Higher Hb Concentration Research Articles

A novel PEG-mediated approach to entrap hemoglobin (Hb) within ZIF-8 nanoparticles: Balancing crystalline structure, Hb content and functionality

Hemoglobin (Hb)-based oxygen carriers are investigated as a potential alternative or supplement to regular blood transfusions, particularly in critical and life-threatening scenarios. These include situations like severe trauma in remote areas, battlefield conditions, instances where blood transfusion is not feasible due to compatibility concerns, or when patients decline transfusions based on religious beliefs.This study introduces a novel method utilizing poly(ethylene glycol) (PEG) to entrap Hb within ZIF-8 nanoparticles (i.e., Hb@ZIF-8 NPs). Through meticulous screening, we achieved Hb@ZIF-8 NPs with a record-high Hb concentration of 34 mg mL−1. These NPs, sized at 168 nm, displayed exceptional properties: a remarkable 95 % oxyhemoglobin content, excellent encapsulation efficiency of 85 %, and resistance to Hb oxidation into methemoglobin (metHb). The addition of PEG emerged as a crucial factor amplifying Hb entrapment within ZIF-8, especially at higher Hb concentrations, reaching an unprecedented 34 mg mL−1. Importantly, PEG exhibited a protective effect, preventing metHb conversion in Hb@ZIF-8 NPs at elevated Hb concentrations.

The relationship between haemoglobin concentrations and obstructive sleep apnea syndrome: A systematic review and meta-analysis

BackgroundThis systematic review and meta-analysis investigates the relationship between haemoglobin (Hb) concentrations and obstructive sleep apnea syndrome (OSAS). MethodsFollowing PRISMA guidelines, we searched PubMed, EMBASE, and Cochrane Library from inception to March 8, 2024. Eligible studies included cross-sectional, cohort, and case-control designs comparing Hb concentrations in OSAS patients and healthy controls. Two reviewers independently screened records and extracted data. The risk of bias was assessed using the Joanna Briggs Institute checklist. ResultsA total of 27 studies involving 6499 OSAS subjects and 5199 controls were included. Hb concentrations were significantly higher in OSAS patients compared to controls (SMD: 0.28; 95 % CI: 0.18 to 0.39; I2 = 84.4 %). Subgroup analysis by OSAS severity showed that severe OSAS patients had higher Hb concentrations than those with mild/moderate OSAS. Sensitivity analyses confirmed the robustness of the findings. However, 7 studies reported opposite results, indicating possible regional or methodological differences. ConclusionHb concentrations are elevated in OSAS patients, with higher levels observed in severe cases. The significant heterogeneity and the predominance of studies from Turkey highlight the need for further research in diverse populations. Limitations include potential publication bias and variability in study designs.

Association between maternal hemoglobin concentration and educational attainment in mid-childhood in a high-resource obstetric setting: a prospective cohort study

BackgroundAlthough maternal Hb levels during pregnancy are commonly associated with perinatal outcomes, their link to childhood neurodevelopment remains uncertain. ObjectiveThis study aimed to examine the associations between maternal hemoglobin (Hb) in early and late pregnancy with offspring mid-childhood educational attainment in a high-resource obstetric setting. Study DesignPregnancy data from a prospective birth cohort (Pregnancy Outcome Prediction Study, Cambridge, UK, 2008-2012, N=3285) were linked to mid-childhood educational outcomes (Department for Education, UK). Regression models adjusted for maternal, child, and socioeconomic factors were used to determine associations between maternal Hb, pregnancy complications, and offspring educational outcomes (ages 5-7). ResultsNo association was observed between maternal Hb at 12 weeks and the likelihood of either adverse pregnancy outcomes or children meeting expected educational standards between ages 5-7. Higher maternal Hb at 28 weeks was associated with an increased risk of small-for-gestational age infants (aOR1.26, 95%CI 1.11-1.59; p=0.002) and preterm birth (aOR1.38, 95%CI 1.11-1.81; p=0.005). There were no adverse birth outcomes associated with anemia. However children of mothers who were anaemic at 28 weeks had ∼40% increased risk of not attaining expected educational standards at age 5 (aOR1.42, 95%CI 1.03-1.95; p=0.03). There was no association between maternal anemia at 28 weeks and educational performance at ages 6-7. No associations were found between high maternal Hb concentrations (top decile) or change Hb concentrations between 12-28 weeks and childhood educational attainment. ConclusionsMaternal anemia at 28 weeks of pregnancy is associated with reduced educational attainment aged 5, but not at older ages (6-7 years). A proactive approach to increasing maternal hemoglobin in high-resource settings is unlikely to impact on long-term childhood educational attainment.

Association between low selenoprotein P concentrations and anaemia in hospitalized heart failure patients.

