Systemic Lupus Erythematosus Pregnant Women Research Articles

Systemic Lupus Erythematosus and Pregnancy Complications and Outcomes: A Mendelian Randomization Study and Retrospective Validation.

Previous studies have shown that pregnant women with systemic lupus erythematosus (SLE) tend to have a higher risk of adverse pregnancy outcomes, but the potential causal role remained unclear. In this study, we aimed to investigate the causal relationship between SLE and some common pregnancy complications and outcomes using two-sample Mendelian randomization (MR). The genetic tools were derived from genome-wide association studies of SLE and pregnancy complications and outcomes. MR analysis was performed using inverse variance weighting as primary method. Sensitivity analyses were performed to evaluate the robustness of the results. A retrospective analysis was conducted on 200 pregnant women with SLE and a control group of pregnant women delivering at Tongji Hospital. In the results, we found that genetic susceptibility to SLE was associated with a higher risk of gestational diabetes mellitus (OR = 1.028, 95% CI: 1.006-1.050), premature delivery (OR = 1.039, 95% CI: 1.013-1.066), polyhydramnios (OR = 1.075, 95% CI: 1.004-1.151) and premature rupture of membranes (OR = 1.030, 95% CI: 1.001-1.060). Some of the retrospective analysis results align with the findings from the MR analysis, indicating that pregnant women with SLE have a higher risk of developing gestational diabetes mellitus and preterm birth. Additionally, although MR analysis did not reveal a causal relationship between SLE and preeclampsia/eclampsia, retrospective analysis discovered that SLE pregnant women are more susceptible to developing preeclampsia/eclampsia (OR = 2.935, 95% CI: 1.118-7.620). Our study findings suggest a potential causal relationship between SLE and increased risks of gestational diabetes and preterm delivery. Clinical data indicate that pregnant women with SLE are more prone to developing preeclampsia/eclampsia. Clinicians need to be vigilant about the occurrence of these conditions when managing pregnant women with SLE.

Detection of Quebec Polyomavirus DNA in Samples from Different Patient Groups.

Polyomaviruses infect many species, including humans. So far, 15 polyomaviruses have been described in humans, but it remains to be established whether all of these are genuine human polyomaviruses. The most recent polyomavirus to be detected in a person is Quebec polyomavirus (QPyV), which was identified in a metagenomic analysis of a stool sample from an 85-year-old hospitalized man. We used PCR to investigate the presence of QPyV DNA in urine samples from systemic lupus erythematosus (SLE) patients (67 patients; 135 samples), multiple sclerosis patients (n = 35), HIV-positive patients (n = 66) and pregnant women (n = 65). Moreover, cerebrospinal fluid from patients with suspected neurological diseases (n = 63), nasopharyngeal aspirates from patients (n = 80) with respiratory symptoms and plasma samples from HIV-positive patients (n = 65) were examined. QPyV DNA was found in urine from 11 (16.4%), 10 (15.4%) and 5 (14.3%) SLE patients, pregnant women, and multiple sclerosis patients, respectively. No QPyV DNA could be detected in the other samples. Alignment with the only available QPyV sequence in the GenBank revealed amino acid substitutions in the HI-loop of capsid protein VP1 in 6/28 of the isolates. Our results show that QPyV viruria can occur, but whether it may cause clinical symptoms in the patients remains to be determined.

Breastfeeding in women affected by systemic lupus erythematosus: Rate, duration and associated factors.

Breastfeeding is a crucial moment for both mothers and child, providing a beneficial effect on child survival, nutrition, development and on maternal health. Despite the prevalent involvement of childbearing women in systemic lupus erythematosus (SLE), breastfeeding is still a neglected topic. The objective of this study was to evaluate breastfeeding frequency, duration and associated factors in SLE women. We consecutively enrolled SLE pregnant women reporting demographic, clinical, serological, gynaecological and obstetric data. Breastfeeding experience was evaluated by using a specific questionnaire. Disease activity was assessed before and during pregnancy as well as during postpartum. A total of 57 pregnancies in 43 SLE women were included in the present study. In almost all the pregnancies, mothers planned to breastfeed their child (96.5%) and forty-one (71.9%) actually did breastfeed. The median time of breastfeeding was 3 months (IQR 7). Non-breastfeeding women showed a more frequent caesarean section (p = 0.0001), IUGR occurrence (p = 0.004) and disease relapse (p = 0.0001) after pregnancy. When comparing patients according with breastfeeding duration (cut-off 6 months), we found a significant more frequent smoking habitus (p = 0.02), caesarean section (p = 0.009), and joint involvement during postpartum (p = 0.0001) in women breastfeeding for less than or equal to 6 months, together with higher median BMI (p = 0.0001). Moreover, breastfeeding duration was positively associated with disease duration and hydroxychloroquine (HCQ) treatment during disease history, pregnancy and postpartum. SLE women didn't show lower breastfeeding rate in comparison with general population but they presented higher prevalence of early discontinuation within three months. Early interruption was positively associated with smoking, BMI, joint involvement; meanwhile disease duration and HCQ treatment during postpartum were positively associated with a longer breastfeeding duration.

