Management of pregnancy in autoimmune rheumatic diseases: maternal disease course, gestational and neonatal outcomes and use of medications in the prospectiveItalian P-RHEUM.it study.

OBJECTIVES: To investigate pregnancy outcomes in women with autoimmune rheumatic diseases (ARD) in the Italian prospective cohort study P-RHEUM.it. METHODS: Pregnant women with different ARD were enrolled for up to 20 gestational weeks in 29 Rheumatology Centres for 5 years (2018-2023). Maternal and infant information were collected in a web-based database. RESULTS: We analysed 866 pregnancies in 851 patients (systemic lupus erythematosus was the most represented disease, 19.6%). Maternal disease flares were observed in 135 (15.6%) pregnancies. 53 (6.1%) pregnancies were induced by assisted reproduction techniques, 61 (7%) ended in miscarriage and 11 (1.3%) underwent elective termination. Obstetrical complications occurred in 261 (30.1%) pregnancies, including 2.3% pre-eclampsia. Two cases of congenital heart block were observed out of 157 pregnancies (1.3%) with anti-Ro/SSA. Regarding treatments, 244 (28.2%) pregnancies were treated with glucocorticoids, 388 (44.8%) with hydroxychloroquine, 85 (9.8%) with conventional synthetic disease-modifying anti-rheumatic drugs and 122 (14.1%) with biological disease-modifying anti-rheumatic drugs. Live births were 794 (91.7%), mostly at term (84.9%); four perinatal deaths (0.5%) occurred. Among 790 newborns, 31 (3.9%) were small-for-gestational-age and 169 (21.4%) had perinatal complications. Exclusive maternal breast feeding was received by 404 (46.7%) neonates. The Edinburgh Postnatal Depression Scale was compiled by 414 women (52.4%); 89 (21.5%) scored positive for emotional distress. CONCLUSIONS: Multiple factors including preconception counselling and treat-to-target with pregnancy-compatible medications may have contributed to mitigate disease-related risk factors, yielding limited disease flares, good pregnancy outcomes and frequency of complications which were similar to the Italian general obstetric population. Disease-specific issues need to be further addressed to plan preventative measures.

Pregnancy in antiphospholipid syndrome: what should a rheumatologist know?

This review focuses on the management of reproductive issues in women who have antiphospholipid syndrome (APS) or are carriers of antiphospholipid antibodies (aPL). The importance of aPL detection during preconception counselling relies on their pathogenic potential for placental insufficiency and related obstetric complications. The risk of adverse pregnancy outcomes can be minimized by individualized risk stratification and tailored treatment aimed at preventing placental insufficiency. Combination therapy of low-dose acetylsalicylic acid and heparin is the mainstay of prophylaxis during pregnancy; immunomodulation, especially with hydroxychloroquine, should be considered in refractory cases. Supplementary ultrasound surveillance is useful to detect fetal growth restriction and correctly tailor the time of delivery. The individual aPL profile must be considered in the stratification of thrombotic risk, such as during assisted reproduction techniques requiring hormonal ovarian stimulation or during the follow-up after pregnancy in order to prevent the first vascular event.

Sleep-disordered breathing and pregnancy outcomes: The impact of maternal oxygen saturation.

OBJECTIVE: To investigate pathological associations between sleep-disordered breathing (SDB) and pregnancy outcomes. METHODS: From May 2016 to September 2019, obese women during their uncomplicated singleton pregnancies underwent screening sleep questionnaires, oxygen saturation monitoring, and, in proper cases, complete overnight polysomnography. Their medical records were also recorded. RESULTS: In all, 112 pregnant women were included in the study cohort; 44 showed an oxygen desaturation index ≥10, and their newborns had a significantly higher rate of congenital abnormalities and respiratory distress syndrome compared with the women with normal pulse oximetry. Stepwise multivariate regression analysis showed that basal oxygen saturation was independently associated with the occurrence of fetal growth restriction. CONCLUSION: Among obese pregnant women, the rate of congenital abnormalities is higher in the ones with altered pulse oximetry. Maternal basal oxygen saturation in the first trimester of pregnancy predicts fetal growth restriction independently of maternal age, ethnicity, body mass index, gravidity, and hypertensive disorders of pregnancy.

