Immunoadsorption plasmapheresis as a treatment for pregnancy complicated by systemic lupus erythematosus with positive antiphospholipid antibodies.

PROBLEM: Our purpose was to study the effect of maternal immunoadsorption plasmapheresis (IA) on the outcome of pregnancies complicated by systemic lupus erythematosus (SLE) with positive antiphospholipid antibodies, which were known to have a strong correlation with abortion or stillbirth. METHOD OF STUDY: Eight pregnancies in 7 patients with SLE were treated according to our protocol. They were all positive for the lupus anticoagulant. The treatments provided in these cases were as follows: an oral low-dose steroid; oral low-dose aspirin; and IA. The outcomes of the pregnancies were then studied. RESULTS: Of eight pregnancies, seven resulted in preterm deliveries, and cesarean sections were performed at 26-36 weeks of gestation. In one case, intrauterine fetal death occurred at 24 weeks of gestation. The other seven pregnancies resulted in live births (survival rate of 87.5%). CONCLUSION: IA improves the outcome of pregnancy complicated by SLE with positive antiphospholipid antibodies, without increasing steroid dosage.     

Pregnancy: Low-dose aspirin for prevention of pregnancy losses in women with primary antiphospholipid syndrome

Pregnancy loss, often recurrent, is one of the most importantclinical manifestations associated with the primary antiphospholipidsyndrome. In these cases, pregnancy wastage is related to thepresence of antiphospholipid antibodies, namely lupus anticoagulantand anticardiolipin antibodies, but patients do not have featuresof systemic lupus erythematosus or any other well-defined autoimmunedisease. We report here on the outcome of 21 consecutive pregnanciesin 18 patients with the syndrome who were treated with low-doseaspirin (100 mg/day) from 1 month before attempting conceptionand throughout the pregnancy. Low-dose prednisone (15–30mg/day) was added for potentially non-obstetric (autoimmune-related)reasons in six pregnancies. Patients were monitored as havinghigh-risk pregnancies. Prior to therapy, the rate of live-bornbabies was 6.1% (46 previous fetal losses and three live-bornbabies), and after therapy, it was 90.5% (21 pregnancies and19 live-born babies). Pre-term delivery due to maternal or fetalindications was required in 15% (3/20) of the viable pregnancies.Except for prematurity (20% of viable pregnancies) and its potentialassociated complications, there were no significant adverseeffects to either mothers or babies. Our treatment modalityis advocated for prevention of pregnancy losses in patientswith the ‘obstetric’ primary antiphospholipid syndrome.     

Pregnancy and Systemic Lupus Erythematosus: Review of Clinical Features and Outcome of 51 Pregnancies at a Single Institution

Systemic lupus erythematosus (SLE) is mainly a disease of fertile women and the coexistence of pregnancy is by no means a rare event. How SLE and its treatment affects pregnancy outcome is still a matter of debate. Assessment of the reciprocal clinical impact of SLE and pregnancy was investigated in a cohort study. We reviewed the clinical features, treatment, and outcomes of 43 pregnant SLE patients with 51 pregnancies followed from 1993 to 2007 at a tertiary university hospital. The age of patients was 28.7?±?5.4 years and SLE was diagnosed at age of 23.0?±?6.1 years. Previous manifestations of SLE included lupus nephritis (14 patients) and secondary antiphospholipid syndrome (11 patients). Thirty-five pregnant patients (69%) were in remission for more than 6 months at the onset of pregnancy. Patients were being treated with low doses of prednisone (29), hydroxychloroquine (20), azathioprine (five), acetylsalicylic acid (51), and low molecular weight heparin (13). Sixteen pregnancy-associated flares were documented, mainly during the second trimester (42%) and also in the following year after delivery (25%). Renal involvement was found in 11 cases (68%). Spontaneous abortion occurred in 6%, 16% had premature deliveries, and 74% were delivered at term. No cases of maternal mortality occurred. No cases of fetal malformation were recorded. There was one intrauterine fetal death and one neonatal death at 24 gestational weeks. Pregnant women with SLE are high risk patients, but we had a 90% success rate in our cohort. A control disease activity strategy to target clinical remission is essential.     

