Ischemia-Modified Albumin May Be a Novel Marker for Predicting Neonatal Neurologic Injury in Small-For-Gestational-Age Infants in Addition to Neuron-Specific Enolase.

Aim This study aims to evaluate hypoxia/ischemia and oxidant stress, and negative neurodevelopmental outcomes in small-for-gestational-age (SGA) infants. Material and Methods Two study groups were established as SGA and appropriate-for-gestational-age (AGA) infants. SGA infants were allocated asymmetric and symmetric SGA infants. Serum levels of neuron-specific enolase (NSE), ischemia-modified albumin (IMA), malondialdehyde (MDA), total antioxidant capacity (TAC), and total oxidant status (TOS) were determined and oxidative stress indexes (OSI) were calculated in all groups. Results Overall, 83 infants were diagnosed SGA, and 85 infants were determined AGA. TOS and OSI levels were significantly higher and TAC levels were significantly lower in SGA group (p < 0.05). MDA and IMA levels were significantly higher in SGA group (p < 0.05). NSE levels in SGA infants were significantly higher (p < 0.05). NSE and IMA were significantly higher in symmetric SGA infants (p < 0.05). TOS, OSI, MDA, TAC levels were not significantly different in SGA infants with abnormal neurological findings (p > 0.05); NSE and IMA levels were significantly higher in SGA group with abnormal neurological findings (p < 0.05). Conclusion SGA infants expose to hypoxia and oxidative stress led to neuronal damage. We suggest that in addition to NSE, IMA blood levels might be a sensitive novel marker for predicting the severity of neuronal damage.

Levels of ischemia-modified albumin in transient tachypnea of the newborn.

AIM: The aim of the article is to evaluate ischemia-modified albumin (IMA) levels in infants with transient tachypnea of the newborn (TTN) and to find out its relation to the disease severity. Patients and METHODS: Infants with > 37 weeks of gestation, without any respiratory and cardiac symptoms and without any maternal health problems, and diagnosed as TTN were allocated as the study group. Patients with obvious retractions, grunting, hypercarbia (Pco 2 > 60 mm Hg) or hypoxia (oxygen saturation < 88% with Fio 2 of 0.60) were managed with nasal continuous positive airway pressure (CPAP). During the postnatal 0 to 24 hours, blood samples were collected in 2 mL for IMA. RESULTS: A total of 47 patients were diagnosed TTN, and allocated as the study group. Of the 47 patients, 43 patients without respiratory symptoms were enrolled as the control group. IMA levels in TTN were found to be significantly higher (p < 0.05). In addition, IMA levels were significantly increased in the nasal CPAP group versus supplemental oxygen therapy groups (p < 0.05). IMA levels were determined to be significantly higher in the > 3 days of oxygen therapy group (p < 0.05). IMA levels with a cutoff point of 0.87 ABSU, sensitivity of 81.1% and specificity of 69.8% predicted TTN (area under the curve [AUC] = 0.85; p < 0.05). IMA levels with > 0.98 ABSU, 78% sensitivity, and 86% specificity indicated the prediction of CPAP requirement (AUC = 0.86; p < 0.05). CONCLUSION: IMA levels were significantly higher in infants with diagnosed TTN. Therefore, IMA may be used as a new marker for predicting TTN and disease severity.

Mean platelet volume (MPV) may simply predict the severity of sepsis in preterm infants.

BACKGROUND: To evaluate the efficacy of serial mean platelet volume (MPV) measurements in diagnosis and followup of sepsis and to compare its effectiveness with C-reactive protein (CRP) and interleukin-6 (IL-6) in sepsis. METHODS: Preterm infants, whose gestational age and weight were matched to each other, were grouped as control (n = 100) and sepsis (n = 91). Platelet indices (MPV, PDW, platelet count), CRP, and IL-6 levels were measured for the control group and on the day of diagnosis (1st day), 3rd, and 7th days of the sepsis group. RESULTS: There were significant differences between the control and sepsis group in terms of platelet count and MPV/PDW levels (p < 0.05). No significant changes were found in either platelet count or MPV and PDW of infants between early and late onset sepsis, nor between culture proven and non proven sepsis, nor among different infectious agents (gram positive/negative and fungal infections) (p > 0.05). Additionally, non-survivors with sepsis had higher levels of MPV and PDW during sepsis episodes on consecutive days (p < 0.05), in contrast to lower platelet counts in non-survivors (p < 0.05). Moreover, a positive correlation was found between MPV and IL-6 and CRP. A MPV value of 10.35 fL was identified as the cut off value in patients probably resulting in sepsis with a sensitivity of 97.8% and specificity of 78.7% (AUC = 0.949; p < 0.001), and a MPV value of 10.75 fL was determined as the cut off value in patients possibly resulting in death at diagnosis with a sensitivity of 95.2% and a specificity of 84.9% (AUC = 0.944; p < 0.001). CONCLUSIONS: The mean platelet volume can be used in addition to CRP and IL-6 at both diagnosis and follow-up of sepsis and the response of antimicrobial treatment.

