Placental neutrophil reverse trans-migration and maternal serum neutrophil extracellular trap expression in HIV infection co-morbid pre-eclampsia in women of African ancestry.

Neutrophil extracellular traps (NETs) and placental neutrophil reverse transmigration (r-TM) are implicated in the pathogenesis of pre-eclampsia (PE). However, the role of the comorbidity of PE and human immunodeficiency virus (HIV) infection in placental neutrophil r-TM and serum NETs remains unknown. Human placental tissue (n = 160) and serum (n = 80) samples were obtained post-ethical approval and divided by pregnancy type and HIV status and across the study population. Immunohistochemistry and morphometry were performed to localize and quantify junctional adhesion molecule-C (JAM-C) expression as an inverse marker of neutrophil r-TM within placental villi. An enzyme-linked immunosorbent assay (ELISA) was performed to quantify the concentration of citrullinated histone H3 (cit-H3) as a marker of NETs. GraphPad Prism (version 8.0.2) was used to compare the results, and a p value of p < 0.05 was considered statistically significant. The localization of JAM-C was observed on the syncytiotrophoblasts (STBs) and endothelial cells of placental villi. The immunoexpression of JAM-C was elevated in PE vs. normotensive (N) placentae. In the exchange villi, JAM-C immunoexpression was higher in the N+ve vs. N-ve group. However, in PE comorbid HIV infection, JAM-C expression was lower in the PE+ve vs. PE-ve group. Citrullinated histone-H3 concentration was lower in the N+ve vs. N-ve group but elevated in early-onset PE (EOPE)+ve vs. late-onset PE (LOPE)+ve group. These results indicate that PE and HIV-infected placentae individually express elevated JAM-C, manifesting in less neutrophil r-TM. However, in exchange villi of PE comorbid with HIV infection reduced JAM-C enhances neutrophil r-TM, thus supporting the synergistic effect of PE comorbid with HIV.

Immunoexpression of neuropilin-1 in the chorionic villi of HIV-infected preeclamptic South African women of African ancestry.

Neuropilin-1 (NRP-1) is an essential regulator of maternal immune tolerance, placentation, and angiogenesis. Its dysregulation in preeclampsia (PE) and human immunodeficiency virus (HIV) infection implicates NRP-1 in disease susceptibility and progression. Therefore, this study investigates placental NRP-1 immunoexpression in HIV-complicated preeclamptic pregnancies in South African women of African ancestry receiving antiretroviral therapy. Immunohistochemistry of recombinant anti-neuropilin-1 antibody was performed on placental tissue from 30 normotensive and 60 early onset (EOPE) and late-onset (LOPE) preeclamptic women stratified by HIV status. Qualitative analysis of NRP-1 immunostaining within the chorionic villi revealed a predominant localization in trophoblasts and syncytial knots as well as endothelial, fibroblast-like, and Hofbauer cells. Following morphometric evaluation, we report that PE and HIV infection and/or antiretroviral usage independently downregulate placental NRP-1 immunoexpression; however, as a comorbidity, this decline is further augmented within the conducting and exchange villi. Furthermore, reduced immunoexpression of NRP-1 in EOPE compared with LOPE villi may be due to maternal-fetal maladaptation. It is plausible that the decreased NRP-1 immunoexpression in PE placentae facilitates syncytiotrophoblast apoptosis and subsequent deportation of NRP-1 into the maternal circulation, contributing to the anti-angiogenic milieu of PE. We hypothesize that the intense NRP-1 immunoreactivity observed in Hofbauer cells at the maternal-fetal interface may contribute to the natural prevention mechanism of HIV vertical transmission.

Inequality in health care services in urban and rural settings in South Africa.

In low- and middle-income countries, urban and rural settings are distinct communities with the latter being more likely to have limited resources, particularly in health care services. We assessed the inequality in health care services in urban and rural settings in South Africa, highlighting the disparities between public and private health services, given that the latter are located mainly in urban settings. Rural settings suffer the highest inequality in the availability of drugs and supplies, overcrowding of health care facilities, delays in transporting patients, inadequate emergency medical services, and lack of experienced health care professionals. Rural settings also preferentially have a shortage of various levels of health care services, and increased security threats by criminals. In addition to specific remedies, the overarching key to solving these challenges is socio-economic growth, as well as visionary and compassionate leadership with integrity and accountability, which ensures policy development, implementation, monitoring, and evaluation.