Pregnancy outcomes in patients with systemic autoimmunity

The impact of maternal systemic autoimmune diseases on pregnancy outcome is not unequivocally defined. We analysed the pregnancy outcome of 221 pregnancies from 181 autoimmune patients, consecutively followed in a single Italian reference centre from 2001 to 2009. All patients were prospectively followed with monthly visits. Pregnancy outcome was compared with the previous obstetrical history. The patient population comprised five groups: primary antiphospholipid syndrome (PAPS, 39 pregnancies), antiphospholipid syndrome associated with a rheumatic disease (APS/RD, 17 pregnancies), other RD (92 pregnancies), isolated autoantibodies (autoAbs) in the absence of a definite autoimmune disease (aAbs, 38 pregnancies) and reactive arthritis or spondyloarthropathies (35 pregnancies). Of these patients, 50.6% had previous pregnancy complications with an anamnestic live-birth rate of 43.4%. In these patients, complications dropped to 28.2% (44/156). This percentage was very similar to that observed in the 221 pregnancies (29.9%, 66/221) with a live-birth rate of 87.3%. Mean neonatal weight was 3018 ± 611 g; mean gestational age at delivery was 38.17 ± 2.79 weeks. Thus, 10.4% of pregnancies resulted in preterm delivery and 10.9% newborns had low weight at delivery. APS/RD patients had the worse outcome: 17.6% resulted in miscarriage, 14.3% resulted in growth restriction and 50% resulted in preterm delivery. This result was mainly due to patients with APS/systemic lupus erythematosus (SLE) that had the lowest gestational age at delivery (30.8 ± 3.56 weeks) and the lowest newborn weight (1499 ± 931 g). Results confirm that a strict follow-up and targeted treatments significantly improve pregnancy outcomes in autoimmune patients with PAPS, SLE and isolated autoAbs. The pregnancy outcome in patients with APS/SLE remains unsatisfactory.     

Pregnancy outcomes in patients with systemic autoimmunity

The impact of maternal systemic autoimmune diseases on pregnancy outcome is not unequivocally defined. We analysed the pregnancy outcome of 221 pregnancies from 181 autoimmune patients, consecutively followed in a single Italian reference centre from 2001 to 2009. All patients were prospectively followed with monthly visits. Pregnancy outcome was compared with the previous obstetrical history. The patient population comprised five groups: primary antiphospholipid syndrome (PAPS, 39 pregnancies), antiphospholipid syndrome associated with a rheumatic disease (APS/RD, 17 pregnancies), other RD (92 pregnancies), isolated autoantibodies (autoAbs) in the absence of a definite autoimmune disease (aAbs, 38 pregnancies) and reactive arthritis or spondyloarthropathies (35 pregnancies). Of these patients, 50.6% had previous pregnancy complications with an anamnestic live-birth rate of 43.4%. In these patients, complications dropped to 28.2% (44/156). This percentage was very similar to that observed in the 221 pregnancies (29.9%, 66/221) with a live-birth rate of 87.3%. Mean neonatal weight was 3018 ± 611 g; mean gestational age at delivery was 38.17 ± 2.79 weeks. Thus, 10.4% of pregnancies resulted in preterm delivery and 10.9% newborns had low weight at delivery. APS/RD patients had the worse outcome: 17.6% resulted in miscarriage, 14.3% resulted in growth restriction and 50% resulted in preterm delivery. This result was mainly due to patients with APS/systemic lupus erythematosus (SLE) that had the lowest gestational age at delivery (30.8 ± 3.56 weeks) and the lowest newborn weight (1499 ± 931 g). Results confirm that a strict follow-up and targeted treatments significantly improve pregnancy outcomes in autoimmune patients with PAPS, SLE and isolated autoAbs. The pregnancy outcome in patients with APS/SLE remains unsatisfactory.     

Treatment of patients with antiphospholipid antibodies during pregnancy.

