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IntroductionIbuprofen is used widely to close patent ductus arteriosus in preterm infants. The anti-inflammatory activity of ibuprofen may also be partly due to its ability to scavenge reactive oxygen species and reactive nitrogen species. We evaluated the interaction between oxidative status and the medical treatment of patent ductus arteriosus with two forms of ibuprofen.Materials and methodsThis study enrolled newborns of gestational age ⩽32 weeks, birth weight ⩽1500 g, and postnatal age 48–96 hours, who received either intravenous or oral ibuprofen to treat patent ductus arteriosus. Venous blood was sampled before ibuprofen treatment from each patient to determine antioxidant and oxidant concentrations. Secondary samples were collected 24 hours after the end of the treatment. Total oxidant status and total antioxidant capacity were measured using Erel’s method.ResultsThis prospective randomised study enrolled 102 preterm infants with patent ductus arteriosus. The patent ductus arteriosus closure rate was significantly higher in the oral ibuprofen group (84.6 versus 62%) after the first course of treatment (p=0.011). No significant difference was found between the pre- and post-treatment total oxidant status and total antioxidant capacity in the groups.DiscussionIbuprofen treatment does not change the total oxidant status or total antioxidant capacity. We believe that the effect of ibuprofen treatment in inducing ischaemia overcomes the scavenging effect of ibuprofen.

Purpose: To determine whether prophylaxis with etanercept, an anti-inflammatory drug, would decrease the severity of lung injury in a neonatal rat model of bronchopulmonary dysplasia (BPD); Materials and Methods: Rat pups were divided into three groups: pups exposed to room air (group 1; n = 10), to hyperoxia + placebo (group 2; n = 9), and to hyperoxia + etanercept (group 3; n = 8). Lung morphology was assessed by alveolar surface area percentage, which is a measure of alveolar size. The severities of lung inflammation and antioxidant capacity were assessed by quantifying tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta), malondialdehyde (MDA), and superoxide dismutase (SOD) from lung homogenate; Results: The percentage of alveolar surface areas were significantly higher in group 3 compared to group 2 (p = .004) and similar in both group 1 and group 3 (p = .21). The mean level of lung MDA was significantly higher in group 2 compared to group 1 and group 3 (p < .05 for both). Lung homogenate SOD activities in group 3 was significantly higher than group 2 (p < .001). Furthermore, group 3 pups had lower levels of TNF-alpha and TGF-beta in lung homogenate than that in group 2 (p < .05 for both) but similar in both group 1 and group 3; Conclusion: Etanercept has favorable effects on alveolarization as well as inflammation and oxidative stress markers in a neonatal rat model of BPD.

SUMMARY Objective Leukocyte contamination during blood transfusion can cause many adverse effects. Filtration can be performed either at bedside during the transfusion or as pre-storage filtration. Pre-storage filtration is superior to bedside filtration because leukocytes are removed prior to storage, thus preventing further adverse effects associated with the storage of these cells. Methods and Materials One hundred and six infants were randomised into two groups: pre-storage filtration (group 1, n = 53) and bedside filtration (group 2, n = 53). C-reactive protein (CRP) and interleukin-6 (IL-6) levels were analysed within 24 h prior to the transfusion and 24 h after completion of the transfusion. Results In group 1, pre-transfusion median CRP and IL-6 levels were 2·95 (0·73–10·25) mg L−1 and 8·59 (3·45–20·55) pg L−1, respectively, and post-transfusion median CRP and IL-6 levels were 2·28 (0·44–12·87) mg L−1 and 6·62 (2·18–27·87) pg L−1, respectively. In group 2, pre-transfusion median CRP and IL-6 levels were 1·30 (0·40–7·84) mg L−1 and 4·40 (2–17·12) pg L−1, respectively, and post-transfusion median CRP and IL-6 levels were 3·50 (0·50–7·85) mg L−1 and 8·30 (3·48–23·75) pg L−1, respectively. There were no differences between pre-storage and post-storage leukoreduction average IL-6 and CRP levels in either group (P > 0·05 for both). Packed red blood cell (PRBC)-related necrotizing enterocolitis was detected in one infant in group 2. Conclusions Because leukocytes in PRBC transfusions can be associated with many undesirable effects, leukoreduction is the best choice to prevent those effects. However, this method is still controversial. We demonstrated that using pre-storage and post-storage leukoreduction methods in erythrocyte transfusions did not change CRP or IL-6 levels, which are indicators of acute-phase response.

Metabolic bone disease (MBD) is one of the important complications of prematurity. Early and adequate nutritional interventions may reduce the incidence and potential complications of MBD. The present study aimed to evaluate bone metabolism in twins via biochemical parameters and quantitative ultrasound (QUS) and to compare the results between twin pairs. Moreover, twin infants were evaluated in terms of potential risk factors likely to have impact on MBD. Forty-three pairs of twins were included in the study. Serum calcium, phosphorus, magnesium, and alkaline phosphatase concentrations were assessed and bone mineral density was measured using QUS (speed of sound, SOS) at postnatal 30 d. Co-twin with the higher birth weight was assigned to Group 1 (n = 36) and the other twin was assigned to Group 2 (n = 36). Birth weight and head circumference were significantly higher in the infants of Group 1 compared with Group 2. No significant difference was found among the groups in terms of gender, history of resuscitation, length of stay in intensive care unit (ICU) or in the incubator, duration of total parenteral nutrition (TPN), type of nutrition, vitamin D use, biochemical parameters, and the SOS value. The factors likely to affect SOS, including type of pregnancy, maternal drug use, gender of infant, birth weight, head circumference at birth, gestational week, length of stay at the ICU, duration of TPN, type of nutrition, resuscitation, vitamin D use, and levels of calcium, phosphorus, magnesium, and alkaline phosphatase were entered into the model. The phosphorus level and the maternal drug use were found to be the factors that significantly reduced SOS, whereas pregnancy after assisted reproductive techniques was found to be a significant enhancing factor.

