228 results on '"Alexander E P Heazell"'
Search Results
2. Evolving pattern of fetal movements throughout a healthy pregnancy
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Lauren O'Connell and Alexander E. P. Heazell
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Adult ,Male ,medicine.medical_specialty ,Placenta ,Pregnancy Trimester, Third ,Case Report ,Miscarriage ,03 medical and health sciences ,Viable pregnancy ,0302 clinical medicine ,Obstetrics and gynaecology ,Pregnancy ,medicine ,Humans ,030212 general & internal medicine ,Fetal Movement ,Fetus ,030219 obstetrics & reproductive medicine ,Placental abruption ,business.industry ,Obstetrics ,General Medicine ,Stillbirth ,medicine.disease ,First trimester ,Pregnancy Trimester, First ,Gestation ,Female ,business - Abstract
A 31-year-old woman with a history of stillbirth due to placental abruption at 29 weeks’ gestation and one first trimester miscarriage documented a continuous record of her perceived fetal movements from 28 to 38 weeks’ gestation. Repeated ultrasound examinations confirmed a viable pregnancy, with normal growth, liquor volume and Doppler profile. She delivered a healthy male infant at 38 weeks and 3 days’ gestation. The data collected give a detailed record of fetal activity in a healthy pregnancy. Perceived fetal activity increased as pregnancy progressed and was greatest in the evenings. We also found that clusters of movements, which have previously been reported as protective against stillbirth, were felt earlier on in pregnancy.
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- 2023
3. Placental expression of estrogen-related receptor gamma is reduced in fetal growth restriction pregnancies and is mediated by hypoxia
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Zhiyong Zou, Lynda K Harris, Karen Forbes, and Alexander E P Heazell
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Fetal Growth Retardation ,Reproductive Medicine ,Pregnancy ,Placenta ,Humans ,Estrogens ,Female ,Cobalt ,RNA, Messenger ,Cell Biology ,General Medicine ,Hypoxia - Abstract
Fetal growth restriction (FGR) describes a fetus which has not achieved its genetic growth potential; it is closely linked to placental dysfunction and uteroplacental hypoxia. Estrogen-related receptor gamma (ESRRG) is regulated by hypoxia and is highly expressed in the placenta. We hypothesized ESRRG is a regulator of hypoxia-mediated placental dysfunction in FGR pregnancies. Placentas were collected from women delivering appropriate for gestational age (AGA; n = 14) or FGR (n = 14) infants. Placental explants (n = 15) from uncomplicated pregnancies were cultured for up to 4 days in 21% or 1% O2, or with 200 μM cobalt chloride (CoCl2), or treated with the ESRRG agonists DY131 under different oxygen concentrations. RT-PCR, Western blotting, and immunochemistry were used to assess mRNA and protein levels of ESRRG and its localization in placental tissue from FGR or AGA pregnancies, and in cultured placental explants. ESRRG mRNA and protein expression were significantly reduced in FGR placentas, as was mRNA expression of the downstream targets of ESRRG, hydroxysteroid 11-beta dehydrogenase 2 (HSD11B2), and cytochrome P-450 (CYP19A1.1). Hypoxia-inducible factor 1-alpha protein localized to the nuclei of the cytotrophoblasts and stromal cells in the explants exposed to CoCl2 or 1% O2. Both hypoxia and CoCl2 treatment decreased ESRRG and its downstream genes’ mRNA expression, but not ESRRG protein expression. DY131 increased the expression of ESRRG signaling pathways and prevented abnormal cell turnover induced by hypoxia. These data show that placental ESRRG is hypoxia-sensitive and altered ESRRG-mediated signaling may contribute to hypoxia-induced placental dysfunction in FGR. Furthermore, DY131 could be used as a novel therapeutic approach for the treatment of placental dysfunction.
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- 2022
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4. Ending Preventable Stillbirths and Improving Bereavement Care: A Scorecard for High- and Upper-Middle Income Countries
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Esti Charlotte de Graaff, Susannah Hopkins Leisher, Hannah Blencowe, Harriet Lawford, Jillian Cassidy, Paul Cassidy, Elizabeth S Draper, Alexander E P Heazell, Mary Kinney, Paula Quigley, Claudia Ravaldi, Claire Storey, Alfredo Vannacci, the EPS in High-Resource Countries Scorecard Collaboration Group, and Vicki Flenady
- Abstract
Background: Despite progress, stillbirth rates in many high- and upper-middle income countries remain high, and the majority of these deaths are preventable. We introduce the Ending Preventable Stillbirths (EPS) Scorecard for High- and Upper Middle-Income Countries, a tool to track progress against the Lancet’s 2016 EPS Series Call to Action, fostering transparency, consistency and accountability. Methods: The Scorecard for EPS in High- and Upper-Middle Income Countries was adapted from the Scorecard for EPS in Low-Income Countries which includes 20 indicators to track progress against the eight Call to Action targets. The Scorecard for High- and Upper-Middle Income Countries includes 23 indicators tracking progress against these same Call to Action targets. For this inaugural version of the Scorecard, 13 high- and upper-middle income countries supplied data. Data were collated and compared between and within countries. Results: Data were complete for 15 of 23 indicators (65%). Five key issues were identified: (1) there is wide variation in stillbirth rates and related perinatal outcomes, (2) definitions of stillbirth and related perinatal outcomes vary widely across countries, (3) data on key risk factors for stillbirth are often missing and equity is not consistently tracked, (4) most countries lack guidelines and targets for critical areas for stillbirth prevention and care after stillbirth and have not set a national stillbirth rate target, and (5) most countries do not have mechanisms in place for reduction of stigma or guidelines around bereavement care. Conclusions: This inaugural version of the Scorecard for High- and Upper-Middle Income Countries highlights important gaps in performance indicators for stillbirth both between and within countries. The Scorecard provides a basis for future assessment of progress and can be used to help holding individual countries accountable, especially for reducing stillbirth inequities for disadvantaged groups.
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- 2023
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5. Information about fetal movements and stillbirth trends: Analysis of time series data
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Alexander E. P. Heazell, Fiona Holland, and Jack Wilkinson
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Obstetrics and Gynecology - Published
- 2023
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6. Determinants of eclampsia in women with severe preeclampsia at Mpilo Central Hospital, Bulawayo, Zimbabwe
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Alexander E. P. Heazell, Solwayo Ngwenya, Brian Jones, Hausitoe Nare, and Desmond Mwembe
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Adult ,Zimbabwe ,medicine.medical_specialty ,Adolescent ,Referral ,Logistic regression ,Severity of Illness Index ,Preeclampsia ,Young Adult ,Pre-Eclampsia ,Pregnancy ,Risk Factors ,Prenatal Diagnosis ,Internal Medicine ,medicine ,Humans ,reproductive and urinary physiology ,Eclampsia ,Obstetrics ,business.industry ,Pregnancy Outcome ,Obstetrics and Gynecology ,Odds ratio ,medicine.disease ,female genital diseases and pregnancy complications ,Confidence interval ,Blood pressure ,Female ,Complication ,business - Abstract
OBJECTIVE Globally, preeclampsia is a significant contributor to adverse maternal outcomes. Once women develop eclampsia, they face considerable risks especially in countries with limited resources to deal with such a life-threatening complication. This study was carried out to investigate determinants of eclampsia in pregnant mothers with severe preeclampsia. STUDY DESIGN This institutional based study was completed at Mpilo Central Hospital, a quaternary referral unit from 1st January 2016 - 31st December 2018. In this study, pregnant women with severe preeclampsia/eclampsia were the study participants. The independent variables included socio-demographic and clinical characteristics, and maternal outcomes. Multivariable logistic regression analyses were used to determine independent association with p
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- 2021
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7. Factors influencing health behaviour change during pregnancy: a systematic review and meta-synthesis
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Alexander E. P. Heazell, Debbie M Smith, Lauren Rockliffe, and Sarah Peters
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Alcohol Drinking ,media_common.quotation_subject ,Health Behavior ,MEDLINE ,Qualitative property ,PsycINFO ,Developmental psychology ,03 medical and health sciences ,0302 clinical medicine ,Pregnancy ,Perception ,medicine ,Humans ,030212 general & internal medicine ,Exercise ,Life Style ,media_common ,Meta synthesis ,030505 public health ,Study quality ,Smoking ,Health behaviour ,medicine.disease ,Psychiatry and Mental health ,Clinical Psychology ,Female ,0305 other medical science ,Psychology - Abstract
Pregnancy is an opportune time for women to make healthy changes to their lifestyle, however, many women struggle to do so. Multiple reasons have been posited as to why this may be. This review aimed to synthesise this literature by identifying factors that influence women's health behaviour during pregnancy, specifically in relation to dietary behaviour, physical activity, smoking, and alcohol use. Bibliographic databases (MEDLINE, PsycINFO, CINAHL-P, MIDIRS) were systematically searched to retrieve studies reporting qualitative data regarding women's experiences or perceptions of pregnancy-related behaviour change relating to the four key behaviours. Based on the eligibility criteria, 30,852 records were identified and 92 studies were included. Study quality was assessed using the CASP tool and data were thematically synthesised. Three overarching themes were generated from the data. These were (1) A time to think about 'me', (2) Adopting the 'good mother' role, and (3) Beyond mother and baby. These findings provide an improved understanding of the various internal and external factors influencing women's health behaviour during the antenatal period. This knowledge provides the foundations from which future pregnancy-specific theories of behaviour change can be developed and highlights the importance of taking a holistic approach to maternal behaviour change in clinical practice.
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- 2021
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8. Parents’ experiences of care offered after stillbirth: An international online survey of high and middle‐income countries
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Margaret M. Murphy, Jan Jaap H. M. Erwich, Alexander E. P. Heazell, Alfredo Vannacci, Claudia Ravaldi, Katherine J. Gold, Mechthild M. Gross, Frances M. Boyle, Claire Storey, Susannah Hopkins Leisher, Aleena M. Wojcieszek, Vicki Flenady, Dell Horey, Paul Cassidy, Jillian Cassidy, and Dimitrios Siassakos
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Parents ,030219 obstetrics & reproductive medicine ,Perinatal bereavement ,business.industry ,Middle income countries ,Obstetrics and Gynecology ,Odds ratio ,Stillbirth ,03 medical and health sciences ,0302 clinical medicine ,Pregnancy ,Surveys and Questionnaires ,Humans ,Social consequence ,Medicine ,Female ,030212 general & internal medicine ,Bereavement Care ,business ,Developing Countries ,High income countries ,Bereavement ,Demography - Abstract
Background Stillbirth, the death of a baby before birth, is associated with significant psychological and social consequences that can be mitigated by respectful and supportive bereavement care. The absence of high-level evidence to support the broad scope of perinatal bereavement practices means that offering a range of options identified as valued by parents has become an important indicator of care quality. This study aimed to describe bereavement care practices offered to parents across different high-income and middle-income countries. Methods An online survey of parents of stillborn babies was conducted between December 2014 and February 2015. Frequencies of nine practices were compared between high-income and middle-income countries. Differences in proportions of reported practices and their associated odds ratios were calculated to compare high-income and middle-income countries. Results Over three thousand parents (3041) with a self-reported stillbirth in the preceding five years from 40 countries responded. Fifteen countries had atleast 40 responses. Significant differences in the prevalence of offering nine bereavement care practices were reported by women in high-income countries (HICs) compared with women in middle-income countries (MICs). All nine practices were reported to occur significantly more frequently by women in HICs, including opportunity to see and hold their baby (OR = 4.8, 95% CI 4.0-5.9). The widespread occurrence of all nine practices was reported only for The Netherlands. Conclusions Bereavement care after stillbirth varies between countries. Future research should look at why these differences occur, their impact on parents, and whether differences should be addressed, particularly how to support effective communication, decision-making, and follow-up care.
