Household Air Pollution and Health: A Multi-country LPG Intervention Trial

Infant, Low Birth Weight Clinical Trial

— HAPIN  

Official title:

Household Air Pollution and Health: A Multi-country LPG Intervention Trial

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02944682
• Other study ID #: IRB00089799
• Secondary ID: 1UM1HL134590-01
• Status: Active, not recruiting
• Phase: N/A
• Start date: September 1, 2017
• Est. completion date: June 30, 2026

Study information

• Verified date: March 2024
• Source: Emory University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is a randomized controlled trial of liquefied petroleum gas (LPG) stove and fuel distribution in 3,200 households in four countries (India, Guatemala, Peru, and Rwanda). Following a common protocol, each intervention site will recruit 800 pregnant women (aged 18-34 years, 9 - <20 weeks gestation), and will randomly assign half their households to receive LPG stoves and an 18-month supply of LPG. Control households are anticipated to continue to cook primarily with solid biomass fuels, and will receive compensation based on a uniform set of trial-wide principles, customized to each site based on formative research. The mother will be followed along with her child until the child is 1 year old. The researchers estimate that 15% of households will have a second, non-pregnant older adult woman (aged 40 to <80 years) who will also be enrolled at baseline and followed during the 18-month follow-up period. To optimize intervention use, the researchers will implement behavior change strategies informed by previous experiences and formative research in Year 1. This study will assess cookstove use, conduct repeated personal exposure assessments of household air pollution, and collect dried blood spots and urinary samples for biomarker analysis and biospecimen storage. The primary outcomes are low birth weight, severe pneumonia incidence, and stunting of the child, and blood pressure in the older adult woman. Secondary outcomes include preterm birth and development in the child, maternal blood pressure during pregnancy, and endothelial function, respiratory impairment, atherosclerosis, carcinogenic metabolites, and quality of life in the older adult woman. Participants in India, Guatemala and Rwanda will be followed until the child is 5 years old to assess the longer-term effects of the intervention.

Description:

Globally, nearly 3 billion people rely on solid fuels for cooking and heating, the vast majority in low- and middle-income countries (LMICs). The resulting household air pollution (HAP) is the third leading risk factor in the 2010 global burden of disease, accounting for an estimated 4.3 million deaths annually, largely among women and young children. Previous interventions have provided cleaner biomass-based cookstoves, but have failed to reduce exposure to levels that produce meaningful health improvements. There have been no large-scale field trials with liquefied petroleum gas (LPG) cookstoves, likely the cleanest scalable intervention. The aim of this study is to conduct a randomized controlled trial of LPG stove and fuel distribution in 3,200 households in four LMICs (India, Guatemala, Peru, and Rwanda) to deliver rigorous evidence regarding potential health benefits across the lifespan. Each intervention site will recruit 800 pregnant women (aged 18-34 years, 9 - <20 weeks gestation), and will randomly assign half their households to receive LPG stoves and an 18-month supply of LPG. Control households are anticipated to continue to cook primarily with solid biomass fuels, and will receive compensation based on a uniform set of trial-wide principles, customized to each site based on formative research. The mother will be followed along with her child until the child is 1 year old. In households with a second, non-pregnant older adult woman (aged 40 to <80 years) the researchers will also enroll and follow her during the 18-month follow-up period in order to assess cardiopulmonary, metabolic, and cancer outcomes. To optimize intervention use, the researchers will implement behavior change strategies. This study will assess cookstove use, conduct repeated personal exposure assessments to HAP (PM2.5, black carbon, carbon monoxide), and collect dried blood spots and urinary samples for biomarker analysis and biospecimen storage on all participants at multiple time points. The primary outcomes are low birth weight, severe pneumonia incidence, and stunting of the child, and blood pressure in the older adult woman. Secondary outcomes include preterm birth and development in the child, maternal blood pressure during pregnancy, and endothelial function, respiratory impairment, atherosclerosis, carcinogenic metabolites, and quality of life in the older adult woman. This study will address the following specific aims: (1) using an intent-to-treat analysis, determine the effect of a randomized LPG stove and fuel intervention on health in four diverse LMIC populations using a common protocol; (2) determine the exposure-response relationships for HAP and health outcomes; and (3) determine relationships between LPG intervention and both targeted and exploratory biomarkers of exposure/health effects. This study will provide evidence, including costs and implementation strategies, to inform national and global policies on scaling up LPG stoves among vulnerable populations. Ultimately, this will facilitate deeper policy-level discussions as well as identify requirements for initiating and sustaining HAP interventions globally. The intervention delivery occurred until the child was one year of age. The researchers will continue to follow participants in India, Guatemala and Rwanda until the child is 5 years old to assess the longer-term effects of the intervention. Previous evidence suggests that the benefits of reduced exposure during the first, critical year of development will continue even if the intervention ends. The researchers will continue using methods employed during the HAPIN trial period. The HAPIN trial provides a unique context in which to address these questions, particularly given the successful intervention and exposure reduction. Participants are well-characterized and health and exposures to air pollution are being documented. Critically, because of its experimental design of the trial, continued follow-up of the cohort will provide rigorous causal inferences about the effects of this 500-day intervention over the most important period of early childhood development.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 3640
• Est. completion date: June 30, 2026
• Est. primary completion date: June 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 79 Years

Eligibility

Inclusion Criteria for Pregnant Women:

• Confirmed pregnancy (hCG positive blood or urine test)
• Aged 18 to <35 years (via self-report)
• Uses biomass stove predominantly
• Lives in study area
• 9 - <20 weeks gestation confirmed by ultrasound
• Singleton pregnancy (one fetus)
• Viable fetus with normal fetal heart rate (120-180 beats per minute) at time of ultrasound
• Continued pregnancy at the time of randomization confirmed by self-report
• Agrees to participate with informed consent

Exclusion Criteria for Pregnant Women:

• Currently smokes cigarettes or other tobacco products
• Plans to move permanently outside study area in the next 12 months
• Uses LPG stove predominantly, or is likely to use LPG predominantly in the near future

Inclusion Criteria for Older Adult Woman in the Same Household:

• Aged 40 to <80 years (via self-report)

Exclusion Criteria for Older Adult Woman in the Same Household:

• Currently smokes cigarettes or other tobacco products
• Pregnant (by self-report)
• Plans to move out of her current household in the next 12 months

Related Conditions & MeSH terms

• Birth Weight
• Infant, Low Birth Weight

Intervention

Other:
• Liquefied petroleum gas (LPG) cookstove
The intervention consists of a high-quality locally-available liquefied petroleum gas (LPG) stove having at least two burners, a continuous supply of LPG fuel for 18 months, and the promotion of stove use on an exclusive basis for cooking. The intervention will be provided free of charge to all intervention households upon enrollment. On a weekly basis, study staff will examine stove condition, perform any repairs necessary, and measure and record weight of LPG tanks in order to anticipate need for refills.

