Neonatal Outcomes of Pregnancy with Immune Thrombocytopenia.

Neonates born to mothers with immune thrombocytopenia (ITP) have an increased risk for neonatal thrombocytopenia and hemorrhagic complications. The aim of this study was to determine the maternal and neonatal outcomes of pregnancies with ITP and also to identify risk factors that predicts neonatal thrombocytopenia. We performed a retrospective analysis of 40 pregnancies with ITP and their 40 neonates. Among the 40 neonates, thrombocytopenia (platelet count of less than 150 × 109/L) was detected in 15 neonates (37.5 %) whom 8 of them had severe thrombocytopenia (platelet count of less than 50 × 109/L). Ten of the 15 neonates with thrombocytopenia required treatment to increase the platelet counts. There was statistically significant association between neonatal thrombocytopenia and maternal splenectomy history and maternal duration of thrombocytopenia. There was no statistically significant correlation between maternal platelet count and neonatal platelet count. Clinicians should pay special attention in these neonates because of risk for development of neonatal thrombocytopenia. Maternal and neonatal outcomes in patients with idiopathic thrombocytopenic purpura is generally good.

Association of Rho-kinase Gene Polymorphisms with Respiratory Distress Syndrome in Preterm Neonates.

BACKGROUND: Respiratory distress syndrome (RDS) of the newborn is one of the most common causes of morbidity and mortality in preterm infants. Our objective was to determine the association between Rho-kinase (ROCK1 and ROCK2) gene polymorphisms and RDS in preterm neonates. METHODS: A total of 193 preterm infants with RDS and 186 preterm infants without respiratory problems were included in this study. Polymorphisms were analyzed in genomic DNA using a BioMark 96.96 dynamic array system. RESULTS: We observed that ROCK1 gene rs2271255 (Lys222Glu) and rs35996865 polymorphisms, and ROCK2 gene rs726843, rs2290156, rs10178332, and rs35768389 (Asp601Val) polymorphisms were associated with RDS. However, no associations were found with rs73963110, rs1515219, rs965665, rs2230774 (Thr431Asn), rs6755196, and rs10929732 polymorphisms. Additionally, 12 haplotypes (6 in ROCK1 and 6 in ROCK2) were found to be markedly associated with RDS. CONCLUSION: This is the first study to examine the involvement of ROCK gene variation in the risk of incident RDS. The results strongly suggest that ROCK gene polymorphisms may modify individual susceptibility to RDS in the Turkish population.

Evaluation of Score for Neonatal Acute Physiology and Perinatal Extension II and Clinical Risk Index for Babies with additional parameters.

BACKGROUND: The aim of this study was to determine mortality risk by calculating Score for Neonatal Acute Physiology and Perinatal Extension II (SNAP-PE-II) and Clinical Risk Index for Babies (CRIB) score, and evaluate prediction of the effects of antenatal corticosteroid and surfactant treatment on mortality. METHODS: This multicenter study was conducted simultaneously in five different centers in four different provinces in Southern Turkey between July 2012 and July 2013. A total of 1668 inborn subjects hospitalized in the neonatal intensive care unit within the first 12 h of delivery, and meeting the selection criteria, were included in the study, and CRIB and SNAP-PE-II were used to determine mortality. RESULTS: The SNAP-PE-II scoring system was applied to all patients, and the CRIB scoring system was used for 310 newborns with gestational age <32 weeks and weighing <1500 g. Of the 1668 patients, 188 died (mortality rate, 11.3%). Cut-off was found to vary with center, which changed specificity and sensitivity of the mortality scores. SNAP-PE-II significantly predicted mortality (P < 0.05) compared with CRIB. SNAP-PE-II also successfully predicted mortality in the group receiving antenatal corticosteroid compared with the group not receiving antenatal corticosteroid. CONCLUSION: SNAP-PE-II was a significant predictor of mortality in newborns with birthweight <1500 g compared with CRIB, and assessment of antenatal corticosteroid use in conjunction with SNAP-PE-II increased the accuracy of the prediction of mortality.

Transcatheter closure of patent ductus arteriosus in under 6 kg and premature infants.

