Factors Determining Black Carbon Exposures among Pregnant Women Enrolled in the HAPIN Trial.

Residential biomass burning is an important source of black carbon (BC) exposure among rural communities in low- and middle-income countries. We collected 7165 personal BC samples and individual/household level information from 3103 pregnant women enrolled in the Household Air Pollution Intervention Network trial. Women in the intervention arm received free liquefied petroleum gas stoves and fuel throughout pregnancy; women in the control arm continued the use of biomass stoves. Median (IQR) postintervention BC exposures were 9.6 µg/m3 (5.2-14.0) for controls and 2.8 µg/m3 (1.6-4.8) for the intervention group. Using mixed models, we characterized predictors of BC exposure and assessed how exposure contrasts differed between arms by select predictors. Primary stove type was the strongest predictor (R2 = 0.42); the models including kerosene use, kitchen location, education, occupation, or stove use hours also provided additional explanatory power from the base model adjusted only for the study site. Our full, trial-wide, model explained 48% of the variation in BC exposures. We found evidence that the BC exposure contrast between arms differed by study site, adherence to the assigned study stove, and whether the participant cooked. Our findings highlight factors that may be addressed before and during studies to implement more impactful cookstove intervention trials.

Cooking with liquefied petroleum gas or biomass and fetal growth outcomes: a multi-country randomised controlled trial.

BACKGROUND: Household air pollution might lead to fetal growth restriction during pregnancy. We aimed to investigate whether a liquefied petroleum gas (LPG) intervention to reduce personal exposures to household air pollution during pregnancy would alter fetal growth. METHODS: The Household Air Pollution Intervention Network (HAPIN) trial was an open-label randomised controlled trial conducted in ten resource-limited settings across Guatemala, India, Peru, and Rwanda. Pregnant women aged 18-34 years (9-19 weeks of gestation) were randomly assigned in a 1:1 ratio to receive an LPG stove, continuous fuel delivery, and behavioural messaging or to continue usual cooking with biomass for 18 months. We conducted ultrasound assessments at baseline, 24-28 weeks of gestation (the first pregnancy visit), and 32-36 weeks of gestation (the second pregnancy visit), to measure fetal size; we monitored 24 h personal exposures to household air pollutants during these visits; and we weighed children at birth. We conducted intention-to-treat analyses to estimate differences in fetal size between the intervention and control group, and exposure-response analyses to identify associations between household air pollutants and fetal size. This trial is registered with ClinicalTrials.gov (NCT02944682). FINDINGS: Between May 7, 2018, and Feb 29, 2020, we randomly assigned 3200 pregnant women (1593 to the intervention group and 1607 to the control group). The mean gestational age was 14·5 (SD 3·0) weeks and mean maternal age was 25·6 (4·5) years. We obtained ultrasound assessments in 3147 (98·3%) women at baseline, 3052 (95·4%) women at the first pregnancy visit, and 2962 (92·6%) at the second pregnancy visit, through to Aug 25, 2020. Intervention adherence was high (the median proportion of days with biomass stove use was 0·0%, IQR 0·0-1·6) and pregnant women in the intervention group had lower mean exposures to particulate matter with a diameter less than 2·5 µm (PM2·5; 35·0 [SD 37·2] µg/m3vs 103·3 [97·9] µg/m3) than did women in the control group. We did not find differences in averaged post-randomisation Z scores for head circumference (0·30 vs 0·39; p=0·04), abdominal circumference (0·38 vs 0·39; p=0·99), femur length (0·44 vs 0·45; p=0·73), and estimated fetal weight or birthweight (-0·13 vs -0·12; p=0·70) between the intervention and control groups. Personal exposures to household air pollutants were not associated with fetal size. INTERPRETATION: Although an LPG cooking intervention successfully reduced personal exposure to air pollution during pregnancy, it did not affect fetal size. Our findings do not support the use of unvented liquefied petroleum gas stoves as a strategy to increase fetal growth in settings were biomass fuels are used predominantly for cooking. FUNDING: US National Institutes of Health and Bill & Melinda Gates Foundation. TRANSLATIONS: For the Kinyarwanda, Spanish and Tamil translations of the abstract see Supplementary Materials section.

