravedad de la lesión pulmonar fue significativamente inferior en el grupo de hiperoxia+NOS (p<0,05). Los niveles tisulares de GSH-Px y SOD se mantuvieron significativamente preservados, y los niveles de MDA y MPO fueron significativamente inferiores en el grupo de hiperoxia+NSO (p<0,05). Conclusión: El NSO redujo significativamente la gravedad de la lesión pulmonar debida a la hiperoxia(AU)

Background: Oxygen-induced lung injury is believed to lead to the development of bronchopulmonary dysplasia in premature infants. We have evaluated the beneficial effects of Nigella sativa oil (NSO) on rats with hyperoxia-induced lung injury. Methods: Thirty newborn Sprague-Dawley rats were randomly divided into 3 groups as hyperoxia (95% O2), hyperoxia+NSO and control (21% O2). Pups in the hyperoxia+NSO group were administered intraperitoneal NSO at a dose of 4ml/kg daily during the study period. Histopathologic, immunochemical, and biochemical evaluations (superoxide dismutase [SOD], glutathione peroxidase [GSH-Px], malonaldehyde [MDA] and myeloperoxidase [MPO]) were performed. Results: In the histopathologic and immunochemical evaluation, severity of lung damage was significantly lower in the hyperoxia+NOS group (P<0.05). Tissue GSH-Px and SOD levels were significantly preserved, and MDA, MPO levels were significantly lower in the hyperoxia+NSO group (P<0.05). Conclusion: NSO significantly reduced the severity of lung damage due to hyperoxia(AU)

Protective Effects of Nigella sativa Oil in Hyperoxia-Induced Lung Injury.

BACKGROUND: Oxygen-induced lung injury is believed to lead to the development of bronchopulmonary dysplasia in premature infants. We have evaluated the beneficial effects of Nigella sativa oil (NSO) on rats with hyperoxia-induced lung injury. METHODS: Thirty newborn Sprague-Dawley rats were randomly divided into 3 groups as hyperoxia (95% O(2)), hyperoxia+NSO and control (21% O(2)). Pups in the hyperoxia+NSO group were administered intraperitoneal NSO at a dose of 4ml/kg daily during the study period. Histopathologic, immunochemical, and biochemical evaluations (superoxide dismutase [SOD], glutathione peroxidase [GSH-Px], malonaldehyde [MDA] and myeloperoxidase [MPO]) were performed. RESULTS: In the histopathologic and immunochemical evaluation, severity of lung damage was significantly lower in the hyperoxia+NOS group (P<.05). Tissue GSH-Px and SOD levels were significantly preserved, and MDA, MPO levels were significantly lower in the hyperoxia+NSO group (P<.05). CONCLUSION: NSO significantly reduced the severity of lung damage due to hyperoxia.

CDP-choline reduces severity of intestinal injury in a neonatal rat model of necrotizing enterocolitis.

BACKGROUND: Cytidine 5'-diphosphocholine (CDP-choline) is an endogenous intermediate in the biosynthesis of phosphatidylcholine, a contributor to the mucosal defense of the intestine. The aim of this study was to evaluate the possible cytoprotective effect of CDP-choline treatment on intestinal cell damage, membrane phospholipid content, inflammation, and apoptosis in a neonatal rat model of necrotizing enterocolitis (NEC). METHODS: We divided a total of 30 newborn pups into three groups: control, NEC, and NEC + CDP-choline. We induced NEC by enteral formula feeding, exposure to hypoxia-hyperoxia, and cold stress. We administered CDP-choline intraperitoneally at 300 mg/kg/d for 3 d starting from the first day of life. We evaluated apoptosis macroscopically and histopathologically in combination with proinflammatory cytokines in the gut samples. Moreover, we determined membrane phospholipid levels as well as activities of xanthine oxidase, superoxide dismutase, glutathione peroxidase, and myeloperoxidase enzymes and the malondialdehyde content of intestinal tissue. RESULTS: Mean clinical sickness score, macroscopic gut assessment score, and intestinal injury score were significantly improved, whereas mean apoptosis score and caspase-3 levels were significantly reduced in pups in the NEC + CDP-choline group compared with the NEC group. Tissue proinflammatory cytokine (interleukin-1ß, interleukin-6, and tumor necrosis factor-α) levels as well as tissue malondialdehyde content and myeloperoxidase activities were reduced, whereas glutathione peroxidase and superoxide dismutase activities were preserved in the NEC + CDP-choline group. In addition, NEC damage reduced intestinal tissue membrane phospholipids, whereas CDP-choline significantly enhanced total phospholipid and phosphatidylcholine levels. Long-term follow-up in additional experiments revealed increased body weight, decreased clinical sickness scores, and enhanced survival in CDP-choline-receiving versus saline-receiving pups with NEC lesions. CONCLUSIONS: Our study reports, for the first time, beneficial effects of CDP-choline treatment on intestinal injury in a neonatal rat model of NEC. Our data suggest that CDP-choline may be used as an effective therapeutic agent to prevent NEC.

