High-sensitivity cardiac troponin T in infants exposed to anti-Ro antibodies.

OBJECTIVES: Cardiac involvement in neonatal lupus erythematosis (NLE) can present as myocarditis/endocardial fibroelastosis (EFE). It is unknown whether high-sensitivity cardiac troponin T (hs-cTnT) is useful in identifying subclinical myocardial inflammation in infants exposed prenatally to anti-Ro antibodies. This study reports hs-cTnT levels in infants exposed to anti-Ro antibodies with/without cardiac NLE and reports cardiac MRI (CMR) findings in a subset of these children. METHODS: The study included 45 consecutive infants exposed prenatally to anti-Ro antibodies with (n = 7) or without (n = 38) cardiac NLE, who were seen at the SickKids NLE Clinic between 2012 and 2014. Hs-cTnT levels were measured at least once, and those infants with values of ≥30 ng/l were offered the opportunity to undergo CMR. Descriptive statistics were performed. RESULTS: Of 38 infants without cardiac NLE, 25 had a hs-cTnT level of ≥30 ng/l (including 1 of >113 ng/l); of these, 8 underwent CMR (all without myocarditis/EFE). All 7 infants with cardiac NLE had at least one hs-cTnT level of ≥30 ng/l, but only 2/7 had a level of >113 ng/l; 4/7 infants with cardiac NLE had CMR (all without myocarditis/EFE); 6/7 infants with cardiac NLE had their steroid treatment adjusted based on the trend in their hs-cTnT levels. CONCLUSION: Only 3/45 anti-Ro antibodies-exposed infants had hs-cTnT values outside the reference range reported in healthy infants. None of 12 infants who had CMR had subclinical myocarditis/EFE. Routine measurement of hs-cTnT in every anti-Ro antibody-exposed infant is not indicated. Further studies are needed to define the role of hs-cTnT as a biomarker for cardiac NLE.

Immunomodulation for unexplained recurrent implantation failure: where are we now?

In brief: Immune dysfunction may contribute to or cause recurrent implantation failure. This article summarizes normal and pathologic immune responses at implantation and critically appraises currently used immunomodulatory therapies. Abstract: Recurrent implantation failure (RIF) may be defined as the absence of pregnancy despite the transfer of ≥3 good-quality blastocysts and is unexplained in up to 50% of cases. There are currently no effective treatments for patients with unexplained RIF. Since the maternal immune system is intricately involved in mediating endometrial receptivity and embryo implantation, both insufficient and excessive endometrial inflammatory responses during the window of implantation are proposed to lead to implantation failure. Recent strategies to improve conception rates in RIF patients have focused on modulating maternal immune responses at implantation, through either promoting or suppressing inflammation. Unfortunately, there are no validated, readily available diagnostic tests to confirm immune-mediated RIF. As such, immune therapies are often started empirically without robust evidence as to their efficacy. Like other chronic diseases, patient selection for immunomodulatory therapy is crucial, and personalized medicine for RIF patients is emerging. As the literature on the subject is heterogenous and rapidly evolving, we aim to summarize the potential efficacy, mechanisms of actions and side effects of select therapies for the practicing clinician.

Development and internal validation of a model predicting severe maternal morbidity using pre-conception and early pregnancy variables: a population-based study in Ontario, Canada.

