Leptin and adiponectin levels in discordant dichorionic twins at 72 hours of age-associations with anthropometric parameters and insulin resistance.

BACKGROUND: Insulin resistance (IR) in adults has been associated with intrauterine growth restriction (IUGR). Leptin and adiponectin correlations with anthropometric parameters and IR at 72 h in discordant twins were tested. METHODS: We included 24 discordant (birth weight discordance ≥20% in relation to the heavier cotwin) and 30 concordant (birth weight discordance ≤10%) twins. RESULTS: A correlation between leptin (but not adiponectin) level and birth weight (BW), birth length and head circumference in IUGR twins was recorded (p<0.05). Insulin sensitivity (IS) and homeostatic model assessment (HOMA)-IR in IUGR twins were similar to appropriate-for-gestational-age cotwins and unrelated to adipokines. In IUGR twins, adiponectin and insulin associated positively. In larger concordant twins' leptin level correlated with HOMA-IR and insulin. CONCLUSIONS: Leptin, but not adiponectin, levels correlate positively with anthropometric parameters in IUGR twins. IR in IUGR twins is unrelated to adipokines in the first few days of life.

Lipids and Adipokines in Cord Blood and at 72 h in Discordant Dichorionic Twins.

BACKGROUND: Intrauterine growth restriction (IUGR) is a risk factor for developing metabolic syndrome later in life. We explored whether adipokine concentrations in cord blood (CB) and on day 3 (D3) were related to impaired fetal growth and lipids in IUGR twins. PATIENTS AND METHODS: Thirty-six discordant (birth weight [BW] discordance ≥20% calculated in relation to the heavier co-twins) and 42 concordant (BW discordance ≤ 10%) twin pairs were included. RESULTS: In IUGR twins, both adiponectin/BW and triglyceride (TG) levels were significantly higher, while total cholesterol, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol were lower in CB. On D3, both leptin and HDL-C levels were significantly lower and TG levels were significantly higher in IUGR twins. In the discordant group, the alterations in lipids were not related to any adipokine. CONCLUSIONS: IUGR is related to lower leptin level and proatherogenic lipid profile (higher TG and lower HDL-C), which are not influenced by adipokine at birth.

Etiology, clinical course and response to the treatment of status epilepticus in children: A 16-year single-center experience based on 602 episodes of status epilepticus.

OBJECTIVE: evaluation of etiology, clinical course and response to the treatment of status epilepticus (SE) in children, with particular investigation of superrefractory SE. MATERIALS AND METHODS: The retrospective study included children with convulsive SE aged 0.2-18 years, treated from 1995 to 2011. Status epilepticus is defined as a continuous seizure or intermittent seizures without full recovery of consciousness between seizures for at least 30 min. Refractory SE is diagnosed if SE lasts for more than 60 min, while superrefractory SE if SE continues or recurs 24 h or more after the onset of an anesthesia therapy, including those cases that recur after reduction or withdrawal of an anesthesia. The etiology was summarized in five categories: idiopathic/cryptogenic, remote symptomatic, febrile SE, acute symptomatic and progressive encephalopathy. The patients were treated according to the same hospital protocol. Midazolam iv and diazepam rectally were given as the first line drugs, phenobarbital/phenytoin iv as the second line drugs. If they failed, third line drugs, midazolam and thiopental were given in continuous intravenous infusion. The medication was defined as effective if seizure clinically stopped within 20 min, without recurrence within the next 6 h. Midazolam was assessed as effective even if it failed as the first line, but was effective in intravenous infusion as the third line drug. RESULTS: The study consisted of 602 SE in 395 children. There were 305 (50.7%) refractory SE episodes, and 43 (7.1%) of superrefractory SE. Idiopathic/cryptogenic and febrile SE was the most common etiology in the first SE, while progressive encephalopathy and remote symptomatic was in recurrent and superrefractory SE. The most effective drugs were: midazolam (306/339) given in mean dose of 0.4 mg/kg (range 0.1-1.2 mg/kg), thiopental (47/57) in mean dose of 4 mg/kg (range 3-5 mg/kg), phenobarbital (91/135) in dose of 20 mg/kg. Midazolam successfully stopped 306/339 SE episodes (90.3%), 67 SE (21.9%) by equal or lower dose than 0.2 mg/kg as the first line drug, while all other 239 episodes (78.9%) were stopped by intravenous infusion in range 0.2-1.2 mg/kg/h (mean 0.4 mg/kg/h) as the third line drug. Adverse effects were frequent in superrefractory SE (60.5%). In 15 patients, corticosteroids contributed to the reduction of seizure recurrence after anesthetic withdrawal and cessation of epilepsia partialis continua. Case fatality rate was 5.1% in all patients, while 21.3% in patients with superrefractory SE. CONCLUSION: Status epilepticus in children was characterized by heterogeneous etiology, prolonged duration and commonly good response to midazolam only given in high doses. Superrefractory SE was not so rare in children, especially among the patients with progressive encephalopathy.