Heart failure (HF) patients with anaemia tend to have a worse outcome, with increased hospitalization rates, decreased exercise tolerance, and higher mortality compared to those without anaemia. Limited research exists on the association between selenium deficiency and anaemia specifically in HF patients, despite previous findings of a correlation in different populations. The BIOSTAT-CHF study demonstrated that higher selenium levels in HF patients were associated to a lower risk of anaemia and iron deficiency. This study investigates the relationship between selenoprotein P (SELENOP) concentrations, a major contributor and functional biomarker of selenium transport, and anaemia, Hb levels, and iron status in hospitalized HF patients. SELENOP was analysed in 320 hospitalized HF subjects, with complete data available for 310 subjects. The relationships between continuous SELENOP concentrations and 1) Hb concentrations, 2) anaemia (Hb<115g/L (women), <130g/L (men)), and 3) iron status (as measured by transferrin receptor 1 (TfR1) which increases in iron deficiency) were evaluated using multivariable logistic and linear regression models. Additionally, SELENOP concentrations in the lowest quartile were related to anaemia, haemoglobin, and iron state in multivariable logistic and linear models. The mean age of the study population was 75.0±11.6years, and 30% were women. Anaemia was present in 133 subjects (42.9%). SELENOP concentrations were positively correlated with haemoglobin concentrations (0.238; P<0.001) and negatively with TfR1 concentrations (-0.238, P<0.001). In multivariable regression models, higher SELENOP concentrations were associated with higher Hb concentrations (B=3.23; P=0.002) and lower TfR1 concentrations (B=-0.20; P<0.001). Furthermore, SELENOP deficiency was associated with lower Hb concentrations (B=-7.64: P=0.001), higher TfR1 concentrations (B=0.31; P=0.003), and higher odds of anaemia in HF patients (odds ratio 2.17; 95% confidence interval 1.23-3.82; P=0.008). In hospitalized heart failure patients, lower concentrations of SELENOP were associated with higher prevalence of anaemia.

Maternal low and high hemoglobin concentrations and associations with adverse maternal and infant health outcomes: an updated global systematic review and meta-analysis

BackgroundGrowing evidence suggests low and high maternal hemoglobin (Hb) concentrations may have adverse consequences for maternal and child health. There remain questions on specific Hb thresholds to define anemia and high Hb as well as how cutoffs may vary by anemia etiology and timing of assessment.MethodsWe conducted an updated systematic review (using PubMed and Cochrane Review) on low (< 110 g/L) and high (≥ 130 g/L) maternal Hb concentrations and associations with a range of maternal and infant health outcomes. We examined associations by timing of Hb assessment (preconception; first, second, and third trimesters, as well as at any time point in pregnancy), varying cutoffs used for defining low and high hemoglobin concentrations and performed stratified analyses by iron-deficiency anemia. We conducted meta-analyses to obtain odds ratios (OR) and 95% confidence intervals.ResultsThe updated systematic review included 148 studies. Low maternal Hb at any time point in pregnancy was associated with: low birthweight, LBW (OR (95% CI) 1.28 (1.22–1.35)), very low birthweight, VLBW (2.15 (1.47–3.13)), preterm birth, PTB (1.35 (1.29–1.42)), small-for-gestational age, SGA (1.11 (1.02–1.19)), stillbirth 1.43 (1.24–1.65)), perinatal mortality (1.75 (1.28–2.39)), neonatal mortality (1.25 (1.16–1.34), postpartum hemorrhage (1.69 (1.45–1.97)), transfusion (3.68 (2.58–5.26)), pre-eclampsia (1.57 (1.23–2.01)), and prenatal depression (1.44 (1.24–1.68)). For maternal mortality, the OR was higher for Hb < 90 (4.83 (2.17–10.74)) than for Hb < 100 (2.87 (1.08–7.67)). High maternal Hb was associated with: VLBW (1.35 (1.16–1.57)), PTB (1.12 (1.00-1.25)), SGA (1.17 (1.09–1.25)), stillbirth (1.32 (1.09–1.60)), maternal mortality (2.01 (1.12–3.61)), gestational diabetes (1.71 (1.19–2.46)), and pre-eclampsia (1.34 (1.16–1.56)). Stronger associations were noted earlier in pregnancy for low Hb and adverse birth outcomes while the role of timing of high Hb was inconsistent. Lower Hb cutoffs were associated with greater odds of poor outcomes; for high Hb, data were too limited to identify patterns. Information on anemia etiology was limited; relationships did not vary by iron-deficiency anemia.ConclusionBoth low and high maternal Hb concentrations during pregnancy are strong predictors of adverse maternal and infant health outcomes. Additional research is needed to establish healthy reference ranges and design effective interventions to optimize maternal Hb during pregnancy.

