Poor In Utero Growth, and Reduced ß-Cell Compensation and High Fasting Glucose From Childhood, Are Harbingers of Glucose Intolerance in Young Indians.

OBJECTIVE: India is a double world capital of early-life undernutrition and type 2 diabetes. We aimed to characterize life course growth and metabolic trajectories in those developing glucose intolerance as young adults in the Pune Maternal Nutrition Study (PMNS). RESEARCH DESIGN AND METHODS: PMNS is a community-based intergenerational birth cohort established in 1993, with serial information on parents and children through pregnancy, childhood, and adolescence. We compared normal glucose-tolerant and glucose-intolerant participants for serial growth, estimates of insulin sensitivity and secretion (HOMA and dynamic indices), and ß-cell compensation accounting for prevailing insulin sensitivity. RESULTS: At 18 years (N = 619), 37% of men and 20% of women were glucose intolerant (prediabetes n = 184; diabetes n = 1) despite 48% being underweight (BMI <18.5 kg/m2). Glucose-intolerant participants had higher fasting glucose from childhood. Mothers of glucose-intolerant participants had higher glycemia in pregnancy. Glucose-intolerant participants were shorter at birth. Insulin sensitivity decreased with age in all participants, and those with glucose intolerance had consistently lower compensatory insulin secretion from childhood. Participants in the highest quintile of fasting glucose at 6 and 12 years had 2.5- and 4.0-fold higher risks, respectively, of 18-year glucose intolerance; this finding was replicated in two other cohorts. CONCLUSIONS: Inadequate compensatory insulin secretory response to decreasing insulin sensitivity in early life is the major pathophysiology underlying glucose intolerance in thin rural Indians. Smaller birth size, maternal pregnancy hyperglycemia, and higher glycemia from childhood herald future glucose intolerance, mandating a strategy for diabetes prevention from early life, preferably intergenerationally.

Long term Immunogenicity of Single Dose of Live Attenuated Hepatitis A Vaccine in Indian Children - Results of 15-Year Follow-up.

OBJECTIVES: To measure anti-HAV antibodies 15 years after a single dose of live attenuated hepatitis A vaccine in Indian children. METHODS: Of the 143 children vaccinated in 2004, 109 were evaluated in 2019, clinically and for anti-HAV antibodies. These children have been assessed clinically every year, and for anti-HAV antibodies in 2004, 2007, 2010 and 2014. RESULTS: Of the 109 children who came for the present assessment, 11 had received additional doses of hepatitis A vaccine in 2004/2007 because of low anti-HAV titre (<20 mIU/mL). In the remaining 98 children, 94 (96%) had seroprotective levels with a geometric mean titre of 79.6 mIU/mL. Seroprotection rate in all 109 children was 86.2%. CONCLUSIONS: Single dose of live attenuated hepatitis A vaccine in Indian children demonstrated robust immunogenicity at 15 years post vaccination.

Birth weight, childhood and adolescent growth and diabetes risk factors in 21-year-old Asian Indians: the Pune Children's Study.

Our objective was to investigate associations of body size (birth weight and body mass index (BMI)) and growth in height, body fat (adiposity) and lean mass during childhood and adolescence, with risk markers for diabetes in young South Asian adults. We studied 357 men and women aged 21 years from the Pune Children's Study birth cohort. Exposures were 1) birth weight, 21-year BMI, both of these mutually adjusted, and their interaction, and 2) uncorrelated conditional measures of growth in height and proxies for gain in adiposity and lean mass from birth to 8 years (childhood) and 8 to 21 years (adolescence) constructed from birth weight, and weight, height, and skinfolds at 8 and 21 years. Outcomes were plasma glucose and insulin concentrations during an oral glucose tolerance test and derived indices of insulin resistance and secretion. Higher 21-year BMI was associated with higher glucose and insulin concentrations and insulin resistance, and lower disposition index. After adjusting for 21-year BMI, higher birth weight was associated with lower 120-min glucose and insulin resistance, and higher disposition index. In the growth analysis, greater adiposity gain during childhood and adolescence was associated with higher glucose, insulin and insulin resistance, and lower disposition index, with stronger effects from adolescent gain. Greater childhood lean gain and adolescent height gain were associated with lower 120-min glucose and insulin. Consistent with other studies, lower birth weight and higher childhood weight gain increases diabetes risk. Disaggregation of weight gain showed that greater child/adolescent adiposity gain and lower lean and height gain may increase risk.