Neonatal Abstinence Syndrome - Diagnostic Dilemmas in the Maternity Ward.

INTRODUCTION: Neonatal abstinence syndrome (NAS) refers to a newborn neurological, gastrointestinal and/or respiratory disorder if a newborn was exposed to psychoactive substances in the intrauterine period. NAS is difficult to diagnose due to unreliability of the data on addictive substances use during pregnancy, limited possibilities of the prenatal exposure diagnosis and postnatal substance detection, which all lead to diagnostic dilemmas. OBJECTIVE: The aim of this study was to indicate the problems in patients with early NAS diagnosis in the maternity ward and the importance of clinical presentation used as a guide toward the diagnosis. METHODS: This retrospective study included five term eutrophic newborns with high Apgar score, good adaptation in the first day and with clinical presentation of NAS during the second day of life. The clinical presentation was dominated by irritability, increased wakefulness, increased muscle tone, shrilly crying, tremors, problems with accepting food, tachypnea, subfebrility and hyperhidrosis. Finnegan scale was introduced in order to diagnose NAS and apply the therapy. Single-medication therapy of phenobarbitone was applied in four cases and a combination of phenobarbitone and morphine in one case. For toxicological analysis newborns'urine samples were used. RESULTS: Conditions such as perinatal asphyxia, infection, hunger, polycythemia, hypoglycemia or hypocalcemia were excluded. Finnegan score implied that pharmacological treatment had to be administered. The discrepancy between the NAS anamnesis and toxicological analysis existed. Response to the treatment was positive in all cases. CONCLUSION: NAS is a multisystemic disorder and should be suspected when it is noticed that children exhibit characteristic signs. However, other pathological conditions have to be excluded. Quantification according to the adopted scales for NAS leads toward appropriate treatment and recovery of the newborns.

Pharmacokinetic variability of amikacin after once-daily and twice-daily dosing regimen in full-term neonates.

The purpose of the study was to compare peak (Cpeak) and trough (Ctrough) amikacin levels after twice-daily (TD) or once-daily dosing (OD) in full-term neonates. Additionally, the study aimed to address amikacin pharmacokinetics and its variability. Data included 31 patients born on term. Amikacin daily dose was 15 or 20 mg/kg depending on the neonate's age. Patients randomly received amikacin every 12 or 24 h. In all patients corresponding Cpeak and Ctrough were taken. Volume of distribution (Vd), clearance (CL) and half-life (t1/2) were calculated. Mean Cpeak of 21.79 µg/ml in the TD group was statistically different from Cpeak of 36.39 µg/ml in the OD group. Average Ctrough in TD (5.67 µg/ml) was statistically different from the corresponding 3.99 µg/ml in the OD group. Mean amikacin Vd, CL, and t1/2 were 0.78 ± 0.38 l/kg, 86.99 ± 48.22 ml/h∙kg, and 6.81 ± 2.51 h, respectively. High interindividual pharmacokinetic variability was observed. Further analysis showed that neonatal age contributed to the pharmacokinetic parameters' values. Statistically significant difference in CL and t1/2 was observed between patients age ≤ 2 and > 2 days on therapy initiation. As expected, amikacin given OD achieved higher Cpeak and lower Ctrough than TD. Based on the results, observed variability in amikacin pharmacokinetics was possibly due to the renal maturation process.

