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Background: Pregnancy is a metabolic state which demands increased iron bioavailability. While in preeclampsia, due to the placental vascular events there is an iron surplus environment along with inflammation and placental hypoxia. Routinely in India iron is supplemented to all pregnant women irrespective of their general physical condition. Hepcidin a regulator of iron metabolism protects the cells from iron mediated cytotoxicity., Objective: To find out whether hepcidin gets induced as a protective mechanism in preeclampsia patients in order to combat the environment of iron overload, oxidative stress, and endothelial dysfunction., Methods: A cross-sectional study with follow up was carried out in a South Indian Tamil population. Forty healthy pregnant women and forty preeclampsia patients in the gestational age 32 ± 4 weeks were recruited ( n  = 80). Biochemical analysis to assess the serum levels of the following were carried out (1) indices of iron homeostasis - serum iron, ferritin, transferrin, hepcidin, (2) endothelial dysfunction -serum assymetric dimethyl arginine (ADMA) (3) oxidative stress - Malon di aldehyde (MDA) and ferric reducing ability of plasma (FRAP). Kolmogorov-Smirnov test, Mann-Whitney U test, Spearman's correlation, linear regression and ROC AUC analysis were performed to understand their relationship with each other., Results: Levels of serum iron, ferritin, transferrin saturation, hepcidin, and MDA/FRAP ratio were elevated significantly in preeclampsia patients compared to controls, while serum transferrin levels were significantly decreased in them. Hepcidin levels showed a significant positive correlation with serum ADMA, and MDA/FRAP. Serum hepcidin, transferrin saturationand MDA/FRAP ratio is useful in differentiating pre-eclampsia patients from healthy pregnant women., Conclusion: Iron supplementation in preeclampsia patients might have led to a state of iron overload, which might have caused oxidative stress and endothelial dysfunction in preeclampsia patients. The rise in hepcidin levels in this scenario may be viewed as a protective mechanism to combat the iron overload mediated cytotoxicity.

Introduction: Preeclampsia can lead to a number of adverse maternal and perinatal effects. The association between iron status [serum iron, ferritin and total iron-binding capacity (TIBC)], unsaturated iron-binding capacity, hepcidin, interleukin-6 (IL-6) levels and preeclampsia is not fully understood. Objective: To assess the levels of iron status, hepcidin and interleukin-6 in women with preeclampsia compared with healthy pregnant women. Method: A case-control study (60 women were recruited in each group) was conducted at Saad Abuelela Maternity Hospital in Khartoum, Sudan. Sociodemographic and clinical data were gathered through a questionnaire. The levels of iron status, hepcidin and IL-6 were measured using applicable methods. Results: There was no significant difference in the median [interquartile range (IQR)] of age, parity or body mass index between the two groups. Moreover, the median (IQR) of the iron status, hepcidin and interleukin-6 did not differ between women with preeclampsia and healthy controls. There were no significant correlations between haemoglobin, hepcidin and IL-6. There were also no significant correlations between serum iron, serum ferritin, hepcidin and IL-6. However, there was a significant positive correlation between hepcidin and IL-6 (r = 0.393, p = 0.002). Conclusion: In this study, women with preeclampsia had levels of iron status, hepcidin and IL-6 similar to those observed in healthy pregnant women. There was no significant correlation between iron status, hepcidin and IL-6. [ABSTRACT FROM AUTHOR]

Ferroptosis is a recently identified form of programmed cell death which is different from apoptosis, pyroptosis, necrosis, and autophagy. It is uniquely defined by redox-active iron-dependent hydroxy-peroxidation of polyunsaturated fatty acid (PUFA)-containing phospholipids and a loss of lipid peroxidation repair capacity. Ferroptosis has recently been implicated in multiple human diseases, such as tumors, ischemia–reperfusion injury, acute kidney injury, neurological diseases, and asthma among others. Intriguingly, ferroptosis is associated with placental physiology and trophoblast injury. Circumstances such as accumulation of lipid reactive oxygen species (ROS) due to hypoxia-reperfusion and anoxia-reoxygenation of trophoblast during placental development, the abundance of trophoblastic iron and PUFA, physiological uterine contractions, or pathological placental bed perfusion, cause placental trophoblasts' susceptibility to ferroptosis. Ferroptosis of trophoblast can cause placental dysfunction, which may be involved in the occurrence and development of placenta-related diseases such as gestational diabetes mellitus, preeclampsia, fetal growth restriction, preterm birth, and abortion. The regulatory mechanisms of trophoblastic ferroptosis still need to be explored further. Here, we summarize the latest progress in trophoblastic ferroptosis research on placental-related diseases, provide references for further understanding of its pathogenesis, and propose new strategies for the prevention and treatment of placental-related diseases. [ABSTRACT FROM AUTHOR]