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- 2021
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9. The potential role of the E SRRG pathway in placental dysfunction
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Lynda K. Harris, Alexander E. P. Heazell, Karen Forbes, and Zhiyong Zou
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0301 basic medicine ,Embryology ,Placenta Diseases ,medicine.drug_class ,Placenta ,Biology ,Preeclampsia ,Andrology ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Pregnancy ,microRNA ,medicine ,Humans ,reproductive and urinary physiology ,Fetal Growth Retardation ,030219 obstetrics & reproductive medicine ,Obstetrics and Gynecology ,Placentation ,Trophoblast ,Cell Biology ,Fetal Growth Retardation/etiology ,Hypoxia (medical) ,medicine.disease ,female genital diseases and pregnancy complications ,Trophoblasts ,030104 developmental biology ,medicine.anatomical_structure ,Reproductive Medicine ,Estrogen ,embryonic structures ,Female ,medicine.symptom ,Function (biology) - Abstract
Normal placental development and function is of key importance to fetal growth. Conversely aberrations of placental structure and function are evident in pregnancy complications including fetal growth restriction (FGR) and preeclampsia. Although trophoblast turnover and function is altered in these conditions, their underlying aetiologies and pathophysiology remains unclear, which hampers development of therapeutic interventions. Here we review evidence that supports a role for estrogen related receptor-gamma (ESRRG) in the development of placental dysfunction in FGR and preeclampsia. This relationship deserves particular consideration because ESRRG is highly expressed in normal placenta, is reduced in FGR and preeclampsia and its expression is altered by hypoxia, which is thought to result from deficient placentation seen in FGR and preeclampsia. Several studies have also found microRNA (miRNA) or other potential upstream regulators of ESRRG negatively influence trophoblast function which could contribute to placental dysfunction seen in FGR and preeclampsia. Interestingly, miRNAs regulate ESRRG expression in human trophoblast. Thus, if ESRRG is pivotally associated with the abnormal trophoblast turnover and function it may be targeted by microRNAs or other possible upstream regulators in the placenta. This review explores altered expression of ESRRG and upstream regulation of ESRRG-mediated pathways resulting in the trophoblast turnover, placental vascularisation, and placental metabolism underlying placental dysfunctions. This demonstrates that the ESRRG pathway merits further investigation as a potential therapeutic target in FGR and preeclampsia.
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- 2021
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10. Development and validation of risk prediction models for adverse maternal and neonatal outcomes in severe preeclampsia in a low-resource setting, Mpilo Central Hospital, Bulawayo, Zimbabwe
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Brian Jones, Solwayo Ngwenya, Hausitoe Nare, Desmond Mwembe, and Alexander E. P. Heazell
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Adult ,Zimbabwe ,medicine.medical_specialty ,Abdominal pain ,Birth weight ,Gestational Age ,Logistic regression ,Risk Assessment ,Sensitivity and Specificity ,Pre-Eclampsia ,Pregnancy ,Internal Medicine ,medicine ,Humans ,Vaginal bleeding ,Poverty ,Retrospective Studies ,Obstetrics ,business.industry ,Pregnancy Outcome ,Obstetrics and Gynecology ,Gestational age ,medicine.disease ,Cross-Sectional Studies ,Logistic Models ,ROC Curve ,Cohort ,Population study ,Female ,medicine.symptom ,business - Abstract
Hypertensive disorders of pregnancy are major causes of global maternal and neonatal morbidity and mortality. This study aimed to develop and validate models to predict composite adverse maternal and neonatal outcome in severe preeclampsia in low-resource settings.A retrospective cross-sectional study of women with severe preeclampsia giving birth in a tertiary referral centre in Zimbabwe between 01/01/2014-31/12/2018. Candidate variables identified from univariable logistic regression (p 0.2) were entered into stepwise backward elimination logistic regression models to predict composite adverse maternal and neonatal outcomes. Models' performance was assessed by the area under the curve of the receiver operator characteristic (AUC ROC). The models were validated internally using bootstrap-based methods and externally using the Preeclampsia Integrated Estimate of RiSk dataset.The co-primary outcomes were composite adverse maternal outcome and composite adverse neonatal outcome.549 women had severe preeclampsia from whom 567 neonates were born. The predictive model for composite adverse maternal outcome included maternal age, gestational age on admission, epigastric pain, vaginal bleeding with abdominal pain, haemoglobin concentration and platelets; the AUC ROC was 0.796 (95% CI 0.758-0.833). External validation showed poor discrimination (AUC ROC 0.494, 95% CI 0.458-0.552). The model for composite adverse neonatal outcome included: gestational age, platelets, alanine transaminase and birth weight; the AUC ROC was 0.902 (95% CI 0.876-0.927).While the models accurately predicted composite adverse maternal and neonatal outcomes in the study population, they did not in another cohort. Understanding factors which affect model performance will help optimize prediction of adverse outcomes in severe preeclampsia.
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- 2021
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11. Care in pregnancies subsequent to stillbirth or perinatal death
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Alexander E. P. Heazell, Louise Stephens, and Nicole Graham
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medicine.medical_specialty ,Placental histopathology ,business.industry ,Obstetrics ,Medicine ,Small for gestational age ,Subsequent pregnancy ,business ,medicine.disease - Published
- 2020
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12. Associations between social and behavioural factors and the risk of late stillbirth – findings from the Midland and North of England Stillbirth case‐control study
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Lesley M. E. McCowan, Robin S. Cronin, Alexander E. P. Heazell, John M. D. Thompson, Edwin A. Mitchell, Lucy K Smith, Jayne Budd, Tomasina Stacey, Devender Roberts, Minglan Li, and Billie Bradford
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Adult ,Domestic Violence ,unemployment ,Adolescent ,perceived stress ,socio-economic status ,Population ,Perceived Stress Scale ,Gestational Age ,Domestic violence ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Pregnancy ,Risk Factors ,Obstetrics and Gynaecology ,Humans ,risk factors ,Medicine ,Social determinants of health ,education ,Socioeconomic status ,Social stress ,Late Stillbirth ,education.field_of_study ,030219 obstetrics & reproductive medicine ,business.industry ,Obstetrics and Gynecology ,Odds ratio ,Middle Aged ,Stillbirth ,Logistic Models ,England ,Socioeconomic Factors ,perinatal mortality ,Case-Control Studies ,social determinants of health ,Multivariate Analysis ,Female ,stillbirth ,business ,Stress, Psychological ,Demography - Abstract
OBJECTIVE To investigate behavioural and social characteristics of women who experienced a late stillbirth compared with women with ongoing live pregnancies at similar gestation. DESIGN Case-control study. SETTING 41 maternity units in the UK. POPULATION Women who had a stillbirth ≥28 weeks' gestation (n = 287) and women with an ongoing pregnancy at the time of interview (n = 714). METHODS Data were collected using an interviewer-administered questionnaire which included questions regarding women's behaviours (e.g. alcohol intake and household smoke exposure) and social characteristics (e.g. ethnicity, employment, housing). Stress was measured by the 10-item Perceived Stress Scale. MAIN OUTCOME MEASURE Late stillbirth. RESULTS Multivariable analysis adjusting for co-existing social and behavioural factors showed women living in the most deprived quintile had an increased risk of stillbirth compared with the least deprived quintile (adjusted odds ratio [aOR] 3.16; 95% CI 1.47-6.77). There was an increased risk of late stillbirth associated with unemployment (aOR 2.32; 95% CI 1.00-5.38) and women who declined to answer the question about domestic abuse (aOR 4.12; 95% CI 2.49-6.81). A greater number of antenatal visits than recommended was associated with a reduction in stillbirth (aOR 0.26; 95% CI 0.16-0.42). CONCLUSIONS This study demonstrates associations between late stillbirth and socio-economic deprivation, perceived stress and domestic abuse, highlighting the need for strategies to prevent stillbirth to extend beyond maternity care. Enhanced antenatal care may be able to mitigate some of the increased risk of stillbirth. TWEETABLE ABSTRACT Deprivation, unemployment, social stress & declining to answer about domestic abuse increase risk of #stillbirth after 28 weeks' gestation.
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- 2020
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13. Prediction of stillbirth: an umbrella review of evaluation of prognostic variables
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Alexander E. P. Heazell, L. Jorgensen, Laura A. Magee, Julie Dodds, Filomena Giulia Sileo, V. B. Kim, R. Townsend, John Allotey, Gordon C. S. Smith, Shakila Thangaratinam, Asma Khalil, Ben W.J. Mol, B. Thilaganathan, Jane Sandall, and P. von Dadelszen
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medicine.medical_specialty ,Prognostic variable ,MEDLINE ,Cochrane Library ,03 medical and health sciences ,0302 clinical medicine ,Predictive Value of Tests ,Pregnancy ,Risk Factors ,Prenatal Diagnosis ,Epidemiology ,medicine ,Humans ,030219 obstetrics & reproductive medicine ,Obstetrics ,business.industry ,Obstetrics and Gynecology ,Stillbirth ,Prognosis ,medicine.disease ,Systematic review ,Data extraction ,Female ,business ,Body mass index - Abstract
Background Stillbirth accounts for over 2 million deaths a year worldwide and rates remains stubbornly high. Multivariable prediction models may be key to individualised monitoring, intervention or early birth in pregnancy to prevent stillbirth. Objectives To collate and evaluate systematic reviews of factors associated with stillbirth in order to identify variables relevant to prediction model development. Search strategy MEDLINE, Embase, DARE and Cochrane Library databases and reference lists were searched up to November 2019. Selection criteria We included systematic reviews of association of individual variables with stillbirth without language restriction. Data collection and analysis Abstract screening and data extraction were conducted in duplicate. Methodological quality was assessed using AMSTAR and QUIPS criteria. The evidence supporting association with each variable was graded. Results The search identified 1198 citations. Sixty-nine systematic reviews reporting 64 variables were included. The most frequently reported were maternal age (n = 5), body mass index (n = 6) and maternal diabetes (n = 5). Uterine artery Doppler appeared to have the best performance of any single test for stillbirth. The strongest evidence of association was for nulliparity and pre-existing hypertension. Conclusion We have identified variables relevant to the development of prediction models for stillbirth. Age, parity and prior adverse pregnancy outcomes had a more convincing association than the best performing tests, which were PAPP-A, PlGF and UtAD. The evidence was limited by high heterogeneity and lack of data on intervention bias. Tweetable abstract Review shows key predictors for use in developing models predicting stillbirth include age, prior pregnancy outcome and PAPP-A, PLGF and Uterine artery Doppler.
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- 2020
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14. Adverse pregnancy outcomes and subsequent development of connective tissue disease in the UK: an epidemiological study
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Hannah Kither, Alexander E. P. Heazell, Ian N. Bruce, Ian P. Crocker, and Clare Tower
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Adult ,medicine.medical_specialty ,autoantibodies ,Population ,Systemic Lupus Erythematosus ,symbols.namesake ,Pregnancy ,Antiphospholipid syndrome ,Median follow-up ,Epidemiology ,Odds Ratio ,Prevalence ,medicine ,Humans ,Poisson regression ,Connective Tissue Diseases ,education ,Retrospective Studies ,education.field_of_study ,Clinical Practice Research Datalink (CPRD) ,business.industry ,Obstetrics ,Pregnancy Outcome ,Obstetrics and Gynecology ,Stillbirth ,medicine.disease ,Connective tissue disease ,United Kingdom ,Pregnancy Complications ,Case-Control Studies ,Relative risk ,symbols ,Female ,Disease Susceptibility ,antiphospholiplid syndrome ,business - Abstract
OBJECTIVE This study assessed prevalence of connective tissue disease (CTDs), systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS) and antiphospholipid antibodies (aPL) in women with previous adverse pregnancy outcome compared with uncomplicated livebirths. DESIGN Retrospective case-control study. SETTING UK Primary Care. POPULATION OR SAMPLE Records of women, 18 years and older, within the Clinical Practice Research Datalink (CPRD) (1 January 2000-31 December 2013). METHODS Clinical Practice Research Datalink was searched for pregnancy terms to identify adverse pregnancy outcome. Each identified case was matched to five livebirths. MAIN OUTCOME MEASURES Diagnosis of SLE, CTD, APS or autoimmune antibodies. Poisson regression was performed to calculate relative risk ratios (RR), comparing adverse pregnancy outcome with livebirth cohorts. RESULTS Clinical Practice Research Datalink identified 20 123 adverse pregnancy outcomes matched to 97 323 livebirths, with a total of 875 590 person-years follow up. Median follow up from study entry was 7.29 years (SD 4.39). Compared with women with an uncomplicated livebirth, women with adverse pregnancy outcome had an increased risk of developing CTD or autoimmune antibodies (RR 3.20, 95% CI 2.90-3.51). Risk was greatest following a stillbirth (RR 5.82, 95% CI 4.97-6.81). For CTD and SLE, the risk was greatest within the first 5 years of adverse pregnancy outcome. Risk for aPL and APS diagnosis was highest ≥5 years from adverse pregnancy outcome. CONCLUSIONS Adverse pregnancy outcome is associated with increased risk of developing maternal CTD, including SLE. Either immunological factors predispose women to adverse pregnancy outcome and subsequent CTD diagnosis or, alternatively, adverse pregnancy outcome initiates autoimmune events which culminate in CTD in later life. TWEETABLE ABSTRACT Stillbirth is associated with increased maternal risk of developing systemic lupus erythematosus (SLE).
