Infant, Low Birth Weight
Conditions
Keywords
Obstetrics, Pregnancy Outcomes, Pediatrics, Atherosclerosis, Cancer, Cardiovascular Disease, Public Health, Environmental Air Pollutants
Brief 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 systolic blood pressure 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.
Detailed 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 systolic blood pressure 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.
Interventions
OTHERLiquefied 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 necessary repairs, and measure and record weight of LPG tanks in order to anticipate need for refills.
Sponsors
Emory University
National Institutes of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Bill and Melinda Gates Foundation
Berkeley Air Monitoring Group
Colorado State University
Global LPG Partnership
Harvard University
Johns Hopkins University
London School of Hygiene and Tropical Medicine
Asociacion Benefica Prisma
Sri Ramachandra University
Universidad del Valle, Guatemala
Universidad Peruana Cayetano Heredia
University of Georgia
Washington University School of Medicine
University of Rwanda
Eagle Research Center
University of Oxford
University of Liverpool
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 79 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Birth weight | Within 24 hours of birth (up to 5 months post-randomization of mother) | Birth weight is assessed by a trained nurse or health worker within 24 hours of birth. Infants are weighed naked or in a pre-weighed blanket. Weight is measured to the nearest 10 g using a digital electronic scale, if performed by the study field staff; otherwise, hospital medical records are used. |
| Incidence of HAPIN Defined Severe Pneumonia | Up to 12 months after birth | The number of times a child has severe pneumonia over their period of follow-up during the first year of life is assessed. For this study pneumonia criteria are adapted from the WHO classification of childhood pneumonia (2014) and there are 3 algorithms for 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. |
| Caregiver Reported Early Childhood Development Instrument (CREDI) Score During Extended Follow-up | 24 months of age | Child development is 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 0-3 years of age. The CREDI assesses 4 domains of child development: 1) motor (fine and gross motor), 2) language (expressive and receptive language), 3) cognitive (executive function, problem solving and reasoning, and pre-academic knowledge), and 4) social-emotional (emotional and behavioral self-regulation, emotional knowledge, and social competence). The CREDI long form consists of up to 108 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. Both domain-specific and overall z-scores are calculated. Total raw scores increase by age (with developmental progression), and higher scores indicate increased development. |
| Malawi Developmental Assessment Tool (MDAT) Score | 36, 48 and 60 months of age | 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. |
| Systolic Blood Pressure Among Older Adult Women | Baseline, 3, 6, 9, 12, and 18 months post-randomization | Systolic blood pressure is assessed in the older adult women in the intervention and control arms using automatic sphygmomanometers (Omron HEM-907XL; Osaka, Japan). The study team uses the procedures adapted from previously validated methods and cardiovascular outcome studies, following recommendations for the American Heart Association and the European Society of Hypertension. |
| Child Linear Growth During Extended Follow-up | 24, 36, 48 and 60 months of age | Linear growth of children is assessed in centimeters of height. |
| Length-for-age z-score 2 standard deviations below the standard | 12 months after birth | 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 is assessed at birth and quarterly thereafter, until the child is 12 months old. Z-scores are calculated using the 2006 World Health Organization (WHO) Multi-Growth Reference Standard (MGRS). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Gestational Systolic Blood Pressure | Baseline (9-20 weeks gestation), 24-28 and 32-36 weeks gestation | Blood pressure is assessed in the pregnant 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. |
| Gestational Diastolic Blood Pressure | Baseline (9-20 weeks gestation), 24-28 and 32-36 weeks gestation | Blood pressure is assessed in the pregnant 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. |
| Systolic Blood Pressure in New Mothers | 9, 12, and 18 months post-randomization | Blood pressure is assessed in the 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. |
| Diastolic Blood Pressure in New Mothers | 9, 12, and 18 months post-randomization | Blood pressure is assessed in the 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. |
| Diastolic Blood Pressure Among Older Adult Women | Baseline, 3, 6, 12 and 18 months post-randomization | Diastolic blood pressure is assessed in the older adult women in the intervention and control arms using automatic sphygmomanometers (Omron HEM-907XL; Osaka, Japan). The study team uses the procedures adapted from previously validated methods and cardiovascular outcome studies, following recommendations for the American Heart Association and the European Society of Hypertension. |
| Mean arterial pressure | Baseline, 3, 6, 12 and 18 months post-randomization | Mean arterial pressure is assessed in the older adult women 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. |
