Activation of Toll-like receptors in meconium aspiration syndrome.

OBJECTIVE: Meconium aspiration syndrome (MAS) is a common cause of neonatal morbidity and mortality. Incomplete understanding of the pathogenesis of MAS has hindered the development of specific therapies. We hypothesized that activation of Toll-like receptors (TLRs) might play a role in the pathogenesis of MAS. The present study evaluated the expression of TLR 1, 4, 7, 8 and 9 in neonates with MAS. STUDY DESIGN: The study included 39 neonates with MAS and 17 healthy gestational age-matched neonates as controls. Neonates with maternal chorioamnionitis, perinatal asphyxia, sepsis and congenital malformations were excluded. Good-quality total RNA from umbilical cord blood was reverse transcribed to prepare cDNA using Bio-Rad reverse transcription kit. This cDNA was used to study the expression status of TLR 1, 4, 7, 8 and 9 by real-time quantitative polymerase chain reaction. RESULTS: Compared with controls, TLR1 and TLR4 were highly expressed, TLR9 was moderately expressed, TLR7 was weakly expressed and TLR8 expression was neutral in neonates with MAS. Within the MAS group, no difference in TLR expression was observed with respect to consistency of meconium, severity of the disease, oxygenation index and outcome. CONCLUSION: There is activation of TLRs in neonates with MAS. We speculate that these TLRs probably act as endogenous ligands for various components of meconium that initiate the inflammatory cascade of MAS and contribute to its pathogenesis.

Clinicodemographic Profile of Children with Seizures in a Tertiary Care Hospital: A Cross-Sectional Observational Study.

Seizures are one of the common causes for hospital admissions in children with significant mortality and morbidity. This study was conducted to study the prevalence and clinicodemographic profile of children with seizures in a tertiary care hospital of western Nepal. This prospective cross-sectional study conducted over a period of 2 years included all admitted children (2 months-16 years) with seizures. Among 4962 admitted children, seizures were present in 3.4% (n = 168) of children, with male preponderance. 138 (82.1%) children had generalized tonic-clonic seizures (GTCS) and 30 (17.9%) children had partial seizures. GTCS were more common than partial seizures in both sexes (male = 82.7%; female = 81.2%) and age groups. There was no statistical significance in the distribution of seizures (GTCS and partial seizures) with sexes (P = 0.813) and age groups (P = 0.955). Mean ages of children having GTCS and partial seizures were 8.2 ± 4.6 years and 8.2 ± 4.2 years, respectively. Loss of consciousness (55.4%), fever (39.9%), vomiting (35.1%), and headache (16.1%) were common complaints in seizure patients. Significant number of GTCS cases had fever (P = 0.041) and neurocysticercosis (n = 72; 43%) was the most common etiology in seizure patients. Idiopathic epilepsy (38 (22.6%)), meningoencephalitis (26 (15.5%)), and febrile convulsions (14 (8.33%)) were other leading disorders in children with seizures.

A study of oxidative stress in neonates delivered through meconium-stained amniotic fluid.

To estimate the levels of malondialdehyde (MDA) and 8-hydroxy-2-deoxyguanosine (8-OH-dG) in cord blood plasma of newborns born through meconium-stained amniotic fluid (MSAF) and also to find out the correlation between their levels with birth weight and gestation, we measured the cord blood plasma levels of MDA and 8-OH-dG in 59 newborns born through MSAF and 50 newborns born through clear liquor. The levels of cord blood plasma MDA and 8-OH-dG were significantly higher in full-term and late-preterm newborns born through MSAF. On further comparison, it was found that both full-term and late-preterm intrauterine growth restricted (IUGR) neonates had higher levels of these markers as compared to babies born as appropriate for gestational age (AGA) through MSAF. Plasma levels of MDA and 8-OH-dG were significantly correlated with birth weight even after controlling the relationship with gestational age for all cases as well as all full-term cases. These markers are also significantly correlated to each other. CONCLUSIONS: The present study suggest that the neonates born through MSAF experience higher degrees of oxidative stress, as evidenced by increased levels of cord blood plasma MDA and 8-OH-dG. What is known: • Aspirated meconium has been found to induce free radical generation and cellular damage in animal studies. • Its role in free radical generation and oxidative damage in human neonates is scarce. What is new: • Neonates born through meconium-stained amniotic fluid experience significant oxidative stress.