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- 2020
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15. Verification of placental growth factor and soluble-fms-like tyrosine kinase 1 assay performance in late pregnancy and their diagnostic test accuracy in women with reduced fetal movement
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Alexander E. P. Heazell, Tim James, Shonagh Haslam, Lindsay Armstrong-Buisseret, and Lucy Bradshaw
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Adult ,Placental growth factor ,medicine.medical_specialty ,medicine.medical_treatment ,Clinical Biochemistry ,030204 cardiovascular system & hematology ,Sensitivity and Specificity ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Pregnancy ,Internal medicine ,medicine ,Humans ,Prospective Studies ,Fetal Movement ,Placenta Growth Factor ,Vascular Endothelial Growth Factor Receptor-1 ,030219 obstetrics & reproductive medicine ,Diagnostic Tests, Routine ,business.industry ,Growth factor ,General Medicine ,medicine.disease ,Late pregnancy ,Pregnancy Complications ,Endocrinology ,embryonic structures ,Fetal movement ,Female ,business ,Tyrosine kinase ,Biomarkers ,Function (biology) ,Soluble fms-like tyrosine kinase-1 - Abstract
Background Placental growth factor (PlGF) and soluble-fms-like tyrosine kinase 1 (sFlt-1) are biomarkers of placental function used to aid the diagnosis and prediction of pregnancy complications. This work verified the analytical performance of both biomarkers and provides preliminary diagnostic accuracy data to identify adverse pregnancy outcome in women with reduced fetal movement. Methods Verification of sFlt-1 and PlGF assays included a comparative accuracy assessment of 24 serum samples analysed at six different sites and laboratory-specific precision estimates. The sFlt-1/PlGF ratio was assessed in serum samples obtained prospectively from 295 women with reduced fetal movement ≥36 weeks’ gestation; diagnostic accuracy was evaluated using 2 × 2 tables and area under the receiver operator characteristic (AUROC) curve. Results Regression analysis showed that performance between sites was good with Passing-Bablok slopes ranging from 0.96 to 1.05 (sFlt-1) and 0.93 to 1.08 (PlGF). All sites had a mean bias Conclusions Analytical performance of the sFlt-1 and PlGF assays was comparable across different sites. The sensitivity of sFlt-1/PlGF to identify adverse pregnancy outcome in women with reduced fetal movement was considered acceptable, in the absence of other tests, to progress to a pilot randomized controlled trial.
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- 2020
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16. Placental Morphology and Cellular Characteristics in Stillbirths in Women With Diabetes and Unexplained Stillbirths
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Daniel Shingleton, Megan C. Sharps, Alan Kerby, Gauri Batra, Alexander E. P. Heazell, and Bernadette Baker
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Adult ,0301 basic medicine ,medicine.medical_specialty ,Placenta ,Pathology and Forensic Medicine ,03 medical and health sciences ,0302 clinical medicine ,Pregnancy ,Diabetes mellitus ,Diabetes Mellitus ,medicine ,Humans ,reproductive and urinary physiology ,030219 obstetrics & reproductive medicine ,Obstetrics ,business.industry ,Placental morphology ,Case-control study ,General Medicine ,Stillbirth ,medicine.disease ,female genital diseases and pregnancy complications ,Pregnancy Complications ,Medical Laboratory Technology ,030104 developmental biology ,Case-Control Studies ,Female ,business - Abstract
Context.— Women with diabetes have increased stillbirth risk. Although the underlying pathophysiological processes are poorly understood, stillbirth is frequently related to abnormal placental structure and function. Objective.— To investigate placental morphology and cellular characteristics in the placentas of women with diabetes who had stillbirths and stillbirths of unexplained cause. Design.— Placentas from women with uncomplicated live births, live births in women with diabetes, unexplained stillbirths, and stillbirths related to diabetes (n = 10/group) underwent clinical histopathologic assessment and were also investigated using immunohistochemical staining to quantify syncytial nuclear aggregates, proliferation, trophoblast area, vascularization, T cells, placental macrophages (Hofbauer cells), and the receptor for advanced glycation end products. Results.— Ki67+ cells were decreased in unexplained stillbirths compared with live births in women with diabetes. Both stillbirth groups had increased cytokeratin 7+/nuclear area compared with controls. Blood vessels/villi were decreased in unexplained stillbirth compared with live births from women with diabetes. Compared with uncomplicated controls, CD163+ macrophages were increased in live births in women with diabetes and unexplained stillbirths, and further increased in stillbirths related to diabetes. There was no change in CD3+ T cells or syncytial nuclear aggregates. Receptor for advanced glycation end products–positive cells were decreased in both stillbirth groups compared with diabetes-related live births. Co-localization of receptor for advanced glycation end products in macrophages was increased in both stillbirth groups compared with live birth groups. Conclusions.— Stillbirths related to diabetes exhibit placental phenotypic differences compared with live births. Further investigation of these parameters may provide understanding of the pathologic mechanisms of stillbirth and aid the development of stillbirth prevention strategies.
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- 2020
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17. When the Fetus Goes Still and the Birth Is Tragic
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Alexander E. P. Heazell and Nicole Graham
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Pregnancy ,Fetus ,medicine.medical_specialty ,030219 obstetrics & reproductive medicine ,Placental abruption ,business.industry ,Obstetrics ,Obstetrics and Gynecology ,Autopsy ,Histopathological examination ,Placental structure ,medicine.disease ,Chorioamnionitis ,female genital diseases and pregnancy complications ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,Placenta ,medicine ,030212 general & internal medicine ,business ,reproductive and urinary physiology - Abstract
Because of the critical role that placental structure and function plays during pregnancy, abnormal placental structure and function is closely related to stillbirth: when an infant dies before birth. However, understanding the role of the placental and specific lesions is incomplete, in part because of the variation in definitions of lesions and in classifying causes of stillbirths. Nevertheless, placental abnormalities are seen more frequently in stillbirths than live births, with placental abruption, chorioamnionitis, and maternal vascular malperfusion most commonly reported. Critically, some placental lesions affect the management of subsequent pregnancies. Histopathological examination of the placenta is recommended following stillbirth.
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- 2020
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18. Associations Between Consumption of Coffee and Caffeinated Soft Drinks and Late Stillbirth—Findings From the Midland and North of England Stillbirth Case-Control Study
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Tomasina Stacey, Kate Timms, Edwin A. Mitchell, Minglan Li, Devender Roberts, John M. D. Thompson, Lesley M. E. McCowan, Robin S. Cronin, Alexander E. P. Heazell, Rebecca E. Scott, Lauren Rockliffe, and Jayne Budd
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Late Stillbirth ,Pregnancy ,business.industry ,Case-control study ,Obstetrics and Gynecology ,General Medicine ,Odds ratio ,medicine.disease ,Confidence interval ,chemistry.chemical_compound ,chemistry ,Environmental health ,Attributable risk ,medicine ,Gestation ,Caffeine ,business - Abstract
Objective The consumption of caffeinated drinks and soft drinks is widespread in society, including by pregnant women. Data regarding the association of caffeine intake and stillbirth are varied. We aimed to investigate the degree of consumption of caffeinated drinks or soft drinks in the last four weeks of pregnancy in women who experienced a late stillbirth compared to women with ongoing live pregnancies at similar gestation. Influences on maternal caffeine intake and soft drink consumption during pregnancy were also investigated. Study Design A case-control study undertaken in 41 maternity units in the United Kingdom. Cases were women who had a singleton non-anomalous stillbirth ≥28 weeks’ gestation (n = 290) and controls were women with an ongoing pregnancy at the time of interview (n = 729). Data were collected using an interviewer-administered questionnaire which included questions regarding consumption of a variety of caffeinated drinks and soft drinks in the last four weeks of pregnancy as well as other behaviours (e.g. cigarette smoking). Results Multivariable analysis adjusting for co-existing demographic and behavioural factors found the consumption of instant coffee, energy drinks and cola were associated with increased risk of stillbirth. There was an independent association between caffeine intake and late stillbirth (adjusted Odds Ratio 1.27, 95 % Confidence Interval (95 %CI) 1.14, 1.43 for each 100 mg increment/day). 15 % of cases and 8% of controls consumed more than the World Health Organisation (WHO) recommendation (>300 mg of caffeine/day; aOR 2.30, 95 % CI 1.40, 4.24). The population attributable risk for stillbirth associated with >300 mg of caffeine/day was 7.4 %. The majority of respondents reduced caffeine consumption in pregnancy. Midwives and internet resources were the most frequently used sources of information which influenced maternal behaviour with regard to soft drinks and caffeine, and this did not differ between cases and controls. Conclusions Women should be informed that consumption of caffeine during pregnancy is associated with increased risk of stillbirth, particularly at levels greater than recommended by the WHO (>300 mg/day). Recommendations from midwives and internet-based resources are likely to be the most effective means to influence maternal behaviour.
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- 2021
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19. A qualitative exploration of influences on eating behaviour throughout pregnancy
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Lauren, Rockliffe, Debbie M, Smith, Alexander E P, Heazell, and Sarah, Peters
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Pregnancy is often conceptualised as a 'teachable moment' for health behaviour change. However, it is likely that different stages of pregnancy, and individual antenatal events, provide multiple distinct teachable moments to prompt behaviour change. Whilst previous quantitative research supports this argument, it is unable to provide a full understanding of the nuanced factors influencing eating behaviour. The aim of this study was to explore influences on women's eating behaviour throughout pregnancy.In-depth interviews were conducted online with 25 women who were less than six-months postpartum. Interviews were audio-recorded and transcribed verbatim. Data were analysed thematically.Five themes were generated from the data that capture influences on women's eating behaviour throughout pregnancy: 'The preconceptual self', 'A desire for good health', 'Retaining control', 'Relaxing into pregnancy', and 'The lived environment'.Mid-pregnancy may provide a more salient opportunity for eating behaviour change than other stages of pregnancy. Individual antenatal events, such as the glucose test, can also prompt change. In clinical practice, it will be important to consider the changing barriers and facilitators operating throughout pregnancy, and to match health advice to stages of pregnancy, where possible. Existing models of teachable moments may be improved by considering the dynamic nature of pregnancy, along with the influence of the lived environment, pregnancy symptoms, and past behaviour. These findings provide an enhanced understanding of the diverse influences on women's eating behaviour throughout pregnancy and provide a direction for how to adapt existing theories to the context of pregnancy.
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- 2021
20. ‘Fetal side’ of the placenta: anatomical mis-annotation of carbon particle ‘transfer’ across the human placenta
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Carolyn J.P. Jones, Gil Mor, Claire T. Roberts, Alexander E. P. Heazell, Rohan M. Lewis, Sarah A. Robertson, Beth Holder, Joanna L. James, Helen Jones, John D. Aplin, Nardhy Gomez-Lopez, and Ana Claudia Zenclussen
- Subjects
Cell biology ,Fetus ,Multidisciplinary ,Science ,Placenta ,General Physics and Astronomy ,Human placenta ,General Chemistry ,Biology ,Carbon ,General Biochemistry, Genetics and Molecular Biology ,Carbon particle ,medicine.anatomical_structure ,Matters Arising ,Pregnancy ,medicine ,Humans ,Female ,Anatomy ,Maternal-Fetal Exchange - Abstract
Matters Arising article, arising from H. Bové et al. Nature Communications https://doi.org/10.1038/s41467-019-11654-3 (2019).
