Maternal Organ Research Articles

Pre-eclampsia.

Pre-eclampsia is a life-threatening disease of pregnancy unique to humans and a leading cause of maternal and neonatal morbidity and mortality. Women who survive pre-eclampsia have reduced life expectancy, with increased risks of stroke, cardiovascular disease and diabetes, while babies from a pre-eclamptic pregnancy have increased risks of preterm birth, perinatal death and neurodevelopmental disabilityand cardiovascular and metabolic disease later in life. Pre-eclampsia is a complex multisystem disease, diagnosed by sudden-onset hypertension (>20 weeks of gestation) and at least one other associated complication, including proteinuria, maternal organ dysfunction or uteroplacental dysfunction. Pre-eclampsia is found only when a placenta is or was recently present and is classified as preterm (delivery <37 weeks of gestation), term (delivery ≥37 weeks of gestation) and postpartum pre-eclampsia. The maternal syndrome of pre-eclampsia is driven by a dysfunctional placenta, which releases factors into maternal blood causing systemic inflammation and widespread maternal endothelial dysfunction. Available treatments target maternal hypertension and seizures, but the only 'cure' for pre-eclampsia is delivery of the dysfunctional placenta and baby, often prematurely. Despite decades of research, the aetiology of pre-eclampsia, particularly of term and postpartum pre-eclampsia, remains poorly defined. Significant advances have been made in the prediction and prevention of preterm pre-eclampsia, which is predicted in early pregnancy through combined screening and is prevented with daily low-dose aspirin, starting before 16 weeks of gestation. By contrast, the prediction of term and postpartum pre-eclampsia is limited and there are no preventive treatments. Future research must investigate the pathogenesis of pre-eclampsia, in particular of term and postpartum pre-eclampsia, and evaluate new prognostic tests and treatments in adequately powered clinical trials.

Study of histopathological changes and the levels of TNF-α in Preterm Preeclamptic women

Preeclampsia (PE) is a significant contributor to maternal morbidity and mortality that manifests as new-onset hypertension after 20 weeks of pregnancy with signs of uteroplacental or maternal organ dysfunction or proteinuria. This condition is linked to intrauterine growth restriction, preterm birth, placental abruption, fetal distress, and fetal death in utero. The findings of the recent study can be summed up as follows: Hematoxylin and eosin staining of placenta tissues revealed a significant area of calcification in the villous stroma. Additionally, increased collagen fibers around blood vessels and varying degrees of mononuclear cell infiltration are caused by capillary and vein congestion. The Masson's Trichrome stain revealed deposited fibrin between decidual cells and extra-villous cytotrophoblasts, which were surrounded by mature intermediate and terminal villi. Congestion of veins with increased fibrin deposits around veins and arterial vessels with increased fibrocytes When the data was statistically analyzed, it was discovered that PE pregnant women had significantly p&lt;0.05 higher levels of serum TNF- α , than normotensive women ( NT ). Finally, the study found a link between preterm PE and women's pregnancy, as well as histopathologic and immunological parameters in preterm PE and NT women.&#x0D;

Aspirin Inhibits Fibronectin Expression and Reverses Fibronectin-Mediated Cell Invasiveness by Activating Akt Signaling in Preeclampsia.

Preeclampsia is a severe gestational hypertensive disorder that may lead to maternal multiple organ dysfunction and adverse fetal outcomes. Aspirin provides a protective effect by reducing the risk of preeclampsia; however, its mechanism of action is unclear. Fibronectin (FN) is a key factor in cell motility and is associated with preeclampsia. Here, we demonstrated that cellular FN expression was elevated in the placenta of preeclamptic patients. The functional roles of plasma and cellular FN in trophoblasts were investigated by treating HTR-8/SVneo cells with exogenous recombinant human FN protein (rhFN) and siRNA, respectively. Trophoblast migration and invasion were inhibited by rhFN and facilitated by FN knockdown. Moreover, rhFN activated ERK and Akt signaling in trophoblasts, and FN-suppressed cell motility was rescued by ERK and/or Akt inhibitors. In this study, aspirin suppressed trophoblast cellular FN expression and reversed FN-mediated cell functions, including cell migration, invasion, and ERK/Akt signal changes. Taken together, the results of this study revealed the effects of FN on trophoblast motility and signaling; aspirin inhibits FN expression and reverses FN-mediated trophoblast biology. These results provide a drug mechanism for disease prevention and a target for preeclampsia intervention.

