Publications
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van Hagen IM, Thorne SA, Taha N, et al., 2018, Pregnancy outcomes in women with rheumatic mitral valve disease results from the registry of pregnancy and cardiac disease, Circulation, Vol: 137, Pages: 806-816, ISSN: 0009-7322
Background:Cardiac disease is 1 of the major causes of maternal mortality. We studied pregnancy outcomes in women with rheumatic mitral valve disease.Methods:The Registry of Pregnancy and Cardiac Disease is an international prospective registry, and consecutive pregnant women with cardiac disease were included. Pregnancy outcomes in all women with rheumatic mitral valve disease and no prepregnancy valve replacement is described in the present study (n=390). A maternal cardiac event was defined as cardiac death, arrhythmia requiring treatment, heart failure, thromboembolic event, aortic dissection, endocarditis, acute coronary syndrome, and hospitalization for other cardiac reasons or cardiac intervention. Associations between patient characteristics and cardiac outcomes were checked in a 3-level model (patient–center–country).Results:Most patients came from emerging countries (75%). Mitral stenosis (MS) with or without mitral regurgitation (MR) was present in 273 women, isolated MR in 117. The degree of MS was mild in 20.9%, moderate in 39.2%, severe in 19.8%, and severity not classified in the remainder. Maternal death during pregnancy occurred in 1 patient with severe MS. Hospital admission occurred in 23.1% of the women with MS, and the main reason was heart failure (mild MS 15.8%, moderate 23.4%, severe 48.1%; P<0.001). Heart failure occurred in 23.1% of patients with moderate or severe MR. An intervention during pregnancy was performed in 16 patients, 14 had percutaneous balloon mitral commissurotomy, and 2 had surgical valve replacement (1 for MS, 1 for MR). In multivariable modeling, prepregnancy New York Heart Association class >1 was an independent predictor of maternal cardiac events. Follow-up at 6 months postpartum was available for 53%, and 3 more patients died (1 with severe MS, 1 with moderate MS, 1 with moderate to severe MR).Conclusions:Although mortality was only 1.9% during pregnancy, ≈50% of the patients with severe rheuma
Roos-Hesselink JW, Budts W, Walker F, et al., 2017, Organisation of care for pregnancy in patients with congenital heart disease, HEART, Vol: 103, Pages: 1854-1859, ISSN: 1355-6037
Edey LF, Georgiou H, O'Dea KP, et al., 2017, Progesterone, the maternal immune system and the onset of parturition in the mouse, Biology of Reproduction, Vol: 98, Pages: 376-395, ISSN: 1529-7268
The role of progesterone (P4) in the regulation of the local (uterine) and systemic innate immune system, myometrial expression of connexin 43 (Cx-43) and cyclooxygenase 2 (COX-2) and the onset of parturition was examined in: 1) naïve mice delivering at term; 2) E16 mice treated with RU486 (P4-antagonist) to induce preterm parturition; and 3) in mice treated with P4 to prevent term parturition.In naïve mice, myometrial neutrophil and monocyte numbers peaked at E18 and declined with the onset of parturition. In contrast, circulating monocytes did not change and although neutrophils were increased with pregnancy, they did not change across gestation. The myometrial mRNA and protein levels of most chemokines/cytokines, Cx-43 and COX-2 increased with, but not before, parturition.With RU486-induced parturition, myometrial and systemic neutrophil numbers increased before and myometrial monocyte numbers increased with parturition only. Myometrial chemokine/cytokine mRNA abundance increased with parturition, but protein levels peaked earlier at between 4.5 and 9h post RU486. Cx-43, but not COX-2, mRNA expression and protein levels increased prior to the onset of parturition.In mice treated with P4, the gestation-linked increase in myometrial monocyte, but not neutrophil, numbers was prevented and expression of Cx-43 and COX-2 was reduced. On E20 of P4 supplementation, myometrial chemokine/cytokine and leukocyte numbers, but not Cx-43 and COX-2 expression, increased.These data show that during pregnancy P4 controls myometrial monocyte infiltration, cytokine and prolabour factor synthesis via mRNA dependent and independent mechanisms and, with prolonged P4 supplementation, P4 action is repressed resulting in increased myometrial inflammation.
