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In pharmacoepidemiology, robust data are needed to judge the impact of drug treatment on pregnancy, pregnancy outcomes and breast-fed infants. As pregnant and breastfeeding women are usually excluded from randomised clinical trials, observational studies are required. One of those data sources are pregnancy registers specifically developed to focus on certain diseases or disease groups. The German Rhekiss register investigates pregnancies in women with chronic inflammatory rheumatic diseases (IRD). Rhekiss is a nationwide, multicentre, longitudinal study, in which women aged 18 years or older with an underlying IRD can be enrolled by a rheumatologist either when planning a pregnancy or in the first half of pregnancy. Data are collected prospectively at regular follow-up visits. Rheumatologists and patients provide information in a web-based system before conception (if enrolment was at the time of pregnancy planning), during and after pregnancy. A smartphone app is available for patients. Maternal and clinical information, general laboratory markers, treatment with antirheumatic and other drugs, adverse events, items related to course and outcome of pregnancy and the health of the child are uniformly assessed for all diseases. Individual information on the IRD includes classification criteria, diagnosis-specific laboratory parameters, clinical parameters and validated instruments to measure disease activity or damage. Furthermore, patient-reported outcome measures are captured. A total of 2013 individual patients have been enrolled in the register, and data on 1801 completed pregnancies are available. In summary, Rhekiss is a comprehensive and complex register that can answer various research questions about pregnancy in women with chronic IRDs., (© 2024 The Author(s). Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.)

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease which frequently affects women of childbearing age. Nowadays, pregnancy is not contraindicated in cases of well-controlled disease activity, but pregnancies are still at higher risk of maternal and fetal complications compared to the general population. During pregnancy and puerperium patients are at risk of disease flare, and obstetric complications are more frequent in cases of active disease at conception/beginning of pregnancy, a history of lupus nephritis, and concomitant presence of antiphospholipid syndrome. To improve pregnancy outcomes in SLE patients, appropriate preconception counseling with changes in medication, if necessary, and close rheumatological and obstetrical monitoring are fundamental. This review aims to summarize the risk factors for adverse pregnancy outcomes and provide an update on developments in medical care for pregnancy in SLE patients., Competing Interests: Declaration of competing interest The authors report no conflicts of interest in this work., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Pregnancies in women with chronic disease are on the rise. This pertains to autoimmune diseases in particular since these tend to affect women of childbearing age. The interaction between pregnancy and autoimmune disease may increase the risk of maternal, fetal, and obstetric complications; additional care may be required., Methods: This review is based on a selective literature search in PubMed (2015-2020)., Results: In women with autoimmune diseases, the course of pregnancy is highly variable. Some autoimmune diseases tend to improve during pregnancy and do not to result in any serious obstetric complications. Others may worsen during pregnancy, with deterioration of the maternal condition as well as obstetric and perinatal complications. In systemic lupus erythematosus and myasthenia gravis, placental transfer of specific autoantibodies may cause fetal or neonatal disease., Conclusion: The care of pregnant women with chronic diseases requires collaboration between specialists of the pertinent levels of care. A stable course of disease before conception, close interdisciplinary care, and pregnancy-compatible medication contribute to a reduction in maternal and perinatal complications.