Ischemia-modified albumin may be a novel marker for the diagnosis and follow-up of necrotizing enterocolitis.

AIM: We investigate the efficacy of serial ischemia-modified albumin (IMA) measurements in diagnosis and follow-up of necrotizing enterocolitis (NEC), and compare its effectiveness with C-reactive protein (CRP), interleukin-6 (IL-6), in NEC. METHODS: Preterm infants, whose gestational age and weight matched each other, were grouped as control (n = 36) and NEC (n = 37). IMA, CRP, IL-6 levels were measured on the third day of life for the control group and on the day of diagnosis (first day), third, and seventh days of NEC. RESULTS: IMA, CRP, and IL-6 levels were significantly increased in NEC patients compared to the control group (P < 0.001) on the follow-up. IMA levels were significantly higher in infants with stage-III NEC than those in infants with stage-II NEC on the first, third, and seventh days (P < 0.001). The area under curve for IMA (0.815 at diagnosis, 0.933 at the third day, 0.935 at the seventh day) were significantly higher than CRP and IL-6 at all days for predicting perforation in infants with NEC (P < 0.001). Similarly, the area under curve for IMA (0.952 at diagnosis, 0.929 at the third day, 0.971 at the seventh day) was significantly higher than CRP and IL-6 at all consequent days of diagnosis for predicting mortality in infants with NEC (P < 0.001). CONCLUSION: Ischemia-modified albumin was found to be superior to CRP and IL-6 in both diagnosis and follow-up of NEC.

Responsiveness to parenteral iron therapy in children with oral iron-refractory iron-deficiency anemia.

UNLABELLED: Intravenous (IV) ferric iron (Fe)-carbohydrate complexes are used for treating Fe deficiency in children with iron-refractory iron-deficiency anemia (IRIDA). An optimal treatment has yet to be determined. There are relatively little publications on the responsiveness to IV iron therapy in children with IRIDA. PATIENTS AND METHOD: This study analyzed responses to IV iron sucrose therapy given to 11 children, ranging in age from 2 to 13 years (mean 4.8 years), with iron-deficiency anemia who were unresponsive to oral iron therapy. RESULTS: The hemoglobin and ferritin values (mean) of the 11 children with IRIDA were 7.7 g/dL and 4.8 ng/mL at diagnosis. Both hemoglobin and ferritin levels increased to 9.5 g/dL, and 24 ng/mL, respectively, at 6 weeks after the first therapy. Although the level of hemoglobin was steady at 6 months after the first, and 6 weeks after the second therapy, the ferritin levels continued to increase up to 30 ng/mL and 47 ng/mL at 6 months after the first and 6 weeks after the second therapy, respectively. CONCLUSION: We recommend that IRIDA should be considered in patients presenting with iron-deficiency anemia of unknown cause that is unresponsive to oral iron therapy. Our results suggest that IV iron therapy should be administered only once in cases of IRIDA. Continued administration of IV iron would be of no benefit to increase hemoglobin levels. On the contrary, ferritin levels may continue to increase resulting in untoward effects of hyperferritinemia.

Possible autosomal recessive inheritance in an infant with acrofacial dysostosis similar to Nager syndrome.

