Size at birth and cognitive ability in late life: A systematic review

Recent evidence suggests that growth restriction in utero may lead to neurocognitive disorders in late life, either through impaired brain development or adverse metabolic programming

Association of preeclampsia with anthropometric measures and blood pressure in Indian children.

BACKGROUND AND OBJECTIVE: Birth weight and post-natal growth are important predictors of adult health. Preeclampsia (PE) is associated with low birth weight and may have long term effects on the health of the children. The current study aims to compare anthropometry and blood pressure between children of mothers with and without PE in an Indian cohort. METHODS: We studied children born to women with (PE; n = 211) and without preeclampsia (non-PE; n = 470) at Bharati Hospital, Pune, India. Anthropometry and blood pressure were measured in children at 3-7 years of age. Weight and height Z-scores were calculated using the WHO 2006 growth reference. Independent t-tests were used to compare means between the two groups, and associations between preeclampsia and child outcomes were analyzed using multiple linear regression, adjusting for potential confounders. RESULTS: Weight and height Z-scores (p = 0.04 and 0.008), and subscapular skinfold thickness (p = 0.03) were higher among children of PE compared with children of non-PE mothers. Systolic blood pressure was also higher in children of PE mothers (1.70 mmHg [95% CI 0.05, 2.90] p = 0.006). BMI and diastolic blood pressure did not differ between groups. In regression models adjusted for newborn weight and gestational age, current age and sex, and maternal height, BMI and socio-economic status, children of PE mothers had higher weight Z-score (0.27 SD [95%CI 0.06, 0.48] p = 0.01), height Z-score (0.28 SD [95%CI 0.09, 0.47] p = 0.005), and subscapular skinfold thickness (0.38 mm [95%CI 0.00, 0.76] p = 0.049). A trend for higher systolic blood pressure (1.59 mmHg [95%CI -0.02, 3.20] p = 0.053) in the children was also observed in the adjusted model. The difference in systolic blood pressure was attenuated after adjusting further for the child's weight and height (1.09 mmHg [95%CI -0.48, 2.67] p = 0.17). There was no evidence of differences in effects between boys and girls. CONCLUSION: Children of PE mothers were taller and heavier, and had higher systolic blood pressure, partly explained by their increased body size, than children of non-PE mothers. In utero exposure to preeclampsia may increase the risk of future cardiovascular disease

Public engagement with cohort participants in Scotland and India: How do participants want to shape mental health research?

Introduction We now have the opportunity to disentangle the complexities of lifespan brain health through linking rich birth cohorts data to novel information utilizing health informatics techniques. Wellcome Trust evidenced that efforts to manage and link digital health data require exploring the attitudes of public and data guardians towards this initiative. Objectives and Approach Our teams in Aberdeen, Mysore and Mumbai have established general population cohorts that have provided evidence on the early-life origins of later-life diseases. In 2016, we engaged with the participants of the Aberdeen Children of the 1950s (62-68,N~8,400) in an event attended by 350 study members. We are also engaging with members and data guardians of Mysore Parthenon Cohort (20-21y,N~500), Mysore Birth Records Cohort (51-83y,N~750), and Mumbai Maternal Nutrition Cohort (5-11y,N~1,600). This qualitative project utilises focus groups and individual interviews. The goal is to understand their attitudes and perceived public benefits towards future novel data collection, data platforms and biorepositories. Results The ACONF event attendees were very willing to volunteer for further studies. The highest support was for ‘provide a blood sample’ (92%) and the lowest for ‘take an online survey’ (83%). They were satisfied with data governance but had incomplete understanding of linkage possibilities with their data. Through the ongoing activities in Mysore and in Mumbai, we aim to achieve the following: 1) Develop awareness of health informatics through public engagement with participants and researchers; 2) Explore attitudes and potential barriers to creation of secure data linkage between imaging, laboratory, health data and outcomes to facilitate future linkage studies; 3) Understand what is required for interoperable, secure data storage and plan future biorepository as a resource for researchers that will build over time in India. Conclusion/Implications The proposed activities will inform preparation of a large scale grant to investigate the hypothesis that early life environment affects future risk of mental illness and cognitive ability globally. They will also begin to create a platform of enduring value for future cross-cultural population research

