Thromboprophylaxis during pregnancy and the puerperium: a systematic review and economic evaluation to estimate the value of future research.

Background: Pharmacological prophylaxis to prevent venous thromboembolism is currently recommended for women assessed as being at high risk of venous thromboembolism during pregnancy or in the 6 weeks after delivery (the puerperium). The decision to provide thromboprophylaxis involves weighing the benefits, harms and costs, which vary according to the individual's venous thromboembolism risk. It is unclear whether the United Kingdom's current risk stratification approach could be improved by further research. Objectives: To quantify the current decision uncertainty associated with selecting women who are pregnant or in the puerperium for thromboprophylaxis and to estimate the value of one or more potential future studies that would reduce that uncertainty, while being feasible and acceptable to patients and clinicians. Methods: A decision-analytic model was developed which was informed by a systematic review of risk assessment models to predict venous thromboembolism in women who are pregnant or in the puerperium. Expected value of perfect information analysis was used to determine which factors are associated with high decision uncertainty and should be the target of future research. To find out whether future studies would be acceptable and feasible, we held workshops with women who have experienced a blood clot or have been offered blood-thinning drugs and surveyed healthcare professionals. Expected value of sample information analysis was used to estimate the value of potential future research studies. Results: The systematic review included 17 studies, comprising 19 unique externally validated risk assessment models and 1 internally validated model. Estimates of sensitivity and specificity were highly variable ranging from 0% to 100% and 5% to 100%, respectively. Most studies had unclear or high risk of bias and applicability concerns. The decision analysis found that there is substantial decision uncertainty regarding the use of risk assessment models to select high-risk women for antepartum prophylaxis and obese postpartum women for postpartum prophylaxis. The main source of decision uncertainty was uncertainty around the effectiveness of thromboprophylaxis for preventing venous thromboembolism in women who are pregnant or in the puerperium. We found that a randomised controlled trial of thromboprophylaxis in obese postpartum women is likely to have substantial value and is more likely to be acceptable and feasible than a trial recruiting women who have had a previous venous thromboembolism. In unselected postpartum women and women following caesarean section, the poor performance of risk assessment models meant that offering prophylaxis based on these models had less favourable cost effectiveness with lower decision uncertainty. Limitations: The performance of the risk assessment model for obese postpartum women has not been externally validated. Conclusions: Future research should focus on estimating the efficacy of pharmacological thromboprophylaxis in pregnancy and the puerperium, and clinical trials would be more acceptable in women who have not had a previous venous thromboembolism. Study registration: This study is registered as PROSPERO CRD42020221094. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR131021) and is published in full in Health Technology Assessment; Vol. 28, No. 9. See the NIHR Funding and Awards website for further award information.

Women who are pregnant or who have given birth in the previous 6 weeks are at increased risk of developing blood clots that can cause serious illness or death. Small doses of blood thinners given by injection are safe in pregnancy and can reduce the risk of blood clots, but they can slightly increase the risk of bleeding. Healthcare professionals use risk assessment tools to decide if a woman is at high risk of blood clots and should be offered blood thinners. We wanted to find out what research would be useful to help them make better decisions. We reviewed previous research to establish which risk assessment tools are best at predicting who will have a blood clot. We then created a mathematical model to predict what would happen when using different risk assessment tools to decide who should be offered blood thinners, both during pregnancy and after giving birth. We found that there was a lot of uncertainty about which women should be offered blood thinners. This was mainly because there have only been a few small studies comparing blood thinners to no treatment in pregnant women or women who have recently given birth. We estimated the value of future studies comparing blood thinners to no treatment, in groups of women with different risk factors, by predicting what information we would gain and how this would be used to improve decisions about using blood thinners. To find out whether these studies would be acceptable and feasible, we held workshops with women who have experienced a blood clot or have been offered blood thinners and surveyed healthcare professionals. We found that a study in obese women who have recently given birth would have substantial value and may be more acceptable than a study in pregnant women with a previous blood clot.

Autoimmune diseases and adverse pregnancy outcomes: an umbrella review.

