Management of pregnancy in women with rheumatoid arthritis

Rheumatoid arthritis (RA) disease activity may improve during pregnancy but postpartum flares are common. Patients taking disease-modifying antirheumatic drugs should be counselled about effective contraception. Knowledge about drug safety in pregnancy is limited but the Therapeutic Goods Administration categories and online resources are a guide to the data currently available. Begin prepregnancy counselling as early as possible to allow for cessation of teratogenic medications and optimisation of RA disease control. For unplanned pregnancies, cease teratogenic medications immediately and refer to a genetic counsellor and maternal–fetal medicine specialist for risk assessment and advice

Preconceptional cardiovascular health and pregnancy outcomes in women with systemic lupus erythematosus

Objective. To estimate the effects of preconceptional cardiovascular (CV) health, measured by American Heart Association (AHA) guidelines, on pregnancy outcomes in women with systemic lupus erythematosus (SLE). Methods. The study included patients in the Hopkins Lupus Pregnancy Cohort. Body mass index (BMI), total cholesterol, and blood pressure (BP) in the most recent clinic visit prior to conception or first trimester were used to determine CV health (ideal, intermediate, or poor health) based on AHA definitions. Outcomes included preterm birth, gestational age at birth, and small for gestational age (SGA). Multivariable linear and logistic regression models with generalized estimating equations estimated the association of each CV health factor and outcome. Results. The analysis included 309 live births. There were 95 preterm births (31%), and of the 293 pregnancies with birth weights, 18% were SGA. Ideal BMI, total cholesterol, and BP were reported in 56%, 85%, and 51% of pregnancies, respectively. Intermediate BMI was associated with decreased odds of SGA (OR 0.26, 95% CI 0.11-0.63), adjusted for race and prednisone use. Intermediate/poor total cholesterol was associated with increased odds of preterm birth (OR 2.21, 95% CI 1.06-4.62). Intermediate/poor BP was associated with decreased gestational age at birth (β -0.96, 95% CI -1.62 to -0.29). Conclusion. Poor/intermediate preconception CV health affects pregnancy outcomes of preterm birth and SGA infants among women with SLE. Efforts to maintain BMI, total cholesterol, and BP within the recommended ideal range prior to pregnancy is important to improve pregnancy outcomes in women with SLE

Gestational weight gain in women with systemic lupus erythematosus

Objective The objective of this study was to estimate the proportion of pregnant women with systemic lupus erythematosus meeting Institute of Medicine guidelines for gestational weight gain and determine correlates of adherence to guidelines. Methods Singleton, live births in the Hopkins Lupus Pregnancy Cohort 1987-2015 were included. Pre-pregnancy weight was the weight recorded 12 months prior to pregnancy/first trimester. Final weight was the last weight recorded in the third trimester. Adherence to Institute of Medicine guidelines (inadequate, adequate, or excessive) was based on pre-pregnancy body mass index. Fisher's exact test and analysis of variance determined factors associated with not meeting guidelines. Stepwise selection estimated predictors of gestational weight gain. Results Of the 211 pregnancies, 34%, 24% and 42% had inadequate, adequate and excessive gestational weight gain, respectively. In exploratory analyses, differences in Institute of Medicine adherence were observed by pre-pregnancy body mass index, race, elevated creatinine during pregnancy and pre-pregnancy blood pressure. Odds of inadequate and excessive gestational weight gain increased 12% with each 1 kg/m2 increase in pre-pregnancy body mass index. Lower maternal education was associated with increased odds of inadequate and excessive gestational weight gain. Conclusions As in the general population, most women with systemic lupus erythematosus did not meet Institute of Medicine guidelines. Our results identified predictors of gestational weight gain to aid in targeted interventions to improve guideline adherence in this population

Effect of pregnancy on disease flares in patients with systemic lupus erythematosus

