Household Air Pollution and Child Lung Function: The Ghana Randomized Air Pollution and Health Study.

Rationale: The impact of a household air pollution (HAP) stove intervention on child lung function has been poorly described. Objectives: To assess the effect of a HAP stove intervention for infants prenatally to age 1 on, and exposure-response associations with, lung function at child age 4. Methods: The Ghana Randomized Air Pollution and Health Study randomized pregnant women to liquefied petroleum gas (LPG), improved biomass, or open-fire (control) stove conditions through child age 1. We quantified HAP exposure by repeated maternal and child personal carbon monoxide (CO) exposure measurements. Children performed oscillometry, an effort-independent lung function measurement, at age 4. We examined associations between Ghana Randomized Air Pollution and Health Study stove assignment and prenatal and infant CO measurements and oscillometry using generalized linear regression models. We used reverse distributed lag models to examine time-varying associations between prenatal CO and oscillometry. Measurements and Main Results: The primary oscillometry measure was reactance at 5 Hz, X5, a measure of elastic and inertial lung properties. Secondary measures included total, large airway, and small airway resistance at 5 Hz, 20 Hz, and the difference in resistance at 5 Hz and 20 Hz (R5, R20, and R5-20, respectively); area of reactance (AX); and resonant frequency. Of the 683 children who attended the lung function visit, 567 (83%) performed acceptable oscillometry. A total of 221, 106, and 240 children were from the LPG, improved biomass, and control arms, respectively. Compared with control, the improved biomass stove condition was associated with lower reactance at 5 Hz (X5 z-score: ß = -0.25; 95% confidence interval [CI] = -0.39, -0.11), higher large airway resistance (R20 z-score: ß = 0.34; 95% CI = 0.23, 0.44), and higher AX (AX z-score: ß = 0.16; 95% CI = 0.06, 0.26), which is suggestive of overall worse lung function. The LPG stove condition was associated with higher X5 (X5 score: ß = 0.16; 95% CI = 0.01, 0.31) and lower small airway resistance (R5-20 z-score: ß = -0.15; 95% CI = -0.30, 0.0), which is suggestive of better small airway function. Higher average prenatal CO exposure was associated with higher R5 and R20, and distributed lag models identified sensitive windows of exposure between CO and X5, R5, R20, and R5-20. Conclusions: These data support the importance of prenatal HAP exposure on child lung function. Clinical trial registered with www.clinicaltrials.gov (NCT01335490).

Household Air Pollution Interventions to Improve Health in Low- and Middle-Income Countries: An Official American Thoracic Society Research Statement.

Background: An estimated 3 billion people, largely in low- and middle-income countries, rely on unclean fuels for cooking, heating, and lighting to meet household energy needs. The resulting exposure to household air pollution (HAP) is a leading cause of pneumonia, chronic lung disease, and other adverse health effects. In the last decade, randomized controlled trials of clean cooking interventions to reduce HAP have been conducted. We aim to provide guidance on how to interpret the findings of these trials and how they should inform policy makers and practitioners.Methods: We assembled a multidisciplinary working group of international researchers, public health practitioners, and policymakers with expertise in household air pollution from within academia, the American Thoracic Society, funders, nongovernmental organizations, and global organizations, including the World Bank and the World Health Organization. We performed a literature search, convened four sessions via web conference, and developed consensus conclusions and recommendations via the Delphi method.Results: The committee reached consensus on 14 conclusions and recommendations. Although some trials using cleaner-burning biomass stoves or cleaner-cooking fuels have reduced HAP exposure, the committee was divided (with 55% saying no and 45% saying yes) on whether the studied interventions improved measured health outcomes.Conclusions: HAP is associated with adverse health effects in observational studies. However, it remains unclear which household energy interventions reduce exposure, improve health, can be scaled, and are sustainable. Researchers should engage with policy makers and practitioners working to scale cleaner energy solutions to understand and address their information needs.

Association between malaria and household air pollution interventions in a predominantly rural area of Ghana.