BACKGROUND: Transcatheter closure of a patent ductus arteriosus (PDA) has always been considered risky for infants weighing <6 kg and preterms. We present our findings regarding transcatheter closures of PDA. METHODS: The inclusion criteria were a weight of <6 kg and the presence of PDA symptoms. The study subjects were divided into two groups: <6 kg and premature infants. RESULTS: A total of 69 infants were included. The mean ages and weights of the <6 kg and the preterms were 5.4 ± 2.7 months and 30.3 ± 19.9 days, and 4.6 ± 0.8 and 1.7 ± 0.3 kg, respectively. Type C PDAs were most frequently observed in the premature group, and type A was in <6 kg. Sixteen of the patients were premature infants, and 81.2% of them had an extremely low birth weight. All of the premature infants had comorbidities, and had been receiving respiratory support therapy. Transcatheter closure was successfully completed in 81.2% of the premature infants and 94.3% of the <6-kg infants. Major complications occurred in 4 patients (one death and three device embolizations). The patient's age was found to be the main risk factor. The most frequently used device was the Amplatzer duct occluder II in additional sizes (84.6%) in the preterms and the Amplatzer duct occluder I (34%) and II (34%) in the <6-kg group. CONCLUSION: The transcatheter closure of PDA is relatively safe and effective in preterms and in infants <6 kg. The selection of a suitable device based on the type of PDA is critical to the success of the procedure.

Endothelial NOS gene Glu298Asp polymorphism in preterm neonates with respiratory distress syndrome.

RATIONALE: Respiratory Distress Syndrome (RDS) due to prematurity is one of the most important causes of morbidity and mortality in Neonatal Intensive Care Units. According to few studies in recent years, endothelial nitric oxide synthase (eNOS) gene polymorphisms are found to be partially responsible for liability to RDS. The purpose of this study was to determine the association between eNOS gene polymorphism and RDS in preterm neonates. PATIENTS AND METHODS: The patient group consisted of 152 premature neonates born before 37 weeks of gestation and diagnosed as RDS. The control group consisted of 125 premature neonates born before 37 weeks of gestation, but was not diagnosed as RDS. Genomic DNA from patients and controls was analyzed by polymerase chain reaction. RESULTS: It was found that Glu/Glu, Glu/Asp, and Asp/Asp genotype frequencies of the eNOS gene polymorphism were 35.2%, 59.2%, and 5.6% of the control group, and 32.9%, 65.1%, and 2.0% of the patient group, respectively (P > 0.05). However, significant increases in Glu/Glu genotype and Glu allele frequencies were noted in the RDS groups when the preterm neonates were divided into two groups (24-30 weeks and 31-36 weeks) by gestational age. Additionally, Glu/Asp genotype and Asp allele were markedly less frequent among the RDS groups (P < 0.05). Asp allele frequency in boys and Glu allele frequency in girls were significantly high in RDS group (P < 0.05). CONCLUSIONS: These data suggest that there were significant gestational age-related differences between RDS and control groups in terms of Glu298Asp polymorphism. Therefore, RDS seems to develop with alterations in eNOS Glu298Asp genotype frequencies in the Turkish population.

Comparison of the efficacy of different-sized Amplatzer duct occluders (I, II, and II AS) in children weighing less than 10 kg.

