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Autoimmune rheumatic diseases (ARD) can affect women and men during fertile age, therefore reproductive health is a priority issue in rheumatology. Many topics need to be considered during preconception counselling: fertility, the impact of disease-related factors on pregnancy outcomes, the influence of pregnancy on disease activity, the compatibility of medications with pregnancy and breastfeeding. Risk stratification and individualized treatment approach elaborated by a multidisciplinary team minimize the risk of adverse pregnancy outcomes (APO). Research has been focused on identifying biomarkers that can be predictive of APO. Specifically, preeclampsia and hypertensive disorders of pregnancy tend to develop more frequently in women with ARD. Placental insufficiency can lead to intrauterine growth restriction and small-for-gestational age newborns. Such APO have been shown to be associated with maternal disease activity in different ARD. Therefore, a key message to be addressed to the woman wishing for a pregnancy and to her family is that treatment with compatible drugs is the best way to ensure maternal and fetal wellbeing. An increasing number of medications have entered the management of ARD, but data about their use in pregnancy and lactation are scarce. More information is needed for most biologic drugs and their biosimilars, and for the so-called small molecules, while there is sufficient evidence to recommend the use of TNF inhibitors if needed for keeping maternal disease under control. Other issues related to the reproductive journey have emerged as "unmet needs", such as sexual dysfunction, contraception, medically assisted reproduction techniques, long-term outcome of children, and they will be addressed in this review paper. Collaborative research has been instrumental to reach current knowledge and the future will bring novel insights thanks to pregnancy registries and prospective studies that have been established in several Countries and to their joint efforts in merging data.

Objectives Pregnancy in SSc is burdened with an increased risk of obstetric complications. Little is known about the underlying placental alterations. This study aimed to better understand pathological changes and the role of inflammation in SSc placentas. Leucocyte infiltration, inflammatory mediators and atypical chemokine receptor 2 (ACKR2) expression in SSc placentas were compared with those in other rheumatic diseases (ORD) and healthy controls (HC). Methods A case–control study was conducted on eight pregnant SSc patients compared with 16 patients with ORD and 16 HC matched for gestational age. Clinical data were collected. Placentas were obtained for histopathological analysis and immunohistochemistry (CD3, CD20, CD11c, CD68, ACKR2). Samples from four SSc, eight ORD and eight HC were analysed by qPCR for ACKR2 expression and by multiplex assay for cytokines, chemokines and growth factors involved in angiogenesis and inflammation. Results The number of placental CD3, CD68 and CD11 cells was significantly higher in patients affected by rheumatic diseases (SSc+ORD) compared with HC. Hepatocyte growth factor was significantly increased in the group of rheumatic diseases patients (SSc+ORD) compared with HC, while chemokine (C-C motif) ligand 5 (CCL5) was significantly higher in SSc patients compared with ORD and HC. CCL5 levels directly correlated with the number of all local inflammatory cells and higher levels were associated with histological villitis. Conclusions Inflammatory alterations characterize placentas from rheumatic disease patients and could predispose to obstetric complications in these subjects.

The objective of this study is to evaluate endothelial progenitor cells (EPCs) CD34+ CD133− and CD34+ CD133+ and soluble HLA-G (sHLA-G) concentrations among undifferentiated connective tissue disease (UCTD) subjects, compared to controls, during pregnancy and in cord blood. This is a case-control study including 29 controls and 29 UCTDs. CD34+ CD133−, CD34+ CD133+, and sHLA-G concentrations were detected in maternal plasma and in cord blood. This study was approved by the Medical-Ethical Committee of our Institution (Current Research Project N. 901-rcr2017i-23 of IRCCS Foundation Policlinico San Matteo of Pavia). Circulating CD34+ CD133− and CD34+ CD133+ counts and sHLA-G (soluble human leucocyte antigen G) concentrations in maternal peripherical blood were higher in UCTD compared to those in controls in first and third trimester of pregnancy and at delivery (p

Autoimmune rheumatic diseases (ARD) can affect women and men during fertile age, therefore reproductive health is a priority issue in rheumatology. Many topics need to be considered during preconception counselling: fertility, the impact of disease-related factors on pregnancy outcomes, the influence of pregnancy on disease activity, the compatibility of medications with pregnancy and breastfeeding. Risk stratification and individualized treatment approach elaborated by a multidisciplinary team minimize the risk of adverse pregnancy outcomes (APO). Research has been focused on identifying biomarkers that can be predictive of APO. Specifically, preeclampsia and hypertensive disorders of pregnancy tend to develop more frequently in women with ARD. Placental insufficiency can lead to intrauterine growth restriction and small-for-gestational age newborns. Such APO have been shown to be associated with maternal disease activity in different ARD. Therefore, a key message to be addressed to the woman wishing for a pregnancy and to her family is that treatment with compatible drugs is the best way to ensure maternal and fetal wellbeing. An increasing number of medications have entered the management of ARD, but data about their use in pregnancy and lactation are scarce. More information is needed for most biologic drugs and their biosimilars, and for the so-called small molecules, while there is sufficient evidence to recommend the use of TNF inhibitors if needed for keeping maternal disease under control. Other issues related to the reproductive journey have emerged as “unmet needs”, such as sexual dysfunction, contraception, medically assisted reproduction techniques, long-term outcome of children, and they will be addressed in this review paper. Collaborative research has been instrumental to reach current knowledge and the future will bring novel insights thanks to pregnancy registries and prospective studies that have been established in several Countries and to their joint efforts in merging data.

The concern about the offspring’s health is one of the reasons for a reduced family size of women with rheumatic diseases (RD). Increased risk of autoimmune diseases (AD) and neurodevelopmental disorders (ND) has been reported in children born to patients with RD. Within a nationwide survey about reproductive issues of women with RD, we aimed at exploring the long-term outcome of their children. By surveying 398 patients who received their diagnosis of RD during childbearing age (before the age of 45), information about the offspring were obtained from 230 women who declared to have had children. A total of 148 (64.3%) patients were affected by connective tissue diseases (CTD) and 82 (35.7%) by chronic arthritis. Data on 299 children (156 males, 52.1%; mean age at the time of interview 17.1 ± 9.7 years) were collected. Twelve children (4.0%), who were born to patients with CTD in 75% of the cases, were affected by AD (8 cases of celiac disease). Eleven children had a certified diagnosis of ND (3.6%; 6 cases of learning disabilities); 9 of them were born to mothers with CTD (5 after maternal diagnosis). No association was found between ND and prenatal exposure to either maternal autoantibodies or anti-rheumatic drugs. Absolute numbers of offspring affected by AD and ND were low in a multicentre cohort of Italian women with RD. This information can be helpful for the counselling about reproductive issues, as the health outcomes of the offspring might not be an issue which discourage women with RD from having children.

Objective To assess the effect of optimal management of pregnancy on a composite outcome of miscarriage and complicated birth among women with rheumatoid arthritis (RA). Methods Data were extracted from health care databases of the Lombardy Region, Italy (2004-2013) as a part of the Record-Linkage on Rheumatic Diseases Study. Analyses included women with RA identified through a copayment exemption code (International Classification of Diseases, Ninth Revision, Clinical Modification code 714.0) and controls from the general population, ages 18-50 years. Seven health care quality indicators (HCQI) were constructed and summarized in 3 pathway indicators: diagnostic, therapeutic, and prenatal follow-up. Complicated birth or miscarriage were used to identify the adverse pregnancy outcome (APO). The relationship between HCQI and APO was analyzed using logistic models, and the results were presented as odds ratios (ORs) and 95% confidence intervals (95% CIs). Results Data from the study cohort included the first pregnancy observed in 443 patients with RA compared with 6,097 women belonging to the general population. In the RA population, patients who followed the 3 pathway indicators had a reduced risk of overall APO, with an OR of 0.60 (95% CI 0.39-0.94), and reduced risk of miscarriage/perinatal death, with an OR of 0.40 (95% CI 0.24-0.69), compared to those who did not follow the pathway indicators. Compared with the general population, patients with RA who met all HCQI during pregnancy displayed a risk of APO with an OR of 0.92 (95% CI 0.61-1.38) and miscarriage/perinatal death with an OR of 0.77 (95% CI 0.47-1.29). Conclusion The adherence to an ideal clinical pathway of pregnancy management in women with RA restored the risk of APO to that expected for the general population.

The objective of this study is to evaluate endothelial progenitor cells (EPCs) CD34

This comprehensive review summarizes retrospective and prospective studies on pregnancy in systemic sclerosis in order to educate physicians on critical management issues. Fertility is normal in women with established systemic sclerosis. Their rates of spontaneous losses are comparable to the general population, except for patients with late diffuse systemic sclerosis and severe internal organ involvement who may have higher risks of abortion. Prematurity is clearly higher among systemic sclerosis women, similarly to other rheumatic diseases such as systemic lupus erythematosus and anti-phospholipid antibody syndrome. A placental vasculopathy has been observed in some women with systemic sclerosis. Overall, the disease generally remains stable in most pregnancies. Women with pulmonary hypertension should avoid pregnancy on account of the high maternal mortality risk. Management of systemic sclerosis patients before and during pregnancy includes evaluation of organ involvement and autoantibody analysis, preconceptional folic acid, and discontinuation of drugs with teratogenic potential (bosentan, mycophenolate mofetil, methotrexate, etc.). Management by high-risk pregnancy teams including neonatologists is very important to ensure the best outcomes.