Do components of adult height predict body composition and cardiometabolic risk in a young adult South Asian Indian population? Findings from a hospital-based cohort study in Pune, India: Pune Children's Study.

OBJECTIVES: We investigated whether the relationship between components of height and cardiovascular disease (CVD) risk may be explained by body composition. We also examined relationships between parental heights and offspring CVD risk. DESIGN: A cohort study using cross-sectional data. SETTING: A secondary care hospital setting in Pune, India. PARTICIPANTS: We studied 357 young adults and their parents in the Pune Children's Study. Primary and secondary outcomes: we measured weight, total height, leg length, sitting height, plasma glucose, insulin and lipids, and blood pressure (BP). Total and regional lean and fat mass were measured by dual X-ray absorptiometry. RESULTS: Leg length was inversely related, and sitting height was directly related to BMI. Total height and leg length were directly related to lean mass, while sitting height was directly related to both lean and fat mass. Leg length was inversely related to systolic BP and 120 min glucose, independent of lean and fat mass. Sitting height was directly related to systolic BP and triglycerides; these relationships were attenuated on adjustment for lean and fat mass. When examined simultaneously, greater leg length was protective and greater sitting height was associated with a more detrimental CVD risk profile. CONCLUSIONS: Shorter adult leg length and greater sitting height are associated with a more adverse CVD risk factor profile. The mechanisms need further study, but our findings suggest a role for lean and fat mass.

Immunogenicity and safety of a liquid Pentavalent (DTwP-Hb-Hib) combination vaccine manufactured by Human Biologicals Institute in 6-8 weeks old healthy infants: A phase III, randomized, single blind, non-inferiority study.

BACKGROUND: A liquid Pentavalent (DTwP-Hb-Hib) combination vaccine, developed by Human Biologicals Institute, underwent a Phase III clinical study in India. In this randomized, single blind, non-inferiority study, the immunogenicity and safety of this Investigational vaccine was compared with Pentavac SD® vaccine in 6-8 weeks old healthy infants. METHODS: A total of 405 healthy infants aged 6-8 weeks old were randomized in 2:1 ratio to receive three doses of either the Investigational liquid Pentavalent (DTwP-Hb-Hib) combination vaccine or Pentavac SD® vaccine at four to six weeks interval. Immunogenicity was compared by estimation of antibody titers before the first dose and 4-6 weeks after the third dose of vaccination. Safety of each vaccine was assessed and compared by collection of data on solicited and unsolicited adverse events throughout the study period. RESULTS: Out of a total of 405 enrolled subjects, 387 subjects completed the study. The seroconversion rates, seroprotection rates and geometric mean titres of the Investigational liquid Pentavalent (DTwP-Hb-Hib) combination vaccine group were found to be comparable and non-inferior to the Pentavac SD® vaccine group at 4-6 weeks after the third dose of vaccination. Pain, erythema and swelling at the site of injection were found to be the most common local adverse events whereas fever, irritability and unusual crying were found to be the most common systemic adverse events in both the vaccine groups. No vaccine related serious adverse event was reported. In this study, both the Investigational vaccine as well as the Comparator vaccine were found to be immunogenic and well tolerated. CONCLUSION: After assessment of the results of the study it was concluded that the Investigational liquid Pentavalent (DTwP-Hb-Hib) combination vaccine developed by Human Biologicals Institute was immunogenic and safe when administered to infants aged 6-8 weeks and was non-inferior in immunogenicity and safety to Pentavac SD® vaccine. Clinical Trial Registry of India Identifier: CTRI/2016/01/006541.

Allergic rhinitis, rhinoconjunctivitis, and eczema: prevalence and associated factors in children.