The acrofacial dysostosis syndromes, which are characterized by malformations of the craniofacial region and limbs, are a clinically heterogeneous group of disorders. Based primarily on the of the pattern of limb defects two major groups have emerged: Nager syndrome with predominantly preaxial malformations plus mandibulofacial dysostosis (severe micrognathia and malar hypoplasia) and Miller syndrome with postaxial malformations plus mandibulofacial dysostosis. Among these syndromes, Nager syndrome is a rare condition but the most common form of acrofacial dysostosis. Most cases are sporadic, while autosomal dominant and autosomal recessive inheritance patterns have been reported. Recently, heterozygous mutations in the SF3B4 gene on chromosome 1q12-q21 were found to be responsible for a subset of sporadic and autosomal dominant cases. We present a female infant born to consanguineous parents with craniofacial features resembling Nager syndrome and a unilateral preaxial limb malformation. Mutation analysis of coding exons of SF3B4 did not identify any mutations. This couple also had a deceased child who had similar clinical features. We conclude that, the presence of consanguinity and absence of mutation in SF3B4, provides evidence in support of a recessive form of Nager syndrome.

Can we safely administer the recommended dose of phenobarbital in very low birth weight infants?

AIM: We investigated whether the recommended phenobarbital loading dose of 15-20 mg/kg with maintenance of 3-4 mg/kg/day can safely be administered to very low birth weight preterm newborns with seizures. METHODS: Twenty-four convulsive preterms of <1,500 g were enrolled in the study. Phenobarbital was administered intravenously with a loading dose of 15 mg/kg in approximately 10-15 min. After 24 h, the maintenance dose of 3 mg/kg/day was administered as a single injection. Blood samples were obtained 2, 24, 48, 72, and 96 h after the phenobarbital loading dose was administered, immediately before the next phenobarbital dose was injected. RESULTS: None of the cases had plasma phenobarbital concentrations above the therapeutic upper limit of 40 µg/mL on the 2nd hour; one case (4.7%), on the 24th; 11 cases (45.8%), on the 48th; 15 cases (62.5%), on the 72nd; and 17 cases (70.8%), on the 96th hour. A negative correlation was detected between the serum concentrations of phenobarbital and gestational age on the 72th (p, 0.036; r, -0.608) and 96th hour (p, 0.043; r, -0.769). CONCLUSIONS: We suggest that particular attention should be done while administering phenobarbital in preterms, as blood levels of phenobarbital are higher than the reference ranges that those are often reached with the recommended doses in these groups of babies.

The effect of phototherapy on fecal calprotectin levels.

OBJECTIVE: Fetal calprotectin levels increase in the early stages of necrotizing enterocolitis. Although the effects of several factors on fetal calprotectin have been studied, the effect of phototherapy is not known. In this study, we analyzed the effect of phototherapy on fetal calprotectin levels. METHODS: Ninety breast-fed newborns (46 male, 44 female) who were hospitalized for indirect hyperbilirubinemia and treated with phototherapy were included to the study. Forty-two of them were term and 44 of them were preterm. Newborns treated with phototherapy (n = 53) constituted the phototherapy group (29 preterm, 24 term) and 37 newborns who did not receive phototherapy (19 preterm, 18 term) constituted the control group. Fecal samples were collected 24 hours after phototherapy had been started. Fecal samples (100 mg) were weighed with sensitive scales and preserved at -80°C after buffering with a special solution. All samples were studied at the same time with a fecal calprotectin kit by using enzyme-linked immunosorbent assay. RESULTS: There were no statistically significant difference between fecal calprotectin levels of term and preterm babies who received phototherapy and babies who did not receive phototherapy. CONCLUSION: There was no effect of 24-hour phototherapy on fecal calprotectin levels in preterm and term newborns.

The relationship between P-wave dispersion and diastolic functions in diabetic children.

OBJECTIVE: The aim of this study was to investigate the relations between the P-wave dispersion and diastolic functions in type 1 diabetic children. PATIENTS: A total of 33 diabetic patients without any cardiovascular disease, with a mean age of 12.3 plus or minus 4.2 years, and 29 healthy controls, with a mean age of 10.4 plus or minus 3.9 years were enrolled for this study. Left and right ventricular functions were assessed by using standard pulsed-wave Doppler echocardiography. P-wave dispersion was calculated by measuring minimum and maximum P-wave duration values on the surface electrocardiogram. RESULTS: For the diabetic patients, P-wave maximum duration and dispersion was found to be significantly increased compared with healthy controls. Likewise, mitral A velocity and A velocity time integral was significantly increased while the isovolumic contraction time was significantly higher in the diabetics. In tricuspid valve measurements, however, A velocity time integral was found to be significantly higher, whereas the deceleration time was significantly lower in the diabetics. No relation was found between the left ventricle diastolic functions and duration of diabetes, HbA1c levels and P-wave dispersion in the diabetic children. No correlation was found between the diastolic functions and P-wave minimum, maximum duration, and dispersion for all the participants. CONCLUSION: In type-1 diabetic children, the diastolic functions of both the ventricles were observed to be affected negatively together. Diabetes might be causing the prolongation of P-wave dispersion, but there was no relationship between the diastolic functions and P-wave dispersion in the diabetic children.