The aim of this study was to compare the efficacy of orally administered Lactobacillus reuteri (L. reuteri) versus nystatin in prevention of fungal colonization and invasive candidiasis in very low birth weight infants.A prospective, randomized comparative study was conducted in preterm infants with a gestational age of ≤32 weeks and birth weight of ≤1500 g. Patients were randomized into two groups, to receive L. reuteri or nystatin. Skin and stool cultures were performed once a week for colonization and blood cultures for invasive infections. The trial was registered to ClinicalTrials.gov under identifier NCT01531192.A total of 300 preterm infants were enrolled (n = 150, for each group). Gastrointestinal colonization and skin colonization rates were not significantly different between the groups (18.7% versus 16%, p = 0.54 and 14% versus 12%, p = 0.6, respectively). Invasive candidiasis was detected in two patients of the probiotic group and one patient of the antifungal group. Proven sepsis, feeding intolerance, and duration of hospitalization were significantly lower in the probiotics group than in the antifungal group.Prophylactic L. reuteri supplementation is as effective as nystatin, and more effective in reducing the incidence of proven sepsis in addition to its favorable effect on feeding intolerance.

Aim Social, emotional, cognitive and language development of infants is provided with early diagnosis of hearing deficit. Hearing deficit is reported with a rate of 1-6 in 1000 live births in healthy newborns, while it reaches up to 10-30 in 1000 live births in newborns with risk factors. We aimed to compile the results of the hearing screening program applied in our hospital. Material and methods The records of the hearing screening program were examined and the results were compiled by reaching the records of the patients who were found to have hearing deficit. Results Hearing test was applied in a total of 142 128 patients between 2005 and 2011. Hearing test was performed by evoked autoaucistic emission for two times in 26 690 of these patients and for three times in 2 412. A diagnosis of hearing deficit was made in 385 patients (0.27%) after application of ARB (Auditory Brainstem Response). The medical records of 171 of the patients who were referred for advanced investigations and treatment were obtained. 116 of these patients had a history of hospitalization in neonatal intensive care unit, while 55 patients had no history of hospitalization in neonatal intensive care unit. 49 of the patients had a gestational age below the 32(th) week and 122 had a gestational age above the 32(th) week. The median gestational age and birth weight values and ranges were found to be 35 (22-43) and 2 140 g (580-4 590 g), respectively. The risk factors included intrauterine growth retardation (n=24), multiple pregnancy (n=22), hyperbilirubinemia (n=74), blood exchange because of hyperbilirubinemia (n=7), sepsis (n=52), hypoglycemia (n=2), use of aminoglycoside and glycopeptide (n=99), use of furosemide (n=27), mechanical ventilation therapy (n=37), polycythemia (n=12), prenatal asphyxia (n=2), respiratory distress syndrome (n=45), chronic lung disease (n=11), surgery for retinopathy of prematurity (n=8) and hearing deficit in the mother or father (n=7). Conclusions In addition to the necessity of performing hearing screening in all newborns, infants with risk factors should be determined, hearing deficit should be screened with repeated hearing tests and social, emotional, cognitive and language development of the infant should be assured.

Background and Objective: It is essential to establish optimum parameters for maintaining the quality of stored milk until the moment of consumption with minimal deterioration of its properties. The aim of the study was to evaluate total antioxidant capacity (TAC) and total oxidation status (TOS) of fresh and freeze-stored samples (at −80 ◦ C) of preterm human milk (HM). Methods: Samples of colostrum were collected from 98 healthy women within the first 4 days after delivery. The total milk volume collected (6 ml) was divided in two aliquot parts: 3 ml for the fresh analysis which was done immediately after the extraction and 3 ml for storage under freezing conditions at −80 ◦ C for three months. The

Objective To investigate the effectivity of pentoxifylline (PTX) and immunoglobulin M (IgM)-enriched intravenous immunoglobulin (IVIG) therapy in the treatment of neonatal sepsis (NS), alone or in combination. Study design This was a prospective, double-blind, controlled study. Newborns with suspicion of sepsis were enrolled in the study. The patients were separated into four groups according to treatment protocol: Group 1 = placebo, Group 2 = pentoxifylline, Group 3 = IgM-enriched IVIG, and Group 4 = pentoxifylline + IgM-enriched IVIG. Blood samples were taken for C-reactive protein, interleukin-6, neutrophil CD64 expression, and tumor necrosis factor-alfa measurements immediately before treatment (1st day), and measurements were repeated on the 2nd and 4th days of the therapy. Results A total of 204 patients, 51 in each group, were recruited into the study. There were no significant differences for symptoms of sepsis among groups, except lethargy. No significant differences were observed among the groups according to laboratory data. Overall mortality rate was 8.8%. The rates of morbidities and mortality among study groups were similar. Conclusion PTX and IgM-enriched IVIG therapies, either alone or in combination, did not reduce the rates of morbidities and mortality in NS.

Twin anemia/polycythemia sequence (TAPS) is characterized by large intertwin hemoglobin (Hb) differences without signs of twin oligopolyhydramnios. The spontaneous form complicates approximately 3-5% of monochorionic twin pregnancies. TAPS placentas are characterized by the presence of only very few and small unidirectional arteriovenous anastomoses, which allow a slow transfusion of blood from the donor to the recipient, gradually leading to highly discordant Hb levels. Neonatal morbidity in TAPS appears to be mainly limited to hematological problems at birth. Donor twins may be severely anemic and require blood transfusions, whereas recipient twins may be severely polycythemic and require partial exchange transfusion (PET). We herein report monochorionic twins with TAPS: the anemic twin was transfused with the blood concomitantly obtained from the polycythemic co-twin during PET. To our knowledge this is the first therapeutic approach using a recipient twin's whole blood as a donor source instead of a foreign blood donor. In this case, we have approached this recently (un)known form of chronic fetofetal transfusion from a different aspect. In our opinion, this will lead to new postnatal therapeutic approaches for optimal TAPS management.

Background Valvular heart disease constitutes the majority of all causes of cardiac disease in pregnancy. The significant physiological haemodynamic changes of pregnancy may cause serious cardiac problems leading to severe maternal and foetal morbidity and mortality. In this study, we evaluate the effect of maternal rheumatic valvular disease requiring definitive operation concurrent with caesarian delivery on maternal and foetal outcome. Methods Between 2003 and 2010, a total of nine pregnant women and nine live births were examined. Immediately after caesarean section, the newborns were examined by the neonatologist and transferred to the neonatal intensive care unit. All the mothers were followed routinely with clinical and echocardiographic examinations. Results The age at the time of delivery ranged between 21 and 36 years (median 31 years). Postoperative period of mothers was uneventful and mean hospital stay was 7.56 ± 3.97 days. Birth weight for the newborns was ranged between 1370 and 2900 g. Six of the newborns were premature (≤37 weeks). Four newborns were small for gestational age (SGA). There was no mortality in newborns. Hospital stay for the newborns ranged between four and 54 days. Conclusions Careful follow-up of pregnancies with valvular heart diseases and determining the optimal time of cardiac intervention are the essential issues. We suggest that careful follow-up of both mother and foetus until at least the 28th gestational week, following which combined caesarian section and cardiac surgery can be performed.

