Véronique Ramoni

Brief report: successful pregnancies but a higher risk of preterm births in patients with systemic sclerosis: an Italian multicenter study

OBJECTIVE To assess fetal and maternal outcomes in women with systemic sclerosis (SSc). METHODS Prospectively collected data on 99 women with SSc from 25 Italian centers were analyzed retrospectively. Women with SSc were observed during 109 pregnancies (from 2000 to 2011), and outcomes were compared to those in the general obstetric population (total of 3,939 deliveries). The maternal age at conception was a mean ± SD 31.8 ± 5.3 years, and the median disease duration at conception was 60 months (range 2-193 months). RESULTS SSc patients, compared to the general obstetric population, had a significantly increased frequency of preterm deliveries (25% versus 12%) and severe preterm deliveries (<34 weeks of gestation) (10% versus 5%), intrauterine growth restriction (6% versus 1%), and babies with very-low birth weight (5% versus 1%). Results of multivariable analysis showed that corticosteroid use was associated with preterm deliveries (odds ratio [OR] 3.63, 95% confidence interval [95% CI] 1.12-11.78), whereas the use of folic acid (OR 0.30, 95% CI 0.10-0.91) and presence of anti-Scl-70 antibodies (OR 0.26, 95% CI 0.08-0.85) were protective. The disease remained stable in most SSc patients, but there were 4 cases of progression of disease within 1 year from delivery, all in anti-Scl-70 antibody-positive women, 3 of whom had a disease duration of <3 years. CONCLUSION Women with SSc can have successful pregnancies, but they have a higher-than-normal risk of preterm delivery, intrauterine growth restriction, and babies with very-low birth weight. Progression of the disease during or after pregnancy is rare, but possible. High-risk multidisciplinary management should be standard for these patients, and pregnancy should be avoided in women with severe organ damage and postponed in women with SSc of recent onset, particularly if the patient is positive for anti-Scl-70 antibodies.

Prevalence and significance of previously undiagnosed rheumatic diseases in pregnancy

Objectives The objective of this study was to evaluate the rates of previously undiagnosed rheumatic diseases during the first trimester of pregnancy and their impact on the pregnancy outcome. Methods Pregnant women in their first trimester were screened using a two-step approach using a self-administered 10-item questionnaire and subsequent testing for rheumatic autoantibodies (antinuclear antibody, anti-double-stranded DNA, anti-extractable nuclear antigen, anticardiolipin antibodies, anti-β2-glycoprotein I antibodies and lupus anticoagulant) and evaluation by a rheumatologist. Overall, the complications of pregnancy evaluated included fetal loss, pre-eclampsia, gestational diabetes, fetal growth restriction, delivery at less than 34 weeks, neonatal resuscitation and admission to the neonatal intensive care unit. Results Out of the 2458 women screened, the authors identified 62 (2.5%) women with previously undiagnosed undifferentiated connective tissue disease (UCTD) and 24 (0.98%) women with previously undiagnosed definite systemic rheumatic disease. The prevalences were seven (0.28%) for systemic lupus erythematosus and Sjogrens syndrome, six (0.24%) for rheumatoid arthritis, three (0.12%) for antiphospholipid syndrome and one (0.04%) for systemic sclerosis. In multiple exact logistic regression, after adjustment for potential confounders, the OR of overall complications of pregnancy were 2.81 (95% CI 1.29 to 6.18) in women with UCTD and 4.57 (95% CI 1.57 to 13.57) in those with definite diseases, respectively, compared with asymptomatic controls. Conclusions In our population approximately 2.5% and 1% of first trimester pregnant women had a previously undiagnosed UCTD and definite systemic rheumatic disease, respectively. These conditions were associated with significant negative effects on the outcome of pregnancy.

