Multimorbidity in pregnancy: Epidemiology and core outcome set

Background: Women are increasingly entering pregnancy with two or more long-term physical or mental health conditions. This can impact on the outcomes for the pregnant women and her offspring. This thesis aims to (i) describe the epidemiology of multimorbidity in pregnancy in the United Kingdom (UK) and (ii) develop a core outcome set for studies of pregnant women with multimorbidity. Methods: The epidemiological study used an observational study design utilising routine health records in the UK. This included primary care records (Clinical Practice Research Datalink [CPRD, UK] and Secure Anonymised Information Linkage [SAIL, Wales]); and secondary care records with linked community prescriptions (Scottish Morbidity Records [SMR]).The study population was pregnant women and the exposure was pre-existing multimorbidity (2 or more long-term conditions). Multimorbidity was operationalised by 79 long-term conditions selected by a multidisciplinary team. Logistic regression was performed to examine the association of maternal multimorbidity with sociodemographic factors. The core outcome set development consisted of four stages: (i) systematic literature search, (ii) focus groups with stakeholders in the UK, (iii) international Delphi surveys, and (iv) virtual consensus meetings. Results: Amongst women pregnant in 2018 in the UK, the prevalence of multimorbidity was 44.2% (95% CI 43.7–44.7%), 46.2% (45.6–46.8%) and 19.8% (18.8– 20.8%) in CPRD, SAIL and SMR respectively. When limited to health conditions that were active in the year before pregnancy, the prevalence of multimorbidity was still high (24.2% [23.8–24.6%], 23.5% [23.0–24.0%] and 17.0% [16.0 to 17.9%] in the respective datasets). Logistic regression showed that pregnant women with multimorbidity were more likely to be older (CPRD England, adjusted OR 1.81 [95% CI 1.04–3.17] 45–49 years vs 15–19 years), multigravid (1.68 [1.50–1.89] gravidity ≥ five vs one), have raised body mass index (1.59 [1.44–1.76], body mass index 30+ vs body mass index 18.5–24.9) and smoked preconception (1.61 [1.46–1.77) vs non-smoker). For the core outcome set development study, 26 studies were included in the systematic literature search (2017 to 2021) reporting 185 outcomes. Three virtual focus groups (n=22) were conducted from December 2021 to March 2022 in the United Kingdom. Thematic analysis of the focus groups added 28 outcomes. Two hundred and nine stakeholders completed the first Delphi survey. One hundred and sixteen stakeholders completed the second Delphi survey where 45 outcomes reached Consensus In (≥70% of all participants rating an outcome as Critically Important). After two rounds of consensus meetings (first meeting n=13, second meeting n=17), the final core outcome set included 11 outcomes: The five maternal outcomes were: maternal death, severe maternal morbidity, change in existing long-term conditions (physical and mental), quality and experience of care, and development of new mental health conditions. The six child outcomes were: survival of baby, gestational age at birth, neurodevelopmental conditions/impairment, quality of life, birth weight, and separation of baby from mother for health care needs. Conclusion: Multimorbidity is highly prevalent in pregnant women in the United Kingdom. We developed a core outcome set to guide future studies for pregnant women with multimorbidity. The next step would be to quantify the association between maternal multimorbidity and outcomes for the women, the pregnancy, and their offspring

Characteristics predicting recommendation for familial breast cancer referral in a cohort of women from primary care

© 2020, The Author(s). Family history of breast and related cancers can indicate increased breast cancer (BC) risk. In national familial breast cancer (FBC) guidelines, the risk is stratified to guide referral decisions. We aimed to identify characteristics associated with the recommendation for referral in a large cohort of women undergoing FBC risk assessment in a recent primary care study. Demographic, family history, psychological and behavioural factors were collected with family history questionnaires, psychological questionnaires and manual data extraction from general practice electronic health records. Participants were women aged 30–60 with no previous history of breast or ovarian cancer. Data from 1127 women were analysed with stepwise logistic regression. Two multivariable logistic models were developed to predict recommendations for referral: using the entire cohort (n = 1127) and in a subgroup with uncertain risks (n = 168). Model performance was assessed by the area under the receiver operating curve (AUC). In all 1127 women, a multivariable model incorporating five family history components (BC aged < 40, bilateral BC, prostate cancer, first degree relative with ovarian cancer, paternal family history of BC) and having a mammogram in the last 3years, performed well (AUC = 0.86). For the 168 uncertain risk women, only paternal family history of BC remained significant (AUC = 0.71). Clinicians should pay particular attention to these five family history components when assessing FBC risk, especially prostate cancer which is not in the current national guidelines

Specialist recommendation for chemoprevention medications in patients at familial risk of breast cancer: a cross-sectional survey in England

