Drug therapy for ulcerative colitis during pregnancy

European Journal of Gastroenterology and Hepatology

Volumn 9, Issue 9, 1997, Pages 854-857

  Modigliani, Robert ^a  

^a SAINT LOUIS HOSPITAL   (France)

Author keywords

Azathioprine and 6 mercaptopurine; Corticosteroids; Cyclosporin; Mesalazine; Methotrexate; Olsalazine; Pregnancy; Sulphasalazine; Ulcerative colitis

Indexed keywords

AZATHIOPRINE; CYCLOSPORIN; MESALAZINE; SALICYLIC ACID DERIVATIVE; STEROID;

CONCEPTION; FEMALE; HUMAN; PREGNANCY; PRIORITY JOURNAL; REMISSION; SHORT SURVEY; ULCERATIVE COLITIS;

EID: 0030772569     PISSN: 0954691X     EISSN: None     Source Type: Journal    
DOI: 10.1097/00042737-199709000-00006     Document Type: Short Survey

References (27)

1. Baird DD, Narendranathan M, Sandler RS: Increased risk of preterm birth for women with inflammatory bowel disease. Gastroenterology 1990, 99:987-994. This paper reports the reproductive history of 177 women with Crohn's disease and 84 women with ulcerative colitis. A reduced fertility is shown, probably due to patient choice rather than to the disease itself. There was no increased risk of pregnancy loss but the risk of preterm birth was significantly elevated in both diseases.
2. Willoughby CP, Truelove SC: Ulcerative colitis in pregnancy. Gut 1980, 21:469-474. A study of 147 women of child-bearing age with ulcerative colitis. Fertility and pregnancy outcome did not differ from that found in the general population. Steroids and sulphasalazine had no obvious deleterious effect on the newborn.
3. Nielsen OH, Andreasson B, Bondesen S, et al.: Pregnancy in ulcerative colitis. Scand J Gastroenterol 1983, 18:735-742. A study of 97 women with ulcerative colitis, who had 173 pregnancies over a 12-year period. Treatment with steroids and sulphasalazine had no influence on the course and outcome of pregnancy. The frequency of malformation, prematurity, and neonatal hyperbilirubinaemia was not higher than in healthy mothers.
4. Jarnerot G, Into-Malmberg MB, Esbjorner E: Placental transfer of sulphasalazine and sulphapyridine and some of its metabolites. Scand J Gastroenterol 1981, 16:693-697. A study performed on 11 pregnant patients with inflammatory bowel disease showing that the concentrations of sulphasalazine and sulphapyridine are similar in the cord serum and the maternal serum. In the newborn, concentrations of sulphasalazine and sulphapyridine were largely below those able to cause displacement of bilirubin from albumin.
5. Mogadam M, Dobbins WO, Korelitz BI, et al.: Pregnancy in inflammatory bowel disease: effect of sulfasalazine and corticosteroids on fetal outcome. Gastroenterology 1981, 80:72-76. This is an American national survey of the outcome of 531 pregnancies in women with inflammatory bowel disease; about half were treated with steroids and/or sulphasalazine and half received neither. The conclusion is that either or both drugs may be used as in non-pregnant patients.
6. Czeizel EA, Dudas I: Prevention of the first occurrence of neural-tube defects with folic acid supplementation. N Engl J Med 1992, 327:1832-1835. A randomized controlled trial showing that periconceptional multivitamin supplementation (including folic acid) reduced the rate of congenital malformations, especially that of neural tube defect.
7. Habal FM, Hui G, Greenberg GR: Oral 5-aminosalicylic acid for inflammatory bowel disease in pregnancy: safety and clinical course. Gastroenterology 1993, 105:1057-1060. This is a study of 17 women with inflammatory bowel disease (10 ulcerative colitis, 7 Crohn's disease) who had a total of 19 pregnancies and received 5-ASA at a mean dose of 1.7g/day. Mesalazine appeared to be safe for the pregnancy and the baby.
8. Trallori G, d'Albasio G, Bardazzi G, et al.: 5-Aminosalicylic acid in pregnancy: clinical report. Ital J Gastroenterol 1994, 26:75-78. The safety of 5-ASA (Asacol) was assessed in 16 women with quiescent ulcerative colitis who had 19 pregnancies over the study period. The authors conclude that treatment with mesalazine does not affect the course of pregnancy nor does it damage the fetus.
9. Marteau Ph, Grand J, Devaux CB: Mesalazine in pregnancy: fetal outcome in 76 IBD patients treated with Pentasa®. Gastroenterology 1995, 108:A871. The largest series of women (n = 76) with inflammatory bowel disease receiving mesalazine (Pentasa®) during pregnancy. Results suggest that mesalazine is safe during pregnancy, with the exception of one case of fetal tubulo-interstitial nephritis (see reference 10).
10. Colombel JF, Brabant G, Gubler MC, et al.: Renal insufficiency in infant: side-effect of prenatal exposure to mesalazine? Lancet 1994, 344:620-621. This letter reports a case of tubulo-interstitial nephritis in a newborn whose mother had been treated with mesalazine (4g/24h) during pregnancy.
11. Lewis JH, Weingold AB: The use of gastrointestinal drugs during pregnancy and lactation. Am J Gastroenterol 1985, 80:912-923. An excellent review on the use of gastrointestinal drugs during pregnancy and lactation, including salicylates, corticosteroids and immunosuppressants.
12. McEwan HP: Ulcerative colitis in pregnancy. Proc R Soc Med 1972, 65:279-281. A study of 38 women with ulcerative colitis, who had 50 pregnancies: normal pregnancy outcome, no apparent deleterious effect of steroids and sulphasalazine.