BACKGROUND: Improvement in the prediction and prevention of severe maternal morbidity (SMM) - a range of life-threatening conditions during pregnancy, at delivery or within 42 days postpartum - is a public health priority. Reduction of SMM at a population level would be facilitated by early identification and prediction. We sought to develop and internally validate a model to predict maternal end-organ injury or death using variables routinely collected during pre-pregnancy and the early pregnancy period. METHODS: We performed a population-based cohort study using linked administrative health data in Ontario, Canada, from April 1, 2006 to March 31, 2014. We included women aged 18-60 years with a livebirth or stillbirth, of which one birth was randomly selected per woman. We constructed a clinical prediction model for the primary composite outcome of any maternal end-organ injury or death, arising between 20 weeks' gestation and 42 days after the birth hospital discharge date. Our model included variables collected from 12 months before estimated conception until 19 weeks' gestation. We developed a separate model for parous women to allow for the inclusion of factors from previous pregnancy(ies). RESULTS: Of 634,290 women, 1969 experienced the primary composite outcome (3.1 per 1000). Predictive factors in the main model included maternal world region of origin, chronic medical conditions, parity, and obstetrical/perinatal issues - with moderate model discrimination (C-statistic 0.68, 95% CI 0.66-0.69). Among 333,435 parous women, the C-statistic was 0.71 (0.69-0.73) in the model using variables from the current (index) pregnancy as well as pre-pregnancy predictors and variables from any previous pregnancy. CONCLUSIONS: A combination of factors ascertained early in pregnancy through a basic medical history help to identify women at risk for severe morbidity, who may benefit from targeted preventive and surveillance strategies including appropriate specialty-based antenatal care pathways. Further refinement and external validation of this model are warranted and can support evidence-based improvements in clinical practice.

Ethnicity and Neonatal Lupus Erythematosus Manifestations Risk in a Large Multiethnic Cohort.

OBJECTIVE: To evaluate the association between ethnicity and neonatal lupus erythematosus (NLE), as well as specific NLE manifestations in a large multiethnic population. METHODS: We conducted a cohort study of the children (≤ 1 yr of age) seen in the NLE clinic at The Hospital for Sick Children (SickKids), between January 2011 and April 2019. The cohort was divided into European, non-European, and mixed European-non-European groups according to parent-reported child's ethnicity (Canada Census categories). Outcomes were NLE and specific NLE manifestations (cardiac, cutaneous, cytopenias, transaminitis, and macrocephaly). The frequency of NLE and specific manifestations were compared between ethnic groups (Fisher exact test). We tested the association between ethnicity and (1) NLE risk, and (2) specific NLE manifestations with logistic regression models, including covariates for child's sex, maternal rheumatic disease status during pregnancy, and maternal use of antimalarials during pregnancy (multiple comparisons threshold P < 0.008). RESULTS: We included 324 children born to 270 anti-Ro antibody-positive mothers. Median age at first visit was 1.8 (IQR 1.4-2.3) months, and median follow-up time was 12 (IQR 2-24) months. The majority was non-European (48%), with 34% European, and 18% mixed European-non-European. There was no significant association between non-European ethnicity (OR 1.18, 95% CI 0.71-1.94, P = 0.51), mixed European-non-European ethnicity (OR 1.13, 95% CI 0.59-2.16, P = 0.70), and NLE risk compared with European ethnicity. We also did not find an association between ethnicity and specific NLE manifestations in univariate or multivariable-adjusted models. CONCLUSION: In a large multiethnic cohort, there was no association between a child's ethnicity and NLE risk or specific NLE manifestations.

2020 American College of Rheumatology Guideline for the Management of Reproductive Health in Rheumatic and Musculoskeletal Diseases

To develop an evidence-based guideline on contraception, assisted reproductive technologies (ART), fertility preservation with gonadotoxic therapy, use of menopausal hormone replacement therapy (HRT), pregnancyassessment and management, and medication use in patients with rheumatic and musculoskeletal disease (RMD). We conducted a systematic review of evidence relating to contraception, ART, fertility preservation,HRT, pregnancy and lactation, and medication use in RMD populations, using Grading of Recommendations Assessment, Development and Evaluation methodology to rate the quality of evidence and a group consensus process todetermine final recommendations and grade their strength (conditional or strong). Good practice statements wereagreed upon when indirect evidence was sufficiently compelling that a formal vote was unnecessary.. This American College of Rheumatology guideline provides 12 ungraded good practice statements and131 graded recommendations for reproductive health care in RMD patients. These recommendations are intended toguide care for all patients with RMD, except where indicated as being specific for patients with systemic lupus erythematosus, those positive for antiphospholipid antibody, and/or those positive for anti-Ro/SSA and/or anti-La/SSBantibodies. Recommendations and good practice statements support several guiding principles: use of safe andeffective contraception to prevent unplanned pregnancy, pre-pregnancy counseling to encourage conception during periods of disease quiescence and while receiving pregnancy-compatible medications, and ongoing physicianpatient discussion with obstetrics/gynecology collaboration for all reproductive health issues, given the overall low level of available evidence that relates specifically to RMD. Guidelines and recommendations developed and/or endorsed by the American College of Rheumatology (ACR) are intended to provide guidance for patterns of practice and not to dictate the care of a particular patient. The ACR considers adherence to the recommendations within this guideline to be voluntary, with the ultimate determination regarding their application to be made by the clinician in light of each patient's individual circumstances. Guidelines and recommendations are intended to promote beneficial or desirable outcomes, but cannot guarantee any specific outcome. Guidelines and recommendations developed and endorsed by the ACR are subject to periodic revision, as warranted by the evolution of medical knowledge, technology, and practice. ACR recommendations are not intended to dictate payment or insurance decisions. These recommendations cannot adequately convey all uncertainties and nuances of patient care. The American College of Rheumatology is an independent, professional, medical and scientific society that does not guarantee, warrant, or endorse any commercial product or service. This guideline provides evidence-based recommendations developed and reviewed by panels of experts and RMD patients. Many recommendations are conditional, reflecting a lack of data or low-level data. We intend that this guideline be used to inform a shared decision-making process between patients and their physicians on issues related to reproductive health that incorporates patients' values, preferences, and comorbidities.