In England, the National Institute for Health and Care Excellence guideline for familial breast cancer recommends chemoprevention for women at high and moderate familial risk of breast cancer. However, prescribing of chemoprevention has not improved since the introduction of the guideline in 2013. The study aims to identify the current practice, in England, of familial cancer specialists offering chemoprevention and recommending prescribing in primary care. This was an anonymised national cross-sectional survey of familial breast cancer risk services in England. Lead clinicians were sent an online survey link. The survey questions included whether chemoprevention was offered/considered for high and moderate risk women, when chemoprevention prescribing and recommendation to primary care started, medications prescribed, age groups considered for chemoprevention and existence of a shared prescribing protocol with primary care. The survey was sent to 115 hospital services, responses from 50 services (43%) were included in the analysis. Of the 40 services offering chemoprevention for high risk women, 15 (38%) did not prescribe but 31 (78%) recommended prescribing to primary care. Of the 31 services considering chemoprevention for moderate risk, eight (26%) did not prescribe with 26 (84%) recommended prescribing to primary care. Only three services reported having a shared protocol with primary care. Within three years of the guidelines, many services recognised the role of chemoprevention for both high and moderate risk with a key role for primary care to initiate prescribing. However, there is still room for improvement

Effectiveness of interventions to identify and manage patients with familial cancer risk in primary care: a systematic review

This systematic review evaluated the effectiveness of strategies to identify and manage patients with familial risk of breast, ovarian, colorectal and prostate cancer in primary careto improve clinical outcomes. MEDLINE, EMBASE, CINAHL and Cochrane library were searched from January 1980 to October 2017. We included randomised controlled trials (RCT) and non-randomised studies of interventions (NRSI). Primary outcomes were cancer incidence, cancer related clinical outcomes or identification of cancer predisposition; secondary outcomes were appropriateness of referral, uptake of preventive strategies, cognitive and psychological effect. From 11842 abstracts, 111 full texts were reviewed and three eligible studies (nine articles) identified. Two were cluster RCTs and one NRSI; all used risk assessment software. No studies identified our primary outcomes, with no consistent outcome across the three studies. In one RCT, intervention improved the proportion of genetic referrals meeting referral guidelines for breast cancer (OR 4.5, 95% CI 1.6 to 13.1). In the other RCT, there was no difference in screening adherence between the intervention and control group. However, there was borderline increased risk perception (OR 1.89, 95% CI 0.99 to 3.59) in the subgroup that under-estimated their colon cancer risk. In the NRSI, there was no change in psychological distress inpatients at increased familial breast cancer risk, but population risk patients had reduced anxiety after intervention (state anxiety mean change –3,95% CI -5 to -2). Future studies should have better defined comparator groups, longer follow up, and assess outcomes using validated tools

An interview study to determine the experiences of cellulitis diagnosis amongst health care professionals in the UK

OBJECTIVES: To explore healthcare professionals (HCPs) experiences and challenges in diagnosing suspected lower limb cellulitis. SETTING: UK nationwide. PARTICIPANTS: 20 qualified HCPs, who had a minimum of 2 years clinical experience as an HCP in the national health service and had managed a clinical case of suspected cellulitis of the lower limb in the UK. HCPs were recruited from departments of dermatology (including a specialist cellulitis clinic), general practice, tissue viability, lymphoedema services, general surgery, emergency care and acute medicine. Purposive sampling was employed to ensure that participants included consultant doctors, trainee doctors and nurses across the specialties listed above. Participants were recruited through national networks, HCPs who contributed to the cellulitis priority setting partnership, UK Dermatology Clinical Trials Network, snowball sampling where participants helped recruit other participants and personal networks of the authors. PRIMARY AND SECONDARY OUTCOMES: Primary outcome was to describe the key clinical features which inform the diagnosis of lower limb cellulitis. Secondary outcome was to explore the difficulties in making a diagnosis of lower limb cellulitis. RESULTS: The presentation of lower limb cellulitis changes as the episode runs its course. Therefore, different specialties see clinical features at varying stages of cellulitis. Clinical experience is essential to being confident in making a diagnosis, but even among experienced HCPs, there were differences in the clinical rationale of diagnosis. A group of core clinical features were suggested, many of which overlapped with alternative diagnoses. This emphasises how the diagnosis is challenging, with objective aids and a greater understanding of the mimics of cellulitis required. CONCLUSION: Cellulitis is a complex diagnosis and has a variable clinical presentation at different stages. Although cellulitis is a common diagnosis to make, HCPs need to be mindful of alternative diagnoses

An interview study of the experiences of cellulitis diagnosis amongst health care professionals

Objectives: To explore healthcare professionals (HCPs) experiences and challenges in diagnosing suspected lower limb cellulitis.Setting: UK nationwide.Participants: 20 qualified HCPs, who had a minimum of 2 years clinical experience as an HCP in the national health service and had managed a clinical case of suspected cellulitis of the lower limb in the UK. HCPs were recruited from departments of dermatology (including a specialist cellulitis clinic), general practice, tissue viability, lymphoedema services, general surgery, emergency care and acute medicine. Purposive sampling was employed to ensure that participants included consultant doctors, trainee doctors and nurses across the specialties listed above. Participants were recruited through national networks, HCPs who contributed to the cellulitis priority setting partnership, UK Dermatology Clinical Trials Network, snowball sampling where participants helped recruit other participants and personal networks of the authors.Primary and secondary outcomes: Primary outcome was to describe the key clinical features which inform the diagnosis of lower limb cellulitis. Secondary outcome was to explore the difficulties in making a diagnosis of lower limb cellulitis.Results: The presentation of lower limb cellulitis changes as the episode runs its course. Therefore, different specialties see clinical features at varying stages of cellulitis. Clinical experience is essential to being confident in making a diagnosis, but even among experienced HCPs, there were differences in the clinical rationale of diagnosis. A group of core clinical features were suggested, many of which overlapped with alternative diagnoses. This emphasises how the diagnosis is challenging, with objective aids and a greater understanding of the mimics of cellulitis required.Conclusion: Cellulitis is a complex diagnosis and has a variable clinical presentation at different stages. Although cellulitis is a common diagnosis to make, HCPs need to be mindful of alternative diagnoses