Gyamfi-Bannerman C, Menon R, Bonney EA, et al., 2017, Novel thoughts on preterm birth research proceedings of the 13th annual preterm birth international collaborative (PREBIC) meeting, SEMINARS IN PERINATOLOGY, Vol: 41, Pages: 438-441, ISSN: 0146-0005
Bracewell-Milnes T, Saso S, Abdalla H, et al., 2017, Metabolomics as a tool to identify biomarkers to predict and improve outcomes in reproductive medicine: a systematic review, Human Reproduction Update, Vol: 23, Pages: 723-736, ISSN: 1355-4786
BACKGROUNDInfertility is a complex disorder with significant medical, psychological and financial consequences for patients. With live-birth rates per cycle below 30% and a drive from the Human Fertilisation and Embryology Authority (HFEA) to encourage single embryo transfer, there is significant research in different areas aiming to improve success rates of fertility treatments. One such area is investigating the causes of infertility at a molecular level, and metabolomics techniques provide a platform for studying relevant biofluids in the reproductive tract.OBJECTIVE AND RATIONALEThe aim of this systematic review is to examine the recent findings for the potential application of metabolomics to female reproduction, specifically to the metabolomics of follicular fluid (FF), embryo culture medium (ECM) and endometrial fluid. To our knowledge no other systematic review has investigated this topic.SEARCH METHODSEnglish peer-reviewed journals on PubMed, Science Direct, SciFinder, were systematically searched for studies investigating metabolomics and the female reproductive tract with no time restriction set for publications. Studies were assessed for quality using the risk of bias assessment and ROBIN-I.OUTCOMESThere were 21 studies that met the inclusion criteria and were included in the systematic review. Metabolomic studies have been employed for the compositional analysis of various biofluids in the female reproductive tract, including FF, ECM, blastocoele fluid and endometrial fluid. There is some weak evidence that metabolomics technologies studying ECM might be able to predict the viability of individual embryos and implantation rate better than standard embryo morphology, However these data were not supported by randomized the controlled trials (RCTs) which showed no evidence that using metabolomics is able to improve the most important reproductive outcomes, such as clinical pregnancy and live-birth rates. This systematic review provides guidance for future
van Hagen IM, Roos-Hesselink JW, Donvito V, et al., 2017, Incidence and predictors of obstetric and fetal complications in women with structural heart disease, HEART, Vol: 103, Pages: 1610-1618, ISSN: 1355-6037
Singh N, Herbert B, Sooranna GR, et al., 2017, Is myometrial inflammation a cause or a consequence of term human labour?, JOURNAL OF ENDOCRINOLOGY, Vol: 235, Pages: 69-83, ISSN: 0022-0795
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- Citations: 33
Lim JCE-S, Cauldwell M, Patel RR, et al., 2017, Management of Marfan Syndrome during pregnancy: A real world experience from a Joint Cardiac Obstetric Service, INTERNATIONAL JOURNAL OF CARDIOLOGY, Vol: 243, Pages: 180-184, ISSN: 0167-5273
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- Citations: 8
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.