Low frequency of flares during pregnancy and post-partum in stable lupus patients.

BACKGROUND: Lupus patients are at risk for pregnancy loss, and it has been generally accepted that women with SLE should have low disease activity prior to conception. However, there are conflicting results regarding the effect of pregnancy on SLE flares. This study aims to identify predictors of flares during and after pregnancy in SLE patients with inactive or stable disease activity during the first trimester and to characterize and estimate the frequency of post-partum flares in these patients. METHODS: SLE patients in the multicenter, prospective PROMISSE (Predictors of Pregnancy Outcome: Biomarkers in Antiphospholipid Antibody Syndrome and Systemic Lupus Erythematosus) study were evaluated for flares during and after pregnancy using the SELENA-SLEDAI Flare Index. Flares during pregnancy were assessed in all 384 patients and post-partum flares in 234 patients with study visits 2-6 months post-partum. Logistic regression models were fit to the data to identify independent risk factors for flare. RESULTS: During pregnancy, 20.8% of patients had mild/moderate flares and 6.25% had severe. Post-partum, 27.7% of patients had mild/moderate flares and 1.7% had severe. The mild flares rarely required treatment. Younger age, low C4 and higher PGA at baseline were independently associated with higher risk of having at least one mild/moderate or severe flare during pregnancy. Older patients were at decreased risk of flare, as well as those with quiescent disease at baseline. No variables evaluated at baseline or the visit most proximal to delivery was significantly associated with risk of flare post-partum. Medications were not associated with flare during or after pregnancy. CONCLUSION: In patients with inactive or stable mild disease activity at the time of conception, lupus disease flares during and after pregnancy are typically mild and occur at similar rates. Flares during pregnancy are predicted by the patients' age and clinical and serological activity at baseline.

2020 American College of Rheumatology Guideline for the Management of Reproductive Health in Rheumatic and Musculoskeletal Diseases.

OBJECTIVE: To develop an evidence-based guideline on contraception, assisted reproductive technologies (ART), fertility preservation with gonadotoxic therapy, use of menopausal hormone replacement therapy (HRT), pregnancy assessment and management, and medication use in patients with rheumatic and musculoskeletal disease (RMD). METHODS: We conducted a systematic review of evidence relating to contraception, ART, fertility preservation, HRT, pregnancy and lactation, and medication use in RMD populations, using Grading of Recommendations Assessment, Development and Evaluation methodology to rate the quality of evidence and a group consensus process to determine final recommendations and grade their strength (conditional or strong). Good practice statements were agreed upon when indirect evidence was sufficiently compelling that a formal vote was unnecessary. RESULTS: This American College of Rheumatology guideline provides 12 ungraded good practice statements and 131 graded recommendations for reproductive health care in RMD patients. These recommendations are intended to guide care for all patients with RMD, except where indicated as being specific for patients with systemic lupus erythematosus, those positive for antiphospholipid antibody, and/or those positive for anti-Ro/SSA and/or anti-La/SSB antibodies. Recommendations and good practice statements support several guiding principles: use of safe and effective contraception to prevent unplanned pregnancy, pre-pregnancy counseling to encourage conception during periods of disease quiescence and while receiving pregnancy-compatible medications, and ongoing physician-patient discussion with obstetrics/gynecology collaboration for all reproductive health issues, given the overall low level of available evidence that relates specifically to RMD. CONCLUSION: This guideline provides evidence-based recommendations developed and reviewed by panels of experts and RMD patients. Many recommendations are conditional, reflecting a lack of data or low-level data. We intend that this guideline be used to inform a shared decision-making process between patients and their physicians on issues related to reproductive health that incorporates patients' values, preferences, and comorbidities.

