Autoimmunity and pregnancy: autoantibodies and pregnancy in rheumatic diseases.

In women who suffer from rheumatic diseases (RDs) the risk of repeated fetal loss, intrauterine growth restriction, and preterm birth remains higher than in the general population. Antiphospholipid antibodies are frequently observed in patients with systemic lupus erythematosus (SLE). They are associated with recurrent pregnancy losses that may occur at any age of gestation. The cause of fetal death is believed to be intraplacental thrombosis, although other pathologic mechanisms have been described. A recent study has described the increased frequency of learning disabilities in the offspring of SLE patients; case reports of neonatal thrombosis are very rare. Transplacental passage of IgG anti-Ro/SS-A antibodies is linked to neonatal lupus (2%). The main manifestation is congenital heart block (CHB) due to the binding of anti-Ro/SS-A antibodies to cardiac conduction tissue and to the consequent inflammatory/fibroid reaction. Neonatal lupus also includes cutaneous, hematologic, and hepatobiliary manifestations, which are typically transient. Incomplete CHB can be treated with fluorinated corticosteroids to prevent the progression and decrease inflammation. Intravenous immunoglobulin, decreasing the tranplacental passage of anti-Ro/SS-A, has been proposed as prophylactic therapy in patients who had one or more child with CHB. Transplacental passage of antiplatelet antibodies, in about 10% of mothers with SLE, can induce thrombocytopenia in the fetus or the neonate. Patients with RD have a higher incidence of anxiety and depression compared to the general population, interfering with parenthood and the upbringing of children.

Pregnancy and autoimmunity: maternal treatment and maternal disease influence on pregnancy outcome.

If a woman suffers from autoimmune disease (AD), several factors can affect pregnancy or neonatal outcome: repeated spontaneous pregnancy losses (frequently related to antiphospholipid antibodies (aPL)), neonatal lupus with complete congenital heart block (CHB) (linked to transplacental passage of IgG anti Ro/SS-A antibodies) and the disease activity itself that can affect the mother, the pregnancy and fetal outcome. If appropriately managed, the antiphospholipid syndrome (APS) is "one of the few tractable causes of pregnancy losses." A recent case control study, on babies from APS-mothers and healthy mothers, did not show any difference in the occurrence of neonatal complications. There are few data about the long-term outcome of babies born to patients with AD. We recently reported increased occurrence of learning disabilities in children born to aPL positive mothers with systemic lupus erythematosus (SLE). The modern management of pregnancy in patients with AD includes the treatment of disease flares, using drugs effective but safe for fetus. Corticosteroids and some immunosuppressive drugs can be used in pregnancy to control maternal disease. A prolonged fetal exposure to dexamethasone was reported to impair cerebral development, but we recently studied 6 children, born to patients treated with dexamathasone because of CHB, showing a normal intelligence quotient. The last 10-year experience shows that fetal exposure to antimalarial drugs should not be regarded as an important risk factor for gestational nor neonatal complications. However, information about long-term outcome of children exposed to immunosuppressive drugs "in utero" are still lacking and more efforts are needed in this research area.

Follow-up of infants exposed to hydroxychloroquine given to mothers during pregnancy and lactation.

OBJECTIVE: To determine the effect of hydroxychloroquine treatment during pregnancy and lactation on babies of mothers affected by rheumatic diseases. STUDY DESIGN AND METHODS: A total of 40 infants born from mothers affected by rheumatic diseases and treated with hydroxychloroquine during pregnancy were enrolled in a prospective observational study. Main outcome measures at birth were incidence of prematurity, congenital malformations and neonatal infections. Of these babies, including 13 who were breast-fed, 24 were followed up during early infancy for visual function and neurodevelopmental outcome. RESULTS: Preterm delivery was the main complication (20.5%). No significant congenital malformations or neonatal infections were detected. All infants, including those who were breast-fed, had normal visual function and neurodevelopmental outcome. CONCLUSIONS: Hydroxychloroquine treatment during gestation and lactation appeared to be safe. The relatively high incidence of preterm deliveries may reflect the maternal disease state.

Validation of tool mark comparisons obtained using a quantitative, comparative, statistical algorithm.

A statistical analysis and computational algorithm for comparing pairs of tool marks via profilometry data is described. Empirical validation of the method is established through experiments based on tool marks made at selected fixed angles from 50 sequentially manufactured screwdriver tips. Results obtained from three different comparison scenarios are presented and are in agreement with experiential knowledge possessed by practicing examiners. Further comparisons between scores produced by the algorithm and visual assessments of the same tool mark pairs by professional tool mark examiners in a blind study in general show good agreement between the algorithm and human experts. In specific instances where the algorithm had difficulty in assessing a particular comparison pair, results obtained during the collaborative study with professional examiners suggest ways in which algorithm performance may be improved. It is concluded that the addition of contextual information when inputting data into the algorithm should result in better performance.

