Long-term follow-up of babies exposed to azathioprine in utero and via breastfeeding

Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Austria.
Journal of Crohn s and Colitis (Impact Factor: 6.23). 04/2011; 5(2):95-100. DOI: 10.1016/j.crohns.2010.10.005
Source: PubMed


Recommendations on breastfeeding under thiopurines are inconsistent due to limited data.
To assess the risk of infections in offspring breastfed by mothers receiving azathioprine (AZA) for inflammatory bowel disease (IBD).
Babies, who were breastfed from their mothers treated either with or without AZA were included from a local pregnancy-registry. Women were asked by structured personal interview on general development, infections, hospitalisations and vaccinations of their offspring.
A group of 11 mothers taking AZA (median 150 mg/d) during pregnancy and lactation and another of 12 patients without using any immunosuppressive therapy breastfed 15 babies each for median 6 months and 8 months, respectively. Median age of children at time of interview was 3.3 and 4.7 years, respectively. All offspring showed age-appropriate mental and physical development. Infections were commonly seen childhood diseases. Similar rates were observed for most of the various infections between offspring with and without azathioprine exposure during breastfeeding. However, common cold more than two episodes/year and conjunctivitis were numerically more often reported in the group without AZA exposure. In an exploratory analysis no difference in the rate of hospitalisations was seen between exposed (0.06 hospitalisations/patient year) versus non-exposed children (0.12 hospitalisations/patient year, p=0.8)
Our study which reports the largest number of babies breastfed with exposure to AZA suggests that breastfeeding does not increase the risk of infections.

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    • "Antimetabolites: effects on CNS and neuropsychological functions in humans There are no reports on adverse side effects of azathioprine on CNS and behavior. In infants exposed to azathioprine in utero and via breastfeeding, age-appropriate mental development has been reported in a long-term follow-up study (Angelberger et al., 2011). However, RA patients treated with DMARDs have been shown to present with the highest rates of depression, anxiety and suicidal ideation compared to patients using methotrexate, leflunomide, hydroxychloroquine and biological drugs (Pinho de Oliveira Ribeiro et al., 2013). "
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    ABSTRACT: 60 years after the first successful kidney transplantation in humans, transplant patients have decent survival rates owing to a broad spectrum of immunosuppressive medication available today. Not only transplant patients, but also patients with inflammatory autoimmune diseases or cancer benefit from these life-saving immunosuppressive and anti-proliferative medications. However, this success is gained with the disadvantage of neuropsychological disturbances and mental health problems such as depression, anxiety and impaired quality of life after long-term treatment with immunosuppressive drugs. So far, surprisingly little is known about unwanted neuropsychological side effects of immunosuppressants and anti-proliferative drugs from the group of so called small molecule-drugs. This is partly due to the fact that it is difficult to disentangle whether and to what extent the observed neuropsychiatric disturbances are a direct result of the patient's medical history or of the immunosuppressive treatment. Thus, here we summarize experimental as well as clinical data of mammalian and human studies, with the focus on selected small-molecule drugs that are frequently employed in solid organ transplantation, autoimmune disorders or cancer therapy and their effects on neuropsychological functions, mood, and behavior. These data reveal the necessity to develop immunosuppressive and anti-proliferative drugs inducing fewer or no unwanted neuropsychological side effects, thereby increasing the quality of life in patients requiring long term immunosuppressive treatment. This article is part of a Special Issue entitled 'Neuroimmunology and Synaptic Function'. Copyright © 2014 Elsevier Ltd. All rights reserved.
    Neuropharmacology 12/2014; 96(Pt A). DOI:10.1016/j.neuropharm.2014.12.008 · 5.11 Impact Factor
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    • "The use of AZA and 6-MP in pregnancy appears safe and well tolerated (13), as also shown from our experience, and recent guidelines for IBD management in adults (4, 14) suggest that AZA should be continued during pregnancy because the risks to the fetus due to disease activity appears greater than risks due to drug toxicity. In addition, a recent study on a large group of subjects treated with these drugs did not show increased number of infections in their breastfed children (15). "
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    ABSTRACT: Inflammatory bowel disease (IBD) frequently affects young patients of childbearing age. Treatments for inflammatory bowel disease include immunosuppressive, cytotoxic and surgical therapies. Azathioprine is frequently used to treat patients with steroid dependent IBD. We report the case of a patient with ulcerative colitis, treated with azathioprine prior to conception and during the subsequent pregnancy with the subsequent successful delivery of healthy twins. Although some potential risks indeed exist, the use of AZA may not be harmful to the mother or the fetus in many instances.
    Gastroenterology and hepatology from bed to bench 04/2011; 4(4):224-7.
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    ABSTRACT: 248 INTRODUCTION Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory diseases that have an increasing incidence and prevalence. The etiology of inflammatory bowel disease (IBD) is precisely unknown, but there are complex interactions of genetic, immunological, and environmental factors (1). IBD is characterized by a peak age of onset during the peak reproductive years (2). Approximately 55% of patients are less than 35 years of age at the time of diagnosis. Of these, 25% will conceive for the first time following diagnosis (3). Parenthood is one of the The peak age of onset of inflammatory bowel disease (IBD) is simultaneous with the peak reproductive years. Patients have many concerns about the impact of IBD on fertility and pregnancy outcomes. The most important reason for voluntary childlessness is the fear of side effects from medications for IBD. Decision making for medical therapy is a complex equation. It is important to summarize available infor-mation about the management of IBD during pregnancy and its interactions. Among IBD patients, those undergoing surgery are at risk for reductions in fertility. Patients with ileal pouches–anal anastomosis (IPAA) experience higher rates of infertility. Disease activity at the time of con-ception is the main determinant of the impact of IBD on adverse pregnancy outcomes. In different nations, disease activity and relapse depend on many factors and may even be slightly lower during pregnancy. The recommended mode of delivery in IBD is still controversial. However, there is an increased rate of cesarean sections in women with IBD. Choosing the appropriate method of delivery should be based on the obstetrician's opinion, however active perianal disease and the presence of an ileoanal pouch are two major exceptions. If women remain on their maintenance therapy, there would be no increased risk of a flare-up during the postpartum period. In most patients, maintaining remission with medication outweighs the risks of their adverse effects. However, the pros and cons must be discussed with the patient and deci-sions should be made on an individual basis. Among all drugs used in IBD treatment, only methotrexate (MTX) and thalidomide are contraindicated in pregnancy.
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