Chorioamnionitis (CA) is an acute inflammation of the membranes and chorion of the placenta. The aim of this study was to determine the effect of histological CA on the short-term outcome of preterm infants.The clinical characteristics and outcomes of the preterm infant including respiratory distress syndrome, duration of mechanical ventilation, patent ductus arteriosus (PDA) requiring medical treatment or ligation, necrotizing enterocolitis, bronchopulmonary dysplasia, death and intraventricular hemorrhage (IVH; grade III-IV) were analyzed.Two hundred and eighty-one infants born at ≤32 weeks gestational ages were included. Infants were divided into two groups: one with histological CA (n = 145) and without histological CA (n = 136). Mean gestational age was 28.8 ± 2.6 weeks and 29.1 ± 2.5 weeks, and mean birth weight was 1138 ± 350 g and 1210 ± 299 g, respectively. There were no differences in gestational age and birth weight among the groups. Compared with the group, histological CA was associated with early onset sepsis (p = 0.007), PDA (p = 0.003), IVH (p = 0.03), and death (p = 0.04).Maternal histological CA is an important risk factor for preterm deliveries and associated with serious morbidities such as early onset sepsis, IVH, PDA and increased mortality.

Objectives and aim Very low birth weight infants require 3 - 4 g/kg/day protein intake to provide satisfactory postnata growth rates and neurodevelopmental outcomes. However, they have fewer functional nephrons, thereby increasing vulnerability for impaired renal functions. The aim of this study was to investigate the effect of different amounts of enteral protein intake during the fortification of human milk on renal glomerular and tubular functions. Material and methods Preterm infants were randomized into three groups in terms of their daily protein intake: standard fortification (3 g/kg/d), moderate fortification (3.3 g/kg/d), and aggressive fortification (3.6 g/kg/d). Serum urea, creatinine (Cr), Cystatin C (Cys-C) and urinary β2 microglobulin (β2M) levels were assessed and compared between groups. Results Serum urea, Cr, Cys-C and urinary β2M levels were similar in all three groups, both on discharge and postnatal Day 14 (p > 0.05). Mean Cr and β2M levels were significantly lower on discharge (p 0.05). Conclusion Enteral protein intake up to 3.6 g/kg/d did not alter the tubular and glomerular functions in very preterm infants. However, the long-term renal effects in these infants maintained on a high protein intake remain unknown and should be addressed in future studies.

Tissue damage in necrotizing enterocolitis (NEC) of infants occurs as a result of an uncontrolled inflammatory response. The aim of this study was to investigate any potential anti-inflammatory effects that Etanercept may have on the inflammatory response in an experimental NEC model in newborn rats. Newborn pups were randomized into three groups immediately after birth (Control, NEC + Placebo and NEC + Etanercept). Pups in the NEC + Placebo and NEC + Etanercept groups were subjected to an NEC-inducing protocol (hypercarbia, hypothermia and hyperoxia) twice a day for 3 days. Pups in the NEC + Etanercept group were given an intraperitoneal injection of Etanercept. Rats were harvested for biochemical and histopathological examinations. The histopathological injury score of rats in the NEC + Placebo group was significantly higher compared to the NEC + Etanercept and Control groups (p

Developmental care in neonatal intensive care unit The incidence of preterm births have increased worldwide and in our country in recent years. Related to advances in neonatal intensive care, the mortality of the preterm births decreases but the morbidity increases. Developmental problems comprise the main portion of the morbidity. Strategies and new approaches are needed to decrease the morbidity. This review is about the approaches of developmental care used in neonatal intensive care units to support the development of preterm babies.

The present investigation was designed to study the effect of blood transfusion on cardiac output and perfusion index. The aim was to demonstrate a relationship between hematocrit, lactate, cardiac output and perfusion index in anemic preterm infants and to investigate significant changes in these parameters induced by RBC transfusion.Anemic infants who were under 35 weeks of gestational age (GA) and were in a stable clinical condition without respiratory or cardiac problems, signs of sepsis, or renal disease at the time of investigation were enrolled in the study. Enrolled infants received 15 ml/kg pure red blood cells over 4 h. Hematocrit and lactate levels were studied before and after transfusion. Cardiac output was measured by an ultrasound device (USCOM 1A) and perfusion index was monitored by pulse oximeter (MasimoRad7).Cardiac output decreased by 9% (p0.05), due to decrease in heart rate by 10% (p0.05) and stroke volume significantly by 5% (p0.05) both in left and right sided cardiac measurements. Perfusion index significantly increased and lactate levels significantly decreased after transfusion (p0.05). Htc was inversely correlated with lactate levels, HR, CI and CO (r = -0.33, p = 0.01; r = -0.53, p = 0; r = -0.37, p = 0.004, r = -0.28, p = 0.03). PI was not significantly correlated with Htc levels before and after transfusion (r = 0.07, p = 0.7 and r = 0.007, p =0.97).Our data support that heart rate, CO and CI and lactate levels increased as a response to anemia in preterm infants and RBC transfusion improved perfusion index suggesting better tissue oxygenation.

Background Although oxidative stress-related diseases mostly affect neonates with extremely low birthweight, healthy preterm and term newborns may also be at risk of oxidative damage. There have been studies concerning factors that affect the level of oxidative stress biomarkers in term and preterm neonates, but there has not been a study of the reference values of oxidative stress biomarkers in healthy newborns having no risk factors. The aim of the present study was to clarify this issue. Methods Serum total antioxidant capacity (TAC) and total oxidant status (TOS) were assessed by Erel's method. TAC and TOS values were measured in 100 term infants, 57 boys and 43 girls, with a mean gestational age of 39 weeks and a mean birthweight of 3174 g. Results All blood samples for TAC and TOS were taken on the fifth day. The median TAC and TOS values for all male and female neonates were 1.92 mmol Trolox equivalent/L (min–max; 1.41–2.09) and 12.93 μmol H2O2/L (min–max: 3.01–53.94), respectively. TAC and TOS values were not statistically different in male and female newborns. TAC and TOS values were not statistically different in newborns who had been delivered via a vaginal route or by cesarean section. Conclusion This study can be used as a guide for the reference range of TAC and TOS values for healthy term newborns.