Cardiac involvement is the most severe manifestation of neonatal lupus. It is usually diagnosed as an advanced (second or third degree) atrio-ventricular (AV) congenital heart block (CHB) starting around 20 weeks of gestation. At this gestational time, a window of opportunity might exist, and fluorinated corticosteroids (FS) have been attempted as a therapeutic option. Unfortunately the quality of the studies is methodologically low, due to the retrospective design and to the rarity of autoimmune CHB. Some case reports and small case series basically suggested a possible utility of FS, mainly in the context of incomplete CHB, while larger observational retrospective studies did not find any efficacy of FS either on mortality, on the rate of pacemaker implantation, to reduce the degree of incomplete CHB or to reduce the development of cardiomyopathy. Of note the distinction between complete and incomplete AV block may be very difficult and time consuming in utero. Overall FS should not be recommended in CHB, but might be considered for a short time for a recent incomplete CHB.

Background Patients with Undifferentiated Connective Tissue Disease (UCTD) are at risk of disease worsening and progression into well-defined rheumatic disease over time1. Only a few studies2-3 from small cohorts regarding the role of pregnancy in UCTD outcome are available, with no clear-cut factors associated with the evolution of the disease. Objectives To evaluate the impact of pregnancy on progression from UCTD into a well-defined rheumatic disease. To analyze the role of UCTD flares during pregnancy, as well as clinical and laboratory features in the evolution of the disease; to compare UCTD evolution in patients with or without pregnancy; to compare UCTD evolution in patients with or without UCTD diagnosis before pregnancy. Methods We collected clinical data from a rheumatologic outpatient clinic regarding women (aged 18-45) with UCTD, from diagnosis to last follow-up. Pregnant women with a previously undiagnosed UCTD were included using a validated two-steps screening method performed at the 1st trimester during the gynecological ultrasound evaluation, as previously reported4. We compared women with at least one pregnancy to non-pregnant women. Student’s t test was applied for unpaired, continuous variables, while chi-square to compare percentages. The rate of progression was compared with Kaplan–Meier estimator and Log-rank test. A Cox regression model was fit to assess the association of flare during pregnancy and of clinical and laboratory features with the evolution of the disease. Results We retrieved data regarding 152 pregnant and 108 non-pregnant patients, mean age of 32 (±6.71) years. We recorded 201 pregnancies. The progression into well-defined disease was observed in 31 (20.4%) pregnant patients and in 5 (4.6%) non-pregnant patients (p We observed 32 flares during pregnancy, mostly with joints involvement (75% of the cases). Having at least one flare during pregnancy, a history of UCTD-related cytopenia and lower levels of C4 in the 6 months before conception were associated with disease evolution. No differences were found as for disease evolution in pregnant patients with or without a previous UCTD diagnosis. Conclusion The rate of progression from UCTD into a well-defined rheumatic disease is significantly higher in women who had a pregnancy. Having a history of UCTD-related cytopenia, or lower C4 levels before conception, or at least one flare of UCTD during pregnancy significantly increases the risk of progression. The timing of the diagnosis of UCTD, in respect with the pregnancy, does not change the risk of flare and progression. References [1] Mosca M, Tani C, Vagnani S, et al. The diagnosis and classification of undifferentiated connective tissue diseases. J Autoimmun. 2014 [2] Mosca M, Neri R, Strigini F, et al. Pregnancy outcome in patients with undifferentiated connective tissue disease: a preliminary study on 25 pregnancies. Lupus 2002 [3] Castellino G, Capucci R, Bernardi S, et al. Pregnancy in patients with undifferentiated connective tissue disease: a prospective case-control study. Lupus 2011 [4] Spinillo A, Beneventi F, Ramoni V, et al. Prevalence and significance of previously undiagnosed rheumatic diseases in pregnancy. Ann Rheum Dis. 2012 Disclosure of Interests Francesca Motta: None declared, Veronique Ramoni: None declared, Roberto Caporali Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Roche, Genzyme, Lilly, MSD, Pfizer, UCB, Vittorio Grosso: None declared, Barbara Vitolo: None declared, Silvana Quaglini: None declared, Carlomaurizio Montecucco Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Sanofi, Genzyme, Lilly, MSD, Pfizer, UCB

Objective: Neonatal Lupus (NL) is a rare syndrome caused by placental transfer of maternal anti-SSA/Ro and anti-La/SSB autoantibodies to the fetus. The rarity of this condition requires the establishment of multidisciplinary registries in order to improve our knowledge.Method: Inclusion criteria in this retrospective study were the maternal confirmed positivity for anti-SSA/Ro and/or anti-SSB/La antibodies, and the presence of II or III degree congenital heart block (CHB) in utero or neonatal period (up to 27 days after birth).Result: Eighty-nine cases of CHB were observed in 85 women with 88 pregnancies that occurred between 1969 and 2017. CHB was mostly detected in utero (84 cases, 94.2%), while five cases were observed in the neonatal period. A permanent pacemaker was implanted in 51 of 73 children born alive (69.8), whereas global mortality rate was 25.8% (23 cases): 16 in utero, five perinatal, and two during childhood. By univariate analysis, factors associated with fetal death were pleural effusion (p = 0.005, OR > 100; CI 95% 2.88->100 and hydrops (p = 0.003, OR = 14.09; CI 95% 2.01–122). Fluorinated steroids (FS) were administered in 71.4% pregnancies, and its use was not associated with better survival. Some centers treated all cases with fluorinated steroids and some centers did not treat any case. CHB was initially incomplete in 24 fetuses, and of them five cases of II degree block reverted to a lower degree block after treatments. Recurrence rate in subsequent pregnancies was 17.6% (3 out of 17). A prophylactic treatment was introduced in 10 of these 16 subsequent (58.8%) pregnancies, mostly with FS or high dose intravenous immunoglobulins.Conclusion: This is the first report from the Italian Registry of neonatal lupus/CHB. The live birth rate was nearly 80%, with nearly two thirds of the children requiring the implantation of a pacemaker. The management of fetuses diagnosed with CHB was heterogeneous across Italian Centers. The registry at present is mainly rheumatological, but involvement of pediatric cardiologists and gynecologists is planned.

Objective The reproductive choices of women affected by rheumatic diseases (RD) can be influenced by several factors, including the quality of physician-patient communication. We conducted a survey on reproductive issues aiming at exploring the unmet needs of women with RD during childbearing age. Methods We administered 65 multiple-choice and 12 open-answer questions about pregnancy counselling, contraception, use of drugs during pregnancy and other women reproductive issues to 477 consecutive women with RD aged 18–55 years followed-up in 24 rheumatology centres in Italy. Analysis was restricted to 398 patients who received their diagnosis of RD before the age of 45. According to the RD diagnosis, patients were subdivided into 2 groups: connective tissue diseases (n = 249) and chronic arthritis (n = 149). Results At the time of interview, women in both groups had a mean age of 40 years. Nearly one third of patients in each group declared not to have received any counselling about either pregnancy desire nor contraception. A smaller family size than desired was reported by nearly 37% of patients, because of concerns related to maternal disease in one fourth of the cases. A “Disease Knowledge Index” (DKI) was created to investigate the degree of patients’ information about the implications of their RD on reproductive issues. Having received counselling was associated with higher DKI values and with a positive impact on family planning. Conclusion Italian women of childbearing age affected by RD reported several unmet needs in their knowledge about reproductive issues. Strategies are needed to implement and facilitate physician-patient communication.

Objectives The aim was to determine whether assisted reproductive technologies (ARTs) confer additional risk in rheumatic patients (in terms of disease flare and fetal–maternal complications) and whether, if performed, their efficacy is affected by maternal disease. Methods Sixty infertile rheumatic women undergoing 111 ART cycles were included. Clinical pregnancy rate, live birth rate, maternal disease flares and maternal–fetal complications were recorded. Results One hundred and eleven ART cycles in 60 women were analysed. We reported 46 pregnancies (41.4%), 3 (3.1%) cases of ovarian hyperstimulation syndrome and no cases of thrombosis during stimulation, pregnancy and puerperium. One or more maternal complication was reported in 13 (30.2%) pregnancies, and fetal complications occurred in 11 fetuses (21.1%). The live birth rate was 98%, but we reported three (6%) perinatal deaths in the first days of life. During puerperium, we recorded one (2.5%) post-partum haemorrhage and one (2.5%) articular flare. Conclusion The safety and efficacy of the ARTs, demonstrated in the general population, seems to be confirmed also in rheumatic patients. No evidence was found to advise against their application, and the choice of therapy should be made depending on the patient’s risk profile, irrespective of whether the pregnancy is natural or artificial induced.