OBJECTIVE: We aim to describe the data collected from India during phase 3 of the International study of asthma and allergy in childhood (ISAAC) study. Prevalence, severity, and population characteristics associated with rhinitis, rhinoconjunctivitis, and eczema were assessed. METHODS: Children from two age groups (6-7 and 13-14 years) were included in the study as per the ISAAC protocol. The symptoms of allergy and associated features were assessed using a questionnaire. RESULTS: The prevalence of allergic rhinitis among the 6-7 years age group was 11.3%, while it was 24.4% in the 13-14 years age group. The prevalence of allergic rhinoconjunctivitis was 3.9% in the 6-7 years age group and 10.9% in the 13-14 years age group. The prevalence of eczema was 2.8% in the 6-7 years age group and 3.7% in the 13-14 years age group. The passage of trucks near home, parental smoking, use of paracetamol, use of antibiotics, cooking with firewood, and television watching were associated with allergic rhinitis, rhinoconjunctivitis, and eczema. Maternal smoking was the strongest of all the associated features for allergic rhinitis, rhinoconjunctivitis, and eczema, especially in the 6-7 years age group (odds ratio: 1.9, 95% CI: 1.5-2.4; odds ratio: 2.9, 95% CI, 2.2-3.9; and odds ratio: 3.5, 95% CI: 2.6-4.8, respectively). CONCLUSION: Allergic conditions like allergic rhinitis, rhinoconjunctivitis, and eczema are prevalent among Indian children and are associated with environmental tobacco smoke, paracetamol use, antibiotic use, television watching, and outdoor and indoor air pollution.

Effectiveness of a 5-year school-based intervention programme to reduce adiposity and improve fitness and lifestyle in Indian children; the SYM-KEM study.

DESIGN: Non-randomised non-blinded school-based intervention study. SETTING: Two schools in the cities of Pune and Nasik, India. PARTICIPANTS: The intervention group comprised children attending a Pune school from 7-10 years until 12-15 years of age. Two control groups comprised children of the same age attending a similar school in Nasik, and children in the Pune intervention school but aged 12-15 years at the start of the study. INTERVENTION: A 5-year multi-intervention programme, covering three domains: physical activity, diet and general health, and including increased extracurricular and intracurricular physical activity sessions; daily yoga-based breathing exercises; making physical activity a 'scoring' subject; nutrition education; healthier school meals; removal of fast-food hawkers from the school environs; and health and nutrition education for teachers, pupils and families. MAIN OUTCOME MEASURES: Body mass index (BMI), waist circumference, physical fitness according to simple tests of strength, flexibility and endurance; diet; and lifestyle indicators (time watching TV, studying and actively playing). RESULTS: After 5 years the intervention children were fitter than controls in running, long jump, sit-up and push-up tests (p<0.05 for all). They reported spending less time sedentary (watching TV and studying), more time actively playing and eating fruit more often (p<0.05). The intervention did not reduce BMI or the prevalence of overweight/obesity, but waist circumference was lower than in the Pune controls (p=0.004). CONCLUSIONS: It was possible to achieve multiple health-promoting changes in an academically competitive Indian school. These changes resulted in improved physical fitness, but had no impact on the children's BMI or on the prevalence of overweight/obesity.

Long-term immunogenicity of single dose of live attenuated hepatitis A vaccine in Indian children.

OBJECTIVES: To assess immunogenicity of a single dose of live attenuated hepatitis A vaccine in Indian children, ten years after immunization. METHODS: Of 143 children vaccinated in 2004, 121 children were evaluated in 2014, clinically and for anti-HAV antibodies. RESULTS: 13 children were early vaccine failures who received two doses of HAV vaccine subsequently. 106 (98%) of 108 remaining children had seroprotective levels with a geometric mean titer of 100.5 mIU/mL. On analysis of all 121 children, the immunogenicity was 87.6%. CONCLUSION: Single dose of live attenuated hepatitis A vaccine provides long-term immunity in Indian children.

Higher glucose, insulin and insulin resistance (HOMA-IR) in childhood predict adverse cardiovascular risk in early adulthood: the Pune Children's Study.