Locations

Country	Name	City	State
Guatemala	Universidad del Valle de Guatemala	Guatemala
India	Sri Ramachandra Institute of Higher Education and Research	Chennai	Tamil Nadu
Peru	Puno Global Non-Communicable Disease Research Site, School of Medicine, Johns Hopkins University	Puno
Rwanda	Rwanda Research Site, London School of Hygiene and Tropical Medicine	Kigali

Sponsors (19)

Lead Sponsor

Collaborator

Emory University

Asociacion Benefica Prisma, Berkeley Air Monitoring Group, Bill and Melinda Gates Foundation, Colorado State University, Eagle Research Center, Global LPG Partnership, Harvard University, Johns Hopkins University, London School of Hygiene and Tropical Medicine, National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Sri Ramachandra University, Universidad del Valle, Guatemala, Universidad Peruana Cayetano Heredia, University of Georgia, University of Oxford, University of Rwanda, Washington University School of Medicine

Countries where clinical trial is conducted

Guatemala,  India,  Peru,  Rwanda, 

References & Publications (40)

Balakrishnan K, Steenland K, Clasen T, Chang H, Johnson M, Pillarisetti A, Ye W, Naeher LP, Diaz-Artiga A, McCracken JP, Thompson LM, Rosa G, Kirby MA, Thangavel G, Sambandam S, Mukhopadhyay K, Puttaswamy N, Aravindalochanan V, Garg S, Ndagijimana F, Hart — View Citation

Barr DB, Puttaswamy N, Jaacks LM, Steenland K, Rajkumar S, Gupton S, Ryan PB, Balakrishnan K, Peel JL, Checkley W, Clasen T, Clark ML; (HAPIN Investigative Team). Design and Rationale of the Biomarker Center of the Household Air Pollution Intervention Network (HAPIN) Trial. Environ Health Perspect. 2020 Apr;128(4):47010. doi: 10.1289/EHP5751. Epub 2020 Apr 29. — View Citation

Burrowes VJ, Piedrahita R, Pillarisetti A, Underhill LJ, Fandino-Del-Rio M, Johnson M, Kephart JL, Hartinger SM, Steenland K, Naeher L, Kearns K, Peel JL, Clark ML, Checkley W; HAPIN Investigators. Comparison of next-generation portable pollution monitors to measure exposure to PM2.5 from household air pollution in Puno, Peru. Indoor Air. 2020 May;30(3):445-458. doi: 10.1111/ina.12638. Epub 2020 Jan 23. — View Citation

Checkley W, Hossen S, Rosa G, Thompson LM, McCracken JP, Diaz-Artiga A, Balakrishnan K, Simkovich SM, Underhill LJ, Nicolaou L, Hartinger SM, Davila-Roman VG, Kirby MA, Clasen TF, Rosenthal J, Peel JL, On Behalf Of Household Air Pollution Intervention Network Hapin Investigators. Facing the Realities of Pragmatic Design Choices in Environmental Health Studies: Experiences from the Household Air Pollution Intervention Network Trial. Int J Environ Res Public Health. 2022 Mar 23;19(7):3790. doi: 10.3390/ijerph19073790. — View Citation

Checkley W, Thompson LM, Sinharoy SS, Hossen S, Moulton LH, Chang HH, Waller L, Steenland K, Rosa G, Mukeshimana A, Ndagijimana F, McCracken JP, Diaz-Artiga A, Balakrishnan K, Garg SS, Thangavel G, Aravindalochanan V, Hartinger SM, Chiang M, Kirby MA, Pap — View Citation

Clasen T, Checkley W, Peel JL, Balakrishnan K, McCracken JP, Rosa G, Thompson LM, Barr DB, Clark ML, Johnson MA, Waller LA, Jaacks LM, Steenland K, Miranda JJ, Chang HH, Kim DY, McCollum ED, Davila-Roman VG, Papageorghiou A, Rosenthal JP; HAPIN Investigators. Design and Rationale of the HAPIN Study: A Multicountry Randomized Controlled Trial to Assess the Effect of Liquefied Petroleum Gas Stove and Continuous Fuel Distribution. Environ Health Perspect. 2020 Apr;128(4):47008. doi: 10.1289/EHP6407. Epub 2020 Apr 29. — View Citation

Clasen TF, Chang HH, Thompson LM, Kirby MA, Balakrishnan K, Diaz-Artiga A, McCracken JP, Rosa G, Steenland K, Younger A, Aravindalochanan V, Barr DB, Castanaza A, Chen Y, Chiang M, Clark ML, Garg S, Hartinger S, Jabbarzadeh S, Johnson MA, Kim DY, Lovvorn — View Citation

Crocker ME, Hossen S, Goodman D, Simkovich SM, Kirby M, Thompson LM, Rosa G, Garg SS, Thangavel G, McCollum ED, Peel J, Clasen T, Checkley W; HAPIN Investigators. Effects of high altitude on respiratory rate and oxygen saturation reference values in healthy infants and children younger than 2 years in four countries: a cross-sectional study. Lancet Glob Health. 2020 Mar;8(3):e362-e373. doi: 10.1016/S2214-109X(19)30543-1. — View Citation

Davila-Roman VG, Toenjes AK, Meyers RM, Lenzen PM, Simkovich SM, Herrera P, Fung E, Papageorghiou AT, Craik R, McCracken JP, Thompson LM, Balakrishnan K, Rosa G, Peel J, Clasen TF, Hossen S, Checkley W, Fuentes LL; HAPIN Investigators. Ultrasound Core Laboratory for the Household Air Pollution Intervention Network Trial: Standardized Training and Image Management for Field Studies Using Portable Ultrasound in Fetal, Lung, and Vascular Evaluations. Ultrasound Med Biol. 2021 Jun;47(6):1506-1513. doi: 10.1016/j.ultrasmedbio.2021.02.015. Epub 2021 Apr 1. — View Citation

Goodman D, Crocker ME, Pervaiz F, McCollum ED, Steenland K, Simkovich SM, Miele CH, Hammitt LL, Herrera P, Zar HJ, Campbell H, Lanata CF, McCracken JP, Thompson LM, Rosa G, Kirby MA, Garg S, Thangavel G, Thanasekaraan V, Balakrishnan K, King C, Clasen T, Checkley W; HAPIN Investigators. Challenges in the diagnosis of paediatric pneumonia in intervention field trials: recommendations from a pneumonia field trial working group. Lancet Respir Med. 2019 Dec;7(12):1068-1083. doi: 10.1016/S2213-2600(19)30249-8. Epub 2019 Oct 4. — View Citation