BACKGROUND: There is a high prevalence of autoimmune conditions in women specially in the reproductive years; thus, the association with adverse pregnancy outcomes has been widely studied. However, few autoimmune conditions/adverse outcomes have been studied more than others, and this umbrella review aims to consolidate existing knowledge in this area with the aim to provide new knowledge and also identify gaps in this research area. METHODS: Medline, Embase, and Cochrane databases were searched from inception to December 2023. Screening, data extraction, and quality appraisal (AMSTAR 2) were done by two independent reviewers. Data were synthesised narratively and quantitatively. Relative risks (RR)/odds ratio (OR) with 95% confidence intervals were reported. RESULTS: Thirty-two reviews were included consisting of 709 primary studies. The review reported the association between 12 autoimmune conditions and 16 adverse pregnancy outcomes. Higher risk of miscarriage is reported in women with Sjögren's syndrome RR 8.85 (95% CI 3.10-25.26) and systemic lupus erythematosus (SLE) OR 4.90 (3.10-7.69). Pre-eclampsia was reported higher in women with type 1 diabetes mellitus (T1DM) OR 4.19 (3.08-5.71) and SLE OR 3.20 (2.54-4.20). Women reported higher risk of diabetes during pregnancy with inflammatory bowel disease (IBD) OR 2.96 (1.47-5.98). There was an increased risk of intrauterine growth restriction in women with systemic sclerosis OR 3.20 (2.21-4.53) and coeliac disease OR 1.71 (1.36-2.14). Preterm birth was associated with T1DM OR 4.36 (3.72-5.12) and SLE OR 2.79 (2.07-3.77). Low birth weight babies were reported in women with women with SLE or systemic sclerosis OR 5.95 (4.54-7.80) and OR 3.80 (2.16-6.56), respectively. There was a higher risk of stillbirth in women with T1DM OR 3.97 (3.44-4.58), IBD OR 1.57 (1.03-2.38), and coeliac disease OR 1.57 (1.17-2.10). T1DM in women was associated with 32% lower odds of small for gestational age baby OR 0.68 (0.56-0.83). CONCLUSIONS: Pregnant women with autoimmune conditions are at a greater risk of developing adverse pregnancy outcomes. Further research is required to develop better preconception to postnatal care for women with autoimmune conditions.

Estimating the value of future research into thromboprophylaxis for women during pregnancy and after delivery: a value of information analysis.

BACKGROUND: Risk assessment models (RAMs) are used to select women at increased risk of venous thromboembolism (VTE) during pregnancy and the puerperium for thromboprophylaxis. OBJECTIVES: To estimate the value of potential future studies that would reduce the decision uncertainty associated with offering thromboprophylaxis according to available RAMs in the following groups: high-risk antepartum women (eg, prior VTE), unselected postpartum women, and postpartum women with risk factors (obesity or cesarean delivery). METHODS: A decision-analytic model was developed to simulate clinical outcomes, lifetime costs, and quality-adjusted life-years for different thromboprophylaxis strategies, including thromboprophylaxis for all, thromboprophylaxis for none, and RAM-based thromboprophylaxis. The expected value of perfect information analysis was used to determine which factors are associated with high decision uncertainty. The value of future research studies was estimated using expected value of sample information analysis. Costs were assessed from a health and social services perspective. RESULTS: The expected value of perfect information analysis identified high decision uncertainty for high-risk antepartum women (£21.8 million) and obese postpartum women (£13.4 million), which was largely attributable to uncertainty regarding the effectiveness of thromboprophylaxis in reducing VTE. A randomized controlled trial of thromboprophylaxis compared with none in obese postpartum women is likely to have substantial value (£2.8 million; 300 participants per arm). A trial in women with previous VTE would have higher value but would be less acceptable. CONCLUSION: Future research should focus on estimating the effectiveness of thromboprophylaxis in obese postpartum women with additional risk factors who have not had a previous VTE.

Autoimmune diseases and adverse pregnancy outcomes: an umbrella review.