Association of pregnancy complications/risk factors with the development of future long-term health conditions in women : overarching protocol for umbrella reviews

Acknowledgments Patient representatives and MuM-PreDiCT team. Funding This work was funded by the Strategic Priority Fund 'Tackling multimorbidity at scale' programme (grant number-MR/W014432/1) delivered by the Medical Research Council and the National Institute for Health and Care Research in partnership with the Economic and Social Research Council and in collaboration with the Engineering and Physical Sciences Research Council.Peer reviewedPublisher PD

Clinical manifestations, risk factors, and maternal and perinatal outcomes of coronavirus disease 2019 in pregnancy: living systematic review and meta-analysis.

OBJECTIVE: To determine the clinical manifestations, risk factors, and maternal and perinatal outcomes in pregnant and recently pregnant women with suspected or confirmed coronavirus disease 2019 (covid-19). DESIGN: Living systematic review and meta-analysis. DATA SOURCES: Medline, Embase, Cochrane database, WHO COVID-19 database, China National Knowledge Infrastructure (CNKI), and Wanfang databases from 1 December 2019 to 26 June 2020, along with preprint servers, social media, and reference lists. STUDY SELECTION: Cohort studies reporting the rates, clinical manifestations (symptoms, laboratory and radiological findings), risk factors, and maternal and perinatal outcomes in pregnant and recently pregnant women with suspected or confirmed covid-19. DATA EXTRACTION: At least two researchers independently extracted the data and assessed study quality. Random effects meta-analysis was performed, with estimates pooled as odds ratios and proportions with 95% confidence intervals. All analyses will be updated regularly. RESULTS: 77 studies were included. Overall, 10% (95% confidence interval 7% to14%; 28 studies, 11 432 women) of pregnant and recently pregnant women attending or admitted to hospital for any reason were diagnosed as having suspected or confirmed covid-19. The most common clinical manifestations of covid-19 in pregnancy were fever (40%) and cough (39%). Compared with non-pregnant women of reproductive age, pregnant and recently pregnant women with covid-19 were less likely to report symptoms of fever (odds ratio 0.43, 95% confidence interval 0.22 to 0.85; I2=74%; 5 studies; 80 521 women) and myalgia (0.48, 0.45 to 0.51; I2=0%; 3 studies; 80 409 women) and were more likely to need admission to an intensive care unit (1.62, 1.33 to 1.96; I2=0%) and invasive ventilation (1.88, 1.36 to 2.60; I2=0%; 4 studies, 91 606 women). 73 pregnant women (0.1%, 26 studies, 11 580 women) with confirmed covid-19 died from any cause. Increased maternal age (1.78, 1.25 to 2.55; I2=9%; 4 studies; 1058 women), high body mass index (2.38, 1.67 to 3.39; I2=0%; 3 studies; 877 women), chronic hypertension (2.0, 1.14 to 3.48; I2=0%; 2 studies; 858 women), and pre-existing diabetes (2.51, 1.31 to 4.80; I2=12%; 2 studies; 858 women) were associated with severe covid-19 in pregnancy. Pre-existing maternal comorbidity was a risk factor for admission to an intensive care unit (4.21, 1.06 to 16.72; I2=0%; 2 studies; 320 women) and invasive ventilation (4.48, 1.40 to 14.37; I2=0%; 2 studies; 313 women). Spontaneous preterm birth rate was 6% (95% confidence interval 3% to 9%; I2=55%; 10 studies; 870 women) in women with covid-19. The odds of any preterm birth (3.01, 95% confidence interval 1.16 to 7.85; I2=1%; 2 studies; 339 women) was high in pregnant women with covid-19 compared with those without the disease. A quarter of all neonates born to mothers with covid-19 were admitted to the neonatal unit (25%) and were at increased risk of admission (odds ratio 3.13, 95% confidence interval 2.05 to 4.78, I2=not estimable; 1 study, 1121 neonates) than those born to mothers without covid-19. CONCLUSION: Pregnant and recently pregnant women are less likely to manifest covid-19 related symptoms of fever and myalgia than non-pregnant women of reproductive age and are potentially more likely to need intensive care treatment for covid-19. Pre-existing comorbidities, high maternal age, and high body mass index seem to be risk factors for severe covid-19. Preterm birth rates are high in pregnant women with covid-19 than in pregnant women without the disease. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020178076. READERS' NOTE: This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication