Mediating pathways in the socio-economic gradient of child development: Evidence from children 6-42 months in Bogota

Research has previously shown a gap of near 0.5 of a standard deviation (SD) in cognition and language development between the top and bottom household wealth quartile in children aged 6–42 months in a large representative sample of low- and middle-income families in Bogota, using the Bayley Scales of Infant and Toddler Development. The gaps in fine motor and socio-emotional development were about half that size. Developmental deficits increased with age. The current study explored the associations amongst child development, household socio-economic status (SES), and a set of potential mediating variables—parental characteristics, child biomedical factors, and the quality of the home environment—in this sample. We ran mediation tests to quantify the contribution of these variables to the SES gap, and explored the role of age as a moderator. Parental education, particularly maternal education, and the quality of the home environment mediated the SES gap in all outcomes examined. Height-for-age mediated a small amount of the deficit in language scales only. More educated mothers provided better home stimulation than less educated mothers and the home environment partly mediated the effect of maternal education. These results suggested that in interventions aimed at promoting child development, those focusing on the quality of the home environment should be effective

Impacts 2 years after a scalable early childhood development intervention to increase psychosocial stimulation in the home: A follow-up of a cluster randomised controlled trial in Colombia

BACKGROUND: Poor early childhood development (ECD) in low- and middle-income countries is a major concern. There are calls to universalise access to ECD interventions through integrating them into existing government services but little evidence on the medium- or long-term effects of such scalable models. We previously showed that a psychosocial stimulation (PS) intervention integrated into a cash transfer programme improved Colombian children's cognition, receptive language, and home stimulation. In this follow-up study, we assessed the medium-term impacts of the intervention, 2 years after it ended, on children's cognition, language, school readiness, executive function, and behaviour. METHODS AND FINDINGS: Study participants were 1,419 children aged 12-24 months at baseline from beneficiary households of the cash transfer programme, living in 96 Colombian towns. The original cluster randomised controlled trial (2009-2011) randomly allocated the towns to control (N = 24, n = 349), PS (N = 24, n = 357), multiple micronutrient (MN) supplementation (N = 24, n = 354), and combined PS and MN (N = 24, n = 359). Interventions lasted 18 months. In this study (26 September 2013 to 11 January 2014), we assessed impacts on cognition, language, school readiness, executive function, and behaviour 2 years after intervention, at ages 4.5-5.5 years. Testers, but not participants, were blinded to treatment allocation. Analysis was on an intent-to-treat basis. We reassessed 88.5% of the children in the original study (n = 1,256). Factor analysis of test scores yielded 2 factors: cognitive (cognition, language, school readiness, executive function) and behavioural. We found no effect of the interventions after 2 years on the cognitive factor (PS: -0.031 SD, 95% CI -0.229-0.167; MN: -0.042 SD, 95% CI -0.249-0.164; PS and MN: -0.111 SD, 95% CI -0.311-0.089), the behavioural factor (PS: 0.013 SD, 95% CI -0.172-0.198; MN: 0.071 SD, 95% CI -0.115-0.258; PS and MN: 0.062 SD, 95% CI -0.115-0.239), or home stimulation. Study limitations include that behavioural development was measured through maternal report and that very small effects may have been missed, despite the large sample size. CONCLUSIONS: We found no evidence that a scalable PS intervention benefited children's development 2 years after it ended. It is possible that the initial effects on child development were too small to be sustained or that the lack of continued impact on home stimulation contributed to fade out. Both are likely related to compromises in implementation when going to scale and suggest one should not extrapolate from medium-term effects of small efficacy trials to scalable interventions. Understanding the salient differences between small efficacy trials and scaled-up versions will be key to making ECD interventions effective tools for policymakers. TRIAL REGISTRATION: ISRCTN18991160

Using the infrastructure of a conditional cash transfer program to deliver a scalable integrated early child development program in Colombia : cluster randomized controlled trial

En: British Medical Journal No. 349, doi: http://dx.doi.org/10.1136/bmj.g5785Objective: To assess the effectiveness of an integrated early child development intervention, combining stimulation and micronutrient supplementation and delivered on a large scale in Colombia, for children’s development, growth, and hemoglobin levels. Design Cluster randomized controlled trial, using a 2×2 factorial design, with municipalities assigned to one of four groups: psychosocial stimulation, micronutrient supplementation, combined intervention, or control. Setting 96 municipalities in Colombia, located across eight of its 32 departments. Participants: 1420 children aged 12-24 months and their primary carers. Intervention Psychosocial stimulation (weekly home visits with play demonstrations), micronutrient sprinkles given daily, and both combined. All delivered by female community leaders for 18 months. Main outcome measures Cognitive, receptive and expressive language, and fine and gross motor scores on the Bayley scales of infant development-III; height, weight, and hemoglobin levels measured at the baseline and end of intervention. Results Stimulation improved cognitive scores (adjusted for age, sex, testers, and baseline levels of outcomes) by 0.26 of a standard deviation (P=0.002). Stimulation also increased receptive language by 0.22 of a standard deviation (P=0.032). Micronutrient supplementation had no significant effect on any outcome and there was no interaction between the interventions. No intervention affected height, weight, or hemoglobin levels. Conclusions: Using the infrastructure of a national welfare program we implemented the integrated early child development intervention on a large scale and showed its potential for improving children’s cognitive development. We found no effect of supplementation on developmental or health outcomes. Moreover, supplementation did not interact with stimulation. The implementation model for delivering stimulation suggests that it may serve as a promising blueprint for future policy on early childhood development

