Evaluating progress and accountability for achieving COP26 Health Programme international ambitions for sustainable, low-carbon, resilient health-care systems.

A global initiative to develop low-carbon, resilient health systems-the COP26 Health Programme-launched at the UN Framework Convention on Climate Change 26th Conference of the Parties (COP26) in 2021. As of May, 2024, 83 nations have committed to participate in this initiative. This analysis evaluates the effectiveness of existing and proposed indicators towards public monitoring and accountability to these commitments. Our findings reveal substantial gaps in data availability and indicator relevance, with many countries reporting process indicators that do not reflect actual progress towards achieving sustainable health-care systems. We found a dearth of suitable indicators and an urgent need to develop robust ones that are adaptable to different health-care system contexts. These indicators should be designed to capture tangible outcomes, support policy making, and prevent greenwashing. Integration of more robust indicators into independent scientific monitoring can support systematic inclusion of health care in global climate strategies, thereby enhancing the overall effectiveness of the COP26 Health Programme.

Ambient air pollution and daily mortality in ten cities of India: a causal modelling study.

BACKGROUND: The evidence for acute effects of air pollution on mortality in India is scarce, despite the extreme concentrations of air pollution observed. This is the first multi-city study in India that examines the association between short-term exposure to PM2·5 and daily mortality using causal methods that highlight the importance of locally generated air pollution. METHODS: We applied a time-series analysis to ten cities in India between 2008 and 2019. We assessed city-wide daily PM2·5 concentrations using a novel hybrid nationwide spatiotemporal model and estimated city-specific effects of PM2·5 using a generalised additive Poisson regression model. City-specific results were then meta-analysed. We applied an instrumental variable causal approach (including planetary boundary layer height, wind speed, and atmospheric pressure) to evaluate the causal effect of locally generated air pollution on mortality. We obtained an integrated exposure-response curve through a multivariate meta-regression of the city-specific exposure-response curve and calculated the fraction of deaths attributable to air pollution concentrations exceeding the current WHO 24 h ambient PM2·5 guideline of 15 µg/m3. To explore the shape of the exposure-response curve at lower exposures, we further limited the analyses to days with concentrations lower than the current Indian standard (60 µg/m3). FINDINGS: We observed that a 10 µg/m3 increase in 2-day moving average of PM2·5 was associated with 1·4% (95% CI 0·7-2·2) higher daily mortality. In our causal instrumental variable analyses representing the effect of locally generated air pollution, we observed a stronger association with daily mortality (3·6% [2·1-5·0]) than our overall estimate. Our integrated exposure-response curve suggested steeper slopes at lower levels of exposure and an attenuation of the slope at high exposure levels. We observed two times higher risk of death per 10 µg/m3 increase when restricting our analyses to observations below the Indian air quality standard (2·7% [1·7-3·6]). Using the integrated exposure-response curve, we observed that 7·2% (4·2%-10·1%) of all daily deaths were attributed to PM2·5 concentrations higher than the WHO guidelines. INTERPRETATION: Short-term PM2·5 exposure was associated with a high risk of death in India, even at concentrations well below the current Indian PM2·5 standard. These associations were stronger for locally generated air pollutants quantified through causal modelling methods than conventional time-series analysis, further supporting a plausible causal link. FUNDING: Swedish Research Council for Sustainable Development.

Evidence of potential impacts of a nutrition-sensitive agroecology program in Andhra Pradesh, India, on dietary diversity, nutritional status, and child development.