The role of biomarkers in early prediction and molecular mechanisms of preeclampsia

Preeclampsia (PE) is defined as new onset hypertension after 20 weeks of gestation with evidence of maternal organ or uteroplacental dysfunction or proteinuria. PE is a leading cause of maternal death, with about 55000 deaths worldwide each year. Toxic substances that damage the maternal vascular endothelium induce PE, resulting in liver and kidney malfunction. It is crucial for obstetricians to identify as early as possible the patients who are at risk for PE. Polycystic ovarian disease, sleeping disorders, urinary infections, periodontal disease, smoking, lifestyle and familial history of PE are the major risk factors involved in this disease. VEGF, sFlt1, sENG, PAPP-A, inhibin A and activin A proteins, fetal hemoglobin, heat shock protein and placental protein have been helpful in predicting or diagnosing PE and in understanding its pathogenesis. In addition, a better understanding of PE pathogenesis would aid in identifying the most effective treatments that do not impair the fetus’ prognosis. The aim of our study is a review of the pathophysiology and biomarkers, such as pro- and anti-angiogenic substances, that may be useful in the detection of PE in the future.

SFlt-1/PlGF Ratio Is Not a Good Predictor of Severe COVID-19 nor of Adverse Outcome in Pregnant Women with SARS-CoV-2 Infection-A Case-Control Study.

Elevated serum levels of sFlt-1 were found in non-pregnant severe COVID-19 patients. The aim was to investigate sFlt-1/PlGF ratio as a predictor of severe disease and adverse outcome in pregnant women with COVID-19. A single-center case-control study was conducted in pregnant women with SARS-CoV-2 infection. SARS-CoV-2-negative pregnant women served as controls. Serum sFlt-1/PlGF ratio was assessed. The primary outcome was severe COVID-19 and the secondary outcome comprised adverse outcomes including severe COVID-19, intensive care unit admission, maternal multiple organ failure, preterm delivery, fetal demise, preeclampsia or hypertension diagnosed after COVID-19, maternal death. 138 women with SARS-CoV-2 infection and 140 controls were included. sFlt-1/PlGF ratio was higher in infected patients (11.2 vs. 24; p < 0.01) and in women with severe disease (50.8 vs. 16.2; p < 0.01). However, it was similar in women with adverse and non-adverse outcome (29.8 vs. 20; p = 0.2). The AUC of sFlt-1/PlGF ratio was 0.66 (95% CI 0.56-0.76) for the prediction of severe COVID-19, and 0.72 (95% CI 0.63-0.79) for the prediction of adverse outcome. sFlt-1 and sFlt-1/PlGF ratio are related to SARS-CoV-2 infection and the severity of COVID-19 during pregnancy. However, sFlt-1/PlGF ratio is not a good predictor of severe COVID-19 or adverse outcome.

Selenium supplementation and pregnancy outcomes

In vertebrates and invertebrates, selenium (Se) is an essential micronutrient, and Se deficiency or excess is associated with gonadal insufficiency and gamete dysfunction in both males and females, leading to implantation failure, altered embryonic development and, ultimately, infertility. During pregnancy, Se excess or deficiency is associated with miscarriage, pre-eclampsia (hypertension of pregnancy), gestational diabetes, fetal growth restriction and preterm birth. None of this is surprising, as Se is present in high concentrations in the ovary and testes, and work in animal models has shown that addition of Se to culture media improves embryo development and survival in vitro in association with reduced reactive oxygen species and less DNA damage. Selenium also affects uterine function and conceptus growth and gene expression, again in association with its antioxidant properties. Similarly, Se improves testicular function including sperm count, morphology and motility, and fertility. In animal models, supplementation of Se in the maternal diet during early pregnancy improves fetal substrate supply and alters fetal somatic and organ growth. Supplementation of Se throughout pregnancy in cows and sheep that are receiving an inadequate or excess dietary intake affected maternal whole-body and organ growth and vascular development, and also affected expression of angiogenic factors in maternal and fetal organs. Supplemental Se throughout pregnancy also affected placental growth, which may partly explain its effects on fetal growth and development, and also affected mammary gland development, colostrum yield and composition as well as postnatal development of the offspring. In conclusion, Se supplementation in nutritionally compromised pregnancies can potentially improve fertility and pregnancy outcomes, and thereby improve postnatal growth and development. Future research efforts should examine in more detail and more species the potential benefits of Se supplementation to reproductive processes in mammals.

