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BACKGROUND: We hypothesized that drinking water, sanitation, handwashing (WSH), and nutritional interventions would improve environmental enteric dysfunction (EED), a potential contributor to stunting. METHODS: Within a subsample of a cluster-randomized, controlled trial in rural Bangladesh, we enrolled pregnant women in 4 arms: control, WSH, child nutrition counseling plus lipid-based nutrient supplements (N), and nutrition plus WSH (N+WSH). Among the birth cohort, we measured biomarkers of gut inflammation (myeloperoxidase, neopterin), permeability (alpha-1-antitrypsin, lactulose, mannitol), and repair (regenerating gene 1ß) at median ages 3, 14, and 28 months. Analysis was intention-to-treat. RESULTS: We assessed 1512 children. At age 3 months, compared to controls, neopterin was reduced by nutrition (-0.21 log nmol/L; 95% confidence interval [CI], -.37, -.05) and N+WSH (-0.20 log nmol/L; 95% CI, -.34, -.06) interventions; similar reductions were observed at 14 months. At 3 months, all interventions reduced lactulose and mannitol (-0.60 to -0.69 log mmol/L). At 28 months, myeloperoxidase was elevated in the WSH and nutrition arms (0.23-0.27 log ng/mL) and lactulose was higher in the WSH arm (0.30 log mmol/L; 95% CI, .07, .53). CONCLUSIONS: Reductions in permeability and inflammation at ages 3 and 14 months suggest that the interventions promoted healthy intestinal maturation; however, by 28 months, the WSH and nutrition arms showed elevated EED biomarkers. These results underscore the importance of developing a better understanding of EED pathophysiology and targeting interventions early in childhood, when they are likely to have the largest benefit to intestinal health. CLINICAL TRIALS REGISTRATION: NCT01590095.
Subject(s)
Hand Disinfection , Sanitation , Bangladesh , Child , Child, Preschool , Female , Humans , Infant , Pregnancy , Rural Population , WaterABSTRACT
While ecologists primarily focus on the immediate impact of ecological subsidies, understanding the importance of ecological subsidies requires quantifying the long-term temporal dynamics of subsidies on recipient ecosystems. Deciduous leaf litter transferred from terrestrial to aquatic ecosystems exerts both immediate and lasting effects on stream food webs. Recently, deciduous leaf additions have also been shown to be important subsidies for planktonic food webs in ponds during autumn; however, the inter-seasonal effects of autumn leaf subsidies on planktonic food webs have not been studied. We hypothesized that autumn leaf drop will affect the spring dynamics of freshwater pond food webs by altering the availability of resources, water transparency, and the metabolic state of ponds. We created leaf-added and no-leaf-added field mesocosms in autumn 2012, allowed mesocosms to ice-over for the winter, and began sampling the physical, chemical, and biological properties of mesocosms immediately following ice-off in spring 2013. At ice-off, leaf additions reduced dissolved oxygen, elevated total phosphorus concentrations and dissolved materials, and did not alter temperature or total nitrogen. These initial abiotic effects contributed to higher bacterial densities and lower chlorophyll concentrations, but by the end of spring, the abiotic environment, chlorophyll and bacterial densities converged. By contrast, zooplankton densities diverged between treatments during the spring, with leaf additions stimulating copepods but inhibiting cladocerans. We hypothesized that these differences between zooplankton orders resulted from resource shifts following leaf additions. These results suggest that leaf subsidies can alter both the short- and long-term dynamics of planktonic food webs, and highlight the importance of fully understanding how ecological subsidies are integrated into recipient food webs.