Objective: Multiple guidelines recommend continuing hydroxychloroquine (HCQ) for SLE during pregnancy based on observational data. The goal of this individual patient data meta-analysis was to identify the potential benefits and harms of HCQ use within lupus pregnancies., Methods: Eligible studies included prospectively collected pregnancies in women with lupus. After a systematic literature search, seven datasets meeting inclusion criteria were obtained. Pregnancy outcomes and lupus activity were compared for pregnancies with a visit in the first trimester in women who did or did not take HCQ throughout pregnancy. Birth defects were not systematically collected. This analysis was conducted in each dataset, and results were aggregated to provide a pooled OR., Results: Seven cohorts provided 938 pregnancies in 804 women. After selecting one pregnancy per patient with a first trimester visit, 668 pregnancies were included; 63% took HCQ throughout pregnancy. Compared with pregnancies without HCQ, those with HCQ had lower odds of highly active lupus, but did not have different odds of fetal loss, preterm delivery or pre-eclampsia. Among women with low lupus activity, HCQ reduced the odds of preterm delivery., Conclusions: This large study of prospectively-collected lupus pregnancies demonstrates a decrease in lupus activity among woman who continue HCQ through pregnancy and no harm to pregnancy outcomes. Like all studies of HCQ in lupus pregnancy, this study is confounded by indication and non-adherence. As this study confirms the safety of HCQ and diminished SLE activity with use, it is consistent with current recommendations to continue HCQ throughout pregnancy., Competing Interests: Competing interests: MC: Funding: AHRQ, Arthritis Foundation; Grants: GSK; Consulting and Advisory Board: UCB. AE: Grant funding: NIH NCATS Award 1KL2TR002554. SB: Grants: NIH, US FDA, PCORI, RRF, CARRA; Consulting: UCB; Travel: FDA; Leadership: CARRA Assistant Scientific Director. DDG: Grants and/or consulting fees from AstraZeneca; Leadership: Member of the Systemic Lupus International Collaborating Clinics group; served on the Medical advisory board of the Lupus foundation of America. MAP: Grant NIH RO-1 AR069572., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To determine whether disease remission or low disease activity state at the beginning of pregnancy in SLE patients is associated with better pregnancy outcome., Methods: Pregnancies in SLE patients prospectively monitored by pregnancy clinics at four rheumatology centres were enrolled. Patient demographics and clinical information were collected at baseline (pregnancy visit before 8 weeks of gestation) including whether patients were in remission according to the Definition of Remission in SLE (DORIS) criteria and and/or Lupus Low Disease Activity State (LLDAS). Univariate and multivariate analysis were performed to determine predictors of disease flare and adverse pregnancy outcomes (APOs) including preeclampsia, preterm delivery, small for gestational age infant, intrauterine growth restriction and intrauterine fetal death., Results: A total of 347 pregnancies were observed in 281 SLE patients. Excluding early pregnancy losses, 212 pregnancies (69.7%) occurred in patients who were in remission at baseline, 33 (10.9%) in patients in LLDAS, and the remainder in active patients. Seventy-three flares (24%) were observed during pregnancy or puerperium, and 105 (34.5%) APOs occurred. Multivariate analysis revealed that patients in disease remission or taking HCQ were less likely to have disease flare, while a history of LN increased the risk. The risk of APOs was increased in patients with shorter disease duration, while being on HCQ resulted a protective variable. An almost significant association between complete remission and a decreased risk of APOs was observed., Conclusions: Prenatal planning with a firm treat-to-target goal of disease remission is an important strategy to reduce the risk of disease flares and severe obstetric complications in SLE pregnancies., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Inflammatory rheumatic diseases often affect women of childbearing age, for whom pregnancy is still associated with increased risks. At the same time, we are gaining more and more insights into risk factors and preventive strategies, enabling almost all women to have successful pregnancies with few adverse outcomes. The cornerstones are planning of the pregnancy under effective disease control and the modification of individual risk factors. Hydroxychloroquine is once again coming into focus as a compound with multiple positive effects. Recommendations published by the American College of Rheumatology (ACR) provide a practical overview of the evidence. Based on the current state of knowledge, rheumatologists can make a lasting contribution to a positive pregnancy outcome for mother and child., (© 2021. Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background and Objective: There is an urgent need for robust data on the trajectories and outcomes of pregnancies in women with inflammatory rheumatic diseases (IRD). In particular when rare outcomes or rare diseases are to be investigated, collaborative approaches are required. However, joint data analyses are often limited by the heterogeneity of the different data sources.To facilitate future research collaboration, a European League Against Rheumatism (EULAR) Task Force defined a core data set with a minimum of items to be collected by pregnancy registries in rheumatology covering the period of pregnancy and the 28-day neonatal phase in women with any underlying IRD., Methods: A stepwise process included a two-round Delphi survey and a face-to-face meeting to achieve consensus about relevant items., Results: A total of 64 multidisciplinary stakeholders from 14 different countries participated in the two rounds of the Delphi process. During the following face-to-face meeting of the EULAR Task Force, consensus was reached on 51 main items covering 'maternal information', 'pregnancy' and 'treatment'. Generic instruments for assessment are recommended for every item. Furthermore, for the five most frequent IRDs rheumatoid arthritis, spondyloarthritis, juvenile idiopathic arthritis, systemic lupus erythematosus and other connective tissue diseases, disease-specific laboratory markers and disease activity measurements are proposed., Conclusion: This is the first consensus-based core data set for prospective pregnancy registries in rheumatology. Its purpose is to stimulate and facilitate multinational collaborations that aim to increase the knowledge about pregnancy course and safety of treatment in women with IRDs during pregnancy., Competing Interests: Competing interests: AM: speaker/consultant fees: Abbvie, BMS, MSD, Novartis, Pfizer, UCB; unrestricted grants: Pfizer and UCBAS: speaker fees: AbbVie, BMS, MSD, Novartis, Pfizer, Roche, Sanofi Aventis, UCBA Zbinden: none. AZink: speaker fees from AbbVie, Janssen, Pfizer, Roche and Sanofi-Aventis. CN-P: consultancy fees from UCB and Alliance Pharma. Speaker fees from UCB, Alliance Pharma, Alexion, Sanofi, Falk, Janssen. DDC: none. DG: none. FF: consultant for UCB, GSK, Roche. Speakers bureau: UCB, GSK. Research grants from UCBLA: speaker/consultant fees: GSK, Novartis, UCB, Eli Lilly, INOVA Diagnostics/Werfen Group. LR: none. MW: none. NC-C: no personal fees. Research grants from UCBRD: received an unrestricted research grant form UCB Pharma BV and from the Dutch Arthritis Association a non-commercial fund raising organisation. RFB: speaker/consultant fees: Abbvie, Biogen, BMS, Celgene, Chugai, GSK, Janssen, Lilly, Medac, MSD, Novartis, Roche, UCBRÖ: None. SCR-G: speaker fees from Sanofi, MSD, UCB, Novartis and Janssen. SS: none. YM: lecture honoraria from Pfizer., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Current research in the field of systemic lupus erythematosus (SLE) and pregnancy focuses on predictors of adverse pregnancy outcomes, the safety and efficacy of hydroxychloroquine (HCQ) in pregnancy and the importance of preconception counselling. In particular, the prospective predictors of pregnancy outcome: biomarkers in antiphospholipid antibody syndrome and SLE (PROMISSE) study adds to the understanding of risk factors for adverse outcomes. There is increasing evidence of the numerous benefits associated with continuing HCQ treatment in pregnancy and for the use of low-dose acetylsalicylic acid in the prevention of preeclampsia. The European League Against Rheumatism (EULAR) has published evidence-based recommendations for the treatment of women with SLE and/or antiphospholipid syndrome before, during and after pregnancy. Rheumatologists caring for women with SLE should be familiar with the current state of knowledge in order to help optimize the management and thus the outcome of pregnancy in their patients.