The Effect of Vitamin D Supplementation in Pregnant Woman for Pre-eclampsia Incidency : A Literature Review

Pre-eclampsia was defined as hypertension after 20 weeks of gestation with evidence of maternal organ dysfunction,uteroplacental, or proteinuria. Maternal vitamin D deficiency may be with an increased risk of pre-eclampsia. Nonetheless, To assess the impact of vitamin D supplementation on the risk of pre-eclampsia, we performed a literature review. We researched Google Scholar; PubMed; Research Gate; and Science Directs using keyword (“Vitamin D” OR “Hydroxyvitamin D (25(OH)D)”OR “25(OH)D” OR “25hydroxycholecalciferol”) AND (“Pregnancy” OR “Pregnant women” OR “Gestation”) AND (“Clinical trial” OR “Clinical study” OR “study” OR “prospective study” OR “Randomized controlled trial” OR “RCT”) from January 2006 – May 2021. A total 4 of 19.431 articles recorded at the identification stage by the criteria for inclusion. The articles are randomized controlled trial (RCT). A total of 329 pregnant woman are given various vitamin D supplements with dose range 400 - 4.000 IU. Some article combine with other vitamin (Calcium, Vitamin C+E) with a certain duration. Maternal ages range 20 years - 40 years with an gestational age 6 to more than 32 weeks. Vitamin D can reduce the risk of pre-eclampsia in pregnant women.

Bioinformatics methods in biomarkers of preeclampsia and associated potential drug applications

BackgroundPreeclampsia is a pregnancy-related condition that causes high blood pressure and proteinuria after 20 weeks of pregnancy. It is linked to increased maternal mortality, organ malfunction, and foetal development limitation. In this view, there is a need critical to identify biomarkers for the early detection of preeclampsia. The objective of this study is to discover critical genes and explore medications for preeclampsia treatment that may influence these genes.MethodsFour datasets, including GSE10588, GSE25906, GSE48424 and GSE60438 were retrieved from the Gene Expression Omnibus database. The GSE10588, GSE25906, and GSE48424 datasets were then removed the batch effect using the “sva” R package and merged into a complete dataset. The differentially expressed genes (DEGs) were identified using the “limma” R package. The potential small-molecule agents for the treatment of PE was further screened using the Connective Map (CMAP) drug database based on the DEGs. Further, Weight gene Co-expression network (WGNCA) analysis was performed to identified gene module associated with preeclampsia, hub genes were then identified using the logistic regression analysis. Finally, the immune cell infiltration level of genes was evaluated through the single sample gene set enrichment analysis (ssGSEA).ResultsA total of 681 DEGs (376 down-regulated and 305 up-regulated genes) were identified between normal and preeclampsia samples. Then, Dexamethasone, Prednisone, Rimexolone, Piretanide, Trazodone, Buflomedil, Scoulerin, Irinotecan, and Camptothecin drugs were screened based on these DEGs through the CMAP database. Two modules including yellow and brown modules were the most associated with disease through the WGCNA analysis. KEGG analysis revealed that the chemokine signaling pathway, Th1 and Th2 cell differentiation, B cell receptor signalling pathway and oxytocin signalling pathway were significantly enriched in these modules. Moreover, two key genes, PLEK and LEP were evaluated using the univariate and multivariate logistic regression analysis from the hub modules. These two genes were further validated in the external validation cohort GSE60438 and qRT-PCR experiment. Finally, we evaluated the relationship between immune cell and two genes.ConclusionIn conclusion, the present study investigated key genes associated with PE pathogenesis that may contribute to identifying potential biomarkers, therapeutic agents and developing personalized treatment for PE.