A strange case of pleuritic pain in the third trimester of pregnancy.

Pulmonary sequestration is an uncommon congenital malformation of the lung, generally diagnosed in childhood or adolescence, corresponding to dysplastic lung tissue not communicating with the rest of vascular or bronchial lung system but receiving an arterial blood supply from systemic arteries. Currently, surgical resection is usually indicated in order to prevent or treat related symptoms or complications, although controversy exists regarding its use in asymptomatic patients and adults. We present the case of a 32-year-old pregnant woman with acute chest pain and vomiting diagnosed with intralobar sequestration at 32+2 weeks of gestation and treated with pulmonary lobectomy after giving birth by cesarean section at 33+0 weeks of gestation.

Variations of C3 and C4 Before and During Pregnancy in Systemic Lupus Erythematosus: Association With Disease Flares and Obstetric Outcomes.

OBJECTIVE: To analyze complement level variations in systemic lupus erythematosus (SLE) pregnancies, focusing on disease flares and obstetric complications. METHODS: SLE pregnancies prospectively followed by multidisciplinary teams from 1987 to 2018 in 2 Italian rheumatology centers were retrospectively analyzed. As reference, pregnancy-modified ranges of normal levels of C3 and C4 were derived from 175 pregnancies from the general obstetric population (GOP), as previously described by our group. RESULTS: Two hundred forty-six pregnancies in 172 patients with SLE were analyzed. Eighty-nine percent were live births. Thirty-five flares were recorded in 30 pregnancies (12.2%) and obstetric complications occurred in 47 pregnancies (19.1%) including 27 pregnancy losses, 11 severely preterm births (2 resulting in perinatal death), and 15 hypertensive disorders. C3 and C4 levels were higher in the GOP than in patients with SLE, at any time point. C3 and C4 levels progressively increased during pregnancy in both GOP and SLE pregnancies without flare and obstetric complications, whereas this physiological increase was not observed in pregnancies with flares or obstetric complications. A significantly higher frequency of low C4 was found in pregnancies with flares (at preconception and in each trimester) and preterm births (at preconception). In multivariate analysis, low C4 at preconception was associated with flares (odds ratio 13.81, 95% CI 3.10-61.43, P < 0.001). CONCLUSION: Low C4 at preconception was found to be an independent risk factor for SLE flare during pregnancy. Not only C3 and C4 levels but also their variations should be observed, as their failure to increase can be useful to predict risk of complications and suggest closer monitoring.

Reproductive Issues and Pregnancy Implications in Systemic Sclerosis.

Systemic sclerosis (SSc) is a rare systemic autoimmune disease that can influence reproductive health. SSc has a strong female predominance, and the disease onset can occur during fertility age in almost 50% of patients. Preconception counseling, adjustment of treatment, and close surveillance during pregnancy by a multidisciplinary team, are key points to minimize fetal and maternal risks and favor successful pregnancy outcomes. The rates of spontaneous pregnancy losses are comparable to those of the general obstetric population, except for patients with diffuse cutaneous SSc and severe internal organ involvement who may carry a higher risk of abortion. Preterm birth can frequently occur in women with SSc, as it happens in other rheumatic diseases. Overall disease activity generally remains stable during pregnancy, but particular attention should be paid to women with major organ disease, such as renal and cardiopulmonary involvement. Women with such severe involvement should be thoroughly informed about the risks during pregnancy and possibly discouraged from getting pregnant. A high frequency of sexual dysfunction has been described among SSc patients, both in females and in males, and pathogenic mechanisms of SSc may play a fundamental role in determining this impairment. Fertility is overall normal in SSc women, while no studies in the literature have investigated fertility in SSc male patients. Nevertheless, some considerations regarding the impact of some immunosuppressive drugs should be done with male patients, referring to the knowledge gained in other rheumatic diseases.