Effects of hemoglobin level on the risk of acute kidney injury in patients with acute myocardial infarction

To investigate the effect of preoperative hemoglobin (Hb) level on the risk of developing acute kidney injury (AKI) after percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI). A retrospective study was conducted. The hospitalized patients diagnosed with AMI who underwent PCI from May 2015 to May 2020 in the department of cardiology in the Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University were enrolled. According to the serum creatinine (SCr) level before and after interventional therapy, the patients were divided into an AKI group and a non-AKI group. The difference in patients' Hb levels between the AKI and non-AKI groups was compared. Univariate and multivariate Logistic regression analyses were used to analyze the effects of Hb levels on the risk of AKI after interventional therapy in patients with AMI. Kaplan-Meier survival curve was used to evaluate the effects of Hb levels on patients with AMI in all-cause death in the hospital. A total of 922 AMI patients were enrolled in this study, of which 165 patients (17.9%) developed AKI. Compared with the non-AKI group, female patients in the AKI group had a higher proportion [35.8% (59/165) vs. 26.9% (204/757)], older (age: 69.78±14.56 vs. 66.61±13.44), with a lower rate of smoking [42.4% (70/165) vs. 51.7% (391/757)] and a higher prevalence of hypertension [73.3% (121/165) vs. 63.5% (481/757)], however, the patients in AKI group also had a worse cardiac function [the proportion of Killip grade 3 or above was higher: 33.9% (56/165) vs. 13.9% (105/757)], lower Hb level (g/L: 127.61±22.18 vs. 132.79±19.45), and there were less patients using angiotensin converting enzyme inhibitor/angiotensin II receptor blocker [ACEI/ARB, 60.0% (99/165) vs. 74.5% (564/757)] and more patients using diuretics [24.8% (41/165) vs. 17.7% (134/757)] in AKI group, the differences were statistically significant (all P < 0.05). Compared with non-AKI group, patients in AKI group had a longer operation time [operation time > 60 minutes: 4.2% (7/165) vs. 1.5% (11/757)] and received more contrast media during the operative procedure [contrast media > 100 mL: 16.4% (27/165) vs. 3.6% (27/757)], the individuals had a higher rate of intra-operative hypotension [16.4% (27/165) vs. 8.2% (62/757)], and more patients were implanted more than 2 stents [8.5% (14/165) vs. 3.6% (27/757), all P < 0.05]. Univariate Logistic regression analysis suggested that each 1 g/L increase in preoperative Hb level was associated with a 1.2% decrease in the risk of postoperative AKI [odds ratio (OR) = 0.988, 95% confidence interval (95%CI) was 0.980-0.996, P = 0.003]. Meanwhile, for every 1 standard deviation increase in preoperative Hb level, the risk of postoperative AKI decreased by 22.1% (OR = 0.779, 95%CI was 0.661-0.918, P = 0.003). The patients were divided into low, medium and high concentration groups according to Hb levels (Hb levels were < 110 g/L, 110-150 g/L, ≥ 150 g/L, respectively), and multivariate Logistic regression analysis showed that the risk of AKI was significantly reduced in the high concentration group compared with that in the low concentration group (OR = 0.463, 95%CI was 0.241-0.888, P = 0.020). The Kaplan-Meier survival curve analysis indicated that the short term survival after coronary intervention in AMI patients with low Hb concentration was significantly lower than that in patients with medium and high Hb concentration (Log-Rank: χ2 = 23.215, P < 0.001). Preoperative lower Hb level is an independent risk factor for postoperative AKI in AMI patients. AMI patients with lower Hb levels have an increased risk of all-cause mortality within 1 month after AMI.

