Emel Okulu

Oral Lactoferrin to Prevent Nosocomial Sepsis and Necrotizing Enterocolitis of Premature Neonates and Effect on T-Regulatory Cells

OBJECTIVE Lactoferrin (LF) is effective in the prevention of sepsis in very low birth weight (VLBW) neonates. T-regulatory cells (Tregs) are important subsets of T lymphocytes that control pathogen-specific immune responses and are essential for intestinal immune homoeostasis. The aim of the present study is to determine whether oral LF at a dosage of 200 mg/d reduces nosocomial sepsis episodes and necrotizing enterocolitis (NEC) in premature infants and to evaluate the possible effects of LF on Treg levels. STUDY DESIGN In this prospective, placebo-controlled, double-blind, randomized trial, infants either VLBW or born before 32 weeks were assigned to receive either placebo (n = 25), or 200 mg LF (n = 25) daily throughout hospitalization. Episodes of culture proven nosocomial sepsis and NEC were recorded. The level of FOXP3 + CD4 + CD25hi lymphocytes was studied by flow cytometry at birth and discharge. A third comparison was made with healthy term neonates (n = 16). RESULTS Fewer sepsis episodes were observed in LF-treated infants (4.4 vs. 17.3/1,000 patient days, p = 0.007) with none developing NEC, without statistical significance. Treg levels at birth and discharge were similar, while preterm infants showed significantly lower levels than term controls. However, individual increases in Treg levels were higher in the LF group. CONCLUSION LF prophylaxis reduced nosocomial sepsis episodes. Treg levels in preterm infants were lower than in term infants and an increase of Treg levels under LF prophylaxis was observed. Increase in Treg levels can be the mechanism for protective effects of LF on nosocomial sepsis.

Effects of umbilical cord milking on the need for packed red blood cell transfusions and early neonatal hemodynamic adaptation in preterm infants born ≤1500 g: a prospective, randomized, controlled trial.

Objective: The aim of this study was to evaluate the effects of umbilical cord milking (UCM) on the need for packed red blood cell (PRBC) transfusion and hematologic and hemodynamic parameters in very-low–birth-weight infants. Methods: The infants were randomized into 2 groups: group 1 (UCM) and group 2 (control). The primary outcome was the number of PRBC transfusions during the first 35 days of life. The secondary outcome measures were the hemodynamic variables during the first 24 hours of life. Results: A total of 44 infants were included with 22 infants in each group. Two of 21 infants in group 1 and 4 of 21 infants in group 2 received transfusion in the first 3 days of life (P=0.384). The number and volume of PRBC transfusions were similar in both groups. However, the levels of hemoglobin (Hb) at the first and 24th hour of life were significantly higher in group 1. Phlebotomy volume was found as a statistically significant risk factor for the need for PRBC transfusion (P=0.005). Conclusions: UCM in delivery room results in a higher Hb level in the first day of life. In these groups of infants, phlebotomy losses may impact the transfusion need.

Clinical characteristics of recessive and dominant congenital hyperinsulinism due to mutation(s) in the ABCC8/KCNJ11 genes encoding the ATP-sensitive potasium channel in the pancreatic beta cell

Abstract Background: Recessive mutations in ABCC8/KCNJ11 of β-cell KATP channel generally cause severe medically unresponsive hyperinsulinemic hypoglycemia (HH). Rarer dominant mutations in these genes have been described that mostly cause milder, medically responsive congenital hyperinsulinism. Rarer dominant mutations in these genes have been described that mostly cause milder, medically responsive congenital hyperinsulinism. To date the phenotype of patients with dominant mutations seems to be different from those with recessive mutations as the majority of patients are responsive to diazoxide therapy. Controversy exists on whether these dominant ABCC8 or KCNJ11 genes mutations predispose to diabetes mellitus in adulthood or not. Subjects: We report the clinical and genetic characteristics of five patients with neonatal HH, three had recessively inherited KATP channel mutations and two with a dominantly acting mutation. As a result of failure to medical therapy, patients with recessive KATP channel mutations underwent a near total pancreatectomy. Two siblings with a novel dominant mutation showed good response to medical treatment. Although the HH remitted in early infancy, they became diabetic at the prepubertal age. Their mother, maternal aunt and maternal grandfather had the same mutation without any medical history of neonatal HH. Conclusion: The clinical presentation of our two patients with a dominant ABCC8 mutation was milder than that of patients with the resessive form of the disease as they responded well to medical management.

