Vitamin D and Toxic Metals in Pregnancy - a Biological Perspective.

Purpose of Review: To discuss the potential biological mechanisms between vitamin D and toxic metals and summarize epidemiological studies examining this association in pregnant women. Recent Findings: We identified four plausible mechanisms whereby vitamin D and toxic metals may interact: nephrotoxicity, intestinal absorption of metals, endocrine disruption, and oxidative stress. Few studies have examined the association between vitamin D and toxic metals in pregnant women. North American studies suggest that higher vitamin D status early in pregnancy are associated with lower blood metals later in pregnancy. However, a trial of vitamin D supplementation in a pregnant population, with higher metal exposures and lower overall nutritional status, does not corroborate these findings. Summary: Given ubiquitous exposure to many toxic metals, nutritional intervention could be a means for prevention of adverse outcomes. Future prospective studies are needed to establish a causal relationship and clarify the directionality of vitamin D and metals. Supplementary Information: The online version contains supplementary material available at 10.1007/s40471-024-00348-0.

Association between serum 25-hydroxyvitamin D and antimüllerian hormone levels in a cohort of African-American women.

OBJECTIVE: To examine the association between serum 25-hydroxyvitamin D [25(OH)D] levels and ovarian reserve as measured using antimüllerian hormone (AMH) levels. DESIGN: Cross-sectional study. SETTING: Detroit, Michigan area. PATIENTS: Data were obtained from a prospective cohort of self-identified Black or African American women aged 23-35 years at the time of enrollment (N = 1,593), who had no prior diagnosis of polycystic ovary syndrome, were not currently pregnant, and were not missing AMH or 25(OH)D level measures. INTERVENTION: Serum 25(OH)D. MAIN OUTCOME MEASURE(S): The serum AMH level was the main outcome. Linear regression was used to examine the associations between categorical 25(OH)D levels (<12, 12-<20, 20-<30, and ≥30 ng/mL) and continuous natural log-transformed AMH levels. Associations between 25(OH)D and high (upper 10th percentile: >7.8 ng/mL) or low AMH (<0.7 ng/mL) levels were estimated with logistic regression. Models were adjusted for age, age-squared, body mass index (kg/m2), hormonal contraceptive use, smoking, and exercise. RESULTS: The 25(OH)D levels were low; 70% of participants were below 20 ng/mL. In fully adjusted models, compared with 25(OH)D levels <12 ng/mL, those with 25(OH)D levels of 12-<20, 20-<30, and ≥30 ng/mL had an AMH level that was 7% (95% confidence interval [CI]: -4, 20), 7% {95% CI: -6, 22}, or 11% {95% CI: -7, 34} higher, respectively. Moreover, these groups had lower odds of having low AMH levels (odds ratio [95% CI]: 0.63 {0.40, 0.99}, 0.60 {0.34, 1.07}, and 0.76 {0.35, 1.65}, respectively), and the highest category of 25(OH)D levels had higher odds of having high AMH levels (odds ratio [95% CI]: 1.42 {0.74, 2.72}). Exclusion of participants with either irregular cycles or very high AMH (>25 ng/mL) levels did not alter the associations. CONCLUSION: Taken together, these results indicate that higher levels of 25(OH)D are associated with slightly higher AMH levels, lower odds of low AMH levels, and higher odds of high AMH levels. This evidence is weak, however, because only a small percentage of participants had high 25(OH)D levels. Future studies should examine populations with a wide distribution of 25(OH)D levels (both high and low), with a clinical trial design, or with longitudinal measures of both 25(OH)D and AMH levels.

Seminar: Extracellular Vesicles as Mediators of Environmental Stress in Human Disease.