Hengstermann M, Diaz-Artiga A, Otzoy-Sucuc R, Laura Maria Ruiz-Aguilar A, Thompson LM; HAPIN Investigators. Developing Visual Messages to Support Liquefied Petroleum Gas Use in Intervention Homes in the Household Air Pollution Intervention Network (HAPIN) Trial in Rural Guatemala. Health Educ Behav. 2021 Oct;48(5):651-669. doi: 10.1177/1090198121996280. Epub 2021 Mar 18. — View Citation

Hennessee I, Kirby MA, Misago X, Mupfasoni J, Clasen T, Kitron U, Rosenthal JP, Hakizimana E. Assessing the Effects of Cooking Fuels on Anopheles Mosquito Behavior: An Experimental Study in Rural Rwanda. Am J Trop Med Hyg. 2022 Feb 21;106(4):1196-1208. doi: 10.4269/ajtmh.21-0997. Print 2022 Apr 6. — View Citation

Iribagiza C, Sharpe T, Coyle J, Nkubito P, Piedrahita R, Johnson M, Thomas EA. Evaluating the Effects of Access to Air Quality Data on Household Air Pollution and Exposure-An Interrupted Time Series Experimental Study in Rwanda. Sustainability 2021; 13 (20): 11523. doi:10.3390/su132011523.

Iribagiza C, Sharpe T, Wilson D, Thomas EA. User-centered design of an air quality feedback technology to promote adoption of clean cookstoves. J Expo Sci Environ Epidemiol. 2020 Nov;30(6):925-936. doi: 10.1038/s41370-020-0250-2. Epub 2020 Jul 16. — View Citation

Johnson M, Pillarisetti A, Piedrahita R, Balakrishnan K, Peel JL, Steenland K, Underhill LJ, Rosa G, Kirby MA, Diaz-Artiga A, McCracken J, Clark ML, Waller L, Chang HH, Wang J, Dusabimana E, Ndagijimana F, Sambandam S, Mukhopadhyay K, Kearns KA, Campbell D, Kremer J, Rosenthal JP, Checkley W, Clasen T, Naeher L; the Household Air Pollution Intervention Network (HAPIN) Trial Investigators. Exposure Contrasts of Pregnant Women during the Household Air Pollution Intervention Network Randomized Controlled Trial. Environ Health Perspect. 2022 Sep;130(9):97005. doi: 10.1289/EHP10295. Epub 2022 Sep 16. — View Citation

Johnson MA, Steenland K, Piedrahita R, Clark ML, Pillarisetti A, Balakrishnan K, Peel JL, Naeher LP, Liao J, Wilson D, Sarnat J, Underhill LJ, Burrowes V, McCracken JP, Rosa G, Rosenthal J, Sambandam S, de Leon O, Kirby MA, Kearns K, Checkley W, Clasen T; HAPIN Investigators. Air Pollutant Exposure and Stove Use Assessment Methods for the Household Air Pollution Intervention Network (HAPIN) Trial. Environ Health Perspect. 2020 Apr;128(4):47009. doi: 10.1289/EHP6422. Epub 2020 Apr 29. — View Citation

Kaufman JD. Invited Perspective: A Critical Part of a Real-World Environmental Health Trial Is to Demonstrate That the Intervention Reduced Exposure. Environ Health Perspect. 2022 Sep;130(9):91304. doi: 10.1289/EHP11697. Epub 2022 Sep 16. No abstract available. — View Citation

Kearns KA, Naeher LP, McCracken JP, Boyd Barr D, Saikawa E, Hengstermann M, Mollinedo E, Panuwet P, Yakimavets V, Lee GE, Thompson LM. Estimating personal exposures to household air pollution and plastic garbage burning among adolescent girls in Jalapa, Guatemala. Chemosphere. 2024 Jan;348:140705. doi: 10.1016/j.chemosphere.2023.140705. Epub 2023 Nov 17. — View Citation

Liao J, Kirby MA, Pillarisetti A, Piedrahita R, Balakrishnan K, Sambandam S, Mukhopadhyay K, Ye W, Rosa G, Majorin F, Dusabimana E, Ndagijimana F, McCracken JP, Mollinedo E, de Leon O, Diaz-Artiga A, Thompson LM, Kearns KA, Naeher L, Rosenthal J, Clark ML, Steenland K, Waller LA, Checkley W, Peel JL, Clasen T, Johnson M; HAPIN Investigators. LPG stove and fuel intervention among pregnant women reduce fine particle air pollution exposures in three countries: Pilot results from the HAPIN trial. Environ Pollut. 2021 Dec 15;291:118198. doi: 10.1016/j.envpol.2021.118198. Epub 2021 Sep 21. — View Citation

Liao J, McCracken JP, Piedrahita R, Thompson L, Mollinedo E, Canuz E, De Leon O, Diaz-Artiga A, Johnson M, Clark M, Pillarisetti A, Kearns K, Naeher L, Steenland K, Checkley W, Peel J, Clasen TF; HAPIN investigators. The use of bluetooth low energy Beacon systems to estimate indirect personal exposure to household air pollution. J Expo Sci Environ Epidemiol. 2020 Nov;30(6):990-1000. doi: 10.1038/s41370-019-0172-z. Epub 2019 Sep 26. Erratum In: J Expo Sci Environ Epidemiol. 2020 May;30(3):587. — View Citation

McCollum ED, McCracken JP, Kirby MA, Grajeda LM, Hossen S, Moulton LH, Simkovich SM, Goodman-Palmer D, Rosa G, Mukeshimana A, Balakrishnan K, Thangavel G, Garg SS, Castanaza A, Thompson LM, Diaz-Artiga A, Papageorghiou AT, Davila-Roman VG, Underhill LJ, H — View Citation

Nicolaou L, Underhill L, Hossen S, Simkovich S, Thangavel G, Rosa G, McCracken JP, Davila-Roman V, Fuentes LL, Quinn AK, Clark M, Diaz A, Pillarisetti A, Steenland K, Waller LA, Jabbarzadeh S, Peel JL, Checkley W; HAPIN Investigators. Cross-sectional analysis of the association between personal exposure to household air pollution and blood pressure in adult women: Evidence from the multi-country Household Air Pollution Intervention Network (HAPIN) trial. Environ Res. 2022 Nov;214(Pt 4):114121. doi: 10.1016/j.envres.2022.114121. Epub 2022 Aug 24. — View Citation