Most authors agree upon the causal association between antiphospholipid antibodies [lupus anticoagulant (LAC) and/or anticardiolipin antibodies] and adverse pregnancy outcome. Placental insufficiency, caused by thrombosis, infarction and maldevelopment, is thought to be the main cause of fetal loss in patients with LAC. Therapy given thus far to prevent fetal loss can be divided into (1) immunosuppression by corticosteroids, azathioprine, or intravenous gamma globulin (IVGG), (2) anti-aggregants to overcome imbalance of thromboxane/prostacycline production in patients with LAC, and (3) anticoagulants to neutralize the possible impairment of clotting inhibitor systems. Different therapeutic success rates have been reported by various authors who used the same combination of therapy. We report the results of different therapy regimens in 154 pregnancies in 31 women with LAC. These patients suffered from SLE with LAC or from APLA syndrome and experienced either recurrent miscarriages or thromboembolic phenomena in the past. With no therapy there were seven (6.8%) live births and 95 (93.2%) failures. Various combinations of corticosteroids, anti-aggregants and anticoagulants were used for treatment. Of 52 treated pregnancies, 27 (51.9%) were successful. Sixteen (69.1%) of 23 pregnancies treated by all three modalities ended in live births. Four of these successful pregnancies occurred after failure of treatment by prednisone and anti-aggregants only. In order to minimize osteoporosis caused by the combination of steroids and heparin, we have used warfarin in the second trimester and have lately substituted low molecular weight heparin for heparin. In the absence of a therapeutic schedule predicated on a large prospective study, therapy during pregnancy in patients having LAC should be individualized according to their obstetric and medical history.(ABSTRACT TRUNCATED AT 250 WORDS)     

Classical complement activation as a footprint for murine and human antiphospholipid antibody-induced fetal loss

Recurrent miscarriage, fetal growth restriction and intrauterine fetal death are frequently occurring complications of pregnancy in patients with systemic lupus erythaematosus (SLE) and antiphospholipid syndrome (APS). Murine models show that complement activation plays a pivotal role in antiphospholipid antibody-mediated pregnancy morbidity, but the exact pathways of complement activation and their potential role in human pregnancy are insufficiently understood. We hypothesized that the classical pathway would play a major role in inducing fetal loss. Pregnant C57BL/6 mice and mice deficient in C1q and factor D were injected with antiphospholipid antibodies or normal human IgG. Mouse placentas were subsequently stained with an anti-C4 antibody and anti-normal human IgG to determine the presence of classical complement activation and IgG binding. Findings in mice were validated in 88 human placentae from 83 women (SLE and APS cases versus controls), which were immunohistochemically stained for C4d, C1q, properdin and MBL. Staining patterns were compared to pregnancy outcome. In murine placentae of mice pretreated with antiphospholipid antibodies, increased C4 deposition was observed, which was associated with adverse fetal outcome but not with IgG binding. In humans, diffuse C4d staining at the feto-maternal interface was present almost exclusively in patients with SLE and/or APS (p < 0.001) and was related to intrauterine fetal death (p = 0.03). Our data show that presence of C4d in murine and human placentae is strongly related to adverse fetal outcome in the setting of SLE and APS. The excessive deposition of C4d supports the concept of severe autoantibody-mediated injury at the fetal-maternal interface. We suggest C4d as a potential biomarker of autoantibody-mediated fetal loss in SLE and APS.     

Monoclonal anticardiolipin antibodies derived from mice with experimental lupus erythematosus: Characterization and the induction of a secondary antiphospholipid syndrome

The primary antiphospholipid syndrome and the antiphospholipid syndrome in systemic lupus erythematosus (SLE) patients (defined as secondary antiphospholipid syndrome) are characterized by the presence of anticardiolipin antibodies, thrombosis, thrombocytopenia, and recurrent fetal loss. To determine the role of anticardiolipin antibodies in the pathogenesis of antiphospholipid syndrome, monoclonal anticardiolipin antibodies were derived from mice in which experimental lupus was induced by a murine monoclonal anti-16/6 Id antibody. Two murine monoclonal anticardiolipin antibodies (2C4C2, 2C4D1) were generated and characterized. The 2C4C2, but not the 2C4D1, monoclonal antibody demonstrated remarkable lupus anticoagulant activity. Furthermore, these murine anticardiolipin monoclonal antibodies appear to recognize antigenic epitopes similar to those recognized by anticardiolipin antibodies found in sera of SLE patients. The monoclonal anticardiolipin antibody 2C4C2 was injected into naive female mice. Following immunization, the mice developed high titers of autoantibodies reacting with cardiolipin, DNA, nuclear extract, 16/6 and anti-16/6 Id, and anticardiolipin antibodies. As early as 8 weeks after immunization these mice exhibited significant leukopenia, thrombocytopenia, and proteinuria with immune complex glomerulonephritis. Moreover, mating of 2C4C2-injected mice with allogenic males resulted in low pregnancy rates and a low number of fetuses with a high percentage of fetal loss. These studies provide a new experimental model for secondary antiphospholipid syndrome demonstrating the role of anticardiolipin antibodies in the pathogenesis of this syndrome.     