N-terminal pro-brain natriuretic peptide in the assessment of respiratory distress in term neonates.

BACKGROUND: N-terminal pro-brain natriuretic peptide (NT-proBNP) is used as a biomarker to differentiate congestive heart failure from lung disease in adults and children. The clinical significance of its use in term neonates has not yet been extensively studied. METHODS: NT-proBNP level was measured in 62 term neonates admitted for respiratory distress (RD): 38 with congenital heart disease (CHD) and 24 with pulmonary disease. The control group consisted of 28 healthy neonates. Findings of auscultation, chest radiography, Silverman-Anderson score and echocardiography were recorded for each patient. Blood samples for measuring NT-proBNP were collected on admission, when blood sampling was indicated for the clinical management of the newborn. RESULTS: In the control group NT-proBNP was significantly higher during the first week of life compared to the rest of the neonatal period (P < 0.001). The RD group, regardless of etiology, had significantly higher NT-proBNP than the control group (P < 0.001). Neonates with more severe RD had significantly higher NT-proBNP (P = 0.002). No significant difference was found between the RD group with CHD and those with pulmonary disease. Neonates with CHD and myocardial hypocontractility had significantly higher NT-proBNP than those with normal contractility (P = 0.022). CONCLUSION: Term neonates with RD have significantly higher NT-proBNP than healthy neonates. A single measurement of NT-proBNP level cannot be used as the sole biomarker for distinguishing between cardiac and pulmonary cause of RD in term neonates.

Risk factors for thrombosis in Serbian children.

Venous and arterial thromboses are increasingly encountered in the pediatric population. We present results of a case-control study of inherited and acquired risk factors for thrombosis in 129 pediatric patients from the first day of life to 18 years. The aims of study were to determine the importance of thrombophilic risk factors and comorbidity as a cause of thrombosis in children. Single thrombophilic risk factor was found in 24.4% (n = 21), whereas combined thrombophilic factors were found in 15.1% (n = 13) patients. A total of 87.2% of the children had recognized thrombophilic risk factors for thrombosis and/or additional comorbid risk factors. The single independent risk factors for thrombosis were mutation of factor V Leiden (P = 0.021), lupus anticoagulant antibodies (P = 0.028), and comorbidity (P = 0.000). Mutation of factor V Leiden [odds ratio (OR), 6.2 (95% confidence interval, CI 1.1-38.1, P = 0.048] was found to be a risk factor for venous thrombosis. Lupus anticoagulant antibodies were related to both venous (P = 0.008) and arterial thrombosis (P = 0.016). The frequency of inherited thrombophilic factors were the same in neonates and adolescents (23%). The prothrombotic gene mutations were present in 18.6% (n = 8) of asymptomatic children. Our study confirms that thrombosis in children is a multifactorial disorder, and associated most with the underlying medical disease (comorbidity) for vein thrombosis [OR, 18.6 (95% CI 3.7-93.4), P = 0.000] and for arterial thrombosis [OR, 10.5 (95% CI 2.2-49.9) P = 0.003]. Inherited thrombophilic disorders contributed to the development of thrombosis in children.

Use of intravenous immunoglobulin in neonates with haemolytic disease and immune thrombocytopenia.

