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.).

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.).

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.

Estimating personal exposures to household air pollution and plastic garbage burning among adolescent girls in Jalapa, Guatemala.

Waste collection services are uncommon in rural areas of low-resource countries, causing waste accumulation and subsequent dumping and burning of garbage. Air pollution from household garbage burning, including plastics, has been observed in Jalapa, Guatemala in addition to household air pollution (HAP) from cooking. Adolescent girls often help with these cooking and household tasks, but little is known about their exposures. We characterized 24-h exposures to HAP and household garbage burning in adolescent girls by measuring fine particulate matter (PM2.5), black carbon (BC), urinary biomarkers of polycyclic aromatic hydrocarbons (PAHs), bisphenol A (BPA), and phthalates. We recruited 60 girls between 13 and 17 years of age who helped with cooking activities and lived with participants of the Household Air Pollution Intervention Network (HAPIN) trial. We recruited n = 30 girls each from the control (wood-burning stove) and intervention (liquefied petroleum gas stove) arms. We also measured real-time kitchen concentrations of BC in 20 homes (33%). PM2.5 and BC were measured in n = 21 control and n = 20 intervention participants. Median concentrations of personal PM2.5 and BC and kitchen BC were lower (p < 0.05) in the intervention arm by 87%, 80%, and 85%, respectively. PAH metabolite concentrations were lower (p < 0.001) for all nine metabolites in intervention (n = 26) compared to control participants (n = 29). Urinary BPA concentrations were 66% higher in participants who reported using cosmetics (p = 0.02), and phthalate concentrations were 63% higher in participants who had reported using hair products during the sample period (p = 0.05). Our results suggest that gas stoves can reduce HAP exposures among adolescents who are not primary cooks at home. Biomarkers of plastic exposure were not associated with intervention status, but some were elevated compared to age- and sex-matched participants of the National Health and Nutrition Examination Survey (NHANES).

Biomass smoke exposure and somatic growth among children: The RESPIRE and CRECER prospective cohort studies in rural Guatemala.

BACKGROUND: Cooking-related biomass smoke is a major source of household air pollution (HAP) and an important health hazard. Prior studies identified associations between HAP exposure and childhood stunting; less is known for underweight and wasting. Few studies had personal HAP measurements. METHODS: 557 households in rural Guatemala were enrolled in the CRECER study, the follow-up study of the RESPIRE randomized intervention trial. They were assigned to three groups that received chimney stoves at different ages of the study children. Multiple personal carbon monoxide (CO) exposure measurements were used as proxies for HAP exposures. Children's heights and weights were measured from 24 to 60 months of age. Height-for-age z-score (HAZ), weight-for-age z-score (WAZ), and weight-for-height z-score (WHZ) were calculated based on the World Health Organization's Multicentre Growth Reference Study. HAZ, WAZ, and WHZ below -2 were classified as stunting, underweight, and wasting, respectively. Generalized linear models and mixed effects models were applied. RESULTS: 541 children had valid anthropometric data, among whom 488 (90.2 %) were stunted, 192 (35.5 %) were underweight, and 2 (0.3 %) were wasted. A 1 ppm higher average CO exposure was associated with a 0.21 lower HAZ (95 % CI: 0.17-0.25), a 0.13 lower WAZ (95 % CI: 0.10-0.17) and a 0.06 lower WHZ (95 % CI: 0.02-0.10).The associations for HAZ were stronger among boys (coefficient = -0.29, 95 % CI: -0.35 - -0.22) than among girls (coefficient = -0.15, 95 % CI: -0.20 - -0.10). A 1 ppm-year higher cumulative CO exposure was associated with a higher risk of moderate stunting among boys (OR = 1.27, 95 % CI: 1.05-1.59), but not among girls. DISCUSSION: In this rural Guatemalan population, higher HAP exposure was associated with lower HAZ and WAZ. The associations between HAP and HAZ/stunting were stronger among boys. Reducing HAP might benefit childhood somatic growth in rural populations of low-income countries.

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).

