Objective.The World Health Organization recommends that infants be exclusively breastfed until the age of 6 months. The first objective was to compare breastfeeding frequencies and time of cessation between women with rheumatoid arthritis (RA) and the general population. The second objective was to identify why patients with RA discontinue breastfeeding.Methods.This study was embedded in the Pregnancy-induced Amelioration of Rheumatoid Arthritis (PARA) study, a nationwide prospective cohort study. From 2002 to 2008, a total of 249 pregnancies were followed from pregnancy until 6 months postpartum. Data on lactation and medication use were collected. Proportion tests were used to compare percentages of breastfeeding between the study population and the general/reference population.Results.At 4–6, 12, and 26 weeks postpartum, 43%, 26%, and 9% of the RA patients breastfed their offspring, respectively, compared with 63%, 46%, and 41% in the general population, respectively (p < 0.001). The main reason for women to discontinue breastfeeding was the restart of medication (n = 129, 57.8%). Nevertheless, more than 40% of these patients restarted medication that was considered compatible with breastfeeding.Conclusion.This large prospective study demonstrates that RA is associated with lower proportions of women breastfeeding their offspring and earlier cessation compared with the general population. A considerable number of patients discontinued breastfeeding so that they could start medication, even though many of the medications are considered safe to use during lactation. Using the results of this study, intervention strategies supporting RA patients who wish to breastfeed may be developed.
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 status or prednisone use) are likely to have low disease activity or remission in the third trimester. Also, women with higher disease activity who are not taking prednisone and who express no autoantibodies still have a fair chance of low disease activity in the last trimester.
ObjectivesTo 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.MethodsIn 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).ResultsHair cortisol and cortisone concentrations were similar in children with and without antenatal prednisone exposure (median cortisol 1.14 pg/mg (IQR 0.67–1.75) and 1.15 pg/mg (IQR 0.65–2.21) and median cortisone 6.76 pg/mg (IQR 5.42–8.86) and 7.40 pg/mg (IQR 5.39–10.73), respectively). Antenatal prednisone exposure and maternal RA disease activity were also not associated with body composition or blood pressure. Hair cortisol concentrations were not different in children born to mothers with RA compared with children from the reference group.ConclusionThis, in its kind, large and unique long-term prospective study demonstrates that low-dose antenatal prednisone exposure and maternal RA disease activity are not associated with negative consequences in prepubertal childhood. The findings of this study are reassuring and support the assumption that low-dose maternal prednisone use during pregnancy is safe for the offspring, at least until the age of approximately 10 years.
ObjectivesThe 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.MethodsFor this study, genome-wide DNA methylation was measured at cytosine-phosphate-guanine (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.ResultsA 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.ConclusionsDNA 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 RA.
RA disease course in following pregnancies cannot be predicted based upon previous pregnancies. However, a flare postpartum seems to predict subsequent flares.