Iron Status and Metabolic Health in Women of Reproductive Age in Southern India

ObjectivesTo examine the associations of iron status with metabolic health outcomes in women of reproductive age (WRA), as part of a population-based biomarker survey in Southern India. MethodsParticipants were WRA (15–40 y; n = 980) who were not pregnant or lactating (2017–2018). Blood samples were analyzed for hemoglobin (Hb; Coulter Counter) and glycated hemoglobin (HbA1c; nephelometry). Serum ferritin (SF) was measured by electrochemiluminescence; soluble transferrin receptor, C-reactive protein, and alpha-1 acid glycoprotein were analyzed via immuno-based assays (Roche). Anthropometric and blood pressure measurements were collected in triplicate. Bioelectrical impedance analysis (BC-418 MA) was used to estimate whole body (WF%) and trunk (TF%) fat in women ≥ 18y. Anemia was defined as Hb < 12.0 g/dL. SF was adjusted for inflammation using Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) methods; iron deficiency (ID) was defined as SF < 15.0 μg/L. Linear and binomial regression were used to examine associations of iron status with metabolic outcomes. ResultsA total of 41.5% of WRA had anemia, and 46.3% had ID (61.5%; BRINDA-adjusted). A total of 23.3% of adults were overweight (BMI: 25.0-<30.0 kg/m2) and 9.6% had obesity (BMI ≥ 30.0 kg/m2). Waist circumference (WC; ≥88.9 cm) and waist-hip ratio (WHR; ≥0.85) were elevated in 13.4% and 20.8% of women, and 25.0% had elevated HbA1c (≥6.5%: 5.0%; ≥5.7-<6.5%: 20.0%). Higher Hb concentrations were associated with increased BMI (β: 0.42 [SE: 0.09]; p < 0.01), WC (0.77 [0.21]; p < 0.01), and WF% (0.89 [0.17]; p < 0.01). Higher SF levels were associated with higher WF% (β: 0.79 [SE: 0.32]; p = 0.01) and TF% (0.92 [0.39]; p = 0.02), and elevated WC (RR: 1.20 [95% CI: 1.02–1.42]). Iron status was not significantly associated with HbA1c or blood pressure. ConclusionsThe burden of adverse metabolic outcomes was substantial in this population. Higher iron status was associated with higher BMI and central adiposity. Evaluating iron status and metabolic outcomes in future studies could help inform screening and interventions to improve the health of WRA. Funding SourcesCenters for Disease Control and Prevention (5U01DD001007), University of South Carolina Disability Research and Dissemination Center; Consejo Nacional de Ciencia y Tecnología (CEGL); NIH 5T32HD087137 (AF); NIH T32DK007158 (HMG).

Association of Maternal Longitudinal Hemoglobin with Small for Gestational Age during Pregnancy: A Prospective Cohort Study.

Background: Few studies have investigated the association of maternal longitudinal hemoglobin (Hb) with small for gestational age during pregnancy. The current study examined the associations of maternal Hb concentrations and Hb changes throughout the middle and late stages of pregnancy with small for gestational age (SGA) in a large prospective cohort study. Methods: This was a prospective cohort study, which enrolled pregnant women at 8–16 weeks of gestation and followed up regularly. Maternal Hb concentrations were measured at the middle (14–27 weeks) and late (28–42 weeks) stages of pregnancy, and the Hb change from the middle to late stage of pregnancy was assessed. The Log-Poisson regression model was used to identify the association of maternal Hb with SGA, including the implications of Hb during specific pregnancy periods and Hb change across the middle to late stages of pregnancy. Of the total 3233 singleton live births, 208 (6.4%) were SGA. After adjusting for potential confounders, compared with Hb 110–119 g/L, Hb ≥ 130 g/L at late pregnancy was significantly associated with a higher risk of SGA (adjusted RR: 2.16; 95% CI: 1.49, 3.13). When Hb changes from the middle to late stages of pregnancy were classified by tertiles, the greatest change in the Hb group (<−6.0 g/L) was significantly associated with a lower risk of SGA (adjusted RR: 0.56; 95% CI: 0.37, 0.85) compared with the intermediate group (−6.0~1.9 g/L). In conclusion, for women at low risk of iron deficiency, both higher Hb concentrations in late pregnancy and less Hb reduction during pregnancy were associated with an increased risk of SGA.

The interactive effects of non-alcoholic fatty liver disease and hemoglobin concentration in the first trimester on the development of gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) is associated with adverse perinatal and maternal outcomes. Epidemiological studies have reported that non-alcoholic fatty liver disease (NAFLD) and a high hemoglobin (Hb) concentration are risk factors for GDM in the middle trimester. However, no consistent conclusions have been reached, especially in Chinese pregnant women. A case-control study was conducted to better understand the associations between NAFLD and Hb concentration in the first trimester and the risk of GDM and their interactive effects. Multivariable logistic regression analysis and a cross-product term of Hb and steatosis were used to evaluate the associations between first trimester Hb concentration, steatosis, and GDM and their interactive effects. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using two-sided statistical tests at an alpha level of 0.05. For the study, 1,017 normal pregnant women, and 343 pregnant women diagnosed with GDM (25.22%) were recruited from the First Hospital of Shanxi Medical University, Shanxi Province, China. NAFLD-associated steatosis was found to be independent risk factors for developing GDM compared with grade 0 steatosis, with ORs of 1.98 (95% CI: 1.35–2.89) and 2.27 (95% CI:1.29–3.96), respectively. Meanwhile, a high Hb concentration was found to be a risk factor for developing GDM compared with the normal Hb concentration (OR = 1.88; 95% CI:1.24–2.83). The risk of developing GDM was more pronounced among pregnant women who had both high-grade steatosis and higher Hb concentrations during their first trimester (OR = 6.24; 95% CI: 1.81–23.66). However, we found no significant interactions between Hb concentration and steatosis grade. In conclusion, our study confirmed that a high Hb concentration and NAFLD-associated steatosis during the first trimester play important roles in predicting the risk of GDM in Chinese women. Future studies are required to verify the interactive effects between NAFLD-associated steatosis and Hb concentration.