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- 2021
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21. Sex-specific effects of bisphenol A on the signaling pathway of ESRRG in the human placenta†
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Zhiyong Zou, Lynda K Harris, Karen Forbes, and Alexander E P Heazell
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Male ,endocrine system ,urogenital system ,bisphenol A ,Placenta ,placental dysfunction ,Cell Biology ,General Medicine ,Pregnancy Proteins ,human placenta ,Reproductive Medicine ,Phenols ,Receptors, Estrogen ,Pregnancy ,sex specific manner ,embryonic structures ,Humans ,Female ,RNA, Messenger ,Benzhydryl Compounds ,hormones, hormone substitutes, and hormone antagonists ,estrogen-related receptor gamma ,Signal Transduction - Abstract
Bisphenol A (BPA) exposure during pregnancy is associated with low fetal weight, particularly in male fetuses. The expression of estrogen-related receptor gamma (ESRRG), a receptor for BPA in the human placenta, is reduced in fetal growth restriction. This study sought to explore whether ESRRG signaling mediates BPA-induced placental dysfunction and determine whether changes in the ESRRG signaling pathway are sex-specific. Placental villous explants from 18 normal term pregnancies were cultured with a range of BPA concentrations (1 nM–1 μM). Baseline BPA concentrations in the placental tissue used for explant culture ranged from 0.04 to 5.1 nM (average 2.3 ±1.9 nM; n = 6). Expression of ESRRG signaling pathway constituents and cell turnover were quantified. BPA (1 μM) increased ESRRG mRNA expression after 24 h in both sexes. ESRRG mRNA and protein expression was increased in female placentas treated with 1 μM BPA for 24 h but was decreased in male placentas treated with 1 nM or 1 μM for 48 h. Levels of 17β-hydroxysteroid dehydrogenase type 1 (HSD17B1) and placenta specific-1 (PLAC1), genes downstream of ESRRG, were also affected. HSD17B1 mRNA expression was increased in female placentas by 1 μM BPA; however, 1 nM BPA reduced HSD17B1 and PLAC1 expression in male placentas at 48 h. BPA treatment did not affect rates of proliferation, apoptosis, or syncytiotrophoblast differentiation in cultured villous explants. This study has demonstrated that BPA affects the ESRRG signaling pathway in a sex-specific manner in human placentas and a possible biological mechanism to explain the differential effects of BPA exposure on male and female fetuses observed in epidemiological studies.
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- 2021
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22. Sexually dimorphic patterns in maternal circulating microRNAs in pregnancies complicated by fetal growth restriction
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Alexander E. P. Heazell, Isabel Lorne, Sylvia Lui, Karen Forbes, Bernadette Baker, and Rebecca Jones
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Male ,Serum ,Physiology ,Offspring ,Placenta ,Biology ,Placental dysfunction ,Gender Studies ,Sexual dimorphism ,Endocrinology ,Human placental lactogen ,Sex Factors ,Pregnancy ,medicine ,QP1-981 ,Humans ,Circulating MicroRNA ,miRNA ,Fetus ,Fetal Growth Retardation ,Research ,Pregnancy Outcome ,Biomarker ,Stillbirth ,medicine.disease ,FGR ,medicine.anatomical_structure ,In utero ,Medicine ,Gestation ,Biomarker (medicine) ,Female - Abstract
Background Current methods fail to accurately predict women at greatest risk of developing fetal growth restriction (FGR) or related adverse outcomes, including stillbirth. Sexual dimorphism in these adverse pregnancy outcomes is well documented as are sex-specific differences in gene and protein expression in the placenta. Circulating maternal serum microRNAs (miRNAs) offer potential as biomarkers that may also be informative of underlying pathology. We hypothesised that FGR would be associated with an altered miRNA profile and would differ depending on fetal sex. Methods miRNA expression profiles were assessed in maternal serum (> 36 weeks’ gestation) from women delivering a severely FGR infant (defined as an individualised birthweight centile (IBC), Highlights Detection and treatment of pregnancies at high risk of fetal growth restriction (FGR) and stillbirth remains a major obstetric challenge; circulating maternal serum microRNAs (miRNAs) offer potential as novel biomarkers.Unbiased analysis of serum miRNAs in women in late pregnancy identified a specific profile of circulating miRNAs in women with a growth-restricted infant.Some altered miRNAs (miR-28-5p, miR-301a-3p) showed sexually dimorphic expression in FGR pregnancies and others a fetal-sex dependent association to a hormonal marker of placental dysfunction (miR-454-3p, miR-29c-3p).miR-301a-3p and miR-28-5p could potentially be used to predict FGR specifically in pregnancies with a male or female baby, respectively, however larger cohort studies are required.Further investigations of these miRNAs and their relationship to placental dysfunction will lead to a better understanding of the pathophysiology of FGR and why there is differing susceptibility of male and female fetuses to FGR and stillbirth. Supplementary Information The online version contains supplementary material available at 10.1186/s13293-021-00405-z.
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- 2021
23. Assessment of the fetus before and during labour
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Alexander E. P. Heazell and Harriet Lamb
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Fetus ,medicine.medical_specialty ,business.industry ,Obstetrics ,Critical Care and Intensive Care Medicine ,medicine.disease ,Cerebral palsy ,03 medical and health sciences ,0302 clinical medicine ,Anesthesiology and Pain Medicine ,medicine.anatomical_structure ,Scalp ,embryonic structures ,Electronic fetal monitoring ,Medicine ,030212 general & internal medicine ,business ,Pregnancy outcomes ,030217 neurology & neurosurgery - Abstract
Perinatal death or cerebral palsy are devastating events for families. In an attempt to prevent these pregnancy outcomes, fetal wellbeing is assessed during labour by a variety of means. In this review, the most common means to confirm fetal wellbeing, the rationale for their use and evidence of their efficacy are discussed. With respect to labour, the indications for continuous electronic fetal monitoring are presented, together with a guide to interpretation of cardiotocograph (CTG) or fetal scalp blood samples (FBS).
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- 2019
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24. The kynurenine pathway; A new target for treating maternal features of preeclampsia?
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Jenny Myers, Alexander E. P. Heazell, Susan L. Greenwood, Mark Wareing, and Stephanie Worton
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Kynurenine pathway ,T-Lymphocytes ,Apoptosis ,Pharmacology ,Vascular dysfunction ,medicine.disease_cause ,Preeclampsia ,Immunomodulation ,Drug Development ,Pre-Eclampsia ,Pregnancy ,medicine ,Humans ,Molecular Targeted Therapy ,Endothelial dysfunction ,Kynurenine ,business.industry ,Immunoregulation ,Obstetrics and Gynecology ,Cell Differentiation ,Vasospasm ,Immune dysregulation ,medicine.disease ,Pathophysiology ,Oxidative Stress ,Reproductive Medicine ,Female ,business ,Metabolic Networks and Pathways ,Oxidative stress ,Developmental Biology - Abstract
In preeclampsia, vasospasm, oxidative stress, endothelial dysfunction, and immune dysregulation are key mediators of maternal disease. A new time-of-disease treatment is needed with the potential to treat these areas of pathophysiology. A review of the literature has indicated that metabolites of the kynurenine pathway have the potential to; (i) induce vasorelaxation of resistance arteries and reduce blood pressure; (ii) exert antioxidant effects and reduce the effects of poly-ADP ribose polymerase activation (iii) prevent endothelial dysfunction and promote endothelial nitric oxide production; (iv) cause T cell differentiation into tolerogenic regulatory T cells and induce apoptosis of pro-inflammatory Th1 cells. This has led to the hypothesis that increasing Kynurenine pathway activity may offer a new treatment strategy for preeclampsia.
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- 2019
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25. Impact of consultant obstetric presence on serious incidents
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Teresa Kelly, Shirley Rowbotham, Alexander E. P. Heazell, Sherif Shawer, and Sarah Vause
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medicine.medical_specialty ,Clinical effectiveness ,media_common.quotation_subject ,Midwifery ,Patient care ,03 medical and health sciences ,Patient safety ,0302 clinical medicine ,Obstetrics and gynaecology ,medicine ,030212 general & internal medicine ,media_common ,Teamwork ,Retrospective review ,030219 obstetrics & reproductive medicine ,business.industry ,Health Policy ,National health service ,Adverse events or outcomes ,Obstetrics ,Family medicine ,Business, Management and Accounting (miscellaneous) ,business - Abstract
Purpose Many organisations, including the Royal College of Obstetricians and Gynaecologists, have recommended increasing the number of hours of consultant obstetric presence in UK National Health Service maternity units to improve patient care. St Mary’s Hospital, Manchester implemented 24-7 consultant presence in September 2014. The paper aims to discuss these issues. Design/methodology/approach To assess the impact of 24-7 consultant presence upon women and babies, a retrospective review of all serious clinical intrapartum incidents occurring between September 2011 and September 2017 was carried out by two independent reviewers; disagreements in classification were reviewed by a senior Obstetrician. The impact of consultant presence was classified in a structure agreed a priori. Findings A total of 72 incidents were reviewed. Consultants were directly involved in the care of 75.6 per cent of cases before 24-7 consultant presence compared to 96.8 per cent afterwards. Negative impact due to a lack of consultant presence fell from 22 per cent of the incidents before 24-7 consultant presence to 9.7 per cent after implementation. In contrast, positive impact of consultant presence increased from 14.6 to 32.3 per cent following the introduction of 24-7 consultant presence. Practical implications Introduction of 24-7 consultant presence reduced the negative impact caused by a lack of, or delay in, consultant presence as identified by serious untoward incident (SUI) reviews. Consultant presence was more likely to have a positive influence on care delivery. Originality/value This is the first assessment of the impact of 24-7 consultant presence on the SUIs in obstetrics.
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- 2019
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26. Breech presentation is associated with lower adolescent tibial bone strength
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Alexander E. P. Heazell, Debbie A Lawlor, Adrian Sayers, Jonathan H Tobias, Kevin Deere, and Alex Ireland
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Male ,musculoskeletal diseases ,0301 basic medicine ,medicine.medical_specialty ,Adolescent ,Endocrinology, Diabetes and Metabolism ,Osteoporosis ,030209 endocrinology & metabolism ,Cohort Studies ,03 medical and health sciences ,Absorptiometry, Photon ,Sex Factors ,0302 clinical medicine ,Bone Density ,Pregnancy ,Breech presentation ,medicine ,Humans ,Longitudinal Studies ,Tibia ,Quantitative computed tomography ,Breech Presentation ,Bone mineral ,bone mass ,Anthropometry ,medicine.diagnostic_test ,business.industry ,Obstetrics ,Cephalic presentation ,ALSPAC ,musculoskeletal system ,medicine.disease ,medicine.anatomical_structure ,Prenatal Exposure Delayed Effects ,Hip bone ,Body Composition ,Female ,Hip Joint ,030101 anatomy & morphology ,Presentation (obstetrics) ,fetal movement ,Tomography, X-Ray Computed ,business - Abstract
Summary: We compared bone outcomes in adolescents with breech and cephalic presentation. Tibia bone mineral content, density, periosteal circumference, and cross-sectional moment of inertia were lower in breech presentation, and females with breech presentation had lower hip CSA. These findings suggest that prenatal loading may exert long-lasting influences on skeletal development. Introduction: Breech position during pregnancy is associated with reduced range of fetal movement, and with lower limb joint stresses. Breech presentation at birth is associated with lower neonatal bone mineral content (BMC) and area, but it is unknown whether these associations persist into later life. Methods: We examined associations between presentation at onset of labor, and tibia and hip bone outcomes at age 17 years in 1971 participants (1062 females) from a UK prospective birth cohort that recruited > 15,000 pregnant women in 1991–1992. Cortical BMC, cross-sectional area (CSA) and bone mineral density (BMD), periosteal circumference, and cross-sectional moment of inertia (CSMI) were measured by peripheral quantitative computed tomography (pQCT) at 50% tibia length. Total hip BMC, bone area, BMD, and CSMI were measured by dual-energy X-ray absorptiometry (DXA). Results: In models adjusted for sex, age, maternal education, smoking, parity, and age, singleton/multiple births, breech presentation (n = 102) was associated with lower tibial cortical BMC (− 0.14SD, 95% CI − 0.29 to 0.00), CSA (− 0.12SD, − 0.26 to 0.02), BMD (− 0.16SD, − 0.31 to − 0.01), periosteal circumference (− 0.14SD, − 0.27 to − 0.01), and CSMI (− 0.11SD, − 0.24 to 0.01). In females only, breech presentation was associated with lower hip CSA (− 0.24SD, − 0.43 to 0.00) but not with other hip outcomes. Additional adjustment for potential mediators (delivery method, birthweight, gestational age, childhood motor competence and adolescent height and body composition) did not substantially affect associations with either tibia or hip outcomes. Conclusions: These findings suggest that prenatal skeletal loading may exert long-lasting influences on skeletal size and strength but require replication.