BACKGROUND: Though anecdotal evidence suggests that smoke from HAP has a repellent effect on mosquitoes, very little work has been done to assess the effect of biomass smoke on malaria infection. The study, therefore, sought to investigate the hypothesis that interventions to reduce household biomass smoke may have an unintended consequence of increasing placental malaria or increase malaria infection in the first year of life. METHODS: This provides evidence from a randomized controlled trial among 1414 maternal-infant pairs in the Kintampo North and Kintampo South administrative areas of Ghana. Logistic regression was used to assess the association between study intervention assignment (LPG, Biolite or control) and placental malaria. Finally, an extended Cox model was used to assess the association between study interventions and all episodes of malaria parasitaemia in the first year of infant's life. RESULTS: The prevalence of placental malaria was 24.6%. Out of this, 20.8% were acute infections, 18.7% chronic infections and 60.5% past infections. The study found no statistical significant association between the study interventions and all types of placental malaria (OR = 0.88; 95% CI 0.59-1.30). Of the 1165 infants, 44.6% experienced at least one episode of malaria parasitaemia in the first year of life. The incidence of first and/or only episode of malaria parasitaemia was however found to be similar among the study arms. CONCLUSION: The findings suggest that cookstove interventions for pregnant women and infants, when combined with additional malaria prevention strategies, do not lead to an increased risk of malaria among pregnant women and infants.

Prenatal Household Air Pollution Is Associated with Impaired Infant Lung Function with Sex-Specific Effects. Evidence from GRAPHS, a Cluster Randomized Cookstove Intervention Trial.

RATIONALE: Approximately 2.8 billion people are exposed daily to household air pollution from polluting cookstoves. The effects of prenatal household air pollution on lung development are unknown. OBJECTIVES: To prospectively examine associations between prenatal household air pollution and infant lung function and pneumonia in rural Ghana. METHODS: Prenatal household air pollution exposure was indexed by serial maternal carbon monoxide personal exposure measurements. Using linear regression, we examined associations between average prenatal carbon monoxide and infant lung function at age 30 days, first in the entire cohort (n = 384) and then stratified by sex. Quasi-Poisson generalized additive models explored associations between infant lung function and pneumonia. MEASUREMENTS AND MAIN RESULTS: Multivariable linear regression models showed that average prenatal carbon monoxide exposure was associated with reduced time to peak tidal expiratory flow to expiratory time (ß = -0.004; P = 0.01), increased respiratory rate (ß = 0.28; P = 0.01), and increased minute ventilation (ß = 7.21; P = 0.05), considered separately, per 1 ppm increase in average prenatal carbon monoxide. Sex-stratified analyses suggested that girls were particularly vulnerable (time to peak tidal expiratory flow to expiratory time: ß = -0.003, P = 0.05; respiratory rate: ß = 0.36, P = 0.01; minute ventilation: ß = 11.25, P = 0.01; passive respiratory compliance normalized for body weight: ß = 0.005, P = 0.01). Increased respiratory rate at age 30 days was associated with increased risk for physician-assessed pneumonia (relative risk, 1.02; 95% confidence interval, 1.00-1.04) and severe pneumonia (relative risk, 1.04; 95% confidence interval, 1.00-1.08) in the first year of life. CONCLUSIONS: Increased prenatal household air pollution exposure is associated with impaired infant lung function. Altered infant lung function may increase risk for pneumonia in the first year of life. These findings have implications for future respiratory health. Clinical trial registered with www.clinicaltrials.gov (NCT 01335490).

Prenatal maternal stress and birth outcomes in rural Ghana: sex-specific associations.

BACKGROUND: In developed countries, prenatal maternal stress has been associated with poor fetal growth, however this has not been evaluated in rural sub-Saharan Africa. We evaluated the effect of prenatal maternal stress on fetal growth and birth outcomes in rural Ghana. METHODS: Leveraging a prospective, rural Ghanaian birth cohort, we ascertained prenatal maternal negative life events, categorized scores as 0-2 (low stress; referent), 3-5 (moderate), and > 5 (high) among 353 pregnant women in the Kintampo North Municipality and Kintampo South District located within the middle belt of Ghana. We employed linear regression to determine associations between prenatal maternal stress and infant birth weight, head circumference, and length. We additionally examined associations between prenatal maternal stress and adverse birth outcome, including low birth weight, small for gestational age, or stillbirth. Effect modification by infant sex was examined. RESULTS: In all children, high prenatal maternal stress was associated with reduced birth length (ß = - 0.91, p = 0.04; p-value for trend = 0.04). Among girls, moderate and high prenatal maternal stress was associated with reduced birth weight (ß = - 0.16, p = 0.02; ß = - 0.18, p = 0.04 respectively; p-value for trend = 0.04) and head circumference (ß = - 0.66, p = 0.05; ß = - 1.02, p = 0.01 respectively; p-value for trend = 0.01). In girls, high prenatal stress increased odds of any adverse birth outcome (OR 2.41, 95% CI 1.01-5.75; p for interaction = 0.04). Sex-specific analyses did not demonstrate significant effects in boys. CONCLUSIONS: All infants, but especially girls, were vulnerable to effects of prenatal maternal stress on birth outcomes. Understanding risk factors for impaired fetal growth may help develop preventative public health strategies. TRIAL REGISTRATION: NCT01335490 (prospective registration). Date of Registration: April 14, 2011. Status of Registration: Completed.

