Evaluation of obstetric outcomes in Brazilian pregnant women with Takayasu arteritis.

OBJECTIVE: Takayasu arteritis (TAK) is a rare chronic granulomatous vasculitis that affects large vessels and usually begins in women of childbearing age, so it is not uncommon for pregnancies to occur in these patients. However, there is limited information about these pregnancies, with reports of adverse maternal and obstetric outcomes. The objective of this study is to evaluate adverse maternal, fetal and neonatal events in pregnant patients with TA. METHODS: This is a cross-sectional study with retrospective data collection. We reviewed 22 pregnancies in 18 patients with TAK, according to the American College of Rheumatology criteria, that were followed up in a high-risk prenatal clinic specialized in systemic autoimmune diseases and thrombophilia (PrAT) at Hospital Universitário Pedro Ernesto, from 1998 to 2021. RESULTS: In twenty-two pregnancies, the mean age of patients was 28.09 years and the mean duration disease was 10.9 years. Of the 18 patients with TAK studied, only one had the diagnosis during pregnancy and had active disease. All other patients had a previous diagnosis of TAK and only 3 had disease activity during pregnancy. Twelve patients (66.6%) had previous systemic arterial hypertension and eleven (61.1%) had renal involvement. Among maternal complications, eight patients (36.3%) developed preeclampsia and six (27.2%) had uncontrolled blood pressure without proteinuria, while 10 (45%) had puerperal complications. Four (18.1%) births were premature, all due to severe preeclampsia and eight newborns (34.7%) were small for gestational age. When all maternal and fetal/neonatal outcomes included in this study were considered, only 6 (27.2%) pregnancies were uneventful. CONCLUSION: Although there were no maternal deaths or pregnancy losses in this study, the number of adverse events was considerably high. Hypertensive disorders and small for gestational age newborns were more common than general population, while the number of patients with active disease was low. These findings suggest that pregnancies in patients with TAK still have several complications and a high-risk prenatal care and delivery are necessary for these patients.

Premature rupture of membranes - A cause of foetal complications among lupus: A cohort study, systematic review and meta-analysis.

OBJECTIVE: The present study aimed to analyse the frequency of premature rupture of membranes (PROMs) among 190 women with systemic lupus erythematosus (SLE) followed up at the Hospital Universitário Pedro Ernesto from 2011 to 2018 and to review the literature on PROM in patients with SLE. METHODS: A cohort study of SLE patients was conducted by analysing the following variables: sociodemographic characteristics, clinical manifestations of lupus, modified disease activity index for pregnancy, drugs used during pregnancy, intercurrent maternal infections and obstetric outcomes. Additionally, seven electronic databases (PubMed, Embase, Cochrane, Scielo, Scielo Brazil, Virtual Health Library Regional Portal and Google Scholar) were systematically searched. The search was updated on 3 February 2020. RESULTS: Infections (relative risk (RR): 3.26, 95% confidence interval (CI): 1.5-6.7, p = .001), history of serositis (RR: 2.59, 95% CI: 1.31-5.11, p = .006) and anti-RNP positivity (RR: 3.08, 95% CI: 1.39-6.78, p = .005) were associated risk factors for PROM, while anti-RNP positivity (RR: 3.37, 95% CI: 1.35-8.40; p = .009) were associated with premature PROM (PPROM). The prevalence of PROM and PPROM was 28.7% and 12.9%, respectively. In the systematic review, the prevalence of PROM and PPROM was 2.7%-35% (I2 = 87.62%) and 2.8%-20% (I2 = 79.56%), respectively. CONCLUSIONS: PROM, both at term and preterm, occurs more frequently in women with lupus than in the general population. A history of serositis, anti-RN, infections and immunosuppression during pregnancy may increase the susceptibility to PROM. The systematic review did not find any study with the main objective of evaluating PROM/PPROM in women with lupus.

The SLICC/ACR Damage Index (SDI) may predict adverse obstetric events in patients with systemic lupus erythematosus.

OBJECTIVE: The objective of this study was to evaluate the potential impact of irreversible damage accrual in women with systemic lupus erythematosus (SLE) and adverse maternal and/or fetal/neonatal outcomes. METHODS: Retrospective cohort study with SLE pregnant patients was carried out from January 2011 to January 2020 at the Hospital University Pedro Ernesto (HUPE) of the State University of Rio de Janeiro, Brazil. Irreversible damage was defined according to SLICC/ACR damage index (SDI). The association of SDI on pregnancy outcomes was established by univariate and multivariate regression models and included demographic and clinical variables. RESULTS: This study included data from 260 patients in their first pregnancies after SLE diagnosis, with a quarter of them (67/260) scoring one or more points on SDI at the beginning of prenatal care. These patients presented more frequently adverse maternal events, namely, disease activity during pregnancy (p = 0.004) and puerperium (p = 0.001), active lupus nephritis (p = 0.04), and hospitalizations (p = 0.004), than those with no SDI score. Similarly, the risks of adverse fetal and neonatal outcomes were also higher among the patients with SDI ≥ 1 (59.7% vs 38.3% p = 0.001) even after controlling data for disease activity (SLEPDAI > 4). Patients with SDI ≥ 1 presented more frequently preterm deliveries (46.3% vs 31.6%; p = 0.01), small for gestational age infants (28.3% vs 18.1%; p = 0.04), and neonatal intensive care unit admission (26.9% vs 1.5%; p < 0.001). The multivariate analyses showed that SDI ≥ 1 is an independent risk factor for hospitalization due to obstetric complications (p = 0.0008) and preterm delivery (p = 0.009). CONCLUSION: Pregnant SLE patients who present irreversible damage accrual may have higher risk of maternal and fetal adverse outcomes, independently of disease activity. These results should be validated in further prospective studies.