Current status and future prospects for the treatment of antiphospholipid syndrome

Antiphospholipid syndrome (APS) is a prothrombotic disease characterized by thrombosis and pregnancy morbidity in the presence of antiphospholipid antibodies (apL). Management of thrombosis is based on long-term oral anticoagulation and patients with arterial events should be treated aggressively. Primary thrombo-prophylaxis is recommended in patients with systemic lupus erythromatosus (SLE) and obstetric APS. Obstetric APS care is based on high-risk management and treatment with aspirin and heparin. Possible future therapies include statins, hydroxychloroquine, rituximab, and new anticoagulant drugs. Current research is focused on targeting components of the complement system, interfering with aPL–mediated cell activation and using tailored peptides to block the pathogenic subpopulation of aPL.     

Intravenous immunoglobulin for the secondary prevention of stillbirth in obstetric antiphospholipid syndrome: A case series and systematic review of literature

ObjectiveTo evaluate the efficacy and safety of intravenous immunoglobulin (IVIg) in secondary prevention of pregnancy complications for patients with obstetric antiphospholipid syndrome (APS) and history of stillbirth.MethodsWe described three cases of obstetric APS patients with history of stillbirth treated with IVIg in four pregnancies. In addition, we conducted a systematic literature review on the use of IVIg in obstetric APS with history of stillbirth.ResultsThree patients with obstetric APS and history of stillbirth were treated with prophylactic IVIg, in addition to standard treatment (hydroxychloroquine, low-dose aspirin, low molecular weight heparin, and prednisone), in four pregnancies (three singleton and one twin). All pregnancies resulted in live healthy newborns. Long-term follow-up re-evaluations (24–53 months) did not shown any sign or symptom of active systemic disease, and the children were healthy.The systematic literature review retrieved only three cases of use of IVIg in obstetric APS patients with history of stillbirth. All three cases resulted in live healthy newborns. Only in one case, mild thrombocytopenia occurred during treatment, although this event was unlikely to be related to IVIg.ConclusionOur experience suggests that IVIg as secondary prevention of APS-related stillbirth is associated with good pregnancy and long-term outcomes, with no relevant safety concerns. However, the literature evidence on this topic is limited to few isolated cases, and further studies are needed to clarify which obstetric APS patients may benefit the most from IVIg.     

Antiphospholipid antibodies in unselected patients with repeated abortion

We have studied, prospectively, the incidence of several antiphospholipid antibodies (lupus anticoagulant, anticardiolipin, anti-phosphatidylserine, anti-phosphatidic acid, anti-phosphatidylinositol and anti-thromboplastin antibodies) in 65 consecutive patients with two or more (range 2-8, mean 3.1) abortions. Lupus anticoagulant activity was detected in seven (10.7%) patients and all of them exhibited other antiphospholipid antibodies. Of the previous pregnancies in these seven women, 88% had ended in spontaneous abortion. Four of them achieved pregnancy after low-dose aspirin therapy was started, and carried successfully to term. It is concluded that antiphospholipid antibodies, namely lupus anticoagulant, should be routinely screened in the recurrent spontaneous aborter.     

Antiphospholipid antibodies in obstetrics: new complexities and sites of action.

The antiphospholipid syndrome, the cause of which remains unknown, is characterized by severe pregnancy complications. Fetal losses have been attributed to thrombosis of the uteroplacental vasculature and placental infarction. Polyclonal and monoclonal antiphospholipid antibodies seem able to recognize a 'plasma cofactor' on the endothelial and trophoblast cell surfaces and to affect cell function, inducing a procoagulant state. Although thrombosis is observed frequently in the decidua and placentas of patients with antiphospholipid antibodies, this observation was not universal, nor present in a sufficient degree to account for the pregnancy loss associated with this syndrome. Recent observations have suggested that antiphospholipid antibodies decreased placental hormone production and trophoblast intercellular fusion and invasion, suggesting that many of the obstetric complications observed in the syndrome may be due to antiphospholipid antibody-induced trophoblast dysfunction. However, the complex antigens on the trophoblast surfaces are still to be characterized and correlated with clinical manifestation. It is clear that successful pregnancies with the syndrome are more likely to occur after maternal treatment. Although prednisone may still be needed to treat manifestations associated with autoimmune disorders, the use of heparin, together with low-dose aspirin, has replaced prednisone for treatment of pregnant women. Maternal treatment and careful monitoring of fetal well-being are mandatory in the management of these high-risk pregnancies.     

