Sonia Zatti

Follow-up of infants exposed to hydroxychloroquine given to mothers during pregnancy and lactation

OBJECTIVE:To determine the effect of hydroxychloroquine treatment during pregnancy and lactation on babies of mothers affected by rheumatic diseases.STUDY DESIGN AND METHODS:A total of 40 infants born from mothers affected by rheumatic diseases and treated with hydroxychloroquine during pregnancy were enrolled in a prospective observational study. Main outcome measures at birth were incidence of prematurity, congenital malformations and neonatal infections. Of these babies, including 13 who were breast-fed, 24 were followed up during early infancy for visual function and neurodevelopmental outcome.RESULTS:Preterm delivery was the main complication (20.5%). No significant congenital malformations or neonatal infections were detected. All infants, including those who were breast-fed, had normal visual function and neurodevelopmental outcome.CONCLUSIONS:Hydroxychloroquine treatment during gestation and lactation appeared to be safe. The relatively high incidence of preterm deliveries may reflect the maternal disease state.

Maternal thrombophilia and the risk of recurrence of preeclampsia

OBJECTIVE The aim of this prospective study was to determine the impact of thrombophilia on the recurrence of preeclampsia. STUDY DESIGN In a multicenter, observational, cohort design, 172 white patients with a previous pregnancy complicated by preeclampsia were observed in the next pregnancy. They were evaluated for heritable thrombophilia (factor V Leiden and factor II G20210A mutations, protein S, protein C, and antithrombin deficiency), hyperhomocystinemia, lupus anticoagulant, and anticardiolipin antibodies. Development of preeclampsia and maternal complications and both gestational age at delivery and birthweight were recorded. RESULTS Sixty women (34.9%) showed the presence of a thrombophilic defect. They had a higher risk for the recurrence of preeclampsia (odds ratio [OR], 2.5; 95% confidence interval [CI], 1.2-5.1), compared to patients without thrombophilia. Similar findings were observed considering only heritable thrombophilia. Thrombophilic patients were at increased risk for the occurrence of very early preterm delivery (< 32 weeks; OR, 11.6; 95% CI, 3.4-43.2). CONCLUSION When counseling white women with a history of preeclampsia, screening for thrombophilia can be useful for preconceptional counseling and pregnancy management.

Autoimmunity and Pregnancy Autoantibodies and Pregnancy in Rheumatic Diseases

Abstract:  In women who suffer from rheumatic diseases (RDs) the risk of repeated fetal loss, intrauterine growth restriction, and preterm birth remains higher than in the general population. Antiphospholipid antibodies are frequently observed in patients with systemic lupus erythematosus (SLE). They are associated with recurrent pregnancy losses that may occur at any age of gestation. The cause of fetal death is believed to be intraplacental thrombosis, although other pathologic mechanisms have been described. A recent study has described the increased frequency of learning disabilities in the offspring of SLE patients; case reports of neonatal thrombosis are very rare. Transplacental passage of IgG anti‐Ro/SS‐A antibodies is linked to neonatal lupus (2%). The main manifestation is congenital heart block (CHB) due to the binding of anti‐Ro/SS‐A antibodies to cardiac conduction tissue and to the consequent inflammatory/fibroid reaction. Neonatal lupus also includes cutaneous, hematologic, and hepatobiliary manifestations, which are typically transient. Incomplete CHB can be treated with fluorinated corticosteroids to prevent the progression and decrease inflammation. Intravenous immunoglobulin, decreasing the tranplacental passage of anti‐Ro/SS‐A, has been proposed as prophylactic therapy in patients who had one or more child with CHB. Transplacental passage of antiplatelet antibodies, in about 10% of mothers with SLE, can induce thrombocytopenia in the fetus or the neonate. Patients with RD have a higher incidence of anxiety and depression compared to the general population, interfering with parenthood and the upbringing of children.

A comprehensive review of the clinical approach to pregnancy and systemic lupus erythematosus.

