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OBJECTIVE: To analyze complement level variations in systemic lupus erythematosus (SLE) pregnancies, focusing on disease flares and obstetric complications. METHODS: SLE pregnancies prospectively followed by multidisciplinary teams from 1987 to 2018 in 2 Italian rheumatology centers were retrospectively analyzed. As reference, pregnancy-modified ranges of normal levels of C3 and C4 were derived from 175 pregnancies from the general obstetric population (GOP), as previously described by our group. RESULTS: Two hundred forty-six pregnancies in 172 patients with SLE were analyzed. Eighty-nine percent were live births. Thirty-five flares were recorded in 30 pregnancies (12.2%) and obstetric complications occurred in 47 pregnancies (19.1%) including 27 pregnancy losses, 11 severely preterm births (2 resulting in perinatal death), and 15 hypertensive disorders. C3 and C4 levels were higher in the GOP than in patients with SLE, at any time point. C3 and C4 levels progressively increased during pregnancy in both GOP and SLE pregnancies without flare and obstetric complications, whereas this physiological increase was not observed in pregnancies with flares or obstetric complications. A significantly higher frequency of low C4 was found in pregnancies with flares (at preconception and in each trimester) and preterm births (at preconception). In multivariate analysis, low C4 at preconception was associated with flares (odds ratio 13.81, 95% CI 3.10-61.43, P < 0.001). CONCLUSION: Low C4 at preconception was found to be an independent risk factor for SLE flare during pregnancy. Not only C3 and C4 levels but also their variations should be observed, as their failure to increase can be useful to predict risk of complications and suggest closer monitoring.
Subject(s)
Complement C3 , Complement C4 , Lupus Erythematosus, Systemic , Pregnancy Complications , Premature Birth , Female , Humans , Infant, Newborn , Pregnancy , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/epidemiology , Pregnancy Complications/epidemiology , Pregnancy Outcome/epidemiology , Premature Birth/epidemiology , Retrospective Studies , Symptom Flare Up , Complement C3/metabolism , Complement C4/metabolismABSTRACT
The concern about the offspring's health is one of the reasons for a reduced family size of women with rheumatic diseases (RD). Increased risk of autoimmune diseases (AD) and neurodevelopmental disorders (ND) has been reported in children born to patients with RD. Within a nationwide survey about reproductive issues of women with RD, we aimed at exploring the long-term outcome of their children. By surveying 398 patients who received their diagnosis of RD during childbearing age (before the age of 45), information about the offspring were obtained from 230 women who declared to have had children. A total of 148 (64.3%) patients were affected by connective tissue diseases (CTD) and 82 (35.7%) by chronic arthritis. Data on 299 children (156 males, 52.1%; mean age at the time of interview 17.1 ± 9.7 years) were collected. Twelve children (4.0%), who were born to patients with CTD in 75% of the cases, were affected by AD (8 cases of celiac disease). Eleven children had a certified diagnosis of ND (3.6%; 6 cases of learning disabilities); 9 of them were born to mothers with CTD (5 after maternal diagnosis). No association was found between ND and prenatal exposure to either maternal autoantibodies or anti-rheumatic drugs. Absolute numbers of offspring affected by AD and ND were low in a multicentre cohort of Italian women with RD. This information can be helpful for the counselling about reproductive issues, as the health outcomes of the offspring might not be an issue which discourage women with RD from having children.
