Familial Hemophagocytic Lymphohistiocytosis Screening in Neonatal Sepsis.

OBJECTIVE: Neonatal sepsis and familial hemophagocytic lymphohistiocytosis (fHLH) have similar clinical and laboratory symptoms and the possibility of overlooking fHLH diagnosis is high in newborns with sepsis. History of consanguineous marriage and/or sibling death, hepatomegaly/splenomegaly, and hyperferritinemia (>500 ng/mL) are likely to support fHLH in newborns with sepsis. Therefore, in newborns with sepsis in whom at least 2 of these 3 criteria were detected, genetic variants was investigated for the definitive diagnosed of fHLH. According to the results of genetic examination, we investigated whether these criteria supporting fHLH could be used as a screening test in fHLH. MATERIALS AND METHODS: fHLH-associated genetic variants were investigated in 22 patients diagnosed with neonatal sepsis who fulfilled at least 2 of the following criteria (1) history of consanguineous marriage and/or sibling death, (2) hepatomegaly/splenomegaly, and (3) hyperferritinemia (>500 ng/mL). RESULTS: Heterozygous variants were determined in 6 patients (27.2%): 3 STXBP2 , 1 STX11 , 1 UNC13D , and 1 PRF1 . Polymorphisms associated with the clinical symptoms and signs of HLH were determined in 5 patients (22.7%): 4 UNC13D , 1 PRF1 . Two patients were in the heterozygous variants and polymorphism associated with the clinical symptoms and signs of HLH groups. In 12 patients, benign polymorphisms were detected in STXBP2 and UNC13D genes. No change in fHLH associated genes were found in 1 patient. CONCLUSION: Some variants and/or polymorphisms identified in our patients have been previously reported in patients with HLH. Therefore, we recommend further investigation of fHLH in patients with neonatal sepsis who fulfill at least 2 of the above 3 criteria.

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.

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.

Mutations in RIPK4 cause the autosomal-recessive form of popliteal pterygium syndrome.

The autosomal-recessive form of popliteal pterygium syndrome, also known as Bartsocas-Papas syndrome, is a rare, but frequently lethal disorder characterized by marked popliteal pterygium associated with multiple congenital malformations. Using Affymetrix 250K SNP array genotyping and homozygosity mapping, we mapped this malformation syndrome to chromosomal region 21q22.3. Direct sequencing of RIPK4 (receptor-interacting serine/threonine kinase protein 4) showed a homozygous transversion (c.362T>A) that causes substitution of a conserved isoleucine with asparagine at amino acid position 121 (p.Ile121Asn) in the serine/threonine kinase domain of the protein. Additional pathogenic mutations-a homozygous transition (c.551C>T) that leads to a missense substitution (p.Thr184Ile) at a conserved position and a homozygous one base-pair insertion mutation (c.777_778insA) predicted to lead to a premature stop codon (p.Arg260ThrfsX14) within the kinase domain-were observed in two families. Molecular modeling of the kinase domain showed that both the Ile121 and Thr184 positions are critical for the protein's stability and kinase activity. Luciferase reporter assays also demonstrated that these mutations are critical for the catalytic activity of RIPK4. RIPK4 mediates activation of the nuclear factor-κB (NF-κB) signaling pathway and is required for keratinocyte differentiation and craniofacial and limb development. The phenotype of Ripk4(-/-) mice is consistent with the human phenotype presented herein. Additionally, the spectrum of malformations observed in the presented families is similar, but less severe than the conserved helix-loop-helix ubiquitous kinase (CHUK)-deficient human fetus phenotype; known as Cocoon syndrome; this similarity indicates that RIPK4 and CHUK might function via closely related pathways to promote keratinocyte differentiation and epithelial growth.

An Acute Complication of Ventriculoperitoneal Shunt with Bladder Perforation and Extrusion through the Urethra in a Newborn: Case Report and Review of the Literature.

Ventriculoperitoneal shunt (VPS) surgery is a standard procedure for the management of hydrocephalus. Bladder perforation is an extremely rare complication of VPS surgery. Herein, we present for the first time an acute complication of VPS with bladder perforation and extrusion through the urethra in a newborn. We also reviewed the complication of VPS with bladder perforation as reported in the literature.