INTRODUCTION: While a number of studies have examined the nutritional impacts of agroecological interventions, few have examined impacts on child development, maternal and child anemia, and men's dietary diversity. Moreover, there have been few such evaluations at scale. We evaluated the impact of a large-scale, multi-component food-based nutrition intervention involving homestead food production, nutrition counselling, cooking demonstrations, and crop planning exercises. METHODS: A cross-sectional assessment was conducted in 2021-2022 of 50 intervention villages where the nutrition-sensitive agroecology program had been implemented since 2018 and 79 control villages where only the agroecology program had been implemented. Data on self-reported dietary intake, caregiver-reported early child development, anthropometric measurements, and hemoglobin concentrations were collected using standardized procedures by trained Nutrition Farming Fellows, who were also responsible for implementing the program. RESULTS: A sample of 3,511 households (1,121 intervention and 2,390 control) participated in the survey. Dietary diversity scores (DDS) among women and men were mean (SD) 6.53 (±1.62) and 6.16 (±1.65), respectively, in intervention villages and 5.81 (±1.58) and 5.39 (±1.61), respectively, in control villages (p<0.01). DDS among children 6-24 months of age in intervention and control villages was 2.99 (±1.52) and 2.73 (±1.62), respectively (p<0.01). Children <2 years of age were less likely to be anemic in intervention versus control villages (59% versus 69%, p<0.01). Children 18-35 months age in intervention villages had higher child development scores than children in control villages (all p<0.05). CONCLUSION: Nutrition-sensitive agroecological programs may be effective in improving diets, nutrition, and child development in rural India.

Pancreatic Beta Cell Function in Infants Varies by Maternal Weight.

The Asian Indian Beta Cell function (ABCs) in Infants Study examined the associations of maternal weight on infant pancreatic beta cell function across 7 months postpartum. Pregnant women aged 18-35 years were recruited in Hyderabad, India. Women were classified by first trimester weight as underweight (UW), BMI < 18.5 kg/m2; normal weight (NW), BMI 18.5-22.9 kg/m2; or overweight (OW), BMI 23.0 through <28.5 kg/m2. At age > 7 months, infants had an oral glucose tolerance test (OGTT, 1.75 g glucose/kg bodyweight) following a 3 h fast. Infant blood samples were assayed for C-peptide and glucose. Infant beta cell function (HOMA2-B; disposition index, DI) and insulin resistance (HOMA2-IR) were compared across maternal weight groups. Mothers (UW n = 63; NW n = 43; OW n = 29) had similar age at delivery and second trimester 50 g glucose challenge test results. Cord HOMA2-B values were 51% greater for IUW (83.5, SD 55.2) and 44% greater for IOW (79.9, SD 60.8) vs. INW (55.4, SD 51.5), forming a U-shaped relationship between maternal weight and HOMA2-B. No qualitative differences in HOMA2-IR were found at birth. However, at 7 months postpartum, HOMA2-IR changed most within IUW (-64% median reduction) and changed the least in IOW (-7% median reduction). At seven months postpartum, DI was higher in IUW vs. the other groups (geometric mean IUW 1.9 SD 2.5; INW 1.3 SD 2.6 or vs. IOW mean 1.2 SD 3.7), reflecting a +49% difference in DI. Evidence from this study illustrates adaptations in the pancreatic functional response of infants associated with the maternal nutritional environment.

Nationwide estimation of daily ambient PM2.5 from 2008 to 2020 at 1 km2 in India using an ensemble approach.

High-resolution assessment of historical levels is essential for assessing the health effects of ambient air pollution in the large Indian population. The diversity of geography, weather patterns, and progressive urbanization, combined with a sparse ground monitoring network makes it challenging to accurately capture the spatiotemporal patterns of ambient fine particulate matter (PM2.5) pollution in India. We developed a model for daily average ambient PM2.5 between 2008 and 2020 based on monitoring data, meteorology, land use, satellite observations, and emissions inventories. Daily average predictions at each 1 km × 1 km grid from each learner were ensembled using a Gaussian process regression with anisotropic smoothing over spatial coordinates, and regression calibration was used to account for exposure error. Cross-validating by leaving monitors out, the ensemble model had an R2 of 0.86 at the daily level in the validation data and outperformed each component learner (by 5-18%). Annual average levels in different zones ranged between 39.7 µg/m3 (interquartile range: 29.8-46.8) in 2008 and 30.4 µg/m3 (interquartile range: 22.7-37.2) in 2020, with a cross-validated (CV)-R2 of 0.94 at the annual level. Overall mean absolute daily errors (MAE) across the 13 years were between 14.4 and 25.4 µg/m3. We obtained high spatial accuracy with spatial R2 greater than 90% and spatial MAE ranging between 7.3-16.5 µg/m3 with relatively better performance in urban areas at low and moderate elevation. We have developed an important validated resource for studying PM2.5 at a very fine spatiotemporal resolution, which allows us to study the health effects of PM2.5 across India and to identify areas with exceedingly high levels.