Reproductive health and pregnancy problems of systemic lupus erythematosus

В настоящее время большинство молодых женщин, страдающих системной красной волчанкой (СКВ), могут успешно забеременеть, выносить и родить здорового ребенка благодаря улучшению возможностей терапевтических подходов и соответствующего снижения заболеваемости и смертности. Исходы беременностей у этих женщин также значительно улучшились за последние десятилетия. Правильный подбор времени зачатия (с учетом активности заболевания и поражения органов-мишеней), тщательный мониторинг пациенток в течение трех триместров и в послеродовом периоде (своевременное выявление и лечение возможных акушерских осложнений или обострений заболеваний у матери), а также концепция междисциплинарного подхода в настоящее время являются основными моментами ведения пациенток с СКВ репродуктивного возраста. Растущие знания о совместимости лекарственных препаратов с беременностью позволили улучшить подходы к лечению таких пациенток, что позволяет контролировать материнское аутоиммунное заболевание без вреда для плода. Отдельное внимание и строгий контроль должны касаться беременных с СКВ в особых клинических ситуациях: пациентки с волчаночным нефритом, с положительным титром антифосфолипидных антител, антифосфолипидным синдромом, пациентки с антителами Ro/SSA и/или La/SSB. Обсуждение вопросов планирования семьи, а также консультирование по вопросам контрацепции должно стать частью повседневной практики для врачей, наблюдающих женщин с СКВ в репродуктивном возрасте. Еще одна проблема заключается в возможном снижении фертильной функции у этих женщин, что может быть связано с разными причинами. Вследствие этого в последние годы растет спрос на вспомогательные методы репродукции, поэтому ревматологи и гинекологи должны быть готовы консультировать пациенток с СКВ и в этой ситуации. В основу данного литературного обзора легли доказательные рекомендации по менеджменту планирования семьи и вопросов здоровья женщин с СКВ и/или антифосфолипидным синдромом, разработанные междисциплинарной группой экспертов Европейской противоревматической лиги 2017 года.

Management and outcomes of pregnancy with or without lupus nephritis: a systematic review and meta-analysis.

BackgroundAlthough it is well established that systemic lupus erythematosus (SLE) negatively affects pregnancy outcomes, there is insufficient evidence on the effect of lupus nephritis (LN) on antenatal management and pregnancy outcomes. We performed a systematic review and meta-analysis to determine the association of LN with management and pregnancy outcomes in SLE patients.MethodsEmbase, Medline, Cochrane, and ClinicalTrials.gov were carefully searched for relevant English and Chinese language studies. A total of 2,987 articles were reviewed. Data were extracted that compared management and pregnancy outcomes in SLE pregnant women with LN vs without LN. Risk of bias was assessed by a modified version of the Newcastle-Ottawa Scale and the STROBE checklist. Combined odds ratios (OR) and 95% confidence intervals (CI) were obtained and sensitivity analysis was performed using RevMan 5.3 software.ResultsSixteen studies, including 1,760 pregnant patients with SLE, were included. Gestational hypertension (OR=5.65, 95% CI=2.94–10.84), preeclampsia (OR=2.84, 95% CI=1.87–4.30), SLE flare (OR=2.66, 95% CI=1.51–4.70), renal flare (OR=15.18, 95% CI=5.89–39.14), proteinuria (OR=8.86, 95% CI=4.75–16.52), and hypocomplementemia (OR=2.86, 95% CI=1.68–4.87) were significantly affected in pregnant women with LN. Anti-Sjögren’s syndrome-related antigen A/Ro autoantibodies were negatively associated with pregnant women with LN (OR=0.57, 95% CI=0.33–0.98). Pregnant women with LN presented a significant decrease in live births (OR=0.62, 95% CI=0.49–0.80) and a significant increase in preterm births (OR=1.92, 95% CI=1.49–2.49) and fetal growth restriction (OR=1.43, 95% CI=1.08–1.91). Regarding antenatal management, steroids (OR=2.48, 95% CI=1.59–3.87) and immunosuppressant treatment (OR=6.77, 95% CI=3.30–13.89) were more frequently used in women with LN.ConclusionThis review identified a significant association between the aforementioned outcomes and SLE pregnant patients with LN. In patients with SLE, LN increased the risks for adverse pregnancy outcomes and the use of medication. Therefore, special treatment and close monitoring should be allocated to pregnant women with LN.

