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Sliwa K, van der Meer P, Viljoen C, et al., 2024, Socio-economic factors determine maternal and neonatal outcomes in women with peripartum cardiomyopathy: A study of the ESC EORP PPCM registry., Int J Cardiol, Vol: 398
BACKGROUND: Peripartum cardiomyopathy (PPCM) is a global disease with substantial morbidity and mortality. The aim of this study was to analyze to what extent socioeconomic factors were associated with maternal and neonatal outcomes. METHODS: In 2011, >100 national and affiliated member cardiac societies of the European Society of Cardiology (ESC) were contacted to contribute to a global PPCM registry, under the auspices of the ESC EORP Programme. We investigated the characteristics and outcomes of women with PPCM and their babies according to individual and country-level sociodemographic factors (Gini index coefficient [GINI index], health expenditure [HE] and human developmental index [HDI]). RESULTS: 739 women from 49 countries (Europe [33%], Africa [29%], Asia-Pacific [15%], Middle East [22%]) were enrolled. Low HDI was associated with greater left ventricular (LV) dilatation at time of diagnosis. However, baseline LV ejection fraction did not differ according to sociodemographic factors. Countries with low HE prescribed guideline-directed heart failure therapy less frequently. Six-month mortality was higher in countries with low HE; and LV non-recovery in those with low HDI, low HE and lower levels of education. Maternal outcome (death, re-hospitalization, or persistent LV dysfunction) was independently associated with income. Neonatal death was significantly more common in countries with low HE and low HDI, but was not influenced by maternal income or education attainment. CONCLUSIONS: Maternal and neonatal outcomes depend on country-specific socioeconomic characteristics. Attempts should therefore be made to allocate adequate resources to health and education, to improve maternal and fetal outcomes in PPCM.
Shah N, Charani E, Ming D, et al., 2024, Antimicrobial stewardship and targeted therapies in the changing landscape of maternal sepsis, Journal of Intensive Medicine, Vol: 4, Pages: 46-61, ISSN: 2667-100X
Pregnant and postnatal women are a high-risk population particularly prone to rapid progression to sepsis with significant morbidity and mortality worldwide. Moreover, severe maternal infections can have a serious detrimental impact on neonates with almost 1 million neonatal deaths annually attributed to maternal infection or sepsis. In this review we discuss the susceptibility of pregnant women and their specific physiological and immunological adaptations that contribute to their vulnerability to sepsis, the implications for the neonate, as well as the issues with antimicrobial stewardship and the challenges this poses when attempting to reach a balance between clinical care and urgent treatment. Finally, we review advancements in the development of pregnancy-specific diagnostic and therapeutic approaches and how these can be used to optimize the care of pregnant women and neonates.
Greer OYO, Anandanadesan R, Shah NM, et al., 2024, Cardiogenic shock in pregnancy, BJOG: an International Journal of Obstetrics and Gynaecology, Vol: 131, Pages: 127-139, ISSN: 1470-0328
Cardiac disease complicates 1%–4% of pregnancies globally, with a predominance in low and middle-income countries (LMICs). Increasing maternal age, rates of obesity, cardiovascular comorbidities, pre-eclampsia and gestational diabetes all contribute to acquired cardiovascular disease in pregnancy. Additionally, improved survival in congenital heart disease (CHD) has led to increasing numbers of women with CHD undergoing pregnancy. Implementation of individualised care plans formulated through pre-conception counselling and based on national and international guidance have contributed to improved clinical outcomes. However, there remains a significant proportion of women of reproductive age with no apparent comorbidities or risk factors that develop heart disease during pregnancy, with no indication for pre-conception counselling. The most extreme manifestation of cardiac disease is cardiogenic shock (CS), where the primary cardiac pathology results in inadequate cardiac output and hypoperfusion, and is associated with significant mortality and morbidity. Key to management is early recognition, intervention to treat any potentially reversible underlying pathology and supportive measures, up to and including mechanical circulatory support (MCS). In this narrative review we discuss recent developments in the classification of CS, and how these may be adapted to improve outcomes of pregnant women with, or at risk of developing, this potentially lethal condition.
