Browsing by Subject "Fetus"

Now showing 1 - 8 of 8
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    Age-Related Changes in MicroRNA Expression and Pharmacogenes in Human Liver
    (Wiley, 2015-08) Burgess, Kimberly S.; Philips, Santosh; Benson, Eric A.; Desta, Zeruesenay; Gaedigk, Andrea; Gaedigk, Roger; Segar, Matthew W.; Liu, Yunlong; Skaar, Todd C.; Department of Pharmacology and Toxicology, IU School of Medicine
    Developmental changes in the liver can significantly impact drug disposition. Due to the emergence of microRNAs (miRNAs) as important regulators of drug disposition gene expression, we studied age-dependent changes in miRNA expression. Expression of 533 miRNAs was measured in 90 human liver tissues (fetal, pediatric [1-17 years], and adult [28-80 years]; n = 30 each). In all, 114 miRNAs were upregulated and 72 were downregulated from fetal to pediatric, and 2 and 3, respectively, from pediatric to adult. Among the developmentally changing miRNAs, 99 miRNA-mRNA interactions were predicted or experimentally validated (e.g., hsa-miR-125b-5p-CYP1A1; hsa-miR-34a-5p-HNF4A). In human liver samples (n = 10 each), analyzed by RNA-sequencing, significant negative correlations were observed between the expression of >1,000 miRNAs and mRNAs of drug disposition and regulatory genes. Our data suggest a mechanism for the marked changes in hepatic gene expression between the fetal and pediatric developmental periods, and support a role for these age-dependent miRNAs in regulating drug disposition.
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    Contribution of obesity to racial and ethnic disparities in the risk of fetal myelomeningocele: a population-based study
    (Elsevier, 2023-11-19) Mustafa, Hiba J.; Burns, Catherine T.; Heydari, Mohammad H.; Javinani, Ali; Bidulescu, Aurelian; Habli, Mounira; Khalil, Asma; Obstetrics and Gynecology, School of Medicine
    Background: Prepregnancy obesity and racial-ethnic disparities has been shown to be associated with meningomyelocele. Objective: This study aimed to investigate the association of maternal periconceptional factors, including race-ethnicity and prepregnancy body mass index, with the prevalence of isolated fetal myelomeningocele. Methods: This was a population-based cross-sectional study using Centers for Disease Control and Prevention birth data from 2016 to 2021. Major structural anomalies or chromosomal abnormalities were excluded. Race-ethnicity was classified as non-Hispanic White (reference population), non-Hispanic Black, non-Hispanic Asian, Hispanic, and others. Maternal prepregnancy body mass index was classified as underweight (<18.5 kg/m2), normal (reference group; 18.5-24.9 kg/m2), overweight (25-29.9 kg/m2), and class I (30-34.9 kg/m2), class II (35-39.9 kg/m2), and class III obesity (≥40 kg/m2). A chi-square test of independence was performed to identify factors significantly associated with myelomeningocele. These factors were then stratified into 3 adjusted clusters/levels. The prevalence was calculated per 10,000 live births. The Cochran-Armitage test for trend was used to detect any significant increasing or decreasing trends. Results: A total of 22,625,308 pregnancies with live birth, including 2866 pregnancies with isolated fetal myelomeningocele, were included in the analysis. The prevalence of isolated fetal myelomeningocele per 10,000 live births varied among different racial/ethnic groups, with the highest prevalence found among the non-Hispanic White (1.60 [1.52-1.67]) and lowest among the non-Hispanic Asian (0.50 [0.40-0.64]) population. The prevalence significantly increased with body mass index, with the highest prevalence found in the population with class III obesity (1.88 per 10,000 live births). Subgroup analysis of the associations between the significant variables (obesity, diabetes, hypertension, and education) and each ethnicity in cases with myelomeningocele showed significant variations in prevalence of these variables among different racial/ethnic groups. Following the model with the 3 levels of adjustment described in the Methods section, prepregnancy overweight and class I, II, and III obesity remained significantly associated with the odds of isolated fetal myelomeningocele. The adjusted odds ratios were 1.32 (95% confidence interval, 1.19-1.46; P<.001) for overweight, 1.55 (95% confidence interval, 1.38-1.75; P<.001) for class I obesity, 1.68 (95% confidence interval, 1.45-1.94; P<.001) for class II obesity, and 1.73 (95% confidence interval, 1.47-2.04; P<.001) for class III obesity. Similarly, following the 3-level adjustment model, the obesity-mediated effect of maternal race-ethnicity on the odds of myelomeningocele remained significant (non-Hispanic Black: adjusted odds ratio, 1.03; 95% confidence interval, 1.02-1.05; P<.001; non-Hispanic Asian: adjusted odds ratio, 1.02; 95% confidence interval, 1.01-1.03; P<.001; Hispanic: adjusted odds ratio, 1.5; 95% confidence interval, 1.03-1.6; P<.001). The test for trend among different racial/ethnic groups did not show significant results across the past 6 years. However, the test for trend showed a significant increase in the prevalence of isolated myelomeningocele associated with class II and III obesity over the past 6 years. Conclusion: There has been a rising trend of fetal isolated myelomeningocele in pregnancies with maternal class II and III obesity over the past 6 years after adjusting for other covariates. Prepregnancy obesity, a modifiable risk factor, is a significant driver of racial/ethnic disparities in the overall risk for isolated fetal myelomeningocele.
