Outcomes of pregnancies fathered by inflammatory bowel disease patients exposed to thiopurines.
OBJECTIVE
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.
Teruel
Carlos
C
Department of Gastroenterology, Hospital Ramón y Cajal, Madrid, Spain. cteruelvegazo@yahoo.es
López-San Román
Antonio
A
Bermejo
Fernando
F
Taxonera
Carlos
C
Pérez-Calle
José Lázaro
JL
Gisbert
Javier P
JP
Martín-Arranz
María
M
Ponferrada
Angel
A
Van Domselaar
Manuel
M
Algaba
Alicia
A
Estellés
Jesús
J
López-Serrano
Pilar
P
Linares
Pablo M
PM
Muriel
Alfonso
A
D001379:Azathioprine / Q000009:adverse effects* / Q000627:therapeutic use; D005220:Fathers; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D008297:Male; D015122:Mercaptopurine / Q000009:adverse effects* / Q000627:therapeutic use; D016017:Odds Ratio; D011247:Pregnancy; D011248:Pregnancy Complications / Q000139:chemically induced*; D011256:Pregnancy Outcome; D013030:Spain; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D015122:Mercaptopurine; D001379:Azathioprine