José Font

Obstetrical outcome of pregnancy in patients with systemic Lupus Erythematosus. A study of 60 cases

OBJECTIVE To analyze the course of maternal diseases and the outcome of pregnancy in patients with systemic Lupus Erythematosus (SLE). STUDY DESIGN During a period of 11 years we prospectively followed 60 pregnancies in 46 SLE patients in a tertiary care center in Barcelona (Spain). The management protocol included: (1) planning of conception when disease was inactive; (2) frequent follow-up visits by an internist-obstetrician team; (3) use of sequential ultrasonographic, Doppler and fetal echocardiographic examinations; (4) serial evaluations of maternal immunological condition; and (5) low dose aspirin from 1 month before attempting conception and throughout pregnancy was added in women with antiphospholipid antibodies. From 1985 until 1994 prednisone prophylaxis was used in all lupus patients during the last month of pregnancy and during the first month of the puerperium; from 1995 onwards this regime was abandoned. RESULTS The mean (S.D.) age of patients was 28.6 (4.8) years (range 20 to 42) and the mean (S.D.) previous duration of SLE was 6.25 (4.8) years (range 0 to 17). SLE was diagnosed during the pregnancy in two cases (3.3%) and the disease was active at conception in four cases (6.7%); at that time nine patients (15%) were taking prednisone. Antiphospholipid antibodies were positive in 16 patients (30.4%) and there were 10 (16.7%) pregnancies in patients having lupus nephropathy. There were three first-trimester miscarriages (5%) and four (6.7%) voluntary abortions. Obstetric complications in the remaining 53 pregnancies included: preterm delivery, 11 cases (20.8%); intrauterine growth retardation, five cases (9.4%); hypertension, 10 patients (18.9%), five of them fulfilling the criteria of preeclampsia; premature rupture of membranes, four patients (7.5%); finally, 13 neonates had a birthweight lower than 2500 g. There were 15 lupus flares (28.3%), giving a flare rate of 0.044 per patient/month. There were five neonatal deaths (perinatal mortality rate, 94 per thousand): one because of complete heart block, three due to severe hyaline membrane disease resulting from extreme prematurity and one intrauterine death in a patient having the Leiden mutation. CONCLUSION Pregnancy in patients with SLE should not be regarded as an unacceptable high-risk condition for the mother or her baby provided that conception is accurately planned and patients are managed according to a careful multidisciplinary treatment schedule.

Risk Factors Associated with Fetal Losses in Treated Antiphospholipid Syndrome Pregnancies: A Multivariate Analysis

PROBLEM: Pregnancies in women with antiphospholipid syndrome (APS) are associated with obstetric complications despite treatment. The present study analyzes risk factors and evaluates fetal outcome in a large sample of treated APS pregnancies.
 METHOD OF STUDY: Seventy‐seven pregnancies in 56 women were included. Twelve selected variables potentially related to the outcome of treated pregnancies were analyzed in a multivariate logistic regression model.
 RESULTS: Treated women delivered 65 live infants at 24–41 weeks gestation (mean 36.7±0.5) but two neonatal deaths occurred. There were seven first‐trimester miscarriages (9%) and five intrauterine fetal demises (6.5%). Thus, the probability of having a live baby under treatment was 82% (95% CI 71.3–89.6%), a figure significantly greater (P<0.001) than that observed before therapy (25.7%; 95% CI 18.7–33.7%). Variables related with fetal outcome in the multivariate model were: preconceptional use of aspirin and abnormal umbilical artery Doppler velocimetry at 23–26 weeks gestation.
 CONCLUSIONS: The present report shows that in treated APS pregnancies: i) aspirin treatment started preconceptionally is an independent and significant prognostic factor associated with favorable fetal outcome; and ii) abnormal velocity waveforms in the umbilical artery predict adverse outcome of pregnancy.

Intravenous immunoglobulin preceding in vitro fertilization-embryo transfer for patients with repeated failure of embryo transfer

OBJECTIVE To determine the effectiveness of immunotherapy with high-dose IV immunoglobulin preceding IVF-ET for patients with repeated failure of ET. DESIGN Prospective, observational. SETTING Assisted Reproduction Unit of the Hospital Clínic i Provincial in Barcelona, a tertiary care setting. PATIENTS Twelve consecutive tubal infertility patients experiencing repeated unexplained IVF-ET failure including at least three ETs replacing three to four fresh embryos each. Two women shared three or more human leukocyte antigens (HLA) with the husband. INTERVENTION During the subsequent new IVF-ET cycle, each patient received 400 mg/kg IV immunoglobulin daily for 5 days during ovarian stimulation, that is, 5 to 7 days before ET. MAIN OUTCOME MEASURES Clinical pregnancies. RESULTS No implantation occurred. There were no side effects. CONCLUSIONS High-dose IV immunoglobulin is not a useful tool for IVF-ET failure.