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    Diverse Perspectives: Considerations About Embryonic Stem Cell Research
    (2006-09-01T18:18:29Z) Indiana University Center for Bioethics, Stem Cell Study Group
    Since the initial isolation of human embryonic stem cells in 1998 (Thomson et al. 1998), important developments in research have offered the promise of valuable therapeutic breakthroughs while continuing to raise significant social, ethical, legal and policy challenges. Among the interests of the Indiana University Center for Bioethics (IUCB) is a desire to engage issues of this kind, and in so doing, to provide a resource to the IU community, to Indiana, and to the entire country. The topic of stem cell research was, therefore, an appropriate one for discussion at the Center. In January 2002, the IUCB created a Stem Cell Study Group (SCSG). Our primary goal was to provide a forum for informed public discussion of the issues by making use of the considerable local scientific, legal and ethical expertise. In other words, we wanted primarily to educate ourselves about these issues. Our secondary goal was to identify and describe those points on which agreement could be achieved, as well as those issues on which agreement proved difficult if not impossible. This paper summarizes our efforts to meet both of these goals.
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    Firearm Injuries during Pregnancy in the USA
    (MDPI, 2023-07-09) Luster, Taylor; Loder, Randall T.; Orthopaedic Surgery, School of Medicine
    Trauma during pregnancy is the leading cause of non-pregnancy-related maternal deaths, with some due to injuries from firearms. It was the purpose of this study to characterize the patterns and presentations of firearm-associated injuries in pregnant women using a national emergency department visit database. Data from the Inter-University Consortium for Political and Social Research Firearm Injury Surveillance Study 1993–2020 were utilized. The data include age, sex, race, type of firearm, perpetrator of injury, intent of injury (unintentional, assault, suicide, or law enforcement), anatomic location of the injury, incident locale, disposition from the emergency department (ED), and whether the patient was shot or not with the firearm. Of the 3.36 million ED visits over this time span for firearm injuries, 4410 were pregnant women. The mean age of the pregnant cohort was 23.6 years, with more Hispanic and fewer White women in the pregnant group compared to the non-pregnant cohort. Pregnant women were more likely to experience an injury involving the lower trunk and had a higher percentage of fatalities and hospital admissions compared to the non-pregnant cohort. Fetal demise occurred in at least 70% of cases. Nearly one half of the assaults (44%) occurred on Saturdays and Sundays. As the cause of these injuries is complex, prevention will require input from multiple sources, including health care providers, social agencies, government agencies, elected officials, and law enforcement.
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    Report and recommendations: research on the fetus appendix -- Part 16
    (2006-07-18T20:56:01Z) United States. National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research
    Part 1 of this report discusses human fetal research. Part 2 explores the value of life. Part 3 considers an ethical appraisal. Part 4 discusses balancing the need for experimentation versus obligation to the fetus. Part 5 proposes fetal research policy. Part 6 discusses moral issues. Part 7 nonviable fetus research. Part 8 covers ethical and public policy. Part 9 explores ethical issues concerning the nonviable fetus. Part 10 discusses moral issues and institutional control. Part 11 discusses defining death in fetuses. Part 12 reports on distinguishing between viable and nonviable. Part 13 relates to the law on fetus experimentation. Part 14 reports on the legal issues involved in research on the fetus. Part 15 assesses the Batelle Report and the Cook Critique. Part 16 covers the stability of the decision to seek induced abortion.
