Intravenous Immunoglobulin Use in Hemolytic Disease Due to ABO Incompatibility to Prevent Exchange Transfusion.

Introduction: Intravenous immunoglobulin (IVIG) has been widely used to treat the hemolytic disease of the newborn (HDN). Although it has been shown that IVIG treatment reduces the duration of phototherapy and hospitalization, the use of IVIG in hemolytic disease due to ABO incompatibility has been controversial in recent years. This study aimed to investigate the role of IVIG in the prevention of exchange transfusion in infants with ABO HDN who presented with bilirubin levels at or above the level of exchange transfusion. Materials and Methods: This study evaluated the data of infants with ABO HDN in the Turkish Neonatal Jaundice Online Registry. The infants with ABO HDN who met the total serum bilirubin level inclusion criteria (within 2-3 mg/dL of exchange transfusion or even above exchange transfusion level) were included in the study according to the guidelines from the American Academy of Pediatrics and the Turkish Neonatal Society. All patients were managed according to the unit protocols recommended by these guidelines and received light-emitting diode (LED) phototherapy. Infants who only received LED phototherapy, and who received one dose of IVIG with LED phototherapy were compared. Results: During the study period, 531 term infants were included in the study according to inclusion criteria. There were 408 cases in the phototherapy-only group, and 123 cases in the IVIG group. The demographic findings and the mean bilirubin and reticulocyte levels at admission were similar between the groups (p > 0.05), whereas the mean hemoglobin level was slightly lower in the IVIG group (p = 0.037). The mean age at admission was earlier, the need for exchange transfusion was higher, and the duration of phototherapy was longer in the IVIG group (p < 0.001, p = 0.001, and p < 0.001, respectively). The rate of re-hospitalization and acute bilirubin encephalopathy (ABE) was higher in the IVIG group (p < 0.001 and p = 0.01, respectively). Conclusion: In this study, we determined that one dose of IVIG did not prevent an exchange transfusion nor decrease the duration of phototherapy in infants, who had bilirubin levels near or at exchange transfusion level, with hemolytic disease due to ABO incompatibility.

An Observational, Prospective, Multicenter, Registry-Based Cohort Study Comparing Conservative and Medical Management for Patent Ductus Arteriosus.

No consensus has been reached on which patent ductus arteriosus (PDAs) in preterm infants require treatment and if so, how, and when they should be treated. A prospective, multicenter, cohort study was conducted to compare the effects of conservative approaches and medical treatment options on ductal closure at discharge, surgical ligation, prematurity-related morbidities, and mortality. Infants between 240/7 and 286/7 weeks of gestation from 24 neonatal intensive care units were enrolled. Data on PDA management and patients' clinical characteristics were recorded prospectively. Patients with moderate-to-large PDA were compared. Among the 1,193 enrolled infants (26.7 ± 1.4 weeks and 926 ± 243 g), 649 (54%) had no or small PDA, whereas 544 (46%) had moderate-to-large PDA. One hundred thirty (24%) infants with moderate-to-large PDA were managed conservatively, in contrast to 414 (76%) who received medical treatment. Eighty (62%) of 130 infants who were managed conservatively did not receive any rescue treatment and the PDA closure rate was 53% at discharge. There were no differences in the rates of late-onset sepsis, necrotizing enterocolitis (NEC), retinopathy of prematurity, intraventricular hemorrhage (≥Grade 3), surgical ligation, and presence of PDA at discharge between conservatively-managed and medically-treated infants (p > 0.05). Multivariate analysis including perinatal factors showed that medical treatment was associated with increased risk for mortality (OR 1.68, 95% Cl 1.01-2.80, p = 0.046), but decreased risk for BPD or death (BPD/death) (OR 0.59, 95%Cl 0.37-0.92, p = 0.022). The preferred treatment options were ibuprofen (intravenous 36%, oral 31%), and paracetamol (intravenous 26%, oral 7%). Infants who were treated with oral paracetamol had higher rates of NEC and mortality in comparison to other treatment options. Infants treated before postnatal day 7 had higher rates of mortality and BPD/death than infants who were conservatively managed or treated beyond day 7 (p = 0.009 and 0.007, respectively). In preterm infants born at <29 weeks of gestation with moderate-to-large PDA, medical treatment did not show any reduction in the rates of open PDA at discharge, surgical or prematurity-related secondary outcomes. In addition to the high incidence of spontaneous closure of PDA in the first week of life, early treatment (<7 days) was associated with higher rates of mortality and BPD/death.