Neurocysticercosis (NCC) with Hydrocephalus, Optic Atrophy and Vision Loss: A Rare Presentation.

Neurocysticercosis (NCC) is one of the most common parasitic infestations (Taenia solium) of central nervous system (CNS) in children. Seizures are the common presenting symptoms. Hydrocephalus and optic atrophy are rare complications which may require neurosurgical interventions. We report a case of NCC with hydrocephalus and bilateral optic atrophy associated with vision loss in a Nepalese patient who improved with anti-parasitic therapy followed by ventriculo-peritoneal (VP) shunting.

Relationship of Oxygen Saturation with Neonatal and Maternal factors in Vaginal and Cesarean Deliveries.

INTRODUCTION: Hypoxemia is the major cause of neonatal morbidity and mortality. The study aims to determine the influence of birth weight, Apgar score, gestation age, body mass index and hemoglobin of mother on levels of SpO2 in healthy newborns born vaginally and through cesarean section. METHODS: A hospital Based, observational study conducted in Department of Pediatrics, Universal College of Medical Sciences-Teaching Hospital, Bhairahawa, Lumbini, Nepal; on 49 vaginal and 49 cesarean deliveries with Apgar Score ≥ 6. SpO2 was estimated by pulse oximeter post-ductally between 1 to 30 minutes of birth. The observed SpO2 values were correlated with neonatal and maternal factors. RESULTS: Vaginal and Cesarean deliveries SpO2 were comparable for birth weight, gestational age, Apgar score of neonates, body mass index and hemoglobin of the mother. Birth weight in vaginally delivered babies and Apgar score in cesarean births showed significant change in SpO2 (P<0.05). At all points of time the SpO2 values were higher in neonates, born by cesarean than those born out of spontaneous vaginal deliveries (P<0.001). CONCLUSIONS: SpO2 levels in neonates born through cesarean section were higher in comparison to thoseborn by vaginal route. Birth weight and Apgar score had correlation with SpO2 in vaginal and cesarean births, respectively.

Effect of prematurity and intrauterine growth restriction on H-reflex recovery cycle in neonates.

OBJECTIVE: The purpose of this work was to assess the effects of prematurity and intrauterine growth restriction on spinal cord synapses using H-reflex. METHODS: 33 babies were investigated at birth. 14 were full term appropriate for gestational age (FT AGA), 10 were full term intrauterine growth restricted (FT IUGR) and 9 were preterm appropriate for gestational age (PT AGA). The maximum amplitude of H-reflex (Hmax), H-reflex latency (HRL), H/M ratio, H-reflex conduction velocity (HRCV), and H-reflex response to double stimuli (conditioning and test) for H-reflex recovery cycle (HRRC) were recorded in right lower limb (soleus muscle) in all the three groups. RESULTS: Percentage recovery values of H-reflex were significantly higher in FT AGA and FT IUGR babies compared to PT AGA neonates for most of inter-stimulus intervals. No significant differences were observed in H-reflex parameters between FT AGA and FT IUGR groups, but HRL and HRCV were significantly affected in PT AGA group. CONCLUSIONS: Delayed H-reflex recovery in preterms may be due to a prolonged state of neurotransmitter delay in Ia terminals following initial activation by the conditioning stimuli. The cause of such prolonged depletion of neurotransmitters could be attributed to a poor neurotransmitter store in synaptic vesicles of spinal cord in preterm neonates.

The immunogenicity and safety of a reduced PRP-content DTPw-HBV/Hib vaccine when administered according to the accelerated EPI schedule.