Subject(s)
Antirheumatic Agents , Autoimmune Diseases , Rheumatic Diseases , Antirheumatic Agents/therapeutic use , Autoantibodies , Autoimmune Diseases/epidemiology , Child , Cohort Studies , Female , Humans , Male , Pregnancy , Rheumatic Diseases/epidemiologyABSTRACT
OBJECTIVES: The aim was to determine whether assisted reproductive technologies (ARTs) confer additional risk in rheumatic patients (in terms of disease flare and fetal-maternal complications) and whether, if performed, their efficacy is affected by maternal disease. METHODS: Sixty infertile rheumatic women undergoing 111 ART cycles were included. Clinical pregnancy rate, live birth rate, maternal disease flares and maternal-fetal complications were recorded. RESULTS: One hundred and eleven ART cycles in 60 women were analysed. We reported 46 pregnancies (41.4%), 3 (3.1%) cases of ovarian hyperstimulation syndrome and no cases of thrombosis during stimulation, pregnancy and puerperium. One or more maternal complication was reported in 13 (30.2%) pregnancies, and fetal complications occurred in 11 fetuses (21.1%). The live birth rate was 98%, but we reported three (6%) perinatal deaths in the first days of life. During puerperium, we recorded one (2.5%) post-partum haemorrhage and one (2.5%) articular flare. CONCLUSION: The safety and efficacy of the ARTs, demonstrated in the general population, seems to be confirmed also in rheumatic patients. No evidence was found to advise against their application, and the choice of therapy should be made depending on the patient's risk profile, irrespective of whether the pregnancy is natural or artificial induced.
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Introduction: Belimumab is a monoclonal antibody against soluble BLyS used for treatment of refractory Systemic Lupus Erythematosus (SLE). Although B cells are the main target of this therapy, a BLyS-dependent T cell activation pathway has also been demonstrated. The aim of the study is to analyze B and T cells phenotype modifications in a cohort of SLE patients treated with belimumab in correlation with serum BLyS levels. Materials and Methods: Fourteen SLE patients were enrolled in the study. Lymphocyte immunophenotyping by flow cytometry and determination of serum BLyS levels by high sensitivity ELISA were performed before the first infusion of belimumab, after 6 and 12 months of treatment. Sex and age-matched healthy controls were enrolled for the comparisons. Results: Baseline number of total B cells, especially switched memory B cells, were lower in SLE patients compared to control subjects. After 6 months of treatment, the total number of B cells, particularly, naive and transitional B cells, was significantly reduced in correlation with the reduction of BLyS levels. No significant association was found between baseline counts of B cells and reduction of SLEDAI-2K over time. In terms of response prediction, a significant association between SLEDAI-2K improvement at 12 months and the decrease of total number of B cells within the first 6 months of therapy was observed. Concerning the T cell compartment, the baseline percentage number of CD8+ effector memory was associated with SLEDAI-2K at baseline and with its improvement after 12 months of therapy. Furthermore, T cell lymphopenia and low number of circulating recent thymic emigrants were also observed compared to control subjects measured at baseline. Discussion: The effects of belimumab on B cell subpopulations could be explained by the direct blockage of soluble BLyS, while the mild effects on T cells might be explained indirectly by the reduction of disease activity by means of therapy. B cell immunophenotyping during belimumab might be useful for monitoring the response to treatment.
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OBJECTIVE: The reproductive choices of women affected by rheumatic diseases (RD) can be influenced by several factors, including the quality of physician-patient communication. We conducted a survey on reproductive issues aiming at exploring the unmet needs of women with RD during childbearing age. METHODS: We administered 65 multiple-choice and 12 open-answer questions about pregnancy counselling, contraception, use of drugs during pregnancy and other women reproductive issues to 477 consecutive women with RD aged 18-55 years followed-up in 24 rheumatology centres in Italy. Analysis was restricted to 398 patients who received their diagnosis of RD before the age of 45. According to the RD diagnosis, patients were subdivided into 2 groups: connective tissue diseases (n = 249) and chronic arthritis (n = 149). RESULTS: At the time of interview, women in both groups had a mean age of 40 years. Nearly one third of patients in each group declared not to have received any counselling about either pregnancy desire nor contraception. A smaller family size than desired was reported by nearly 37% of patients, because of concerns related to maternal disease in one fourth of the cases. A "Disease Knowledge Index" (DKI) was created to investigate the degree of patients' information about the implications of their RD on reproductive issues. Having received counselling was associated with higher DKI values and with a positive impact on family planning. CONCLUSION: Italian women of childbearing age affected by RD reported several unmet needs in their knowledge about reproductive issues. Strategies are needed to implement and facilitate physician-patient communication.