2020 American College of Rheumatology Guideline for the Management of Reproductive Health in Rheumatic and Musculoskeletal Diseases.

OBJECTIVE: To develop an evidence-based guideline on contraception, assisted reproductive technologies (ART), fertility preservation with gonadotoxic therapy, use of menopausal hormone replacement therapy (HRT), pregnancy assessment and management, and medication use in patients with rheumatic and musculoskeletal disease (RMD). METHODS: We conducted a systematic review of evidence relating to contraception, ART, fertility preservation, HRT, pregnancy and lactation, and medication use in RMD populations, using Grading of Recommendations Assessment, Development and Evaluation methodology to rate the quality of evidence and a group consensus process to determine final recommendations and grade their strength (conditional or strong). Good practice statements were agreed upon when indirect evidence was sufficiently compelling that a formal vote was unnecessary. RESULTS: This American College of Rheumatology guideline provides 12 ungraded good practice statements and 131 graded recommendations for reproductive health care in RMD patients. These recommendations are intended to guide care for all patients with RMD, except where indicated as being specific for patients with systemic lupus erythematosus, those positive for antiphospholipid antibody, and/or those positive for anti-Ro/SSA and/or anti-La/SSB antibodies. Recommendations and good practice statements support several guiding principles: use of safe and effective contraception to prevent unplanned pregnancy, pre-pregnancy counseling to encourage conception during periods of disease quiescence and while receiving pregnancy-compatible medications, and ongoing physician-patient discussion with obstetrics/gynecology collaboration for all reproductive health issues, given the overall low level of available evidence that relates specifically to RMD. CONCLUSION: This guideline provides evidence-based recommendations developed and reviewed by panels of experts and RMD patients. Many recommendations are conditional, reflecting a lack of data or low-level data. We intend that this guideline be used to inform a shared decision-making process between patients and their physicians on issues related to reproductive health that incorporates patients' values, preferences, and comorbidities.

Longitudinal profiling of human blood transcriptome in healthy and lupus pregnancy.

Systemic lupus erythematosus carries an increased risk of pregnancy complications, including preeclampsia and fetal adverse outcomes. To identify the underlying molecular mechanisms, we longitudinally profiled the blood transcriptome of 92 lupus patients and 43 healthy women during pregnancy and postpartum and performed multicolor flow cytometry in a subset of them. We also profiled 25 healthy women undergoing assisted reproductive technology to monitor transcriptional changes around embryo implantation. Sustained down-regulation of multiple immune signatures, including interferon and plasma cells, was observed during healthy pregnancy. These changes appeared early after embryo implantation and were mirrored in uncomplicated lupus pregnancies. Patients with preeclampsia displayed early up-regulation of neutrophil signatures that correlated with expansion of immature neutrophils. Lupus pregnancies with fetal complications carried the highest interferon and plasma cell signatures as well as activated CD4+ T cell counts. Thus, blood immunomonitoring reveals that both healthy and uncomplicated lupus pregnancies exhibit early and sustained transcriptional modulation of lupus-related signatures, and a lack thereof associates with adverse outcomes.

Infertility treatment and risk of severe maternal morbidity: a propensity score-matched cohort study.