Ambulatory monitoring demonstrates an acute association between cookstove-related carbon monoxide and blood pressure in a Ghanaian cohort.

BACKGROUND: Repeated exposure to household air pollution may intermittently raise blood pressure (BP) and affect cardiovascular outcomes. We investigated whether hourly carbon monoxide (CO) exposures were associated with acute increases in ambulatory blood pressure (ABP); and secondarily, if switching to an improved cookstove was associated with BP changes. We also evaluated the feasibility of using 24-h ambulatory blood pressure monitoring (ABPM) in a cohort of pregnant women in Ghana. METHODS: Participants were 44 women enrolled in the Ghana Randomized Air Pollution and Health Study (GRAPHS). For 27 of the women, BP was measured using 24-h ABPM; home blood pressure monitoring (HBPM) was used to measure BP in the remaining 17 women. Personal CO exposure monitoring was conducted alongside the BP monitoring. RESULTS: ABPM revealed that peak CO exposure (defined as ≥4.1 ppm) in the 2 hours prior to BP measurement was associated with elevations in hourly systolic BP (4.3 mmHg [95% CI: 1.1, 7.4]) and diastolic BP (4.5 mmHg [95% CI: 1.9, 7.2]), as compared to BP following lower CO exposures. Women receiving improved cookstoves had lower post-intervention SBP (within-subject change in SBP of -2.1 mmHg [95% CI: -6.6, 2.4] as compared to control), though this result did not reach statistical significance. 98.1% of expected 24-h ABPM sessions were successfully completed, with 92.5% of them valid according to internationally defined criteria. CONCLUSIONS: We demonstrate an association between acute exposure to carbon monoxide and transient increases in BP in a West African setting. ABPM shows promise as an outcome measure for assessing cardiovascular health benefits of cookstove interventions. TRIAL REGISTRATION: The GRAPHS trial was registered with clinicaltrials.gov on 13 April 2011 with the identifier NCT01335490 .

Prenatal Household Air Pollution Exposure and Childhood Blood Pressure in Rural Ghana.

BACKGROUND: The association between prenatal household air pollution (HAP) exposure and childhood blood pressure (BP) is unknown. OBJECTIVE: Within the Ghana Randomized Air Pollution and Health Study (GRAPHS) we examined time-varying associations between a) maternal prenatal and b) first-year-of-life HAP exposure with BP at 4 years of age and, separately, whether a stove intervention delivered prenatally and continued through the first year of life could improve BP at 4 years of age. METHODS: GRAPHS was a cluster-randomized cookstove intervention trial wherein n=1,414 pregnant women were randomized to one of two stove interventions: a) a liquefied petroleum gas (LPG) stove or improved biomass stove, or b) control (open fire cooking). Maternal HAP exposure over pregnancy and child HAP exposure over the first year of life was quantified by repeated carbon monoxide (CO) measurements; a subset of women (n=368) also performed one prenatal and one postnatal personal fine particulate matter (PM2.5) measurement. Systolic and diastolic BP (SBP and DBP) were measured in n=667 4-y-old children along with their PM2.5 exposure (n=692). We examined the effect of the intervention on resting BP z-scores. We also employed reverse distributed lag models to examine time-varying associations between a) maternal prenatal and b) first-year-of-life HAP exposure and resting BP z-scores. Among those with PM2.5 measures, we examined associations between PM2.5 and resting BP z-scores. Sex-specific effects were considered. RESULTS: Intention-to-treat analyses identified that DBP z-score at 4 years of age was lower among children born in the LPG arm (LPG ß=-0.20; 95% CI: -0.36, -0.03) as compared with those in the control arm, and females were most susceptible to the intervention. Higher CO exposure in late gestation was associated with higher SBP and DBP z-score at 4 years of age, whereas higher late-first-year-of-life CO exposure was associated with higher DBP z-score. In the subset with PM2.5 measurements, higher maternal postnatal PM2.5 exposure was associated with higher SBP z-scores. DISCUSSION: These findings suggest that prenatal and first-year-of-life HAP exposure are associated with child BP and support the need for reductions in exposure to HAP, with interventions such as cleaner cooking beginning in pregnancy. https://doi.org/10.1289/EHP13225.

Geospatial determinants of maternal and child exposure to fine particulate matter in Kintampo, Ghana: Levels within the household and community, by surrounding building density and near roadways.