Objective: Prior studies found conflicting results about whether lupus is likely to flare during or after pregnancy. Using a large cohort of pregnant and non-pregnant women with lupus, we estimated the effect of pregnancy on disease flares in systemic lupus erythematosus. Methods: Data were collected in the Hopkins Lupus Cohort 1987-2015. Women aged 14-45 years with >1 measurement of disease activity were included. The time-varying exposures were classified as pregnancy, postpartum or non-pregnant/non-postpartum periods. Flares were defined as: (1) change in Physician Global Assessment (PGA)≥1 from previous visit and (2) change in Safety of Estrogens in Lupus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI)≥4 from previous visit. A stratified Cox model estimated HRs with bootstrap 95% CIs. Results: There were 1349 patients, including 398 pregnancies in 304 patients. There was an increased rate of flare defined by PGA during pregnancy (HR: 1.59; 95% CI 1.27 to 1.96); however, this effect was modified by hydroxychloroquine (HCQ) use, with the HR of flares in pregnancy compared with non-pregnant/non-postpartum periods estimated to be 1.83 (95% CI 1.34 to 2.45) for patients with no HCQ use and 1.26 (95% CI 0.88 to 1.69) for patients with HCQ use. The risk of flare was similarly elevated among non-HCQ users in the 3 months postpartum, but not for women taking HCQ after delivery. Conclusions: Our study supports and extends previous findings that the incidence of flare is increased during pregnancy and within the 3 months postpartum. Continuing HCQ, however, appeared to mitigate the risk of flare during and after pregnancy

An Autoreactive Antibody from an SLE/HIV-1 Individual Broadly Neutralizes HIV-1

Broadly HIV-1–neutralizing antibodies (BnAbs) display one or more unusual traits, including a long heavy chain complementarity-determining region 3 (HCDR3), polyreactivity, and high levels of somatic mutations. These shared characteristics suggest that BnAb development might be limited by immune tolerance controls. It has been postulated that HIV-1–infected individuals with autoimmune disease and defective immune tolerance mechanisms may produce BnAbs more readily than those without autoimmune diseases. In this study, we identified an HIV-1–infected individual with SLE who exhibited controlled viral load (\u3c5,000 copies/ml) in the absence of controlling HLA phenotypes and developed plasma HIV-1 neutralization breadth. We collected memory B cells from this individual and isolated a BnAb, CH98, that targets the CD4 binding site (CD4bs) of HIV-1 envelope glycoprotein 120 (gp120). CH98 bound to human antigens including dsDNA, which is specifically associated with SLE. Anti-dsDNA reactivity was also present in the patient’s plasma. CH98 had a mutation frequency of 25% and 15% nt somatic mutations in the heavy and light chain variable domains, respectively, a long HCDR3, and a deletion in the light chain CDR1. The occurrence of anti-dsDNA reactivity by a HIV-1 CD4bs BnAb in an individual with SLE raises the possibility that some BnAbs and SLE-associated autoantibodies arise from similar pools of B cells

Identifying the unmet information and support needs of women with autoimmune rheumatic diseases during pregnancy planning, pregnancy and early parenting: mixed-methods study

Background Autoimmune rheumatic diseases (ARDs) such as inflammatory arthritis and Lupus, and many of the treatments for these diseases, can have a detrimental impact on fertility and pregnancy outcomes. Disease activity and organ damage as a result of ARDs can affect maternal and foetal outcomes. The safety and acceptability of hormonal contraceptives can also be affected. The objective of this study was to identify the information and support needs of women with ARDs during pregnancy planning, pregnancy and early parenting. Methods This mixed methods study included a cross-sectional online survey and qualitative narrative interviews. The survey was completed by 128 women, aged 18–49 in the United Kingdom with an ARD who were thinking of getting pregnant in the next five years, who were pregnant, or had young children (< 5 years old). The survey assessed quality-of-life and information needs (Arthritis Impact Measurement Scale Short Form and Educational Needs Assessment Tool), support received, what women found challenging, what was helpful, and support women would have liked. From the survey participants, a maximum variation sample of 22 women were purposively recruited for qualitative interviews. Interviews used a person-centered participatory approach facilitated by visual methods, which enabled participants to reflect on their experiences. Interviews were also carried out with seven health professionals purposively sampled from primary care, secondary care, maternity, and health visiting services. Results Survey findings indicated an unmet need for information in this population (ENAT total mean 104.85, SD 30.18). Women at the pre-conception stage reported higher needs for information on pregnancy planning, fertility, giving birth, and breastfeeding, whereas those who had children already expressed a higher need for information on pain and mobility. The need for high quality information, and more holistic, multi-disciplinary, collaborative, and integrated care consistently emerged as themes in the survey open text responses and interviews with women and health professionals. Conclusions There is an urgent need to develop and evaluate interventions to better inform, support and empower women of reproductive age who have ARDs as they navigate the complex challenges that they face during pregnancy planning, pregnancy and early parenting