Household air pollution from solid cooking fuel use during gestation has been associated with adverse pregnancy and birth outcomes. The Household Air Pollution Intervention Network (HAPIN) trial was a randomized controlled trial of free liquefied petroleum gas (LPG) stoves and fuel in Guatemala, Peru, India, and Rwanda. A primary outcome of the main trial was to report the effects of the intervention on infant birth weight. Here we evaluate the effects of a LPG stove and fuel intervention during pregnancy on spontaneous abortion, postpartum hemorrhage, hypertensive disorders of pregnancy, and maternal mortality compared to women who continued to use solid cooking fuels. Pregnant women (18-34 years of age; gestation confirmed by ultrasound at 9-19 weeks) were randomly assigned to an intervention (n = 1593) or control (n = 1607) arm. Intention-to-treat analyses compared outcomes between the two arms using log-binomial models. Among the 3195 pregnant women in the study, there were 10 spontaneous abortions (7 intervention, 3 control), 93 hypertensive disorders of pregnancy (47 intervention, 46 control), 11 post postpartum hemorrhage (5 intervention, 6 control) and 4 maternal deaths (3 intervention, 1 control). Compared to the control arm, the relative risk of spontaneous abortion among women randomized to the intervention was 2.32 (95% confidence interval (CI): 0.60, 8.96), hypertensive disorders of pregnancy 1.02 (95% CI: 0.68, 1.52), postpartum hemorrhage 0.83 (95% CI: 0.25, 2.71) and 2.98 (95% CI: 0.31, 28.66) for maternal mortality. In this study, we found that adverse maternal outcomes did not differ based on randomized stove type across four country research sites.

Post-birth exposure contrasts for children during the Household Air Pollution Intervention Network randomized controlled trial.

Exposure to household air pollution is a leading cause of ill-health globally. The Household Air Pollution Intervention Network (HAPIN) randomized controlled trial evaluated the impact of a free liquefied petroleum gas stove and fuel intervention on birth outcomes and maternal and child health. As part of HAPIN, an extensive exposure assessment was conducted. Here, we report on PM 2.5 and CO exposures of young children (≤ 15 months old) reconstructed using a Bluetooth-beacon based time-activity monitoring system coupled with microenvironmental pollutant monitors. Median (IQR) exposures to PM 2.5 were 65.1 (33 - 128.2) µg/m 3 in the control group and 22.9 (17.2 - 35.3) µg/m3 in the intervention group; for CO, median (IQR) exposures were 1.1 (0.3 - 2.9) ppm and 0.2 (0 - 0.7) ppm for control and intervention group, respectively. Exposure reductions were stable over time and consistent with previous findings for the children's mothers. In the intervention group, 75% of children's reconstructed exposures were below the WHO interim target guideline value of 35 µg/m 3 , while 26% were below the standard in the control group. Our findings suggest that an LPG fuel and stove intervention can substantially reduce children's exposure to household air pollution.

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).

A rare isocyanide derived from an unprecedented neutral yttrium(ii) bis(amide) complex.

A room temperature stable complex formulated as Y(NHAr*)2 has been prepared, where Ar* = 2,6-(2,4,6-(iPr)3C6H2)C6H3, by KC8 reduction of ClY(NHAr*)2. Based on EPR evidence, Y(NHAr*)2 is an example of a d1 Y(ii) complex with significant delocalization of the unpaired electron density from the metal to the ligand. The isolation of molecular divalent metal complexes is challenging for rare earth elements such as yttrium. In fact, stabilization of the divalent state requires judicious ligand design that allows the metal center to be coordinatively saturated. Divalent rare earth elements tend to be reactive towards various substrates. Interestingly, Y(NHAr*)2 reacts as a radical donor towards t BuNC to generate an unusual yttrium isocyanide complex, CNY(NHAr*)2, based on spectroscopic evidence and single-crystal X-ray diffraction data.

Seroprevalence of high incidence congenital infections among pregnant women in Coatepeque, Guatemala and surrounding areas, 2017-2018.

Maternal infections during pregnancy can potentially cause birth defects and severe adverse effects in infants. From 2017 to 2018, we investigated the seroprevalence of five antibodies among 436 mother-infant pairs enrolled in a pregnancy cohort study in Coatepeque, Guatemala. Upon enrollment (< 20 weeks gestational age) and shortly after delivery, we measured the prevalence of IgG and IgM antibodies against Toxoplasma gondii (T. gondii), rubella, and cytomegalovirus (CMV) in mothers and newborns and used rapid tests to detect HIV and syphilis (Treponema pallidum) in mothers. The mean cohort age was 24.5 years. Maternal T. gondii IgM and IgG seropositivity was 1.9% and 69.7%, respectively. No women were positive for HIV, syphilis, or rubella IgM. Maternal rubella IgG seropositivity was 80.8% and significantly increased with age. Maternal CMV IgM and IgG seropositivity were 2.3% and 99.5%, respectively. Of the 323 women tested at both timepoints, IgM reactivation occurred in one woman for T. gondii infection and in eight for CMV. No newborn was seropositive for CMV IgM or rubella IgM. One newborn was seropositive for T. gondii IgM. Congenital T. gondii and CMV infections are important public health issues for pregnant women, newborns, and healthcare providers in Coatepeque and Guatemala.

