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Objective: To explore possible genes related to the development of persistent pulmonary hypertension of the newborn (PPHN). Methods: The authors identified 285 single nucleotide polymorphisms (SNPs) of 11 candidate genes (BMPR2, EPAS1, PDE3A, VEGFA, ENG, NOTCH3, SOD3, CPS1, ABCA3, ACVRL1, and SMAD9), using an Illumina Asian Screening Array-24 v1.0 BeadChip Array. The FastLmmC and R package was used for statistical analyses. The chi-square test and Cochrane-Armitage trend test were used to compare the allele and genotype frequencies between the groups and to test the genetic models, respectively. Results: A total of 45 PPHN infants and 294 control subjects were analyzed. The most common cause of PPHN was meconium aspiration syndrome. Among the 285 SNPs, 17 SNPs from 6 candidate genes (BMPR2, EPAS1, PDE3A, VEGFA, ENG, and NOTCH3) were significantly associated with PPHN (P < 0.05). After using the Bonferroni correction (P < 0.00018), only the rs17034984 SNP located in intron 1 of the EPAS1 gene remained significantly different between the PPHN and control subjects (P = 0.00014). The frequency of the TC/TT genotype of rs17034984 in the gene with the dominant model was significant in the patients with PPHN (OR = 5.38, 95% CI: 2.15–13.49). The T allele frequency of rs17034984 in the gene showed a significant difference compared with the control subjects (OR = 4.89, 95% CI: 2.03–11.82). Conclusions: The present study suggests that the rs17034984 variant of EPAS1 gene is associated with PPHN.

In this review, we report the available data regarding efficacy, safety and pharmacokinetics of colistin in the treatment of multidrug-resistant Gram-negative bacteria in neonates and infants. Seventeen clinical studies, involving 312 patients, and 3 pharmacokinetics studies were identified. Blood stream infection was the most common source of infection, followed by pneumonia and meningitis/ventriculitis. In most cases, colistin was administered in association with other antibiotics. The most common route of administration was intravenous, with colistimethate doses ranging from 25,000 to 225,000 IU/kg/day divided into 2 or 3 doses. A recent pharmacokinetic study suggested that the appropriate intravenous dose should be >150,000 IU/kg/day. Microbiologic cure was obtained in 94.2% of patients and survival was 76.6%. The combination of intraventricular and intravenous colistin should be used in meningitis/ventriculitis. Nebulized colistin should be used as adjunctive treatment, but not as monotherapy. Nephrotoxicity and apnea were reported in 5.8% and 3.9% of patients respectively.The use of colistin for multidrug-resistant Gram-negative infections in neonates and infants is effective and safe, but the quality of studies is moderate. The optimal intravenous dose should be higher than that indicated in most reports.

Objective: To determine the risk factors and outcomes of persistent pulmonary hypertension of the newborn (PPHN)-associated pneumothorax (PTX).Study design: The medical records of infants diagnosed...

Objective This study aims to determine the risk factors and outcome of persistent pulmonary hypertension of the newborn (PPHN)-associated acute kidney injury (AKI). Study Design Infants diagnosed with PPHN at Hat Yai Hospital from January 2012 to December 2016 were retrospectively reviewed. Results Of the 109 included PPHN infants, 28.4% (31/109) died, and AKI was found in 28.4% following neonatal KDIGO classification. Of the 31, 19 who died (61.3%) reached stage 1, 3 (9.7%) reached stage 2, and 9 (29.0%) reached stage 3. AKI (all stages combined) was significantly associated with increased mortality with an odds ratio (OR) of 8.71 (95% confidence interval [CI], 3.37–22.49). Multivariate logistic regression analysis indicated that male gender (adjusted OR = 8.56; 95% CI = 0.84–85.09) and urine output of Conclusion The incidence of AKI in PPHN was high in this study, and this complication was also significantly associated with higher mortality. In PPHN neonates, AKI should be especially closely monitored in males and infants who have a urine output of

Vernix caseosa aspiration is an extremely rare condition resulting in high mortality if complicated by persistent hypertension of the newborn (PPHN). Herein we offer the first case report of PPHN due to massive vernix caseosa aspiration documented by histopathological examination. This case report is presented to provide a synopsis of the pathoetiology of PPHN related to vernix caseosa aspiration syndrome as likely to be encountered by neonatologists and general pediatricians involved with neonatal care.

