Need and Viability of Newborn Screening Programme in India: Report from a Pilot Study.

India, a country with the second largest population in the world, does not have a national newborn screening programme as part of its health policy. With funding support from the Grand Challenges Canada, a pilot newborn screening programme was implemented for the Udupi district of South India to study the need and viability of a national programme in India. Six disorders were selected for the study based on the availability of funding and recommendation from pediatricians in the district. Here, we report the observed incidence during the study. A cost-effectiveness analysis of implementing newborn screening in India was performed. It is evident from our analysis that the financial loss for the nation due to these preventable diseases is much higher than the overall expenditure for screening, diagnosis, and treatment. This cost-effectiveness analysis justifies the need for a national newborn screening programme in India.

Effectiveness of a training program for bleeding disorders among accredited social health activists in Udupi District, Karnataka, India.

INTRODUCTION: Hemophilia and other bleeding disorders are underreported and cause significant morbidity and mortality in resource-constrained countries. Training and the creation of awareness among accredited social heath activists (ASHAs) will aid in the early detection of bleeding disorders at the community level. OBJECTIVE: To develop awareness and skills for the screening and identification of cases with bleeding symptoms among ASHAs in Udupi District, Karnataka, India. METHODS: An interventional study was undertaken in Udupi District, which has three taluks and approximately 233 villages. All ASHAs with a current role (586) from rural Udupi were provided a competency-based training program at the community health center using a specifically designed training manual for the identification of cases with bleeding disorders. A pre-test/post-test evaluation was performed to discover the training outcomes. RESULTS: Sixteen (2.7%) participants had average knowledge in the first post-test, and 570 (92.2%) participants had good knowledge. Thirty-nine (6.6%) participants had average knowledge in second post-test, and 547 (94.3%) participants had good knowledge. The effectiveness of the training program was assessed using Friedman's two-way test. A significant difference in knowledge scores (χ2 = 955.1) was found at baseline evaluation and end of the training test 1 and at 30 days of training test 2 among the ASHAs. CONCLUSION: Accredited social heath activists health care workers, who are the most important link between the community and health services, successfully created public awareness concerning the early detection of bleeding disorders.

A Randomized Trial of Factor VIII and Neutralizing Antibodies in Hemophilia A.

BACKGROUND: The development of neutralizing anti-factor VIII alloantibodies (inhibitors) in patients with severe hemophilia A may depend on the concentrate used for replacement therapy. METHODS: We conducted a randomized trial to assess the incidence of factor VIII inhibitors among patients treated with plasma-derived factor VIII containing von Willebrand factor or recombinant factor VIII. Patients who met the eligibility criteria (male sex, age <6 years, severe hemophilia A, and no previous treatment with any factor VIII concentrate or only minimal treatment with blood components) were included from 42 sites. RESULTS: Of 303 patients screened, 264 underwent randomization and 251 were analyzed. Inhibitors developed in 76 patients, 50 of whom had high-titer inhibitors (≥5 Bethesda units). Inhibitors developed in 29 of the 125 patients treated with plasma-derived factor VIII (20 patients had high-titer inhibitors) and in 47 of the 126 patients treated with recombinant factor VIII (30 patients had high-titer inhibitors). The cumulative incidence of all inhibitors was 26.8% (95% confidence interval [CI], 18.4 to 35.2) with plasma-derived factor VIII and 44.5% (95% CI, 34.7 to 54.3) with recombinant factor VIII; the cumulative incidence of high-titer inhibitors was 18.6% (95% CI, 11.2 to 26.0) and 28.4% (95% CI, 19.6 to 37.2), respectively. In Cox regression models for the primary end point of all inhibitors, recombinant factor VIII was associated with an 87% higher incidence than plasma-derived factor VIII (hazard ratio, 1.87; 95% CI, 1.17 to 2.96). This association did not change in multivariable analysis. For high-titer inhibitors, the hazard ratio was 1.69 (95% CI, 0.96 to 2.98). When the analysis was restricted to recombinant factor VIII products other than second-generation full-length recombinant factor VIII, effect estimates remained similar for all inhibitors (hazard ratio, 1.98; 95% CI, 0.99 to 3.97) and high-titer inhibitors (hazard ratio, 2.59; 95% CI, 1.11 to 6.00). CONCLUSIONS: Patients treated with plasma-derived factor VIII containing von Willebrand factor had a lower incidence of inhibitors than those treated with recombinant factor VIII. (Funded by the Angelo Bianchi Bonomi Foundation and others; ClinicalTrials.gov number, NCT01064284; EudraCT number, 2009-011186-88.).

Correlation of cord blood lipid heterogeneity in neonates with their anthropometry at birth.

OBJECTIVE: Fetus with intrauterine stress may exhibit programmed changes that can alter its metabolism and bear severe risk for diseases in adult life. The current study was designed to assess the correlation between cord blood lipid profile with the anthropometric data in neonates. MATERIALS AND METHODS: 146 newborn babies born at Dr. T M A Pai Hospital, Udupi were screened and their birth weight, length, head circumference and abdominal circumference were noted at birth. Umbilical cord blood samples were analyzed for total cholesterol, triglycerides (TG), high density lipoprotein (HDL) and low density lipoprotein (LDL). Infants were also grouped further based on gestational age (GA) and sex-adjusted birth weight percentiles into three groups i.e. Small for gestational age (SGA), Appropriate for gestational age (AGA) and Large for gestational age (LGA) for comparison of their lipid profiles. Inclusion criteria were normal fetal heart rate at birth and an APGAR score >7. Statistical significance of relation between lipid profile and anthropometry was done using ANOVA and Pearson correlation coefficient. RESULTS: Triglycerides were significantly higher in babies with higher ponderal index (PI) than those with lower PI (P = 0.011). The TG level of SGA babies were significantly higher as compared to AGA group (P = 0.001). The LDL levels in neonates with higher abdominal circumference were significantly lower than those with lower AC (P = 0.019). Mean HDL levels were higher in neonates with larger AC, but not statistically significant. Maternal BMI had no influence on neonates' lipid profile. CONCLUSION: Abnormal intrauterine milieu created by maternal changes during gestation may bear a profound impact on lipid metabolism in neonates, which may account for their differences in lipid profile and anthropometry at birth.

