Climate Change-Related Environmental Exposures and Perinatal and Maternal Health Outcomes in the U.S.

PURPOSE: Climate change poses one of the greatest risks to human health as air pollution increases, surface temperatures rise, and extreme weather events become more frequent. Environmental exposures related to climate change have a disproportionate effect on pregnant women through influencing food and water security, civil conflicts, extreme weather events, and the spread of disease. Our research team sought to identify the current peer-reviewed research on the effects of climate change-related environmental exposures on perinatal and maternal health in the United States. DESIGN AND METHODS: A systematic literature review of publications identified through a comprehensive search of the PubMed and Web of Science databases was conducted using a modified Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) approach. The initial search across both databases identified a combined total of 768 publications. We removed 126 duplicates and 1 quadruplet, and the remaining 639 publications were subjected to our pre-set inclusion and exclusion criteria. We excluded studies outside of the United States. A total of 39 studies met our inclusion criteria and were retained for thematic analysis. FINDINGS: A total of 19 studies investigated the effect of either hot or cold temperature exposure on perinatal and maternal health outcomes. The effect of air pollution on perinatal outcomes was examined in five studies. A total of 19 studies evaluated the association between natural disasters (hurricanes, flash floods, and tropical cyclones) and perinatal and maternal health outcomes. High and low temperature extremes were found to negatively influence neonate and maternal health. Significant associations were found between air pollutant exposure and adverse pregnancy outcomes. Adverse pregnancy outcomes were linked to hurricanes, tropical cyclones, and flash floods. CONCLUSIONS: This systematic review suggests that climate change-related environmental exposures, including extreme temperatures, air pollution, and natural disasters, are significantly associated with adverse perinatal and maternal health outcomes across the United States.

The Impact of Asymptomatic Human Immunodeficiency Virus-Positive Disease Status on Inpatient Complications Following Spine Surgery: A Propensity Score-Matched Analysis.

In the United States, nearly 1.2 million people > 12 years old have human immunodeficiency virus (HIV), which is associated with postoperative complications following orthopedic procedures. Little is known about how asymptomatic HIV (AHIV) patients fare postoperatively. This study compares complications after common spine surgeries between patients with and without AHIV. The Nationwide Inpatient Sample (NIS) was retrospectively reviewed from 2005-2013, identifying patients aged > 18 years who underwent 2-3-level anterior cervical discectomy and fusion (ACDF), ≥4-level thoracolumbar fusion (TLF), or 2-3-level lumbar fusion (LF). Patients with AHIV and without HIV were 1:1 propensity score-matched. Univariate analysis and multivariable binary logistic regression were performed to assess associations between HIV status and outcomes by cohort. 2-3-level ACDF (n = 594 total patients) and ≥4-level TLF (n = 86 total patients) cohorts demonstrated comparable length of stay (LOS), rates of wound-related, implant-related, medical, surgical, and overall complications between AHIV and controls. 2-3-level LF (n = 570 total patients) cohorts had comparable LOS, implant-related, medical, surgical, and overall complications. AHIV patients experienced higher postoperative respiratory complications (4.3% vs. 0.4%,). AHIV was not associated with higher risks of medical, surgical, or overall inpatient postoperative complications following most spine surgical procedures. The results suggest the postoperative course may be improved in patients with baseline control of HIV infection.

The Impact of Osteoporosis on 2-Year Outcomes in Patients Undergoing Long Cervical Fusion.

INTRODUCTION: Osteoporosis affects nearly 200 million individuals worldwide. Given this notable disease burden, there have been increased efforts to investigate complications in patients with osteoporosis undergoing cervical fusion (CF). However, there are limited data regarding long-term outcomes in osteoporotic patients in the setting of ≥4-level cervical fusion. METHODS: The New York State Statewide Planning and Research Cooperative System database was used to identify patients who underwent posterior or combined anterior-posterior ≥4-level CF for cervical radiculopathy or myelopathy from 2009 to 2011, with a minimum follow-up surveillance of 2 years. The following were compared between patients with and without osteoporosis: demographics, hospital-related parameters, medical/surgical complications, readmissions, and revisions. Binary multivariate stepwise logistic regression was used to identify independent predictors of outcomes. RESULTS: A total of 2,604 patients were included (osteoporosis: n = 136 (5.2%); nonosteoporosis: n = 2,468). Patients with osteoporosis were older (66.9 ± 11.2 vs. 60.0 ± 11.4 years, P < 0.001), more often female (75.7% vs. 36.2%, P < 0.001), and White (80.0% vs. 65.3%, P = 0.007). Both cohorts had comparable comorbidity burdens (Charlson/Deyo: 1.1 ± 1.2 vs. 1.0 ± 1.3, P = 0.262), total hospital charges ($100,953 ± 94,933 vs. $91,618 ± 78,327, P = 0.181), and length of stay (9.7 ± 10.4 vs. 8.4 ± 9.6 days, P = 0.109). Patients with osteoporosis incurred higher rates of overall medical complication rates (41.9% vs. 29.4%, P = 0.002) and individual surgical complications, such as nonunion (2.9% vs. 0.7%, P = 0.006). Osteoporosis was associated with medical complications (OR = 1.57, P = 0.021), surgical complications (OR = 1.52, P = 0.030), and readmissions (OR = 1.86, P = 0.003) at 2 years. DISCUSSION: Among patients who underwent multilevel cervical fusion, those with osteoporosis had higher risk of adverse postoperative outcomes at two years. These data indicate that preoperative screening and management of osteoporosis may be important for optimizing long-term outcomes in patients who require multilevel CF. DATA AVAILABILITY AND TRIAL REGISTRATION NUMBERS: The data used in this study are available for public use at https://www.health.ny.gov/statistics/sparcs/.