Impact of heatwaves on all-cause mortality in India: A comprehensive multi-city study.

BACKGROUND: Heatwaves are expected to increase with climate change, posing a significant threat to population health. In India, with the world's largest population, heatwaves occur annually but have not been comprehensively studied. Accordingly, we evaluated the association between heatwaves and all-cause mortality and quantifying the attributable mortality fraction in India. METHODS: We obtained all-cause mortality counts for ten cities in India (2008-2019) and estimated daily mean temperatures from satellite data. Our main extreme heatwave was defined as two-consecutive days with an intensity above the 97th annual percentile. We estimated city-specific heatwave associations through generalised additive Poisson regression models, and meta-analysed the associations. We reported effects as the percentage change in daily mortality, with 95% confidence intervals (CI), comparing heatwave vs non-heatwave days. We further evaluated heatwaves using different percentiles (95th, 97th, 99th) for one, two, three and five-consecutive days. We also evaluated the influence of heatwave duration, intensity and timing in the summer season on heatwave mortality, and estimated the number of heatwave-related deaths. FINDINGS: Among âˆ¼ 3.6 million deaths, we observed that temperatures above 97th percentile for 2-consecutive days was associated with a 14.7 % (95 %CI, 10.3; 19.3) increase in daily mortality. Alternative heatwave definitions with higher percentiles and longer duration resulted in stronger relative risks. Furthermore, we observed stronger associations between heatwaves and mortality with higher heatwave intensity. We estimated that around 1116 deaths annually (95 %CI, 861; 1361) were attributed to heatwaves. Shorter and less intense definitions of heatwaves resulted in a higher estimated burden of heatwave-related deaths. CONCLUSIONS: We found strong evidence of heatwave impacts on daily mortality. Longer and more intense heatwaves were linked to an increased mortality risk, however, resulted in a lower burden of heatwave-related deaths. Both definitions and the burden associated with each heatwave definition should be incorporated into planning and decision-making processes for policymakers.

Cardiovascular disease in low- and middle-income countries associated with environmental factors.

There is a growing recognition that the profound environmental changes that have occurred over the past century pose threats to human health. Many of these environmental factors, including air pollution, noise pollution, as well as exposure to metals such as arsenic, cadmium, lead, and other metals, are particularly detrimental to the cardiovascular health of people living in low-to-middle income countries (LMICs). Low-to-middle income countries are likely to be disproportionally burdened by cardiovascular diseases provoked by environmental factors. Moreover, they have the least capacity to address the core drivers and consequences of this phenomenon. This review summarizes the impact of environmental factors such as climate change, air pollution, and metal exposure on the cardiovascular system, and how these specifically affect people living in LMICs. It also outlines how behaviour changes and interventions that reduce environmental pollution would have significant effects on the cardiovascular health of those from LMICs, and globally.

Household cooking fuel and gallbladder cancer risk: a multi-centre case-control study in India.