Vascular Endothelial Growth Factor Receptor 2: Molecular Mechanism and Therapeutic Potential in Preeclampsia Comorbidity with Human Immunodeficiency Virus and Severe Acute Respiratory Syndrome Coronavirus 2 Infections.

This review explored the role of vascular endothelial growth factor receptor-2 (VEGFR-2) in the synergy of preeclampsia (PE), human immunodeficiency virus (HIV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Downregulation of VEGFR-2 in PE promotes endothelial dysfunction and prevents endothelial cell (EC) migration, proliferation, and differentiation. The HIV-1 accessory protein, tat (trans-activator of transcription), prevents VEGFR-2 signaling via the vascular endothelial growth factor A (VEGF-A) ligand. Combined antiretroviral therapy (cART) may cause immune reconstitution, impaired decidualization, and endothelial injury, thus may be a risk factor for PE development. The VEGF/VEGFR-2 interaction may be associated with SARS-CoV-2-related pulmonary oedema. Endothelial dysfunction and heightened inflammation are both associated with PE, HIV, and SARS-CoV-2 infection; therefore, it is plausible that both characteristics may be exacerbated in the synergy of these events. In addition, this review explored microRNAs (miR) regulating VEGFR-2. An overexpression of miR-126 is evident in PE, HIV, and SARS-CoV-2 infection; thus, modulating the expression of miR-126 may be a therapeutic strategy. However, the involvement of microRNAs in PE, HIV, and SARS-CoV-2 infection needs further investigating. Since these conditions have been evaluated independently, this review attempts to predict their clinical manifestations in their synergy, as well as independently; thereby providing a platform for early diagnosis and therapeutic potential in PE, HIV, and SARS-CoV-2 infection.

An observational study of pro- and anti-angiogenic factors in hypertensive disorders of pregnancy in women of African ancestry.

Hypertensive disorders in pregnancy (HDPs) are the leading cause of maternal and perinatal deaths worldwide. Despite the widely reported multisystemic pathophysiology of pre-eclampsia and other HDPs, it is unknown whether these disorders represent a continuum or separate entities making clinical diagnosis a challenge. This study aimed to investigate angiogenic, metabolic and immunoregulatory specific profiles of hypertensive and gestationally matched normotensive pregnancies. A total of 200 pregnancies from a regional hospital in South Africa, via convenience sampling, were quantitatively analysed for circulating sFlt-1; PlGF; VEGF; sENG; PAPP-A; PP13; ADAMTS 12; TGF-ß1 in maternal serum samples using ELISA technique. Serum protein markers TGF-ß1, sENG and PAPP-A were significantly increased (p < .05) in early-onset pre-eclampsia vs. NG1 groups. sFlt-1 was significantly higher in late-onset pre-eclampsia vs NG2 groups. The GH group showed a significant increase in TGF-ß1 and PAPP-A vs. NG1 counterpart. ADAMTS12 and sENG were significantly lower in gestational hypertension vs. early-onset pre-eclampsia. No significant differences were seen in PlGF, VEGF and PP13 levels across the groups. These changes show the HDP spectrum has distinct characteristics on the angiogenic profile. Based on these results, further validation of diagnostic and prognostic biomarkers of pre-eclampsia and gestational hypertension is warranted.Impact statementWhat is already known on this subject? Hypertensive pregnancy disorders are a public health problem with adverse effects on both mother and neonate. The elusive pathogenesis of this syndrome combined with the late prevalence of symptoms leaves clinicians with a myriad of theories and indefinite treatments. The investigation into conventional anti-/angiogenic factors has been extensively studied in pre-eclampsia patients only. The overlapping clinical presentation of pre-eclampsia and gestational hypertension further complicates the diagnosis of disorders.What do the results of this study add? The investigation of novel angiogenic, metabolic and inflammatory markers will firstly contribute to generating a database for researchers both nationally and internationally. This combinatory triad of markers will assist in elucidating and differentiating between early- and late-onset preeclampsia versus gestational hypertension. The results of our cohort study suggest possible early diagnostic markers for pre-eclampsia and gestational hypertension.What are the implications of these findings for clinical practice and/or further research? Research in this area will contribute to an improvement in early disease management which will ultimately lead to a reduction in health care costs and mortality rate locally and globally. It will also enforce diagnostic and prognostic markers for hypertensive pregnancy diseases and warrant further investigation into the proteins primarily involved in the trophoblastic invasion. This will then clarify whether these two closely related hypertensive disorders represent a continuum or two separate entities.