Crawford MA, Sinclair AJ, Wang Y, et al., 2023, Docosahexaenoic acid explains the unexplained in visual transduction, Entropy: international and interdisciplinary journal of entropy and information studies, Vol: 25, ISSN: 1099-4300
In George Wald's Nobel Prize acceptance speech for "discoveries concerning the primary physiological and chemical visual processes in the eye", he noted that events after the activation of rhodopsin are too slow to explain visual reception. Photoreceptor membrane phosphoglycerides contain near-saturation amounts of the omega-3 fatty acid docosahexaenoic acid (DHA). The visual response to a photon is a retinal cis-trans isomerization. The trans-state is lower in energy; hence, a quantum of energy is released equivalent to the sum of the photon and cis-trans difference. We hypothesize that DHA traps this energy, and the resulting hyperpolarization extracts the energized electron, which depolarizes the membrane and carries a function of the photon's energy (wavelength) to the brain. There, it contributes to the creation of the vivid images of our world that we see in our consciousness. This proposed revision to the visual process provides an explanation for these previously unresolved issues around the speed of information transfer and the purity of conservation of a photon's wavelength and supports observations of the unique and indispensable role of DHA in the visual process.
Dos Santos F, Dennehy N, Steer PJ, et al., 2023, B-type natriuretic peptide in low-risk pregnancy and pregnancy with congenital heart disease, INTERNATIONAL JOURNAL OF GYNECOLOGY & OBSTETRICS, Vol: 163, Pages: 218-225, ISSN: 0020-7292
Short D, Johnson H, Shah N, et al., 2023, Insight Report: Online public involvement session on the views of parents with experience of preterm birth in relation to a personalised medicine approach to the treatment of preterm birth using amniocentesis.
Cauldwell M, Adamson D, Batia K, et al., 2023, Direct current cardioversion in pregnancy: a multicentre study, BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Vol: 130, Pages: 1269-1274, ISSN: 1470-0328
van der Zande JA, Tutarel O, Ramlakhan KP, et al., 2023, Pregnancy outcomes in women with Ebstein's anomaly: data from the Registry of Pregnancy And Cardiac disease (ROPAC), OPEN HEART, Vol: 10, ISSN: 2053-3624
Roos-Hesselink JW, van der Zande JA, Johnson MR, 2023, Pregnancy outcomes in women with heart disease: how to improve?, EUROPEAN HEART JOURNAL, Vol: 44, Pages: 1541-1543, ISSN: 0195-668X
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- Citations: 1
Bracewell-Milnes T, Hossain A, Jones BP, et al., 2023, Does egg-sharing negatively impact on the chance of the donor or recipient achieving a live birth?, HUMAN FERTILITY, Vol: 26, Pages: 266-275, ISSN: 1464-7273
Nashat H, Patel R, Johnson MR, et al., 2023, Percutaneous intervention of severe native coarctation of the aorta presenting in pregnancy: a case report, EUROPEAN HEART JOURNAL-CASE REPORTS, Vol: 7
Patel D, Borrelli N, Patey O, et al., 2023, Effect of bariatric surgery on maternal cardiovascular system, ULTRASOUND IN OBSTETRICS & GYNECOLOGY, Vol: 61, Pages: 207-214, ISSN: 0960-7692
Cocker ATH, Whettlock EM, Browne B, et al., 2022, Isolation of single cells from human uterus in the third trimester of pregnancy: myometrium, decidua, amnion and chorion, Oxford Open Immunology, Vol: 3, Pages: 1-12, ISSN: 2633-6960
During pregnancy, interactions between uterine immune cells and cells of the surrounding reproductive tissues are thought to be vital for regulating labour. The mechanism that specifically initiates spontaneous labour has not been determined, but distinct changes in uterine immune cell populations and their activation status have been observed during labour at term gestation. To understand the regulation of human labour by the immune system, the ability to isolate both immune cells and non-immune cells from the uterus is required. Here, we describe protocols developed in our laboratory to isolate single cells from uterine tissues, which preserve both immune and non-immune cell populations for further analysis. We provide detailed methods for isolating immune and non-immune cells from human myometrium, chorion, amnion and decidua, together with representative flow cytometry analysis of isolated cell populations present. The protocols can be completed in tandem and take approximately 4–5 h, resulting in single-cell suspensions that contain viable leucocytes, and non-immune cells in sufficient numbers for single-cell analysis approaches such as flow cytometry and single cell RNA sequencing (scRNAseq).