BACKGROUND: Combination vaccines improve coverage, compliance and effectively introduce new antigens to mass vaccination programmes. This was a phase III, observer-blind, randomized study of GSK Biologicals diphtheria-tetanus-whole cell pertussis vaccine combined with hepatitis B and Haemophilus influenzae type b vaccines, containing a reduced amount of polyribosyl-ribitol-phosphate (PRP) and a DTPw component manufactured at a different site (DTPw-HBV/Hib2.5 [Kft]). The primary aim of this study was to demonstrate that DTPw-HBV/Hib2.5 [Kft] was not inferior to the licensed DTPw-HBV/Hib (Tritanrix(tm)-HepB/Hiberix(tm)) vaccine or the DTPw-HBV/Hib2.5 vaccine, also containing a reduced amount of PRP, with respect to the immune response to the PRP antigen, when administered to healthy infants, according to the Expanded Programme for Immunization (EPI) schedule at 6, 10 and 14 weeks of age. METHODS: 299 healthy infants were randomised to receive either DTPw-HBV/Hib2.5 [Kft] DTPw-HBV/Hib2.5 or DTPw-HBV/Hib according to the 6-10-14 week EPI schedule. Blood samples were analysed prior to the first dose of study vaccine and one month after the third vaccine dose for the analysis of immune responses. Solicited local and general symptoms such as pain, redness and swelling at the injection site and drowsiness and fever, unsolicited symptoms (defined as any additional adverse event) and serious adverse events (SAEs) were recorded up to 20 weeks of age. RESULTS: One month after the third vaccine dose, 100% of subjects receiving DTPw-HBV/Hib2.5 [Kft] or DTPw-HBV/Hib and 98.8% of subjects receiving DTPw-HBV/Hib2.5 vaccine had seroprotective levels of anti-PRP antibodies (defined as anti-PRP antibody concentration ≥0.15 µg/ml). Seroprotective antibody concentrations were attained in over 98.9% of subjects for diphtheria, tetanus and hepatitis B. The vaccine response rate to pertussis antigen was at least 97.8% in each group. Overall, the DTPw-HBV/Hib2.5 [Kft] vaccine was well tolerated in healthy infants; no SAEs were reported in any group. CONCLUSIONS: The DTPw-HBV/Hib2.5 [Kft] vaccine was immunogenic and well-tolerated when administered according to the EPI schedule to Indian infants. TRIAL REGISTRATION: http://www.clinicaltrials.gov NCT00473668.

A study of clinico-haematological profiles of pancytopenia in children.

We report on the clinico-haematological profile of pancytopenia in children from the Departments of Pediatrics and Pathology, Institute of Medical Sciences, Banaras Hindu University, India, over a period of 30 months. Pancytopenia was defined as: haemoglobin <10 g/dL, absolute neutrophil count 1.5 x 10(9)/L and platelet count <100 x 10(9)/L. A detailed history, clinical examination and haematological parameters were recorded. Bone marrow aspiration and trephine biopsy were carried out in all cases. One hundred and five cases aged 1.5-18 years, with a mean age of 8.6 years, were included in the study. Aplastic anaemia was the most common cause of pancytopenia (43%) followed by acute leukaemia (25%). Infections were the third most common cause of pancytopenia of which kala azar was the most common. Megaloblastic anaemia was seen in 6.7%.

Immune thrombocytopenic purpura.

Immune thrombocytopenic purpura (ITP) is the commonest cause of sudden onset thrombocytopenia in a healthy child. The condition is frequently preceded by a viral infection. The hematological parameters are essentially normal except a low platelet count. Bone marrow examination is not routinely indicated except in specific situations. The pros and cons of drug treatment have been discussed as the disease is benign with excellent prognosis in majority of the cases. The various treatment options including low and high dose steroids, intravenous immunoglobulins and anti D have been discussed at length with other modalities of treatment and role of splenectomy. Current therapeutic options with rituximab and other drugs for stimulating platelet production in chronic cases have also been included in discussion.

Predictors of mortality in very low birth weight neonates in India.

INTRODUCTION: Very low birth weight (VLBW) neonates constitute approximately 4-7 percent of all live births and their mortality is very high. The objective of the present study was to determine the predictors of mortality in VLBW neonates. METHODS: A retrospective cohort of VLBW neonates admitted over three years was studied. Exclusion criteria were: (1) neonates weighing less than 500 g and with gestational age less than 26 weeks; (2) presence of lethal congenital malformations; and (3) death in the delivery room or within 12 hours of life. The outcome measure was in-hospital death. Medical records were reviewed and data was analysed. Univariate analysis and logistic regression analysis were done to determine the predictors of mortality. RESULTS: A total of 260 cases were enrolled, of which a total of 96 (36.9 percent) babies died. The survival rate was found to increase with the increase in birth weight and gestational age. Univariate analysis showed maternal per vaginal bleeding, failure to administer steroid antenatally, Apgar score less than or equal to 5 at one minute, apnoea, gestational age, neonatal septicaemia and shock are the factors directly responsible for neonatal mortality. Logistic regression equation showed maternal bleed (1.326), apnoea (3.159), birth weight (0.037), gestational age (0.063), hypothermia (1.132) and shock (3.49) predicted 65 percent of mortality in VLBW babies. CONCLUSION: Common antenatal and perinatal predictors of mortality in VLBW infants in India include maternal bleed, failure to administer antenatal steroids, low Apgar score, apnoea, extreme prematurity, neonatal septicaemia and shock.