The aim of this study was to determine the postnatal risk factors associated with hearing loss as well as the prevalence of hearing loss among high-risk preterm infants in newborn hearing screening (NHS). We performed a retrospective study of high-risk preterm infants born with a gestational age ≤32 weeks and/or a birth weight ≤1,500 g. A NHS procedure was performed by automated auditory brainstem response (AABR) and automated evoked otoacoustic emission (TEOAE). Infants who failed TEOAE or AABR or both tests were referred to a tertiary audiology center for diagnosis confirmation and management. Postnatal risk factors associated with hearing loss were evaluated and compared for preterm infants with and without hearing loss. 1,360 high-risk preterm infants were assessed. Permanent hearing loss was found in 19 (1.4%) infants. Multivariate analysis revealed that proven sepsis (p = 0.019), mechanical ventilation ≥5 days (p = 0.024), loop diuretics (p = 0.001), patent ductus arteriosus ligation (p = 0.018) and operation for retinopathy of prematurity (ROP) (p = 0.034) were significant related factors for the hearing loss. This study showed a low prevalence of hearing loss and an association between operation for ROP and hearing loss in preterm infants, which has not been defined previously. Our results suggest that every neonatal intensive care unit should determine their own risk factors and take precautions to prevent hearing loss for these high-risk preterm infants.

Background The aim of red blood cell (RBC) transfusion is to improve tissue oxygenation and relieve anemia-related symptoms in preterm infants. We sought to assess regional cerebral (rSO2C) and mesenteric (rSO2M) tissue oxygenation using a near-infrared spectroscopy (NIRS) method and vital signs (heart rate, arterial oxygen saturation, mean arterial blood pressure) in symptomatic preterm infants with anemia who received RBC transfusions. Study Design and Methods Twenty-three symptomatic patients with anemia who were at least 1 month old, whose gestational age was less than 30 weeks, and whose hematocrit level was not more than 27% were involved in the transfusion group. The control group consisted of preterm infants (Hct ≥ 32) matched for gestational age and postnatal days. The transfusion group was divided into two subgroups based on transfusion duration (2 or 4 hr). Both study groups were monitored for vital signs and rSO2C, rSO2M, and mesenteric-cerebral oxygenation ratio (MCOR) via NIRS for 24 hours simultaneously and compared with the control group. NIRS variables and vital signs obtained before, during, and after transfusion were compared both within and between 2- and 4-hour groups. Results rSO2C, rSO2S, and MCOR increased during and after transfusions, while cerebral fractional oxygen extraction (FOEC) and mesenteric fractional oxygen extraction (FOEM) decreased. No significant difference was found between subgroups for NIRS measurements and vital signs. A weak correlation between hemoglobin concentration and FOEC and FOEM was found. Conclusion RBC transfusion improved cerebral-mesenteric oxygenation and MCOR in symptomatic infants with anemia, independent of the transfusion duration.

Surfactant treatment in the early hours of life significantly decreases the rates of death and air leak, and increases survival without bronchopulmonary dysplasia (BPD) in preterm infants. We aimed to compare the impact of early surfactant (ES) administration to late selective (LS) treatment on neonatal outcomes in preterm infants.All preterm infants between 25 and 30 wks gestational age and who were not entubated in the delivery room and did not have any major congenital malformation or perinatal asphyxia were randomized to ES treatment (200 mg/kg Curosurf® administration in 1 hour after birth) or LS treatment (200 mg/kg Curosurf®administration in the first 6 h of life if needed). The patients were treated by nasal continuous positive airway pressure (nCPAP) treatment regardless of the surfactant requirement. Outcomes were the necessity of mechanical ventilation, nCPAP duration, the oxygen requirement duration, the rates of BPD, retinopathy of prematurity (ROP) and mortality, and the assessment of the following situations; (pneumothorax, patent ductus arteriosus (PDA), necrotizing enterocolitis (NEC), and intraventricular hemorrhage (IVH) ≥ grade III).Among 159 infants enrolled in the study, 79 were randomized to ES and 80 to LS treatment groups. Thirty-five patients (44%) in the LS treatment group needed surfactant administration. Necessity of second dose surfactant administration was 8.9% in the ES treatment group. Although necessity of mechanical ventilation, nCPAP duration, oxygen need duration, rates of PDA, NEC, BPD, ROP stage3 and mortality did not show a significant difference between groups, the ES treatment group had lower rates of pneumothorax and IVH ≥ grade III when compared to the LS treatment group.ES treatment decreases IVH (≥ grade III) and pneumothorax rates but does not have any effect on BPD when compared to LS.

Objective: To assess the Turkish National Newborn Screening Programme (NNSP) for congenital hypothyroidism (CH). Retrospective study based on the data from NNSP. Methods: Since December 2006, a nationwide screening programme for CH has been conducted in Turkey by the Turkish Directorate of Public Health (TDPH) in cooperation with several institutions. We evaluated the database between January 2008 and July 2010 of this programme. According to the methodology of the NNSP, between three and five days of age (or at discharge from the hospital, if this occurs earlier) blood specimens were routinely collected from neonates on filter paper, by puncturing the heel. The accepted thyroid-stimulating hormone cut-off level for recall was 20 mU/L initially and 15 mU/L subsequently. The incidence of possible CH by years was reported. Results: During the evaluation period, 3223765 newborns were tested. The mean annual incidence of possible CH showed a gradual increase over the years (1:888 in 2008, 1:592 in 2009, and 1:469 in 2010). Regional differences were noted. Although the mean age of blood sampling did not change by years, the mean age at notification for suspected CH decreased from 19.2 to 15.7 days from 2008 to 2010. Conclusions: We reported the first assessment of NNSP in Turkey. An improvement in performance measures for the CH screening programme has been noted. Knowledge on incidence of confirmed CH is not yet available in the database. Conflict of interest:None declared.

