Pregnancy and neonatal outcomes in women with axial spondyloarthritis: pooled data analysis from the European Network of Pregnancy Registries in Rheumatology (EuNeP).

OBJECTIVE: To investigate outcome and course of pregnancies in women with axial spondyloarthritis (axSpA) in a pooled data analysis of pregnancy registries in rheumatology. METHODS: Prospectively followed women with axSpA, fulfilling ASAS classification criteria and for whom a pregnancy outcome was reported, were eligible for the analysis. Anonymised data of four registries was pooled. Rates of adverse pregnancy outcomes were calculated. Systemic inflammation, disease activity and treatment patterns with tumour necrosis factor inhibitor (TNFi) before, during and after pregnancy were analysed. RESULTS: In a total of 332 pregnancies from 304 axSpA women, 98.8% of the pregnancies resulted in live birth. Mean maternal age was 31 years and disease duration 5 years. Most of these patients received pre-conception counselling (78.4%). Before pregnancy, 53% received TNFi treatment, 27.5% in first and 21.4% in third trimester. Pregnancy and neonatal outcomes were favourable with rates of 2.2% for pre-eclampsia, 4.9% for preterm birth, 3.1% for low birth weight and 9.5% for small for gestational age. Neonates were delivered by caesarean section in 27.7% of pregnancies, of which 47.4% were emergencies. Pooled mean CRP was 4 mg/L before conception peaking in the second trimester at 9.4 mg/L. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was below 4 at all time-points. CONCLUSIONS: Pooled rates of most outcomes were better than what had been reported in the literature and within expected rates of those reported for the general population. Pre-conception counselling, planned pregnancies and a tight management in expert centres applying a tailored treatment approach may have contributed to the favourable pregnancy outcomes.

Nurses experience increased clinical and organisational competence by working with a medical quality register, RevNatus - a qualitative study.

BACKGROUND: RevNatus is a consent-based, nationwide medical quality register that collects data on patients with inflammatory rheumatic diseases during pregnancy and one year postpartum. The entering of data takes place in outpatient clinics in rheumatology wards in hospitals. The aim of this study is to explore how rheumatology nurses experience organizing and working with the medical quality register RevNatus in addition to their normal clinical patient-care tasks. METHODS: Qualitative focus group interviews and individual in-depth interviews were conducted in 2018 to gain insights into how nurses organize performing quality register work and clinical work simultaneously. Data were analysed using systematic text condensation. RESULTS: The informants represented seven different rheumatology outpatient clinics in Norway. The analyses showed that working with RevNatus increased the nurses' knowledge about pregnancy and rheumatic diseases, improved the content of their nurse consultations and found the 'register form' as a useful template to structure the nurse consultations. The nurses took the main responsibility for RevNatus, but lack of routines and uncoordinated collaboration with the rheumatologists and secretaries made the nurses spend too much time verifying the accuracy of data or post-registering missing data. CONCLUSION: The nurses experienced work with RevNatus as time-consuming, but the register work increased both their clinical and organisational competences. Routines and collaboration within the registry team are important to ensure the data quality and reduce the workload.

Influence of disease activity and medications on offspring birth weight, pre-eclampsia and preterm birth in systemic lupus erythematosus: a population-based study.

OBJECTIVES: Exploring the associations between disease activity and medications with offspring birth weight, pre-eclampsia and preterm birth in systemic lupus erythematosus (SLE). METHODS: Data from the Medical Birth Registry of Norway (MBRN) were linked with data from RevNatus, a nationwide observational register recruiting women with inflammatory rheumatic diseases. Singleton births in women with SLE included in RevNatus 2006-2015 were cases (n=180). All other singleton births registered in MBRN during this time (n=498 849) served as population controls. Z-score for birth weight adjusted for gestational age and gender was calculated. Disease activity was assessed using Lupus Activity Index in Pregnancy. We compared z-scores for birth weight, pre-eclampsia and preterm birth in cases with inactive disease, cases with active disease and population controls. RESULTS: Z-scores for birth weight in offspring were lower in inactive (-0.64) and active (-0.53) diseases than population controls (-0.11). Inactive disease did not predict pre-eclampsia while active disease yielded OR 5.33 and OR 3.38 compared with population controls and inactive disease, respectively. Preterm birth occurred more often in inactive (OR 2.57) and active (OR 8.66) diseases compared with population controls, and in active compared with inactive disease (OR 3.36). CONCLUSIONS: SLE has an increased odds for low birth weight and preterm birth, amplified by active disease. The odds for pre-eclampsia is elevated in active, but not inactive disease. This calls for tight follow-up targeting inactive disease before and throughout pregnancy.