AIMS/HYPOTHESIS: The Pune Children's Study aimed to test whether glucose and insulin measurements in childhood predict cardiovascular risk factors in young adulthood. METHODS: We followed up 357 participants (75% follow-up) at 21 years of age who had undergone detailed measurements at 8 years of age (glucose, insulin, HOMA-IR and other indices). Oral glucose tolerance, anthropometry, plasma lipids, BP, carotid intima-media thickness (IMT) and arterial pulse wave velocity (PWV) were measured at 21 years. RESULTS: Higher fasting glucose, insulin and HOMA-IR at 8 years predicted higher glucose, insulin, HOMA-IR, BP, lipids and IMT at 21 years. A 1 SD change in 8 year variables was associated with a 0.10-0.27 SD change at 21 years independently of obesity/adiposity at 8 years of age. A greater rise in glucose-insulin variables between 8 and 21 years was associated with higher cardiovascular risk factors, including PWV. Participants whose HOMA-IR measurement remained in the highest quartile (n = 31) had a more adverse cardiovascular risk profile compared with those whose HOMA-IR measurement remained in the lowest quartile (n = 28). CONCLUSIONS/INTERPRETATION: Prepubertal glucose-insulin metabolism is associated with adult cardiovascular risk and markers of atherosclerosis. Our results support interventions to improve glucose-insulin metabolism in childhood to reduce cardiovascular risk in later life.

Immunogenicity and safety of the pentavalent human-bovine (WC3) reassortant rotavirus vaccine (PRV) in Indian infants.

OBJECTIVE: To evaluate the immunogenicity and safety of a pentavalent rotavirus vaccine (PRV) in Indian infants. STUDY DESIGN: Open-label, single-arm multicentric study. SETTING: Hospital facilities (out patients): SUBJECTS: One hundred and ten (110) healthy Indian infants were enrolled between the ages of 6 weeks and 12 weeks. INTERVENTION: Three doses of oral pentavalent rotavirus vaccine (PRV) were administered with an interval of 4 to 10 weeks (28 to 70 days). MAIN OUTCOME MEASURES: Immunogenicity of PRV was based on the proportion of infants exhibiting a > 3-fold rise in serum anti rotavirus IgA antibodies (from pre dose 1 to 14 days post dose 3). Safety was evaluated for 14 days after each dose. RESULTS: Of the 110 infants enrolled, 83% exhibited at least a 3-fold rise (seroconversion) in serum anti rotavirus IgA antibodies. There were no clinically significant adverse events reported. CONCLUSIONS: A 3-dose regimen of PRV was found to be immunogenic and well tolerated in healthy Indian infants. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov; NCT00496054:

Immunogenicity of single dose live attenuated hepatitis a vaccine.

A long-term immunogenicity study of a single dose live attenuated H2 strain hepatitis A vaccine is being conducted in healthy Indian children at KEM Hospital, Pune. 131 of the original 143 children vaccinated in 2004, were evaluated for anti-HAV antibodies 30 months post vaccination (2007). Seroprotective antibody levels >20 mIU/mL were demonstrated in 87.8 % subjects with an overall GMT of 92.02 mIU/mL. No hepatitis like illness was recorded in any of the subjects since vaccination.

Immunogenicity and reactogenicity of two recombinant hepatitis B vaccines in small infants: a randomized, double-blind comparative study.

Hepatitis B infection is very common in infants, especially in countries with limited resources. Hepatitis B vaccination is recommended in the routine immunization schedules in many countries, including India. We compared immunogenicity and reactogenicity of two recombinant hepatitis B (HB) vaccines in healthy infants. A total of 262 evaluable Indian infants received three doses of 10 microg of an Indian (GeneVac-B) or European (Engerix-B) HB vaccine in a double-blind, randomized fashion. The first dose, given at birth, was followed by a dose at age 6 and 14 weeks. All the subjects were initially seronegative for HB surface antigen (HBsAg) and anti-HB antibodies (anti-HBs). The post-vaccination anti-HBs titers were assessed by ELISA at the time of second and third dose, and 1 month after the third dose. Seroconversion and seroprotection were defined as anti-HBs titers > or =1 mIU/ml and > or =10 mIU/ml, respectively. After first dose, the seroconversion rates were 20% and 17%, in Indian and European vaccine recipients, respectively. The second and third dose increased the seroconversion to 84% and 80%, and to 98% and 98%, respectively. Correspondingly, the seroprotection rates after the first dose was 11% and 10%, and consequently 54% and 58%, and 97% and 95%. None of the differences between vaccines reached statistically significant proportions. Geometric Mean Titer after third dose was 383 mIU/ml and 285 mIU/ml, respectively, also this difference remaining insignificant. Adverse events were similar in both vaccine groups. Immunogenicity and reactogenicity of the Indian and European Hepatitis B vaccines were comparable, when immunization was started at birth.

