4 research outputs found

    Clomifene and Assisted Reproductive Technology in Humans Are Associated with Sex-Specific Offspring Epigenetic Alterations in Imprinted Control Regions

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    Children conceived with assisted reproductive technology (ART) have an increased risk of adverse outcomes, including congenital malformations and imprinted gene disorders. In a retrospective North Carolina-based-birth-cohort, we examined the effect of ovulation drugs and ART on CpG methylation in differentially methylated CpGs in known imprint control regions (ICRs). Nine ICRs containing 48 CpGs were assessed for methylation status by pyrosequencing in mixed leukocytes from cord blood. After restricting to non-smoking, college-educated participants who agreed to follow-up, ART-exposed (n = 27), clomifene-only-exposed (n = 22), and non-exposed (n = 516) groups were defined. Associations of clomifene and ART with ICR CpG methylation were assessed with linear regression and stratifying by offspring sex. In males, ART was associated with hypomethylation of the PEG3 ICR [β(95% CI) = −1.46 (−2.81, −0.12)] and hypermethylation of the MEG3 ICR [3.71 (0.01, 7.40)]; clomifene-only was associated with hypomethylation of the NNAT ICR [−5.25 (−10.12, −0.38)]. In female offspring, ART was associated with hypomethylation of the IGF2 ICR [−3.67 (−6.79, −0.55)]. Aberrant methylation of these ICRs has been associated with cardiovascular disease and metabolic and behavioral outcomes in children. The results suggest that the increased risk of adverse outcomes in offspring conceived through ART may be due in part to altered methylation of ICRs. Larger studies utilizing epigenome-wide interrogation are warranted

    Associations between Maternal Cadmium Exposure with Risk of Preterm Birth and Low Birth Weight: Effect of Mediterranean Diet Adherence on Affected Prenatal Outcomes

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    Prenatal cadmium exposure at non-occupational levels has been associated with poor birth outcomes. The intake of essential metals, such as iron and selenium, may mitigate cadmium exposure effects. However, at high levels, these metals can be toxic. The role of dietary patterns rich in these metals is less studied. We used a linear and logistic regression in a cohort of 185 mother–infant pairs to assess if a Mediterranean diet pattern during pregnancy modified the associations between prenatal cadmium exposure and (1) birth weight and (2) preterm birth. We found that increased cadmium exposure during pregnancy was associated with lower birth weight (β = −210.4; 95% CI: −332.0, −88.8; p = 0.008) and preterm birth (OR = 0.11; 95% CI: 0.01, 0.72; p = 0.04); however, these associations were comparable in offspring born to women reporting high adherence to a Mediterranean diet (β = −274.95; 95% CI: −701.17, 151.26; p = 0.20) and those with low adherence (β = −64.76; 95% CI: −359.90, 230.37; p = 0.66). While the small sample size limits inference, our findings suggest that adherence to a Mediterranean dietary pattern may not mitigate cadmium exposure effects. Given the multiple organs targeted by cadmium and its slow excretion rate, larger studies are required to clarify these findings

    Using Community-Based Participatory Research Principles to Develop More Understandable Recruitment and Informed Consent Documents in Genomic Research

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    <div><p>Background</p><p>Heart Healthy Lenoir is a transdisciplinary project aimed at creating long-term, sustainable approaches to reduce cardiovascular disease risk disparities in Lenoir County, North Carolina using a design spanning genomic analysis and clinical intervention. We hypothesized that residents of Lenoir County would be unfamiliar and mistrustful of genomic research, and therefore reluctant to participate; additionally, these feelings would be higher in African-Americans.</p><p>Methodology</p><p>To test our hypothesis, we conducted qualitative research using community-based participatory research principles to ensure our genomic research strategies addressed the needs, priorities, and concerns of the community. African-American (n = 19) and White (n = 16) adults in Lenoir County participated in four focus groups exploring perceptions about genomics and cardiovascular disease. Demographic surveys were administered and a semi-structured interview guide was used to facilitate discussions. The discussions were digitally recorded, transcribed verbatim, and analyzed in ATLAS.ti.</p><p>Results and Significance</p><p>From our analysis, key themes emerged: transparent communication, privacy, participation incentives and barriers, knowledge, and the impact of knowing. African-Americans were more concerned about privacy and community impact compared to Whites, however, African-Americans were still eager to participate in our genomic research project. The results from our formative study were used to improve the informed consent and recruitment processes by: 1) reducing misconceptions of genomic studies; and 2) helping to foster participant understanding and trust with the researchers. Our study demonstrates how community-based participatory research principles can be used to gain deeper insight into the community and increase participation in genomic research studies. Due in part to these efforts 80.3% of eligible African-American participants and 86.9% of eligible White participants enrolled in the Heart Healthy Lenoir Genomics study making our overall enrollment 57.8% African-American. Future research will investigate return of genomic results in the Lenoir community.</p></div