BACKGROUND: The prevalence of autoimmune conditions is two-fold higher in women than in men, especially during the reproductive years. Autoimmune conditions have been associated with a greater risk of adverse pregnancy outcomes, and some conditions have been studied more than others with inconsistent findings. The objective of this umbrella review was to identify, appraise, synthesise, and consolidate findings from published systematic reviews of autoimmune conditions and adverse pregnancy outcomes. METHODS: In this umbrella review, we searched Medline, Embase, and Cochrane databases for systematic reviews from inception to Sept 30, 2022, without language restrictions. We used the Medical Subject Headings and free text search for autoimmune conditions and pregnancy outcomes. Screening, data extraction, and quality appraisal (AMSTAR 2) were done by two independent reviewers. Data was extracted using a standardised form, which was piloted before use. Data were synthesised narratively and quantitatively. Odds ratios (ORs) with 95% CIs were reported. The protocol has been registered to PROSPERO (CRD42022334992). FINDINGS: We selected 33 reviews, which included 709 primary studies. Pregnant women with autoimmune conditions were at high risk of both adverse maternal and fetal outcomes. The risk of miscarriage was increased in pregnant women with Sjögren's syndrome (relative risk [RR] 8·85, 95% CI 3·10-25·26), systemic lupus erythematosus (SLE; OR 4·90, 95% CI 3·10-7·69), thyroid autoimmunity (OR 2·77, 2·10-3·65), systemic sclerosis (OR 1·60, 1·29-2·22), and coeliac disease (OR 1·38, 1·12-1·69). The risk of pre-eclampsia was increased in pregnant women with type 1 diabetes (T1DM; OR 4·19, 3·08-5·71) and SLE (OR 3·20, 2·54 - 4·20). The risk of gestational diabetes was increased in pregnant women with inflammatory bowel disease (IBD; OR 2·96, 1·47-5·98) and thyroid autoimmunity (OR 1·49, 1·07-2·07). The risk of intrauterine growth restriction (IUGR) was increased in pregnant women with systemic sclerosis (OR 3·20, 2·21-4·53) and coeliac disease (OR 1·71, 1·36-2·14). The risk of delivering a small-for-gestational age baby was increased in pregnant women with SLE (OR 2·49, 1·88-3·31) and rheumatoid arthritis (OR 1·49, 1·22-1·82). The risks of other fetal outcomes such as stillbirth, preterm birth, and low birthweight were also increased in pregnant women with autoimmune disorders. T1DM in women was associated with lower odds of small-for-gestational-age outcome (OR 0·68, 0·56-0·83). INTERPRETATION: Pregnant women with autoimmune conditions are at greater risk of developing adverse pregnancy outcomes. Further research is required to develop better preconception to post-natal care for women with autoimmune conditions. FUNDING: Medical Research Council (MRC) and the National Institute for Health and Care Research (NIHR).

Detection and evaluation of signals associated with exposure to individual and combination of medications in pregnancy: a signal detection study protocol.

INTRODUCTION: Considering the high prevalence of polypharmacy in pregnant women and the knowledge gap in the risk-benefit safety profile of their often-complex treatment plan, more research is needed to optimise prescribing. In this study, we aim to detect adverse and protective effect signals of exposure to individual and pairwise combinations of medications during pregnancy. METHODS AND ANALYSIS: Using a range of real-world data sources from the UK, we aim to conduct a pharmacovigilance study to assess the safety of medications prescribed during the preconception period (3 months prior to conception) and first trimester of pregnancy. Women aged between 15 and 49 years with a record of pregnancy within the Clinical Practice Research Datalink (CPRD) Pregnancy Register, the Welsh Secure Anonymised Information Linkage (SAIL), the Scottish Morbidity Record (SMR) data sets and the Northern Ireland Maternity System (NIMATS) will be included. A series of case control studies will be conducted to estimate measures of disproportionality, detecting signals of association between a range of pregnancy outcomes and exposure to individual and combinations of medications. A multidisciplinary expert team will be invited to a signal detection workshop. By employing a structured framework, signals will be transparently assessed by each member of the team using a questionnaire appraising the signals on aspects of temporality, selection, time and measurement-related biases and confounding by underlying disease or comedications. Through group discussion, the expert team will reach consensus on each of the medication exposure-outcome signal, thereby excluding spurious signals, leaving signals suggestive of causal associations for further evaluation. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Independent Scientific Advisory Committee, SAIL Information Governance Review Panel, University of St. Andrews Teaching and Research Ethics Committee and Office for Research Ethics Committees Northern Ireland (ORECNI) for access and use of CPRD, SAIL, SMR and NIMATS data, respectively.