Effects of Cooking with Liquefied Petroleum Gas or Biomass on Stunting in Infants.

BACKGROUND: Household air pollution is associated with stunted growth in infants. Whether the replacement of biomass fuel (e.g., wood, dung, or agricultural crop waste) with liquefied petroleum gas (LPG) for cooking can reduce the risk of stunting is unknown. METHODS: We conducted a randomized trial involving 3200 pregnant women 18 to 34 years of age in four low- and middle-income countries. Women at 9 to less than 20 weeks' gestation were randomly assigned to use a free LPG cookstove with continuous free fuel delivery for 18 months (intervention group) or to continue using a biomass cookstove (control group). The length of each infant was measured at 12 months of age, and personal exposures to fine particulate matter (particles with an aerodynamic diameter of ≤2.5 µm) were monitored starting at pregnancy and continuing until the infants were 1 year of age. The primary outcome for which data are presented in the current report - stunting (defined as a length-for-age z score that was more than two standard deviations below the median of a growth standard) at 12 months of age - was one of four primary outcomes of the trial. Intention-to-treat analyses were performed to estimate the relative risk of stunting. RESULTS: Adherence to the intervention was high, and the intervention resulted in lower prenatal and postnatal 24-hour personal exposures to fine particulate matter than the control (mean prenatal exposure, 35.0 µg per cubic meter vs. 103.3 µg per cubic meter; mean postnatal exposure, 37.9 µg per cubic meter vs. 109.2 µg per cubic meter). Among 3061 live births, 1171 (76.2%) of the 1536 infants born to women in the intervention group and 1186 (77.8%) of the 1525 infants born to women in the control group had a valid length measurement at 12 months of age. Stunting occurred in 321 of the 1171 infants included in the analysis (27.4%) of the infants born to women in the intervention group and in 299 of the 1186 infants included in the analysis (25.2%) of those born to women in the control group (relative risk, 1.10; 98.75% confidence interval, 0.94 to 1.29; P = 0.12). CONCLUSIONS: An intervention strategy starting in pregnancy and aimed at mitigating household air pollution by replacing biomass fuel with LPG for cooking did not reduce the risk of stunting in infants. (Funded by the National Institutes of Health and the Bill and Melinda Gates Foundation; HAPIN ClinicalTrials.gov number, NCT02944682.).

Effects of a liquefied petroleum gas stove intervention on stillbirth, congenital anomalies and neonatal mortality: A multi-country household air pollution intervention network trial.

Household air pollution (HAP) from cooking with solid fuels used during pregnancy has been associated with adverse pregnancy outcomes. The Household Air Pollution Intervention Network (HAPIN) trial was a randomized controlled trial that assessed the impact of a liquefied petroleum gas (LPG) stove and fuel intervention on health in Guatemala, India, Peru, and Rwanda. Here we investigated the effects of the LPG stove and fuel intervention on stillbirth, congenital anomalies and neonatal mortality and characterized exposure-response relationships between personal exposures to fine particulate matter (PM2.5), black carbon (BC) and carbon monoxide (CO) and these outcomes. Pregnant women (18 to <35 years of age; gestation confirmed by ultrasound at 9 to <20 weeks) were randomly assigned to intervention or control arms. We monitored these fetal and neonatal outcomes and personal exposure to PM2.5, BC and CO three times during pregnancy, we conducted intention-to-treat (ITT) and exposure-response (E-R) analyses to determine if the HAPIN intervention and corresponding HAP exposure was associated with the risk of fetal/neonatal outcomes. A total of 3200 women (mean age 25.4 ± 4.4 years, mean gestational age at randomization 15.4 ± 3.1 weeks) were included in this analysis. Relative risks for stillbirth, congenital anomaly and neonatal mortality were 0.99 (0.60, 1.66), 0.92 (95 % CI 0.52, 1.61), and 0.99 (0.54, 1.85), respectively, among women in the intervention arm compared to controls in an ITT analysis. Higher mean personal exposures to PM2.5, CO and BC during pregnancy were associated with a higher, but statistically non-significant, incidence of adverse outcomes. The LPG stove and fuel intervention did not reduce the risk of these outcomes nor did we find evidence supporting an association between personal exposures to HAP and stillbirth, congenital anomalies and neonatal mortality.

