Angela Botta

Risk factors for pregnancy failure in patients with anti-phospholipid syndrome treated with conventional therapies: a multicentre, case–control study

OBJECTIVE To identify the risk factors associated with pregnancy failure in patients with APS treated with conventional therapy. METHODS A multicentre, case-control study was conducted to compare APS patients with successful and unsuccessful pregnancy outcomes. We retrospectively considered 410 pregnancies of women diagnosed with primary APS. The study focused on 57 unsuccessful pregnancies (considered the study population) and 57 successful pregnancies (considered the control population) matched for age and therapy. All the patients had been treated with conventional protocol treatments including low-dose aspirin and/or heparin. The clinical and laboratory features of the two groups of women diagnosed with APS were compared. RESULTS The independent risk factors for pregnancy failure were: (i) the presence of SLE or other autoimmune diseases [odds ratio (OR) 6.0; 95% CI 1.7, 20.8; P = 0.01]; (ii) history of both thrombosis and pregnancy morbidity (OR 12.1; 95% CI 1.3, 115.3; P = 0.03); and (iii) triple [Immunoglobulin (Ig) G/IgM aCLs plus IgG/IgM anti-β(2) glycoprotein I antibodies plus LA] aPL positivity (OR 4.1; 95% CI 1.0, 16.7; P = 0.05). APS patients diagnosed on the basis of a single positive test and/or history of pregnancy morbidity alone were generally found to have successful pregnancies. CONCLUSION It would seem from these findings that the risk of pregnancy failure in APS women planning to conceive can be stratified on the basis of some specific clinical and laboratory features.

European registry of babies born to mothers with antiphospholipid syndrome

Objectives This study aimed to describe the long-term outcome and immunological status of children born to mothers with antiphospholipid syndrome, to determine the factors responsible for childhood abnormalities, and to correlate the childs immunological profile with their mothers. Methods A prospective follow-up of a European multicentre cohort was conducted. The follow-up consisted of clinical examination, growth data, neurodevelopmental milestones and antiphospholipid antibodies (APL) screening. Children were examined at 3, 9, 24 months and 5 years. Results 134 children were analysed (female sex in 65 cases, birth weight 3000±500 g, height 48±3 cm). Sixteen per cent had a preterm birth (<37 weeks; n=22), and 14% weighted less than 2500 g at birth (n=19). Neonatal complications were noted in 18 cases (13%), with five infections (4%). During the 5-year follow-up, no thrombosis or systemic lupus erythematosus (SLE) was noted. Four children displayed behavioural abnormalities, which consisted of autism, hyperactive behaviour, feeding disorder with language delay and axial hypotony with psychomotor delay. At birth lupus anticoagulant was present in four (4%), anticardiolipin antibodies (ACL) IgG in 18 (16%), anti-β2 glycoprotein-I (anti-β2GPI) IgG/M in 16 (15%) and three (3%), respectively. ACL IgG and anti-β2GPI disappeared at 6 months in nine (17%) and nine (18%), whereas APL persisted in 10% of children. ACL and anti-β2GPI IgG were correlated with the same mothers antibodies before 6 months of age (p<0.05). Conclusion Despite the presence of APL in children, thrombosis or SLE were not observed. The presence of neurodevelopmental abnormalities seems to be more important in these children, and could justify long-term follow-up.