A treatment strategy with nifedipine versus labetalol for women with pregnancy hypertension: study protocol for a randomised controlled trial (Giant PANDA).

BACKGROUND: Approximately one in ten women have high blood pressure during pregnancy. Hypertension is associated with adverse maternal and perinatal outcomes, and as treatment improves maternal outcomes, antihypertensive treatment is recommended. Previous trials have been unable to provide a definitive answer on which antihypertensive treatment is associated with optimal maternal and neonatal outcomes and the need for robust evidence evaluating maternal and infant benefits and risks remains an important, unanswered question for research and clinical communities. METHODS: The Giant PANDA study is a pragmatic, open-label, multicentre, randomised controlled trial of a treatment initiation strategy with nifedipine (calcium channel blocker), versus labetalol (mixed alpha/beta blocker) in 2300 women with pregnancy hypertension. The primary objective is to evaluate if treatment with nifedipine compared to labetalol in women with pregnancy hypertension reduces severe maternal hypertension without increasing fetal or neonatal death or neonatal unit admission. Subgroup analyses will be undertaken by hypertension type (chronic, gestational, pre-eclampsia), diabetes (yes, no), singleton (yes, no), self-reported ethnicity (Black, all other), and gestational age at randomisation categories (11 + 0 to 19 + 6, 20 + 0 to 27 + 6, 28 + 0 to 34 + 6 weeks). A cost-effectiveness analysis using an NHS perspective will be undertaken using a cost-consequence analysis up to postnatal hospital discharge and an extrapolation exercise with a lifetime horizon conditional on the results of the cost-consequence analysis. DISCUSSION: This trial aims to address the uncertainty of which antihypertensive treatment is associated with optimal maternal and neonatal outcomes. The trial results are intended to provide definitive evidence to inform guidelines and linked, shared decision-making tools, thus influencing clinical practice. TRIAL REGISTRATION: EudraCT number: 2020-003410-12, ISRCTN: 12,792,616 registered on 18 November 2020.

Maternal multimorbidity and preterm birth in Scotland: an observational record-linkage study.

BACKGROUND: Multimorbidity is common in women across the life course. Preterm birth is the single biggest cause of neonatal mortality and morbidity. We aim to estimate the prevalence of multimorbidity in pregnant women and to examine the association between maternal multimorbidity and PTB. METHODS: This is a retrospective cohort study using electronic health records from the Scottish Morbidity Records. All pregnancies among women aged 15 to 49 with a conception date between 1 January 2014 and 31 December 2018 were included. Multimorbidity was defined as the presence of two or more pre-existing long-term physical or mental health conditions, and complex multimorbidity as the presence of four or more. It was calculated at the time of conception using a predefined list of 79 conditions published by the MuM-PreDiCT consortium. PTB was defined as babies born alive between 24 and less than 37 completed weeks of gestation. We used Generalised Estimating Equations adjusted for maternal age, socioeconomic status, number of previous pregnancies, BMI, and smoking history to estimate the effect of maternal pre-existing multimorbidity. Absolut rates are reported in the results and tables, whilst Odds Ratios (ORs) are adjusted (aOR). RESULTS: Thirty thousand five hundred fifty-seven singleton births from 27,711 pregnant women were included in the analysis. The prevalence of pre-existing multimorbidity and complex multimorbidity was 16.8% (95% CI: 16.4-17.2) and 3.6% (95% CI: 3.3-3.8), respectively. The prevalence of multimorbidity in the youngest age group was 10.2%(95% CI: 8.8-11.6), while in those 40 to 44, it was 21.4% (95% CI: 18.4-24.4), and in the 45 to 49 age group, it was 20% (95% CI: 8.9-31.1). In women without multimorbidity, the prevalence of PTB was 6.7%; it was 11.6% in women with multimorbidity and 15.6% in women with complex multimorbidity. After adjusting for maternal age, socioeconomic status, number of previous pregnancies, Body Mass Index (BMI), and smoking, multimorbidity was associated with higher odds of PTB (aOR = 1.64, 95% CI: 1.48-1.82). CONCLUSIONS: Multimorbidity at the time of conception was present in one in six women and was associated with an increased risk of preterm birth. Multimorbidity presents a significant health burden to women and their offspring. Routine and comprehensive evaluation of women with multimorbidity before and during pregnancy is urgently needed.