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- 2019
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27. Women’s Experiences of a Specialist Antenatal Service for Pregnancies After a Stillbirth or Neonatal Death: A Qualitative Interview Study and Social Return on Investment Analysis
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Louise Stephens, Alexander E. P. Heazell, Christine Hughes, Debbie M Smith, Suzanne Thomas, Tracey A Mills, and A. Michael Arundale
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Service (business) ,medicine.medical_specialty ,Qualitative interviews ,Family medicine ,medicine ,Social return on investment ,Neonatal death ,Psychology - Abstract
Background Pregnancy after the death of a baby is associated with a series of emotional and psychological challenges for pregnant women and their families. Specialist antenatal services have been proposed to address the increased biomedical and psychological risks in pregnancies after perinatal death. This study aimed to explore the pregnancy and postnatal experiences of women in a pregnancy after a perinatal death who were attending a specialist antenatal service and to evaluate the economic impact of the service.Methods To explore women’s views and experiences of care during their pregnancy this study used face-to-face semi-structured interviews following a topic guide comprising of four sections (history leading to care pathway, their experience of coping with new pregnancy after loss, support and advice for others). Following inductive thematic analysis, a deductive approach was taken to map themes to Stroebe and Schutt’s Dual Process Model of Grief.A Social Return on Investment (SROI) analysis informed by contributions from a subgroup of women and staff participants. Information was obtained from focus groups discussions, questionnaires and interviews. The SROI was reported as the ratio of the value generated by the clinic and the costs of providing the service.Results Thematic analysis of interviews (n=20) described how perinatal death was a quiet, unspoken subject and that navigating subsequent pregnancies relied on expecting the worst and hoping for the best. Mapping these themes onto the Dual Process Model of Grief found being pregnant complicated the grieving process, as increased awareness of the risk of stillbirth drew parents’ focus back to loss. Attendance at a specialist service was valued; SROI analysis found that for £1 invested, £6.10 of value was generated, mostly relating to the birth of a live baby, reduced negative psychological symptoms and fewer focussed contacts with health professionals.Conclusions Specialist antenatal care in pregnancies after perinatal death was viewed favourably by parents. Women’s experiences can be used to synthesise and develop models of care that aim to meet their needs but comparative studies are required to determine whether these models are superior to routine high-risk care and to identify which components are most valued.
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- 2021
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28. Pandemic stress and SARS-CoV-2 infection are associated with pathological changes at the maternal-fetal interface
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Dorothée Bouron-Dal Soglio, Sylvie Girard, Alexander E. P. Heazell, Dina El Demellawy, Solenn Dal Soglio, Kate Widdows, Marie-Eve Brien, Didier Menzies, Youssef Nasr, Camille Couture, Isabelle Boucoiran, and Megan C. Sharps
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Adult ,Male ,medicine.medical_specialty ,Canada ,Placenta Diseases ,Adolescent ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Placenta ,Psychological Distress ,Article ,Cohort Studies ,Young Adult ,Pregnancy ,Pandemic ,medicine ,Maternal fetal ,Humans ,Pregnancy Complications, Infectious ,Pathological ,Pandemics ,Obstetrics ,Chorangiosis ,business.industry ,SARS-CoV-2 ,Incidence (epidemiology) ,Infant, Newborn ,Pregnancy Outcome ,Obstetrics and Gynecology ,COVID-19 ,Middle Aged ,medicine.disease ,Infectious Disease Transmission, Vertical ,United Kingdom ,Coronavirus disease 2019 (COVID-19) ,medicine.anatomical_structure ,Reproductive Medicine ,Case-Control Studies ,Maternal-Fetal Relations ,Female ,France ,business ,Infection ,Pandemic stress ,Stress, Psychological ,Developmental Biology - Abstract
INTRODUCTION: The reported effects of SARS-CoV-2 on pregnancy outcomes are conflicting; studies frequently overlook the placenta, which is critical for the health of the mother and infant(s). This study aimed to determine the effect of pandemic stress ± SARS CoV-2 infection on placental histopathology. METHODS: Women were recruited in Canada (n = 69); France (n = 21) or in the UK (n = 25), between March and October 2020. Historic controls (N = 20) were also included. Placenta and fetal membrane samples were collected rapidly after delivery and were fixed and stained for histopathological analysis. Maternal demographical data and obstetric outcomes were recorded. RESULTS: Over 80% of the placentas from SARS-CoV-2+ pregnancies had histopathological abnormalities: predominantly structural (71-86%) or inflammatory (9-22%), depending on geographical location. Excessive fibrin was seen in all sites, whereas deciduitis (Canada), calcifications (UK), agglutinations and chorangiosis (France) predominated in different locations. The frequency of abnormalities was significantly higher than in SARS-CoV-2 negative women (50%, p
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- 2021
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29. Identification of factors associated with stillbirth in Zimbabwe - a cross sectional study
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Tina Lavender, Rebecca Smyth, Alexander E. P. Heazell, Kushupika Dube, Kieran Blaikie, and Chris J Sutton
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Zimbabwe ,medicine.medical_specialty ,Season of birth ,Cross-sectional study ,Reproductive medicine ,wa_395 ,Logistic regression ,Pregnancy ,Risk Factors ,wq_225 ,medicine ,Humans ,Past medical history ,Obstetrics ,business.industry ,Research ,Obstetrics and Gynecology ,Gynecology and obstetrics ,Odds ratio ,Stillbirth ,medicine.disease ,Cross-Sectional Studies ,RG1-991 ,Female ,Neonatal death ,business - Abstract
Introduction 98% of the 2.6 million stillbirths per annum occur in low and middle income countries. However, understanding of risk factors for stillbirth in these settings is incomplete, hampering efforts to develop effective strategies to prevent deaths. Methods A cross-sectional study of eligible women on the postnatal ward at Mpilo Hospital, Zimbabwe was undertaken between 01/08/2018 and 31/03/2019 (n = 1779). Data were collected from birth records for maternal characteristics, obstetric and past medical history, antenatal care and pregnancy outcome. A directed acyclic graph was constructed with multivariable logistic regression performed to fit the corresponding model specification to data comprising singleton pregnancies, excluding neonatal deaths (n = 1734), using multiple imputation for missing data. Where possible, findings were validated against all women with births recorded in the hospital birth register (n = 1847). Results Risk factors for stillbirth included: previous stillbirth (29/1691 (2%) of livebirths and 39/43 (91%) of stillbirths, adjusted Odds Ratio (aOR) 2628.9, 95% CI 342.8 to 20,163.0), antenatal care (aOR 44.49 no antenatal care vs. > 4 antenatal care visits, 95% CI 6.80 to 291.19), maternal medical complications (aOR 7.33, 95% CI 1.99 to 26.92) and season of birth (Cold season vs. Mild aOR 14.29, 95% CI 3.09 to 66.08; Hot season vs. Mild aOR 3.39, 95% CI 0.86 to 13.27). Women who had recurrent stillbirth had a lower educational and health status (18.2% had no education vs. 10.0%) and were less likely to receive antenatal care (20.5% had no antenatal care vs. 6.6%) than women without recurrent stillbirth. Conclusion The increased risk in women who have a history of stillbirth is a novel finding in Low and Middle Income Countries (LMICs) and is in agreement with findings from High Income Countries (HICs), although the estimated effect size is much greater (OR in HICs ~ 5). Developing antenatal care for this group of women offers an important opportunity for stillbirth prevention.
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- 2021
30. Advanced maternal age is associated with placental oxidative damage but this is not exacerbated in the presence of Fetal Growth Restriction
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Alexander E. P. Heazell, Michelle Desforges, Xiaojia Li, and Mark Dilworth
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Andrology ,Oxidative damage ,Reproductive Medicine ,business.industry ,Fetal growth ,Obstetrics and Gynecology ,Medicine ,Advanced maternal age ,business ,Developmental Biology - Published
- 2021
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31. Assessing recurrence of chronic histiocytic intervillositis in treated pregnancies and the potential role of maternal anti-HLA antibodies
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Ian P. Crocker, Alexander E. P. Heazell, Chloe A. Brady, and Laura Ford
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Reproductive Medicine ,Chronic histiocytic intervillositis ,business.industry ,Immunology ,Obstetrics and Gynecology ,Medicine ,Hla antibodies ,business ,Developmental Biology - Published
- 2021
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32. Morphological Changes in Placentas from Prolonged Pregnancy
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Alan Kerby, Stacey Lee, Alexander E. P. Heazell, Megan C. Sharps, and Amber Carroll
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Andrology ,Pregnancy ,Reproductive Medicine ,business.industry ,medicine ,Obstetrics and Gynecology ,medicine.disease ,business ,Developmental Biology - Published
- 2021
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33. A prospective cohort study providing insights for markers of adverse pregnancy outcome in older mothers
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Samantha C. Lean, Rebecca Jones, Stephen A Roberts, and Alexander E. P. Heazell
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Adult ,medicine.medical_specialty ,Aging ,Placental dysfunction ,Logistic regression ,Cohort Studies ,Pregnancy ,Risk Factors ,medicine ,Humans ,Advanced maternal age ,Prospective Studies ,Prospective cohort study ,Inflammation ,Obstetrics ,business.industry ,Research ,Pregnancy Outcome ,Obstetrics and Gynecology ,Gynecology and obstetrics ,Odds ratio ,Stillbirth ,medicine.disease ,Confidence interval ,United Kingdom ,Hormones ,Oxidative Stress ,ROC Curve ,Case-Control Studies ,Infant, Small for Gestational Age ,RG1-991 ,Intensive Care, Neonatal ,Gestation ,Small for gestational age ,Premature Birth ,Female ,Inflammation Mediators ,business ,Placental Hormones ,Biomarkers ,Maternal Age - Abstract
Background Advanced maternal age (≥35 years) is associated with increased rates of adverse pregnancy outcome. Better understanding of underlying pathophysiological processes may improve identification of older mothers who are at greatest risk. This study aimed to investigate changes in oxidative stress and inflammation in older women and identify clinical and biochemical predictors of adverse pregnancy outcome in older women. Methods The Manchester Advanced Maternal Age Study (MAMAS) was a multicentre, observational, prospective cohort study of 528 mothers. Participants were divided into three age groups for comparison 20–30 years (n = 154), 35–39 years (n = 222) and ≥ 40 years (n = 152). Demographic and medical data were collected along with maternal blood samples at 28 and 36 weeks’ gestation. Multivariable analysis was conducted to identify variables associated with adverse outcome, defined as one or more of: small for gestational age ( Results Maternal smoking was associated with adverse outcome irrespective of maternal age (Adjusted Odds Ratio (AOR) 4.22, 95% Confidence Interval (95%CI) 1.83, 9.75), whereas multiparity reduced the odds (AOR 0.54, 95% CI 0.33, 0.89). In uncomplicated pregnancies in older women, lower circulating anti-inflammatory IL-10, IL-RA and increased antioxidant capacity (TAC) were seen. In older mothers with adverse outcome, TAC and oxidative stress markers were increased and levels of maternal circulating placental hormones (hPL, PlGF and sFlt-1) were reduced (p Conclusions This study identified alterations in circulating inflammatory and oxidative stress markers in older women with adverse outcome providing preliminary evidence of mechanistic links. Further, larger studies are required to determine if these markers can be developed into a predictive model of an individual older woman’s risk of adverse pregnancy outcome, enabling a reduction in stillbirth rates whilst minimising unnecessary intervention.
