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.

Therapeutic apheresis during pregnancy: A single center experience.

INTRODUCTION: Therapeutic apheresis (TA) represents a treatment option for pre-existing conditions or diseases occurring during gestation. Although pregnancy is not a contraindication per se, due to the lack of evidence-based guidelines and presumed risk of maternal/fetal adverse events there is a general resistance to its application. MATERIAL AND METHODS: Between January 2005 and August 2017, at the Apheresis Unit of the University Hospital of Padua 936 TA procedures were performed during 57 pregnancies in 48 patients: 813 Plasma Exchange sessions, 119 Immunoadsorptions, 4 Red Blood Cell exchanges. The treated disease were as follows: antiphospholipid syndrome (18 patients), autoimmune congenital heart block (18), myasthenia gravis (3), Rh alloimmunization (2), systemic sclerosis (1), suspected autoimmune encephalitis (1), severe hypertriglyceridaemia (1), post partum hemolytic-uremic syndrome (1), sickle cell disease (1), lupus nephritis (1) and thrombotic thrombocytopenic purpura (1). RESULTS: In the time period considered the apheresis sessions applied to pregnant women were 7.1% of the total (n = 13.251). The median age at the first treatment was 33 years. The median week of gestation (WG) at the beginning of treatments was 21. Twenty (2.1%) sessions were complicated by adverse events, none requiring or prolonging hospitalization. There were 50 live births, 5 spontaneous abortions and 2 voluntary terminations of pregnancy. Median WG at delivery was 35 and caesarean section was performed in 46 cases. CONCLUSIONS: Our data showed that TA in pregnancy is well tolerated. Close collaboration between clinician, obstetrician and TA specialist is crucial to ensure a good outcome of high-risk pregnancies.

Management of pregnant women with antiphospholipid antibodies.

INTRODUCTION: Important advancements in pregnancy outcome have been reported in women with antiphospholipid antibodies (aPL), despite the fact that the treatment of aPL related pregnancy morbidity is not guided by consistent findings from well-designed trials. Areas covered: The current study draws a picture of the studies in the literature by performing a Medline search of relevant English language articles and reports our experience in managing different subsets of obstetric antiphospholipid syndrome (APS), defined on the basis of their clinical and laboratory characteristics. The management of pregnant women with non-criteria APS manifestations and that of aPL carriers during their first pregnancy is also examined. Expert commentary: A heparin/aspirin combination constitutes conventional treatment for APS affected pregnant women. As this strategy fails in approximately 20-30% of cases, uncovering other options for women refractory to conventional treatment or at high risk of pregnancy complications has become an urgent undertaking. Some attempts have been made to prescribe additional treatments in the effort to improve live birth rates and/or reduce pregnancy complications, which often occur even in patients treated conventionally. The evidence from some studies and an individual risk/benefit assessment should instead guide treatment decisions for pregnant patients with non-criteria APS manifestations and aPL carriers.

Low titer, isolated anti Ro/SSA 60 kd antibodies is correlated with positive pregnancy outcomes in women at risk of congenital heart block.

Congenital heart block (CHB) is an autoantibody mediated disorder presumably caused by placental transmission of maternal autoantibodies to Ro/SSA 52 kd, p200, Ro/SSA 60 kd, La/SSB ribonucleoproteins. This study investigated the clinical significance of isolated anti-Ro/SSA 52 kd, anti-p200, anti-Ro/SSA 60 kd, and anti-La/SSB antibodies in positive pregnant patients. One hundred sixty-three pregnant women positive to anti-Ro/SSA 52 kd and/or anti-Ro/SSA 60 kd and/or anti-La/SSB antibodies were prospectively enrolled in the study. Anti-Ro52, anti-Ro60, anti-p200, and anti-La antibodies were assayed using home-made ELISA assays. Isolated antibody positivity was found in 25 women (15.3%), while multiple antibody positivity in 138 (84.7%). Twenty-four developed CHB, and the 139 had a favorable pregnancy outcome. The prevalence of isolated anti-Ro/SSA 60 kd antibodies was significantly higher (p < 0.046) as the prevalence of lower mean antibody titers (p < 0.0001) in the later group. Confirmation of these results by large-scale studies could lead clinicians to recommend less stringent fetal echocardiography monitoring in women with isolated anti-Ro/SSA 60 kd antibodies.

Apheresis and intravenous immunoglobulins used in addition to conventional therapy to treat high-risk pregnant antiphospholipid antibody syndrome patients. A prospective study.