The transcatheter closure of patent ductus arteriosus (PDA) may cause more complications in small children. Amplatzer (St. Jude Medical, Plymouth, MN) has produces three types of devices for ductal occlusion: the Amplatzer duct occluder I (ADO I) and II (ADO II) and the recently introduced ADO II additional sizes (ADO II AS). We performed this study to determine the efficacy and complication rates in children who weigh <10 kg for the three types of devices used in our clinic. Between February 2007 and March 2012, 77 patients weighing <10 kg had their PDAs occluded with ADOs. The mean age of the patients was 0.76 ± 0.44 years (range 17 days-2 years), and their mean weight was 6.73 ± 2.05 (range 1.2-9.9) kg. In total, 54 girls (70.1 %) and 23 boys (29.9 %) with a mean pulmonary ductus diameter of 2.55 ± 1.0 (1.08-5.94) mm were included in the study. The ADO I was used in 26 patients (33.8 %); the ADO II was used in 43 patients (55.8 %); and the ADO II AS was used in 8 patients (10.4 %). The mean ages of patients with the ADO I, ADO II, and ADO II AS were 1.07 ± 0.48, 0.66 ± 0.31, and 0.28 ± 0.17 years (p < 0.05), respectively. Their mean weights were 7.86 ± 1.45, 6.50 ± 1.85, and 4.36 ± 2.49 kg (p < 0.05), respectively. Their mean narrowest ductal diameters were 3.11 ± 0.96, 2.25 ± 1.06, and 2.33 ± 1.01 mm (p < 0.05), respectively. The use of the ADO II and ADO II AS was found to be more common in type C defects. One patient with the ADO I and 5 patients with the ADO II (7.8 %) developed varying degrees of left pulmonary artery stenosis or iatrogenic aortic coarctation. In 1 patient, the ADO II AS was replaced with the ADO II due to a significant residual shunt observed during the procedure. Each of the ADOs has its own advantages and disadvantages. Although the ADO I is convenient for medium- and large-sized defects, the ADO II and ADO II AS can be used both anterogradely and retrogradely. The ADO II AS is safe and efficient to use in small infants.

Epidural hematoma and cephalohematoma with congenital hypofibrinogenemia.

Cerebral hematoma described as the bleeding into the cerebrum leads to an expanding mass of blood that damages surrounding neural tissues. It is a very rare clinical finding of congenital hypofibrinogenemia. In this case study we are reporting a 5-year old boy with massive epidural hematoma and recurrent cephalohematoma as a result of minor trauma.

An infant with prolonged circumcision bleeding and unexplained coagulopathy.

Tyrosinemia type I is a rare autosomal recessive disorder. Fulminant onset of liver failure can occur in the first few months of life. Because all of the clotting factors are produced exclusively in the liver except factor VIII, coagulation abnormalities are very common in patients with severe liver disease. Rarely a significant coagulopathy in the absence of overt signs of liver disease may be seen in hereditary tyrosinemia. We present a 4 weeks-old tyrosinemic infant who presented with severe bleeding after circumcision and no other signs of liver failure. The diagnosis of tyrosinemia should be kept in mind in differential diagnosis of bleeding disorders especially a severe coagulopathy unresponsive to vitamin K, and fresh frozen plasma, even when other signs of liver failure are absent.

Protective effects of Y-27632 on hypoxia/reoxygenation-induced intestinal injury in newborn rats.

BACKGROUND/PURPOSE: Necrotizing enterocolitis (NEC) is a major cause of mortality in neonates and is associated with a disruption in the protective intestinal barrier. The precise cause of NEC is elusive. However, ischemia/reperfusion injury of the intestine has been considered a major contributing factor. We examined the role of Y-27632, a selective Rho-kinase inhibitor, on a hypoxia/reoxygenation (H/R)-induced intestinal injury of newborn rat pups. METHODS: Hypoxia/reoxygenation was achieved by placing rat pups in an airtight chamber aerated with 95% N(2) + 5% CO(2) for 10 minutes followed by 10-minute 100% oxygen. Forty newborn rat pups were randomly allocated into 4 groups. Group 1 served as untreated controls. The pups in group 2 were subjected to H/R only. In groups 3 and 4, the rats were treated with intraperitoneal injection of 0.3 and 3 mg kg(-1) day(-1) of Y-27632 for 5 days following H/R, respectively. The pups were killed 6 days following the H/R injury. Intestine specimens were evaluated for histopathology and biochemical investigation. RESULTS: The microscopic lesions in H/R rat pups were virtually the same as those seen in neonatal NEC, with severe destruction of villi and crypts. Hypoxia/reoxygenation resulted in significant elevation in malondialdehyde levels, but decreased tissue nitric oxide levels (P < .05). Protective effects of Y-27632 on H/R-induced intestinal injury of newborn rat pups were observed with a significant decrease in the intestinal injury score, suppression in malondialdehyde levels, and increase in nitric oxide levels (P < .05). CONCLUSIONS: In this experimental study, Y-27632 significantly attenuated H/R-induced intestinal injury. These findings indicate that inhibition of Rho-kinase may offer a novel therapeutic approach in the treatment of NEC.

