Barbara Acaia

Heparin in pregnant women with previous placenta-mediated pregnancy complications: a prospective, randomized, multicenter, controlled clinical trial

To assess whether antithrombotic prophylaxis with low-molecular-weight heparin effectively prevents recurrence of late pregnancy complications, 135 women with previous history of preeclampsia, hemolytic anemia, elevated liver enzymes and low platelet count syndrome, intrauterine fetal death, fetal growth restriction, or placental abruption who had been referred within the 12th gestational week were randomized to medical surveillance alone (n = 68) or combined to open-label nadroparin (3800 IU daily subcutaneous injections) treatment (n = 67) in the setting of a randomized, parallel-group, superiority trial, run in Italy from April 2007 to April 2010. Primary outcome was a composite end point of late-pregnancy complications. Analysis was by intention to treat. The study was stopped for futility at the time of the first planned interim analysis. Among the 128 women eventually available for final analyses, 13 of the 63 (21%) randomized to nadroparin compared with 12 of the 65 (18%) on medical surveillance alone progressed to the primary end point. The absolute event risk difference between treatment arms (2.2; -1.6 to 16.0) was not statistically significant (P = .76). Thus, nadroparin did not prevent late-pregnancy complications in women at risk of recurrence. This finding challenges the role of antithrombotic prophylaxis with low-molecular-weight heparin in the prevention of recurrent late pregnancy complications The trial was registered at http://ricerca-clinica.agenziafarmaco.it as EudraCT 2006-004205-26.

Antiphospholipid antibodies as cause of pregnancy loss

Antiphospholipid antibodies detected by lupus anticoagulant, anticardiolipin or anti-beta2 glycoprotein I assays were associated with fetal loss. Rather than being diagnostic tools only, antiphospholipid antibodies are thought to be pathogenic. The strongest demonstration of their pathogenic role lies in the ability to induce fetal resorptions - the experimental equivalents of the human fetal losses - when passively infused in pregnant naive animals. However, still debated is how the antibodies might induce the obstetrical manifestations. Thrombotic events at the placental levels might be related to endothelial cell activation, inhibition of protein C/S system and fibrinolysis as well as to Annexin V displacement. However, the thrombophilic state apparently cannot explain all the miscarriages and a direct antibody-mediated damage on the trophoblast has been suggested. During differentiation to syncytium, trophoblasts express cell membrane anionic phospholipids that can bind beta2 glycoprotein I, the main cationic phospholipid binding protein recognized by the antiphospholipid antibodies. Adhered b2-glycoprotein I might be recognized by the antibodies that, once bound, strongly interfere with in vitro trophoblast cell maturation so resulting in a defective placentation. These mechanisms have been suggested to play a role in early fetal loss, while thrombotic events would be responsible for miscarriages late in the pregnancy.

Dynamics and significance of placebo response in primary dysmenorrhea.

&NA; A total of 55 patients with primary dysmenorrhea who had shown a favorable response to a preliminary treatment cycle with placebo were admitted to a double‐blind study on placebo versus antiprostaglandin agents (naproxen and pirprofen). To evaluate the placebo effect and its duration, the treatment was given for 4 successive cycles. Whereas the antiprostaglandin agents were effective in most of the patients (in 80% of the pirprofen group and 85.7% of the naproxen group) and this efficacy was maintained throughout the study, a favorable response to placebo was observed in 84% in the first cycle, 29% in the second, 16% in the third and 10% in the fourth. The incidence of side effects was similar in the placebo and the active treatment groups (35.4% vs. 37.5%). It is postulated that a placebo effect in dysmenorrhea is due to a central analgesic mechanism mediated by endorphin release or possibly to psychological dynamics (mental or conditioning theories). However, this effect loses efficacy with time possibly due to a decreased susceptibility to the opioid action of the central nervous circuits responsible for menstrual pain perception or to deconditioning mechanisms.

