Erythropoiesis and Red Cell Indices Undergo Adjustments during Pregnancy in Response to Maternal Body Size but not Inflammation

During human pregnancy, iron requirements gradually increase, leading to higher amounts of erythropoietin (EPO) and reticulocytes, and changes in erythrocyte size and density. Women with pregestational obesity experience “obesity hypoferremia” during pregnancy, which alters iron homeostasis. In this study we aimed to describe the relationship between EPO and iron nutrition status during nonanemic pregnancy, and to explore whether obesity and inflammation influence erythropoiesis and red cell indices. We conducted a secondary analysis of a cohort followed throughout pregnancy. Participants were nonanemic women assigned to two study groups based on pregestational body mass index (pgBMI): adequate weight (AW, n = 53) or obesity (Ob, n = 40). All received a multivitamin supplement. At gestational ages (GA) 13, 21, 28 and 34, we measured hemoglobin and red cell indices with an ACT-5DIFF hematology counter, and reticulocyte percentage by manual cell counting. EPO, interleukin (IL–6) and markers of iron status, i.e., hepcidin, serum transferrin receptor (sTfr) and ferritin, were measured by ELISA. Bivariate correlations showed that EPO was positively associated with pgBMI, GA, sTfr and IL-6, but negatively associated with hepcidin, ferritin and hemoglobin, and unrelated to iron intake. Generalized linear models adjusted for confounding factors showed that EPO and erythrocyte concentrations were significantly higher in women in the Ob group, while mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and red cell distribution width (RDW) were lower; reticulocytes and mean corpuscular hemoglobin concentration (MCHC) were not different. Differences were not altered when controlling for inflammation (IL–6). These changes suggest that, in addition to altering iron metabolism, a larger maternal body size during pregnancy results in higher erythropoiesis without increasing hemoglobin, which is exhibited in the latter being distributed among more and smaller erythrocytes

Obesity Is Associated with Changes in Iron Nutrition Status and Its Homeostatic Regulation in Pregnancy

The influence of obesity on maternal iron homeostasis and nutrition status during pregnancy remains only partially clarified. Our study objectives were (1) to describe how obesity influences broad iron nutrition spectrum biomarkers such as available or circulating iron (serum transferrin receptor (sTfr) and serum iron), iron reserves (ferritin), and functional iron (hemoglobin); and (2) to depict the regulating role of hepcidin. The above was carried out while considering influential factors such as initial iron nutrition status, iron intake, and the presence of inflammation. Ninety three non-anemic pregnant adult women were included, 40 with obesity (Ob) and 53 with adequate weight (AW); all took ≈30 mg/day of supplementary iron. Information on iron intake and blood samples were obtained at gestational weeks 13, 20, 27, and 35. A series of repeated measure analyses were performed using General Linear Models to discern the effect of obesity on each iron indicator; iron intake, hepcidin, and C-reactive protein were successively introduced as covariates. Available and circulating iron was lower in obese women: sTfr was higher (p = 0.07) and serum iron was lower (p = 0.01); and ferritin and hemoglobin were not different between groups. Hepcidin was higher in the Ob group (p = 0.01) and was a significant predictor variable for all biomarkers. Obesity during pregnancy dysregulates iron homeostasis, resembling “obesity hypoferremia„

Bone Turnover Markers Changes Induced by Plateletpheresis May Be Minimized with Oral Supplementation of Calcium, Minerals, and Vitamin D before the Procedures: A Non-Randomized, Controlled Study

Apheresis allows the collection of specific blood components but changes serum calcium (Ca), magnesium (Mg), copper (Cu), zinc (Zn), and hormones involved in bone metabolism due to citrate infusion. We assessed the effect of oral supplementation of calcium, vitamin D, and minerals as pills or an enriched diet before plateletpheresis donation on levels of divalent cations, hormones, and bone turnover markers that may prevent metabolic changes. Methods: Non-randomized controlled study including 134 donors. Serum parathyroid hormone (PTH), Ca, Mg, Zn, Cu, osteocalcin (OC), vitamin D, and type-1 collagen C-terminal telopeptide (CTX-1) levels were measured at baseline and post-procedure. Donors were divided into four groups: supplemented with calcium carbonate and vitamin D (cal + vitd); those receiving calcium, minerals, and vitamin D (cal + vitd + min); those receiving a calcium-rich diet (diet) and a control group (control). Results: PTH levels increased >1-fold, whereas tCa, tMg, Zn, Cu, iCa, iMg, and vitamin D levels decreased immediately after apheresis amongst donors of any group; when these levels were measured two weeks later, donors in the calcium-vitd and cal + vitd + min groups returned to basal values; donors in the cal + vitd + min group were the only group that kept their levels of OC and CTX unchanged at the different study times. Conclusions: Bone turnover markers changes induced by plateletpheresis may be minimized with oral supplementation of calcium, minerals, and vitamin D two days before the procedures

Early-Life Dietary Cadmium Exposure and Kidney Function in 9-Year-Old Children from the PROGRESS Cohort