Pregnant women with triple antibody positive antiphospholipid syndrome (APS) who have had thrombosis or a history of early, severe pregnancy complications are generally considered at high risk of pregnancy loss. The objectives of this study were to investigate the efficacy and safety of a relatively new treatment protocol used in addition to conventional therapy in high-risk pregnant patients affected with primary APS. The study's two inclusion criteria were: (1) the presence of triple antiphospholipid positivity, (2) previous thrombosis and/or a history of one or more early, severe pregnancy complications. Eighteen pregnancies occurring between 2002 and 2015 in 14 APS patients, (mean age 34.8±3.6 SD) were monitored. All 14 (100%) patients had triple antiphospholipid positivity. In addition, six of them (42.8%) had a history of thrombosis, four (28.6%) had one or more previous early and severe pregnancy complications, and four (30.8%) met both clinical study criteria. The study protocol included weekly plasmapheresis or immunoadsorption and fortnightly 1g/kg intravenous immunoglobulins. Seventeen of the pregnancies (94.4%) produced live neonates, all born between the 26th and 37th weeks of gestation (mean 33.1±3.5 SD). One female (5.5%), born prematurely at 24 weeks, died of sepsis a week after birth. There were two cases (11.1%) of severe pregnancy complications. No treatment side effects were registered. Given the high live birth rate and the safety associated to it, the study protocol described here could be taken into consideration by medical teams treating high-risk APS pregnant patients.

Dysregulation of gene expression in human fetal endothelial cells from gestational diabetes in response to TGF-ß1.

Enhanced biosynthesis of several cytokines, such as, transforming growth factor-ß1 (TGF-ß1), is detected in gestational diabetes mellitus (GDM). In this study, we addressed the question of whether the exposure to the abnormal milieu of GDM in vivo affects gene expression pattern of human umbilical vein endothelial cells (HUVEC) in response to TGF-ß1. We found that HUVEC isolated from GDM (dHUVEC) had reduced migratory capacity versus those of healthy women (nHUVEC) and this quiescent phenotype was associated with higher expression levels of the TGF-ßtype I receptor ALK5 and a slight increase in the endogenous production of TGF-ß1 (mainly in its latent form). Moreover, we performed transcriptome analysis, using microarray technology, of dHUVEC versus nHUVEC, after 3h treatment with exogenous TGF-ß1 (10 ng/ml). The treatment of dHUVEC with TGF-ß1 caused downregulation of the transcription of multiple genes involved in development, cell movement and migration of cells versus TGF-ß1-treated nHUVEC. These changes in transcriptome profile might contribute to GDM-dependent alterations in cardiac morphogenesis and placental development.

Women's choice of positions during labour: return to the past or a modern way to give birth? A cohort study in Italy.

BACKGROUND: Childbirth medicalization has reduced the parturient's opportunity to labour and deliver in a spontaneous position, constricting her to assume the recumbent one. The aim of the study was to compare recumbent and alternative positions in terms of labour process, type of delivery, neonatal wellbeing, and intrapartum fetal head rotation. METHODS: We conducted an observational cohort study on women at pregnancy term. Primiparous women with physiological pregnancies and single cephalic fetuses were eligible for the study. We considered data about maternal-general characteristics, labour process, type of delivery, and neonatal wellbeing at birth. Patients were divided into two groups: Group-A if they spent more than 50% of labour in a recumbent position and Group-B when in alternative ones. RESULTS: 225 women were recruited (69 in Group-A and 156 in Group-B). We found significant differences between the groups in terms of labour length, Numeric Rating Scale score and analgesia request rate, type of delivery, need of episiotomy, and fetal occiput rotation. No differences were found in terms of neonatal outcomes. CONCLUSION: Alternative maternal positioning may positively influence labour process reducing maternal pain, operative vaginal delivery, caesarean section, and episiotomy rate. Women should be encouraged to move and deliver in the most comfortable position.

Pharmacological anti-thrombotic prophylaxis after elective caesarean delivery in thrombophilia unscreened women: should maternal age have a role in decision making?