Bacterial profile of the oropharynx in infants: an assessment of the confounding factors for colonization.

OBJECTIVE: To determine the composition of non pathogenic microflora (NPM) and pathogenic microflora (PM) and the assessment of factors affecting their colonization in the oropharynx. METHODS: Oropharyngeal swabs were obtained from 464 infants, aged 15 days to I year, with or without clinical signs and symptoms of upper respiratory tract infection (URTI), for the current study.Culture was done on blood and chocolate agar, and the colonies were identified using standard microbiological procedures. RESULTS: The influence of age, presence of siblings and feeding patterns on colonization of oropharynx and the profile of NPM and PM in symptomatic and asymptomatic infants was studied. Colonization of oropharynx by NPM decreased with age whereas by PM increased with age significantly. Isolation of PM significantly increased in cases having siblings less than 18 years of age at home. Season showed a significant influence on the colonization of microflora in the oropharynx. Colonization by NPM was significantly higher in exclusively breast fed (EBF) infants, whereas by PM was higher in mixed fed (MF) infants. Symptomatic infants were higher in the MF group than in EBF group. Certain species of NPM exhibited significant inhibitory effects on colonization of PM. CONCLUSIONS: Assessment of the factors influencing the oropharyngeal colonization of microflora in infants identifies the risk factors for various infections in later life.

Erythrocyte indicators of oxidative changes in patients with graded traumatic head injury.

CONTEXT: Acute oxidative stress following a traumatic head injury (HI) has been implicated in inducing severe secondary brain damage and influencing the clinical outcome of HI patients. AIMS: This study was performed to evaluate and compare the oxidative changes in patients with varying severity of HI in the early posttraumatic period using erythrocyte indicators. SETTINGS AND DESIGN: Head injury patients were divided into two groups based on their Glasgow Coma Scale (GCS) scores recorded at admission to the hospital on the day of trauma itself. Accordingly, the study included 30 severe HI (SHI, GCS scores 8 or less) and 25 Mild HI (MHI, GCS scores more than 8) patients. Thirty age and sex-matched healthy individuals were included in this comparative study as controls. MATERIALS AND METHODS: Blood samples were obtained from controls and HI patients (within 24 h of trauma onset). Erythrocyte oxidative changes were studied by estimating thiobarbituric acid reactive substances (TBARS), glutathione (GSH), superoxide dismutase (SOD) and glutathione reductase (GR). RESULTS: Erythrocyte TBARS levels were significantly higher and GSH levels were significantly lower in SHI and MHI patients as compared to controls. The SOD activity was significantly increased only in SHI patients and remained unchanged in MHI patients as compared to controls. As compared to MHI patients, erythrocyte TBARS levels were significantly higher, GSH levels were significantly lower and SOD activity was markedly elevated in SHI patients. Erythrocyte GR activity did not show significant changes in both groups of patients as compared to controls. CONCLUSION: Oxidative stress is evident in both SHI and MHI patients in the early posttraumatic period as reflected by their erythrocyte indicators, but the severity of oxidative stress has varied relatively with the severity of head injury. The present findings provide indications that early oxidative changes could influence the neurological recovery of HI patients.

Time-relative changes in the erythrocyte antioxidant enzyme activities and their relationship with Glasgow Coma Scale scores in severe head injury patients in the 21-day posttraumatic study period.

BACKGROUND: Reactive oxygen species are indicated to play a prime role in the pathophysiology of brain damage following a severe head injury (SHI). AIM: The current study was designed to understand the time-relative changes and relationship between erythrocyte antioxidant enzyme activities and Glasgow Coma Scale (GCS) scores of SHI patients in the 21-day posttraumatic study period. SETTINGS AND DESIGN: The study included 24 SHI patients and 25 age- and sex-matched normal controls (NC). Activities of superoxide dismutase (SOD), glutathione reductase (GR) and glutathione peroxidase (GSH-Px) were assayed in these patients and controls. The GCS scores of these patients were also recorded for the comparative study. MATERIALS AND METHODS: Venous blood samples were collected on day 7 (D7) and D21 from SHI patients and NC for the assay of SOD, GR and GSH-Px activities. These changes were correlated with age and changes in GCS scores of patients. STATISTICAL ANALYSIS: A one-way analysis of variance (ANOVA) was used to compare mean values of each parameter between group 1 (NC), group 2 (D7 changes in SHI patients) and group 3 (D21 changes in SHI patients). ANOVA was followed by Bonferroni post hoc tests. The Pearson correlation was applied to correlate between the antioxidant parameters and age and GCS scores of these patients. RESULTS: A significant increase in erythrocyte SOD and GSH-Px activities was observed in group 3 as compared to groups 1 and 2. The increase in GSH-Px activity was significant in group 2 as compared to group 1. Although not significant, there was an increase in mean GR activity in groups 2 and 3 as compared to group 1. CONCLUSION: These findings indicate that SHI patients have shown significantly enhanced erythrocyte SOD and GSH-Px activities during the 21-day posttraumatic study period.