Low dose 'Sprinkles'-- an innovative approach to treat iron deficiency anemia in infants and young children.

UNLABELLED: Iron supplementation programs using pediatric tablets or drops have not been successful in the control of anemia amongst infants and children in India. Sprinkles is an innovative multi-micronutrient home fortification strategy to control iron deficiency and anemia. OBJECTIVE: We aimed to determine the hematologic response to different doses and forms of iron in Sprinkles and iron drops. SETTING: Twenty two villages of Vadu Rural Health Program, KEM Hospital, Pune. DESIGN: Double blind clustered randomized community-based trial. SUBJECTS: Children (n=432) aged 6 to 18 mo age with Hb between 70 to 100 g/L were enrolled. METHODS: Selected villages were randomized into 5 groups: Sprinkles 12.5, 20 or 30 mg ferrous fumarate, Sprinkles 20 mg micronized ferric pyrophosphate or drops 20 mg ferrous glycine sulphate (DROPS) for 8 weeks. Household socio-demographic information was collected at baseline. Side effects and compliance were monitored through weekly visits. Hemoglobin was estimated at baseline, 3 and 8 weeks. Ferritin was assessed at baseline and 8 weeks. RESULTS: Baseline characteristics were similar across all groups. Hemoglobin increased significantly (P<0.0001) in all groups at 8 weeks with no difference between groups. Ferritin increased (P<0.0001) significantly in all groups with no difference across the groups. Compliance (overall range: 42 to 62 %) was lowest for DROPS. Side effects were significantly higher among DROPS compared to Sprinkles (p>0.05). CONCLUSIONS: Sprinkles 12.5 mg FF dose is as efficacious as higher doses of iron in Sprinkles or DROPS in increasing hemoglobin. Sprinkles FF 12.5 mg is recommended as it has fewer reported side effects and better compliance compared to DROPS.

Evaluation of immunogenicity and tolerability of a live attenuated hepatitis a vaccine in Indian children.

An open non comparative study of a live attenuated H2 strain Hepatitis A vaccine of Chinese origin was carried out in 143 healthy Indian children aged 1 to 12 years (mean age 4.87 2.76 years; 88 boys, 55 girls). At baseline, all were negative for IgG HAV antibodies and had normal hematological and biochemical indices. Two months after a single dose of the vaccine (given subcutaneously), 137 children (i.e. 95.8 %) developed protective antibodies of IgG > 20 mIU / mL. The hematological and biochemical parameters remained within normal limits. There were no adverse events in any except mild fever in one child. In conclusion, live attenuated H2 strain Hepatitis A vaccine in a single dose was found to be immunogenic and safe in Indian children.

Supplementation with flax oil and vitamin C improves the outcome of Attention Deficit Hyperactivity Disorder (ADHD).

Considerable clinical and experimental evidence now supports the idea that deficiencies or imbalances in certain highly unsaturated fatty acids may contribute to a range of common developmental disorders including Attention Deficit Hyperactivity Disorder (ADHD). Few intervention studies with LCPUFA supplementation have reported inconsistent and marginal results. This pilot study evaluates the effect of alpha linolenic acid (ALA)-rich nutritional supplementation in the form of flax oil and antioxidant emulsion on blood fatty acids composition and behavior in children with ADHD. Post-supplementation levels of RBC membrane fatty acids were significantly higher than pretreatment levels as well as the levels in control. There was significant improvement in the symptoms of ADHD reflected by reduction in total hyperactivity scores of ADHD children derived from ADHD rating scale.

Transcutaneous absorption of topically massaged oil in neonates.