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- 2020
34. Chronic histiocytic intervillositis: A breakdown in immune tolerance comparable to allograft rejection?
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Chloe A. Brady, Charlotte Williams, Alexander E. P. Heazell, Ian P. Crocker, Megan C. Sharps, Amena Shelleh, and Gauri Batra
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Graft Rejection ,0301 basic medicine ,medicine.medical_specialty ,Placenta Diseases ,placenta ,medicine.medical_treatment ,miscarriage ,Immunology ,Reviews ,Review ,Autoimmune Diseases ,Miscarriage ,03 medical and health sciences ,0302 clinical medicine ,Pregnancy ,Immune Tolerance ,medicine ,Humans ,Immunology and Allergy ,Pathological ,Autoimmune disease ,030219 obstetrics & reproductive medicine ,Obstetrics ,business.industry ,Obstetrics and Gynecology ,Histiocytes ,Immunosuppression ,Intervillous space ,Allografts ,medicine.disease ,macrophages ,Pregnancy Complications ,HLA ,030104 developmental biology ,Reproductive Medicine ,Chronic histiocytic intervillositis ,Maternal Exposure ,Chronic Disease ,Female ,stillbirth ,Chorionic Villi ,business ,Pregnancy disorder - Abstract
Chronic histiocytic intervillositis (CHI) is a pregnancy disorder characterized by infiltration of maternal macrophages into the intervillous space of the human placenta, often with accompanying perivillous fibrin deposition. CHI is associated strongly with foetal growth restriction and increased risk of miscarriage and stillbirth. Although rare, affecting 6 in every 10 000 pregnancies beyond 12 weeks’ gestation, the rate of recurrence is high at 25%–100%. To date, diagnosis of CHI can only be made post‐delivery upon examination of the placenta due to a lack of diagnostic biomarkers, and criteria vary across publications. No treatment options have shown proven efficacy, and CHI remains a serious obstetric conundrum. Although its underlying aetiology is unclear, due to the presence of maternal macrophages and the reported increased incidence in women with autoimmune disease, CHI is hypothesized to be an inappropriate immune response to the semi‐allogeneic foetus. Given this lack of understanding, treatment approaches remain experimental with limited rationale. However, there is recent evidence that immunosuppression and antithrombotic therapies may be effective in preventing recurrence of associated adverse pregnancy outcomes. With similarities noted between the pathological features of CHI and acute rejection of solid organ transplants, further investigation of this hypothesis may provide a basis for tackling CHI and other immune‐related placental conditions. This review will explore parallels between CHI and allograft rejection and identify areas requiring further confirmation and exploitation of this comparison.
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- 2020
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35. Delayed delivery of the second twin in a dichorionic diamniotic twin pregnancy for 136 days
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Nicola R. Solomon and Alexander E. P. Heazell
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medicine.medical_specialty ,Second twin ,Obstetrics ,business.industry ,Twins ,Obstetrics and Gynecology ,Reproductive Medicine ,Dichorionic Diamniotic Twin Pregnancy ,Delayed delivery ,Pregnancy ,medicine ,Pregnancy, Twin ,Humans ,Female ,business - Published
- 2020
36. A systematic scoping review to identify the design and assess the performance of devices for antenatal continuous fetal monitoring
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Jayawan H B Wijekoon, Dexter J. L. Hayes, Kajal K. Tamber, Stephen J. Carey, and Alexander E. P. Heazell
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Embryology ,Maternal Health ,Cochrane Library ,Electrocardiography ,0302 clinical medicine ,Electronics Engineering ,Pregnancy ,Accelerometry ,Abdomen ,Medicine and Health Sciences ,Medicine ,030212 general & internal medicine ,Fetal Monitoring ,Fetal Movement ,030219 obstetrics & reproductive medicine ,Multidisciplinary ,Gestational age ,Obstetrics and Gynecology ,Prenatal Care ,Signal Processing, Computer-Assisted ,Heart Rate, Fetal ,Bioassays and Physiological Analysis ,Fetal movement ,Engineering and Technology ,Female ,Anatomy ,Research Article ,Biotechnology ,medicine.medical_specialty ,Science ,MEDLINE ,Equipment ,Fetal position ,Gestational Age ,Bioengineering ,Prenatal care ,CINAHL ,Research and Analysis Methods ,03 medical and health sciences ,Humans ,Amniotic fluid index ,Intensive care medicine ,Electrodes ,Measurement Equipment ,Fetuses ,business.industry ,Electrophysiological Techniques ,Biology and Life Sciences ,Reference Electrodes ,Women's Health ,Medical Devices and Equipment ,Cardiac Electrophysiology ,Electronics ,Accelerometers ,business ,Developmental Biology - Abstract
BackgroundAntepartum fetal monitoring aims to assess fetal development and wellbeing throughout pregnancy. Current methods utilised in clinical practice are intermittent and only provide a ‘snapshot’ of fetal wellbeing, thus key signs of fetal demise could be missed. Continuous fetal monitoring (CFM) offers the potential to alleviate these issues by providing an objective and longitudinal overview of fetal status. Various CFM devices exist within literature; this review planned to provide a systematic overview of these devices, and specifically aimed to map the devices’ design, performance and factors which affect this, whilst determining any gaps in development.MethodsA systematic search was conducted using MEDLINE, EMBASE, CINAHL, EMCARE, BNI, Cochrane Library, Web of Science and Pubmed databases. Following the deletion of duplicates, the articles’ titles and abstracts were screened and suitable papers underwent a full-text assessment prior to inclusion in the review by two independent assessors.ResultsThe literature searches generated 4,885 hits from which 43 studies were included in the review. Twenty-four different devices were identified utilising four suitable CFM technologies: fetal electrocardiography, fetal phonocardiography, accelerometry and fetal vectorcardiography. The devices adopted various designs and signal processing methods. There was no common means of device performance assessment between different devices, which limited comparison. The device performance of fetal electrocardiography was reduced between 28 to 36 weeks’ gestation and during high levels of maternal movement, and increased during night-time rest. Other factors, including maternal body mass index, fetal position, recording location, uterine activity, amniotic fluid index, number of fetuses and smoking status, as well as factors which affected alternative technologies had equivocal effects and require further investigation.ConclusionsA variety of CFM devices have been developed, however no specific approach or design appears to be advantageous due to high levels of inter-device and intra-device variability.
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- 2020
37. Associations between consumption of coffee and caffeinated soft drinks and late stillbirth-Findings from the Midland and North of England stillbirth case-control study
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Edwin A. Mitchell, Minglan Li, Devender Roberts, Lauren Rockliffe, John M. D. Thompson, Jayne Budd, Tomasina Stacey, Robin S. Cronin, Alexander E. P. Heazell, Rebecca E. Scott, Kate Timms, and Lesley M. E. McCowan
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Male ,Carbonated Beverages ,Coffee ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Pregnancy ,Environmental health ,Medicine ,Humans ,030212 general & internal medicine ,Late Stillbirth ,030219 obstetrics & reproductive medicine ,business.industry ,Case-control study ,Obstetrics and Gynecology ,Odds ratio ,Stillbirth ,medicine.disease ,Confidence interval ,United Kingdom ,Reproductive Medicine ,chemistry ,England ,Case-Control Studies ,Attributable risk ,Gestation ,Female ,business ,Caffeine - Abstract
Objective The consumption of caffeinated drinks and soft drinks is widespread in society, including by pregnant women. Data regarding the association of caffeine intake and stillbirth are varied. We aimed to investigate the degree of consumption of caffeinated drinks or soft drinks in the last four weeks of pregnancy in women who experienced a late stillbirth compared to women with ongoing live pregnancies at similar gestation. Influences on maternal caffeine intake and soft drink consumption during pregnancy were also investigated. Study Design A case-control study undertaken in 41 maternity units in the United Kingdom. Cases were women who had a singleton non-anomalous stillbirth ≥28 weeks’ gestation (n = 290) and controls were women with an ongoing pregnancy at the time of interview (n = 729). Data were collected using an interviewer-administered questionnaire which included questions regarding consumption of a variety of caffeinated drinks and soft drinks in the last four weeks of pregnancy as well as other behaviours (e.g. cigarette smoking). Results Multivariable analysis adjusting for co-existing demographic and behavioural factors found the consumption of instant coffee, energy drinks and cola were associated with increased risk of stillbirth. There was an independent association between caffeine intake and late stillbirth (adjusted Odds Ratio 1.27, 95 % Confidence Interval (95 %CI) 1.14, 1.43 for each 100 mg increment/day). 15 % of cases and 8% of controls consumed more than the World Health Organisation (WHO) recommendation (>300 mg of caffeine/day; aOR 2.30, 95 % CI 1.40, 4.24). The population attributable risk for stillbirth associated with >300 mg of caffeine/day was 7.4 %. The majority of respondents reduced caffeine consumption in pregnancy. Midwives and internet resources were the most frequently used sources of information which influenced maternal behaviour with regard to soft drinks and caffeine, and this did not differ between cases and controls. Conclusions Women should be informed that consumption of caffeine during pregnancy is associated with increased risk of stillbirth, particularly at levels greater than recommended by the WHO (>300 mg/day). Recommendations from midwives and internet-based resources are likely to be the most effective means to influence maternal behaviour.
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- 2020
38. Umbilical cord characteristics and their association with adverse pregnancy outcomes: A systematic review and meta-analysis
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Laura Clapham, Julia Banks, Jane Warland, Dexter J. L. Hayes, Robert W. Bendon, Alexander E. P. Heazell, Mana M. Parast, Junichi Hasegawa, Ryckman, Kelli K, Hayes, Dexter JL, Warland, Jane, Parast, Mana M, Bendon, Robert W, Hasegawa, Junichi, Banks, Julia, Clapham, Laura, and Heazell, Alexander EP
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Embryology ,Maternal Health ,Reproductive health and childbirth ,Umbilical cord ,Nuchal Cord ,Umbilical Cord ,Diagnostic Radiology ,0302 clinical medicine ,Pregnancy ,Ultrasound Imaging ,Medicine and Health Sciences ,030212 general & internal medicine ,Prospective Studies ,030219 obstetrics & reproductive medicine ,Multidisciplinary ,Obstetrics ,Radiology and Imaging ,Obstetrics and Gynecology ,Stillbirth ,medicine.anatomical_structure ,Research Design ,Meta-analysis ,Cohort ,Medicine ,Gestation ,Female ,umbilical cord abnormalities (UCA) ,Nuchal cord ,Stillbirths ,Research Article ,medicine.medical_specialty ,Cord ,General Science & Technology ,Imaging Techniques ,Science ,MEDLINE ,Research and Analysis Methods ,03 medical and health sciences ,Diagnostic Medicine ,medicine ,Humans ,Fetal Death ,Retrospective Studies ,business.industry ,Biology and Life Sciences ,medicine.disease ,Brain Disorders ,stillbirths ,Pregnancy Complications ,Birth ,Women's Health ,business ,Developmental Biology - Abstract
ObjectiveCurrent data on the role of the umbilical cord in pregnancy complications are conflicting; estimates of the proportion of stillbirths due to cord problems range from 3.4 to 26.7%. A systematic review and meta-analysis were undertaken to determine which umbilical cord abnormalities are associated with stillbirth and related adverse pregnancy outcomes.MethodsMEDLINE, EMBASE, CINAHL and Google Scholar were searched from 1960 to present day. Reference lists of included studies and grey literature were also searched. Cohort, cross-sectional, or case-control studies of singleton pregnancies after 20 weeks' gestation that reported the frequency of umbilical cord characteristics or cord abnormalities and their relationship to stillbirth or other adverse outcomes were included. Quality of included studies was assessed using NIH quality assessment tools. Analyses were performed in STATA.ResultsThis review included 145 studies. Nuchal cords were present in 22% of births (95% CI 19, 25); multiple loops of cord were present in 4% (95% CI 3, 5) and true knots of the cord in 1% (95% CI 0, 1) of births. There was no evidence for an association between stillbirth and any nuchal cord (OR 1.11, 95% CI 0.62, 1.98). Comparing multiple loops of nuchal cord to single loops or no loop gave an OR of 2.36 (95% CI 0.99, 5.62). We were not able to look at the effect of tight or loose nuchal loops. The likelihood of stillbirth was significantly higher with a true cord knot (OR 4.65, 95% CI 2.09, 10.37).ConclusionsTrue umbilical cord knots are associated with increased risk of stillbirth; the incidence of stillbirth is higher with multiple nuchal loops compared to single nuchal cords. No studies reported the combined effects of multiple umbilical cord abnormalities. Our analyses suggest specific avenues for future research.
