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P331 The safety of tioguanine exposure during pregnancy: a case series of seventy-three pregnancies

Crouwel, F.(1);Simsek, M.(1);De Boer, M.A.(2);Mulder, C.J.J.(1);Buiter, H.J.C.(3);De Boer, N.K.(1);

(1)Amsterdam UMC- location VUmc, Department of Gastroenterology and Hepatology, Amsterdam, The Netherlands;(2)Amsterdam UMC- location VUmc, Department of Obstetrics and Gynaecology, Amsterdam, The Netherlands;(3)Amsterdam UMC- location VUmc, Department of Radiology and Nuclear Medicine, Amsterdam, The Netherlands; On behalf of the tioguanine pregnancy study group and the Dutch Initiative on Crohn and Colitis (ICC)

Background

Azathioprine and mercaptopurine exposure during conception and pregnancy has been considered safe in patients with inflammatory bowel disease (IBD). Its use is not associated with a higher risk of preterm birth or low birthweight. Data on the safety of tioguanine, an alternative thiopurine-derivate, in pregnant IBD patients is limited. In a small case series, tioguanine appeared safe for both mother and fetus. In this study, we describe the teratogenicity and safety of tioguanine during pregnancy in a large group of IBD patients.

Methods

We performed a preliminary analysis of our ongoing multicenter descriptive case series of female IBD patients who were treated with tioguanine at some point during their pregnancy. Data regarding disease and medication history, pregnancy course and neonatal outcomes, such as preterm birth, miscarriage, birthweight, Apgar scores and congenital abnormalities were collected by the treating physician.

Results

Seventy-three pregnancies, including three twin pregnancies were collected. Most women (80%) had Crohn’s disease and the mean age during delivery was 31 years (range 21-42). Tioguanine was used throughout the entire pregnancy in 89% with a median daily dose of 20 mg. Five (6.8%) of these pregnancies resulted in a miscarriage, all within the first 13 weeks. No congenital abnormalities were reported in all seventy-one live born children. 

In the singleton pregnancies the median birthweight was 3375 gram (IQR 3075-3739, N=61, 4 missing values) with a median gestational age of 39.0 weeks (IQR 38.3-40.0, N=61). Four children (6.5%) were born prematurely (<37 weeks). Two of them were born after a spontaneous onset of labor with respectively 33+6 and 35+6 weeks, while in the other two labor was induced due to a placental abruption (32+1 weeks) or HELLP syndrome (31+4 weeks). Three children (4.9%) had a low birthweight (<2500 gram), all of them born prematurely, and five patients (8.3%, N=60, 5 missing values) were born small for gestational age (<10th percentile).

The median Apgar score after 1 and 5 minutes was respectively 9 (IQR 8-9, N=58) and 10 (IQR 9-10, N=59). Two neonates (3.4%), one born pre-and dysmature and the other a premature second-born twin, had an Apgar score (<7) after 5 minutes.

Conclusion

In this large case-series, tioguanine exposure during pregnancy was not associated with an increased risk of congenital abnormalities, low birthweight or preterm birth in IBD patients. These data support the safe use of tioguanine during pregnancy in IBD.

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