Previous pregnancy outcome is an important determinant of subsequent pregnancy outcome in women with systemic lupus erythematosus.

Women with systemic lupus erythematosus (SLE) have increased adverse pregnancy outcomes. The reasons for these problems include maternal disease, clinical or serologic activity, medication use, and residual organ impairment from prior disease flares. In retrospective studies, pregnancy data are often treated cross-sectionally, with births rather than mothers as the unit of analysis. Multiple pregnancies from the same mother may be highly correlated with each other. In an unmatched retrospective study, the first two pregnancy outcomes in lupus patients with anticardiolipin antibody (anti-CL IgG or IgM isotype) (cases N = 47) and without anticardiolipin antibody (controls, N = 125) were assessed according to birth order. A good outcome was defined as a full-term (> 38 weeks) live birth without neonatal complications. All other pregnancy outcomes were considered adverse outcomes. Therapeutic abortions and ectopic or molar pregnancies were excluded. Both cases and controls with an adverse outcome in their first pregnancy had at least a 50% chance of another adverse outcome in their second pregnancy. Cases with a late miscarriage (fetal loss at 14 to 20 weeks' gestation) in their first pregnancy had the highest risk, 80%, of an adverse outcome in their second pregnancy. Both previous pregnancy loss and anti-CL antibody status should be considered in the analysis of pregnancy outcomes in women with SLE.     

The effects of IgG purified from women with SLE and associated pregnancy loss on rat embryos in culture

PROBLEM: Recurrent fetal loss occurs in approximately 1% of women. Autoimmune causes have been suggested as a factor in some of these cases. High rates of intrauterine fetal growth retardation and increased incidence of prematurity is associated with systemic lupus erythematosus (SLE) and the anti-phospholipid syndrome (APS). Autoantibodies from sera of SLE/APS patients affect reproductive outcome in pregnant mice, as was studied in vivo, where injection of immunoglobulin (Ig)G purified from patients with APS to mice caused fetal resorptions and growth retardation. METHODS: In order to investigate the direct effect of IgG purified from women with SLE or APS on the growth and viability of embryos, we cultured 11.5-day old-rat embryos in their yolk sacs in the presence of IgG purified from SLE and APS patients. RESULTS: IgG purified from SLE and recurrent pregnancy loss (RPL) patients affected directly the embryo and yolk sac reducing their growth. The purified IgG positive for anti-cardiolipin/anti-DNA antibodies reduced yolk sac and embryonic growth more than sera negative for these antibodies. CONCLUSION: Various antiphospholipid antibodies affect differently the growth and development of the embryo and the placenta.     

Obstetric complications associated with the lupus anticoagulant

We identified eight patients with the lupus anticoagulant (an autoantibody acquired by some patients with systemic lupus erythematosus), by observation of an increased activated partial thromboplastin time and abnormal results on a tissue thromboplastin-inhibition test. The patients had experienced a total of 30 spontaneous abortions and fetal deaths in 31 previous pregnancies (96.8 per cent). During their next pregnancy, the patients were treated with 40 to 50 mg of prednisone per day and 81 mg of aspirin per day. The therapy shortened their activated partial thromboplastin times, produced normal values for tissue thromboplastin inhibition, and reduced the rate of pregnancy loss to 37.5 per cent. However, preeclampsia developed in the five patients who gave birth to live infants, and fetal growth retardation occurred in three cases. The corticosteroid and low-dose aspirin regimen appears to improve perinatal outcome in cases in which the mother has the lupus anticoagulant, but such practices as careful fetal surveillance and preterm delivery when appropriate are also important to successful obstetric management of such cases.     

Pregnancy outcome in recurrent spontaneous abortion associated with antiphospholipid antibodies: a comparative study of intravenous immunoglobulin versus prednisone plus low-dose aspirin

PROBLEM: To compare the use of intravenous immunoglobulins (IVIG) with prednisone plus low-dose aspirin (LDA) in treating pregnant women with a history of recurrent fetal loss having the antiphospholipid antibody (aPL), in terms of live-birth rate and maternal and perinatal morbidity. METHOD: A prospective, two-centers trial study included 82 recurrent aborters with aPL syndrome. Twenty-nine were treated with prednisone and LDA in one center, 53 received IVIG in the other center. Maternal and fetal outcomes and pregnancy complications were compared between groups. RESULTS: Live-birth rates were equivalent between groups (78 vs 76%). Mean birth weight was higher in the IVIG group than in the prednisone plus LDA group. In the prednisone- plus LDA-treated patients, gestational hypertension and gestational diabetes were found significantly more often than in the IVIG-treated group (14 vs 5% and 14 vs 5%, respectively). CONCLUSION: In patients with aPL syndrome, IVIG treatment improved pregnancy outcome, with significantly lower pregnancy complication rates, when compared with prednisone plus LDA therapy.     