Pillarisetti A, Ye W, Balakrishnan K, Rosa G, Diaz-Artiga A, Underhill LJ, Steenland K, Peel JL, Kirby MA, McCracken J, Waller L, Chang H, Wang J, Dusabimana E, Ndagijimana F, Sambandam S, Mukhopadhyay K, Kearns KA, Campbell D, Kremer J, Rosenthal J, Ghosh A, Clark M, Checkley W, Clasen T, Naeher L, Piedrahita R, Johnson M. Post-birth exposure contrasts for children during the Household Air Pollution Intervention Network randomized controlled trial. medRxiv [Preprint]. 2023 Jul 6:2023.07.04.23292226. doi: 10.1101/2023.07.04.23292226. — View Citation

Puttaswamy N, Saidam S, Rajendran G, Arumugam K, Gupton S, Williams EW, Johnson CL, Panuwet P, Rajkumar S, Clark ML, Peel JL, Checkley W, Clasen T, Balakrishnan K, Barr DB. Cross-validation of biomonitoring methods for polycyclic aromatic hydrocarbon metabolites in human urine: Results from the formative phase of the Household Air Pollution Intervention Network (HAPIN) trial in India. J Chromatogr B Analyt Technol Biomed Life Sci. 2020 Oct 1;1154:122284. doi: 10.1016/j.jchromb.2020.122284. Epub 2020 Jul 29. — View Citation

Quinn AK, Williams K, Thompson LM, Rosa G, Diaz-Artiga A, Thangavel G, Balakrishnan K, Miranda JJ, Rosenthal JP, Clasen TF, Harvey SA; HAPIN Investigators. Compensating control participants when the intervention is of significant value: experience in Guatemala, India, Peru and Rwanda. BMJ Glob Health. 2019 Aug 21;4(4):e001567. doi: 10.1136/bmjgh-2019-001567. eCollection 2019. — View Citation

Quinn AK, Williams KN, Thompson LM, Harvey SA, Piedrahita R, Wang J, Quinn C, Pillarisetti A, McCracken JP, Rosenthal JP, Kirby MA, Diaz Artiga A, Thangavel G, Rosa G, Miranda JJ, Checkley W, Peel JL, Clasen TF. Fidelity and Adherence to a Liquefied Petroleum Gas Stove and Fuel Intervention during Gestation: The Multi-Country Household Air Pollution Intervention Network (HAPIN) Randomized Controlled Trial. Int J Environ Res Public Health. 2021 Nov 29;18(23):12592. doi: 10.3390/ijerph182312592. — View Citation

Rajamani KD, Sambandam S, Mukhopadhyay K, Puttaswamy N, Thangavel G, Natesan D, Ramasamy R, Sendhil S, Natarajan A, Aravindalochan V, Pillarisetti A, Johnson M, Rosenthal J, Steenland K, Piedhrahita R, Peel J, Clark ML, Boyd Barr D, Rajkumar S, Young B, Jabbarzadeh S, Rosa G, Kirby M, Underhill LJ, Diaz-Artiga A, Lovvorn A, Checkley W, Clasen T, Balakrishnan K. Visualizing Field Data Collection Procedures of Exposure and Biomarker Assessments for the Household Air Pollution Intervention Network Trial in India. J Vis Exp. 2022 Dec 23;(190). doi: 10.3791/64144. — View Citation

Sambandam S, Mukhopadhyay K, Sendhil S, Ye W, Pillarisetti A, Thangavel G, Natesan D, Ramasamy R, Natarajan A, Aravindalochanan V, Vinayagamoorthi A, Sivavadivel S, Uma Maheswari R, Balakrishnan L, Gayatri S, Nargunanathan S, Madhavan S, Puttaswamy N, Garg SS, Quinn A, Rosenthal J, Johnson M, Liao J, Steenland K, Piedhrahita R, Peel J, Checkley W, Clasen T, Balakrishnan K. Exposure contrasts associated with a liquefied petroleum gas (LPG) intervention at potential field sites for the multi-country household air pollution intervention network (HAPIN) trial in India: results from pilot phase activities in rural Tamil Nadu. BMC Public Health. 2020 Nov 26;20(1):1799. doi: 10.1186/s12889-020-09865-1. — View Citation

Simkovich SM, Hossen S, McCollum ED, Toenjes AK, McCracken JP, Thompson LM, Castanaza A, Diaz A, Rosa G, Kirby MA, Mukeshimana A, Myers R, Lenzen PM, Craik R, Jabbarzadeh S, Elon L, Garg SS, Balakrishnan K, Thangavel G, Peel JL, Clasen TF, Davila-Roman VG, Papageorghiou AT, de Las Fuentes L, Checkley W; HAPIN Investigators. Lung Ultrasound Protocol and Quality Control of Image Interpretation Using an Adjudication Panel in the Household Air Pollution Intervention Network (HAPIN) Trial. Ultrasound Med Biol. 2023 May;49(5):1194-1201. doi: 10.1016/j.ultrasmedbio.2023.01.005. Epub 2023 Feb 19. — View Citation

Simkovich SM, Thompson LM, Clark ML, Balakrishnan K, Bussalleu A, Checkley W, Clasen T, Davila-Roman VG, Diaz-Artiga A, Dusabimana E, Fuentes LL, Harvey S, Kirby MA, Lovvorn A, McCollum ED, Mollinedo EE, Peel JL, Quinn A, Rosa G, Underhill LJ, Williams KN, Young BN, Rosenthal J; HAPIN Investigators. A risk assessment tool for resumption of research activities during the COVID-19 pandemic for field trials in low resource settings. BMC Med Res Methodol. 2021 Apr 12;21(1):68. doi: 10.1186/s12874-021-01232-x. — View Citation

Simkovich SM, Underhill LJ, Kirby MA, Crocker ME, Goodman D, McCracken JP, Thompson LM, Diaz-Artiga A, Castanaza-Gonzalez A, Garg SS, Balakrishnan K, Thangavel G, Rosa G, Peel JL, Clasen TF, McCollum ED, Checkley W; HAPIN Investigators. Resources and Geographic Access to Care for Severe Pediatric Pneumonia in Four Resource-limited Settings. Am J Respir Crit Care Med. 2022 Jan 15;205(2):183-197. doi: 10.1164/rccm.202104-1013OC. — View Citation