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    Reports and recommendations: research on the fetus appendix -- Part 15
    (2006-07-18T21:28:35Z) United States. National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research
    Part 1 of this report discusses human fetal research. Part 2 explores the value of life. Part 3 considers an ethical appraisal. Part 4 discusses balancing need for experimentation versus obligation to the fetus. Part 5 proposes fetal research policy. Part 6 discusses moral issues. Part 7 nonviable fetus research. Part 8 covers ethical and public policy. Part 9 explores ethical issues concerning the nonviable fetus. Part 10 discusses moral issues and institutional control. Part 11 discusses defining death in fetuses. Part 12 reports on distinguishing between viable and nonviable. Part 13 relates to the law on fetus experimentation. Part 14 reports on the legal issues involved in research on the fetus. Part 15 assesses the Batelle Report and the Cook Critique. Part 16 covers the stability of the decision to seek induced abortion.
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    The impact of HIV and ART exposure during pregnancy on fetal growth: a prospective study in a South African cohort
    (BMC, 2023-06-03) Mtintsilana, Asanda; Norris, Shane A.; Dlamini, Siphiwe N.; Nyati, Lukhanyo H.; Aronoff, David M.; Koethe, John R.; Goldstein, Jeffrey A.; Prioreschi, Alessandra; Medicine, School of Medicine
    Background: In utero exposure to human immunodeficiency virus (HIV) and antiretroviral (ART) is associated with adverse birth outcomes, which are often attributed to alterations in placental morphology. This study used structural equation models (SEMs) to examine the impact of HIV and ART exposure on fetal growth outcomes and whether these associations are mediated by placental morphology in urban-dwelling Black South African women. Methods: This prospective cohort study included pregnant women living with HIV (WLWH, n = 122) and not living with HIV (WNLWH, n = 250) that underwent repeated ultrasonography during pregnancy, and at delivery, to determine fetal growth parameters in Soweto, South Africa. The size and the velocity of fetal growth measures (i.e., head and abdominal circumference, biparietal diameter, and femur length) were calculated using the Superimposition by Translation and Rotation. Placenta digital photographs taken at delivery were used to estimate morphometric parameters and trimmed placental weight was measured. All WLWH were receiving ART for the prevention of vertical transmission of HIV. Results: A trend towards a lower placental weight and significantly shorter umbilical cord length was reported in WLWH compared to their counterparts. After sex stratification, umbilical cord length was significantly shorter in males born to WLWH than in male fetuses born to WNLWH (27.3 (21.6-32.8) vs. 31.4 (25.0-37.0) cm, p = 0.015). In contrast, female fetuses born to WLWH had lower placental weight, birth weight (2.9 (2.3-3.1) vs. 3.0 (2.7-3.2) kg), and head circumference (33 (32-34) vs. 34 (33-35) cm) than their counterparts (all p ≤ 0.05). The SEM models showed an inverse association between HIV and head circumference size and velocity in female fetuses. In contrast, HIV and ART exposure was positively associated with femur length growth (both size and velocity) and abdominal circumference velocity in male fetuses. None of these associations appeared to be mediated via placental morphology. Conclusion: Our findings suggest that HIV and ART exposure directly affects head circumference growth in females and abdominal circumference velocity in male fetuses; but may improve femur length growth in male fetuses only.
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    Use of amplicon-based sequencing for testing fetal identity and monogenic traits with Single Circulating Trophoblast (SCT) as one form of cell-based NIPT
    (PLOS, 2021-04-15) Zhuo, Xinming; Wang, Qun; Vossaert, Liesbeth; Salman, Roseen; Kim, Adriel; Van den Veyver, Ignatia; Breman, Amy; Beaudet, Arthur; Medical and Molecular Genetics, School of Medicine
    A major challenge for cell-based non-invasive prenatal testing (NIPT) is to distinguish individual presumptive fetal cells from maternal cells in female pregnancies. We have sought a rapid, robust, versatile, and low-cost next-generation sequencing method to facilitate this process. Toward this goal, single isolated cells underwent whole genome amplification prior to genotyping. Multiple highly polymorphic genomic regions (including HLA-A and HLA-B) with 10-20 very informative single nucleotide polymorphisms (SNPs) within a 200 bp interval were amplified with a modified method based on other publications. To enhance the power of cell identification, approximately 40 Human Identification SNP (Applied Biosystems) test amplicons were also utilized. Using SNP results to compare to sex chromosome data from NGS as a reliable standard, the true positive rate for genotyping was 83.4%, true negative 6.6%, false positive 3.3%, and false negative 6.6%. These results would not be sufficient for clinical diagnosis, but they demonstrate the general validity of the approach and suggest that deeper genotyping of single cells could be completely reliable. A paternal DNA sample is not required using this method. The assay also successfully detected pathogenic variants causing Tay Sachs disease, cystic fibrosis, and hemoglobinopathies in single lymphoblastoid cells, and disease-causing variants in three cell-based NIPT cases. This method could be applicable for any monogenic diagnosis.