Ultrasound Core Laboratories (UCL) are used in multicenter trials to assess imaging biomarkers to define robust phenotypes, to reduce imaging variability and to allow blinded independent review with the purpose of optimizing endpoint measurement precision. The Household Air Pollution Intervention Network, a multicountry randomized controlled trial (Guatemala, Peru, India and Rwanda), evaluates the effects of reducing household air pollution on health outcomes. Field studies using portable ultrasound evaluate fetal, lung and vascular imaging endpoints. The objective of this report is to describe administrative methods and training of a centralized clinical research UCL. A comprehensive administrative protocol and training curriculum included standard operating procedures, didactics, practical scanning and written/practical assessments of general ultrasound principles and specific imaging protocols. After initial online training, 18 sonographers (three or four per country and five from the UCL) participated in a 2 wk on-site training program. Written and practical testing evaluated ultrasound topic knowledge and scanning skills, and surveys evaluated the overall course. The UCL developed comprehensive standard operating procedures for image acquisition with a portable ultrasound system, digital image upload to cloud-based storage, off-line analysis and quality control. Pre- and post-training tests showed significant improvements (fetal ultrasound: 71% ± 13% vs. 93% ± 7%, p < 0.0001; vascular lung ultrasound: 60% ± 8% vs. 84% ± 10%, p < 0.0001). Qualitative and quantitative feedback showed high satisfaction with training (mean, 4.9 ± 0.1; scale: 1 = worst, 5 = best). The UCL oversees all stages: training, standardization, performance monitoring, image quality control and consistency of measurements. Sonographers who failed to meet minimum allowable performance were identified for retraining. In conclusion, a UCL was established to ensure accurate and reproducible ultrasound measurements in clinical research. Standardized operating procedures and training are aimed at reducing variability and enhancing measurement precision from study sites, representing a model for use of portable digital ultrasound for multicenter field studies.

Women and children in rural regions of low-income countries are exposed to high levels of household air pollution (HAP) as they traditionally tend to household chores such as cooking with biomass fuels. Early life exposure to air pollution is associated with aeroallergen sensitization and developing allergic diseases at older ages. This prospective cohort study assigned HAP-reducing chimney stoves to 557 households in rural Guatemala at different ages of the study children. The children’s air pollution exposure was measured using personal CO diffusion tubes. Allergic outcomes at 4–5 years old were assessed using skin prick tests and International Study of Asthma and Allergies in Childhood (ISAAC)-based questionnaires. Children assigned to improved stoves before 6 months old had the lowest HAP exposure compared to the other groups. Longer exposure to the unimproved stoves was associated with higher risks of maternal-reported allergic asthma (OR = 2.42, 95% CI: 1.11–5.48) and rhinitis symptoms (OR = 2.01, 95% CI: 1.13–3.58). No significant association was found for sensitization to common allergens such as dust mites and cockroaches based on skin prick tests. Reducing HAP by improving biomass burning conditions might be beneficial in preventing allergic diseases among children in rural low-income populations.

Worldwide, roughly 3.8 billion people heat or cook with wood and other solid fuels,1 which exposes them to numerous household air pollutants associated with ill health.2 Household air pollution exerts an immense toll on human health, contributing to an estimated 2.31 million deaths in 2019. Although rural U.S. populations have lower average ambient exposures to particulate matter ≤2.5μm in aerodynamic diameter [fine PM (PM2.5)] than urban populations,3 rural homes that are heated with woodstoves have higher exposure to indoor air pollution than those that use other sources of heating, such as electricity.4 Of the 12.5 million U.S. homes that burn wood for space heating, 3.5 million use woodstoves as the primary source of heating.5 For homes that use inefficient woodstoves, indoor levels of PM2.5 can exceed the U.S. Environmental Protection Agency National Ambient Air Quality Standard of <35 μg/m3 over a 24-h period.4,6,7,8 Given that PM2.5 exposure is associated with adverse health effects, such as child lower respiratory tract infections (LRTIs),2 it is important that people who heat their homes with wood not only have access to interventions that reduce these household exposures, but also that they use them consistently and correctly.