Plastic waste generation and emissions from the domestic open burning of plastic waste in Guatemala.

Domestic, or household-level, open burning of plastic waste is a source of air pollutants and greenhouse gases that are often neglected in emission inventories. Domestic open burning is a considerable concern in Guatemala due to the lack of access to waste collection services, particularly in rural areas. This paper offers the first attempt to estimate emissions from the domestic open burning of waste at the city and departmental levels in Guatemala. Data were collected from the Xalapán region of Jalapa, Guatemala and analyzed to determine the change in plastic waste generation over time as well as the socioeconomic factors that may affect the extent of plastic waste generation and burning. The annual per capita masses of plastic waste burned were used to estimate emissions from domestic open burning of plastic waste in the region of Xalapán, the cities of Jutiapa and Guatemala city, and all 22 departments in Guatemala. Our results show that rural areas burn more waste domestically, likely because of a lack of access to waste collection, and 30.4% of OC, 24.0% of BC, 23.6% of PM2.5, and 2.4% of CO2 emissions in Guatemala may not be accounted for by excluding open plastic burning as a source.

Lung Ultrasound Protocol and Quality Control of Image Interpretation Using an Adjudication Panel in the Household Air Pollution Intervention Network (HAPIN) Trial.

OBJECTIVE: Lung ultrasound (LUS) is an alternative to chest radiography to confirm a diagnosis of pneumonia. For research and disease surveillance, methods to use LUS to diagnose pneumonia are needed. METHODS: In the Household Air Pollution Intervention Network (HAPIN) trial, LUS was used to confirm a clinical diagnosis of severe pneumonia in infants. We developed a standardized definition of pneumonia, protocols for recruitment and training of sonographers, along with LUS image acquisition and interpretation. We use a blinded panel approach to interpretation with LUS cine-loops randomized to non-scanning sonographers with expert review. DISCUSSION: We obtained 357 lung ultrasound scans: 159, 8 and 190 scans were collected in Guatemala, Peru and Rwanda, respectively. The diagnosis of primary endpoint pneumonia (PEP) required an expert tie breaker in 181 scans (39%). PEP was diagnosed in 141 scans (40%), not diagnosed in 213 (60%), with 3 scans (<1%) deemed uninterpretable. Agreement among the two blinded sonographers and the expert reader in Guatemala, Peru and Rwanda was 65%, 62% and 67%, with a prevalence-and-bias-corrected kappa of 0.30, 0.24 and 0.33, respectively. CONCLUSION: Use of standardized imaging protocols, training and an adjudication panel resulted in high confidence for the diagnosis of pneumonia using LUS.

Baseline associations between household air pollution exposure and blood pressure among pregnant women in the Household Air Pollution Intervention Network (HAPIN) multi-country randomized controlled trial.

Cooking and heating using solid fuels can result in dangerous levels of exposure to household air pollution (HAP). HAPIN is an ongoing randomized controlled trial assessing the impact of a liquified petroleum gas stove and fuel intervention on HAP exposure and health in Guatemala, India, Peru, and Rwanda among households that rely primarily on solid cooking fuels. Given the potential impacts of HAP exposure on cardiovascular outcomes during pregnancy, we seek to characterize the relationship between personal exposures to HAP and blood pressure among pregnant women at baseline (prior to intervention) in the study. We assessed associations between PM2.5 (particulate matter with an aerodynamic diameter ≤2.5 µm), BC (black carbon), and CO (carbon monoxide) exposures and blood pressure at baseline, prior to intervention, among 3195 pregnant women between 9 and 19 weeks of gestation. We measured 24-hour personal exposure to PM2.5/BC/CO and gestational blood pressure. Multivariable linear regression models were used to evaluate associations between personal exposures to three air pollutants and blood pressure parameters. Trial-wide, we found moderate increases in systolic blood pressure (SBP) and decreases in diastolic blood pressure (DBP) as exposure to PM2.5, BC, and CO increased. None of these associations, however, were significant at the 0.05 level. HAP exposure and blood pressure associations were inconsistent in direction and magnitude within each country. We observed effect modification by body mass index (BMI) in India and Peru. Compared to women with normal weights, obese women in India and Peru (but not in Rwanda or Guatemala) had higher SBP per unit increase in log transformed PM2.5 and BC exposures. We did not find a cross-sectional association between HAP exposure and blood pressure in pregnant women; however, HAP may be associated with higher blood pressure in pregnant women who are obese, but this increase was not consistent across settings.