Systemic vasculitis and pregnancy: A multicenter study on maternal and neonatal outcome of 65 prospectively followed pregnancies

OBJECTIVE Systemic vasculitis (SV) are uncommon diseases that rarely affect women during their reproductive age; little data, mainly retrospective, is available on this topic. The aim of our study was to evaluate maternal/neonatal outcome and disease course before, during and after pregnancy. METHODS Sixty-five pregnancies in 50 women with SV were followed by a multispecialistic team in 8 institutions between 1995 and 2014. Clinical data on pregnancy, 1year before and 1year after delivery was retrospectively collected. The rate of pregnancy complications was compared to that of a General Obstetric Population (GOP) of 3939 women. RESULTS In 2 patients the diagnosis of SV was done during pregnancy; 59 out of the remaining 63 started when maternal disease was quiescent. We recorded 56 deliveries with 59 live births, 8 miscarriages and 1 fetal death. In SV, preterm, particularly early preterm (<34weeks) deliveries and cesarean sections appeared significantly more frequent than in GOP (11.3% vs 5.0%, p=0.049 and 48.2% vs 31.0%, p=0.009). Vasculitis-related complications occurred in 23 pregnancies (35.4%), with 5 severe events (7.7%) including 3 cases of transient ischemic attack (TIA). Data about the post-partum period were available for 56 pregnancies: 12 flares (21.4%) occurred, with 1 severe event (1.8%). CONCLUSION SV patients can have successful pregnancies (especially during a disease remission phase) despite an increased rate of preterm delivery. Severe flares were limited, but the occurrence of 3 TIA suggests that particular attention should be given to possible thrombotic complications in SV patients during pregnancy and puerperium.

Congenital heart block not associated with anti-Ro/La antibodies: comparison with anti-Ro/La-positive cases.

Objective. To study anti-Ro/La-negative congenital heart block (CHB). Methods. Forty-five fetuses with CHB were evaluated by analysis of anti-Ro/La antibodies using sensitive laboratory methods. Results. There were 9 cases of anti-Ro/La-negative CHB; 3 died (33.3%). Only 3 (33.3%) were complete in utero and 5 (55.5%) were unstable. No specific etiology was diagnosed. Six infants (66.6%) were given pacemakers. There were 36 cases of anti-Ro/La-positive CHB. All except 2 infants (94.4%) had complete atrioventricular block in utero. Ten died (27.8%), one (2.7%) developed severe dilated cardiomyopathy, and 26 (72.2%) were given pacemakers. Conclusion. Nine of the 45 consecutive CHB cases (20%) were anti-Ro/La-negative with no known cause. They were less stable and complete than the anti-Ro/La positive cases.

Prevalence of undiagnosed autoimmune rheumatic diseases in the first trimester of pregnancy. Results of a two-steps strategy using a self-administered questionnaire and autoantibody testing

Objective  To evaluate the prevalence of undiagnosed rheumatic diseases in the first trimester of pregnancy.

Passively acquired anti-SSA/Ro antibodies are required for congenital heart block following ovodonation but maternal genes are not.

Anti-SSA/Ro antibodies are necessary but not sufficient to provoke autoimmune-associated congenital heart block (CHB). Genetic factors are likely contributory. Accordingly, HLA-related candidates and single-nucleotide polymorphisms in the promoter region of tumor necrosis factor α and codon 10 in transforming growth factor β1 (TGFβ1) were evaluated in a unique family: the surrogate mother (anti-SSA/Ro positive), the biologic father, and the CHB-affected child (product of ovodonation). There was an HLA mismatch between the affected child and the surrogate mother. However, both the biologic and the surrogate mothers shared DQ2 and the profibrosing leucine polymorphism at codon 10 of TGFβ. In conclusion, we observed that CHB can develop in a genetically unrelated child exposed in utero to anti-SSA/Ro antibodies. Testing for anti-SSA/Ro antibodies might be considered in women undergoing artificial fertilization. It is possible that there is no direct association of maternal genes beyond a contributory role in generating the autoantibody.

Uterine artery Doppler velocimetry and obstetric outcomes in connective tissue diseases diagnosed during the first trimester of pregnancy.

To evaluate the effect of connective tissue disease (CTD) diagnosed during the first trimester on uterine arteries (UtA) Doppler velocities and on pregnancy outcomes.