Goland S, van Hagen IM, Elbaz-Greener G, et al., 2017, Pregnancy in women with hypertrophic cardiomyopathy: data from the European Society of Cardiology initiated Registry of Pregnancy and Cardiac disease (ROPAC), EUROPEAN HEART JOURNAL, Vol: 38, Pages: 2683-2690, ISSN: 0195-668X
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- Citations: 57
Baris L, Shotan A, Van Hagen IM, et al., 2017, Pregnancy in women with ventricular dysfunction: data from the European Society of Cardiology Registry of Pregnancy and Cardiac Disease (ROPAC), Publisher: OXFORD UNIV PRESS, Pages: 1272-1272, ISSN: 0195-668X
Van Hagen IM, Baart S, Khioe RFS, et al., 2017, Influence of socioeconomic factors on pregnancy outcome in women with structural heart disease: data from ROPAC, an ESC registry, Publisher: OXFORD UNIV PRESS, Pages: 350-350, ISSN: 0195-668X
Karda R, Perocheau DP, Suff N, et al., 2017, Continual conscious bioluminescent imaging in freely moving somatotransgenic mice, Scientific Reports, Vol: 7, ISSN: 2045-2322
Luciferase bioimaging in living animals is increasingly being applied in many fields of biomedical research. Rodent imaging usually involves anaesthetising the animal during data capture, however, the biological consequences of anaesthesia have been largely overlooked. We have evaluated luciferase bioimaging in conscious, unrestrained mice after neonatal intracranial or intravascular administration of lentiviral, luciferase reporter cassettes (biosensors); we present real-time analyses from the first day of life to adulthood. Anaesthetics have been shown to exert both neurotoxic and neuroprotective effects during development and in models of brain injury. Mice subjected to bioimaging after neonatal intracranial or intravascular administration of biosensors, targeting the brain and liver retrospectively showed no significant difference in luciferase expression when conscious or unconscious throughout development. We applied conscious bioimaging to the assessment of NFκB and STAT3 transcription factor activated reporters during the earliest stages of development in living, unrestrained pups. Our data showed unique longitudinal activities for NFκB and STAT3 in the brain of conscious mice. Conscious bioimaging was applied to a neonatal mouse model of cerebral palsy (Hypoxic-Ischaemic Encephalopathy). Imaging of NFκB reporter before and after surgery showed a significant increase in luciferase expression, coinciding with secondary energy failure, in lesioned mice compared to controls.
Cauldwell M, Quail M, Smith GS, et al., 2017, Effect of pregnancy on ventricular and aortic dimensions in repaired tetralogy of Fallot, Journal of the American Heart Association, Vol: 6, ISSN: 2047-9980
Background: To assess whether the cardiovascular adaptation to pregnancy in women with repaired tetralogy of Fallot (TOF) adversely affects haemodynamic stability; in particular with respect to right ventricular (RV) dilatation, pulmonary regurgitation or aortic root dilatation. Methods and Results: Retrospective cohort study of women with repaired TOF with paired Cardiovascular Magnetic Resonance (CMR) scans before and after their first pregnancy (baseline RV end systolic volume index 49mL/m2 and RV end diastolic volume index 118mL/m2) matched with a comparison group of nulliparous women with TOF. Cases were matched for age at baseline CMR scan, time between follow up of CMR scans, QRS duration, RV ejection fraction and indexed RV end systolic and diastolic volume at baseline. The effect of pregnancy and time on parameters was assessed using mixed effects modelling. Nineteen women with repaired TOF who had completed their first pregnancy were identified and matched with 38 nulliparous women. We observed no deleterious effects of pregnancy on RV volumes, aortic dimensions or exercise data. There was an effect of pregnancy observed in both LV EDV and LV SV, consistent with a sustained small increase in LV SV due to pregnancy (53ml/m2 to 55ml/m2).Conclusion: Women with repaired TOF and with mild to moderate RV dilatation considering pregnancy can be reassured that pregnancy is unlikely to cause deterioration in their cardiovascular status. We recommend that women are routinely assessed and followed up before and after pregnancy and that pre pregnancy counselling is tailored to their individual clinical status.
Zöllner J, Howe LG, Edey LF, et al., 2017, The response of the innate immune and cardiovascular systems to LPS in pregnant and nonpregnant mice., Biology of Reproduction, Vol: 97, Pages: 258-272, ISSN: 1529-7268
Sepsis is the leading cause of direct maternal mortality, but there are no data directly comparing the response to sepsis in pregnant and nonpregnant (NP) individuals. This study uses a mouse model of sepsis to test the hypothesis that the cardiovascular response to sepsis is more marked during pregnancy. Female CD1 mice had radiotelemetry probes implanted and were time mated. NP and day 16 pregnant CD-1 mice received intraperitoneal lipopolysaccharide (LPS; 10 μg, serotype 0111: B4). In a separate study, tissue and serum (for RNA, protein and flow cytometry studies), aorta and uterine vessels (for wire myography) were collected after LPS or vehicle control administration. Administration of LPS resulted in a greater fall in blood pressure in pregnant mice compared to NP mice. This occurred with similar changes in the circulating levels of cytokines, vasoactive factors, and circulating leukocytes, but with a greater monocyte and lesser neutrophil margination in the lungs of pregnant mice. Baseline markers of cardiac dysfunction and apoptosis as well as cytokine expression were higher in pregnant mice, but the response to LPS was similar in both groups as was the ex vivo assessment of vascular function. In pregnant mice, nonfatal sepsis is associated with a more marked hypotensive response but not a greater immune response. We conclude that endotoxemia induces a more marked hypotensive response in pregnant compared to NP mice. These changes were not associated with a more marked systemic inflammatory response in pregnant mice, although monocyte lung margination was greater. The more marked hypotensive response to LPS may explain the greater vulnerability to some infections exhibited by pregnant women.