Subject(s)
Autoimmune Diseases/epidemiology , Health Knowledge, Attitudes, Practice , Rheumatic Diseases/diagnosis , Rheumatic Diseases/immunology , Surveys and Questionnaires , Adolescent , Adult , Autoimmune Diseases/diagnosis , Cohort Studies , Family Planning Services , Female , Humans , Interviews as Topic , Italy , Middle Aged , Pregnancy , Reproductive Health , Retrospective Studies , Risk Assessment , Severity of Illness Index , Young AdultABSTRACT
OBJECTIVE: To investigate efficacy, safety and survival of belimumab and to identify predictors of drug response and drug discontinuation in patients with active SLE in clinical practice. PATIENTS AND METHODS: Data of SLE patients, treated with belimumab, from 11 Italian prospective cohorts were analyzed. SLEDAI-2K, anti-dsDNA, C3, C4, prednisone daily dose, DAS-28, 24-h proteinuria, CLASIa (Cutaneous LE Disease Area and Severity Index Activity) were recorded at baseline and every 6 months. SLE Responder Index-4 (SRI-4) was calculated at 12 and 24 months. Demographic and clinical features and comorbidities were included in the univariate and multivariate analysis. Adverse events were recorded at each visit. Statistics was performed using the SPSS software. RESULTS: We studied 188 SLE patients, mean follow-up 17.5 ± 10.6 months. The most frequent manifestations, which required the use of belimumab, were polyarthritis (45.2%) and skin rashes (25.5%). SRI-4 was achieved by 77.0% and 68.7% of patients at 12 and 24-months. Independent predictors of 12-month response were SLEDAI-2K ≥ 10 (OR 40.46, p = 0.001) and polyarthritis (OR 12.64, p = 0.001) and of 24-month response were SLEDAI-2K ≥ 10 (OR 15.97, p = 0.008), polyarthritis (OR 32.36, p = 0.006), and prednisone ≥7.5 mg/day (OR 9.94, p = 0.026). We observed a low rate of severe adverse events. Fifty-eight patients (30.8%) discontinued belimumab after a mean follow-up of 10.4 ± 7.5 months. The drug survival was 86.9%, 76.9%, 69.4%, 67.1%, and 61.9% at 6, 12, 18, 24, and 30 months, respectively. No factors associated with drug discontinuation were found. CONCLUSION: Belimumab is effective and safe when used in clinical practice setting.
Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Immunosuppressive Agents/therapeutic use , Lupus Erythematosus, Systemic/drug therapy , Adolescent , Adult , Biomarkers, Pharmacological/metabolism , Child , Cohort Studies , Follow-Up Studies , Humans , Lupus Erythematosus, Systemic/mortality , Population Groups , Prospective Studies , Survival Analysis , Withholding Treatment , Young AdultABSTRACT
OBJECTIVE: To assess the longterm frequency of thrombotic recurrences, obstetrical complications, organ damage, severe comorbidities, and evolution toward connective tissue disease (CTD) in primary antiphospholipid syndrome (PAPS). METHODS: Medical records of patients with PAPS followed in 6 centers for ≥ 15 years were retrospectively reviewed. RESULTS: One hundred fifteen patients were studied: 88% women, followed between 1983 and 2014 with a mean (± SD) age at diagnosis of 33 (± 10) years. During a median followup of 18 years (range 15-30), 50 patients (44%) had at least a thrombotic event for a total of 75 events and an annual incidence of 3.5%. Thromboses were more frequent in patients with previous thrombotic history (p = 0.002). A catastrophic antiphospholipid syndrome occurred in 6 patients (5%). The use of oral anticoagulants in patients with thrombotic onset did not appear to be protective against recurrences (p = 0.26). Fifty-two women had 87 pregnancies, successful in 78%. Twenty-nine percent of patients accrued functional damage. Damage was significantly associated with a thrombotic history (p = 0.004) and with arterial events (p < 0.001), especially stroke, but not with demographics, serology, or treatment. Twenty-four major bleeding episodes were recorded in 18 patients, all receiving anticoagulants. Severe infections affected 6 patients (5%), with 1 fatality. A solid cancer was diagnosed in 8 patients (7%). Altogether, 16 patients (14%) developed an autoimmune disease and 13 (11%) a full-blown picture of CTD. CONCLUSION: Despite therapy, a high proportion of patients experienced new thrombotic events and organ damage, while evolution toward CTD was infrequent.