Autoimmune hemolytic anemia.

OBJECTIVE: To study the clinico-hematological profile and treatment outcome in children suffering from auto immune hemolytic anemia (AIHA). METHODS: Twelve children were diagnosed with auto immune hemolytic anemia over a period of four years. Direct antiglobulin test was positive in all the cases. Other causes of hemolytic anemia like thalassemia syndromes, hereditary spherocytosis, G6PD deficiency were excluded by appropriate tests. The children were followed up for 6 months to 4 years. RESULTS: The age ranged from 7 mth to 9 yr with a mean age of 4.51 yr. All patients had pallor as the presenting complaint followed by splenomegaly (83.3%), jaundice (66.7%), fever (50%) and bleeding manifestations (16.7%). 9 patients had primary disease and 3 had secondary disease. Tubercular infection was seen in 2 patients with secondary disease. Jaundice was seen equally in both the groups. Oral prednisolone produced remission in 83.3% cases. 4 patients (3 in primary and one in secondary group) had relapse after initial response. All responded to a second course of steroids but had subsequent relapses and developed a chronic course. CONCLUSION: Autoimmune hemolytic anemia is an uncommon cause of hemolytic anemia in children. Tubercular infection is an underlying pathology in cases of secondary autoimmune hemolytic anemia. Although oral steroids induce remission in most of the cases, relapses are common.

Correlation between clinical features and degree of immunosuppression in HIV infected children.

We conducted this study to find out correlation of CD4% with clinical status in 102 HIV infected antiretroviral naive children. Mean age of presentation was 4.8 years. Perinatal transmission was the commonest mode of transmission (94%). Fever (53%), chronic diarrhea (36%), and cough (29%) were the commonest presenting symptoms. Protein energy malnutrition was seen in 56.7% of children. 33.3% children were asymptomatic, whereas 45.1% were in WHO clinical stages III and IV at the time of presentation. The most common opportunistic infection was tuberculosis. CD4% correlated significantly with the deterioration of the WHO clinical stages (P<0.01) and increasing grades of protein energy malnutrition (P< 0.05).

A study of bone marrow failure syndrome in children.

BACKGROUND: Bone marrow failure syndrome (BMFS), or aplastic anemia, includes peripheral blood single cytopenias, as well as pancytopenia due to inability of the marrow to effectively produce blood cells. AIM: To study the clinico-hematological profile and etiological factors of bone marrow failure syndrome in children. SETTING AND DESIGN: This prospective study was carried out in the Department of Pediatrics of a university teaching hospital over 36 months. MATERIALS AND METHODS: Children with pancytopenia (Hb 9 /L, platelet count<100x10(9)/L) and bone marrow cellularity<25% were included in the study. History of exposure to drugs, socioeconomic status, ethnicity and occupation of father were noted. Bone marrow aspiration; trephine biopsy; Ham test; viral studies for hepatitis A, B and C; and cytogenetic investigations were carried out. STATISTICAL ANALYSIS: Relative risk was estimated by odds ratio (OR) with 95% confidence interval (CI) in matched cases and controls. RESULTS: Of the 53 children studied, 6 (11.3%) were diagnosed as Fanconi anemia. Two cases had features of myelodysplastic syndrome. Forty-five children were labeled as acquired aplastic anemia, of whom one had evidence of hepatitis B infection and two patients (5.8%) had paroxysmal nocturnal hemoglobinuria. Aplastic anemia was more common in children from family with lower socioeconomic status; in Muslims; and where the father's occupation was weaving, dyeing and painting. However, the number was small to make statistically significant conclusions. No correlation could be established with exposure to drugs. CONCLUSION: Fanconi anemia was responsible for approximately one-tenth of the cases of bone marrow failure syndrome. Majority of the patients had acquired aplastic anemia. Hepatitis B infection was an uncommon cause of acquired aplastic anemia.

