背景:免疫介导的炎性疾病(IMID)通常影响育龄妇女。在怀孕期间治疗这些妇女的挑战之一是控制疾病,同时尽量减少或避免使用可能增加母亲或胎儿风险的疾病改善抗风湿药物(DMARDs)。生物治疗改变了这些患者的管理。本研究旨在评估IMID孕妇在先入为主或在怀孕期间暴露于生物DMARDs的母胎安全性和围产期结局,并将其与使用常规DMARDs的妇女和一组健康孕妇进行比较。
方法:我们在单中心对患有IMID的孕妇进行了前瞻性随访的回顾性研究。我们分析了基线孕产妇人口统计学特征,疾病,DMARDs,和母胎结局。
结果:研究了244例妊娠的队列。128名患者符合风湿性和肌肉骨骼疾病(RMD)或炎症性肠病(IBD)的分类标准,在同一研究期间,对116例健康女性的妊娠情况进行了评估.IMID患者在免疫抑制治疗下发生了101例妊娠(89.84%),78.91%的IMID怀孕是在cDMARD(33.59%的专有cDMARD),在bDMARD下56.25%,和27.34%口服糖皮质激素。抗TNF是最常见的(88.88%)bDMARD,并且在50.78%的IMID中使用。在37.10%的IMID怀孕中至少有一次耀斑,9.38%的人经历了一次以上。在耀斑中,43.48%发生在孕早期,妊娠中期34.78%,排名第三的19.57%。与IBD相比,RMD患者的耀斑发生率更高(p=0.041;OR2.15,95CI:1.03-4.52)。在妊娠第八周之前,耀斑与bDMARD的停药有关(p=0.016),但特别是在第二(p=0.042)和第三三个月(p=0.012)。产妇感染是一种罕见的并发症(7.66%),尽管在IMID患者中更常见(p=0.004),但与cDMARD或bDMARD无关。IMID患者更需要辅助生殖技术(ART)(p=0.001,OR2.83,95CI:1.02-7.90)。在接受bDMARD治疗的妊娠中进行了更多的剖宫产(p=0.020),尤其是在接受抗TNF治疗的妊娠中。非整倍体计算风险和胎儿畸形与DMARDs无关(cDMARDs,bDMARDs,或其组合),也不与任何DMARDs单独孕前或妊娠期间。然而,在IMID患者中,小于胎龄(SGA)的新生儿较高,它与DMARD的使用无关。
结论:一般来说,需要使用bDMARDs治疗的IMID患者在妊娠前有更严重或难治性疾病.在我们的队列中,我们发现bDMARDs患者发生耀斑的风险更高,尤其是那些被提前暂停的时候。在产妇结局中,我们发现IMID患者更经常需要ART.这可能是,首先,因为母亲的年龄。在胎儿结局中,IMID和健康患者的先天性畸形没有差异,并且与DMARDs没有相关性.
结论:使用bDMARDs在疾病控制方面是有效的,从母婴角度来看是安全的,早产没有增加,SGA,畸形,或感染。
BACKGROUND: Immune-mediated inflammatory diseases (IMIDs) typically affect women of childbearing age. One of the challenges in treating these women during pregnancy is to manage the disease while minimizing or avoiding the use of disease-modifying antirheumatic drugs (DMARDs) that may increase the risk to the mother or fetus. Biologic therapy has transformed the management of these patients. This study aimed to evaluate the maternal-fetal safety and perinatal outcomes in pregnant women with IMID exposed to biologic DMARDs either preconceptionally or during pregnancy and compare them with women using conventional DMARDs and a group of healthy pregnant women.
METHODS: We conducted a retrospective study with prospective follow-up of pregnant women with IMID at a single center. We analyzed baseline maternal demographic characteristics, diseases, DMARDs, and maternal-fetal outcomes.
RESULTS: A cohort of 244 pregnancies was studied. One hundred twenty-eight patients met classificatory criteria for rheumatic and musculoskeletal diseases (RMD) or inflammatory bowel disease (IBD), and 116 pregnancies of healthy women were evaluated from the same study period. One hundred and one pregnancies in IMID patients (89.84 %) occurred under immunosuppressive treatment, 78.91 % of IMID pregnancies were under cDMARD (33.59 % exclusive cDMARD), 56.25 % under bDMARD, and 27.34 % under oral glucocorticoids. Anti-TNF was the most frequent (88.88 %) bDMARD and was used in 50.78 % of the IMIDs. There was at least one flare in 37.10 % of the IMID pregnancies, and 9.38 % experienced more than one. Among flares, 43.48 % happened in the first trimester, 34.78 % in the second trimester, and 19.57 % in the third. Flares were more frequent in the RMD patients compared with IBD (p = 0.041; OR 2.15, 95%CI: 1.03-4.52). Flare was associated with discontinuation of bDMARD before the eighth week of gestation (p = 0.016), but especially in the second (p = 0.042) and third trimester (p = 0.012). Maternal infections were an infrequent complication overall (7.66 %), although more frequent in patients with IMIDs (p = 0.004) but were not associated with cDMARD or bDMARD. IMID patients needed assisted reproductive techniques (ART) more often (p = 0.001, OR 2.83, 95%CI: 1.02-7.90). More cesarean sections were performed in gestations under treatment with bDMARD (p = 0.020) and especially in those under treatment with anti-TNF. Aneuploidies calculation risk and fetal malformations were not correlated with DMARDs (cDMARDs, bDMARDs, or its combination) nor with any of the DMARDs individually preconcepcionally or during gestation. Small for gestational age (SGA) newborns were higher in patients with IMIDs however, it was not associated with
DMARD use.
CONCLUSIONS: In general, patients with IMIDs who require treatment with bDMARDs have a more severe or refractory disease prior to gestation. In our cohort, we found a higher risk of flare among patients with bDMARDs, especially when those were suspended early. Among maternal outcomes, we found that IMID patients needed ART more often. This is probably, first of all, because of maternal age. Among fetal outcomes, there are no differences in congenital malformations in the IMIDs and healthy patients and were not correlated with DMARDs.
CONCLUSIONS: The use of bDMARDs was effective in disease control and safe from a maternal-fetal point of view, with no increase in prematurity, SGA, malformations, or infections.