Role of placental inflammatory mediators and growth factors in patients with rheumatic diseases with a focus on systemic sclerosis.

OBJECTIVES: Pregnancy in SSc is burdened with an increased risk of obstetric complications. Little is known about the underlying placental alterations. This study aimed to better understand pathological changes and the role of inflammation in SSc placentas. Leucocyte infiltration, inflammatory mediators and atypical chemokine receptor 2 (ACKR2) expression in SSc placentas were compared with those in other rheumatic diseases (ORD) and healthy controls (HC). METHODS: A case-control study was conducted on eight pregnant SSc patients compared with 16 patients with ORD and 16 HC matched for gestational age. Clinical data were collected. Placentas were obtained for histopathological analysis and immunohistochemistry (CD3, CD20, CD11c, CD68, ACKR2). Samples from four SSc, eight ORD and eight HC were analysed by qPCR for ACKR2 expression and by multiplex assay for cytokines, chemokines and growth factors involved in angiogenesis and inflammation. RESULTS: The number of placental CD3, CD68 and CD11 cells was significantly higher in patients affected by rheumatic diseases (SSc+ORD) compared with HC. Hepatocyte growth factor was significantly increased in the group of rheumatic diseases patients (SSc+ORD) compared with HC, while chemokine (C-C motif) ligand 5 (CCL5) was significantly higher in SSc patients compared with ORD and HC. CCL5 levels directly correlated with the number of all local inflammatory cells and higher levels were associated with histological villitis. CONCLUSIONS: Inflammatory alterations characterize placentas from rheumatic disease patients and could predispose to obstetric complications in these subjects.

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.

Management of idiopathic recurrent pericarditis during pregnancy.

BACKGROUND: Data concerning idiopathic recurrent pericarditis in pregnancy are scarce. OBJECTIVES: To evaluate the management and outcome of idiopathic recurrent pericarditis during pregnancy. METHODS AND RESULTS: Twenty-one pregnancies were evaluated in fourteen women with a history of recurrent idiopathic pericarditis (mean maternal age 31.5 years, mean gestational age 39.0 weeks), and subdivided in 2 cohorts: eight pregnancies were analyzed retrospectively (2002-2010), thirteen (2011-2017) prospectively and followed according a predefined management protocol. Ten pregnancies were uneventful, three ended in spontaneous early abortion, one fetal death occurred at 19 weeks. Recurrences of pericarditis occurred in eight and were treated by adding NSAIDs in two cases; in five cases the dose of corticosteroids was increased and in two cases aspirin was started/increased; paracetamol was always allowed. Colchicine was used in two cases in the prospective cohort. HELLP syndrome occurred in one patient, which resolved after delivery, and one patient experienced arterial hypertension and elevated transaminase. All infants had a good outcome (mean birth weight 3114 g, 10 males). Birth weight was significantly lower in the retrospective cohort (respectively 2806 g vs. 3320 g, p-value 0.017) in which higher doses of corticosteroids were used (median dose respectively 10.0 mg vs. 2.5 mg, p-value 0.048). Five recurrences of pericarditis occurred after delivery, easily treated with standard therapy. CONCLUSION: General outcomes of pregnancy in patients with idiopathic recurrent pericarditis is good, especially when patients are carefully followed by multidisciplinary teams according to standardized protocols.

Pregnancy in systemic sclerosis.

This comprehensive review summarizes retrospective and prospective studies on pregnancy in systemic sclerosis in order to educate physicians on critical management issues. Fertility is normal in women with established systemic sclerosis. Their rates of spontaneous losses are comparable to the general population, except for patients with late diffuse systemic sclerosis and severe internal organ involvement who may have higher risks of abortion. Prematurity is clearly higher among systemic sclerosis women, similarly to other rheumatic diseases such as systemic lupus erythematosus and anti-phospholipid antibody syndrome. A placental vasculopathy has been observed in some women with systemic sclerosis. Overall, the disease generally remains stable in most pregnancies. Women with pulmonary hypertension should avoid pregnancy on account of the high maternal mortality risk. Management of systemic sclerosis patients before and during pregnancy includes evaluation of organ involvement and autoantibody analysis, preconceptional folic acid, and discontinuation of drugs with teratogenic potential (bosentan, mycophenolate mofetil, methotrexate, etc.). Management by high-risk pregnancy teams including neonatologists is very important to ensure the best outcomes.

