Risk Factors and Clinical Characteristics of Metabolic Bone Disease of Prematurity.

OBJECTIVE: The study aimed to analyze the risk factors and clinical features of metabolic bone disease of prematurity (MBDP) in premature infants compared with infants of similar gestational age and birth weight without MBDP. STUDY DESIGN: This retrospective case-control study was performed by comparing 81 cases of MBDP with 63 controls to identify potential risk factors. Premature infants with a gestational age ≤33 weeks and birth weight <1,500 g were included. Medical records were examined in terms of maternal conditions, potential risk factors, and clinical characteristics. RESULTS: Bone fractures and invasive ventilator dependence were the most common clinical features of MBDP. Duration of invasive ventilation and total mechanical ventilation days, necrotizing enterocolitis, corticosteroid use, anticonvulsive drug use, duration of dexamethasone and caffeine use, total parenteral nutrition, and length of hospitalization were significantly higher in neonates with MBDP (p < 0.05). Breastfed neonates and those receiving human milk fortifier had a lower incidence of MBDP than those premature formula or mixed feeding (p < 0.05). Anticonvulsive drug use (odds ratio: 2.935; 95% confidence interval: 1.265-6.810) was identified as a risk factor for MBDP at multiple regression analysis. CONCLUSION: Our results show that anticonvulsive drug use is a significant risk factor for the development of MBDP. If long-term use is not required, anticonvulsive drugs should be stopped as soon as possible. Further studies involving patients with MBDP are required to determine the risk factors and clinical features. KEY POINTS: · MBDP is a multifactorial disorder.. · Anticonvulsive drug use is an important risk factor for the development of MBDP.. · Bone fractures and invasive ventilator dependence are the most common clinical features of MBDP..

Familial Hemophagocytic Lymphohistiocytosis With Heterozygous STX11 and Homozygous UNC13D Mutations Diagnosed in the Neonatal Period.

Patients with primary hemophagocytic lymphohistiocytosis may present with different mutations and phenotypic findings. It is usually presented as case reports because of its rare occurrence. Here, we discuss a case diagnosed with familial hemophagocytic lymphohistiocytosis 3, that presented in the neonatal period and was detected to have homozygous UNC13D and heterozygous STX11 mutations.

A dangerous causative microorganism of early onset neonatal sepsis: Stenotrophomonas maltophilia. Two case reports and a review of the literature.

Stenotrophomonas maltophilia (S. maltophilia) is an important aerobic, non-fermentative, Gram-negative, multidrug resistant organism. Although this microorganism is frequently reported as a causative agent of nosocomial infections in neonatal intensive care unit, a few cases were reported about as a causative microorganism of early-onset neonatal sepsis (EONS). We report two cases with EONS caused by S. maltophilia and also, we reviewed the EONS reported caused by S. maltophilia.

Vitamin D Deficiency Prevalence in Late Neonatal Hypocalcemia: A Multicenter Study

Objective: Late neonatal hypocalcemia (LNH) is a common metabolic problem associated with hypoparathyroidism, high phosphate intake and vitamin D deficiency, often presenting with seizures. In this cross-sectional study, we aimed to evaluate the role of vitamin D deficiency in LNH in Turkey and to describe the characteristics of affected newborns. Methods: Conducted with a cross-sectional design and with the participation of 61 neonatal centers from December 2015 to December 2016, the study included term neonates with LNH (n=96) and their mothers (n=93). Data were registered on the FAVOR Web Registry System. Serum samples of newborns and mothers were analyzed for calcium, phosphate, magnesium, albumin, alkaline phosphatase, intact parathyroid hormone (iPTH) and 25 hydroxyvitamin D [25(OH)D] levels. Results: The median (range) onset time of hypocalcemia was 5.0 (4.0-8.0) days of age, with a male preponderance (60.4%). The median (range) serum 25(OH)D levels of the neonates and their mothers were 6.3 (4.1-9.05) and 5.2 (4.7-8.8) ng/mL, respectively. The prevalence of vitamin D deficiency (<12 ng/mL) was high in both the neonates (86.5%) and mothers (93%). Serum 25(OH)D levels of the infants and mothers showed a strong correlation (p<0.001). While the majority (93.7%) of the neonates had normal/high phosphorus levels, iPTH levels were low or inappropriately normal in 54.2% of the patients. Conclusion: Vitamin D deficiency prevalence was found to be high in LNH. Efforts to provide vitamin D supplementation during pregnancy should be encouraged. Evaluation of vitamin D status should be included in the workup of LNH.

