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Inflammatory Bowel Diseases (IBD) and Pregnancy NASSIF Tania July 2005 IBD and Fertility No significant difference within general population Fertility decreased in active Crohn‘s disease (CD) or in women operated for IBD* Several studies : total colectomy with ileo-anal anastomosis → dysparunia (20-38%) and decreased fertility ** Ileo-rectal anastomosis : less risk and may be recommended in young women *** * Korelitz, Gastroenterol Clin north Am 1998 ** Ravid A, Gastroenterology 2001 *** Olsen KO, Ann Surg 2003 IBD and Contraception Intrauterine device (IUD) : - No recommendation from experts to change the type of contraception in women with IUD taking steroids. - No significant interference with amino-salicylates* Oral contraception : No risk of taking contraceptive pills in patients with ulcerative colitis (UC) who have had intestinal resection ** * Zelissen PM, Scand J Gastroenterol 1988 ** Nilsson LO, Contraception 1985 Risk of transmission of IBD Relative risk (RR) in patients descendence : 2 to 13 % of the general population UC : risk of UC is 5,1 – CD of 2,6 CD : risk of CD is 12,8 – UC of 4 If only one parent is sick, the risk of transmission is between 1,5 to 3,5% More important risk if mother affected* (not confirmed) Higher risk if both parents are affected : - 36% of infants born to couples affected with IBD had an IBD** - Risk of CD is 22% in 10 years and 33% in 22 years in infants whose both parents have CD*** *Akolkar PN, Am J Gastroenterol 1997 **Bennett RA, Gastroenterology 1991 ***Laharie D, Gastroenterology 2001 Effects of IBD on pregnancy I Abortion and fetal death : - Spontaneous abortions are more frequent if active disease (35%)* - Fetal death is 1% in the general population, 2% if active CD ** - Increased risk in UC women taking 5ASA ± corticoids (treatment or disease responsible ??)*** Congenital malformations : - Risk in the general population is 3 to 4% - No significant increase of malformations incidence in literature**** * Tennenbaum R, Gastroenterol Clin Biol, 1999 ** Cleandre D, J Gynecol Obstet Biol Reprod 1993 *** Norgard B, Gut 2003 **** Moser MA, Am J Gastroenterol 2000 Effects of IBD on pregnancy II Prematurity and hypotrophy : - Stop smoking ++ - Careful follow up (3d trimester) - In UC, increased risk of prematurity (birth before the 37th week) and hypotrophy (Odds Ratio respectively of 1,6 and 2,4)* - The mean birth weight is inferior to 185 g % the general population - The risk of relapse during pregnancy is of 20% - Predictive factors : ileal disease, intestinal resection, insufficient treatment** and if the disease appears after pregnancy *** * Fonager K, Am J Gastroenterol 1998 ** Moser MA, Am J Gastroenterol 2000 *** Baird DD, Gastroenterology 1991 Pregnancy and natural history of IBD The IBD activity at conception, increases the risk of persistent activity during pregnancy*: - risk of relapse is 20-25% if inactive IBD - will be as 50% if active IBD on conception Avoid pregnancy during an active phase of IBD… Some studies suggested that pregnancy could decrease and the future activity of IBD** ***: less risk of relapse during 3 years after a pregnancy (immune response caused by pregnancy?) * Korelitz BI, Gastroenterol Clin North Am 1998 ** Nwokolo CU, Gut 1994 *** Castiglione F, Ital J Gastroenterol 1996 Exploration of IBD activity in pregnant women Radiological exams with X-rays should be avoided if not necessary Radiations < 0,10 Gy are tolerated* th The CNS is particularly sensitive between the 10 and th the 17 week of gestation MRI can be done without danger during pregnancy** Colonoscopy and medications used for sedation don’t seem to be harmful (To use just in case they are strictly important for therapeutic decision!!!)*** *Toppenberg KS, Am Fam Physician 1999 ** Forstner R, AJR Am J Roentgenol 1996 ***Cappell MS, Gastroenterol Clin North Am 1998 Security of medications during pregnancy I Almost all medications used for IBD cross the placenta barrier ▪ Corticosteroids : - Prednisone and prednisolone can be used without particular restriction for IBD treatment in pregnant women* - The fetus is exposed to just 10 % of maternal dose ** - Bethamethasone and dexamethasone (not often used for IBD) → adrenal insufficiency in new-born - Budesonide in aerosol (asthma) doesn’t increase the risk of malformation ***, but no information on budesonide as intestinal and colonic liberation * Koren G, N Eng J Med 1998 **Blanford AT, Am J Obstet Gynecol 1977 *** Kallen B, Obstet Gynecol 1999 Security of medications during pregnancy II ▪ Sulfasalazine and 5-ASA : - Sulfasalazine and 5-ASA at doses < 3 g /d don’t increase the risk of congenital malformations or nuclear jaundice* - Supplementation with folic acid is important in women under sulfasalazine and wanting a pregnancy (child-bearing age) (risk of neural tube defects) - All series evaluating mesalazine < 2,4 g/day → no danger (1 case of severe fetal nephropathy with 4 g /d)** - Topic treatments with 5-ASA are harmless*** Prescription of little doses, and if