Effects of a Household Air Pollution Intervention with Liquefied Petroleum Gas on Cardiopulmonary Outcomes in Peru. A Randomized Controlled Trial.

Rationale: Approximately 40% of people worldwide are exposed to household air pollution (HAP) from the burning of biomass fuels. Previous efforts to document health benefits of HAP mitigation have been stymied by an inability to lower emissions to target levels. Objectives: We sought to determine if a household air pollution intervention with liquefied petroleum gas (LPG) improved cardiopulmonary health outcomes in adult women living in a resource-poor setting in Peru. Methods: We conducted a randomized controlled field trial in 180 women aged 25-64 years living in rural Puno, Peru. Intervention women received an LPG stove, continuous fuel delivery for 1 year, education, and behavioral messaging, whereas control women were asked to continue their usual cooking practices. We assessed for stove use adherence using temperature loggers installed in both LPG and biomass stoves of intervention households. Measurements and Main Results: We measured blood pressure, peak expiratory flow (PEF), and respiratory symptoms using the St. George's Respiratory Questionnaire at baseline and at 3-4 visits after randomization. Intervention women used their LPG stove exclusively for 98% of days. We did not find differences in average postrandomization systolic blood pressure (intervention - control 0.7 mm Hg; 95% confidence interval, -2.1 to 3.4), diastolic blood pressure (0.3 mm Hg; -1.5 to 2.0), prebronchodilator peak expiratory flow/height2 (0.14 L/s/m2; -0.02 to 0.29), postbronchodilator peak expiratory flow/height2 (0.11 L/s/m2; -0.05 to 0.27), or St. George's Respiratory Questionnaire total score (-1.4; -3.9 to 1.2) over 1 year in intention-to-treat analysis. There were no reported harms related to the intervention. Conclusions: We did not find evidence of a difference in blood pressure, lung function, or respiratory symptoms during the year-long intervention with LPG. Clinical trial registered with www.clinicaltrials.gov (NCT02994680).

Androgens, brain and androgen deprivation therapy in paraphilic disorders: A narrative review.

Sexual delinquency is a global problem where those with paraphilic disorders, such as paedophiles, are more likely to commit and reoffend. Androgen deprivation therapy (ADT) has been suggested as a solution. The objective of this narrative review is to present current information on its risks, benefits and limitations as a treatment for paraphilias. The importance of testosterone in sexual function, the effect of its deficiency by age or by pharmacological treatment (anti-androgens, GnRH agonists and GnRH antagonists) and the effect of testosterone replacement therapy will be reviewed. The relationship between androgens, brain, sexual behaviour and pathophysiology of paraphilic disorders will also be explored. ADT reduces sexual urges, but has adverse effects and, because its reversible nature, it does not ensure less recidivism. Likewise, the research quality of ADT drugs is limited and not enough to support their use. Child sex offenders, and not paraphilic subjects who have not committed assaults, show signs of elevated prenatal exposure to androgens and a higher methylation state of the androgen receptor gene. Sexual behaviour is regulated by subcortical (hypothalamus, brainstem and spinal cord) and cortical structures of the brain, in addition to brain circuits (dopaminergic, serotonergic). Those with paraphilic disorders show abnormalities at these levels that could relate to the risk of sexual offences. In conclusion, androgens represent a significant part of the pathophysiology of paraphilias and therefore, ADT seems promising. Nonetheless, more studies are needed to make definite conclusions about the efficacy of long-term ADT in paraphilic patients.

The association between asthma emergency department visits and satellite-derived PM2.5 in Lima, Peru.