Laboratory criteria of the obstetrical antiphospholipid syndrome - Data from a multicentric prospective European women cohort

A debate on updating the laboratory criteria of antiphospholipid syndrome (APS) was recently opened in view to lower the risk of over diagnosis of the syndrome. Based on data related to thrombotic APS, it proposes the exclusion of anticardiolipin antibodies (aCL) and anti-beta2-glycoprotein 1 (a-beta2-GPI) IgM detection. Here, we examine this possibility in a study which focuses on obstetrical APS (OAPS). We report new data on a prospective multicenter European cohort of 109 pregnant women having APS. Among them, 73 had purely obstetrical APS, not associated to autoimmune diseases or thrombosis. Isolated antibodies and isolated aCL positivity were present in 50/109 (46%) and in 34/109 (31%) of the women, respectively. An isolated a-beta2-GPI IgM was present in three women. These results suggest that aCL and a-beta2-GPI IgM cannot be dropped for the diagnosis and classification of OAPS. The low level of some antibodies associated with severe obstetrical complications raise the issue of keeping or not the same laboratory criteria for OAPS and for thrombotic APS and whether additional criteria after large prospective studies could further improve diagnosis.

Predictors of Pregnancy Outcome in Antiphospholipid Syndrome: A Review

In pregnant women, antiphospholipid syndrome (APS) is associated with an increased risk of preeclampsia, fetal intrauterine growth restriction, and other complications related to uteroplacental insufficiency. In the last two decades, several studies were performed to identify the predictive role of some parameters in relation to obstetric outcome in APS patients. Among these, the uterine velocimetry Doppler is the most studied. It provides a non-invasive method for the study of uteroplacental blood flow, being able to detect a condition of impaired placental perfusion, due to the presence of circulating antiphospholipid antibodies (aPL). To date, the uterine artery Doppler velocimetry resulted to be a useful tool to identify APS pregnancies at higher risk of adverse pregnancy outcome. False-positive IgM for toxoplasmosis, others, rubella, cytomegalovirus, herpes viruses (TORCH) complex is associated to a worse pregnancy outcome because it reflects a dysregulation of the immune system which may amplify placental autoimmune damage. Moreover low levels of complement components are related to an increased incidence of obstetrical complications, suggesting that placental deposition of immune complexes and activation of complement cascade may contribute to placental failure APS related. The abnormal uterine Doppler velocimetry, false-positive TORCH IgM and low levels of complement components can be considered prognostic indexes of poor pregnancy outcome in APS.

Complementemia and obstetric outcome in pregnancy with antiphospholipid syndrome

Objective: To investigate the predictive value of serum C3 and C4 complement component levels in relation to pregnancy outcome in patients with antiphospholipid syndrome (APS). Materials and methods: A prospective study of 47 pregnancies associated with APS was performed. Pregnancy outcome was analyzed in terms of: fetal loss, preterm delivery (≤34 gestational weeks), fetal intrauterine growth restriction (IUGR), birth weight <2500 g and preeclampsia. Week at delivery, neonatal birth weight and neonatal birth weight percentile were also investigated. Hypocomplementemia, positivity for anti-dsDNA and triple positivity for antiphospholipid antibodies (aPL) were related to pregnancy outcome. Results: Forty-three pregnancies ended in live births with a fetal loss rate of 8.5%. Fetal death, preterm delivery and birth weight <2500 g were associated with hypocomplementemia (p = 0.019, p = 0.0002, p < 0.0001 respectively). Lower neonatal birth weight, lower neonatal birth weight percentile and lower week at delivery were associated with hypocomplementemia (p < 0.0001, p = 0.0003, p < 0.0001 respectively) and with triple aPL positivity (p = 0.008, p = 0.014, p = 0.03 respectively). A poor pregnancy outcome was confirmed among primary APS (PAPS) pregnancies with hypocomplementemia. Multivariate analysis confirmed that hypocomplementemia was an independent predictor of lower neonatal birth weight (p = 0.0001) and lower week at delivery (p = 0.002). Conclusion: Hypocomplementemia could be considered a novel prognostic factor for pregnancy outcome in APS patients.

Obstetrical APS : Is there a place for hydroxychloroquine to improve the pregnancy outcome?