Pregnancy requires a special management in women with inflammatory rheumatic diseases (RDs), with the aim of controlling maternal disease activity and avoiding fetal complications. Despite the heterogeneous course of RDs during pregnancy, their impact on pregnancy largely relates to the extent of active inflammation at the time of conception. Therefore, accurate evaluation of disease activity is crucial for the best management of pregnant patients. Nevertheless, there are limitations in using conventional measures of disease activity in pregnancy, as some items included in these instruments can be biased by symptoms or by physiological changes related to pregnancy and the pregnancy itself may influence laboratory parameters used to assess disease activity. This article aims to summarize the current literature about the available instruments to measure disease activity during pregnancy in RDs. Systemic lupus erythematosus is the only disease with instruments that have been modified to account for several adaptations which might interfere with the attribution of signs or symptoms to disease activity during pregnancy. No modified-pregnancy indices exist for women affected by other RDs, but standard indices have been applied to pregnant patients. The current body of knowledge shows that the physiologic changes that occur during pregnancy need to be either adapted from existing instruments or developed to improve the management of pregnant women with RDs. Standardized instruments to assess disease activity during pregnancy would be helpful not only for clinical practice but also for research purposes. info:eu-repo/semantics/publishedVersion

Background:Data about the obstetric outcomes of pregnant women with Systemic Sclerosis (SSc) mainly derive from retrospective studies. Moreover, little evidence is available to define if pregnancy impacts on SSc course and if children of SSc mothers have a normal post-natal development.Objectives:To assessed the obstetric, pediatric and rheumatologic outcomes of SSc pregnancies in a prospective controlled studyMethods:Prospective recruitment of three cohorts.1) 110 pregnant women with SSc.2) 218 control pregnancies without systemic autoimmune diseases3) 78 non-pregnant control SSc with a matching subject in cohort-1.SSc was characterized for disease activity, severity, cutaneous/organ involvement and therapy. Women and their offspring were followed until 21 months after enrollment (ie, 12 months after expected delivery).Results:Gestational and neonatal outcomesMiscarriages and fetal death occurred in 7% and 5% of SSc pregnancies. Compared to control pregnancies, SSc pregnancies had higher rates of gestational hypertension (12% Vs 4%, p=0.004), pre-eclampsia (9% Vs 1%, p=0.002), fetal growth-restriction (13% Vs 4%, p=0.004), prematurity (26% Vs 7%, pUnivariate and multivariate analyses were performed for relevant outcomes. For example, pre-eclampsia positively associated with baseline skin score and its evolution during pregnancy (p=0.015 and 0.013), immunosuppressive agents, bosentan and iloprost at baseline (p=0.001, 0.041 and 0.007), and twin pregnancy(p=0.006). Multivariate logistic regression for pre-eclampsia in SSc identified baseline arterial hypertension, immunosuppressive agents or of iloprost, twin pregnancy and assisted conception as risk factors (p=0.000, 0.002, 0.0025, 0.000 and 0.027), and baseline calcium channel blockers as protective factors (p=0.001).SSc course during pregnancyAs compared to matched non-pregnant SSc, SSc pregnant women had lower Medsger disease severity index (0.6 +/-0.9 Vs 1.0 +/-1.1, p=0.022), health assessment questionnaire (HAQ, 0.21 +/-0.38 Vs 0.40 +/-0.55, p=0.026), and lower rate of iv iloprost (21% Vs 42%, p=0.006). Pregnant and non-pregnant SSc women had a similar disease course during the 21 months of follow-up, despite a lower use of immunosuppressive agents (17% Vs 36%, p=0.014). Two scleroderma-renal-crises (SRC) occurred during pregnancy (one was a relapse of a previous SRC; the other occurred at week 33, and resolved after premature delivery of a SGA newborn and ACE-inhibitors, preventing differentiation from pre-eclampsia).Conclusion:SSc pregnancies have generally a favorable obstetric/pediatric outcome, albeit at a higher risk of gestational hypertension, pre-eclampsia, fetal growth restriction, prematurity, delivery of SGA newborn and requirement of neonatal-ICU. Pregnancy does not impact on SSc course, although SRC during late pregnancy and pre-eclampsia might be hardly discriminated.References:[1]Taraborelli M et al., Arthritis Rheum, 2012.Disclosure of Interests:None declared

Background:Congenital heart block (CHB) is due to placental transfer of maternal anti-Ro/SSA autoantibodies to the fetus. The prevalence of CHB has been estimated as 1-2% in anti-Ro/SSA women while the recurrence rate is 16-19% (1). This condition is associated with a high rate of fetal/neonatal mortality and most of the cases requires pacemaker (PM) pacing. Given the rarity of CHB, limited data are available regarding the long-term follow-up of the offspring other than the cardiovascular complications.Objectives:The results of the Italian Registry of the autoimmune congenital heart block were recently described (2). A peculiarity of this cohort was that most of the mothers had an established diagnosis of systemic autoimmune disease at CHB detection, in contrast with other registries where CHB was mostly incidentally detected in healthy women. Here we report an update, with the preliminary data regarding the long-term outcome of patients with CHB, their unaffected siblings and health controls born from mothers positive for Ro/SSA.Methods:Data regarding demography, treatment, maternal, neonatal outcome, and follow-up were collected through an online electronic datasheet. A dedicated questionnaire was created with the aim to investigate general health, cardiovascular follow-up, and frequency of autoimmune diseases.Results:One-hundred and five cases of CHB in 99 patients were included from 1969 to December 2020. CHB was mostly detected in utero (97 cases, 92.3%) with 8 neonatal cases. Third degree CHB occurred in 71 cases (67.6%). Child mortality was observed in 29 (27.6%) cases: 20 in utero, 7 during neonatal period and 2 during childhood. Overall, a PM was implanted in 54 out of the 85 live births (63.5%). Then, our cohort was divided into 2 subgroups: pregnancy that occurred before (N=61) and after 2010 (N=44) with the aim to evaluate possible differences among the subgroups. Whereas mortality, PM, CHB degree were similar, CHB more frequently occurred in the last 10 years among Ro/SSA asymptomatic carriers than in the group of pregnancies before 2010 (53.6% vs 32.8%, p=0.038). Questionnaires from 14 surviving CHB cases, 8 unaffected siblings 12 controls born from mothers Ro/SSA positive were collected. Among CHB cases, 6 were males and 8 females, median age 12 years (range 6-28). All presented a third degree CHB, 10 required a neonatal PM pacing and one had an implantable ECG recorder. PM was substituted at least once in 9 patients, the oldest patient had to change it four times. No dilated cardiomyopathy occurred and most of the patients maintain an annual follow-up. Two cases of autoimmune diseases were registered among CHB cases, one idiopathic juvenile arthritis and one Cogan’s vasculitis, both born from mothers with Sjogren Syndrome. Four cases of neurodevelopmental disorders occurred: three cases of learning disabilities (one in each group) and one case of speech disorder in the sibling group. In addition, a CHB case presented a stress disorder linked to frequent hospitalizations.Conclusion:This registry is an ongoing project aiming at collecting all Italian CHB. Moreover, here we reported the preliminary data concerning the evaluation of long-term follow-up of CHB patients. Our data, even if need to be confirmed in larger cohort, seems reassuring: no differences were reported comparing CHB patients with unaffected siblings or controls.References:[1]Brito-Zéron et al. Nat Rev Rheumatol 2015;11:301-312.[2]Fredi M et al. Front Cardiovasc Med. 2019 Feb 28;6:11.Disclosure of Interests:None declared

To investigate the rates and coexistence of autoimmune thyroid and connective tissue diseases (CTD) during the first trimester of pregnancy and their influence on pregnancy outcome.A cohort study of 150 women with CTD diagnosed during first trimester of pregnancy and 150 negative controls.Screening of CTD by a self-reported questionnaire, rheumatic and thyroid autoantibody detection, clinical rheumatological evaluation and obstetric outcomes.Out of 3852 women screened, 61 (1.6%) were diagnosed with undefined connective tissue disease (UCTD), 28 (0.7%) with major CTD (six rheumatoid arthritis, five systemic lupus erythematosus, eight Sjogren syndrome, five anti-phospholipid syndrome, two systemic sclerosis, one mixed CTD and one monoarticular arthritis) and 61 (1.6%) had insufficient criteria for a diagnosis of a rheumatic disease. The overall prevalence of either thyroid peroxidase (TPO-a) or thyroglobulin (TG-a) autoantibodies detection was 8% (12/150) among controls, 62.3% (38/61) among UCTD and 60.7% (17/28) in women with a major CTD (p.001 compared to controls for both comparisons). After adjustment for confounders, overall CTDs (major or undefined) (OR=3.54, 95% CI; 1.61-7.78) and TPO-a plus TG-a positivity (OR=2.78, 95% CI;1.29-5.98) were independently associated with increased risks of moderate-severe complications of pregnancy (miscarriage, fetal growth restriction, preeclampsia, delivery before 34 weeks).Rheumatic and thyroid autoantibodies during pregnancy are closely associated. Thyroid antibodies could add to the risk of adverse pregnancy outcome associated with connective tissue diseases.