The effect of newly diagnosed undifferentiated connective tissue disease on pregnancy outcome

OBJECTIVE The purpose of this study was to evaluate pregnancy outcome in a cohort of patients with newly diagnosed undifferentiated connective tissue disease (UCTD). STUDY DESIGN We conducted a nested case-control study that compared 41 patients who had early UCTD that was diagnosed at 11-14 weeks of pregnancy with 82 healthy control subjects. RESULTS During pregnancy, UCTD progressed to a definite connective tissue disease in 2 of 41 patients (4.9%). Sixteen of the 41 patients (39%) with UCTD tested positive for anti-Ro (SSA) antibodies. Compared with the control subjects, the women with UCTD had higher rates of small for gestational age (SGA; 12/40 vs 11/80; P = .05). The rate of complications of pregnancy (preterm delivery at </= 37 weeks of gestation, SGA, preeclampsia, late fetal loss) was 39% (16/41) among cases and 13.4% (11/82) in control subjects (adjusted odds ratio, 3.98; 95% CI, 1.59-9.49). CONCLUSION Pregnant patients with UCTD are at increased risk of SGA and complications of pregnancy.

Effect of Additional Treatments Combined with Conventional Therapies in Pregnant Patients with High-Risk Antiphospholipid Syndrome: A Multicentre Study

The effect of additional treatments combined with conventional therapy on pregnancy outcomes was examined in high-risk primary antiphospholipid syndrome (PAPS) patients to identify the most effective treatment strategy. The studys inclusion criteria were (1) positivity to lupus anticoagulant alone or associated with anticardiolipin and/or anti-β2 glycoprotein I antibodies; (2) a history of severe maternal-foetal complications (Group I) or a history of one or more pregnancies refractory to conventional therapy leading to unexplained foetal deaths not associated with severe maternal-foetal complications (Group II). Two different additional treatments were considered: oral-low-dose steroids (10-20 mg prednisone daily) and/or 200 to 400 mg daily doses of hydroxychloroquine and parenteral-intravenous immunoglobulins at 2 g/kg per month and/or plasma exchange. The studys primary outcomes were live birth rates and pregnancy complications. A total of 194 pregnant PAPS patients attending 20 tertiary centres were retrospectively enrolled. Hydroxychloroquine was found to be linked to a significantly higher live birth rate with respect to the other oral treatments in the Group II patients. The high (400 mg) versus low (200 mg) doses of hydroxychloroquine (p = 0.036) and its administration before versus during pregnancy (p = 0.021) were associated with a significantly higher live birth rate. Hydroxychloroquine therapy appeared particularly efficacious in the PAPS patients without previous thrombosis. Parenteral treatments were associated with a significantly higher live birth rate with respect to the oral ones (p = 0.037), particularly in the Group I patients. In conclusion, some additional treatments were found to be safe and efficacious in high-risk PAPS pregnant women.

Apheresis in high risk antiphospholipid syndrome pregnancy and autoimmune congenital heart block

In the first part a prospective cohort study was reported to evaluate the efficacy and safety of a treatment protocol including plasma exchange (PE) or PE plus intravenous immunoglobulins (IVIG) or immunoadsorption (IA) plus IVIG administered in addition to conventional therapy to 22 pregnant women with high-risk APS. The results indicate that PE or IA treatments administered along with IVIG and conventional antithrombotic therapy could be a valuable and safe therapeutic option in pregnant APS women with triple antiphospholipid antibody positivity along with a history of thrombosis and/or one or more severe pregnancy complications. In the second part the efficacy and safety of PE combined with IVIG and steroids were evaluated for the treatment of 10 patients with autoimmune congenital heart block (CHB) by comparing maternal features, pregnancy outcome and side effects with those of 24 CHB patients treated with steroids only. The patients treated with the combined therapy showed a statistically significant regression of 2nd degree blocks, an increase in heart rate at birth and a significantly lower prevalence of pacing in the first year of life. Moreover, no side effects were observed except for a few steroid-related events. If these results are confirmed by large-scale studies, the apheretic procedures could lead to improved outcomes in the treatment of these devastating diseases.