To jedyna praca jaką znam, w której wykazano wpływ AZA na rozwój płodu u ludzi. Poniżej prace, gdzie tego nie wykazano. Pozostaje pytanie czy np Aza stosuje się u kobiet o cięszym przebieu i stąd wyniki to nie tylko wpływ leczenie, ale samej choroby. Wiadomo jednak, że najbardziej szkodzi zaostrzenie i
nieleczenie. Decyzja jest zawsze jednostkowa i podejmowana jest przez rodziców po konsultacji z lekarzem.
Therapeutic drug use in women with Crohn's disease and birth outcomes: a Danish nationwide cohort study.Nørgård B, Pedersen L, Christensen LA, Sørensen HT.
Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus C, Denmark.
BACKGROUND: Crohn's disease (CD) is associated with increased risk of adverse birth outcomes. However, existing studies have not taken into account the impact of drug treatment. We examined the impact of drug treatment on birth outcomes--low birth weight (LBW), preterm birth, LBW at term, and congenital abnormalities (CAs)--among CD women. METHODS: A nationwide Danish cohort study of 900 children born to CD women between 1996 and 2004, based on the National Registry of Patients, the Birth Registry, and the nationwide prescription database. Pregnancies were classified according to receipt of prescriptions for CD medication: no drugs (reference group), 5-aminosalicylic acid (5-ASA)/sulfasalazine, steroids, and azathioprine (AZA)/6-mercaptopurine (6-MP). We used logistic regression analyses to estimate the relative risk of birth outcomes with 95% confidence intervals. We used a proxy measure for disease activity. RESULTS: Preterm births were more prevalent among steroid- and AZA/6-MP-exposed women (12.3% and 25%, respectively) compared with the reference group (6.5%).
CAs were more prevalent among AZA/6-MP-exposed compared with reference group (15.4%vs 5.7%). Among steroid exposed, the risk of preterm birth was 1.4 (95% CI 0.6-3.3). Among AZA/6-MP exposed, the risk of preterm birth and CAs was 4.2 (95% CI 1.4-12.5) and 2.9 (95% CI 0.9-8.9), respectively. CONCLUSIONS: The relative risk of adverse birth outcomes among CD women varied by type of drugs prescribed during pregnancy. The risk of preterm birth and CAs was greater when AZA/6-MP was prescribed, even after adjusting for confounders. However, further information is needed to determine whether the associations are causal.
Pregnancy outcome of women exposed to azathioprine during pregnancy.Goldstein LH, Dolinsky G, Greenberg R, Schaefer C, Cohen-Kerem R, Diav-Citrin O, Malm H, Reuvers-Lodewijks ME, Rost van Tonningen-van Driel MM, Arnon J, Ornoy A, Clementi M, Di Gianantonio E, Koren G, Braunstein R, Berkovitch M.
Clinical Pharmacology Unit, Teratogen Information Service, Assaf Harofeh Medical Center, Sackler School of Medicine, Tel Aviv University, Israel.
BACKGROUND: Azathioprine (AZP) interferes with nucleic acid synthesis and is teratogenic in animals. In view of the paucity of information on the use of AZP during pregnancy we investigated this subject in a prospective, controlled, multicenter study. Our objective was too determine whether exposure to AZP during pregnancy increases the risk for major malformations and to determine the effect on pregnancy outcome. METHODS: Pregnant women on AZP who contacted one of seven teratogen information services were compared to a cohort of pregnant women who contacted two of the seven teratogen information services and took nonteratogenic treatments during their pregnancy. RESULTS: Follow-up was completed on 189 women in the AZP group and compared to 230 women in the control group. The rate of major malformations did not differ between groups with six neonates in each; the AZP rate was 3.5% and the control group rate was 3.0% (p = .775; OR 1.17; CI: 0.37, 3.69). The mean birth weight and gestational age were lower in the AZP group (2,995 g vs. 3,252 g [p = .001, difference of mean: 257, 95% CI: 106.3, 408.1] and 37.8 weeks vs. 39.1 weeks [p = .001, difference of mean: 1.3, 95% CI: .5, 2.0], respectively). The AZP group had more cases of prematurity (21.4% vs. 5.2% [p < .001; OR 4.0; 95% CI: 2.0, 8.06]) and low birth weight (23% vs. 6.0% [p < .001; OR 3.81; 95% CI: 2.0, 7.2]). CONCLUSIONS:
These results suggest that AZP (50-100 mg/day) does not triple the rate of birth defects; however, it is associated with lower birth weight, gestational age, and prematurity. Larger studies are needed to confirm these observations.
Pregnancy and breastfeeding in patients with Crohn's disease.Mottet C, Juillerat P, Pittet V, Gonvers JJ, Froehlich F, Vader JP, Michetti P, Felley C.
Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.
christian.mottet@chuv.ch
Crohn's disease commonly affects women of childbearing age. Available data on Crohn's disease and pregnancy show that women with Crohn's disease can expect to conceive successfully, carry to term and deliver a healthy baby. Control of disease activity before conception and during pregnancy is critical, to optimize both maternal and fetal health. Generally speaking, pharmacological therapy for Crohn's disease during pregnancy is similar to pharmacological therapy for nonpregnant patients. Patients maintained in remission by way of pharmacological therapy should continue it throughout their pregnancy. Sulfasalazine, mesalazine and corticosteroids are safe,
azathioprine and 6-mercaptopurine are reasonably safe with few discordant data, infliximab seems safe as well, whereas methotrexate is contraindicated during pregnancy. During breastfeeding, mesalazine and prednisone are considered safe, azathioprine/6-mercaptopurine, budesonide and infliximab probably safe and methotrexate is contraindicated. Copyright 2008 S. Karger AG, Basel.
Azathioprine treatment during lactation.Christensen LA, Dahlerup JF, Nielsen MJ, Fallingborg JF, Schmiegelow K.
Department of Medicine V, Arhus University Hospital, Arhus, Denmark.
lachr@as.aaa.dk
BACKGROUND:
Thiopurines are widely used to maintain remission in inflammatory bowel disease.
Treatment during pregnancy is generally recommended to improve the chance of a normal birth outcome, but advice concerning breastfeeding is conflicting. Aim To estimate the exposure of breastfed infants to 6-mercaptopurine, as a metabolite of azathioprine, from maternal milk. METHODS: Eight lactating women with inflammatory bowel disease receiving maintenance therapy with azathioprine 75-200 mg daily were studied. Milk and plasma samples were obtained 30 and 60 min after drug administration and hourly for the following 5 h. RESULTS: The variation in the bioavailability of the drug was reflected in a wide range of peak plasma values of 6-mercaptopurine within the first 3 h. A similar curve, but with an hour's delay and at significantly lower concentrations varying from 2-50 microg/L, was seen in maternal milk. After 6 h an average of 10% of the peak values were measured. CONCLUSIONS: The major part of 6-mercaptopurine in breast milk is excreted within the first 4 h after drug intake. On the basis of maximum concentration measured, the infant ingests mercaptopurine of <0.008 mg/kg bodyweight/24 h. The findings confirm that breastfeeding during treatment with azathioprine seems safe and should be recommended, considering the extensive beneficial effects.