Pro-Inflammatory Cytokines are Elevated in Pregnant Women with Systemic Lupus Erythematosus in Association with the Activation of TLR4.

Autoimmune systemic lupus erythematosus (SLE) is associated with inflammatory activity and frequently causes complications in pregnant women. The aim of the current study was to investigate the serum levels of chemokines and cytokines (CKs) in SLE women during pregnancy and to examine the activation of toll-like receptor 4 (TLR-4) signaling in the deregulation of chemokines and CKs. Blood samples from pregnant women with or without SLE were assayed for the levels of CKs (interleukin (IL)-1β, IL-6, IL-8, and IFN-α), chemokines (IP-10 and RANTES) with enzyme-linked immunosorbent assay (ELISA) and were examined for toll like receptor (TLR)-2, -4, -7, -8 and -9. Then the peripheral blood mononuclear cells (PBMCs) from the SLE or normal pregnant women were treated with lipopolysaccharide (LPS) and were assayed for the CKs promotion. It was demonstrated that there were higher serum concentrations of IL-1p, IL-8, IFN-t, and IP-10 (p < 0.05, p < 0.01 or p < 0.0001) in the SLE pregnant women than in the non-SLE pregnant women. Additionally, the TLR-4 at the mRNA level in the PBMCs was also significantly higher in the SLE pregnant women than in the non-SLE pregnant women (p < 0.05). Moreover, the upregulated IL-1β, IL-8, IFN-α or IP-10 was associated with the promoted TLR-4 level in PBMCs of those SLE patients. In addition, the PBMCs from the SLE pregnant women were more responsive to LPS stimulation. There was more promoted IL-1β, IL-8, or IFN-α in the PBMCs from the SLE pregnant women. High levels of pro-inflammatory CKs and chemokines were promoted during pregnancy in women with SLE, possibly increasing their risk for pregnancy complications. In addition, the TLR4 signaling might play an important role in such CKs promotion.

Azathioprine during pregnancy in systemic lupus erythematosus patients is not associated with poor fetal outcome.

The objective of this study was to evaluate the risk of adverse fetal outcome in systemic lupus erythematosus (SLE) women exposed to azathioprine during pregnancy. We reviewed the medical records of SLE pregnant women followed from January 2005 to April 2013. The patients were evaluated at least once in each trimester and postpartum. Relevant fetal outcomes were extracted, such as rate of liveborns, fetal loss (spontaneous abortion and stillbirth), term delivery, preterm birth, neonatal death, low birth weight, low birth weight at term, and congenital malformations. A detailed history of drug use during pregnancy was obtained. We studied 178 pregnancies (in 172 women), 87 of them were exposed to azathioprine (AZA-group) and the remaining 91 were not exposed (NO AZA-group). Exposure to other drugs was similar in both groups. The rate of live births, spontaneous abortions mean birth weight, weeks of gestation, rate of birth weight <2500g, and low birth weight at term did not differ between groups. No infant had major congenital abnormalities. Multivariate analysis showed that preeclampsia, premature rupture of membranes (PROM), lupus flare, and anti-DNA positive were associated with an increased risk of poor fetal outcome. Our study suggests that the use of azathioprine is safe and lacks of teratogenity in patients with SLE and pregnancy. Exposure to azathioprine during pregnancy is not associated with poor fetal outcome.

Clinical and serological risk factors of systemic lupus erythematosus outcomes during pregnancy

