Safety of Tioguanine During Pregnancy in Inflammatory Bowel Disease.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam, The Netherlands.
Sophie A
SA
van den Berg
Department of Obstetrics and Gynaecology, VU University Medical Center, Amsterdam, The Netherlands.
Marjon
M
de Boer
Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands.
Andrea E
AE
van der Meulen-de Jong
Department of Gastroenterology and Hepatology, Onze Lieve Vrouwe Gasthuis Amsterdam, Amsterdam, The Netherlands.
Jeroen M
JM
Jansen
Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands.
Frank
F
Hoentjen
Department of Gastroenterology and Hepatology, Medical Spectrum Twente, Enschede, The Netherlands.
Maurice G V M
MG
Russel
Department of Gastroenterology and Hepatology, St Antonius Hospital, Nieuwegein, The Netherlands.
Nofel
N
Mahmmod
Department of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam, The Netherlands Department of Internal Medicine, Geriatrics and Gastroenterology, Orbis Medical Center, Sittard-Geleen, The Netherlands.
Adriaan A
AA
van Bodegraven
Department of Gastroenterology and Hepatology, Erasmus Medical Center, Rotterdam, The Netherlands.
C Janneke
CJ
van der Woude
Department of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam, The Netherlands.
Chris J J
CJ
Mulder
Department of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam, The Netherlands khn.deboer@vumc.nl.
Nanne K H
NK
de Boer
D000293:Adolescent; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D001724:Birth Weight; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D008297:Male; D011247:Pregnancy; D011248:Pregnancy Complications; D011256:Pregnancy Outcome; D012189:Retrospective Studies; D013866:Thioguanine / Q000008:administration & dosage*; D016896:Treatment Outcome; D055815:Young Adult
D000964:Antimetabolites, Antineoplastic; D013866:Thioguanine
Pregnancy; inflammatory bowel disease; tioguanine