Introduction Skin-to-skin contact during the first hour of birth is recommended for healthy newborn infants and their mothers and improves early stabilisation and breastfeeding outcomes. Kangaroo Mother Care (KMC), involving prolonged skin-to-skin contact (SSC) and exclusive breastfeeding, provides an optimal physiological transition from intrauterine to extrauterine life for preterm and low birth weight infants, improving survival by 32% and conferring multiple clinical and neurodevelopmental benefits. Extending the duration of SSC contact beyond the first hour may similarly confer underexplored benefits to normal birth weight infants, including improved stabilisation, breastfeeding, growth, and maternal-infant bonding. The study aims to evaluate the effect of KMC during the first 72 hours on early weight loss, weight gain velocity and breastfeeding quality in normal birthweight infants. Methods and Analysis This multicentre, individually randomised, controlled, open-label superiority trial will enrol 516 healthy singleton neonates with birth weight ≥2500 grams and their mothers with uncomplicated vaginal deliveries from 3 public health facilities in Uttar Pradesh, India. Dyads will be randomised (1:1) and stratified by site to either intervention or control groups. The intervention involves prolonged KMC (≥8 hours of daily SSC with exclusive breastfeeding in the KMC position) during the initial 3 days after birth, with a recommendation to continue KMC at home throughout the newborn period. Both intervention and control groups will receive a common minimum care package, including breastfeeding initiation through uninterrupted SSC in the first hour, essential newborn care counselling, vaccinations and other standard facility care. The primary outcomes are: 1) mean percentage weight loss at 48 hours; 2) weight gain velocity up to 28 days; and 3) the proportion of dyads with moderate-to-poor quality breastfeeding scores (BBAT <7) at age 7 completed days. Secondary outcomes include exclusive breastfeeding rates, maternal breastfeeding experience, incidence of possible serious bacterial infection, maternal depression, and maternal-infant bonding. Data will be collected electronically using standardised tools with quality control measures. Primary outcomes will be analysed using Linear Mixed-Effects Models (continuous) and Mixed-Effects Logistic Regression (binary) on an Intention-to-Treat basis, adjusting for study site, parity, infant sex, and baseline birth weight. A p-value <0.05 will be considered statistically significant. Ethics and Dissemination The study is approved by the institutional ethics committees of the Community Empowerment Lab and King Georges Medical University. Written informed consent will be obtained from participating mothers. All findings will be disseminated regardless of the outcome, through publication in peer-reviewed journals, presentations at international conferences, and policy briefings to local health authorities. Data will be deposited in an open-access repository to promote data sharing and transparency. The results are intended to inform national and international guidelines on essential newborn care for the global population of healthy, term infants. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial CTRI/2024/01/062057, ISRCTN14346778 ### Funding Statement This work was supported by Indian Council of Medical Research (Project number: IIRP-2023-7329). The sponsor has no role in the design, conduct, analysis and reporting of the trial, but provides study oversight through a scientific review committee. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study is approved by the institutional ethics committees of the Community Empowerment Lab and King George's Medical University. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Since this is a study protocol, this is not applicable.

Caregiver-infant interactions shape infants' early visual experience; however, there is limited work from low-and middle-income countries (LMIC) in characterizing the visual cognitive dynamics of these interactions. Here, we present an innovative dyadic visual cognition pipeline using machine learning methods which captures, processes, and analyses the visual dynamics of caregiver-infant interactions across cultures. We undertake two studies to examine its application in both low (rural India) and high (urban UK) resource settings. Study 1 develops and validates the pipeline to process caregiver-infant interaction data captured using head-mounted cameras and eye-trackers. We use face detection and object recognition networks and validate these tools using 12 caregiver-infant dyads (4 dyads from a 6-month-old UK cohort, 4 dyads from a 6-month-old India cohort, and 4 dyads from a 9-month-old India cohort). Results show robust and accurate face and toy detection, as well as a high percent agreement between processed and manually coded dyadic interactions. Study 2 applied the pipeline to a larger data set (25 6-month-olds from the UK, 31 6-month-olds from India, and 37 9-month-olds from India) with the aim of comparing the visual dynamics of caregiver-infant interaction across the two cultural settings. Results show remarkable correspondence between key measures of visual exploration across cultures, including longer mean look durations during infant-led joint attention episodes. In addition, we found several differences across cultures. Most notably, infants in the UK had a higher proportion of infant-led joint attention episodes consistent with a child-centered view of parenting common in western middle-class families. In summary, the pipeline we report provides an objective assessment tool to quantify the visual dynamics of caregiver-infant interaction across high- and low-resource settings.