Liquefied Petroleum Gas or Biomass Cooking and Severe Infant Pneumonia.

BACKGROUND: Exposure to household air pollution is a risk factor for severe pneumonia. The effect of replacing biomass cookstoves with liquefied petroleum gas (LPG) cookstoves on the incidence of severe infant pneumonia is uncertain. METHODS: We conducted a randomized, controlled trial involving pregnant women 18 to 34 years of age and between 9 to less than 20 weeks' gestation in India, Guatemala, Peru, and Rwanda from May 2018 through September 2021. The women were assigned to cook with unvented LPG stoves and fuel (intervention group) or to continue cooking with biomass fuel (control group). In each trial group, we monitored adherence to the use of the assigned cookstove and measured 24-hour personal exposure to fine particulate matter (particles with an aerodynamic diameter of ≤2.5 µm [PM2.5]) in the women and their offspring. The trial had four primary outcomes; the primary outcome for which data are presented in the current report was severe pneumonia in the first year of life, as identified through facility surveillance or on verbal autopsy. RESULTS: Among 3200 pregnant women who had undergone randomization, 3195 remained eligible and gave birth to 3061 infants (1536 in the intervention group and 1525 in the control group). High uptake of the intervention led to a reduction in personal exposure to PM2.5 among the children, with a median exposure of 24.2 µg per cubic meter (interquartile range, 17.8 to 36.4) in the intervention group and 66.0 µg per cubic meter (interquartile range, 35.2 to 132.0) in the control group. A total of 175 episodes of severe pneumonia were identified during the first year of life, with an incidence of 5.67 cases per 100 child-years (95% confidence interval [CI], 4.55 to 7.07) in the intervention group and 6.06 cases per 100 child-years (95% CI, 4.81 to 7.62) in the control group (incidence rate ratio, 0.96; 98.75% CI, 0.64 to 1.44; P = 0.81). No severe adverse events were reported to be associated with the intervention, as determined by the trial investigators. CONCLUSIONS: The incidence of severe pneumonia among infants did not differ significantly between those whose mothers were assigned to cook with LPG stoves and fuel and those whose mothers were assigned to continue cooking with biomass stoves. (Funded by the National Institutes of Health and the Bill and Melinda Gates Foundation; HAPIN ClinicalTrials.gov number, NCT02944682.).

Exposure-response relationships for personal exposure to fine particulate matter (PM2·5), carbon monoxide, and black carbon and birthweight: an observational analysis of the multicountry Household Air Pollution Intervention Network (HAPIN) trial.

BACKGROUND: Household air pollution (HAP) from solid fuel use is associated with adverse birth outcomes, but data for exposure-response relationships are scarce. We examined associations between HAP exposures and birthweight in rural Guatemala, India, Peru, and Rwanda during the Household Air Pollution Intervention Network (HAPIN) trial. METHODS: The HAPIN trial recruited pregnant women (9-<20 weeks of gestation) in rural Guatemala, India, Peru, and Rwanda and randomly allocated them to receive a liquefied petroleum gas stove or not (ie, and continue to use biomass fuel). The primary outcomes were birthweight, length-for-age, severe pneumonia, and maternal systolic blood pressure. In this exposure-response subanalysis, we measured 24-h personal exposures to PM2·5, carbon monoxide, and black carbon once pre-intervention (baseline) and twice post-intervention (at 24-28 weeks and 32-36 weeks of gestation), as well as birthweight within 24 h of birth. We examined the relationship between the average prenatal exposure and birthweight or weight-for-gestational age Z scores using multivariate-regression models, controlling for the mother's age, nulliparity, diet diversity, food insecurity, BMI, the mother's education, neonate sex, haemoglobin, second-hand smoke, and geographical indicator for randomisation strata. FINDINGS: Between March, 2018, and February, 2020, 3200 pregnant women were recruited. An interquartile increase in the average prenatal exposure to PM2·5 (74·5 µg/m3) was associated with a reduction in birthweight and gestational age Z scores (birthweight: -14·8 g [95% CI -28·7 to -0·8]; gestational age Z scores: -0·03 [-0·06 to 0·00]), as was an interquartile increase in black carbon (7·3 µg/m3; -21·9 g [-37·7 to -6·1]; -0·05 [-0·08 to -0·01]). Carbon monoxide exposure was not associated with these outcomes (1·7; -3·1 [-12·1 to 5·8]; -0·003 [-0·023 to 0·017]). INTERPRETATION: Continuing efforts are needed to reduce HAP exposure alongside other drivers of low birthweight in low-income and middle-income countries. FUNDING: US National Institutes of Health (1UM1HL134590) and the Bill & Melinda Gates Foundation (OPP1131279).