Women with systemic lupus erythematosus get pregnant more easily than women with rheumatoid arthritis.

Objectives: To examine possible differences in the ability to get pregnant and time to pregnancy (TTP) in women with SLE and RA, and to study possible influencing factors. Methods: Data from RevNatus, a Norwegian nationwide prospective observational register including women with inflammatory rheumatic diseases when planning pregnancy or after conception, was used. We compared rate of achieved pregnancy, the pregnancy outcomes live birth or pregnancy loss, and TTP between women with SLE (n = 53) and women with RA (n = 180). TTP was compared between the groups using Kaplan-Meier plots, and Cox proportional hazard regression was performed adjusting for maternal age, parity and medication use. RAND-36 was used to assess health-related quality of life (HRQoL) in women achieving and not achieving pregnancy. Results: Women with SLE had a pregnancy ratio of 1.91 (95% CI: 1.27, 2.88, P = 0.002) compared with women with RA, and a substantially shorter median TTP (3.0 vs 7.0 months, P = 0.001). Higher maternal age, medication use and low HRQoL in the physical domains may influence the ability to achieve pregnancy and prolong TTP in women with RA. Women with SLE not achieving pregnancy had lower HRQoL scores than SLE-women achieving pregnancy, while women with RA had generally low scores in physical domains whether or not achieving pregnancy, indicating poor HRQoL. Conclusions: In the studied cohort, women with SLE got pregnant more easily than women with RA.

Patient satisfaction with nursing consultations in a rheumatology outpatient clinic: a 21-month randomised controlled trial in patients with inflammatory arthritides.

OBJECTIVE: To study the effect of individual nursing consultations in patients treated with disease-modifying antirheumatic drugs (DMARDs) in a rheumatology outpatient setting. METHODS: Patients with inflammatory arthritides (IA) who had started with a DMARD regimen 3 months before were randomised to two different follow-up consultation systems: either follow-up by a clinical nurse specialist (CNS) or by a medical doctor (MD) in rheumatology 3, 9 and 21 months after randomisation. The primary outcome was patient satisfaction measured by Leeds Satisfaction Questionnaire (LSQ). Secondary outcomes included coping, disease activity, pain, fatigue, patient's global assessment of disease activity and health related quality of life. Effects at 9 and 21 months were estimated by Least Square means calculated from the final mixed model. RESULTS: Of 68 patients randomised, 65 patients completed assessments at 21 months. Statistically significant improvements in favour of the CNS group were found in all LSQ subscales (all p values<0.001) and in overall satisfaction at 9 months (adjusted mean between-group difference 0.74, 95% CI -0.96 to -0.52) and at 21 months (-0.69, 96% CI -0.87 to -0.50). Disease activity Score 28 joint count (DAS-28) was improved from baseline to 9 months in both groups and improvement was maintained at 21 months, but without any group difference. No statistically significant between-group differences were found in any of the other secondary outcomes. CONCLUSIONS: Patients with IA are likely to benefit from nurse consultations in terms of increased satisfaction with care compared with MD consultations and without loss of efficacy in terms of clinical outcomes. The study is registered as a clinical trial at the ClinicalTrials.gov (NCT00403676).

Breastfeeding in women with systemic lupus erythematosus: results from a Norwegian quality register.