BackgroundPregnancy is the only physiological condition in which Rheumatoid Arthritis (RA) remits spontaneously in approximately 50% of the pregnancies [1]. Although various factors, like hormones and immunoglobulins have been investigated, there is no clear explanation for the gestational improvement [2]. Understanding the influence of pregnancy and especially the impact of subsequent pregnancies, may provide more insight into the pathophysiological mechanisms underlying RA. To our knowledge there has not been any prospective study on this subject until now.ObjectivesTo determine if changes in disease activity in women with Rheumatoid Arthritis (RA) in one pregnancy are predictive for a subsequent pregnancy.MethodsThis study is embedded in the Pregnancy induced Amelioration of Rheumatoid Arthritis (PARA)-study, a nationwide prospective cohort study [3]. There is data available on 27 women who participated during two pregnancies from first trimester unto delivery resulting in a life birth. RA disease courses are categorized as improvement, deterioration, both improvement and deterioration and no change. Improvement and deterioration is determined by calculating changes in DAS28 [3].ResultsIn the first pregnancy in total 10 women (37,0%) improved, 6 (22,2%) deteriorated, 6 women (22,2%) both improved and deteriorated, and 5 (18,5%) had no change. In their second pregnancy 10 women (37,0%) improved, 5 (18,5%) deteriorated, 4 women (14,8%) both improved and deteriorated, and 7 (25,9%) had no change at all. Only 4 women (14,8%) had a comparable disease activity course during their first and second pregnancy, whereas treatment remained mostly similar (see figure 1).ConclusionsThis prospective study demonstrates that the course of RA-disease activity in subsequent pregnancies is different. This means that we cannot predict the course of the disease activity in following pregnancies based upon an earlier pregnancy.ReferencesBarrett, J.H., et al., Does rheumatoid arthritis remit during pregnancy and relapse postpartum? Results from a nationwide study in the United Kingdom performed prospectively from late pregnancy. Arthritis Rheum, 1999. 42(6): p. 1219-27.Ostensen, M. and P.M. Villiger, The remission of rheumatoid arthritis during pregnancy. Semin Immunopathol, 2007. 29(2): p. 185-91.de Man, Y.A., et al., Disease activity of rheumatoid arthritis during pregnancy: results from a nationwide prospective study. Arthritis Rheum, 2008. 59(9): p. 1241-8.Disclosure of InterestH. Ince-Askan Grant/research support from: This study is funded by the Dutch Arthritis Association (Reumafonds). J. Hazes Grant/research support from: This study is funded by the Dutch Arthritis Association (Reumafonds). R. Dolhain Grant/research support from: This study is funded by the Dutch Arthritis Association (Reumafonds).
BackgroundPregnancy is the only natural condition in which Rheumatoid Arthritis (RA) remits spontaneously in approximately half of the pregnancies [1]. Many physicians try to taper or stop medication when a women conceives in order to prevent drug related side effects for mother and child. However, 50% of the patients still has active disease in the third trimester of pregnancy1. Factors that can identify patients in whom medication can be safely tapered during pregnancy are therefore needed.ObjectivesTo determine clinical factors associated with lower disease activity in the third trimester during pregnancy in women with Rheumatoid Arthritis (RA) and thereby to identify patients in whom medication can be safely tapered during pregnancy.MethodsThis study is embedded in the Pregnancy induced Amelioration of Rheumatoid Arthritis (PARA)-study, a nationwide prospective cohort study. There was data available on 190 pregnancies from first trimester unto delivery. Disease activity was measured using the Disease Activity Score in 28 joints (DAS28). A multivariate linear regression analysis was performed on the DAS28 in the third trimester. Independent covariates in these models: the DAS28 in the first trimester, prednisone and sulfasalazine use in the first trimester, parity, methotrexate use in past, autoantibody status (either rheumatoid factor or ACPA positive), presence of erosions and duration of RA.ResultsIn the multivariate linear regression model, see table 1., a higher DAS28 in the first trimester, the use of prednisone and the presence of autoantibodies were statistically significantly associated with a higher DAS28 in the third trimester (p-values <0.001, 0.032 and 0.014 respectively).ConclusionsThe DAS28 in the first trimester, the autoantibody status and the use of prednisone were associated with RA disease activity in the third trimester. Female RA patients who have a lower DAS28 in the first trimester are likely to have lower disease activity in the third trimester, especially if they are autoantibody negative and if they do not use prednisone. In these patients, it may be considered to safely taper their medication.Referencesde Man YA, Dolhain RJ, van de Geijn FE, Willemsen SP, Hazes JM. Disease activity of rheumatoid arthritis during pregnancy: results from a nationwide prospective study. Arthritis Rheum 2008;59:1241–8.FundingDr. R.J.E.M. Dolhain received unrestricted research grants from the Dutch Arthritis Association (Reumafonds), a non-commercial fund raising organization, and from UCB Pharma BV.Conflicts of interestNone.Disclosure of InterestNone declared
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