Sedoanalgesia modality during laser photocoagulation for retinopathy of prematurity: Intraoperative complications and early postoperative follow-up.

BACKGROUND: Laser photocoagulation (LPC) is a surgical procedure used in the treatment of premature retinopathy that may cause retinal detachment and blindness if not diagnosed and treated early. The anesthesia method used in LPC varies from sedoanalgesia to general anesthesia and airway management varies from spontaneous ventilation to endotracheal intubation. In this study, we aimed to evaluate the effectiveness of sedoanalgesia applications and this anesthesia procedure concerning intraoperative and postoperative complications by avoiding intubation and mechanical ventilation in premature infants with a fragile population. METHODS: This retrospective study included 89 patients who underwent laser photocoagulation under anesthesia for premature retinopathy. Patients' demographic characteristics, preoperative risk factors, anesthesia technique, especially airway management, changes in ventilation status during surgery, intraoperative complications, postoperative complications, and intensive care follow-up, were recorded and analyzed statistically. RESULTS: Two of the 89 patients who underwent laser photocoagulation were excluded from this study because they were followed up intubated. The number of patients who received mask ventilation due to intraoperative complications was 12 (13.8%). The mean operation time was 36.2±10.1 minutes. In 86.2% (n=75) of the patients, the surgical procedure was completed with sedoanalgesia while maintaining spontaneous ventilation. CONCLUSION: Sedoanalgesia application during the surgical intervention of patients with Retinopathy of Prematurity (ROP) requiring early diagnosis and emergency treatment will minimize intraoperative and postoperative complications. We believe that sedoanalgesia as an anesthetic method can be applied as an effective alternative method while preserving spontaneous ventilation.

Changing trend of microbiologic profile and antibiotic susceptibility of the microorganisms isolated in the neonatal nosocomial sepsis: a 14 years analysis.

Objective: Neonatal sepsis, especially nosocomial sepsis (NS) is one of the main causes of mortality and morbidity in neonates. Our aim was to investigate microorganisms responsible for NS and antimicrobial susceptibility patterns and to compare them in a different period.Methods: Blood culture registers from the Microbiology Laboratory were reviewed for the study population. The neonates with proven NS were enrolled in the study. Microorganisms responsible for NS and antimicrobial susceptibility patterns were recordedResults: The incidence of Gram-positive, Gram-negative, and fungal microorganisms were 61.6% (n = 570), 27.1% (n = 251) and 11.3% (n = 104), respectively. The most common isolated Gram-positive, Gram-negative pathogens and fungi were Coagulase-negative staphylococci (CoNS), Klebsiella pneumoniae, and C. guilliermondii. There was an increasing resistance rate among common nosocomial pathogens especially oxacillin resistant CoNS strains and increasing rate for extended-spectrum beta-lactamase (ESBL) positive microorganisms. Low susceptibility was detected to commonly used antibiotics for empirical treatment in neonatal sepsis.Conclusions: Our result showed that multiresistant microorganisms, especially oxacillin-resistant staphylococci and gram-negative bacilli resistant to cephalosporin have an increasing rate. Every unit should evaluate the causative agents and antimicrobial susceptibilities in order to select an appropriate regime for nosocomial sepsis. Periodic surveillance of organisms and their antibiotic resistance patterns in every unit might help physicians for proper selection of antibiotics for treatment of neonatal NS.

Preventive Effects of Probiotic Supplementation on Neonatal Hyperbilirubinemia Caused by Isoimmunization.

OBJECTIVE: Probiotic supplementation can help to improve recovery from jaundice by reducing enterohepatic circulation through the regulation of intestinal microbial flora. The aim of our study was to investigate the effect of probiotic supplementation on neonatal hyperbilirubinemia caused by isoimmunization alone. STUDY DESIGN: Sixty neonates were randomly divided into a placebo group and a probiotic group (Lactobacillus rhamnosus GG). Serum total bilirubin (STB) levels were measured at birth and at 4, 8, 16, 24, and 36 hours of treatment (and at 48, 60, and 72 hours if necessary). Duration of phototherapy, rephototherapy requirements, and daily meconium evacuation were recorded. RESULTS: STB and rebound STB levels at 36 hours were lower in the probiotic group than in the placebo group (p = 0.01 and p = 0.006, respectively). Meconium evacuation was more frequent in the probiotic group than in the placebo group on the second and third days of life (p = 0.002 and 0.009, respectively). CONCLUSION: Probiotics do not affect STB levels in the first 24 hours of life or duration of phototherapy in neonates with jaundice caused by blood group incompatibility. The effect of probiotic supplementation by reducing enterohepatic circulation occurs at 36 hours of life in newborns with isoimmunization.

