29 results found
Singh N, Herbert B, Sooranna G, et al., 2021, Is there an inflammatory stimulus to human term labour?, PLOS ONE, Vol: 16, Pages: e0256545-e0256545
<jats:p>Inflammation is thought to play a pivotal role in the onset of term and some forms of preterm labour. Although, we recently found that myometrial inflammation is a consequence rather than a cause of term labour, there are several other reproductive tissues, including amnion, choriodecidua parietalis and decidua basalis, where the inflammatory stimulus to labour may occur. To investigate this, we have obtained amnion, choriodecidual parietalis and decidua basalis samples from women at various stages of pregnancy and spontaneous labour. The inflammatory cytokine profile in each tissue was determine by Bio-Plex Pro® cytokine multiplex assays and quantitative RT-PCR. Active motif assay was used to study transcription activation in the choriodecidua parietalis. Quantitative RT-PCR was use to study the pro-labour genes (<jats:italic>PGHS-2</jats:italic>, <jats:italic>PGDH</jats:italic>, <jats:italic>OTR and CX43</jats:italic>) in all of the tissues at the onset of labour and <jats:italic>oxytocin (OT)</jats:italic> mRNA expression in the choriodecidual parietalis and decidua basalis. Statistical significance was ascribed to a P value <0.05. In the amnion and choriodecidua parietalis, the mRNA levels of various cytokines decreased from preterm no labour to term no labour samples, but the protein levels were unchanged. The choriodecidua parietalis showed increase in the protein levels of IL-1β and IL-6 in the term early labour samples. In the amnion and decidua basalis, the protein levels of several cytokines rose in term established labour. The multiples of the median derived from the 19-plex cytokine assay were greater in term early labour and term established labour samples from the choriodecidua parietalis, but only in term established labour for myometrium. These data suggest that the inflammatory stimulus to labour may begin in the choriodecidua parietalis, but the absence of any change in p
Bracewell-Milnes T, Holland JC, Jones BP, et al., 2021, Exploring the knowledge and attitudes of women of reproductive age from the general public towards egg donation and egg sharing: a UK-based study., Hum Reprod, Vol: 36, Pages: 2189-2201
STUDY QUESTION: What are the knowledge and views of UK-based women towards egg donation (ED) and egg sharing (ES)? SUMMARY ANSWER: Lacking knowledge of the practices of ED and ES could be an influential factor in donor egg shortages, rather than negative perceptions or lack of donor anonymity and financial incentives. WHAT IS KNOWN ALREADY: The increasing age of women trying to conceive has led to donor egg shortages, with ED and ES failing to meet demand. Indeed, in recent years in the UK, ES numbers have fallen. This results in long waiting lists, forcing patients abroad for fertility treatment to take up cross border reproductive care. Previous research suggests a lack of knowledge of ED among members of the general public; however, no study has yet assessed knowledge or views of ES in the general public. STUDY DESIGN, SIZE, DURATION: Six hundred and thirty-five UK-based women over 18 years were voluntarily recruited from social media community groups by convenience sampling. The recruitment period was from February to April 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants completed a previously validated questionnaire regarding female fertility, ED and ES, including knowledge, perceptions and approval of the practices and relevant legislation. This included ranking key benefits and issues regarding egg sharing. The questionnaire was completed using the online Qualtrics survey software. Statistical analysis was conducted using SPSS. MAIN RESULTS AND THE ROLE OF CHANCE: Regarding knowledge of ED and ES, 56.3% and 79.8%, respectively had little or no prior knowledge. Upon explanation, most approved of ED (85.8%) and ES (70.4%). A greater proportion of respondents would donate to a family member/friend (49.75%) than to an anonymous recipient (35.80%). Overall, ES was viewed less favourably than ED, with ethical and practical concerns highlighted. Women aged 18-30 years were significantly more likely to approve of egg donation practice compa
Greer O, Woon EV, Shah NM, et al., 2021, Uterine Natural Killer Cell function in Recurrent Miscarriage and Implantation Failure: A Systematic Review, Publisher: OXFORD UNIV PRESS, Pages: 312-312, ISSN: 0268-1161
Woon EV, Greer O, Shah N, et al., 2021, Uterine Natural Killer Cells in Recurrent Miscarriage and Implantation Failure: An Updated Systematic Review and Meta-analysis, Publisher: OXFORD UNIV PRESS, Pages: 329-330, ISSN: 0268-1161
