Sevim Ünal

Pulmonary hypertension and reopening of the ductus arteriosus in an infant treated with diazoxide

Abstract Diazoxide is the main therapeutic agent for persistent hyperinsulinemic hypoglycemia. Generally, it is tolerated well, but rarely it can cause severe life-threatening complications. We report a neonate who was treated with diazoxide for hyperinsulinemic hypoglycemia. On the 6th day of the treatment we observed sepsis-mimicking symptoms, mild pulmonary hypertension, and re-opening of the ductus arteriosus. All these findings resolved dramatically shortly after discontinuation of treatment. To our knowledge, this is the first reported case of re-opening of the ductus arteriosus due to diazoxide toxicity.

The implementation of neonatal peritoneal dialysis in a clinical setting.

Objective: To investigate etiology, outcome and complications related to neonatal peritoneal dialysis (PD). Methods: Neonates treated with PD in our neonatal intensive care unit during 2007–2010 were analyzed retrospectively. Results: Among 4036 hospitalized neonates; 20 neonates (0.5%) who underwent 21 cycles of PD [7 preterm, 13 term; 13 female, 7 male] were included. The mean birth weight was 2930.2 ± 720.6 g (1120–4570), mean gestational age was 37.5 ± 3.5 weeks (27–41). The etiologic disorders included inborn errors of metabolism (propionic acidemia, methylmalonic acidemia, citrullinemia, glutaric aciduria type2, maple syrup urine disease, 10), or acute renal failure secondary to perinatal asphyxia (4), sepsis (2), prematurity (2), hypoplastic left heart syndrome (1), kernicterus (1). The complications included peritonitis (2), early leakage (4), hemorrhage (1), catheter removal (3) and occlusion (2). The mortality rate was 50%. The gestational ages and birth weights of surviving neonates were higher (p < 0.05). Among surviving neonates, chronic renal failure (1), severe (4) and moderate neuromotor impairment (2) developed within 4–43 months. Conclusion: PD, although invasive, is an effective therapy in neonates. The complexity and invasiveness of the procedure is probably responsible for high rate of complications and mortality. If appropriate catheter selection and technique in the placement should be done, PD might improve outcome.

Heparin Infusion to Prevent Umbilical Venous Catheter Related Thrombosis in Neonates

OBJECTIVE To investigate umbilical venous catheter (UVC) related thrombosis by Doppler echocardiographic evaluation of neonates infused with heparin or placebo. METHODS We conducted a prospective study to determine UVC-related thrombosis in term and nearterm neonates. Heparin or placebo (0.5 IU/mL) was infused at a rate of 1 mL/hr to the study and control group. Doppler echocardiography was performed at 1, 3, and 5 days after UVC insertion. RESULTS Forty-six neonates (63% males) with a mean gestational age of 38.2 ± 1.8 weeks, and a mean birth-weight of 2993 ± 563 grams were included. No UVC-related thrombosis was observed in the study group, which included 19 neonates. Among the 27 neonates in the control group, one neonate developed UVC-related thrombosis. There were no statistical differences between the groups for gestational age, birth weight, postnatal age, UVC duration, mortality, mechanical ventilation, and inotrope requirement, and hemagram or coagulation profile. The complications were as follows, mild pulmonary hemorrhage, 6.5% (3); leak-out, 4.3% (2); peritoneal leakage, 2.2% (1); occlusion, 2.2% (1); gastrointestinal findings, 6.5% (3); sepsis, 10.9% (5); and catheter-related thrombosis, 2.2% (1). CONCLUSION This study demonstrated that heparin infusion of 0.5 IU/mL through the UVC had no effect on catheter-related thrombosis in term and near-term neonates. Randomized controlled trials are necessary to conclusively evaluate the effect of heparin on UVC-related thrombosis.

A Novel Homozygous Mutation in the KCNJ11 Gene of a Neonate with Congenital Hyperinsulinism and Successful Management with Sirolimus

Congenital hyperinsulinism (CHI) is the most common cause of neonatal persistent hypoglycemia caused by mutations in nine known genes. Early diagnosis and treatment are important to prevent brain injury. The clinical presentation and response to pharmacological therapy may vary depending on the underlying pathology. Genetic analysis is important in the diagnosis, treatment, patient follow-up, and prediction of recurrence risk within families. Our patient had severe hypoglycemia and seizure following birth. His diagnostic evaluations including genetic testing confirmed CHI. He was treated with a high-glucose infusion, high-dose diazoxide, nifedipine, and glucagon infusion. A novel homozygous mutation (p.F315I) in the KCNJ11 gene, leading to diazoxide-unresponsive CHI, was identified. Both parents were heterozygous for this mutation. Our patient’s clinical course was complicated by severe refractory hypoglycemia; he was successfully managed with sirolimus and surgical intervention was not required. Diazoxide, nifedipine, and glucagon were discontinued gradually following sirolimus therapy. The patient was discharged at 2 months of age on low-dose octreotide and sirolimus. His outpatient clinical follow-up continues with no episodes of hypoglycemia. We present a novel homozygous p.F315I mutation in the KCNJ11 gene leading to diazoxide-unresponsive CHI in a neonate. This case illustrates the challenges associated with the diagnosis and management of CHI, as well as the successful therapy with sirolimus.

