The complement system plays a double role in pregnancy exerting both protective and damaging effects at placental level. Complement activation at fetal-maternal interface participates in protection ...against infectious agents and helps remove apoptotic and necrotic cells. Locally synthesized C1q contributes to the physiologic vascular remodeling of spiral arteries characterized by loss of smooth muscle cells and transformation into large dilated vessels. Complement activation triggered by the inflammatory process induced by embryo implantation can damage trophoblast and other decidual cells that may lead to pregnancy complications if the cells are not protected by the complement regulators CD55, CD46, and CD59 expressed on cell surface. However, uncontrolled complement activation induces placental alterations resulting in adverse pregnancy outcomes. This may occur in pathological conditions characterized by placental localization of complement fixing antibodies directed against beta2-glycoprotein 1, as in patients with anti-phospholipid syndrome, or circulating immune complexes deposited in placenta, as in patients with systemic lupus erythematosus. In other diseases, such as preeclampsia, the mechanism of complement activation responsible for complement deposits in placenta is unclear. Conflicting results have been reported on the relevance of complement assays as diagnostic and prognostic tools to assess complement involvement in pregnant patients with these disorders.
Females are generally more affected by autoimmune diseases, a fact that underlines the relationship with pregnancy and the safety of anti-rheumatic drugs in pregnancy and lactation. Biologic ...therapies are increasingly prescribed to treat and maintain remission in a significant number of systemic autoimmune rheumatic diseases. The experience with the use of biologics during gestation is extremely lacking because of the observational nature of the available studies and the difficulty in designing proper clinical trials in pregnancy. Among the studied biologics, more information was published on TNFα inhibitors and, in particular, on their potential passage through the placenta and impact on the fetus. Currently, a fragment of anti-TNFα monoclonal IgG, certolizumab pegol, is considered safe with almost no placental transfer. Subsequent observations are suggesting a comparable safety for the soluble TNFα receptor etanercept. Another biologic, eculizumab, the anti-C5a antibody used to treat complement-mediated microangiopathies, is also considered safe due to the unique engineered IgG2/4κ formulation that limits its passage through the placental barrier. Still, long-term data about children born to women treated with biologics in pregnancy are not attainable. Data on breastfeeding are currently available for several biologics. This article reviews the literature available about which drugs are considered safe during pregnancy and lactation, which are not, and on future prospects.
Antiphospholipid antibodies (aPL) are risk factors for thrombosis and adverse pregnancy outcomes (APO). The management of the so called "aPL carriers" (subjects with aPL positivity without the ...clinical criteria manifestations of APS) is still undefined. This study aims at retrospectively evaluating the outcomes and the factors associated with APO and maternal complications in 62 pregnant aPL carriers.
Medical records of pregnant women regularly attending the Pregnancy Clinic of 3 Rheumatology centers from January 1994 to December 2015 were retrospectively evaluated. Patients with concomitant autoimmune diseases or other causes of pregnancy complications were excluded.
An aPL-related event was recorded in 8 out of 62 patients (12.9%) during pregnancy: 2 thrombosis and 6 APO. At univariate analysis, factors associated with pregnancy complications were acquired risk factors (p:0.008), non-criteria aPL manifestations (p:0.024), lupus-like manifestations (p:0.013), and triple positive aPL profile (p:0.001). At multivariate analysis, only the association with a triple aPL profile was confirmed (p:0.01, OR 21.3, CI 95% 1.84-247). Patients with triple aPL positivity had a higher rate of pregnancy complications, despite they were more frequently receiving combined treatment of low dose aspirin (LDA) and low molecular weight heparin (LMWH) at prophylactic dose.
This study highlights the importance of risk stratification in pregnant aPL carriers, in terms of both immunologic and non-immunologic features. Combination treatment with LDA and LMWH did not prevent APO in some cases, especially in carriers of triple aPL positivity. Triple positive aPL carriers may deserve additional therapeutic strategies during pregnancy.
Objective:
This retrospective cohort study describes the modulation of disease activity during gestation and in the year following delivery as well as maternal and neonatal outcomes in a monocentric ...cohort of women with juvenile idiopathic arthritis (JIA).
Methods:
Disease activity was assessed using DAS28-CRP before conception and every 3 months during pregnancy and in the first year postpartum. The risk of complicated pregnancies was measured applying a generalized estimating equation model. Changes in disease activity during gestation and in the first year postpartum were assessed in a linear mixed model for repeated measures.
