Medicine use in pregnancy is extremely common, but there are significant knowledge gaps surrounding the safety, dosage and long-term effects of drugs used. Pregnant women have been purposively excluded from clinical trials of the majority of treatments for conditions that may occur concurrently with pregnancy. There is minimal information on the pharmacokinetics of many existing treatments, and no systematic capture of long-term outcome data to help inform choices. Treatments commonly used in pregnancy are thus often old and untested, not optimised in dose, and prescribed off-label without adequate safety information. In addition, there has been a staggering lack of investment in drug development for obstetric conditions for decades. This is a major public health concern, with pregnancy complications the leading cause of mortality in children under five years old globally, and health in pregnancy a major determinant of women's long-term health and wellbeing. There is an acute need for adequate investment and legislation to boost inclusion of pregnant women in clinical studies, capture high-quality information on medication use in pregnancy in general, and encourage new medicinal product development for obstetric conditions.
ABSTRACT
ObjectivesOutcomes at birth such as prematurity and birthweight are important determinants of later life health and social outcomes including education attainment, cognitive and behavioural development and a large number of health outcomes. Recently, it has become clear that characteristics of the physical environment, including air pollution, plays an important role in mediating outcomes of pregnancy. Vitamin D deficiency from lack of sunlight has also shown associations with pregnancy outcomes but this has not been replicated in intervention studies of vitamin D supplementation. Recent clinical evidence has pointed to a sunlight pathway that is independent of vitamin D, which instead mediates blood pressure through the production of Nitric Oxides in the skin from exposure to the UVA component of sunlight. This pathway might explain the lack of association with vitamin D supplementation and provides a plausible pathway for direct effects of sunlight exposure for pregnancy outcomes. In this study, we examined the effect of exposure to sunlight during pregnancy hypothesising that higher levels of exposure might reduce risks of premature birth and low birthweight.
ApproachWe used routinely collected maternity health data covering all births in Scotland in the period 2000-2010 (~ 550000 births). Using the mothers residential postcode at birth we attached estimates of UV exposure for each trimester of pregnancy based on a combination of MET office spatially detailed sun hours data and satellite derived solar insolation data. We modelled the effect of UV exposure for birthweight and risk of preterm birth with adjustment for confounding variables including smoking, parity and maternal stature. Sensitivity analysis using sibling pairs with discordant UV exposures was also explored to test the robustness of the findings to residual confounding.
ResultsResults are not available at time of writing but will be available for the conference presentation and will discuss the effects of UV exposure for both the risk of premature birth and low birthweight.
ConclusionsTogether with clinical evidence, findings from this study may serve to highlight a possible need to revisit public health advice regarding reducing UV exposure during pregnancy and may provide evidence for possible interventions including sun lamp therapy for pregnant mothers.