Symposium 2-1 - Role of exosomes in placenta-maternal body axis for organ specific damage of preeclampsia

Exosomes are extra-cellular vesicles that are released from many cells, which are taken up by distant organs and alter those cell phenotype. Preeclampsia (PE) is characterized by hypertension and diverse organ damage. However, the underlying causes of specific maternal organ damage remain largely unexplained. We focused on exosomes released by placenta and aimed to investigate whether they have a role in maternal organ damage in PE. We obtained exosomes from placentas of pregnant women with and without PE who gave birth at the University of Tokyo Hospital. Isolated exosomes were administered to pregnant mice from E11.5 to examine their effects on the mother and fetuses. A significant increase in proteinuria was observed in pregnant mice treated with exosomes derived from placenta of PE patients (PE group) compared to those of normal pregnancies (normal group). Whereas, blood pressure and the fetus size and numbers were not affected. This phenomenon was due to the selective uptake of PE exosomes in kidney, which was mediated by surface molecules on the exosomes. Gene expression analysis of kidney in PE group showed pathway changes associated with potential damage in kidney function. Moreover, pathological analysis revealed glomerular endotheliosis, which is a characteristic of PE. In other organs, pathological changes that could be related to the pathogenesis of PE were observed in the brain and liver in the PE group. Our results indicate the existence of an exosome-mediated organ-specific connection between placenta and maternal organs, which may explain organ-selective damages in PE patients.

Antihypertensive drug prescription trends for pregnant women with hypertension in acute hospitals in Japan.

Hypertensive disorders of pregnancy cause maternal organ damage. Therefore, appropriate management with antihypertensive medication is required from the first trimester. We aimed to clarify the antihypertensive drug prescription trends in pregnant women with hypertension in Japan. The administrative data of pregnant outpatients aged 16-49 years who visited acute hospitals between 2013 and 2020 were included. The annual antihypertensive drug prescription trends were evaluated based on their prescription proportions. The most prescribed drug in 2020 was nifedipine, followed by methyldopa and amlodipine. The proportion of nifedipine prescriptions significantly increased from 33.5 to 40.8% during the study period, whereas that of methyldopa significantly decreased from 16.6 to 11.6%. There was no change in the prescription trend of amlodipine. Dihydropyridine calcium channel blockers were the most commonly prescribed drug for pregnant women with hypertension.

Non-invasive prenatal screening for fetal triploidy using single nucleotide polymorphism-based testing: Differential diagnosis and clinical management in cases showing an extra haplotype.

ObjectiveAn extra haplotype is infrequently encountered in single nucleotide polymorphism(SNP)‐based non‐invasive prenatal testing (NIPT) and is usually attributed to an undetected twin or triploidy. We reviewed a large series to establish relative frequencies of these outcomes and identify alternative causes.MethodsIn 515,804 women receiving NIPT from September 2017 through March 2019, all results with an extra haplotype were reviewed. Known viable and vanished twin pregnancies were excluded. For positive cases, pregnancy outcome information was sought.ResultsOf 1005 results with an extra haplotype (1 in 513), pregnancy outcome was available for 773 cases: 11% were confirmed or suspected triploidy; 65% to vanished twin; 10% with pregnancy loss. Rare explanations included complete mole, chimera, undisclosed donor egg pregnancy, maternal organ transplant and one instance of maternal neoplasm. Among triploid cases that were detected and independently confirmed, 23/27 (85%) were diandric.ConclusionSNP‐based NIPT, with detection of an extra haplotype, is 11% predictive of triploidy. For results with an extra haplotype, ultrasound is recommended to establish viability, evaluate for twins (viable or vanished), and detect findings consistent with triploidy. Review of patient history, serum screening, and ultrasound will reduce the number of CVS or amniocenteses necessary to confirm a diagnosis of triploidy.