Challenging cases in rheumatic pregnancies.

This article describes three complicated cases in rheumatology and pregnancy. The first case elucidates the challenges in treating SLE in conjunction with pulmonary arterial hypertension, while the second case features an SLE-affected pregnancy with development of portal hypertension secondary to portal vein thrombosis related to APS. The third case is a pregnant woman with stable SLE who developed thrombotic microangiopathy caused by atypical haemolytic uraemic syndrome, and failed to improve despite multiple measures including biopsy and elective preterm delivery. There are grave and unique challenges for women with autoimmune disease, but adverse outcomes can sometimes be avoided with careful and multidisciplinary medical management. Pre-conception counselling with regard to medications and disease treatment should also include discussion of the advisability of pregnancy, which may be difficult for a patient, but present the best course for optimizing health outcomes.

Understanding and Managing Pregnancy in Patients with Lupus.

Systemic lupus erythematosus (SLE) is a chronic, multisystemic autoimmune disease that occurs predominantly in women of fertile age. The association of SLE and pregnancy, mainly with active disease and especially with nephritis, has poorer pregnancy outcomes, with increased frequency of preeclampsia, fetal loss, prematurity, growth restriction, and newborns small for gestational age. Therefore, SLE pregnancies are considered high risk condition, should be monitored frequently during pregnancy and delivery should occur in a controlled setting. Pregnancy induces dramatic immune and neuroendocrine changes in the maternal body in order to protect the fetus from immunologic attack and these modifications can be affected by SLE. The risk of flares depends on the level of maternal disease activity in the 6-12 months before conception and is higher in women with repeated flares before conception, in those who discontinue useful medications and in women with active glomerulonephritis at conception. It is a challenge to differentiate lupus nephritis from preeclampsia and, in this context, the angiogenic and antiangiogenic cytokines are promising. Prenatal care of pregnant patients with SLE requires close collaboration between rheumatologist and obstetrician. Planning pregnancy is essential to increase the probability of successful pregnancies.

Antiphospholipid Antibodies and Antiphospholipid Syndrome during Pregnancy: Diagnostic Concepts.

Antiphospholipid syndrome (APS) comprises of a wide spectrum of clinical and obstetric manifestations linked to the presence of antiphospholipid antibodies (aPL). APS was described in the context of lupus, and later as an isolated syndrome or primary APS. The presence of aPL, especially the lupus anticoagulant test, is associated with adverse pregnancy outcomes, such as fetal death, recurrent early miscarriages, pre-eclampsia, and placental insufficiency, but does not seem to influence infertility. High quality scientific data to support these associations, however, are lacking, and controversies arise about the definition of positive aPL (low vs medium-high titers) or even the definition of the adverse events. This review discusses APS classification criteria and the current debate about it.

Management of obstetric antiphospholipid syndrome.

Recurrent early miscarriages (excluding chromosomal anomalies), late fetal loss, and maternal thrombosis are characteristic of obstetric antiphospholipid syndrome (APS). Obstetric complications such as preeclampsia, fetal growth restriction, premature delivery, and fetal death also occur in higher frequency in APS patients than in the general population. A high-risk obstetric center is needed for proper evaluation of and intervention with pregnant women with APS. Association with lupus carries additional risk of thrombosis when antiphospholipid antibodies (aPLs) are present. Gestational results with live births are improved to about 80% when antithrombotic therapy is used, but failure in 20% to 30% of the cases despite correct treatment with low-dose aspirin with or without heparin reveals new pathways for pregnancy loss in APS and unmet needs. At the moment, there is no recommendation to investigate patients with infertility for the presence of aPLs.

Pregnancy may aggravate arterial hypertension in women with Takayasu arteritis.

BACKGROUND: Takayasu arteritis (TA) is a rare chronic granulomatous inflammatory disease of the aorta and/or its major branches and more frequently affects female patients before menopause. Since persistent inflammation may lead to arterial ischemia, hypertension is an important complication of TA. OBJECTIVES: To evaluate gestational results and complications in patients with TA. METHODS: We conducted a retrospective analysis of the medical records of patients with TA admitted to the high risk pregnancy clinic for women with systemic autoimmune diseases at Hospital Universitário Pedro Ernesto. RESULTS: From 1998 to 2011 we followed 11 pregnancies in 9 patients with TA; the patients' age ranged from 17 to 42 years and disease duration from 2 to 28 years. In 7 of the 11 pregnancies, uncontrolled blood pressure occurred before labor and preeclampsia was diagnosed in one. Two deliveries were preterm, one newborn was treated for sepsis, and four (36%) had intrauterine growth restriction (IUGR). CONCLUSIONS: Close monitoring improves the perinatal outcomes in patients with TA who are more prone to develop hypertension, preeclampsia and IUGR. Disease activity was not observed in our group of patients during pregnancy. Coordinated care between the obstetric, rheumatologic and cardiologic teams is the ideal setting to follow pregnant women with TA.