BACKGROUND: Asthma affects millions of people worldwide. Lima, Peru is one of the most polluted cities in the Americas but has insufficient ground PM2.5 (particulate matter that are 2.5 µm or less in diameter) measurements to conduct epidemiologic studies regarding air pollution. PM2.5 estimates from a satellite-driven model have recently been made, enabling a study between asthma and PM2.5. OBJECTIVE: We conducted a daily time-series analysis to determine the association between asthma emergency department (ED) visits and estimated ambient PM2.5 levels in Lima, Peru from 2010 to 2016. METHODS: We used Poisson generalized linear models to regress aggregated counts of asthma on district-level population weighted PM2.5. Indicator variables for hospitals, districts, and day of week were included to account for spatial and temporal autocorrelation while assessing same day, previous day, day before previous and average across all 3-day exposures. We also included temperature and humidity to account for meteorology and used dichotomous percent poverty and gender variables to assess effect modification. RESULTS: There were 103,974 cases of asthma ED visits during the study period across 39 districts in Lima. We found a 3.7% (95% CI: 1.7%-5.8%) increase in ED visits for every interquartile range (IQR, 6.02 µg/m3) increase in PM2.5 same day exposure with no age stratification. For the 0-18 years age group, we found a 4.5% (95% CI: 2.2%-6.8%) increase in ED visits for every IQR increase in PM2.5 same day exposure. For the 19-64 years age group, we found a 6.0% (95% CI: 1.0%-11.0%) increase in ED visits for every IQR in average 3-day exposure. For the 65 years and up age group, we found a 16.0% (95% CI: 7.0%-24.0%) decrease in ED visits for every IQR increase in PM2.5 average 3-day exposure, although the number of visits in this age group was low (4,488). We found no effect modification by SES or gender. DISCUSSION: Results from this study provide additional literature on use of satellite-driven exposure estimates in time-series analyses and evidence for the association between PM2.5 and asthma in a low- and middle-income (LMIC) country.

Meteorological factors and childhood diarrhea in Peru, 2005-2015: a time series analysis of historic associations, with implications for climate change.

BACKGROUND: Global temperatures are projected to rise by ≥2 °C by the end of the century, with expected impacts on infectious disease incidence. Establishing the historic relationship between temperature and childhood diarrhea is important to inform future vulnerability under projected climate change scenarios. METHODS: We compiled a national dataset from Peruvian government data sources, including weekly diarrhea surveillance records, annual administered doses of rotavirus vaccination, annual piped water access estimates, and daily temperature estimates. We used generalized estimating equations to quantify the association between ambient temperature and childhood (< 5 years) weekly reported clinic visits for diarrhea from 2005 to 2015 in 194 of 195 Peruvian provinces. We estimated the combined effect of the mean daily high temperature lagged 1, 2, and 3 weeks, in the eras before (2005-2009) and after (2010-2015) widespread rotavirus vaccination in Peru and examined the influence of varying levels of piped water access. RESULTS: Nationally, an increase of 1 °C in the temperature across the three prior weeks was associated with a 3.8% higher rate of childhood clinic visits for diarrhea [incidence rate ratio (IRR): 1.04, 95% confidence interval (CI): 1.03-1.04]. Controlling for temperature, there was a significantly higher incidence rate of childhood diarrhea clinic visits during moderate/strong El Niño events (IRR: 1.03, 95% CI: 1.01-1.04) and during the dry season (IRR: 1.01, 95% CI: 1.00-1.03). Nationally, there was no evidence that the association between temperature and the childhood diarrhea rate changed between the pre- and post-rotavirus vaccine eras, or that higher levels of access to piped water mitigated the effects of temperature on the childhood diarrhea rate. CONCLUSIONS: Higher temperatures and intensifying El Niño events that may result from climate change could increase clinic visits for childhood diarrhea in Peru. Findings underscore the importance of considering climate in assessments of childhood diarrhea in Peru and globally, and can inform regional vulnerability assessments and mitigation planning efforts.

Association between iron supplementation and the presence of diarrhoea in Peruvian children aged 6-59 months: analysis of the database of the Demographic and Family Health Survey in Peru (DHS, Peru), years 2009-2019.

INTRODUCTION: According to the WHO, anaemia is a severe public health problem when the prevalence is ≥ 40 %. In 2019, in Peru, 40·1 % of children (aged 6 to 35 months) are diagnosed as anaemic. This is a concern since, despite the efforts of the governments to reduce the prevalence, the problem has stagnated since 2011. The treatment applied to deal with anaemia is Fe supplementation. Although Fe is essential for cell function, an excess can produce adverse responses, such as gut inflammation affecting microbiota and resulting in diarrhoeic episodes. OBJECTIVE: To determine the association between diarrhoea and Fe supplementation in children with and without anaemia, controlling for different socio-demographic variables. DESIGN: We conducted via logistic regression to obtain diarrhoea prevalence ratios (PR), adjusted by age, sex, geographic region, water and sanitation service, and rurality. The survey asked for recent episodes of diarrhoea during the last 7 d; similarly, after the consumption of Fe supplements during the last 12 months before the survey. SETTING: Peru. PARTICIPANTS: The Demographic and Family Health Survey (DHS) is conducted annually at home among 14 202 children on average (2009-2019). RESULTS: Fe supplementation in the last 7 d (PR = 1·09) or the last 12 months (PR = 1·19) (P < 0·0001) was associated with an increased risk of diarrhoea. The same association was observed between Fe supplementation and the presence of anaemia. CONCLUSIONS: Fe supplementation is associated with diarrhoea and overuse in children should be avoided.