Johnson MR, Hesselink JWR, 2017, Pregnancy, Marfan syndrome, and type-B aortic dissection, BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Vol: 125, Pages: 494-494, ISSN: 1470-0328
Cauldwell M, Steer PJ, Swan L, et al., 2017, The management of the third stage of labour in women with heart disease, Heart, Vol: 103, Pages: 945-951, ISSN: 1355-6037
Objective In women with heart disease (HD), the third stage of labour is managed with a reduced dose of oxytocin because it can have significant adverse cardiovascular effects. However, women with HD have high rates of postpartum haemorrhage (PPH); consequently, we designed a prospective study to investigate whether higher doses of oxytocin can be given safely and would reduce rates of PPH.Methods We performed a single centre, prospective, cohort study comparing the standard ‘low-dose’ oxytocin infusion (10 U of oxytocin in 500 mL of normal saline given intravenously at 36 mL/hour for 4 hours (12 mU/min), n=29) to the low-dose infusion and an additional 2 U of oxytocin given over 10 min immediately after birth (n=30). Maternal blood pressure was measured every minute for 10 min, continuous ECG (Holter) monitoring was performed and any symptoms (chest pain, dyspnoea) were recorded. Total blood loss and serum troponins were measured at 12 hours.Results There were no cardiac symptoms, arrhythmias, change in the ST segment or increase in serum troponins. The fall in blood pressure and increase in heart rate were greater with the additional oxytocin, but neither were statistically or clinically significant. The blood loss was significantly less in women receiving additional oxytocin (505 vs 849 mL) and the proportion of women having a PPH was lower.Conclusions The use of an additional 2 U of oxytocin for the management of third stage in women with HD had no cardiac consequences and was associated with a significantly lower blood loss. Further larger studies on a larger population of women with HD are needed.
Cauldwell M, Ghonim S, Uebing A, et al., 2017, Preconception counseling, predicting risk and outcomes in women with mWHO 3 and 4 heart disease, International Journal of Cardiology, Vol: 234, Pages: 76-80, ISSN: 0167-5273
ObjectiveAll women with CHD, especially those with more severe disease, should be offered preconception counseling (PCC), to discuss the risk of complications and to plan a future pregnancy. Several scoring system have been devised to estimate the risk of adverse events in pregnancies complicated by maternal heart disease (HD) and while comparisons have been made across the whole population, none have focused on the high-risk population.MethodsRetrospective cohort study that included women classed as modified WHO (mWHO) 3 and 4 who had a pregnancy from at least 20 weeks gestation between 1994 and 2015 managed within our institution. We assessed how well the quoted risk (at PCC) of an adverse event (maternal or fetal) related to the actual rate of occurrence. We calculated NYHA and CARPREG scores for all patients, and the clinician assessment of percentage risk, to predict the occurrence of an adverse outcome.ResultsWe identified 76 mWHO 3 and 4 women who had a total of 102 pregnancies. However, only in 63 pregnancies had the woman attended PCC. Both maternal and fetal adverse events were common. NYHA did not significantly predict any adverse events, whilst a CARPREG score of > 3 score predicted heart failure and mWHO4 score predicted maternal death. However, the best prediction of adverse outcomes was a composite quoted risk (percent) given at PCC.ConclusionsWomen must have access to PCC as those with worse CARPREG and mWHO scores encounter greater adverse events.