This study aims to compare the efficacy of orally administered Saccharomyces boulardii versus nystatin in prevention of fungal colonization and invasive fungal infections in very low birth weight infants.A prospective, randomized comparative study was conducted in preterm infants with a gestational age of ≤ 32 weeks and birth weight of ≤ 1,500 g. They were randomized into two groups, to receive S. boulardii or nystatin. Skin and stool cultures were performed for colonization and blood cultures for invasive infections, weekly.A total of 181 infants were enrolled (S. boulardii group, n = 91; nystatin group, n = 90). Fungal colonization of the skin (15.4 vs 18.9 %, p = 0.532) and the stool (32.2 vs 27 %, p = 0.441) were not different between the probiotic and nystatin groups. Two patients had Candida-positive blood culture in the nystatin group whereas none in the probiotic group. Feeding intolerance, clinical sepsis, and number of sepsis attacks were significantly lower in the probiotics group than in the nystatin group.Prophylactic S. boulardii supplementation is as effective as nystatin in reducing fungal colonization and invasive fungal infection, more effective in reducing the incidence of clinical sepsis and number of sepsis attacks and has favorable effect on feeding intolerance.

To compare the effectiveness of oral clarithromycin versus placebo treatment in preventing feeding intolerance in very low birth weight (VLBW) infants.A prospective, randomised controlled trial in which two groups of preterm infants (birth weight1500 g) were randomised to clarithromycin (7.5 mg/kg/dose every 12 h) or placebo treatment. During the period, 38 infants, whose parents accepted participation, were enrolled in the study. Feeding intolerance and time to achieve full enteral feeding were considered as primary outcome measures.Feeding intolerance was significantly longer in placebo than clarithromycin (p = 0.031). Time to achieve full feeding after beginning the treatment was equal among the groups.This is the first randomised controlled study of clarithromycin and placebo treatment that compares the improvement of feeding intolerance in VLBW infants. Our findings indicate a dramatic improvement in feeding intolerance after oral clarithromycin treatment. But according to our results, clarithromycin-treated infants were not able to attain full enteral feeding more quickly than placebo. This may be due to prophylactic usage of clarithromycin. Significant differences might have resulted if only infants who had feeding intolerance were recruited.

The aim of this study was to explore the effects of early oral ibuprofen administration on the incidence of hemodynamically significant patent ductus arteriosus (hsPDA) and define the association between serum ibuprofen levels and ductal closure.Preterm infants with a gestational age of Nineteen infants who received one course (three doses) of prophylactic ibuprofen in the intervention group and 17 infants in the control group who underwent an echocardiographic examination on the fourth day of life were analyzed. hsPDA was observed in five (26 %) infants in the intervention group and ten (58 %) infants in the control group (p = 0.09). In the intervention group two infants experienced gastrointestinal bleeding two infants had spontaneous intestinal perforation, and two infants developed acute kidney failure. Mean serum ibuprofen level was 28.7 +/- 16.9 mg/L in the intervention group, and there was no correlation between ibuprofen level obtained on the fourth day and ductal closure.Oral ibuprofen prophylaxis reduces the rates of hsPDA even it is not statistically significant. The ductal closure rate did not correlate with serum ibuprofen levels. Due to high prevalence of adverse events observed, our data do not support the use of oral ibuprofen for prophylaxis of hsPDA.

Objective: We evaluated the characteristics of babies with nonimmune hydrops fetalis born at our hospital during a four-year period. Material and Methods: All newborns with a prenatal or early neonatal diagnosis of nonimmune hydrops fetalis based on clinical history, physical and laboratory examination during the period between January 2008 and December 2011 were evaluated retrospectively. results: A total of 39 newborns with hydrops fetalis were included in this study. Twenty two infants (56.4%) were diagnosed in the antenatal period, and the etiological factor was evident in the prenatal period in 8 infants (20.5%). The most common finding was skin edema in all patients (100%), while neonatal ascites (84.6%) was the second most common sign. Findings related with nonimmune hydrops fetalis were as follows: congenital heart disease (2/39), arrythmia (2/39), congenital cystic adenomatoid malformation (2/39), chylothorax (2/39), cystic hygroma (1/39), twin-totwin transfusion syndrome (7/39), anemia (3/39), genetic/chromosomal abnormalities (5/39), and perforated intrauterine meconium ileus (1/39). No obvious cause was identified in 35.8% (14/39) of cases and these were classified as idiopathic. The mortality rate was 76.9%, and 16 of them (41%) died within the first 24 hours of life. conclusion: The mortality rate is still very high in nonimmune hydrops fetalis. The most common signs were skin edema and neonatal ascites in the antenatal period. Diseases of organs and systems were frequent among the causes of nonimmune hydrops fetalis. Comprehensive diagnostic testing and examinations should therefore be performed as soon as possible.

The aim of the present study was to characterize the pharmacokinetic profile of oral ibuprofen on consecutive 3 d by trough serum levels, and if possible to define a cut-off level for ductal closure in preterm infants. The study enrolled 20 preterm infants with gestational age ≤30 weeks, birth weight1250 g and hemodynamically significant patent ductus arteriosus (hsPDA). Patients received oral ibuprofen at an initial dose of 10 mg/kg, followed by 5 mg/kg at 24 and 48 h. Patients were compared for serum ibuprofen levels in addition to their demographic and clinical data in case of their response to the treatment. hsPDA closed in 16 (80%) of the patients. Although mean ibuprofen levels on consecutive 3 d showed a plateau in general, ibuprofen serum levels on the first treatment day were statistically low in patients with unclosed hsPDA (p = 0.003). The optimal cut-off value for serum ibuprofen level on the first treatment day was measured as 5.5 mg/l with 100% sensitivity and 93% specificity. Serum ibuprofen level on the first treatment day seems to be an important factor for a successful ductal closure. Target concentration approach by the evaluation of trough level may be applicable to real-time dosing strategy.