Results:
Thirty-one women (49 pregnancies) with persisting JIA and at least one conception were enrolled. Adjusted DAS28-CRP levels remained stable from preconception through the first trimester, but increased significantly in the second and decreased not significantly in the third. In the postpartum, adjusted disease activity peaked at 3 months after delivery, stabilized at 6 months to decrease at 1 year, although not significantly. Preconceptional DAS28-CRP and number of biological drugs predicted disease activity fluctuation during gestation. The number of biological drugs and the length of gestational exposure to biologics significantly predicted pregnancy morbidity. In particular, JIA women had a higher probability of preterm delivery compared with healthy and disease controls. Adjusted for breastfeeding and DAS28-CRP score in the third trimester, postconceptional exposure to biologics was inversely related with disease activity in the postpartum: the longer the patient continued treatment, the lower the probability of experiencing an adverse pregnancy outcome.
Conclusion:
These data offer novel insights on how treatment affects disease activity during pregnancy and postpartum as well as obstetric outcomes in women with JIA.
To determine whether prevalence and severity of pain symptoms are related to endometriosis stage and site, with particular reference to deep infiltrating vaginal lesions.
Systematic assessment of ...chronic pelvic pain symptoms.
University hospital endometriosis center.
A total of 244 consecutive symptomatic patients with endometriosis diagnosed at laparoscopy or laparotomy.
Assessment of dysmenorrhea and nonmenstrual pain by means of a 10-point linear analog scale, a 7-point multidimensional rating scale, and a 3-point verbal scale; evaluation of deep dyspareunia with the first and third systems only.
Prevalence and severity of pain symptoms in relation to endometriosis stage and site of lesions. Correlation between revised American Fertility Society score and symptoms severity, as well as between two pain scales to assess dysmenorrhea and nonmenstrual pain.
Eighty-eight women had stage I and II disease and 156 had stage III and IV disease. Only ovarian endometriosis was present in 108 patients, only peritoneal implants were present in 37, combined ovarian and peritoneal lesions were present in 57, and histologically confirmed vaginal endometriosis was present in 42. The frequency and severity of deep dyspareunia and the frequency of dysmenorrhea were less in patients with only ovarian endometriosis than in those with lesions at other sites. Patients with vaginal endometriosis had a significantly increased risk of deep dyspareunia compared with those whose lesions were at other sites (odds ratio, 2.55; 95% confidence interval, 1.21 to 5.39). Stage per se, independent of lesion site, was not correlated with frequency and severity of dysmenorrhea and nonmenstrual pain. The severity of deep dyspareunia was related inversely to the endometriosis score (Spearman correlation coefficients for linear analog and verbal rating scales, respectively, −0.22 and −0.20). Kendall test by ranks revealed a correlation between linear analog and multidimensional pain scales in the rating of both dysmenorrhea and nonmenstrual pain (respectively, tau-b, 0.59 and tau-b, 0.68).
Endometriosis stage in the current classification was not related consistently to pain symptoms. The presence of vaginal lesions was associated frequently with severe deep dyspareunia. Dysmenorrhea and nonmenstrual pelvic pain were assessed with equal accuracy by a linear analog and a multidimensional scale.
Abstract
Objectives
aPL, the serum biomarkers of APS, are the most common acquired causes of pregnancy morbidity (PM). This study investigates the impact of aPL positivity fulfilling classification ...criteria (‘criteria aPL’) and at titres lower than thresholds considered by classification criteria (‘low-titre aPL’) on PM and assesses the effectiveness of low-dose aspirin (LDASA), low molecular weight heparin (LMWH) and HCQ in reducing the probability of PM (PPM).
Methods
Longitudinal data on 847 pregnancies in 155 women with persistent aPL at any titre and 226 women with autoimmune diseases and negative aPL were retrospectively collected. A generalized estimating equations model for repeated measures was applied to quantify PPM under different clinical situations.
Results
EUREKA is a novel algorithm that accurately predicts the risk of aPL-associated PM by considering aPL titres and profiles. aPL significantly impact PPM when at low titres and when fulfilling classification criteria. PPM was further stratified upon the aPL tests: aCL IgG/IgM and anti-β2-glycoprotein I (β2GPI) IgM, alone or combined, do not affect the basal risks of PPM, an increase occurs in case of positive LA or anti-β2GPI IgG. LDASA significantly affects PPM exclusively in women with low-titre aPL without anti-β2GPI IgG. The LDASA + LMWH combination significantly reduces PPM in all women with low-titre aPL and women with criteria aPL, except those carrying LA and anti-β2GPI IgG. In this group, the addition of HCQ further reduces PPM, although not significantly.
Conclusion
EUREKA allows a tailored therapeutic approach, impacting everyday clinical management of aPL-positive pregnant women.
Cystic fibrosis (CF) causes infertility and subfertility due to various factors, including altered cervical mucus, delayed puberty, and hormonal imbalances. With the introduction of the CFTR ...modulator therapy elexacaftor-tezacaftor-ivacaftor, we have observed an increase in unplanned pregnancies among women undergoing ETI treatment in our CF center, despite repeated recommendations for strict fertility monitoring. It appears that these pregnancies are more likely attributed to reduced attention to the possibility of conception rather than contraceptive failure. The perception of subfertility developed by women with CF over time, before the era of modulators, can influence their long-term habits and lead to the underuse of contraceptive methods. While further research is needed to fully understand the effects of ETI on fertility, healthcare providers should be attentive to the fertility concerns of women with CF, particularly those treated with modulators in adulthood.
