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OBJECTIVE: To assess the effects of COVID-19 vaccines in women before or during pregnancy on SARS-CoV-2 infection-related, pregnancy, offspring and reactogenicity outcomes. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Major databases between December 2019 and January 2023. STUDY SELECTION: Nine pairs of reviewers contributed to study selection. We included test-negative designs, comparative cohorts and randomised trials on effects of COVID-19 vaccines on infection-related and pregnancy outcomes. Non-comparative cohort studies reporting reactogenicity outcomes were also included. QUALITY ASSESSMENT, DATA EXTRACTION AND ANALYSIS: Two reviewers independently assessed study quality and extracted data. We undertook random-effects meta-analysis and reported findings as HRs, risk ratios (RRs), ORs or rates with 95% CIs. RESULTS: Sixty-seven studies (1 813 947 women) were included. Overall, in test-negative design studies, pregnant women fully vaccinated with any COVID-19 vaccine had 61% reduced odds of SARS-CoV-2 infection during pregnancy (OR 0.39, 95% CI 0.21 to 0.75; 4 studies, 23 927 women; I2=87.2%) and 94% reduced odds of hospital admission (OR 0.06, 95% CI 0.01 to 0.71; 2 studies, 868 women; I2=92%). In adjusted cohort studies, the risk of hypertensive disorders in pregnancy was reduced by 12% (RR 0.88, 95% CI 0.82 to 0.92; 2 studies; 115 085 women), while caesarean section was reduced by 9% (OR 0.91, 95% CI 0.85 to 0.98; 6 studies; 30 192 women). We observed an 8% reduction in the risk of neonatal intensive care unit admission (RR 0.92, 95% CI 0.87 to 0.97; 2 studies; 54 569 women) in babies born to vaccinated versus not vaccinated women. In general, vaccination during pregnancy was not associated with increased risk of adverse pregnancy or perinatal outcomes. Pain at the injection site was the most common side effect reported (77%, 95% CI 52% to 94%; 11 studies; 27 195 women). CONCLUSION: COVID-19 vaccines are effective in preventing SARS-CoV-2 infection and related complications in pregnant women. PROSPERO REGISTRATION NUMBER: CRD42020178076.
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Vacinas contra COVID-19 , COVID-19 , Complicações Infecciosas na Gravidez , Resultado da Gravidez , SARS-CoV-2 , Humanos , Gravidez , Vacinas contra COVID-19/efeitos adversos , Vacinas contra COVID-19/administração & dosagem , COVID-19/prevenção & controle , Feminino , Complicações Infecciosas na Gravidez/prevenção & controle , Recém-NascidoRESUMO
Maternal outcomes throughout pregnancy, childbirth, and the postnatal period are influenced by interlinked and interdependent vulnerabilities. A comprehensive understanding of how various threats and barriers affect maternal and perinatal health is critical to plan, evaluate and improve maternal health programmes. This paper builds on the introductory paper of the Series on the determinants of maternal health by assessing vulnerabilities during pregnancy, childbirth, and the postnatal period. We synthesise and present the concept of vulnerability in pregnancy and childbirth, and map vulnerability attributes and their dynamic influence on maternal outcomes in early and late pregnancy and during childbirth and the postnatal period, with a particular focus on low-income and middle-income countries (LMICs). We summarise existing literature and present the evidence on the effects of various reparative strategies to improve pregnancy and childbirth outcomes. Lastly, we discuss the implications of the identified vulnerability attributes and reparative strategies for the efforts of policymakers, healthcare professionals, and researchers working towards improving outcomes for women and birthing people in LMICs.