Association between air pollution in Lima and the high incidence of COVID-19: findings from a post hoc analysis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) originated in the People's Republic of China in December 2019. Thereafter, a global logarithmic expansion of cases occurred. Some countries have a higher rate of infections despite the early implementation of quarantine. Air pollution might be related to high susceptibility to the virus and associated case fatality rates (deaths/cases*100). Lima, Peru, has the second highest incidence of COVID-19 in Latin America and also has one the highest levels of air pollution in the region. METHODS: This study investigated the association of levels of PM2.5 exposure in previous years (2010-2016) in 24 districts of Lima with cases, deaths and case fatality rates for COVID-19. Multiple linear regression was used to evaluate this association controlled by age, sex, population density and number of food markets per district. The study period was from March 6 to June 12, 2020. RESULTS: There were 128,700 cases in Lima and 2382 deaths due to COVID-19. The case fatality rate was 1.93%. Previous exposure to PM2.5 (2010-2016) was associated with the number of COVID-19- cases (ß = 0.07; 95% CI: 0.034-0.107) and deaths (ß = 0.0014; 95% CI: 0.0006-0.0.0023) but not with the case fatality rate. CONCLUSIONS: After adjusting for age, sex and number of food markets, the higher rates of COVID-19 in Metropolitan Lima are attributable to the increased PM2.5 exposure in the previous years, among other reasons. Reduction in air pollution from a long-term perspective and social distancing are needed to prevent the spread of virus outbreaks.

PM2.5 exposure on daily cardio-respiratory mortality in Lima, Peru, from 2010 to 2016.

BACKGROUND: There have been no studies of air pollution and mortality in Lima, Peru. We evaluate whether daily environmental PM2.5 exposure is associated to respiratory and cardiovascular mortality in Lima during 2010 to 2016. METHODS: We analyzed 86,970 deaths from respiratory and cardiovascular diseases in Lima from 2010 to 2016. Estimated daily PM2.5 was assigned based on district of residence. Poisson regression was used to estimate associations between daily district-level PM2.5 exposures and daily counts of deaths. RESULTS: An increase in 10 µg/m3 PM2.5 on the day before was significantly associated with daily cardiorespiratory mortality (RR 1.029; 95% CI: 1.01-1.05) across all ages and in the age group over 65 (RR 1.04; 95% CI: 1.005-1.09) which included 74% of all deaths. We also observed associations with circulatory deaths for all age groups (RR 1.06; 95% CI: 1.01-1.11), and those over 65 (RR 1.06; 95% CI 1.00-1.12). A borderline significant trend was seen (RR 1.05; 95% CI 0.99-1.06; p = 0.10) for respiratory deaths in persons aged over 65. Trends were driven by the highest quintile of exposure. CONCLUSIONS: PM2.5 exposure is associated with daily cardiorespiratory mortality in Lima, especially for older people. Our data suggest that the existing limits on air pollution exposure are too high.

Correction to: Association of PM2.5 concentration with health center outpatient visits for respiratory diseases of children under 5 years old in Lima, Peru.

The original version of this article [1], published on 15 January 2020, contained incorrect name of the co- author. In this Correction the affected part of the article is shown.

Association of PM2.5 concentration with health center outpatient visits for respiratory diseases of children under 5 years old in Lima, Peru.

BACKGROUND: Lima is one of the more polluted cities in Latin America. High levels of PM2.5 have been shown to increase health center outpatient visits of respiratory diseases. METHODS: Health center outpatient visits for children < 5 years for childhood respiratory disease (acute lower respiratory infections (ALRI), pneumonia and acute bronchiolitis/asthma) from 498 public clinics in Lima were available on a weekly basis from 2011 to 2015 from Peru's Ministry of Health (MINSA). The association between the average weekly concentrations of PM2.5 was evaluated in relation to the number of weekly health center outpatient visits for children. Weekly PM2.5 values were estimated using a recently developed model that combined data observed from ground monitors, with data from space satellite and meteorology. Ground monitoring data came from 10 fixed stations of the Peruvian National Service of Meteorology and Hydrology (SENAMHI) and from 6 mobile stations located in San Juan de Miraflores by Johns Hopkins University. We conducted a time-series analysis using a negative binomial model. RESULTS: We found a significant association between exposure to PM2.5 and all three types of respiratory diseases, across all age groups. For an interquartile increase in PM2.5, we found an increase of 6% for acute lower respiratory infections, an increase of 16-19% for pneumonia, and an increase of 10% for acute bronchiolitis / asthma. CONCLUSIONS: Higher emissions of environmental pollutants such as PM2,5 could be a trigger for the increase of health center outpatients visits for respiratory diseases (ALRI, pneumonia and asthma), which are themselves risk factors for mortality for children in Lima province, Peru.