Cognitive function and disability in late Life: An ecological validation of the 10/66 battery of cognitive tests among community dwelling older adults in south India

This is the peer reviewed version of the following article: Krishna, M., Beulah, E., Jones, S., Sundarachari, R., Soroja .A., Kumaran, K., Kalyanaraman, K., Karat, S. C., Copeland, J. R. M., Prince, M. & Fall, C. (2015). Cognitive function and disability in late Life: An ecological validation of the 10/66 battery of cognitive tests among community dwelling older adults in South India. International Journal of Geriatric Psychiatry. 31(8) 879-891, which has been published in final form at https://doi.org/10.1002/gps.4404. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-ArchivingKey Points • 10/66 cognitive tests are well suited for identification of older adults with cognitive and functional impairment at a population level in LMIC setting. • Lower scores on individual domains of the 10/66 battery of cognitive tests are associated with higher levels of disability and functional impairment. • It is feasible to administer 10/66 cognitive assessments in participant's own homes in India. • 10/66 cognitive tests are education and culture fair, suitable for use in population based research in India

Consortium on Vulnerability to Externalizing Disorders and Addictions (cVEDA):A developmental cohort study protocol

Background: Low and middle-income countries like India with a large youth population experience a different environment from that of high-income countries. The Consortium on Vulnerability to Externalizing Disorders and Addictions (cVEDA), based in India, aims to examine environmental influences on genomic variations, neurodevelopmental trajectories and vulnerability to psychopathology, with a focus on externalizing disorders. Methods: cVEDA is a longitudinal cohort study, with planned missingness design for yearly follow-up. Participants have been recruited from multi-site tertiary care mental health settings, local communities, schools and colleges. 10,000 individuals between 6 and 23 years of age, of all genders, representing five geographically, ethnically, and socio-culturally distinct regions in India, and exposures to variations in early life adversity (psychosocial, nutritional, toxic exposures, slum-habitats, socio-political conflicts, urban/rural living, mental illness in the family) have been assessed using age-appropriate instruments to capture socio-demographic information, temperament, environmental exposures, parenting, psychiatric morbidity, and neuropsychological functioning. Blood/saliva and urine samples have been collected for genetic, epigenetic and toxicological (heavy metals, volatile organic compounds) studies. Structural (T1, T2, DTI) and functional (resting state fMRI) MRI brain scans have been performed on approximately 15% of the individuals. All data and biological samples are maintained in a databank and biobank, respectively. Discussion: The cVEDA has established the largest neurodevelopmental database in India, comparable to global datasets, with detailed environmental characterization. This should permit identification of environmental and genetic vulnerabilities to psychopathology within a developmental framework. Neuroimaging and neuropsychological data from this study are already yielding insights on brain growth and maturation patterns.</p

Protocol for the EMPHASIS study; epigenetic mechanisms linking maternal pre-conceptional nutrition and children's health in India and Sub-Saharan Africa.

BACKGROUND: Animal studies have shown that nutritional exposures during pregnancy can modify epigenetic marks regulating fetal development and susceptibility to later disease, providing a plausible mechanism to explain the developmental origins of health and disease. Human observational studies have shown that maternal peri-conceptional diet predicts DNA methylation in offspring. However, a causal pathway from maternal diet, through changes in DNA methylation, to later health outcomes has yet to be established. The EMPHASIS study (Epigenetic Mechanisms linking Pre-conceptional nutrition and Health Assessed in India and Sub-Saharan Africa, ISRCTN14266771) will investigate epigenetically mediated links between peri-conceptional nutrition and health-related outcomes in children whose mothers participated in two randomized controlled trials of micronutrient supplementation before and during pregnancy. METHODS: The original trials were the Mumbai Maternal Nutrition Project (MMNP, ISRCTN62811278) in which Indian women were offered a daily snack made from micronutrient-rich foods or low-micronutrient foods (controls), and the Peri-conceptional Multiple Micronutrient Supplementation Trial (PMMST, ISRCTN13687662) in rural Gambia, in which women were offered a daily multiple micronutrient (UNIMMAP) tablet or placebo. In the EMPHASIS study, DNA methylation will be analysed in the children of these women (~1,100 children aged 5-7 y in MMNP and 298 children aged 7-9 y in PMMST). Cohort-specific and cross-cohort effects will be explored. Differences in DNA methylation between allocation groups will be identified using the Illumina Infinium MethylationEPIC array, and by pyrosequencing top hits and selected candidate loci. Associations will be analysed between DNA methylation and health-related phenotypic outcomes, including size at birth, and children's post-natal growth, body composition, skeletal development, cardio-metabolic risk markers (blood pressure, serum lipids, plasma glucose and insulin) and cognitive function. Pathways analysis will be used to test for enrichment of nutrition-sensitive loci in biological pathways. Causal mechanisms for nutrition-methylation-phenotype associations will be explored using Mendelian Randomization. Associations between methylation unrelated to supplementation and phenotypes will also be analysed. CONCLUSION: The study will increase understanding of the epigenetic mechanisms underpinning the long-term impact of maternal nutrition on offspring health. It will potentially lead to better nutritional interventions for mothers preparing for pregnancy, and to identification of early life biomarkers of later disease risk

