Maternal and children’s outcomes for pregnant women with pre-existing multiple long-term conditions: a study protocol of an observational study in the United Kingdom

Introduction One in five pregnant women have multiple long-term conditions in the United Kingdom (UK). Studies have shown that maternal multiple long-term conditions are associated with adverse outcomes. This observational study aims to compare maternal and children’s outcome for pregnant women with multiple long-term to those without multiple long-term conditions. Methods and analysis Pregnant women aged 15 to 49 years old with a conception date between 2000 and 2019 in the UK will be included. The data source will be routine health records from all four UK nations (Clinical Practice Research Datalink [CPRD, England], Secure Anonymised Information Linkage [SAIL, Wales], Scotland routine health records and Northern Ireland Maternity System [NIMATS]), and the Born in Bradford prospective birth cohort. The exposure of two or more pre-existing, long-term physical or mental health conditions will be defined from a list of health conditions predetermined by women and clinicians. The association of maternal multiple long-term conditions with (i) antenatal, (ii) peripartum, (iii) postnatal and long-term, and (iv) mental health outcomes, for both women and their children will be examined. Outcomes of interest will be guided by a core outcome set. Comparisons will be made between pregnant women with and without multiple long-term conditions using logistic and Cox regression. Generalised estimating equation will account for the clustering effect of women who had more than one pregnancy episode. Where appropriate, multiple imputation with chained equation will be used for missing data. Federated analysis will be conducted for each dataset and results will be pooled using meta-analysis. Ethics and dissemination Approval has been obtained from the respective data sources in each UK nation: CPRD: Independent Scientific Advisory Committee (reference: 20_181R); SAIL: Information Governance Review Panel; Scotland: National Health Service Scotland Public Benefit and Privacy Panel for Health and Social Care (HSC-PBPP), The University Teaching and Research Ethics Committee (UTREC) from the University of St Andrews; NIMATS: Honest Broker Service Governance Board; Born in Bradford: Bradford National Health Service Research Ethics Committee (ref 07/H1302/112). Study findings will be submitted for publications in peer reviewed journals and presented at key conferences for health and social care professionals involved in the care of pregnant women with multiple long-term conditions and their children. Strengths and limitations of this study ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work is 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 Research (NIHR) in partnership with the Economic and Social Research Council and in collaboration with the Engineering and Physical Sciences Research Council. The views expressed are those of the author and not necessarily those of the funders, the NIHR or the UK Department of Health and Social Care. The funders had no role in study design, decision to publish, or preparation of the manuscript. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics approval Clinical Practice Research Datalink (CPRD): CPRD has broad National Research Ethics Service Committee ethics approval for purely observational research using the primary care data and established data linkages. The study has been reviewed and approved by CPRD's Independent Scientific Advisory Committee (reference: 20_181R). Secure Anonymised Information Linkage (SAIL): In accordance with UK Health Research Authority guidance, ethical approval is not mandatory for studies using only anonymised data. The study has been approved by SAIL Information Governance Review Panel. Scotland dataset: The study has been approved by the National Health Service Scotland Public Benefit and Privacy Panel for Health and Social Care (HSC-PBPP) and The University Teaching and Research Ethics Committee (UTREC) from the University of St Andrews. Northern Ireland Maternity System (NIMATS): The study has been approved by the Honest Broker Service Governance Board. Born in Bradford: Ethics approval was granted by Bradford National Health Service Research Ethics Committee (ref 07/H1302/112) for the Born in Bradford cohort. The proposed study is purely observational and will use anonymised research data. The study will not involve participant recruitment. Therefore, consent to participate is not required. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes In the proposed study, the data that support the findings are available from CPRD, SAIL, Scotland National Health Service Scotland Public Benefit and Privacy Panel for Health and Social Care, NIMATS and Born in Bradford, but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of CPRD, SAIL, Scotland National Health Service Scotland Public Benefit and Privacy Panel for Health and Social Care, NIMATS and Born in Bradford. * BMI : Body mass index CPRD : Clinical Practice Research Datalink ICD-10 : International Classification of Disease 10th version MICE : Multiple imputation with chain equation NICE : National Institute for Health and Care Excellence NIMATS : Northern Ireland Maternity System OPCS : Operating Procedures Codes PPI : Patient and public involvement SAIL : Secure Anonymised Information Linkage UK : United Kingdom