Ramlakhan KP, Malhame I, Marelli A, et al., 2022, Hypertensive disorders of pregnant women with heart disease: the ESC EORP ROPAC Registry, EUROPEAN HEART JOURNAL, Vol: 43, Pages: 3749-3761, ISSN: 0195-668X
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- Citations: 4
Woon EV, Greer O, Shah N, et al., 2022, Number and function of uterine natural killer cells in recurrent miscarriage and implantation failure: a systematic review and meta-analysis, Human Reproduction Update, Vol: 28, Pages: 548-582, ISSN: 1355-4786
BACKGROUND: Uterine natural killer cells (uNK) are the most abundant lymphocytes found in the decidua during implantation and in first trimester pregnancy. They are important for early placental development, especially trophoblast invasion and transformation of the spiral arteries. However, inappropriate uNK function has been implicated in reproductive failure, such as recurrent miscarriage (RM) or recurrent implantation failure (RIF). Previous studies have mainly focused on peripheral NK cells (pNK), despite the well-documented differences in pNK and uNK phenotype and function. In recent years, there has been an explosion of studies conducted on uNK, providing a more suitable representation of the immune environment at the maternal-fetal interface. Here, we summarize the evidence from studies published on uNK in women with RM/RIF compared to controls.OBJECTIVE AND RATIONALE: (AUTHOR: edited to journal style.) The objectives of this systematic review and meta-analysis are to evaluate: differences in uNK level in women with RM/RIF compared to controls; pregnancy outcome in women with RM/RIF stratified by high and normal uNK levels; correlation between uNK and pNK in women with RM/RIF; and differences in uNK activity in women with RM/RIF compared to controls.SEARCH METHODS: MEDLINE, EMBASE, Web of Science and Cochrane Trials Registry were searched from inception up to December 2020 and studies were selected in accordance with PRISMA guidelines. Meta-analyses were performed for uNK level, pregnancy outcome and uNK/ pNK correlation. Narrative synthesis was conducted for uNK activity. Risk of bias was assessed by ROBINS-I and publication bias by Egger’s test.OUTCOMES: Our initial search yielded 4636 articles, of which 60 articles were included in our systematic review. Meta-analysis of CD56+ uNK level in women with RM compared to controls showed significantly higher levels in women with RM in subgroup analysis of endometrial samples [standardized mean difference (S
Lai PF, Young RC, Tribe RM, et al., 2021, Evaluating aminophylline and progesterone combination treatment to modulate contractility and labor‐related proteins in pregnant human myometrial tissues, Pharmacology Research & Perspectives, Vol: 9, Pages: 1-18, ISSN: 2052-1707
Progesterone (P4) and cyclic adenosine monophosphate (cAMP) are regarded as pro-quiescent factors that suppress uterine contractions during pregnancy. We previously used human primary cells in vitro and mice in vivo to demonstrate that simultaneously enhancing myometrial P4 and cAMP levels may reduce inflammation-associated preterm labor. Here, we assessed whether aminophylline (Ami; phosphodiesterase inhibitor) and P4 can reduce myometrial contractility and contraction-associated proteins (CAPs) better together than individually; both agents are clinically used drugs. Myometrial tissues from pregnant non-laboring women were treated ex vivo with Ami acutely (while spontaneous contracting) or throughout 24-h tissue culture (±P4); isometric tension measurements, PKA assays, and Western blotting were used to assess tissue contractility, cAMP action, and inflammation. Acute (1 h) treatment with 250 and 750 μM Ami reduced contractions by 50% and 84%, respectively, which was not associated with a directly proportional increase in whole tissue PKA activity. Sustained myometrial relaxation was observed during 24-h tissue culture with 750 μM Ami, which did not require P4 nor reduce CAPs. COX-2 protein can be reduced by 300 nM P4 but this did not equate to myometrial relaxation. Ami (250 μM) and P4 (100 and 300 nM) co-treatment did not prevent oxytocin-augmented contractions nor reduce CAPs during interleukin-1β stimulation. Overall, Ami and P4 co-treatment did not suppress myometrial contractions more than either agent alone, which may be attributed to low specificity and efficacy of Ami; cAMP and P4 action at in utero neighboring reproductive tissues during pregnancy should also be considered.