PURPOSE: Gallbladder cancers (GBC), unique to certain geographical regions, are lethal digestive tract cancers, disproportionately affecting women, with limited information on risk factors. METHODS: We evaluated the association between household cooking fuel and GBC risk in a hospital-based case-control study conducted in the North-East and East Indian states of Assam and Bihar. We explored the potential mediation by diet, fire-vents, 'daily exposure duration' and parity (among women). We recruited biopsy-confirmed GBC (n = 214) men and women aged 30-69 years between 2019 and 2021, and controls frequency-matched by age, sex and region (n = 166). Information about cooking fuel, lifestyle, personal and family history, female reproductive factors, socio-demographics, and anthropometrics was collected. We tested associations using multivariable logistic regression analyses. RESULTS: All participants (73.4% women) were categorised based on predominant cooking fuel use. Group-1: LPG (Liquefied Petroleum Gas) users in the previous 20 years and above without concurrent biomass use (26.15%); Group-2: LPG users in the previous 20 years and above with concurrent secondary biomass use (15.9%); Group-3: Biomass users for ≥ 20 years (57.95%). Compared to group-1, accounting for confounders, GBC risk was higher in group-2 [OR: 2.02; 95% CI: 1.00-4.07] and group-3 [OR: 2.01; 95% CI: 1.08-3.73] (p-trend:0.020). These associations strengthened among women that attenuated with high daily consumption of fruits-vegetables but not with fire-vents, 'daily exposure duration' or parity. CONCLUSION: Biomass burning was associated with a high-risk for GBC and should be considered as a modifiable risk factor for GBC. Clean cooking fuel can potentially mitigate, and a healthy diet can partially reduce the risk among women.

The burgeoning cardiovascular disease epidemic in Indians - perspectives on contextual factors and potential solutions.

Cardiovascular diseases (CVD) are the leading cause of death and disability in India. The CVD epidemic in Indians is characterized by a higher relative risk burden, an earlier age of onset, higher case fatality and higher premature deaths. For decades, researchers have been trying to understand the reason for this increased burden and propensity of CVD among Indians. It can partly be explained by population-level changes and the remaining by increased inherent biological risk. While increased biological risk can be attributed to phenotypic changes caused by early life influences, six major transitions can be considered largely responsible for the population-level changes in India-epidemiological, demographic, nutritional, environmental, social-cultural and economic. Although conventional risk factors explain substantial population attributable risk, the thresholds at which these risk factors operate are different among Indians compared with other populations. Therefore, alternate explanations for these ecological differences have been sought and multiple hypotheses have been proposed over the years. Prenatal factors that include maternal and paternal influences on the offspring, and postnatal factors, ranging from birth through childhood, adolescence and young adulthood, as well as inter-generational influences have been explored using the life course approach to chronic disease. In addition to this, recent research has illustrated the importance of the role of inherent biological differences in lipid metabolism, glucose metabolism, inflammatory states, genetic predispositions and epigenetic influences for the increased risk. A multifaceted and holistic approach to CVD prevention that takes into consideration population-level as well as biological risk factors would be needed to control the burgeoning CVD epidemic among Indians.

Co-Benefits of Largescale Organic farming On huMan health (BLOOM): Protocol for a cluster-randomised controlled evaluation of the Andhra Pradesh Community-managed Natural Farming programme in India.

The BLOOM study (co-Benefits of Largescale Organic farming On huMan health) aims to determine if a government-implemented agroecology programme reduces pesticide exposure and improves dietary diversity in agricultural households. To achieve this aim, a community-based, cluster-randomised controlled evaluation of the Andhra Pradesh Community-managed Natural Farming (APCNF) programme will be conducted in 80 clusters (40 intervention and 40 control) across four districts of Andhra Pradesh state in south India. Approximately 34 households per cluster will be randomly selected for screening and enrolment into the evaluation at baseline. The two primary outcomes, measured 12 months post-baseline assessment, are urinary pesticide metabolites in a 15% random subsample of participants and dietary diversity in all participants. Both primary outcomes will be measured in (1) adult men ≥18 years old, (2) adult women ≥18 years old, and (3) children <38 months old at enrolment. Secondary outcomes measured in the same households include crop yields, household income, adult anthropometry, anaemia, glycaemia, kidney function, musculoskeletal pain, clinical symptoms, depressive symptoms, women's empowerment, and child growth and development. Analysis will be on an intention-to-treat basis with an a priori secondary analysis to estimate the per-protocol effect of APCNF on the outcomes. The BLOOM study will provide robust evidence of the impact of a large-scale, transformational government-implemented agroecology programme on pesticide exposure and dietary diversity in agricultural households. It will also provide the first evidence of the nutritional, developmental, and health co-benefits of adopting agroecology, inclusive of malnourishment as well as common chronic diseases. Trial registration: Study registration: ISRCTN 11819073 (https://doi.org/10.1186/ISRCTN11819073). Clinical Trial Registry of India CTRI/2021/08/035434.