OBJECTIVE: To study the transcutaneous absorption of traditionally massaged oil in newborns and to specifically compare the effects of (i) essential fatty acid (EFA) rich - safflower oil and (ii) saturated fat rich coconut oil, on fatty acid profiles of massaged babies. DESIGN: A short term randomised controlled study. SETTING: Tertiary care NICU of a large teaching hospital and a research laboratory of a University complex. METHODS: 120 study babies were randomly assigned to three oil groups (i) safflower oil (n = 40) (ii) coconut oil (n = 40) and (iii) no oil controls (n = 40). In each group, babies were selected in three subsets as per their gestational ages viz (a) less than 34 weeks, (b) 34-37 weeks, (c) greater than 37 weeks. 5 mL of the designated oil was massaged four times a day for five days under controlled conditions of temperature and feeding. Pre and post oil massage samples of blood were analysed for triglycerides and fatty acid profiles using gas chromatography. RESULTS: Post oil triglyceride values were significantly raised in both the oil groups and also in controls. However, the quantum of rise was significantly higher in oil groups as compared to controls. Fatty acid profiles (gas chromatography) showed significant rise in EFAs (linolenic acid and arachidonic acid) in safflower oil group and saturated fats in coconut oil group. Changes were more evident in term babies. There were no side effects associated with the massage. CONCLUSIONS: This study shows that topically applied oil can be absorbed in neonates and is probably available for nutritional purposes. The fatty acid constituents of the oil can influence the changes in the fatty acid profiles of the massaged babies.

Higher offspring birth weight predicts the metabolic syndrome in mothers but not fathers 8 years after delivery: the Pune Children's Study.

In Europid populations, low birth weight of offspring predicts insulin resistance in the mother and cardiovascular disease in both parents. We investigated the association between birth weight of offspring and obesity and cardiovascular risk in the parents of 477 8-year-old children born at the King Edward Memorial Hospital, Pune, India. Eight years after the birth of the child, mothers (33 years of age, n = 459) of heavier babies were taller and more obese (BMI, fat mass, and waist circumference, all P < 0.001) than mothers of lighter babies. Increasing offspring birth weight predicted higher homeostasis model assessment for insulin resistance (P < 0.01) and metabolic syndrome in mothers (P < 0.001) (adjusted for offspring sex and birth order, maternal age, and socioeconomic status) but not hyperglycemia. Fathers (39 years of age, n = 398) of heavier babies were taller and heavier, independent of maternal size (P < 0.01, both), but were not more insulin resistant. Unlike other reports, lower offspring birth weight did not predict insulin resistance in fathers. Thus, urban Indian parents have a higher risk of being obese 8 years after delivery of a heavier child. Mothers but not fathers of heavier babies also have a higher risk of being insulin resistant and developing the metabolic syndrome. Our findings highlight the need for a better understanding of the relation between fetal growth and future health before contemplating public health interventions to improve fetal growth.

Copper metabolic defects and liver disease: environmental aspects.

Copper (Cu) is an essential trace element for many biological processes. Cu homeostasis is generally well maintained by inbuilt controls in intestinal absorption, biliary excretion and intrahepatic storage. Copper deficiency disorders are rare. Acute Cu toxicity occurs occasionally in accidental poisoning with Cu sulfate. Chronic Cu toxicity in the form of liver cirrhosis and damage to other organs is seen classically in Wilson's Disease (genetic abnormality of Cu metabolism) and in the presumed environmental disorder Indian Childhood Cirrhosis (ICC). The clinical, epidemiological and treatment aspects of ICC are described. The evidence linking ICC to environmental Cu is (i) greatly increased hepatic Cu; (ii) early introduction of Cu contaminated milk boiled or stored in brass vessels; (iii) dramatic decline in ICC throughout the country coincident with change in feeding vessels; and (iv) continued long-term remission in d-penicillamine-treated patients after withdrawal of the drug. The nature and role of a second factor in the causation of ICC remains unclear, although a genetic predisposition is strongly suspected. Scattered reports of an ICC-like illness from the West (Idiopathic Cu Toxicosis, Endemic Tyrolean Infantile Cirrhosis), suggest that different mechanisms (environmental, genetic or both) can lead to the same end stage liver disease-'ecogenetic' disorders.