Subject(s)
Food Chain , Plankton , Plant Leaves , Ponds , Seasons , Animals , Cladocera , Copepoda , Ecosystem , Fresh Water , Nitrogen/analysis , Phosphorus/analysis , Ponds/chemistry , ZooplanktonABSTRACT
BACKGROUND: Postacute sequelae of COVID-19 (PASC), also known as long COVID, is a broad grouping of a range of long-term symptoms following acute COVID-19. These symptoms can occur across a range of biological systems, leading to challenges in determining risk factors for PASC and the causal etiology of this disorder. An understanding of characteristics that are predictive of future PASC is valuable, as this can inform the identification of high-risk individuals and future preventative efforts. However, current knowledge regarding PASC risk factors is limited. OBJECTIVE: Using a sample of 55,257 patients (at a ratio of 1 patient with PASC to 4 matched controls) from the National COVID Cohort Collaborative, as part of the National Institutes of Health Long COVID Computational Challenge, we sought to predict individual risk of PASC diagnosis from a curated set of clinically informed covariates. The National COVID Cohort Collaborative includes electronic health records for more than 22 million patients from 84 sites across the United States. METHODS: We predicted individual PASC status, given covariate information, using Super Learner (an ensemble machine learning algorithm also known as stacking) to learn the optimal combination of gradient boosting and random forest algorithms to maximize the area under the receiver operator curve. We evaluated variable importance (Shapley values) based on 3 levels: individual features, temporal windows, and clinical domains. We externally validated these findings using a holdout set of randomly selected study sites. RESULTS: We were able to predict individual PASC diagnoses accurately (area under the curve 0.874). The individual features of the length of observation period, number of health care interactions during acute COVID-19, and viral lower respiratory infection were the most predictive of subsequent PASC diagnosis. Temporally, we found that baseline characteristics were the most predictive of future PASC diagnosis, compared with characteristics immediately before, during, or after acute COVID-19. We found that the clinical domains of health care use, demographics or anthropometry, and respiratory factors were the most predictive of PASC diagnosis. CONCLUSIONS: The methods outlined here provide an open-source, applied example of using Super Learner to predict PASC status using electronic health record data, which can be replicated across a variety of settings. Across individual predictors and clinical domains, we consistently found that factors related to health care use were the strongest predictors of PASC diagnosis. This indicates that any observational studies using PASC diagnosis as a primary outcome must rigorously account for heterogeneous health care use. Our temporal findings support the hypothesis that clinicians may be able to accurately assess the risk of PASC in patients before acute COVID-19 diagnosis, which could improve early interventions and preventive care. Our findings also highlight the importance of respiratory characteristics in PASC risk assessment. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1101/2023.07.27.23293272.
Subject(s)
COVID-19 , Post-Acute COVID-19 Syndrome , Humans , COVID-19/epidemiology , Cohort Studies , Female , Male , United States/epidemiology , Middle Aged , Aged , Adult , Risk Factors , Machine LearningABSTRACT
Background: Water, sanitation, hygiene (WSH), nutrition (N), and combined (N+WSH) interventions are often implemented by global health organizations, but WSH interventions may insufficiently reduce pathogen exposure, and nutrition interventions may be modified by environmental enteric dysfunction (EED), a condition of increased intestinal permeability and inflammation. This study investigated the heterogeneity of these treatments' effects based on individual pathogen and EED biomarker status with respect to child linear growth. Methods: We applied cross-validated targeted maximum likelihood estimation and super learner ensemble machine learning to assess the conditional treatment effects in subgroups defined by biomarker and pathogen status. We analyzed treatment (N+WSH, WSH, N, or control) randomly assigned in-utero, child pathogen and EED data at 14 months of age, and child LAZ at 28 months of age. We estimated the difference in mean child length for age Z-score (LAZ) under the treatment rule and the difference in stratified treatment effect (treatment effect difference) comparing children with high versus low pathogen/biomarker status while controlling for baseline covariates. Results: We analyzed data from 1,522 children, who had median LAZ of -1.56. We found that myeloperoxidase (N+WSH treatment effect difference 0.0007 LAZ, WSH treatment effect difference 0.1032 LAZ, N treatment effect difference 0.0037 LAZ) and Campylobacter infection (N+WSH treatment effect difference 0.0011 LAZ, WSH difference 0.0119 LAZ, N difference 0.0255 LAZ) were associated with greater effect of all interventions on growth. In other words, children with high myeloperoxidase or Campylobacter infection experienced a greater impact of the interventions on growth. We found that a treatment rule that assigned the N+WSH (LAZ difference 0.23, 95% CI (0.05, 0.41)) and WSH (LAZ difference 0.17, 95% CI (0.04, 0.30)) interventions based on EED biomarkers and pathogens increased predicted child growth compared to the randomly allocated intervention. Conclusions: These findings indicate that EED biomarker and pathogen status, particularly Campylobacter and myeloperoxidase (a measure of gut inflammation), may be related to impact of N+WSH, WSH, and N interventions on child linear growth.