Rationale: Pneumonia is the leading cause of death in children worldwide. Identifying and appropriately managing severe pneumonia in a timely manner improves outcomes. Little is known about the readiness of healthcare facilities to manage severe pediatric pneumonia in low-resource settings. Objectives: As part of the HAPIN (Household Air Pollution Intervention Network) trial, we sought to identify healthcare facilities that were adequately resourced to manage severe pediatric pneumonia in Jalapa, Guatemala (J-GUA); Puno, Peru (P-PER); Kayonza, Rwanda (K-RWA); and Tamil Nadu, India (T-IND). We conducted a facility-based survey of available infrastructure, staff, equipment, and medical consumables. Facilities were georeferenced, and a road network analysis was performed. Measurements and Main Results: Of the 350 healthcare facilities surveyed, 13% had adequate resources to manage severe pneumonia, 37% had pulse oximeters, and 44% had supplemental oxygen. Mean (±SD) travel time to an adequately resourced facility was 41±19 minutes in J-GUA, 99±64 minutes in P-PER, 40±19 minutes in K-RWA, and 31±19 minutes in T-IND. Expanding pulse oximetry coverage to all facilities reduced travel time by 44% in J-GUA, 29% in P-PER, 29% in K-RWA, and 11% in T-IND (all P<0.001). Conclusions: Most healthcare facilities in low-resource settings of the HAPIN study area were inadequately resourced to care for severe pediatric pneumonia. Early identification of cases and timely referral is paramount. The provision of pulse oximeters to all health facilities may be an effective approach to identify cases earlier and refer them for care and in a timely manner.

Objective: Household Air Pollution Intervention Network (HAPIN) investigators tested a complex, non-pharmacological intervention in four low- and middle-income countries as a strategy to mitigate household air pollution and improve health outcomes across the lifespan. Intervention households received a liquefied petroleum gas (LPG) stove, continuous fuel delivery and regular behavioral reinforcements for 18 months, whereas controls were asked to continue with usual cooking practices. While HAPIN was designed as an explanatory trial to test the efficacy of the intervention on four primary outcomes, it introduced several pragmatic aspects in its design and conduct that resemble real-life conditions. We surveyed HAPIN investigators and asked them to rank what aspects of the design and conduct they considered were more pragmatic than explanatory. Methods: We used the revised Pragmatic Explanatory Continuum Indicator Summary (PRECIS-2) to survey investigators on the degree of pragmatism in nine domains of trial design and conduct using a five-point Likert rank scale from very explanatory (1) to very pragmatic (5). We invited 103 investigators. Participants were given educational material on PRECIS-2, including presentations, papers and examples that described the use and implementation of PRECIS-2. Results: Thirty-five investigators (mean age 42 years, 51% female) participated in the survey. Overall, only 17% ranked all domains as very explanatory, with an average (±SD) rank of 3.2 ± 1.4 across domains. Fewer than 20% of investigators ranked eligibility, recruitment or setting as very explanatory. In contrast, ≥50% of investigators ranked the trial organization, delivery and adherence of the intervention and follow-up as very/rather explanatory whereas ≤17% ranked them as rather/very pragmatic. Finally, <25% of investigators ranked the relevance of outcomes to participants and analysis as very/rather explanatory whereas ≥50% ranked then as rather/very pragmatic. In-country partners were more likely to rank domains as pragmatic when compared to investigators working in central coordination (average rank 3.2 vs. 2.8, respectively; Wilcoxon rank-sum p < 0.001). Conclusion: HAPIN investigators did not consider their efficacy trial to be rather/very explanatory and reported that some aspects of the design and conduct were executed under real-world conditions; however, they also did not consider the trial to be overly pragmatic. Our analysis underscores the importance of using standardized tools such as PRECIS-2 to guide early discussions among investigators in the design of environmental health trials attempting to measure efficacy.

BACKGROUND: Ambient fine particulate matter [PM ≤2:5 lm in aerodynamic diameter (PM2:5)] is a major health risk for children, particularly in South Asia, which currently experiences the highest PM2:5 levels globally. Nevertheless, there is comparatively little epidemiological evidence from this region to quantify the effects of PM2:5 on child survival. OBJECTIVES: We estimated the association between PM2:5 exposure and child survival in India. METHODS: We constructed a large, retrospective, and nationally representative cohort of children <5 years of age, born between 2009–2016, from the publicly available, cross-sectional 2015–2016 Demographic Health Surveys in India. In utero and post-delivery lifetime average ambient PM2:5 exposures were estimated with data from satellite remote sensing, meteorology, and land use information (model R2 = 0.82). We used Cox proportional hazards regression to estimate the association between both average in utero and post-delivery lifetime PM2:5 and all-cause child mortality, control-ling for individual-and household-level covariates, seasonality, location, and meteorology. RESULTS: Over 7,447,724 child-months of follow-up, there were 11,559 deaths at <5 years of age reported by the children’s mothers. The mean concentrations of 9-month in utero and post-delivery lifetime average ambient PM2:5 exposure were 71:1 lg=m3 (range: 20:9–153:5 lg=m3) and 73:7 lg=m3 (range: 14:0–247:3 lg=m3), respectively. Estimated child mortality adjusted hazard ratios were 1.023 [95% confidence interval (CI): 1.008, 1.038] and 1.013 (95% CI: 1.001, 1.026) per 10-lg=m3 increase of in utero and post-delivery lifetime PM2:5, with both exposures in the model. DISCUSSION: This study adds to the growing body of evidence about the adverse health effects of PM2:5 by demonstrating the association between ex-posure, both in utero and post-delivery, on child survival at the national level in India. Strategies to reduce ambient air pollution levels, including steps to minimize in utero and early life exposures, are urgently needed in India and other countries where exposures are above recommended guide-line values. https://doi.org/10.1289/EHP8910.