Subject(s)
Anticoagulants/therapeutic use , Antiphospholipid Syndrome/drug therapy , Thrombosis/etiology , Adult , Antiphospholipid Syndrome/complications , Disease Progression , Female , Follow-Up Studies , Humans , Male , Middle Aged , Retrospective Studies , Treatment Outcome , Young AdultABSTRACT
OBJECTIVE: To investigate effectiveness and safety of belimumab in patients with active systemic lupus erythematosus (SLE) in a clinical practice setting. METHODS: Sixty-seven patients with active SLE, mean ± SD age 39.3 ± 10.2 years, from 2 Italian prospective cohorts were treated with belimumab (10 mg/kg on day 0, 14, 28, and then every 28 days) added to background therapy. The Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index, the Disease Activity Score in 28 joints (DAS28), 24-hour proteinuria, the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) activity score, anti-double-stranded DNA (anti-dsDNA), C3 and C4 levels, and prednisone daily dose were recorded at baseline, month 3, 6, 9, 12, 18, and 24. Arthritis was subdivided into "classical" (CLP) and "rheumatoid-like"; skin manifestations into acute (ACLE), subacute (SCLE), and chronic. SLE flares, defined according to the SLEDAI Flare Index, were calculated before and after belimumab initiation. Adverse events were carefully evaluated during treatment. Statistics were performed by the SPSS package (version 21.0). RESULTS: Mean ± SD followup was 16.2 ± 9.5 months. Main refractory manifestations treated with belimumab were musculoskeletal (37.3%), mucocutaneous (22.4%), and renal (23.9%). SLEDAI-2K, prednisone daily dose, anti-dsDNA, DAS28, CLASI, and 24-hour proteinuria decreased during treatment. DAS28 score decreased in patients with polyarthritis (P < 0.001), particularly in those with CLP (P < 0.001), and CLASI decreased in patients with skin manifestation (P = 0.003), either ACLE (P = 0.051) or SCLE (P = 0.047). Flare rate was lower 1 and 2 years after belimumab initiation than in the periods before (P = 0.001). Belimumab was well-tolerated and no damage accrual was observed after initiation. CONCLUSION: Belimumab was effective and safe in a clinical practice setting; it decreased the number of flares and hindered damage progression in patients with active SLE.
Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Immunosuppressive Agents/therapeutic use , Lupus Erythematosus, Systemic/drug therapy , Adult , Disease Progression , Female , Humans , Male , Middle Aged , Prospective Studies , Treatment OutcomeABSTRACT
Nowadays, most of the young women affected by Systemic Lupus Erythematosus (SLE) can carry out one or more pregnancies thanks to the improvement in treatment and the consequent reduction in morbidity and mortality. Pregnancy outcome in these women has also greatly improved in the last decades. A correct timing for pregnancy (tailored on disease activity and established during a preconception counselling), together with a tight monitoring during the three trimesters and the post-partum period (to timely identify and treat possible obstetric complications or maternal disease flares), as well as the concept of multidisciplinary management, are currently milestones of the management of pregnancy in SLE patients. Nevertheless, the increasing knowledge on the compatibility of drugs with pregnancy has allowed a better treatment of these patients, by choosing medications that control maternal disease activity without harming the foetus. However, particular attention and strict monitoring should be dedicated to SLE pregnant women in particular clinical settings: patients with lupus nephritis and patients with aPL positivity or Antiphospholipid syndrome, who are at higher risk for maternal and foetal complications, but also patients with anti-Ro/SSA and/or anti-La/SSB antibodies, because of the risk of neonatal lupus. A discussion on family planning, as well as counselling on contraception, should be part of the everyday-practice for physicians caring for SLE women during their reproductive age. Another issue is the possible reduction of fertility in these women, that can be due to different reasons. Consequently, the request for assisted reproduction techniques has been increasing in the last years, so that rheumatologists and gynaecologists should be prepared to counsel SLE patients also in this particular setting.