H-reflex and motor nerve conduction studies in growth retarded newborn babies.

OBJECTIVE: To demonstrate the accelerated postnatal maturation/myelination in growth retarded babies compensating the deficit suffered by them during intrauterine life. METHODS: We studied 16 babies within the first 3 days of birth. These included 6 full term appropriate for gestational age babies (FT AGA) and 10 full term intrauterine growth retarded (FT IUGR). A separate group of 16 babies was examined at 2 months of age. In this group 7 were FT AGA and 9 were FT IUGR at the time of birth. H-reflex latency (HRL), motor nerve conduction velocity (MNCV) and H-reflex excitability (H/M) were measured in the right lower limb. Anthropometric measurements of the babies were also recorded meticulously. All the babies were neurologically normal on clinical evaluation. RESULT: At birth, MNCV was significantly lower in FT IUGR babies compared to FT AGA babies. However at the age of 2 months the MNCV of both FT AGA and FT IUGR was comparable. Other parameters (HRL and H/M) in the IUGR babies were comparable with normal babies both at birth and 2 months of age. In FT IUGR babies crown-heel length and weight was significantly lower than FT AGA babies both at the time of birth and at 2 months of age. CONCLUSION AND SIGNIFICANCE: The findings suggest that FT IUGR babies demonstrate accelerated postnatal peripheral neural maturation. At 2 months of age, the motor nerve conduction velocity of these growth retarded babies was comparable to that observed in normal AGA babies of similar age. This provides an insight into the functional aspect of the proven theories of decreased peripheral myelination in FT IUGR babies with subsequent rapid postnatal myelination that renders these babies neurologically equivalent to FT AGA babies despite not achieving comparable anthropometric parameters.

Newer diagnostic tests for bacterial diseases.

In diagnosing bacterial infections, the rapid identification of bacteremia at an early stage of the disease is critical for a favorable outcome. Furthermore, it is important that exact information be obtained on the stage of the disease rapidly in order to choose and initiate the appropriate therapy. In recent years many new techniques have been added in the diagnostic tools. During the past decade, there has been unprecedented progress in molecular biology as well as in the application of nucleic acid technology to the study of the epidemiology of human infection. Highly sensitive molecular techniques are found to be capable of detecting minute amounts of specific microbial DNA sequences and their complex genetic variations. Moreover, altered levels of biomarkers such as procalcitonin, C-reactive protein, tumor necrosis factor alpha and several interleukins are also found to be promising to define systemic inflammatory response syndrome as indirect evidences of bacterial infections. Lastly, many rapid culture methods are coming up to achieve faster bacterial diagnosis. In this review we will focus on these three newer methods for the early diagnosis of bacterial infections. These approaches will help to expedite the diagnosis of especially early infections and might be a further step towards the improvement of therapeutic methods.

Role of antibiotics in meconium aspiration syndrome.

BACKGROUND: Meconium aspiration syndrome (MAS) is a major cause of severe respiratory distress in newborns and the role of antibiotics in its management is not well defined. OBJECTIVE: To determine the role of routine antibiotic therapy in the management of MAS. METHODS: After excluding the possibility of sepsis, 144 patients with MAS were randomised into two groups. Group A (study group) received ampicillin and gentamicin for 7 days, commencing between 24 and 36 hours of life, and group B, the controls, received no antibiotics. Both groups received similar supportive management. The primary outcome measure was the development of infection. Details of clinical progress during hospitalisation were recorded. All were followed up for a minimum of 3 months. RESULTS: The patient profiles were similar in both groups. Five patients (three in the study group, two controls) developed culture-positive sepsis during their hospital stay. No significant difference was detected between the groups regarding period of oxygen dependency (5.8 vs 5.9 days), day of starting feeds (4.0 vs 4.2), day of achievement of full feeds (9.4 vs 9.3), clearance of chest radiograph (11.7 vs 12.9 days) or duration of hospital stay (13.7 vs 13.5 days). The most common radiological features were parenchymal infiltrates followed by hyperinflation. The incidence of complications was similar in both groups. CONCLUSION: Routine antibiotic therapy is not necessary for managing MAS.