ACE gene polymorphism in premature neonates with respiratory distress syndrome.

The purpose of this study was to investigate the relationship between angiotensin-converting enzyme gene insertion/deletion (I/D) polymorphism and respiratory distress syndrome (RDS) in premature neonates. The patient group consisted of 101 premature neonates born before 37 weeks of gestation and diagnosed as RDS. The control group consisted of 100 premature neonates born before 37 weeks of gestation, but was not diagnosed as RDS. Genomic DNA from patients and controls was analyzed by polymerase chain reaction. D/D genotype was significantly higher in patient group (60.4% patients vs. 37.0% controls, p<0.05), whereas in the controls I/D genotype was markedly higher (33.7% patients vs. 61.0% controls, p<0.05). However, no marked change was observed with I/I genotype (5.9% patients vs. 2.0% controls). A significant increase of D alleles was observed in patients, whereas I allele was higher in controls (p<0.05). These results demonstrated the existence of higher frequency of the D/D genotype and D allele in premature neonates with RDS. These data may suggest that carriers of the D/D genotype and D allele are at increased risk of RDS development in premature neonates.

mRNA expressions of inducible nitric oxide synthase, endothelial nitric oxide synthase, and neuronal nitric oxide synthase genes in meningitis patients.

Meningitis is an inflammation of the protective membranes covering the brain and spinal cord caused by bacteria, fungi, or viruses with various clinical symptoms. Although meningitis is not so prevalent, it remains the most serious contagious disease. The aim of our study was to investigate the effect of gene expressions of nitric oxide synthases (NOS) on meningitis patients. Using samples taken from 61 meningitis patients, inducible NOS, endothelial NOS (eNOS), and neuronal NOS mRNA levels were assessed in both blood and cerebrospinal fluid (CSF). A control group was constructed of 64 healthy persons. The gene expression analysis was made using real-time polymerase chain reaction method. There was no neuronal NOS expression in either group, whereas inducible NOS expression was detected in 40 blood samples and 12 CSF samples from meningitis patients. However, there were no marked differences between groups (p=0.5104). eNOS expression was detected in all blood and CSF samples, which was markedly higher in patients (p=0.0367). Because the increase in eNOS expression increases NO production, eNOS expression in meningitis patients is of great importance. This increase of eNOS in meningitis patients compared with healthy subjects may lead to novel treatments for reducing the severity of the disease.

Gene expression and promoter region polymorphisms of interleukin-10 in meningitis patients.

Meningitis is an inflammatory disease caused by bacteria, fungi, and viruses with various clinical symptoms. Interleukin-10 (IL-10) levels have been shown to be increased in blood or cerebrospinal fluid of patients with meningitis, but the association of IL-10 gene promoter polymorphisms or gene expression with meningitis has not been evaluated. IL-10 gene promoter polymorphisms A-592C, T-819C, and A-1082G in 61 patients with meningitis and 64 healthy controls were determined by real-time polymerase chain reaction analysis. mRNA from blood and cerebrospinal fluid samples was extracted, and real-time polymerase chain reaction was performed for IL-10 gene expression. No statistically significant differences were found in the allele and genotypic frequencies between patients and control subjects. Expression of IL-10 in meningitis at mRNA levels was detected in the infiltrating leukocytes. IL-10 gene expression in blood from patients was significantly higher than the control group. Our results suggest that there was no association between promoter polymorphisms of IL-10 and meningitis, but a significant increase of IL-10 gene expression was present in patients with meningitis.

Association between the Glu298Asp and T(-786)C polymorphisms of the endothelial nitric oxide synthase gene and respiratory distress in preterm neonates.