Kadiwar S, Smith JJ, Ledot S, et al., 2021, Were pregnant women more affected by COVID-19 in the second wave of the pandemic?, Lancet, Vol: 397, Pages: 1539-1540
Briggs E, Greer O, Shah NM, et al., 2020, Hyponatraemia compounding pre-eclamptic toxaemia in a patient with type 1 diabetes., BMJ case reports, Vol: 13, ISSN: 1757-790X
We report a case of profound, symptomatic hyponatraemia in association with pre-eclamptic toxaemia (PET) in a 38-year-old nulliparous woman with type 1 diabetes mellitus. This patient developed hypertension and proteinuria at 31+6 weeks' gestation and was admitted for management of pre-eclampsia. Severe headache, visual disturbance and nausea were associated with a hyponatraemia of 115 mmol/L followed by ketoacidosis. This was reversed through fluid restriction, supplementation with 1.8%-3.0% hypertonic saline and a volume-reduced variable-rate insulin infusion. Clinical stability was achieved and she was subsequently worked up for an induction of labour for worsening pre-eclampsia. Hyponatraemia in the context of PET has been previously reported as rare. However, it has complications that may significantly compound the sequelae of severe PET. We propose that specific and focused monitoring of serum sodium levels should become common practice in the management of women with this condition to allow for timely, measured correction of abnormalities.
Saeed Z, Greer O, Shah NM, 2020, Is the Host Viral Response and the Immunogenicity of Vaccines Altered in Pregnancy?, Antibodies (Basel), Vol: 9
The intricacy of the maternal immune system arises from its ability to prevent a maternal immune response against a semi-allogenic fetus, while protecting the mother against harmful pathogens. However, these immunological adaptations may also make pregnant women vulnerable to developing adverse complications from respiratory viral infections. While the influenza and SARS pandemics support this theory, there is less certainty regarding the clinical impact of SARS-CoV-2 in pregnancy. In the current COVID-19 pandemic, vaccine development is key to public preventative strategies. Whilst most viral vaccines are able to induce a seroprotective antibody response, in some high-risk individuals this may not correlate with clinical protection. Some studies have shown that factors such as age, gender, and chronic illnesses can reduce their effectiveness and in this review, we discuss how pregnancy may affect the efficacy and immunogenicity of vaccines. We present literature to support the hypothesis that pregnant women are more susceptible to respiratory viral infections and may not respond to vaccines as effectively. In particular, we focus on the clinical implications of important respiratory viral infections such as influenza during pregnancy, and the pregnancy induced alterations in important leukocytes such as TFH, cTFH and B cells, which play an important role in generating long-lasting and high-affinity antibodies. Finally, we review how this may affect the efficacy of vaccines against influenza in pregnancy and highlight areas that require further research.
Shah NM, Edey LF, Imami N, et al., 2020, Human labour is associated with altered regulatory T cell function and maternal immune activation., Clin Exp Immunol, Vol: 199, Pages: 182-200
During human pregnancy, regulatory T cell (Treg ) function is enhanced and immune activation is repressed allowing the growth and development of the feto-placental unit. Here, we have investigated whether human labour is associated with a reversal of the pregnancy-induced changes in the maternal immune system. We tested the hypothesis that human labour is associated with a decline in Treg function, specifically their ability to modulate Toll-like receptor (TLR)-induced immune responses. We studied the changes in cell number, activation status and functional behaviour of peripheral blood, myometrial (myoMC) and cord blood mononuclear cells (CBMC) with the onset of labour. We found that Treg function declines and that Treg cellular targets change with labour onset. The changes in Treg function were associated with increased activation of myoMC, assessed by their expression of major histocompatibility complex (MHC) class II molecules and CBMC inflammatory cells. The innate immune system showed increased activation, as shown by altered monocyte and neutrophil cell phenotypes, possibly to be ready to respond to microbial invasion after birth or to contribute to tissue remodelling. Our results highlight changes in the function of the adaptive and innate immune systems that may have important roles in the onset of human labour.