BACKGROUND: Knowledge on breastfeeding among women with systemic lupus erythematosus (SLE) is sparse. We wanted to identify the frequency of breastfeeding in SLE, and to compare breastfeeding women with SLE to non-breastfeeding women to examine possible differences in disease characteristics and self-reported health data between the groups. METHODS: Prospective data on women with SLE from RevNatus, a consent-based Norwegian nationwide quality register was used for this study. Data were collected during January 2016 to September 2021. We used data registered at inclusion when planning pregnancy or in 1st trimester, and 6 weeks, 6 and 12 months after delivery. Breastfeeding and non-breastfeeding patients were compared according to demographic, serological and obstetric data as well as disease activity, medication, self-reported pain, and fatigue. RESULTS: A total of 114 pregnancies in 101 SLE women were included in the analysis. A majority of the women (78%) breastfed six weeks postpartum. Six and 12 months after delivery, breastfeeding rates were 54% and 30% respectively. Six weeks postpartum, non-breastfeeding women showed higher prevalence of emergency caesarean delivery (p = 0.038), preeclampsia (p = 0.056) and lower educational level (p = 0.046) compared to breastfeeding women. 12 months after delivery, we observed a higher frequency of multiparity among breastfeeding women (p = 0.017) compared to non-breastfeeding. Overall, we found low disease activity in both groups at all registrations in the follow-up, and disease activity did not differ between the groups. More than 70% of both breastfeeding and non-breastfeeding women used hydroxychloroquine (HCQ). CONCLUSIONS: Breastfeeding rate in women with SLE was high six weeks postpartum. Multiparous women breastfed longer than primiparas. Disease activity, use of HCQ, and self-reported health data were comparable between the groups. Our data indicate that health professionals should encourage women with SLE to breastfeed.

Caesarean section in women with axial spondyloarthritis and psoriatic arthritis: a population-based study.

BACKGROUND: There is sparse documentation on pregnancy outcomes in women with axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA). Data on disease activity are often lacking, preventing the direct investigation of the effect of inflammation on pregnancy outcomes. A caesarean section (CS) implies a higher risk for complications than vaginal delivery. It delays mobilisation after birth necessary to counteract inflammatory pain and stiffness. OBJECTIVE: To explore a possible association of inflammatory active disease and CS rates in women with axSpA and PsA. METHODS: Data from the Medical Birth Registry of Norway (MBRN) were linked with data from RevNatus, a Norwegian nationwide observational register recruiting women with inflammatory rheumatic diseases. Singleton births in women with axSpA (n=312) and PsA (n=121) included in RevNatus 2010-2019 were cases. Singleton births, excluding mothers with rheumatic inflammatory diseases, registered in MBRN during the same period time (n=575 798) served as population controls. RESULTS: CS occurred more frequently in both axSpA (22.4%) and PsA (30.6%) groups compared with population controls (15.6%), with even higher frequencies in inflammatory active axSpA (23.7%) and PsA (33.3%) groups. Compared with population controls, women with axSpA had higher risk for elective CS (risk difference 4.4%, 95% CI 1.5% to 8.2%) but not emergency CS. Women with PsA had higher risk for emergency CS (risk difference 10.6%, 95% CI 4.4% to 18.7%) but not elective CS. CONCLUSION: Women with axSpA had higher risk for elective and women with PsA for emergency CS. Active disease amplified this risk.

Patient Care Pathways for Pregnancy in Rare and Complex Rheumatic Diseases: Results From an International Survey.

OBJECTIVE: To map existing organizational care pathways in clinical centers of expertise that care for pregnant women affected by rare and complex connective tissue diseases (rcCTDs). METHODS: An international working group composed of experts in the field of pregnancy in rcCTDs co-designed a survey focused on organizational aspects related to the patient's pathway before, during, and after pregnancy. The survey was distributed to subject experts through referral sampling. RESULTS: Answers were collected from 69 centers in 21 countries. Patients with systemic lupus erythematosus and/or antiphospholipid syndrome were followed by more than 90% of centers, whereas those with disorders such as IgG4-related diseases were rarely covered. In the majority of centers, a multidisciplinary team was involved, including an obstetrician/gynecologist in 91.3% of cases and other healthcare professionals less frequently. Respondents indicated that 96% of the centers provided routine pre-pregnancy care, whereas the number of patient visits during pregnancy varied across centers. A formalized care pathway was described in 49.2% of centers, and 20.3% of centers had a predefined protocol for the monitoring of pregnant patients. Access to therapies during pregnancy also was heterogeneous among different centers. CONCLUSION: In international referral centers, a high level of care is provided to patients with rcCTDs before, during, and after pregnancy. No significant discrepancies were found between European and non-European countries. However, this work highlights a potential benefit to streamlining the care approaches across countries to optimize pregnancy and perinatal outcomes among patients with rcCTDs.