In this study, we sought to evaluate the pharmacokinetics of colistin after intravenous administration of colistimethate sodium (CMS) in the critically ill neonates with Gram-negative bacterial infections. A single intravenous dose of CMS [approximately 150,000 IU/kg, equivalent to 5 mg/kg colistin base activity (CBA)] was administered to 7 critically ill neonates. Mean (±SD) maximum plasma colistin concentration and area under the time-concentration curve from 0 to infinity were 3.0 ± 0.7 µg/mL and 25.3 ± 10.4 µg·h/mL, respectively. Time to maximum concentration, half-life, apparent volume of distribution and clearance were 1.3 ± 0.9 hours, 9.0 ± 6.5 hours, 7.7 ± 9.3 L/kg and 0.6 ± 0.3 L/h/kg, respectively. After a dose regimen of 5 mg/kg CBA every 24 hours, the average concentration expected at steady state is 1.1 ± 0.4 µg/mL. In critically ill neonates, a single intravenous dose of 5 mg CBA/kg (approximately 150,000 IU/kg of CMS) resulted in suboptimal plasma concentrations of colistin. According to our pharmacokinetics data, the dosage of CMS currently used in critically ill neonates is insufficient.

OBJECTIVE To assess the current practice preferences in diagnosis and management of persistent hypertension of the newborn (PPHN) of neonatologists or pediatricians with expertise in neonatal care. STUDY DESIGN Investigators identified potential participants worldwide through a literature search. They were emailed the URL of an online 25-item questionnaire through the web survey site SurveyMonkey®. Additional respondents were also acquired through a professional online discussion group. The survey was conducted during July - September 2015. RESULTS Overall, there were 200 respondents from 51 different countries. Of these, the average 2014 mortality rate of the 90 respondents who completed this section of the questionnaire was 8.3% (interquartile range (IQR): 0-20.3). Echocardiography together with pre-to-post ductal oxygen pulse oximetry (SpO2) gradient was the most common PPHN diagnostic method. The most frequent first-line pulmonary vasodilator was inhaled nitric oxide (155/199, 77.9%). Oral sildenafil was most commonly used as second-line adjunctive therapy by 46.3% (81/175). Dopamine (139/198, 70.2%) was chosen to be the initial inotropic agent and normal saline (191/199, 96.0%) was the preferred initial fluid resuscitation for hypotension. Sedation and analgesia were routinely used for PPHN treatment. Twenty-one percent (42/199) of respondents also used muscle relaxants to control respiratory distress. The most commonly used targets for partial pressure of oxygen, partial pressure of carbon dioxide, SpO2 and hemoglobin were 71-80 mmHg (60/197, 30.4%), 36-45 mmHg (100/199, 50.2%), 91-95% (111/199, 55.8%), and 13-15 gm/dL (156/196, 79.6%), respectively. CONCLUSIONS This survey shows that the management of PPHN varies widely around the world. The major PPHN diagnostic method is echocardiography together with bedside SpO2 monitoring. The study numbers show the main differences are between developed and developing countries. Further studies exploring evidence-based principles of diagnosis and management in PPHN are warranted.

Objectives: To explore the incidence, etiologies, diagnostic methods, treatment options and outcomes in neonates with persistent pulmonary hypertension of the newborn (PPHN) and to identify mortali...

Persistent pulmonary hypertension of the newborn (PPHN) is a complication of several respiratory diseases characterized by an elevation in pulmonary vascular resistance with resultant right-to-left shunting of blood and severe hypoxemia in the neonatal period. PPHN carries a high rate of morbidity and mortality, particularly in limited-resource settings (low-income and/or developing country). Echocardiography remains the gold standard for diagnosis of PPHN. Modern therapies such as inhaled nitric oxide, high-frequency oscillatory ventilation, extracorporeal membrane oxygenation, and/or other pulmonary vasodilators agents can reduce the mortality rate of PPHN. Unfortunately, echocardiography and the use of these modern therapies are often difficult for a medical institution to provide for patients in developing countries, even when a timely diagnosis of PPHN has been made. In this review, the practical challenges of timely diagnosis of PPHN and efficient use of available treatment options faced by pediatricians or neonatologists in limited-resource settings are discussed.