Funding EAVE II funded by the Medical Research Council (MR/R008345/1) with the support of BREATHE - The Health Data Research Hub for Respiratory Health (MC_PC_19004), which is funded through the UK Research and Innovation Industrial Strategy Challenge Fund and delivered through Health Data Research UK. Additional support has been provided through the Scottish Government DG Health and Social Care. COPS receive additional funding from Tommy's charity (1060508; SC039280). SJS is supported by Wellcome Trust (209560/Z/17/Z) ; Peer reviewed ; Publisher PDF
Introduction The effects of SARS-CoV-2 in pregnancy are not fully delineated. We will describe the incidence of COVID-19 in pregnancy at population level in Scotland, in a prospective cohort study using linked data. We will determine associations between COVID-19 and adverse pregnancy, neonatal and maternal outcomes and the proportion of confirmed cases of SARS-CoV-2 infection in neonates associated with maternal COVID-19. Methods and analysis Prospective cohort study using national linked data sets. We will include all women in Scotland, UK, who were pregnant on or became pregnant after, 1 March 2020 (the date of the first confirmed case of SARS-CoV-2 infection in Scotland) and all births in Scotland from 1 March 2020 onwards. Individual-level data will be extracted from data sets containing details of all livebirths, stillbirth, terminations of pregnancy and miscarriages and ectopic pregnancies treated in hospital or attending general practice. Records will be linked within the Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II) platform, which includes primary care records, virology and serology results and details of COVID-19 Community Hubs and Assessment Centre contacts and deaths. We will perform analyses using definitions for confirmed, probable and possible COVID-19 and report serology results (where available). Outcomes will include congenital anomaly, miscarriage, stillbirth, termination of pregnancy, preterm birth, neonatal infection, severe maternal disease and maternal deaths. We will perform descriptive analyses and appropriate modelling, adjusting for demographic and pregnancy characteristics and the presence of comorbidities. The cohort will provide a platform for future studies of the effectiveness and safety of therapeutic interventions and immunisations for COVID-19 and their effects on childhood and developmental outcomes. Ethics and dissemination COVID-19 in Pregnancy in Scotland is a substudy of EAVE II(, which has approval from the National Research Ethics Service Committee. Findings will be reported to Scottish Government, Public Health Scotland and published in peer-reviewed journals.
Funding: EAVE II funded by the Medical Research Council (MR/R008345/1) with the support of BREATHE - The Health Data Research Hub for Respiratory Health [MC_PC_19004], which is funded through the UK Research and Innovation Industrial Strategy Challenge Fund and delivered through Health Data Research UK. Additional support has been provided through the Scottish Government DG Health and Social Care. COPS receive additional funding from Tommy's charity (1060508; SC039280). SJS is supported by Wellcome Trust (209560/Z/17/Z). ; Introduction The effects of SARS-CoV-2 in pregnancy are not fully delineated. We will describe the incidence of COVID-19 in pregnancy at population level in Scotland, in a prospective cohort study using linked data. We will determine associations between COVID-19 and adverse pregnancy, neonatal and maternal outcomes and the proportion of confirmed cases of SARS-CoV-2 infection in neonates associated with maternal COVID-19. Methods and analysis Prospective cohort study using national linked data sets. We will include all women in Scotland, UK, who were pregnant on or became pregnant after, 1 March 2020 (the date of the first confirmed case of SARS-CoV-2 infection in Scotland) and all births in Scotland from 1 March 2020 onwards. Individual-level data will be extracted from data sets containing details of all livebirths, stillbirth, terminations of pregnancy and miscarriages and ectopic pregnancies treated in hospital or attending general practice. Records will be linked within the Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II) platform, which includes primary care records, virology and serology results and details of COVID-19 Community Hubs and Assessment Centre contacts and deaths. We will perform analyses using definitions for confirmed, probable and possible COVID-19 and report serology results (where available). Outcomes will include congenital anomaly, miscarriage, stillbirth, termination of