Background:Systemic Sclerosis (SSc) is one of the rheumatic diseases burdened with obstetrical complications. An Italian multicenter study showed that women with SSc have a higher-than-normal risk of intrauterine growth restriction, preterm delivery, very-low birth weight babies and pregnancy should be discouraged in patients with severe organ damage. However, with a multidisciplinary management, patients with SSc can have successful outcomes1. Little is known about the pathogenesis of obstetrical complications, as studies on placenta are case reports or description of a few cases2,3.Objectives:The aim of this study was to analyze the placental alterations with a focus on the role of inflammation in the pathogenesis of obstetrical complications in SSc, including the study of the atypical chemokine receptor 2 (ACKR2), involved in immune modulation and known to be highly expressed in circulating leucocytes in SSc patients4-6.Methods:Eight SSc pregnant patients were compared with 16 patients with other rheumatic diseases (ORD) and 16 healthy controls (HC), matched for gestational age. Clinical data were collected. Placentas biopsies were obtained for histopathological analysis and immunohistochemistry for CD3, CD20, CD11c, CD68 and ACKR2. Frozen placenta samples from 4 SSc, 8 ORD and 8 HC were analyzed by qPCR for ACKR2 gene expression and proteins were extracted for multiplex assay for cytokines, chemokines and growth factors involved in angiogenesis and inflammation. Statistical analysis was performed with parametric or non-parametric tests depending on samples distribution.Results:The number of placental CD3 (pConclusion:The higher number of placental inflammatory cells and the alterations in the levels of HGF and especially CCL5 could play a role in the pathogenesis of the obstetrical complications in SSc. ACKR2 does not seem involved in the obstetrical complications of SSc.References:[1]Taraborelli M, et al. Arthritis Rheum. 2012[2]Ibba-Manneschi L, et al. Ann Rheum Dis. 2010[3]Doss BJ, et al. Hum Pathol. 1998[4]Graham GJ. Eur J Immunol. 2009[5]Martinez de la Torre Y, et al. Proc Natl Acad Sci U S A. 2007[6]Codullo V, et al. Ann Rheum Dis. 2011Disclosure of Interests:None declared

Background:neonatal lupus syndrome (NLS) is an acquired disease caused by the trasplacental passage of anti-SSA antibodies. Congenital heart block (CHB) represents the most serious manifestation of NLS. The rate of CHB in Anti-SSA positive pregnant women ranges from 1 to 5% in different studiesObjectives:to retrospectively assess the prevalence of CHB in a cohort of anti-SSA positive pregnant women followed in 3 Italian tertiary centersMethods:pregnancies of anti-SSA positive women attending the pregnancy clinic of ASST Pini CTO/Policlinico Mangiagalli, Rheumatology Division of Spedali Civili, Brescia and Rheumatology Division of Ospedale S Matteo, Pavia from 2009 to 2019 were included. Patients underwent monthly clinical examination. Fetal heart rate was assessed weekly by Doppler ultrasound from 14thto 26thgestational week. On week 14 and 26, a fetal echocardiography was performed. A EKG was performed at birthResults:351 prospectively followed pregnancies in 292 anti-SSA/Ro positive women were included. Table 1 reports diagnosis. None of the prospectively followed pregnancies were complicated by complete CHB. Seven additional patients were referred to our clinics after diagnosis of CHB and were subsequently found to be anti-SSA positive, reporting no symptoms of diseases. Considering the 7 additional pregnancies, the incidence of CHB was 1.9%. We observed 3 neonates (0.8%) with cutaneous NLS and 1 case of transient increase of liver enzymes. In another neonate, a 1thdegree A-V block was found after birth. A complete analysis of maternal and fetal outcome was possible in 244 cases (Table 2) and compared with 3158 unselected healthy controls. Among these 244 cases, 65% were taking hydroxychloroquineTable 1.patients diagnosisn%Sjogren’s Syndrome58`20Systemic lupus erythematosus7626UCTD7425Asymptomatic Ro carriers5619Other2810292100Table 2.maternal and fetal outcomehealthy controls N=3158Anti-SSA/Ro ptsN=244P valuePrevious CHB n (%)2 (0.8)Anti-SSB pos n (%)46 (18.8)aPL pos n (%)49 (20)PregnancyLive births3158241Preeclampsia, n (%)43 (1.1)2 (0.8)nsDeliveryDelivery 401 (12.6) /201 (6)35 (15.6) / 14 (6)ns / nsCesarean Section, n (%)897 (29.3)115 (47.5)Conclusion:none of the patients prospectively followed in our centers before and during pregnancy developed complete CHB. If the 7 cases of anti-SSA positivity diagnosed after CHB detection were included in the analysis, the incidence of CHB was comparable to previous reports. Our data suggest that a strict follow up and proper treatment of anti-SSA positive patients with or without an autoimmune disease before and during pregnancy can reduce the risk of NLS. Further studies are warranted to confirm a possible protective role of anti-rheumatic treatments, including HCQReferences:[1]Fredi M. Front Cardiovasc Med. 2019Disclosure of Interests:Maria Gerosa: None declared, Micaela Fredi: None declared, Laura Andreoli: None declared, Cecilia Chighizola: None declared, Lorenza Maria Argolini: None declared, Davide Donzelli: None declared, Tamara Vojinovic: None declared, Véronique Ramoni: None declared, Elisa Bellis: None declared, Laura Trespidi: None declared, Federica Gazzola: None declared, Enrico Ferrazzi: None declared, Sonia Zatti: None declared, Fausta Benvenuti: None declared, Pier Luigi Meroni: None declared, Franco Franceschini: None declared, Carlomaurizio Montecucco: None declared, Rolando Cimaz: None declared, Roberto Caporali Consultant of: AbbVie; Gilead Sciences, Inc.; Lilly; Merck Sharp & Dohme; Celgene; Bristol-Myers Squibb; Pfizer; UCB, Speakers bureau: Abbvie; Bristol-Myers Squibb; Celgene; Lilly; Gilead Sciences, Inc; MSD; Pfizer; Roche; UCB, Angela Tincani: None declared

Background With the therapeutic advances of the last decades yielding to stable disease remission in the majority of patients, the goal of a successful pregnancy appears to be attainable for women affected by Rheumatoid Artrhitis (RA). However, individual risk stratification and measures to minimise it (e.g. withdrawal and wash-out of teratogenic drugs) are essential for the management of pregnancy in RA.(1 Objectives This analysis aims to evaluate the adherence to a reference clinical pathway of diagnostic, pharmacological and follow-up management in women with RA, and the influence of the adherence to this pathway on the outcome of pregnancy. Methods Data were extracted from the Lombardy Region’s (Italy) health databases for the period between 2004–2013. Patients with RA were identified through the chronic disease certification by rheumatologist (ICD9-CM code 714.0). Among these, women between the ages of 18 and 51 were selected. Data of controls from general population were also extracted. Conception has been approximated from the date of delivery or abortion. Seven healthcare quality indicators have been constructed: 1) screening of blood chemistry tests, 2) pre-conception musculoskeletal imaging, 3) pre-pregnancy antiphospholipid antibody tests, 4) ANA test and anti-ENA (antiRo/SSA) test, 5) no exposure or wash-out from teratogenic drugs (MTX/LEF); 6) no exposure to biological drugs; 7) rheumatological follow-up in outpatient visits. These 7 indicators were then summarised in 3 pathway indicators: 1) diagnostic pathway, 2) therapeutic pathway, 3) follow-up. The pregnancy outcome was defined on the basis of the DRG of complicated birth or abortion. Subanalysis on abortion was also done. The relationship between quality indicators and outcome variables was analysed using logistic models crude and adjusted for age and comorbidities, and the results presented as odds ratios (OR) and 95% confidence intervals (95% CI). Results 443 pregnancies of patients with RA were identified, with median age of 34 (IQR 31–37), median disease duration at conception of 3.8 years (IQR 1.83–6.19), 157 (35.4%) of which with unfavourable outcome pregnancy outcome, of which 115 pregnancy losses. The increase or decrease of risk for those who meet specific quality indicators and pathway indicators showed a better outcome for patients screened for autoantibodies and with no exposure or washout from MTX/LEF (Table). The comparisons of those who followed the ideal pathway or not compared to the general population showed a significant increase of risk only for patients not following the ideal pathway (Table). Conclusions The optimal management of pregnancy (stratification of pre-conceptional obstetric risk, modulation of therapy) in women with RA is associated with a reduced risk of unfavourable pregnancy outcome, bringing back that risk to that expected for a general obstetric control population. Reference [1] Gotestam Skorpen C, et al. The EULAR points to consider for use of antirheumatic drugs before pregnancy, and during pregnancy and lactation. Ann Rheum Dis2016May;75(5):795–810. Disclosure of Interest None declared

Background Rheumatic Diseases (RD) frequently affect women during reproductive age, therefore counselling on family planning is crucial for their quality of life. Children’s outcome is a major topic, but no large studies are available. Objectives To assess the long-term health conditions of children born to women with RD in a large multicentre cohort. Methods 24 Rheumatology Centres distributed the questionnaire (65 multiple-choice and 12 open-answer questions) to consecutive patients (18–55 years) in September 2015. Data were analysed dividing children upon maternal diagnosis: Chronic Arthritides (CA) and Connective Tissue Diseases (CTD). Results Data were collected for 320 children (166 males, 52%) born to 184 mothers (63 CA and 121 CTD). At the time of interview, children had a mean age of 17.1±9.6 years. Preterm delivery ( Conclusions In this long-term follow-up of children born to mothers with RD in this large, multicenter study of randomly interviewed women each AIID did not display a significantly increased frequency as compared to the literature; only coeliac showed a mild increased frequency. Children with LD had a tendency to cluster in the group of mothers with CTD, especially after maternal diagnosis (4/63, 6.3%), with a higher frequency as compared to general paediatric population. No significant relationships between ND/LD and prematurity, intrauterine drug exposure or maternal autoantibodies were identified. Acknowledgements Statistical analysis supported by an unrestricted grant by UCB Pharma. The authors wish to thank Patients Associations and Participants to the survey. Disclosure of Interest None declared

