We conducted a randomized, controlled study to assess the need for hydroxychloroquine (HCQ) during lupus pregnancy and to assess safety. Twenty consecutive pregnant patients with similar characteristics were enrolled. The HCQ group included eight patients with systemic lupus erythematosus (SLE) and two with discoid lupus erythematosus (DLE). The placebo (PL) group included nine patients with SLE and one with DLE. The HCQ group had no flare-ups. SLEPDAI scores were similar at study entry, and at conclusion the placebo group had significantly higher scores. One patient had improvement of skin lesions and another of arthritis, allowing a decrease of prednisone dose. There were no retinal effects. Three patients in the PL group flared up, two with skin rashes, one also with arthritis and uveitis, and one (previously in remission on HCQ) with hemolytic anemia, polyserositis and anti-dsDNA antibody. Toxemia was diagnosed in only three patients in the PL group (one fetal death). Comparing prednisone dosage change, we noted a decrease in the HCQ and an increase in the PL group. Delivery age and Apgar scores were higher in the HCQ group. Neonatal examination did not reveal congenital abnormalities, nor did a neuro-ophthalmological and auditory evaluation at 1.5-3 y of age. In spite of the small number of patients studied, we noted beneficial effects of HCQ during lupus pregnancy, as measured by SLEPDAI and decrease in prednisone dose with no detriment to patients' health.

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.

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Women with persistently circulating antiphospholipid antibodies (aPL) have a higher incidence of recurrent abortions, fetal losses, pre-eclampsia, and placental insufficiency. Current treatment of patients with antiphospholipid syndrome (APS) during pregnancy with heparin and aspirin can act by preventing clot formation and improving live birth rates, but other obstetric morbidities remain high, especially in patients with a history of thrombotic events. In addition to the classical thrombotic placental events, other factors involving inflammation and complement activation seem to play a role in certain complications. In this article, we will review how medications interfere in the pathogenic mechanisms of APS, discuss the impact of current recommended treatment on pregnancy morbidity, and analyze new promising therapies.

Statistical data indicate that rates of caesarean births are increasing worldwide, 1 being particularly high in some countries, including Brazil; 2 however, consensus ends here. This is a controversial subject, particularly with regard to what would be the ideal caesarean rate and what are the determinants of high caesarean rates in some countries. Although factors that seem to contribute to a rise in caesarean rates all over the world are probably common to different countries, the reasons why countries with similar characteristics have distinct caesarean rates whereas high rates are observed in countries with different social and economic status are questions that reinforce this conundrum. 1Rates of caesarean births in Brazil have increased in the last decades. 2 In the early 1970s the rate of caesarean births in Brazil was close to 15%. The rate increased to 30% in the early 1980s, achieving 40% in the early 1990s. The stability observed in the period 1990-2000 was followed by an additional increase, which took the caesarean rates above 50% in 2012;2,3 however, these rates should be viewed in more detail, taking into account geographic and financial variations.Regarding regional differences, caesarean rates are in the range 35-45% in some states of Brazil, especially those in the north and north-east regions, which are more rural and poorer. On the other hand, states in the south, southeast, and central west regions, which are typically urban and wealthier states, have rates in the range 55-65%.3 As shown in Figure 1, the caesarean rate for Brazil as a whole is markedly affected by the high incidence of caesarean sections performed in the richest states of the country, which are also more densely populated, and where the number of deliveries is greater.The most remarkable discrepancies are observed when caesarean delivery rates in the public and private sectors are compared. According to population-based studies, caesarean rates in the private sector are significantly higher (80-90%) 2,4 than in the public system (35-45%). 2,4 As the vast majority of health care in the private sector is provided through health insurance, the percentage rates of caesarean births in Brazilian states are significantly associated with the local coverage of private health insurance (Figure 2). These data indicate that the high rates of caesarean sections in Brazil are related to the characteristics of the private sector of the health system. In this context, it is important to emphasise that the obstetric care provided by health insurance is centred on the doctor, without the participation of other professionals, and in opposition to the guidelines and models of multidisciplinary attendance recommended by Brazilian and international organisations.5 Most private obstetricians, as well as anaesthetists and paediatricians, go to the hospital after a phone call to tell them that their patients have gone into labour, regardless of the day of the week or time of day. 6This feature obviously does not favour intended vaginal deliveries, w...