Cadmium (Cd) is a toxic metal associated with adverse health effects, including kidney injury or disease. The aims of this study were to estimate dietary Cd exposure during childhood, and to evaluate the association of early-life dietary Cd with biomarkers of glomerular kidney function in 9-year-old Mexican children. Our study included 601 children from the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) cohort with up to five follow-up food frequency questionnaires from 1 to 9 years of age; and 480 children with measures of serum creatinine, cystatin C, and blood nitrogen urea (BUN), as well as 9-year-old estimated glomerular filtration rate. Dietary Cd was estimated through food composition tables. Multiple linear regression models were used to analyze the association between 1 and 9 years, cumulative dietary Cd, and each kidney parameter. Dietary Cd exposure increased with age and exceeded the tolerable weekly intake (TWI = 2.5 µg/kg body weight) by 16–64% at all ages. Early-life dietary Cd exposure was above the TWI and we observed inverse associations between dietary Cd exposure and kidney function parameters. Additional studies are needed to assess kidney function trajectories through adolescence. Identifying preventable risk factors including environmental exposures in early life can contribute to decreasing the incidence of adult kidney disease

Nephrotoxic Metal Mixtures and Preadolescent Kidney Function

Exposure to metals including lead (Pb), cadmium (Cd), and arsenic (As), may impair kidney function as individual toxicants or in mixtures. However, no single medium is ideal to study multiple metals simultaneously. We hypothesized that multi-media biomarkers (MMBs), integrated indices combining information across biomarkers, are informative of adverse kidney function. Levels of Pb, Cd, and As were quantified in blood and urine in 4–6-year-old Mexican children (n = 300) in the PROGRESS longitudinal cohort study. We estimated the mixture effects of these metals, using weighted quantile sum regression (WQS) applied to urine biomarkers (Umix), blood biomarkers (Bmix), and MMBs, on the cystatin C-based estimated glomerular filtration rate (eGFR) and serum cystatin C assessed at 8–10 years of age, adjusted for covariates. Quartile increases in Umix and the MMB mixture were associated with 2.5% (95%CI: 0.1, 5.0) and 3.0% (95%CI: 0.2, 5.7) increased eGFR and −2.6% (95% CI: −5.1%, −0.1%) and −3.3% (95% CI: −6.5%, −0.1%) decreased cystatin C, respectively. Weights indicate that the strongest contributors to the associations with eGFR and serum cystatin C were Cd and Pb, respectively. MMBs detected mixture effects distinct from associations with individual metals or media-type, highlighting the benefits of incorporating information from multiple exposure media in mixtures analyses

Association between 25-OH Vitamin D Deficiency and COVID-19 Severity in Pregnant Women

Evidence from studies in the general population suggests an association between vitamin D insufficiency/deficiency and COVID-19 susceptibility and disease severity. The present study was performed on 165 third-trimester pregnant women at the time of delivery. Seventy-nine women tested negative for SARS-CoV-2. From 86 women testing positive, 32 were asymptomatic, 44 presented a mild form of the disease, and 10 experienced severe symptoms. Serum 25-OH vitamin D levels were measured on blood samples collected on admission. Low vitamin D levels were detected in symptomatic but not asymptomatic COVID-19 patients compared to healthy women (p = 0.0227). In addition, 20 (45.4%) pregnant women in the mild COVID-19 group and 6 (60%) in the severe group were vitamin D deficient (p = 0.030). On the other hand, lasso regression analysis showed that 25-OH vitamin D deficiency is an independent predictor of severe COVID-19 with an odds ratio (OR) of 5.81 (95% CI: 1.108–30.541; p = 0.037). These results show the relationship between vitamin D deficiency in pregnant women and the severity of COVID-19 infection and support the recommendation to supplement with vitamin D to avoid worse COVID-19 outcomes during pregnancy

Prenatal Metal Exposures and Associations with Kidney Injury Biomarkers in Children

Prenatal exposure to arsenic (As), cadmium (Cd), mercury (Hg), and lead (Pb) may be nephrotoxic, yet limited studies have examined subclinical kidney injury biomarkers in children. We assessed whether metal exposure in the second trimester (2T), a crucial time of kidney development, is associated with altered urine kidney injury and function biomarkers in preadolescent children. Analyses included 494 children participating in a birth cohort study in Mexico City. Concentrations of As, Cd, and Pb were measured from pregnant women in 2T blood and urine, and Hg in urine only. Kidney biomarkers were measured from children in urine at age 8–12 years. We assessed the associations between individual metals and (1) kidney biomarkers using linear regression and (2) a multi-protein kidney mixture using weighted quantile sum (WQS) regression. Associations of separate urine and blood metal mixtures with individual kidney biomarkers were assessed via WQS. Within the multi-protein mixture, the association with increased urinary As was predominated by urine alpha-1-microglobulin (A1M), interferon gamma-induced protein 10 (IP10), and fatty acid binding protein 1; the association with increased urinary Cd was predominated by A1M, clusterin, and albumin. The urine metal mixture was associated with increased albumin (0.23 ng/mL; 95% confidence interval (CI): 0.10, 0.37), IP10 (0.15 ng/mL; 95% CI: 0.02, 0.28), and cystatin C (0.17 ng/mL; 95% CI: 0.04, 0.31); these associations were mainly driven by urinary As and Cd. We observed null associations between prenatal blood or urine metal mixtures and estimated glomerular filtration rate. Higher prenatal urinary metals, individually and as a mixture were associated with altered kidney injury biomarkers in children. Further research and longer participant follow-up are required to ascertain the risk of kidney disease later in life