INTRODUCTION:Reflux bile acids are believed to promote esophageal adenocarcinoma (EAC), but the role of systemic bile acids is unknown. This study aimed to assess associations between systemic bile acids and stages of Barrett's esophagus (BE) progression. METHODS:Subjects with and without BE were enrolled in this multicenter cross-sectional study. Targeted serum bile acid profiling was performed, and a subset of subjects completed a validated food frequency questionnaire. RNA sequencing was performed on BE or gastric cardia tissue to assess bile acid associations with gene expression. RESULTS:A total of 141 subjects were enrolled with serum bile acids profiled (49 non-BE; 92 BE: 44 no dysplasia, 25 indefinite/low grade dysplasia, 23 high-grade dysplasia/EAC). Lower Healthy Eating Index score, older age, higher body mass index, and no proton pump inhibitor use were associated with increased levels of multiple bile acids. Global bile acid pools were distinct between non-BE and stages of BE neoplasia ( P = 0.004). Increasing cholic acid was associated with high-grade dysplasia/EAC compared with non-BE, even after adjusting for EAC risk factors (adjusted odds ratio 2.03, 95% confidence interval 1.11-3.71) as was the combination of unconjugated primary bile acids (adjusted odds ratio 1.81, 95% confidence interval 1.04-3.13). High cholic acid levels were associated with tissue gene expression changes including increased DNA replication and reduced lymphocyte differentiation genes. DISCUSSION:Alterations in serum bile acids are independently associated with advanced neoplasia in BE and may contribute to neoplastic progression. Future studies should explore associated gut microbiome changes, proneoplastic effects of bile acids, and whether these bile acids, particularly cholic acid, represent potential biomarkers or viable therapeutic targets for advanced neoplasia in BE.

INTRODUCTION:Early neoplastic progression of Barrett's esophagus (BE) is often treated with endoscopic therapy. Although effective, some patients are refractory to therapy or recur after apparent eradication of the BE. The goal of this study was to determine whether genomic alterations within the treated BE may be associated with persistent or recurrent disease. METHODS:We performed DNA sequencing on pre-treatment esophageal samples from 45 patients who were successfully treated by endoscopic therapy and did not recur as well as pre-treatment and post-treatment samples from 40 patients who had persistent neoplasia and 21 patients who had recurrent neoplasia. The genomic alterations were compared between groups. RESULTS:The genomic landscape was similar between all groups. Patients with persistent disease were more likely to have pre-treatment alterations involving the receptor tyrosine kinase pathway ( P = 0.01), amplifications of oncogenes ( P = 0.01), and deletions of tumor suppressor genes ( P = 0.02). These associations were no longer significant after adjusting for patient age and BE length. More than half of patients with persistent (52.5%) or recurrent (57.2%) disease showed pre-treatment and post-treatment samples that shared at least 50% of their driver mutations. DISCUSSION:Pre-treatment samples were genomically similar between those who responded to endoscopic therapy and those who had persistent or recurrent disease, suggesting there is not a strong genomic component to treatment response. Although it was expected to find shared driver mutations in pre-treatment and post-treatment samples in patients with persistent disease, the finding that an equal number of patients with recurrent disease also showed this relation suggests that many recurrences represent undetected minimal residual disease.

Background:Poor air quality has been linked to cognitive deficits in children, but this relationship has not been examined in the first year of life when brain growth is at its peak.Methods:We measured in-home air quality focusing on particulate matter with diameter of <2.5 μm (PM2.5) and infants' cognition longitudinally in a sample of families from rural India.Results:Air quality was poorer in homes that used solid cooking materials. Infants from homes with poorer air quality showed lower visual working memory scores at 6 and 9 months of age and slower visual processing speed from 6 to 21 months when controlling for family socio-economic status.Conclusions:Thus, poor air quality is associated with impaired visual cognition in the first two years of life, consistent with animal studies of early brain development. We demonstrate for the first time an association between air quality and cognition in the first year of life using direct measures of in-home air quality and looking-based measures of cognition. Because indoor air quality was linked to cooking materials in the home, our findings suggest that efforts to reduce cooking emissions should be a key target for intervention.Funding:Bill & Melinda Gates Foundation grant OPP1164153.