IntroductionSLE is an important risk factor for mother and fetus during pregnancy. Aim of the workTo identify clinical and serological risk factors that may cause poor maternal and fetal outcomes in pregnant systemic lupus erythematosus (SLE) patients. Patients and methodsForty selected SLE pregnant women (group A) versus 35 non-pregnant SLE patients (group B). SLE disease activity index (SLEDAI) and flares were evaluated for both groups. Laboratory investigations included double stranded DNA, anticardiolipin antibodies (aCL), and complements (C3 & C4). SLE pregnant patients were followed up in the second and third trimesters by ultrasonography and fetal Doppler were done to assess fetal outcome. Risk factors for poor maternal and fetal outcome were recorded. ResultsSLEDAI was increased in both groups more in group A. Lupus flares were increased during pregnancy as it occurred in (62.5%) of group A compared to (37.14%) in group B where severe flares were more frequent in group A. Gestational hypertension and active SLEDAI were found statistically significant for poor maternal outcome. Fetal outcome included full term 37.5%, prematurity 25%, intra-uterine growth retardation (IUGR) 22.5%, stillbirth 12.5%, abortion 7.5% and congenital heart block (CHB) 2.5%. Factors significantly associated with poor fetal outcome were severe flares and active renal disease where fetal loss significantly associated with aCL antibodies. Full term was more common in patients with no flares. ConclusionThese data demonstrate that pregnancy in SLE patients should be considered as a high-risk pregnancy and conception should be planned during a quiescent period. Close monitoring for optimal disease control of flares, lupus nephritis, gestational hypertension and aCL antibodies is recommended.

Anti-prolactin autoantibodies in pregnant women with systemic lupus erythematosus: maternal and fetal outcome

The aim of this study was to determine in pregnant women with systemic lupus erythematosus (SLE) the frequency of anti-prolactin autoantibodies and to compare the outcome of pregnancy in SLE women with and without anti-prolactin autoantibodies. Ninety-nine consecutive SLE pregnant women and 151 healthy pregnant women were studied prospectively. Patients with or without anti-prolactin autoantibodies were identified by gel filtration chromatography and affinity chromatography for IgG. Serum total and free prolactin (PRL) levels and molecular heterogeneity of PRL at each trimester of pregnancy were determined. The frequency of anti-PRL autoantibodies in SLE pregnant women was 13.1%. Serum total PRL levels were significantly higher in women with anti-PRL autoantibodies compared with SLE women without anti-PRL autoantibodies and in healthy pregnant women; and serum free PRL levels were lower in the third trimester in women with anti-PRL autoantibodies than in healthy pregnant women. In contrast, serum total and free PRL levels were significantly lower in the second and third trimester in SLE pregnant women without anti-PRL autoantibodies compared with healthy pregnant women. All adverse outcomes of pregnancy studied were more frequent in SLE women without anti-PRL autoantibodies than anti-PRL autoantibody-positive SLE women. Moreover, both maternal and fetal main complications were significantly higher in SLE women without anti-PRL autoantibodies than anti-PRL autoantibody-positive SLE women (P </=0.03). We conclude that the frequency of anti-PRL autoantibodies in lupus pregnancy was 13.1%. SLE pregnant women with anti-PRL autoantibodies had fewer adverse outcomes of pregnancy. The presence of anti-PRL autoantibodies could be of potential use as a prognostic marker for outcomes of pregnancy in SLE.

T(H)1/T(H)2 cytokine profile, metalloprotease-9 activity and hormonal status in pregnant rheumatoid arthritis and systemic lupus erythematosus patients.

During the course of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), several immune and neuroendocrine changes associated with pregnancy may exert positive (amelioration) or negative (exacerbation) effects on the clinical outcome. In order to shed light on the mechanisms underlying these responses, we performed a prospective longitudinal study in RA and SLE pregnant women, including healthy pregnant women as a control group. Cytokine messenger RNA (mRNA) expression assessed by quantitative competitive polymerase chain reaction (PCR) in peripheral blood mononuclear cells (PBMC), cytokine levels and lymphocyte proliferation responses (LPR) following phytohaemagglutinin (PHA) stimulation of PBMC, plasma metalloprotease-9 activity (MMP-9) and hormonal status during pregnancy were determined. TNFa was the most abundant cytokine mRNA expressed in PBMC in all groups studied (healthy pregnant women, RA and SLE pregnant patients). However, a general TH2 response reflected by high IL-10 levels was found in RA, as well as SLE, patients. A significant change in IFN-gamma was observed in RA patients but only during the first trimester of pregnancy. This compared with a major TH1 response in healthy pregnant women. Interestingly, our study showed a homogeneous hormonal pattern in RA and SLE patients. Although decreased cortisol levels were observed in all patients studied, this is possibly related to the remission of disease activity status brought about by steroid treatment before and during pregnancy. In summary, we suggest that complex immune and hormonal networks are involved in pregnancy and that rheumatic diseases are very dynamic immune processes that cannot be described with a clear-cut cytokine profile. Furthermore, the observations in this study may reflect treatment-related immune effects more than those associated with disease.