Anti-SSA/Ro positivity and congenital heart block: obstetric and foetal outcome in a cohort of anti-SSA/Ro positive pregnant patients with and without autoimmune diseases.

OBJECTIVES: Neonatal lupus (NL) is an acquired disease caused by the transplacental passage of anti-SSA/Ro antibodies. The rate of congenital heart block (CHB), its most serious manifestation, ranges from 1 to 5%. The aim of this study was to retrospectively assess the prevalence of CHB in anti-SSA/Ro positive pregnant women with or without systemic autoimmune diseases from 2010 to 2020. METHODS: Patients underwent monthly visit and a shared follow-up programme of weekly (16th-24th week) foetal heart rate assessment by obstetric ultrasound. RESULTS: 322 pregnancies in 258 anti-SSA/Ro patients were included; 314 were followed from the beginning of pregnancy because of the known presence of anti-SSA/Ro autoantibodies and 1 case of CHB occurred in an anti-SSA/Ro+ asymptomatic subject (0.3%). In the same period, 8 additional patients were referred to our clinics after in utero CHB diagnosis and subsequent discovery of anti-SSA/Ro without a disease diagnosis. Globally, 9 cases of congenital CHB (2.8%) occurred: 7 complete, 1 II-III degree and 1 rst degree CHB. Anti-SSB/La positivity was associated with a higher risk of CHB (7.8% vs. 1.2%; p=0.0071). No differences in maternal or foetal outcomes were found in comparison with a large cohort of unselected pregnancies except for caesarian section. Hydroxychloroquine (HCQ) was used in 58.3% pregnancies, with a different prevalence according with maternal diagnosis. CONCLUSIONS: Our data suggest that anti-SSA/Ro positive patents with a de ned systemic autoimmune disease undergoing a strict follow-up since positive pregnancy test display a low risk of pregnancy complications, including but not limited to NL.

Frequency of positive antiphospholipid antibodies in pregnant women with SARS-CoV-2 infection and impact on pregnancy outcome: A single-center prospective study on 151 pregnancies.

Background: At the beginning of the SARS-CoV-2 pandemic, there was a lack of information about the infection's impact on pregnancy and capability to induce de novo autoantibodies. It soon became clear that thrombosis was a manifestation of COVID-19, therefore the possible contribution of de novo antiphospholipid antibodies (aPL) raised research interest. We aimed at screening SARS-CoV-2 positive pregnant patients for aPL. Methods: The study included consecutive pregnant women who were hospitalized in our Obstetric Department between March 2020 and July 2021 for either a symptomatic SARS-CoV-2 infection or for other reasons (obstetric complications, labour, delivery) and found positive at the admission nasopharyngeal swab. All these women underwent the search for aPL by means of Lupus Anticoagulant (LA), IgG/IgM anti-cardiolipin (aCL), IgG/IgM anti-beta2glycoprotein I (aB2GPI). Data about comorbidities, obstetric and neonatal complications were collected. Results: 151 women were included. Sixteen (11%) were positive for aPL, mostly at low titre. Pneumonia was diagnosed in 20 women (5 with positive aPL) and 5 required ICU admission (2 with positive aPL). Obstetric complications occurred in 10/16 (63%) aPL positive and in 36/135 (27%) negative patients. The occurrence of HELLP syndrome and preeclampsia was significantly associated with positive aPL (p=0,004). One case of maternal thrombosis occurred in an aPL negative woman. aPL positivity was checked after at least 12 weeks in 7/16 women (44%): 3 had become negative; 2 were still positive (1 IgG aB2GPI + IgG aCL; 1 IgM aB2GPI); 1 remained positive for IgG aCL but became negative for aB2GPI; 1 became negative for LA but displayed a new positivity for IgG aCL at high titre. Conclusions: The frequency of positive aPL in pregnant women with SARS-CoV-2 infection was low in our cohort and similar to the one described in the general obstetric population. aPL mostly presented as single positive, low titre, transient antibodies. The rate of obstetric complications was higher in aPL positive women as compared to negative ones, particularly hypertensive disorders. Causality cannot be excluded; however, other risk factors, including a full-blown picture of COVID-19, may have elicited the pathogenic potential of aPL and contributed themselves to the development of complications.