Congenital esophageal diverticulum in a very low birth weight infant: case report and review of literature.

BACKGROUND: A diverticulum is an outpouching of a tubular organ that is classified as congenital and acquired according to the involved layers of the gastrointestinal wall. Congenital true diverticulum has been very rarely seen in neonatal period and it is very difficult to diagnose it especially in premature infants. CASE: A male infant was born with birth weight of 1000 g at 28th gestational week, was hospitalized for prematurity and respiratory distress. During follow up intermittent CO2 retention was observed in blood gases. On the 17th day of hospitalization, esophageal dilatation was detected on X-ray and barium swallowed esophagram showed a saccular pouch on the distal esophagus. The patient was operated on 26th day of life and pathological specimen revealed true diverticulum of esophagus. The patient died due to respiratory failure and septic shock during hospitalization. CONCLUSION: To the best of our knowledge this case is the smallest and youngest preterm infant diagnosed with congenital esophageal diverticulum. Prolonged and intermittent CO2 retention such as in our case can be an atypical symptom of congenital diverticulum and it should be suspected in the differential diagnosis. Congenital esophageal diverticulum may be also seen in extremely preterm infants and can present with unusual symptoms.

An observational, prospective, multicenter study on rescue high-frequency oscillatory ventilation in neonates failing with conventional ventilation.

BACKGROUND: To achieve gas exchange goals and mitigate lung injury, infants who fail with conventional ventilation (CV) are generally switched to high-frequency oscillatory ventilation (HFOV). Although preferred in many neonatal intensive care units (NICUs), research on this type of rescue HFOV has not been reported recently. METHODS: An online registry database for a multicenter, prospective study was set to evaluate factors affecting the response of newborn infants to rescue HFOV treatment. The study population consisted of 372 infants with CV failure after at least 4 hours of treatment in 23 participating NICUs. Patients were grouped according to their final outcome as survived (Group S) or as died or received extracorporeal membrane oxygenation (ECMO) (Group D/E). Patients' demographic characteristics and underlying diseases in addition to their ventilator settings, arterial blood gas (ABG) analysis results at 0, 1, 4, and 24 hours, type of device, ventilation duration, and complications were compared between groups. RESULTS: HFOV as rescue treatment was successful in 58.1% of patients. Demographic and treatment parameters were not different between groups, except that infants in Group D/E had lower birthweight (BW) (1655 ± 1091 vs. 1858 ± 1027 g, p = 0.006), a higher initial FiO2 setting (83% vs. 72%, p < 0.001), and a higher rate of nitric oxide exposure (21.8% vs. 11.1%, p = 0.004) in comparison to infants who survived (Group S). The initial cut-offs for a successful response on ABG were defined as pH >7.065 (OR: 19.74, 95% CI 4.83-80.6, p < 0.001), HCO3 >16.35 mmol/L (OR: 1.06, 95% CI 1.01-1.1, p = 0.006), and lactate level <3.75 mmol/L (OR: 1.09%95 CI 1.01-1.16, p = 0.006). Rescue HFOV duration was associated with retinopathy of prematurity (p = 0.005) and moderate or severe chronic lung disease (p < 0.001), but not with patent ductus arteriosus or intraventricular hemorrhage, in survivors (p > 0.05). CONCLUSION: Rescue HFOV as defined for this population was successful in more than half of the patients with CV failure. Although the response was not associated with gestational age, underlying disease, device used, or initial MV settings, it seemed to be more effective in patients with higher BW and those not requiring nitric oxide. Initial pH, HCO3, and lactate levels on ABG may be used as predictors of a response to rescue HFOV.

Neonatal atrial flutter: Three cases and review of the literature.