BACKGROUND: Personal exposure to fine particulate matter (PM2.5) from household air pollution is well-documented in sub-Saharan Africa, but spatiotemporal patterns of exposure are poorly characterized. OBJECTIVE: We used paired GPS and personal PM2.5 data to evaluate changes in exposure across location-time environments (e.g., household and community, during cooking and non-cooking hours), building density and proximity to roadways. METHODS: Our study included 259 sessions of geolocated, gravimetrically-calibrated one-minute personal PM2.5 measurements from participants in the GRAPHS Child Lung Function Study. The household vicinity was defined using a 50-meter buffer around participants' homes. Community boundaries were developed using a spatial clustering algorithm applied to an open-source dataset of building footprints in Africa. For each GPS location, we estimated building density (500 m buffer) and proximity to roadways (100 m buffer). We estimated changes in PM2.5 exposure by location (household, community), time of day (morning/evening cooking hours, night), building density, and proximity to roadways using linear mixed effect models. RESULTS: Relative to nighttime household exposure, PM2.5 exposure during evening cooking hours was 2.84 (95%CI = 2.70-2.98) and 1.80 (95%CI = 1.54-2.10) times higher in the household and community, respectively. Exposures were elevated in areas with the highest versus lowest quartile of building density (FactorQ1vsQ4 = 1.60, 95%CI = 1.42-1.80). The effect of building density was strongest during evening cooking hours, and influenced levels in both the household and community (31% and 65% relative increase from Q1 to Q4, respectively). Being proximal to a trunk, tertiary or track roadway increased exposure by a factor of 1.16 (95%CI = 1.07-1.25), 1.68 (95%CI = 1.45-1.95) and 1.27 (95%CI = 1.06-1.53), respectively. IMPACT: Household air pollution from cooking with solid fuels in sub-Saharan Africa is a major environmental concern for maternal and child health. Our study advances previous knowledge by quantifying the impact of household cooking activities on air pollution levels in the community, and identifying two geographic features, building density and roadways, that contribute to maternal and child daily exposure. Household cooking contributes to higher air pollution levels in the community especially in areas with greater building density. Findings underscore the need for equitable clean household energy transitions that reach entire communities to reduce health risks from household and outdoor air pollution.

Identifying sensitive windows of prenatal household air pollution on birth weight and infant pneumonia risk to inform future interventions.

BACKGROUND: Prenatal household air pollution impairs birth weight and increases pneumonia risk however time-varying associations have not been elucidated and may have implications for the timing of public health interventions. METHODS: The Ghana Randomized Air Pollution and Health Study (GRAPHS) enrolled 1,414 pregnant women from Kintampo, Ghana and measured personal carbon monoxide (CO) exposure four times over pregnancy. Birth weight was measured within 72-hours of birth. Fieldworkers performed weekly pneumonia surveillance and referred sick children to study physicians. The primary pneumonia outcome was one or more physician-diagnosed severe pneumonia episode in the first year of life. We employed reverse distributed lag models to examine time-varying associations between prenatal CO exposure and birth weight and infant pneumonia risk. RESULTS: Analyses included n = 1,196 mother-infant pairs. In models adjusting for child sex; maternal age, body mass index (BMI), ethnicity and parity at enrollment; household wealth index; number of antenatal visits; and evidence of placental malaria, prenatal CO exposures from 15 to 20 weeks gestation were inversely associated with birth weight. Sex-stratified models identified a similar sensitive window in males and a window at 10-weeks gestation in females. In models adjusting for child sex, maternal age, BMI and ethnicity, household wealth index, gestational age at delivery and average postnatal child CO exposure, CO exposure during 34-39 weeks gestation were positively associated with severe pneumonia risk, especially in females. CONCLUSIONS: Household air pollution exposures in mid- and late- gestation are associated with lower birth weight and higher pneumonia risk, respectively. These findings support the urgent need for deployment of clean fuel stove interventions beginning in early pregnancy.

Using time-resolved monitor wearing data to study the effect of clean cooking interventions on personal air pollution exposures.