Stopping bDMARDs at the beginning of pregnancy is associated with disease flares and preterm delivery in women with rheumatoid arthritis.

Objectives: Women with Rheumatoid Arthritis (RA) can experience flares during pregnancy that might influence pregnancy outcomes. We aimed at assessing the disease course during pregnancy and identifying risk factors for flares. Methods: Data about prospectively-followed pregnancies in RA were retrospectively collected before conception, during each trimester and in the post-partum period. Clinical characteristics, disease activity (DAS28-CRP3), medication use, and pregnancy outcomes were analysed with regard to disease flares. Results: Among 73 women who had a live birth, 64 (88%) were in remission/low disease activity before conception. During pregnancy, a flare occurred in 27 (37%) patients, mainly during first and second trimester. Flares during pregnancy were associated with the discontinuation of bDMARDs at positive pregnancy test (55% of patients with flare vs. 30% of patients with no flare, p 0.034, OR 2.857, 95% CI 1.112-8.323) and a previous use of >1 bDMARDs (33% of patients with flare vs. 10% of patients with no flare, p 0.019, OR 4.1, 95%CI 1.204-13.966). Preterm pregnancies were characterised by higher values of CRP [10 mg/L (5-11) vs. 3 mg/L (2.5-5), p 0.01] and DAS28-CRP3 [4.2 (1.9-4.5) vs. 1.9 (1.7-2.6), p 0.01] during the first trimester as compared with pregnancies at term. Preterm delivery was associated with the occurrence of flare during pregnancy (flare 27% vs. no-flare 7%, p 0.034, OR 4.625, 95%CI 1.027-20.829). Conclusion: Preterm delivery in RA patients was associated with flares during pregnancy. Flares occurred more frequently after the discontinuation of bDMARDs at positive pregnancy test. Women with aggressive RA on treatment with bDMARDs should be considered as candidates for continuing bDMARDs during pregnancy in order to reduce the risk of flare and adverse pregnancy outcomes.

Managing puerperium in patients with systemic autoimmune diseases: an update.

INTRODUCTION: Puerperium is a critical period for patients affected by autoimmune rheumatic diseases for the risk of disease's flares and difficulties in treating lactating mothers. We want to summarize the literature data about psychological and pharmacological management of these patients and possible risk factors of disease's flares. AREAS COVERED: We made a narrative review on recent studies about puerperium in rheumatic autoimmune diseases patients. EXPERT OPINION: The physicians involved in management of patients during puerperium and in the follow-up of babies need to agree on maternal treatment because they need to reassure mothers about the safety of the prescribed medications. Furthermore, women with rheumatic diseases could present some musculoskeletal limitations and psychological problems, such as postpartum depression, which can lead to a sense of inadequacy to the mother's task. Families and physicians should be aware of these possible complications and support the new mothers providing correct counseling and practical help.

Obstetric consequences of a false-positive diagnosis of large-for-gestational-age fetus.