Inorganic arsenic exposure induces sex-disparate effects and exacerbates ischemia-reperfusion injury in the female heart.

Arsenic is a common contaminant in drinking water throughout the world, and recent studies support a link between inorganic arsenic (iAS) exposure and ischemic heart disease in men and women. Female hearts exhibit an estrogen-dependent reduction in susceptibility to myocardial ischemic injury compared with males, and as such, female hearts may be more susceptible to the endocrine-disrupting effects of iAS exposure. However, iAS exposure and susceptibility to ischemic heart injury have not been examined in mechanistic studies. Male and female mice (8 wk) were exposed to environmentally relevant concentrations of sodium arsenite (0, 10, 100, and 1,000 parts/billion) via drinking water for 4 wk. Pre- and postexposure echocardiography was performed, and postexposure plasma was collected for 17ß-estradiol measurement. Hearts were excised and subjected to ischemia-reperfusion (I/R) injury via Langendorff perfusion. Exposure to 1,000 parts/billion iAS led to sex-disparate effects, such that I/R injury was exacerbated in female hearts but unexpectedly attenuated in males. Assessment of echocardiographic parameters revealed statistically significant structural remodeling in iAS-treated female hearts with no change in function; males showed no change. Plasma 17ß-estradiol levels were not significantly altered by iAS in male or female mice versus nontreated controls. Although total eNOS protein levels did not change in whole heart homogenates from iAS-treated male or female mice, eNOS phosphorylation (Ser1177) was significantly elevated in iAS-treated male hearts. These results suggest that iAS exposure can induce sex-disparate effects and modulate susceptibility to ischemic heart injury by targeting distinct sex-dependent pathways. NEW & NOTEWORTHY This is the first mechanistic study examining iAS exposure on myocardial ischemia-reperfusion injury in male and female mice. Following iAS exposure, ischemia-reperfusion injury was exacerbated in female hearts but attenuated in males. iAS treatment induced statistically significant cardiac remodeling in females, with no change in males. iAS treatment also enhanced phosphorylated eNOS levels at Ser1177, but only in male hearts. These results suggest that iAS alters susceptibility to myocardial I/R injury through distinct sex-dependent pathways.

S-Nitrosoglutathione Reductase Is Essential for Protecting the Female Heart From Ischemia-Reperfusion Injury.

RATIONALE: Protein S-nitros(yl)ation (SNO) has been implicated as an essential mediator of nitric oxide-dependent cardioprotection. Compared with males, female hearts exhibit higher baseline levels of protein SNO and associated with this, reduced susceptibility to myocardial ischemia-reperfusion injury. Female hearts also exhibit enhanced S-nitrosoglutathione reductase (GSNO-R) activity, which would typically favor decreased SNO levels as GSNO-R mediates SNO catabolism. OBJECTIVE: Because female hearts exhibit higher SNO levels, we hypothesized that GSNO-R is an essential component of sex-dependent cardioprotection in females. METHODS AND RESULTS: Male and female wild-type mouse hearts were subjected to ex vivo ischemia-reperfusion injury with or without GSNO-R inhibition (N6022). Control female hearts exhibited enhanced functional recovery and decreased infarct size versus control males. Interestingly, GSNO-R inhibition reversed this sex disparity, significantly reducing injury in male hearts, and exacerbating injury in females. Similar results were obtained with male and female GSNO-R-/- hearts using ex vivo and in vivo models of ischemia-reperfusion injury. Assessment of SNO levels using SNO-resin assisted capture revealed an increase in total SNO levels with GSNO-R inhibition in males, whereas total SNO levels remained unchanged in females. However, we found that although GSNO-R inhibition significantly increased SNO at the cardioprotective Cys39 residue of nicotinamide adenine dinucleotide (NADH) dehydrogenase subunit 3 in males, SNO-NADH dehydrogenase subunit 3 levels were surprisingly reduced in N6022-treated female hearts. Because GSNO-R also acts as a formaldehyde dehydrogenase, we examined postischemic formaldehyde levels and found that they were nearly 2-fold higher in N6022-treated female hearts compared with nontreated hearts. Importantly, the mitochondrial aldehyde dehydrogenase 2 activator, Alda-1, rescued the phenotype in GSNO-R-/- female hearts, significantly reducing infarct size. CONCLUSIONS: These striking findings point to GSNO-R as a critical sex-dependent mediator of myocardial protein SNO and formaldehyde levels and further suggest that different therapeutic strategies may be required to combat ischemic heart disease in males and females.