Relationship of p53 with other Oncogenes, Cytokines and Systemic Lupus Erythematosus Activity

Introduction: Defects in the regulation of apoptosis of autoreactive lymphocytes are involved in the pathogenesis of systemic lupus erythematosus (SLE). The apoptotic process relies on adequate functioning of numerous molecules, including oncogenes and diverse cytokines. p53 has been implicated in the control of the cell cycle through the stimulation of apoptosis of these autoreactive cells. Objective: To study the role of the p53 pathway on the regulation of apoptosis in SLE patients and analyze the relationship of the p53 oncoprotein with disease activity and other oncogenes (bcl-2, Fas) and cytokines (interleukin-10, IL-10, and tumor necrosis factor-α, TNF-α), implicated in the apoptotic process and the pathogenesis of SLE. Patients and Methods: p53 and bcl-2 antigen expression were determined in lyzed lymphocytes from 74 patients with SLE and 30 healthy controls. Serum levels of soluble-Fas (sFas) and cytokines IL-10 and TNF-α were studied by enzyme-linked immunonosorbent assay. Results: SLE patients had higher levels of p53 protein (0.16 ± 0.33 ng/dl) than controls (0.014 ± 0.02 ng/dl; p = 0.006). Patients with active SLE had higher levels of p53 (0.31 ± 0.48 ng/dl) than those with inactive disease (0.08 ± 0.17 ng/dl; p = 0.003) who in turn had higher levels than controls (0.01 ± 0.02 ng/dl; p = 0.035). A significant correlation was found between p53 levels and the SLE disease activity index (R = +0.24/ p = 0.04), anti-DNA antibodies (R = +0.23/p = 0.048) and IL-10 levels (R = +0.4/p = 0.004). No correlation was found between p53 levels and bcl-2, sFas or TNF-α levels. Conclusions: The p53 oncoprotein may play a role in the pathogenesis and activity of SLE. IL-10 may influence SLE activity by inhibiting the p53 and bcl-2/Fas apoptosis pathway of autoreactive cells.

Antiphospholipid Antibody Testing in Patients with Pregnancy Loss

Correspondence: J. Balasch, M.D., Department of Obstetrics and Gynaecology, Hospital Clinic i Provincial, C/Casanova 143, 08036-Barcelona, Spain There is no doubt that the discovery of clinical associations with antiphospholipid antibodies (aPL); mainly lupus anticoagulant (LA) and anticardiolipin antibodies (aCL) has opened a new, exciting and controversial area of investigation linking different specialties’-3 . First recognized in patients with systemic lupus erythematosus (SLE) and later in other rheumatologic and non-rheumatologic conditions, it is now well known that the association of these antibodies

Lupus anticoagulant as a marker of autoimmunity in recurrent pregnancy loss; a case report

We present a patient with primary antiphospholipid syndrome, as defined by nine pregnancy losses, the presence of lupus anticoagulant (LAC), and the absence of clinical signs and symptoms of autoimmunity. A successful pregnancy was achieved by treatment with low-dose prednisone (15 mg daily) and aspirin (100 mg daily). The patient was followed-up throughout her two last pregnancies and a 6 months postpartum period. Our data indicate that LAC serves as a marker of disease in women with previous pregnancy wastages, and that aspirin-prednisone therapy is beneficial in carefully selected patients.

Diagnostic interest of the monoclonal antibody CA1 in malignant pleural effusion.

The Ca1 antibody was used in an immunohistochemical procedure on smears of cells from 40 patients with malignant pleural effusion. The control group consisted of 25 benign pleural effusions with a high percentage of reactive mesothelial cells. The Ca1 Me Ab was positive in 19 (79%) of the 24 pleural effusions with positive malignant cytology. In all the benign cases the Ca1 Mc Ab was negative (100% specificity). The Ca1 Mc Ab detected malignant mesothelial cells in two cases and was negative with reactive mesothelial cells and other nucleated cells present in the pleural effusion. We conclude that the Ca1 antibody offers a useful diagnostic method for malignant pleural effusions, when the morphological interpretation is doubtful.