Genetic polymorphisms in the gene that codes for endothelial nitric oxide synthase (eNOS) have been associated with less nitric oxide availability and with various cardiovascular diseases in humans. The objective of this study was to analyze the genotype distributions and allele frequencies for the Glu298Asp (G894T) and T(-786)C polymorphisms of the eNOS gene among neonates with respiratory distress in comparison to healthy control subjects. Fifty premature neonates with respiratory distress and 55 neonates without any respiratory problem were included in the study. Genomic DNA from all the neonates was analyzed by polymerase chain reaction. A polymerase chain reaction-restriction fragment length polymorphism analysis of eNOS gene polymorphisms was performed, and the results were compared. There were no significant differences between the groups regarding either genotype distributions or the allele frequencies for the Glu298Asp and T(-786)C polymorphisms. These results suggest that eNOS Glu298Asp and T(-786)C polymorphisms are not associated with development of respiratory distress.

Hydrops fetalis associated with chorioangioma and thrombosis of umbilical vein.

Placental chorioangioma and thrombosis of an umbilical vein varix are rare etiologic factors of non-immune hydrops fetalis. Herein, we report a patient who had hydrops fetalis associated with placental chorioangioma and thrombosis of an umbilical vein varix. This is the first report of coexistence of non-immune hydrops fetalis with placental chorioangioma and thrombosis of an umbilical vein varix.

ACE gene deletion/deletion polymorphism may be a protective factor for respiratory distress in preterm infants.

The objective in this study was to evaluate the angiotensin converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism in premature infants with and without respiratory distress within the first 24 hours of life. Totally, 87 premature babies who were followed up in the neonatal unit were included in the study. Of these babies, 41 had respiratory distress, and constituted the patient group. The remaining 46 babies who did not have respiratory distress constituted the control group. Blood samples were obtained from the babies within the first few days of life prior to administration of any blood product. The ACE gene insertion (I) and deletion (D) polymorphism was investigated using polymerase chain reaction method. The I/I polymorphism was frequent in the patient group and the D/D polymorphism was frequent in the control group (p < 0.05). There was no relationship between the ACE gene polymorphism and hospital stay, ventilation or oxygen consumption duration of the patients. In addition, taking into consideration the gestational age, no association was found between ACE gene polymorphism and birth weights of the babies. The I/I genotype was considered a risk factor for pulmonary disorders in neonates as the I/I variant was more frequent in the neonates with respiratory distress than in healthy newborns. The ACE I/I genotype is associated with an increased risk of respiratory disorders among premature infants and the D/D genotype is a protective factor for respiratory disorders, but these infants with ACE D/D genotype might be at risk for the development of cardiovascular disorders later in life.

The effects of anticancer drugs on levels of nitric oxide and adrenomedullin.

Nephrotoxicity is one of the most important complications of anticancer treatment. Ifosfamide, platinum and methotrexate (MTX) affect renal tubular epithelial cells. Nitric oxide (NO) serves many functions within the kidney. Adrenomedullin (AM) is a potent vasodilator peptide, and may function as a circulating hormone and an autocrine/paracrine mediator involved in the regulation of the cardiovascular system, blood pressure, and renal function. It also has a renoprotective effect and inhibits the generation of reactive oxygen metabolites. To our knowledge, no studies have investigated the effects of anticancer drugs on levels of AM and NO. We investigated the effects of these drugs on the levels of AM and total nitrite, a stable product of NO, and their relations to renal functions. The study was performed in 18 patients (13 males, 5 females) who received chemotherapeutic regimens including high-dose MTX or ifosfamide and platinum. Total nitrite was quantitated by means of the Griess reaction, while AM level was measured by high performance liquid chromatography (HPLC). Plasma total nitrite level (micromol/L) was decreased after chemotherapy (78.73 +/- 47.28 vs. 46.69 +/- 13.89, p: 0.002). A statistically significant difference was found between fractional excretion (FE) of total nitric oxide (FE(NO)) before and after chemotherapy (25.89 +/- 23.11 vs. 51.74 +/- 40.01, p: 0.008). The differences in plasma AM levels (pmol/ml) before (25.07 +/- 4.98) and after (30.20 +/- 1.39) chemotherapy were also statistically significant (p: 0.005). FE(AM) after chemotherapy (1.41 +/- 1.01) was found to be higher than before chemotherapy (0.64 +/- 0.43) (p: 0.000). Our results indicate that some chemotherapeutic agents (high-dose MTX, ifosfamide, and cisplatinium) may cause renal tubular damage. FE(AM) and FE(NO) may also be used for the detection of subclinical acute tubular nephrotoxicity. However, further detailed researches will be necessary to establish the certain role of NO and AM in toxicities of chemotherapeutic agents.