COMPARISON OF D-DIMER LEVELS IN PREECLAMPSIA AND NORMAL PREGNANCY

Background: Preeclampsia is associated with deposition of fibrin in microvasculature and maternal organ dysfunction. D-dimer is used as a marker of degradation and production of fibrin in the body. The objective of this study was to determine the mean plasma D-dimer levels among pregnant women and to compare mean plasma D-dimer levels between preeclamptic patients and women without preeclampsia. Methods: A cross sectional study was designed and conducted in the Obs/Gyn Department, Hayatabad Medical Complex, Peshawar. A total of 154 pregnant women fulfilling inclusion criteria were included. Non-probability consecutive sampling was used for collection of samples. Mean±SD was calculated for quantitative variables while qualitative variables were presented in the form of frequency and percentage. Independent sample t-test was used to compare mean plasma D-dimer levels between preeclampsia and normal patients. Stratification was done on the basis of age, gestational age, BMI, and booking status. Post-stratification t-test was applied and p?0.05 was considered significant. Results: The mean age of patients was 27.73±2.68 years (Range: 18–34 years). The mean gestational age was 37.43±1.15 weeks (Range: 35–40 weeks). Preeclamptics were 58 (37.7%) while 96 (62.3%) were normotensive. The mean plasma D-dimer levels in total cases was 0.50±0.41 ng/ml (Range: 0.115–1.156). The mean plasma D-dimer level in preeclamptics and normal cases was 1.02±0.07 and 0.18±0.04 (ng/ml) respectively (p&lt;0.00). Conclusion: Mean plasma D-dimer level was higher in preeclamptic patients as compared to normotensive pregnant women showing a significant correlation between preeclampsia and plasma D-dimer level in third trimester of pregnancy. Pak J Physiol 2022;18(1):20?2

The impact of fetal growth restriction in diagnosing preeclampsia on the severity of maternal features.

We aimed to assess the impact of fetal growth restriction (FGR) as a diagnostic criterion for preeclampsia (PE) on the severity of maternal preeclamptic features by comparing it with other diagnostic criteria for PE, maternal organ dysfunction. We performed a retrospective cohort study of singleton pregnancies. Based on the status at diagnosis, PE cases preceded by FGR without maternal organ dysfunction (Group F; n = 28) and those preceded by maternal organ dysfunction without FGR (Group M; n = 87) were analyzed. Group F had an earlier PE diagnosis (32.5 ± 4.9 vs. 36.7 ± 3.5 weeks, p < 0.01) and delivery (33.7 ± 4.5 vs. 37.5 ± 3.1 weeks, p < 0.01) than Group M. No significant differences in maternal morbidities were observed between the groups, including severe hypertension (75.0 vs. 60.0%), need for intravenous antihypertensives (42.9 vs. 48.3%) or magnesium sulfate (60.7 vs. 54.5%), or a composite of major maternal complications (17.9 vs. 21.8%). When limited to early-onset PE diagnosed before 34 weeks of gestation (17 and 17 cases in Group F and M, respectively), the frequencies of maternal morbidities (severe hypertension: 70.6 vs. 52.9%, intravenous antihypertensives: 35.3 vs. 35.3%, magnesium sulfate: 58.8 vs. 47.1%, major complications: 29.4 vs. 23.5%) and the duration from diagnosis until delivery (11.2 ± 14.7 vs. 16.5 ± 21.7 days) were comparable between two groups. Our results suggest that the presence of FGR on PE diagnosis is associated with the development of severe maternal symptoms as much as that of maternal organ dysfunction at diagnosis, and it may be reasonable to include FGR in PE diagnostic criteria.

Early prediction of preeclampsia in pregnancy with cell-free RNA

Liquid biopsies that measure circulating cell-free RNA (cfRNA) offer an opportunity to study the development of pregnancy-related complications in a non-invasive manner and to bridge gaps in clinical care1–4. Here we used 404 blood samples from 199 pregnant mothers to identify and validate cfRNA transcriptomic changes that are associated with preeclampsia, a multi-organ syndrome that is the second largest cause of maternal death globally5. We find that changes in cfRNA gene expression between normotensive and preeclamptic mothers are marked and stable early in gestation, well before the onset of symptoms. These changes are enriched for genes specific to neuromuscular, endothelial and immune cell types and tissues that reflect key aspects of preeclampsia physiology6–9, suggest new hypotheses for disease progression and correlate with maternal organ health. This enabled the identification and independent validation of a panel of 18 genes that when measured between 5 and 16 weeks of gestation can form the basis of a liquid biopsy test that would identify mothers at risk of preeclampsia long before clinical symptoms manifest themselves. Tests based on these observations could help predict and manage who is at risk for preeclampsia—an important objective for obstetric care10,11.