Anti-phospholipid antibody mediated fetal loss: still an open question from a pathogenic point of view:

Antiphospholipid antibodies (aPL) are associated with recurrent miscarriages and pregnancy complications, however their pathogenic mechanisms are still matter of research. Thrombotic events at the placental level cannot explain all of the clinical manifestations. It has been suggested that aPL may be responsible for a local acute inflammatory response mediated by complement activation and neutrophil infiltration eventually leading to fetal loss. However histological and immunohistological studies on human placental samples do support such a mechanism only in part and with no any clear relationship with the pregnancy outcome. A direct effect of aPL on both maternal and fetal placental tissues has been reported through the reactivity of the antibodies with beta2 glycoprotein I (β2GPI) expressed on the cell membranes. These events do not require an inflammatory response and can be in part related to the inhibition of growth factors favouring a physiological placentation. Understanding the different pathogenic mechanisms of aPL-associated miscarriages may help in improving our therapeutic approach particularly in recurrent cases not responsive to the usual treatment. Lupus (2010) 19, 453—456.

Short-term reproductive prognosis when no cause can be found for recurrent miscarriage

Summary. The short‐term reproductive prognosis of recurrent miscarriage for which no cause was found has been evaluated in 95 couples investigated between 1980 and 1986 at the First Obstetric and Gynaecological Clinic of the University of Milan. The actuarial overall 3‐year livebirth delivery rate was 64%, increasing constantly with time. The reproductive success rate decreased with the number of previous miscarriages from 80% in women with two, to 60% with three and 46% with four or more miscarriages. No effect of age and socio‐economic status emerged. There was a positive association between the number of previous miscarriages and the risk of miscarriage in the next pregnancy. Compared with women with two miscarriages the relative risk of another miscarriage was 2·3 for those with three previous miscarriages and 5·0 for those with four or more (χ21 for trend adjusted for age = 5·2, P= 0·02).

A small randomised trial of low-dose aspirin in women at high risk of pre-eclampsia

OBJECTIVE To determine if aspirin (ASA) therapy reduces the incidence of pre-eclampsia in women at high risk of this condition. STUDY DESIGN Randomised clinical trial. We recruited pregnant women with gestational age at randomisation <14 weeks, who satisfied the following criteria: chronic hypertension, history of severe pre-eclampsia or eclampsia or intrauterine growth retardation (IUGR) or intrauterine foetal death. Nineteen women in the no-treatment group and 16 in the ASA group were successfully followed up. RESULTS The mean birthweight was higher in the ASA group than in the no-treatment group (2790 g (S.D. 340 g) versus 2616 g (S.D. 779 g)), but the difference was not statistically significant. We found no statistically significant differences between the groups in the proportion of infants with birthweight below 2500 g (13.3% versus 29.4%) and the number of cases with pregnancy-induced hypertension (PIH)/pre-eclampsia (31.3% versus 36.8%). CONCLUSION These limited data give some support to the potential favourable effect of early treatment with ASA in pregnant women at risk of PIH and IUGR.

Obstetric and vascular APS: Same autoantibodies but different diseases?

Beta2 glycoprotein I (β2GPI)-dependent antiphospholipid antibodies (aPLs) are the main pathogenic autoantibody population and at the same time the laboratory diagnostic tool for the antiphospholipid syndrome (APS). These antibodies are responsible for both the vascular and the obstetric manifestations of the syndrome but the pathogenic mechanisms behind these manifestations are not the same. For example, thrombotic events do not appear to play a major role in APS miscarriages and a direct reactivity of β2GPI-dependent aPLs on decidual and trophoblast cells was reported. A local expression of β2GPI on these tissues was reported both in physiological conditions and in APS women, thus explaining the local tropism of the autoantibodies. The two hit hypothesis was suggested to explain why the vascular manifestations of APS may occur only occasionally in spite of the persistent presence of aPLs. This is not apparently the case for the obstetric variant of the syndrome, making the difference even more striking. A different pathogenesis may also provide the rationale for the well-known fact that the vascular and the obstetric manifestations may occur independently although in a minority of cases.

