van den Berg Sophie A, de Boer Marjon, van der Meulen-de Jong Andrea E, Jansen Jeroen M, Hoentjen Frank, Russel Maurice G V M, Mahmmod Nofel, van Bodegraven Adriaan A, van der Woude C Janneke, Mulder Chris J J, de Boer Nanne K H
Department of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam, The Netherlands.
Department of Obstetrics and Gynaecology, VU University Medical Center, Amsterdam, The Netherlands.
J Crohns Colitis. 2016 Feb;10(2):159-65. doi: 10.1093/ecco-jcc/jjv189. Epub 2015 Oct 26.
Conventional thiopurine [azathioprine and mercaptopurine] treatment during pregnancy in patients with inflammatory bowel disease [IBD] is considered to be safe; however data on the safety and teratogenicity of the non-conventional thiopurine tioguanine [TG] in pregnant IBD patients are lacking. We aim to describe the safety and teratogenicity of TG treatment during pregnancy in IBD patients.
This was a retrospective, multicentre descriptive case series of female IBD patients using TG during pregnancy. Data on disease and medication history, pregnancy complications, pregnancy outcome, mode of delivery, preterm birth, birthweight, congenital abnormalities, laboratory signs of myelosuppression or hepatotoxicity, and 6-thioguaninenucleotide [6-TGN] concentrations in mother and neonate were collected.
In all, 13 patients [77% Crohn's disease, 23% ulcerative colitis] used TG [median dose 18 g/day] during pregnancy; 19 pregnancies, including 1 twin pregnancy, were included. Spontaneous abortion occurred in three pregnancies. In 7 of the 16 ongoing pregnancies a caesarean section was performed. One neonate had a mild congenital abnormality [distal shaft hypospadias]. In the singleton pregnancies, the median birthweight was 3410 g at a median of gestational age of 39 weeks. No preterm birth [< 37 weeks] or low birthweight [< 2500 g] was observed in the singleton newborns. In the twin pregnancy an induction of labour was performed at 35 + 1 weeks of gestation because of pre-eclampsia. Both neonates had a low birthweight.
This relatively small case series supports safe use of TG in pregnant IBD patients. Still, consideration should be given to the indication and continuation of TG during pregnancy.
炎症性肠病(IBD)患者孕期使用传统硫嘌呤类药物(硫唑嘌呤和巯嘌呤)被认为是安全的;然而,关于非传统硫嘌呤类药物硫鸟嘌呤(TG)在IBD孕妇中的安全性和致畸性的数据尚缺乏。我们旨在描述IBD患者孕期使用TG治疗的安全性和致畸性。
这是一项回顾性、多中心描述性病例系列研究,纳入孕期使用TG的IBD女性患者。收集疾病和用药史、妊娠并发症、妊娠结局、分娩方式、早产、出生体重、先天性异常、骨髓抑制或肝毒性的实验室指标以及母亲和新生儿的6-硫鸟嘌呤核苷酸(6-TGN)浓度等数据。
共有13例患者(77%为克罗恩病,23%为溃疡性结肠炎)在孕期使用TG(中位剂量18毫克/天);纳入19次妊娠,其中包括1次双胎妊娠。3次妊娠发生自然流产。16次持续妊娠中有7次进行了剖宫产。1例新生儿有轻度先天性异常(远端尿道下裂)。单胎妊娠中,中位出生体重为3410克,中位孕周为39周。单胎新生儿中未观察到早产(<37周)或低出生体重(<2500克)。双胎妊娠因先兆子痫于孕35 + 1周引产。两个新生儿均为低出生体重。
这个相对较小的病例系列支持IBD孕妇安全使用TG。尽管如此,孕期仍应考虑TG的适应证及继续使用情况。