Background: Pregnancy-induced hypertension is the new onset of high blood pressure after 20 weeks of gestation in women with previously normal blood pressure. To the best of our knowledge, no study has been conducted in our country to investigate the association between this pregnancy problem and iron-folic acid supplementation. The aim of this study was to determine the association between iron-folic acid supplementation and pregnancy-induced hypertension (PIH) in pregnant women at public hospitals in the Wolaita Sodo zone. Methods: An institution-based case–control study was conducted among pregnant women who visited public hospitals in the Wolaita Sodo zone from March 3, 2022, to August 30, 2022. A consecutive sampling method was used to select the study participants. The total sample size was 492, of which 164 were cases and 328 were controls. The data were collected by conducting face-to-face interviews and measurements. The data were entered into EpiData version 4.6 and exported to STATA 14 for analysis. Those variables with a p-value less than 0.05 were considered statistically significant. Descriptive statistics and odds ratios were presented using texts, tables, and figures. Results: A total of 471 women participated in this study, yielding a response rate of 96%. The cases had a mean age of 25 ± 4.43, while the controls had a mean age of 25 ± 3.99. The mean age at first pregnancy among cases was 20 ± 2.82 and among controls was 20 ± 2.97. The average number of deliveries for cases and controls was 1.97 ± 1.41 and 1.95 ± 1.38, respectively. There is no significant association between iron-folic acid supplementation and PIH. Pregnant women with high hemoglobin levels had higher odds of PIH as compared to those without it (AOR = 3.65; 95% CI: 1.0–12.9). Eating kocho (AOR = 14.4; 95% CI: 1.2–16.7) was positively associated with PIH. Conclusions: There is no association between iron-folic acid supplementation during pregnancy and pregnancy-induced hypertension. Pregnant women with high hemoglobin levels had higher odds of PIH as compared to those without it. There is an association between kocho consumption and PIH. More research should be done using stronger designs. [ABSTRACT FROM AUTHOR]

Therefore, SF concentration is a good indicator of the risk of adverse maternal and fetal pregnancy outcomes and can help provide personalized guidance for pregnant women with respect to iron supplementation at different stages of pregnancy. In Supplementary Table 1, compared with the lowest quartile, the AOR of Small head circumference in the highest SF concentration quartile was 2.05 (95% Cl: 1.10, 3.80) and 1.97 (95% Cl: 1.05, 3.69) at 16-18 weeks of gestation and 28-32 weeks of gestation, respectively. The changes of SF concentrations were determined by subtracting the SF measured at 16-18th weeks of gestation from that measured at 28-32th weeks of gestation. There was no significant difference between SF concentration and adverse pregnancy outcomes among pregnancy women without GDM. [Extracted from the article]

Iron is essential for cell survival, and iron deficiency is a known risk factor for many reproductive diseases. Paradoxically, such disorders are also more common in cases of iron overload. Here, we evaluated the role of ferroptosis in women's health, particularly focusing on pre-eclampsia (PE). PE is a multisystem disorder and is one of the leading causes of maternal and perinatal morbidity and mortality, especially when the condition is of early onset. Nevertheless, the exact etiological mechanism of PE remains unclear. Interestingly, ferroptosis, as a regulated iron-dependent cell death pathway, involves a lethal accumulation of lipid peroxides and shares some characteristics with PE pathophysiology. In this review, we comprehensively reviewed and summarized recent studies investigating the molecular mechanisms involved in the regulation and execution of ferroptosis, as well as ferroptosis mechanisms in the pathology of PE. We propose that ferroptosis not only plays an important role in PE, but may also become a novel therapeutic target for PE. [ABSTRACT FROM AUTHOR]

Purpose: Ferroptosis is associated with oxidative stress (OS) and is caused by iron-dependent lipid-peroxidative damage, but its role in PE is unclear. The aim of this study is to determine whether pannexin 1 (Panx1) and toll-like receptor 4 (TLR4) are key regulators of ferroptosis in PE. Methods: The study included 65 patients with PE and 25 healthy pregnant women. In normal and PE placental tissues, OS and ferroptosis markers, including Fe2+, malondialdehyde (MDA), reduced glutathione (GSH) levels, heme oxygenase-1 (HO-1) and glutathione peroxidase 4 (Gpx4) activity, were estimated. Panx1 and solute carrier family 7 member 11 (SLC7A11) mRNA expression levels were relatively quantified in placental tissues using real‐time polymerase chain reaction (RT‐PCR), while serum Panx1, serum TLR4, and placental activating transcription factor 3 (ATF3) levels were measured by ELISA. Results: In placental tissues, Panx1 and TLR4 expression levels were significantly increased in patients with PE compared to controls and were positively correlated with pro-ferroptosis mediators such as placental Fe2+ and MDA levels and negatively correlated with anti-ferroptosis regulators such as placental GSH level, HO-1, and Gpx4 activity. Additionally, Panx1 and TLR4 had a positive correlation with ATF3 and a negative correlation with SLC7A11. Serum Panx1 and TLR4 levels were positively correlated with their placental tissue expression and showed good diagnostic capabilities for ferroptosis in PE. Conclusion: Therefore, Panx1 and TLR4 are suggested to induce ferroptosis in PE via SLC7A11-mediated signaling pathways, offering a novel perspective on PE pathogenesis and novel diagnostic tools for PE. [ABSTRACT FROM AUTHOR]