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A regulated stress response is essential for healthy child growth and development trajectories. We conducted a cluster-randomized trial in rural Bangladesh (funded by the Bill & Melinda Gates Foundation, ClinicalTrials.gov NCT01590095) to assess the effects of an integrated nutritional, water, sanitation, and handwashing intervention on child health. We previously reported on the primary outcomes of the trial, linear growth and caregiver-reported diarrhea. Here, we assessed additional prespecified outcomes: physiological stress response, oxidative stress, and DNA methylation (N = 759, ages 1-2 years). Eight neighboring pregnant women were grouped into a study cluster. Eight geographically adjacent clusters were block-randomized into the control or the combined nutrition, water, sanitation, and handwashing (N + WSH) intervention group (receiving nutritional counseling and lipid-based nutrient supplements, chlorinated drinking water, upgraded sanitation, and handwashing with soap). Participants and data collectors were not masked, but analyses were masked. There were 358 children (68 clusters) in the control group and 401 children (63 clusters) in the intervention group. We measured four F2-isoprostanes isomers (iPF(2α)-III; 2,3-dinor-iPF(2α)-III; iPF(2α)-VI; 8,12-iso-iPF(2α)-VI), salivary alpha-amylase and cortisol, and methylation of the glucocorticoid receptor (NR3C1) exon 1F promoter including the NGFI-A binding site. Compared with control, the N + WSH group had lower concentrations of F2-isoprostanes isomers (differences ranging from -0.16 to -0.19 log ng/mg of creatinine, P < 0.01), elevated post-stressor cortisol (0.24 log µg/dl; P < 0.01), higher cortisol residualized gain scores (0.06 µg/dl; P = 0.023), and decreased methylation of the NGFI-A binding site (-0.04; P = 0.037). The N + WSH intervention enhanced adaptive responses of the physiological stress system in early childhood.
Subject(s)
DNA Methylation , Epigenesis, Genetic , Hand Disinfection , Sanitation , Humans , Female , Bangladesh , Male , Infant , Child, Preschool , Pregnancy , Oxidative Stress , Stress, Physiological , Rural Population , Adult , Diarrhea/prevention & control , Receptors, Glucocorticoid/metabolism , Receptors, Glucocorticoid/geneticsABSTRACT
BACKGROUND: Hundreds of millions of children in low- and middle-income countries are exposed to chronic stressors, such as poverty, poor sanitation and hygiene, and sub-optimal nutrition. These stressors can have physiological consequences for children and may ultimately have detrimental effects on child development. This study explores associations between biological measures of chronic stress in early life and developmental outcomes in a large cohort of young children living in rural Bangladesh. METHODS: We assessed physiologic measures of stress in the first two years of life using measures of the hypothalamic-pituitary-adrenal (HPA) axis (salivary cortisol and glucocorticoid receptor gene methylation), the sympathetic-adrenal-medullary (SAM) system (salivary alpha-amylase, heart rate, and blood pressure), and oxidative status (F2-isoprostanes). We assessed child development in the first two years of life with the MacArthur-Bates Communicative Development Inventories (CDI), the WHO gross motor milestones, and the Extended Ages and Stages Questionnaire (EASQ). We compared development outcomes of children at the 75th and 25th percentiles of stress biomarker distributions while adjusting for potential confounders using generalized additive models, which are statistical models where the outcome is predicted by a potentially non-linear function of predictor variables. RESULTS: We analyzed data from 684 children (49% female) at both 14 and 28 months of age; we included an additional 765 children at 28 months of age. We detected a significant relationship between HPA axis activity and child development, where increased HPA axis activity was associated with poor development outcomes. Specifically, we found that cortisol reactivity (coefficient -0.15, 95% CI (-0.29, -0.01)) and post-stressor levels (coefficient -0.12, 95% CI (-0.24, -0.01)) were associated with CDI comprehension score, post-stressor cortisol was associated with combined EASQ score (coefficient -0.22, 95% CI (-0.41, -0.04), and overall glucocorticoid receptor methylation was associated with CDI expression score (coefficient -0.09, 95% CI (-0.17, -0.01)). We did not detect a significant relationship between SAM activity or oxidative status and child development. CONCLUSIONS: Our observations reveal associations between the physiological evidence of stress in the HPA axis with developmental status in early childhood. These findings add to the existing evidence exploring the developmental consequences of early life stress.
