Title of Project: Prenatal Indoor Air Pollution Exposure and Maternal Asthma Health Among High Risk Obstetric Patients

Principal Investigator: Sonali Bose, MD, MPH

Co-Investigators: Angela Bianco, MD; Homero Harari, PhD; Rachel Meislin, MD

Project Period:  January 18, 2022– January 17, 2023

Pilot Award Amount: $50,000


Abstract: Poor asthma control during pregnancy is associated with significant adverse pregnancy complications for women, as well as an increased risk of post-natal respiratory disorders in their children. However, the influence of upstream environmental factors on maternal asthma morbidity have not been explored, and this knowledge is a critical foundation to improving maternal and child respiratory health. While indoor environmental exposures to fine particulate air pollution (PM2.5) have been demonstrated as a risk factor for poor asthma control in other populations, the impact of indoor air quality on maternal asthma morbidity during pregnancy is unknown. Our overarching hypothesis is that indoor exposure to fine particulate matter during pregnancy is associated with prenatal asthma morbidity, leading to adverse perinatal/ pediatric outcomes. We propose a feasibility pilot, in which we leverage our existing clinical collaboration between Mount Sinai OB-GYN and Respiratory Institute (RI) investigators to recruit an ethnically-diverse sample of pregnant patients and determine optimal methods to more comprehensively assess indoor PM2.5 and maternal asthma morbidity throughout gestation. To accomplish this, we will deploy indoor environmental monitors at repeated points in the pregnancy. In addition, we will integrate an existing clinical platform designed to remotely capture respiratory health data (currently being used at the RI to monitor post-COVID patients), including repeated validated asthma control questionnaires and spirometric lung function among pregnant mothers with active asthma. Identification of environmental determinants of increased asthma morbidity among urban pregnant women fills a significant gap in our understanding of factors contributing to poor perinatal outcomes within a vulnerable subpopulation. Data from this study will inform a larger longitudinal study powered to examine associations between a range of indoor pollutants/allergens and their mixtures and perinatal asthma-related complications, setting the stage for future interventions to mitigate pregnancy complications and transgenerational effects of maternal asthma on child respiratory health.

Title of Project: Air Pollution, Mitochondrial Heteroplasmy (MH), and Vaccine Efficacy in Children

Principal Investigator (MPI): Mike He PhD; Maayan Yitshak-Sade, PhD; Elena Colicino, PhD

Co-Investigators: Itai Kloog, PhD; Allan Just, PhD; Corina Lesseur, MD, PhD; Robert O. Wright, MD, MPH

Project Period: January 18, 2022– January 17, 2023

Pilot Award Amount: $25,000

Abstract: The mitochondrion is one of the primary targets of oxidative stress to environmental exposure. Mitochondrial heteroplasmy (MH), the presence of subpopulations of mitochondria carrying mutations of their DNA sequence, is considered a marker of cumulative lifetime oxidative stress. The COVID-19 pandemic has generated rising interest in infectious disease epidemiology, and in particular questions about the role that air pollution plays in infectious disease transmission and vaccine effectiveness. Existing research has linked numerous environmental exposures to decreased effectiveness of routine prophylactic vaccinations, but no prior studies have assessed these associations with air pollution. We will link these three topics by studying the mitochondrial genome (mtDNA) and its direct association with fine particulate matter (PM2.5) as well as its indirection association in the epidemiologic pathway of PM2.5 and vaccine efficacy. We will include children in the ages of 4 to 5, enrolled in the Programming Research in Growth, Environment and Social Stress (PROGRESS) longitudinal birth cohort. Biosamples required for this proposal has already been collected through PROGRESS, making this study both time and cost-efficient. We will obtain PM2.5 predictions from satellite-based models with high spatial and temporal resolution. We will assess the association between prenatal and postnatal PM2.5 exposure and tetanus and diphtheria antibody concentrations or mitochondrial heteroplasmy. Finally, we will explore whether mitochondrial heteroplasmy mediates the association of PM2.5 and tetanus and diphtheria antibody concentrations. Data generated through this project will serve as the foundation for a future K99/R00 proposal that will investigate the effects of air pollution mixtures on MH frequency and vaccine antibody concentrations. The multi-PI team include a combination of early-stage and established investigators that provide a spectrum of expertise in exposure sciences, epidemiology, epi/genetics, toxicology, and biostatistics. The proposal uses both the Integrated Health Sciences Facility Core as well as the Biostatistics and Bioinformatics Facility Core.