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., Human Reproduction, Vol: 36, Pages: 2189-2201, ISSN: 0268-1161
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
Li JKH, Lai PF, Tribe RM, et al., 2021, Transcription factors regulated by cAMP in smooth muscle of the myometrium at human parturition., Biochemical Society Transactions, Vol: 49, Pages: 997-1011, ISSN: 0300-5127
Cyclic adenosine monophosphate (cAMP) contributes to maintenance of a quiescent (relaxed) state in the myometrium (i.e. uterine smooth muscle) during pregnancy, which most commonly has been attributed to activation of protein kinase A (PKA). PKA-mediated phosphorylation of cytosolic contractile apparatus components in myometrial smooth muscle cells (mSMCs) are known to promote relaxation. Additionally, PKA also regulates nuclear transcription factor (TF) activity to control expression of genes important to the labour process; these are mostly involved in actin-myosin interactions, cell-to-cell connectivity and inflammation, all of which influence mSMC transition from a quiescent to a contractile (pro-labour) phenotype. This review focuses on the evidence that cAMP modulates the activity of TFs linked to pro-labour gene expression, predominantly cAMP response element (CRE) binding TFs, nuclear factor κB (NF-κB), activator protein 1 (AP-1) family and progesterone receptors (PRs). This review also considers the more recently described exchange protein directly activated by cAMP (EPAC) that may oppose the pro-quiescent effects of PKA, as well as explores findings from other cell types that have the potential to be of novel relevance to cAMP action on TF function in the myometrium.
Maric T, Kanu C, Mandalia S, et al., 2021, Fetal fractional limb volumes in pregnancies following bariatric surgery, ACTA OBSTETRICIA ET GYNECOLOGICA SCANDINAVICA, Vol: 100, Pages: 272-278, ISSN: 0001-6349
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- Citations: 2
Bracewell-Milnes T, Saso S, Jones B, et al., 2021, A systematic review exploring the patient decision-making factors and attitudes towards pre-implantation genetic testing for aneuploidy and gender selection, ACTA OBSTETRICIA ET GYNECOLOGICA SCANDINAVICA, Vol: 100, Pages: 17-29, ISSN: 0001-6349
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- Citations: 10
Cífková R, Johnson MR, Kahan T, et al., 2020, Peripartum management of hypertension: a position paper of the ESC Council on Hypertension and the European Society of Hypertension, European Heart Journal - Cardiovascular Pharmacotherapy, Vol: 6, Pages: 384-393, ISSN: 2055-6845
Hypertensive disorders are the most common medical complications in the peripartum period associated with a substantial increase in morbidity and mortality. Hypertension in the peripartum period may be due to the continuation of pre-existing or gestational hypertension, de novo development of pre-eclampsia or it may be also induced by some drugs used for analgesia or suppression of postpartum haemorrhage. Women with severe hypertension and hypertensive emergencies are at high risk of life threatening complications, therefore, despite the lack of evidence-based data, based on expert opinion, antihypertensive treatment is recommended. Labetalol intravenously and metyldopa orally are then the two most frequently used drugs. Short-acting oral nifedipine is suggested to be used only if other drugs or iv access are not available. Induction of labour is associated with improved maternal outcome and should be advised for women with gestational hypertension or mild pre-eclampsia at 37 weeks᾽ gestation. This position paper provides the first interdisciplinary approach to the management of hypertension in the peripartum period based on the best available evidence and expert consensus.