Aim To design a health system model for scaling-up Kangaroo mother care (KMC) and assess its impact on the population-level coverage and quality of KMC in Uttar Pradesh, India. Methods We co-developed the model with mothers and health system stakeholders using human-centred design over multiple cycles of implementation, learning and data-driven refinement. Infants with birthweight High delivery load facilities were equipped with a KMC Lounge to ensure comfort, respectful care of mothers and high-quality KMC over prolonged periods. Systems to ensure weighing at birth, referral of infants with birthweight <2000 g to KMC facilities, initiation of KMC for all stable low birthweight infants, improving quality of care within KMC facilities and supporting families to continue KMC at home post discharge, were integrated into existing services. KMC was initiated in 93.3% of eligible infants with effective coverage of 52.7% and 64.8% at discharge and 7 days post discharge, respectively. Conclusion The model addressed critical barriers to KMC implementation and adoption, contributing to its scale-up across the state.

Stunting is associated with poor long-term cognitive, academic and economic outcomes, yet the mechanisms through which stunting impacts cognition in early development remain unknown. In a first-ever neuroimaging study conducted on infants from rural India, we demonstrate that stunting impacts a critical, early-developing cognitive system—visual working memory. Stunted infants showed poor visual working memory performance and were easily distractible. Poor performance was associated with reduced engagement of the left anterior intraparietal sulcus, a region involved in visual working memory maintenance and greater suppression in the right temporoparietal junction, a region involved in attentional shifting. When assessed one year later, stunted infants had lower problem-solving scores, while infants of normal height with greater left anterior intraparietal sulcus activation showed higher problem-solving scores. Finally, short-for-age infants with poor physical growth indices but good visual working memory performance showed more positive outcomes suggesting that intervention efforts should focus on improving working memory and reducing distractibility in infancy.

Aim To estimate incremental costs of an implementation model for scaling up Kangaroo Mother Care (KMC) for neonates with birthweight <2000 g. Methods Seven sites across Ethiopia and India collected data for 2018-19 to calculate incremental recurrent costs (of health worker time, supplies, and operations) and start-up costs for KMC scale up. The costs were estimated per live newborn Scaling up KMC in study districts required average incremental costs of US$59 (95% CI US$ 52-67) in Ethiopia and US$72 (95% CI US$ 41-103) in India per eligible newborn in the population. Most of these costs were recurrent; the annualised start-up costs per eligible newborn ranged from 12%-25% of total costs in Ethiopia and 9%-16% in India. The major cost driver was human resources, followed by initial and recurrent training, supplies, and communications costs. Incremental infrastructure costs were only 2%-6% of total costs in both countries. Most of the costs were for activities at the KMC implementing facility, accounting for 79%-88% of the total costs in Ethiopia and 89%-93% of those in India. Conclusion The costs for successful scale up of KMC seem affordable but must be included in programme budgets.

Objective: We evaluated the prospective association of midlife leisure-time physical activity (LTPA) and sedentary behavior (SB), and their temporal patterns, with MRI-measured carotid atherosclerotic morphology. Methods: Participants enrolled in the Carotid MRI substudy (2004-2006) of the Atherosclerosis Risk in Com-munities (ARIC) Study and with self-reported assessments of LTPA and SB at visits 1 (1987-1989) and 3 (1993-1995) were included in this study. LTPA was ascertained using the ARIC/Baecke physical activity ques-tionnaire and categorized according to the American Heart Association's metric of poor, intermediate, or ideal physical activity. SB, measured as TV viewing frequency, was categorized as high, medium, and low. We used multivariable adjusted linear and logistic regression models to examine the associations between midlife (visit 3 only) and persistent (visit 1 to 3) LTPA and TV viewing with carotid artery plaque burden and components. Results: Among the 1,582 (mean age: 59 years, 43% male, 18% Black) participants, 45.7%, 21.7%, and 32.6% reported ideal, intermediate, or poor LTPA, respectively. High TV viewing was reported in 33.8% of participants, with 46.4% and 19.8% reporting medium or low TV viewing, respectively. Compared to poor LTPA, ideal LTPA in midlife was not associated with total wall volume (ss=0.01, 95% CI:-0.01, 0.03), maximum carotid wall thickness (ss=0.06, 95% CI:-0.08, 0.21), normalized wall index (ss=-0.01, 95% CI:-0.03, 0.01), or maximum stenosis (ss=-0.11, 95% CI:-1.98, 1.76). Low or middle, compared to high, TV viewing was also not associated with carotid artery measures of plaque burden. Compared to poor LTPA or high TV viewing, ideal LTPA (odds ratio (OR): 0.82, 95% CI: 0.55, 1.23) and low TV viewing (OR=0.90, 95% CI: 0.56, 1.44) was not associated with odds of lipid core presence, respectively. Conclusion: Overall, this study does not provide strong evidence for an association between LTPA and SB with carotid plaque measures.