Pregnancy Complications Can Foreshadow Future Disease-Long-Term Outcomes of a Complicated Pregnancy.

During gestation, the maternal body should increase its activity to fulfil the demands of the developing fetus as pregnancy progresses. Each maternal organ adapts in a unique manner and at a different time during pregnancy. In an organ or system that was already vulnerable before pregnancy, the burden of pregnancy can trigger overt clinical manifestations. After delivery, symptoms usually reside; however, in time, because of the age-related metabolic and pro-atherogenic changes, they reappear. Therefore, it is believed that pregnancy acts as a medical stress test for mothers. Pregnancy complications such as gestational hypertension, preeclampsia and gestational diabetes mellitus foreshadow cardiovascular disease and/or diabetes later in life. Affected women are encouraged to modify their lifestyle after birth by adjusting their diet and exercise habits. Blood pressure and plasmatic glucose level checking are recommended so that early therapeutic intervention can reduce long-term morbidity. Currently, the knowledge of the long-term consequences in women who have had pregnancy-related syndromes is still incomplete. A past obstetric history may, however, be useful in determining the risk of diseases later in life and allow timely intervention.

The effects of maternal hypertension on the early neonatal platelet count.

To examine the relationship between maternal hypertension and early neonatal platelet counts. This single site retrospective cohort study compared initial platelet counts in the first day of life of infants born to mothers with preeclampsia with severe features (PSF) (n = 224) and infants born to normotensive mothers using multivariable logistic and Quasi-Poisson regressionmodels. There was no statistical difference in initial platelet counts or likelihood of thrombocytopenia (aOR = 1.19, 95% CI 0.68-2.08) between infants born to mothers with PSF and infants born to normotensive mothers after multivariable adjustment. Initial platelet counts and thrombocytopenia risk were unaffected by the presence of maternal end organ dysfunction. Small for gestational age (SGA) status was the most significant risk factor for the development of thrombocytopenia (aOR = 2.24, 95% CI 1.13-4.30). Maternal PSF does not directly affect neonatal initial platelet counts. SGA status confers the greatest risk of early thrombocytopenia.

Preeclampsia – long-term effects on mother and child

Preeclampsia (PE) is a pregnancy complication that affects 5% to 8% of all pregnancies. It is a leading cause of maternal mortality that contributes annually more than 60,000 maternal deaths all over the world. Data submitted so far by clinicians are still insufficient to completely understand the disease. Despite many researches, the prediction of patients suffering from PE remains difficult. Moreover therapeutic methods are also limited and concentrated on symptomatic treatment and early termination of pregnancy. The aim of the presented article is to review current research on the PE and its long-term effects on mother and child. PE is defined as a hypertension developing after 20 weeks of gestation with at least one of the following symptoms: proteinuria, maternal organ dysfunction or foetal growth restriction. Because initially patients may be completely asymptomatic, the diagnosis is usually difficult. Untreated PE may lead to the death of both mother and neonate. In later life it predisposes woman and child to cardiovascular and metabolic diseases. Maternal consequences are related to increased risk of hypertension, stroke, thrombosis or chronic kidney disease, whilst offspring implications are directly correlated with hypertension, increased body mass index, hormonal changes and reductions in cognitive functions. In the future there is a need to develop more effective diagnostic methods of PE. Comprehensive understanding of the pathophysiology would allow to avoid many negative long-term effects and reduce its mortality rate.

The roles of free iron, heme, haemoglobin, and the scavenger proteins haemopexin and alpha-1-microglobulin in preeclampsia and fetal growth restriction.

