研究妊娠对多发性硬化症病程的长期影响[j]神经病学JO神经病学FD Lippincott Williams & Wilkins SP e1296 OP e1308 DO 10.1212/WNL.0000000000206774半岛投注体育官网Gavoille, Antoine A1 Rollot, Fabien A1 Casey, Romain A1 Debouverie, Marc A1 Le Page, Emmanuelle A1 Ciron, Jonathan A1 De Seze, Jerome A1 Ruet, aurlie A1 Maillart, Elisabeth A1 Labauge, Pierre A1 Zephir, Helene A1 Papeix, Caroline A1 Defer, Gilles A1 lebron - frenay, Christine A1 Moreau, Thibault A1 Laplaud, David Axel A1 Berger, Eric A1 Stankoff, Bruno A1 Clavelou, Pierre A1 Thouvenot, Eric A1 Heinzlef, Olivier A1 Pelletier, Jean A1 Al Khedr, Abdullatif A1 Casez，Olivier A1 Bourre, Bertrand A1 Cabre, Philippe A1 Wahab, Abir A1 Magy, Laurent A1 Camdessanche, Jean-Philippe A1 Maurousset, Aude A1 Moulin, sol ne A1 Ben, Nasr Haifa A1 Boulos, Dalia Dimitri A1 Hankiewicz, Karolina A1 Neau, Jean-Philippe A1 Pottier, Corinne A1 Nifle, Chantal A1 Rabilloud, Muriel A1 Subtil, Fabien A1 Vukusic, Sandra A1，背景和目的妊娠的长期安全性问题是多发性硬半岛投注体育官网化症(MS)患者的一个主要问题，但其研究存在反向因果关系的偏倚(残疾程度较高的女性不太可能怀孕)。采用因果推理方法，我们旨在评估妊娠对MS患者残疾和复发风险的无偏长期影响，以及继发的短期影响(围产期和产后)和延迟影响(分娩后1年以上)。方法:我们进行了一项观察性队列研究，数据来自1990年至2020年期间在法国斑块观察中心登记的多发性硬化症患者。我们纳入了发病时年龄在18-45岁的MS女性患者，临床随访2年以上，且具有≥3项扩展疾病状态量表(EDSS)测量值。结果是随访结束时的平均EDSS评分和随访期间的年复发概率。在整个研究人群中使用纵向目标最大似然估计器预测反事实结果。在随访期间暴露于至少一次怀孕的患者与反事实情况进行比较，在反事实情况下，与观察到的相反，他们不会暴露于任何怀孕。从早期暴露患者的第一次妊娠(在随访的前3年)开始分析短期和延迟效应。我们纳入了9100例患者，中位随访时间为7.8年，其中2125例(23.4%)患者暴露于至少1次妊娠。 Pregnancy had no significant long-term causal effect on the mean EDSS score at 9 years (causal mean difference [95% CI] = 0.00 [−0.16 to 0.15]) or on the annual probability of relapse (causal risk ratio [95% CI] = 0.95 [0.93–1.38]). For the 1,253 early-exposed patients, pregnancy significantly decreased the probability of relapse during the perpartum year and significantly increased it during the postpartum year, but no significant delayed effect was found on the EDSS and relapse rate.Discussion Using a causal inference approach, we found no evidence of significantly deleterious or beneficial long-term effects of pregnancy on disability. The beneficial effects found in other studies were probably related to a reverse causation bias.DAG=directed acyclic graph; EDSS=Expanded Disease Status Scale; IPW=inverse probability weighting; LTMLE=longitudinal targeted maximum likelihood estimator; MS=multiple sclerosis; OFSEP=Observatoire Français de la Sclérose en Plaques; PP=primary progressive; RR=relapsing-remitting; SP=secondary progressive

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