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With increasing evidence of emotional well-being disorders associated with polycystic ovary syndrome (PCOS), effective screening processes are of utmost importance. We studied the impact of using questionnaires to screen for emotional and psychosexual well-being across different models of care for PCOS. We analysed the data from the surveys to assess the difference in the prevalence of emotional and psychosexual ill-being across ethnicity and region. In this prospective cohort study, we invited all women attending consultations for PCOS in Birmingham, UK, and Bengaluru and Navi Mumbai, India. Those who consented to participate in the study were invited to complete a pre-clinic survey about socio-demographic data, Hospital Anxiety and Depression Scale (HADS), Body Image Concern Inventory (BICI), Beliefs about Obese Person scale (BAOP), and Female Sexual Function Index score (FSFI) and a post-clinic survey on clinic experience, lifestyle advice, and specialist referral. A total of 115 women were included in this study. The rate of questionnaire completion was 98.3% (113/115), 97.4% (112/115), 93.04% (107/115), and 84.3% (97/115) for HADS, BICI, BAOP, and FSFI, respectively. In the post-clinic survey, 28.8% reported they were screened for anxiety, 27.1% for depression, and 45.8% for body image concerns. The prevalence of anxiety, depression, and body dysmorphic disorder through pre-clinic survey was 56.5% (50.0% UK vs 59.5% India, P = 0.483), 16.5% (13.9% UK vs 17.7% India, P = 0.529), and 29.6% (36.1% UK vs 26.6% India, P = 0.208), respectively. Surveys with validated questionnaires can improve screening for emotional and psychosexual well-being associated with PCOS which may be missed by ad hoc screening during consultations.
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OBJECTIVE: To assess the association of ethnicity and birthplace on emotional and psychosexual well-being in women with polycystic ovary syndrome (PCOS). DESIGN: Cross-sectional study. SETTING: Community recruitment via social media campaigns. POPULATION: Women with PCOS completing an online questionnaire in September-October 2020 (UK) and May-June 2021 (India). METHODS: The survey has five components, with a baseline information and sociodemographic section followed by four validated questionnaires: Hospital Anxiety and Depression Scale (HADS); Body Image Concern Inventory (BICI); Beliefs About Obese Persons Scale (BAOP); and Female Sexual Function Index (FSFI). MAIN OUTCOME MEASURES: We used adjusted linear and logistic regression models, adjusting for age, education, marital status and parity, to evaluate the impact of ethnicity and birthplace on questionnaire scores and outcomes (anxiety and/or depression, HADS ≥ 11; body dysmorphic disorder (BDD), BICI ≥ 72). RESULTS: A total of 1008 women with PCOS were included. Women of non-white ethnicity (613/1008) reported higher rates of depression (OR 1.96, 95% CI 1.41-2.73) and lower BDD (OR 0.57, 95% CI 0.41-0.79) than white women (395/1008). Women born in India (453/1008) had higher anxiety (OR 1.57, 95% CI 1.00-2.46) and depression (OR 2.20, 95% CI 1.52-3.18) but lower BDD rates (OR 0.42, 95% CI 0.29-0.61) than women born in the UK (437/1008). All sexual domains, excluding desire, scored lower for non-white women and women born in India. CONCLUSIONS: Non-white women and women born in India reported higher emotional and sexual dysfunction, whereas white women and women born in the UK reported higher body image concerns and weight stigma. Ethnicity and birthplace need to be considered for tailored, multidisciplinary care.
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Síndrome do Ovário Policístico , Feminino , Humanos , Estudos Transversais , Etnicidade , Inquéritos e Questionários , Índia/epidemiologia , Reino Unido/epidemiologiaRESUMO
BACKGROUND: Existing evidence on the effects of race and ethnicity on pregnancy outcomes is restricted to individual studies done within specific countries and health systems. We aimed to assess the impact of race and ethnicity on perinatal outcomes in high-income and upper-middle-income countries, and to ascertain whether the magnitude of disparities, if any, varied across geographical regions. METHODS: For this individual participant data (IPD) meta-analysis we used data from the International Prediction of Pregnancy Complications (IPPIC) Network of studies on pregnancy complications; the full dataset comprised 94 studies, 53 countries, and 4â539â640 pregnancies. We included studies that reported perinatal