The association between cord hormones and transient tachypnea of newborn in late preterm and term neonates who were delivered by cesarean section

Abstract Objective: Failure of adequate and timely clearance of fetal lung fluid has been implicated in transient tachypnea of the newborn (TTN). There has been lack of human data on the association between endocrinological adaptation and fetal lung fluid clearance. Although TTN development in term or late preterm newborns delivered by cesarean section (CS) is well known, whether stress hormones levels at birth contribute to it or not is not known. The aim of the study was to assess the possible association between low adrenocorticothrophic hormone (ACTH), cortisol and free triiodothyronin (fT3) levels at birth and TTN in late preterm and term infants. Study design: We compared cord blood concentrations of epinephrine, cortisol, ACTH, fT4, fT3 and thyroid stimulating hormone in two groups of term and late pretrem infants born by CS: those who developed TTN and a comparison group without respiratory distress. Results: While there were no significant demographic differences between patient and control groups, cord ACTH, cortisol and fT3 were significantly lower and epinephrine was higher in infants developing TTN (p < 0.05). Conclusions: Lower cord levels of cortisol, ACTH and fT3 in patients with TTN may indicate the possible relation of these hormones in fetal lung fluid clearance and postnatal pulmonary adaptation through their modulatory effect on epithelial sodium channel and Na-K-ATPase.

Transient neonatal diabetes with two novel mutations in the KCNJ11 gene and response to sulfonylurea treatment in a preterm infant.

Abstract Neonatal diabetes mellitus (NDM) is a rare condition that can be either transient or permanent. KATP channel (Kir6.2 or SUR1) mutation, chromosome 6 abnormalities, insulin, or glucokinase gene mutations can lead to isolated NDM. Cases caused by Kir6.2 mutation usually result in permanent NDM (PNDM) rather than transient NDM (TNDM). The majority of patients with the Kir6.2 or SUR1 mutation can be successfully managed with a sulfonylurea agent, without the need for insulin. We report a preterm male with NDM having two novel missense mutations, E322A and D352H, in the KCNJ11 gene. At 2 months of age, successful transition from insulin to glibenclamide (glyburide) therapy of the patient was managed. At 5 months of age, his diabetes went in to remission.

Efficacy and safety of intravenous colistin in preterm infants with nosocomial sepsis caused by Acinetobacter baumannii.

OBJECTIVES To describe the efficacy of intravenous colistin on clinical and microbiological outcomes in preterm infants with nosocomial sepsis in neonatal intensive care unit (NICU) and define adverse events observed with this treatment. METHODS The records of preterm infants who received colistin with or without positive cultures in the NICU were retrospectively reviewed. Patients were evaluated for response to therapy and side effects. RESULTS A total of 21 preterm infants with medians of 28 weeks (23-36) gestational age and 870 g (620-2,650) birth weight were included. The median duration and dose of colistin therapy were 9 days (3-26) and 3 mg/kg/d (2-5). Recovery rate in patients including all with/without positive culture was 81% (17/21). Microbiological clearance by colistin was 69% (9/13). The major side effect observed was acute kidney injury (19%). At least 24% of infants required electrolyte supplementation during the colistin therapy. Magnesium levels were significantly lower at the end of the colistin therapy (p < 0.001). Acute kidney injury and electrolyte disturbances including hypomagnesemia were reversible in all surviving patients. CONCLUSION We suggest that renal function tests and serum electrolytes should be monitored closely and replaced in case of any need during the colistin therapy in preterm infants.

Management of patent ductus arteriosus in preterm infants: clinical judgment might be a fair option

Abstract Objective: The objective of this study was to find out the percentage of preterm infants that needed treatment for patent ductus arteriosus (PDA), when treatment decision was based on clinical signs and symptoms, besides echocardiographic findings. Methods: Daily echocardiographic evaluation was conducted in 39 preterms ≤296/7 weeks’ gestation. Patients with ductus arteriosus were closely followed-up for clinical symptoms of PDA for treatment decision until ductus arteriosus was closed either spontaneously or by treatment. Results: PDA was found in 25 (64%) infants. Mean gestational age and birth weight (BW) of the patients with PDA were 27.8 ± 1.2 and 998 ± 221 g, respectively. PDA closed spontaneously or had minimal ductal shunting before any signs and symptoms attributable to PDA were observed in 16 (41%) infants. Mean ductus size/BW ratio and mean left atrial/aortic root ratio were significantly higher in 9 (23%) symptomatic patients (2.06 ± 0.75 versus 1.32 ± 0.75 mm, p = 0.012 and 1.31 ± 0.52 versus 1.19 ± 0.2 mm, p = 0.043, respectively). PDA closure was observed after the first dose of ibuprofen in six of nine patients. Conclusion: Correlation of clinical signs with echocardiographic findings for the decision of PDA treatment can be appropriate to prevent unnecessary medical treatments.