Prevalence and hematological characteristics of beta-thalassemia trait in Gaziantep urban area, Turkey.

Thalassemia is one of the most common hereditary disorders in the Mediterranean region and studies have shown that the prevalence of beta-thalassemia trait is high in the southern part of Turkey. Gaziantep is a city located near this region and, therefore, the authors investigated the prevalence and hematological characteristics of the beta-thalassemia traits in primary school students in Gaziantep. Sixty primary schools were selected from a list of all primary schools using a systematic sampling method. Data were collected by a face-to-face questionnaire. Osmotic fragility testing (OFT) using single-tube 0.36% NaCl solution was used for the screening of beta-thalassemia. Students who were positive in regard to OFT went through a series of testing, including a complete blood count, serum ferritin levels, serum iron, and hemoglobin electroforesis. Chi-square test was used in statistical analysis. Of the 2439 students enrolled to the study from the selected 60 classrooms, 1353 (55.5%) were male and 1086 (44.5%) were female. The OFT was positive in 115 (4.7%) of the participants. CEA and confirmatory HPLC results of the students who were positive OFT indicated that 70 (60.8%) had normal results, 33(28.7%) showed high HbA2 levels, 7 (6.1%) showed high HbA2 and HbF levels, 5(5.2%) showed high HbA2 and Fe-deficiency anemia, and none showed increased HbF levels. The overall prevalence of beta-thalassemia trait was 1.84%. No gender differentials and highest rates among the Kahramanmaras (3.5%) and Sanliurfa (1.7%) born students were the other significant findings of this study. Implementation of a routine carrier-screening program offering genetic counseling, prenatal diagnosis, and selective termination of affected fetuses would be a wise approach to eliminate this disease from the region.

Increased oxidative stress and altered activities of erythrocyte free radical scavenging enzymes in autism.

There is great evidence in recent years that oxygen free radicals play an important role in the pathophysiology of many neuropsychiatric disorders. The present study was performed to assess the changes in red blood cells thiobarbituric acid-reactive substances (TBARS) levels, and superoxide dismutase (SOD), catalase (CAT), adenosine deaminase (ADA) and xanthine oxidase (XO) activities in patients with autism (n = 27) compared to age- and sex-matched normal controls (n = 26). In the autistic group, increased TBARS levels (p < 0.001) and XO (p < 0.001) and SOD (p < 0.001) activity, decreased CAT (p < 0.001) activity and unchanged ADA activity were detected. It is proposed that antioxidant status may be changed in autism and this new situation may induce lipid peroxidation. These findings indicated a possible role of increased oxidative stress and altered enzymatic antioxidants, both of which may be relevant to the pathophysiology of autism.

Association of asthma with gastroesophageal reflux disease in children.

BACKGROUND: The objective in this study was to assess the association of gastroesophageal reflux disease (GERD) with asthma in pediatric patients. METHODS: Thirty-six pediatric patients who were diagnosed as having bronchial asthma were included in the study. The male-to-female ratio was 2 to 1. The diagnosis of GER was made by 24-hour pH monitoring. RESULTS: GER was present in 27 of 36 (75%) patients, of whom 19 (70%) were male and 8 (30%) were female patients. The GER frequency was found to be different between the supine and upright positions (p < 0.05). GER was more frequent in the upright position. However, duration of GER was longer in the supine position than the upright position (p < 0.05). Overall reflux duration was similar in both positions (p > 0.05). CONCLUSIONS: Demonstration of the relationship between asthma and GER suggests that GER is involved substantially in the pathogenesis and/or symptomatology of asthma. The patients with asthma should be evaluated for the presence of GER even in the absence of GER-related symptoms.