Yilmaz-Semerci S, Bornaun H, Kurnaz D, Cebeci B, Babayigit A, Büyükkale G, Çetinkaya M. Neonatal atrial flutter: Three cases and review of the literature. Turk J Pediatr 2018; 60: 306-309. Atrial flutter (AFl) is known to be a seldom type of fetal and neonatal arrhythmia. Although it could end in severe morbidities such as hydrops fetalis or even death, with early prenatal diagnosis and prompt therapeutic approaches the majority of AFl cases show good prognosis. Neonatal AFl might be resistant to first step therapies. Therefore, secondary agents like flecainide, amiodarone, sotalol and cardioversion, if required, could be influent in perinatal tachyarrhythmia. In addition, close follow-up even after discharge is very important to keep all follow-up appointments. Herein, we present three cases of fetal/neonatal AFl in light of the literature and discuss the characteristics, diagnosis and treatment options.

Angioedema Associated With Nebulized Recombinant Human DNase in a Preterm Infant: Case Report.

Pulmonary atelectasis leads to difficulties in weaning of the neonates from mechanical ventilation. The management of persistent atelectasis in neonates constitutes a common challenge for physicians. Several reports suggested Recombinant human DNase (rhDNase) as a beneficial therapy for neonates with persistent atelectasis by reducing mucous viscosity. No adverse effect associated with rhDNase treatment was reported in neonates. Herein, we report probable adverse reactions associated with rhDNase use in a preterm infant. Therefore, we suggest that clinicians must be aware of this reaction in neonates and should carefully follow up these infants for the development of adverse reactions. We think that more clinical experience and data are needed to define its tolerability and adverse effect profile in neonates.

The Turkish Neonatal Jaundice Online Registry: A national root cause analysis.

BACKGROUND: Neonatal jaundice (NNJ) is common, but few root cause analyses based on national quality registries have been performed. An online registry was established to estimate the incidence of NNJ in Turkey and to facilitate a root cause analysis of NNJ and its complications. METHODS: A multicenter prospective study was conducted on otherwise healthy newborns born at ≥35 weeks of gestation and hospitalized for only NNJ in 50 collaborator neonatal intensive care units across Turkey over a 1-year period. Patients were analyzed for their demographic and clinical characteristics, treatment options, and complications. RESULTS: Of the 5,620 patients enrolled, 361 (6.4%) had a bilirubin level ≥25 mg/dL on admission and 13 (0.23%) developed acute bilirubin encephalopathy. The leading cause of hospital admission was hemolytic jaundice, followed by dehydration related to a lack of proper feeding. Although all infants received phototherapy, 302 infants (5.4%) received intravenous immunoglobulin in addition to phototherapy and 132 (2.3%) required exchange transfusion. The infants who received exchange transfusion were more likely to experience hemolytic causes (60.6% vs. 28.1%) and a longer duration of phototherapy (58.5 ± 31.7 vs. 29.4 ± 18.8 h) compared to infants who were not transfused (p < 0.001). The incidence of short-term complications among discharged patients during follow-up was 8.5%; rehospitalization was the most frequent (58%), followed by jaundice for more than 2 weeks (39%), neurological abnormality (0.35%), and hearing loss (0.2%). CONCLUSIONS: Severe NNJ and bilirubin encephalopathy are still problems in Turkey. Means of identifying at-risk newborns before discharge during routine postnatal care, such as bilirubin monitoring, blood group analysis, and lactation consultations, would reduce the frequency of short- and long-term complications of severe NNJ.

Neonatal Appendicitis as a Rare Cause of Intestinal Perforation in a Preterm Neonate.

Intestinal perforation or inflammation due to appendicitis is rarely encountered in the neonatal period. The diagnosis may be delayed due to the lack of specific clinical symptoms and its rarity in this patient population. Early surgical treatment is the main treatment strategy with a good prognosis. However, delayed diagnosis may result in complications and even death. Herein, we describe a late preterm female neonate without any risk factors who had a diagnosis of perforated appendicitis at postnatal day 5. To the authors' knowledge, this case represents the earliest presentation of neonatal perforated appendicitis elucidated by prompt diagnostic laparotomy. Neonatal appendicitis should be considered in the differential diagnosis of infants with abdominal clinical findings.

Hepatic Abscesses in Preterm Infants: Report of Three Cases and Review of the Literature.