Greer O, Shah NM, Johnson MR, 2020, Maternal sepsis update: current management and controversies, The Obstetrician & Gynaecologist, Vol: 22, Pages: 45-55, ISSN: 1467-2561
•Sepsis is a leading cause of maternal morbidity and mortality, globally and in the UK.•In pregnancy and the puerperium, women may be more susceptible to rapid deterioration of illness following an infection.•Sepsis has a complex pathophysiology and the immunological and cardiovascular adaptations of normal pregnancy may have an adverse impact on the maternal response to infection. Furthermore, physiological changes of pregnancy, which mimic those of sepsis, often delay optimal management.•‘Bedside’ identification of pathogens and their antibiotic resistance patterns may help to improve clinical outcomes.•Recent updates in sepsis management, areas of controversy and the importance of translational research and clinical trials for pregnancy and the puerperium are discussed.
Cocker ATH, Shah NM, Raj I, et al., 2020, Pregnancy Gestation Impacts on HIV-1-Specific Granzyme B Response and Central Memory CD4 T Cells., Front Immunol, Vol: 11
Pregnancy induces alterations in peripheral T-cell populations with both changes in subset frequencies and anti-viral responses found to alter with gestation. In HIV-1 positive women anti-HIV-1 responses are associated with transmission risk, however detailed investigation into both HIV-1-specific memory responses associated with HIV-1 control and T-cell subset changes during pregnancy have not been undertaken. In this study we aimed to define pregnancy and gestation related changes to HIV-1-specific responses and T-cell phenotype in ART treated HIV-1 positive pregnant women. Eleven non-pregnant and 24 pregnant HIV-1 positive women were recruited, peripheral blood samples taken, fresh cells isolated, and compared using ELISpot assays and flow cytometry analysis. Clinical data were collected as part of standard care, and non-parametric statistics used. Alterations in induced IFNγ, IL-2, IL-10, and granzyme B secretion by peripheral blood mononuclear cells in response to HIV-1 Gag and Nef peptide pools and changes in T-cell subsets between pregnant and non-pregnant women were assessed, with data correlated with participant clinical parameters and longitudinal analysis performed. Cross-sectional comparison identified decreased IL-10 Nef response in HIV-1 positive pregnant women compared to non-pregnant, while correlations exhibited reversed Gag and Nef cytokine and protease response associations between groups. Longitudinal analysis of pregnant participants demonstrated transient increases in Gag granzyme B response and in the central memory CD4 T-cell subset frequency during their second trimester, with a decrease in CD4 effector memory T cells from their second to third trimester. Gag and Nef HIV-1-specific responses diverge with pregnancy time-point, coinciding with relevant T-cell phenotype, and gestation associated immunological adaptations. Decreased IL-10 Nef and both increased granzyme B Gag response and central memory CD4 T cells implies that amplified a
Shah NM, Imami N, Kelleher P, et al., 2019, Pregnancy-related immune suppression leads to altered influenza vaccine recall responses., Clin Immunol, Vol: 208
Pregnancy is a risk factor for severe influenza infection. Despite achieving seroprotective antibody titres post immunisation fewer pregnant women experience a reduction in influenza-like illness compared to non-pregnant cohorts. This may be due to the effects that immune-modulation in pregnancy has on vaccine efficacy leading to a less favourable immunologic response. To understand this, we investigated the antigen-specific cellular responses and leukocyte phenotype in pregnant and non-pregnant women who achieved seroprotection post immunisation. We show that pregnancy is associated with better antigen-specific inflammatory (IFN-γ) responses and an expansion of central memory T cells (Tcm) post immunisation, but low-level pregnancy-related immune regulation (HLA-G, PIBF) and associated reduced B-cell antibody maintenance (TGF-β) suggest poor immunologic responses compared to the non-pregnant. Thus far, studies of influenza vaccine immunogenicity have focused on the induction of antibodies but understanding additional vaccine-related cellular responses is needed to fully appreciate how pregnancy impacts on vaccine effectiveness.
Greer O, Shah NM, Sriskandan S, et al., 2019, Sepsis: Precision-Based Medicine for Pregnancy and the Puerperium., Int J Mol Sci, Vol: 20
Sepsis contributes significantly to global morbidity and mortality, particularly in vulnerable populations. Pregnant and recently pregnant women are particularly prone to rapid progression to sepsis and septic shock, with 11% of maternal deaths worldwide being attributed to sepsis. The impact on the neonate is considerable, with 1 million neonatal deaths annually attributed to maternal infection or sepsis. Pregnancy specific physiological and immunological adaptations are likely to contribute to a greater impact of infection, but current approaches to the management of sepsis are based on those developed for the non-pregnant population. Pregnancy-specific strategies are required to optimise recognition and management of these patients. We review current knowledge of the physiology and immunology of pregnancy and propose areas of research, which may advance the development of pregnancy-specific diagnostic and therapeutic approaches to optimise the care of pregnant women and their babies.