outcomes (neonatal death, stillbirth, preterm birth, and small-for-gestational-age babies) in at least two racial or ethnic groups (White, Black, south Asian, Hispanic, or other). For our two-step random-effects IPD meta-analysis, we did multiple imputations for confounder variables (maternal age, BMI, parity, and level of maternal education) selected with a directed acyclic graph. The primary outcomes were neonatal mortality and stillbirth. Secondary outcomes were preterm birth and a small-for-gestational-age baby. We estimated the association of race and ethnicity with perinatal outcomes using a multivariate logistic regression model and reported this association with odds ratios (ORs) and 95% CIs. We also did a subgroup analysis of studies by geographical region. FINDINGS: 51 studies from 20 high-income and upper-middle-income countries, comprising 2â198â655 pregnancies, were eligible for inclusion in this IPD meta-analysis. Neonatal death was twice as likely in babies born to Black women than in babies born to White women (OR 2·00, 95% CI 1·44-2·78), as was stillbirth (2·16, 1·46-3·19), and babies born to Black women were at increased risk of preterm birth (1·65, 1·46-1·88) and being small for gestational age (1·39, 1·13-1·72). Babies of women categorised as Hispanic had a three-times increased risk of neonatal death (OR 3·34, 95% CI 2·77-4·02) than did those born to White women, and those born to south Asian women were at increased risk of preterm birth (OR 1·26, 95% CI 1·07-1·48) and being small for gestational age (1·61, 1·32-1·95). The effects of race and ethnicity on preterm birth and small-for-gestational-age babies did not vary across regions. INTERPRETATION: Globally, among underserved groups, babies born to Black women had consistently poorer perinatal outcomes than White women after adjusting for maternal characteristics, although the risks varied for other groups. The effects of race and ethnicity on adverse perinatal outcomes did not vary by region. FUNDING: National Institute for Health and Care Research, Wellbeing of Women.
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Morte Perinatal , Complicações na Gravidez , Nascimento Prematuro , Gravidez , Lactente , Recém-Nascido , Humanos , Feminino , Nascimento Prematuro/epidemiologia , Países em Desenvolvimento , Resultado da Gravidez/epidemiologia , Natimorto/epidemiologia , Retardo do Crescimento FetalRESUMO
INTRODUCTION: The prevalence of COVID-19 and its impact varied between countries and regions. Pregnant women are at high risk of COVID-19 complications compared with non-pregnant women. The magnitude of variations, if any, in SARS-CoV-2 infection rates and its health outcomes among pregnant women by geographical regions and country's income level is not known. METHODS: We performed a random-effects meta-analysis as part of the ongoing PregCOV-19 living systematic review (December 2019 to April 2021). We included cohort studies on pregnant women with COVID-19 reporting maternal (mortality, intensive care admission and preterm birth) and offspring (mortality, stillbirth, neonatal intensive care admission) outcomes and grouped them by World Bank geographical region and income level. We reported results as proportions with 95% confidence intervals (CI). RESULTS: We included 311 studies (2 003 724 pregnant women, 57 countries). The rates of SARS-CoV-2 infection in pregnant women varied significantly by region (p<0.001) and income level (p<0.001), with the highest rates observed in Latin America and the Caribbean (19%, 95% CI 12% to 27%; 13 studies, 38 748 women) and lower-middle-income countries (13%, 95% CI 6% to 23%; 25 studies, 100 080 women). We found significant differences in maternal and offspring outcomes by region and income level. Lower-middle-income countries reported significantly higher rates of maternal mortality (0.68%, 95% CI 0.24% to 1.27%; 3 studies, 31 136 women), intensive care admission (4.53%, 95% CI 2.57% to 6.91%; 54 studies, 23 420 women) and stillbirths (1.09%, 95% CI 0.48% to 1.88%; 41 studies, 4724 women) than high-income countries. COVID-19 complications disproportionately affected South Asia, which had the highest maternal mortality rate (0.88%, 95% CI 0.16% to 1.95%; 17 studies, 2023 women); Latin America and the Caribbean had the highest stillbirth rates (1.97%, 95% CI 0.9% to 3.33%; 10 studies, 1750 women). CONCLUSION: The rates of SARS-CoV-2 infection in pregnant women vary globally, and its health outcomes mirror the COVID-19 burden and global maternal and offspring inequalities. PROSPERO REGISTRATION NUMBER: CRD42020178076.