Nitrogen dioxide exposures from biomass cookstoves in the Peruvian Andes.

BACKGROUND: Household air pollution from biomass cookstoves is a major contributor to global morbidity and mortality, yet little is known about exposures to nitrogen dioxide (NO2 ). OBJECTIVE: To characterize NO2 kitchen area concentrations and personal exposures among women with biomass cookstoves in the Peruvian Andes. METHODS: We measured kitchen area NO2 concentrations at high-temporal resolution in 100 homes in the Peruvian Andes. We assessed personal exposure to NO2 in a subsample of 22 women using passive samplers. RESULTS: Among 97 participants, the geometric mean (GM) highest hourly average NO2 concentration was 723 ppb (geometric standard deviation (GSD) 2.6) and the GM 24-hour average concentration was 96 ppb (GSD 2.6), 4.4 and 2.9 times greater than WHO indoor hourly (163 ppb) and annual (33 ppb) guidelines, respectively. Compared to the direct-reading instruments, we found similar kitchen area concentrations with 48-hour passive sampler measurements (GM 108 ppb, GSD 3.8). Twenty-seven percent of women had 48-hour mean personal exposures above WHO annual guidelines (GM 18 ppb, GSD 2.3). In univariate analyses, we found that roof, wall, and floor type, as well as higher SES, was associated with lower 24-hour kitchen area NO2 concentrations. PRACTICAL IMPLICATIONS: Kitchen area concentrations and personal exposures to NO2 from biomass cookstoves in the Peruvian Andes far exceed WHO guidelines. More research is warranted to understand the role of this understudied household air pollutant on morbidity and mortality and to inform cleaner-cooking interventions for public health.

Inflammatory pathway employed by Red Maca to treat induced benign prostatic hyperplasia in rats.

Benign prostatic hyperplasia (BPH) is a pathology characterised by an increase in prostate size associated with low urinary tract symptoms. Finasteride (F), a 5a-reductase inhibitor, is the standard treatment for BPH reducing prostate weight but also sexual desire. The Peruvian plant known as Red Maca (RM) (Lepidium meyenii) inhibits BPH in rats and mice. The aim of the study was to assess the inflammatory effect of RM and finasteride in rats with testosterone enanthate (TE)-induced BPH. Thirty rats were divided into 5 groups: Control, TE (50 mg/rat), TE + F (0.6 mg/kg), and two groups of TE + RM 40/80 (40 or 80 mg). After treatments, tumour necrosis factor alpha (TNFa), interleukin 4 (IL4) and interferon gamma (INFg) as well as testosterone and oestradiol were evaluated and inflammatory cells (neutrophils, mast cells and lymphocytes) in prostate were quantified. Red Maca and finasteride treatments decreased inflammatory cells counts in prostate, inhibiting TNFa by different pathways. Finasteride increased IL4 whereas Red Maca increased INFg. In conclusion, data suggest that finasteride acts on Th2 response by increasing IL4 in prostate, while Red Maca acts on Th1 response mediated by INFg.

In vitro culture of spermatogonial stem cells isolated from adult alpaca (Vicugna pacos) testes analysed with Dolichos biflorus by flow cytometry.

Spermatogonial stem cell (SSC) is known for its self-renewal capacity. We have studied the in vitro proliferation of isolated SSC from adult alpaca (Vicugna pacos) testes. A total of 107 samples were evaluated of which 31 were evaluated at baseline, 36 were cultivated in DMEM and 40 in STEMPRO media. Half of the cultivated samples was analysed after 14 days, and the rest after 21 days. Round cell subpopulations were identified with FITC-DBA by flow cytometry: strongly positive DBA (sDBA+) as SSC, weakly positive DBA (wDBA+) as in early differentiation and negative DBA as differentiated. At the beginning, 4.16% of the cells were SSC, 37.61% wDBA+ while 54.12% were DBA-. After 14 days, 42.28% of SSC, 44.68% wDBA+ and 11.07% DBA- were found in DMEM while 47.09% of SSC, 32.57% wDBA+ and 18.48% DBA- in STEMPRO. After 21 days 38.66% were SSC, 52.78% wDBA and 7.65% DBA- in DMEM and on STEMPRO media 47.92% SSC, 44.20% wDBA+, 4.93% DBA-. There is a significant difference between the number of initial and SSC cultivated, as well as between DBA- (p < 0.05), while there is no significant difference between the wDBA+ (p > 0.05). Our results suggest that both culture media are appropriate for the in vitro proliferation of alpacas SSC.