Sooranna GR, Shah NM, Singh N, et al., 2019, The Immune Modulatory Effects of Both Progesterone and a Combination of Progesterone and Aminophylline on the Maternal Immune System., 66th Annual Scientific Meeting of the Society-for-Reproductive-Investigation (SRI), Publisher: SAGE PUBLICATIONS INC, Pages: 293A-293A, ISSN: 1933-7191
Briggs E, Greer O, Shah NM, et al., 2019, Hyponatraemia and pre-eclampsia, Publisher: WILEY, Pages: 41-41, ISSN: 1470-0328
Shah NM, Lai PF, Imami N, et al., 2019, Progesterone-Related Immune Modulation of Pregnancy and Labor., Frontiers in endocrinology, Vol: 10, ISSN: 1664-2392
Pregnancy involves a complex interplay between maternal neuroendocrine and immunological systems in order to establish and sustain a growing fetus. It is thought that the uterus at pregnancy transitions from quiescent to laboring state in response to interactions between maternal and fetal systems at least partly <i>via</i> altered neuroendocrine signaling. Progesterone (P4) is a vital hormone in maternal reproductive tissues and immune cells during pregnancy. As such, P4 is widely used in clinical interventions to improve the chance of embryo implantation, as well as reduce the risk of miscarriage and premature labor. Here we review research to date that focus on the pathways through which P4 mediates its actions on both the maternal reproductive and immune system. We will dissect the role of P4 as a modulator of inflammation, both systemic and intrinsic to the uterus, during human pregnancy and labor.
Shah NM, Imami N, Johnson MR, 2018, Progesterone Modulation of Pregnancy-Related Immune Responses, FRONTIERS IN IMMUNOLOGY, Vol: 9, ISSN: 1664-3224
Progesterone (P4) is an important steroid hormone for the establishment and maintenance of pregnancy and its functional withdrawal in reproductive tissue is linked with the onset of parturition. However, the effects of P4 on adaptive immune responses are poorly understood. In this study, we took a novel approach by comparing the effects of P4 supplementation longitudinally, with treatment using a P4 antagonist mifepristone (RU486) in mid-trimester pregnancies. Thus, we were able to demonstrate the immune-modulatory functions of P4. We show that, in pregnancy, the immune system is increasingly activated (CD38, CCR6) with greater antigen-specific cytotoxic T cell responses (granzyme B). Simultaneously, pregnancy promotes a tolerant immune environment (IL-10 and regulatory-T cells) that gradually reverses prior to the onset of labor. P4 suppresses and RU486 enhances antigen-specific CD4 and CD8 T cell inflammatory cytokine (IFN-γ) and cytotoxic molecule release (granzyme B). P4 and RU486 effectively modulate immune cell-mediated interactions, by regulating differentiated memory T cell subset sensitivity to antigen stimulation. Our results indicate that P4 and RU486, as immune modulators, share a reciprocal relationship. These data unveil key contributions of P4 to the modulation of the maternal immune system and suggests targets for future modulation of maternal immune function during pregnancy.