BACKGROUND: Extracellular vesicles (EVs), membrane-bound particles containing a variety of RNA types, DNA, proteins, and other macromolecules, are now appreciated as an important means of communication between cells and tissues, both in normal cellular physiology and as a potential indicator of cellular stress, environmental exposures, and early disease pathogenesis. Extracellular signaling through EVs is a growing field of research for understanding fundamental mechanisms of health and disease and for the potential for biomarker discovery and therapy development. EVs are also known to play important roles in mediating the effects of exposure to environmental stress. OBJECTIVES: This seminar addresses the application of new tools and approaches for EV research, developed in part through the National Institutes of Health (NIH) Extracellular RNA Communication Program, and reflects presentations and discussions from a workshop held 27-28 September 2021 by the National Institute of Environmental Health Sciences (NIEHS) and the National Center for Advancing Translational Sciences (NCATS) on "Extracellular Vesicles, Exosomes, and Cell-Cell Signaling in Response to Environmental Stress." The panel of experts discussed current research on EVs and environmental exposures, highlighted recent advances in EV isolation and characterization, and considered research gaps and opportunities toward identifying and characterizing the roles for EVs in environmentally related diseases, as well as the current challenges and opportunities in this field. DISCUSSION: The authors discuss the application of new experimental models, particularly organ-on-chip (OOC) systems and in vitro approaches and how these have the potential to extend findings in population-based studies of EVs in exposure-related diseases. Given the complex challenges of identifying cell-specific EVs related to environmental exposures, as well as the general heterogeneity and variability in EVs in blood and other accessible biological samples, there is a critical need for rigorous reporting of experimental methods and validation studies. The authors note that these efforts, combined with cross-disciplinary approaches, would ensure that future research efforts in environmental health studies on EV biomarkers are rigorous and reproducible. https://doi.org/10.1289/EHP12980.

A Rare Presentation of Polyangiitis Overlapping Syndrome.

This case follows a 38-year-old Caucasian male with no known medical history who presented to the emergency department for syncope. He also endorsed a two-month history of fevers, weight loss, oral ulcers, rashes, joint swelling and arthralgias. After extensive workup, he was given a working diagnosis of granulomatosis with polyangiitis (GPA). Conflicting diagnostic evidence made it increasingly difficult to distinguish between GPA and eosinophilic granulomatosis with polyangiitis. In conclusion, we believe the patient may be better diagnosed with polyangiitis overlapping syndrome.

Circulating miRNAs in the first trimester and pregnancy complications: a systematic review.

Most pregnancy complications originate with early placentation. MicroRNAs (miRNAs) may play an important role in placentation and function as biomarkers of future pregnancy complications. We summarized from the literature all first trimester circulating miRNAs associated with pregnancy complications of placental origin and further identified the miRNAs which have the most evidence as potential early biomarkers for pregnancy complications. We conducted a systematic review following PRISMA reporting guidelines (PROSPERO CRD42020183421). We identified all first trimester serum or plasma miRNAs associated with a pregnancy complication of placental origin (preeclampsia, intrauterine growth restriction (IUGR), gestational hypertension, preterm delivery) and the number of times those miRNAs were identified, as a measure of replication. Twenty-one studies examined 118 unique miRNAs, and 87 were associated with at least one pregnancy complication; preeclampsia was the most common. Seven miRNAs were significantly associated with a pregnancy complication in at least two studies: miR-125b, miR-518b, miR-628-3p, miR-365a-3p, miR-520h, miR-374a-5p, miR-191-5p. Few miRNAs were associated with more than one pregnancy complication: miR-518b and miR-520h with preeclampsia and gestational hypertension, miR-374a-5p and miR-191-5p with preterm birth and preeclampsia. Our systematic review suggests seven miRNAs as potential biomarkers of pregnancy complications. These complications are thought to originate with early placental defects and these miRNAs may also be biomarkers of placental pathology. First-trimester biomarkers of pregnancy complications can facilitate early detection and interventions.

Central Venous Catheter Placement Gone Awry: A Case Report of Right Internal Jugular Central Line Entering Subclavian Artery.

While central venous access is necessary for a variety of situations including inadequate peripheral venous access, medication administration, hemodynamic monitoring, vasopressor administration, and hemodialysis, complications during the insertion process are not uncommon. In the United States, in both critically ill medical patients and surgical patients, millions of central venous catheters are inserted yearly. Complications occurring during or immediately following insertion include cardiac, pulmonary, and vascular injuries as well as issues with catheter placement. This case report describes a rare malposition of the central venous cannula into the subclavian artery. Few case reports of accidental subclavian artery catheterization have been published following internal jugular vein insertion. While arterial puncture is a well-recognized complication, accidental subclavian artery catheterization is even rarer than carotid artery cannulation. In the literature review, only two documented case reports for reference were found. There are severe risks associated with arterial cannulation including atherosclerotic plaque dislodgement, stroke, hemothorax, pseudoaneurysm, arteriovenous fistula formation, and death. This case follows a 78-year-old man who was brought in by emergency medical services (EMS) minimally responsive with hemodynamic instability - hypothermic, hypotensive, and tachycardic. The emergent decision was made to proceed with central venous catheter placement in the emergency department and placement was initially confirmed with radiologic evidence. Over the admission course, the patient had improvement in hemodynamic instability with minimal change in mental status, however, the need for further testing revealed the central line that was previously functioning without difficulty was arterial. Imaging demonstrated catheter traversed the internal jugular vein and inserting into the right subclavian artery requiring emergent transfer for vascular and cardiothoracic surgery intervention. While a rare complication, this case, differing from previously documented reports due to the delay in discovery, exemplifies how further investigation may be warranted to confirm catheter placement prior to removal to reduce the risk of life-threatening situations.