Chronic Exposure to Drinking Water Arsenic and Gallbladder Cancer Risk: Preliminary Evidence from Endemic Regions of India.

BACKGROUND: Evidence linking arsenic in drinking water to digestive tract cancers is limited. We evaluated the association between arsenic levels in groundwater and gallbladder cancer risk in a case-control study (2019-2021) of long-term residents (≥10years) in two arsenic-impacted and high gallbladder cancer risk states of India-Assam and Bihar. METHODS: We recruited men and women aged 30 to 69 years from hospitals (73.4% women), with newly diagnosed, biopsy-confirmed gallbladder cancer (N = 214) and unrelated controls frequency-matched for 5-year age, sex, and state (N = 166). Long-term residential history, lifestyle factors, family history, socio-demographics, and physical measurements were collected. Average-weighted arsenic concentration (AwAC) was extrapolated from district-level groundwater monitoring data (2017-2018) and residential history. We evaluated gallbladder cancer risk for tertiles of AwAC (µg/L) in multivariable logistic regression models adjusted for important confounders [Range: 0-448.39; median (interquartile range), T1-0.45 (0.0-1.19); T2-3.75 (2.83-7.38); T3-17.6 (12.34-20.54)]. RESULTS: We observed a dose-response increase in gallbladder cancer risk based on AwAC tertiles [OR = 2.00 (95% confidence interval, 1.05-3.79) and 2.43 (1.30-4.54); Ptrend = 0.007]. Participants in the highest AwAC tertile consumed more tubewell water (67.7% vs. 27.9%) and reported more sediments (37.9% vs. 18.7%) with unsatisfactory color, odor, and taste (49.2% vs. 25.0%) than those in the lowest tertile. CONCLUSIONS: These findings suggest chronic arsenic exposure in drinking water at low-moderate levels may be a potential risk factor for gallbladder cancer. IMPACT: Risk factors for gallbladder cancer, a lethal digestive tract cancer, are not fully understood. Data from arsenic-endemic regions of India, with a high incidence of gallbladder cancer, may offer unique insights. Tackling 'arsenic pollution' may help reduce the burden of several health outcomes.

Assessment of health status and impact of pollution from thermal power plant on health of population and environment around the plant in Udupi District, Karnataka.

Background: Coal-fired thermal power plants (TPPs) have a serious impact on soil, air, and water quality resulting in deterioration of health and environment around the plant. Objective: The present study was undertaken with the objectives of assessing the respiratory health status of the population around the plant and to measure selected heavy metals in fly ash, air, water, and soil samples. Materials and Methods: The current cross-sectional study was conducted among 3533 adult residents living in two strata within 10 km radius around the TPP in Udupi district of Karnataka state. Data were collected by using semi-structured questionnaire and spirometry and environmental air monitoring by DustTrak aerosol monitor, water, and soil samples were collected for analysis. Results: Majority of the study participants were in the age group of >45 years (41.4%). 70.6% were females and 0.39% were trans-genders. 4.3% were suffering from various respiratory problems. Bivariable logistic regression showed subjects aged 46-65 years and >65 years have 2.91 times and 4.42 times higher odds of respiratory disease as compared to those with age ≤45 years. Multivariable logistic regression showed significant association between higher age group (P < 0.0001) and in subjects who had closed window during cooking (P < 0.006). Levels of heavy metals in soil samples and particulate matter 2.5 were well within permissible limits whereas the ground water samples had excess levels of iron, manganese, and copper. Conclusion: The present study has implications for policymaking to protect the environment and health of vulnerable populations in industrial clusters and the vicinity of power plants.

Impact of large-scale, government legislated and funded organic farming training on pesticide use in Andhra Pradesh, India: a cross-sectional study.