Subject(s)
Child Development , Hydrocortisone , Child , Humans , Child, Preschool , Female , Male , Hydrocortisone/metabolism , Hypothalamo-Hypophyseal System/metabolism , Receptors, Glucocorticoid/metabolism , Bangladesh , Pituitary-Adrenal System/metabolism , Biomarkers/metabolism , Saliva/metabolism , Stress, Psychological/metabolismABSTRACT
Background: Real-world data, such as administrative claims and electronic health records, are increasingly used for safety monitoring and to help guide regulatory decision-making. In these settings, it is important to document analytic decisions transparently and objectively to assess and ensure that analyses meet their intended goals. Methods: The Causal Roadmap is an established framework that can guide and document analytic decisions through each step of the analytic pipeline, which will help investigators generate high-quality real-world evidence. Results: In this paper, we illustrate the utility of the Causal Roadmap using two case studies previously led by workgroups sponsored by the Sentinel Initiative - a program for actively monitoring the safety of regulated medical products. Each case example focuses on different aspects of the analytic pipeline for drug safety monitoring. The first case study shows how the Causal Roadmap encourages transparency, reproducibility, and objective decision-making for causal analyses. The second case study highlights how this framework can guide analytic decisions beyond inference on causal parameters, improving outcome ascertainment in clinical phenotyping. Conclusion: These examples provide a structured framework for implementing the Causal Roadmap in safety surveillance and guide transparent, reproducible, and objective analysis.
ABSTRACT
Background: Hundreds of millions of children in low- and middle-income countries are exposed to chronic stressors, such as poverty, poor sanitation and hygiene, and sub-optimal nutrition. These stressors can have physiological consequences for children and may ultimately have detrimental effects on child development. This study explores associations between biological measures of chronic stress in early life and developmental outcomes in a large cohort of young children living in rural Bangladesh. Methods: We assessed physiologic measures of stress in the first two years of life using measures of the hypothalamic-pituitary-adrenal (HPA) axis (salivary cortisol and glucocorticoid receptor gene methylation), the sympathetic-adrenal-medullary (SAM) system (salivary alpha-amylase, heart rate, and blood pressure), and oxidative status (F2-isoprostanes). We assessed child development in the first two years of life with the MacArthur-Bates Communicative Development Inventories (CDI), the WHO gross motor milestones, and the Extended Ages and Stages Questionnaire (EASQ). We compared development outcomes of children at the 75th and 25th percentiles of stress biomarker distributions while adjusting for potential confounders (hereafter referred to as contrasts) using generalized additive models, which are statistical models where the outcome is predicted by a potentially non-linear function of predictor variables. Results: We analyzed data from 684 children (49% female) at both 14 and 28 months of age; we included an additional 765 children at 28 months of age. We observed 135 primary contrasts of the differences in child development outcomes at the 75th and 25th percentiles of stress biomarkers, where we detected significant relationships in 5 out of 30 contrasts (17%) of HPA axis activity, 1 out of 30 contrasts (3%) of SAM activity, and 3 out of 75 contrasts (4%) of oxidative status. These findings revealed that measures of HPA axis activity were associated with poor development outcomes. We did not find consistent evidence that markers of SAM system activity or oxidative status were associated with developmental status. Conclusions: Our observations reveal associations between the physiological evidence of stress in the HPA axis with developmental status in early childhood. These findings add to the existing evidence exploring the developmental consequences of early life stress.
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Background: Poor immune function increases children's risk of infection and mortality. Several maternal factors during pregnancy may affect infant immune function during the postnatal period. Objectives: We aimed to evaluate whether maternal micronutrients, stress, estriol, and immune status during the first or second trimester of pregnancy were associated with child immune status in the first two years after birth. Methods: We conducted observational analyses within the water, sanitation, and hygiene (WASH) Benefits Bangladesh randomized controlled trial. We measured biomarkers in 575 pregnant women and postnatally in their children. Maternal biomarkers measured during the first and second trimester of pregnancy included nutrition status via vitamin D (25-hydroxy-D [25(OH)D]), ferritin, soluble transferrin receptor (sTfR), and retinol-binding protein (RBP); cortisol; estriol. Immune markers were assessed in pregnant women at enrollment and their children at ages 14 and 28 mo, including C-reactive protein (CRP), alpha-1-acid glycoprotein (AGP), and 13 cytokines (including IFN-γ). We generated a standardized sum score of log-transformed cytokines. We analyzed IFN-γ individually because it is a critical immunoregulatory cytokine. All outcomes were prespecified. We used generalized additive models and reported the mean difference and 95% confidence intervals at the 25th and 75th percentiles of exposure distribution. Results: At child age 14 mo, concentrations of maternal RBP were inversely associated with the cytokine sum score in children (-0.34 adjusted difference between the 25th and 75th percentile [95% confidence interval -0.61, -0.07]), and maternal vitamin A deficiency was positively associated with the cytokine sum score in children (1.02 [0.13, 1.91]). At child age of 28 mo, maternal RBP was positively associated with IFN-γ in children (0.07 [0.01, 0.14]), whereas maternal vitamin A deficiency was negatively associated with child AGP (-0.07 [-0.13, -0.02]). Maternal iron deficiency was associated with higher AGP concentrations in children at age 14 mo (0.13 [0.04, 0.23]), and maternal sTfR concentrations were positively associated with child CRP concentrations at age 28 mo (0.18 [0, 0.36]). Conclusion: Maternal deficiencies in vitamin A or iron during the first 2 trimesters of pregnancy may shape the trajectory of a child's immune status.