OBJECTIVE: To compare delivery outcomes between true-positive (TP) and false-positive (FP) large-for-gestational-age (LGA) fetuses, appropriate-for-gestational-age (AGA) fetuses, and false-negative (FN) LGA fetuses. METHODS: Retrospective cohort study of singleton pregnancies at risk for macrosomia without contraindication to vaginal delivery, receiving an ultrasound scan at 34-37 weeks of pregnancy. RESULTS: In all, 430 pregnancies were included: 155 TP LGA, 87 FP LGA, 177 AGA and 11 FN LGA newborns. Cesarean section rate during labor was significantly higher in FP LGA than in AGA (19% vs. 8.7%) but not significantly different between FP LGA and TP LGA (19% vs. 32.4%). Median birth weight z score was significantly higher in TP LGA (1.9) compared with the FP LGA and AGA (0.91 and 0.84, respectively), whereas no significant differences were found between FP LGA and AGA. Admission to a neonatal intensive care unit was significantly more frequent in TP LGA than AGA, whereas shoulder dystocia, postpartum hemorrhage, and third- to fourth-degree perineal tears were similar between the different groups. CONCLUSION: A false-positive diagnosis of LGA fetus is associated with a significant increase of cesarean section during labor. Therefore, a suspicious ultrasound may result in reduction of the clinical threshold for the diagnosis of abnormal labor.

Maternal, pregnancy and neonatal outcomes of twin gestations in women with rheumatic diseases: A single-center, case-control study.

OBJECTIVE: To assess maternal, pregnancy and neonatal outcomes of twin pregnancy (TP) in women with rheumatic diseases (RD) (Group A) as compared to those of singleton pregnancy (SP) in women with RD (Group B) and TP in the general obstetric population (GOP) (Group C). METHODS: Case-control study including TP in RD during the period 2009-2020 at single institution. Women in Group A were matched with women of the same age at conception and affected by the same RD (Group B). Women in Group A and C were also matched. RESULTS: Fifty-three women with RD (13 in Group A and 40 in Group B) and 39 healthy controls were included. RD was quiescent in 85% of patients in both Groups A and B. Spontaneous conception was more frequent in Group B (98%), as compared to A (62%) (p = 0.002). Emergency cesarean section and premature delivery were more frequent in Group A as compared to B and C (54% vs 15% vs 23%, p = 0.008, 69% vs 13% vs 39%, p < 0.000 and p = 0.054, respectively). Five babies (21%) in Group A required admission to the neonatal intensive care unit (NICU), but none in Group B (p = 0.007). CONCLUSION: This is the first case-control study assessing the outcomes of TP in women with RD. An increased risk of preterm delivery, emergency cesarean section and admission to NICU as compared to both SP in RD and TP in the GOP was observed. Multidisciplinary management is warranted to minimize these risks.

The Influence of Treatment of Inflammatory Arthritis During Pregnancy on the Long-Term Children's Outcome.

The management of reproductive issues in women with inflammatory arthritis has greatly changed over decades. In the 1980-1990s, women with refractory forms of arthritis were either not able to get pregnant or did choose not to get pregnant because of their disabling disease. Hence, the traditional belief that pregnancy can induce a remission of arthritis. The availability of biologic agents has allowed a good control of aggressive forms of arthritis. The main topic of discussion during preconception counselling is the use of drugs during pregnancy and breastfeeding. Physicians are now supported by international recommendations released by the European League Against Rheumatism and the American College of Rheumatology, but still they must face with cultural reluctance in accepting that a pregnant woman can take medications. Patient-physician communication should be centered on the message that active maternal disease during pregnancy is detrimental to fetal health. Keeping maternal disease under control with drugs which are not harmful to the fetus is the best way to ensure the best possible outcome for both the mother and the baby. However, there might be concerns about the influence of the in utero exposure to medications on the newborn's health conditions. Particularly, studies suggesting an increased risk of autism-spectrum-disorders in children born to women with rheumatoid arthritis has raised questions about neuropsychological impairment in the offspring of women with chronic arthritis. As a multidisciplinary group of rheumatologists and child neuropsychiatrists, we conducted a study on 16 women with chronic forms of arthritis whose diagnosis was determined before pregnancy and their 18 school-age children. The children underwent a complete neurological examination and validated tests/questionnaires. Behavioral aspects of somatization and anxiety/depression (internalizing problem) or an "adult profile" were found in nearly one third of children. Children at a high risk of neurodevelopmental problems were born to mothers with a longer history of arthritis and were breastfeed for less than 6 months of age or were not breastfeed at all. No association was found with other maternal characteristics such as autoantibody existence and disease activity during and after the pregnancy.