Simkovich SM, Underhill LJ, Kirby MA, Goodman D, Crocker ME, Hossen S, McCracken JP, de Leon O, Thompson LM, Garg SS, Balakrishnan K, Thangavel G, Rosa G, Peel JL, Clasen TF, McCollum ED, Checkley W. Design and conduct of facility-based surveillance for severe childhood pneumonia in the Household Air Pollution Intervention Network (HAPIN) trial. ERJ Open Res. 2020 Mar 23;6(1):00308-2019. doi: 10.1183/23120541.00308-2019. eCollection 2020 Jan. — View Citation

Steenland K, Pillarisetti A, Kirby M, Peel J, Clark M, Checkley W, Chang HH, Clasen T. Modeling the potential health benefits of lower household air pollution after a hypothetical liquified petroleum gas (LPG) cookstove intervention. Environ Int. 2018 Feb;111:71-79. doi: 10.1016/j.envint.2017.11.018. Epub 2017 Nov 26. — View Citation

Williams KN, Quinn A, North H, Wang J, Pillarisetti A, Thompson LM, Diaz-Artiga A, Balakrishnan K, Thangavel G, Rosa G, Ndagijimana F, Underhill LJ, Kirby MA, Puzzolo E, Hossen S, Waller LA, Peel JL, Rosenthal JP, Clasen TF, Harvey SA, Checkley W; HAPIN Investigators. Fidelity and adherence to a liquefied petroleum gas stove and fuel intervention: The multi-country Household Air Pollution Intervention Network (HAPIN) trial. Environ Int. 2023 Sep;179:108160. doi: 10.1016/j.envint.2023.108160. Epub 2023 Aug 19. — View Citation

Williams KN, Thompson LM, Sakas Z, Hengstermann M, Quinn A, Diaz-Artiga A, Thangavel G, Puzzolo E, Rosa G, Balakrishnan K, Peel J, Checkley W, Clasen TF, Miranda JJ, Rosenthal JP, Harvey SA; Household Air Pollution Intervention Network (HAPIN) trial Investigators; HAPIN Investigators. Designing a comprehensive behaviour change intervention to promote and monitor exclusive use of liquefied petroleum gas stoves for the Household Air Pollution Intervention Network (HAPIN) trial. BMJ Open. 2020 Sep 29;10(9):e037761. doi: 10.1136/bmjopen-2020-037761. — View Citation

Wilson DL, Williams KN, Pillarisetti A. 2020. An Integrated Sensor Data Logging, Survey, and Analytics Platform for Field Research and Its Application in HAPIN, a Multi-Center Household Energy Intervention Trial. Sustainability. 2020; 12 (5): 1805. doi:10.3390/su12051805.

Ye W, Steenland K, Quinn A, Liao J, Balakrishnan K, Rosa G, Ndagijimana F, Ntivuguruzwa JD, Thompson LM, McCracken JP, Diaz-Artiga A, Rosenthal JP, Papageorghiou A, Davila-Roman VG, Pillarisetti A, Johnson M, Wang J, Nicolaou L, Checkley W, Peel JL, Clasen TF; Household Air Pollution Intervention Network (HAPIN) trial Investigators. Effects of a Liquefied Petroleum Gas Stove Intervention on Gestational Blood Pressure: Intention-to-Treat and Exposure-Response Findings From the HAPIN Trial. Hypertension. 2022 Aug;79(8):1887-1898. doi: 10.1161/HYPERTENSIONAHA.122.19362. Epub 2022 Jun 16. — View Citation

Ye W, Thangavel G, Pillarisetti A, Steenland K, Peel JL, Balakrishnan K, Jabbarzadeh S, Checkley W, Clasen T; HAPIN Investigators. Association between personal exposure to household air pollution and gestational blood pressure among women using solid cooking fuels in rural Tamil Nadu, India. Environ Res. 2022 May 15;208:112756. doi: 10.1016/j.envres.2022.112756. Epub 2022 Jan 20. — View Citation

Younger A, Alkon A, Harknett K, Kirby MA, Elon L, Lovvorn AE, Wang J, Ye W, Diaz-Artiga A, McCracken JP, Castanaza Gonzalez A, Monroy Alarcon L, Mukeshimana A, Rosa G, Chiang M, Balakrishnan K, Garg SS, Pillarisetti A, Piedrahita R, Johnson M, Craik R, Papageorghiou AT, Toenjes A, Quinn A, Williams KN, Underhill L, Chang HH, Naeher LP, Rosenthal J, Checkley W, Peel JL, Clasen TF, Thompson LM; HAPIN investigators. Effects of a LPG stove and fuel intervention on adverse maternal outcomes: A multi-country randomized controlled trial conducted by the Household Air Pollution Intervention Network (HAPIN). Environ Int. 2023 Aug;178:108059. doi: 10.1016/j.envint.2023.108059. Epub 2023 Jun 28. — View Citation

Younger A, Ye W, Alkon A, Harknett K, Kirby MA, Elon L, Lovvorn AE, Wang J, Diaz-Artiga A, McCracken JP, Castanaza Gonzalez A, Alarcon LM, Mukeshimana A, Rosa G, Chiang M, Balakrishnan K, Garg SS, Pillarisetti A, Piedrahita R, Johnson MA, Craik R, Papageorghiou AT, Toenjes A, Williams KN, Underhill LJ, Hartinger SM, Nicolaou L, Chang HH, Naeher LP, Rosenthal J, Checkley W, Peel JL, Clasen TF, Thompson LM; Household Air Pollution Intervention Network (HAPIN) Investigators. Effects of a liquefied petroleum gas stove intervention on stillbirth, congenital anomalies and neonatal mortality: A multi-country household air pollution intervention network trial. Environ Pollut. 2024 Mar 15;345:123414. doi: 10.1016/j.envpol.2024.123414. Epub 2024 Jan 27. — View Citation