Thrombocytopenia in Chronic Liver Disease: Challenges and Treatment Strategies.

Thrombocytopenia is a common hematologic complication seen in patients with chronic liver disease (CLD). The pathophysiology of thrombocytopenia in CLD is multifactorial, primarily stemming from platelet sequestration and decreased platelet production. This review focuses on the pathophysiology and current treatment options in the treatment of thrombocytopenia in chronic liver disease. While platelet transfusions are the gold standard of treatment, considerations ought to be given to CLD patients who can benefit from transjugular intrahepatic portosystemic shunt and splenic artery embolization. Finally, the recent approval of thrombopoietin receptor agonists for use in CLD patients paves a way for a safe and effective alternative method of improving platelet levels and reducing the need for recurrent platelet transfusions.

Effect of vitamin D supplementation during pregnancy on mid-to-late gestational blood pressure in a randomized controlled trial in Bangladesh.

OBJECTIVE: To examine the dose-dependent effect of maternal vitamin D during pregnancy on blood pressure from mid-to-late gestation within the context of a randomized, placebo-controlled trial of vitamin D supplementation in Bangladesh (n = 1298). METHODS: Healthy women without hypertension were enrolled at 17-24 weeks gestation and randomized to one of four vitamin D doses during pregnancy: placebo, 4200, 16 800 or 28 000 IU/week. This substudy examined 1257 women with blood pressure measured at enrollment with at least one other timepoint (measurements included at 24 weeks, 30 weeks, and weekly from 36 weeks until delivery). Effects of vitamin D on SBP or DBP were analyzed using mixed-effects models. RESULTS: Vitamin D did not have an effect on SBP or DBP at 24 or 30 weeks; blood pressure was higher at 36 weeks for the highest dose versus placebo [mean difference (95% CI) mmHg: SBP = 2.3 (0.9-3.7); DBP = 1.9 (0.7-3.0)]. The differences in changes in SBP and DBP between vitamin D groups and placebo across intervals were small (P > 0.10), but the difference for 28 000 IU/week versus placebo was the highest from 30 to 36 weeks [SBP 0.2 (-0.1 to 0.5) and DBP 0.2 (-0.0 to 0.4) mmHg]. CONCLUSION: Vitamin D supplementation starting mid-pregnancy did not affect SBP or DBP until late gestation, and then only at the highest dose. These results do not support the clinical use of vitamin D in pregnancy to lower maternal blood pressure.

Vitamin D metabolites across the menstrual cycle: a systematic review.

BACKGROUND: Accurate estimation of vitamin D status is important for health research and can impact prevention and treatment of deficiency in women of reproductive age. We aimed to assess if blood concentrations of 25-hydroxyvitamin D [25(OH)D] or 1,25-dihydroxyvitamin D [1,25(OH)2D] change across the menstrual cycle. METHODS: We conducted a systematic search in PubMed, Web of Science, CAB and BIOSIS of literature published until December 2018 which reported concentrations of vitamin D metabolites at two or more identified points among women with regular menstrual cycles. RESULTS: Ten longitudinal studies met the inclusion criteria; nine studies measured 1,25(OH)2D and five studies measured 25(OH)D. Study size ranged from 5 to 47 subjects, with an age range of 18-47 years. One study found a decrease in concentration of 25(OH)D in the periovulatory and luteal phase. Four studies found no changes in concentrations of 25(OH)D. Two studies found a rise in 1,25(OH)2D within the follicular phase, including a 128% increase from day 1 to 15 and a 56% increase from day 0 to 12. Two studies found rises in 1,25(OH)2D concentrations from the follicular to luteal phase of 13 and 26%. Five studies did not find any changes in concentrations of 1,25(OH)2D. CONCLUSIONS: No conclusion can be drawn on the pattern of 1,25(OH)2D concentrations across the normal menstrual cycle due to inconsistencies in study findings. Evidence is currently insufficient to assess 25(OH)D concentrations across the cycle. Future studies should aim to measure 1,25(OH)2D and 25(OH)D longitudinally, to understand relationships with other hormones and the potential impact on estimates of vitamin D deficiency.