Imperial College London

ProfessorMarkJohnson

Faculty of MedicineDepartment of Surgery & Cancer

Clinical Chair in Obstetrics
 
 
 
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Contact

 

+44 (0)20 8846 7887mark.johnson

 
 
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Location

 

H3.35Chelsea and Westminster HospitalChelsea and Westminster Campus

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Summary

 

Publications

Publication Type
Year
to

423 results found

Maric T, Kanu C, Johnson MR, Savvidou MDet al., 2019, Maternal, neonatal insulin resistance and neonatal anthropometrics in pregnancies following bariatric surgery., Metabolism, Vol: 97, Pages: 25-31

OBJECTIVE: An increasing number of women present pregnant having undergone bariatric surgery, a popular treatment for sustainable weight loss. The aim of the study was to investigate the effect, if any, of bariatric surgery on maternal and neonatal insulin resistance (IR) and neonatal body fat composition. METHODS: Maternal IR, at 28 weeks of gestation during 2-hour 75 g oral glucose tolerance test (OGTT), neonatal IR, from umbilical cord venous blood, and neonatal birthweight and body fat composition (calculated by measuring skin folds) at birth were evaluated in 41 post-bariatric and 82 pregnant women with similar early pregnancy body mass index but no history of such surgery. Insulin resistance was assessed using the homeostasis model assessment of IR (HOMA-IR). RESULTS: In the post-bariatric surgery group, compared to the no surgery group, maternal HOMA-IR (1.15 [1.04-2.07] vs 2.20 [1.53-3.38]; p < 0.01), neonatal birthweight (p < 0.01) and body fat (p < 0.01) were significantly lower whereas neonatal cord HOMA-IR was similar (1.29 [0.65-2.39] vs 1.19 [0.46-1.93]; p = 0.49). In the no surgery group, there was a positive correlation between maternal and neonatal HOMA-IR (p = 0.03) and between neonatal HOMA-IR and body fat (p < 0.01). However, no such significant correlations were detected in the post-bariatric surgery group. CONCLUSION: Pregnancy following bariatric surgery is associated with a reduction in maternal IR and altered neonatal body composition with significantly lower birthweight and adiposity but no improvement in cord IR.

Journal article

Herbert BR, Markovic D, Georgiou E, Lai PF, Singh N, Yulia A, Johnson MRet al., 2019, Aminophylline and progesterone prevent inflammation-induced preterm parturition in the mouse, Biology of Reproduction, ISSN: 1529-7268

Although progesterone (P4) supplementation is the most widely used therapy for the prevention of preterm labor (PTL), reports of its clinical efficacy have been conflicting. We have previously shown that the anti-inflammatory effects of P4 can be enhanced by increasing intracellular cAMP levels in primary human myometrial cells. Here we have examined whether adding aminophylline (Am), a non-specific phosphodiesterase (PDE) inhibitor that increases intracellular cyclic adenosine monophosphate (cAMP) levels, to P4 might improve its efficacy using in vivo and in vitro models of PTL. In a mouse model of lipopolysaccharide (LPS)-induced PTL, we found that the combination of P4 and Am delayed the onset of LPS-induced PTL, while the same dose of P4 and Am alone had no effect. Pup survival was not improved by either agent alone or in combination. Myometrial prolabor and inflammatory cytokine gene expression was reduced, but the reduction was similar in P4 and P4/Am treated mice. There was no effect of the combination of P4 and Am on an ex vivo assessment of myometrial contractility. In human myometrial cells and myometrial tissue explants, we found that the combination had marked anti-inflammatory effects, reducing cytokine and COX-2 mRNA and protein levels to a greater extent than either agent alone. These data suggest that the combination of P4 and Am has a more potent anti-inflammatory effect than either agent alone and may be an effective combination in women at high-risk of PTL.