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1. Ecological differences among co-occurring taxa are often invoked as an explanation for the maintenance of biodiversity. Whether these differences facilitate coexistence, which allows unequal competitors to remain in systems and thus maintain biodiversity, is still unclear. 2. Here, we used observational and experimental studies to test for ecological partitioning in ways that would promote coexistence among three co-occurring damselfly genera. We evaluated two necessary conditions for coexistence: (i) that the damselfly genera differ in their abilities to engage in interactions with other damselfly genera and environmental conditions such that their relative abundances covary differently along environmental gradients and (ii) that an increase in intrageneric abundance is more detrimental to performance-related demographic features of each genus than increases in intergeneric abundances. 3. Observational studies across 40 lakes showed that relative abundances of each genus covaried differently along an environmental gradient of lake abiotic and biotic features consistent with ecological partitioning. Field experiments in which we manipulated both intra- and intergeneric densities demonstrated that per capita growth rates of each genus are negatively density-dependent and are only limited by increases in intra- not intergeneric densities. 4. Collectively, these results show a clear signature of ecological partitioning among each genus, which should prevent competitive exclusion and maintain each genus in this system. The results do not guarantee local coexistence among the three genera but are consistent with criteria that should promote their coexistence. Our results also suggest that a food web model coupling keystone predation and apparent competition is likely necessary to explain the ecological dynamics of persistence among these genera.
Subject(s)
Biodiversity , Food Chain , Insecta/physiology , Animals , Lakes , Models, Biological , New Hampshire , Ponds , Population Dynamics , Seasons , Species Specificity , Statistics, Nonparametric , VermontABSTRACT
Background: Previously, we demonstrated that a water, sanitation, handwashing, and nutritional intervention improved linear growth and was unexpectedly associated with shortened childhood telomere length (TL) (Lin et al., 2017). Here, we assessed the association between TL and growth. Methods: We measured relative TL in whole blood from 713 children. We reported differences between the 10th percentile and 90th percentile of TL or change in TL distribution using generalized additive models, adjusted for potential confounders. Results: In cross-sectional analyses, long TL was associated with a higher length-for-age Z score at age 1 year (0.23 SD adjusted difference in length-for-age Z score [95% CI 0.05, 0.42; FDR-corrected p-value = 0.01]). TL was not associated with other outcomes. Conclusions: Consistent with the metabolic telomere attrition hypothesis, our previous trial findings support an adaptive role for telomere attrition, whereby active TL regulation is employed as a strategy to address 'emergency states' with increased energy requirements such as rapid growth during the first year of life. Although short periods of active telomere attrition may be essential to promote growth, this study suggests that a longer overall initial TL setting in the first 2 years of life could signal increased resilience against future telomere erosion events and healthy growth trajectories. Funding: Funded by the Bill and Melinda Gates Foundation. Clinical trial number: NCT01590095.
Subject(s)
Child Development , Telomere Homeostasis , Telomere/chemistry , Bangladesh , Child, Preschool , Cross-Sectional Studies , Female , Humans , Infant , Infant, Newborn , Male , Rural Population , Telomere/metabolismABSTRACT
Accurate estimates of the burden of SARS-CoV-2 infection are critical to informing pandemic response. Confirmed COVID-19 case counts in the U.S. do not capture the total burden of the pandemic because testing has been primarily restricted to individuals with moderate to severe symptoms due to limited test availability. Here, we use a semi-Bayesian probabilistic bias analysis to account for incomplete testing and imperfect diagnostic accuracy. We estimate 6,454,951 cumulative infections compared to 721,245 confirmed cases (1.9% vs. 0.2% of the population) in the United States as of April 18, 2020. Accounting for uncertainty, the number of infections during this period was 3 to 20 times higher than the number of confirmed cases. 86% (simulation interval: 64-99%) of this difference is due to incomplete testing, while 14% (0.3-36%) is due to imperfect test accuracy. The approach can readily be applied in future studies in other locations or at finer spatial scale to correct for biased testing and imperfect diagnostic accuracy to provide a more realistic assessment of COVID-19 burden.