Factors Associated With Time to Pregnancy in Women With Axial Spondyloarthritis: A Registry-Based Multicenter Study.

OBJECTIVE: The present study was undertaken to study time to pregnancy (TTP) and factors associated with TTP in women with axial spondyloarthritis (SpA) compared to women with rheumatoid arthritis (RA). METHODS: We included 274 women with axial SpA and 317 women with RA from the Norwegian nationwide registry RevNatus. For all the women, we had retrospectively collected data on TTP, and a subgroup also had prospectively collected data. We compared TTP in women with axial SpA to women with RA using Kaplan-Meier plots and a log rank test. To identify factors associated with TTP, we used Cox proportional hazards regression. RESULTS: TTP exceeded 12 months in 21% of women with axial SpA. In the subgroup followed prospectively, 32% had TTP that exceeded 12 months. Longer TTP was associated with older age, nulliparity, and longer disease duration, with hazard ratios of 0.97 (95% confidence interval [95% CI] 0.94-1.00), 0.66 (95% CI 0.50-0.88), and 0.94 (95% CI 0.91-0.98), respectively. Disease activity, medication, and self-reported health-related quality of life were not associated with TTP. We found no statistically significant differences between axial SpA and RA in regard to TTP. CONCLUSION: In women with axial SpA, longer TTP was associated with older age, nulliparity, and longer disease duration.

Rehabilitation in warm climate for young adults with inflammatory arthritis: A 12-month randomized controlled trial.

OBJECTIVES: To investigate if an intensive rehabilitation programme, including intensive exercise and patient education, for young adults with inflammatory arthritis, conducted in a warm climate, has long-term effects on general health status compared with usual care. DESIGN: Open randomized controlled trial. PATIENTS: A total of 64 patients with inflammatory arthritis, aged 20-35 years. METHODS: Patients underwent randomized allocation to an intensive 17-day rehabilitation programme in a warm climate (intervention group) or to usual care with no structured rehabilitation (control group). The primary outcomes were physical function, assessed by the "30-second Sit to Stand test"(30sSTS), and coping, measured by the "Effective Musculoskeletal Consumer Scale" (EC17). RESULTS: A total of 64 patients (mean age 27.5 years, 62.5% female) were randomized. Thirty out of 32 patients completed the intervention. At 12-month follow-up, 7 patients were lost to follow-up; 4 from the intervention group and 3 from the control group. The intervention group showed significant improvement in the physical function test at 3 months; estimated mean difference (95% confidence interval): 5.5 (2.8-8.1), 6 months 3.6 (0.4-6.8) and 12 months 4.0 (0.0-7.9), compared with the control group. There were no differences in coping between the 2 groups at 3, 6 or 12 months. CONCLUSION: Rehabilitation in a warm climate improves physical functioning, but not coping, in young adults with inflammatory arthritis.

[Systemic lupus erythematosus and pregnancy]. / Systemisk lupus erythematosus og svangerskap.

BACKGROUND: Systemic lupus erythematosus (SLE) often starts in women of fertile age. Due to the unpredictable nature of the disease and the increased risk of the disease flaring up during pregnancy, women with SLE have previously often been advised to avoid pregnancy. This summary reviews current insights in pregnancy management of women with SLE. METHOD: Search in the Medline database (period 1980-2005) using keywords: SLE, lupus nephritis, antiphospholipid antibody, neonatal lupus and pregnancy. RESULTS: Previous studies of pregnant women with SLE have had different designs, sample sizes, selections of patients, definitions and measures of outcome. Women with previous pregnancy losses, an ongoing active disease with nephritis or hypertension and positive antiphospholipid antibodies, have an increased risk of pregnancy loss. The most favourable pregnancy outcomes are achieved when conception takes place during a remission of the disease. INTERPRETATION: There are few absolute contraindications for pregnancies in women with SLE. Women with SLE may experience uncomplicated pregnancies, but they need to plan their pregnancies as the risk for complications is increased. Best results are achieved through the cooperation of rheumatologists, gynaecologists and nephrologists. Glucocorticosteroids, hydroxychlorocine, azathioprine and anticoagulation may be used during pregnancy.