Inflammatory rheumatic diseases preferentially affect women of childbearing age. Immunological alterations can have positive or negative effects on the maternal disease. Most of these women can have a successful pregnancy with careful medical and obstetric care. Nevertheless, complications are more frequent than in healthy women. Pregnancies should therefore be planned during inactive phases of the disease and patients should be educated in advance about possible maternal and child risks and about treatment options compatible with pregnancy. In pregnancy, individualized and interdisciplinary care can promote a stable course of the disease and reduce the risks for mother and child. Especially with respect to a compatible treatment, detailed information for the patients is necessary for a shared decision making.

Background: Pregnancy represents a complex challenge to clinicians treating women with chronic inflammatory disease. Many clinicians face a situation of heightened sensitivity to the potential risks and uncertainties associated with the effect of pharmacological treatment on pregnancy outcomes. This may create an environment vulnerable to clinical inertia, whereby behavioural factors such as cognitive heuristics and biases, and other factors such as attitudes to risk and emotion can contribute. This systematic review was undertaken to assess if clinical inertia has been investigated/identified in this setting and took a behavioural science approach to identify and understand the potential determinants of clinical inertia in this treatment setting., Methods: A systematic literature search was conducted to identify publications which investigated or described clinical inertia or its determinants (e.g. heuristics, biases etc.). Results were coded for thematic analysis using two inter-related behavioural models: the COM-B model and the Theoretical Domains Framework., Results: Whilst studies investigating or describing clinical inertia in this treatment setting were not identified, the behavioural analysis revealed a number of barriers to the pharmacological management of women of fertile age affected by chronic inflammatory disease. Factors which may be influencing clinician's behaviour were identified in all domains of the COM-B model. The primary factors identified were a lack of knowledge of treatment guidelines and fears concerning the safety of medications for mother and fetus. Lack of experience of treating pregnant patients was also identified as a contributing factor to undertreatment., Conclusion: Using a behavioural approach, it was possible to identify potential factors which may be negatively influencing clinician's behaviour in this treatment setting, although specific research was limited.

