Department of Medicine, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
Neurology. 2012 Sep 11;79(11):1130-5. doi: 10.1212/WNL.0b013e3182698c64. Epub 2012 Aug 29.
To systematically review the literature regarding safety of disease-modifying drug (DMD) use during pregnancy on perinatal and developmental outcomes in offspring of patients with multiple sclerosis (MS).
A PubMed and EMBASE search up to February 2012 was conducted with a manual search of references from relevant articles. Selected studies were evaluated using internationally accepted criteria.
Fifteen studies identified 761 interferon β-, 97 glatiramer acetate-, and 35 natalizumab-exposed pregnancies. Study quality ranged from poor to good; no study was rated excellent. Small sample sizes limited most studies. Compared with data for unexposed pregnancies, fair- to good-quality prospective cohort studies reported that interferon β exposure was associated with lower mean birth weight, shorter mean birth length, and preterm birth (<37 weeks), but not low birth weight (<2,500 g), cesarean delivery, congenital anomaly (including malformation), or spontaneous abortion. Fewer studies of fair quality were available for glatiramer acetate and natalizumab. Glatiramer acetate exposure was not associated with lower mean birth weight, congenital anomaly, preterm birth, or spontaneous abortion. Natalizumab exposure did not appear to be associated with shorter mean birth length, lower mean birth weight, or lower mean gestational age. No studies examined mitoxantrone or fingolimod exposure. One study of paternal DMD use during conception found no effect on gestational age or birth weight. Few studies examined longer-term developmental outcomes.
Further studies are needed to determine the potential risks associated with preconceptional and in utero DMD exposure in patients with MS. Discontinuation of DMDs before conception is still recommended.
系统评价多发性硬化症（MS）患者妊娠期间使用疾病修正药物（DMD）的安全性，以评估其对母婴围产期及后代发育结局的影响。
检索 PubMed 和 EMBASE 数据库，检索时间截至 2012 年 2 月，同时对相关文章的参考文献进行手工检索。采用国际公认的标准对入选研究进行质量评估。
共检索到 15 项研究，纳入 761 例干扰素 β、97 例培美曲塞、35 例那他珠单抗暴露的妊娠。研究质量评分从低到高不等，没有评分优秀的研究。由于样本量小，大多数研究的结论受到限制。与未暴露组相比，质量尚可的前瞻性队列研究发现干扰素 β 暴露与较低的平均出生体重、较短的平均出生身长和早产（<37 周）相关，但与低出生体重（<2500g）、剖宫产、先天性畸形（包括畸形）或自然流产无关。关于培美曲塞和那他珠单抗的研究质量稍差。培美曲塞暴露与较低的平均出生体重、先天性畸形、早产或自然流产无关。那他珠单抗暴露似乎与较短的平均出生身长、较低的平均出生体重或较低的平均胎龄无关。尚无研究评估米托蒽醌或芬戈莫德的暴露。一项关于父代 DMD 在受孕时使用对胎龄或出生体重影响的研究未发现相关影响。很少有研究评估较长时间的发育结局。
需要进一步研究以确定 MS 患者在受孕前及围孕期使用 DMD 相关的潜在风险。仍建议在受孕前停止 DMD 治疗。