Palivizumab use during respiratory syncytial virus outbreak in the neonatal intensive care unit

We read with great interest the papers by Dizdar et al. and by O’Connell et al. about the use of palivizumab during a respiratory syncytial virus (RSV) outbreak in neonatal intensive care units (NICUs), suggesting that palivizumab administration might have a role in controlling RSV outbreak and recommended early administration of palivizumab to terminate transmission as quickly as possible. We recently experienced a similar outbreak in our NICU, and controlled it according to the suggestions made in this paper. There were ten preterm (median gestational age: 29.3 weeks; range: 26.2e32 weeks; birth weight: 848e1520 g), two late preterm (>35 weeks’ gestational age) and four term infants in the NICU when two term newborns with bronchopneumonia and respiratory insufficiency were admitted to the NICU isolation unit between 29 February 2012 and 12 March 2012. Polymerase chain reaction (PCR) screening including RSV (A, B), coronavirus (A, B, C, D, E, OC43, HKU1), parainfluenza (1, 2, 3, 4), rhinovirus (A, B, C), influenza (A, B), bocavirus (1, 2, 3, 4), metapneumovirus and enterovirus, revealed RSV type B infection in these two patients. Although patients with RSV were cared for in separate isolation rooms, another preterm infant who had recovered from respiratory distress syndrome developed further respiratory distress after a week. Nasopharyngeal secretions obtained from this infant also revealed RSV type B infection and we decided to screen the remaining 15 infants for RSV. None of the asymptomatic patients was RSV PCR positive. In order to prevent an escalating NICU outbreak, palivizumab prophylaxis was administered to nine preterm infants, all of whom were <32 weeks of gestational age at birth, and one patient who had a congenital heart disease at a dosage of 15 mg/kg, in addition to strict contact precautions. Patients with RSV bronchiolitis recovered after about 10 days and we did not observe any additional cases with RSV. RSV infection was brought into the NICU by two patients with RSV bronchiolitis. Following this, one preterm patient, who was recovering from respiratory distress, developed RSV bronchiolitis. As NICUs like ours embrace a family-centred model for patient care, greater difficulties complying with effective infection control measures may emerge. We agree with Dizdar et al. and O’Connell et al. that palivizumab prophylaxis may have a role in the control of RSV epidemics in the NICU. If we had not given palivizumab prophylaxis after detection of index cases, a larger RSV outbreak might have occurred in our NICU. After a few small RSV NICU outbreaks in Turkey, the Turkish Neonatal Society now recommends RSV prophylaxis for premature infants in the NICU who are already candidates for the prophylaxis programme as outpatients when at least three RSV-positive patients are present in the NICU. This recommendation is similar to the one reported by the Spanish Neonatal Society which suggests palivizumab prophylaxis for preterm infants and newborns with haemodynamically significant congenital heart disease when such outbreaks occur.

Perinatal risk factors and mode of delivery associated with mortality in very low birth weight infants.

Abstract Objective: To investigate the association of perinatal risk factors including delivery mode with mortality in very low birthweight (VLBW) in a tertiary hospital setting. Methods: Medical records of 241 live-born VLBW infants (≤1500 g) were retrospectively reviewed. Details of maternal, obstetrical, perinatal risk factors and their associations with infant mortality were evaluated. Results: The overall infant mortality rate was 23.2%. Mortality was significantly higher for infants born at ≤27 gestational weeks and with a birthweight of ≤750 g (p = 0.000 and p = 0.000, respectively), showing a steep decrease thereafter. On ROC analysis, a cut off of 26.5 weeks was determined for mortality with a sensitivity of 57.1% and a specificity of 90.3% (area under the curve = 0.792, 95% CI: 0.719–0.866). On multivariate regression analysis, gestational week at birth, birthweight, antenatal steroid treatment and pathologic Doppler ultrasound findings were found as independent risk factors for mortality. Conclusions: Gestational week at birth, birthweight and antenatal steroid treatment remain the most important perinatal risk factors for infant mortality in VLBW infants. Mode of delivery does not seem to be associated with mortality when adjusted for other perinatal risk factors.

Hand intubation of a tiny neonate with a large obstructive mass in the oral cavity.

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