Subject(s)
Lupus Erythematosus, Systemic/immunology , Pregnancy Complications/immunology , Antiphospholipid Syndrome/complications , Antiphospholipid Syndrome/immunology , Autoantibodies/immunology , Contraception , Counseling , Disease Management , Female , Fertility , Humans , Lactation , Lupus Erythematosus, Systemic/diagnosis , Lupus Erythematosus, Systemic/therapy , Lupus Nephritis/diagnosis , Lupus Nephritis/immunology , Lupus Nephritis/therapy , Pregnancy , Pregnancy Complications/diagnosis , Pregnancy Complications/therapy , Pregnancy Outcome , Reproductive Techniques, AssistedABSTRACT
PROBLEM: Cyclosporin A (CYS A) is an immunosuppressant agent administered in autoimmune diseases, and its use during pregnancy and lactation is a debated topic. METHOD OF STUDY: The demographic characteristics, the activity of the underlying disease, and the onset of fetal-maternal complications have been investigated in 21 consecutive patients (2 RA, 14 SLE, 2 PA, 1 SjS, 1 DM, 1 Churg-Strauss vasculitis), treated with CYS A throughout 29 gestations. A subanalysis of the SLE group was performed. RESULTS: We recorded a live birth rate of 86.2%. The median gestational age at birth was 38.2 weeks. The prevalence of maternal-fetal complications showed no differences with general population. Disease flares appeared in 4% of patients during gestation and in 12% during puerperium. CONCLUSION: We found no evidence justifying the suspension of CYS A when a pregnancy occurs. The drug does not appear to promote maternal-fetal complications and should be continued in patients who benefit from therapy. Data regarding breast-feeding during therapy are still scarce, but no evidence of toxicity has emerged.
Subject(s)
Autoimmune Diseases/drug therapy , Autoimmune Diseases/epidemiology , Cyclosporine/therapeutic use , Immunosuppressive Agents/therapeutic use , Pregnancy Complications/epidemiology , Adolescent , Adult , Breast Feeding , Female , Humans , Italy/epidemiology , Postpartum Period , Pregnancy , Pregnancy Outcome , Prevalence , Young AdultABSTRACT
OBJECTIVE: Subcutaneous (SC) abatacept (ABA) is comparable to intravenous (IV) formulation in terms of efficacy and safety profile. Our work analyzed the switch to SC formulation from IV administration in patients with rheumatoid arthritis. METHODS: Fifty-one patients treated with SC ABA were included. Clinical data were obtained from clinical charts. RESULTS: Fourteen patients relapsed and needed to return to the IV administration. Neither clinical and laboratory features nor the previous therapies were identified as risk factors for SC formulation inefficacy. Disease activity decreased after the return to IV infusions. CONCLUSION: SC ABA showed a risk of relapse in 27% of cases. The reinsertion of the IV administration quickly reinstated disease control.
Subject(s)
Antirheumatic Agents/administration & dosage , Arthritis, Rheumatoid/drug therapy , Immunoconjugates/administration & dosage , Abatacept , Adult , Aged , Antirheumatic Agents/adverse effects , Antirheumatic Agents/therapeutic use , Drug Substitution , Female , Humans , Immunoconjugates/adverse effects , Immunoconjugates/therapeutic use , Infusions, Intravenous , Injections, Subcutaneous , Italy , Male , Middle Aged , Treatment OutcomeABSTRACT
OBJECTIVE: The aim of this article is to assess the predictive value of second trimester mean uterine artery Doppler pulsatility index (mUtA PI) for pregnancy complications in women with systemic lupus erythematosus (SLE). METHODS: Cohort study of consecutive pregnancies complicated with SLE during a period of 12 years is used. SLE diagnosis was made before pregnancy. mUtA PI was measured between 23 + 0 and 26 + 6 weeks' gestation. Pregnancy and neonatal outcomes were collected. Small for gestational age (SGA) was defined as birth weight <10th percentile. Adverse pregnancy outcome (APO) was defined as one of the following: pre-eclampsia (PE), SGA, placental abruption, stillbirth, or neonatal death. Differential diagnosis between PE and renal flare was made according to SLE-disease activity index. RESULTS: There are 70 pregnancies in 64 women. PE was observed in four cases (6%), SGA in five cases (7%), and APO in seven cases (10%). mUtA PI showed a sensitivity and a specificity of 1.0 (95% CI 0.5-1.0) and 1.0 (95% CI 0.95-1.0) for PE, 0.40 (95% CI 0.12-0.77) and 0.97 (95% CI 0.89-0.99) for SGA, and 0.57 (95% CI 0.25-0.84) and 1.0 (95% CI 0.94-1.0) for APO, respectively. CONCLUSION: Our findings suggest that uterine artery Doppler is confirmed to be a high sensitivity and a high specificity test for predicting PE even in SLE patients.
