Systematic Review and Meta-analysis on the Effects of Thiopurines on Birth Outcomes from Female and Male Patients with Inflammatory Bowel Disease

Abstract

Thiopurine exposure in women with IBD was not associated with LBW or congenital abnormalities, but was associated with preterm birth. Exposure in men at the time of conception was not associated with congenital abnormalities.

Pregnancy and inflammatory bowel diseases: Current perspectives, risks and patient management

“…AZA and 6-MP both target the expansion of T lymphocytes, and suppress lymphocyte survival to depress inflammatory responses in IBD. These drugs effectively establish and maintain remission of IBD and are especially helpful in patients who have do not respond strongly to milder therapies (such as aminosalicylates), or are steroid-dependent [112] . There are variable and conflicting data on side effects of immunomodulators in humans.…”

“…It was also found that there was a risk for increased preterm deliveries, LBW, and "small for gestational age" babies in AZA treatment associated pregnancies. A meta-analysis performed in 2012 showed that men fathering children who were exposed to thiopurine around the time of conception did not increase rates of congenital birth defects and so did not recommend discontinuation of treatment in men [112] . However, if there is a medical history of unexplained infertility or miscarriages, men should discontinue taking thiopurines at least four months before conception to improve fertility [114] .…”

“…However, the Goldstein study did confirm a statistically significant difference in premature birth and LBW associated with AZA. Akbari et al [112] 2012 performed a meta-analysis and found that exposure to thiopurines during conception was not clearly associated with birth abnormalities and concluded that maternal use of thiopurine was not associated with low LBW, but confirmed an increase in the risk of preterm births associated with thiopurine exposure. In fact, preterm birth had an increased odds of 70% and was the only outcome found to be significantly affected by thiopurine use.…”

“…In fact, preterm birth had an increased odds of 70% and was the only outcome found to be significantly affected by thiopurine use. Again, whether this is directly related to thiopurine use, or simply the result of the more more severe disease state in which thiopurines are more often required is unclear [112] . For example, other studies have demonstrated a more severe disease course in IBD was also significantly associated with preterm births not related to drug loading [50,112] .…”

“…Again, whether this is directly related to thiopurine use, or simply the result of the more more severe disease state in which thiopurines are more often required is unclear [112] . For example, other studies have demonstrated a more severe disease course in IBD was also significantly associated with preterm births not related to drug loading [50,112] . Furthermore, data from the Pregnancy in Inflammatory Bowel Disease and Neonatal Outcomes (PIANO) registry in 2012 found no evidence for an increased frequency of gestational or fetal complications in Group A (6-MP/AZA) as compared to other groups.…”