Nowadays, most of the young women affected by Systemic Lupus Erythematosus (SLE) can carry out one or more pregnancies thanks to the improvement in treatment and the consequent reduction in morbidity and mortality. Pregnancy outcome in these women has also greatly improved in the last decades. A correct timing for pregnancy (tailored on disease activity and established during a preconception counselling), together with a tight monitoring during the three trimesters and the post-partum period (to timely identify and treat possible obstetric complications or maternal disease flares), as well as the concept of multidisciplinary management, are currently milestones of the management of pregnancy in SLE patients. Nevertheless, the increasing knowledge on the compatibility of drugs with pregnancy has allowed a better treatment of these patients, by choosing medications that control maternal disease activity without harming the foetus. However, particular attention and strict monitoring should be dedicated to SLE pregnant women in particular clinical settings: patients with lupus nephritis and patients with aPL positivity or Antiphospholipid syndrome, who are at higher risk for maternal and foetal complications, but also patients with anti-Ro/SSA and/or anti-La/SSB antibodies, because of the risk of neonatal lupus. A discussion on family planning, as well as counselling on contraception, should be part of the everyday-practice for physicians caring for SLE women during their reproductive age. Another issue is the possible reduction of fertility in these women, that can be due to different reasons. Consequently, the request for assisted reproduction techniques has been increasing in the last years, so that rheumatologists and gynaecologists should be prepared to counsel SLE patients also in this particular setting.

Fetal weight estimation in gestational diabetic pregnancies: comparison between conventional and three‐dimensional fractional thigh volume methods using gestation‐adjusted projection

To evaluate the accuracy of gestation‐adjusted birth‐weight estimation using a three‐dimensional (3D) fractional thigh volume (TVol) method in pregnant women with gestational diabetes mellitus (GDM), and to compare it with the conventional two‐dimensional method of Hadlock et al.

The Efficacy and Safety of Cyclosporin A in Pregnant Patients with Systemic Autoimmune Diseases

Cyclosporin A (CYS A) is an immunosuppressant agent administered in autoimmune diseases, and its use during pregnancy and lactation is a debated topic.

The role of second trimester uterine artery Doppler in pregnancies with systemic lupus erythematosus

The aim of this article is to assess the predictive value of second trimester mean uterine artery Doppler pulsatility index (mUtA PI) for pregnancy complications in women with systemic lupus erythematosus (SLE).

Antiphospholipid syndrome and pregnancy

Since the 1960s, antiphospholipid antibodies have been known to be associated with repeated miscarriages and fetal losses. Other complications of pregnancy, such as preterm birth, with pre-eclampsia or severe placental insufficiency were also frequently reported and are included in the current classification criteria of the antiphospholipid syndrome. The titer, isotype or antigen specificity of the antibodies may be important in risk determination. The pathogenesis of pregnancy failures is not only linked to the thrombophilic effect of antiphospholipid antibodies but also to a direct effect of antibodies on trophoblast differentiation and invasion. The study of experimental animal models provided sound evidence of the pathogenic role of antiphospholipid antibodies both in lupus-prone and -naive mice. The classification of pregnant antiphospholipid syndrome patients as being at a ‘high risk’ has completely changed their prognosis due to obstetric monitoring and the application of effective therapy. In fact, despite the high rates of complications and preterm delivery, a successful outcome can now be achieved in a large majority of cases.

FRI0411 A Multicenter Prospective Evaluation of the Risk Profile in Pregnant Patients with Persistent Positivity for Antiphospholipid Antibodies (APL)