The levels of hemoglobin are positively associated with arterial stiffness in community-dwelling Chinese adults

Background and aimsHemoglobin (Hb) concentrations are known to be related to cardiovascular diseases. This study investigated the association between Hb levels and arterial stiffness, as assessed by measurement of the brachial-ankle pulse wave velocity (baPWV). Methods and results3576 adults (2139 males and 1437 females) from the general Chinese population who had their physical check-ups in the health examination centers of Jiangmen Central Hospital were enrolled into the study. The anthropometrics and laboratory data as well as the baPWV and Hb levels were subsequently obtained. Age-adjusted partial correlation and multivariable stepwise linear regression analyses were used to evaluate the relationships between Hb and baPWV for men and women separately. In both sexes, Hb levels were positively associated with body mass index, total cholesterol, low-density lipoprotein cholesterol, triglycerides, glutamic-pyruvic transaminase, γ-glutamyltranspeptidase, uric acid and baPWV, but negatively correlated with the estimated glomerular filtration rate. Multivariable linear regression analysis showed that Hb was significantly and independently associated with arterial stiffness in men (β = 0.043, 95% CI 0.010–0.077, p < 0.05) and women (β = 0.035, 95% CI 0.001–0.069, P < 0.05), after adjustment for confounding factors. ConclusionThe data indicate that high Hb concentration significantly correlate with increased baPWV in general Chinese population.

Hb adaptation to hypoxia in high-altitude fishes: Fresh evidence from schizothoracinae fishes in the Qinghai-Tibetan Plateau

Uncovering the genetic basis of hypoxic adaptation is one of the most active research areas in evolutionary biology. Among air-breathing vertebrates, modifications of hemoglobin (Hb) play a pivotal role in mediating an adaptive response to high-altitude hypoxia. However, the relative contributions in water-breathing organisms are still unclear. Here, we tested the Hb concentration of fish at different altitudes. All species showed species-specific Hb concentration, which has a non-positive correlation with altitude. Moreover, we investigated the expression of Hb genes by the RNA-seq and quantitative real-time PCR (qRT-PCR), and Hb composition by two-dimensional electrophoresis (2-DE). The results showed that the multiple Hb genes and isoforms are co-expressed in schizothoracinae fishes endemic to the Qinghai-Tibetan Plateau (QTP). Phylogenetic analyses of Hb genes indicated that the evolutionary relationships are not easily reconciled with the organismal phylogeny. Furthermore, evidence of positive selection was found in the Hb genes of schizothoracinae fishes through the selection pressure analysis. We demonstrated that positively selected sites likely facilitated the functional divergence of Hb isoforms. Taken together, this study indicated that the long-term maintenance of high Hb concentration may be a disadvantage for physiologically acclimating to high altitude hypoxia. Meanwhile, the genetically based modification of Hb-O2 affinity in schizothoracinae fishes might facilitate the evolutionary adaptation to Tibetan aqueous environments.

High and Low Haemoglobin Levels in Early Pregnancy Are Associated to a Higher Risk of Miscarriage: A Population-Based Cohort Study.

To evaluate whether women with anaemia or high haemoglobin (Hb) in early pregnancy would be at higher risk of miscarriage, this population-based cohort study involved 9453 women whose pregnancies were monitored at primary care centres between 2007 and 2012. The computerised clinical histories were used to collect: Hb measurements (up to 14 weeks of gestation), miscarriage before or by 24 weeks of gestation, and other maternal characteristics. The relation between anaemia (Hb < 110 g/L), normal Hb (110–140 g/L, reference), and high Hb concentrations (≥140 g/L) with miscarriage were expressed as adjusted OR with 95%CI. Restricted cubic spline models were applied to evaluate the dose-response relationships. A total of 520 (5.5%) women were recorded as having a miscarriage. The rate of miscarriage in anaemia, normal Hb, and high Hb concentrations was 8.4%, 5.1%, and 10.2%, respectively. Compared with women with normal Hb at the first trimester, the multivariable-adjusted OR for miscarriage was 2.11 (95%CI, 1.38–3.21) for women with anaemia and 1.83 (95%CI, 1.29–2.58) for women with high Hb. Hb concentrations showed a U-shaped association with miscarriage, with the lowest incidence among women with Hb of 120–130 g/L. These data highlight the importance of considering anaemia and high Hb levels in early pregnancy as harmful indicators for miscarriage.