BACKGROUND: The extent to which infertility treatment predicts severe maternal morbidity is not well known. We examined the association between infertility treatment and severe maternal morbidity in pregnancy and the postpartum period. METHODS: We conducted a cohort study using population-based registries from Ontario between 2006 and 2012. Pregnancies achieved using infertility treatment (ovulation induction, intrauterine insemination or in vitro fertilization with or without intracytoplasmic sperm injection) were compared with unassisted pregnancies using propensity score matching, based on demographic, reproductive and obstetric factors. The primary outcome was a validated composite of severe maternal morbidity or maternal death from 20 weeks' gestation to 42 days postpartum. We also calculated the odds ratio of a woman having 1, 2, or 3 or more severe maternal morbidity indicators in relation to invasive (e.g., in vitro fertilization) or noninvasive (e.g., intrauterine insemination) infertility treatment. RESULTS: We matched 11 546 infertility treatment pregnancies with 47 553 untreated pregnancies. Severe maternal morbidity or maternal death occurred in 356 infertility-treated pregnancies (30.8 per 1000 deliveries) versus 1054 untreated pregnancies (22.2 per 1000 deliveries); relative risk 1.39 (95% confidence interval [CI] 1.23-1.56). The likelihood of a woman having 3 or more severe maternal morbidity indicators was increased in women who received invasive infertility treatment (odds ratio [OR] 2.28, 95% CI 1.56-3.33) but not in those who received noninvasive infertility treatment (OR 0.99, 95% CI 0.57-1.72). INTERPRETATION: Women who undergo infertility treatment, particularly in vitro fertilization, are at somewhat higher risk of severe maternal morbidity or death. Efforts are needed to identify patient- and treatment-specific predictors of severe maternal morbidity that may influence the type of treatment a woman is offered.

Effect of endometrial injury on in vitro fertilization pregnancy rates: a randomized, multicentre study.

PURPOSE: To determine if endometrial injury prior to the first or second in vitro fertilization (IVF) cycle affects clinical pregnancy rates. METHODS: This study was a randomized, multicentre, controlled study performed at three Canadian outpatient fertility clinics. Patients undergoing their first or second IVF cycle were randomized to a single endometrial injury 5-10 days prior to the start of gonadotropins in an IVF cycle compared to no injury. The primary outcome was clinical pregnancy rate. Secondary outcomes were live birth rates, implantation rate, endometrial thickness, number of oocytes retrieved and the rate of embryo cryopreservation. RESULTS: Fifty-one women were randomized (25 in the en dometrial injury group and 26 in the control group); however, the study was terminated prematurely due to slow recruitment (target 332 patients). Groups were similar at baseline for: age, duration of infertility, BMI, day 3 FSH, and the number having first IVF cycle. The groups were similar for gonadotropin dose, endometrial thickness, number of oocytes retrieved, and embryo cryopreservation rate. The clinical pregnancy rate in the endometrial injury group was 52% (13/25) and 46% (12/26) in the control group (p = 0.45). Live birth rate in the endometrial injury group was 52% (13/25) and 35% (9/26) in the control group (p = 0.17). The implantation rate was also similar (58% vs. 45%, p = 0.17). CONCLUSIONS: This study did not detect a difference in implantation, clinical pregnancy or live birth rates; however, the lack of difference in this study may be because it was underpowered. CLINICAL TRIALS REGISTRATIONS: gov: NCT01983423.

Outcome of pregnancy in women with psoriatic arthritis compared to healthy controls.

OBJECTIVES: The mean age at onset of psoriatic arthritis (PsA) ranges between the 4th-6th decades of life. However, little is known about fertility and pregnancy outcome in PsA patients. The aim of this study was to examine whether fertility and pregnancy outcome of PsA patients are different from healthy controls and to evaluate PsA and psoriasis disease activity perception during pregnancy and the year postpartum. METHODS: A questionnaire-based study, including demographic, fertility, pregnancy outcome, and disease activity questions, was conducted in PsA patients and healthy controls. The inclusion criterion was diagnosis of PsA before at least 1 pregnancy. Descriptive statistics are provided. T tests and Pearson chi-square tests were used to analyze the differences between continuous and categorical variables, respectively. RESULTS: The 74 PsA patients and 74 healthy controls were not significantly different in most of the demographic variables. The mean number of pregnancies, children, and infertility diagnosis were not significantly different between the groups. The pregnancy outcomes in the PsA group (n = 151) and in the control group (n = 189) were similar in: live birth (76% vs. 76%, P = 0.3), vaginal delivery (48% vs. 51%, P = 0.6), gestation age (38.5 vs. 38.3, P = 0.3), weight at birth (3.4 kg vs. 3.4 kg, P = 0.5), low rate of maternal and fetal complications, and the duration and rate of breastfeeding. Most (58%) patients reported favorable joint activity during pregnancy and 50% reported worsening during the 1st postpartum year. CONCLUSIONS: PsA patients do not have more infertility or worse pregnancy outcomes compared to healthy controls.