Disease Activity During Pregnancy and the First Year Postpartum in Women With Systemic Lupus Erythematosus.

OBJECTIVE: Disease activity measured by validated methods has been sparsely examined during and after pregnancy in women with systemic lupus erythematosus (SLE). The aim of this study was to describe the longitudinal course of disease activity during pregnancy and the first year postpartum using the Lupus Activity Index in Pregnancy (LAI-P). METHODS: RevNatus is a nationwide Norwegian prospective observational register including women diagnosed with inflammatory rheumatic diseases. LAI-P is a modified version of the LAI, with a good ability to assess disease activity in pregnant women with SLE. These indexes were used to assess disease activity at 6 visits (in trimesters 1, 2, and 3, and at 6 weeks, 6 months, and 12 months postpartum). The longitudinal course of disease activity was analyzed using an ordinal logistic mixed model. RESULTS: A total of 757 visits (145 pregnancies) in women with SLE were included in the analysis. More than half (51.6%) of the disease activity scores indicated remission, and only 6.3% indicated moderate disease activity. The model showed a statistically significant and clinically relevant change in disease activity over time, and a higher disease activity 6 and 12 months postpartum compared to the third trimester and 6 weeks postpartum. CONCLUSION: The majority of women had low or no disease activity at conception and during pregnancy, with higher disease activity at 6 and 12 months after delivery. This points to the importance of tight disease control not only before and during pregnancy but also in the first year postpartum.

[Reversible infertility from nonsteroidal anti-inflammatory drugs]. / Reversibel infertilitet ved ikke-steroide antiinflammatoriske midler.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) and selective cyclooxygenase-2 inhibitors may interfere with ovulation and the rupture of the follicle, causing reversible infertility. METHOD: Literature review. RESULTS: Reversible infertility is shown both in animal and human studies of these drugs. As determined by ultrasound, the drugs may delay or inhibit ovulation. These findings are also confirmed by a few randomized controlled studies showing an increase in time from the luteinizing hormone surge to rupture of the follicle and an increased size of the unruptured follicle. Most of the hormone analyses show values in accordance with the ovulation/menstrual cycle. Also, two epidemiological studies have shown an association between NSAID use and spontaneous abortion. These studies have methodological weaknesses and their findings have to be elucidated in future studies. INTERPRETATION: Women with fertility problems should avoid not only the selective cyclooxygenase-2 inhibitors, but also the traditional NSAIDs. However, women with rheumatic disease responding well to therapy should consult their physicians before stopping treatment. Reduced dose of a NSAID and temporary stop of drug treatment early in the menstrual cycle, or alternative drug treatment, may be a solution. NSAIDs should not be used in the last eight weeks of pregnancy.

State of the art: Reproduction and pregnancy in rheumatic diseases.

Throughout the last decade, increasing awareness has been raised on issues related to reproduction in rheumatic diseases including basic research to clarify the important role of estrogens in the etiology and pathophysiology of immune/inflammatory diseases. Sub- or infertility is a heterogeneous condition that can be related to immunological mechanisms, to pregnancy loss, to disease burden, to therapy, and to choices in regard to family size. Progress in reproductive medicine has made it possible for more patients with rheumatic disease to have children. Active disease in women with rheumatoid arthritis (RA) affects their children's birth weight and may have long-term effects on their future health status. Pregnancy complications as preeclampsia and intrauterine growth restriction are still increased in patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS), however, biomarkers can monitor adverse events, and several new therapies may improve outcomes. Pregnancies in women with APS remain a challenge, and better therapies for the obstetric APS are needed. New prospective studies indicate improved outcomes for pregnancies in women with rare diseases like systemic sclerosis and vasculitis. TNF inhibitors hold promise for maintaining remission in rheumatological patients and may be continued at least in the first half of pregnancy. Pre-conceptional counseling and interdisciplinary management of pregnancies are essential for ensuring optimal pregnancy outcomes.

Coping with arthritis is experienced as a dynamic balancing process. A qualitative study.

