Altered DNA methylation in children born to mothers with rheumatoid arthritis during pregnancy

Objectives The main objective of this study was to determine whether the DNA methylation profile of children born to mothers with rheumatoid arthritis (RA) is different from that of children born to mothers from the general population. In addition, we aimed to determine whether any differences in methylation are associated with maternal RA disease activity or medication use during pregnancy. Methods For this study, genome-wide DNA methylation was measured at cytosine-phosphateguanine (CpG) sites, using the Infinium Illumina HumanMethylation 450K BeadChip, in 80 blood samples from children (mean age=6.8 years) born to mothers with RA. As controls, blood samples from 354 children (mean age=6.0 years) from the population-based Generation R Study were used. Linear mixed models were performed to investigate differential methylation between the groups, corrected for relevant confounders. Results A total of 147 CpGs were differentially methylated between blood samples of children born to mothers with RA and the control blood samples. The five most significantly associated CpGs were cg06642177, cg08867893, cg06778273, cg07786668 and cg20116574. The differences in methylation were not associated with maternal RA disease activity or medication use during pregnancy. Conclusions DNA methylation at 147 CpGs differed between children born to mothers with RA and children born to mothers from the general population. It remains unknown whether the identified associations are causal, and if so whether they are caused by the disease or treatment. More research, including replication of these results, is necessary in order to strengthen the relevance of our findings for the later-life health of children born to mothers with R

Associations between antenatal prednisone exposure and long-term cortisol and cortisone concentrations in children born to women with rheumatoid arthritis: results from a nationwide prospective cohort study

Objectives To identify whether children with antenatal prednisone exposure have chronically elevated cortisol and cortisone concentrations, an altered body composition or higher blood pressure. In addition, to identify whether maternal rheumatoid arthritis disease (RA) activity is associated with these alterations. Methods In this prospective study, 56 children (mean age=10.0 years) with and 61 children (mean age=9.6 years) without antenatal prednisone exposure, born to women with RA, were included. Hair cortisol and cortisone were analysed using liquid chromatography–tandem mass spectrometry. Linear regression models were built to analyse differences between the two groups, corrected for relevant covariates. Hair cortisol concentrations were also compared between the study population and an age-matched healthy reference group(n=150 children, mean age=9.8 years). Results Hair cortisol and cortisone concentrations were similar in children with and without antenatal predniso

Fab glycosylation of immunoglobulin G does not associate with improvement of rheumatoid arthritis during pregnancy

Background: Changes in immunoglobulin G (IgG) constant domain (Fc) glycosylation are associated with changes in rheumatoid arthritis (RA) disease activity in response to pregnancy. Here, we sought to determine whether the same holds true for variable domain (Fab) glycosylation. Methods: IgGs were captured from RA and control sera obtained before (RA only), during and after pregnancy, followed by Fc and Fab separation, glycan release, and mass spectrometric detection. In parallel,

Pregnancy and rheumatoid arthritis

Fertility is impaired in female patients with rheumatoid arthritis (RA), which is related to disease activity and the use of certain medication. During pregnancy, disease activity usually improves, but less than previously thought Especially in women with high disease activity, the pregnancy outcome is also impaired. All of this underscores the importance of strict control of disease activity in RA patients who wish to conceive. Management of RA disease activity during pregnancy might be a challenge as the treatment options are limited. Evidence is accumulating that tumor necrosis factor (TNF) blockers can be safely used during pregnancy, particularly during the first trimester and the beginning of the second trimester. Far less is known about the problems faced by male RA patients who wish to conceive, in terms of not only fertility and pregnancy outcome but also the safety of medication. In this paper, the fertility issues in patients with RA, the pregnancy-associated improvement of RA, the pregnancy outcomes, including the long-term effects on the offspring, and treatment options, including those during lactation and for male patients wishing to conceive, will be reviewed. (C) 2015 Elsevier Ltd. All rights reserved

Identifying Clinical Factors Associated With Low Disease Activity and Remission of Rheumatoid Arthritis During Pregnancy

Objective: To identify a combination of clinical factors associated with low disease activity and remission in the third trimester during pregnancy in women with rheumatoid arthritis (RA). Methods: This study is embedded in the Pregnancy-Induced Amelioration of Rheumatoid Arthritis study, a prospective cohort study. There were data available on 190 pregnancies from first trimester until delivery. Multivariate regression analyses were performed on the disease activity (Disease Activity Score in 28 joints [DAS28] using the C-reactive protein [CRP] level) in the third trimester. Independent covariates were the DAS28-CRP-3 in first trimester, prednisone and sulfasalazine use in the first trimester, parity, methotrexate use in the past, autoantibody status, the presence of erosions, and RA disease duration. Results: In multivariate regression models, the DAS28-CRP-3, use of prednisone in the first trimester, and the presence of autoantibodies were negatively associated with low disease activity (DAS28-CRP-3 <3.2) in the third trimester (P<0.05), and the DAS28-CRP-3 and presence of autoantibodies were also associated with remission (DAS28-CRP-3 <2.6) (P<0.001). Subgroup analysis revealed that the associations of prednisone use and presence of autoantibodies were only present in patients with moderate-to-high disease activity (DAS28-CRP-3 ≥3.2) in the first trimester. Conclusion: RA patients who have a low DAS28-CRP-3 in the first trimester (irrespective of autoantibody stat