Introduction: Preeclampsia is a serious complication of pregnancy and is associated with increased maternal and perinatal morbidity and mortality. Increased iron and ferritin concentration is associated to a higher risk of preeclampsia and prophylactic iron supplementation can sometimes be harmful to pregnant women who are otherwise not iron deficient. Aim: To analyse serum iron, serum ferritin, serum Transferrin Receptor (sTFR) levels, Total Iron Binding Capacity (TIBC) among iron supplemented preeclamptic cases and normotensive pregnant controls. Materials and Methods: This prospective, observational, case control study was conducted in Jaipur National University Institute of Medical Sciences and Research Center (JNUIMSRC), Jaipur, Rajasthan, India for a period of one year from (February 2019- January 2020). A total of 200 pregnant females, all on iron supplementation during the course of their pregnancy, 100 in preeclampsia group (case group); 100 in normotensive group (control group), in third trimester and between 18-45 years of age were enrolled in the study. Serum iron, serum ferritin, sTFR and TIBC were estimated using fully automated analysers. Results: Median Interquartile Range (IQR) of serum ferritin levels in cases were higher than the controls (41 (30-70) vs 24 (17-44); p<0.001). Serum ferritin in cases were also found to correlate positively with systolic (r=0.37, p=0.001) Blood Pressure (BP) whereas TIBC correlated negatively with diastolic BP (r= -0.238, p-value=0.017). The median IQR differences of TIBC values among cases and controls were insignificant {485 (404-523) vs 493 (448-544)} and differences of median IQR of sTFR values among cases and controls were significant {8.5(7-9) vs 8.9 (8-10)}. Subjects with serum feritin levels >40 ng/mL had three times increased risk of PE (Odds ratio =3, 95% Cl=1.571- 5.157). Conclusion: Elevated serum ferritin, decreased sTFR levels and correlation of Ferritin and TIBC to BP in preeclampsia compels us to put cautionary remarks over testing these parameters before continuing with iron supplements. This may prevent a possible iron related added complications in preeclampsia and help clinicians decide about restricting/lowering iron supplement doses in case a situation of iron overload arise. [ABSTRACT FROM AUTHOR]

Iron is required for energy production, DNA synthesis, and cell proliferation, mainly as a component of the prosthetic group in hemoproteins and as part of iron-sulfur clusters. Iron is also a critical component of hemoglobin and plays an important role in oxygen delivery. Imbalances in iron metabolism negatively affect these vital functions. As the crucial barrier between the fetus and the mother, the placenta plays a pivotal role in iron metabolism during pregnancy. Iron deficiency affects 1.2 billion individuals worldwide. Pregnant women are at high risk of developing or worsening iron deficiency. On the contrary, in frequent hemoglobin diseases, such as sickle-cell disease and thalassemia, iron overload is observed. Both iron deficiency and iron overload can affect neonatal development. This review aims to provide an update on our current knowledge on iron and heme metabolism in normal and pathological pregnancies. The main molecular actors in human placental iron metabolism are described, focusing on the impact of iron deficiency and hemoglobin diseases on the placenta, together with normal metabolism. Then, we discuss data concerning iron metabolism in frequent pathological pregnancies to complete the picture, focusing on the most frequent diseases. [ABSTRACT FROM AUTHOR]

Maternal diet and nutritional status are of key importance with regard to the short- and long-term health outcomes of both the mother and the fetus. Multiple pregnancies are a special phenomenon in the context of nutrition. The presence of more than one fetus may lead to increased metabolic requirements and a faster depletion of maternal macro- and micro- nutrient reserves than in a singleton pregnancy. The aim of this systematic review was to gather available knowledge on the supply and needs of mothers with multiple pregnancies in terms of micronutrients and the epidemiology of deficiencies in that population. It was constructed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement (PRISMA). The authors conducted a systematic literature search with the use of three databases: PubMed/MEDLINE, Scopus and Embase. The last search was run on the 18 October 2020 and identified 1379 articles. Finally, 12 articles and 1 series of publications met the inclusion criteria. Based on the retrieved studies, it may be concluded that women with multiple pregnancies might be at risk of vitamin D and iron deficiencies. With regard to other microelements, the evidence is either inconsistent, scarce or absent. Further in-depth prospective and population studies are necessary to determine if nutritional recommendations addressed to pregnant women require adjustments in cases of multiple gestations. [ABSTRACT FROM AUTHOR]