| Pulse pressure | Baseline, 3, 6, 12 and 18 months post-randomization | Pulse pressure is assessed in the older adult women 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. |
| Fetal Growth | Baseline, Gestation Week 24-28 and Gestation Week 32-36 | Pregnant women have ultrasounds at Baseline and during gestation weeks 24-28 and gestation weeks 32-36 to measure fetal growth outcomes. Specifically, the researchers evaluate head circumference (HC), abdominal circumference (AC), femur length (FL) and estimated fetal weight (EFW) during gestation. The researchers are comparing (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 weeks gestation and 32-36 weeks 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. |
| Gestational age at birth | Up to 5 months (within 24 hours of birth, 3-5 months post randomization) | Gestational age at birth is measured in weeks, as continuous outcome, among all live births. |
| Preterm birth | Up to 5 months (within 24 hours of birth, 3-5 months post randomization) | Preterm birth is defined as delivery of a living infant prior to 37 completed weeks of gestation. |
| WHO Non-severe Pneumonia | Up to 12 months after birth | 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. |
| WHO Severe Pneumonia | Up to 12 months after birth | 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. |
| Hospitalization for respiratory illness | Up to 12 months after birth | Cumulative incidence of hospitalizations for a respiratory illness during the first year of life. |
| St. George Respiratory Questionnaire (SGRQ) Score | Baseline, 18 months post-randomization | Adult respiratory health and well-being is 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. |
| Short Form 36 Survey (SF-36) Score Among Older Adult Women | Baseline, 18 months post-randomization | 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). |
| Weight | 24, 36, 48 and 60 months of age of the child | Weight is measured in kilograms (kg). Weight in new mothers in Rwanda is measured when the child is 24 months old. For new mothers in Guatemala weight is measured when the child is 24 and 36 months old. In older adult women, weight is measured when the child is 24 months old. Weight is measured in children at 24, 36, 48 and 60 months of age. |
| Body Mass Index (BMI) | 24, 36, 48 and 60 months of age of the child | BMI is calculated as weight in kilograms divided by height in meters (m) squared (kg/m\^2). BMI in new mothers in Rwanda is calculated from height and weight measurements obtained when the child is 24 months old. For new mothers in Guatemala BMI is calculated from height and weight measurements obtained when the child is 24 and 36 months old. In older adult women, BMI is calculated from height and weight measurements obtained when the child is 24 months old. |
| Height | 24 and 36 months of age of the child | Height is measured in meters. Height in new mothers in Rwanda is measured when the child is 24 months old. For new mothers in Guatemala height is measured when the child is 24 and 36 months old. In older adult women, height is measured when the child is 24-months old. |
| Child Blood Pressure | 24 (Rwanda only) and 60 months of age | Blood pressure is assessed in the children using automatic sphygmomanometers (OMRON HEM-907XL; Osaka, Japan). The study team uses the procedures adapted from previously validated methods and cardiovascular outcome studies, following recommendations for the American Heart Association and the European Society of Hypertension. |
| Child Linear Growth | Birth (3-5 months post-randomization), and 3, 6, 9, and 12 months of age | Linear growth of children is assessed in centimeters at birth and quarterly thereafter, until the child is 12 months old. |
| Caregiver Reported Early Childhood Development Instrument (CREDI) Score | 3 and 12 months of age | Child development is 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 0-3 years of age. The CREDI assesses 4 domains of child development: 1) motor (fine and gross motor), 2) language (expressive and receptive language), 3) cognitive (executive function, problem solving and reasoning, and pre-academic knowledge), and 4) social-emotional (emotional and behavioral self-regulation, emotional knowledge, and social competence). The CREDI long form consists of up to 108 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. Both domain-specific and overall z-scores are calculated. Total raw scores increase by age (with developmental progression), and higher scores indicate increased development. |
| WHO Pocket Book Non-severe Pneumonia | Up to 12 months after birth | 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. |
| WHO Pocket Book Severe Pneumonia | Up to 12 months after birth | 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. |
| Hypoxemic Pneumonia | Up to 12 months after birth | 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. |
| Ultrasound or Radiograph Pneumonia | Up to 12 months after birth | 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. |
| Brachial artery reactivity testing (BART) | Baseline, 18 months post-randomization | 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) |
| Carotid intima-media thickness (CIMT) Among Older Adult Women | Baseline, 18 months post-randomization | 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. |
Countries
Guatemala, India, Peru, Rwanda
Contacts
PRINCIPAL_INVESTIGATORThomas Clasen, PhD
Emory University
PRINCIPAL_INVESTIGATORJennifer Peel, PhD
Colorado State University
PRINCIPAL_INVESTIGATORWilliam Checkley, MD PhD
Johns Hopkins School of Medicine
Outcome results
None listed