Although moderate therapeutic hypothermia is the only proven neuroprotective therapy in neonatal hypoxic ischemic encephalopathy secondary to perinatal asphyxia (PA), there is lack of data for its effect on hemostasis. To investigate the effect of neonatal asphyxia on hemostasis and to evaluate the effect of whole body cooling on hematological parameters. Hematological parameters evaluated on the first day of patients with PA before start of hypothermia were compared with those of healthy controls. The effects of whole body cooling on the same parameters were also evaluated on the fourth day. A total of 17 neonates with PA and 15 healthy controls were included. Mean values for prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (aPTT), and d-dimer obtained on the first day were significantly higher in the PA group compared to healthy controls (P ≤ .001 for all comparisons), whereas platelet count, levels of fibrinogen, factors II, V, VII, IX, X, and XI were significantly lower (P ≤ .005 for all comparisons). Levels of factor XIII were normal in both groups. In the study group, mean values for PT, INR, aPTT, and d-dimer evaluated on postnatal day 4 were significantly lower compared to values obtained on the first day of birth in PA group (P < .05 for all comparisons), with statistically significant increases in mean levels of fibrinogen, factor II, V, VII, IX, X, and XII (P < .05 for all comparisons). PA results in significant reductions in levels of factors of the extrinsic pathway and has been associated with thrombocytopenia and disseminated intravascular coagulation. Hypothermia may actually improve the clinical picture in such patients rather than aggravating the hemostatic disturbance, particularly with the implementation of supportive treatment.

To evaluate the efficacy of nasal intermittent mandatory ventilation (NIMV) in reducing the duration of respiratory distress compared with nasal continuous positive airway pressure (NCPAP) in transient tachypnea of the newborn (TTN).In this randomized-prospective study, 40 infants with a gestational age ≥ 37 weeks and birth weight ≥ 2000 g with TTN were randomized to either nonsynchronized NIMV (n = 20) or NCPAP (n = 20). The primary end point was the reduction of the duration of respiratory distress. Secondary end points were the duration and level of oxygen supplementation, the incidence of complications such as pneumothorax, pneumonia and respiratory failure requiring entubation.There were no significant difference in the duration of respiratory support (28.0 ± 19.2 h versus 32.2 ± 23.3 h, p = 0.231), O2 therapy (31.2 ± 15.6 h versus 29.0 ± 19.3 h, p = 0.187), duration of TTN (67.6 ± 36.5 h versus 63.3 ± 39.1 h, p = 0.480) and hospitalization (6.2 ± 2.6 d versus 5.4 ± 2.0 d, p = 0.330) between the groups. The rate of complications were not significantly different between the groups.Our study indicates that NIMV is well tolerated and as effective as NCPAP in the treatment of TTN.

BACKGROUND: The primary aim of this randomized study was to describe the feasibility of early administration of surfactant via a thin catheter during spontaneous breathing (Take Care) and compare early mechanical ventilation (MV) requirement with the InSurE (Intubate, Surfactant, Extubate) procedure. METHODS: Preterm infants, who were

Hepatitis B virus (HBV) infection continues to be a serious global health problem. During the course of HBV vaccination, we observed C-reactive protein (CRP) elevation in term infants without sepsis. Therefore, we prospectively studied interleukin-6 (IL-6) and CRP responses to HBV immunization. In 70 healthy term infants without signs and symptoms of sepsis and sepsis risk factors, IL-6, CRP, and white blood cell count levels were determined before and 24 h after immunization. Significant increases in CRP levels were seen 24 h after vaccination (p < 0.001). Although CRP levels of 22 infants at second evaluation were above the cutoff level for sepsis (4.82 mg/L), they had no clinical signs and symptoms of sepsis. After 48–72 h, CRP levels of these infants returned to normal levels with no blood culture positivity. Conclusion: our study showed that HBV vaccine is responsible for CRP elevation in term infants after vaccination at birth. To the best of our knowledge, this is the first study evaluating CRP response to HBV vaccine at birth in term infants. We suggest that this response should be considered in differentiation of early neonatal sepsis to avoid unnecessary antibiotic use.

Objective Although neurodevelopmental outcomes related to the management of patent ductus arteriosus with intravenous indomethacin and ibuprofen are known, little data on the long-term effects of oral ibuprofen can be found in the literature. Method A follow-up study of 99 infants with birth weight ≤ 1,500 g and gestational age ≤ 32 weeks who received either oral or intravenous ibuprofen for patent ductus arteriosus was conducted to assess at 18 to 24 months (corrected age), abnormal neurological, neurosensory, and cognitive impairment were defined as follows:neurological outcomes included moderate/severe cerebral palsy, neurosensory outcomes included bilateral hearing loss and blindness in either eye, and cognitive impairment included mental developmental index score Results The 18- to 24-month (corrected age) long-term outcomes of 30 subjects who received oral ibuprofen were compared with 27 subjects who received intravenous ibuprofen by certified and experienced examiners who were blind to the definitions of the groups. The results revealed that the long-term outcomes of the treatment regimens did not significantly differ. Conclusions Preterm infants who were treated with oral ibuprofen for patent ductus arteriosus had similar neurological, neurosensory, and cognitive outcomes to patients who received intravenous ibuprofen at 2 years of age.

OBJECTIVE Transient tachypnea of the newborn (TTN) results from inadequate neonatal lung fluid clearance. Low-dose dopamine induces natriuresis in the kidneys and it has been assumed that, at this low dosage, dopamine increases renal perfusion in critically ill patients. Medium doses have positive inotropic and chronotropic effects via increased β-receptor activation. Recent studies have demonstrated that dopamine stimulates the clearance of pulmonary edema. Furthermore, β-adrenergic agonists regulate Na+ channels and Na-K-ATPase activity in the pulmonary epithelium. This study investigated the effect of dopamine at different dosages on TTN treatment. METHODS A prospective controlled study examined 60 infants with TTN older than 34 weeks of gestation who required at least 24 h of O2 and nasal continuous positive airway pressure (nCPAP) treatment. The infants were randomized into three groups of 20: controls, infants treated with low-dose dopamine (3 μg/kg/min), and infants treated with a medium dose (5 μg/kg/min). The control and study groups were compared in terms of the requirement for mechanical ventilation, and the durations of nCPAP, oxygen requirement, and hospitalization. RESULTS The requirement for mechanical ventilation, and durations of nCPAP, oxygen requirement, and hospitalization did not differ significantly among the three groups (P=0.54, 0.16 and 0.11, respectively). CONCLUSION Dopamine treatment in low-moderate doses does not improve the outcome in TTN. Thus, further studies in this area are needed.