BACKGROUND/AIM: Intravenous immunoglobulin is a blood product made of human polyclonal immunoglobulin G. The mode of action of intravenous immunoglobulin is very complex. It is indicated in treatment of neonatal immune thrombocytopenia and haemolytic disease of the newborn. The aim of the study was to present our experience in the use of intravenous immunoglobulin in a group of term neonates. METHODS: We analysed all relevant clinical and laboratory data of 23 neonates who recieved intravenous immunoglobulin during their hospitalization in Neonatal Intensive Care Unit of Mother and Child Health Care Institute over a five year period, from 2006. to 2010. RESULTS: There were 11 patients with haemolytic disease of the newborn and 12 neonates with immune thrombocytopenia. All of them recieved 1-2 g/kg intravenous immunoglobulin in the course of their treatment. There was no adverse effects of intravenous immunoglobulin use. The use of intravenous immunoglobulin led to an increase in platelet number in thrombocytopenic patients, whereas in those with haemolytic disease serum bilirubin level decreased significantly, so that some patients whose bilirubin level was very close to the exchange transfusion criterion, avoided this procedure. CONCLUSION: The use of intravenous immunoglobulin was shown to be an effective treatment in reducing the need for exchange transfusion, duration of phototherapy and the length of hospital stay in neonates with haemolytic disease. When used in treatment of neonatal immune thrombocytopenia, it leads to an increase in the platelet number, thus decreasing the risk of serious complications of thrombocytopenia.

Two seasons' experience with pandemic A H1N1 influenza infection in neonates.

There are only a few reports on influenza A H1N1 infection in neonates. In this paper, we present our additional experience on the clinical characteristics, epidemiology and treatment of influenza A H1N1 (2009) infection in 10 newborn infants (aged 9-24 days). Influenza A H1N1 infection was confirmed by real-time reverse transcription-polymerase chain reaction of the nasopharyngeal swab specimens. The majority of neonates presented with fever, respiratory symptoms and lethargy. The respiratory illness ranged from mild symptoms to severe pneumonia requiring mechanical ventilation. Antiviral treatment with oseltamivir was started in five patients (50%). One lethal outcome was observed, while nine patients (90%) had complete recovery. To our knowledge, this is the largest presented series of neonatal cases with different clinical symptoms. We discuss the necessity of initiation of oseltamivir in infants with different clinical features.

[Non-immune hydrops fetalis--clinical experience in newborn infants].

INTRODUCTION: Non-immune hydrops fetalis is a condition of excessive accumulation of extravascular fluid without identifiable circulating antibody to erythrocytes membrane antigens. In newborn infants it is characterized by skin oedema and pleural, pericardial or peritoneal effusion. In the era of routine Rh immunization for the prevention of foetal erythroblastosis, non-immune pathophysiologic mechanisms are presented in 76-87% of all hydropic newborns. Non-immune hydrops fetalis can be associated with numerous and various disorders. The mortality rate may exceed 50%. This study was aimed at presenting our clinical experience in treating newborn infants with non-immune hydrops fetalis. MATERIAL AND METHODS: A retrospective-prospective study included newborn infants with non-immune hydrops fetalis, who were treated in the Neonatal Intensive Care Unit of Mother and Child Health Institute of Serbia between January 1, 2001 and October 31, 2010. All valid data about aetiology, diagnosis, clinical course and outcome were recorded. RESULTS: The diagnosis of non-immune hydrops fetalis was made in 11 newborns. The etiologic diagnosis was established in 8 patients: anaemia due to fetomaternal transfusion in 4 patients and conatal cytomegalovirus infection, intracranial haemorrhage, isolated pulmonary lymphangiectasia and diffuse skin and mediastinal lymphangiomatosis in the remaining 4 patients. CONCLUSION: Non-immune hydrops of newborn infant is associated with a high mortality rate and requires complex diagnostic and therapeutic procedures. An optimal management of neonates with non-immune hydrops fetalis demands a multidisciplinary approach to the treatment in a neonatal intensive care unit.

Clinical characteristics of respiratory syncytial virus infection in neonates and young infants.