Covalent immobilization of Aspergillus niger amyloglucosidase (ANAG) with ethylenediamine-functionalized and glutaraldehyde-activated active carbon (EFGAAC) obtained from sesame seed shell.

This study was aimed the covalently immobilization of Aspergillus niger amyloglucosidase (ANAG) onto activated carbon (AC) obtained from sesame seed shell. AC was firstly functionalized with ethylenediamine, and after then activated with glutaraldehyde. 99.80% immobilization yield and 99.83% activity yield were obtained as the result of optimization of immobilization conditions (pH and molarity of immobilization buffer, AC amount, and reaction time). The optimum pH (5.5) and the optimum temperature range (55-60 °C) for ANAG were not affected by immobilization. After immobilization, Vmax value decreased from 1464.1 µmol D-glucose/L.min to 1342.3 µmol D-glucose/L.min, while Km value decreased from 116.3 g maltodextrin/L to 109.9 g maltodextrin/L. The immobilized enzyme retained 99.30% and 98.30% of its initial activity, respectively after twenty repeated uses and after twenty days of storage in 5 mL sodium phosphate buffer (0.1 M, pH 5.5) at +4 °C in a refrigerator. Finally, glucose syrup was produced from maltodextrin solution having 1% (w/v) concentration by using the immobilized ANAG. Maltodextrin was completely converted to glucose after four hours. Consequently, it can be said that the immobilized ANAG obtained in this study can be used in the industrial production of glucose syrup.

Antenatal Bartter Syndrome Caused by a Novel Homozygous Mutation in SLC12A1 Gene.

Antenatal Bartter syndrome (BS) is an autosomal recessive hereditary renal tubular disorder caused by mutation in the solute carrier family 12 member 1 (SLC12A1) gene on chromosome 15q21.1. This syndrome is characterized by polyuria, hyponatremia, hypokalemic hypochloremic metabolic alkalosis, and hypercalciuria associated with increased urinary loss of electrolytes. Herein, we report a very low-birth-weight premature newborn with antenatal BS caused by a novel homozygous mutation in the SLC12A1 gene, c.596G>A (p.R199H).

Clinical signs and symptoms of toxic serum digoxin levels in neonates.

Mutlu M, Aslan Y, Kader S, Aktürk-Acar F, Dilber E. Clinical signs and symptoms of toxic serum digoxin levels in neonates. Turk J Pediatr 2019; 61: 244-249. Digoxin is widely used in the treatment of congestive heart failure and some arrhythmias. Digoxin toxicity may occur easily because digoxin has a narrow therapeutic index. This retrospective study was conducted to evaluate the clinical signs and symptoms of toxic serum digoxin levels in neonates. Medical reports of the neonates who had serum digoxin concentrations > 2 nanogram/milliliter (ng/ml) were reviewed in terms of patient demographics, serum digoxin concentrations, signs and symptoms of digoxin toxicity, serum digoxin and electrolyte levels, renal function tests, electrocardiograms, echocardiography, and treatments applied. Digoxin toxic levels were identified in the 13 neonates. Of the 13 neonates with digoxin toxic level, 9 (69%) were term and 8 (62%) were female. Twenty-three percent (3/13) of newborn infants were symptomatic. Symptomatic patients had statistically significantly higher serum digoxin levels, at 7.76±2.76 (5.4-10.8) ng/ml, than asymptomatic patients, at 3.31±1.09 (2.02-4.95) (p=0.036). Symptoms related to toxic digoxin levels were observed in the three neonates with plasma digoxin levels > 5 ng/ml. Gastrointestinal and central nervous system symptoms were the major clinic findings. Despite high digoxin levels, no digoxin-related arrhythmia was observed on electrocardiography, other than sinus bradycardia. Two premature neonates were treated with digoxin-specific antibody Fab fragments (DigiFab®) and hypokalemia developed in both of them. Our data suggests that symptoms related with digoxin toxic levels were observed in neonates with plasma digoxin levels > 5 ng/ml. Serum digoxin levels should be measured in case of signs and symptoms of digoxin toxicity or risk factors for such toxicity.

Homozygous congenital factor VII deficiency with a novel mutation, associated with severe spontaneous intracranial bleeding in a neonate.