Effect of in utero hydroxychloroquine exposure on the development of cutaneous neonatal lupus erythematosus.

OBJECTIVE: Cutaneous neonatal lupus (cNL) occurs in possibly 5%-16% of anti-Ro±anti-La antibody-exposed infants. Data suggest in utero exposure to hydroxychloroquine (HCQ) may prevent cardiac NL. The aim was to assess whether in utero exposure to HCQ decreases the risk of cNL and/or delays onset. METHODS: A multicentre case-control study was performed with 122 cNL cases and 434 controls born to women with a rheumatological disease who had documentation of maternal anti-Ro±anti-La antibodies at pregnancy and confirmation of medication use and the child's outcome. A secondary analysis was performed on 262 cNL cases, irrespective of maternal diagnosis, to determine if HCQ delayed time to cNL onset. RESULTS: Twenty (16%) cNL cases were exposed to HCQ compared with 146 (34%) controls (OR 0.4 (95% CI 0.2 to 0.6); p<0.01). Exposure to HCQ was associated with a reduced risk of cNL; exposure to anti-La antibody and female gender were associated with an increased risk of cNL. Exposure to HCQ remained significantly associated with a reduced cNL risk in the analyses limited to mothers with systemic lupus erythematosus and those who developed rash ≤1 month. When analysing all 262 cNL cases, HCQ-exposed infants were older (6.0 (95% CI 5.7 to 6.3) weeks) at cNL onset versus HCQ-non-exposed infants (4.4 (95% CI 3.9 to 5.0) weeks), but the difference was not statistically significant (p=0.21). CONCLUSION: Exposure to HCQ was associated with a reduced risk of cNL. Among cNL cases, those exposed to HCQ tend to have later onset of rash. Both findings suggest a protective effect of HCQ on cNL.

Maternal and Fetal Outcomes in a Cohort of Patients Exposed to Tumor Necrosis Factor Inhibitors throughout Pregnancy.

OBJECTIVE: Tumor necrosis factor inhibitors (TNFi) are increasingly used in pregnancy but are frequently withheld in the second or third trimesters. We evaluated the maternal and fetal outcomes of women who continued their TNFi throughout pregnancy compared to women who interrupted TNFi during pregnancy. METHODS: We retrospectively analyzed the outcomes of women seen in clinic with rheumatoid arthritis (RA), psoriatic arthritis, juvenile idiopathic arthritis (JIA), or ankylosing spondylitis, who were exposed to TNFi during pregnancy. We separated pregnancies into 2 groups based on the level of TNFi exposure and compared outcomes. RESULTS: In Group 1 (TNFi exposure in first trimester only), 11 women had 14 pregnancies and 12 live births. There were 2 first-trimester losses (2/14, 14%), one in the setting of active RA. Five pregnancies (5/14, 35.7%) were complicated by a disease flare. Eight patients (8/12, 66%) flared postpartum. In Group 2 (TNFi exposure throughout pregnancy), 29 women had 32 pregnancies and 34 live births. Three (3/28, 10.7%) adverse pregnancy outcomes were reported in 2 patients. One patient had a twin pregnancy and delivered at 33 weeks after developing preterm premature rupture of membranes at 32 weeks in the setting of a JIA flare. Her second pregnancy was complicated by active JIA before and throughout gestation, and hemolysis, elevated liver enzyme levels, and low platelet levels (HELLP) syndrome at 39 weeks. Another patient with comorbid antiphospholipid syndrome underwent a cesarean birth at 36 weeks for suspicion of HELLP syndrome. Six (6/32, 18.7%) postpartum flares occurred. CONCLUSION: Women who discontinued their TNFi during pregnancy had a higher risk of peri- or postpartum flare compared to those who continued their TNFi throughout pregnancy.