Disease course and obstetric outcomes of pregnancies in juvenile idiopathic arthritis: are there any differences among disease subtypes? A single-centre retrospective study of prospectively followed pregnancies in a dedicated pregnancy clinic.

To study disease activity during pregnancy and obstetric outcomes in patients with juvenile idiopathic arthritis (JIA) upon different subsets and with focus on medication use. Retrospective observational study of 22 pregnancies in 16 JIA patients (95.5% Caucasian) who were followed between 2010 and 2018. Disease activity, flares and medications were recorded before conception, during each trimester and postpartum period. Pregnancies occurred in 10 (45.5%) oligoarticular extended (OLA-E), 6 (27.3%) in polyarticular (PLA), 4 in (18.2%) systemic (SYS), 1 (4.5%) in oligoarticular persistent (OLA-P) and 1 (4.5%) in enthesitis-related arthritis (ERA) JIA patients. The median age at disease diagnosis and at conception was 5.5 and 28 years (respectively). The median disease duration was 20 years. Nineteen (95%) pregnancies started in a period of stable disease remission. Among the 22 pregnancies, 20 ended with a live birth (90.9%). No spontaneous miscarriages occurred; two voluntary interruption of pregnancy were performed. There were 7 flares in 6/20 pregnancies (35%) and 8 flares (8/22, 36.4%) occurred in postpartum period, all of them in OLA-E and PLA patients. Seven patients (35%) were taking biological disease-modifying anti-rheumatic drugs (bDMARDs) at conception, and 6 of them stopped this treatment at positive pregnancy test. Five patients resumed bDMARDs either during pregnancy (3 exposed during the third trimester) or puerperium due to a flare. Four preterm deliveries (20%) were recorded, all in patients who had a flare during pregnancy. The preconception counselling should include the evaluation of disease subset, as OLA-E and PLA may flare more than other subsets, especially if bDMARDs are discontinued at positive pregnancy test. Continuation of bDMARDs during pregnancy should be considered to minimize the risk of adverse pregnancy outcomes, particularly preterm delivery. Key Points • In our cohort, all the flares during pregnancy and 75% of postpartum flares were observed in patients who withdrew bDMARDs and cDMARDs at the beginning of pregnancy. • Flares were observed only in PLA and OLA-E patients. • Preterm delivery occurred in 20% of the pregnancies; all of these patients had a disease flare during pregnancy.

Insulinoma Identified in Puerperium: Association with Pregnancy and Literature Review.

Postpartum hypoglycemia in non-diabetic women is a rare condition. We report the case of a 34-year-old woman who experienced neuroglycopenia 2 days after delivery. Corresponding to severe hypoglycemia, we found inappropriately elevated insulin and C-peptide levels. Following magnetic resonance imaging a lesion of 10×8 mm was detected in the head of the pancreas. An ultrasound-guided fine needle aspiration of the mass confirmed the diagnostic suspicion of a pancreatic neuroendocrine tumor. Complete surgical enucleation of the insulinoma resulted in immediate and permanent resolution of the hypoglycemia. The postoperative course was uneventful. Histopathological and immunohistochemical analyses were consistent with insulinoma. The diagnostic approach to postpartum hypoglycemia represents a challenge for multidisciplinary teamwork. LEARNING POINTS: Although insulinomas are extremely rare during pregnancy, most cases are recognized or become symptomatic during the first trimester.Symptoms of insulinomas may be initially masked due to changes in glucose metabolism and insulin resistance associated with pregnancy.In pregnancy, surgical treatment should be avoided whenever possible because of the risks to both mother and fetus; conservative treatment, including dietary intake, intravenous glucose and glucagon, should be initiated to control the hypoglycemia symptoms.

Primary Hyperparathyroidism in Pregnancy: A Case Report.