Journal article

Baris L, Cornette J, Johnson MR, Sliwa K, Roos-Hesselink JWet al., 2019, Postpartum cardiomyopathy and endocrinopathy, HEART, Vol: 105, Pages: 1047-+, ISSN: 1355-6037

Journal article

Bauersachs J, König T, van der Meer P, Petrie MC, Hilfiker-Kleiner D, Mbakwem A, Hamdan R, Jackson AM, Forsyth P, de Boer RA, Mueller C, Lyon AR, Lund LH, Piepoli MF, Heymans S, Chioncel O, Anker SD, Ponikowski P, Seferovic PM, Johnson MR, Mebazaa A, Sliwa Ket al., 2019, Pathophysiology, diagnosis and management of peripartum cardiomyopathy: a position statement from the Heart Failure Association of the European Society of Cardiology Study Group on peripartum cardiomyopathy, European Journal of Heart Failure, ISSN: 1388-9842

Peripartum cardiomyopathy (PPCM) is a potentially life-threatening condition typically presenting as heart failure with reduced ejection fraction (HFrEF) in the last month of pregnancy or in the months following delivery in women without another known cause of heart failure. This updated position statement summarizes the knowledge about pathophysiological mechanisms, risk factors, clinical presentation, diagnosis and management of PPCM. As shortness of breath, fatigue and leg oedema are common in the peripartum period, a high index of suspicion is required to not miss the diagnosis. Measurement of natriuretic peptides, electrocardiography and echocardiography are recommended to promptly diagnose or exclude heart failure/PPCM. Important differential diagnoses include pulmonary embolism, myocardial infarction, hypertensive heart disease during pregnancy, and pre-existing heart disease. A genetic contribution is present in up to 20% of PPCM, in particular titin truncating variant. PPCM is associated with high morbidity and mortality, but also with a high probability of partial and often full recovery. Use of guideline-directed pharmacological therapy for HFrEF is recommended in all patients respecting contraindications during pregnancy/lactation. The oxidative stress-mediated cleavage of the hormone prolactin into a cardiotoxic fragment has been identified as a driver of PPCM pathophysiology. Pharmacological blockade of prolactin release using bromocriptine as a disease-specific therapy in addition to standard therapy for heart failure treatment has shown promising results in two clinical trials. Thresholds for devices (implantable cardioverter-defibrillators, cardiac resynchronization therapy and implanted long-term ventricular assist devices) are higher in PPCM than in other conditions because of the high rate of recovery. The important role of education and counselling around contraception and future pregnancies is emphasised.

Journal article

Baris L, Cornette J, Johnson MR, Sliwa K, Roos-Hesselink JWet al., 2019, PPCM and the endocrine system., Heart, Vol: 105, Pages: 1047-1048, ISSN: 1468-201X

We sincerely thank Dr Jolobe for the response to our paper1 and very much appreciate the interesting addition2 to the discussion on this difficult topic. It is true that autoimmunity has been proposed to play a role in the aetiology of Peripartum Cardiomyopathy (PPCM), as we mention in our introduction. Furthermore, it is indeed well known that congestive heart failure due to (dilated) cardiomyopathy can occur in patients with hypopituitarism or acute pituitary failure,3 4 as well as in adrenal insufficiency3 and thyroid dysfunction.5 However, there are numerous case reports supporting that this is certainly not exclusive to a peripartum onset.6–8 According to the latest definition from the Heart Failure Association of the European Society of Cardiology (ESC) Working Group on PPCM, PPCM is defined as an idiopathic cardiomyopathy presenting with heart failure secondary to left ventricular systolic dysfunction towards the end of pregnancy or in the months following delivery, where no other cause of heart failure is found.9 We therefore believe that the women Dr Jolobe mentions in the response, while very interesting and certainly worth discussing in the context of our paper, did not suffer from PPCM. Of course, the endocrine system and specifically the pituitary will undergo major changes during pregnancy, and many cases of acute heart failure due to Sheenan syndrome and postpartum haemorrhage have been reported in the literature.3 10 11 However, cardiomyopathy secondary to Sheenan syndrome is just that. While the peripartum onset mimics PPCM and thus poses a diagnostic dilemma, it is important to make the distinction for, as Dr Jolobe rightly points out, patients may not benefit from conventional heart failure therapy.11 We therefore wholeheartedly agree with Dr Jolobe that in women with peripartum-onset heart failure of unknown cause, evaluation of the endocrine status is mandatory.