Complement activation predicts adverse pregnancy outcome in patients with systemic lupus erythematosus and/or antiphospholipid antibodies.

OBJECTIVE: Studies in mouse models implicate complement activation as a causative factor in adverse pregnancy outcomes (APOs). We investigated whether activation of complement early in pregnancy predicts APOs in women with systemic lupus erythematosus (SLE) and/or antiphospholipid (aPL) antibodies. METHODS: The PROMISSE Study enrolled pregnant women with SLE and/or aPL antibodies (n=487) and pregnant healthy controls (n=204) at <12 weeks gestation and evaluated them monthly. APOs were: fetal/neonatal death, preterm delivery <36 weeks because of placental insufficiency or preeclampsia and/or growth restriction <5th percentile. Complement activation products were measured on serial blood samples obtained at each monthly visit. RESULTS: APO occurred in 20.5% of SLE and/or aPL pregnancies. As early as 12-15 weeks, levels of Bb and sC5b-9 were significantly higher in patients with APOs and remained elevated through 31 weeks compared with those with normal outcomes. Moreover, Bb and sC5b-9 were significantly higher in patients with SLE and/or aPL without APOs compared with healthy controls. In logistic regression analyses, Bb and sC5b-9 at 12-15 weeks remained significantly associated with APO (ORadj=1.41 per SD increase; 95% CI 1.06 to 1.89; P=0.019 and ORadj=1.37 per SD increase; 95% CI 1.05 to 1.80; P=0.022, respectively) after controlling for demographic and clinical risk factors for APOs in PROMISSE. When analyses were restricted to patients with aPL (n=161), associations between Bb at 12-15 weeks and APOs became stronger (ORadj=2.01 per SD increase; 95% CI 1.16 to 3.49; P=0.013). CONCLUSION: In pregnant patients with SLE and/or aPL, increased Bb and sC5b-9 detectable early in pregnancy are strongly predictive of APOs and support activation of complement, particularly the alternative pathway, as a contributor to APOs.

Contribution of Socioeconomic Status to Racial/Ethnic Disparities in Adverse Pregnancy Outcomes Among Women With Systemic Lupus Erythematosus.

OBJECTIVE: We examined rates of adverse pregnancy outcomes (APO) by race/ethnicity among women with systemic lupus erythematosus (SLE), with and without antiphospholipid antibodies (aPL), and whether socioeconomic status (SES) accounted for differences. METHODS: Data were from the PROMISSE (Predictors of Pregnancy Outcome: Biomarkers in Antiphospholipid Antibody Syndrome and Systemic Lupus Erythematosus) study, a multicenter study that enrolled 346 patients with SLE and 62 patients with SLE and aPL (50% white, 20% African American, 17% Hispanic, 12% Asian/Pacific Islander). Measures of SES were educational attainment, median community income, and community education. Logistic regression analyses were conducted to determine odds of APO for each racial/ethnic group, controlling first for age and clinical variables, and then for SES. RESULTS: The frequency of APO in white women with SLE, with and without aPL, was 29% and 11%, respectively. For African American and Hispanic women it was approximately 2-fold greater. In African American women with SLE alone, adjustment for clinical variables attenuated the odds ratio (OR) from 2.7 (95% confidence interval [95% CI] 1.3-5.5) to 2.3 (95% CI 1.1-5.1), and after additional adjustment for SES, there were no longer significant differences in APO compared to whites. In contrast, in SLE patients with aPL, whites, African Americans, and Hispanics had markedly higher risks of APO compared to white SLE patients without aPL (OR 3.5 [95% CI 1.4-7.7], OR 12.4 [95% CI 1.9-79.8], and OR 10.4 [95% CI 2.5-42.4], respectively), which were not accounted for by clinical or SES covariates. CONCLUSION: This finding suggests that for African American women with SLE without aPL, SES factors are key contributors to disparities in APO, despite monthly care from experts, whereas other factors contribute to disparities in SLE with aPL.

