IBD in Pregnancy

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  Notes
 
 
Slide 1 : Inflammatory Bowel Diseases (IBD) and Pregnancy NASSIF Tania July 2005
Slide 2 : 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
Slide 3 : 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
Slide 4 : 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
Slide 5 : 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
Slide 6 : 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
Slide 7 : 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 the future activity of IBD**and***: 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
Slide 8 : Exploration of IBD activity in pregnant women Radiological exams with X-rays should be avoided if not necessary Radiations < 0,10 Gy are tolerated* The CNS is particularly sensitive between the 10th and the 17th 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
Slide 9 : 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
Slide 10 : 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
Slide 11 : 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
Slide 12 : 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
Slide 13 : 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 the 50-60th, 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
Slide 14 : 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
Slide 15 : 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
Slide 16 : 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
Slide 17 : 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
Slide 18 : 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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