Role of immunoglobulin in neuronal apoptosis in a neonatal rat model of hypoxic ischemic brain injury.

The objective of the present study was to evaluate the neuroprotective effects of immunoglobulin (Ig) in a neonatal hypoxic ischemic (HI) rat model. Seven-day-old rat pups were randomly assigned to control, hypoxia and hypoxia + Ig groups. The rats in the hypoxia +Ig group were intraperitoneally administered 1 g/kg Ig once, immediately after hypoxia. Saline was administered to the rats in the hypoxia group at the same time point. Eight rats from each of the Ig + hypoxia and hypoxia groups were sacrificed by decapitation 4 and 24 h following the administration of Ig or saline. The rats of the control group were sacrificed at the 4 h time-point. Caspase-3 activity, as well as IL-1ß, IL-6 and TNF-α mRNA expression levels, were studied in the left ischemic hemispheres. Induction of cerebral ischemia increased the TNF-α, IL-6 and IL-1ß mRNA expression levels significantly at 4 and 24 h in the left ischemic hemispheres in the hypoxia group compared with those in the control group. The systemic administration of Ig following HI encephalopathy significantly reduced the TNF-α, IL-6 and IL-1ß mRNA expression levels in the ischemic tissue in the Ig + hypoxia group compared with those in the hypoxia group. In the hypoxia group, caspase-3 activity in the left half of the brain was found to be significantly increased compared with that in the control group. Caspase-3 activity in the Ig + hypoxia group was significantly lower than that in the hypoxia group. The observations of the present study indicate that Ig administration may be an efficient treatment approach for reducing cerebral apoptosis associated with hypoxic ischemia.

Effects of hyperglycemia on the developing brain in newborns.

BACKGROUND: Hyperglycemia is a common problem in preterm neonates and is associated with increased risk of mortality and severe morbidities such as brain damage. However, available data about the effects of severity of hyperglycemia on the developing brain in the early life is limited. Therefore, we evaluated the effects of moderate and severe hyperglycemia on the developing brain. METHOD: Thirty newborn Sprague-Dawley rats were randomly divided into three groups as control, moderate hyperglycemia (30% dextrose), and severe hyperglycemia (50% dextrose). Pups in the hyperglycemia groups were administered subcutaneous sterile dextrose solution at a dose of 4 mL/kg daily from the second day to the eleventh day of life. Blood glucose levels were measured every day in all study groups. Rat brain tissues were removed at the end of the study. Histopathologic and immunohistochemical (caspase-9, -8, and -3) examination and biochemical analysis including xanthine oxidase, total antioxidant status, total oxidant status, and malondialdehyde activities were performed. RESULTS: Weight of the brain tissues in rats with hyperglycemia groups was significantly lower than the control group (P < 0.05). Weight of the brain tissues in rats with moderate hyperglycemia was lower than that of the severe hyperglycemia (P < 0.05). In the histopathologic and immunochemical evaluation, severity of brain damage and apoptosis were significantly higher in the severe hyperglycemia group, especially at the level of the hippocampus (P < 0.05). Tissue malondialdehyde, xanthine oxidase levels, and total oxidant status were significantly increased in the severe hyperglycemia group, whereas total antioxidant status was significantly decreased in the severe hyperglycemia group (P < 0.001). CONCLUSION: Brain damaging effects of severe hyperglycemia were observed in the developing brains of the rat pups. It might be inferred that severe hyperglycemia can damage the developing brain especially in preterm infants.

Is the strength of direct antiglobulin test important for the duration of phototherapy?