The development of a core outcome set for studies of pregnant women with multimorbidity.

BACKGROUND: Heterogeneity in reported outcomes can limit the synthesis of research evidence. A core outcome set informs what outcomes are important and should be measured as a minimum in all future studies. We report the development of a core outcome set applicable to observational and interventional studies of pregnant women with multimorbidity. METHODS: We developed the core outcome set in four stages: (i) a systematic literature search, (ii) three focus groups with UK stakeholders, (iii) two rounds of Delphi surveys with international stakeholders and (iv) two international virtual consensus meetings. Stakeholders included women with multimorbidity and experience of pregnancy in the last 5 years, or are planning a pregnancy, their partners, health or social care professionals and researchers. Study adverts were shared through stakeholder charities and organisations. RESULTS: Twenty-six studies were included in the systematic literature search (2017 to 2021) reporting 185 outcomes. Thematic analysis of the focus groups added a further 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). Thirteen stakeholders reviewed 15 Borderline outcomes in the first consensus meeting and included seven additional outcomes. Seventeen stakeholders reviewed these 52 outcomes in a second consensus meeting, the threshold was ≥80% of all participants voting for inclusion. The final core outcome set included 11 outcomes. The five maternal outcomes were as follows: 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 as follows: 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. CONCLUSIONS: Multimorbidity in pregnancy is a new and complex clinical research area. Following a rigorous process, this complexity was meaningfully reduced to a core outcome set that balances the views of a diverse stakeholder group.

Key outcomes for reporting in studies of pregnant women with multiple long-term conditions: a qualitative study.

BACKGROUND: Maternal multiple long-term conditions are associated with adverse outcomes for mother and child. We conducted a qualitative study to inform a core outcome set for studies of pregnant women with multiple long-term conditions. METHODS: Women with two or more pre-existing long-term physical or mental health conditions, who had been pregnant in the last five years or planning a pregnancy, their partners and health care professionals were eligible. Recruitment was through social media, patients and health care professionals' organisations and personal contacts. Participants who contacted the study team were purposively sampled for maximum variation. Three virtual focus groups were conducted from December 2021 to March 2022 in the United Kingdom: (i) health care professionals (n = 8), (ii) women with multiple long-term conditions (n = 6), and (iii) women with multiple long-term conditions (n = 6) and partners (n = 2). There was representation from women with 20 different physical health conditions and four mental health conditions; health care professionals from obstetrics, obstetric/maternal medicine, midwifery, neonatology, perinatal psychiatry, and general practice. Participants were asked what outcomes should be reported in all studies of pregnant women with multiple long-term conditions. Inductive thematic analysis was conducted. Outcomes identified in the focus groups were mapped to those identified in a systematic literature search in the core outcome set development. RESULTS: The focus groups identified 63 outcomes, including maternal (n = 43), children's (n = 16) and health care utilisation (n = 4) outcomes. Twenty-eight outcomes were new when mapped to the systematic literature search. Outcomes considered important were generally similar across stakeholder groups. Women emphasised outcomes related to care processes, such as information sharing when transitioning between health care teams and stages of pregnancy (continuity of care). Both women and partners wanted to be involved in care decisions and to feel informed of the risks to the pregnancy and baby. Health care professionals additionally prioritised non-clinical outcomes, including quality of life and financial implications for the women; and longer-term outcomes, such as children's developmental outcomes. CONCLUSIONS: The findings will inform the design of a core outcome set. Participants' experiences provided useful insights of how maternity care for pregnant women with multiple long-term conditions can be improved.

The SPROUT study: A survey on current management practice of reproductive aspects in women of childbearing age with systemic autoimmune rheumatic diseases.