Woon EV, Day A, Bracewell-Milnes T, et al., 2020, Immunotherapy to improve pregnancy outcome in women with abnormal natural killer cell levels/activity and recurrent miscarriage or implantation failure: A systematic review and meta-analysis., Journal of Reproductive Immunology, Vol: 142, Pages: 1-12, ISSN: 0165-0378
There is a trend towards offering immunotherapy to women with unexplained reproductive failure based on abnormal Natural Killer (NK) cell levels. Previous systematic reviews evaluating immunotherapy usage have not focused on women with abnormal level of NK cells. To address the gap in literature, this systematic review aims to evaluate the efficacy of immunotherapy to improve pregnancy outcome in women with recurrent miscarriage (RM) or implantation failure (RIF) specifically selected based on abnormal levels and/or activity of NK cells. Six databases were searched for peer-reviewed studies following PRISMA guidelines. Risk of bias assessment was conducted using RoB2 for randomized controlled trials (RCT) and ROBINS-I for non-RCT. Of 1025 studies identified, seven studies on intravenous immunoglobulin (IVIG) (four), prednisolone (one), etanercept (one) and intralipid (one) were included. Meta-analysis of the non-RCT IVIG studies (557 participants; 312 intervention, 245 controls) showed livebirth in favour of intervention (RR 2.57; 95 % CI = 1.79-3.69; p < 0.05), however there were significant heterogeneity (I2 = 62 %) and moderate to severe risk of bias in these studies. Individual RCTs reported improved livebirth outcome in etanercept, intralipid and prednisolone and this was significant in the former two (p < 0.05). In conclusion, there may be some benefit of immunotherapy, but paucity of high quality evidence means that it is not possible to support the use of immunotherapy even when selected based on abnormal NK cell level/activity. Further research with application of scientifically validated immunological biomarkers in well-planned large scale RCTs will determine whether immunotherapy is beneficial in this subpopulation of women.
Sliwa K, Petrie MC, van der Meer P, et al., 2020, Clinical presentation, management, and 6-month outcomes in women with peripartum cardiomyopathy: an ESC EORP registry, EUROPEAN HEART JOURNAL, Vol: 41, Pages: 3787-3797, ISSN: 0195-668X
Baris L, Hakeem A, Moe T, et al., 2020, Acute Coronary Syndrome and Ischemic Heart Disease in Pregnancy: Data From the EURObservational Research Programme-European Society of Cardiology Registry of Pregnancy and Cardiac Disease, JOURNAL OF THE AMERICAN HEART ASSOCIATION, Vol: 9
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- Citations: 14
West K, Kanu C, Maric T, et al., 2020, Longitudinal metabolic and gut bacterial profiling of pregnant women with previous bariatric surgery, Gut, Vol: 69, Pages: 1452-1459, ISSN: 0017-5749
Due to the global increase in obesity rates and success of bariatric surgery in weight reduction, an increasing number of women now present pregnant with a previous bariatric procedure. This study investigates the extent of bariatric-associated metabolic and gut microbial alterations during pregnancy and their impact on fetal development.DesignA parallel metabonomic (1H NMR spectroscopy) and gut bacterial (16S rRNA gene amplicon sequencing) profiling approach was used to determine maternal longitudinal phenotypes associated with malabsorptive/mixed (n=25) or restrictive (n=16) procedures, compared to women with similar early pregnancy body mass index but without bariatric surgery (n=70). Metabolic profiles of offspring at birth were also analysed.ResultsPrevious malabsorptive, but not restrictive, procedures induced significant changes in maternal metabolic pathways involving branched-chain and aromatic amino acids with decreased circulation of leucine, isoleucine and isobutyrate, increased excretion of microbial-associated metabolites of protein putrefaction (phenylacetlyglutamine, p-cresol sulfate, indoxyl sulfate and p-hydroxyphenylacetate), and a shift in the gut microbiota. Urinary concentration of phenylacetylglutamine was significantly elevated in malabsorptive patients relative to controls (P=0.001) and was also elevated in urine of neonates born from these mothers (P=0.021). Furthermore, the maternal metabolic changes induced by malabsorptive surgery were associated with reduced maternal insulin resistance and fetal/birth weight.ConclusionMetabolism is altered in pregnant women with a previous malabsorptive bariatric surgery. These alterations may be beneficial for maternal outcomes, but the effect of elevated levels of phenolic and indolic compounds on fetal and infant health should be investigated further.
