Cumhur Aydemir

Randomised controlled trial of prophylactic fluconazole versus nystatin for the prevention of fungal colonisation and invasive fungal infection in very low birth weight infants

Background Invasive fungal infections are a major cause of morbidity and mortality in preterm infants. The authors conducted the first prospective, randomised controlled trial of nystatin compared with fluconazole for the prevention of fungal colonisation and invasive fungal infection in very low birth weight (VLBW) neonates. Methods During a 12-month period, all VLBW neonates were assigned randomly to receive nystatin (1 ml suspension, 100 000 U/ml, every 8 h), fluconazole (3 mg/kg body weight, every third day) or placebo from birth until day 30 of life (day 45 for neonates weighing <1000 g at birth). The authors performed weekly surveillance cultures and systemic fungal susceptibility testing. Results During the study period, 278 infants (fluconazole group, n=93; nystatin group, n=94; control group, n=91) weighing <1500 g at birth were admitted. There were no differences in birth weight, gestation, gender or risk factors for fungal infection among the groups. Fungal colonisation occurred in 11.7% of the nystatin group and 10.8% of the fluconazole group, as compared with 42.9% of the control group. The incidence of invasive fungal infection was 4.3% in the nystatin group and 3.2% in the fluconazole group, as compared with 16.5% in the control group. There were no differences in fungal colonisation and invasive fungal infection between the nystatin and fluconazole groups. Conclusions Prophylactic nystatin and fluconazole reduce the incidence of colonisation and invasive fungal infection in VLBW neonates. The authors believe that nystatin is an alternative to fluconazole, because nystatin is safe, inexpensive, well tolerated and effective.

Screening for Retinopathy of Prematurity in a Large Tertiary Neonatal Intensive Care Unit in Turkey: Frequency and Risk Factors

Purpose: We aimed to determine applicable guidelines for screening of retinopathy of prematurity (ROP), and evaluate the contribution of risk factors for severe ROP. Methods: A prospective cohort study of neonates with a gestational age (GA) < 34 weeks or birth weight < 2000g who were admitted to the Neonatal Intensive Care Unit (NICU) of a tertiary level hospital was conducted. The study group was classified into three groups according to eye examination findings as no ROP, mild ROP and severe ROP. Results: Of the 700 neonates screened, the frequencies of ROP for any stage and severe ROP were 32.7% and 3.1%, respectively. Laser photocoagulation was needed in 9.6% of neonates with ROP. None of the neonates with a GA ≥ 31 weeks required treatment. Any ROP was detected in 199 (53.6%) of the babies < 32 weeks (n = 371), 22 (5.9%) of whom were treated with laser photocoagulation. Independent risk factors for severe ROP in babies < 32 weeks GA were birth weight, duration of mechanical ventilation and patent ductus arteriosus (PDA). Conclusion: This is the largest prospective cohort study including infants younger than 34 weeks GA from Turkey. Our data which belongs to the last 1-year period shows lower incidence of severe ROP when compared to previous reports from Turkey. According to our data, screening babies smaller than 32 weeks GA or 1500g birth weight seems reasonable. In the presence of long duration of mechanical ventilation and PDA, screening should be intensified.

Fecal calprotectin levels are increased in infants with necrotizing enterocolitis

Objective: To investigate the value of fecal calprotectin in diagnosis and predicting severity of necrotizing enterocolitis (NEC) in preterm infants. Methods: A prospective controlled study was conducted including preterm infants with stage 2 to 3 NEC, and birth weight and gestational age-matched controls. Fecal samples were obtained both at the time of NEC diagnosis and 3–5 days later from the patients, and at similar postnatal age from controls. Results: Twenty-five infants with stage 2 to 3 NEC and 25 controls were enrolled. Median fecal calprotectin concentrations were 1,282 and 365 µg/g at diagnosis in infants with NEC and controls, respectively. Fecal calprotectin levels of infants with NEC were significantly higher than those of the control group both in the first and second samples. Although the fecal calprotectin levels gradually decreased from the time of diagnosis to the second sampling time in stage 2 NEC, in stage 3 NEC fecal calprotectin concentrations increased to a higher level. A fecal calprotectin value of 792 µg/g was found to be 76% sensitive and 92% specific for the diagnosis of definite NEC. Conclusion: Fecal calprotectin increases in infants with NEC and serial measurements may be useful as a noninvasive prognostic marker for progression of disease.

A randomized, controlled trial of poractant alfa versus beractant in the treatment of preterm infants with respiratory distress syndrome.