Noise estimation in magnitude MR datasets.

Estimating the noise parameter in magnitude magnetic resonance (MR) images is important in a wide range of applications. We propose an automatic noise estimation method that does not rely on a substantial proportion of voxels being from the background. Specifically, we model the magnitude of the observed signal as a mixture of Rice distributions with common noise parameter. The expectation-maximization (EM) algorithm is used to estimate all parameters, including the common noise parameter. The algorithm needs initializing values for which we provide some strategies that work well. The number of components in the mixture model also needs to be estimated en route to noise estimation and we provide a novel approach to doing so. Our methodology performs very well on a range of simulation experiments and physical phantom data. Finally, the methodology is demonstrated on four clinical datasets.

Anticardiolipin and anti-beta2 glycoprotein I antibodies in infants born to mothers with antiphospholipid antibody-positive autoimmune disease: a follow-up study.

Infants born from mothers with antiphospholipid antibody (aPL) -positive autoimmune disease were prospectively evaluated for anticardiolipin and anti-beta2 glycoprotein I antibodies (group 1) and for growth and neurological development. The results were compared with those obtained from two age-matched control groups (group 2 and 3). All infants were negative for anticardiolipin at 12 months of life, whereas 14 (63.6%), eight (33.3%), and 10 (55.5%) of infants from group 1, 2, and 3, respectively, were positive for anti-beta2 glycoprotein I. At follow-up, all infants had normal growth and neurological development. No thrombotic complication was observed. The negativity of anticardiolipin in all infants at 12 months suggests that anticardiolipin detection is the best assay to evaluate the disappearance of maternal aPL and to estimate the potential risk of thrombosis associated with these antibodies. The high rate of anti-beta2 glycoprotein I positivity in all three groups of infants may indicate that the synthesis of this antibody is stimulated by aspecific factors.

Autoantibodies and prediction of reproductive failure.

PROBLEM: To determine which autoantibodies are associated with reproductive failure. METHOD OF STUDY: Sera from 269 patients with autoimmune disease and/or reproductive failure were analyzed for anti-phospholipid (aPL), anti-annexin-V, anti-lactoferrin, anti-thyroglobulin, anti-thyroid peroxidase, anti-prothrombin, anti-nuclear, and anti-saccharomycetes cerevisiae antibodies (ASCA), by enzyme-linked immunosorbent assay. Patients were classified as: recurrent pregnancy loss (RPL), infertility, and autoimmune diseases. The results were compared with those of 120 healthy volunteers. RESULTS: In autoimmune diseases, the prevalence of anti-prothrombin, anti-annexin, anti-phospholipid and anti-nuclear antibodies was significantly higher than in the control group, OR 11.0 [CI, 3.5-35.2], 33 [CI, 7.2-174.2], 13 [CI, 1.4-309.7], and 16.1 [CI 2.4-122], respectively. In infertility, the antibodies with significantly higher levels than controls were: aPL OR, 5.11 [CI 1.2-25.4], and anti-prothrombin antibodies, OR, 5.15 [CI, 2.1-12.7]. In RPL, ASCA, anti-prothrombin and aPL were more prevalent than in controls, OR 3.9 [CI, 1.5-10.6], 5.4 [CI, 2.4-12.5] and 4.8[CI, 1.2-22.2] for each antibody, respectively. Anti-prothrombin antibodies and aPL were more significantly associated with late pregnancy losses than early losses. CONCLUSION: ASCA antibodies have not previously been described in RPL. Nor are anti-prothrombin antibodies usually assessed in infertility or RPL. If these results are confirmed in further studies, these antibodies might be assessed routinely in reproductive failure.

Anti-inflammatory and immunosuppressive drugs and reproduction.

Rheumatic diseases in women of childbearing years may necessitate drug treatment during a pregnancy, to control maternal disease activity and to ensure a successful pregnancy outcome. This survey is based on a consensus workshop of international experts discussing effects of anti-inflammatory, immunosuppressive and biological drugs during pregnancy and lactation. In addition, effects of these drugs on male and female fertility and possible long-term effects on infants exposed to drugs antenatally are discussed where data were available. Recommendations for drug treatment during pregnancy and lactation are given.