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COVID-19 , Nascimento Prematuro , Gravidez , Recém-Nascido , Feminino , Humanos , Natimorto/epidemiologia , SARS-CoV-2 , Nascimento Prematuro/epidemiologia , Mortalidade MaternaRESUMO
OBJECTIVES: Supporting cancer patients during COVID-19 has posed unique challenges for health care providers. We investigated patient and carer-charity interactions to explore the role of charities and identify concerns expressed by patients. The study aims to address these concerns and learn how health care providers can support patients. METHODS: Digital interactions on forum posts and social media were collected from four gynaecological cancer charities from March-May 2019 (before COVID-19) and 2020 (during COVID-19). Thematic analysis of forum posts and semistructured charity staff interviews investigated patient and charity-focused perspectives. RESULTS: Thematic analysis of forum posts and charity staff interviews (n = 8) revealed three consistent themes: (1) Health care changes and the effect on cancer management concerns; (2) psychological impact of lockdown isolation and anxiety of changed treatment; (3) the complexity of shielding guidance on self-risk assessment. Patients valued cancer charities' responses through digital and conventional methods (webinars, social media, forums, and websites). CONCLUSION: Gynaecological cancer patients had concerns about the risk and impact of changed treatment plans, contacting charities as the first port of call when anxious not to burden health systems. Real-time analysis of charities' communications can be used to identify concerns and to proactively provide patient support, together with health care providers.
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COVID-19 , Neoplasias , Humanos , Instituições de Caridade , Cuidadores , Controle de Doenças TransmissíveisRESUMO
OBJECTIVES: To map the care provided to pregnant women with epilepsy in UK maternity units and identify future research priorities by conducting a nationwide survey of healthcare professionals. STUDY DESIGN: A prospective cross-sectional electronic survey was conducted between 29 April and 30 October 2021. The survey included 23 questions developed and refined with relevant stakeholders, including a woman with lived experience of epilepsy and pregnancy. We used descriptive analyses to summarise responses and estimated proportions with medians and interquartile ranges. RESULTS: 144 individual healthcare professionals from 94 hospitals, representing 77 NHS Trusts, participated in the survey. Obstetricians were the most common responders (45%, 65/144) and almost half (47%, 7/15) of regions had a survey response rate per NHS Trust greater than 50%. Six pregnant women with epilepsy, on average, were booked into antenatal care per hospital per month, and 49% (46/94) of hospitals saw women for specialist antenatal care in the first trimester. The care provided across healthcare systems varied, with multiple pathways for referral to specialist care within regions. Midwife referral was the most used care pathway (80%, 75/94). Less than a third of hospitals (31%, 29/94) ran joint obstetric/neurology clinics for pregnant women with epilepsy. Most survey respondents (81%, 117/144) were confident talking to pregnant women about their risk of seizures but only a minority (20%, 29/144) used validated calculators to assess this risk. There was broad agreement across healthcare professionals that the priorities for research should focus on how to improve communication and address pregnant women's concerns regarding epilepsy and pregnancy, and to develop further understanding on the optimal use and long-term effects of anti-seizure medication. CONCLUSION: Our UK nationwide survey of hospital-based maternity services for pregnant women with epilepsy identified wide variation in when, how and by whom these women are seen, with differences between and within the UK regions. This survey highlights areas for improvement in the care of pregnant women with epilepsy.
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Epilepsia , Gestantes , Estudos Transversais , Atenção à Saúde , Epilepsia/terapia , Feminino , Humanos , Gravidez , Estudos Prospectivos , Reino UnidoRESUMO
Simulation-based learning (SBL) is well-established in medical education and has gained popularity, particularly during the COVID-19 pandemic when in-person teaching is infeasible. SBL replicates real-life scenarios and provides a fully immersive yet safe learning environment to develop clinical competency. Simulation via Instant Messaging - Birmingham Advance (SIMBA) is an exemplar of SBL, which we previously showed to be effective in endocrinology and diabetes. Previous studies reported the efficacy of SBL in acute medicine. We studied SIMBA as a learning intervention for healthcare professionals interested in acute medicine and defined our aims using the Kirkpatrick model: (i) develop an SBL tool to improve case management; (ii) evaluate experiences and confidence before and after; and (iii) compare efficacy across training levels.Three sessions were conducted, each representing a PDSA cycle (Plan-Do-Study-Act), consisting of four cases and advertised to healthcare professionals at our hospital and social media. Moderators facilitated progression through 25 min simulations and adopted patient and clinical roles as appropriate. Consultants chaired discussion sessions using relevant guidelines. Presimulation and postsimulation questionnaires evaluated self-reported confidence, feedback and intended changes to clinical practice.Improvements were observed in self-reported confidence managing simulated cases across all sessions. Of participants, 93.3% found SIMBA applicable to clinical practice, while 89.3% and 88.0% felt SIMBA aided personal and professional development, respectively. Interestingly, 68.0% preferred SIMBA to traditional teaching methods. Following participant feedback, more challenging cases were included, and we extended the time for simulation and discussion. The transcripts were amended to facilitate more participant-moderator interaction representing clinical practice. In addition, we refined participant recruitment over the three sessions. In cycle 1, we advertised incentives: participation counted towards teaching requirements, certificates and feedback. To rectify the reduction in participants in cycle 2, we implemented new advertisement methods in cycle 3, including on-site posters, reminder emails and recruitment of the defence deanery cohort.