Prenatal exposure to antimalarials decreases the risk of cardiac but not non-cardiac neonatal lupus: a single-centre cohort study.

Objective: Recent studies have suggested that prenatal exposure to HCQ reduces the risk of cardiac neonatal lupus. The aim of this study is to assess if maternal intake of antimalarials (AMs) throughout pregnancy lowered the risk of cardiac and non-cardiac neonatal lupus. Methods: Consecutive children seen between 1 January 1984 to 1 October 2013 born to women with a CTD and positive anti-Ro and/or anti-La antibodies were eligible for this single-centre retrospective cohort study. A total of 315 individuals were screened and 268 participants were included. Exposure to AMs was defined as HCQ or chloroquine throughout pregnancy. Outcomes were cardiac and non-cardiac neonatal lupus. Frequentist and Bayesian analyses were performed. We hypothesized that prenatal AM exposure would decrease the risk of cardiac but not non-cardiac neonatal lupus. Results: A total of 268 pregnancies were included; 73 were exposed to AMs throughout pregnancy. Ninety-nine children developed neonatal lupus, 117 remained unaffected and 52 children did not develop cardiac neonatal lupus but could not be categorized as unaffected since their full non-cardiac neonatal lupus status was unknown. Logistic regression suggested a protective effect of AM on cardiac neonatal lupus, but results were not statistically significant [odds ratio (OR) 0.21; P = 0.07]. Bayesian analysis showed that the probability of obtaining a protective effect (OR < 1.0) for cardiac neonatal lupus was significant (98.7%). The effect of AMs on non-cardiac neonatal lupus was not significant (OR 0.78; P = 0.21). Conclusion: In this large single-centre cohort study, exposure to AMs throughout pregnancy was associated with a decreased probability of developing cardiac but not non-cardiac neonatal lupus.

Kidney Outcomes and Risk Factors for Nephritis (Flare/De Novo) in a Multiethnic Cohort of Pregnant Patients with Lupus.

BACKGROUND AND OBJECTIVES: Kidney disease is a critical concern in counseling patients with lupus considering pregnancy. This study sought to assess the risk of renal flares during pregnancy in women with previous lupus nephritis in partial or complete remission, particularly in those with antidouble-stranded DNA antibodies and low complement levels, and the risk of new-onset nephritis in patients with stable/mildly active SLE. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We assessed active nephritis (renal flares and de novo kidney disease) and associated predictors during pregnancy in patients with lupus with urine protein ≤1000 mg and serum creatinine <1.2 mg/dl at baseline; 373 patients (52% ethnic/racial minorities) enrolled between 2003 and 2012 were prospectively followed in the Predictors of Pregnancy Outcome: Biomarkers in Antiphospholipid Syndrome and Systemic Lupus Erythematosus Study. Active nephritis was defined by proteinuria increase of >500 mg and/or red blood cell casts. RESULTS: Of 118 patients with previous kidney disease, 13 renal flares (11%) occurred (seven of 89 in complete remission and six of 29 in partial remission) compared with four with de novo kidney involvement (2%) in 255 patients without past kidney disease (P<0.001). Active nephritis was not associated with ethnicity, race, age, creatinine, BP, or antihypertensive and other medications. In multivariable logistic regression analyses, patients with past kidney disease in complete or partial remission more often experienced active nephritis (adjusted odds ratio, 6.88; 95% confidence interval, 1.84 to 25.71; P=0.004 and adjusted odds ratio, 20.98; 95% confidence interval, 4.69 to 93.98; P<0.001, respectively) than those without past kidney disease. Low C4 was associated with renal flares/de novo disease (adjusted odds ratio, 5.59; 95% confidence interval, 1.64 to 19.13; P<0.01) but not low C3 or positive anti-dsDNA alone. CONCLUSIONS: De novo kidney involvement in SLE, even in ethnic/racial minorities, is uncommon during pregnancy. Past kidney disease and low C4 at baseline independently associate with higher risk of developing active nephritis. Antibodies to dsDNA alone should not raise concern, even in patients with past kidney disease, if in remission.