We prospectively evaluated the differences in clinical responses and short-term outcomes in preterm infants with respiratory distress syndrome (RDS) treated with poractant alfa or beractant. Premature infants with RDS were randomized to poractant alfa or beractant treatment between July 2008 and June 2009. Patients were followed until 40 weeks of corrected gestational age or death. The fraction of inspired oxygen (Fio(2)) after surfactant treatment, need for repeat doses, and duration of respiratory support and hospitalization were evaluated between groups. Sixty-one infants received poractant alfa and 65 received beractant. Significantly more patients in the beractant group required ≥2 doses of surfactant compared with the poractant alfa group (31% versus 12%, p = 0.023). Extubation rate within the first 3 days after surfactant administration was higher in the poractant alfa group than in the beractant group (81% versus 55.9%, p = 0.004). Posttreatment Fio(2) requirement in the poractant alfa group was significantly lower than in the beractant group on days 1, 3, and 5. Overall mortality and morbidities were similar between groups. Survival free of bronchopulmonary dysplasia (BPD) at the end of study period was 78.7% and 58.5% in poractant alfa and beractant groups, respectively (p = 0.015). Our study confirms the rapid onset of action, less need for redosing, rapid extubation, and higher survival free of BPD in preterm infants treated with poractant alfa.

Complete deficiency of the IL-12 receptor β1 chain: three unrelated Turkish children with unusual clinical features

Complete interleukin-12 receptor β1 deficiency is the most frequent known genetic etiology of the syndrome of Mendelian susceptibility to mycobacterial diseases (MSMD, OMIM 209950). Eleven disorders caused by different types of mutations in five different gene defects related to the IL-12 and IL-23/interferon (IFN)-γ axis have been described to date [2]. Refer to Fig. 1 for the pathways of IL-12/IL-23-dependent interferon IFN-gamma immunity. Patients with MSMD are vulnerable to the BacillusCalmette-Guerin (BCG) vaccine species Mycobacterium bovis, environmental mycobacteria and M. tuberculosis. Infectious diseases other than those caused by Salmonella species, the latter of which infect almost one-half of all patients, are rare [1, 3, 6]. We report here various and unusual clinical manifestations of three unrelated patients with complete IL-12Rβ1 deficiency due to three different mutations in the IL-12RB1 gene, of which two are novel (711insC, 628–644dup). The first patient was an 1-year-old infant girl who had BCG lymphadenitis at 6 months of age and disseminated mycobacterial infection complicated with spontaneous pneumomediastinum and subcutaneous emphysema at 12 months of age. She was treated with isoniazide, rifampin, ethambutol, amikacin, clarithromycin and clofazimine. Pre-tracheal fasciotomy was undertaken for subcutaneous emphysema. A complete IL-12 receptor β1 deficiency associated with the 711insC mutation in IL-12RB1 was detected (Fig. 2). The patient is still in remission. The second patient was an 19-month-old infant boy who presented with five episodes of infections attributable to Salmonella and two episodes of Salmonella enteritidis meningitis. There was no mycobacterial disease, including no adverse reaction to BCG immunization that was practiced at the age of 2 months. He was treated with meropenem, rIFN-γ and external ventricular drainage and then ventriculo-peritoneal shunting for hydrocephalus. Immunologic and molecular genetic examinations revealed complete IL-12Rβ1 deficiency and a IL-12RB1 783+ 1G>A mutation (Fig. 2) [3]. The third patient, a 4.5-year-old boy, had fistulized BCG lymphadenitis in early childhood followed by disseminated mycobacterial infection and splenic abscess with Salmonella bacteremia at 44 months of age. He was treated with meropenem and with isoniazide, rifampin, ethambutol, clarithromycin and amikacin. The patient improved; however, he was lost to follow-up and has been reported to have died. DNA sequencing revealed a 628–644dup mutation in IL-12RB1 (Fig. 2). A complete IL-12 receptor β1 deficiency is suspected. All three patients had persistent oral moniliasis. Among a total of 56 cases of IL-12 receptor β1 deficiency reported in the literature, the rate of infection with BCG M. bovis is 73% (27/37), environmental mycobacteria 21% (22/56), non-typhoidal Salmonella species 46% (26/56) and tuberculosis 7% (4/56) [4–6]. Paracoccidioides brasiliensis-disseminated disease has also recently been reported in an IL-12Rβ1-deficient patient. None of the 37 patients with BCG disease subsequently G. Tanir (*) . N. Tuygun . C. Aydemir . E. C. Boduroglu Dr. Sami Ulus Children Health and Diseases Training and Research Center, Hosdere Caddesi 166/3, Yukari Ayranci, 06550 Ankara, Turkey e-mail: gonultanir58@yahoo.com Fax: +90-312-3170353

Treatment of severe amitriptyline intoxication with plasmapheresis

Tricyclic antidepressant poisoning is one of the most common causes of serious intoxication. Here, we report a 2‐year‐old girl with severe amitriptyline (70 mg/kg) intoxication. She was in comatose, had generalized tonic clonic seizure, ventricular tachycardia, and wide QRS complexes. Although she did not respond to classical therapies, very good clinical response to plasmapheresis was obtained and she developed no complications. Thus, plasmapheresis may be an effective treatment modality in poisoning with drugs, which bind to plasma proteins with high affinity. J. Clin. Apheresis, 2009.