Background: The collaborative initiative of the European Network of Pregnancy Registers in Rheumatology (EuNeP) aims to combine data available in nationwide pregnancy registers to increase knowledge on pregnancy outcomes in women with inflammatory rheumatic diseases (IRD) and on drug safety during pregnancy and lactation. The objective of this study was to describe the similarities and differences of the member registers., Methods: From all registers, information about their structure and design was collected, as well as which parameters regarding demographics, maternal outcomes, treatment, course and outcome of pregnancy, and development of the child were available in the respective datasets. Furthermore, the current recruitment status was reported., Results: The four registers (EGR2 (France), RePreg (Switzerland), RevNatus (Norway), and Rhekiss (Germany)) collect information prospectively and nationwide. Patients can be enrolled before conception or during pregnancy. To date, more than 3500 patients in total have been included, and data on 2200 pregnancies with an outcome are available. The distribution of diagnoses in the respective registers varies considerably, and only three entities (rheumatoid arthritis, psoriatic arthritis, and spondyloarthritis) are captured by all the registers. Broad consistency was found in non-disease-specific data items, but differences regarding instruments and categories as well as frequency of data collection were revealed. Disease-specific data items are less homogeneously collected., Conclusion: Although the registers in this collaboration have similar designs, we found numerous differences in the variables collected. This survey of the status quo of current pregnancy registers is the first step towards identifying data collected uniformly across registers in order to facilitate joint analyses., Trial Registration: Not applicable.

Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease with a high prevalence in females of childbearing age. Pregnancy in SLE nowadays has favorable outcomes for the majority of women. However, flares of disease activity, preeclampsia, fetal loss, and preterm birth are well-known risks in such pregnancies. Anti-SS-A(Ro)/SS-B(La) antibodies put fetuses at risk for congenital heart block and neonatal lupus. Several risk factors for adverse pregnancy outcomes have been identified. Women with antiphospholipid antibodies or antiphospholipid syndrome and lupus nephritis represent a group with high risk for obstetric complications. Factors such as appropriate preconception counseling and medication adjustment, strict disease control prior to pregnancy, and intensive surveillance during and after pregnancy are essential to improve pregnancy outcome. The aim of this review article is to update on the medical care of pregnancy in these women to ensure the best maternal and fetal prognosis., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objectives: Develop recommendations for women's health issues and family planning in systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS)., Methods: Systematic review of evidence followed by modified Delphi method to compile questions, elicit expert opinions and reach consensus., Results: Family planning should be discussed as early as possible after diagnosis. Most women can have successful pregnancies and measures can be taken to reduce the risks of adverse maternal or fetal outcomes. Risk stratification includes disease activity, autoantibody profile, previous vascular and pregnancy morbidity, hypertension and the use of drugs (emphasis on benefits from hydroxychloroquine and antiplatelets/anticoagulants). Hormonal contraception and menopause replacement therapy can be used in patients with stable/inactive disease and low risk of thrombosis. Fertility preservation with gonadotropin-releasing hormone analogues should be considered prior to the use of alkylating agents. Assisted reproduction techniques can be safely used in patients with stable/inactive disease; patients with positive antiphospholipid antibodies/APS should receive anticoagulation and/or low-dose aspirin. Assessment of disease activity, renal function and serological markers is important for diagnosing disease flares and monitoring for obstetrical adverse outcomes. Fetal monitoring includes Doppler ultrasonography and fetal biometry, particularly in the third trimester, to screen for placental insufficiency and small for gestational age fetuses. Screening for gynaecological malignancies is similar to the general population, with increased vigilance for cervical premalignant lesions if exposed to immunosuppressive drugs. Human papillomavirus immunisation can be used in women with stable/inactive disease., Conclusions: Recommendations for women's health issues in SLE and/or APS were developed using an evidence-based approach followed by expert consensus., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

A European League Against Rheumatism (EULAR) task force was established to define points to consider on use of antirheumatic drugs before pregnancy, and during pregnancy and lactation. Based on a systematic literature review and pregnancy exposure data from several registries, statements on the compatibility of antirheumatic drugs during pregnancy and lactation were developed. The level of agreement among experts in regard to statements and propositions of use in clinical practice was established by Delphi voting. The task force defined 4 overarching principles and 11 points to consider for use of antirheumatic drugs during pregnancy and lactation. Compatibility with pregnancy and lactation was found for antimalarials, sulfasalazine, azathioprine, ciclosporin, tacrolimus, colchicine, intravenous immunoglobulin and glucocorticoids. Methotrexate, mycophenolate mofetil and cyclophosphamide require discontinuation before conception due to proven teratogenicity. Insufficient documentation in regard to fetal safety implies the discontinuation of leflunomide, tofacitinib as well as abatacept, rituximab, belimumab, tocilizumab, ustekinumab and anakinra before a planned pregnancy. Among biologics tumour necrosis factor inhibitors are best studied and appear reasonably safe with first and second trimester use. Restrictions in use apply for the few proven teratogenic drugs and the large proportion of medications for which insufficient safety data for the fetus/child are available. Effective drug treatment of active inflammatory rheumatic disease is possible with reasonable safety for the fetus/child during pregnancy and lactation. The dissemination of the data to health professionals and patients as well as their implementation into clinical practice may help to improve the management of pregnant and lactating patients with rheumatic disease., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Pregnancy in women with rheumatic diseases represents a challenge for patients and physicians and requires optimal shared decision-making strategies. However, the majority of women can have a successful pregnancy and the vast majority of babies are born healthy. Specific preconception care should be offered to women with rheumatic diseases to optimize and increase the chances of a successful pregnancy. A careful assessment of possible risks and the justified use of antirheumatic drugs before, during and after pregnancy are key issues.