Background: Treatment options for the closure of a hemodynamically significant patent ductus arteriosus (hsPDA) include medical therapy such as ibuprofen and indomethacin and surgical ligation. Objective: To evaluate the efficacy of intravenous paracetamol in preterm infants with hsPDA whose feeding was contraindicated or had feeding intolerance. Methods: Preterm infants with hsPDA were started on intravenous paracetamol treatment with parental consent. Paracetamol was administered at a dose of 60 mg/kg/day, in four divided doses, for a period of 3 days. In the absence of closure of hsPDA, treatment was extended up to 6 days, after which echocardiographic examination was performed. Results: A total of 10 preterm infants were included in the study with a median gestational age of 274/7 weeks (minimum–maximum: 24–29) and a median birth weight of 775 g (590–990). The first dose of intravenous paracetamol was given after a median of 6 days (2–15). On echocardiographic examination, median internal ductal diameter was 2 mm (1.5–3), with a median left atrium-to-aortic root ratio of 1.95 (1.6–2.2). Intravenous paracetamol resulted in successful closure of hsPDA in all patients. Conclusions: This study is the first case series in the literature which used intravenous paracetamol treatment for hsPDA. We believe that intravenous paracetamol could be used as an alternative drug for infants. Further prospective randomized-controlled trials are needed to evaluate the efficacy of intravenous paracetamol for the closure of hsPDA.

Background: Fortification of human milk (HM) is a common clinical practice to adapt breast milk to the nutritional needs of very low birth weight (VLBW) infants. The optimal method for HM fortification remains to be determined, and a variety of protocols are currently used in neonatal intensive care units. Objective: It is believed that standard fortification is insufficient to meet the needs of VLBW infants. Therefore, we designed a randomized prospective study that investigated the effects of varying levels of blind fortification on short-term growth and metabolic responses of preterm infants. Methods: Eligible infants were randomized into 3 groups: standard fortification (SF), moderate fortification (MF), and aggressive fortification (AF). Short-term growth, feeding intolerance, and urea, calcium, phosphorus, and alkaline phosphatase levels were assessed. Results: There were 26, 29, and 29 infants in the SF, MF, and AF groups, respectively. The baseline characteristics of the groups were similar. Daily weight gain and length at discharge did not differ among the groups; however, head circumference was significantly higher in the MF and AF groups compared with the SF group. Urea, calcium, phosphorus, and alkaline phosphatase levels were similar between the groups. Conclusion: We demonstrated that blind fortification of HM, even with higher amounts than recommended by manufacturers, did not cause any measured adverse effects on the metabolic response of preterm infants. Anthropometric measurements (except head circumference) were not different between the different dosages of fortification.

Background The aim of this study was to investigate any changes in mean platelet volume (MPV) in patients with neonatal sepsis (NS). Methods Subjects were stratified into two groups: proven sepsis (Group 1a) and clinical sepsis (Group 1b). The control group (Group 2) consisted of healthy newborns matched for gestational age and birth weight. Results A total of 100 patients with NS (35 with proven sepsis and 65 with clinical sepsis) and 50 healthy controls were enrolled. A comparison of markers of sepsis obtained at baseline revealed white blood cell count (WBC), C-reactive protein (CRP), interleukin-6 (IL-6), and MPV levels to be significantly higher in newborns with sepsis compared to healthy controls (P = 0.01

Compared with term infants, late preterm infants are immature physiologically and metabolically, and have higher risks for medical complications such as respiratory distress, hypoglycemia, hyperbilirubinemia, sepsis, feeding difficulty and poor neurodevelopmental outcomes. The incidence of late preterm birth is increasing. We evaluated the clinical and demographic characteristics, short-term outcomes and clinical courses of late preterm infants admitted to our neonatal intensive care unit (NICU). Data from NICU admissions of 605 late preterm and 1477 term infants in the 1-year period between June 2010 and May 2011 were analyzed. There were 2004 late preterm deliveries and 18,854 total deliveries. Of late preterm infants, 30% were admitted to the NICU. The mean gestational age and birth weight were 35(1/7) weeks and 2352 g, respectively. The admission diagnoses were respiratory distress (46.5%), low birth weight (17.5%), jaundice (13.7%), feeding difficulty (13.1%), polycythemia (8.1%) and hypoglycemia (4%); these morbidity rates were higher than those in term infants (p0.001). The overall mean hospitalization period was 7.5 ± 9.1 days. The respective mortality and rehospitalization rates were 2.1% and 4.4%, which were higher than those for term infants (p0.001). In conclusion, late preterm infants should be followed closely for the complications just after birth, and preventive strategies should be developed.

Patent ductus arteriosus is a common problem in very low birth weight infants. Prostaglandin synthesis inhibitors such as indomethacin and ibuprofen are widely used preferred medications for ductal closure but the question of which one should be preferred is controversial. There are some studies in the literature comparing their pharmacokinetics, efficacy, side effects and long-term outcomes. In this review we aimed to focus on prostaglandin synthesis inhibitors with their pharmacodynamic and pharmacokinetic in relation to oral and intravenous forms. Oral ibuprofen seems to be an effective and cheap alternative to the intravenous forms. Studies in extremely low birth weight infants that also evaluate the neurodevelopment will clarify its use.

To determine whether there is an association between platelet counts and patent ductus arteriosus (PDA) incidence and/or closure in preterm newborns.Premature infants with hemodynamically significant PDA (n=154) and a control group without PDA (n=207) who were hospitalized in the NICU were retrospectively evaluated. Platelet counts and other platelet indices including mean platelet volume (MPV) and platelet distribution width (PDW) of the infants in both groups during the first 3 days of life were recorded. Ibuprofen was started in infants with hemodynamically significant PDA and echocardiography was repeated 48 h thereafter to assess the closure of ductus.Median gestational age and birth weight of the infants with PDA were 28 (range 26-29) weeks and 1060 (range 892-1250) g respectively. Platelet counts were significantly lower in the patient group than in the control group (p0.001). Multivariate analysis including gestational age, presence of RDS, presence of thrombocytopenia and PDW showed that hemodynamically significant PDA was independently associated with platelet count150,000 (OR=2.13, 95% CI 1.26-3.61; p=0.005), high PDW (17) (OR=2.68, 95% CI 1.41-5.09; p=0.003) and the presence of RDS (OR=2.25, 95% CI 1.41-3.59; p=0.001). Baseline platelet counts of the infants in whom ductus closed or persisted after ibuprofen treatment were similar.PDA was associated with low platelet count and high PDW but not with other platelet indices in preterm infants. We could not show an association between platelet counts and persistence or closure after medical treatment.