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COVID-19 , Educação Médica , Competência Clínica , Humanos , Aprendizagem , PandemiasRESUMO
OBJECTIVES: To assess the rates of SARS-CoV-2 positivity in babies born to mothers with SARS-CoV-2 infection, the timing of mother-to-child transmission and perinatal outcomes, and factors associated with SARS-CoV-2 status in offspring. DESIGN: Living systematic review and meta-analysis. DATA SOURCES: Major databases between 1 December 2019 and 3 August 2021. STUDY SELECTION: Cohort studies of pregnant and recently pregnant women (including after abortion or miscarriage) who sought hospital care for any reason and had a diagnosis of SARS-CoV-2 infection, and also provided data on offspring SARS-CoV-2 status and risk factors for positivity. Case series and case reports were also included to assess the timing and likelihood of mother-to-child transmission in SARS-CoV-2 positive babies. DATA EXTRACTION: Two reviewers independently extracted data and assessed study quality. A random effects model was used to synthesise data for rates, with associations reported using odds ratios and 95% confidence intervals. Narrative syntheses were performed when meta-analysis was inappropriate. The World Health Organization classification was used to categorise the timing of mother-to-child transmission (in utero, intrapartum, early postnatal). RESULTS: 472 studies (206 cohort studies, 266 case series and case reports; 28 952 mothers, 18 237 babies) were included. Overall, 1.8% (95% confidence interval 1.2% to 2.5%; 140 studies) of the 14 271 babies born to mothers with SARS-CoV-2 infection tested positive for the virus with reverse transcriptase polymerase chain reaction (RT-PCR). Of the 592 SARS-CoV-2 positive babies with data on the timing of exposure and type and timing of tests, 14 had confirmed mother-to-child transmission: seven in utero (448 assessed), two intrapartum (18 assessed), and five during the early postnatal period (70 assessed). Of the 800 SARS-CoV-2 positive babies with outcome data, 20 were stillbirths, 23 were neonatal deaths, and eight were early pregnancy losses; 749 babies were alive at the end of follow-up. Severe maternal covid-19 (odds ratio 2.4, 95% confidence interval 1.3 to 4.4), maternal death (14.1, 4.1 to 48.0), maternal admission to an intensive care unit (3.5, 1.7 to 6.9), and maternal postnatal infection (5.0, 1.2 to 20.1) were associated with SARS-CoV-2 positivity in offspring. Positivity rates using RT-PCR varied between regions, ranging from 0.1% (95% confidence interval 0.0% to 0.3%) in studies from North America to 5.7% (3.2% to 8.7%) in studies from Latin America and the Caribbean. CONCLUSION: SARS-CoV-2 positivity rates were found to be low in babies born to mothers with SARS-CoV-2 infection. Evidence suggests confirmed vertical transmission of SARS-CoV-2, although this is likely to be rare. Severity of maternal covid-19 appears to be associated with SARS-CoV-2 positivity in offspring. 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.