Subject(s)
Coronavirus Infections/epidemiology , Pneumonia, Viral/epidemiology , Bayes Theorem , Betacoronavirus/isolation & purification , COVID-19 , COVID-19 Testing , Clinical Laboratory Techniques/methods , Coronavirus Infections/diagnosis , Coronavirus Infections/virology , Humans , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/virology , SARS-CoV-2 , United States/epidemiologyABSTRACT
Background: Shorter childhood telomere length (TL) and more rapid TL attrition are widely regarded as manifestations of stress. However, the potential effects of health interventions on child TL are unknown. We hypothesized that a water, sanitation, handwashing (WSH), and nutritional intervention would slow TL attrition during the first two years of life. Methods: In a trial in rural Bangladesh, we randomized geographical clusters of pregnant women into individual water treatment, sanitation, handwashing, nutrition, combined WSH, combined nutrition plus WSH (N + WSH), or control arms. We conducted a substudy enrolling children from the control arm and the N + WSH intervention arm. Participants and outcome assessors were not masked; analyses were masked. Relative TL was measured at 1 and 2 years after intervention, and the change in relative TL was reported. Analysis was intention-to-treat. Results: Between May 2012 and July 2013, in the overall trial, we randomized 720 geographical clusters of 5551 pregnant women to a control or an intervention arm. In this substudy, after 1 year of intervention, we assessed a total of 662 children (341 intervention and 321 control) and 713 children after 2 years of intervention (383 intervention and 330 control). Children in the intervention arm had significantly shorter relative TL compared with controls after 1 year of intervention (difference −163 base pairs (bp), p=0.001). Between years 1 and 2, TL increased in the intervention arm (+76 bp) and decreased in the controls (−23 bp) (p=0.050). After 2 years, there was no difference between the arms (p=0.305). Conclusions: Our unexpected finding of increased telomere attrition during the first year of life in the intervention group suggests that rapid telomere attrition during this critical period could reflect the improved growth in the intervention group, rather than accumulated stress. Funding: Funded by The Bill and Melinda Gates Foundation. Clinical trial number: NCT01590095.
Stress negatively affects health by causing changes in cells. As a result, excess stress may predispose people to fall ill more often or age faster. It is difficult to measure stress. Some studies suggest that measuring the ends of chromosomes, known as telomeres, may be one way to measure stress. Like the plastic tips on shoelaces, telomeres protect chromosomes from fraying. All peoples' telomeres shorten over their lifetime with each cell division. Many studies show that telomeres shorten faster in people who experience more stress. When telomeres become too short, cells die faster without being replaced, and the body ages. Most studies on telomere length have looked at adults. Few studies have looked at children early in life or asked whether there are ways to intervene to stop or reverse stress-related telomere shortening. The first two years of life are a crucial period for the developing brain and immune system, which could set children on a lifelong course toward health or disease. Young children living in low-resource settings often encounter many sources of stress, like poor nutrition, infectious diseases or violence. Studies are needed to determine if interventions in early childhood aimed at reducing some sources of stress improve telomere length or long-term health. Now, Lin et al. show that interventions to provide safe water, sanitation, handwashing facilities, and better nutrition to children in rural Bangladesh unexpectedly shortened telomeres. As part of a larger study, pregnant women in rural Bangladesh were divided, at random, into groups. One group received a suite of interventions, which included more sanitary toilets, handwashing facilities, and nutritional supplements for their infants. Another group served as a control and did not receive this extra help. Lin et al. looked at telomere length, growth, and infections in a subset of 713 children whose mothers participated in the study. Children who got the extra help grew faster and were less likely to get diarrhea or parasitic infections than the children in the control group. Unexpectedly, children in the intervention group had shorter telomeres at 14 months of age than the children in the control group. Lin et al. suggest that the telomere shortening in the intervention group might be a consequence of rapid growth and immune system development in the first year of life rather than resulting from biological stress. More studies are needed to ask whether telomere shortening is indeed linked to faster growth and development early in life. The strong and unexpected findings highlight how little is known about how the length of telomeres can be used to predict future health or disease. Interpreting the length of telomeres over a person's lifetime could prove more nuanced than originally thought.