Liquefied Petroleum Gas or Biomass for Cooking and Effects on Birth Weight.

BACKGROUND: Exposure during pregnancy to household air pollution caused by the burning of solid biomass fuel is associated with adverse health outcomes, including low birth weight. Whether the replacement of a biomass cookstove with a liquefied petroleum gas (LPG) cookstove would result in an increase in birth weight is unclear. METHODS: We performed a randomized, controlled trial involving pregnant women (18 to <35 years of age and at 9 to <20 weeks' gestation as confirmed on ultrasonography) in Guatemala, India, Peru, and Rwanda. The women were assigned in a 1:1 ratio to use a free LPG cookstove and fuel (intervention group) or to continue using a biomass cookstove (control group). Birth weight, one of four prespecified primary outcomes, was the primary outcome for this report; data for the other three outcomes are not yet available. Birth weight was measured within 24 hours after birth. In addition, 24-hour personal exposures to fine particulate matter (particles with a diameter of ≤2.5 µm [PM2.5]), black carbon, and carbon monoxide were measured at baseline and twice during pregnancy. RESULTS: A total of 3200 women underwent randomization; 1593 were assigned to the intervention group, and 1607 to the control group. Uptake of the intervention was nearly complete, with traditional biomass cookstoves being used at a median rate of less than 1 day per month. After randomization, the median 24-hour personal exposure to fine particulate matter was 23.9 µg per cubic meter in the intervention group and 70.7 µg per cubic meter in the control group. Among 3061 live births, a valid birth weight was available for 94.9% of the infants born to women in the intervention group and for 92.7% of infants born to those in the control group. The mean (±SD) birth weight was 2921±474.3 g in the intervention group and 2898±467.9 g in the control group, for an adjusted mean difference of 19.6 g (95% confidence interval, -10.1 to 49.2). CONCLUSIONS: The birth weight of infants did not differ significantly between those born to women who used LPG cookstoves and those born to women who used biomass cookstoves. (Funded by the National Institutes of Health and the Bill and Melinda Gates Foundation; HAPIN ClinicalTrials.gov number, NCT02944682.).

Biomonitoring Human Exposure to Household Air Pollution and Association with Self-reported Health Symptoms - A Stove Intervention Study in Peru.

BACKGROUND: Household air pollution (HAP) from indoor biomass stoves contains harmful pollutants, such as polycyclic aromatic hydrocarbons (PAHs), and is a leading risk factor for global disease burden. We used biomonitoring to assess HAP exposure and association with self-reported symptoms in 334 non-smoking Peruvian women to evaluate the efficacy of a stove intervention program. METHODS: We conducted a cross-sectional study within the framework of a community randomized control trial. Using urinary PAH metabolites (OH-PAHs) as the exposure biomarkers, we investigated whether the intervention group (n=155, with new chimney-equipped stoves) were less exposed to HAP compared to the control group (n=179, with mostly open-fire stoves). We also estimated associations between the exposure biomarkers, risk factors, and self-reported health symptoms, such as recent eye conditions, respiratory conditions, and headache. RESULTS: We observed reduced headache and ocular symptoms in the intervention group than the control group. Urinary 2-naphthol, a suggested biomarker for inhalation PAH exposure, was significantly lower in the intervention group (GM with 95% CI: 13.4 [12.3, 14.6] µg/g creatinine) compared to control group (16.5 [15.0, 18.0] µg/g creatinine). Stove type and/or 2-naphthol was associated with a number of self-reported symptoms, such as red eye (adjusted OR with 95% CI: 3.80 [1.32, 10.9]) in the past 48h. CONCLUSIONS: Even with the improved stoves, the biomarker concentrations in this study far exceeded those of the general populations and were higher than a no-observed-genotoxic-effect-level, indicating high exposure and a potential for increased cancer risk in the population.