A retrospective identification of risk factors associated with fetal macrosomia.

Despite extensive work on macrosomia, it is impossible to predict women at risk. Current prediction strategies which include clinical examination and ultrasound are imprecise. This study aims to determine the risk factors associated with macrosomia. It was a descriptive, retrospective chart review of women delivered of macrosomic neonates over a two-year period from 2015-2016. Detailed clinical and demographic information was recorded. Statistical analysis was carried out using SPSS (version 25.0 IBM, Armonk, New York, USA). Of 22 244 singleton deliveries, 415 were macrosomic infants (1.9%). The mean birth weight for macrosomic infants was 4.39 ± 0.43 (range 4-5.15) kg and males were more in number and weight. Macrosomic infants occurred more in age groups 25-29 years and peaked with BMI ≥30 kg/m2. Majority were cesarean sections compared to vaginal deliveries (56.6% vs 43.4%; p=0.006) respectively. Vaginal delivery of macrosomic infants was associated with complications. Significant differences were found between fetal macrosomia and clinical characteristics such as body mass index, parity, advanced maternal age, and male fetal sex. Hypoglycaemia was most frequent in infants born to non-diabetic mothers (98.1%). Antenatal risk factors are important in the prediction of macrosomia, but fetal and maternal outcome depends on labour management.

The Renin-Angiotensin System, Hypertension, and SARS-CoV-2 Infection: a Review.

PURPOSE OF REVIEW: This review focuses on the associations between the renin-angiotensin system, hypertension, and severe acute respiratory syndrome (SARS-COV-2) infection. A brief prelude on the current state of affairs with COVID-19 is given. In addition to an overview of ACE2, Ang II, and Ang (1-7), this review presents a brief statement on hypertension, including the function of enzymes involved in the control of hypertension, cardiovascular disease, diabetes mellitus, and other malignancies. RECENT FINDINGS: There is currently no data in support of the concerns raised with the use of ACEIs/ARBs. Many researchers have voiced concerns that the use of ACEIs and ARBs may increase tissue ACE2 levels. These researchers therefore recommend that individuals on ACEIs/ARB's medications withhold such antihypertensive drugs, unless advised by their physicians to do so. SARS-CoV-2 uses ACE2 receptors as the port of entry to human hosts. ACE2 and ACE are different enzymes and ACE inhibitors do not inhibit ACE2. Therefore, the use of ARB's or ACEIs should not be discontinued if an individual is infected by SARS-CoV-2. Further studies are required to investigate the effect of ACEIs and ARBs on ACE2 expression and COVID-19.

The Involvement of MicroRNAs in SARS-CoV-2 Infection Comorbid with HIV-Associated Preeclampsia.

PURPOSE OF REVIEW: This review investigated the potential role of microRNAs (miRNAs) in the synergy of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, preeclampsia (PE), and human immunodeficiency virus (HIV) infection. Maternal health is a great concern when treating pregnant women fighting this triad of diseases, which is highly prevalent in South Africa. MicroRNAs are involved in fine-tuning of physiological processes. Disruptions to the balance of this minute protein can lead to various physiological changes that are sometimes pathological. RECENT FINDINGS: MicroRNAs have recently been implicated in PE and have been linked to the anti-angiogenic imbalance evident in PE. Recent in silico studies have identified potential host miRNAs with anti-viral properties against SARS-CoV-2 infection. Studies have demonstrated dysregulated expression of several miRNAs in HIV-1 infection along with the ability of HIV-1 to downregulate anti-viral host microRNAs. This review has highlighted the significant gap in literature on the potential of miRNAs in women with HIV-associated PE in synergy with the novel SARS-CoV-2 infection. In addition, this review has provided evidence of the critical role that the epigenetic regulatory mechanism of miRNA plays in viral infections and PE, thereby providing a foundation for further research investigating the potential of therapeutic miRNA development with fewer side-effects for pregnant women.

Current Updates on Pre-eclampsia: Maternal and Foetal Cardiovascular Diseases Predilection, Science or Myth? : Future cardiovascular disease risks in mother and child following pre-eclampsia.