Spermatogonial stem cells identified by molecular expression of PLZF, integrin ß1 and reactivity to Dolichos biflorus agglutinin in alpaca adult testes.

The identification system of spermatogonial stem cell (SSC) was established in alpaca using the molecular expression as well as the reactivity pattern to Dolichos biflorus agglutinin (DBA) by flow cytometry. Twenty-four testicles with their epididymis were recovered from adult alpacas at the slaughterhouse of Huancavelica-Perú. Samples were transported to the Laboratory of Reproductive Physiology at Universidad Nacional Mayor de San Marcos. Testes were selected for our study when the progressive motility of epididymal spermatozoa (ESPM) was above 30%. Isolation of SSC was performed with two enzymatic digestions. Finally, sperm viability was evaluated by means of the trypan blue vital stain in spermatogonial round cells. Samples with more than 80% viability were selected. Isolated cells cultured for 2 days were used for identifying the presence of SSCs by the expression of integrin ß1 (116 bp) and PLZF (206 bp) genes. Spermatogonia were classified according to the DBA reactivity. Spermatogonia with a strong positive to DBA (sDBA+ ) were classified as SSC (Mean ± SEM=4.44 ± 0.68%). Spermatogonia in early differentiation stages stained weakly positive with DBA (wDBA+ ) (Mean ± SEM=37.44 ± 3.07%) and differentiated round cells as DBA negative (Mean ± SEM=54.12 ± 3.18%). With the use of molecular and DBA markers, it is possible to identify easily the spermatogonial stem cells in alpaca.

New Insights into the Genetic Basis of Monge's Disease and Adaptation to High-Altitude.

Human high-altitude (HA) adaptation or mal-adaptation is explored to understand the physiology, pathophysiology, and molecular mechanisms that underlie long-term exposure to hypoxia. Here, we report the results of an analysis of the largest whole-genome-sequencing of Chronic Mountain Sickness (CMS) and nonCMS individuals, identified candidate genes and functionally validated these candidates in a genetic model system (Drosophila). We used PreCIOSS algorithm that uses Haplotype Allele Frequency score to separate haplotypes carrying the favored allele from the noncarriers and accordingly, prioritize genes associated with the CMS or nonCMS phenotype. Haplotypes in eleven candidate regions, with SNPs mostly in nonexonic regions, were significantly different between CMS and nonCMS subjects. Closer examination of individual genes in these regions revealed the involvement of previously identified candidates (e.g., SENP1) and also unreported ones SGK3, COPS5, PRDM1, and IFT122 in CMS. Remarkably, in addition to genes like SENP1, SGK3, and COPS5 which are HIF-dependent, our study reveals for the first time HIF-independent gene PRDM1, indicating an involvement of wider, nonHIF pathways in HA adaptation. Finally, we observed that down-regulating orthologs of these genes in Drosophila significantly enhanced their hypoxia tolerance. Taken together, the PreCIOSS algorithm, applied on a large number of genomes, identifies the involvement of both new and previously reported genes in selection sweeps, highlighting the involvement of multiple hypoxia response systems. Since the overwhelming majority of SNPs are in nonexonic (and possibly regulatory) regions, we speculate that adaptation to HA necessitates greater genetic flexibility allowing for transcript variability in response to graded levels of hypoxia.

Nitrogen balance after a single oral consumption of sacha inchi (Plukenetia volúbilis L.) protein compared to soy protein: a randomized study in humans.

