David Faden

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.

Risk of congenital complete heart block in newborns of mothers with anti-Ro/SSA antibodies detected by counterimmunoelectrophoresis:. A prospective study of 100 women.

OBJECTIVE To assess the true prevalence of congenital complete heart block (CCHB) in infants of anti-Ro/SSA-positive women known to have connective tissue disease (CTD) and, secondarily, to evaluate the prevalence of other electrocardiographic abnormalities in these newborns at birth. METHODS A prospective study was conducted in 4 referral hospitals. One hundred anti-Ro/SSAA-positive mothers were followed up before they became pregnant and during the index pregnancy. Counterimmunoelectrophoresis and immunoblotting were used to test for antibodies to extractable nuclear antigens. RESULTS Of the 100 women with anti-Ro/SSA antibodies, 2 had infants who developed CCHB in utero (2%). The CCHB was detected at 22 weeks and 20 weeks, respectively. One of the 2 mothers had primary Sjögrens syndrome (SS), and the other had undifferentiated CTD (UCTD). No case of CCHB occurred among the infants of 53 mothers with systemic lupus erythematosus (SLE). No fetal death occurred due to CCHB. In 2 centers, electrocardiography was recorded in 24 unselected newborns, and 4 were found to have sinus bradycardia. CONCLUSION The prevalence of CCHB in newborns of prospectively followed up women already known to be anti-Ro/SSA positive and with known CTD was 2%. This finding is useful with regard to preconception counseling of these women. The risk of delivering an infant with CCHB may be higher in mothers with primary SS or UCTD than in those with SLE. Additional electrocardiographic abnormalities such as sinus bradycardia and prolongation of the QT interval may be present in their children.

Pregnancy outcome in 100 women with autoimmune diseases and anti-Ro=SSA antibodies: a prospective controlled study

Anti-Ro/SSA antibodies are associated with neonatal lupus but are also considered a possible cause for unexplainedpregnancy loss and adverse pregnancy outcome. In a large multicentres cohort study we have prospectivelyfollowed 100 anti-Ro/SSA positivewomen (53 systemic lupus erythematosus (SLE)) during their 122 pregnancies and 107 anti-Ro/SSA negative women (58 SLE) (140 pregnancies).Anti-Ro/SSA antibodies were tested by immunoblot and counterimmunoelectrophoresis. Mean gestational age at delivery (38 vs 37.9 weeks), prevalence of pregnancy loss (9.9 vs 18.6%), preterm birth (21.3 vs 13.9%), cesarean sections (49.2 vs 53.4%), premature rupture of membranes(4.9 vs 8.1%), preeclampsia(6.6 vs 8.1%), intrauterinegrowth retardation(0 vs 2.3%) and newborns small for gestationalage (11.5 vs 5.8%) were similar in anti-Ro/SSA positive and negative SLE mothers; findings were similar in non-SLE women. Two cases of congenital heart block were observed out of 100 anti-Ro/SSA positive women. In conclusion, anti-Ro/SSA antibodies are responsiblefor congenitalheart block but do not affect other pregnancyoutcomes,both in SLE and in non-SLE women. The general outcome of these pregnancies is now very good, if prospectively followedby multidisciplinaryteams with ample experiencein this field.

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.

Anti-beta 2 glycoprotein I antibodies in a general obstetric population: preliminary results on the prevalence and correlation with pregnancy outcome. Anti-β2 glycoprotein I antibodies are associated with some obstetrical complications, mainly preeclampsia-eclampsia

OBJECTIVE To evaluate the prevalence in normal pregnancies of anti-32 glycoprotein I (anti-beta2GPI) antibodies, and their association with obstetrical complications. STUDY DESIGN Prospective study of anti-beta2GPI and anticardiolipin (CL) antibodies in 510 healthy pregnant women at 15-18 weeks. According to the results, women were categorized into three groups: group I, negative for both antibodies; group II, positive for anti-beta2GPI antibodies; group III, positive for aCL only. The rates of fetal loss, abruptio placentae, preeclampsia-eclampsia, and fetal growth retardation were compared in the three groups. RESULTS Anti-beta2GPI antibodies were found in 20 women (3.9%) and aCL in 8 patients (1.6%). Obstetrical complications were more frequent, even if not significantly different, in group II, 15%, than in group I, 4.1% (difference 10.9%; 95% confidence interval (CI): 1.6-20.2%; p=0.0575), while no complications were seen in group III. Preeclampsia-eclampsia were significantly more frequent in group II (10%) than in group I (0.8%; difference 9.2%; 95% CI: 4.4-14%; p=0.021). The prevalence of fetal growth retardation was not significantly different in the two groups (5% vs. 2%, respectively). COMMENT Our findings indicate that anti-beta2GPI antibodies are associated with some obstetrical complications, mainly preeclampsia-eclampsia, even if more conventional antiphospholipid antibodies are not present. This observation suggests that these antibodies should be investigated in such cases, in order to improve the outcome of subsequent pregnancies, as well as in women with a history of early and/or recurrent severe preeclampsia in order to start a prophylactic treatment (i.e. low-dose aspirin or heparin).

Autoantibodies and Prediction of Reproductive Failure

Problem  To determine which autoantibodies are associated with reproductive failure.

Prevention of fetal loss in experimental antiphospholipid syndrome by low-molecular-weight heparin

OBJECTIVE The purpose of this study was to compare the effectiveness of low-molecular-weight heparin with regular heparin in the prevention of fetal resorption in mice with the antiphospholipid syndrome. STUDY DESIGN Antiphospholipid syndrome was passively induced in ICR mice by injecting them with anticardiolipin antibodies on the first day of pregnancy. Subsequently, these mice were treated with low-molecular-weight heparin in two different doses, with regular heparin, and with a placebo. On gestational day 17 the mice were killed by cervical dislocation, and the pregnancy outcome was evaluated. Statistical analysis was performed by means of a one-way analysis of variance using Bonferronis t test. RESULTS Treatment with low-molecular-weight heparin resulted in a resorption rate of 22.4% as opposed to 41.4% in mice with antiphospholipid syndrome that were given regular heparin and 51.7% in nontreated controls. CONCLUSION We conclude that low-molecular-weight heparin can prevent fetal resorptions in mice with antiphospholipid syndrome.

Autoimmunity and Pregnancy Autoantibodies and Pregnancy in Rheumatic Diseases

Abstract:  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.

The immune development in a child born to a cyclosporin A-treated woman with systemic lupus erythematosus/polymyositis.

The case of a woman affected by an overlap syndrome systemic lupus erythematosus/polymyositis (PM), who presented with active myositis at the start of the pregnancy, is reported. Therapy with cyclosporin, corticosteroids, hydroxychloroquine and high-dose intravenous immunoglobulin induced a progressive remission of clinical and laboratory signs of myositis. At 33 weeks of gestation, after a premature pre-term rupture of membrane, a male child was delivered. Although premature, and small for gestational age, he had a normal growth, and did not show any clinical sign suggestive of immune deficiency. Lymphocyte phenotypical and functional studies, as well as response to vaccination, were also normal.

Idiopathic Eosinophilic Pneumonia and Pregnancy: Report of a Case

A case of chronic eosinophilic pneumonia and pregnancy is reported. In 1989, a 24-year-old woman with chronic eosinophilic pneumonia became pregnant. We decided not to stop steroid therapy. Except for premature preterm rupture of the membrane she had a uneventful pregnancy and a male infant with no distress syndrome.