The aim of this study was to investigate the process of coping in people living with chronic inflammatory arthritis. Semi-structured individual face-to-face interviews with 26 persons having rheumatoid arthritis, psoriatic arthritis or unspecified polyarthritis were performed. The informants were asked how they experienced to live with arthritis and how they coped with challenges due to the arthritis. The main finding was that the informants experienced the process of coping with arthritis as a dynamic, iterative, balancing process. They balanced between different states, entitled "go on as usual", "listen to the body", "adjustments" and "attitude towards life". The informants preferred to be in a "go on as usual" state as this was seen as normal life. However, disease fluctuations with pain, fatigue and stiffness disturbed the balance and made the informants "listen to the body", a state where they became aware of how the disease affected them, followed by the "adjustment" state. Adjustments were composed of different efforts to ease the arthritis influence and for regaining balance. The "attitude towards life" influenced the overall process of coping. A redefined view of what the informants considered to be normal life thus happened through longer periods of imbalance. The process of coping with arthritis was found to be a dynamic, iterative, balancing process where patients redefined what they considered as normal life through the course of the disease.

Performance in leisure-time physical activities and self-efficacy in females with rheumatoid arthritis.

The purpose of this study was to examine leisure-time physical activities (LTPAs) and their association with self-efficacy in females with rheumatoid arthritis (RA) (n = 238). Their self-reported performance in LTPAs was measured by the Interest Checklist and efficacy beliefs by using the Arthritis Self-Efficacy Scales (ASES). LTPAs were classified as active or less active according to how many LTPAs they performed. The participants had reduced their participation in LTPAs by almost one-third during the last year. Active individuals performed the vigorous activities more often, they had a higher level of education, were working to a significantly greater extent, and reported better function, higher scores on the self-efficacy scales, and lower joint pain and fatigue. Multivariate analyses demonstrated that a high level of LTPAs was independently related to less fatigue (OR 0.98, p = 0.004), positive self-efficacy in coping with RA functions (OR 1.03, p = 0.015), and higher employment level (OR 0.42, p = 0.039). Only a quarter of the responders were physically active in their leisure time in the present study. Less active individuals reduced their performance in LTPAs to a much higher degree than active individuals during the last year. Partaking in a high amount of LTPAs was related to less fatigue and higher efficacy beliefs.

Drug insight: Anti-tumor necrosis factor therapy for inflammatory arthropathies during reproduction, pregnancy and lactation.

Tumor necrosis factor (TNF) antagonists are widely used to reduce disease activity and joint damage, and to improve health-related quality of life in patients suffering from rheumatoid arthritis, ankylosing spondylitis, or psoriatic arthritis. To date, no increased risk of embryotoxicity or teratogenicity, or adverse pregnancy outcome (such as birth defects, premature birth, and low birth weight) has been reported in patients with inflammatory arthropathies treated with anti-TNF therapy, compared with the general population. However, the available data are limited, and methotrexate, which is commonly used in combination with anti-TNF drugs, is teratogenic. Until more data are available, no firm conclusions can be reached regarding the safety of anti-TNF therapy in pregnancy. Nevertheless, in selected cases where there is high disease activity, anti-TNF therapy might be recommended, depending on the results of individual risk-benefit analyses. Fully informed consent from the mother is needed in such cases. Anti-TNF agents are not usually used during lactation, although the risk of toxicity is probably negligible.

Pregnancy outcome in patients with primary Sjögren's syndrome. a case-control study.

OBJECTIVE: To study the outcome of pregnancy in patients with primary Sjögren's syndrome (pSS). METHODS: A questionnaire covering demographic data and the outcome of pregnancies was answered by 58 patients with pSS and 157 controls. For 36 patients and 93 controls, we analyzed detailed data about pregnancy, birth, and status of the newborn from the Medical Birth Registry of Norway (MFR) for birth order one, 2, and 3. Thirty-two of 36 patients registered in MFR were diagnosed with pSS after the last birth. RESULTS: Pregnancy outcomes were not different in patients compared to controls. Two patients (3.4%) reported giving birth to a child with congenital heart block. CONCLUSION: PSS had no impact on pregnancy outcome before disease onset. The most important condition associated with pSS in anti-SSA positive mothers was congenital heart block in the offspring.