Impact of simulated flight conditions on supraventricular and ventricular ectopy.

Though billions of passengers and crew travel by air each year and are exposed to altitude equivalents of 7000-8000 feet, the health impact of cabin oxygenation levels has not been well studied. The hypoxic environment may produce ectopic heartbeats that may increase the risk of acute in-flight cardiac events. We enrolled forty older and at-risk participants under a block-randomized crossover design in a hypobaric chamber study to examine associations between flight oxygenation and both ventricular (VE) and supraventricular ectopy (SVE). We monitored participant VE and SVE every 5 min under both flight and control conditions to investigate the presence and rate of VE and SVE. While the presence of VE did not differ according to condition, the presence of SVE was higher during flight conditions (e.g. OR ratio = 1.77, 95% CI: 1.21, 2.59 for SVE couplets). Rates of VE and SVE were higher during flight conditions (e.g. RR ratio = 1.25, 95% CI: 1.03, 1.52 for VE couplets, RR ratio = 1.76, 95% CI: 1.39, 2.22 for SVE couplets). The observed higher presence and rate of ectopy tended to increase with duration of the flight condition. Further study of susceptible passengers and crew may elucidate the specific associations between intermittent or sustained ectopic heartbeats and hypoxic pathways.

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.).

Exposure Contrasts of Pregnant Women during the Household Air Pollution Intervention Network Randomized Controlled Trial.

BACKGROUND: Exposure to PM2.5 arising from solid fuel combustion is estimated to result in ∼2.3 million premature deaths and 91 million lost disability-adjusted life years annually. Interventions attempting to mitigate this burden have had limited success in reducing exposures to levels thought to provide substantive health benefits. OBJECTIVES: This paper reports exposure reductions achieved by a liquified petroleum gas (LPG) stove and fuel intervention for pregnant mothers in the Household Air Pollution Intervention Network (HAPIN) randomized controlled trial. METHODS: The HAPIN trial included 3,195 households primarily using biomass for cooking in Guatemala, India, Peru, and Rwanda. Twenty-four-hour exposures to PM2.5, carbon monoxide (CO), and black carbon (BC) were measured for pregnant women once before randomization into control (n=1,605) and LPG (n=1,590) arms and twice thereafter (aligned with trimester). Changes in exposure were estimated by directly comparing exposures between intervention and control arms and by using linear mixed-effect models to estimate the impact of the intervention on exposure levels. RESULTS: Median postrandomization exposures of particulate matter (PM) with aerodynamic diameter ≤2.5µm (PM2.5) in the intervention arm were lower by 66% at the first (71.5 vs. 24.1 µg/m3), and second follow-up visits (69.5 vs. 23.7 µg/m3) compared to controls. BC exposures were lower in the intervention arm by 72% (9.7 vs. 2.7 µg/m3) and 70% (9.6 vs. 2.8 µg/m3) at the first and second follow-up visits, respectively, and carbon monoxide exposure was 82% lower at both visits (1.1 vs. 0.2 ppm) in comparison with controls. Exposure reductions were consistent over time and were similar across research locations. DISCUSSION: Postintervention PM2.5 exposures in the intervention arm were at the lower end of what has been reported for LPG and other clean fuel interventions, with 69% of PM2.5 samples falling below the World Health Organization Annual Interim Target 1 of 35 µg/m3. This study indicates that an LPG intervention can reduce PM2.5 exposures to levels at or below WHO targets. https://doi.org/10.1289/EHP10295.

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.