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- 2020
39. The role of maternal awareness of reduced fetal movements to reduce perinatal mortality remains unclear
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Alexander E. P. Heazell
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Pregnancy ,medicine.medical_specialty ,Perinatal mortality ,Obstetrics ,business.industry ,Perinatal Death ,MEDLINE ,Reduced fetal movements ,Obstetrics and Gynecology ,Stillbirth ,medicine.disease ,Fetal movement ,medicine ,Humans ,Female ,business ,Fetal Movement ,Perinatal Mortality - Published
- 2020
40. Standard care informed by the result of a placental growth factor blood test versus standard care alone in women with reduced fetal movement at or after 36+0 weeks’ gestation: a pilot randomised controlled trial
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Alexander E. P. Heazell, Eleanor J Mitchell, Sam Ratcliffe, C. Storey, Lucy Bradshaw, Peter J. Godolphin, and Lindsay Armstrong-Buisseret
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medicine.medical_specialty ,Placental biomarker ,Adverse pregnancy outcome ,Population ,Psychological intervention ,placental dysfunction ,Medicine (miscellaneous) ,Placental dysfunction ,030204 cardiovascular system & hematology ,Feasibility study ,law.invention ,03 medical and health sciences ,sFlt-1/PlGF ratio ,0302 clinical medicine ,Randomized controlled trial ,law ,Medicine ,Blood test ,030212 general & internal medicine ,education ,Reduced fetal movement ,lcsh:R5-920 ,Pregnancy ,education.field_of_study ,medicine.diagnostic_test ,business.industry ,Obstetrics ,feasibility study ,medicine.disease ,placental biomarker ,Fetal movement ,Gestation ,Biomarker (medicine) ,adverse pregnancy outcome ,lcsh:Medicine (General) ,business - Abstract
Background Biomarkers of placental function can potentially aid the diagnosis and prediction of pregnancy complications. This randomised controlled pilot trial assessed whether for women with reduced fetal movement (RFM), intervention directed by the measurement of a placental biomarker in addition to standard care was feasible and improved pregnancy outcome compared with standard care alone. Methods Women aged 16–50 years presenting at eight UK maternity units with RFM between 36+0 and 41+0 weeks’ gestation with a viable singleton pregnancy and no indication for immediate delivery were eligible. Participants were randomised 1:1 in an unblinded manner to standard care and a biomarker blood test result revealed and acted on (intervention arm) or standard care where the biomarker result was not available (control arm). The objectives were to determine the feasibility of a main trial by recruiting 175–225 participants over 9 months and to provide proof of concept that informing care by measurement of placental biomarkers may improve outcome. Feasibility was assessed via the number of potentially eligible women, number recruited, reasons for non-recruitment and compliance. Proof of concept outcomes included the rates of the induction of labour and caesarean birth, and a composite adverse pregnancy outcome. Results Overall, 2917 women presented with RFM ≥ 36 weeks, 352 were approached to participate and 216 (61%) were randomised (intervention n = 109, control n = 107). The main reason for not approaching women was resource/staff issues (n = 1510). Ninety-seven women declined the trial, mainly due to not liking blood tests (n = 24) or not wanting to be in a trial (n = 21). Compliance with the trial interventions was 100% in both arms. Labour was induced in 97 (45%) participants (intervention n = 49, control n = 48), while 17 (9%) had planned caesarean sections (intervention n = 9, control n = 8). Overall, 9 (8%) babies in the intervention arm had the composite adverse pregnancy outcome versus 4 (4%) in the control arm. Conclusions A main trial using a placental biomarker in combination with delivery, as indicated by the biomarker, in women with RFM is feasible. The frequency of adverse outcomes in this population is low, hence, a large sample size would be required along with consideration of the most appropriate outcome measures. Trial registration ISRCTN, ISRCTN12067514; registered 8 September 2017.
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41. When the Fetus Goes Still and the Birth Is Tragic: The Role of the Placenta in Stillbirths
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Nicole, Graham and Alexander E P, Heazell
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Pregnancy Complications ,Pregnancy ,Placenta ,Humans ,Female ,Gestational Age ,Stillbirth ,Abruptio Placentae ,Fetal Death - Abstract
Because of the critical role that placental structure and function plays during pregnancy, abnormal placental structure and function is closely related to stillbirth: when an infant dies before birth. However, understanding the role of the placental and specific lesions is incomplete, in part because of the variation in definitions of lesions and in classifying causes of stillbirths. Nevertheless, placental abnormalities are seen more frequently in stillbirths than live births, with placental abruption, chorioamnionitis, and maternal vascular malperfusion most commonly reported. Critically, some placental lesions affect the management of subsequent pregnancies. Histopathological examination of the placenta is recommended following stillbirth.
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- 2020
42. Development and Validation of Multivariable Risk Prediction Models for Adverse Maternal and Neonatal Outcomes in Severe Preeclampsia: Findings from a Cross-Sectional Study in a Low-Resource Setting at Mpilo Central Hospital, Bulawayo, Zimbabwe
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Hausitoe Nare, Brian Jones, Alexander E. P. Heazell, Desmond Mwembe, and Solwayo Ngwenya
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Pregnancy ,medicine.medical_specialty ,Referral ,business.industry ,Cross-sectional study ,Obstetrics ,Birth weight ,Gestational age ,Logistic regression ,medicine.disease ,medicine ,Global health ,Population study ,business - Abstract
Background: Hypertensive disorders of pregnancy are major causes of global maternal, fetal and neonatal morbidity and mortality. This research aimed to develop and validate multivariable prediction models for composite adverse maternal outcomes and neonatal outcomes in severe preeclampsia for use in low-resource settings. Methods: This was a retrospective cross-sectional study. Predictor variables with a p
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- 2020
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43. No 369 - Prise en charge de la grossesse aprés une mortinaissance
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Alexander E. P. Heazell, Megan E. Fockler, Jon Barrett, Noor Niyar N. Ladhani, and Louise Stephens
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03 medical and health sciences ,030219 obstetrics & reproductive medicine ,0302 clinical medicine ,business.industry ,Obstetrics and Gynecology ,Medicine ,030212 general & internal medicine ,business ,Humanities - Abstract
RESUME Objectif L'objectif principal de la presente declaration de consensus est d'elaborer des enonces de consensus qui guideront la pratique clinique et des recommandations pour les soins prenataux et les soins intrapartum, et les considerations psychosociales dont il faut tenir compte pour prendre soin des femmes enceintes ayant des antecedents de mortinaissance. Utilisateurs cibles Les cliniciens participant a la prise en charge obstetrique des femmes ayant des antecedents de mortinaissance ou d'autres formes de deces perinatal. Population cible Les femmes et les familles recevant des soins apres une grossesse s'etant soldee par une mortinaissance ou une autre forme de deces perinatal. Evidence La presente directive clinique resume la litterature publiee et enonce un consensus general sur la prise en charge des grossesses suivant une mortinaissance ou un deces perinatal. Nous avons interroge les bases de donnees MEDLINE, Embase et Cochrane au moyen des mots-cles : « previous stillbirth », « perinatal loss » et « subsequent pregnancy ». Nous avons ensuite etudie les resultats et lu les articles pertinents. Nous avons egalement consulte les references des articles retenus et les documents citant des etudes pertinentes. Les donnees ont ensuite ete presentees pendant une reunion de consensus, et les enonces ont ete formules. En raison du manque de donnees probantes, nous avons egalement consulte les cheminements de soins de cliniques specialisees. Validation Le contenu et les lignes directrices ont ete elabores par les auteurs principaux en consultation avec les participants a la rencontre. Le Conseil d'administration de la Societe des obstetriciens et gynecologues du Canada a approuve la version finale avant publication. La qualite des donnees probantes a ete evaluee au moyen des criteres de l'approche GRADE (Grading of Recommendations Assessment, Development and Evaluation) [tableau 1]. L'interpretation des recommandations solides et conditionnelles est decrite dans le tableau 2. Le resume des conclusions peut etre fourni sur demande. Avantages, inconvenients, couts Nous avons explore une approche multidisciplinaire de prestation des soins prenataux et intrapartum aux femmes et aux familles ayant des antecedents de mortinaissance ou de deces perinatal. Bien qu'il manque de donnees probantes dans ce domaine, certains membres du groupe de travail fournissent ces soins a des femmes et a des familles dans plusieurs pays et nous ont fait part de leurs connaissances et de leurs experiences dans le but de guider les soins. Mis-a-jour Une revue des donnees probantes sera menee cinq ans apres la publication de la presente directive clinique afin d'evaluer si une mise a jour complete ou partielle s'impose. Cependant, si de nouvelles donnees probantes importantes sont publiees avant la fin du cycle de cinq ans, le processus pourrait etre accelere afin que certaines recommandations soient mises a jour rapidement. Commanditaires La presente directive clinique a ete elaboree a l'aide de ressources financees par la Societe des obstetriciens et gynecologues du Canada et le Programme pour les femmes et les bebes du Centre Sunnybrook des sciences et la sante tableau 1,2. Declarations sommaires et recommandations 1Le principal facteur de risque de mortinaissance recurrente est le fait d'avoir des antecedents de mortinaissance. Le risque de recurrence des femmes peut etre stratifie en fonction de la cause connue de la mortinaissance initiale et des autres facteurs de risque maternels connus (qualite des preuves : elevee). 2Au moment de la mortinaissance, des tests devraient etre menes selon le tableau clinique. Tous les parents devraient se voir offrir une autopsie ou un examen equivalent, un examen pathologique du placenta, un depistage genetique de source fœtale et une recherche d'hemorragie fœto-maternelle (qualite des preuves : moyenne). 3Les femmes ayant des antecedents de mortinaissance presentent aussi un risque accru d'autres issues defavorables de la grossesse, comme l'accouchement premature, le poids insuffisant a la naissance et le decollement placentaire (qualite des preuves : moyenne). 4Lors de la visite initiale, si la mortinaissance precedente n'a pas fait l'objet d'une investigation adequate, il convient de noter qu'aucun test universel n'est recommande. Les antecedents cliniques et les examens au moment de la mortinaissance devraient guider les tests au cas par cas (qualite des preuves : moyenne). 5L'evaluation biochimique de la fonction placentaire et l'examen Doppler de l'artere uterine systematiques ne sont pas universellement recommandes en raison de leur faible valeur predictive et de leur inutilite dans l'ajustement de la stratification du risque, puisque le risque de recurrence est deja eleve (qualite des preuves : moyenne). 6L'aspirine a faible dose peut reduire le risque de deces perinatal chez les femmes a risque d'insuffisance placentaire. Certaines femmes ayant des antecedents de mortinaissance peuvent se trouver dans cette categorie (qualite des preuves : elevee). 7Les femmes ayant des antecedents de mortinaissance peuvent etre a risque de retard de croissance fœtal durant la grossesse subsequente et peuvent tirer avantage d'echographies repetees pour mesurer la croissance (qualite des preuves : elevee). Bien qu'il y ait peu de donnees probantes appuyant les examens systematiques du profil biophysique, la surveillance accrue peut etre benefique pour certaines femmes et leurs familles, mais elle peut causer de l'anxiete chez d'autres. La frequence et le calendrier de surveillance fœtale devraient etre determines en fonction des antecedents medicaux, des circonstances entourant la mortinaissance initiale et des preferences des parents (qualite des preuves : moyenne). 8Les decisions quant au moment de l'accouchement devraient tenir compte des circonstances entourant la mortinaissance precedente, du tableau clinique de la grossesse en cours et de l'etat emotionnel de la femme et de sa famille, ainsi que des inconvenients connus de l'accouchement avant 39 semaines. Dans certains cas precis, l'accouchement a terme precoce (de 37 a 39 semaines) peut etre pertinent. Il n'existe pas de donnees probantes appuyant l'accouchement avant 37 semaines pour le facteur de risque de mortinaissance seulement (qualite des preuves : moyenne). 9Les familles sont particulierement touchees par une mortinaissance anterieure. Cet evenement change leur vie, et entraine des couts psychologiques, physiques et sociaux continus qui persistent durant la grossesse subsequente et par la suite. Les besoins psychosociaux des familles sont accrus durant les grossesses suivant une mortinaissance. Les systemes et processus actuels de prise en charge de la grossesse devraient chercher a bien repondre a ces besoins (qualite des preuves : elevee). 10La prestation adequate des soins comprend du soutien des soins et des services medicaux et psychosociaux coherents et prodigues en temps opportun par des equipes de soins competentes et connues des familles qui connaissent bien les consequences persistantes d'une mortinaissance sur les grossesses subsequentes. Tous les soins offerts aux familles ayant vecu une mortinaissance devraient etre axes sur la protection et la promotion de la sante de la femme et de sa famille, et sur les choix eclaires (qualite des preuves : elevee). 11Le soutien par les pairs est souvent benefique pour les parents qui vivent une grossesse apres une mortinaissance. Les fournisseurs de soins devraient discuter des options de soutien par les pairs et les encourager a s'en prevaloir (qualite des preuves : moyenne). 12Les femmes et les familles qui ont vecu une mortinaissance sont tres susceptibles d'avoir besoin de soutien emotionnel, et toute la famille devrait se voir offrir des possibilites de soutien durant la grossesse et la periode postpartum. De nombreuses sequelles psychologiques sont associees aux grossesses suivant une mortinaissance, notamment la depression, le stress post-traumatique et l'anxiete. Chez certaines personnes, des taux eleves de symptomes d'anxiete et de depression sont presents tout au long de la grossesse et apres la naissance. Les reactions au deuil sont aussi variees et devraient etre reconnues. Les fournisseurs de soins devraient faire valoir les forces de la famille et offrir un depistage psychosocial, un suivi cible, des aiguillages et un traitement, au besoin (qualite des preuves : elevee).