Background Essential health and nutrition services for pregnant women, newborns, and children, particularly in low- and middle-income countries (LMICs), are disrupted by the COVID-19 pandemic. This formative research was conducted at five LMICs to understand the pandemic’s impact on barriers to and mitigation for strategies of care-seeking and managing possible serious bacterial infection (PSBI) in young infants. Methods We used a convergent parallel mixed-method design to explore the possible factors influencing PSBI management, barriers, and facilitators at three levels: 1) national and local policy, 2) the health systems, public and private facilities, and 3) community and caregivers. We ascertained trends in service provision and utilisation across pre-lockdown, lockdown, and post-lockdown periods by examining facility records and community health worker registers. Results The pandemic aggravated pre-existing challenges in the identification of young infants with PSBI; care-seeking, referral, and treatment due to several factors at the policy level (limited staff and resource reallocation), health facility level (staff quarantine, sub-optimal treatment in facilities, limited duration of service availability, lack of clear guidelines on the management of sick young infants, and inadequate supplies of protective kits and essential medicines) and at the community level (travel restrictions, lack of transportation, and fear of contracting the infection in hospitals). Care-seeking shifted to faith healers, traditional and informal private sources, or home remedies. However, caregivers were willing to admit their sick young infants to the hospital if advised by doctors. A review of facility records showed low attendance (<50%) of sick young infants in the OPD/emergencies during lockdowns in Bangladesh, India (both sites) and Pakistan, but it gradually increased as lockdowns eased. Stakeholders suggested aspirational and pragmatic mitigation strategies. Conclusions We obtained useful insights on health system preparedness during catastrophes and strategies to strengthen services and improve utilisation regarding PSBI management. The current pandemic provides an opportunity for implementing various mitigation strategies at the policy, health system, and community levels to improve preparedness.

To design a health system model for scaling-up Kangaroo mother care (KMC) and assess its impact on the population-level coverage and quality of KMC in Uttar Pradesh, India. We co-developed the model with mothers and health system stakeholders using human-centred design over multiple cycles of implementation, learning and data-driven refinement. Infants with birthweight <2000 g in the study district were prospectively followed to assess the ‘effective coverage’ of KMC. Effective coverage referred to the proportion of eligible infants receiving ≥8 h of daily skin-to-skin contact and exclusive breastfeeding. High delivery load facilities were equipped with a KMC Lounge to ensure comfort, respectful care of mothers and high-quality KMC over prolonged periods. Systems to ensure weighing at birth, referral of infants with birthweight <2000 g to KMC facilities, initiation of KMC for all stable low birthweight infants, improving quality of care within KMC facilities and supporting families to continue KMC at home post discharge, were integrated into existing services. KMC was initiated in 93.3% of eligible infants with effective coverage of 52.7% and 64.8% at discharge and 7 days post discharge, respectively. The model addressed critical barriers to KMC implementation and adoption, contributing to its scale-up across the state.

BACKGROUND:Newborn oil massage is a widespread practice. Vigorous massage with potentially harmful products and forced removal of vernix may disrupt skin barrier integrity. Hospitalized, very-preterm infants treated with sunflower seed oil (SSO) have demonstrated improved growth but community-based data on growth and health outcomes are lacking. OBJECTIVES:We aimed to test whether SSO therapy enhances neonatal growth and reduces morbidity at the population level. METHODS:We conducted an open-label, controlled trial in rural Uttar Pradesh, India, randomly allocating 276 village clusters equally to comparison (usual care) and intervention comprised of promotion of improved massage practices exclusively with SSO, using intention-to-treat and per-protocol mixed-effects regression analysis. RESULTS:We enrolled 13,478 and 13,109 newborn infants in demographically similar intervention and comparison arms, respectively. Adherence to exclusive SSO increased from 22.6% of intervention infants enrolled in the first study quartile to 37.2% in the last quartile. Intervention infants gained significantly more weight, by 0.94 g · kg-1 · d-1 (95% CI: 0.07, 1.82 g · kg-1 · d-1, P = 0.03), than comparison infants by intention-to-treat analysis. Restricted cubic spline regression revealed the largest benefits in weight gain (2-4 g · kg-1 · d-1) occurred in infants weighing <2000 g at birth. Weight gain in intervention infants was higher by 1.31 g · kg-1 · d-1 (95% CI: 0.17, 2.46 g · kg-1 · d-1; P = 0.02) by per-protocol analysis. Morbidities were similar by intention-to-treat analysis but in per-protocol analysis rates of hospitalization and of any illness were reduced by 36% (OR: 0.64; 95% CI: 0.44, 0.94; P = 0.02) and 44% (OR: 0.56; 95% CI: 0.40, 0.77; P < 0.001), respectively, in treated infants. CONCLUSIONS:SSO therapy improved neonatal growth, and reduced morbidities when applied exclusively, across the facility-community continuum of care at the population level. Further research is needed to improve demand for recommended therapy inside hospital as well as in community settings, and to confirm these results in other settings.This trial was registered at www.isrctn.com as ISRCTN38965585 and http://ctri.nic.in as CTRI/2014/12/005282.