Preeclampsia (PE) is a complex pregnancy syndrome characterised by maternal hypertension and organ damage after 20 weeks of gestation and is associated with an increased risk of cardiovascular disease later in life. Extracellular haemoglobin (Hb) and its metabolites heme and iron are highly toxic molecules and several defence mechanisms have evolved to protect the tissue. We will discuss the roles of free iron, heme, Hb, and the scavenger proteins haemopexin and alpha-1-microglobulin in pregnancies complicated by PE and fetal growth restriction (FGR). In PE, oxidative stress causes syncytiotrophoblast (STB) stress and increased shedding of placental STB-derived extracellular vesicles (STBEV). The level in maternal circulation correlates with the severity of hypertension and supports the involvement of STBEVs in causing maternal symptoms in PE. In PE and FGR, iron homeostasis is changed, and iron levels significantly correlate with the severity of the disease. The normal increase in plasma volume taking place during pregnancy is less for PE and FGR and therefore have a different impact on, for example, iron concentration, compared to normal pregnancy. Excess iron promotes ferroptosis is suggested to play a role in trophoblast stress and lipotoxicity. Non-erythroid α-globin regulates vasodilation through the endothelial nitric oxide synthase pathway, and hypoxia-induced α-globin expression in STBs in PE placentas is suggested to contribute to hypertension in PE. Underlying placental pathology in PE with and without FGR might be amplified by iron and heme overload causing oxidative stress and ferroptosis. As the placenta becomes stressed, the release of STBEVs increases and affects the maternal vasculature.

Preeclampsia and late fetal growth restriction.

There is a strong but complex relationship between fetal growth restriction and preeclampsia. According to the International Society for the Study of Hypertension in Pregnancy the coexistence of gestational hypertension and fetal growth restriction identifies preeclampsia with no need for other signs of maternal organ impairment. While early-onset fetal growth restriction and preeclampsia are often strictly associated, such association becomes looser in the late preterm and term periods. The incidence of preeclampsia decreases dramatically from early preterm fetal growth restriction (39-43%) to late preterm fetal growth restriction (9-32%) and finally to term fetal growth restriction (4-7%). Different placental and cardiovascular mechanism underlie this trend: isolated fetal growth restriction has less frequent placental vascular lesions than fetal growth restriction associated with preeclampsia; moreover, late preterm and term fetal growth restriction show different patterns of maternal cardiac output and peripheral vascular resistance in comparison with preeclampsia. Consequently, current strategies for first trimester screening of placental dysfunction, originally implemented for preeclampsia, do not perform well for late-onset fetal growth restriction: the sensitivity of first trimester combined screening for small-for-gestational age newborns delivered at less than 32 weeks is 56-63%, and progressively decreases for those delivered at 32-36 weeks (43-48%) or at term (21-26%). Moreover, while the test is more sensitive for small-for-gestational age associated with preeclampsia at any gestational age, its sensitivity is much lower for small-for-gestational age without preeclampsia at 32-36 weeks (31-37%) or at term (19-23%).

Kidney Injury Caused by Preeclamptic Pregnancy Recovers Postpartum in a Transgenic Rat Model.

Preeclampsia (PE) is characterized by the onset of hypertension (≥140/90 mmHg) and presence of proteinuria (>300 mg/L/24 h urine) or other maternal organ dysfunctions. During human PE, renal injuries have been observed. Some studies suggest that women with PE diagnosis have an increased risk to develop renal diseases later in life. However, in human studies PE as a single cause of this development cannot be investigated. Here, we aimed to investigate the effect of PE on postpartum renal damage in an established transgenic PE rat model. Female rats harboring the human-angiotensinogen gene develop a preeclamptic phenotype after mating with male rats harboring the human-renin gene, but are normotensive before and after pregnancy. During pregnancy PE rats developed mild tubular and glomerular changes assessed by histologic analysis, increased gene expression of renal damage markers such as kidney injury marker 1 and connective-tissue growth factor, and albuminuria compared to female wild-type rats (WT). However, four weeks postpartum, most PE-related renal pathologies were absent, including albuminuria and elevated biomarker expression. Only mild enlargement of the glomerular tuft could be detected. Overall, the glomerular and tubular function were affected during pregnancy in the transgenic PE rat. However, almost all these pathologies observed during PE recovered postpartum.