Effects of a scalable home-visiting intervention on child development in slums of urban India: evidence from a randomised controlled trial

Background: An estimated 63.4 million Indian children under 5 years are at risk of poor development. Home visits that use a structured curriculum to help caregivers enhance the quality of the home stimulation environment improve developmental outcomes. However, achieving effectiveness in poor urban contexts through scalable models remains challenging. Methods: Using a cluster randomised controlled trial, we evaluated a psychosocial stimulation intervention, comprising weekly home visits for 18 months, in urban slums of Cuttack, Odisha, India. The intervention is complementary to existing early childhood services in India and was run and managed through a local branch of a national NGO. The study ran from August 2013 to July 2015. We enrolled 421 children aged 10–20 months from 54 slums. Slums were randomised to intervention or control. Primary outcomes were children's cognitive, receptive language, expressive language and fine motor development assessed using the Bayley‐III. Prespecified intent‐to‐treat analysis investigated impacts and heterogeneity by gender. Trial registrations: ISRCTN89476603, AEARCTR‐0000169. Results: Endline data for 378 (89.8%) children were analysed. Attrition was balanced between groups. We found improvements of 0.349 of a standard deviation (SD; p = .005, stepdown p = .017) to cognition while impacts on receptive language, expressive language and fine motor development were, respectively, 0.224 SD (p = .099, stepdown p = .184), 0.192 SD (p = .085, stepdown p = .184) and 0.111 (p = .385, stepdown p = .385). A child development factor improved by 0.301 SD (p = .032). Benefits were larger for boys. The quality of the home stimulation environment also improved. Conclusions: This study shows that a potentially scalable home‐visiting intervention is effective in poor urban areas

Using the infrastructure of a conditional cash transfer program to deliver a scalable integrated early child development program in Colombia: cluster randomized controlled trial

To assess the effectiveness of an integrated early child development intervention, combining stimulation and micronutrient supplementation and delivered on a large scale in Colombia, for children's development, growth, and hemoglobin levels

Molecular Mechanisms of Kidney Injury and Repair

Chronic kidney disease (CKD) will become the fifth global cause of death by 2040, thus emphasizing the need to better understand the molecular mechanisms of damage and regeneration in the kidney. CKD predisposes to acute kidney injury (AKI) which, in turn, promotes CKD progression. This implies that CKD or the AKI-to-CKD transition are associated with dysfunctional kidney repair mechanisms. Current therapeutic options slow CKD progression but fail to treat or accelerate recovery from AKI and are unable to promote kidney regeneration. Unraveling the cellular and molecular mechanisms involved in kidney injury and repair, including the failure of this process, may provide novel biomarkers and therapeutic tools. We now review the contribution of different molecular and cellular events to the AKI-to-CKD transition, focusing on the role of macrophages in kidney injury, the different forms of regulated cell death and necroinflammation, cellular senescence and the senescence-associated secretory phenotype (SAPS), polyploidization, and podocyte injury and activation of parietal epithelial cells. Next, we discuss key contributors to repair of kidney injury and opportunities for their therapeutic manipulation, with a focus on resident renal progenitor cells, stem cells and their reparative secretome, certain macrophage subphenotypes within the M2 phenotype and senescent cell clearance

The D-score: a metric for interpreting the early development of infants and toddlers across global settings

Introduction: Early childhood development can be described by an underlying latent construct. Global comparisons of children’s development are hindered by the lack of a validated metric that is comparable across cultures and contexts, especially for children under age 3 years. We constructed and validated a new metric, the Developmental Score (D-score), using existing data from 16 longitudinal studies. / Methods: Studies had item-level developmental assessment data for children 0–48 months and longitudinal outcomes at ages >4–18 years, including measures of IQ and receptive vocabulary. Existing data from 11 low-income, middle-income and high-income countries were merged for >36 000 children. Item mapping produced 95 ‘equate groups’ of same-skill items across 12 different assessment instruments. A statistical model was built using the Rasch model with item difficulties constrained to be equal in a subset of equate groups, linking instruments to a common scale, the D-score, a continuous metric with interval-scale properties. D-score-for-age z-scores (DAZ) were evaluated for discriminant, concurrent and predictive validity to outcomes in middle childhood to adolescence. / Results: Concurrent validity of DAZ with original instruments was strong (average r=0.71), with few exceptions. In approximately 70% of data rounds collected across studies, DAZ discriminated between children above/below cut-points for low birth weight (<2500 g) and stunting (−2 SD below median height-for-age). DAZ increased significantly with maternal education in 55% of data rounds. Predictive correlations of DAZ with outcomes obtained 2–16 years later were generally between 0.20 and 0.40. Correlations equalled or exceeded those obtained with original instruments despite using an average of 55% fewer items to estimate the D-score. / Conclusion: The D-score metric enables quantitative comparisons of early childhood development across ages and sets the stage for creating simple, low-cost, global-use instruments to facilitate valid cross-national comparisons of early childhood development