OBJECTIVE: Herein, a neonate with congenital FVII deficiency is presented. BASIC METHOD: Diagnosis of congenital FVII deficiency was confirmed by genetic analysis using next-generation sequencing method (MiSeq-Illumina). RESULT: Our patient was found to have a novel homozygous mutation. CONCLUSION: Early diagnosis and treatment of congenital FVII deficiency can be crucial.

Effects of Lactobacillus rhamnosus GG as a probiotic on neonatal hyperbilirubinemia.

Mutlu M, Irmak E, Aslan Y, Kader S. Effects of Lactobacillus rhamnosus GG as a probiotic on neonatal hyperbilirubinemia. Turk J Pediatr 2018; 60: 482-487. Undeveloped intestinal microflora and increased enterohepatic circulation of the newborn contribute to increase of plasma bilirubin level in the first days of life. This study was undertaken to determine the role of probiotic support started immediately after birth on neonatal hyperbilirubinemia in babies born by normal spontaneous vaginal delivery and breastfed only. A total of 150 healthy term newborns were included in the study and allocated in the study and control groups. Immediately after birth, newborns in the study group received probiotic in liquid drop form (Maflor® drops containing Lactobacillus Rhamnosus GG 109 colony forming units, Mamsel Ilac, Turkey), at a dose of 5 drops a day, orally for 10 days. Newborns in the control group received 5 drops of saline solution per day orally, instead. Serum bilirubin levels (cord, 3rd, 5th and 10th days of life) and defecation frequency were recorded. Mean total bilirubin levels on the 3rd, 5th and 10th days were significantly lower and mean defecation frequency was significantly higher in the probiotic group compared to the controls (p < 0.05 for each). Negative correlations were determined between defecation frequency and the 3rd, 5th and 10th day-total bilirubin levels (r=-0.804, p < 0.001; r=-0.818, p < 0.001; r=-0.648, p < 0.001, respectively). Probiotic (Lactobacillus rhamnosus GG) support initiated immediately after birth has a positive effect on bilirubin metabolism and may reduce the risk of hyperbilirubinemia.

Urinary tract infections in neonates with unexplained pathological indirect hyperbilirubinemia: Prevalence and significance.

BACKGROUND: It is controversial to test for urinary tract infection (UTI) in patients with unexplained indirect hyperbilirubinemia in the first 2 weeks of life. We aimed to study the prevalence and significance of UTIs in such neonates who were requiring phototherapy. METHODS: Subjects were 2- to 14-day-old neonates with indirect bilirubin levels above phototherapy limit with no other abnormality in their bilirubinaemia-related etiologic workup. UTI was diagnosed by 2 consecutive positive cultures obtained by catheterisation, documenting growth of >10,000 colonies of the same microorganism with consistent antibiograms. The UTI (+) patients were evaluated by renal ultrasonography (US), and some were followed up for possible recurrent UTI. RESULTS: 262 neonates were included in the study. UTI prevalence was 12.2%, and bacteraemia was 6.2% among UTI (+) patients. The two most common pathogens (81.2%) were Escherichiacoli and Klebsiella. pneumonia. All UTI (+) patients had undergone US, revealing 12.5% pelvicaliectasis, other 12.5% increased renal parenchymal echogenicity, 3.1% concurrent pelvicaliectasis and increased renal parenchymal echogenicity. 53.1% of UTI (+) patients had undergone follow-up, after which 23.5% recurrent UTI were found at the end of a mean of 52 months. CONCLUSION: We suggest that the neonates with unexplained pathological jaundice should be tested for possible UTI. Consequently, all newborns with UTI shall be evaluated by the urinary US and followed up for recurrent UTI.

ACCIDENTAL DUPLICATION: Investigation of the effect of hemoglobin F and A levels on development of retinopathy of prematurity.

The Publisher regrets that this article is an accidental duplication of an article that has already been published, http://dx.doi.org/10.1016/j.jaapos.2017.03.006. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

Comparison of methods and formulas used in umbilical venous catheter placement.