Background Respiratory failure is a most serious neonatal disorder. A severity of illness assessment should be performed for mechanically ventilated infants to predict the probability of hospital mortality and to assist clinical decision making. Objectives To evaluate the ability of the Score for Neonatal Acute Physiology, version II (SNAP-II) to predict the mortality risk for the infants who are mechanically ventilated with positive pressure ventilation (PPV) at a neonatal intensive care unit (NICU). Methods A prospective observational cohort study was performed in a 12-bed level III NICU at Hat Yai Hospital between January 2010 and December 2010. Results During the study period, 46 infants were ventilated with PPV at admission. Of these, 8 died (17%) and 30 survived (83%). The overall mean SNAP-II score was significantly higher in the group of infants who died compared with those who survived (36.5 ± 11.5 vs. 22.3 ± 13.6, P < 0.01, respectively).The area under the receiver operating characteristic curve for the SNAP-II was 0.79 (95% confidence interval (CI) 0.66 to 0.92, P = 0.01). Every one-point increment of SNAP-II was associated with an odds ratio of 1.08 (95% CI 1.02 to 1.14, P < 0.01). The stratification of the two sets of scores when compared between groups showed that infants who had SNAP-II scores of ≥32 had the highest mortality risk with an odds ratio of 9.7 (95% CI 1.7 to 56.5) with sensitivity of 75.0% and specificity of 76.3%. Conclusion SNAP-II scores can significantly predict mortality in infants requiring mechanical PPV.

Background: Meconium aspiration syndrome (MAS)-associated persistent pulmonary hypertension of the newborn (PPHN) is a serious respiratory disease in neonates. Objective: The objective was to examine the risk factors and outcomes of MAS-associated PPHN (MAS-PPHN). Patients and Methods: The records of neonates diagnosed with MAS with and without PPHN at Hat Yai Hospital from January 2015 to December 2017 were retrospectively reviewed. Results: During the study period, the cases of 211 MAS neonates were analyzed. The overall incidence of MAS based on born inside hospital was 7.7 per 1000 live births. Of these, 36 (17.1%) developed PPHN with a 2.4% (5/211) mortality rate. The mean gestational age and birth weight of all MAS neonates were 39.2 ± 1.6 weeks and 3043 ± 584 g, respectively. MAS-PPHN neonates had a significantly lower Apgar score at 5 min of

Background: Even though pulse oximetry screening (POS) is widely used for the early detection of critical congenital heart disease (CCHD) in unrecognized newborns, the missing cases of CCHD are still found in our practice. Aims: To evaluate the accuracy of POS for CCHD in asymptomatic term newborns and to identify the missing cases. Subjects and Methods: This retrospective cohort study was performed in asymptomatic term newborns born from June 2016 to September 2017 at Hatyai Hospital. Central electronic medical records (including POS and echocardiograms) during birth hospitalization and subsequent medical records at 6 months after discharge were reviewed. Statistical Analysis Used: The diagnostic accuracy of POS for CCHD was assessed by using sensitivity and specificity (with 95% confidence interval [CI]). Results: A total of 7137 asymptomatic term newborns were enrolled. POS had a sensitivity of 42.86% (95% CI 9.90–81.59) and a specificity of 99.96% (95% CI 99.88–99.99). Nearly 57.14% (4 out of 7 cases of CCHD) constituted secondary target group. All the late diagnoses (3 cases) were of coarctation of the aorta (COA). The mortality rate of late detected CCHD was 33.3%. Conclusions: POS displayed low detection rate in secondary target group, particularly those with COA. POS decreased late detection of CCHD by 57.1%. The mortality rate of COA was high in late detection. It was found that the appropriate time span for POS follow-up should be up to 4 months.