In obstetrical practice, the best prevention strategy for pregnant women aged >35 years without known thrombosis risk factors who underwent elective caesarean delivery (CD) is controversial. We performed an observational-longitudinal cohort study on pregnant women aged >35 years who delivered at term by elective caesarean section after a physiological single pregnancy to evaluate the role of maternal age in the decision-making process of whether or not to perform low-molecular-weight heparin (LMWH) prophylaxis during the post-partum period after elective CD in healthy women with unknown inherited thrombophilia status. During the 6 post-partum weeks, we followed two groups: GROUP-A (349 women treated for 7 days with low-molecular-weight heparin) and GROUP-B (180 women not treated with LMWH treatment). The outcomes were as follows: onset of thromboembolic events during the post-partum period; non-obstetrical-linked maternal haemorrhage; blood transfusion; re-laparotomy; detection of a surgical site haematoma; length of hospitalisation; and treatment suspension because of decreased platelet count. Except for the parity number, the two groups were homogeneous with regard to general features. In both the groups, we reported no cases of thromboembolic events during the follow-up period. Maternal haemorrhage requiring transfusion occurred in 16 women in GROUP-A and none in GROUP-B. Among the GROUP-A women, 11 demonstrated a surgical site haematoma and 4 required re-laparotomy. No cases of treatment suspension were reported. Pneumatic compression stockings represent a better, low cost and safe way to prevent post-partum venous thromboembolic episodes after elective caesarean section in an unscreened population. Pharmacological prophylaxis after elective caesarean section should be performed only in case of clear and known adjunctive risk factors, independent of maternal age.

Which uterotonic is better to prevent the postpartum hemorrhage? Latest news in terms of clinical efficacy, side effects, and contraindications: a systematic review.

BACKGROUND: Postpartum hemorrhage (PPH) is a potentially fatal complication of vaginal and cesarean deliveries. The active management of the third stage of labor provides administration of prophylactic uterotonic drugs just before or immediately after delivery, since they reduce the risk of PPH by 60%. OBJECTIVE: Overview on all available uterotonics for PPH prevention to clarify indications and contraindications in choice among drugs. SEARCH STRATEGY: Systematic review of the literature. MAIN RESULTS: Oxytocin is the first choice for PPH prophylaxis. Ergot alkaloids, syntometrine, and prostaglandins are second-line uterotonic agents. Misoprostol is not effective as oxytocin but it may be used when the latter is not available. Carbetocin should be used instead of continuous oxytocin infusion in elective cesarean sections for PPH prevention and to decrease the need for therapeutic uterotonics. CONCLUSIONS: Prophylactic oxytocics should be offered routinely in the third stage of labor in all women. The prophylactic use of uterotonics should be individualized.

Effective anatomical and functional status of the lower uterine segment at term: estimating the risk of uterine dehiscence by ultrasound.

OBJECTIVE: To define the role of lower uterine segment (LUS) evaluation at term. DESIGN: Observational case-control study. SETTING: University hospital. PATIENT(S): Ninety-four patients were divided into two groups. Group A consisted of 45 multiparous single fetus pregnant women with up to two previous cesarean sections (CS). Group B consisted of 49 multiparous pregnant women with up to three vaginal deliveries and no uterine scars. INTERVENTION(S): Total LUS and myometrial thickness were measured by sonogram in all patients before undergoing a CS. MAIN OUTCOME MEASURE(S): The primary outcome is a correlation between echographic measurements and features of the LUS at the time of CS. The secondary outcome is a definition of a correlation between the number of previous CS, interdelivery interval time, and features of the LUS (grades I-IV). RESULT(S): Sonographic measurements revealed significant differences in LUS size and myometrial thickness between the two groups. Grades III and IV of LUS were only observed in group A. An interdelivery interval <18 months, LUS thickness ≤ 3.0 mm, and myometrial thickness < 1.5 mm were statistically significant predictors of LUS grades III and IV. Number of previous CS showed no correlation with surgical LUS status. CONCLUSION(S): Sonographic evaluation of the LUS may be a noninvasive, reproducible, and safe technique for defining the risk of uterine dehiscence, with a sensitivity of 100% and specificity of 85% (positive predictive value, 45%; negative predictive value, 100%).

Nowadays which emergency contraception? Comparison between past and present: latest news in terms of clinical efficacy, side effects and contraindications.

Despite many highly effective methods of contraception are available nowadays, many pregnancies are unintended. Emergency contraception (EC) is the use of drug or device after unprotected intercourse to prevent an unwanted pregnancy. It is a woman's last chance to prevent unintended pregnancy. Nevertheless the confusion about mechanisms of action, side effects, clinical efficacy and controindications makes the intervention underused in every setting investigated. So far levonorgestrel (LNG) has been considered the gold standard for oral EC. Today, a new type of second generation progesterone receptor modulator, ulipristal acetate (UPA) has been proposed as a more effective drug than LNG in prevention of unwanted pregnancies by delaying or inhibiting ovulation; even if many other devices are disposable in commerce. We revised the literature to concern most of the data available on the role of EC and moreover clarifying the available methods, the action windows of the accessible devices, the adverse events and the controindications.