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COVID-19/transmissão , Transmissão Vertical de Doenças Infecciosas , Complicações Infecciosas na Gravidez , Resultado da Gravidez/epidemiologia , SARS-CoV-2 , COVID-19/diagnóstico , Teste de Ácido Nucleico para COVID-19 , Teste para COVID-19/métodos , Feminino , Humanos , Recém-Nascido , GravidezRESUMO
Interventions to reduce household air pollution (HAP) are key to reducing associated morbidity and mortality in low- and middle- income countries (LMICs); especially among pregnant women and young children. This systematic review aims to determine the effectiveness of interventions aimed to reduce HAP exposure associated with domestic solid biomass fuel combustion, compared to usual cooking practices, for improving health outcomes in pregnant women and children under five in LMIC settings. A systematic review and meta-analysis was undertaken with searches undertaken in MEDLINE, EMBASE, CENTRAL, GIM, ClinicalTrials.gov, and Greenfile in August 2020. Inclusion criteria were experimental, non-experimental, or quasi-experimental studies investigating the impact of interventions to reduce HAP exposure and improve associated health outcomes among pregnant women or children under 5 years. Study selection, data extraction, and quality assessment using the Effective Public Health Practice Project tool were undertaken independently by two reviewers. Seventeen out of 7293 retrieved articles (seven pregnancy, nine child health outcome; 13 studies) met the inclusion criteria. These assessed improved cookstoves (ICS; n = 10 studies), ethanol stoves (n = 1 study), and Liquefied Petroleum Gas (LPG; n = 2 studies) stoves interventions. Meta-analysis showed no significant effect of ICS interventions compared to traditional cooking for risk of preterm birth (n = 2 studies), small for gestational age (n = 2 studies), and incidence of acute respiratory infections (n = 6 studies). Although an observed increase in mean birthweight was observed, this was not statistically significant (n = 4). However, ICS interventions reduced the incidence of childhood burns (n = 3; observations = 41 723; Rate Ratio: 0.66 [95% CI: 0.45-0.96]; I2 : 46.7%) and risk of low birth weight (LBW; n = 4; observations = 3456; Odds Ratio: 0.73 [95% CI: 0.61-0.87]; I2 : 21.1%). Although few studies reported health outcomes, the data indicate that ICS interventions were associated with reduced risk of childhood burns and LBW. The data highlight the need for the development and implementation of robust, well-reported and monitored, community-driven intervention trials with longer-term participant follow-up.
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Poluição do Ar em Ambientes Fechados , Poluição do Ar , Nascimento Prematuro , Poluição do Ar/análise , Poluição do Ar em Ambientes Fechados/análise , Biomassa , Criança , Pré-Escolar , Culinária , Países em Desenvolvimento , Feminino , Humanos , Recém-Nascido , Avaliação de Resultados em Cuidados de Saúde , GravidezRESUMO
BACKGROUND: Skeletal dysplasia (SD) conditions are rare genetic diseases of the skeleton, encompassing a heterogeneous group of over 400 disorders, and represent approximately 5% of all congenital anomalies. Developments in genetic and treatment technologies are leading to unparalleled therapeutic advances; thus, it is more important than ever to molecularly confirm SD conditions. Data on 'rates-of-molecular yields' in SD conditions, through exome sequencing approaches, is limited. Figures of 39% and 52.5% have been reported in the USA (n = 54) and South Korea (n = 185) respectively. METHODS: We discuss a single-centre (in the UK) experience of whole-exome sequencing (WES) in a cohort of 15 paediatric patients (aged 5 months to 12 years) with SD disorders previously molecularly unconfirmed. Our cohort included patients with known clinical diagnoses and undiagnosed skeletal syndromes. Extensive phenotyping and expert radiological review by a panel of international SD radiology experts, coupled with a complex bioinformatics pipeline, allowed for both gene-targeted and gene-agnostic approaches. RESULTS: Significant variants leading to a likely or confirmed diagnosis were identified in 53.3% (n = 8/15) of patients; 46.7% (n = 7/15) having a definite molecular diagnosis and 6.7% (n = 1/15) having a likely molecular diagnosis. We discuss this in the context of a rare disease in general and specifically SD presentations. Of patients with known diagnoses pre-WES (n = 10), molecular confirmation occurred in 7/10 cases, as opposed to 1/5 where a diagnosis was unknown pre-test. Thus, diagnostic return is greatest where the diagnosis is known pre-test. For WGS (whole genome sequencing, the next iteration of WES), careful case selection (ideally of known diagnoses pre-test) will yield highest returns. CONCLUSIONS: Our results highlight the cost-effective use of WES-targeted bioinformatic analysis as a diagnostic tool for SD, particularly patients with presumed SD, where detailed phenotyping is essential. Thorough co-ordinated clinical evaluation between clinical, radiological, and molecular teams is essential for improved yield and clinical care. WES (and WGS) yields will increase with time, allowing faster diagnoses, avoiding needless investigations, ensuring individualised patient care and patient reassurance. Further diagnoses will lead to increased information on natural history/mechanistic details, and likely increased therapies and clinical trials.