Subject(s)
Abruptio Placentae/diagnostic imaging , Fetal Growth Retardation/diagnostic imaging , Lupus Erythematosus, Systemic/diagnostic imaging , Pre-Eclampsia/diagnostic imaging , Pulsatile Flow , Uterine Artery/diagnostic imaging , Uterus/blood supply , Adult , Cohort Studies , Female , Humans , Infant, Newborn , Infant, Small for Gestational Age , Perinatal Death , Predictive Value of Tests , Pregnancy , Pregnancy Complications/diagnostic imaging , Pregnancy Outcome , Pregnancy Trimester, Second , Retrospective Studies , Stillbirth , Ultrasonography, Doppler , Ultrasonography, PrenatalSubject(s)
Antibodies, Monoclonal, Humanized , Glucocorticoids , Lupus Erythematosus, Systemic , Administration, Intravenous , Adult , Antibodies, Antinuclear/blood , Antibodies, Antiphospholipid/blood , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/adverse effects , Dose-Response Relationship, Drug , Drug Monitoring , Drug Therapy, Combination/methods , Female , Follow-Up Studies , Glucocorticoids/administration & dosage , Glucocorticoids/adverse effects , Humans , Immunosuppressive Agents/administration & dosage , Immunosuppressive Agents/adverse effects , Italy , Lupus Erythematosus, Systemic/blood , Lupus Erythematosus, Systemic/diagnosis , Lupus Erythematosus, Systemic/drug therapy , Lupus Erythematosus, Systemic/physiopathology , Patient Acuity , Treatment OutcomeABSTRACT
IgA antiphospholipid antibodies (aPL) are not currently recognized as formal laboratory criteria for the Antiphospholipid Syndrome (APS). This is mainly due to methodological issues (different study designs, use of various non-standardized IgA assays). However, there are experimental data showing the pathogenic role of IgA anti-cardiolipin antibodies (aCL) and IgA anti-ß2glycoprotein I antibodies (anti-ß2GPI). Isolated IgA aCL are not very common, therefore their testing could be useful in the case of strong suspicion of APS but negative results for other aPL tests. IgA anti-ß2GPI seem to be the most prevalent isotype in patients with Systemic Lupus Erythematosus (SLE), with a significant association with thrombotic events. Such a clinical relevance has been recently recognized by the inclusion of these autoantibodies among the aPL tests in the novel SLICC classification criteria for SLE. Emerging interest has been raised by IgA anti-ß2GPI against domain 4/5 as a novel subgroup of clinically relevant aPL.
Subject(s)
Antiphospholipid Syndrome/diagnosis , Autoantibodies/analysis , Immunoglobulin A/analysis , Lupus Erythematosus, Systemic/diagnosis , beta 2-Glycoprotein I/immunology , Antibodies, Anticardiolipin/analysis , Biomarkers/analysis , HumansABSTRACT
OBJECTIVE: To evaluate the association between serum complement levels (C3 and C4) and obstetric complications. METHODS: Fifty-seven pregnancies in primary APS (PAPS) patients were compared with 49 pregnancies in patients with UCTD and SS. A group of 175 healthy pregnant women were studied to calculate a normality range for C3 and C4 during pregnancy. Such a range was applied to define hypocomplementaemia in PAPS and UCTD/SS. RESULTS: Both groups of patients (PAPS and UCTD/SS) showed significantly lower levels of C3 and C4 in each trimester as compared with healthy women; conversely, no significant difference was found between PAPS and UCTD/SS. Comparing PAPS pregnancies with and without complications, no difference was found in the prevalence of low C3 or low C4. CONCLUSION: No association was found between hypocomplementaemia and obstetric complications in PAPS. However, both cases of pre-eclampsia were characterized by low C3 throughout pregnancy. There is evidence that the complement system is a contributor to the mechanisms of aPL-mediated damage, but its predictive role on the final pregnancy outcome does not seem to be of major impact.