The SPROUT (Survey on reproduction in RheUmaTology) study explored current practice in women of childbearing age with systemic autoimmune rheumatic diseases, investigating the counselling on contraception, the prescription of low dose acetylsalicylic acid (LDASA) to pregnant patients and the management of disease activity in the post-partum period. The SPROUT questionnaire was designed ad hoc and promoted in the three months before the "11th International Conference on Reproduction, Pregnancy and Rheumatic Disease". Between June and August 2021, 121 physicians responded to the survey. Even though 66.8% of the participants declared themselves to be confident in counselling surrounding birth control, only 62.8% of physicians always discuss contraception and family planning with women of childbearing age. Approximately 20% of respondents do not prescribe LDASA to pregnant women with rheumatic diseases, and wide heterogeneity exists in the dose and timing of LDASA prescription. Most respondents (43.8%) restart treatment with biological agents soon after delivery to prevent disease flares, opting for a drug compatible with breastfeeding while 41.3% of physicians continue biologics throughout pregnancy and post-partum. The SPROUT study highlighted the necessity to further foster physicians' education and identified the management of disease activity after delivery as a matter for discussion between all the clinicians involved in the care of pregnant women with rheumatic conditions.

Prevalence of polypharmacy in pregnancy: a systematic review.

OBJECTIVES: The use of medications among pregnant women has been rising over the past few decades but the reporting of polypharmacy has been sporadic. The objective of this review is to identify literature reporting the prevalence of polypharmacy among pregnant women, the prevalence of multimorbidity in women taking multiple medications in pregnancy and associated effects on maternal and offspring outcomes. DESIGN: MEDLINE and Embase were searched from their inception to 14 September 2021 for interventional trials, observational studies and systematic reviews reporting on the prevalence of polypharmacy or the use of multiple medications in pregnancy were included.Data on prevalence of polypharmacy, prevalence of multimorbidity, combinations of medications and pregnancy and offspring outcomes were extracted. A descriptive analysis was performed. RESULTS: Fourteen studies met the review criteria. The prevalence of women being prescribed two or more medications during pregnancy ranged from 4.9% (4.3%-5.5%) to 62.4% (61.3%-63.5%), with a median of 22.5%. For the first trimester, prevalence ranged from 4.9% (4.7%-5.14%) to 33.7% (32.2%-35.1%). No study reported on the prevalence of multimorbidity, or associated pregnancy outcomes in women exposed to polypharmacy. CONCLUSION: There is a significant burden of polypharmacy among pregnant women. There is a need for evidence on the combinations of medications prescribed in pregnancy, how this specifically affects women with multiple long-term conditions and the associated benefits and harms. TWEETABLE ABSTRACT: Our systematic review shows significant burden of polypharmacy in pregnancy but outcomes for women and offspring are unknown. PROSPERO REGISTRATION NUMBER: CRD42021223966.

Treating Vestibular Migraine When Pregnant and Postpartum: Progress, Challenges and Innovations.

Vestibular migraine is a leading cause of vertigo in pregnancy and, although not a distinct migraine subtype, is an episodic syndrome associated with migraine. Vestibular migraine is associated with diverse symptoms such as vertigo, aura, allodynia, osmophobia, nausea, vomiting and tinnitus, many of which may be exacerbated by, masked or even dismissed in pregnancy. Vestibular migraine is likely an underdiagnosed and undertreated condition in pregnancy. The aetiology of vestibular migraine remains incompletely understood, although various theories have been proposed, including genetic predisposition, neurochemical dysregulation and pro-inflammatory mechanisms, all of which are derived from the pathophysiology of classical migraine. Physiologic changes to the endocrine, haematologic and vascular systems in pregnancy may affect pathophysiological processes in vestibular migraine, and can alter the course of symptoms experienced in pregnancy. These changes also predispose to secondary headache disorders, which may have similar presentations. There has been considerable progress in therapeutic advances in vestibular migraine prophylaxis and treatment outside of pregnancy. There is currently no significant evidence base for acute treatment or prophylaxis for pregnant patients, with treatment recommendations extrapolated from studies on classical migraine, and offered on a benefit versus risk basis. Challenges commonly encountered include difficulty establishing a diagnosis, in addition to recognising and treating neuropsychiatric and gestational co-morbidities. Anxiety, depression, hypertensive disorders and cardiovascular disease are closely associated with migraine, and important contributors to morbidity and mortality during pregnancy. Identifying and treating vestibular migraine during pregnancy offers a unique opportunity to impact future patient health through screening and early treatment of associated co-morbidities. There have been innovations in classical migraine therapy that may confer benefit in vestibular migraine in pregnancy, with emphasis on lifestyle modification, effective prophylaxis, abortive therapies, cognitive behaviour therapy and management of vestibular migraine-related comorbidities.