Effect of EGLN1 Genetic Polymorphisms on Hemoglobin Concentration in Andean Highlanders

The physiological characteristics of Andean natives living at high altitudes have been investigated extensively, with many studies reporting that Andean highlanders have a higher hemoglobin (Hb) concentration than other highlander populations. It has previously been reported that positive natural selection has acted independently on the egl-9 family hypoxia inducible factor 1 (EGLN1) gene in Tibetan and Andean highlanders and is related to Hb concentration in Tibetans. However, no study has yet revealed the genetic determinants of Hb concentration in Andeans even though several single-nucleotide polymorphisms (SNPs) in EGLN1 have previously been examined. Therefore, we explored the relationship between hematological measurements and tag SNPs designed to cover the whole EGLN1 genomic region in Andean highlanders living in Bolivia. Our findings indicated that haplotype frequencies estimated from the EGLN1 SNPs were significantly correlated with Hb concentration in the Bolivian highlanders. Moreover, we found that an Andean-dominant haplotype related to high Hb level may have expanded rapidly in ancestral Andean highlander populations. Analysis of genotype data in an ~436.3 kb genomic region containing EGLN1 using public databases indicated that the population structure based on EGLN1 genetic markers in Andean highlanders was largely different from that in other human populations. This finding may be related to an intrinsic or adaptive physiological characteristic of Andean highlanders. In conclusion, the high Hb concentrations in Andean highlanders can be partly characterized by EGLN1 genetic variants.

Hemoglobin concentrations and adverse birth outcomes in South Asian pregnant women: findings from a prospective Maternal and Neonatal Health Registry

BackgroundWhile the relationship between hemoglobin (Hb) concentrations and pregnancy outcomes has been studied often, most reports have focused on a specific Hb cutoff used to define anemia. Fewer studies have evaluated pregnancy outcomes across the entire range of Hb values. Moreover, to date, most studies of the relationship of Hb concentrations to pregnancy outcomes have been done in high-income countries. Thus, we have sought to determine the relationship between the range of maternal Hb concentrations and adverse birth outcomes among South Asian pregnant women.MethodsFor this study, we used data collected from two South Asian countries (Pakistan – Sindh Province and two sites in India - Belagavi and Nagpur) in a prospective maternal and newborn health registry study. To assess the association between Hb concentrations and various maternal and fetal outcomes, we classified the Hb concentrations into seven categories. Regression analyses adjusting for multiple potential confounders were performed to assess adverse pregnancy outcomes across the range of Hb concentrations.FindingsBetween January 2012 and December 2018, 130,888 pregnant women were enrolled in the South Asian sites had a Hb measurement available, delivered and were included in the analyses. Overall, the mean Hb concentration of pregnant women from the sites was 9.9 g/dL, 10.0 g/dL in the Indian sites and 9.5 g/dL in the Pakistan site. Hb concentrations < 7 g/dL were observed in 6.9% of the pregnant Pakistani women and 0.2% of the Indian women. In both the Pakistani and Indian sites, women with higher parity and women with no formal education had lower Hb concentrations. In the Pakistani site, women > 35 years of age, women with ≥4 children and those who enrolled in the third trimester were more likely to have Hb concentrations of < 7 g/dL but these associations were not found for the Indian sites. When adjusting for potential confounders, for both India and Pakistan, lower Hb concentrations were associated with stillbirth, preterm birth, lower mean birthweight, and increased risk of low birthweight. In the Pakistani site, there was evidence of a U-shaped relationship between Hb concentrations and low birth weight, and neonatal mortality, and in India with hypertensive disease.InterpretationThis study documented the relationship between maternal Hb concentrations and adverse pregnancy outcomes in women from the Pakistani and Indian sites across the range of Hb values. Both low and high Hb concentrations were associated with risk of at least some adverse outcomes. Hence, both low and high values of Hb should be considered risk factors for the mother and fetus.

Role of haemoglobin oxygen affinity for oxygen uptake during exercise

Role of haemoglobin oxygen affinity for oxygen uptake during exercise

Preconception Hb concentration with risk of spontaneous abortion: a population-based cohort study in over 3·9 million women across rural China.

Evidence on the relationship between maternal Hb concentration and spontaneous abortion (SA) risk is limited and conflicting. The purpose of the study was to evaluate whether maternal preconception anaemia or high Hb concentration is associated with risk of SA. A population-based cohort study established between 2013 and 2017. Local maternal and child care service centres in each county. In total, 3 971 428 women aged 20-49 years, who participated in National Free Pre-Pregnancy Checkups Project from 2013 to 2016 and successfully got pregnant before 2017 in rural China. A total of 101 700 (2·56 %) women were recorded having SA, with highest SA rate in women with severe anaemia (4·58 %). Compared with women with Hb of 110-149 g/l, the multivariable-adjusted OR for SA was 1·52 (95 % CI: 1·25, 1·86) for women with Hb < 70 g/l, 0·92 (0·84, 1·01) for 70-99 g/l, 0·80 (0·77, 0·83) for 100-109 g/l, 1·11 (1·08, 1·15) for 150-159 g/l, 1·12 (1·04, 1·20) for 160-169 g/l and 1·02 (0·93, 1·12) for ≥ 170 g/l, respectively. An approximate U-shaped curve for the risk of SA with Hb concentrations was observed when Hb concentrations less than 145 g/l, above which the association plateaued (Pnon-linear < 0·001). Severe anaemia and high Hb concentration before pregnancy were associated with an increased risk of SA. Women with mild anaemia prior to pregnancy had lower risk of SA. Underlying mechanisms need to be further studied.