* Note: There are 40 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in fine particulate matter (PM2.5) exposure	Personal monitoring equipment will be used to assess exposure to fine particulate matter (PM2.5) over a 24-hour period in intervention and control participants (pregnant women, older adult women, and children). Exposure for pregnant women will be measured at baseline, 24-28 weeks gestation, 32-36 weeks gestation, and 24 months after delivery. Exposure in the child will be measured at 3, 6, 12, 24, 36, 48 and 60 months of age. Exposure in the older adult women will be measured at baseline, 3, 6, 12 and 18 months post-randomization, and at 24 months after delivery. Additionally, PM2.5 in the home will be measured 6 months, 12 months and 24 months after delivery of the child.	Baseline, 3, 5, 9, 12 and 18 months post-randomization, 24, 36, 48, 60 months of age
Other	Change in Carbon monoxide (CO) exposure	Personal monitoring equipment will be used to assess exposure to carbon monoxide (CO) over a 24-hour period in intervention and control participants (pregnant women, older adult women, and children). Exposure for pregnant women will be measured at baseline, 24-28 weeks gestation, 32-36 weeks gestation, and 24 months after delivery. Children will be measured up to 12 months after delivery, and at 24, 36, 48 and 60 months of age. Older adult women will be measured up to 12 months after delivery, and at 24 months after delivery. Additionally, CO in the home will be measured 6 months, 12 months and 24 months after delivery of the child.	Baseline, 3, 5, 9, 12 and 18 months post-randomization, 24, 36, 48, 60 months of age
Other	Change in Black carbon (BC) exposure	Personal monitoring equipment will be used to assess exposure to black carbon (BC) over a 24-hour period in intervention and control participants (pregnant women, older adult women, and children). Exposure for pregnant women will be measured at baseline, 24-28 weeks gestation, 32-36 weeks gestation, and 24 months after delivery. Children will be measured up to 12 months after delivery, and at 24, 36, 48 and 60 months of age. Older adult women will be measured up to 12 months after delivery, and at 24 months after delivery. Additionally, BC in the home will be measured 6 months, 12 months and 24 months after delivery of the child.	Baseline, 3, 5, 9, 12 and 18 months post-randomization, 24, 36, 48, 60 months of age
Other	Maternal Perceived Stress Scale (PSS)	The 10-item Cohen's Perceived Stress Scale (PPS) assesses the way an individual appraises their life events as stressful (e.g., "In the last month, how often have you felt difficulties were piling up so high that you could not overcome them?") (Cohen, 1983). Likert-level responses ranged from 0 (never) to 4 (very often), meaning a high PPS score would result in a high level of perceived stress. A Spanish language PPS created and tested and found to be valid and reliable (Vallijo et al., 2018).	3 months to 12 months of age
Other	Maternal death	Death of a woman while pregnant or within 42 days of termination of pregnancy irrespective of the duration and site of the pregnancy.	Pregnancy through 42 days post-partum
Other	Spontaneous abortion	Fetal death before 19 weeks 6 days.	Baseline through 20 weeks gestation
Other	Early preterm birth	Births at less than 34 weeks completed gestation, among all live births.	Birth
Other	Preterm delivery	Including preterm birth and stillbirth	Birth
Other	Stillbirth	Any fetal deaths occurring at or after 20 weeks' gestation OR indicated on Serious Adverse Event form OR on Pregnant Woman Medical History form OR on verbal autopsy form.	Up to birth
Other	Neonatal death	Death between birth and 28 days.	Birth through 28 days
Other	Change in Child Blood Pressure	Blood pressure will be assessed in the children using automatic sphygmomanometers (OMRON HEM-907XL; Osaka, Japan). The study team will use the procedures adapted from previously validated methods and cardiovascular outcome studies, following recommendations for the American Heart Association and the European Society of Hypertension.	48 and 60 months of age
Other	Change in Messenger Ribonucleic Acid (mRNA) Expression and microRNA in Older Adult Women	Two buccal cell scrapes will be collected by gently scraping the buccal mucosa on both sides of the mouth with a small plastic collection spoon. Nasal turbinate brush samples can be collected using a soft cytobrush on each turbinate. Collection is gentle and causes no discomfort to study participants. Both samples will be processed in the laboratory according to procedures detailed in the protocol. This will occur in the older adult women in an NCI substudy.	Baseline, 18 months post-randomization
Other	Change in Microbiome Operational Taxonomic Units (OTUs) in Older Adult Women	For the oral rinse, participants will vigorously rinse their mouth and the rinsates are collected in a centrifuge tube. The tube is centrifuged and the pellet and supernatant are removed to separate cryovials, labeled and frozen. This will occur in the older adult women in an NCI substudy.	Baseline, 18 months post-randomization
Other	Change in Epigenetics (DNA methylation) in Older Adult Women	Two buccal cell scrapes will be collected by gently scraping the buccal mucosa on both sides of the mouth with a small plastic collection spoon. A 5-mL venous blood sample will be collected in an ethylenediaminetetraacetic acid (EDTA) vacutainer tube by standard clinical venipuncture of a cubital vein. Both samples will be transported and processed in the laboratory according to procedures detailed in the protocol. This will occur in the older adult women in an NCI substudy.	Baseline, 18 months post-randomization
Other	Change in Metabolomics and MicroRNA in Older Adult Women	A 5-mL venous blood sample will be collected in an EDTA vacutainer tube by standard clinical venipuncture of a cubital vein. The sample will be transported and processed in the laboratory according to procedures detailed in the protocol. This will occur in the older adult women in an NCI substudy.	Baseline, 18 months post-randomization
Primary	Birth weight	Birth weight will be assessed by a trained nurse or health worker within 24 hours of birth. Infants will be weighed naked or in a pre-weighed blanket. Weight will be measured to the nearest 10 g using a digital electronic scale, if performed by the study field staff; otherwise, hospital medical records will be used.	Within 24 hours of birth (up to 5 months post-randomization of mother)
Primary	Incidence of HAPIN Defined Severe Pneumonia	The number of times a child has severe pneumonia over their period of follow-up during the first year of life will be assessed. HAPIN pneumonia criteria are adapted from the WHO classification of childhood pneumonia (2014) and there are 3 algorithms for HAPIN case criteria: 1) the presence of cough and/or difficult breathing and at least 1 general danger sign plus evidence of pneumonia on lung imaging (i.e., lung ultrasound or chest x-ray), or 2) the presence of cough and/or difficult breathing and hypoxemia (measured either via pulse oximetry (SpO2), or observing a child requiring advanced respiratory support (i.e., intubation and mechanical ventilation, non-invasive ventilation with continuous or bi-level positive airway pressure support, or high-flow nasal cannula oxygen), or 3) children who die prior to evaluation but their death is attributed to pneumonia by verbal autopsy. Cases of pneumonia are recorded children present to HAPIN health facilities with respiratory symptoms.	Up to 12 months after birth