Background Cardiac neonatal lupus is due to placental transfer of maternal anti-Ro/SSA and anti-La/SSB autoantibodies to the fetus and mainly includes congenital heart block (CHB) and dilated cardiomyopathy. The prevalence of CHB has been estimated as 1%–2% in anti-Ro/SSA women while the recurrence rate is 16%–19%(.1 This condition is associated with a high rate of fetal/neonatal mortality and in the majority of cases requires pacemaker pacing.2–6 Objectives The rarity of this condition requires the establishment of collaborative registries in order to improve our knowledge. Here we report the data of the ongoing Italian Registry of the autoimmune congenital heart block (Lu.Ne), which was created in 2016 Methods The aim was to collect retrospective and prospective pregnancies complicated with CHB in patients with antibodies. Data regarding demography, treatment, maternal and neonatal outcome and follow-up were collected through an online electronic datasheet prepared in a Research Electronic Data Capture platform. Results Eighty-six cases of CHB were collected in 82 women with 85 pregnancies that occurred between 1969–2016. CHB was mostly detected in utero (81 cases, 90.6%) with 5 neonatal CHB. Demographic description of the mothers, pregnancy outcomes and treatment are reported in table 1. Child mortality was observed in 22 (25.5%) cases: 12 fetal, 5 termination of pregnancy and 5 postnatal. Maternal and fetal risk factors for fetal mortality were analysed and, at univariate analysis, factors associated with death were an earlier detection of CHB (20.9±0.9 weeks vs 24.8±5.4 weeks; p=0.007), hydrops (p=0.002;OR=11.3;CI95%1.84–69.2) and pericardial effusion (p=0.025;OR >100;CI95%2.88->100). Conclusions The Lu.Ne registry is an ongoing project aiming at collecting all Italian CHB. Our data showed similar rate of fetal/neonatal death and of PM implantation previously reported. We confirmed that hydrops and pericardial effusion are risk factors for fetal death. A peculiarity of our cohorts is that the majority of the mothers (59%) had an established diagnosis of systemic autoimmune disease at CHB detection. This is in contrast with other registries showing that usually CHB was incidentally detected in healthy women and related to the recruiting Centres all belonging to Rheumatology Society. The collection of cases from Gynaecological and Paediatric Centres, planned in the next months, will complete our analysis References [1] Brucato, et al. Arth Rheum2001;1831–35. [2] Eliasson H, et al. Circulation2011;124:1919–26. [3] Izmirly PM, et al. Circulation2011;124:1927–35. [4] Levesque K, et al. Autoimmun Rev2015;14:1154–60. [5] Lopes LM, et al. Circulation2008;118:1268–75. [6] Van den Berg NW, et al. Int J Cardiol2016;225:167–171. Acknowledgements This project was funded by Italian Society of Rheumatology Disclosure of Interest None declared

Background Rheumatic Diseases (RD) frequently affect women during reproductive age, therefore counselling on family planning is crucial for their quality of life. Children’s outcome is a major topic, but no large studies are available. This study aimed at assessing the long-term health conditions of children born to women with RD. Methods 24 Italian Rheumatology Centres distributed the questionnaire (65 multiple-choice and 12 open-answer questions) to consecutive patients (aged 18–55) during September 2015. Data were analysed dividing children upon maternal diagnosis: Chronic Arthritides (CA) and Connective Tissue Diseases (CTD). Results Data were collected for 320 children born to 184 mothers (63 CA and 121 CTD). At the time of interview, children had a mean age of 17.1±9.6 years. Pre-term delivery ( The occurrence of an autoimmune/inflammatory disease (AIID) and/or neurodevelopmental disorders (ND)/learning disabilities (LD) is reported in table 1. Twelve children (3.7%) were diagnosed with an AIID, mostly coeliac disease (8/12, 67%). Eleven children (3.4%) were diagnosed as having a ND and/or LD by a Paediatric Neuropsychiatrist. Data of in utero exposure to maternal autoantibodies and/or anti-rheumatic drugs were retrieved for 280 children (87.5%) and a comparison was performed between affected (n=11) and not-affected children (n=258). No association was found with ND/LD and in utero exposure to autoantibodies (ANA, anti-Ro, anti-dsDNA, aPL) or drugs (HCQ,AZA or steroids), neither with sex, preterm birth, birth weight or maternal diagnosis. Conclusions The long-term follow-up of children born to mothers with RD did not raise particular concerns in terms of relevant health problems. In particular, each AIID did not display a significantly increased frequency as compared to the literature. Children with ND/LD had a tendency to cluster in the group of mothers with CTD, especially after maternal diagnosis, with a higher frequency as compared to GPP (7.9% vs 3%). Our data suggest that the development of ND/LD in children of patients with RD cannot be linked exclusively to maternal disease. The results of this study can be reassuring for patients with RD about problems in the offspring possibly related to their disease.

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 study's 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 study's 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.

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ, The term 'undifferentiated connective tissue disease' (UCTD) is generally used to describe clinical entities characterised by clinical and serological manifestations of systemic autoimmune diseases but not fulfilling the criteria for defined connective tissue diseases (CTDs). In this narrative review, we summarise the results of a systematic literature research, which was performed as part of the ERN ReCONNET project, aimed at evaluating existing clinical practice guidelines (CPGs) or recommendations. No specific CPG on UCTD were found, potential areas of intervention are absence of a consensus definition of UCTD, need for specific monitoring and therapeutic protocols, stratification of UCTD based on the risk of developing a defined CTD and preventive measure for the future development of a more severe condition. Patients feel uncertainty regarding the name of the disease and feel the need of a better education and understanding of these conditions and its possible changes over time., This publication was funded by the European Union’s Health Programme (2014-2020).

Objective To investigate the presence of autoimmune rheumatic disorders among women with autoimmune thyroid disorders diagnosed during the first trimester of pregnancy and subsequent pregnancy outcomes. Design Case-control study. Setting Tertiary obstetric and gynecologic center. Patient(s) Pregnant women in the first trimester of pregnancy. Intervention(s) Clinical, laboratory, ultrasonographic evaluations. Main Outcome Measure(s) Thyroid-stimulating hormone (TSH) level; antibodies against thyroperoxidase, thyroid globulin and TSH receptor detection; screening for rheumatic symptoms and antinuclear antibodies (ANA); uterine artery pulsatility index evaluation; pregnancy complication onset. Result(s) Out of 3,450 women enrolled, 106 (3%) were diagnosed with autoimmune thyroid disorders. ANA were present in 18 (16.9%) of 106 cases and 26 (12.6%) of 206 controls. Of the cases, 28 (26.4%) of 106 reported rheumatic symptoms, 5 of these were diagnosed with Sjogren syndrome or with undefined connective tissue disease. Autoimmune thyroid diseases are statistically significantly associated with a higher risk of preeclampsia, fetal growth restriction, and overall pregnancy complications compared with controls, with a higher uterine artery pulsatility index, suggesting a defective placentation in thyroid disorders. The effect of ANA-positivity on moderate/severe adverse pregnancy outcomes was statistically significant among the patients with thyroid disorders (9 of 18 as compared to 8 of 88, odds ratio 9.65; 95% confidence interval, 2.613–7.81). Conclusion(s) Connective tissue diseases are frequently associated with autoimmune thyroid disorders diagnosed during the first trimester of pregnancy. Thyroid autoimmunity and ANA positivity independently increased the risk of adverse pregnancy outcomes.

Autoimmune rheumatic diseases in pregnancies are associated with increased adverse obstetric outcomes. We compared maternal soluble human leucocyte antigen-G (sHLA-G) blood levels in subjects with a rheumatic disease preexisting pregnancy and unaffected controls. Third-trimester blood maternal sHLA-G concentrations were significantly higher in subjects with rheumatic diseases than in controls (mean 93.1ng/ml [SD 42.1] vs 58.1ng/ml [SD 96.3], p=0.003). Cord blood sHLA-G concentrations were significantly higher in rheumatic disease than in those born to control mothers (median 41.2ng/ml [IQR: 3.3-44.0] vs 17.9ng/ml [IQR: 17.2-88.1], p=0.007). A strict positive correlation (r=0.88, p