Journal article

Pollock T, Kanu C, Lai P, Johnson M, Savvidou Met al., 2019, Placental expression of corticotrophin-releasing hormone and tumour necrosis factor in pregnancies with previous bariatric surgery compared to those without, Publisher: WILEY, Pages: 60-61, ISSN: 1470-0328

Conference paper

Cauldwell M, Steer P, Johnson MR, 2019, Response to 'Pregnancy in women with pre-existent ischaemic heart disease', HEART, Vol: 105, Pages: 893-894, ISSN: 1355-6037

Journal article

Cauldwell M, Steer PJ, Curtis SL, Mohan A, Dockree S, Mackillop L, Parry HM, Oliver J, Sterrenberg M, Wallace S, Malin G, Partridge G, Freeman LJ, Bolger AP, Siddiqui F, Wilson D, Simpson M, Walker N, Hodson K, Thomas K, Bredaki F, Mercaldi R, Walker F, Johnson MRet al., 2019, Maternal and fetal outcomes in pregnancies complicated by Marfan syndrome., Heart, Pages: 1-7, ISSN: 1355-6037

OBJECTIVES: Information to guide counselling and management for pregnancy in women with Marfan syndrome (MFS) is limited. We therefore conducted a UK multicentre study. METHODS: Retrospective observational study of women with MFS delivering between January 1998 and March 2018 in 12 UK centres reporting data on maternal and neonatal outcomes. RESULTS: In total, there were 258 pregnancies in 151 women with MFS (19 women had prior aortic root replacements), including 226 pregnancies ≥24 weeks (two sets of twins), 20 miscarriages and 12 pregnancy terminations. Excluding miscarriages and terminations, there were 221 live births in 139 women. Only 50% of women received preconception counselling. There were no deaths, but five women experienced aortic dissection (1.9%; one type A and four type B-one had a type B dissection at 12 weeks and subsequent termination of pregnancy). Five women required cardiac surgery postpartum. No predictors for aortic dissection could be identified. The babies of the 131 (65.8%) women taking beta-blockers were on average 316 g lighter (p<0.001). Caesarean section rates were high (50%), particularly in women with dilated aortic roots. In 55 women, echocardiographic aortic imaging was available prepregnancy and postpregnancy; there was a small but significant average increase in AoR size of 0.84 mm (Median follow-up 2.3 months) CONCLUSION: There were no maternal deaths, and the aortic dissection rate was 1.9% (mainly type B). There with no identifiable factors associated with aortic dissection in our cohort. Preconception counselling rates were low and need improvement. Aortic size measurements increased marginally following pregnancy.

Journal article

Zöllner J, Howe LG, Edey LF, O'Dea KP, Takata M, Leiper J, Johnson MRet al., 2019, LPS-induced hypotension in pregnancy: The effect of progesterone supplementation, Shock, ISSN: 1073-2322

Our previous work has shown that pregnancy exacerbates the hypotensive response to both infection and LPS. The high levels of progesterone (P4) associated with pregnancy have been suggested to be responsible for the pregnancy-induced changes in the cardiovascular response to infection. Here, we test the hypothesis that P4 supplementation exacerbates the hypotensive response of the maternal cardiovascular to LPS.Female CD1 mice had radiotelemetry probes implanted to measure haemodynamic function non-invasively and were time-mated. From day 14 of pregnancy, mice received either 10 mg of P4 or vehicle alone per day and on day 16, intraperitoneal LPS (10 μg of serotype 0111:B4) was injected. In two identically treated cohorts of mice, tissue and serum (for RNA, protein studies) were collected at 6 and 12 hours.Administration of LPS resulted in a fall in blood pressure in vehicle treated, but not P4 supplemented mice. This occurred with similar changes in the circulating levels of cytokines, vasoactive factors and in both circulating and tissue inflammatory cell numbers, but with reduced left ventricular expression of cytokines in P4-supplemented mice. However, left ventricular expression of markers of cardiac dysfunction and apoptosis were similar.This study demonstrates that P4 supplementation prevented LPS-induced hypotension in pregnant mice in association with reduced myocardial inflammatory cytokine gene expression. These observations suggest that rather than being detrimental, P4 supplementation has a protective effect on the maternal cardiovascular response to sepsis.

Journal article

Bonney EA, Johnson MR, 2019, The role of maternal T cell and macrophage activation in preterm birth: Cause or consequence?, PLACENTA, Vol: 79, Pages: 53-61, ISSN: 0143-4004

Journal article

Stanfield Z, Lai PF, Lei K, Johnson MR, Blanks AM, Romero R, Chance MR, Mesiano S, Koyutürk Met al., 2019, Myometrial transcriptional signatures of human parturition, Frontiers in Genetics, Vol: 10, ISSN: 1664-8021

Download ArticleExport citation1,163TOTAL VIEWSArticle has an altmetric score of 1Want to win $100,000 to host your own conference?Suggest a Research TopicSHARE ON0000NewORIGINAL RESEARCH ARTICLEFront. Genet., 01 April 2019 | https://doi.org/10.3389/fgene.2019.00185Myometrial Transcriptional Signatures of Human ParturitionZachary Stanfield1,2*, Pei F. Lai3, Kaiyu Lei4 Mark R. Johnson3,5, Andrew M. Blanks6, Roberto Romero7,8,9, Mark R. Chance2,10,11, Sam Mesiano12,13 and Mehmet Koyutürk10,14*1Systems Biology and Bioinformatics Program, Case Western Reserve University, Cleveland, OH, United States2Department of Nutrition, Case Western Reserve University, Cleveland, OH, United States3Imperial College Parturition Research Group, Department of Obstetrics and Gynecology, Imperial College School of Medicine, Chelsea and Westminster Hospital, London, United Kingdom4BGI Clinical Laboratories (Shenzhen) Co., Ltd., Shenzhen, China5Imperial College Parturition Research Group, Institute of Reproductive and Developmental Biology, London, United Kingdom6Cell and Developmental Biology, Clinical Sciences Research Laboratory, Division of Biomedical Sciences, Warwick Medical School, Coventry, United Kingdom7Perinatology Research Branch, NICHD, NIH, United States Department of Health and Human Services, Detroit, MI, United States8Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, United States9Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI, United States10Center for Proteomics and Bioinformatics, Case Western Reserve University, Cleveland, OH, United States11Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, United States12Department of Reproductive Biology, Case Western Reserve University, Cleveland, OH, United States13Department of Obstetrics and Gynecology, University Hospitals of Cleveland, Case Western Reserve University, Cleveland, OH, United State

Journal article

Stanfield Z, Johnson MR, Blanks AM, Romero R, Chance MR, Mesiano S, Koyuturkm Met al., 2019, Myometrial transcriptional signatures of human parturition, Frontiers in Genetics, Vol: 10, ISSN: 1664-8021

The process of parturition involves the transformation of the quiescent myometrium (uterine smooth muscle) to the highly contractile laboring state. This is thought to be driven by changes in gene expression in myometrial cells. Despite the existence of multiple myometrial gene expression studies, the transcriptional programs that initiate labor are not known. Here, we integrated three transcriptome datasets, one novel (NCBI Gene Expression Ominibus: GSE80172) and two existing, to characterize the gene expression changes in myometrium associated with the onset of labor at term. Computational analyses including classification, singular value decomposition, pathway enrichment, and network inference were applied to individual and combined datasets. Outcomes across studies were integrated with multiple protein and pathway databases to build a myometrial parturition signaling network. A high-confidence (significant across all studies) set of 126 labor genes were identified and machine learning models exhibited high reproducibility between studies. Labor signatures included both known (interleukins, cytokines) and unknown (apoptosis, MYC, cell proliferation/differentiation) pathways while cyclic AMP signaling and muscle relaxation were associated with non-labor. These signatures accurately classified and characterized the stages of labor. The data-derived parturition signaling networks provide new genes/signaling interactions to understand phenotype-specific processes and aid in future studies of parturition.

Journal article

Shah NM, Lai PF, Imami N, Johnson MRet 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 via 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.

Journal article

Roos-Hesselink J, Baris L, Johnson M, De Backer J, Otto C, Marelli A, Jondeau G, Budts W, Grewal J, Sliwa K, Parsonage W, Maggioni AP, van Hagen I, Vahanian A, Tavazzi L, Elkayam U, Boersma E, Hall Ret al., 2019, Pregnancy outcomes in women with cardiovascular disease: evolving trends over 10 years in the ESC Registry Of Pregnancy And Cardiac disease (ROPAC), European Heart Journal, ISSN: 1522-9645

AIMS: Reducing maternal mortality is a World Health Organization (WHO) global health goal. Although maternal deaths due to haemorrhage and infection are declining, those related to heart disease are increasing and are now the most important cause in western countries. The aim is to define contemporary diagnosis-specific outcomes in pregnant women with heart disease. METHODS AND RESULTS: From 2007 to 2018, pregnant women with heart disease were prospectively enrolled in the Registry Of Pregnancy And Cardiac disease (ROPAC). Primary outcome was maternal mortality or heart failure, secondary outcomes were other cardiac, obstetric, and foetal complications. We enrolled 5739 pregnancies; the mean age was 29.5. Prevalent diagnoses were congenital (57%) and valvular heart disease (29%). Mortality (overall 0.6%) was highest in the pulmonary arterial hypertension (PAH) group (9%). Heart failure occurred in 11%, arrhythmias in 2%. Delivery was by Caesarean section in 44%. Obstetric and foetal complications occurred in 17% and 21%, respectively. The number of high-risk pregnancies (mWHO Class IV) increased from 0.7% in 2007-2010 to 10.9% in 2015-2018. Determinants for maternal complications were pre-pregnancy heart failure or New York Heart Association >II, systemic ejection fraction <40%, mWHO Class 4, and anticoagulants use. After an increase from 2007 to 2009, complication rates fell from 13.2% in 2010 to 9.3% in 2017. CONCLUSION: Rates of maternal mortality or heart failure were high in women with heart disease. However, from 2010, these rates declined despite the inclusion of more high-risk pregnancies. Highest complication rates occurred in women with PAH.

Journal article

Vieira MC, Relph S, Copas A, Healey A, Coxon K, Alagna A, Briley A, Johnson M, Lawlor DA, Lees C, Marlow N, McCowan L, Page L, Peebles D, Shennan A, Thilaganathan B, Khalil A, Sandall J, Pasupathy D, Brocklehurst P, Tebbs S, Dore C, Seed P, Delaney L, Cresswell J, Petty S, Ajay B, Wright B, O'Donnell H, Howard M, Wayman E, Galea P, Dhanjal M, Iaschi E, Hodge V, Samarage H, Chita S, Napolitano R, Tsikimi I, Ghalustians F, Bakalis S, Cicero S, Peregrine E, Smith L, Janga D, Hutt R, Chandraharan Eet al., 2019, The DESiGN trial (DEtection of small for gestational age neonate), evaluating the effect of the Growth Assessment Protocol (GAP): study protocol for a randomised controlled trial, Trials, Vol: 20, ISSN: 1745-6215

BackgroundStillbirth rates in the United Kingdom (UK) are amongst the highest of all developed nations. The association between small-for-gestational-age (SGA) foetuses and stillbirth is well established, and observational studies suggest that improved antenatal detection of SGA babies may halve the stillbirth rate. The Growth Assessment Protocol (GAP) describes a complex intervention that includes risk assessment for SGA and screening using customised fundal-height growth charts. Increased detection of SGA from the use of GAP has been implicated in the reduction of stillbirth rates by 22%, in observational studies of UK regions where GAP uptake was high. This study will be the first randomised controlled trial examining the clinical efficacy, health economics and implementation of the GAP programme in the antenatal detection of SGA.Methods/designIn this randomised controlled trial, clusters comprising a maternity unit (or National Health Service Trust) were randomised to either implementation of the GAP programme, or standard care. The primary outcome is the rate of antenatal ultrasound detection of SGA in infants found to be SGA at birth by both population and customised standards, as this is recognised as being the group with highest risk for perinatal morbidity and mortality. Secondary outcomes include antenatal detection of SGA by population centiles, antenatal detection of SGA by customised centiles, short-term maternal and neonatal outcomes, resource use and economic consequences, and a process evaluation of GAP implementation. Qualitative interviews will be performed to assess facilitators and barriers to implementation of GAP.DiscussionThis study will be the first to provide data and outcomes from a randomised controlled trial investigating the potential difference between the GAP programme compared to standard care for antenatal ultrasound detection of SGA infants. Accurate information on the performance and service provision requirements of the GAP protoc

Journal article

West K, Kanu C, Maric T, Johnson M, Holmes E, Savvidou Met al., 2019, Maternal and neonatal metabolomic profile in pregnancies following bariatric surgery, Publisher: WILEY, Pages: 30-30, ISSN: 1470-0328

Conference paper

Nasri NM, Leiper J, Johnson M, 2019, Neutrophils Infiltration Leads to Acute Lung Injury in CCR2 Deficiency Sepsis Mice Model., 66th Annual Scientific Meeting of the Society-for-Reproductive-Investigation (SRI), Publisher: SAGE PUBLICATIONS INC, Pages: 122A-122A, ISSN: 1933-7191

Conference paper

Sooranna GR, Shah NM, Singh N, Johnson MRet 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

Conference paper

Nasri NM, Leiper J, Johnson M, 2019, Gender Dimorphism Following Sepsis Induction in a Mouse Model., 66th Annual Scientific Meeting of the Society-for-Reproductive-Investigation (SRI), Publisher: SAGE PUBLICATIONS INC, Pages: 214A-214A, ISSN: 1933-7191

Conference paper

Li JK, Kim H, Johnson M, 2019, Investigating PKA and AKIP Mediated Regulation of NF-kB Transcriptional Activity in Primary Myometrial Cells., 66th Annual Scientific Meeting of the Society-for-Reproductive-Investigation (SRI), Publisher: SAGE PUBLICATIONS INC, Pages: 218A-219A, ISSN: 1933-7191

Conference paper

Baris L, Cornette J, Johnson MR, Sliwa K, Roos-Hesselink JWet al., 2019, Peripartum cardiomyopathy: disease or syndrome?, Heart, Vol: 105, Pages: 357-362, ISSN: 1355-6037

© 2019 Author(s) (or their employer(s)). Re-use permitted under CC BY-NC. Peripartum cardiomyopathy (PPCM) is a rare form of pregnancy-associated heart failure and is considered to be a diagnosis of exclusion. There are many hypotheses on the aetiology of PPCM; however, the exact pathophysiological mechanism remains unknown. It shows many resemblances to other conditions, such as familial dilated cardiomyopathy or myocarditis, and therefore it can be hard to make a definite diagnosis. We describe four cases of peripartum-onset heart failure in women who were suspected of having PPCM. We discuss the differential diagnosis, pathophysiological mechanisms and various diagnostic modalities.

Journal article

Varley A, Koschinski A, Jayarajan V, Johnson MR, Zaccolo Met al., 2019, Real-Time Visualisation of the cAMP Signalling Dynamics in Human Primary Myometrial Cells Using Targeted FRET Reporters., 66th Annual Scientific Meeting of the Society-for-Reproductive-Investigation (SRI), Publisher: SAGE PUBLICATIONS INC, Pages: 308A-308A, ISSN: 1933-7191

Conference paper

Varley A, Yulia A, Lei K, Jayarajan V, Singh N, Sooranna SR, Johnson MRet al., 2019, Novel and Transformative Changes in the cAMP Effector Pathway in Three Distinct Types of Preterm Labour., 66th Annual Scientific Meeting of the Society-for-Reproductive-Investigation (SRI), Publisher: SAGE PUBLICATIONS INC, Pages: 219A-220A, ISSN: 1933-7191