Total antioxidant capacity and total oxidant status after surfactant treatment in preterm infants with respiratory distress syndrome

Background Oxidative damage is important in the pathogenesis of respiratory distress syndrome (RDS). However, data on the effect of surfactant therapy on oxidative stress in vivo are limited. We aimed to evaluate the oxidant/antioxidant status in preterm infants with RDS via measurement of total antioxidant capacity (TAC) and total oxidant status (TOS), to determine the effect of surfactant on oxidant/antioxidant balance and to assess the association between TAC, TOS and clinical outcomes of the patients. Methods Sixty-nine infants with RDS were included. Blood samples for determining TAC and TOS were collected before and 48 h after surfactant treatment. TAC and TOS levels were analysed in serum. Patients were followed up until discharge or death. Results Post-surfactant TAC levels were significantly higher than pre-surfactant TAC levels (P = 0.029). TAC/TOS ratio significantly increased after surfactant treatment (P = 0.018). Infants <28 weeks of gestational age had lower levels of baseline TAC than those ≥28 weeks of gestational age (P = 0.020), whereas TOS levels were similar. Baseline TAC/TOS ratio was lower in infants who died in the study period than those who survived (P = 0.023). After controlling gestational age, baseline TAC levels were significantly and inversely correlated with the duration of total respiratory support (r = −0.343; P = 0.009) and hospitalization (r = −0.341; P = 0.009). TAC or TOS levels were not associated with the development of bronchopulmonary dysplasia or other complications as determined during the investigation period. Conclusions Oxidant–antioxidant balance shifts in favour of the antioxidant system after surfactant treatment. Lower TAC/TOS ratio in preterm infants may be associated with increased mortality.

The role of plasma N-terminal pro-B-type natriuretic peptide in predicting the severity of transient tachypnea of the newborn

BACKGROUND/AIM Transient tachypnea of the newborn (TTN) is a consequence of inadequate neonatal lung fluid clearance. Natriuretic peptides play an important role in the regulation of extracellular fluid volume. The aim of the study was to investigate the relation between plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels and TTN, and to find out its role in predicting disease severity. METHODS A prospective controlled study involving 67 infants with TTN and 33 controls ≥34 weeks gestational age was conducted. Study and control groups were compared for plasma NT-proBNP levels measured on the 6th, 24th, 72nd and 120th hours of life. Cardiac systolic functions were evaluated by echocardiography. RESULTS NT-proBNP levels were significantly higher in neonates with TTN compared to controls at 6th, 24th, 72nd and 120th hours (p<0.001). NT-proBNP levels at 24th and 72nd hours were significantly higher in infants with prolonged tachypnea (p=0.007 and p=0.03) and in those who required respiratory support (p=0.006 and p<0.001). Tachypnea duration was correlated with NT-proBNP levels at 24h (r=0.41, p=0.001). At a cut-off value of 6575 pg/ml, NT-proBNP had a sensitivity of 85% and specificity of 64% to predict mechanical ventilation requirement. Cardiac systolic functions were normal in all TTN patients. CONCLUSION Plasma NT-proBNP levels are increased in neonates with TTN. Measurement of plasma NT-proBNP can be useful for predicting infants who will have prolonged tachypnea and mechanical ventilation requirement.

Umbilical Artery Intima-Media and Wall Thickness in Infants of Diabetic Mothers

Background: Large for gestational age (LAG) neonates who had been exposed to an intrauterine environment of either diabetes or maternal obesity are at increased risk of developing the metabolic syndrome. This can be explained by exposure to high glucose and insulin levels in utero which alter fetal adaptation and programming. Objectives: The aim of the study was to evaluate the onset of preclinical atherosclerosis in utero. Methods: We measured umbilical artery wall thickness (ruWT) in the third trimester by obstetric ultrasound and umbilical artery intima-media thickness (uIMT) in pathologic specimens of umbilical cords obtained shortly after delivery and investigated the relation between these measurements and serum insulin level and C-peptide level in cord blood and assessed insulin resistance with the homeostasis model assessment of insulin resistance (HOMA-IR) in infants of diabetic mothers (IDMs), i.e. the study group, which was divided into a large for gestational age group (LGA)-IDM group and an appropriate for gestational age group (AGA)-IDM group and compared with a control group. Results: The LGA-IDM group had significantly higher insulin (p < 0.001), C-peptide (p = 0.018) and HOMA-IR levels (p < 0.001) compared with the AGA-IDM and control groups. The LGA-IDM group had significantly larger ruWT (p = 0.013) and uIMT (p < 0.001) compared with the AGA-IDM and the control groups. The LGA-IDM group had increased uIMT and ruWT that correlated with the severity of maternal hyperglycemia. Conclusions: Measurement of ruWT in the third trimester is feasible, reproducible and strongly correlated with pathological serum insulin, C-peptide in cord blood and HOMA-IR levels.

Neonatal non-ketotic hyperglycinemia: report of five cases.

© 2008 Japan Pediatric Society Non-ketotic hyperglycinemia (NKH), also called glycine encephalopathy (OMIM 238300), is a rare autosomal recessive disorder of glycine metabolism. There are four forms of glycine encephalopathy: neonatal, infantile, transient, and late. 1 The neonatal form develops within days after birth with acute neurological deterioration, rapidly progressing to a coma and often to death. The few surviving patients suffer from severe mental and developmental retardation as well as convulsions. 1,2 The authors report fi ve new patients with neonatal NKH and discuss the clinical course and treatment modalities.