Title of Project: Development of a novel retrospective biomarker of fluoride exposure using spatial mapping of teeth by laser induced breakdown spectroscopy (LIBS)

Principal Investigator (MPI): Mauro Martinez, PhD; Christine Austin, PhD

Co-Investigators: Manish Arora, BDS, MPH, PhD, FICD

Project Period: January 18, 2022– January 17, 2023

Pilot Award Amount: $25,000


Abstract: Fluoride exposure has been associated with adverse health effects in the brain, kidney and other tissues. An important aspect to studying the health effects associated with fluoride exposure is capturing the timing of exposure. However, longitudinal measures of fluoride in traditional matrices is challenging. This project proposes a new method to quantify fluoride in teeth using laser induced breakdown spectroscopy (LIBS) that will reconstruct a history of early life fluoride exposure through quantitative mapping of fluoride in deciduous teeth. LIBS is an emission technique that measures fluoride in its atomic and molecular state, as calcium mono fluoride (CaF) that can be formed under the sampling environment. The quantification of fluoride requires a series of matrix-matched reference materials. As no such standard series is available commercially, we will use a new method to generate matrix-match standards of hydroxyapatite with known concentrations of fluoride. This new material will imitate teeth under laser ablation, enabling the optimization of LIBS acquisition parameters for high sensitivity and linearity at fluoride concentration ranges expected in teeth from individuals exposed to fluoridated and non-fluoridated water. We will validate this method within an animal model of fluoride exposure by testing the association between fluoride levels in teeth measured by LIBS and the fluoride dose, and by comparing LIBS values against that measured using an ion-selective electrode, an established technique that requires pulverization and acid digestion of the whole tooth. This method will develop a retrospective biomarker of fluoride exposure from the 2nd trimester to one year old at monthly intervals, and is minimally destructive so subsequent analysis can be performed on the same sample. This new biomarker will open a new perspective for future epidemiological studies to identify critical windows of early life fluoride exposure.

Title of Project: School Ventilation and SARS-CoV-2 Test Positivity: A Community-Based Study

Principal Investigator (MPI): Nicholas DeFelice, PhD; Maida Galvez, MD, MPH

Co-I: Laura McGuinn, PhD; Rachel Vreeman, MD, MS; Alison Lee, MD, MS, Chris Gennings, PhD, Nicole Bouvier, MD; Efrain Guerrero

Project Period: January 18, 2022– January 17, 2023

Pilot Award Amount: $25,000


Abstract: During the COVID-19 pandemic, governments have implemented a range of public health measures including school closures to slow the spread of SARS-CoV-2. While the direct risk of COVID-19 infection in children is lower relative to the adult population, the indirect harms of the pandemic are substantial. School closures, in particular, can have immediate and long-lasting impacts on child development. In New York City (NYC), the calculated magnitude of student-level learning losses due to COVID-19 and the transition away from classroom-based instruction was on average 125 (69%) and 212 (118%) days of reading and math, respectively, relative to a typical 180-day school year. Opening schools to in-person learning is an important step in re-opening the economy; however, it comes with the risk of increasing contact networks. Together with our community partner, KIPP New York City public schools, we will explore the increased potential for transmission due to in-person schooling, by building statistical models where we will characterize (1) built environment profiles for each school and (2) mitigation measures for in-person schooling, and also explore associations with burden of COVID-19. We will collect data on school-level ventilation and additional mitigation strategies that were implemented within KIPP NYC and NYC schools, and relate these strategies to infection monitoring data. Finally, we will assess parents support of school-level mitigation strategies and whether this differs by certain demographic factors. Our ultimate goal is to identify cost effective and optimal environmental strategies to minimize transmission potential due to in-person schooling, and recommend robust, effective risk mitigation interventions to prevent the spread of SARS-CoV-2 and other respritory diseases. The findings from this pilot study will be used in multiple NIH grant applications, including R01s and K25 awards.

Title of Project: Association between Air Pollution, Stress, and Sleep Efficiency in 6 -7-year-old Children living in East Harlem

Principal Investigator (MPI): Terry Thompson, DHA, MPH; Maida Galvez, MD, MPH

Co-Investigators: Robert O. Wright, MD, MPH; Sarah Evans, PHD, MPH; Leon Hsu, ScD; Ray Lopez, BA; Luz Guel, BA, BS