Conference paper

Cauldwell M, Steer PJ, Curtis S, Mohan AR, Dockree S, Mackillop L, Parry H, Oliver J, Sterrenburg M, Bolger A, Siddiqui F, Simpson M, Walker N, Bredaki F, Walker F, Johnson MRet al., 2019, Maternal and fetal outcomes in pregnancies complicated by the inherited aortopathy Loeys-Dietz syndrome, BJOG: An International Journal of Obstetrics and Gynaecology, Vol: 126, Pages: 1025-1031, ISSN: 1470-0328

ObjectivePregnancies in women with Loeys–Dietz syndrome (LDS) are rare and are typically documented in case reports only. Early reports suggested high rates of maternal complications during pregnancy and the puerperium, including aortic dissection and uterine rupture, but information on fetal outcomes was very limited.DesignA retrospective cohort study.SettingEight specialist UK centres.SamplePregnant women with LDS.MethodsData was collated on cardiac, obstetric, and neonatal outcomes.Main outcome measuresMaternal and perinatal outcomes in pregnancies complicated by LDS.ResultsTwenty pregnancies in 13 women with LDS were identified. There was one miscarriage, one termination of pregnancy, and 18 livebirths. In eight women the diagnosis was known prior to pregnancy but only one woman had preconception counselling. In four women the diagnosis was made during pregnancy through positive genotyping, and the other was diagnosed following delivery. Five women had a family history of aortic dissection. There were no aortic dissections in our cohort during pregnancy or postpartum. Obstetric complications were common, including postpartum haemorrhage (33%) and preterm delivery (50%). In all, 14/18 (78%) of deliveries were by elective caesarean section, at a median gestational age at delivery of 37 weeks. Over half the infants (56%) were admitted to the neonatal unit following delivery.ConclusionWomen with LDS require multidisciplinary specialist management throughout pregnancy. Women should be referred for preconception counselling to make informed decisions around pregnancy risk and outcomes. Early elective preterm delivery needs to be balanced against a high infant admission rate to the neonatal unit.

Journal article

Cauldwell M, Steer P, Sterrenburg M, Wallace S, Malin G, Ulivi G, Everett T, Jakes AD, Head CEG, Mohan AR, Haynes S, Simpson M, Brennand J, Johnson MRet al., 2019, Birth weight in pregnancies complicated by maternal heart disease, Heart, Vol: 105, Pages: 391-398, ISSN: 1355-6037

Objective To assess median and percentile birthweight distribution in women with various groups of heart disease relative to a contemporaneous comparison group. Methods Data on birth weight and gestational age were collected from 1321 pregnancies ≥24 weeks' gestation in 1053 women with heart disease from seven UK maternity units. Women were assigned to one of 16 groups according to their cardiac lesion. In units where it was possible, data on two births, one delivering before and one after index cases, were collected, giving 2307 comparators. Birthweight percentiles (corrected for gestational age, sex and parity) were calculated using Aberdeen norms. We assessed the association of birth weight with cardiac lesion, maternal hypoxaemia (saturations <90%), systemic ventricular function and beta-blockers. Results 1321 pregnancies in women with heart disease and 2307 comparators were studied. Almost all groups with heart disease had lower median and percentile birth weights than comparators, significantly in 10 groups, the biggest effect seen in women with Fontan circulation, pulmonary hypertension, prosthetic heart valves, systemic right ventricle, Marfan syndrome, repaired tetralogy of Fallot and cardiomyopathy (in that order). In 307 pregnancies, women took beta-blockers; median birth weight adjusted for maternal age, parity and the effect of the cardiac lesion was 3116.7 g (IQR 790.4) when beta-blockers were used and 3354.3 g (IQR 634.1) when they were not (p<0.001). 17 women had saturations <90%, and median birth weight was significantly lower, 3105.4 g (IQR 1288.9) versus 3387.7 g (IQR 729.8) (p=0.006). Conclusion Our findings identify specific groups of women with heart disease at risk of having a small baby.