It is not unusual for patients with "rare" conditions, such as skeletal dysplasias, to remain undiagnosed until adulthood. In such cases, a pregnancy may unexpectedly reveal hidden problems and ...special needs. A 28 year old primigravida was referred to us at 17 weeks for counselling with an undiagnosed skeletal dysplasia with specific skeletal anomalies suggesting the collagen 2 disorder, spondyloperipheral dysplasia (SPD; MIM 156550).She was counselled about the probability of dominant inheritance and was offered a prenatal diagnosis by sonography. US examination at 17, 18 and 20 weeks revealed fetal macrocephaly, a narrow thorax, and shortening and bowing of long bones. The parents elected to continue the pregnancy. At birth the baby showed severe respiratory distress for four weeks which then resolved. Mutation analysis of both mother and child revealed a hitherto undescribed heterozygous nonsense mutation in the C-propeptide coding region of COL2A1 confirming the diagnosis of SPD while reinforcing the genotype-phenotype correlations between C-propeptide COL2A1 mutations and the SPD-Torrance spectrum. This case demonstrates the importance of a correct diagnosis even in adulthood, enabling individuals affected by rare conditions to be made aware about recurrence and pregnancy-associated risks, and potential complications in the newborn.
Anti‐phospholipid antibodies and reproductive failures Beltagy, Asmaa; Trespidi, Laura; Gerosa, Maria ...
American journal of reproductive immunology (1989),
April 2021, 2021-04-00, 20210401, Letnik:
85, Številka:
4
Journal Article
Recenzirano
Anti‐phospholipid syndrome (APS) recapitulates the link between autoimmunity and pregnancy failure: Acquired anti‐phospholipid antibodies (aPL) play a pathogenic role in pregnancy complications. The ...diagnosis of obstetric APS can easily be pursued when women present with laboratory and clinical features fulfilling the international classification criteria. Standard therapeutic approach to obstetric APS consists in the association of anti‐platelet agents and anticoagulants. Most patients achieve a live birth thanks to conventional treatment; however, approximately 20% fail to respond and are managed with additional therapeutic tools added on the top of conventional treatment. Surely, a refinement of risk stratification tools would allow early identification of high‐risk pregnancies that warrant tailored treatment. In real life, obstetricians and rheumatologists face complex diagnostic scenarios including women with pregnancy morbidities other than those mentioned in classification criteria such as one or two early losses and premature birth after 34 weeks due to preeclampsia or placental insufficiency, women with low‐titer aPL not fulfilling criteria laboratory requirements, women with positive non‐criteria aPL, asymptomatic aPL carriers, and infertile women found to be aPL‐positive. This review focuses on some of the several unanswered questions related to diagnostic, prognostic, and therapeutic aspects in obstetric APS.
Abstract
Objectives
To compare clinical features, laboratory data and fetal-maternal outcomes between 1000 women with obstetric APS (OAPS) and 640 with aPL-related obstetric complications not ...fulfilling Sydney criteria (non-criteria OAPS, NC-OAPS).
Methods
This was a retrospective and prospective multicentre study from the European Registry on Obstetric Antiphospholipid Syndrome.
Results
A total of 1650 women with 5251 episodes, 3601 of which were historical and 1650 latest episodes, were included. Altogether, 1000 cases (OAPS group) fulfilled the Sydney classification criteria and 650 (NC-OAPS group) did not. Ten NC-OAPS cases were excluded for presenting thrombosis during follow-up. All cases were classified as category I (triple positivity or double positivity for aPL) or category II (simple positivity). Overall, aPL laboratory categories showed significant differences: 29.20% in OAPS vs 17.96% in NC-OAPS (P < 0.0001) for category I, and 70.8% in OAPS vs 82% in NC-OAPS (P < 0.0001) for category II. Significant differences were observed when current obstetric complications were compared (P < 0.001). However, major differences between groups were not observed in treatment rates, livebirths and thrombotic complications. In the NC-OAPS group, 176/640 (27.5%) did not fulfil Sydney clinical criteria (subgroup A), 175/640 (27.34%) had a low titre and/or non-persistent aPL positivity but did meet the clinical criteria (subgroup B) and 289/640 (45.15%) had a high aPL titre but did not fulfil Sydney clinical criteria (subgroup C).
Conclusion
Significant clinical and laboratory differences were found between groups. Fetal-maternal outcomes were similar in both groups when treated. These results suggest that we could improve our clinical practice with better understanding of NC-OAPS patients.
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