Summary. Background: Infections caused by extensive drug-resistant Acinetobacter baumannii (XDR-AB) have been increasingly observed and are associated with a high mortality rate. We present our experience using aerosolized colistin for the treatment of ventilator-associated pneumonia (VAP) due to XDR-AB in neonates. Methods: The clinical data of neonates who received aerosolized 4 mg per kg of colistin base twice daily as an adjunctive therapy for VAP caused by XDR-AB between July 2008 and September 2009 were retrospectively reviewed. The outcomes were compared with the neonates with VAP from XDR-AB in October 2006–September 2007 who did not receive aerosolized colistin. Results: During the study period, eight neonates (three preterm and five term neonates) with VAP caused by XDR-AB received aerosolized colistin. All isolated pathogens from the tracheobronchial specimens of the eight patients were XDR-AB susceptible to colistin only. Six patients received aerosolized colistin without concomitant intravenous colistin. All children were cured with eradication of XDR-AB from respiratory secretions. Seven patients survived and were discharged from the hospital, and one died from bacterial sepsis unrelated to the VAP episode. There were no clinical or laboratory adverse events related to aerosolized colistin. Compared to the seven neonates in the earlier period, the neonates who received aerosolized colistin had higher birth weight and gestational age, and lower mortality rate (13% vs. 71%, P ¼ 0.04). Conclusions: Aerosolized colistin may be a useful adjunctive therapy in VAP due to XDR-AB. The use of aerosolized colistin in neonates should be investigated in a

To describe the clinical characteristics, diagnostic methods, treatment modalities, and complications, and identify the mortality risk factors, of infants with short-term persistent pulmonary hypertension of the newborn (PPHN).The clinical data of infants diagnosed with PPHN at Hat Yai Hospital from January 2010 to February 2014 were retrospectively reviewed. Cox proportional hazard regression analysis was performed to assess factors associated with mortality.The records of 119 infants were analyzed. Of these, 47 died giving an in-hospital mortality rate of 39.5%. The prevalence of PPHN (based on inborn births) was 2.8 per 1000 live births. The mean gestational age and birth weight were 39.1 ± 1.6 weeks and 3044 ± 563 g, respectively. Multivariate Cox regression analysis indicated that pneumothorax [adjusted hazard ratio (HR) = 2.07 (95% CI 1.09-3.93)] and acute kidney injury [adjusted HR = 2.99 (95% CI 1.59-5.61)] were factors associated independently with an increased risk for death, while infants who received total parenteral nutrition [adjusted HR = 0.22 (95% CI 0.10-0.50)] had lower mortality.A high mortality rate of PPHN was observed in this study. Significantly higher mortality was noted in infants complicated with pneumothorax and acute kidney injury.

The purpose of this study was to evaluate the pulmonary and systemic pharmacokinetics of colistin following a single dose of nebulized colistimethate sodium (CMS) in mechanically ventilated neonates. We administered a single dose of nebulized CMS (approximately 120,000 IU/kg of CMS, equivalent to 4 mg/kg colistin base activity) to 6 ventilated neonates with ventilator-associated pneumonia. The median gestational age was 39 weeks (range, 32-39 weeks). Mean (± SD) tracheal aspirate colistin maximum concentration (Cmax), area under the concentration-time curve (AUC 0-24) and t1/2 were 24.0 ± 8.2 μg/mL, 147.6 ± 53.5 μg · hours/mL and 9.8 ± 5.5 hours, respectively. The plasma concentrations of colistin were low. In neonates, a single nebulized dose of CMS (120,000 IU) resulted in high local concentrations for at least 12 hours and low systemic concentrations of colistin. Twice daily nebulization might be more appropriate.

A preterm female infant was born at 28 weeks of gestation, weighing 840 g. She was intubated soon after delivery and diagnosed with respiratory distress syndrome. She required positive pressure ventilation for 10 days, at which time she was extubated and placed on nasal continuous positive airway pressure (CPAP) for apnoea prophylaxis. On day 14 of …

An infected cephalhematoma is a rare condition in neonates. We report a case of an 18-day-old neonate who was diagnosed with an infected cephalhematoma caused by an extended spectrum beta-lactamase (ESBL)-producing Escherichia coli complicated with septicemia, meningitis, and skull osteomyelitis. He was successfully treated with meropenem and surgical incision and drainage. ESBL-producing E. coli may cause infection of a cephalhematoma in neonates.

