Vitamin K Antagonists for Pregnant Women With Antiphospholipid Antibodies: A Scoping Review.

Objective: To describe characteristics of published research on the safety and efficacy of vitamin K antagonists (VKA) for pregnant patients with antiphospholipid antibodies (aPL), including their methodological characteristics and knowledge gaps.

Methods: This study followed the Joanna Briggs Institute methodology for scoping reviews and used the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews protocol system. Studies were primarily identified through searching electronic databases including MEDLINE, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials.

Genetics of Neonatal Lupus Erythematosus Risk and Specific Manifestations.

Objective: Neonatal lupus erythematosus (NLE) is a passively acquired autoimmune disease in infants born to anti-Ro and/or anti-La autoantibody-positive mothers. Genetics may affect NLE risk. We analyzed the genetics of infants and anti-Ro antibody-positive mothers, with NLE and NLE-specific manifestations.

Intravenous immunoglobulin for patients with unexplained recurrent implantation failure: a 6-year single center retrospective review of clinical outcomes.

The effectiveness of intravenous immunoglobulin (IVIg) for patients with unexplained recurrent implantation failure (uRIF) remains debated. We retrospectively analysed outcomes of uRIF patients treated with IVIg compared to a separate control uRIF cohort within our center (01/2014-12/2021). Primary outcomes included live birth, miscarriage, or transfer failure.

2023 ACR/EULAR antiphospholipid syndrome classification criteria.

Objective: To develop new antiphospholipid syndrome (APS) classification criteria with high specificity for use in observational studies and trials, jointly supported by the American College of Rheumatology (ACR) and EULAR.

Methods: This international multidisciplinary initiative included four phases: (1) Phase I, criteria generation by surveys and literature review; (2) Phase II, criteria reduction by modified Delphi and nominal group technique exercises; (3) Phase III, criteria definition, further reduction with the guidance of real-world patient scenarios, and weighting via consensus-based multicriteria decision analysis, and threshold identification; and (4) Phase IV, validation using independent adjudicators' consensus as the gold standard.

Results: The 2023 ACR/EULAR APS classification criteria include an entry criterion of at least one positive antiphospholipid antibody (aPL) test within 3 years of identification of an aPL-associated clinical criterion, followed by additive weighted criteria (score range 1-7 points each) clustered into six clinical domains (macrovascular venous thromboembolism, macrovascular arterial thrombosis, microvascular, obstetric, cardiac valve, and hematologic) and two laboratory domains (lupus anticoagulant functional coagulation assays, and solid-phase enzyme-linked immunosorbent assays for IgG/IgM anticardiolipin and/or IgG/IgM anti-β-glycoprotein I antibodies).

Intravenous immunoglobulin use in patients with unexplained recurrent pregnancy loss.

Problem: Recurrent pregnancy loss (RPL) affects up to 4% of couples attempting to conceive. RPL is unexplained in over 50% of cases and no effective treatments exist. Due to the immune system's pivotal role during implantation and pregnancy, immune-mediated RPL may be suspected and immunomodulatory treatments like intravenous immunoglobulin (IVIg) have been administered but remain controversial.

Maternal Anti-Ro Antibody Titers Obtained With Commercially Available Immunoassays Are Strongly Associated With Immune-Mediated Fetal Heart Disease.

Objective: Anti-Ro antibody-positive mothers are frequently referred for serial echocardiography due to the fetal risk of developing heart block and endocardial fibroelastosis. Little is known why only some and not all offspring develop these cardiac manifestations of neonatal lupus (CNL). This prospective study examined associations between anti-Ro antibody titers and fetal CNL.

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.

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.

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.

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).

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.

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.

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.

The Affordability and Accessibility of Ontario's Publicly Funded IVF Program: A Survey of Patients.

Objective: On December 21, 2015, the Province of Ontario created the Ontario Fertility Program to fund one cycle of in vitro fertilization (IVF) to improve IVF affordability and access for Ontarians below age 43. The objective of this study was to determine whether the Program was meeting this goal, based on the experiences of participating patients.

Methods: Participation in an electronic survey was invited through posters and brochures placed within the waiting rooms of all 25 IVF clinics providing funded IVF in Ontario and by a survey link placed on websites focused on fertility issues.

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.

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.

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.

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.

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.

Bleeding complications and antithrombotic treatment in 264 pregnancies in antiphospholipid syndrome.

Purpose The purpose of this study was to evaluate the safety of antithrombotic treatments prescribed during pregnancy in patients with antiphospholipid syndrome (APS). Methods This international, multicenter study included two cohorts of patients: a retrospective French cohort and a prospective US cohort (PROMISSE study). Inclusion criteria were (1) APS (Sydney criteria), (2) live pregnancy at 12 weeks of gestation (WG) with (3) follow-up data until six weeks post-partum.

Severe maternal morbidity in women with high BMI in IVF and unassisted singleton pregnancies.

Study Question: Is there a synergistic risk of severe maternal morbidity (SMM) in overweight/obese women who conceived by IVF compared to normal-weight women without IVF?

Summary Answer: SMM was more common in IVF pregnancies, and among overweight/obese women, but we did not detect a synergistic effect of both factors.

What Is Known Already: While much is known about the impact of overweight and obesity on success rates after IVF, there is less data on maternal health outcomes.

Study Design, Size, Duration: This is a population-based cohort study of 114 409 singleton pregnancies with conceptions dating from 11 January 2013 until 10 January 2014 in Ontario, Canada.

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.

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.

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.