Corrigendum to: Hemolytic Dynamics of Weekly Primaquine Antirelapse Therapy Among Cambodians With Acute Plasmodium vivax Malaria With or Without Glucose-6-Phosphate Dehydrogenase Deficiency.

BACKGROUND Hemoglobin (Hb) data are limited in Southeast Asian glucose-6-phosphate dehydrogenase (G6PD) deficient (G6PD-) patients treated weekly with the World Health Organization-recommended primaquine regimen (ie, 0.75 mg/kg/week for 8 weeks [PQ 0.75]). METHODS We treated Cambodians who had acute Plasmodium vivax infection with PQ0.75 and a 3-day course of dihydroartemisinin/piperaquine and determined the Hb level, reticulocyte count, G6PD genotype, and Hb type. RESULTS Seventy-five patients (male sex, 63) aged 5-63 years (median, 24 years) were enrolled. Eighteen were G6PD deficient (including 17 with G6PD Viangchan) and 57 were not G6PD deficient; 26 had HbE (of whom 25 were heterozygous), and 6 had α-/β-thalassemia. Mean Hb concentrations at baseline (ie, day 0) were similar between G6PD deficient and G6PD normal patients (12.9 g/dL [range, 9‒16.3 g/dL] and 13.26 g/dL [range, 9.6‒16 g/dL], respectively; P = .46). G6PD deficiency (P = <.001), higher Hb concentration at baseline (P = <.001), higher parasitemia level at baseline (P = .02), and thalassemia (P = .027) influenced the initial decrease in Hb level, calculated as the nadir level minus the baseline level (range, -5.8-0 g/dL; mean, -1.88 g/dL). By day 14, the mean difference from the day 7 level (calculated as the day 14 level minus the day 7 level) was 0.03 g/dL (range, -0.25‒0.32 g/dL). Reticulocyte counts decreased from days 1 to 3, peaking on day 7 (in the G6PD normal group) and day 14 (in the G6PD deficient group); reticulocytemia at baseline (P = .001), G6PD deficiency (P = <.001), and female sex (P = .034) correlated with higher counts. One symptomatic, G6PD-deficient, anemic male patient was transfused on day 4. CONCLUSIONS The first PQ0.75 exposure was associated with the greatest decrease in Hb level and 1 blood transfusion, followed by clinically insignificant decreases in Hb levels. PQ0.75 requires monitoring during the week after treatment. Safer antirelapse regimens are needed in Southeast Asia. CLINICAL TRIALS REGISTRATION ACTRN12613000003774.

Hemolytic Dynamics of Weekly Primaquine Antirelapse Therapy Among Cambodians With Acute Plasmodium vivax Malaria With or Without Glucose-6-Phosphate Dehydrogenase Deficiency.

BackgroundHemoglobin (Hb) data are limited in Southeast Asian glucose-6-phosphate dehydrogenase (G6PD) deficient (G6PD−) patients treated weekly with the World Health Organization–recommended primaquine regimen (ie, 0.75 mg/kg/week for 8 weeks [PQ 0.75]).MethodsWe treated Cambodians who had acute Plasmodium vivax infection with PQ0.75 and a 3-day course of dihydroartemisinin/piperaquine and determined the Hb level, reticulocyte count, G6PD genotype, and Hb type.ResultsSeventy-five patients (male sex, 63) aged 5–63 years (median, 24 years) were enrolled. Eighteen were G6PD deficient (including 17 with G6PD Viangchan) and 57 were not G6PD deficient; 26 had HbE (of whom 25 were heterozygous), and 6 had α-/β-thalassemia. Mean Hb concentrations at baseline (ie, day 0) were similar between G6PD deficient and G6PD normal patients (12.9 g/dL [range, 9‒16.3 g/dL] and 13.26 g/dL [range, 9.6‒16 g/dL], respectively; P = .46). G6PD deficiency (P = <.001), higher Hb concentration at baseline (P = <.001), higher parasitemia level at baseline (P = .02), and thalassemia (P = .027) influenced the initial decrease in Hb level, calculated as the nadir level minus the baseline level (range, −5.8–0 g/dL; mean, −1.88 g/dL). By day 14, the mean difference from the day 7 level (calculated as the day 14 level minus the day 7 level) was 0.03 g/dL (range, −0.25‒0.32 g/dL). Reticulocyte counts decreased from days 1 to 3, peaking on day 7 (in the G6PD normal group) and day 14 (in the G6PD deficient group); reticulocytemia at baseline (P = .001), G6PD deficiency (P = <.001), and female sex (P = .034) correlated with higher counts. One symptomatic, G6PD-deficient, anemic male patient was transfused on day 4.ConclusionsThe first PQ0.75 exposure was associated with the greatest decrease in Hb level and 1 blood transfusion, followed by clinically insignificant decreases in Hb levels. PQ0.75 requires monitoring during the week after treatment. Safer antirelapse regimens are needed in Southeast Asia.Clinical Trials RegistrationACTRN12613000003774.