Period: January 18, 2022– January 17, 2023

Pilot Award Amount: $25,000


Abstract: Environmental toxicants, broadly defined to encompass chemical and non-chemical risk factors, present in the built environment, can adversely impact children’s growth and development. Children are particularly vulnerable to environmental exposures because of the sensitive nature of children’s neurodevelopment, a prenatal life stage marked by cell differentiation. Recently Bose et al. found an association between prenatal PM2.5 exposure and poorer sleep outcomes (i.e., sleep quantity and quality) in childhood. Yet, little is known about the relationship between air quality and sleep efficiency among children, within the larger context of household and psychosocial conditions. To address this knowledge gap, this pilot research study will examine potential relationships between indoor air quality and its effects on sleep patterns among twenty-five Hispanic children, 6-7 years old living in East Harlem. Aims are: 1) Engage with the Community Advisory Board (CAB) to assess environmental factors that may affect neighborhood air quality and child sleep in East Harlem via study design, and implementation of home and child appropriate healthy resources to assess caregiver understanding and perception of air pollution and household environmental risk factors that may affect child sleep. 2) Quantify associations between household PM2.5 exposure and sleep quantity and quality using indoor air monitors, continuous actigraphy, and a validated sleep questionnaire. 3) Working closely with the CAB, create reports for study participants outlining individual and aggregate study findings and steps they can take to improve air quality and child sleep. Reports will be tailored to the community needs and health literacy levels and educational resources adapted from existing materials from the Mount Sinai Pediatric Environmental Health Specialty Unit and the Institute for Exposomics Research. We will apply Community Advisory Board (CAB) involvement and community-partnered approaches throughout all stages of this study to ensure the needs of the study population are met.

Title of Project: The Impact of Prenatal Pesticide Exposure on Child Respiratory Outcomes in Mexico City

Principal Investigator: Cecilia Alcala, PhD, MPH; Maria Jose Rosa, DrPH

Co-Investigators: Syam Andra, PhD; Shelley Liu, PhD; Robert O. Wright, MD, MPH

Project Period:  January 18, 2022– January 17, 2023

Pilot Award Amount: $25,000


Abstract: In utero exposure to pesticides may adversely affect the developing respiratory system. There is limited assessment of prenatal pesticide exposure in urban settings particularly in Latin America and their association with adverse respiratory outcomes remains understudied. Sex differences have also been observed when exploring the effects of pesticide exposure. However, research on sex differences in the association between prenatal pesticide exposure and adverse respiratory outcomes is lacking. Thus, we aim to leverage the Programming Research in Obesity, Growth, Environment, and Social Stressors (PROGRESS) cohort in Mexico to assess in utero pesticide exposure to organophosphate insecticides, and to evaluate their association with childhood lung function, and respiratory and atopic disease in childhood. We will analyze spot urine samples that were collected during the second trimester of pregnancy for dialkyl phosphates specific organophosphorus pesticide metabolites. Pulmonary function was assessed through spirometry (pre and post bronchodilator) and asthma, wheezing, and atopic disease was measured via the validated Spanish version of the International Study of Asthma and Allergies in Childhood survey (ISAAC). We hypothesize that higher prenatal pesticide exposure will be associated with adverse pulmonary function and asthma, wheezing, atopic disease, and sex differences will be observed.

Title of Project: Effect of Electronic Cigarette During Pregnancy on Maternal Urinary Metabolomics and the Neonatal Meconium Microbiome Related to Glucose Metabolism

Principal Investigator: Kirtan Kaur, PhD, MS, MPhil; Jia Chen, ScD

Co-Investigators: Lauren Petrick, PhD; Jianzhong Hu, PhD; Corina Lesseur, MD, PhD; Laura Stroud, PhD

Project Period:  January 18, 2022– January 17, 2023

Pilot Award Amount: $20,000


Abstract: Electronic cigarette (e-cig) use is on the rise and viewed as a safer alternative to regular cigarettes. Pregnant women are amongst those who often hold this view and have been documented to use e-cigs during pregnancy. There are limited studies exploring the effects of e-cig use on health outcomes, in particular among pregnant women. E-cig liquids are formulated with sugar alcohol bases, additives and flavorings (i.e., propylene glycol, vegetable glycerin) that can adversely impact glucose metabolism, which can be more detrimental to the dynamic maternal metabolism during pregnancy and to her developing fetus. This pioneering pilot study will assess how e-cig use during pregnancy impacts glucose homeostasis using urinary metabolomic analysis as well as the initial neonatal gut microbiome. An additional exploratory aim will examine whether birth outcomes (i.e., gestational age, birthweight) are associated with e-cig-related changes in metabolites and specific microbial profiles related to glucose metabolism. We will take advantage of a newly established birth cohort study focusing on the effects of maternal smoking behaviors during pregnancy and postnatal health outcomes. Maternal urine samples are collected in the second and third trimesters and neonate meconium is collected at birth. The urinary metabolome will be assayed with LC-MS and the meconium microbiome assessed by 16S rRNA sequencing. A targeted statistical pipeline will be used to focus the analysis on metabolites and microbe species relevant to glucose metabolism and insulin resistance. Lastly, birth outcome data will be gathered and assessed for correlations with the e-cig-related changes in the maternal urinary metabolome and neonatal meconium microbiome. Understanding how prenatal e-cig use can impact maternal metabolism and the initial neonatal microbiome and may subsequently bias both towards dysregulated glucose metabolism is important to evaluating e-cig safety.