Journal article

Cauldwell M, Johnson M, Jahangiri M, Roos-Hesselink Jet al., 2019, Cardiac interventions and cardiac surgery and pregnancy, International Journal of Cardiology, Vol: 276, Pages: 43-47, ISSN: 0167-5273

Both cardiac surgery and cardiac interventions are rare in pregnancy but are generally more common in the developing world. Women with known cardiac disease should receive contemporaneous preconception counselling to assess all risks associated with pregnancy including whether surgery or cardiac interventions may need to be considered prior to pregnancy. Some women may need to undergo emergency surgery or procedures during pregnancy and decisions regarding this should be multidisciplinary including cardiologists, cardiac surgeons, anaesthetists, obstetricians and neonatologists. In this review we discuss both conditions where surgery or percutaneous interventions may need to be considered and both the outcomes for the mother and her baby.

Journal article

Zöllner J, Lambden S, Nasri NM, Leiper J, Johnson MRet al., 2019, Rapid onset of severe septic shock in the pregnant mouse†, Biology of Reproduction, Vol: 100, Pages: 505-513, ISSN: 1529-7268

AIMS: Globally, sepsis is a major cause of mortality through the combination of cardiovascular collapse and multiorgan dysfunction. Pregnancy appears to increase the risk of death in sepsis, but the exact reason for the greater severity is unclear. In this study, we used polymicrobial sepsis induced by cecal ligation and puncture (CLP) and high-dose intraperitoneal lipopolysaccharide (LPS; 10 or 40 mg, serotype 0111: B4) to test the hypotheses that pregnant mice are more susceptible to sepsis and that this susceptibility was mediated through an excessive innate response causing a more severe cardiovascular collapse rather than a reduction in microbe killing. METHODS AND RESULTS: Initial studies found that mortality rates were greater, and that death occurred sooner in pregnant mice exposed to CLP and LPS. In pregnant and nonpregnant CD1 mice monitored with radiotelemetry probes, cardiovascular collapse occurred sooner in pregnant mice, but once initiated, occurred over a similar timescale. In a separate study, tissue, serum, and peritoneal fluid (for protein, flow cytometry, nitric oxide, and bacterial load studies) were collected. At baseline, there was no apparent Th1/Th2 bias in pregnant mice. Post CLP, the circulating cytokine response was the same, but leukocyte infiltration in the lung was greater in pregnant mice, but only TNFα levels were greater in lung tissue. The bacterial load in blood and peritoneal fluid was similar in both groups. CONCLUSION: Sepsis-related mortality was markedly greater in pregnant mice. Cardiovascular collapse and organ dysfunction occurred sooner in pregnancy, but bacterial killing was similar. Circulating and tissue cytokine levels were similar, but immune cell extravasation into other organs was greater in pregnant mice. These data suggest that an excessive innate immune system response as shown by the exaggerated lung infiltration of leukocytes may be responsible for the greater mortality. Approaches that reduce off-site t

Journal article

Sliwa K, Azibani F, Baard J, Osman A, Zuhlke L, Lachmann A, Libhaber E, Chin A, Ntsekhe M, Soma-Pillay P, Johnson MR, Roos-Hesselink J, Anthony Jet al., 2018, Reducing late maternal death due to cardiovascular disease - A pragmatic pilot study, INTERNATIONAL JOURNAL OF CARDIOLOGY, Vol: 272, Pages: 70-76, ISSN: 0167-5273

Journal article

Bracewell-Milnes T, Saso S, Nikolaou D, Norman-Taylor J, Johnson M, Thum M-Yet al., 2018, Investigating the effect of an abnormal cervico-vaginal and endometrial microbiome on assisted reproductive technologies: A systematic review, AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Vol: 80, ISSN: 1046-7408

Journal article

Ogundipe E, Tusor N, Wang Y, Johnson MR, Edwards AD, Crawford MAet al., 2018, Randomized controlled trial of brain specific fatty acid supplementation in pregnant women increases brain volumes on MRI scans of their newborn infants, PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS, Vol: 138, Pages: 6-13, ISSN: 0952-3278

Journal article

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