Shah NM, Sooranna G, Imami N, et al., 2018, Progesterone suppressed ex vivo pregnancy immune responses are reversed with the progesterone antagonist RU486, 65th Annual Scientific Meeting of the Society-for-Reproductive-Investigation (SRI), Publisher: Sage, Pages: 314A-314A, ISSN: 1933-7191
Shah NM, Edey L, Sooranna G, et al., 2018, Labour is associated with a decline in Treg function and their modulation of TLR-Ligand induced immune responses, 65th Annual Scientific Meeting of the Society-for-Reproductive-Investigation (SRI), Publisher: Sage Publications Inc., Pages: 314A-314A, ISSN: 1071-5576
Shah NM, Herasimtschuk AA, Boasso A, et al., 2017, Changes in T Cell and Dendritic Cell Phenotype from Mid to Late Pregnancy Are Indicative of a Shift from Immune Tolerance to Immune Activation., Frontiers in Immunology, Vol: 8, ISSN: 1664-3224
During pregnancy, the mother allows the immunologically distinct fetoplacental unit to develop and grow. Opinions are divided as to whether this represents a state of fetal-specific tolerance or of a generalized suppression of the maternal immune system. We hypothesized that antigen-specific T cell responses are modulated by an inhibitory T cell phenotype and modified dendritic cell (DC) phenotype in a gestation-dependent manner. We analyzed changes in surface markers of peripheral blood T cells, ex vivo antigen-specific T cell responses, indoleamine 2,3-dioxygenase (IDO) activity (kynurenine/tryptophan ratio, KTR), plasma neopterin concentration, and the in vitro expression of progesterone-induced blocking factor (PIBF) in response to peripheral blood mononuclear cell culture with progesterone. We found that mid gestation is characterized by reduced antigen-specific T cell responses associated with (1) predominance of effector memory over other T cell subsets; (2) upregulation of inhibitory markers (programmed death ligand 1); (3) heightened response to progesterone (PIBF); and (4) reduced proportions of myeloid DC and concurrent IDO activity (KTR). Conversely, antigen-specific T cell responses normalized in late pregnancy and were associated with increased markers of T cell activation (CD38, neopterin). However, these changes occur with a simultaneous upregulation of immune suppressive mechanisms including apoptosis (CD95), coinhibition (TIM-3), and immune regulation (IL-10) through the course of pregnancy. Together, our data suggest that immune tolerance dominates in the second trimester and that it is gradually reversed in the third trimester in association with immune activation as the end of pregnancy approaches.
, 2017, Maternal Medicine Poster Abstracts, Publisher: Wiley, Pages: 82-121, ISSN: 1470-0328
Shah N, Imami N, Johnson MR, 2015, Changes in T Cell, Dendritic Cell and NK Cell Phenotype, and T Cell Function From Mid To Late Pregnancy Indicate a Shift From Immune Tolerance To Increased Immune Activation., REPRODUCTIVE SCIENCES, Vol: 22, Pages: 279A-279A, ISSN: 1933-7191
Shah N, Imami N, Johnson M, 2014, Antigenic Readiness, Enhanced Immune Response and Modified Tolerant Phenotypes Follows Flu Vaccination in Pregnancy, REPRODUCTIVE SCIENCES, Vol: 21, Pages: 411A-411A, ISSN: 1933-7191
Shah N, Westrop S, Low-Beer N, et al., 2013, Expanded CD56+subset in HIV-1-positive mothers on HAART is associated with premature delivery, HIV MEDICINE, Vol: 14, Pages: 32-32, ISSN: 1464-2662
Shah N, Westrop S, Low-Beer N, et al., 2013, Premature Delivery in HIV plus Mothers on HAART Is Associated with an Expanded Peripheral Blood CD56+Subset, 60th Annual Scientific Meeting of the Society-for-Gynecologic-Investigation (SGI), Publisher: SAGE PUBLICATIONS INC, Pages: 197A-197A, ISSN: 1933-7191
Shah N, Imami N, Johnson M, 2013, Pregnancy Is Associated with Greater PIBF Expression on Peripheral Blood CD8+T-Cells In-Vitro, 60th Annual Scientific Meeting of the Society-for-Gynecologic-Investigation (SGI), Publisher: SAGE PUBLICATIONS INC, Pages: 323A-323A, ISSN: 1933-7191
Shah N, Agarwal N, Ratcliff S, et al., 2012, A comparative audit of total abdominal hysterectomy, subtotal hysterectomy, vaginal hysterectomy and laparoscopically assisted vaginal hysterectomy in a London District General Hospital, BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Vol: 119, Pages: 230-230, ISSN: 1470-0328
Shah N, Imami N, Johnson M, 2012, T-cell phenotypic profile in pregnancy: link between immune activation and exhaustion, BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Vol: 119, Pages: 62-62, ISSN: 1470-0328
Shah N, Benlarech A, Imami N, et al., 2012, Phenotypic analysis of dendritic cell lineage and maturity, and T-Cell exhaustion indicate dampened immune activation in pregnancy, Joint International Congress of the American-Society-for-Reproductive-Immunology (ASRI) and the European-Society-for-Reproductive-Immunology (ESRI), Publisher: ELSEVIER IRELAND LTD, Pages: 50-50, ISSN: 0165-0378
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