Among the most prominent features associated with antiphospholipid syndrome (APS) are cerebral ischaemic events (CVE). Pregnancy with APS increases the risk of thrombosis, including CVE. This study was undertaken to assess the risk of obstetric complications and recurrence of CVE during pregnancy in women with APS and previous CVE. We prospectively observed 23 pregnancies in 20 women (median age 31 years) with primary (n = 8) or secondary APS (n = 12). Eight patients had transient ischaemic attacks (TIA) and 12 had stroke before pregnancy. All patients received aspirin 100 mg daily in combination with low molecular weight heparin (LMWH) during their pregnancies. The live birth rate was 91.3% (n = 21). Obstetrical complications consisted mainly of preeclampsia (n = 8, 34.8%) and preterm delivery (n = 9, 42.9%). The risk for preeclampsia increased in patients who were positive for multiple antiphospholipid antibodies (aPL) (odds ratio (OR) 3.06 (95% confidence interval (CI) 1.01-9.32)) per positive aPL test (i.e anticardiolipin antibody, anti-ß2-glycoprotein I antibody, lupus anticoagulant) (p 0.049). Three patients experienced recurrent CVE in the context of pregnancy (one during pregnancy, two in the postpartum period). We found an increased, but not significant, risk of a new episode of cerebral ischaemia in patients with pregnancies complicated by preeclampsia (two out of the eight preeclampsia (p 0.15). Despite treatment, there is a significant risk for pregnancy complications in APS patients with previous CVE. Especially in the context of preeclampsia, anticoagulation should be given rigorously to prevent recurrence of CVE.

The treatment of inflammatory rheumatic diseases, such as rheumatoid arthritis, spondylitis ankylosans and systemic lupus erythematosus, is improving continuously. This has lead to an increasing number of young patients with a wish to have children. Greater insight into the course of rheumatic diseases during pregnancy and post partum has enabled optimized support for women with rheumatic diseases wishing to have children. To ensure a favorable outcome, pregnancy should be started during a period of disease stability and should be monitored closely. A careful assessment of possible risks and the justified use of antirheumatic drugs before, during and after pregnancy are key issues for success.

Purpose of Review: This review discusses how inflammatory rheumatic diseases [rheumatoid arthritis, ankylosing spondylitis, systemic lupus erythematosus (SLE)] of the mother can influence the course of pregnancy and the development of the fetus. Antirheumatic drug therapy of the mother and strategies to prevent fetal complications namely in SLE must be considered with care., Recent Findings: The current literature is presented discussing hypotheses about the immunologic mechanisms leading to amelioration or exacerbation of the rheumatic symptoms in rheumatoid arthritis and ankylosing spondylitis during pregnancy. In SLE, several recent studies have been published concerning fetal complications in the antiphospholipid syndrome and in Ro/SSA-positive and La/SSB-positive mothers and how to diagnose, treat, or prevent these., Summary: Today, women with inflammatory rheumatic diseases are normally fertile and can be encouraged to become pregnant, when there is a stable and quiescent phase of the disease. This is in particular important for patients with SLE, although pregnancy outcome in SLE has improved over the last decades. Pregnancy in SLE is still a high-risk period during the disease course with the highest risk in women with active lupus nephritis. In contrast, women with rheumatoid arthritis develop amelioration of the rheumatic symptoms during the course of pregnancy in most cases; female ankylosing spondylitis patients are likely to show unaltered or aggravated symptoms of back pain and impaired function.

Inflammatory rheumatic diseases often affect females of childbearing age and pregnancy remains a challenge for this group of patients and their physicians. However, the majority of patients can now have successful pregnancies and deliver healthy babies as a result of our improved knowledge of the risks encountered during pregnancy, better preventive and therapeutic measures, and in particular close rheumatological, obstetric and neonatal monitoring. To ensure a favorable outcome, pregnancy should be planned to take place during a period of disease stability, monitored closely (physical examination, laboratory tests, and Doppler ultrasound), and treated appropriately.