PURPOSE: Hepatic abscess is a rare but potentially fatal entity in neonates. The aim of this study was to provide valuable data for diagnosis, management and prevention of hepatic abscess in preterm infants. METHODS: A retrospective chart review was made for patients diagnosed with hepatic abscesses between 2012 and 2015. Methods included clinical and radiological review of records and evaluation of potential risk factors. RESULTS: A total of three infants with hepatic abscesses were identified. All of them had low birth weight and low gestational age. Predisposing factors included prematurity, late sepsis, umbilical catheterization, necrotizing enterocolitis and previous antibiotic therapy. Isolated organisms from blood included Staphylococcus spp. in two cases and Pseudomonas spp. in one case. To the best of our knowledge, this is the first preterm case of hepatic abscess caused by Pseudomonas aeruginosa in the literature. All patients responded well to antibiotic therapy alone, and no interventional drainage was required. CONCLUSION: We suggest evaluating all preterm neonates who have severe sepsis and/or necrotizing enterocolitis signs and who do not respond to prolonged antibiotic therapy with detailed abdominal ultrasound for possible hepatic abscesses as early diagnosis, and treatment favors prognosis.

Treatment of neonatal fungal infective endocarditis with recombinant tissue plasminogen: activator in a low birth weight infant case report and review of the literature.

With advances in medical sciences, an increase in survival rates of low birth weight; increased incidence in use of catheter and antibiotics, and total parenteral nutrition are reported, therefore, the rate of fungal infections in late and very late onset neonatal sepsis have increased. Although fungal endocarditis rarely occur in newborns, it has a high morbidity and mortality. Antifungal therapy is often insufficient in cases who develop fungal endocarditis and surgical treatment is not preferred due to its difficulty and high mortality. Herein, fungal endocarditis in a preterm newborn treated with single-dose recombinant tissue plasminogen activator in addition to antifungal therapy is presented and relevant literature has been reviewed. The vegetation completely disappeared following treatment and no complication was observed.

The utility of serial plasma sE-selectin measurements in the prediction of retinopathy of prematurity in premature infants.

BACKGROUND: sE-selectin has recently been suggested as a surrogate marker for prediction of ROP development. AIMS: The possible role of serial plasma sE-selectin measurements in early prediction and diagnosis of ROP was evaluated. STUDY DESIGN: Prospective observational study SUBJECTS: Forty six preterm infants aged <34weeks of gestation and weighing <1500 g were enrolled. Of these, 26 constituted the ROP group and 20 constituted the no-ROP group. sE-selectin levels were measured serially in blood samples on the 1st day and on 14th and 28th postnatal days. OUTCOME MEASURES: The primary outcome measure was to evaluate the role of sE-selectin concentrations in prediction of ROP. RESULTS: The mean gestational age and birth weight were significantly lower in the ROP group. The mean sE-selectin concentrations in ROP group were significantly greater than those in no-ROP group at each time point (1st, 14th and 28th days of postnatal life). A receiver operating characteristic (ROC) analysis showed that at a plasma concentration of ≥86ng/mL on the 1st postnatal day, sE-selectin had a sensitivity of 100% and a specificity of 94.1% with a positive predictive value of 96.3% and a negative predictive value of 100%. Plasma sE-selectin concentrations were significantly greater in infants who developed ROP in three different time points. CONCLUSIONS: This study shows for the first time that measurement of plasma sE-selectin concentrations as early as the first day of life might help identify preterm infants at risk of ROP.

Efficacy of prophylactic fluconazole therapy in decreasing the incidence of Candida infections in extremely low birth weight preterm infants.

OBJECTIVE: Systemic fungal infections are major causes of morbidity and mortality, and are associated with significant neurodevelopmental impairment in premature infants. Our objective was to evaluate the efficacy of fluconazole prophylaxis in prevention of systemic fungal infections among preterm infants. STUDY DESIGN: This observational pre-post cohort study was performed in preterm infants with a birth weight of < 1,000 g who were given prophylactic fluconazole starting on the first postnatal day at a dose of 3 mg/kg twice a week. These infants were compared with preterm infants who were not given prophylaxis. RESULTS: Prophylaxis group consisted of 90 infants and control group consisted of 107 infants. Systemic fungal infection was observed in five patients (4.7%) in the control group while no fungal infection was detected in the prophylaxis group (p = 0.03). There were no significant differences between two groups in terms of demographic features, maternal and neonatal risk factors, and all-cause mortality rates. No adverse reactions were seen during the prophylaxis period. CONCLUSIONS: We suggest that intravenous fluconazole prophylaxis at a dose of 3 mg/kg twice a week is a safe and effective strategy for decreasing systemic fungal infections even in neonatal intensive care units with low rates of invasive Candida infection.