13. Baioco PJ, Korelitz BI: The influence of inflammatory bowel disease and its treatment on pregnancy and fetal outcome. J Clin Gastroenterol 1984, 6:211-216. A study of one private practice, assessing the course of pregnancy (n = 147) and fetal outcome in 124 women with inflammatory bowel disease. The authors conclude that these patients are at greater risk of fetal complications than the average population, but that disease activity is more likely to be responsible for this risk than drug treatment.
14. Hawthorne AB, Logan RFA, Hawkey CJ, et al.: Randomised controlled trial of azathioprine withdrawal in ulcerative colitis. BMJ 1992, 305:20-22. An important withdrawal, controlled randomized trial showing that stopping azathioprine in patients with quiescent ulcerative colitis results in significantly more relapse than continuing the drug.
15. Adler DJ, Korelitz BI: Therapeutic efficacy of 6-mercaptopurine in refractory ulcerative colitis. Am J Gastroenterol 1990, 85:717-722. This is a retrospective study of 81 patients with resistant ulcerative colitis treated with 6-mercaptopurine. The response rate was of 63%; it is concluded that 6-mercaptopurine is effective in inducing and maintaining remission and eliminating steroids in refractory ulcerative colitis.
16. Scott JR: Fetal growth retardation associated with maternal administration of immunosuppressive drugs. Am J Obstet Gynecol 1976, 128:668-676. An experimental work showing that azathioprine given to female rats during pregnancy caused an increased incidence of fetal death and growth retardation.
17. Coté CJ, Meuwissen HJ, Pickering RJ: Effect on the neonate of prednisone and azathioprine administered to the mother during pregnancy. J Pediatr 1974, 85:324-328. A case report (with a review of the literature) of a male infant whose mother received azathioprine and prednisone throughout pregnancy, and who developed reversible lymphopenia, low immunoglobulin G (IgG) and IgM serum levels.
18. Price HV, Salaman JR, Laurence KM, et al.: Immunosuppressive drugs and the foetus. Transplantation 1976, 21:294-298. A report of two infants born to kidney transplant recipients who were on prednisone and azathioprine: the neonates had lymphopenia, low cortisol levels and chromosomal aberrations which all disappeared within 32 months.
19. Davison JM, Lindheimer MD: Pregnancy in women with renal allografts. Semin Nephrol 1984, 4:240-251. A review of 1202 gestations in 789 women with renal allografts receiving azathioprine: no frequent or predominant developmental abnormalities reported.
20. Registration Committee of the European Dialysis and Transplant Association: Successful pregnancies in women treated by dialysis and kidney transplantation. Br J Obstet Gynaecol 1980, 87:839-845. A report of 97 kidney transplant recipients receiving prednisone and azathioprine who gave birth to 110 babies. Abnormalities were noted at birth in seven children whose mothers received higher doses of azathioprine than those with a normal baby. The role of azathioprine in these abnormalities is unclear.
21. Alstead EM, Ritchie JK, Lennard-Jones JE: Safety of azathioprine in pregnancy in inflammatory bowel disease. Gastroenterology 1990, 99:443-446. A retrospective review of 16 pregnancies in 14 women receiving azathioprine for IBD (the drug was maintained throughout pregnancy in seven of them) showed no abnormalities or subsequent health problems in the children.
22. Francella A, Dayan A, Rubin P, et al.: 6-Mercaptopurine (6-MP) is safe therapy for child bearing patients with inflammatory bowel disease (IBD): a case controlled study. Gastroenterology 1996, 110:A909. A case control study of women with IBD who took 6-MP and (1) conceived after stopping the drug (n = 95), (2) conceived on 6-MP, then stopped the drug (n = 64); (3) conceived on 6-MP and continued the drug during the whole pregnancy (n = 8). The control group comprised 180 pregnancies in women who had never taken 6-MP before. The course of pregnancy and the neotnatal period was similar in the control and 6-MP groups.
23. Burakoff R, Opper F: Pregnancy and nursing. Gastroenterology Clin N Am 1995, 24:689-698. Outstanding and thorough review of the problems associated with pregnancy in women with inflammatory bowel disease.
24. Lichtiger S, Present D, Kornbluth A, et al.: Cyclosporin in severe ulcerative colitis refractory to steroid therapy. N Engl J Med 1994, 330:1841-1845. Important trial showing that intravenous cyclosporin avoids the need for colectomy in 80% of acute severe, steroid-resistant UC.
25. Bertschinger P, Himmelmann A, Risti B, et al.: Cyclosporine treatment of severe ulcerative colitis during pregnancy. Am J Gastroenterol 1995, 90:330. The only published case of a women having received cyclosporin for fulminant ulcerative colitis at 29 week of gestation, with a good result for both the mother (no colectomy) and the baby.
26. Connell WR: Safety of drug therapy for inflammatory bowel disease in pregnant and nursing women. Inflamm Bowel Dis 1996, 2:33-47. Excellent and recent clinical review.
27. Shaheen FAM, Al-sulaiman MH, Al-Khader AA: Long-term nephrotoxicity after exposure to cyclosporin in utero. Transplantation 1993, 56:224-225.