Maternal and child outcomes for pregnant women with pre-existing multiple long-term conditions: protocol for an observational study in the UK.

INTRODUCTION: One in five pregnant women has multiple pre-existing long-term conditions in the UK. Studies have shown that maternal multiple long-term conditions are associated with adverse outcomes. This observational study aims to compare maternal and child outcomes for pregnant women with multiple long-term conditions to those without multiple long-term conditions (0 or 1 long-term conditions). METHODS AND ANALYSIS: Pregnant women aged 15-49 years old with a conception date between 2000 and 2019 in the UK will be included with follow-up till 2019. The data source will be routine health records from all four UK nations (Clinical Practice Research Datalink (England), Secure Anonymised Information Linkage (Wales), Scotland routine health records and Northern Ireland Maternity System) and the Born in Bradford 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 (a) antenatal, (b) peripartum, (c) postnatal and long-term and (d) 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 modified Poisson 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 random-effects meta-analyses. ETHICS AND DISSEMINATION: Approval has been obtained from the respective data sources in each UK nation. Study findings will be submitted for publications in peer-reviewed journals and presented at key conferences.

Polypharmacy during pregnancy and associated risk factors: a retrospective analysis of 577 medication exposures among 1.5 million pregnancies in the UK, 2000-2019.

BACKGROUND: The number of medications prescribed during pregnancy has increased over the past few decades. Few studies have described the prevalence of multiple medication use among pregnant women. This study aims to describe the overall prevalence over the last two decades among all pregnant women and those with multimorbidity and to identify risk factors for polypharmacy in pregnancy. METHODS: A retrospective cohort study was conducted between 2000 and 2019 using the Clinical Practice Research Datalink (CPRD) pregnancy register. Prescription records for 577 medication categories were obtained. Prevalence estimates for polypharmacy (ranging from 2+ to 11+ medications) were presented along with the medications commonly prescribed individually and in pairs during the first trimester and the entire pregnancy period. Logistic regression models were performed to identify risk factors for polypharmacy. RESULTS: During the first trimester (812,354 pregnancies), the prevalence of polypharmacy ranged from 24.6% (2+ medications) to 0.1% (11+ medications). During the entire pregnancy period (774,247 pregnancies), the prevalence ranged from 58.7 to 1.4%. Broad-spectrum penicillin (6.6%), compound analgesics (4.5%) and treatment of candidiasis (4.3%) were commonly prescribed. Pairs of medication prescribed to manage different long-term conditions commonly included selective beta 2 agonists or selective serotonin re-uptake inhibitors (SSRIs). Risk factors for being prescribed 2+ medications during the first trimester of pregnancy include being overweight or obese [aOR: 1.16 (1.14-1.18) and 1.55 (1.53-1.57)], belonging to an ethnic minority group [aOR: 2.40 (2.33-2.47), 1.71 (1.65-1.76), 1.41 (1.35-1.47) and 1.39 (1.30-1.49) among women from South Asian, Black, other and mixed ethnicities compared to white women] and smoking or previously smoking [aOR: 1.19 (1.18-1.20) and 1.05 (1.03-1.06)]. Higher and lower age, higher gravidity, increasing number of comorbidities and increasing level of deprivation were also associated with increased odds of polypharmacy. CONCLUSIONS: The prevalence of polypharmacy during pregnancy has increased over the past two decades and is particularly high in younger and older women; women with high BMI, smokers and ex-smokers; and women with multimorbidity, higher gravidity and higher levels of deprivation. Well-conducted pharmaco-epidemiological research is needed to understand the effects of multiple medication use on the developing foetus.

Anti-CD20 therapies in pregnancy and breast feeding: a review and ABN guidelines.