Effects of maternal smoking on fetal organs.

BACKGROUND: Unfavorable effects of in-utero smoke exposure have been shown in several studies. OBJECTIVES: In this experimental study, the authors aimed at showing detrimental effects of cigarette smoke on fetal tissues by assessing apoptosis that is detected by performing TUNEL staining. MATERIAL AND METHODS: Designed groups were smoke exposed rats before and during pregnancy and control groups. Rat offsprings were sacrificed when they were 12 days old. RESULTS: Lung, kidney, adrenal and gonad tissues were harvested for histopathologic analysis and assessed by TUNEL (Terminal dUTP Nick End Labeling) staining. CONCLUSIONS: Smoke exposure caused increased apoptotic activity in lung parenchyma of study groups.

Increased fecal calprotectin in preterm infants with necrotizing enterocolitis.

BACKGROUND: Necrotizing entrocolitis (NEC) remains a potentially fatal disease in premature infants despite the recent advances in neonatal care. It is a disease with a multifactorial etiology leading to the one common final pathway of necrosis and inflammmation of the neonatal intestine. METHODS: Calprotectin is a calcium and zinc-binding protein in human neutrophils. Its concentration rises in various organic bowel diseases in adults and is resistant to degradation and has been proposed as a useful, simple, and rapid diagnostic method of inflammatory bowel disease that shows gastrointestinal inflammation in children and adults. RESULTS: We found that infants with necrotizing enterocolitis had increased fecal calprotectin concentrations, and there was a correlation between calprotectin concentrations and severity of NEC. CONCLUSIONS: We concluded that fecal calprotectin is a useful marker for diagnosis and severity of NEC in preterm infants.

Beneficial effects of Nigella sativa oil on intestinal damage in necrotizing enterocolitis.

AIM: The aim of this study was to determine the beneficial effects of Nigella sativa oil (NSO) on rats with necrotizing enterocolitis (NEC). MATERIAL AND METHODS: Thirty newborn Sprague-Dawley rats were randomly divided into three groups as NEC, NEC + NSO, and control. NEC was induced by enteral formula feeding, exposure to hypoxia-hyperoxia and cold stress. Pups in the NEC + NSO group were administered NOS at a dose of 2 ml/kg daily by intraperitoneal route from the first day until the end of the study. Proximal colon and ileum were excised for histopathologic, apoptosis (TUNEL) and biochemical evaluation, including xanthine oxidase (XO), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malonaldehyde (MDA), and myeloperoxdase (MPO) activities. RESULTS: Pups in the NEC + NOS group had better clinical sickness scores and weight gain compared to the NEC group (p < 0.05). In the macroscopic assessment, histopathologic and apoptosis evaluation (TUNEL), severity of bowel damage was significantly lower in the NEC + NOS group compared to the NEC group (p < 0.05). Tissue GSH-Px and SOD levels were significantly preserved in the NEC + NSO group (p < 0.05), whereas, tissue MDA, MPO levels of the NEC + NSO group were significantly lower than those in the NEC group (p < 0.05). CONCLUSION: NSO significantly reduced the severity of intestinal damage in NEC.

Combination of Laser Photocoagulation and Intravitreal Bevacizumab in Aggressive Posterior Retinopathy of Prematurity.

The response to combined laser photocoagulation and a single intravitreal injection of 0.75 mg bevacizumab to each eye on separate days in two patients with aggressive, posterior retinopathy of prematurity (ROP) is described. Combined treatment resulted in regression of zone-1 disease in Case 1, which had no retinal detachment. However, no significant regression or unfavorable anatomic response was observed in the second case with retinal detachment. Although the combination of laser photocoagulation and intravitreal bevacizumab injection seems to be well tolerated, inducing prompt regression of agressive zone-1 ROP without retinal detachment, further controlled studies with long-term follow-up are necessary for their use in the treatment of ROP with for potentially dangerous growth factor inhibitors in premature babies.

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.

Congenital cytomegalovirus infection associated with severe lung involvement in a preterm neonate: a causal relationship?

We report a preterm neonate with congenital cytomegalovirus (CMV) infection associated with severe lung involvement progressing to early chronic lung disease (CLD) and death. The present case represents the earliest and the most severe lung involvement depending on recurrent maternal CMV infection reported in the literature. Neonatal mortality and progression to early CLD should be considered in the list of possible neonatal sequelae resulting from recurrent maternal CMV infection.