Pregnancy outcomes in relation to disease activity and anti-rheumatic treatment strategies in women with rheumatoid arthritis: a matched cohort study from Sweden and Denmark

Author:

Hellgren Karin12ORCID,Secher Anne Emilie3,Glintborg Bente34ORCID,Rom Ane Lilleøre567ORCID,Gudbjornsson Bjorn8,Michelsen Brigitte910,Granath Fredrik1,Hetland Merete Lund34ORCID

Affiliation:

1. Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Insititutet

2. Department of Medicine Solna, Rheumatology, Theme Inflammation & Infection, Karolinska University Hospital, Stockholm, Sweden

3. Center for Arthritis Research (COPECARE), Center for Rheumatology and Spine Diseases, Centre for Head and Orthopaedics, Rigshospitalet, Glostrup, Denmark

4. Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen

5. Department of Obstetrics, The Juliane Marie Centre

6. Department of Obstetrics, The Research Unit for Women’s and Children’s Health, The Juliane Marie Centre, Copenhagen University Hospital Rigshospitalet, Copenhagen

7. Research Unit of Gynecology and Obstetrics, Department of Clinical Research, University of Southern Denmark, Odense, Denmark

8. Centre for Rheumatology Research (ICEBIO), University Hospital, Faculty of Medicine, University of Iceland, Reykjavik, Iceland

9. Department of Rheumatology and Research, Diakonhjemmet Hospital, Oslo

10. Division of Rheumatology, Department of Medicine, Hospital of Southern Norway Trust, Kristiansand, Norway

Abstract

Abstract Objectives To explore the association of maternal RA to pregnancy outcomes, especially preterm birth (PTB) and small for gestational age (SGA), in relation to disease activity and anti-rheumatic treatment before and during pregnancy. Methods By linking prospective clinical rheumatology registers (CRR) in Sweden (the Swedish Rheumatology Quality Register, SRQ) and Denmark (the Danish clinical quality register, DANBIO) with medical birth registers, we identified 1739 RA-pregnancies and 17 390 control-pregnancies (matched 1:10 on maternal age, birth year, parity) with delivery 2006–18. Disease activity (DAS28, CRP, HAQ score) and anti-rheumatic treatment 9 months before and during pregnancy were identified through CRR and prescribed drug registers. Using logistic regression, we estimated adjusted odds ratios (aOR) with 95% CI for PTB and SGA overall and stratified by disease activity and anti-rheumatic treatment before and during pregnancy, adjusting for maternal characteristics. Results We found increased aOR of PTB [1.92 (1.56–2.35)] and SGA [1.93 (1.45–2.57)] in RA-pregnancies vs control-pregnancies. For RA-pregnancies with DAS28-CRP ≥4.1 vs <3.2 during pregnancy, aOR was 3.38 (1.52–7.55) for PTB and 3.90 (1.46–10.4) for SGA. Use of oral CS (yes/no) during pregnancy resulted in an aOR of 2.11 (0.94–4.74) for PTB. The corresponding figure for biologics was 1.38 (0.66–2.89). Combination therapy, including biologics before pregnancy, was a marker of increased risk of both PTB and SGA. Conclusion During pregnancy, disease activity rather than treatment seems to be the most important risk factor for PTB and SGA in RA. Women with RA should be carefully monitored during pregnancy, especially if they have moderate to high disease activity or/and are treated with extensive anti-rheumatic treatment.

Funder

NordForsk, FOREUM, the Danish Rheumatism Association

Swedish Rheumatism Association

King Gustaf V:s 80 years Foundation

Swedish Research Council

Region Stockholm

Publisher

Oxford University Press (OUP)

Subject

Pharmacology (medical),Rheumatology

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