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Collaborative Biostatistical Research

$225,693ZIAFY2023ESNIH

National Institute Of Environmental Health Sciences

Investigators

Linked publications, trials & patents

Abstract

We have been working on several research projects within this project during this reporting year. Here are some accomplishments. 1. Initiated a new project with colleagues in the Division of Population Health Research at NICHD (NIH) to investigate the Effects of Climate Change on Reproductive Health, Pregnancy, and Birth Outcomes in the U.S. Growing evidence indicates that climate change affects human fertility, pregnancy, and childbirth. An important gap in the literature is the lack of a comprehensive evaluation of the effects of climate change on male and female fertility, pregnancy, and childbirth. The goal of our project is to investigate how spatiotemporal changes in human fertility, pregnancy, and childbirth in the US are associated with climate change. This research leverages reproductive outcomes, demographic and socioeconomic indicators data collected in NICHDs Division of Population Health Research (DiPHR) preconception cohort studies spanning 13 years that include 4000 participants across eight states around the country (Colorado, Iowa, Illinois, Michigan, New York, Pennsylvania, Texas, and Utah). These data are being integrated with various publicly available climate parameters obtained from EPA, NOAA and other agencies. Using the resulting database, we shall investigate how changes in climate indicators are associated with a wide variety of reproductive endpoints, including semen quality parameters, female endocrine parameters, pregnancy, pregnancy loss, and pregnancy outcomes and complications. Novel statistical methodologies will be developed for analyzing such complex data. 2. Initiated a new project to evaluate the changes in the oral and gut microbial compositions, and their metagenomes, microbial growth dynamics, and microbial biproducts such as short chain fatty acids (SCFA) and various metabolites before a subject develops HIV infection. Increasingly research is revealing that the internal environment, specifically the microbiota and the metabolites produced by them, play an important role in HIV/AIDS, particularly in their involvement in immune responses and inflammation. Here we propose a highly innovative study of HIV/AIDS that will evaluate changes in the oral and gut microbial compositions, and their metagenomes, microbial growth dynamics, and microbial biproducts such as short chain fatty acids (SCFA) and various metabolites. To achieve this, we will use unique, cryopreserved biospecimens obtained in the 1980s from men who have sex with men (MSM) in the Multicenter AIDS Cohort Study (MACS), now part of the MACS-WIHS Combined Cohort Study (MWCCS). The oral washes, fecal and plasma samples were obtained from MSM before and after well-documented HIV infection and progression to AIDS, years before the advent of effective antiretroviral therapy (ART), as well as from MSM controls who were not infected with HIV. An additional innovation in this proposal is that we will integrate the oral microbiome with data on our previously studied gut microbiome in the same participants (Chen et al., 2021) to draw inferences regarding HIV infection and progression to HIV/AIDS. By doing so, this new study takes innovative approaches (a) to understand the role of these two anatomic site microbiomes in susceptibility to primary HIV infection and subsequent progression to AIDS, (b) to estimate risk of, and time to, developing AIDS, along with uncertainty estimates well before AIDS, (c) to delineate potential biomarkers for HIV/AIDS to help screen the risk for clinical disease well before the onset of the disease, and (d) to provide a unique, pre-ART dataset to compare with current, ongoing studies of the oral and gut microbiomes in men and women with and without HIV in the MWCCS (to be conducted in a future study). 3. It is established in the literature that per- and polyfluoroalkyl substances (PFAS) disrupt hormonal signaling and we know that uterine fibroids are hormonally mediated. This motivated us to investigate the associations between PFAS and fibroid changes during pregnancy. This project was conducted using data obtained from the Fetal Growth Study, Division of Population Health Research (DiPHR), NICHD. Led by Drs. Mitro and Grantz (NICHD), in this project we investigated perfluorohexanesulfonic acid (PFHxS), perfluorooctanesulfonic acid (PFOS), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA) in plasma obtained from 2,621 women during the pregnancy. Results of the study suggest that some of the PFAS were associated with fibroid growth during pregnancy. For details one may refer to https://doi.org/10.1289/EHP11606. 4. There is considerable discussion in the literature on the associations between the vaginal microbiota and spontaneous preterm birth, and other pregnancy related complications. The disagreements in the literature, in part, may be due to the study design, heterogeneity in the populations, and others. In a study in collaboration with Dr. Romero and colleagues at NICHD, using the data from a large longitudinal study consisting of 474 predominantly African-American women who have a high prevalence of pregnancy complications, we evaluated the associations between vaginal microbiota and maternal characteristics including BMI, parity, and gestational age. For details one may refer to https://journals.asm.org/doi/full/10.1128/spectrum.03429-22

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