Hellgren Karin, Secher Anne Emilie, Glintborg Bente, Rom Ane Lilleøre, Gudbjornsson Bjorn, Michelsen Brigitte, Granath Fredrik, Hetland Merete Lund
Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Insititutet.
Department of Medicine Solna, Rheumatology, Theme Inflammation & Infection, Karolinska University Hospital, Stockholm, Sweden.
Rheumatology (Oxford). 2022 Aug 30;61(9):3711-3722. doi: 10.1093/rheumatology/keab894.
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.
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.
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.
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.
探讨孕妇类风湿关节炎(RA)与妊娠结局的关联,尤其是早产(PTB)和小于胎龄儿(SGA),以及妊娠前和妊娠期间的疾病活动度和抗风湿治疗情况。
通过将瑞典(瑞典风湿病质量登记处,SRQ)和丹麦(丹麦临床质量登记处,DANBIO)的前瞻性临床风湿病登记册与医疗出生登记册相链接,我们识别出1739例患RA的妊娠和17390例对照妊娠(按产妇年龄、出生年份、产次1:10匹配),分娩时间为2006 - 2018年。通过CRR和处方药登记册确定妊娠前9个月及妊娠期间的疾病活动度(DAS28、CRP、HAQ评分)和抗风湿治疗情况。使用逻辑回归分析,我们估计了PTB和SGA总体的调整优势比(aOR)及95%置信区间,并按妊娠前和妊娠期间的疾病活动度及抗风湿治疗进行分层,同时对产妇特征进行了调整。
我们发现患RA的妊娠与对照妊娠相比,PTB的aOR升高[1.92(1.56 - 2.35)],SGA的aOR升高[1.93(1.45 - 2.57)]。对于妊娠期间DAS28 - CRP≥4.1与<3.2的患RA妊娠,PTB的aOR为3.38(1.52 - 7.55),SGA的aOR为3.90(1.46 - 10.4)。妊娠期间使用口服糖皮质激素(是/否)导致PTB的aOR为2.11(0.94 - 4.74)。生物制剂的相应数字为1.38(0.66 - 2.89)。联合治疗,包括妊娠前使用生物制剂,是PTB和SGA风险增加的一个标志。
在妊娠期间,疾病活动度而非治疗似乎是RA患者发生PTB和SGA的最重要风险因素。患RA的女性在妊娠期间应受到密切监测,尤其是如果她们有中度至高度疾病活动度或/且接受广泛的抗风湿治疗。