BACKGROUND: The use of pesticides in agriculture has been associated with the destruction of biodiversity and damage to human health. A marked reduction in pesticide use is urgently required globally, but whether this can be achieved rapidly and at scale is unclear. We aimed to assess whether government-legislated and funded organic farming training in Andhra Pradesh, India, reduced pesticide use by farmers and sales of pesticides by pesticide retailers. METHODS: We did a cross-sectional survey between Aug 11 and Nov 26, 2020, among farmers and pesticide retailers in Kurnool District of Andhra Pradesh (India). We assessed the impact of the Andhra Pradesh Community Managed Natural Farming (APCNF) programme, which aims to transition 100% of the agricultural land of Andhra Pradesh (population approximately 49 million, 6 million of whom are farmers) to organic farming practices by 2030. We did cross-sectional phone interview surveys of farmers and face-to-face surveys of pesticide retailers. We used multivariable Poisson regression models to estimate relative risks (RRs) and logistic regression models to estimate odds ratios (ORs). FINDINGS: 962 farmers were invited to participate, of whom 894 (93%) consented (709 conventional farmers and 149 APCNF farmers). 47 pesticide retailers were invited to participate, of whom 38 (81%) consented. APCNF farmers had practised APCNF for a median of 2 years (IQR 1-3). APCNF farmers were less likely to use pesticides than conventional farmers (adjusted RR 0·65 [95% CI 0·57-0·75]), although pesticide use remained high among both APCNF and conventional farmers (73 [49%] of 148 APCNF farmers vs 695 [99%] of 700 conventional farmers; p<0·0001). APCNF farmers had lower pesticide expenditures than conventional farmers (median US$0 [IQR 0-170] for APCNF farmers vs $175 [91-281] for conventional farmers; p=0·0001). Increased frequency of meeting with agricultural extension workers was associated with reduced pesticide use among ACPNF farmers. Seven (18%) of 38 retailers reported a decrease in sales of pesticides in the past 4 years; no difference in the odds of reporting a decrease in pesticide sales in the past 4 years was identified between APCNF retailers and conventional retailers (OR 0·95 [95% CI 0·58-1·57]). INTERPRETATION: Despite a major government drive for organic agriculture, about half of APCNF farmers continued to use pesticides and no impact on pesticide sales at local retailers was observed. A combination of policy instruments (eg, bans on highly hazardous pesticides), not solely training for farmers, might be needed to eliminate pesticide use in agriculture. FUNDING: Scottish Funding Council and UK Research and Innovation.

Impact of the COVID-19 pandemic on agricultural production, livelihoods, and food security in India: baseline results of a phone survey.

The aim of this study was to evaluate the impact of the COVID-19 lockdown on agricultural production, livelihoods, food security, and dietary diversity in India. Phone interview surveys were conducted by trained enumerators across 12 states and 200 districts in India from 3 to 15 May 2020. A total of 1437 farmers completed the survey (94% male; 28% 30-39 years old; 38% with secondary schooling). About one in ten farmers (11%) did not harvest in the past month with primary reasons cited being unfavorable weather (37%) and lockdown-related reasons (24%). A total of 63% of farmers harvested in the past month (primarily wheat and vegetables), but only 44% had sold their crop; 12% were still trying to sell their crop, and 39% had stored their crop, with more than half (55%) reporting lockdown-related issues as the reason for storing. Seventy-nine percent of households with wage-workers witnessed a decline in wages in the past month and 49% of households with incomes from livestock witnessed a decline. Landless farmers were about 10 times more likely to skip a meal as compared to large farmers (18% versus 2%), but a majority reported receiving extra food rations from the government. Nearly all farmers reported consuming staple grains daily in the past week (97%), 63% consumed dairy daily, 40% vegetables daily, 26% pulses daily, and 7% fruit daily. These values are much lower than reported previously for farmers in India around this time of year before COVID-19: 94-95% dairy daily, 57-58% pulses daily, 64-65% vegetables daily, and 42-43% fruit daily. In conclusion, we found that the COVID-19 lockdown in India has primarily impacted farmers' ability to sell their crops and livestock products and decreased daily wages and dietary diversity. Supplementary Information: The online version contains supplementary material available at 10.1007/s12571-021-01164-w.