Primary hyperparathyroidism (PHP) is the third most common endocrine disorder. We report the case of a 28-year-old woman who experienced general weakness, hyperemesis gravidarum and hypercalcemia at 11 weeks of gestation. Corresponding to hypercalcemia, we found inappropriately elevated parathyroid hormone levels. Through neck computed tomography a solitary adenoma of the parathyroid gland, measuring 6 × 2.9 × 11 mm has been documented. An ultrasound-guided fine needle aspiration from the mass confirmed the suspicious of a benign tumor. Left superior parathyroidectomy resulted in immediate and permanent resolution of hypercalcemia. The postoperative course was uneventful. Histopathological and immunohistochemical analyses were consistent with parathyroid adenoma. The diagnostic approach to hypercalcemia in pregnancy represents a challenge for multidisciplinary teamwork.

Infertility in women with systemic autoimmune diseases.

Infertility consists by definition in" failure to achieve a clinical pregnancy after 12 months or more of regular unprotected intercourse" while the term subfertility means a delay to achieve pregnancy. Several factors can contribute to infertility or subfertility in patients with systemic autoimmune diseases. The association of systemic autoimmune conditions with endometriosis, celiac disease and thyroid autoimmunity that are well known causes of infertility and/or subfertility need to be taken in consideration when difficulties in the onset of pregnancy is reported. The majority of the used antirheumatic drugs do not interfere with fertility. However, the use of cyclophosphamide, limited to severe disease, can provoke premature ovarian failure; to preserve fertility a preventive treatment is available. Nonsteroidal anti-inflammatory drugs can cause temporary infertility and corticosteroids are associated to a prolonged time to pregnancy in some rheumatic diseases. Data on the association of antiphospholipid antibodies (aPL) with infertility are still debated but in general an increased rate of aPL is described patients undergoing medically assisted reproductive techniques. In systemic lupus erythematosus aPL and other autoantibodies (i.e. anti-oocytes) can contribute to the infertility of some patients. Subfertility, rather than infertility, is observed in patients with rheumatoid arthritis; the particular physical conditions of these women can also account for this. Physicians should not forget the patients' age, that is mandatory in order to preserve their chance to have children.

Triple Antiphospholipid (aPL) Antibodies Positivity Is Associated With Pregnancy Complications in aPL Carriers: A Multicenter Study on 62 Pregnancies.

Objective: Antiphospholipid antibodies (aPL) are risk factors for thrombosis and adverse pregnancy outcomes (APO). The management of the so called "aPL carriers" (subjects with aPL positivity without the clinical criteria manifestations of APS) is still undefined. This study aims at retrospectively evaluating the outcomes and the factors associated with APO and maternal complications in 62 pregnant aPL carriers. Methods: Medical records of pregnant women regularly attending the Pregnancy Clinic of 3 Rheumatology centers from January 1994 to December 2015 were retrospectively evaluated. Patients with concomitant autoimmune diseases or other causes of pregnancy complications were excluded. Results: An aPL-related event was recorded in 8 out of 62 patients (12.9%) during pregnancy: 2 thrombosis and 6 APO. At univariate analysis, factors associated with pregnancy complications were acquired risk factors (p:0.008), non-criteria aPL manifestations (p:0.024), lupus-like manifestations (p:0.013), and triple positive aPL profile (p:0.001). At multivariate analysis, only the association with a triple aPL profile was confirmed (p:0.01, OR 21.3, CI 95% 1.84-247). Patients with triple aPL positivity had a higher rate of pregnancy complications, despite they were more frequently receiving combined treatment of low dose aspirin (LDA) and low molecular weight heparin (LMWH) at prophylactic dose. Conclusion: This study highlights the importance of risk stratification in pregnant aPL carriers, in terms of both immunologic and non-immunologic features. Combination treatment with LDA and LMWH did not prevent APO in some cases, especially in carriers of triple aPL positivity. Triple positive aPL carriers may deserve additional therapeutic strategies during pregnancy.