Objective To analyze the impact of different classes of lupus nephritis as risk variables for maternal and fetal adverse outcomes in a cohort of pregnant lupus patients. Methods This is a cohort study with retrospective and prospective data collection, conducted at the University Hospital of State University of Rio de Janeiro, Brazil, from 2011 to 2016. A total of 147 pregnancies of 137 systemic lupus erythematosus patients of whom 66 had lupus nephritis were included. Demographic and clinical features, as well as maternal and fetal outcomes were observed for each nephritis histological class among systemic lupus erythematosus patients and compared with those without nephritis. Categorical variables were expressed as absolute and relative frequencies and numerical variables as means and standard deviation. The chi-square test with Fisher's correction and Student's t-test were used for statistical analysis. A pvalue < 0.05 was considered statistically significant. Results Systemic lupus erythematosus patients with proliferative nephritis (classes III/IV, n = 54) presented more frequent disease flares ( p = 0.02), continuous active disease during pregnancy and puerperium ( p = 0.006), hospitalization due to systemic lupus erythematosus ( p < 0.001), hospitalization not directly associated to systemic lupus erythematosus ( p = 0.04), higher frequency of cesarean delivery ( p = 0.03) and preeclampsia ( p = 0.01) than patients without nephritis. Permanent damage measured by Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index was more frequent in classes III/IV than among the other patients. The frequency of adverse fetal outcomes such as prematurity and admission to neonatal intensive care unit were not different among systemic lupus erythematosus patients with or without nephritis. However, perinatal deaths were more frequent in patients with all classes of nephritis ( p = 0.003). Conclusion Systemic lupus erythematosus patients with proliferative nephritis (classes III/IV) have a higher frequency of adverse maternal outcomes. This is probably due to the major impact of proliferative forms of nephritis on women's global heath, which is corroborated by the higher Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index findings, although we cannot exclude the negative influence of disease activity for the maternal adverse events. The findings indicate a need for further lupus nephritis classification beyond the nonspecific term nephritis in the context of lupus pregnancy as the impact on maternal and fetal outcomes varies according to histological class.

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.

Objective To evaluate mean serum levels of vascular endothelial growth factor (VEGF), placental growth factor (PlGF), and soluble Flt‐1 (sFlt‐1) in pregnant patients with systemic lupus erythematosus (SLE) with inactive disease, active lupus nephritis, and preeclampsia for differential diagnosis between these conditions. Methods Pregnant women with SLE, with singleton pregnancies and no other autoimmune diseases, were classified according to disease activity (inactive SLE and active lupus nephritis) and the presence of preeclampsia. Serum samples were collected within 3 weeks of delivery and frozen for subsequent blinded analysis through the enzyme‐linked immunosorbent assay method. Results A total of 71 women were included, with 41 classified as having inactive SLE (group 1; Systemic Lupus Erythematosus Pregnancy Disease Activity Index [SLEPDAI] score <4), 15 with a diagnosis of active lupus nephritis (group 2, SLEPDAI score ≥4, including renal criteria), and 15 with a diagnosis of preeclampsia (group 3). Patients in group 3 had higher mean levels of sFlt‐1 and lower mean levels of PlGF compared to groups 1 and 2, both findings with statistical significance. The sFlt‐1:PlGF ratio was also significantly higher in patients with preeclampsia, while mean VEGF levels were higher in pregnant woman with active lupus nephritis compared to patients with preeclampsia or inactive SLE. Conclusion Evaluation of serum VEGF, PlGF, and sFlt‐1 levels can differentiate between preeclampsia, inactive SLE, and active lupus nephritis during pregnancy.