Building capacity for air pollution epidemiology in India.

Air pollution represents a major public health threat in India affecting 19% of the world's population at extreme levels. Despite this, research in India lags behind in large part due to a lack of comprehensive air pollution exposure assessment that can be used in conjunction with health data to investigate health effects. Our vision is to provide a consortium to rapidly expand the evidence base of the multiple effects of ambient air pollution. We intend to leapfrog current limitations of exposure assessment by developing a machine-learned satellite-informed spatiotemporal model to estimate daily levels of ambient fine particulate matter measuring less than 2.5 µm (PM2.5) at a fine spatial scale across all of India. To catalyze health effects research on an unprecedented scale, we will make the output from this model publicly available. In addition, we will also apply these PM2.5 estimates to study the health outcomes of greatest public health importance in India, including cardiovascular diseases, chronic obstructive pulmonary disease, pregnancy (and birth) outcomes, and cognitive development and/or decline. Thus, our efforts will directly generate actionable new evidence on the myriad effects of air pollution on health that can inform policy decisions, while providing a comprehensive and publicly available resource for future studies on both exposure and health effects. In this commentary, we discuss the motivation, rationale, and vision for our consortium and a path forward for reducing the enormous burden of disease from air pollution in India.

Effect of supplemental nutrition in pregnancy on offspring's risk of cardiovascular disease in young adulthood: Long-term follow-up of a cluster trial from India.

BACKGROUND: Undernutrition during intrauterine life and early childhood is hypothesised to increase the risk of cardiovascular disease (Developmental Origins of Health and Disease Hypothesis), but experimental evidence from humans is limited. This hypothesis has major implications for control of the cardiovascular disease epidemic in South Asia (home to a quarter of world's population), where a quarter of newborns have low birth weight. We investigated whether, in an area with prevalent undernutrition, supplemental nutrition offered to pregnant women and their offspring below the age of 6 years was associated with a lower risk of cardiovascular disease in the offspring when they were young adults. METHODS AND FINDINGS: The Hyderabad Nutrition Trial was a community-based nonrandomised controlled intervention trial conducted in 29 villages near Hyderabad, India (1987-1990). Protein-calorie food supplement was offered daily to pregnant and lactating women (2.09 MJ energy and 20-25 g protein) and their offspring (1.25 MJ energy and 8-10 g protein) until the age of six years in the 15 intervention villages, but not in the 14 control villages. A total of 1,826 participants (949 from the intervention villages and 877 from the control villages, representing 70% of the cohort) at a mean age of 21.6 years (62% males) were examined between 2009 and 2012. The mean body mass index (BMI) of the participants was 20 kg/m2 and the mean systolic blood pressure was 115 mm Hg. The age, sex, socioeconomic position, and urbanisation-adjusted effects of intervention (beta coefficients and 95% confidence intervals) on outcomes were as follows: carotid intima-media thickness, 0.01 mm (-0.01 to 0.03), p = 0.36; arterial stiffness (augmentation index), -1.1% (-2.5 to 0.3), p = 0.097; systolic blood pressure, 0.5 mm Hg (-0.6 to 1.6), p = 0.36; BMI, -0.13 kg/m2 (-0.75 to 0.09), p = 0.093; low-density lipoprotein (LDL) cholesterol, 0.06 mmol/L (-0.07 to 0.2), p = 0.37; and fasting insulin (log), -0.06 mU/L (-0.19 to 0.07), p = 0.43. The limitations of this study include nonrandomised allocation of intervention and lack of data on compliance, and potential for selection bias due to incomplete follow-up. CONCLUSIONS: Our results showed that in an area with prevalent undernutrition, protein-calorie food supplements offered to pregnant women and their offspring below the age of 6 years were not associated with lower levels of cardiovascular risk factors among offspring when they were young adults. Our findings, coupled with evidence from other intervention studies to date, suggest that policy makers should attach limited value to cardiovascular health benefits of maternal and child protein-calorie food supplementation programmes.