AIM: Central venous access is frequently provided by way of umbilical venous catheter placement in critically ill newborns. This study compared the methods of Dunn, Shukla-Ferrara, and Revised Shukla-Ferrara in determining the appropriate insertion length of umbilical vein catheters. MATERIAL AND METHODS: This prospective observational study was carried out in 121 newborns with umbilical venous catheter, group 1 (n=41) used Dunn method, group 2 (n=40) used the Shukla-Ferrara formula, and group 3 used revised Shukla-Ferrara formula (n=40). Catheter tip position was evaluated with an anterior-posterior chest radiograph after insertion of the umbilical venous catheter. The ideal position for the umbilical venous catheter was defined as the catheter tip being visible between the 9th and 10th thoracic vertebrae on an anterior-posterior chest radiograph. The position of the umbilical venous catheter was considered too high if the tip of the catheter was higher than the 9th thoracic vertebra and too low if the tip was below the 10th thoracic vertebra. The following data were collected: appropriate, inappropriate (low, high) placement, and complications of umbilical venous catheterization. RESULTS: In the Shukla-Ferrara group, 53% (17/32) of umbilical venous catheters were placed directly in the appropriate position, compared with 40% (12/30) in the revised Shukla-Ferrara group and 38% (11/29) in the Dunn method group. Umbilical venous catheter-related complications developed in two patients, thrombus in one, and catheter-related blood stream infection in the other. CONCLUSIONS: This study showed that the Shukla-Ferrara formula is more accurate in predicting the insertion length for umbilical venous catheters, though statistical significance was not found. Further studies with larger samples are needed on this topic.

Investigation of the effect of hemoglobin F and A levels on development of retinopathy of prematurity.

PURPOSE: To investigate the effect of hemoglobin F (HbF) and hemoglobin A (HbA) levels on development of retinopathy of prematurity (ROP) in premature infants. METHODS: In this prospective study, blood samples were collected from the side of the heel of 49 premature infants at postnatal months 0, 1, 2, and 3. HbF and HbA levels were measured in all samples and analyzed statistically. Furthermore, correlation analysis was performed regarding development of ROP, blood transfusion, and HbF and HbA levels. RESULTS: A total of 49 infants were included. The mean gestational age of the premature infants was 30.9 ± 2.7 weeks (range, 25-35 weeks); mean birth weight, 1542 ± 582 g (range, 520-3240 g). Of the 49 premature infants, stage 1 ROP or above developed in 26 (53%). Mean HbF levels were lower at postnatal months 1 and 2 in premature infants with ROP compared to those without ROP (P = 0.013 and 0.02, respectively); however, mean HbA levels were higher in the infants with ROP than the others (P = 0.034 and 0.029, respectively). Analysis of covariance that ignored transfusion revealed no difference between the means of Hb variants in the infants with and without ROP (P = 0.572 and 0.486). CONCLUSIONS: Blood transfusion significantly altered the levels of HbF and HbA in premature infants, and Hb variants have no direct effect on development of ROP.

ARC syndrome.

Mutlu M, Aslan Y, Aktürk-Acar F, Çakir M, Erduran E, Kalyoncu M. ARC syndrome. Turk J Pediatr 2017; 59: 487-490. Arthrogryposis-renal dysfunction-cholestasis (ARC) is an autosomal recessive multisystem disorder characterized by arthrogryposis, renal tubular dysfunction and neonatal cholestasis with low gamma glutamyl transpeptidase activity. Most of the mutations in ARC syndrome are associated with the vacuolar protein sorting 33B (VPS33B) gene on chromosome 15q26.1. Herein, we report a female newborn with ARC syndrome caused by homozygous mutations in VPS33B [IVS1-2A > C (c.97-2A > C)].

Determination of regional screening criteria for retinopathy ofprematurity in the Eastern Black Sea region of Turkey.

BACKGROUND/AIM: To establish a regional screening protocol for retinopathy of prematurity (ROP). MATERIALS AND METHODS: Data were analyzed from the hospital records of 1241 infants with gestational age (GA) at birth ≤36 weeks and birth weight (BW) of ≤3600 g. RESULTS: The mean GA of the infants was 32.05 ± 2.7 weeks and the mean BW was 1780.5 ± 576 g. ROP at any stage was detected in 703 of the 1241 infants (555 female). Eleven infants with type 1 ROP were treated with 810 nm diode laser photocoagulation. No treatment was needed in infants born after 33 weeks of gestation and weighing over 1760 g. Logistic regression analysis showed a significant relationship between the development of ROP and GA, BW, number of deliveries, respiratory distress syndrome, and treatment with oxygen or mechanical ventilation. Receiver operating characteristic curve analysis showed that a GA of 33 weeks or a BW of 1770 g appears to be an appropriate criterion for identifying infants who may require ROP treatment. CONCLUSION: GA ≤ 33 weeks and BW ≤ 1770 g can be used as screening criteria in terms of ROP in infants for the Eastern Black Sea region.