PURPOSE OF REVIEW: Cardiovascular diseases (CVD), including pre-eclampsia (PE), remain the major cause of death and morbidity in women. This review elucidates the current knowledge, state of research and scientific information available on the post-event implications and complications of PE regarding maternal and foetal cardiovascular health. Does PE expose, predispose or aggravate a predilection to maternal and foetal CVD later in life? RECENT FINDINGS: Women with a history of PE are reported to have stiffer arteries and are more likely to develop cardiovascular problems with time, especially aortic stenosis and mitral regurgitation, which were not hitherto linked with hypertensive pregnancy. Foetal cells persistence in the mother long after pregnancy, now clearly established in the lungs of mice postpartum, is suggested to portend an overexpression of STOX1, which may potentiate later life CVD. Moreover, the conventional theories of in utero stress and developmental reprogramming may not adequately explain the risk of later life CVD predilection in offspring born to mothers with pre-eclampsia as recent data has shown that siblings of offspring born from pre-eclamptic pregnancies are also at higher risk of hypertension later in life, irrespective of whether subsequent pregnancies were pre-eclamptic or normotensive. The mechanism involved in adverse cardiovascular outcome in offspring of pre-eclamptic pregnancies is most likely an intricate interaction of foetal programming, environmental and genetic factors. In light of available evidence, the question of whether PE is just a pointer or predisposing factor to maternal development of CVDs in later life begs for answers to facilitate definitive clinical solutions and preventive approaches.

The COVID-19 Pandemic: an Appraisal of its Impact on Human Immunodeficiency Virus Infection and Pre-Eclampsia.

PURPOSE OF REVIEW: The impact of the coronavirus disease 2019 (COVID-19) pandemic is profound, with distressing consequences on many individuals, especially those with co-morbidities. Pregnant women are one such group of individuals who are at in increased risk of contracting COVID-19, due to their immunocompromised state. In South Africa, HIV infection and pre-eclampsia are the leading causes of maternal morbidity and mortality, with South Africa being the HIV epicentre of the world. The relationship between COVID-19 superimposed on HIV infection and preeclampsia is complex and uncertain due to their different immune responses, and therefore requires further research. RECENT FINDINGS: Notably evidence suggests that pregnant women with chronic comorbidities (HIV and pre-eclampsia) may be at a greater risk of contracting or encountering complications from COVID-19. Maternal stress, during a pandemic, as well as home delivery have become potential options for pregnant woman. Nonetheless there is currently a paucity of information on the combined effect of COVID-19 in HIV-associated preeclampsia. Understanding the pathogenesis of COVID-19 could potentially aid in developing effective treatment strategies for COVID-19 in HIV associated preeclampsia. This review article presents a comprehensive analysis of the current data in relation to COVID-19 and its effect on pregnant women, including symptoms, pathogenesis and the possible risk of vertical transmission. This paper also reviews its' interactions and effects on preeclamptic and HIV positive pregnant women with suspected or confirmed COVID-19.

A Narrative Review of the Renin-Angiotensin-Aldosterone System in the Placenta and Placental Bed of HIV Infected Women of African Ancestry with Preeclampsia.

PURPOSE OF REVIEW: Both HIV infection and preeclampsia (PE), a pregnancy-specific disorder of hypertension and multi-system organ involvement, have high prevalence rates especially in low-to-middle-income countries. The immunoexpression of specific renin-angiotensin-aldosterone system (RAAS) receptors in the placenta and placental bed interface may forecast the risk of PE. RECENT FINDINGS: Preeclampsia is a leading risk factor for mortality worldwide and remains a challenge in HIV-infected individuals especially those on antiretroviral therapy (ART). Irregular RAAS stimulation may be linked to the pathophysiology of hypertension in HIV infection and in PE. The AT1 receptor is expressed across all trimesters of pregnancy, within placental tissue, eliciting vasoconstriction. This increased expression is associated with the severity of PE, implying that the increased expression may be involved in the pathogenesis of this pregnancy disorder. The AT2 receptor expression in normotensive pregnancies was shown to be lower as compared to non-pregnant individuals. Furthermore, in the PE placental bed, the AT2 receptor is the predominant receptor subtype and is found in extravillous trophoblast cells where they facilitate vasodilation. However, AT4R in placentae of PE pregnancies are found to be significantly reduced compared to normotensives pregnancies. The data on the role played by the RAAS pathway in pregnancy is conflicting. Investigation into a tissue-based RAAS with emphasis on immune-expression within the placenta and placental bed may help resolve this conundrum.