Sacha inchi is a seed produced in the Peruvian Amazonian and its oil is recognized by the lowering lipids effect in humans. The remaining material transformed to flour has a higher amount of protein, but, the nitrogen balance once ingested orally has not been studied. The present study was designed to evaluate the nitrogen balance after single consumption of 30 g of sacha inchi flour and compared with that obtained after consumption of 30 g soybean flour in adult men and women. This was a double-blind cohort study in 15 men and 15 women between 18 and 55 years old. Fifteen subjects received soy meal and 15 subjects received sacha inchi meal. Group receiving sacha inchi flour has comparable initial parameters as those receiving soybean flour (p > 0.05). Blood samples at different times were obtained. Urine for 24 h was collected to calculate nitrogen balance, p < 0.05 was considered significant. Plasma insulin levels increased post-prandial with a peak at 30 min. Thereafter, a reduction occurred. The magnitude of changes in insulin levels was similar in sacha inchi and soybean groups (p < 0.05). Lipid profile and inflammatory marker, C-reactive protein (CRP) and interleukin 6 (IL6) was not different at 0 or 24 h after sacha inchi or soy flour administration. The nitrogen balance was negative in the study but similar between both groups (p > 0.05). In conclusion, protein consumption of sacha inchi flour has the same nitrogen balance as soybean flour, shows acceptability for a single consumption and does not present serious adverse effects.

Antioxidant and neuroprotector effect of Lepidium meyenii (maca) methanol leaf extract against 6-hydroxy dopamine (6-OHDA)-induced toxicity in PC12 cells.

Reactive oxygen species (ROS) are normally produced during cell metabolism, there is strong evidence to suggest that ROS produced in excess impair the cell and may be etiologically related to various neurodegenerative diseases. This study was undertaken to examine the effects of Lepidium meyenii (MACA) methanol leaf extract on neurotoxicity in PC12 cell exposed to 6-hydroxydopamine (6-OHDA). Fresh samples of "maca" leaves were processed in order to obtain foliar extracts and to evaluate the neurobiological activity on PC12 cells, subjected to the cytotoxic effect of 6-OHDA through the determination of the capacity antioxidant, cell viability and cytotoxicity assays on PC12 cells. The results of the tests of antioxidant activity, showed maximum values of 2262.37 and 1305.36 expressed in Trolox equivalents (TEAC), for the methanolic and aqueous fractions respectively. Cell viability assays at a dose of 10 µg extract showed an increase of 31% and 60% at 6 and 12 h of pretreatment, respectively. Cytotoxicity assays at the same dose and exposure time showed a 31.4% and 47.8% reduction in lactate dehydrogenase (LDH) activity and an increase in superoxide dismutase (SOD) activity. The results allow us to affirm that the methanolic foliar extract of "maca" presents in vitro neurobiological activity of antioxidant protection, increase in cell viability and reduction of cytotoxicity against oxidative stress generated by 6-OHDA. In conclusion, the present study shows a protective role for Lepidium meyenii leaf extract on 6-OHDA-induced toxicity by an antioxidant effect.

Preterm birth risk at high altitude in Peru.

OBJECTIVE: High altitude has been implicated in a variety of adverse pregnancy outcomes including preeclampsia and stillbirth. Smaller studies show conflicting data on the association between high altitude and preterm birth (PTB). The objective of this study was to assess the association between altitude and PTB. STUDY DESIGN: A retrospective cohort study was performed using data from the Perinatal Information System, which includes deliveries from 43 hospitals in Peru from 2000 through 2010. Altitude was classified into the following categories: low (0-1999 m), moderate (2000-2900 m), and high (3000-4340 m). The primary outcome was PTB (delivery <37 weeks). Secondary outcomes were cesarean delivery and small for gestational age (SGA). Deliveries less than 23 weeks are not included in the database. χ(2) analyses were performed to compare categorical variables, and a logistic regression was used to calculate the odds ratios and control for confounders. Clustering by hospital was accounted for using generalized estimating equations. RESULTS: A total of 550,166 women were included (68% low, 15% moderate, 17% high altitude). The overall PTB rate was 5.9%, with no difference in the PTB rate among the 3 altitudes (5.6%, 6.2%, 6.8%, P = .13). There was a significant difference in cesarean rates (28.0%, 26.6%, 20.6%, P < .001) with a 34% decreased risk at high vs low altitude adjusted for confounders (adjusted odds ratio, 0.66; 95% confidence interval, 0.51-0.85). There was a difference in SGA (3.3%, 3.6%, 5.0%, P = .02) with a 51% increased risk at high vs low altitude adjusted for confounders (adjusted odds ratio, 1.49; 95% confidence interval, 1.14-1.93). CONCLUSION: High altitude is not associated with PTB. At high altitude, the cesarean rate was reduced and the SGA rate was increased.