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44. The structure and utility of the placental pathology report
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Alexander E. P. Heazell, W. Tony Parks, Gitta Turowski, Anne Flem Jacobsen, and Susan Arbuckle
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Microbiology (medical) ,medicine.medical_specialty ,Placenta Diseases ,Pathology and Forensic Medicine ,Cerebral palsy ,03 medical and health sciences ,0302 clinical medicine ,Pregnancy ,Diabetes mellitus ,Placenta ,Pathology ,medicine ,Placental pathology ,Humans ,Immunology and Allergy ,Pathological ,Fetus ,030219 obstetrics & reproductive medicine ,business.industry ,Obstetrics ,General Medicine ,medicine.disease ,Pathophysiology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,embryonic structures ,Female ,business - Abstract
The placenta is one of the most exciting organs. It is dynamic; its morphology and function continuously develop and adjust over its brief life span. It mediates the physiology of two distinct yet highly interconnected individuals. The pathology that develops in the placenta, and the adaptations the placenta undergoes to mitigate this pathology, may influence the later life health of the mother and baby (Circ Res, 116, 2015, 715; Hum Reprod Update, 17, 2011, 397; Nutr Rev 71, 2013, S88; Placenta, 36, 2015, S20). Pathological placenta examination may reveal macroscopic and microscopic patterns that provide valuable information to the obstetricians, neonatologists, and pediatricians caring for the family. The placenta often plays a key role in understanding adverse fetal outcomes such as hypoxic brain injury, cerebral palsy, fetal growth restriction, stillbirth, and neonatal death (Placenta, 35, 2014, 552; Placenta, 52, 2017, 58; Placenta, 30, 2009, 700; Obstet Gynecol, 114, 2009, 809; Clin Perinatol, 33, 2006, 503; Pediatr Dev Pathol, 11, 2008, 456; Arch Pathol Lab Med, 124, 2000, 1785). Moreover, it may help to understand the pathophysiology of pregnancy, improve management of subsequent pregnancies, and assist in medicolegal assessment. Placental pathologic examination may even provide evidence of susceptibility to adult-onset diseases such as diabetes (Pediatr Dev Pathol, 6, 2003, 54; Diabetes Metab, 36, 2010, 682; BJOG, 113, 2006, 1126; Int J Gynaecol Obstet, 104, 2009, S25; Zentralbl Gynakol, 97, 1975, 875). Pathologic examination of the placenta may thus be of tremendous value, particularly for those women experiencing an adverse pregnancy outcome. However, this potential utility may be entirely wasted, if the findings are not communicated in an effective manner to the appropriate clinicians. An optimized, readily understandable report of pathological findings is essential for clinical utility.
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- 2018
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45. 'They told me all mothers have worries', stillborn mother's experiences of having a ‘gut instinct’ that something is wrong in pregnancy: Findings from an international case–control study
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Jayne Budd, Edwin A. Mitchell, Alexander E. P. Heazell, Tomasina Stacey, Jane Warland, Louise M. O'Brien, Christin Coomarasamy, Warland, Jane, Heazell, Alexander EP, Stacey, Tomasina, Coomarasamy, Christin, Budd, Jayne, Mitchell, Edwin author, and O'Brien, Louise
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Adult ,media_common.quotation_subject ,Mothers ,Developmental psychology ,Cohort Studies ,03 medical and health sciences ,Maternity care ,0302 clinical medicine ,Pregnancy ,Surveys and Questionnaires ,Maternity and Midwifery ,Negativity bias ,medicine ,Humans ,Prospective Studies ,030212 general & internal medicine ,maternal intuition ,media_common ,Instinct ,030219 obstetrics & reproductive medicine ,Recall ,Case-control study ,Obstetrics and Gynecology ,Stillbirth ,medicine.disease ,Mother-Child Relations ,gut feeling ,Feeling ,Content analysis ,Case-Control Studies ,fetal movements ,stillbirth ,Female ,Grief ,Psychology - Abstract
Objective: To describe and explore 'gut instinct' that something was wrong in women who identified that they experienced gut instinct during pregnancy. Method: A case-control study utilising an international web-based questionnaire. Stillborn cases ( n = 146) and liveborn controls ( n = 234) answered the gut instinct question within 30 days of the pregnancy ending. Of those, 84 cases and 27 controls also provided qualitative comment data. Descriptive statistics were used for the question, with a fixed option and summative content analysis was used to analyse the comment data. Findings: In all, 110 (75%) of the stillborn cases answered "yes" to the gut instinct question vs only 28 (12%) of the controls who had a livebirth meaning the risk of stillbirth was 22.5 fold higher in those who experience "gut instinct" than in those who do not experience this feeling. Four themes were identified from the comment data namely: When the gut instinct occurred; How the gut instinct made the woman feel; Dreams and other related phenomena; Reassured by someone or something. Conclusions: Women who had a stillborn baby reported a "gut instinct" that something was wrong more frequently than mothers of a live born baby. Our findings may be influenced by recall negativity bias, and a prospective study is needed to confirm or refute our findings. The possibility that "maternal intuition" exists during pregnancy and responds to changes in fetal or placental health merits further exploration. Implications for practice: Maternity care providers should be alert to the woman when she expresses intuitive feelings, as well as asking her to report her concerns and act appropriately to assess and manage fetal wellbeing. Refereed/Peer-reviewed
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46. Improved management of stillbirth using a care pathway
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Alexander E. P. Heazell, Elizabeth Martindale, Antony John Tomlinson, and Karen Bancroft
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medicine.medical_specialty ,Evidence-based practice ,Health Service Quality Assurance, Evidence-based practice ,media_common.quotation_subject ,Audit ,Health Professions, Clinical effectiveness ,Health Service Quality Assurance, Teamwork ,Unit (housing) ,03 medical and health sciences ,0302 clinical medicine ,Nursing ,Health care ,medicine ,Care pathway ,030212 general & internal medicine ,Practical implications ,media_common ,Teamwork ,030219 obstetrics & reproductive medicine ,business.industry ,Health Professions, Midwifery ,Health Policy ,Health Service Quality Assurance ,Integrated care ,Obstetrics ,Family medicine ,Business, Management and Accounting (miscellaneous) ,Health Service Quality Assurance, Clinical guidance ,business - Abstract
Purpose Each year approximately 3,200 women have a stillbirth in the UK. Although national evidence-based guidance has existed since 2010, case reviews continue to identify suboptimal clinical care and communication with parents. Inconsistencies in management include induction and management of labour and the frequency of investigation after stillbirth. The paper aims to discuss these issues. Design/methodology/approach An audit of stillbirths was performed in 2014 in 13 maternity units in the North West of England, this confirmed variation in practice described nationally. An integrated care pathway (ICP) was developed from national guidelines to enable optimal care for the management of stillbirth, reduce variation, standardise investigations and coordinate patient-focussed care. This was launched in 2015 and updated in 2016 to resolve the issues that were apparent after implementation. Findings Each participating unit had commenced using the ICP by May 2015. Following implementation there were changes in care, most notably from diverse methods for the induction of labour to guideline-directed induction of labour. There were trends towards better care in terms of information given, choices offered, more appropriate analgesia in labour and improved post-delivery investigation for cause. Staff feedback about the ICP was positive. Practical implications The use of this ICP improved care for women who had a stillbirth and their families. Issues with implementing a changed care pathway meant that further iterations were required, ongoing improvement is expected following the refinement of the ICP. Originality/value ICPs have been used for various clinical conditions. However, this is the first example of their use in women who had a stillbirth.
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47. Care of pregnant women with decreased fetal movements: Update of a clinical practice guideline for Australia and New Zealand
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Alexander E. P. Heazell, Susan McDonald, Lisa M. Daly, Yogesh Chadha, Frederik Frøen, Kassam Mahomed, Glenn Gardener, Wendy Burton, Vicki Flenady, Victoria Bowring, David Ellwood, Adrienne Gordon, Jane E. Norman, and Jeremy Oats
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Pregnancy ,medicine.medical_specialty ,030219 obstetrics & reproductive medicine ,business.industry ,media_common.quotation_subject ,Obstetrics and Gynecology ,Decreased fetal movement ,General Medicine ,Guideline ,Prenatal care ,medicine.disease ,Clinical Practice ,03 medical and health sciences ,0302 clinical medicine ,Perinatal health ,Excellence ,Family medicine ,Fetal movement ,medicine ,030212 general & internal medicine ,business ,media_common - Abstract
The National Health and Medical Research Council (NHMRC) Centre of Research Excellence in Stillbirth and the Perinatal Society of Australia and New Zealand (PSANZ) have recently partnered in updating an important clinical practice guideline, Care of pregnant women with decreased fetal movements. This guideline offers 12 recommendations and a suggested care pathway, with the aim to improve the quality of care for women reporting decreased fetal movements through an evidence-based approach. Adoption of the guideline by clinicians and maternity hospitals could result in earlier identification of higher-risk pregnancies, improved perinatal health outcomes for women and their babies, and reduced stillbirth rates.
- Published
- 2018
- Full Text
- View/download PDF
48. Interventions to increase maternal awareness of fetal movements no more effective than standard care
- Author
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Alexander E. P. Heazell
- Subjects
medicine.medical_specialty ,Fetus ,Standard care ,business.industry ,medicine ,Psychological intervention ,Humans ,Obstetrics and Gynecology ,Awareness ,Intensive care medicine ,business ,Fetal Movement - Published
- 2021
- Full Text
- View/download PDF
49. Placental expression of 8 microRNAs identified as potential upstream regulators of estrogen related receptor γ (ERRγ) in pregnancies complicated by fetal growth restriction
- Author
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Zhiyong Zou, Lynda K. Harris, Alexander E. P. Heazell, and Karen Forbes
- Subjects
Estrogen-related receptor ,Reproductive Medicine ,microRNA ,Fetal growth ,Placental expression ,Obstetrics and Gynecology ,Upstream (networking) ,Biology ,Developmental Biology ,Cell biology - Published
- 2021
- Full Text
- View/download PDF
50. Understanding the associations and significance of fetal movements in overweight or obese pregnant women: a systematic review
- Author
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Lesley M. E. McCowan, John M. D. Thompson, Billie Bradford, Alexander E. P. Heazell, and Christopher J. D. McKinlay
- Subjects
medicine.medical_specialty ,Statistics as Topic ,Decreased fetal movement ,Overweight ,03 medical and health sciences ,0302 clinical medicine ,Pregnancy ,medicine ,Body Size ,Humans ,Obesity ,030212 general & internal medicine ,Fetal Movement ,Gynecology ,Fetus ,030219 obstetrics & reproductive medicine ,business.industry ,Obstetrics ,Obstetrics and Gynecology ,General Medicine ,medicine.disease ,Pregnancy Complications ,Fetal movement ,Female ,Observational study ,medicine.symptom ,business ,Cohort study - Abstract
Introduction Presentation with decreased fetal movement (DFM) is associated with fetal growth restriction and stillbirth. Some studies report that DFM is frequent among overweight or obese mothers. We aimed to determine the significance and associations of fetal movements in women of increased body size. Material and methods This systematic review was conducted in accordance with the PRISMA statement and the protocol was registered with PROSPERO (CRD42016046352). Major databases were explored from inception to September 2017, using a predefined search strategy. We restricted inclusion to studies published in English and considered studies of any design that compared fetal movements in women of increased and normal body size. Two authors independently extracted data and assessed quality. Results We included 23 publications from 19 observational studies; data were extracted from 10 studies. Increased maternal body size was not associated with altered perception of fetal movement (four studies, 95 women, very low-quality evidence), but was associated with increased presentation for DFM (two cohort studies, 20 588 women, OR 1.56, 95% CI 1.27-1.92: three case-control studies, 3445 women, OR 1.32, 95% CI 1.12-1.54; low-quality evidence). Among women with DFM, increased maternal body size was associated with increased risk of stillbirth and fetal growth restriction (one study, 2168 women, very low-quality evidence). Conclusions This systematic review identified limited evidence that women with increased body size are more likely to present with DFM but do not have impaired perception of fetal movements. In women with DFM, increased body size is associated with worse pregnancy outcome, including stillbirth.
- Published
- 2017
- Full Text
- View/download PDF
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