The assessment of time-dependent myocardial changes in infants with perinatal hypoxia.

Objective: The aim of the study was to assess myocardial damage in infants due to perinatal hypoxia. Methods: The findings of 29 infants with perinatal hypoxia and 20 healthy infants were compared. Blood gas analysis, serum lactate, cardiac troponin I (cTnI), troponin T (cTnT), creatine kinase-MB (CK-MB) and B-type natriuretic peptide (BNP) were evaluated. Echocardiography together with tissue Doppler imaging was performed. Results: cTnT, CK-MB and BNP were higher in patients at the first day. There were positive correlations between the left ventricular (LV) myocardial performance index (MPI) and cTnT at first day and also at first month. LV ejection fraction and fractional shortening were lower at first day and at first month in patients. Myocardial systolic (Sm) and diastolic (Em and Am) velocities at all segments were lower at first day, and interventricular septum Sm, LV Sm, LV Em, right ventricular Em and LV Am were still lower at first month in patients. Isovolumic relaxation time at all segments together with LV MPI was higher at first day, ejection time values were lower and MPI values were higher at all segments at first month in patients. Conclusions: These findings demonstrated that the signs of myocardial damage due to perinatal hypoxia still present at first month.

Intracardiac Thrombus in Children: The Fine Equilibrium Between the Risk and the Benefit

The medical records of 16 patients diagnosed as intracardiac thrombus were searched. The size, location and outcome of thrombus together with demographic data of patients were assessed. The median age of the patients was 2.2 years. Six patients were newborn and two patients were infant. The median size of thrombus was 9 mm. The localization was right atrium in seven, right ventricle in five, left ventricle in one, pulmonary artery in one, and superior vena cava in two patients. There was prematurity in five, ciyanotic congenital heart disease in one, blood culture positivity in three, malignancy in four, nephrotic syndrome in one, indwelling catheters in 10, and acquired or genetic thrombophilia in six patients as risk factors. In the treatment, the first choice was tissue plasminogen activator in two patients, heparin infusion in one patient and low molecular weight heparin in remaining 12 patients. In nine patients, therapy included parenteral antimicrobials together with anticoagulants. The result was complete resolution in 15 patients and in one patient thrombus was surgically removed. The median time was 16 (2–70) days for 50% resolution and 26 (3–93) days for complete resolution. There was a statistically significant (P = .027 and r = 0.5) correlation between the size and the complete resolution time. There was no anticoagulant therapy related major complication. In patients with intracardiac thrombus, selection of anticoagulant therapy may decrease the risk of complications. Surgery is rarely required and thrombolytics are not usually necessary for resolution of thrombus.

Clinical characteristics and phenotype–genotype analysis in Turkish patients with congenital hyperinsulinism; predominance of recessive KATP channel mutations

OBJECTIVE Congenital hyperinsulinism (CHI) is the commonest cause of hyperinsulinaemic hypoglycaemia in the neonatal, infancy and childhood periods. Its clinical presentation, histology and underlying molecular biology are extremely heterogeneous. The aim of this study was to describe the clinical characteristics, analyse the genotype-phenotype correlations and describe the treatment outcome of Turkish CHI patients. DESIGN AND METHODS A total of 35 patients with CHI were retrospectively recruited from four large paediatric endocrine centres in Turkey. Detailed clinical, biochemical and genotype information was collected. RESULTS Diazoxide unresponsiveness was observed in nearly half of the patients (n=17; 48.5%). Among diazoxide-unresponsive patients, mutations in ABCC8/KCNJ11 were identified in 16 (94%) patients. Among diazoxide-responsive patients (n=18), mutations were identified in two patients (11%). Genotype-phenotype correlation revealed that mutations in ABCC8/KCNJ11 were associated with an increased birth weight and early age of presentation. Five patients had p.L1171fs (c.3512del) ABCC8 mutations, suggestive of a founder effect. The rate of detection of a pathogenic mutation was higher in consanguineous families compared with non-consanguineous families (87.5 vs 21%; P<0.0001).Among the diazoxide-unresponsive group, ten patients were medically managed with octreotide therapy and carbohydrate-rich feeds and six patients underwent subtotal pancreatectomy. There was a high incidence of developmental delay and cerebral palsy among diazoxide-unresponsive patients. CONCLUSIONS This is the largest study to report genotype-phenotype correlations among Turkish patients with CHI. Mutations in ABCC8 and KCNJ11 are the commonest causes of CHI in Turkish patients (48.6%). There is a higher likelihood of genetic diagnosis in patients with early age of presentation, higher birth weight and from consanguineous pedigrees.