The function of adipsin and C9 protein in the complement system in HIV-associated preeclampsia.

OBJECTIVE: In preeclampsia, there are excessive complement components expressed due to increased complement activation; therefore, this study investigated the concentration of adipsin and C9 in HIV-associated preeclampsia. METHOD: The study population (n = 76) was stratified by pregnancy type (normotensive pregnant and preeclampsia) and by HIV status. Serum was assayed for the concentration of adipsin and C9 using a Bioplex immunoassay procedure. RESULTS: Maternal weight did not differ (p = 0.1196) across the study groups. The concentration of adipsin was statistically different between the PE vs normotensive pregnant groups, irrespective of HIV status (p = 0.0439). There was no significant difference in adipsin concentration between HIV-negative vs HIV-positive groups, irrespective of pregnancy type (p = 0.6290). Additionally, there was a significant difference in adipsin concentration between HIV-negative normotensive vs HIV-negative preeclampsia (p < 0.05), as well as a difference between HIV-negative preeclampsia vs HIV-positive preeclampsia (p < 0.05). C9 protein expression was not statistically different between the normotensive and PE groups, regardless of HIV status (p = 0.5365). No statistical significance in C9 expression was found between HIV-positive vs HIV-negative groups, regardless of pregnancy type (p = 0.3166). Similarly, no statistical significance was noted across all study groups (p = 0.0774). CONCLUSION: This study demonstrates that there is a strong correlation between the up-regulation of adipsin and PE and that adipsin is a promising biomarker to use as a diagnostic tool for PE.

HIV Associated Preeclampsia: A Multifactorial Appraisal.

Introduction: This review explores angiogenesis, vascular dysfunction, the complement system, RAAS, apoptosis and NETosis as potential pathways that are dysregulated during preeclampsia, HIV infection and ART usage. Results: HIV-1 accessory and matrix proteins are protagonists for the elevation of oxidative stress, apoptosis, angiogenesis, and elevation of adhesion markers. Despite the immunodeficiency during HIV-1 infection, HIV-1 exploits our cellular defence arsenal by escaping cell-mediated lysis, yet HIV-1 infectivity is enhanced via C5a release of TNF-α and IL-6. This review demonstrates that PE is an oxidatively stressed microenvironment associated with increased apoptosis and NETosis, but with a decline in angiogenesis. Immune reconstitution in the duality of HIV-1 and PE by protease inhibitors, HAART and nucleoside reverse transcriptase, affect similar cellular pathways that eventuate in loss of endothelial cell integrity and, hence, its dysfunction. Conclusions: HIV-1 infection, preeclampsia and ARTs differentially affect endothelial cell function. In the synergy of both conditions, endothelial dysfunction predominates. This knowledge will help us to understand the effect of HIV infection and ART on immune reconstitution in preeclampsia.

Exosomal Th1/Th2 cytokines in preeclampsia and HIV-positive preeclamptic women on highly active anti-retroviral therapy.

Preeclampsia (PE) is a hypertensive disorder of pregnancy which is a leading cause of maternal and foetal morbidity and mortality. Furthermore, HIV/Highly Active Anti-Retroviral Treatment has been associated with the increased risk of preeclampsia due to maternal immune reconstitution, which complicates the clinical diagnosis of PE in these patients. It is therefore necessary to identify biomarkers involved in the pathology of both disorders with the intent to diagnose. Exosomal cytokines represent ideal biomarkers of PE and inflammatory conditions due to their immunomodulatory role in pregnancy. We therefore quantified exosomal Th1 (IL-2 and TNF-α) and Th2 cytokines (IL-10) in maternal circulation. A significant dysregulation in total exosomes, placental-derived exosomes and exosomal cytokines in PE and HIV-positive PE pregnant woman on Highly Active Antiretroviral Treatment (HAART) was observed (p < 0.01). Additionally, we observed a significant shift towards Th1 immunity in PE which becomes amplified in HIV-positive PE pregnant woman on HAART (p < 0.01). Moreover, we show the potential application of exosomal Tumor necrosis factor alpha (TNF-α) as a biomarker of PE and PE in HIV-positive pregnant women on HAART (CI: 95%, LHR > 10, sensitivity of 100% and specificity of 90%). These findings are in support of exosome release and exosome cytokine encapsulation as a tightly regulated process in favour of maintaining the immune microenvironment, which can orchestrate either normal pregnancy, or the pathogenesis of preeclampsia and preeclampsia in HIV/HAART pregnancies.