An Interpretive Phenomenological Analysis (IPA) of coercion towards community dwelling older adults with dementia: Findings from MYsore studies of Natal effects on Ageing and Health (MYNAH)

The final publication is available at Springer via http://dx.doi.org/10.1007/s00127-016-1286-4Purpose Limited availability of specialist services places a considerable burden on caregivers of Persons with Dementia (PwD) in Low- and Middle-Income Countries (LMICs). There are limited qualitative data on coercive behavior towards PwD in an LMIC setting. Aim The aim of this study was to find relevant themes of the lived experience of relatives as caregivers for PwD in view of their use of coercive measures in community setting in South India. Method Primary caregivers (n = 13) of PwDs from the Mysore study of Natal effects on Ageing and Health (MYNAH) in South India were interviewed to explore the nature and impact of coercion towards community dwelling older adults with dementia. The narrative data were coded using an Interpretative Phenomenological Analysis (IPA) approach for thematic analysis and theory formation. Results Caregivers reported feeling physical and emotional burn-out, a lack of respite care, an absence of shared caregiving arrangements, limited knowledge of dementia, and a complete lack of community support services. They reported restrictions on their lives through not being able take employment, a poor social life, reduced income and job opportunities, and restricted movement that impacted on their physical and emotional well-being. Inappropriate use of sedatives, seclusion and environmental restraint, and restricted dietary intake, access to finances and participation in social events, was commonly reported methods of coercion used by caregivers towards PwD. Reasons given by caregivers for employing these coercive measures included safeguarding of the PwD and for the management of behavioral problems and physical health. Conclusion There is an urgent need for training health and social care professionals to better understand the use of coercive measures and their impact on persons with dementia in India. It is feasible to conduct qualitative research using IPA in South India

Metabolic programming in early life in humans

An association of low birth weight with an increased risk of adult cardiovascular disease and diabetes led to the developmental origins of health and disease (DOHaD) hypothesis, which proposes that undernutrition during early development permanently ‘programmes’ organ structure and metabolism, leading to vulnerability to later cardio-metabolic disease. High birth weight caused by maternal gestational diabetes is also associated with later diabetes, suggesting that fetal over-nutrition also has programming effects. Post-natal factors (excess weight gain/obesity, smoking, poor diets and physical inactivity) interact with fetal exposures to increase disease risk. Animal studies have shown permanent metabolic effects in offspring after alterations to maternal or early post-natal diets but evidence in humans is largely limited to observational and quasi-experimental situations such as maternal famine exposure. Randomized trials of maternal nutritional interventions during pregnancy have so far had limited follow-up of the offspring. Moreover, interventions usually started after the first trimester and therefore missed key peri-conceptional or early pregnancy events such as epigenetic changes, placentation and fetal organogenesis. Recent and ongoing trials intervening pre-conceptionally and powered for long-term offspring follow-up will address these issues. While current preventive strategies for cardio-metabolic disease focus on high-risk individuals in mid-life, DOHaD concepts offer a ‘primordial’ preventive strategy to reduce disease in future generations by improving fetal and infant development