pregnancy, preterm birth, neonatal infection, severe maternal disease and maternal deaths. We will perform descriptive analyses and appropriate modelling, adjusting for demographic and pregnancy characteristics and the presence of comorbidities. The cohort will provide a platform for future studies of the effectiveness and safety of therapeutic interventions and immunisations for COVID-19 and their effects on childhood and developmental outcomes. Ethics and dissemination COVID-19 in Pregnancy in Scotland is a substudy of EAVE II(, which has approval from the National Research Ethics Service Committee. Findings will be reported to Scottish Government, Public Health Scotland and published in peer-reviewed journals. ; Publisher PDF ; Peer reviewed
Introduction: The effects of SARS-CoV-2 in pregnancy are not fully delineated. We will describe the incidence of COVID-19 in pregnancy at population level in Scotland, in a prospective cohort study using linked data. We will determine associations between COVID-19 and adverse pregnancy, neonatal and maternal outcomes and the proportion of confirmed cases of SARS-CoV-2 infection in neonates associated with maternal COVID-19. Methods and analysis: Prospective cohort study using national linked data sets. We will include all women in Scotland, UK, who were pregnant on or became pregnant after, 1 March 2020 (the date of the first confirmed case of SARS-CoV-2 infection in Scotland) and all births in Scotland from 1 March 2020 onwards. Individual-level data will be extracted from data sets containing details of all livebirths, stillbirth, terminations of pregnancy and miscarriages and ectopic pregnancies treated in hospital or attending general practice. Records will be linked within the Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II) platform, which includes primary care records, virology and serology results and details of COVID-19 Community Hubs and Assessment Centre contacts and deaths. We will perform analyses using definitions for confirmed, probable and possible COVID-19 and report serology results (where available). Outcomes will include congenital anomaly, miscarriage, stillbirth, termination of pregnancy, preterm birth, neonatal infection, severe maternal disease and maternal deaths. We will perform descriptive analyses and appropriate modelling, adjusting for demographic and pregnancy characteristics and the presence of comorbidities. The cohort will provide a platform for future studies of the effectiveness and safety of therapeutic interventions and immunisations for COVID-19 and their effects on childhood and developmental outcomes. Ethics and dissemination: COVID-19 in Pregnancy in Scotland is a substudy of EAVE II(, which has approval from the National Research Ethics Service Committee. Findings will be reported to Scottish Government, Public Health Scotland and published in peer-reviewed journals.
Funding: This research is part of the Data and Connectivity National Core Study, led by Health Data Research UK in partnership with the Office for National Statistics and funded by UK Research and Innovation (grant ref MC_PC_20058). SVK acknowledges funding from a NRS Senior Clinical Fellowship (SCAF/15/02), the Medical Research Council (MC_UU_00022/2) and the Scottish Government Chief Scientist Office (SPHSU17). ; Background The dynamics of acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission and severity of disease among children and young people (CYP) across different settings are of considerable clinical, public health and societal interest. Severe COVID-19 cases, requiring hospitalisations, and deaths have been reported in some CYP suggesting a need to extend vaccinations to these age groups. As part of the ongoing Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II) study, we aim to investigate the uptake, effectiveness and safety of COVID-19 vaccines in children and young people (CYP) aged 0 to 17 years in Scotland. Specifically, we will estimate: (i) uptake of vaccines against COVID-19, (ii) vaccine effectiveness (VE) against the outcomes of symptomatic SARS-CoV-2 infection, hospitalisation, intensive care unit (ICU) admissions, and death; (iii) VE for first/second dose timing among different age groups and risk groups; and (iv) the safety of vaccines. Methods and analysis We will conduct an open prospective cohort study classifying exposure as time-varying. We will compare outcomes amongst first dose vaccinated and second dose vaccinated CYP to those not yet vaccinated. A Test Negative Design (TND) case control study will be nested within this national cohort to investigate VE against symptomatic infection. The primary