Neurologists increasingly use anti-CD20 therapies, including for women of childbearing age, despite these medications being unlicensed for use in pregnancy. Current evidence suggests that women can safely conceive while taking anti-CD20 therapy. Women should not be denied treatment during pregnancy when it is clinically indicated, although they should be counselled regarding live vaccinations for their infant. Women receiving regular ocrelizumab for multiple sclerosis should preferably wait 3 months before trying to conceive. There are few data around ofatumumab in pregnancy, and while there is probably a class effect across all anti-CD20 therapies, ofatumumab may need to be continued during pregnancy to maintain efficacy. We recommend that anti-CD20 therapies can be safely given while breast feeding. It is important to make time to discuss treatments with women of childbearing age to help them choose their most suitable treatment. Outcomes should be monitored in pregnancy registries.

The impact of preconception counselling on maternal and fetal outcomes in women with chronic medical conditions: A systematic review.

BACKGROUND: Beyond diabetes mellitus little data reports outcomes of women with chronic medical conditions who have received pre-conception counselling (PCC). This study aimed to perform a systematic review of the literature to evaluate evidence regarding the impact of PCC on maternal and fetal outcomes in women with chronic medical conditions aside from diabetes mellitus. METHODS: A systematic review was conducted in accordance with PRISMA. PubMed, Cochrane, Ovid Medline and Web of Science were searched. Two reviewers screened abstracts and full texts. Inclusion criteria included studies relating to chronic medical disorders of interest published between database inception and 21st May 2022, reporting outcomes relating to disease activity and perinatal outcomes. RESULTS: The search yielded 11,814 results of which six met criteria for inclusion. Two papers describe the demographics of women more likely to receive PCC which included younger age, shorter disease duration, nulliparity, IVF pregnancy and higher education/job security. Two reported the effects of PCC on women's behaviour with improvements demonstrated in correct medication adherence, folic acid intake and smoking cessation. Five studies reported outcomes related to disease activity; those receiving PCC were more likely to have quiescent disease during pregnancy. Improvements in pregnancy outcomes were described including reduced rates of small for gestational age, low birth weight, preterm birth, congenital abnormality and obstetric complications. DISCUSSION: A paucity of data exists relating to pregnancy outcomes in women with chronic medical conditions receiving PCC. Reported outcomes are favorable, supporting the routine inclusion of PCC in preparation for pregnancy in such patients.

Immunology of pregnancy and reproductive health in autoimmune rheumatic diseases. Update from the 11th International Conference on Reproduction, Pregnancy and Rheumatic Diseases.

Autoimmune rheumatic diseases (ARD) can affect women and men during fertile age, therefore reproductive health is a priority issue in rheumatology. Many topics need to be considered during preconception counselling: fertility, the impact of disease-related factors on pregnancy outcomes, the influence of pregnancy on disease activity, the compatibility of medications with pregnancy and breastfeeding. Risk stratification and individualized treatment approach elaborated by a multidisciplinary team minimize the risk of adverse pregnancy outcomes (APO). Research has been focused on identifying biomarkers that can be predictive of APO. Specifically, preeclampsia and hypertensive disorders of pregnancy tend to develop more frequently in women with ARD. Placental insufficiency can lead to intrauterine growth restriction and small-for-gestational age newborns. Such APO have been shown to be associated with maternal disease activity in different ARD. Therefore, a key message to be addressed to the woman wishing for a pregnancy and to her family is that treatment with compatible drugs is the best way to ensure maternal and fetal wellbeing. An increasing number of medications have entered the management of ARD, but data about their use in pregnancy and lactation are scarce. More information is needed for most biologic drugs and their biosimilars, and for the so-called small molecules, while there is sufficient evidence to recommend the use of TNF inhibitors if needed for keeping maternal disease under control. Other issues related to the reproductive journey have emerged as "unmet needs", such as sexual dysfunction, contraception, medically assisted reproduction techniques, long-term outcome of children, and they will be addressed in this review paper. Collaborative research has been instrumental to reach current knowledge and the future will bring novel insights thanks to pregnancy registries and prospective studies that have been established in several Countries and to their joint efforts in merging data.