Tirlapur N, O'Dea K, Soni S, et al., 2017, Pathological Stretch Of Endothelial Cells Activates Marginated Monocytes To Release Microvesicles In An In Vitro Model Of Ventilator-Induced Lung Injury, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Goland SS, Van Hagen IM, Elbaz-Greener G, et al., 2017, Pregnancy in women with hypertrophic cardiomyopathy: data from the European Society of Cardiology initiated Registry of Pregnancy and Cardiac disease (ROPAC), Publisher: WILEY, Pages: 82-82, ISSN: 1388-9842
Ertekin E, van Hagen IM, Salam AM, et al., 2017, Corrigendum to 'Ventricular tachyarrhythmia during pregnancy in women with heart disease: Data from the ROPAC, a registry from the European Society of Cardiology' [Int. J. Cardio. 220 (2016) 13-136], International Journal of Cardiology, Vol: 232, Pages: 348-348, ISSN: 0167-5273
Cocker A, Dermont S, Khan W, et al., 2017, Altered CD4 and NK cell profile with inverse IFN gamma and IL-10 antiviral response in HIV-1(+) pregnancies, 64th Annual Scientific Meeting of the Society-for-Reproductive-Investigation (SRI), Publisher: Elsevier, Pages: 294A-294A, ISSN: 1071-5576
Das A, Sooranna S, Johnson MR, 2017, Can the Anti-Inflammatory Effect of Progesterone Be Enhanced in Stretched IL-1 beta Stimulated Human Amnion Cells?, 64th Annual Scientific Meeting of the Society-for-Reproductive-Investigation (SRI), Publisher: SAGE PUBLICATIONS INC, Pages: 282A-282A, ISSN: 1933-7191
Sivarajasingam SP, Das A, Herbert BR, et al., 2017, Immunological changes in the choriodecidua, placenta and amnion in preterm deliveries secondary to chorioamnionitis., 64th Annual Scientific Meeting of the Society-for-Reproductive-Investigation (SRI), Publisher: Elsevier, Pages: 174A-175A, ISSN: 1071-5576
Zollner J, Lambden S, Nasri NM, et al., 2017, Pharmacological Inhibition of the Dimethylarginine-Dimethylaminohydrolase 1 (DDAH1) Enzyme Improves Survival and Haemodynamic Function in a Rodent Model of Severe Sepsis in Pregnancy., 64th Annual Scientific Meeting of the Society-for-Reproductive-Investigation (SRI), Publisher: SAGE PUBLICATIONS INC, Pages: 111A-111A, ISSN: 1933-7191
Lei K, Georgiou EX, Yulia A, et al., 2017, Progesterone and the Repression of Myometrial Inflammation: The Roles of MKP-1 and the AP-1 System., 64th Annual Scientific Meeting of the Society-for-Reproductive-Investigation (SRI), Publisher: SAGE PUBLICATIONS INC, Pages: 107A-107A, ISSN: 1933-7191
Sassine AJ, Sooranna GR, Singh N, et al., 2017, Placental Fatty Acid Translocase (FAT/CD36) and Tranport Protein-4 (FATP-4) Are Less Expressed in the Human Preterm Than Term Placenta., 64th Annual Scientific Meeting of the Society-for-Reproductive-Investigation (SRI), Publisher: SAGE PUBLICATIONS INC, Pages: 280A-280A, ISSN: 1933-7191
Maric T, Kanu C, Johnson M, et al., 2017, Insulin resistance in neonates of post-bariatric pregnant women, Publisher: WILEY, Pages: 127-128, ISSN: 1470-0328
Yulia A, Singh N, Lei K, et al., 2017, The effects of inflammation and stretch on cyclic AMP levels and pathways components in myometrial tissues, Publisher: WILEY, Pages: 52-52, ISSN: 1470-0328
Zollner J, Nasri NM, Leiper J, et al., 2017, Worse Outcomes in a Severe Sepsis Model in Pregnancy Were Not Associated with a TH1/Th2 Cytokine Bias or Immunosuppression., 64th Annual Scientific Meeting of the Society-for-Reproductive-Investigation (SRI), Publisher: SAGE PUBLICATIONS INC, Pages: 240A-241A, ISSN: 1933-7191
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