Hemoglobin alters vitamin carrier uptake and vitamin D metabolism in proximal tubule cells: implications for sickle cell disease.

Kidney disease, including proximal tubule (PT) dysfunction, and vitamin D deficiency are among the most prevalent complications in sickle cell disease (SCD) patients. Although these two comorbidities have never been linked in SCD, the PT is the primary site for activation of vitamin D. Precursor 25-hydroxyvitamin D [25(OH)D] bound to vitamin D-binding protein (DBP) is taken up by PT cells via megalin/cubilin receptors, hydroxylated to the active 1,25-dihydroxyvitamin D [1,25(OH)2D] form, and released into the bloodstream. We tested the hypothesis that cell-free hemoglobin (Hb) filtered into the PT lumen impairs vitamin D uptake and metabolism. Hb at concentrations expected to be chronically present in the ultrafiltrate of SCD patients competed directly with DBP for apical uptake by PT cells. By contrast, uptake of retinol binding protein was impaired only at considerably higher Hb concentrations. Prolonged exposure to Hb led to increased oxidative stress in PT cells and to a selective increase in mRNA levels of the CYP27B1 hydroxylase, although protein levels were unchanged. Hb exposure also impaired vitamin D metabolism in PT cells, resulting in reduced ratio of 1,25(OH)2D:25(OH)D. Moreover, plasma levels of 1,25(OH)2D were reduced in a mouse model of SCD. Together, our data suggest that Hb released by chronic hemolysis has multiple effects on PT function that contribute to vitamin D deficiency in SCD patients.

Anemia and Iron, Vitamin B12, and Folate Deficiencies in Women of Reproductive Age in Ecuador: Results from the Ecuadorian National Health and Nutrition Survey (P10-027-19)

ObjectivesTo examine the burden of anemia and deficiencies of iron, vitamin B12, and folate in women of reproductive age (WRA) in Ecuador. MethodsData from the 2012 Ecuadorian National Health and Nutrition Survey (ENSANUT-ECU) were analyzed to examine the burden of anemia and micronutrient deficiencies among 7658 women of reproductive age (12–49 y; n = 7383 non-pregnant, n = 275 pregnant). Venous blood samples were collected, and hemoglobin (Hb) was assessed viathe sodium lauryl sulfate method. Samples were centrifuged, processed, and stored < -50°C until analysis. Serum ferritin (SF), vitamin B12, serum folate, and red blood cell (RBC) folate were measured viachemiluminescence. Hemoglobin was adjusted for altitude; and anemia was defined as Hb <11.0 g/dL in pregnant women and <12.0 g/dL in non-pregnant women. Iron deficiency and insufficiency were defined as SF <15.0 μg/L and <20.0 μg/L, respectively. Vitamin B12 deficiency and insufficiency were defined as <148.0 pmol/L and <221.0 pmol/L; and folate deficiency was defined as serum folate <7.0 nmol/L and RBC folate <342.0 nmol/L. Survey logistic and linear regression were used to examine associations of micronutrients with hemoglobin concentrations and anemia. ResultsIn analyses among non-pregnant women, 11.3% were anemic, 14.4% were iron deficient, and 21.1% had iron insufficiency. A total of 4.3% of women had vitamin B12 deficiency, 23.9% had vitamin B12 insufficiency; and <1% of women were folate deficient. The prevalence of micronutrient deficiencies was higher in pregnant women, compared to non-pregnant women: 31.1% of pregnant women were iron deficient, 43.0% were iron insufficient, 21.3% were vitamin B12 deficient, and 55.4% were vitamin B12 insufficient. In non-pregnant WRA, higher SF (P < 0.0001), vitamin B12 (P < 0.01), and serum folate (P < 0.0001) concentrations were associated with higher Hb concentrations; and higher SF (OR: 0.96, 95% CI: 0.95, 0.97; P < 0.0001) and serum folate (OR: 0.98, 95% CI: 0.97, 0.98; P < 0.0001) concentrations were associated with lower odds of anemia. In pregnant women, SF (P < 0.01) and serum folate (P = 0.002) concentrations were associated with higher hemoglobin concentrations. ConclusionsFindings suggest that the burden of anemia, iron deficiency, and vitamin B12 insufficiency is high among women of reproductive age in Ecuador. Funding SourcesNot applicable.