The covalent immobilization of ß-galactosidase from Aspergillus oryzae and alkaline protease from Bacillus licheniformis on amino-functionalized multi-walled carbon nanotubes in milk.

This study aimed was to covalently immobilize ß-galactosidase from Aspergillus oryzae and protease from Bacillus licheniformis on amino-functionalized multi-walled carbon nanotubes. In this study, a two-level factorial design was employed to investigate the impact of seven continuous variables (activation pH, glutaraldehyde molarity, activation time (0-8 h), buffer solution pH (8-0), buffer solution molarity, MWCNT-NH 2 -glutaraldehyde quantity, and stabilization time (0-180 h)) on the immobilization efficiency and enzymatic activity of protease and ß-galactosidase. Furthermore, the effect of time on the percentage of enzymatic activity was examined during specific intervals (24, 48, 72, 96, and 120 h) of the immobilization process. The analysis of variance results for protease enzymatic activity revealed a notable influence of the seven variables on immobilization efficiency and enzymatic activity. Additionally, the findings indicate that activation time, buffer pH, MWCNT-NH 2 -glutaraldehyde quantity, and stabilization time significantly affect the activity of the protease enzyme. The interplay between buffer pH and stabilization time is also significant. Indeed, both activation time and the quantity of MWCNT-NH 2 -glutaraldehyde exert a reducing effect on enzyme activity. Notably, the influence of MWCNT-NH 2 -glutaraldehyde quantity is more significant (p < 0.05). In terms of beta-galactosidase enzymatic activity, the study results highlight that among the seven variables considered, only the glutaraldehyde molarity, activation time, and the interplay of activation time and the quantity of MWCNT-NH 2 -glutaraldehyde can exert a statistically significant positive impact on the enzyme's activity (p < 0.05). The combination of activation time and buffer solution molarity, as well as the interactive effect of buffer pH and MWCNT-NH2-glutaraldehyde, can lead to a significant improvement in the stabilization efficiency of the protease of carbon nanotubes. The analysis of variance results demonstrated that the efficiency of covalently immobilizing ß-galactosidase from Aspergillus oryzae on amino-functionalized multi-walled carbon nanotubes is influenced by the molarity of glutaraldehyde, buffer pH, stabilization time, and the interplay of activation time + buffer pH, buffer pH + activation time, activation time + buffer molarity, and glutaraldehyde molarity + MWCNT-NH 2 -glutaraldehyde (p < 0.05). Through the optimization and selection of optimal formulations, the obtained results indicate enzyme activities and stabilization efficiencies of 64.09 % ± 72.63 % and 65.96 % ± 71.77 % for protease and beta-galactosidase, respectively. Moreover, increasing the enzyme stabilization time resulted in a reduction of enzyme activity. Furthermore, an increase in pH, temperature, and the duration of milk storage passing through the enzyme-immobilized carbon nanotubes led to a decrease in enzyme stabilization efficiency, and lactose hydrolysis declined progressively over 8-h. Hence, the covalent immobilization of ß-galactosidase from Aspergillus oryzae and protease from Bacillus licheniformis onto amino-functionalized multi-walled carbon nanotubes is anticipated to be achievable for milk applications.

Extremely rare cause of hyperkalemia: ileostomy‒induced hyperkalemia in extremely low birth weight infants.

BACKGROUND: Hyperkalemia is one of the most serious electrolyte disturbances, and it can cause lethal cardiac arrhythmia. Although hyperkalemia associated with ileostomies has been reported in adults, to the best of our knowledge, it has not previously been reported in neonates. CASE: We report ileostomy‒induced hyperkalemia that persisted during the ileostomy and resolved promptly after the closure of the ileostomy in two extremely low birth weight (ELBW) infants, with birth weights of 850 g and 840 g and gestational ages of 27 weeks and 27 weeks 6 days. CONCLUSIONS: These cases highlight that disruption of intestinal integrity in ELBW infants may cause hyperkalemia. Ensuring the integrity of the gastrointestinal tract plays an important role in the treatment of electrolyte disorders such as hyperkalemia in ELBW infants with an ileostomy.

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.

Neonatal hemochromatosis: a case report with unique presentation.