INTRODUCTION/AIM: Infection with respiratory syncytial virus (RSV) occurs during the first year of life in 50% of children and 20%-40% of them have signs of lower respiratory tract infection (bronchiolitis or pneumonia). There is an increased risk for complicated course and death from RSV infection in premature infants, especially those with bronchopulmonary dysplasia (BPD) or congenital heart disease. The aim of our study was to analyze clinical characteristics of laboratory confirmed RSV infection in order to evaluate the need for preventive measures in neonates and young infants. METHODS: The prospective study included children under age of 12 months admitted to our hospital in the period November 2008-March 2009 who were positive for RSV by enzyme immunoassay membrane test. The course of disease was assessed by clinical score and radiographic findings. RESULTS: Infection with RSV was confirmed in 91 patients: 21 (23.0%) were under the age of 30 days, 37 (40.7%) were between 31-60 days, and 33 patients (36.3%) were older than 60 days (p > 0.05). The highest hospitalization rate was in January--33 patients (36.3%; p < 0.01). Disease severity score in these age groups (AG) were: 8.4 +/- 0.4 (AG 0-30 days); 9.0 +/- 0.3 (AG 31-60 days) and 8.3 +/- 0.3 (AG > 60 days), without statistically significant difference among the groups (p > 0.05). Clinical scores in patients with and without risk factors were 10.5 +/- 0.5 and 8.3 +/- 0.2, respectively (p < 0.01). Pathological radiographic findings were observed in 72 (79.1%) and complications (apnea, significant atelectasis, encephalopathy) occured in 15 (16.5%) patients. The average length of hospital stay in complicated and uncomplicated course of the disease was 9 days and 6 days, respectively (p < 0.01). Therapy in 85 (93.4%) patients included bronchodilators, while systemic glucocorticoids and oxygen therapy were used in 51 (56.0%) and 44 (48.4%) patients, respectively. Death occured in 2 (2.2%) patients, both from a high risk group (the patient with BPD and the other one with congenital heart disease and Down syndrome). CONCLUSION: Infection with RSV in our settings showed marked seasonal characteristics with highest hospitalization rate in January. Although the course and outcome of the disease were favorable in the majority of our patients, the need for hospitalization and administration of therapy with possible side effects warrants that general measures for prevention of respiratory infections are followed especially in the first year of life. Severe disease and death are more probable in neonates and infants with risk factors. In these children passive immunisation with specific monoclonal antibody (e.g. palivizumab) during RSV season should be considered.

Outcome of status epilepticus in children treated in the intensive care unit: a study of 302 cases.

PURPOSE: The aim of the study was to evaluate the outcome of status epilepticus (SE) in children and to define predictors for morbidity, mortality, and SE recurrence. METHODS: The study included 302 children (age 2 months to less than 18 years; mean age ± SD 4.7 ± 4.2 years) with 489 episodes of SE. Etiology, treatment, and clinical and electroencephalography (EEG) features of SE and their impact on the outcome were analyzed. The outcome was classified into three categories: unchanged neurologic status, neurologic consequences, and lethal outcome. Univariate and multivariate Cox hazard regression analyses were used to define predictors of mortality, morbidity, and SE recurrence. KEY FINDINGS: Neurologic status was unchanged in 235 children (77.8%) and neurologic consequences occurred in 39 patients (12.9%); case-fatality ratio was 9.3% and recurrence rate was 21%. Mortality was related to progressive encephalopathy, preexisting neurologic abnormalities, specific EEG findings, and generalized convulsive type of SE. Neurologic consequences were associated with younger age, progressive encephalopathy, duration of SE >24 h, prior epilepsy, and specific EEG findings. Multivariate analyses showed that etiology of SE and prior neurologic abnormalities were independent predictors of mortality, whereas younger age, etiology, and very long duration of SE were predictors of morbidity. SIGNIFICANCE: Outcome of SE in children is favorable in most of the cases, but mortality and morbidity rates are still high. Etiology and prior neurologic abnormalities were the main predictors of mortality, whereas the main predictor of morbidity was underlying etiology.

Hemophilia in the newborn without family history--pattern of clinical presentation of three patients.

INTRODUCTION: Hemophilia is the most frequently diagnosed inborn clotting factor deficiency in the newborn. In about half of the cases diagnosis is made during neonatal period. However, due to different clinical presentation comparing to older children, hemophilia in the newborn could be misdiagnosed, especially in the setting of negative family history. CASE REPORT: Clinical features of three newborns with negative family history for hemophilia are described. All three newborns were the first born children with uneventful perinatal history, and they were referred for investigation of convulsions, soft tissue tumorous mass and sepsis, respectively. Prompt diagnosis of underlying bleeding disorder and adequate substitution therapy lead to the good outcome in all three boys. CONCLUSION: Symptoms and signs of hemophilia in the newborn could be at time misleading and contribute to delayed treatment. High index of suspicion on inherited bleeding disorder is warranted in every neonate with intracranial bleeding.