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Sequenciamento do ExomaRESUMO
KIAA0753-related skeletal ciliopathy is a recently described recessive disorder causing skeletal dysplasia and overlapping features of certain ciliopathies; Joubert, Jeune and Oro-facial-digital syndromes. We describe a ninth case that expands the phenotype; a 10-year-old girl with rhizomelic short stature (-5.6 SD), macrocephaly, developmental delay, CNS anomalies (thin corpus callosum, bilateral ventriculomegaly), cone-rod dystrophy, nystagmus, mild conductive hearing loss and recurrent chest infections secondary to confirmed ciliary dyskinesia. Testing for FGFR3 achondroplasia-related hotspots and mucopolysaccharidosis were negative. Whole-exome sequencing, aged eight, via skeletal dysplasia panel analysis and subsequent whole-genome sequencing (via the 100,000 genomes project) found no cause. WGS data reanalysis using exomiser uncovered compound heterozygous pathogenic KIAA0753 variants (frameshift and splice site). Further clinical and radiological surveys were consistent with the expected phenotype. We discuss the emerging phenotype of this uncommon disorder. This report details the sixth published case of skeletal dysplasia in all cases of KIAA0753-related disease and the first case to describe a novel c.1830-2A>G splice variant. Our case is the eldest woman reported to date (aged ten years) and the only known case to report associated hearing loss, leg-length discrepancy, pectus carinatum, respiratory ciliary dyskinesia and late-onset (9 years old) neuro-degenerative regression.
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Ciliopatias/genética , Proteínas Associadas aos Microtúbulos/genética , Anormalidades Múltiplas/genética , Doenças do Desenvolvimento Ósseo/genética , Criança , Deficiências do Desenvolvimento/genética , Síndrome de Ellis-Van Creveld/genética , Anormalidades do Olho/genética , Feminino , Mutação da Fase de Leitura/genética , Predisposição Genética para Doença/genética , Humanos , Doenças Renais Císticas/genética , Megalencefalia/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Mutação/genética , Síndromes Orofaciodigitais/genética , Linhagem , Sequenciamento do ExomaRESUMO
Hypochondroplasia (HCH) is a rare autosomal dominant skeletal dysplasia condition caused by FGFR3 mutations leading to disproportionate short stature. Classically HCH presents in toddlers or school-age children, as limb-to-trunk disproportion and is often mild and easily overlooked during infancy. We report experiences from a single-center UK HCH-cohort of 31 patients, the rate of antenatal HCH detection in our cohort (13/31, 41.9%) and describe relevant case-data for this subset of 13 patients. Inclusion criteria were patients with confirmed molecular HCH diagnosis (by age 3 years) and presenting with short long-bones or large head size on antenatal ultrasound scan. We then conducted a systematic literature review using PUBMED and MEDLINE, analyzing patients with HCH and related antenatal findings. Antenatally suspected (with subsequent molecular confirmation) HCH has been reported 15 times in the literature (2004-2019). Key markers (consistent in both groups) included reduced; femur length, humeral length and increased; biparietal diameter and head circumference. HCH is increasingly detected both antenatally and in infancy, contrary to previous descriptions. This is likely due to greater HCH awareness, improved imaging, and easier molecular testing. Thus, one should consider HCH outside the classical presenting period. Studying the natural history of younger patients with HCH is important with the advent of several targeted FGFR3 therapies currently in trials for Achondroplasia, that may soon be trialed in HCH.