The Role of the Renin-Angiotensin-Aldosterone System in Preeclampsia: a Review.

PURPOSE OF REVIEW: Preeclampsia (PE) is a complex human pregnancy-specific condition and is clinically characterized by new onset hypertension and proteinuria in the second half of pregnancy. The precise etiology of PE is unknown, but much of the pathophysiology has been elucidated, and it is accepted that the disorder is multifactorial in nature. Historically, because of the presence of proteinuria, the role of the renin-angiotensin-aldosterone system (RAAS) has been considered in the etiology of PE. However, the results of studies (including maternal circulatory angiotensin II, urinary angiotensinogen, plasma renin and prorenin, AT1 receptor antibodies, and gene polymorphisms) on the role of the RAAS in the etiology of PE have proved controversial. The purpose of this narrative review was to evaluate the contemporary literature on the RAAS and its role in the pathophysiology of pregnancy. RECENT FINDINGS: The current review shows that although the RAAS has a role in the development of normal pregnancy, it does not have a significant role in the pathophysiology of PE except for the AT1-AA components. Despite many researchers having measured increases in s[P}RR and [P]RR, this may be independent of the RAAS. Our view is in keeping with contemporary thinking that the placenta rather than the RAAS plays a central role in elaborating pro-inflammatory factors (antiangiogenic and angiogenic) into the maternal circulation resulting in widespread endothelial dysfunction in all organ systems including the renal system.

The Role of Neutrophils and Their Extracellular Traps in the Synergy of Pre-eclampsia and HIV Infection.

PURPOSE OF THE REVIEW: In our innate immune system, neutrophils are the first cells to sense signals of infection and to proceed to kill the invading pathogen. This is mediated by their production of neutrophil extracellular traps (NETS) to entrap pathogenic micro-organisms, preventing their amplification and dissemination. Pre-eclampsia (PE) is the leading cause of global maternal mortality, yet to date, there is no cure nor a gold-standard diagnostic strategy. The purpose of this review is to discover the role of neutrophils in PE as early identification markers. Additionally, this review aims to explore the role of neutrophils in HIV-infected pregnancies with PE as a source of synergy. RECENT FINDINGS: Recent findings demonstrate an elevation of neutrophils and neutrophil extracellular traps (NETs) in PE placentae. This is due to their activation by excessive release of syncytiotrophoblast microparticles (STBM). There is also an elevation of NETs in HIV-infected placentae-where histone H3 entraps HIV by binding to its glycoprotein envelope. Additionally, histones H1 and H2A inhibit HIV infection. It is interesting to note that women with both PE and HIV infection have supressed NETs. This review focuses on the role of neutrophils in the synergy of PE and HIV infection. It is plausible that the deregulation of NETs in the synergy of pre-eclamptic HIV-infected women is strategic for the entrapment of the HIV-1 virus. Finally, it is plausible that neutrophils and NETS may act as early biomarkers of PE development. Graphical abstract.

An Insight into the Angiogenic and Lymphatic Interplay in Pre-eclampsia Comorbid with HIV Infection.

PURPOSE OF REVIEW: To provide insight on the imbalance of angiogenic and lymphangiogenic factors in pre-eclampsia, as well as highlight polymorphism in genes related to angiogenesis and lymphangiogenesis. RECENT FINDINGS: The pregnancy-specific disorder pre-eclampsia is diagnosed by the presence of hypertension with/without proteinuria, after 20 weeks of gestation. The pathogenesis of pre-eclampsia remains ambiguous, but research over the years has identified an imbalance in maternal and foetal factors. Familial predisposition and gene variation are also linked to pre-eclampsia development. The sFlt-1/PIGF ratio has attracted great attention over the years; more recently several researchers have reported that a sFlt-1/PIGF ratio of ≤ 38 can be used to predict short-term absence of pre-eclampsia. This ratio has the potential to prevent adverse pregnancy outcomes and reduce healthcare costs significantly. Genome-wide studies have additionally identified variation in the foetal gene near Flt-1. The development of preeclampsia is not limited to the maternal interface, but foetal involvement as well as genetic interplay is associated with the disorder.

The second victim phenomenon in health care: A literature review.