Subject(s)
Antiphospholipid Syndrome/complications , Complement C3/metabolism , Complement C4/metabolism , Pregnancy Complications/prevention & control , Adult , Antiphospholipid Syndrome/blood , Case-Control Studies , Female , Humans , Pregnancy , Pregnancy Complications/etiology , Pregnancy Outcome , Pregnancy Trimesters , Prenatal Diagnosis , Prospective Studies , Reference Values , Retrospective Studies , Young AdultABSTRACT
Multidisciplinary approach and patient counselling have been the key points in the improvement of the management of pregnancy in women with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). Most of these women can have successful pregnancy when thoroughly informed and instructed on several different issues. Disease activity should be in stable remission prior to pregnancy in order to reduce the chance for flare during pregnancy. To this purpose, medications must be modulated: "safe" drugs should be continued throughout pregnancy, embryotoxic/foetotoxic drugs should be withdrawn timely, and beneficial drugs such as low dose aspirin and heparin should be added for prophylaxis of maternal and foetal outcome, especially in the presence of antiphospholipid antibodies. The safety profile of anti-rheumatic drugs during pregnancy and breastfeeding should be kept constantly updated, as new data from inadvertent exposure accumulates and new drugs (especially biological agents) are available. Patients may carry autoantibodies that can negatively affect the baby, being neonatal lupus the prototypical case of passively acquired autoimmunity. Research has been greatly active in this field and more information on risk stratification and management are now available for counselling. The effect of both autoantibodies and drug exposure has been evaluated in the offspring: some concerns about learning disabilities have been raised, but these are treatable conditions that are likely to be overcome. To counsel a woman with SLE/APS during childbearing age means also to deal with contraception. Despite the "preferred choice" - combined oral contraceptive - may not be suitable for most of the patients, other options are available and should be offered and discussed with the patient. Fertility is not generally affected in SLE/APS patients, but those cases who require assisted reproduction techniques should be carefully evaluated and managed.
Subject(s)
Antiphospholipid Syndrome/immunology , Lupus Erythematosus, Systemic/immunology , Pregnancy Complications/immunology , Antiphospholipid Syndrome/drug therapy , Child , Child of Impaired Parents , Contraception , Female , Fertility , Humans , Lactation/drug effects , Lactation/immunology , Lupus Erythematosus, Systemic/drug therapy , Pregnancy , Pregnancy Complications/drug therapy , Reproductive Techniques, AssistedABSTRACT
Rheumatic diseases can affect women during their childbearing age. Therefore, physicians should introduce a discussion with the patients about pregnancy and its problems. Lupus pregnancies can be successful, even in patients with renal disease, when planned in remission state; the use of low dose aspirin was shown to be an independent predictor of good outcome, so it can be suggested as a preventive measure. Pregnancies in women with Antiphospholipid Syndrome can fail even if properly treated, especially when associated with a systemic autoimmune disease, a history of both thrombosis and pregnancy morbidity, and a triple positivity of antiphospholipid antibody assays. Women with systemic sclerosis have generally a good obstetric outcome, except for an increase rate of preterm deliveries. Severe disease complications were sometimes reported, but their relationship with gestation is not clear yet. Although data on human pregnancy are still preliminary, anti-TNF agents are classified as non teratogens in contrast to methotrexate and leflunomide. So women affected by aggressive chronic arthritis may be treated with anti-TNF in the pre-conceptional period, discontinuing the drug as soon as pregnancy starts. In order to increase maternal compliance and cope with difficult cases, a multidisciplinary team (rheumatologists/internists, obstetricians and neonatologists) should take care of patients during pregnancy.