Our aim was to assess trends in neonatal mortality in 2009, evaluate advances in health policy, determine new goals to preserve a higher quality health service, and to prevent neonatal deaths. Data were gathered from the system of the General Directorate of Mother and Child and Family Planning. Maternal age, birth weight, gestational week, delivery at a health center, delivery by trained assistant, antenatal visits, and cause of death were evaluated. The neonatal mortality rate was 10/1,000 in Turkey in 2009, significantly better than rates of 26 in 1998, 17 in 2003, and 13 in 2008. The percentage of pregnant women making a minimum of four antenatal visits was around 80 %. Most deaths were attributable to prematurity and its complications, including 47.2 % of early neonatal mortality (ENM) and 36.1 % of late neonatal mortality (LNM). In ENM, the next-most common causes of death were congenital anomalies other than heart and genetic disorders (17.5 %), infections (6.5 %), asphyxia (6.1 %), and congenital heart disease (4.0 %), whereas in LNM, they were infections (19.9 %), congenital anomalies other than heart and genetic disorders (13.1 %), congenital heart disease (7.7 %), and asphyxia (3.8 %). Neonatal mortality in Turkey has declined within 8 years to level similar to that reached by Organisation for Economic Co-operation and Development countries over 30 years. Our findings show that each of the major causes of the neonatal death can be prevented by available interventions. Interventions to prevent prematurity, early diagnosis of congenital anomalies, and the prevention of infections would contribute to further reductions in neonatal mortality in Turkey.

Summary Introduction Neonatal sepsis remains an important clinical syndrome despite advances in neonatology. Current hematology analyzers can determine cell volume (V), conductivity for internal composition of cell (C) and light scatter for cytoplasmic granularity and nuclear structure (S), and standard deviations which are effective in the diagnosis of sepsis. Statistical models can be used to strengthen the diagnosis. Effective modeling of molecular activity (EMMA) uses combinatorial algorithm of the selection parameters for regression equation based on modified stepwise procedure. It allows obtaining different regression models with different combinations of parameters. Methods We investigated these parameters in screening of neonatal sepsis. We used LH780 hematological analyzer (Beckman Coulter, Fullerton, CA, USA). We combined these parameters with interleukin-6 (IL-6) and C-reactive protein (CRP) and developed models by EMMA. Results A total of 304 newborns, 76 proven sepsis, 130 clinical sepsis and 98 controls, were enrolled in the study. Mean neutrophil volume (MNV) and volume distribution width (VDW) were higher in both proven and clinical sepsis groups. We developed three models using MNV, VDW, IL-6, and CRP. These models gave more sensitivity and specificity than the usage of each marker alone. Conclusions We suggest to use the combination of MNV and VDW with markers such as CRP and IL-6, and use diagnostic models created by EMMA.

Proadrenomedullin (pro-ADM) for the diagnosis of proven and clinical sepsis in a newborn cohort including preterm newborns has not been investigated. We aimed to investigate the value of pro-ADM as a new marker by comparing it with conventional markers in neonatal sepsis (NS). Participants were stratified into three groups; proven sepsis (Group 1a), clinical sepsis (Group 1b), and the control group (Group 2), which consisted of newborns of matched gestational age and birth weight. Sequential measurements of white blood cell count, C-reactive protein (CRP), interleukin-6 (IL-6), and pro-ADM were compared. A total of 76 patients with NS (31 with proven sepsis and 45 with clinical sepsis) and 52 healthy controls were enrolled. Mean baseline serum levels of CRP, IL-6, and pro-ADM were significantly higher in both Group 1a and Group 1b as compared with healthy controls (P < 0.001 for both). Although mean baseline CRP and IL-6 levels were similar between groups, mean baseline pro-ADM level was higher in the proven sepsis group than in the clinical sepsis group (P < 0.001). The use of pro-ADM in combination with other acute-phase reactants such as CRP and IL-6 for the diagnosis and follow-up of patients with NS has high sensitivity and specificity.

SUMMARY Objective Our aim was to determine the relationship between red blood cell transfusion and necrotising enterocolitis (NEC) in all admitted very low birth weight (VLBW) infants with or without transfusion. Study Design All VLBW neonates were categorised into five groups: (i) subjects that developed NEC 48 h after transfusion (n = 31); (iii) subjects that were never transfused but developed NEC, (n = 50); (iv) subjects that were transfused but did not develop NEC, (n = 250) and (v) subjects that were neither transfused nor developed NEC (n = 301). Results A group of 647 infants were enrolled in the study. Mean gestational age and birth weight of the patients were 29 ± 3·1 weeks and 1157 ± 237 g, respectively. The mean age at the onset of NEC in the NEC groups were 20 ± 2·3 days, 12 ± 3 days and 11 ± 2·6 days, respectively (P

Objective: To investigate the role of interleukin-6 (IL-6) and C-reactive protein (CRP) in non-thyroidal illness (NTI) in premature infants. Methods: Serum levels of IL-6 and CRP, thyroid-stimulating hormone (TSH), total thyroxine (T4), free T4 (fT4), total triiodothyronine (T3), and free T3 (fT3) were determined at the 1st, 2nd and 4th weeks of postnatal life in 148 premature infants born before 33 weeks of gestation. Results: At the 1st week, serum T3 was negatively correlated with IL-6(r= -0.33, p= 0.001) and CRP (r= -0.17, p= 0.03). Serum T3 was negatively and more strongly correlated with IL-6 (r= -0.49, p= 0.001) and CRP (r=- 0.33,p= 0.03) at the 2nd week, at which time sepsis frequency and low T3 rates were the highest. At the 4th week, mortality rate was higher among infants with lower T3 levels. Conclusions: High IL-6 and CRP values related to neonatal sepsis might have a significant role in the pathogenesis of NTI in premature infants. Conflict of interest:None declared.