Introduction: The incidence of esophageal adenocarcinoma (EAC) has increased dramatically over the past half century. Changes in dietary patterns over this time may partially account for this trend. Prior studies have found inverse associations between fiber intake and both Barrett’s esophagus (BE) and EAC, and studies of fat intake have reported increased risk or no association. However, it is unknown whether fiber or fat intake contribute to neoplastic progression in BE patients. Methods: We performed a multi-center case-control study of patients with and without BE. We collected demographic, anthropometric, and clinical data and categorized BE by worst degree of histology ever. Subjects completed the NCI DHQII, a validated food frequency questionnaire assessing dietary intake over the preceding 12 months. We used multivariable logistic regression analyses to assess associations of energy adjusted fat and fiber intake with BE and with advanced neoplasia (high grade dysplasia or EAC vs. no dysplasia/indefinite/low grade dysplasia). Four models were developed: 1) fat and fiber intake; 2) Model 1 and EAC risk factors (age, sex, BMI, smoking history, family history); 3) Model 2 and aspirin and statin use; 4) reduced parsimonious model (final model: age, sex, family history). Results: We enrolled 162 subjects; 108 subjects (37 non-BE, 71 BE; 21 with advanced neoplasia) completed the questionnaire and were analyzed. Compared to controls, BE patients were older and more likely (p< 0.01) to be male, aspirin users, statin users, and ever smokers. BE patients had significantly higher energy-adjusted fiber intake but no difference in fat intake compared to controls. (Figure A-B) Adjusted for fat intake, increased fiber intake was associated with reduced odds of BE (per g/1000 kcal, OR 0.81, 95%CI 0.70-0.93), with similar associations in all the models (Table). There was no association between fat intake and BE. There was no significant association between fat or fiber intake and stages of progression to EAC (Figure C-D), and neither fat nor fiber intake was associated with advanced neoplasia in multivariable analyses. (Table) Conclusion: Fiber intake was inversely associated with BE but not with stages of progression to EAC. There was no association between fat intake and BE or dysplasia or EAC, but this may reflect our small sample size. Future larger studies are warranted to elucidate the mechanisms by which fiber may protect against the development of BE.Figure 1.: Comparisons of energy-adjusted intake of A) fat and B) fiber between BE and non-BE subjects. Comparisons of energy-adjusted intake of C) fat and D) fiber across stages of progression to EAC. Table 1. - Multivariable logistic regression models for associations between energy-adjusted fat (% kcal) and fiber (g/1000 kcal) intake with BE (vs. no BE) and with advanced neoplasia (HGD/EAC vs. ND/IND/LGD). (ORs per unit increase) Model 1 Model 2 Model 3 Model 4 BE Fat 1.01 (0.95- 1.08 1.03 (0.95- 1.08) 1.03 (0.94- 1.11) 1.03 (0.95- 1.11) Fiber 0.81 (0.70- 0.93) 0.82 90.67- 0.99) 0.82 (0.67-1.00) 0.80 (0.66- 0.97) Advanced neoplasia Fat 1.00 (0.93- 1.08 1.00 (0.92- 1.09) 1.02 (0.93- 1.12) 1.01 (0.98- 1.09) Fiber 0.94 (0.75- 1.18) 0.85 (0.65- 1.1) 0.87 (0.65- 1.16) 0.96 (0.75- 1.24)