Ramlakhan KP, Johnson MR, Roos-Hesselink JW, 2020, Pregnancy and cardiovascular disease, Nature Reviews Cardiology, Vol: 17, Pages: 718-731, ISSN: 1759-5002
Cardiovascular disease complicates 1-4% of pregnancies - with a higher prevalence when including hypertensive disorders - and is the leading cause of maternal death. In women with known cardiovascular pathology, such as congenital heart disease, timely counselling is possible and the outcome is fairly good. By contrast, maternal mortality is high in women with acquired heart disease that presents during pregnancy (such as acute coronary syndrome or aortic dissection). Worryingly, the prevalence of acquired cardiovascular disease during pregnancy is rising as older maternal age, obesity, diabetes mellitus and hypertension become more common in the pregnant population. Management of cardiovascular disease in pregnancy is challenging owing to the unique maternal physiology, characterized by profound changes to multiple organ systems. The presence of the fetus compounds the situation because both the cardiometabolic disease and its management might adversely affect the fetus. Equally, avoiding essential treatment because of potential fetal harm risks a poor outcome for both mother and child. In this Review, we examine how the physiological adaptations during pregnancy can provoke cardiometabolic complications or exacerbate existing cardiometabolic disease and, conversely, how cardiometabolic disease can compromise the adaptations to pregnancy and their intended purpose: the development and growth of the fetus.
Dos Santos F, Baris L, Varley A, et al., 2020, Mechanical heart valves and pregnancy: Issues surrounding anticoagulation. Experience from two obstetric cardiac centres, Obstetric Medicine, Vol: 14, Pages: 95-101, ISSN: 1753-495X
BackgroundPregnant women with mechanical heart valves are at significant risk of obstetric/cardiac complications. This study compares the anticoagulation management in two obstetric cardiac centres.MethodsRetrospective case-note review from Chelsea and Westminster/Royal Brompton Hospitals (CR) and Erasmus Medical Centre (EMC). Main outcome measure was mechanical heart valve thrombosis.ResultsNineteen pregnancies from CR and 25 pregnancies from EMC were included. Most women were on low-molecular-weight heparin (LMWH) throughout pregnancy at CR, whereas at EMC most had LMWH in the first trimester and vitamin K antagonists in subsequent trimesters. Peak anti-factor Xa were performed monthly at CR, levels 0.39–1.51 IU/mL (mean 0.82 IU/mL). Anticoagulation management peri-partum was inconsistent. Delivery was mainly by Caesarean section at CR (74%) and vaginal delivery at EMC (64%). No maternal deaths and only one mechanical heart valve thrombosis at CR. Two mechanical heart valve thromboses and one maternal death at EMC.ConclusionPeri-partum anticoagulation strategies, anticoagulation monitoring and mode of delivery inconsistencies reported.