Background Rheumatic diseases (RD) predominantly affect young women during reproductive age. Pregnancy, contraception and family planning (FP) are crucial for the quality of life of these patients. Objectives We aimed to investigate 9women9s health9 through a self-reported questionnaire. Answers from patients with connective tissue diseases (CTD) vs chronic arthritis (CA) were compared. Methods 24 centres distributed the questionnaire (65 multiple-choice and 12 open-answer questions) to women with RD (18–45years) regularly attending their outpatient clinics. Results Answers were collected from 249 CTD vs 149 CA patients. Their desire to have children was influenced by RD in 40% of cases: half of them reduced the number of children they wanted (Table 1). 39% CA vs 29% CTD were afraid of being mother because of disability. 24% CTD vs. 18% CA had at least one miscarriage; 21% CTD vs. 2% CA had more than one. 31% CTD and 34% CA were never asked about their desire to have children. 61% CTD vs 70% CA received counselling about contraception, given by a gynaecologist (G) (58% vs 64%), rheumatologist (R) (22% vs 14%) or both (7% vs 9%). 60% in both groups received a counselling before pregnancy: 34% vs 39% from R and G, 14% vs 22% by R. This positively changed family planning in 64% vs 59%. We created a Knowledge Index (based on the average of the normalized performed scores on 6 key questions for different sections): 55% CTD patients vs 44% CA had a medium-high score. A higher score directly correlated with the desire to became pregnant and with a multidisciplinary counselling. Conclusions This survey suggested that CTD have a major impact on FP and family size, possibly mediated by the increased rate of miscarriages as compared to CA. Concerns about reproductive issues could be positively overcome by adequate counselling. Rheumatologists should implement the discussion about FP and the compatibility of drugs with pregnancy in the management of young women with RD, especially those with CTD for whom contraception and pregnancy have particular implications. Acknowledgements Statistical analysis supported by an unrestricted grant by UCB Pharma Thanks to Patients9 Associations and Participants Disclosure of Interest None declared

Background Rheumatic diseases (RD) affect women during reproductive age. Children9s outcome is a major topic for counselling on family planning, but no large studies are available. Objectives We aimed at assessing the long-term health conditions of children born to mothers with RD through a self-reported questionnaire. Methods 24 Rheumatology Centers distributed the questionnaire (65 multiple choice and 12 open-answer questions) to consecutive women with RD attending their outpatient clinic during September 2015. Data were compared according to maternal diagnosis (MD) -chronic arthritis (CA) or connective tissue disease (CTD)- and to the timing of pregnancy (before or after MD of RD). Results The survey yielded data about 269 children born to 184 mothers (63 CA, 121 CTD). According to MD, children had a mean age of 17.1 (±9.6 SD) and 14.4 (±9.0 SD) years at the time of interview, and male children were 52/93 (56%) and 91/176 (52%), respectively. Twenty-nine children in the CA group (31.2%) and 64 in the CTDs group (36.4%) were born after MD of RD. Pre-term delivery (before 37 weeks) was observed in 48 cases (17.8%), mostly children born to mothers with CTD (37/48, 77%). Regarding school performance, 12 children (4.5%) repeated one year of school, in 7 cases for indolence, in 3 for learning disabilities (LD)/health problems (HP), in 2 for family problems. Eleven of these children were born before MD. Overall, 9 children (3.3%) were diagnosed with a LD and 53 children were affected by HP requiring either hospitalization or evaluation by a Specialist (Table). Three children (1%) were affected by autoimmune disease. Conclusions The long-term follow-up of children born to women with RD is reassuring of an outcome similar to that of the general pediatric population (GPP). Autoimmune diseases are not frequent. Problems seem to cluster in children born to CTD, especially after MD, with a higher frequency of LD (6.3% vs 2.5–3.5% of GPP), but no particular pattern of exposure to maternal autoantibodies nor drugs was observed. Acknowledgements Statistical analysis supported by an unrestricted grant by UCB Pharma Thanks to Patients Associations and Participants to the survey Disclosure of Interest None declared

Background Systemic lupus erythematosus (SLE) primarily affects women of childbearing age. Despite the overall favorable outcome, pregnancy represents a challenge for both patients and clinicians. Since the complications rate is linked to the disease activity, the achievement of remission is recommended before pregnancy. Prednisone represents a cornerstone in SLE management and is safely used, at low doses ( Objectives We aimed to investigate whether this drug is safe and effective as the immediate release prednisone (IRP) in SLE pregnant patients. Methods We retrospectively evaluated 9 female patients, fulfilling the ACR criteria for SLE, consulting our Centers in a 4-years observational range. All of them, thanks to a stable disease (not requiring treatment regimen modifications within 12 months), experienced a successful pregnancy during the observation. All the cases were taking low-dose MRP (5 to 7.5 mg/daily) as a baseline treatment, from at least 6 months. They were matched to 9 controls, defined as SLE patients with the same age and duration of disease, taking the same prednisone dose, from at least 6 months, in the IR formulation. Overall pregnancy outcome features; SLE disease activity (calculated at least once during pregnancy, SLEPDAI) and at baseline/post-partum (SLEDAI) score; patient9s global assessment (VAS) at baseline, during pregnancy and in postpartum (mm); need of treatment changes throughout pregnancy and at postpartum (%) were assessed. Homogeneity tests, percentages and scores comparison were run out by non-parametric statistical analysis. Results Mean MRP age group was 26±7; disease duration, 4±8 years; IR one, respectively, 28±6 and 3±9 (both, p=ns). SLEDAI at baseline was 1±0.1 among MPR and 1±0.3 among IR women; SLEPDAI, 1±0.9 and 2±0.2 (both, p=ns). No major perinatal complications were detected. Preterm births, cesarean section rates, newborns weight and APGAR scores did not differ between the two subpopulations (all, p=ns). SLEDAI assessed at postpartum was 2.8±0.6 in MRP subjects and 3.4±0.4 in IR (p Conclusions Activity (SLEDAI) score was significantly higher at postpartum and treatment had to be increased in IR patients, in comparison to the MRP, to manage SLE. VAS, conversely, was significantly higher among IR, both during pregnancy and postpartum. No major perinatal side effects were observed during the study; minor and expected complications rates did not differ between the two subpopulations. Despite the limited number of subjects, MRP treatment seems to be as safe, but more effective, in comparison to the standard IR one, during pregnancy of SLE-affected women. Disclosure of Interest None declared

Background Always more frequently rheumatic patients (pts) ask for Assisted Reproductive Technologies (ART) for infertility problems. The main concern is determined by the ovarian stimulation, associated with an increased risk of disease flare and thrombosis. Objectives To describe a case series of ART cycles in pts affected by rheumatic diseases, analyzing pregnacy rate and outcome, fetal-maternal complications and disease flares. Methods We included all the consecutive pts evaluated in the Pregnancy Clinic of 5 Italian Rheumatology Units after having performed ≥1 ART cycle from 1997 to 2016. Results We included 60 pts: infertility was primary (no previous spontaneous conception) in 68% of cases, idiopathic in 76.5%, of male origin in 8.3%, of female origin in 15%, mixed in 0.2%. One hundred and eleven ART cycles were performed: 13IUI, 44FIVET (3eterologous), 53ICSI (14eterologous), 1embryodonation. Antiphospholipid antibodies were positive in 23 (38.3%) pts and in 45 (40.5%) cycles. Procedures were unstimulated in 14 (12.6%) stimulated in 97 (59.5%) cases: with GnRH-Antagonist in 26 (26.8%), GnRH-agonist in 60 (61.8%), gonadotropins only in 7 (7.3%) and with clomiphene in 4 (4.1%) cases. We registered 3 (3%) cases of Ovarian Hyperstimulation Syndrome, all after Agonist protocol. Overall we observed 46 pregnancies, with a pregnancy rate of 38.7% for omologous procedures and of 55.5% for eterologous. No miscarriages were reported. Pregnancies ended with 35 single and 5 twin birth, 6 are still ongoing: we recorded 4 (8.9%) perinatal deaths: 1 baby died at birth for multiple malformations and 3 died in the first days of life for extreme prematurity. One or more fetal complications were reported in 11 (27.5%) pregnancies: 3PROM, 3IUGR, 3oligohydramnios, 4fetal malformation (2 severe, 1multiple and fatal). The mean age of the women suffering from fetal complications was significantly lower (p:0.03). One or more maternal complications were reported in 13 (32.5%) pregnancies: 4gestational diabetis, 2thrombocytopenia, 2pre-eclampsia, 2placenta previa, 1hypothyroidism, 1gestational hypertension, 1cholestasis of pregnancy. Disease Flares were reported in 5 (12.5%) pregnancies: 4 articular (2 in RA patients, 2 in SLE patients), 1haematological (in SLE patient, after spontaneous therapy discontinuation). No cases of thrombosis were reported.During puerperium: 1 (2.5%) post-partum hemorrage (no LMWH ongoing), 1 articular flare (2.5%). Additional informations are available in Table 1. Conclusions We didn9t found any good reasons to discourage ART performance in rheumatic pts: the safety seems to be high and the complications rate is in line with that reported in general population. An adequate prophylaxis during stimulation, pregnancy and puerperium seems to provide a good protection from thrombotic complications. Disclosure of Interest None declared

Objective Fetal exposure to maternal anti-SSA/Ro antibodies is necessary but not sufficient for the development of autoimmune congenital heart block (CHB), suggesting that other factors, such as fetal genetic predisposition, are important. Given the previously described association between major histocompatibility complex alleles and CHB risk, we undertook the present study to test the hypothesis that a variant form of HLA–C Asn80Lys, which binds with high affinity to an inhibitory killer cell immunoglobulin-like receptor (KIR) and thus renders natural killer (NK) cells incapable of restricting inflammation, contributes to the development of CHB. Methods Members of 192 pedigrees in the US and Europe (194 cases of CHB, 91 unaffected siblings, 152 fathers, 167 mothers) and 1,073 out-of-study controls were genotyped on the Immunochip single-nucleotide polymorphism microarray. Imputation was used to identify associations at HLA–C Asn80Lys (Asn, C1; Lys, C2) and KIR. Tests for association were performed using logistic regression. McNemar's test and the pedigree disequilibrium test (PDT) were used for matched analyses between affected and unaffected children. Results Compared with out-of-study controls of the same sex, the C2 allele was less frequent in the mothers (odds ratio [OR] 0.63, P = 0.0014) and more frequent in the fathers (OR 1.40, P = 0.0123), yielding a significant sex-by-C2 interaction (P = 0.0002). The C2 allele was more frequent in affected siblings than in unaffected siblings (OR 3.67, P = 0.0025), which was consistent with the PDT results (P = 0.016); these results were observed in both sexes and across the US and European cohorts. There was no difference in the frequency of the inhibitory KIR genotype (KIR AA) between affected and unaffected children (P = 0.55). Conclusion These data establish C2 as a novel genetic risk factor associated with CHB. This observation supports a model in which fetuses with C2 ligand expression and maternal anti-SSA/Ro positivity may have impaired NK cell surveillance, resulting in unchecked cardiac inflammation and scarring.