Wheezing, asthma, and atopy in premature infants at 2 years of age

BACKGROUND/AIM We aimed to evaluate wheezing, bronchial asthma (BA), and atopy in premature infants at 2 years of age via a cross-sectional study. MATERIALS AND METHODS Premature infants at <37 weeks of gestational age (GA) were assessed for atopy by skin-prick test and serum immunoglobulin E level at 2 years of age. The familys and infants histories of allergy, BA, atopy, and wheezing were obtained by questionnaire and from hospital records. RESULTS There were 98 infants, with mean birth weight (BW) 1517.4 ± 486.5 g and GA 30.8 ± 2.9 weeks. The frequencies of wheezing, asthma, and bronchopulmonary dysplasia (BPD) were 32.7%, 16.3%, and 14.3%, respectively. Skin-prick tests were positive for 11 subjects, with allergy to cereals for 7 infants, egg for 3, and peanut for 1. Wheezing was related to GA, BW, respiratory distress syndrome, mechanical ventilation, sepsis, asphyxia, smoking, antenatal steroid, BA, palivizumab prophylaxis, number of people in the household, and duration of hospitalization (P < 0.05). Wheezing was negatively correlated to GA. Family history of BA, smoking, and number of people in the household were linked to BA (P < 0.05). CONCLUSION Wheezing was related to degree of premature birth, but BA was linked to BA in the family and smoking. Increased gestation should improve the infants respiratory health up to 2 years of age.

Feeding Intolerance and Vomiting Caused by Duodenal Pancreatic Heterotopia in a Neonate

211 ABS TRACT Öz Pancreatic heterotopia (PH) is a congenital abnormality defined by the presence of an ectopic pancreatic tissue outside the usual anatomic location of the pancreas. The frequency of the disorder is reported to be 0.2-15% in autopsies, 1-2% in laparotomies. The most common locations are the stomach, duodenum and jejunum. The symptoms develop as per the localization particularly in the elderly. We presented a term neonate with a birth weight of 4460 gr hospitalized due to bilious vomiting 10 days after birth. The neonate presented 17% of dehydration, jaundice, and hypochloremic alkalosis on admission. Upper gastrointestinal contrast study demonstrated delayed passage. A mass of lace appearance in the second part of the duodenum was observed by endoscopy and was surgically excised. The diagnosis of PH was made through histopathological analysis. We want to highlight that although relatively rare, PH should be considered in the differential diagnosis of neonates with vomiting and feeding intolerance. The mass must be excised, if the symptoms develop.

Intravenous iloprost and oral sildenafil as rescue medicine in newborns with persistent pulmonary hypertension resistant to conventional therapy

Objectives: To review the data of 11 term newborns with persistent pulmonary hypertension of the newborn (PPHN) resistant to conventional therapy and treated with intravenous (IV) iloprost and oral sildenafil as rescue medicine. Materials and Methods: Iloprost was started 2 ng/kg/min intravenously, if oxygenation index (OI) 25 in spite of conventional methods in 24 h. During follow-up, if OI remains 25, iloprost dosage was increased by 1 ng/kg/min by 6-h intervals. If there was improvement in OI in 24 h, treatment continued with IV iloprost and thereafter with inhaled iloprost during weaning. However, if there was no improvement in OI, treatment continued with 0.25 mg/kg/dose oral sildenafil given at 4 doses. If OI remains 25, sildenafil dosage was increased by 0.25 mg/kg at each following dose. Similarly, if there was improvement in OI in 24 h, treatment continued with oral sildenafil and thereafter with inhaled iloprost during weaning. Results: In 5 patients, treatment continued with oral sildenafil because of no response to IV iloprost. The treatment continued median 5 days in subjects given IV iloprost, and median 6 days with oral sildenafil. The extubation time was median 10 days and the follow-up continued median 17 days. The mean systolic pulmonary artery pressure was 63.3 mmHg before treatment, and 38.5 mmHg before discharge ( P Conclusion: These results showed that, the use of IV iloprost and oral sildenafil as rescue medicine in patients with resistant PPHN could be effective and safe.