The purpose of this study was to evaluate the relationship between the grades of positivity of the direct antiglobulin test (DAT) and their effects on the duration of phototherapy for neonatal jaundice. DAT reactions of blood samples were graded as (1+), (2+), (3+) and (4+). DAT was positive in 80 neonates who were exposed to phototherapy due to jaundice. Patients with positive DAT reactions are classified in the study as follows: 34 newborns were DAT (1+), 18 newborns were DAT (2+), 16 newborns were DAT (3+) and 12 newborns were DAT (4+). We found that higher grades of positivity of DAT are associated with extended duration of phototherapy (r = 0.436, p < 0.05). Additionally, DAT (4+) reactions are more predictive for a prolonged duration of phototherapy requirement than the other grades (p < 0.0001).

Microvillus inclusion disease associated with necrotizing enterocolitis in a premature infant.

Microvillus inclusion disease is one of the congenital diarrheal disorders characterized by the appearance of inclusion bodies on the intestinal epithelium. To date there are a few cases and also a few other associated finding reports related to this life-threatening disease in literature. In this report, we present a premature infant with microvillus inclusion disease that was associated with necrotizing enterocolitis. Thus, we should be aware of the appearance of necrotizing enterocolitis in patients with microvillus inclusion disease, especially when contributing factors are present.

Neonatal multiple sulfatase deficiency with a novel mutation and review of the literature.

Multiple sulfatase deficiency is a rare autosomal recessive disorder in which affected individuals present a complex phenotype due to the impaired activity of all sulfatases. There are different types of multiple sulfatase deficiency; among them, the neonatal form is the most severe, with a broad range of mucopolysaccharidosis-like symptoms and death within the first year of life. The disorder is caused by homozygous or compound heterozygous mutations in the sulfatase-modifying factor-1 (SUMF1) gene. In this article, we describe a non-ichthyotic neonatal multiple sulfatase deficiency patient with a novel mutation in the SUMF1 gene. The missense mutation c.777C>G, for which the patient was homozygous, had been caused by a p.N259K amino acid substitution. We evaluated the patient using clinical findings, neuroimaging studies and molecular analysis via the literature; we also wanted to note the difficulties in the diagnosis of this rare disease.

Investigation of the serum glucocorticoid kinase 1 gene in patients with transient tachypnea of the newborn.

OBJECTIVE: The aim of this study was to investigate whether there is a role of the serum glucocorticoid kinase (SGK) 1 gene, which has an effect on the control of the epithelial sodium channels. MATERIALS AND METHOD: This study included patients who were diagnosed with transient tachypnea of the newborn (TTN) with more than 37 weeks of gestation. As the control group, healthy newborns of the same gestational age were included. From each group, within the first 5 d of their lives, 2 cc of whole blood was taken in EDTA tubes, and stored at -80 °C. The DNA extraction was performed. RESULTS: There were 32 patients in the TTN, and also 32 patients in the control group. The heterozygous allele rs1057293 (3/28) and rs1743966 (8/28) were located in the encoder region of the SGK 1 gene. In addition, in encoding region of the SGK 1 gene, the Arg97Ile (1/28), which causes the amino acid changes, had a genotype frequency of 0.0357, and a mutation was identified in Arg97Ile. DISCUSSION: We have defined polymorphisms rs1057293 and rs1743966 in the SGK 1 gene, and the Arg97Ile mutation, for the first time in patients with TTN. This pilot study gave us some clues about a genetic basis of TTN phenotype, next to the lack of the pulmonary maturation.

The role of VEGF and its soluble receptor VEGFR-1 in preterm newborns of preeclamptic mothers with RDS.