Background and aims SLE often affects women of childbearing age. Prednisone is safely used during pregnancy. Modified-release prednisone (MRP) is a treatment option, but no data exist regarding gestation: we aimed to compare its safety and effectiveness to the immediate release formulation (IRP) in SLE pregnancies. Methods During a 5 year period, we enrolled 18 SLE female patients experiencing a pregnancy. Nine (cases), taking low-dose MRP (5 to 7.5 mg/daily) as a baseline treatment, were matched to 9 controls (same age and disease duration), taking the same prednisone dose in the IR formulation. Pregnancy outcome; SLEDAI/SLEPDAI; patient’s VAS and need of treatment changes were assessed at baseline, during pregnancy and at postpartum. Results SLEDAI at baseline was 2±0.1 among MPR and 2±0.3 among IR women; SLEPDAI, 3±0.9 and 3±0.2 (both, p=ns). No major perinatal complications were detected. Preterm births, caesarean section rates, newborns weight and APGAR scores did not differ between the two subpopulations (all, p=ns). SLEDAI at postpartum was 3.8±0.6 in MRP subjects and 5.4±0.4 in IR (p Conclusions Among IR patients, activity was significantly higher during postpartum and treatment had to be increased. VAS was significantly different (higher among IR), both during pregnancy and postpartum. MRP seems to be as safe, but more effective, in comparison the IR, during pregnancy of SLE women.

Antiinflammatory drugs have greatly improved the quality of life and management of several rheumatic conditions. However, the benefits of antiinflammatory therapies should be weighed against the potential consequences, with careful evaluation of side effects. The aim of the present chapter is to summarize current evidence on potential cardiovascular effects of antiinflammatory therapies including either adverse or potentially desirable effects. Nonsteroidal antiinflammatory drugs (NSAIDs) and disease-modifying antirheumatic drugs (DMARDs) are reviewed, with a focus on hydroxychloroquine, methotrexate, sulfasalazine, minocycline, varespladib, leflunomide, and colchicine.

Objective To evaluate the effect of connective tissue disease (CTD) diagnosed during the first trimester on uterine arteries (UtA) Doppler velocities and on pregnancy outcomes. Method Pregnant women were screened for CTDs during the first trimester, using a questionnaire, testing for autoantibodies, rheumatologic examination and UtA Doppler evaluations. Results Out of 3932 women screened, 491 (12.5%) were screened positive at the questionnaire; of them, 165(33.6%) tested positive for autoantibodies, including 66 eventually diagnosed with undifferentiated connective tissue disease (UCTD), 28 with a definite CTD and 71 with insufficient criteria for a diagnosis. Controls were 326 women screened negative for autoantibodies. In logistic analysis, women diagnosed with either UCTD (OR = 7.9, 95% CI = 2.3–27.3) or overt CTD (OR = 24.9, 95% CI = 6.7–92.4), had increased rates of first trimester bilateral UtA notches compared with controls. The rates of bilateral UtA notches persisting in the second (15/94 vs 0/326, p

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.

Perfusion of human foetal heart with anti-Ro ⁄SSA antibodies induces transient heart block. Anti-Ro ⁄SSA antibodies may cross-react with T- and L-type calcium channels, and anti-p200 antibodies may cause calcium to accumulate in rat heart cells. These actions may explain a direct electrophysiological effect of these antibodies. Congenital complete heart block is the more severe manifestation of so-called ‘‘Neonatal Lupus’’. In clinical practice, it is important to distinguish in utero complete versus incomplete atrioventricular (AV) block, as complete AV block to date is irreversible, while incomplete AV block has been shown to be potentially reversible after fluorinated steroid therapy. Another issue is the definition of congenital AV block, as cardiologists have considered congenital blocks detected months or years after birth. We propose as congenital blocks detected in utero or within the neonatal period (0‐27 days after birth). The possible detection of first degree AV block in utero, with different techniques, might be a promising tool to assess the effects of these antibodies. Other arrhythmias have been described in NL or have been linked to anti-Ro ⁄SSA antibodies: first degree AV block, in utero and after birth, second degree (i.e. incomplete block), sinus bradycardia and QT prolongation, both in infants and in adults, ventricular arrhythmias (in adults). Overall, these arrhythmias have not a clinical relevance, but are important for research purposes.

Anti-Ro/SSA antibodies are associated with neonatal lupus (congenital heart block (CHB), neonatal transient skin rash, hematological and hepatic abnormalities), but do not negatively affects other gestational outcomes, and the general outcome of these pregnancies is now good, when followed by experienced multidisciplinary teams. The prevalence of CHB, defined as an atrioventricular block diagnosed in utero, at birth, or within the neonatal period (0–27 days after birth), in the offspring of an anti-Ro/SSA-positive women is 1–2%, of neonatal lupus rash around 10–20%, while laboratory abnormalities in asymptomatic babies can be detected in up to 27% of cases. The risk of recurrence of CHB is ten times higher. Most of the mothers are asymptomatic at delivery and are identified only by the birth of an affected child. Half of these asymptomatic women develop symptoms of a rheumatic disease, most commonly arthralgias and xerophtalmia, but few develop lupus nephritis. A standard therapy for CHB is still matter of investigation, although fluorinated corticosteroids have been reported to be effective for associated cardiomyopathy. Serial echocardiograms and obstetric sonograms, performed at least every 1–2 weeks starting from the 16th week of gestational age, are recommended in anti-Ro/SSA-positive pregnant women to detect early fetal abnormalities that might be a target of preventive therapy.

Objective To evaluate the prevalence of undiagnosed rheumatic diseases in the first trimester of pregnancy. Design We screened for rheumatic diseases in 1210 consecutive pregnant women during the first trimester of pregnancy using a 10-item questionnaire. Setting A university hospital in northern Italy. Population One hundred and thirty-seven (11.3%) women who answered positively to at least one question constituted the cases and were compared with 107 negative controls. Methods Cases and controls were tested for rheumatic autoantibodies (antinuclear antibody, anti-double-stranded DNA, anti-extractable nuclear antigen, anticardiolipin antibody, anti-β2-glycoprotein I antibodies and lupus anticoagulant) and were evaluated by a rheumatologist for a definite diagnosis of rheumatic disease. Main outcome measures Prevalence of undiagnosed rheumatic disease in the first trimester of pregnancy. Results The overall rate of positivity to the antibodies tested was 43.1% (59/137) among cases and 9.3% (10/107) in the controls (P < 0.001). A definitive diagnosis of rheumatic disease was made in 35 cases (25.5%) and in none of the controls (P

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, 1. year before and 1. year 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 (

Undifferentiated connective tissue diseases (UCTDs) are a heterogeneous group of disorders characterized by symptoms and signs suggestive of systemic autoimmune rheumatic disease (ARD), but which do not fulfill all the established criteria for definite diagnosis of a condition. Although a third of UCTDs can progress to a definite ARD within months or years, most UCTDs can remain stable for years with minimal disease activity. The annual incidence of UCTD in the general population ranges from 14 to 140 per 100 000 people. UCTDs are associated with the persistence of several circulating autoantibodies including antinuclear, antiphospholipid or antithyroid antibodies. Immunological evaluation of subjects with UCTDs suggests a proinflammatory state and dysregulation of the Th1/Th2 balance. Autoantibodies have well-known deleterious effects on placentation and have been associated with an increased risk of prematurity, fetal growth restriction (FGR), preeclampsia, and congenital atrioventricular heart block. Although epidemiological and biological data suggest a potential negative impact on reproductive outcomes, the relationship between UCTD and pregnancy outcomes has not been adequately studied. While awaiting definitive data from large studies, obstetricians should be aware that rheumatic disorders in their early, incomplete, or undifferentiated phases can adversely affect pregnancy outcomes, increasing the likelihood of pregnancy loss, FGR, preeclampsia, and prematurity.