Aim: This study aimed to explore the knowledge on the second victim phenomenon (SVP) in health care, more specifically within the speciality of obstetrics. Methods: An extensive electronic search of multiple databases, with additional hand searching of the reference lists of pertinent articles regarding the SVP, was performed from May 2017 to December 2018. Results: A review of the literature suggests consistent evidence of the substantial impact of adverse medical events on health-care professionals across a range of specialities. The effects of an adverse medical event for the health-care professional are ominous, with many experiencing feelings of sadness, guilt and anxiety, as well as some displaying symptoms consistent with post-traumatic stress disorder. Negative effects may be exacerbated for health-care professionals in the case of an adverse maternal event due to its highly sensitive and dramatic nature, involving both maternal and neonatal lives. The provision of timely and effective support at the individual and more specifically the organisational level has been positively correlated with a second victim's recovery. Yet, limited organisations have formal support interventions designed specifically for the needs of the second victim. Conclusions: It is evident that the consequences of adverse medical events on health-care professionals can be intense and numerous. The unique nature and high sensitivities surrounding obstetric care have the potential to exacerbate the negative consequences for the health-care professional following an adverse event. Still, there remains a dearth of information of the extent of adverse medical events and the SVP in the speciality of obstetrics.

Role of basic fibroblast growth factor in human immunodeficiency virus associated pre-eclampsia.

AIM: Cell signaling is vital to ensure successful trophoblast invasion. This study assessed the level of serum basic fibroblast growth factor (FGF-2) in human immunodeficiency virus (HIV) associated pre-eclampsia (PE). METHODS: Using a Bio-plex Multiplex Immunoassay, FGF-2 (pg/mL) was analyzed in blood sera collected from 80 pregnant women attending a large regional hospital in Durban, South Africa. Study groups consisted of normotensive and pre-eclamptic pregnant women stratified according to their HIV status. Data analysis was performed using graphpad prism statistics software, version 5.00. RESULTS: In this study, we report a significant decrease of FGF-2 serum level in pre-eclamptic compared to normotensive pregnant women groups (25.38 ± 6.69 pg/mL vs 61.79 ± 11.25 pg/mL), irrespective of their HIV status. Similarly, there was a significant decrease in FGF-2 serum level in HIV positive compared to HIV negative group (33.80 ± 9.62 pg/mL vs 52.15 ± 9.49 pg/mL), irrespective of their pregnancy type. CONCLUSION: This study demonstrates a downregulation of serum FGF-2 expression in pre-eclamptic compared to normotensive pregnant women. This decline may be responsible for the defective trophoblast invasion and/or to PE severity. The decline in FGF-2 expression in HIV infection is probably due to the effect of HIV Tat protein on angiogenesis.

The Role of Highly Active Antiretroviral Therapy (HAART) on Interleukin 17A (IL-17A) in Normotensive and Preeclamptic Black South African Women.

Introduction: Interleukin 17A has been implicated in the pathophysiology of both human immune deficiency virus and preeclampsia. This study evaluated serum levels of IL-17A based on pregnancy type, gestational age, HIV status, and duration of HAART. Material and Methods. A sample size of 250 was analysed: normotensives (n = 150; N) and preeclamptics (n = 100; PE). Normotensives were further stratified into HIV negative (n = 90), HAART-acute (n = 30), and HAART-chronic (n = 30). The PE group was divided into early onset (n = 50; EOPE) and late onset (n = 50; LOPE). The EOPE and LOPE groups were subdivided into HIV negative (n = 30), HAART-acute (n = 10), and HAART-chronic (n = 10). Analysis of IL-17A was performed using a multiple Bio-Plex immunoassay method. Results: Pregnancy type: the levels of IL-17A were increased in PE compared to N (P = 0.0014). Gestational age: the levels of IL-17A were increased in EOPE compared to N group (P = 0.0113). A significant increase in the levels of IL-17A in LOPE compared to N was observed (P = 0.0063). HIV status: the levels of IL-17A were increased in PE compared to N (P = 0.0114) and in EOPE compared to N groups (P = 0.0071). HAART duration: the concentration of IL-17A was increased in HAART-chronic PE compared to N groups (P = 0.0062). There was also an increase in the levels of IL-17A in EOPE compared to N (P = 0.0029). Conclusion: The study demonstrates that IL-17A is involved in the pathophysiology of PE and that in the presence of HIV infection, chronic HAART administration predisposes women to the development of EOPE.