The D-score:a metric for interpreting the early development of infants and toddlers across global settings

Introduction Early childhood development can be described by an underlying latent construct. Global comparisons of children's development are hindered by the lack of a validated metric that is comparable across cultures and contexts, especially for children under age 3 years. We constructed and validated a new metric, the Developmental Score (D-score), using existing data from 16 longitudinal studies. Methods Studies had item-level developmental assessment data for children 0-48 months and longitudinal outcomes at ages &gt;4-18 years, including measures of IQ and receptive vocabulary. Existing data from 11 low-income, middle-income and high-income countries were merged for &gt;36 000 children. Item mapping produced 95 'equate groups' of same-skill items across 12 different assessment instruments. A statistical model was built using the Rasch model with item difficulties constrained to be equal in a subset of equate groups, linking instruments to a common scale, the D-score, a continuous metric with interval-scale properties. D-score-for-age z-scores (DAZ) were evaluated for discriminant, concurrent and predictive validity to outcomes in middle childhood to adolescence. Results Concurrent validity of DAZ with original instruments was strong (average r=0.71), with few exceptions. In approximately 70% of data rounds collected across studies, DAZ discriminated between children above/below cut-points for low birth weight

Key Factors Associated With Pulmonary Sequelae in the Follow-Up of Critically Ill COVID-19 Patients

Introduction: Critical COVID-19 survivors have a high risk of respiratory sequelae. Therefore, we aimed to identify key factors associated with altered lung function and CT scan abnormalities at a follow-up visit in a cohort of critical COVID-19 survivors. Methods: Multicenter ambispective observational study in 52 Spanish intensive care units. Up to 1327 PCR-confirmed critical COVID-19 patients had sociodemographic, anthropometric, comorbidity and lifestyle characteristics collected at hospital admission; clinical and biological parameters throughout hospital stay; and, lung function and CT scan at a follow-up visit. Results: The median [p25–p75] time from discharge to follow-up was 3.57 [2.77–4.92] months. Median age was 60 [53–67] years, 27.8% women. The mean (SD) percentage of predicted diffusing lung capacity for carbon monoxide (DLCO) at follow-up was 72.02 (18.33)% predicted, with 66% of patients having DLCO < 80% and 24% having DLCO < 60%. CT scan showed persistent pulmonary infiltrates, fibrotic lesions, and emphysema in 33%, 25% and 6% of patients, respectively. Key variables associated with DLCO < 60% were chronic lung disease (CLD) (OR: 1.86 (1.18–2.92)), duration of invasive mechanical ventilation (IMV) (OR: 1.56 (1.37–1.77)), age (OR [per-1-SD] (95%CI): 1.39 (1.18–1.63)), urea (OR: 1.16 (0.97–1.39)) and estimated glomerular filtration rate at ICU admission (OR: 0.88 (0.73–1.06)). Bacterial pneumonia (1.62 (1.11–2.35)) and duration of ventilation (NIMV (1.23 (1.06–1.42), IMV (1.21 (1.01–1.45)) and prone positioning (1.17 (0.98–1.39)) were associated with fibrotic lesions. Conclusion: Age and CLD, reflecting patients’ baseline vulnerability, and markers of COVID-19 severity, such as duration of IMV and renal failure, were key factors associated with impaired DLCO and CT abnormalities

Admixture in Latin America: Geographic Structure, Phenotypic Diversity and Self-Perception of Ancestry Based on 7,342 Individuals

The current genetic makeup of Latin America has been shaped by a history of extensive admixture between Africans, Europeans and Native Americans, a process taking place within the context of extensive geographic and social stratification. We estimated individual ancestry proportions in a sample of 7,342 subjects ascertained in five countries (Brazil, Chile, Colombia, México and Perú). These individuals were also characterized for a range of physical appearance traits and for self-perception of ancestry. The geographic distribution of admixture proportions in this sample reveals extensive population structure, illustrating the continuing impact of demographic history on the genetic diversity of Latin America. Significant ancestry effects were detected for most phenotypes studied. However, ancestry generally explains only a modest proportion of total phenotypic variation. Genetically estimated and self-perceived ancestry correlate significantly, but certain physical attributes have a strong impact on self-perception and bias self-perception of ancestry relative to genetically estimated ancestry