SummaryPrevious thrombosis, diagnosis of systemic lupus erythematosus (SLE) and triple antiphospholipid (aPL) antibody positivity have recently been found to be independent factors associated to pregnancy failure during conventional therapy in women with antiphospholipid syndrome (APS). This study aimed to assess the effect of various treatment strategies on pregnancy outcomes in women with APS and the risk factors for pregnancy failure. One hundred ninety-six pregnancies of 156 patients diagnosed with APS were analysed: 118 (60.2%) of these had previous thrombosis, 81 (41.3%) were diagnosed with SLE, and 107 (54.6%) had triple aPL positivity. One hundred seventy-five (89.3%) were treated with conventional therapies (low-dose aspirin [LDA] or prophylactic doses of heparin + LDA or therapeutic doses of heparin + LDA), while 21 (10.7%) were prescribed other treatments in addition to conventional therapy. The pregnancies were classified into seven risk profiles depending on the patients’ risk factors – thrombosis, SLE, and triple aPL positivity – and their single, double or triple combinations. It was possible to find significant difference in outcomes correlated to treatments only in the thrombosis plus triple aPL positivity subset, and logistic regression analysis showed that additional treatments were the only independent factor associated to a favourable pregnancy outcome (odds ratio=9.7, 95% confidence interval= 1.1–88.9, p-value

Background Undifferentiated connective tissue disease (UCTD) is a group of systemic autoimmune conditions not fulfilling the classification criteria for a definite connective tissue disease (CTD). While an average of 20–40% of UCTD patients develop a defined CTD during follow-up, the remaining patients maintain an undefined diseases. Objectives The objective was to assess flare or differentiation into well-defined CTD of UCTD newly diagnosed during pregnancy and to evaluate the prevalence of obstetric complications in the context of the new diagnosis. Methods We examined 54 patients with UCTD newly diagnosed during pregnancy, followed during pregnancy and after delivery at our rheumatologic unit. Diagnosis of UCTD was made at the time of pregnancy. Women in their first trimester (T0) were screened using a two-step approach using a self-administered 10-item questionnaire, a subsequent testing for rheumatic autoantibodies (ANA, anti-dsDNA, ENA, anticardiolipin antibodies, anti-β2-glycoprotein I antibodies and lupus anticoagulant) and evaluation by a rheumatologist, who made the final diagnosis. The same questionnaire was re-administered at least one year after delivery (T1) and the same rheumatic autoantibodies were tested at the same time. Results Fourty-two patients (77.77%) showed persistence or worsening of symptoms and 45 (83.33%) had at least one positivity for autoantibodies at T1. The diagnosis of UCTD was confirmed in 29 patients (53.70%). Sixteen (16/54) women (29.62%) received a final diagnosis of another rheumatic disease: 12 patients with systemic lupus erythematosus (22.22%), 2 (3.70%) antiphospholipid syndrome, 1 (1.85%) spondyloarthritis and 1 (1.85%) Behcet disease. Amelioration of symptoms with a resulting unconfirmed diagnosis was seen among 9/54 (16.67%) of them. We then focused on the pregnancy that was ongoing at T0. We observed some obstetrical complications: 3 miscarriages, 3 fetal loss, 6 hypertensive disorders, 4 intrauterine growth restriction, 6 preterm deliveries and 8 small for gestational age babies. These major obstetrical complications were not significantly different in the three different groups of new diagnoses. Also in the univariate analysis performed through Fisher9s test for each single obstetric complication there was no significant difference between groups. Conclusions The questionnaire is an optimal screening method to detect undiagnosed rheumatic diseases in pregnancy, in particular UCTDs. Furthermore, in spite of their evolution or remission, UCTDs are always associated with negative effects on the outcome of pregnancy. References Spinillo A, Beneventi F, Epis OM, Montanari L, Mammoliti D, Ramoni V, et al. Prevalence of undiagnosed autoimmune rheumatic diseases in the first trimester of 87 pregnancy. Results of a two-steps strategy using a self-administered questionnaire and autoantibody testing. BJOG An Int J Obstet Gynaecol 2008;115:51–7. Spinillo A, Beneventi F, Ramoni V, Caporali R, Locatelli E, Simonetta M, et al. Prevalence and significance of previously undiagnosed rheumatic diseases in pregnancy. Ann Rheum Dis 2012;71:918–23. Disclosure of Interest None declared

Background About 25% of pregnant RA patients remain active during pregnancy and need continuation of effective therapy to maintain low disease activity [1]. Recent evidence supports the use of TNF inhibitors (TNFi) to achieve these goals [2]. The overall safety of TNFi exposure during pregnancy has been demonstrated [3–4]. Certolizumab pegol (CZP) has received particular interest because of its low transplacental transfer, an advantage compared to several other TNFi [5]. A recent study analyzing CZP exposure during gestation has not shown harmful effects on pregnancy outcomes [6]. Since there are few data on child outcome, our case series adds observations on the safety of CZP in pregnancy. Objectives The study purpose consists in assessing CZP exposure safety during pregnancy in a group of RA patients. Methods During a 48 months period, we retrospectively evaluated 8 RA patients exposed to CZP in the 1st and/or the 2nd trimester of pregnancy. All patients had signed an informed consent regarding the potential risk of biologic agents for the fetus. Details regarding demographic and clinical presentation as well as pregnancy outcome and child health were collected. Data on child development during the first 6 months of life were obtained. Results The eight enrolled patients had been treated with CZP for 6 to 18 months. Three patients received methotrexate (MTX) and other TNFi (infliximab or etanercept) before pregnancy, which were discontinued 6–24 months before conception. During pregnancy all patients were treated with the standard dose of CZP 200 mg every 2 or 3 weeks. In addition, all patients received low-dose prednisone ranging from 5±2.5 mg daily. Two subjects were in addition on sulfasalazine 500 mg x 3/day, and three others on hydroxychloroquine (HCQ) 200 mg twice daily. In 6/8 patients, CZP treatment was continued throughout the first trimester. In 2 cases high disease activity required continuation of CZP until the end of the second trimester. No obstetric, neonatal or perinatal severe complication was observed. Except for one SGA child all neonates were healthy at birth. One child was hospitalized at the age of 4 months for disseminated Candida albicans infection, but recovered completely with amphotericin B treatment. All other children developed normally during the first 6 months of life. None of the newborn was breastfed, due to the lack of data on safety. All babies were vaccinated according to the mandatory Italian schedule (includes no live vaccine during the first 6 months of life); one child had the 5th month dose postponed to the 6th month of life. Conclusions The limits of our case series consist in the small numbers and the lack of measuring CZP levels in cord blood. However, our data add to the experience that CZP might be considered in pregnant RA patients when disease activity requires continuation of therapy throughout pregnancy. References Ostensen M, et al. Autoimm Rev 2015;14:370–86. Chambers CD, et al. Birth Defects Res A Clin Mol Teratol 2012;94:607–11. Marchioni RM, et al. World J Gastroenterol 2013;19:2591–602. Weber-Schoendorfer C, et al. Br J Clin Pharmacol. 2015;80:727–39. Mahadevan U, et al. Clin Gastroenterol Hepatol 2013;11:293–4. Clowse MED, et al. J Rheumatol 2015;42:2270–8. Disclosure of Interest None declared

Background Data on pregnancy in Systemic Sclerosis (SSc) are limited;we recently published IMPRESS,a retrospective multicenter study that compared 109 pregnancies from 99 SSc women with a general obstetric population (GOP).In SSc women preterm deliveries (PD, Methods This is a fully prospective,multicenter case-control study of 3 groups of people: 1) 100 pregnant SSc patients, 2) 200 not-pregnant SSc women (matched for age, auto-antibody pattern, limited/diffuse/sine scleroderma – L/D/S – form and obstetric history), 3) 200 healthy pregnant women (matched for age and obstetric history).We will prospectively investigate disease activity during pregnancy and further year,pregnancy outcome and children health status at birth and at 1 year Results 39 pregnancies are currently ongoing,22 patients have already delivered:8 ACA+ (6 L,1 D,1 S),13 Scl70+ (7 L,4 D, 2 S),1 RNA-P3+ D, 2 L form without SSc-specific autoantibodies.We observed 4 miscarriages (1 ACA+, 2 Scl70+,1 RNA-P3+), 1 therapeutic abortion at W22 (ACA+ D in treatment with prednisone 15mg/d and cyclophosphamide),1 early voluntary termination,2 SPD in Scl70+ L (1 cesarean section at W30, due to IUGR and fetal heart rate alteration;1 spontaneous in twin pregnancy: one twin with VLBW and both of them with respiratory distress at birth), 2 PD (both of them in SCl70+ L disease at W 36), 1 pre-eclampsia at W 37 in Scl70+ limited disease, with pulmonary embolism during post-partum. Till now,16 mothers and 28 SSc controls had completed one year surveillance after delivery.We observed disease progression in two cases: the ACA+D patient treated with prednisone and cyclophosphamide who underwent therapeutic abortion showed a kidney function worsening till hemodyalisis;the Scl70+L patient who underwent twin pregnancy showed significant worsening in pulmonary function testing,without specific findings at chest CT. One child,born at W36 from Scl70+L mother, died at 3 months due to cardiac malformation and aesopaghus atresia;all other children showed a regular growth at 12 months pediatric evaluation Conclusions IMPRESS 2 is still going on,and we hope to answer to important questions: 1) are complications of SSc more frequent during pregnancy? 2) Are some autoantibodies protective for prematurity? 3) Which is the impact of prematurity on children development? Disclosure of Interest None declared