Background: Approximately 3 to 4 billion people worldwide are exposed to household air pollution, which has been associated with increased blood pressure (BP) in pregnant women in some studies. Methods: We recruited 3195 pregnant women in Guatemala, India, Peru, and Rwanda and randomly assigned them to intervention or control groups. The intervention group received a gas stove and fuel during pregnancy, while the controls continued cooking with solid fuels. We measured BP and personal exposure to PM2.5, black carbon and carbon monoxide 3× during gestation. We conducted an intention-to-treat and exposure-response analysis to determine if household air pollution exposure was associated with increased gestational BP. Results: Median 24-hour PM2.5dropped from 84 to 24 μg/m3after the intervention; black carbon and carbon monoxide decreased similarly. Intention-to-treat analyses showed an increase in systolic BP and diastolic BP in both arms during gestation, as expected, but the increase was greater in intervention group for both systolic BP (0.69 mm Hg [0.03-1.35]; P=0.04) and diastolic BP (0.62 mm Hg [0.05-1.19]; P=0.03). The exposure-response analyses suggested that higher exposures to household air pollution were associated with moderately higher systolic BP and diastolic BP; however, none of these associations reached conventional statistical significance. Conclusions: In intention-to-treat, we found higher gestational BP in the intervention group compared with controls, contrary to expected. In exposure-response analyses, we found a slight increase in BP with higher exposure, but it was not statistically significant. Overall, an intervention with gas stoves did not markedly affect gestational BP.

The Household Air Pollution Intervention Network trial is a multi-country study on the effects of a liquefied petroleum gas (LPG) stove and fuel distribution intervention on women's and children's health. There is limited data on exposure reductions achieved by switching from solid to clean cooking fuels in rural settings across multiple countries. As formative research in 2017, we recruited pregnant women and characterized the impact of the intervention on personal exposures and kitchen levels of fine particulate matter (PM2.5) in Guatemala, India, and Rwanda. Forty pregnant women were enrolled in each site. We measured cooking area concentrations of and personal exposures to PM2.5 for 24 or 48 h using gravimetric-based PM2.5 samplers at baseline and two follow-ups over two months after delivery of an LPG cookstove and free fuel supply. Mixed models were used to estimate PM2.5 reductions. Median kitchen PM2.5 concentrations were 296 μg/m3 at baseline (interquartile range, IQR: 158–507), 24 μg/m3 at first follow-up (IQR: 18–37), and 23 μg/m3 at second follow-up (IQR: 14–37). Median personal exposures to PM2.5 were 134 μg/m3 at baseline (IQR: 71–224), 35 μg/m3 at first follow-up (IQR: 23–51), and 32 μg/m3 at second follow-up (IQR: 23–47). Overall, the LPG intervention was associated with a 92% (95% confidence interval (CI): 90–94%) reduction in kitchen PM2.5 concentrations and a 74% (95% CI: 70–79%) reduction in personal PM2.5 exposures. Results were similar for each site. Conclusions: The intervention was associated with substantial reductions in kitchen and personal PM2.5 overall and in all sites. Results suggest LPG interventions in these rural settings may lower exposures to the WHO annual interim target-1 of 35 μg/m3. The range of exposure contrasts falls on steep sections of estimated exposure-response curves for birthweight, blood pressure, and acute lower respiratory infections, implying potentially important health benefits when transitioning from solid fuels to LPG.