outcomes will be (i) uptake of vaccines against COVID-19, (ii) time to COVID-19 infection, hospitalisation, ICU admissions or death, and (iii) adverse events related to vaccines. Vaccination status (unvaccinated, one dose and two doses) will be defined as a time-varying exposure. Data from multiple sources will be linked using a unique identifier. We will conduct descriptive analyses to explore trends in vaccine uptake, and association between different exposure variables and vaccine uptake will be determined using multivariable logistic regression models. VE will be assessed from time-dependent Cox models or Poisson regression models, adjusted for relevant confounders, including age, sex, socioeconomic status, and comorbidities. We will employ self-controlled study designs to determine the risk of adverse events following COVID-19 vaccination. Ethics and dissemination Ethics approval was obtained from the National Research Ethics Committee, South East Scotland 02. We will present findings of this study at international conferences, in peer-reviewed journals and to policy-makers. ; Publisher PDF ; Peer reviewed
This study is part of the EAVE II project. EAVE II is funded by the MRC (MC_PC_19075) with the support of BREATHE—The Health Data Research Hub for Respiratory Health (MC_PC_19004), which is funded through the UK Research and Innovation Industrial Strategy Challenge Fund and delivered through Health Data Research UK. This research is part of the Data and Connectivity National Core Study, led by Health Data Research UK in partnership with the Office for National Statistics and funded by UK Research and Innovation (MC_PC_20058). Additional support has been provided through Public Health Scotland, the Scottish Government Director General Health and Social Care, and the University of Edinburgh. The original EAVE project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme (11/46/23). The views expressed are those of the authors and not necessarily those of the NIHR, the Department of Health and Social Care, or the UK Government. We thank Dave Kelly from Albasoft (Inverness, UK) for his support with making primary care data available, and Wendy Inglis-Humphrey, Vicky Hammersley, and Laura Brook (University of Edinburgh, Edinburgh, UK) for their support with project management and administration. ; Peer reviewed ; Publisher PDF
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This analysis is part of the Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II) study. EAVE II is funded by the Medical Research Council (MR/R008345/1) with the support of BREATHE – The Health Data Research Hub for Respiratory Health (MC_PC_19004), which is funded through the UK Research and Innovation Industrial Strategy Challenge Fund and delivered through Health Data Research UK. Additional support has been provided through the Scottish Government DG Health and Social Care. SAS and AS are also supported by the COVID-19 Longitudinal Health and Wellbeing National Core Study, funded by the Medical Research Council (MC_PC_20030). SVK acknowledges funding from a NRS Senior Clinical Fellowship (SCAF/15/02), the Medical Research Council (MC_UU_00022/2) and the Scottish Government Chief Scientist Office (SPHSU17). JM is partly funded by the National Institute for Health Research Applied Research Collaboration West (NIHR ARC West). ; Objectives COVID-19 has resulted in the greatest disruption to National Health Service (NHS) care in its over 70-year history. Building on our previous work, we assessed the ongoing impact of pandemic-related disruption on provision of emergency and elective hospital-based care across Scotland over the first year of the pandemic. Design We undertook interrupted time-series analyses to evaluate the impact of ongoing pandemic-related disruption on hospital NHS care provision at national level and across demographics and clinical specialties spanning the period 29 March 2020?28 March 2021. Setting Scotland, UK. Participants Patients receiving hospital care from NHS Scotland. Main outcome measures We used the percentage change of accident and emergency attendances, and emergency and planned hospital admissions during the pandemic compared to the average admission rate for equivalent weeks in 2018-2019. Results As restrictions were ...