The use of the conventional APS treatment (the combination of low-dose aspirin and LMWH) dramatically improved the obstetrical prognosis in primary obstetrical APS (OAPS). The persistence of adverse pregnancy outcome raises the need to find other drugs to improve obstetrical outcome. Hydroxychloroquine is widely used in patients with various autoimmune diseases, particularly SLE. Antimalarials have many anti-inflammatory, anti-aggregant and immune-regulatory properties: they inhibit phospholipase activity, stabilize lysosomal membranes, block the production of several pro-inflammatory cytokines and, in addition, impair complement-dependent antigen-antibody reactions. There is ample evidence of protective effects of hydroxychloroquine in OAPS similar to the situation in SLE arising from in vitro studies of pathophysiological working mechanism of hydroxychloroquine. However, the clinical data on the use of hydroxychloroquine in primary APS are lacking and prospective studies are necessary.

The impact of primary Sjogren's syndrome on pregnancy outcome: Our series and review of the literature

OBJECTIVE Firstly, to investigate the pregnancy outcome of women with primary Sjogrens Syndrome (pSS) in a case-control study; secondly, to perform a review of the literature in order to clarify if the pregnancy outcome is affected by pSS and influenced by the disease clinical onset. METHOD OF STUDY Thirty-four pregnancies with pSS and 136 controls were retrospectively collected. RESULTS Six pregnancies occurred before the pSS diagnosis and 28 after the pSS diagnosis. Two cases were complicated by intrauterine atrio-ventricular block. A statistically significant increase of the rate of spontaneous abortions, preterm deliveries and cesarean section was found in pSS pregnancies. The mean neonatal birth weight and the mean neonatal birth weight percentile were significantly lower in the offspring of women with pSS in comparison to controls. Similar pregnancy outcome was observed in women with pSS diagnosis before and after the index pregnancy. CONCLUSIONS Women with pSS experienced complicated pregnancies more frequently than controls, regardless of the onset of the symptoms, showing that the immunological disturbance is present throughout the reproductive life.

Uterine prolapse in pregnancy

We present a case of a patient developing uterine prolapse during pregnancy. The cervix reached the introitus at 10 weeks gestation and subsequentely protruted progressively as the pregnancy advanced. The patient was conservatively treated with bed rest and the main maternal and fetal risks are avoided. At 4 months postpartum follow-up there was no evidence of uterine prolapse.

False-positive IgM for CMV in pregnant women with autoimmune disease: a novel prognostic factor for poor pregnancy outcome.

Our aims were to assess the frequency of false-positive IgM antibodies for cytomegalovirus in pregnant women with autoimmune diseases and in healthy women (controls) and to determine their relationship with pregnancy outcome. Data from 133 pregnancies in 118 patients with autoimmune diseases and from 222 pregnancies in 198 controls were assessed. When positive IgM for cytomegalovirus was detected, IgG avidity, cytomegalovirus isolation and polymerase chain reaction for CMV-DNA in maternal urine and amniotic fluid samples were performed in order to identify primary infection or false positivity. A statistically significantly higher rate of false-positive IgM was found in pregnancies with autoimmune diseases (16.5%) in comparison with controls (0.9%). A worse pregnancy outcome was observed among patients with autoimmune disease and false cytomegalovirus IgM in comparison with those without false positivity: earlier week of delivery (p = 0.017), lower neonatal birth weight (p = 0.0004) and neonatal birth weight percentile (p = 0.002), higher rate of intrauterine growth restriction (p = 0.02) and babies weighing less than 2000 g (p = 0.025) were encountered. The presence of false cytomegalovirus IgM in patients with autoimmune diseases could be used as a novel prognostic index of poor pregnancy outcome: it may reflect a non-specific activation of the immune system that could negatively affect pregnancy outcome. Lupus (2010) 19, 844—849.

Use of an intrauterine inflated catheter balloon in massive post-partum hemorrhage: A series of 52 cases

Massive post‐partum hemorrhage (PPH) is an important cause of maternal death that occurs as a complication of delivery. We report a large case series to evaluate the efficacy of uterine balloon tamponade to treat PPH avoiding hysterectomy.