OBJECTIVE: We measured vascular endothelial growth factor (VEGF) and soluble VEGF receptor 1(sVEGFR-1) concentrations in cord blood and tracheal aspirate fluid (TAF) in order to investigate the role of them in lung maturation and the severity of respiratory distress syndrome (RDS) in preterm newborns, born to preeclamptic mothers. METHODS: Newborns were divided into two groups as preterms born to preeclamptic mothers and preterms born to healthy mothers. They were also divided into two groups as severe RDS (sRDS) and mild RDS (mRDS) according to the need of surfactant and extent or type of ventilatory support. The concentrations of VEGF and sVEGFR-1 in cord blood and TAF (only in preterms with sRDS) were assayed by standardized enzyme-linked immunosorbent assay. RESULTS: When the patients were evaluated as sRDS and mRDS, cord blood VEGF and VEGF/sVEGFR-1 concentrations of preterms with sRDS were significantly lower than the concentrations of preterms with mRDS. Conversely, cord blood sVEGFR-1 concentrations of preterms with sRDS were significantly higher than the concentrations of preterms with mRDS. VEGF and sVEGFR-1 concentrations in TAF could be compared only between sRDS preterms, born to preeclampsia (+) and (-) mothers. No statistical significance was detected between the two groups when sVEGFR-1, VEGF and VEGF/sVEGFR-1 concentrations in TAF were compared. CONCLUSION: Preeclampsia seems not to have an important effect on VEGF and sVEGFR-1 concentrations of preterm newborns both in cord blood and in TAF. Low VEGF and high sVEGFR-1 concentrations seem to be associated with the severity of RDS irrespective of preeclampsia, suggesting that VEGF may be one of the main components of lung maturation.

Octreotide treatment in a neonate with non-chylous pleural effusion.

Fetal pleural effusion is a rare condition. While it may regress spontaneously, it may also continue up to the post-natal period. This condition may be treated by thoracentesis, thoracoabdominal shunt application and pleurodesis in the intrauterine period while thoracentesis or tube thoracostomy may be used in the post-natal period. In cases where the fluid is defined to represent chylothorax, octreotide, a somatostatin analogue, may be administered for treatment. In this case report, we discussed the outcomes of treatment with octreotide administered in a neonatal case under follow-up due to fetal pleural effusion and with non-chylous ascites detected in the post-natal period.

The effects of intraperitoneal pentoxifylline treatment in rat pups with hypoxic-ischemic encephalopathy.

BACKGROUND: The aim of this study was to evaluate the effects of postischemic treatment with pentoxifylline on the cytokine gene expressions and neuronal apoptosis in neonatal rat model of hypoxic-ischemic encephalopathy. METHODS: Seven-day-old Wistar rat pups (n = 40) of either sex, delivered spontaneously, were used in this experimental study. Control group (n = 8): after median neck incision was made, neither ligation nor hypoxia was performed, ischemia group (n = 16): 0.5 mL of saline was injected intraperitoneally immediately after hypoxia. Pentoxifylline and ischemia groups (n = 16): the rat pups were administered intraperitoneally 60 mg/kg of pentoxifylline immediately after hypoxia. Eight rats from ischemia and pentoxifylline + ischemia groups were sacrificed 4 and 24 hours after drug administration. Control group mice were decapitated 4 hours after hypoxia. Caspase-3 activity, interleukin-1ß, and tumor necrosis factor-α messenger RNA expression levels were studied in the left half of the brain. RESULTS: Induction of cerebral ischemia increased tumor necrosis factor-α and interleukin-1ß messenger RNA expression levels significantly at 4 hours and 24 hours following ischemia in the left ischemic hemispheres in the ischemia group as compared with the control group. Systemic administration of pentoxifylline immediately after hypoxic-ischemic encephalopathy significantly reduced the tumor necrosis factor-α and interleukin-1ß messenger RNA expression levels in ischemic tissue as compared with the ischemia group. Caspase-3 activities in the left half of the brains of ischemia group were found to be increased significantly as compared with control group. Caspase-3 activities in the brains of pentoxifylline + ischemia groups were significantly lower than in that of ischemia group. CONCLUSIONS: Based on the significantly lower interleukin-1ß and tumor necrosis factor-α gene expression measured after 4 and 24 hours and significantly reduced caspase-3 activity measured colorimetrically in the animals treated with pentoxifylline, our findings suggest that pentoxifylline may reduce brain damage due to hypoxic-ischemic injury.

Cerebellar herniation after lumbar puncture in galactosemic newborn.

Cerebral edema resulting in elevated intracranial pressure is a well-known complication of galactosemia. Lumbar puncture was performed for the diagnosis of clinically suspected bacterial meningitis. Herniation of cerebral tissue through the foramen magnum is not a common problem in neonatal intensive care units because of the open fontanelle in infants. We present the case of a 3-week-old infant with galactosemia who presented with signs of cerebellar herniation after lumbar puncture.