Primary	Length-for-age z-score 2 standard deviations below the standard	The primary outcome measured is stunting at one year of age, defined as a length-for-age z-score (LAZ) that is 2 standard deviations below the median of the growth standard. Infant length will be assessed at birth and quarterly thereafter, until the child is 12 months old. Z-scores will be calculated using the 2006 World Health Organization (WHO) Multi-Growth Reference Standard (MGRS).	12 months after birth
Primary	Change in Systolic Blood Pressure	Systolic blood pressure will be assessed in the older adult women in the intervention and control arms using automatic sphygmomanometers (Omron HEM-907XL; Osaka, Japan). The study team will use the procedures adapted from previously validated methods and cardiovascular outcome studies, following recommendations for the American Heart Association and the European Society of Hypertension.	Baseline, 3, 5, 9, 12, and 18 months post-randomization, 24, 36, 48, and 60 months of age
Primary	Change in Child Linear Growth	Linear growth of children will be assessed in centimeters of height from the time of birth until 60 months of age.	Birth (3-5 months post-randomization), 3, 6, 9, 12, 24, 36, 48 and 60 months of age
Primary	Change in Caregiver Reported Early Childhood Development Instrument (CREDI) Score	Child development will be assessed with the Caregiver Reported Early Childhood Development Instrument (CREDI). The CREDI is a population-level measure of early childhood development (ECD) for children from 0-2 years of age. The CREDI assesses 5 domains of child development: 1) motor development (fine and gross motor), 2) language development (expressive and receptive language), 3) cognitive development (executive function, problem solving and reasoning, and pre-academic knowledge), 4) socio-emotional development (emotional and behavioral self-regulation, emotional knowledge, and social competence), and 5) mental health (internalizing and externalizing behaviors). The CREDI long form has 117 items and the number of questions answered depends on the age of the child. Responses of "yes" are coded as 1 and "no" is coded as 0; certain items are reverse coded. Total raw scores increase by age (with developmental progression), and higher scores indicate increased development.	3 months of age to 24 months of age
Primary	Change in Malawi Developmental Assessment Tool (MDAT) Score	The MDAT measures gross motor (39 items), fine motor (42 items), language/cognition (40 items) and social skills (36 items). Originally developed and validated in rural Malawi, it has now been used in over 25 countries with more than 8,000 children as both a clinical and research tool. The MDAT is a continuous test with start and stop rules. Most items are administered directly to the child and items that are not easily observed (e.g., child speaks in full sentences; child understands sharing with others; child can dress self) are administered by parent report. Children receive either a pass or fail for each item, and summed pass scores can produce a composite score as well as domain-specific scores. Total scores range from 0 to 157 where higher scores indicate greater neurodevelopment.	36, 48 and 60 months of age
Secondary	Change in Maternal Blood Pressure	Blood pressure will be assessed in the pregnant women in the intervention and control arms using automatic sphygmomanometers (OMRON HEM-907XL; Osaka, Japan). After delivery, blood pressure will be measured in the new mothers when the child is 24, 36, 48 and 60 months old. The study team will use the procedures adapted from previously validated methods and cardiovascular outcome studies, following recommendations for the American Heart Association and the European Society of Hypertension.	Baseline (9-20 weeks gestation), 24-28 and 32-36 weeks gestation, 24, 36, 48 and 60 months of age
Secondary	Change in Diastolic blood pressure	Diastolic blood pressure will be assessed in the older adult women and new mothers in the intervention and control arms using automatic sphygmomanometers (Omron HEM-907XL; Osaka, Japan). The study team will use the procedures adapted from previously validated methods and cardiovascular outcome studies, following recommendations for the American Heart Association and the European Society of Hypertension.	Baseline, 3, 6, 12 and 18 months post-randomization, 24, 36, 48, and 60 months of age
Secondary	Mean arterial pressure	Mean arterial pressure will be assessed in the older adult women and new mothers in the intervention and control arms using automatic sphygmomanometers (Omron HEM-907XL; Osaka, Japan). Mean arterial pressure is calculated as DBP+(SBP-DBP)/3, where SBP=systolic blood pressure and DBP=diastolic blood pressure.	Baseline, 3, 6, 12 and 18 months post-randomization, 24, 36, 48, and 60 months of age
Secondary	Pulse pressure	Pulse pressure will be assessed in the older adult women and new mothers in the intervention and control arms using automatic sphygmomanometers (Omron HEM-907XL; Osaka, Japan). pressure. Pulse pressure is the difference between systolic blood pressure and diastolic blood pressure.	Baseline, 3, 6, 12 and 18 months post-randomization, 24, 36, 48, and 60 months of age
Secondary	Fetal Growth	Pregnant women will have ultrasounds at Baseline and during gestation weeks 24-28 and gestation weeks 32-36 to measure fetal growth outcomes. Specifically, we will evaluate head circumference (HC), abdominal circumference (AC), femur length (FL) and estimated fetal weight (EFW) during gestation. We will compare (i) z-scores of individual fetal growth measurements (HC, AC, FL, EFW) at the 2 growth ultrasound visits between intervention and control participants (separately at 24-28 wks gestation and 32-36 wks gestation); (ii) differences in proportions of the 2.5th percentiles of each of these measurements evaluated separately at 24-28 and 32-36 weeks gestation; (iii) Z-score trajectories of HC, AC, FL and EFW as a function of gestational age and intervention; and (iv) prevalence of small for gestational age (SGA) during the fetal period through birth as measured by WHO INTERGROWTH 21st standards.	Baseline, Gestation Week 24-28 and Gestation Week 32-36
Secondary	Gestational age at birth	In weeks, as continuous outcome, among all live births.	Up to 5 months (within 24 hours of birth, 3-5 months post randomization)
Secondary	Preterm birth	Preterm birth is defined as delivery of a living infant prior to 37 completed weeks of gestation.	Up to 5 months (within 24 hours of birth, 3-5 months post randomization)
Secondary	WHO Non-severe Pneumonia	Cumulative incidence of WHO non-severe pneumonia (2014 definition and 2013 definition) during the first year of life. Cases of pneumonia are recorded whenever children present to HAPIN health facilities with respiratory symptoms.	Up to 12 months after birth
Secondary	WHO Severe Pneumonia	Cumulative incidence of WHO non-severe pneumonia (2014 definition and 2013 definition) during the first year of life. Cases of pneumonia are recorded whenever children present to HAPIN health facilities with respiratory symptoms.	Up to 12 months after birth
Secondary	Hospitalization for respiratory illness	Cumulative incidence of hospitalizations for a respiratory illness during the first year of life.	Up to 12 months after birth
Secondary	WHO Pocket Book Non-severe Pneumonia	Cumulative incidence of WHO non-severe pneumonia during the first year of life, as defined in the second edition of the "Pocket book of hospital care for children" (2013). Cases of pneumonia are recorded whenever children present to HAPIN health facilities with respiratory symptoms.	Up to 12 months after birth