Maric T, Kanu C, Muller DC, et al., 2020, Fetal growth and fetoplacental circulation in pregnancies following bariatric surgery: a prospective study, Publisher: WILEY, Pages: 839-846, ISSN: 1470-0328
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- Citations: 3
Sliwa K, Azibani F, Johnson MR, et al., 2020, Effectiveness of implanted cardiac rhythm recorders with electrocardiographic monitoring for detecting arrhythmias in pregnant women with symptomatic arrhythmia and/or structural heart disease a randomized clinical trial, JAMA Cardiology, Vol: 5, Pages: 458-463, ISSN: 2380-6583
Importance Arrhythmias are an important cause of maternal morbidity and mortality but remain difficult to diagnose.Objective To compare implantable loop recorder (ILR) plus 24-hour Holter electrocardiographic (ECG) monitoring with standard 24-hour Holter ECG monitoring alone in terms of acceptability, ability to identify significant arrythmias, and effect on management and pregnancy outcome in women who were symptomatic or at high risk of arrythmia because of underlying structural heart disease.Design, Setting, and Participants This single-center, prospective randomized clinical trial recruited 40 consecutive patients from the Cardiac Disease and Maternity Clinic at Groote Schuur Hospital in Cape Town, South Africa. Pregnant patients with symptoms of arrhythmia and/or structural heart disease at risk of arrhythmia were included.Intervention Patients were randomized to standard care (SC; 24-hour Holter ECG monitoring [n = 20]) or standard care plus ILR (SC-ILR; 24-hour Holter ECG monitoring plus ILR [n = 20]). Only 17 consented to ILR insertion, and the 3 who declined ILR were allocated to the SC group.Main Outcomes and Measures Arrhythmias considered included atrial fibrillation, atrial flutter, premature ventricular complexes, supraventricular tachycardia, ventricular tachycardia, or ventricular fibrillation.Results Among the 40 women in this trial, the mean (SD) age was 28.4 (5.5) years. Holter monitoring detected arrhythmias in 3 of 23 patients (13%) in the SC group and 4 of 17 patients (24%) in the SC-ILR group compared with 9 of 17 patients (53%) patients who had arrhythmias detected by ILR. Seven patients (4 with supraventricular tachycardia, 1 with premature ventricular complexes, and 2 with paroxysmal atrial fibrillation recorded by ILR) did not have arrhythmias detected by 24-hour Holter monitoring. Three of these 7 patients (43%) had a change in management as a result of their ILR recordings. There were no maternal deaths.
Hua R, Edey LF, O'Dea KP, et al., 2020, CCR2 mediates the adverse effects of LPS in the pregnant mouse, Biology of Reproduction, Vol: 102, Pages: 445-455, ISSN: 0006-3363
In our earlier work, we found that intrauterine (i.u.) and intraperitoneal (i.p.) injection of LPS (10-μg serotype 0111:B4) induced preterm labor (PTL) with high pup mortality, marked systemic inflammatory response and hypotension. Here, we used both i.u. and i.p. LPS models in pregnant wild-type (wt) and CCR2 knockout (CCR2-/-) mice on E16 to investigate the role played by the CCL2/CCR2 system in the response to LPS. Basally, lower numbers of monocytes and macrophages and higher numbers of neutrophils were found in the myometrium, placenta, and blood of CCR2-/- vs. wt mice. After i.u. LPS, parturition occurred at 14 h in both groups of mice. At 7 h post-injection, 70% of wt pups were dead vs. 10% of CCR2-/- pups, but at delivery 100% of wt and 90% of CCR2-/- pups were dead. Myometrial and placental monocytes and macrophages were generally lower in CCR2-/- mice, but this was less consistent in the circulation, lung, and liver. At 7 h post-LPS, myometrial ERK activation was greater and JNK and p65 lower and the mRNA levels of chemokines were higher and of inflammatory cytokines lower in CCR2-/- vs. wt mice. Pup brain and placental inflammation were similar. Using the IP LPS model, we found that all measures of arterial pressure increased in CCR2-/- but declined in wt mice. These data suggest that the CCL2/CCR2 system plays a critical role in the cardiovascular response to LPS and contributes to pup death but does not influence the onset of inflammation-induced PTL.
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