higher doses are required → alternative treatment or watch out for fetal kidney** * Diav-Citrin O, Gastroenterology 1998 ** Colombel JF, Lancet 1994 *** Bell CM, Am J Gastroenterol 1997 Security of medications during pregnancy III ▪ Antibiotics and Probiotics: - Metronidazole is recommended for use in the second and the third trimesters only; short courses during the first trimester are harmless - Avoid quinolones because of potential arthropathy * - Probiotics are harmless in pregnant women** ▪ Methotrexate: - Teratogenic and responsible of chromosomal aberrations, spontaneous abortions and fetal growth retardation*** - Contra-indicated formally during pregnancy, discuss therapeutic abortion if pregnancy occurs under Methotrexate - Stop at least 1 year before conception * Berkovitch M, obstet Gynecol 1994 ** Marteau P, scand J Nutr 2001 *** Roubenoff R, Semin Arthitis Rheuma 1988 Security of medications during pregnancy IV ▪ Azathioprine and 6-mercaptopurine (MP): - It is recommended to avoid 6-MP and azathioprine in women in childbearing age group or to stop these medications if possible 3 months before conception - Iatrogenic risks are minimal, to put on balance with the risk of relapse of disease during pregnancy and the consequences on mother and fetus - If pregnancy occurs under azathioprine, keep medication with strict follow up of maternal leukocytosis * Davison JM, Br J obstet Gynecol 1985 Security of medications during pregnancy V ▪ Other immunosuppressives: - Cyclosporine is responsible of fetal growth retardation, prematurity and severe fetal nephropathy, the prevalence of major malformations doesn’t differ from the general population* - Infliximab seems not to be responsible of more malformations from that expected in the general population (abstract)** - Thalidomide was responsible of severe malformations in th the 50-60 , especially of limbs (phocomely), and disgenesis of kidneys, heart and the eyes (efficient contraception is necessary !!!)*** * Bar OB, Transplantation 2001 ** Katz JA, Gastroenterology 2001 (abstract) *** Koren G, N Engl J Med 1998 Security of medications during pregnancy VI Anti-diarrheic medications: - Contradictory studies about Loperamide : . One study has found 6 major malformations in 108 women exposed during the first trimester of pregnancy* . Another one couldn’t find any malformation in 89 women - Loperamide at the end of pregnancy has been accused of possible intestinal occlusion in new-born** Loperamide can be prescribed during pregnancy but avoid prescription at high doses the days before delivery * Einarson A, Can J Gastroenterol 2000 ** De Gennes C, Journees Francaises de Pharmacovigilance (abstract) 1995 Delivery and Perineal lesions In patients with CD, episiotomy may predispose to recto- vaginal fistula* The presence of active CD ano-perineal lesions at time of delivery is an indication for cesarean It is not proven that preventive cesarean decrease the risk of relapse of ano-perineal lesions in silent forms** Avoid vaginal delivery in case of rigid and/or non compliant perineum The indication of a cesarean in IBD must be large, especially with fear of alteration of fecal continence (ATCD of ileo-anal anastomosis – ano-perineal lesions) * Ganchrow MI, Dis Colon Rectum 1975 ** Ilnyckyji A, Am J Gastroenterol 1999 Divers No modification in surgical indications during pregnancy in case of acute complications of IBD (intestinal occlusion, inflammatory colitis, abscess…)* Enteral nutrition has been suggested in small series as possible treatment of CD in pregnant woman** Attention on lipid emulsions because they may be responsible for fatty emboli to the placenta*** * Hill J, J R Soc Med 1997 ** Teahon K, Gut 1991 *** Badgett T, J Matern Fetal Med 1997 Medications and breast feeding Persons who were breast-fed are thought to have a decreased risk of CD (contradictory results in UC)* Corticoids are authorized (0,1% of maternal dose) (wait 4 hrs after the medication if dose > 20 mg / day) Immunosuppressives are contra-indicated** Quinolones are contra-indicated (arthropathy !)*** Loperamide can be used during lactation**** Use Metronidazole only in brief duration * Thompson NP, Eur J Gastroenterol Hepatol 2000 ** Ramsey-Goldman R, Rheum Dis Clin North Am 1997 *** Giamarellou H, Am J Med 1989 **** Hagemann TM, J Hum Lact 1998 Men and IBD Fertility : - Fertility is not affected - Treatment by sulfazalasine can decrease fertility in men (quantitative and qualitative anomalies of spermatozoids), reversible after stopping or switching to 5-ASA* - Azathioprine does not seem to modify fertility** Risks for fetus : - Effect of analogues of purins on gametes*** - Studies are contradictory - 1 case of Wilms' tumor in one infant whose father had taken azathioprine at time of conception VIDAL : avoid conception if one or both parents are treated, keep an effective contraception for at least 3 months * Narendranathan m, J clin gastroenterol 1989 ** Dejaco C, Gastroenterology 2001 *** Korelitz BI, Am J Gastroenterol 2001
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