Acute liver failure (ALF) is a relatively rare condition in neonates, and early diagnosis and treatment are crucial for the treatable conditions. Neonatal hemochromatosis (NH) is a rare clinical condition that is clinically defined as severe neonatal liver disease associated with hepatic and extrahepatic iron deposition in a distribution similar to that seen in hereditary hemochromatosis. Although a few cases have been reported with spontaneous remission, early and aggressive medical treatment is essential for improving the outcome. Despite aggressive treatment, some patients may require liver transplantation. We report a five-day-old male infant with NH and associated Duarte variant galactosemia, renal tubulopathy and hypertyrosinemia, who was successfully treated with combination medical treatment. Combination therapy may reduce the need for liver transplantation in infants with NH. Early diagnosis and aggressive treatment are important as in galactosemia or tyrosinemia for the outcome. Thus, NH may be listed as a treatable cause of ALF in neonates.

Acquired methemoglobinemia in infants.

OBJECTIVE: This study aimed to determine the etiologic factors of acquired methemoglobinemia in infants younger than three months in our region. METHODS: This study was carried out retrospectively in infants with methemoglobinemia admitted to Karadeniz Technical University, Pediatric Clinic, during the period 2000-2009. Infants with methemoglobinemia were identified according to the medical records or ICD-10 code. RESULTS: Nine infants with acquired methemoglobinemia (8 male, 1 female) were included in the study. Seven cases were associated with the use of prilocaine for circumcision, one case with the use of prilocaine-lidocaine for local pain therapy, and one case with neonatal sepsis caused by Staphylococcus aureus. CONCLUSION: Prilocaine should not be used in infants less than three months of age because of the risk of methemoglobinemia. Ascorbic acid is an effective therapy if methylene blue is not obtained. It should not be forgotten that sepsis caused by S. aureus may cause methemoglobinemia in infants.

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.

Intravenous amiodarone used alone or in combination with digoxin for life-threatening supraventricular tachyarrhythmia in neonates and small infants.

OBJECTIVES: The purpose of this study was to report the efficacy of intravenous amiodarone alone or in combination with digoxin in neonates and small infants with life-threatening supraventricular tachyarrhythmia (SVT). METHODS: We retrospectively analyzed 9 neonates and small infants with life-threatening or resistant SVT who were treated with intravenous amiodarone alone or in combination with digoxin. RESULTS: This report consists of 8 patients with reentrant SVT and 1 with atrial flutter. On admission, 7 patients had a congestive heart failure and 3 of whom had cardiovascular collapse. Intravenous rapid bolus of adenosine caused a sustained sinus rhythm in 4 patients. These patients were given digoxin initially, but recurrence of persistent tachyarrhythmia necessitated the use of intravenous amiodarone in all these patients. Amiodarone was given initially to the other 4 patients in whom adenosine caused only temporary conversion to the sinus rhythm. It was effective in 2 patients. In the other 2, digoxin was added to therapy for tachycardia control. Amiodarone alone or in combination with digoxin effectively controlled reentrant SVT in all patients. This combined treatment caused ventricular rate control in patient with atrial flutter, and conversion to the stable sinus rhythm was achieved at approximately 8 months. CONCLUSIONS: Intravenous amiodarone alone or in combination with digoxin was found to be safe and effective in controlling refractory and life-threatening SVT in neonates and small infants.

A Turner syndrome case associated with anal atresia, interrupted aortic arch and multicystic dysplastic kidney.

Although renal and cardiac malformations are commonly seen in Turner syndrome (TS), anorectal malformations, multicystic dysplastic kidney and interrupted aortic arch are quite rare in TS. A newborn with TS with three quite rare congenital malformations (imperforate anus/anal atresia associated with rectovestibular fistula, interrupted aortic arch, and multicystic dysplastic kidney) is presented.

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.

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.

Intraosseous noninvoluting congenital hemangioma of the mandible in a neonate.

Hemangiomas are benign tumors of the capillary endothelium involved in varied clinical and pathologic entities. Congenital hemangioma is quite rare compared to infantile hemangioma. Hemangiomas rarely occur in bone. Intraosseous hemangiomas are most commonly found in the vertebral column and skull. The mandible is the most frequently affected skull bone. Intraosseous hemangiomas commonly present in the second decade of life. Here, we report a neonate with noninvoluting congenital hemangioma of the mandible. To our knowledge, she is the youngest patient reported in the literature.

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).