Inflammatory Bowel Disease

Subject Category: Inflammatory Bowel Disease

Am J Gastroenterol 2010; 105:2003–2008; doi:10.1038/ajg.2010.138; published online 10 August 2010

Outcomes of Pregnancies Fathered by Inflammatory Bowel Disease Patients Exposed to Thiopurines

Carlos Teruel MD1, Antonio López-San Román PhD1, Fernando Bermejo PhD2, Carlos Taxonera MD3, José Lázaro Pérez-Calle PhD4, Javier P Gisbert PhD5, María Martín-Arranz MD6, Ángel Ponferrada MD7, Manuel Van Domselaar PhD1, Alicia Algaba BSc2, Jesús Estellés MD3, Pilar López-Serrano PhD4, Pablo M Linares MD5 and Alfonso Muriel BSc8

  1. 1Department of Gastroenterology, Hospital Ramón y Cajal, Madrid, Spain
  2. 2Department of Gastroenterology, Hospital de Fuenlabrada, Fuenlabrada, Madrid, Spain
  3. 3Department of Gastroenterology, Hospital Clínico San Carlos, Madrid, Spain
  4. 4Department of Gastroenterology, Hospital Fundación Alcorcón, Alcorcón, Madrid, Spain
  5. 5Department of Gastroenterology, Hospital de la Princesa, Madrid, and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain
  6. 6Department of Gastroenterology, Hospital La Paz, Madrid, Spain
  7. 7Department of Gastroenterology, Hospital Infanta Leonor, Madrid, Spain
  8. 8Department of Statistics, Hospital Ramón y Cajal, Madrid, Spain

Correspondence: Carlos Teruel MD, Department of Gastroenterology, Hospital Ramón y Cajal, Ctra. Colmenar Viejo, km. 9,100, Madrid, Spain. E-mail: cteruelvegazo@yahoo.es

Received 12 September 2009; Accepted 25 February 2010; Published online 10 August 2010.

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Abstract

OBJECTIVES:

 

Immunomodulators are used as maintenance treatment of inflammatory bowel disease (IBD). Data regarding their possible effects in the course of pregnancy when the father is exposed at the time of conception are limited.

METHODS:

 

To evaluate the outcomes of pregnancies of which the fathers were exposed to thiopurines at the time of conception. A series of male patients followed in seven IBD clinics in Madrid, Spain, was studied. Any exposure to thiopurines during the 3 months preceding conception was considered significant. Controls were pregnancies fathered by patients who either had never been treated with thiopurines or had interrupted them >3 months before conception. Statistical comparisons and multivariate analysis were carried out with the generalized estimating equations model.

RESULTS:

 

There were 46 conceptions in the exposed group (mercaptopurine 9, azathioprine 37) and 84 in the control group. In the exposed group, there were more Crohn's patients (82.6% vs. 53.6%), the duration of the disease was longer (median: 8 vs. 5 years), fathers were slightly older (mean: 34.2 vs. 32.7 years), and there were fewer patients on mesalamine (15.2% vs. 47.6%). Otherwise, baseline characteristics were similar in both groups. There were no significant differences regarding unsuccessful pregnancies—namely, spontaneous abortions, ectopic pregnancies, anembryonic pregnancies, or fetal deaths (10.9% exposed group vs. 13.1% control group; odds ratio (OR): 0.79, confidence interval (CI): 0.22–2.85), preterm births (4.3% vs. 2.4%; OR: 1.3, CI: 0.22–7.61), low birth weight (6.5% vs. 6%; OR: 1.06, CI: 0.25–4.54), or congenital malformations (2.2% vs. 2.4%; OR: 0.82, CI: 0.08–9). No infant neoplasms were detected. The proportion of conceptions that needed >1 year to be achieved was higher in the exposed group, but this was not statistically significant (15.2% vs. 8.3%; OR: 1.92, CI: 0.54–6.88). Multivariate analysis was carried out for unsuccessful pregnancies and fertility impairment, and it showed that, although mesalamine exposure confounded the effect of the exposure to thiopurines on these outcomes, this effect was still nonsignificant (respectively, OR: 0.49, CI: 0.17–1.44; OR: 2.82, CI: 0.7–11.38).

CONCLUSIONS:

 

Our data do not support the practice of routinely recommending to male patients that they interrupt thiopurines when wanting to conceive.