Nasal Lavage in Pregnant Women with Seasonal Allergic Rhinitis: A Randomized Study

Background: Nasal rinsing appears particularly suitable in the management of pregnant women with seasonal allergic rhinitis since no deleterious effects on the fetus are to be expected. However, to date, no studies have specifically investigated this option. Methods: Pregnant women with seasonal allergic rhinitis were randomized to intranasal lavage with hypertonic saline solution 3 times daily (n = 22) versus no local therapy (n = 23) during a 6-week period corresponding to the pollen season. Patients were invited to keep a daily record of rhinitis symptoms (rhinorrea, obstruction, nasal itching and sneezing), to record consumption of oral antihistamine and to undergo rhinomanometry. Results: The rhinitis score was similar at study entry but a statistically significant improvement in this score was observed in the study group during all subsequent weeks (p < 0.001 for weeks 2–6). The mean number of daily antihistamines use per patient per week was significantly reduced at weeks 2, 3 and 6 (p < 0.001, p < 0.001 and p = 0.001, respectively). Baseline rhinomanometry performed at week 1 showed similar nasal resistance in the study and control groups. In contrast, a statistically significant difference emerged in the 2 following evaluations. At week 3, nasal resistance in the study and control groups was 0.96 ± 0.44 and 1.38 ± 0.52 Pa/ml/s, respectively (p = 0.006). At week 6, it was 0.94 ± 0.38 and 1.35 ± 0.60 Pa/ml/s, respectively (p = 0.006). No adverse effect was reported in the active group. Conclusions: Nasal rinsing is a safe and effective treatment option in pregnant women with seasonal allergic rhinitis.

Chorioamnionitis and neonatal outcome in preterm infants: a clinical overview.

Abstract The term chorioamnionitis is used to refer to an intrauterine infection/inflammation occurring between the maternal tissues and the fetal membranes (choriodecidual space) or in the fetal annexes (chorioamniotic membranes, amniotic fluid, umbilical cord). Histological examination of the placenta is the gold standard for diagnosis. However, clinical, biochemical and microbiological criteria are also used to define the disease. The literature contains a large body of evidence showing that chorioamnionitis is the leading cause of very preterm birth and, therefore, contributes significantly to neonatal morbidity and mortality. In recent decades, numerous studies have attempted to establish whether, and to what extent, intrauterine infection/inflammation might negatively affect the short- and long-term outcome of preterm infants. The question is still unanswered. The discrepancy observed across studies can be attributed largely to the use of different inclusion and exclusion criteria, diagnostic criteria and methods, and to whether or not potential confounding factors, such as gestational age were considered. Anyhow, the association between chorioamnionitis and severe prematurity requires serious efforts by researchers to clarify the mechanisms linking intrauterine infection/inflammation with preterm birth, and thus to identify strategies that may guide clinicians’ diagnostic and therapeutic choices, with regard to both mothers and infants.

Neonatal lupus: fetal myocarditis progressing to atrioventricular block in triplets

We report a case of neonatal lupus syndrome (NLS) in an in vitro fertilization induced triplet pregnancy. Echocardiographicsigns of myocarditiswere evident at the 21st week of gestation(w.g.) in twin I, with a subsequentdevelopmentof a complete atrioventricular(AV) block at the 25th w.g.; twin III also displayed echocardiographic signs of myocarditis at the same time. Treatment with dexamethasone (4mg/day) was started at the 25th w.g. A complete echocardiographicregression of the myocarditis signs was achieved, while AV block was unaffected.Caesarian section was performed at the 31.5 w.g. after a premature rupture of the membranes. Complete AV block was confirmed in twin I with a heart rate of 51beats/min that required a pacemaker implant 40 days after. Twin III developed a first-degree AV block that switched to a periodic second-degreeblock later, while twin II displayed only liver enzyme abnormalities.