Funding: This study is being funded by the UKRI Centre on the Dynamics of Ethnicity 4 (ES/W000849/1). PH, SVK, AHL and KJH are funded by the Medical Research Council (MC_UU_00022/2) and Scottish Government Chief Scientist Office (SPHSU17). SVK is funded by a NRS Senior Clinical Fellowship (SCAF/15/02). EAVE II is funded by the Medical Research Council (MR/R008345/1) with the support of BREATHE-The Health Data Research Hub for Respiratory Health (MC_PC_19004), which is funded through the UK Research and Innovation Industrial Strategy Challenge Fund and delivered through Health Data Research UK; with additional support from the Scottish Government DG Health and Social Care. ; Introduction Evidence from previous pandemics, and the current COVID-19 pandemic, has found that risk of infection/severity of disease is disproportionately higher for ethnic minority groups, and those in lower socioeconomic positions. It is imperative that interventions to prevent the spread of COVID-19 are targeted towards high-risk populations. We will investigate the associations between social characteristics (such as ethnicity, occupation and socioeconomic position) and COVID-19 outcomes and the extent to which characteristics/risk factors might explain observed relationships in Scotland. The primary objective of this study is to describe the epidemiology of COVID-19 by social factors. Secondary objectives are to (1) examine receipt of treatment and prevention of COVID-19 by social factors; (2) quantify ethnic/social differences in adverse COVID-19 outcomes; (3) explore potential mediators of relationships between social factors and SARS-CoV-2 infection/COVID-19 prognosis; (4) examine whether occupational COVID-19 differences differ by other social factors and (5) assess quality of ethnicity coding within National Health Service datasets. Methods and analysis We will use a national cohort comprising the adult population of Scotland who completed the 2011 Census and were living in Scotland on 31 March 2020 (~4.3 million people). Census data will be linked to the Early Assessment of Vaccine and Anti-Viral Effectiveness II cohort consisting of primary/secondary care, laboratory data and death records. Sensitivity/specificity and positive/negative predictive values will be used to assess coding quality of ethnicity. Descriptive statistics will be used to examine differences in treatment and prevention of COVID-19. Poisson/Cox regression analyses and mediation techniques will examine ethnic and social differences, and drivers of inequalities in COVID-19. Effect modification (on additive and multiplicative scales) between key variables (such as ethnicity and occupation) will be assessed. Ethics and dissemination Ethical approval was obtained from the National Research Ethics Committee, South East Scotland 02. We will present findings of this study at international conferences, in peer-reviewed journals and to policy-makers. ; Publisher PDF ; Peer reviewed
Funding: COPS is a sub-study of EAVE II, which is funded by the Medical Research Council (MR/R008345/1) with the support of BREATHE - The Health Data Research Hub for Respiratory Health [MC_PC_19004; AS], which is funded through the UK Research and Innovation Industrial Strategy Challenge Fund and delivered through Health Data Research UK. Additional support has been provided through Public Health Scotland and Scottish Government DG Health and Social Care and the Data and Connectivity National Core Study, led by Health Data Research UK in partnership with the Office for National Statistics and funded by UK Research and Innovation. COPS has received additional funding from Tommy's charity and support from Sands charity. SJS is funded by a Wellcome Trust Clinical Career Development Fellowship (209560/Z/17/Z; SJS). SVK acknowledges funding from a NRS Senior Clinical Fellowship (SCAF/15/02; SVK), the Medical Research Council (MC_UU_00022/2; SVK) and the Scottish Government Chief Scientist Office (SPHSU17; SVK). ; Population-level data on COVID-19 vaccine uptake in pregnancy and SARS-CoV-2 infection outcomes are lacking. We describe COVID-19 vaccine uptake and SARS-CoV-2 infection in pregnant women in Scotland, using whole population data from a national, prospective cohort. Between the start of COVID-19 vaccine programme in Scotland, on 8 December 2020, and 31 October 2021, 25,917 COVID-19 vaccinations were given to 18,457 pregnant women. Vaccine coverage was substantially lower in pregnant women than in the general female population 18-44 years: 32.3% of women giving birth in October 2021 had two doses of vaccine compared to 77.4% in all women. The extended perinatal mortality rate for women who gave birth within 28 days of a COVID-19 diagnosis was 22.6 per 1,000 births (95% CI 12.9-38.5; pandemic background rate 5.6 per 1,000 births (452/80,456; 95% CI 5.1-6.2). 77.4% (3,833/ 4,950; 95% CI 76.2-78.6) of SARS-CoV-2 infections, 90.9% (748/823; 95% CI 88.7-92.7) of SARS-CoV-2 associated with hospital admission, and ...