Background: Clean cookstove interventions can theoretically reduce exposure to household air pollution and benefit health, but this requires near-exclusive use of these types of stoves with the simultaneous disuse of traditional stoves. Previous cookstove trials have reported low adoption of new stoves and/or extensive continued traditional stove use. Methods: The Household Air Pollution Intervention Network (HAPIN) trial randomized 3195 pregnant women in Guatemala, India, Peru, and Rwanda to either a liquefied petroleum gas (LPG) stove and fuel intervention (n = 1590) or to a control (n = 1605). The intervention consisted of an LPG stove and two initial cylinders of LPG, free fuel refills delivered to the home, and regular behavioral messaging. We assessed intervention fidelity (delivery of the intervention as intended) and adherence (intervention use) through to the end of gestation, as relevant to the first primary health outcome of the trial: infant birth weight. Fidelity and adherence were evaluated using stove and fuel delivery records, questionnaires, visual observations, and temperature-logging stove use monitors (SUMs). Results: 1585 women received the intervention at a median (interquartile range) of 8.0 (5.0–15.0) days post-randomization and had a gestational age of 17.9 (15.4–20.6) weeks. Over 96% reported cooking exclusively with LPG at two follow-up visits during pregnancy. Less than 4% reported ever running out of LPG. Complete abandonment of traditional stove cooking was observed in over 67% of the intervention households. Of the intervention households, 31.4% removed their traditional stoves upon receipt of the intervention; among those who retained traditional stoves, the majority did not use them: traditional stove use was detected via SUMs on a median (interquartile range) of 0.0% (0.0%, 1.6%) of follow-up days (median follow-up = 134 days). Conclusions: The fidelity of the HAPIN intervention, as measured by stove installation, timely ongoing fuel deliveries, and behavioral reinforcement as needed, was high. Exclusive use of the intervention during pregnancy was also high.

Objectives Despite global efforts to increase facility-based delivery (FBD), 90% of women in rural Ethiopia deliver at home without a skilled birth attendant. Men have an important role in increasing FBD due to their decision-making power, but this is largely unexplored. This study aimed to determine the FBD care attributes preferred by women and men, and whether poverty or household decision-making are associated with choice to deliver in a facility. Setting and participants We conducted a cross-sectional discrete choice experiment in 109 randomly selected households in rural Ethiopia in September-October 2015. We interviewed women who were pregnant or who had a child < 2 years old and their male partners. Results Both women and men preferred health facilities where medications and supplies were available (OR=3.08; 95% CI 2.03 to 4.67 and OR=2.68; 95% CI 1.79 to 4.02, respectively), a support person was allowed in the delivery room (OR=1.69; 95% CI 1.37 to 2.07 and OR=1.74; 95% CI 1.42 to 2.14, respectively) and delivery cost was low (OR=1.15 95% CI 1.12 to 1.18 and OR=1.14; 95% CI 1.11 to 1.17, respectively). Women valued free ambulance service (OR=1.37; 95% CI 1.09 to 1.70), while men favoured nearby facilities (OR=1.09; 95% CI 1.06 to 1.13) with friendly providers (OR=1.30; 95% CI 1.03 to 1.64). Provider preferences were complex. Neither women nor men preferred female doctors to health extension workers (HEW) (OR=0.92; 95% CI 0.59 to 1.42 and OR=0.74; 95% CI 0.47 to 1.14, respectively), male doctors to HEW (OR=1.33; 95% CI 0.89 to 1.99 and OR=0.75; 95% CI 0.50 to 1.12, respectively) or female over male nurses (OR=0.68; 95% CI 0.94 to 1.71 and OR=1.03; 95% CI 0.77 to 2.94, respectively). While both women and men preferred male nurses to HEW (OR=1.86; 95% CI 1.23 to 2.80 and OR=1.95; 95% CI 1.30 to 2.95, respectively), men (OR=1.89; 95% CI 1.29 to 2.78), but not women (OR=1.47; 95% CI 1.00 to 2.13) preferred HEW to female nurses. Both women and men preferred female doctors to male nurses (OR=1.71; 95% CI 1.27 to 2.29 and OR=1.44; 95% CI 1.07 to 1.92, respectively), male doctors to female nurses (OR=1.95; 95% CI 1.44 to 2.62 and OR=1.41; 95% CI 1.05 to 1.90, respectively) and male doctors to male nurses (OR=2.47; 95% CI 1.84 to 3.32 and OR=1.46; 95% CI 1.09 to 1.95, respectively), while only women preferred male doctors to female doctors (OR=1.45; 95% CI 1.09 to 1.93 and OR=1.01; 95% CI 0.76 to 1.35, respectively) and only men preferred female nurses to female doctors (OR=1.34; 95% CI 0.98 to 1.84 and OR=1.39; 95% CI 1.02 to 1.89, respectively). Men were disproportionately involved in making household decisions (X 2 (1, n=216)=72.18, p < 0.001), including decisions to seek healthcare (X 2 (1, n=216)=55.39, p < 0.001), yet men were often unaware of their partners' prenatal care attendance (X 2 (1, n=215)=82.59, p < 0.001). Conclusion Women's and men's preferences may influence delivery service choices. Considering these choices is one way the Ethiopian government and health facilities may encourage FBD in rural areas.