Narongsak Nakwan1,2, Jeerawan Wannaro2, Narongwit Nakwan31Neonatal Intensive Care Unit, 2Department of Pediatrics, 3Department of Medicine, Hat Yai Medical Education Center, Hat Yai Hospital, Songkhla, ThailandAim: To describe the clinical, bacteriological features, and outcome of Acinetobacter lwoffii infection in the neonatal population.Method: We retrospectively reviewed the medical records of four neonatal cases of A. lwoffii infection admitted to the Hat Yai Hospital, January 2005 to December 2009.Results: Four cases (one in 2007, and three in 2008) were identified as having A. lwoffii infection. Of the four cases, three presented with late-onset infection (after 72 hours of age), while 1 presented with early-onset (within the first 72 hours of age). All cases were inserted with umbilical catheters, required positive pressure mechanical ventilation, and had been treated previously with antibiotic drugs at time of diagnosis. Antimicrobial susceptibility testing of seven isolates (three in blood, three in sputum, and one in cerebrospinal fluid) was performed using the disk diffusion method. The most tested isolates were susceptible to netilmicin, imipenem, cefoperazone/sulbactam, while most were simultaneously generally resistant to amikacin, gentamicin, ceftazidime, ceftriaxone, cefepime, ciprofloxacin, and clindamicin. The treatment of A. lwoffii infection in the four cases varied. Only one case was successfully treated with imipenem, while three cases died from severe ventilator-associated pneumonia, and severe sepsis.Conclusion: This study increases awareness of A. lwoffii infection in the neonatal population, particularly in premature infants with several risk factors for nosocomial infection, including central intravascular catheters and prolonged mechanical ventilation.Keywords: Acinetobacter lwoffii, Acinetobacter infection, newborn infant

AIM: To evaluate the ability of the Score for Neonatal Acute Physiology-Version II (SNAP-II) to predict mortality in infants with persistent pulmonary hypertension of the newborn (PPHN). METHODS: A prospective cohort study of 41 infants with PPHN admitted to our neonatal intensive care unit between June 2008 and March 2010, who underwent a SNAP-II test within 12 h of admission. RESULTS: Of the 41 infants, 14 died (34.1%) and 27 survived (65.9%). The SNAP-II scores were significantly higher in infants who died (50.1 ± 18.5 vs. 35.7 ± 16.8, P=0.02). Each point increase in the SNAP score increased the odds of mortality by 1.04 [95% confidence interval (CI) 1.01-1.07, P

ary We present a case of erythema nodosum leprosum (ENL) reaction with dse alveolar haemorrhage (DAH) in a patient who completely recovered with pulsed methylprednisolone. Our case illustrates that ENL could be a predisposing factor for DAH and a high dose of corticosteroid plays an important role in successfully treating such a patient.

Isolated cerebellar cryptococcoma in an immunocompetent patient is a rare condition. We report a case of an immunocompetent adult with isolated cerebellar cryptococcoma. The patient presented with chronic headaches for one year and was found to have multiple cerebellar abscesses on imaging. Our patient underwent resection of the lesion and the cryptococcoma was subsequently diagnosed by histological examination. We initiated treatment with antifungal medicine and was successfully treated after 6 months of therapy. A cryptococcoma may be a cause of isolated cerebellar abscess in immunocompetent patients despite not finding cryptococcal antigen in the serum.

Neonatal infection due to Cryptococcus neoformans is extremely rare. We report a case of a 21-day-old neonate diagnosed with cryptococcal septicemia who was successfully treated with amphotericin B. He was born to a human immunodeficiency virus (HIV) seronegative mother. This report alerts general pediatricians and neonatologists to consider Cryptococcus neoformans infection as a possible cause of sepsis in newborn infants.