Funding Information: AS, JM, and CR are members of the Scottish Government Chief Medical Officer's COVID-19 Advisory Group. JM is a member of the New and Emerging Respiratory Virus Threats Advisory Group (NERVTAG) and AS is a member of the NERVTAG Risk Stratification Subgroup and an unfunded member of Astra-Zeneca's COVID-19 Strategic Consultancy Group: Thrombocytopenia Taskforce. JM is a member of the Scientific Advisory Group on Emergencies (SAGE) and chairs the COVID Scottish National Incident Management Team and the Scientific Committee of the European Centre for Disease Prevention and Control/WHO-funded IMOVE-COVID-19 group. CM reports research funding from Medical Research Council (MRC), Health Data Research UK, National Institute for Health Research (NIHR), and Scottish Chief Scientist Office (CSO). SJS reports research funding from Wellcome Trust, MRC, NIHR, and Scottish CSO. CRS declares funding from the MRC, NIHR, Scottish CSO, and the New Zealand Ministry for Business, Innovation and Employment and Health Research Council during the conduct of this study. SVK is co-chair of the Scottish Government's Expert Reference Group on COVID-19 and ethnicity, is a member of the SAGE subgroup on ethnicity, and acknowledges funding from a NHS Research Scotland Senior Clinical Fellowship, MRC, and Scottish CSO. CR is a member of the Scientific Pandemic Influenza Group on Modelling and the Medicines and Healthcare Products Regulatory Agency Vaccine Benefit and Risk Working Group. JLKM is a member of the COVID Scottish National Incident Management Team. SdL has received funding through his University from AstraZeneca. FDRH acknowledges part support from the NIHR Applied Research Collaboration Oxford Thames Valley and the NIHR Oxford University Hospital Biomedical Research Centre. All other authors declare no competing interests. Funding Information: EAVE II is funded by the Medical Research Council (MR/R008345/1) with the support of BREATHE?The Health Data Research Hub for Respiratory Health [MC_PC_19004], which is funded through the UK Research and Innovation Industrial Strategy Challenge Fund and delivered through Health Data Research UK. Additional support has been provided through Public Health Scotland and Scottish Government Director-General Health and Social Care. We thank Dave Kelly from Albasoft for his support with making primary care data available and James Pickett, Wendy Inglis-Humphrey, Vicky Hammersley, Maria Georgiou, Laura Gonzalez Rienda, Pam McVeigh, Amanda Burridge, Sumedha Asnani-Chetal, and Afshin Dastafshan for their support with project management and administration. We acknowledge the support of the EAVE II Patient Advisory Group. UA, CM, AA-L, and AFF acknowledge funding from Chief Scientist Office Rapid Research in COVID-19 programme (COV/SAN/20/06) and Health Data Research UK (measuring and understanding multimorbidity using routine data in the UK?HDR-9006; CFC0110). SVK acknowledges funding from a NHS Research Scotland Senior Clinical Fellowship (SCAF/15/02), the Medical Research Council (MC_UU_00022/2), and the Scottish Government's Chief Scientist Office (SPHSU17). SJS is funded by a Wellcome Trust Clinical Career Development Fellowship (209560/Z/17/Z). Funding Information: EAVE II is funded by the Medical Research Council (MR/R008345/1) with the support of BREATHE—The Health Data Research Hub for Respiratory Health [MC_PC_19004], which is funded through the UK Research and Innovation Industrial Strategy Challenge Fund and delivered through Health Data Research UK. Additional support has been provided through Public Health Scotland and Scottish Government Director-General Health and Social Care. We thank Dave Kelly from Albasoft for his support with making primary care data available and James Pickett, Wendy Inglis-Humphrey, Vicky Hammersley, Maria Georgiou, Laura Gonzalez Rienda, Pam McVeigh, Amanda Burridge, Sumedha Asnani-Chetal, and Afshin Dastafshan for their support with project management and administration. We acknowledge the support of the EAVE II Patient Advisory Group. UA, CM, AA-L, and AFF acknowledge funding from Chief Scientist Office Rapid Research in COVID-19 programme (COV/SAN/20/06) and Health Data Research UK (measuring and understanding multimorbidity using routine data in the UK—HDR-9006; CFC0110). SVK acknowledges funding from a NHS Research Scotland Senior Clinical Fellowship (SCAF/15/02), the Medical Research Council (MC_UU_00022/2), and the Scottish Government's Chief Scientist Office (SPHSU17). SJS is funded by a Wellcome Trust Clinical Career Development Fellowship (209560/Z/17/Z). ; Peer reviewed ; Publisher PDF