Congenital Chagas disease in a non-endemic area: Results from a control programme in Bergamo province, Northern Italy.

INTRODUCTION: In non-endemic countries, one of the most important routes of transmission of Trypanosoma cruzi is vertical transmission. The objective of this work is to report the results of the screening activities for the control of congenital Chagas Disease (CD) implemented in Bergamo province between January 2014 and December 2016. METHODS: The programme addressed Bolivian pregnant women settled in Bergamo province. All the eight hospitals offering antenatal and delivery care in that area were involved. We retrospectively calculated the coverage rate of the screening programme, the prevalence of CD in this population, as well as transmission rate to their offspring. RESULTS: During the study period, 376 Bolivian women accounted for 387 deliveries. The coverage rate of serologic screening was 85.6%. Confirmed seropositive women were 28, accounting for a prevalence of CD of 8.7% (95% IC 5.9-11.5). Among 29 children born to positive mothers, one infected child was detected (transmission rate of 4.3%, 95% IC 0-12.6) and treated accordingly. Other 13 children previously born from the same mothers were retrieved and tested for CD: no additional congenital cases were diagnosed. DISCUSSION: Our screening programme presented a high coverage, although widely variable in the different birthing facilities. National guidelines recommending CD testing in pregnant women would help to increase case detection countrywide.

Management of pericardial diseases during pregnancy.

Relatively few data have been published on the management of pericardial diseases during pregnancy. Pericardial involvement is sporadic during pregnancy, and pregnant women do not show any specific predisposition to pericardial diseases. The more common form of pericardial involvement is hydropericardium, usually as a benign mild effusion recorded in about 40% of pregnant women by the third trimester, followed by pericarditis as the more common disease requiring medical therapy. The general management of these conditions is not different from those of nonpregnant women, although specific precautions should be followed for specific diagnostic and therapeutic issues during pregnancy. If possible, pregnancy should be planned in a phase of disease quiescence. Nonselective cyclooxygenase inhibitors and aspirin can be used safely during the first and second trimester, but should be withdrawn later and in any case at gestational week 32, because of the possible effects on ductus arteriosus and renal function. Low-medium doses of prednisone are allowed during all pregnancy and breastfeeding. Colchicine is generally contraindicated during pregnancy, except in women with familial Mediterranean fever. These pregnancies should be followed by a dedicated multidisciplinary teams.

Transabdominal uterine arteries Doppler at 12-14th and 20-24th week of gestation and pregnancy outcome: a prospective study.

OBJECTIVE: To identify women at actual risk of pre-eclampsia and poor pregnancy outcome in a selected group of high risk patients. STUDY DESIGN: Prospective study of women with previous pre-eclampsia and/or intra uterine growth retardation, intra uterine death (> or =20th week), chronic hypertension, three or more previous spontaneous abortions. All subjects were followed-up till pregnancy outcome. Gestational week at delivery and birth weight were recorded. Other outcome measures were: intra uterine growth retardation, pregnancy-induced hypertension, pre-eclampsia, abruptio placenta, admission in neonatal intensive care unit. RESULTS: 139 patients were enrolled and followed-up until the end of pregnancy. Abnormal Doppler results at 12-14th week examination were associated with intra uterine growth retardation, fetal death/spontaneous abortion and small for gestational age birth. CONCLUSIONS: This study indicates that early evaluation of arterial uterine RI and presence of notches may be predictive of low birth weight and intra uterine growth retardation in a high risk population.