Reaching a consensus on research priorities for supporting women with autoimmune rheumatic diseases during pre-conception, pregnancy and early parenting: A Nominal Group Technique exercise with lay and professional stakeholders

Background:Women with autoimmune rheumatic diseases (ARDs) find it difficult to get information and support with family planning, pregnancy, and early parenting. A systematic approach to prioritising research is required to accelerate development and evaluation of interventions to meet the complex needs of this population. Methods:A Nominal Group Technique (NGT) exercise was carried out with lay and professional stakeholders (n=29). Stakeholders were prepared for debate through presentation of available evidence. Stakeholders completed three tasks to develop, individually rank, and reach consensus on research priorities: Task 1 – mapping challenges and services using visual timelines; Task 2 - identifying research topics; Task 3 - individually ranking research topics in priority order. Results of the ranking exercise were fed back to the group for comment. Results:The main themes emerging from Task 1 were the need for provision of information, multi-disciplinary care, and social and peer support. In Task 2, 15 research topics and 58 sub-topics were identified around addressing the challenges and gaps in care identified during Task 1. In Task 3, a consensus was reached on the ten research topics that should be given the highest priority. These were individually ranked, resulting in the following order of priorities (from 1 – highest to 10 – lowest): 1. Shared decision-making early in the care pathway; 2. Pre-conception counseling; 3. Information about medication use during pregnancy/breastfeeding; 4. Personalised care planning; 5. Support for partners/family members; 6. Information about local support/disease specific issues; 7. Shared decision-making across the care pathway; 8. Peer-support; 9. Social inequalities in care, and; 10. Guidance on holistic/alternative therapies. Conclusions:This systematic approach to identification of research priorities from a multi-disciplinary and lay perspective indicated that activities should focus on development and evaluation of interventions that increase patient involvement in clinical decision-making, multi-disciplinary models of care, and timely provision of information

Autoimmune diseases and pregnancy: analysis of a series of cases

BACKGROUND: An autoimmune disease is characterized by tissue damage, caused by self-reactivity of different effector mechanisms of the immune system, namely antibodies and T cells. All autoimmune diseases, to some extent, have implications for fertility and obstetrics. Currently, due to available treatments and specialised care for pregnant women with autoimmune disease, the prognosis for both mother and child has improved significantly. However these pregnancies are always high risk. The purpose of this study is to analyse the fertility/pregnancy process of women with systemic and organ-specific autoimmune diseases and assess pathological and treatment implications. METHODS: The authors performed an analysis of the clinical records and relevant obstetric history of five patients representing five distinct autoimmune pathological scenarios, selected from Autoimmune Disease Consultation at the Hospital of Braga, and reviewed the literature. RESULTS: The five clinical cases are the following: Case 1-28 years old with systemic lupus erythematosus, and clinical remission of the disease, under medication with hydroxychloroquine, prednisolone and acetylsalicylic acid, with incomplete miscarriage at 7 weeks of gestation without signs of thrombosis. Case 2-44 years old with history of two late miscarriages, a single preterm delivery (33 weeks) and multiple thrombotic events over the years, was diagnosed with antiphospholipid syndrome after acute myocardial infarction. Case 3-31 years old with polymyositis, treated with azathioprine for 3 years with complete remission of the disease, took the informed decision to get pregnant after medical consultation and full weaning from azathioprine, and gave birth to a healthy term new-born. Case 4-38 years old pregnant woman developed Behcet's syndrome during the final 15 weeks of gestation and with disease exacerbation after delivery. Case 5-36 years old with autoimmune thyroiditis diagnosed during her first pregnancy, with difficult control over the thyroid function over the years and first trimester miscarriage, suffered a second miscarriage despite clinical stability and antibody regression. CONCLUSIONS: As described in literature, the authors found a strong association between autoimmune disease and obstetric complications, especially with systemic lupus erythematosus, antiphospholipid syndrome and autoimmune thyroiditis