Objective To evaluate peritonitis in children receiving peritoneal dialysis (PD) in southern Thailand. Patients and Methods We reviewed the records of patients who received PD at the Department of Pediatrics, Prince of Songkla University from January 1994 to December 2003. Results Forty-six patients had PD performed for 228.6 patient-months. Their mean age was 9.5±4.8 years (range 3.0 months-16.7 years). Twenty-eight patients had complications with 61 episodes of peritonitis. The age, sex and causes of renal failure did not display any differences between patients who had or did not have peritonitis (p=0.2, 0.6 and 0.6, respectively). The first peritonitis occurrence was on average at 2.7±4.0 patient-months (median 0.4, range 0–12.5) following catheter insertion, with an average incidence rate of one infection per 3.5±4.8 patient-months (median 1.0, range 0–23.2). The causative agents were both gram-positive and gram-negative bacteria, and fungi at 24%, 44%, and 8% respectively (24% of the cultures did not grow). There was no significant difference in causative agents between home- and hospital-acquired peritonitis (p=1.0). Conclusion PD-related peritonitis in this study occurred earlier and more often than in other studies, probably because all of our PDs were performed immediately after catheter insertion.

doi: 10.1007/s12519-011-0288-2 ©Children's Hospital, Zhejiang University School of Medicine, China and Springer-Verlag Berlin Heidelberg 2011. All rights reserved. A female infant, weighing 2740 g, was vaginally born at 42 weeks of gestation. The Apgar scores were 7 and 8 at 1 and 5 minutes, respectively. After birth, the infant immediately developed respiratory distress, and required conventional ventilation, with an initial peak positive pressure of 15 cmH2O, positive end-expiratory pressure of 4 cmH2O, frequency of 40/min, and supplemental oxygen of 100%. A chest radiograph taken within the first hour following birth revealed retained fetal lung fluid with homogenous round opacity at the right upper lung (Fig. A). At 3 hours of life, she developed severe hypoxemia with 75% of pre-ductal saturation (SpO2) and 64% of post-ductal SpO2, leading to a clinical diagnosis of persistent pulmonary hypertension of the newborn (PPHN). Her respiration support was substantially changed to high frequency oscillatory ventilation with a mean airway pressure of 12 cmH2O, delta-pressure of 40 cmH2O, frequency of 10 Hz, and supplemental oxygen of 100%. The results of an arterial blood gas taken at 6 hours of life were PaCO2 79 mmHg, PaO2 54 mmHg, and pH 7.12. Serial chest X-rays at 24 hours of life revealed disappeared fetal lung fl uid and the round opacity became more obvious (Fig. B). At 3 days of life, she was weaned from supplemental oxygen, inotropic therapy, and sedative drugs, and respiratory support was switched to conventional ventilation at her 4 days of life. Computed tomography demonstrated a posterior mediastinal mass with faint internal calcifications and tracheal displacement (Fig. C). Ventilator dependency suspected to be secondary to an airway obstruction led to the attending physician performing a thoracotomy on the 12th day, which revealed a tumor which was later removed. Histology of the tumor showed small round cells in a pseudorosette formation, compatible with a poorly differentiated neuroblastoma (Fig. D). Unfortunately, the patient died of septicemia 2 months later. Congenital neuroblastoma is the most common malignant solid tumor in newborns, accounting for 54% of all neonatal malignancies. However, intrathoracic lesion is very rare in this age group. All reported neonatal intrathoracic neuroblastomas have presented with respiratory symptoms and required respiratory Congenital intrathoracic neuroblastoma presenting as persistent pulmonary hypertension in a newborn

A full-term male neonate was born by vaginal delivery developed respiratory distress, noisy breathing and central cyanosis shortly after birth. He required intubation with a low setting of conventional ventilation, and his respiratory status dramatically improved. A 5 French catheter was passed nasally with difficulty bilaterally. CT scans of the nasal cavity revealed a marked narrowing of the anterior nasal passage, which was compatible with congenital nasal pyriform aperture stenosis (CNPAS) (figure 1). At 24 h …

Background: Klebsiella rhinoscleromatis is the etiologic bacterium of rhinoscleroma. While rare, it has been implicated as a cause of septicemia. Only five cases of septicemia due to K. rhinoscleromatis have been reported previously. Objective: Report a case of K. rhinoscleromatis septicemia in Thailand and literature review. Results: K. rhinoscleromatis septicemia was observed in a 71-years-old-female diabetic patient suffering with acute fever. Keywords: Bacterial infection, gram-negative bacteremia, Klebsiella, rhinoscleroma, rhinoscleromatis