Assuntos
Acondroplasia/diagnóstico , Osso e Ossos/anormalidades , Nanismo/diagnóstico , Diagnóstico Precoce , Deformidades Congênitas dos Membros/diagnóstico , Lordose/diagnóstico , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/genética , Acondroplasia/genética , Acondroplasia/patologia , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/patologia , Nanismo/diagnóstico por imagem , Nanismo/genética , Nanismo/patologia , Feminino , Fêmur/diagnóstico por imagem , Fêmur/patologia , Humanos , Deformidades Congênitas dos Membros/diagnóstico por imagem , Deformidades Congênitas dos Membros/genética , Deformidades Congênitas dos Membros/patologia , Lordose/diagnóstico por imagem , Lordose/genética , Lordose/patologia , Mutação/genética , Gravidez , Reino UnidoRESUMO
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 6 October 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: 192 studies were included. Overall, 10% (95% confidence interval 7% to 12%; 73 studies, 67 271 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 (41%). Compared with non-pregnant women of reproductive age, pregnant and recently pregnant women with covid-19 were less likely to have symptoms (odds ratio 0.28, 95% confidence interval 0.13 to 0.62; I2=42.9%) or report symptoms of fever (0.49, 0.38 to 0.63; I2=40.8%), dyspnoea (0.76, 0.67 to 0.85; I2=4.4%) and myalgia (0.53, 0.36 to 0.78; I2=59.4%). The odds of admission to an intensive care unit (odds ratio 2.13, 1.53 to 2.95; I2=71.2%), invasive ventilation (2.59, 2.28 to 2.94; I2=0%) and need for extra corporeal membrane oxygenation (2.02, 1.22 to 3.34; I2=0%) were higher in pregnant and recently pregnant than non-pregnant reproductive aged women. Overall, 339 pregnant women (0.02%, 59 studies, 41 664 women) with confirmed covid-19 died from any cause. Increased maternal age (odds ratio 1.83, 1.27 to 2.63; I2=43.4%), high body mass index (2.37, 1.83 to 3.07; I2=0%), any pre-existing maternal comorbidity (1.81, 1.49 to 2.20; I2=0%), chronic hypertension (2.0, 1.14 to 3.48; I2=0%), pre-existing diabetes (2.12, 1.62 to 2.78; I2=0%), and pre-eclampsia (4.21, 1.27 to 14.0; I2=0%) were associated with severe covid-19 in pregnancy. In pregnant women with covid-19, increased maternal age, high body mass index, non-white ethnicity, any pre-existing maternal comorbidity including chronic hypertension and diabetes, and pre-eclampsia were associated with serious complications such as admission to an intensive care unit, invasive ventilation and maternal death. Compared to pregnant women without covid-19, those with the disease had increased odds of maternal death (odds ratio 2.85, 1.08 to 7.52; I2=0%), of needing admission to the intensive care unit (18.58, 7.53 to 45.82; I2=0%), and of preterm birth (1.47, 1.14 to 1.91; I2=18.6%). The odds of admission to the neonatal intensive care unit (4.89, 1.87 to 12.81, I2=96.2%) were higher in babies born to mothers with covid-19 versus those without covid-19. CONCLUSION: Pregnant and recently pregnant women with covid-19 attending or admitted to the hospitals for any reason are less likely to manifest symptoms such as fever, dyspnoea, and myalgia, and are more likely to be admitted to the intensive care unit or needing invasive ventilation than non-pregnant women of reproductive age. Pre-existing comorbidities, non-white ethnicity, chronic hypertension, pre-existing diabetes, high maternal age, and high body mass index are risk factors for severe covid-19 in pregnancy. Pregnant women with covid-19 versus without covid-19 are more likely to deliver preterm and could have an increased risk of maternal death and of being admitted to the intensive care unit. Their babies are more likely to be admitted to the neonatal unit. 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. This version is update 1 of the original article published on 1 September 2020 (BMJ 2020;370:m3320), and previous updates can be found as data supplements (https://www.bmj.com/content/370/bmj.m3320/related#datasupp). When citing this paper please consider adding the update number and date of access for clarity.