BACKGROUND: Personal monitoring can estimate individuals' exposures to environmental pollutants; however, accuracy depends on consistent monitor wearing, which is under evaluated. OBJECTIVE: To study the association between device wearing and personal air pollution exposure. METHODS: Using personal device accelerometry data collected in the context of a randomized cooking intervention in Ghana with three study arms (control, improved biomass, and liquified petroleum gas (LPG) arms; N = 1414), we account for device wearing to infer parameters of PM2.5 and CO exposure. RESULTS: Device wearing was positively associated with exposure in the control and improved biomass arms, but weakly in the LPG arm. Inferred community-level air pollution was similar across study arms (~45 µg/m3). The estimated direct contribution of individuals' cooking to PM2.5 exposure was 64 µg/m3 for the control arm, 74 µg/m3 for improved biomass, and 6 µg/m3 for LPG. Arm-specific average PM2.5 exposure at near-maximum wearing was significantly lower in the LPG arm as compared to the improved biomass and control arms. Analysis of personal CO exposure mirrored PM2.5 results. CONCLUSIONS: Personal monitor wearing was positively associated with average air pollution exposure, emphasizing the importance of high device wearing during monitoring periods and directly assessing device wearing for each deployment. SIGNIFICANCE: We demonstrate that personal monitor wearing data can be used to refine exposure estimates and infer unobserved parameters related to the timing and source of environmental exposures. IMPACT STATEMENTS: In a cookstove trial among pregnant women, time-resolved personal air pollution device wearing data were used to refine exposure estimates and infer unobserved exposure parameters, including community-level air pollution, the direct contribution of cooking to personal exposure, and the effect of clean cooking interventions on personal exposure. For example, in the control arm, while average 48 h personal PM2.5 exposure was 77 µg/m3, average predicted exposure at near-maximum daytime device wearing was 108 µg/m3 and 48 µg/m3 at zero daytime device wearing. Wearing-corrected average 48 h personal PM2.5 exposures were 50% lower in the LPG arm than the control and improved biomass and inferred direct cooking contributions to personal PM2.5 from LPG were 90% lower than the other arms. Our recommendation is that studies assessing personal exposures should examine the direct association between device wearing and estimated mean personal exposure.

Efficacy of a monovalent (D614) SARS-CoV-2 recombinant protein vaccine with AS03 adjuvant in adults: a phase 3, multi-country study.

Background: The literature on first generation COVID-19 vaccines show they were less effective against new SARS-CoV-2 variants of concern including Omicron (BA.1, BA.2, BA.4 and BA.5 subvariants). New vaccines developed against variant strains may provide cross-protection against emerging variants when used as boosters and facilitate vaccination across a range of countries, healthcare settings and populations. However, there are no data on such vaccines when used as a primary series. Methods: A global Phase 3, multi-stage efficacy study (NCT04904549) among adults (≥18 years) was conducted in 53 research centres in eight countries (United States, Honduras, Japan, Colombia, Kenya, India, Ghana, Nepal). Participants were randomized 1:1 to receive two intramuscular injections of a monovalent SARS-CoV-2 recombinant protein vaccine with AS03-adjuvant (10 µg of the spike (S) protein from the ancestral D614 strain) or placebo on Day 1 (D01) and Day 22 (D22). The primary efficacy endpoint was prevention of virologically confirmed SARS-CoV-2 infection with symptoms of COVID-19-like illness (CLI) ≥14 days after the second injection (post-dose 2 [PD2]) in participants who were SARS-CoV-2 naïve on D01 + D22. Safety and reactogenicity were also evaluated. Findings: Between May 26 and November 7, 2021, 10,114 participants received ≥1 study injection, and 9441 participants received both injections. 2108 (20.8%) participants were SARS-CoV-2 naïve at D01 and D22. The primary endpoint was analysed in a subset of the full analysis set (the modified full analysis set PD2 [mFAS-PD2], excluding participants who did not complete the vaccination schedule or received vaccination despite meeting one of the contraindication criteria, had onset of symptomatic COVID-19 between the first injection and before 14 days after the second injection, or participants who discontinued before 14 days after the second injection [n = 9377; vaccine, n = 4702; placebo, n = 4675]). Data were available for 2051 SARS-CoV-2 naïve and 7159 non-naïve participants. At the cut-off date (January 28, 2022), symptomatic COVID-19 was reported in 169 naïve participants (vaccine, n = 81; placebo, n = 88) ≥14 days PD2, with a vaccine efficacy (VE) of 15.3% (95% CI, -15.8; 38.2). VE regardless of D01/D22 serostatus was 32.9% (95% CI, 15.3; 47.0) and VE in non-naïve participants was 52.7% (95% CI, 31.2; 67.9). Viral genome sequencing was performed up to the data cut-off point and identified the infecting strain in 99/169 adjudicated cases in the PD2 naïve population (Delta [25], Omicron [72], other variants [3], one participant had infection with both Delta and Omicron variants and has been included in the totals for both Delta and Omicron). The vaccine was well-tolerated with an acceptable safety profile. Interpretation: In the context of changing circulating viral variants, it is challenging to induce protection in naïve individuals with a two-dose priming schedule based on the parental D614 strain. However, while the primary endpoint of this trial was not met, the results show that a monovalent D614 vaccine can still be of value in individuals previously exposed to SARS-CoV-2. Funding: This study was funded in whole or in part by Sanofi and by federal funds from the Biomedical Advanced Research and Development Authority, part of the office of the Administration for Strategic Preparedness and Response at the U.S. Department of Health and Human Services under contract number HHSO100201600005I, and in collaboration with the U.S. Department of Defense Joint Program Executive Office for Chemical, Biological, Radiological, and Nuclear Defense under contract number W15QKN-16-9-1002. The views presented here are those of the authors and do not purport to represent those of the Department of the Army, the Department of Health and Human Services, or the U.S. government.

Characterizing sleep-wake patterns in mothers and children in an agrarian community: results from the Ghana Randomized Air Pollution and Health Study.

STUDY OBJECTIVES: Several studies have examined sleep patterns in rural/indigenous communities, however little is known about sleep characteristics in women of reproductive age, and children within these populations. We investigate sleep-wake patterns in mothers and children (ages 3-5 years) leveraging data from the Ghana Randomized Air Pollution and Health Study (GRAPHS). METHODS: The GRAPHS cohort comprises of rural/agrarian communities in Ghana and collected multiday actigraphy in a subset of women and children to assess objective sleep-wake patterns. Data were scored using the Cole-Kripke and Sadeh algorithms for mothers/children. We report descriptive, baseline characteristics and objective sleep measures, compared by access to electricity/poverty status. RESULTS: We analyzed data for 58 mothers (mean age 33 ± 6.6) and 64 children (mean age 4 ± 0.4). For mothers, mean bedtime was 9:40 pm ± 56 min, risetime 5:46 am ± 40 min, and total sleep time (TST) was 6.3 h ± 46 min. For children, median bedtime was 8:07 pm (interquartile range [IQR]: 7:50,8:43), risetime 6:09 am (IQR: 5:50,6:37), and mean 24-h TST 10.44 h ± 78 min. Children with access to electricity had a reduced TST compared to those without electricity (p = 0.02). Mean bedtime was later for both mothers (p = 0.05) and children (p = 0.08) classified as poor. CONCLUSIONS: Mothers in our cohort demonstrated a shorter TST, and earlier bed/risetimes compared to adults in postindustrialized nations. In contrast, children had a higher TST compared to children in postindustrialized nations, also with earlier sleep-onset and offset times. Investigating objective sleep-wake patterns in rural/indigenous communities can highlight important differences in sleep health related to sex, race/ethnicity, and socioeconomic status, and help estimate the impact of industrialization on sleep in developed countries.

Poor early childhood growth is associated with impaired lung function: Evidence from a Ghanaian pregnancy cohort.

OBJECTIVES: Nearly 40% of African children under 5 are stunted. We leveraged the Ghana randomized air pollution and health study (GRAPHS) cohort to examine whether poorer growth was associated with worse childhood lung function. STUDY DESIGN: GRAPHS measured infant weight and length at birth and 3, 6, 9,12 months, and 4 years of age. At age 4 years, n = 567 children performed impulse oscillometry. We employed multivariable linear regression to estimate associations between birth and age 4 years anthropometry and lung function. Next, we employed latent class growth analysis (LCGA) to generate growth trajectories through age 4 years. We employed linear regression to examine associations between growth trajectory assignment and lung function. RESULTS: Birth weight and age 4 weight-for-age and height-for-age z-scores were inversely associated with airway resistance (e.g., R5 , or total airway resistance: birth weight ß = -0.90 cmH2O/L/s, 95% confidence interval [CI]: -1.64, -0.16 per 1 kg increase; and R20 , or large airway resistance: age 4 height-for-age ß = -0.40 cmH2O/L/s, 95% CI: -0.57, -0.22 per 1 unit z-score increase). Impaired growth trajectories identified through LCGA were associated with higher airway resistance, even after adjusting for age 4 body mass index. For example, children assigned to a persistently stunted trajectory had higher R5 (ß = 2.71 cmH2O/L/s, 95% CI: 1.07, 4.34) and R20 (ß = 1.43 cmH2O/L/s, 95% CI: 0.51, 2.36) as compared to normal. CONCLUSION: Children with poorer anthropometrics through to age 4 years had higher airway resistance in early childhood. These findings have implications for lifelong lung health, including pneumonia risk in childhood and reduced maximally attainable lung function in adulthood.

Corrigendum to "Prenatal household air pollutant exposure is associated with reduced size and gestational age at birth among a cohort of Ghanaian infants" [Environ. Int. 155 (2021) 106659].

[This corrects the article PMC8628363.].

Bacterial and Fungal Gut Community Dynamics Over the First 5 Years of Life in Predominantly Rural Communities in Ghana.

BACKGROUND: Bacterial and fungal microbiotas are increasingly recognized as important in health and disease starting early in life. However, microbiota composition has not yet been investigated in most rural, low-resource settings, and in such settings, bacterial and fungal microbiotas have not been compared. Thus, we applied 16S and ITS2 amplicon sequencing, respectively, to investigate bacterial and fungal fecal microbiotas in rural Ghanaian children cross-sectionally from birth to 5 years of age. Corresponding maternal fecal and breast milk microbiotas were additionally investigated. RESULTS: While bacterial communities differed systematically across the age spectrum in composition and diversity, the same was not observed for the fungal microbiota. We also identified a novel and dramatic change in the maternal postpartum microbiota. This change included much higher abundance of Escherichia coli and much lower abundance of Prevotella in the first vs. fourth week postpartum. While infants shared more bacterial taxa with their mother's stool and breast milk than with those of unrelated mothers, there were far fewer shared fungal taxa. CONCLUSION: Given the known ability of commensal fungi to influence host health, the distinct pattern of their acquisition likely has important health consequences. Similarly, the dynamics of mothers' bacterial microbiotas around the time of birth may have important consequences for their children's health. Both topics require further study.

Infant Nasopharyngeal Microbiota Subphenotypes and Early Childhood Lung Function: Evidence from a Rural Ghanaian Pregnancy Cohort.

Early life respiratory microbiota may increase risk for future pulmonary disease. Associations between respiratory microbiota and lung health in children from low- and middle-income countries are not well-described. Leveraging the Ghana Randomized Air Pollution and Health Study (GRAPHS) prospective pregnancy cohort in Kintampo, Ghana, we collected nasopharyngeal swabs in 112 asymptomatic children aged median 4.3 months (interquartile range (IQR) 2.9, 7.1) and analyzed 22 common bacterial and viral pathogens with MassTag polymerase chain reaction (PCR). We prospectively followed the cohort and measured lung function at age four years by impulse oscillometry. First, we employed latent class analysis (LCA) to identify nasopharyngeal microbiota (NPM) subphenotypes. Then, we used linear regression to analyze associations between subphenotype assignment and lung function. LCA suggest that a two-class model best described the infant NPM. We identified a higher diversity subphenotype (N = 38, 34%) with more pathogens (median 4; IQR 3.25, 4.75) and a lower diversity subphenotype (N = 74, 66%) with fewer pathogens (median 1; IQR 1, 2). In multivariable linear regression models, the less diverse NPM subphenotype had higher small airway resistance (R5-R20 ß = 17.9%, 95% CI 35.6, 0.23; p = 0.047) compared with the more diverse subphenotype. Further studies are required to understand the role of the microbiota in future lung health.

Prenatal and Postnatal Household Air Pollution Exposures and Pneumonia Risk: Evidence From the Ghana Randomized Air Pollution and Health Study.

BACKGROUND: Nearly 40% of the world's population is exposed daily to household air pollution. The relative impact of prenatal and postnatal household air pollution exposure on early childhood pneumonia, a leading cause of mortality, is unknown. RESEARCH QUESTION: Are prenatal or postnatal household air pollution, or both, associated with pneumonia risk in the first year of life? STUDY DESIGN AND METHODS: The Ghana Randomized Air Pollution and Health Study enrolled 1,414 nonsmoking, pregnant women before 24 weeks' gestation with prospective follow-up to the child's age of 1 year. We measured 72-h personal household air pollution exposures, indexed by carbon monoxide (CO), four times prenatally and three times postnatally. Weekly fieldworker surveillance identified ill-appearing children for physician pneumonia assessment. We used quasi-Poisson models to examine associations between prenatal and postnatal CO and physician-diagnosed pneumonia and severe pneumonia. Sex-specific effects were examined. RESULTS: Of the 1,306 live births, 1,141 infants were followed up with 55,605 child-weeks of fieldworker surveillance. The estimated risk for pneumonia and severe pneumonia in the first year of life increased by 10% (relative risk [RR], 1.10; 95% CI, 1.04-1.16) and 15% (RR, 1.15; 95% CI, 1.03-1.28), respectively, per 1-part per million (ppm) increase in average prenatal CO exposure and by 6% (RR, 1.06; 95% CI, 0.99-1.13) per 1-ppm increase in average postnatal CO exposure. Sex-stratified analyses suggest that in girls, higher prenatal CO exposure was associated with pneumonia risk, while no association was seen in boys. INTERPRETATION: Prenatal household air pollution exposure increased risk of pneumonia and severe pneumonia in the first year of life. Clean-burning interventions may be most effective when begun prenatally. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01335490; URL: www.clinicaltrials.gov.

Prenatal and Postnatal Household Air Pollution Exposure and Infant Growth Trajectories: Evidence from a Rural Ghanaian Pregnancy Cohort.

BACKGROUND: The exposure-response association between prenatal and postnatal household air pollution (HAP) and infant growth trajectories is unknown. OBJECTIVES: To evaluate associations between prenatal and postnatal HAP exposure and stove interventions on growth trajectories over the first year of life. METHODS: The Ghana Randomized Air Pollution and Health Study enrolled n=1,414 pregnant women at ≤24wk gestation from Kintampo, Ghana, and randomized them to liquefied petroleum gas (LPG), improved biomass, or open fire (control) stoves. We quantified HAP exposure by repeated, personal prenatal and postnatal carbon monoxide (CO) and, in a subset, fine particulate matter [PM with an aerodynamic diameter of ≤2.5µm (PM2.5)] assessments. Length, weight, mid-upper arm circumference (MUAC) and head circumference (HC) were measured at birth, 3, 6, 9, and 12 months; weight-for-age, length-for-age (LAZ), and weight-for-length z (WLZ)-scores were calculated. For each anthropometric measure, we employed latent class growth analysis to generate growth trajectories over the first year of life and assigned each child to a trajectory group. We then employed ordinal logistic regression to determine associations between HAP exposures and growth trajectory assignments. Associations with stove intervention arm were also considered. RESULTS: Of the 1,306 live births, 1,144 had valid CO data and anthropometric variables measured at least once. Prenatal HAP exposure increased risk for lower length [CO odds ratio (OR)= 1.17, 95% CI: 1.01, 1.35 per 1-ppm increase; PM2.5 OR= 1.07, 95% CI: 1.02, 1.13 per 10-µg/m3 increase], lower LAZ z-score (CO OR= 1.15, 95% CI: 1.01, 1.32 per 1-ppm increase) and stunting (CO OR= 1.25, 95% CI: 1.08, 1.45) trajectories. Postnatal HAP exposure increased risk for smaller HC (CO OR= 1.09, 95% CI: 1.04, 1.13 per 1-ppm increase), smaller MUAC and lower WLZ-score (PM2.5 OR= 1.07, 95% CI: 1.00, 1.14 and OR= 1.09, 95% CI: 1.01, 1.19 per 10-µg/m3 increase, respectively) trajectories. Infants in the LPG arm had decreased odds of having smaller HC and MUAC trajectories as compared with those in the open fire stove arm (OR= 0.58, 95% CI: 0.37, 0.92 and OR= 0.45, 95% CI: 0.22, 0.90, respectively). DISCUSSION: Higher early life HAP exposure (during pregnancy and through the first year of life) was associated with poorer infant growth trajectories among children in rural Ghana. A cleaner-burning stove intervention may have improved some growth trajectories. https://doi.org/10.1289/EHP8109.

Prenatal household air pollutant exposure is associated with reduced size and gestational age at birth among a cohort of Ghanaian infants.

BACKGROUND: Low birth weight and prematurity are important risk factors for death and disability, and may be affected by prenatal exposure to household air pollution (HAP). METHODS: We investigate associations between maternal exposure to carbon monoxide (CO) during pregnancy and birth outcomes (birth weight, birth length, head circumference, gestational age, low birth weight, small for gestational age, and preterm birth) among 1288 live-born infants in the Ghana Randomized Air Pollution and Health Study (GRAPHS). We evaluate whether evidence of malaria during pregnancy, as determined by placental histopathology, modifies these associations. RESULTS: We observed effects of CO on birth weight, birth length, and gestational age that were modified by placental malarial status. Among infants from pregnancies without evidence of placental malaria, each 1 ppm increase in CO was associated with reduced birth weight (-53.4 g [95% CI: -84.8, -21.9 g]), birth length (-0.3 cm [-0.6, -0.1 cm]), gestational age (-1.0 days [-1.8, -0.2 days]), and weight-for-age Z score (-0.08 standard deviations [-0.16, -0.01 standard deviations]). These associations were not observed in pregnancies with evidence of placental malaria. Each 1 ppm increase in maternal exposure to CO was associated with elevated odds of low birth weight (LBW, OR 1.14 [0.97, 1.33]) and small for gestational age (SGA, OR 1.14 [0.98, 1.32]) among all infants. CONCLUSIONS: Even modest reductions in exposure to HAP among pregnant women could yield substantial public health benefits, underscoring a need for interventions to effectively reduce exposure. Adverse associations with HAP were discernible only among those without evidence of placental malaria, a key driver of impaired fetal growth in this malaria-endemic area.