Umbilical and uterine artery flow velocity waveforms in pregnant women with systemic lupus erythematosus treated with aspirin and glucocorticosteroids.

Pregnancy in systemic lupus erythematosus (SLE) is at high risk to the mother and fetus. Impaired utero-placental perfusion may increase fetal loss and intrauterine growth retardation. We assessed the changes in impedance to blood flow in the umbilical and uterine arteries in five patients with SLE treated with low dose aspirin and corticosteroids, using Doppler ultrasound longitudinally throughout pregnancy. Blood flow velocity waveforms of the umbilical and uterine arteries were studied by transabdominal and transvaginal Doppler ultrasound, respectively. Resistance index (RI) was measured every two to four weeks from week 10 to term, and the values obtained were compared to those of normal pregnancies. All five patients delivered uneventfully. One neonate was delivered at 36 weeks (2550 g) and one neonate was growth retarded (1900 g at 38 weeks). Three women delivered at 39 weeks (3585 g, 2850 g, and 2800 g). Most umbilical artery RI values obtained throughout pregnancy were above the 95th percentile of normal pregnancies. The highest values of RI of the umbilical artery were assessed in the case of fetal growth retardation. However, most measurements of RI of the uterine artery were under the 95th percentile of normal. The improved pregnancy outcome in patients with SLE treated with aspirin and corticosteroids seems to correlate with their normal uterine artery flow velocity wave forms.     

Antiphospholipid antibodies in 146 women with repeated pregnancy losses

Antiphospholipid antibodies are associated with arterial and venous thrombosis and recurrent abortions. However, the prevalence of these antibodies in repeated miscarriages varies in different reports. To obtain quantitative data with restricted criteria and discuss the origin of the variability on the literature, we investigated the presence of antiphospholipid antibodies in 146 women who had 2 or more consecutive pregnancy losses and in 99 women whose pregnancies were successful. Antiphospholipid antibodies (lupus anti-coagulant or anticardiolipin antibodies of 20 or more IgG units) were found in 45% of women with pregnancy losses and in 9% of controls (p < 0.001). The type of loss was determined according to the trimester of pregnancy and the time of the fetal loss. 68% of patients with antiphospholipid antibodies had at least one fetal loss on the second or third trimester compared with 45% of patients without fetal loss (p < 0.01). Further studies should be conducted using more rigorous definition of clinical and laboratory characteristics in a way to allow better comparison between studies.     

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.     

Pregnancy Outcomes in Japanese Patients with SLE: Retrospective Review of 55 Pregnancies at a University Hospital

Systemic lupus erythematosus (SLE) is mainly a disease of fertile women and the coexistence of pregnancy is by no means a rare event. How SLE and its treatment affect pregnancy outcomes is still a matter of debate. We performed a retrospective analysis of 41 SLE patients (55 pregnancies) who were followed at our university hospital from January 2000 to December 2009. The mean age of patients was 30.6?±?4.8 years and mean disease duration was 6.6?±?5.3 years. After exclusion of artificial abortions, live birth rate was 84%. Significantly, more women with stillbirth pregnancies were complicated with antiphospholipid syndrome (APS) than women with live birth pregnancies (two of eight stillbirth pregnancies (25%) versus one of 42 live birth pregnancies (2%); p?=?0.014) and hypocomplementemia at conception (four of eight stillbirth pregnancies (50%) versus six of 42 live birth pregnancies (14%); p?=?0.021). Compared with nonrenal pregnancies, renal pregnancies were younger at SLE disease onset, had a lower positivity of anti-RNP antibody, and were more complicated with pregnancy-induced hypertension. Past maximum dose of prednisolone, the dose of prednisolone at conception, and percentage of past steroid pulse therapy were higher in renal pregnancies. Outcomes of pregnancies were not significantly different both for mothers and for infants between renal and nonrenal pregnancies. We conclude that it is necessary to provide SLE mothers with the proper information before pregnancy. Women with APS or hypocomplementemia should be regarded with particular attention. Optimal management of mothers and infants requires collaborative efforts of rheumatologists and obstetricians.