Background Antiphospholipd antibodies positivity (aPL) are considered as risk factors for a poor obstetric outcome. Several clinical and laboratory features have been associated with the risk of a pregnancy failure. Objectives To determine risk factors of having poor pregnancy outcome in patients (pts) with established aPL positivity with or without a diagnosis of primary antiphospholipid syndrome (APS) despite the administration of the accepted “conventional treatment” (low dose aspirin (LDA) and heparin (H)) when indicated. Methods We considered 276 pregnancies in 193 women prospectively followed in the 3 Institutions involved between 2000 and 2014. None of the pts had a concomitant systemic autoimmune disease. Data were collected from clinical charts using a common database and included the 3 assays to detect aPL. We considered as “poor pregnancy outcome” the occurrence of a pregnancy loss (early miscarriages and fetal loss), perinatal deaths, preterm deliveries before the 34 weeks and HELLP Syndrome. Results Among the 193 pts, 127 fulfilled the classification criteria for APS and 66 did not. According to their clinical history and/or the laboratory, the patients were divided in 4 groups: 87 pts with pure obstetric APS (O-PAPS, 121 pregnancies), 40 thrombotic with or without obstetric APS (T-PAPS, 66 pregnancies), 32 incomplete APS (incomplete clinical or laboratory criteria, 47 pregnancies) and 34 aPL carriers without any clinical manifestation prior to the index pregnancy (42 pregnancies). The mean age at the pregnancy onset was 32.5 years (SD 5.09), the global rate of live births was 86.9%; poor obstetrical outcome was observed in 48 pregnancies (17.4%); the outcome in the groups is detailed in table 1. In the table 2 we reported the several features that resulted, at the univariate analysis, with a significant prevalence among the pts with poor obstetric outcome regardless of the group. A thrombotic event occurred in 5 pts: 2 during pregnancies (1 O-APS and 1 aPL carrier) and 3 during puerperium, with 2 deep venous thrombosis with pulmonary embolism in 1 O-APS and 1 T-APS and 1 myocardial infarction after an early miscarriage in a T-APS. Finally 1 T-APS had a catastrophic syndrome during puerperium, and 3 pts (2 T-APS and 1 aPL carrier) had an onset or a relapse of mild-moderate thrombocytopenia (without HELLP syndrome). The combination of LDA plus H was administered in 94% of pregnancies that fulfilled the criteria for APS, while the rate was 57% for the incomplete APS and 39% for aPL carriers. Conclusions Our preliminary results show that, regardless of a high rate of use of the conventional therapy, a poor obstetrical outcome and the occurrence of several severe maternal complications were not uncommon, especially in T-PAPS and aPL carriers. Several factors (irrespectively of the diagnosis) seem to be associated with serological, clinical and acquired features. Disclosure of Interest None declared

OC26.02: Fetal weight estimation in pregnancy complicated by obesity: comparison between conventional and a new 3D ultrasound method

Rose &McCallum, Schild (2 formulae), Scott, Shepard, Siemer, Thurnau, Weiner (2 fomulae) and Warsof). To assess the accuracy of the formulae the differences between FBW and EFW (expressed as grams, as percentage of FBW and as absolute percentage (|FBW − EFW|/FBW) were calculated. To assess whether the accuracy changes with increasing FBW a linear regression analysis was performed. Results: 193 pregnancies fulfilled the inclusion criteria with a mean FBW of 1001g. The mean differences between FBW and EFW were within 10% with the formulae from Hadlock I and III, Scott, Hadlock IV, Hadlock II and Masal (absolute percentage of FBW: 9.2%, 9.2%, 9.3%, 9.4%, 9.9% and 9.9%). Of those, EFW and FBW was within 10% of the FBW in more than 60% of the cases with the formulae from Hadlock I and III and with the Scott formula (64.2%, 61.1%, 60.6%). Linear regression showed that with the Hadlock I and III formulae the accuracy did not change with increasing fetal weight (r=0.936 and p=0.938, p<0,0001, intercept and slope not significantly different from 0 and 1). With these weight estimation formulae, the 95% limits of agreement between FBW and EFW were −19% to 19% (Hadlock I) and −17.3% to 20.1% (Hadlock III) of the FBW. Conclusion: Of the 23 commonly available weight estimation formulae, the Hadlock I (BPD-HC-AC-FL) and III (BPD-AC-FL) formulae were most accurate in estimating fetal weight in fetuses with a birth weight of 1500g or less.