An unusual cause of bilateral scrotal abscess in a preterm infant: Candida albicans

Acute scrotal abscess is a rare condition in neonates. Most of these abscesses were reported to be unilateral and caused by Staphylococcus and Salmonella spp. Herein, we report a bilateral scrotal abscess in a preterm infant and Candida albicans was isolated from the scrotal fluid culture. To our knowledge, this is the first bilateral scrotal abscess in a preterm infant caused by C. albicans. Therefore, this organism must be suspected in differential diagnosis of acute scrotal abscess in neonates, especially in preterm infants.

An unusual cause of bilateral scrotal abscess in a preterm infant: Candida albicans.

Acute scrotal abscess is a rare condition in neonates. Most of these abscesses were reported to be unilateral and caused by Staphylococcus and Salmonella spp. Herein, we report a bilateral scrotal abscess in a preterm infant and Candida albicans was isolated from the scrotal fluid culture. To our knowledge, this is the first bilateral scrotal abscess in a preterm infant caused by C. albicans. Therefore, this organism must be suspected in differential diagnosis of acute scrotal abscess in neonates, especially in preterm infants.

Neonatal Bartter syndrome and unilateral ectopic renal cyst as new renal causes of hydrops fetalis: two case reports and review of the literature.

Non-immune hydrops fetalis (NIHF) is a challenging entity as it represents the end stage of several different disorders. Renal and genitourinary causes of NIHF are rare and include congenital renal malformations, tumors and ureter-urethra disorders. Herein, two NIHF cases with different renal causes were presented. The first case that had antenatal NIHF was diagnosed neonatal Bartter syndrome. The second case of NIHF with antenatal large cyst in the surrenal gland area required surgery and ectopic renal cyst was diagnosed. To our best of knowledge, these are the first reports of NIHF associated with neonatal Bartter syndrome and ectopic renal cyst in neonates. Although it may be coincidental, these cases suggest that both neonatal Bartter syndrome and unilateral ectopic renal cyst may cause NIHF development in neonates by several different mechanisms. Therefore, these two rare entities should be suspected in cases of NIHF with similar findings.

Transient leukemia-associated pericardial tamponade in a neonate with Down syndrome.

Approximately 10% of neonates with Down syndrome may develop a form of megakaryoblastic leukemia that usually disappear spontaneously during the first months of the life. Although it seems to have a benign course, it may also be lethal and severe in some cases, especially in the form of hydrops and/or cardiopulmonary failure. Herein, we report a male infant with Down syndrome who was admitted with respiratory distress due to severe pericardial effusion leading to pericardial tamponade in the first 2 weeks of life. Pericardiosentesis and pericardial tube replacement in combination with steroid therapy was performed. He responded well to these therapies and his leukemia resolved on the fourth month of life. This case suggests that severe pericardial effusion and pericardial tamponade may be life-threatening complications of transient leukemia of Down syndrome and also it may be managed successfully with appropriate treatments.

Neonatal hyperbilirubinemia and organic anion transporting polypeptide-2 gene mutations.

The aim of this study was to investigate the genotypic distribution of organic anion transporting polypeptide 2 (OATP-2) gene mutations and the relationship with hyperbilirubinemia of unknown etiology. Polymerase chain reaction, restriction fragment length polymorphism, and agarose gel electrophoresis techniques were used for detection of OATP-2 gene mutations in 155 newborn infants: 37 with unexplained hyperbilirubinemia, 65 with explained hyperbilirubinemia, and 53 without hyperbilirubinemia. In the OATP-2 gene, we identified A→G transitions at nucleotide positions 388 and 411 and observed six polymorphic forms. The 388/411-411 mutation was the most common form (43%) in subjects with hyperbilirubinemia of unknown etiology. Male sex [odds ratio (OR): 3.08] and two polymorphic forms of the OATP-2 gene [the 388/411-411 A→G mutation (OR: 3.6) and the 388-411 mutation (OR: 2.4)] increased the risk of neonatal hyperbilirubinemia. In male infants with the 388 A→G mutation of the OATP-2 gene, the levels of unconjugated bilirubin in plasma were significantly increased compared with those observed in females. The polymorphic forms of 388 nucleotide of the OATP-2 gene were identified as risk factors for hyperbilirubinemia of unknown etiology.