azathiaprine or mercaptopurine (Rampton 20001).  It is also used in nonsurgical treatment of  ectopic pregnancy due to its abortifacient properties (Bermas and Hill 1995 and Reprotox #1036)).  Patients who take this medication may experience: hypersensitive pneumonitis, hepatic fibrosis, myelotoxicity, nausea, increased hepatic enzyme activity, skin rash and reversible     oligospermia (Connell and Miller 1999).  Methotrexate does not appear to have any long term effects on fertility (Bermas and Hill 1995).


Methotrexate is contraindicated in pregnancy for many reasons.  It is a folic acid antagonist which crosses the placenta, and therefore poses a potential increased risk for neural tube defects.  Additionally, methotrexate is embryotoxic and teratogenic in animals and humans (Bermas and Hill 1995, Connell and Sandborn 1999, Connell and Miller 1999 and Rampton 2001).  Many  abnormalities such as large fontanelles, craniosynostosis, abnormal head shape, hypertelorism, and skeletal deformities have all been reported with use of methotrexate in human pregnancy (Connell and Miller 1999).  These abnormalities were primarily noted in children born to    mothers given 10mg of methotrexate.  Studies on this population of women also revealed a    miscarriage rate of approximately 44%. The average dose used in these women was from 7.5mg-10mg (Bermas and Hill 1995).  There appears to be a critical time period for exposure of 6-8 weeks postconception. There are cases of first trimester exposure to methotrexate in which no teratogenic effect was detected. Four cases of exposure to methotrexate during the early first  trimester (0 -6 weeks post conception) all resulted in healthy newborns. An additional study identified eight pregnancies for which methotrexate was given to treat rheumatoid arthritis early in pregnancy. There were five healthy newborns and three spontaneous abortions.


Methotrexate has also been associated with fetal growth retardation resulting from bone marrow suppression.  Finally, there are case reports of an association between maternal methotrexate use and fetal chromosome abnormalities (Connell and Miller 1999).  Rampton (2001) recommends that use of this medication in either partner be discontinued six months prior to conception.

References:

Bermas BL and Hill JA (1995) Review:  Effects of Immunosuppressive Drugs During Pregnancy.  Arthritis and Rheumatism 3 (12):1722-1732


Connell and Miller (1999) Treating Inflammatory Bowel Disease During Pregnancy Drug Safety 4:311-323


Connell WR and Sandborn WJ (1999) Drug Therapy for IBD During Pregnancy.

www.ccfa.org/medcentral/library/family/drugpreg.htm


Crohn's and Colitis Foundation of America (1999) Questions & Answers about

Crohn's Disease. www.ccfa.org/Physician/crohnsb.html


Diav-Citrin O et al (2001). Pregnancy outcome after gestational exposure to metronidazole: a prospective controlled cohort study. Teratology 63:186-192.


Korelitz BI (1990) Antimetabolites in Inflammatory Bowel Disease: Long Term

Experience.  Mount Sinai J of Medicine 57(5):297-304


Kornfeld D, Cnattingius S, Ekbom A (1997) Pregnancy outcomes in women with

Inflammatory bowel disease - A population-based cohort study. Am J Obstet

Gynecol 177(4):942-946


Mogadam M, Dobbins WO, Korelitz BI, Ahmed SW (1981) Pregnancy in InflammatoryBowel Disease: Effect of Sulfasalazine and Corticosteroids on Fetal Outcome. Gastroent 80:72-76


Moore AJ, Okun NB, Mayes DC, BaileyRJ (2000) Crohn's Pregnancy and Birth Weight. Am J of Gastroent 95(4):1019-1026




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Antibacterials

Metronidazole


Metronidazole (Flagyl®) is mostly used for treatment of perianal Crohn's disease.  Mothers    taking metronidazole may experience nausea, anorexia, metallic taste, glossitis, and peripheral neuropathy.  Sporadic cases of midline facial defects in humans, as well as rare reports of bone disorders, have been reported (Connell and Sandborn1999).  Therefore, it has been suggested

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