Use of Thiopurines During Conception and Pregnancy Is Not Associated With Adverse Pregnancy Outcomes or Health of Infants at One Year in a Prospective Study.
OBJECTIVE
Most data on the safety of thiopurine therapy for inflammatory bowel disease (IBD) during pregnancy come from retrospective studies, which makes it difficult to adjust for confounding factors. We performed a prospective cohort study to determine whether thiopurine use affects pregnancy outcomes or health outcomes of children.


METHODS
We performed a prospective study of all women who visited the IBD preconception outpatient clinic at our tertiary health center in The Netherlands from December 2008 through May 2016. Patients were counseled before pregnancy and seen bimonthly during pregnancy. We collected and analyzed data on medication use, as well as lifestyle and clinical factors, during conception and pregnancy. Pregnancy outcomes (live birth, spontaneous abortion, elective abortion, and stillbirth), birth outcomes (gestational age, birth weight, and congenital abnormalities), and health outcomes of infants 1 year after birth were compared between women who did and did not use a thiopurine during conception and pregnancy. In addition, health outcomes of infants 1 year after birth were compared with infants born to mothers without IBD from the same geographic region.


RESULTS
Our study comprised 309 women with confirmed IBD (216 with Crohn's disease, 85 with ulcerative colitis, and 8 with IBD unclassified). During the study period, 311 pregnancies of 232 women resulted in a live birth; a thiopurine was used during 108 pregnancies (35%). After correction for diagnosis, fertility treatment, and disease activity, there was no association between thiopurine use and spontaneous abortions. Birth outcomes were similar between women who did and did not use a thiopurine. Among infants 1 year of age, there were no differences in median growth, number of infections, allergies, adverse reactions to vaccinations, or chronic diseases between those born to women who did and did not use a thiopurine or between women with and without IBD.


CONCLUSIONS
In this prospective cohort study, we found no association between maternal thiopurine use during pregnancy and increased spontaneous abortions, adverse birth outcomes, or adverse health outcomes of infants 1 year after birth.
Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands. Electronic address: kanisshannon@gmail.com.
Shannon L
SL
Kanis
Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands.
Alison
A
de Lima-Karagiannis
Department of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam, The Netherlands.
Nanne K H
NKH
de Boer
Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands.
C Janneke
CJ
van der Woude
D000328:Adult; D000893:Anti-Inflammatory Agents / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007223:Infant; D000068104:Infant Health; D007231:Infant, Newborn; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D008297:Male; D009426:Netherlands; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy*; D011256:Pregnancy Outcome; D011446:Prospective Studies; D011687:Purines / Q000009:adverse effects* / Q000627:therapeutic use
D000893:Anti-Inflammatory Agents; D011687:Purines
Drug; Immunomodulators; Infant; Neonate; Risk; Side Effect