Elevated blood pressure (BP) is a leading risk factor for the global burden of disease. Household air pollution (HAP), resulting from the burning of biomass fuels, may be an important cause of elevated BP in resource-poor communities. We examined the exposure-response relationship of personal exposures to HAP -fine particulate matter (PM2.5), carbon monoxide (CO), and black carbon (BC) - with BP measures in women aged 40-79 years across four resource-poor settings in Guatemala, Peru, India and Rwanda. BP was obtained within a day of 24-h personal exposure measurements at baseline, when participants were using biomass for cooking. We used generalized additive models to characterize the shape of the association between BP and HAP, accounting for the interaction of personal exposures and age and adjusting for a priori identified confounders. A total of 418 women (mean age 52.2 ± 7.9 years) were included in this analysis. The interquartile range of exposures to PM2.5 was 42.9-139.5 µg/m3, BC was 6.4-16.1 µg/m3, and CO was 0.5-2.9 ppm. Both SBP and PP were positively associated with PM2.5 exposure in older aged women, achieving statistical significance around 60 years of age. The exact threshold varied by BP measure and PM2.5 exposures being compared. For example, SBP of women aged 65 years was on average 10.8 mm Hg (95% CI 1.0-20.6) higher at 232 µg/m3 of PM2.5 exposure (90th percentile) when compared to that of women of the same age with personal exposures of 10 µg/m3. PP in women aged 65 years was higher for exposures ≥90 µg/m3, with mean differences of 6.1 mm Hg (95% CI 1.8-10.5) and 9.2 mm Hg (95% CI 3.3-15.1) at 139 (75th percentile) and 232 µg/m3 (90th percentile) respectively, when compared to that of women of the same age with PM2.5 exposures of 10 µg/m3. Our findings suggest that reducing HAP exposures may help to reduce BP, particularly among older women.

Characterization of a [4Fe-4S]-dependent LarE sulfur insertase that facilitates nickel-pincer nucleotide cofactor biosynthesis in Thermotoga maritima.

Sulfur-insertion reactions are essential for the biosynthesis of several cellular metabolites, including enzyme cofactors. In Lactobacillus plantarum, a sulfur-containing nickel-pincer nucleotide (NPN) cofactor is used as a coenzyme of lactic acid racemase, LarA. During NPN biosynthesis in L. plantarum, sulfur is transferred to a nicotinic acid-derived substrate by LarE, which sacrifices the sulfur atom of its single cysteinyl side chain, forming a dehydroalanine residue. Most LarE homologs contain three conserved cysteine residues that are predicted to cluster at the active site; however, the function of this cysteine cluster is unclear. In this study, we characterized LarE from Thermotoga maritima (LarETm) and show that it uses these three conserved cysteine residues to bind a [4Fe-4S] cluster that is required for sulfur transfer. Notably, we found LarETm retains all side chain sulfur atoms, in contrast to LarELp. We also demonstrate that when provided with L-cysteine and cysteine desulfurase from Escherichia coli (IscSEc), LarETm functions catalytically with IscSEc transferring sulfane sulfur atoms to LarETm. Native mass spectrometry results are consistent with a model wherein the enzyme coordinates sulfide at the nonligated iron atom of the [4Fe-4S] cluster, forming a [4Fe-5S] species, and transferring the noncore sulfide to the activated substrate. This proposed mechanism is like that of TtuA that catalyzes sulfur transfer during 2-thiouridine synthesis. In conclusion, we found that LarE sulfur insertases associated with NPN biosynthesis function either by sacrificial sulfur transfer from the protein or by transfer of a noncore sulfide bound to a [4Fe-4S] cluster.

Effects of a Liquefied Petroleum Gas Stove Intervention on Gestational Blood Pressure: Intention-to-Treat and Exposure-Response Findings From the HAPIN Trial.

BACKGROUND: Approximately 3 to 4 billion people worldwide are exposed to household air pollution, which has been associated with increased blood pressure (BP) in pregnant women in some studies. METHODS: We recruited 3195 pregnant women in Guatemala, India, Peru, and Rwanda and randomly assigned them to intervention or control groups. The intervention group received a gas stove and fuel during pregnancy, while the controls continued cooking with solid fuels. We measured BP and personal exposure to PM2.5, black carbon and carbon monoxide 3× during gestation. We conducted an intention-to-treat and exposure-response analysis to determine if household air pollution exposure was associated with increased gestational BP. RESULTS: Median 24-hour PM2.5 dropped from 84 to 24 µg/m3 after the intervention; black carbon and carbon monoxide decreased similarly. Intention-to-treat analyses showed an increase in systolic BP and diastolic BP in both arms during gestation, as expected, but the increase was greater in intervention group for both systolic BP (0.69 mm Hg [0.03-1.35]; P=0.04) and diastolic BP (0.62 mm Hg [0.05-1.19]; P=0.03). The exposure-response analyses suggested that higher exposures to household air pollution were associated with moderately higher systolic BP and diastolic BP; however, none of these associations reached conventional statistical significance. CONCLUSIONS: In intention-to-treat, we found higher gestational BP in the intervention group compared with controls, contrary to expected. In exposure-response analyses, we found a slight increase in BP with higher exposure, but it was not statistically significant. Overall, an intervention with gas stoves did not markedly affect gestational BP.