The role of influenza and parainfluenza infections in nasopharyngeal pneumococcal acquisition among young children.

BACKGROUND: Animal models suggest that influenza infection favors nasopharyngeal acquisition of pneumococci. We assessed this relationship with influenza and other respiratory viruses in young children. METHODS: A case-control study was nested within a prospective cohort study of acute respiratory illness (ARI) in Andean children <3 years of age (RESPIRA-PERU study). Weekly household visits were made to identify ARI and obtain nasal swabs for viral detection using real-time reverse-transcription polymerase chain reaction. Monthly nasopharyngeal (NP) samples were obtained to assess pneumococcal colonization. We determined whether specific respiratory viral ARI episodes occurring within the interval between NP samples increased the risk of NP acquisition of new pneumococcal serotypes. RESULTS: A total of 729 children contributed 2128 episodes of observation, including 681 pneumococcal acquisition episodes (new serotype, not detected in prior sample), 1029 nonacquisition episodes (no colonization or persistent colonization with the same serotype as the prior sample), and 418 indeterminate episodes. The risk of pneumococcal acquisition increased following influenza-ARI (adjusted odds ratio [AOR], 2.19; 95% confidence interval [CI], 1.02-4.69) and parainfluenza-ARI (AOR, 1.86; 95% CI, 1.15-3.01), when compared with episodes without ARI. Other viral infections (respiratory syncytial virus, human metapneumovirus, human rhinovirus, and adenovirus) were not associated with acquisition. CONCLUSIONS: Influenza and parainfluenza ARIs appeared to facilitate pneumococcal acquisition among young children. As acquisition increases the risk of pneumococcal diseases, these observations are pivotal in our attempts to prevent pneumococcal disease.

A household-based study of acute viral respiratory illnesses in Andean children.

BACKGROUND: Few community studies have measured the incidence, severity and etiology of acute respiratory illness (ARI) among children living at high-altitude in remote rural settings. METHODS: We conducted active, household-based ARI surveillance among children aged <3 years in rural highland communities of San Marcos, Cajamarca, Peru from May 2009 through September 2011 (RESPIRA-PERU study). ARI (defined by fever or cough) were considered lower respiratory tract infections if tachypnea, wheezing, grunting, stridor or retractions were present. Nasal swabs collected during ARI episodes were tested for respiratory viruses by real-time, reverse-transcriptase polymerase chain reaction. ARI incidence was calculated using Poisson regression. RESULTS: During 755.1 child-years of observation among 892 children in 58 communities, 4475 ARI were observed, yielding an adjusted incidence of 6.2 ARI/child-year (95% confidence interval: 5.9-6.5). Families sought medical care for 24% of ARI, 4% were classified as lower respiratory tract infections and 1% led to hospitalization. Of 5 deaths among cohort children, 2 were attributed to ARI. One or more respiratory viruses were detected in 67% of 3957 samples collected. Virus-specific incidence rates per 100 child-years were: rhinovirus, 236; adenovirus, 73; parainfluenza virus, 46; influenza, 37; respiratory syncytial virus, 30 and human metapneumovirus, 17. Respiratory syncytial virus, metapneumovirus and parainfluenza virus 1-3 comprised a disproportionate share of lower respiratory tract infections compared with other etiologies. CONCLUSIONS: In this high-altitude rural setting with low-population density, ARI in young children were common, frequently severe and associated with a number of different respiratory viruses. Effective strategies for prevention and control of these infections are needed.