Secondary	WHO Pocket Book Severe Pneumonia	Cumulative incidence of WHO severe pneumonia during the first year of life, as defined in the second edition of the "Pocket book of hospital care for children" (2013). Cases of pneumonia are recorded whenever children present to HAPIN health facilities with respiratory symptoms.	Up to 12 months after birth
Secondary	Hypoxemic Pneumonia	Cumulative incidence of hypoxemic pneumonia during the first year of life. Cases of pneumonia are recorded whenever children present to HAPIN health facilities with respiratory symptoms.	Up to 12 months after birth
Secondary	Ultrasound or Radiograph Pneumonia	Cumulative incidence of lung ultrasound or chest radiograph pneumonia during the first year of life. Cases of pneumonia are recorded whenever children present to HAPIN health facilities with respiratory symptoms.	Up to 12 months after birth
Secondary	Change in Brachial artery reactivity testing (BART)	Brachial artery reactivity testing (BART) measures endothelial function via flow-mediated dilatation to reactive hyperemia following the release of arm blood-flow occlusion. In this test, baseline artery diameter is measured, then a blood pressure cuff is inflated to induce distal arm ischemia for 5 minutes and after releasing the pressure, the post-occlusion brachial artery diameter is measured. The ratio of post- to pre-occlusion artery diameter represents endothelial function where lower values indicate worse endothelial function. (Peru only)	Baseline, 18 months
Secondary	Change in Carotid intima-media thickness (CIMT)	The carotid intima-media thickness test (CIMT) is used to determine the extent of carotid atherosclerotic vascular disease. The test measures the thickness of the inner two layers of the carotid artery and can detect plaque build up prior to physical symptoms being experienced. The carotid ultrasound will be performed with a portable ultrasound by trained sonographers.	Baseline, 18 months post-randomization, and when child is 24 months of age
Secondary	Change in St. George Respiratory Questionnaire (SGRQ) Score	Adult respiratory health and well-being will be assessed with the St. George Respiratory Questionnaire (SGRQ). The SGRQ measures impaired health and perceived well-being among individuals with chronic airway disease. The SGRQ has sections assessing symptoms, activities that cause breathlessness or are limited because of breathlessness, and the impacts of respiratory problems on employment, sense of control of health, panic, stigmatization, medication use, side effects of therapies, expectations for health and disturbances of daily life. The questionnaire includes multiple choice, true/false and open-ended questions.	Baseline, 18 months
Secondary	Change in Short Form 36 Survey (SF-36) Score	The Short Form 36 survey (SF-36) is a standardized, preference-based 36 item questionnaire evaluating quality of life. The survey has 8 sections (vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning, and mental health). Possible scores range from 0 (lowest quality of life) to 100 (highest quality of life).	Baseline, 18 months
Secondary	Change in Weight	Weight will be measured in the pregnant women/new mothers, the older adult women, and the children. Weight is measured in kilograms (kg). Weight in pregnant women will be measured at baseline, 24-28 weeks gestation, and 32-36 weeks gestation, and in new mothers when the child is 24- and 36-months old. In older adult women, it will be measured at baseline, 3, 6, 9, 12 and 18 months post-randomization, and when the child is 24-months old. Weight in children will be measured at birth, and at 3, 6, 9, 12, 24, 36, 48 and 60 months of age.	Baseline, 3, 6, 9, 12 and 18 months post-randomization, 24, 36, 48 and 60 months of age
Secondary	Change in Body Mass Index (BMI)	BMI will be calculated for the pregnant women, the older adult women, and the children. BMI is calculated as weight in kilograms divided by height in meters (m) squared (kg/m²). BMI in pregnant women will be calculated at baseline, 24-28 weeks gestation, and 32-36 weeks gestation, and in new mothers when the child is 24- and 36-months old. In older adult women, it will be calculated at baseline, 3, 6, 9, 12 and 18 months post-randomization, and when the child is 24-months old. Weight in children will be calculated at birth, and at 3, 6, 9, 12, 24, 36, 48 and 60 months of age.	Baseline, 3, 6, 9, 12 and 18 months post-randomization, 24, 36, 48 and 60 months of age
Secondary	Change in Height	Height in women will be measured in centimeters. Height in pregnant women will be measured at baseline, 24-28 weeks gestation, and 32-36 weeks gestation, and in new mothers when the child is 24- and 36-months old. In older adult women, it will be measured at baseline, 3, 6, 9, 12 and 18 months post-randomization, and when the child is 24-months old. This measurement will be used to compute the body mass index.	Baseline, 3, 6, 9, 12 and 18 months post-randomization, 24 months of age
Secondary	Change in Urinary Biomarkers	Multiple exposure biomarkers will be measured: 3-OH Cotinine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), levoglucosan, 8OH-deoxyguanosine (8OHdG), and Volatile Organic Chemicals (VOC) metabolites. Exposure biomarkers (especially for children whose urine may be limited) will be prioritized as follows: polycyclic aromatic hydrocarbon (PAH) biomarkers, levoglucosan, volatile organic chemicals (VOC) biomarkers, heavy metals, and tobacco-related biomarkers. Urinary biomarkers will be measured in pregnant women at baseline, 24-28 weeks gestation, and 32-36 weeks gestation, and in new mothers when the child is 24-months old. Biomarkers will be measured in older adult women at baseline, 3, 6, 9, 12 and 18 months post-randomization. Biomarkers will be measured in children at 3, 6, 12 and 24 months of age.	Baseline, 3, 6, 9, 12 and 18 months post-randomization, 3, 6, 12 and 24 months of age
Secondary	Change in Dried Blood Spot (DBS) Biomarkers	The main biomarkers to be measured from the dried blood spots is: inflammation markers, endothelial markers of cardiovascular disease, oxidative stress markers, Hb, HbA1C, tumor-associated antigen antibodies, cytochrome P450, p53 tumor-associated antigen (TAA), lipids, metabolomics, MiRNA, heavy metals. DBS biomarkers will be measured in pregnant women at baseline, 24-28 weeks gestation, and 32-36 weeks gestation, and in new mothers when the child is 24-months old. DBS biomarkers will be measured in older adult women at baseline, 3, 6, 9, 12 and 18 months post-randomization. DBS biomarkers will be measured in children at 3, 6, 12 and 24 months of age.	Baseline, 3, 6, 9, 12 and 18 months post-randomization, 3, 6, 12 and 24 months of age
Secondary	Child Lung Function	Lung function measurements will be made using the forced oscillation technique (FOT) with the Tremoflo C-100 device with disposable mouthpieces. FOT is a technique that can identify early changes in the airways. The FOT device measures the relationship between externally applied pressure waves and the resulting air flow to measure respiratory impedance. Values produced at high frequencies correspond to the proximal and large airways, and values produced at low frequencies correspond to distal and small airways. This measurement will be conducted in children in Guatemala.	36, 48 and 60 months of age
Secondary	Death	Death of all participants will be documented	Up to Study Exit (up to 60 months of age of child)