Neonatal cellulitis and sepsis caused by group A streptococcus.

We report a case of late onset neonatal invasive group A streptococcal disease characterized with rapidly progressing cellulitis and development of sepsis. The infection was acquired from benign and mild skin infection of the child's mother. The causative agent was group A streptococcus, belonging to the emm type 53.2, which usually causes mild skin disease.

[Use of mechanical ventilation in pediatric patients].

BACKGROUND/AIM: Major aims of mechanical ventilation (MV) in pediatrics mean the contribution to complete recovery of acute disorder or to establishing stability of previously long-term changed health condition. MV is used today in 16-46% of patients treated in pediatric intensive care units. The aim of this paper was to get insight into the presence of the disease and pathologic conditions and outcome of MV regarding previous health condition of pediatric patients. METHODS: This retrospective study included 476 pediatric patients (beyond neonatal age) who underwent mechanical ventilation (MV). On the basis of previous health status the patients were classified in two groups: the group A consisted of 157 children with no previous chronic disease leading to MV and the group H comprised of 319 children who received MV due to worsening ofprevious chronic disease. RESULTS: In both groups of pediatric patients there was significant predominance of younger age patients. Acute and chronic neurological disorders were the most frequent conditions requiring use of MV. Out of a total number (476) of the patients, 178 patients (37.40%) died. In the group A 17 patients (10.9%) died, while in the group H mortality rate was significantly higher (161 or 50.5% patients died; p < 0.01; RR 4.85; CI 3.1-7.6). Total duration time of MV in all the patients was 7 525 days, with 1 345 days (15%) accounted for the group A and 4 567 days (85%) for the group H. Mean MV duration was 7.48 (+/- 9.23) days for the patients in the group A which is significantly shorter in comparison to mean 21.8 (+/- 57.96) days for the group H patients (p < 0.001). CONCLUSION: These results point out significant contribution of MV to better outcome in pediatric patients with different acute disorders. Clear dominance of chronically ill children requiring mechanical ventilation due to acute worsening of their condition implies new complexity of problems regarding organization of pediatric intensive care and treatment.

Disseminated neonatal herpes caused by herpes simplex virus types 1 and 2.

Disseminated neonatal herpes simplex virus (HSV) infection is characterized by progressive multiple organ failure and high mortality rates. It can result from infection with either HSV-1 or HSV-2. We report a case of disseminated neonatal herpes that was caused by HSV-1 and HSV-2.

[C-reactive protein and cytokines in the diagnosis of neonatal sepsis].

INTRODUCTION: Accurate evaluation and correct treatment of neonates for possible sepsis still represent the most challenging clinical tasks. Early diagnosis of neonatal sepsis is largely based on the measurement of serum concentrations of different mediators of systemic inflammation, as well as, on a group of proteins named acute phase reactants. Among acute phase reactants, C-reactive protein (CRP) has been the most extensively used and investigated so far. SYNTHESIS AND BIOLOGICAL ROLE OF CRP: This article reviews current knowledge on the synthesis, structure and biologic roles of CRP. Also, we present our original results in regard to the kinetics of serum CRP concentration during the first 24 hours of systemic injection, as well as different patterns of CRP dynamics associated with the initial choice of antibiotics, complications and the final outcome of systemic injection. INTERLEUKINS AND PROCALCITONIN IN DIAGNOSIS OF SEPSIS: Because CRP is specific, but somewhat late marker of neonatal sepsis, possible diagnostic use of other indicators of inflammation, i.e. interleukins 6 and 8, and procalcitonin during neonatal sepsis is also considered. The theoretical advantage of these early indicators is discussed in comparative analysis of the time of their activation after initial infections stimuli. CONCLUSION: In conclusion, we point to the diagnostic accuracy of serial measurements of serum CRP levels. As an alternative, simultaneous measurement of CRP and serum levels using a faster marker, such as procalcitonin, is recommended.