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1
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Araújo FR, da Silva AL, de Oliveira L, Correa-Silva S, Bevilacqua E. Cytotoxicity and induction of proinflammatory cytokines in placental explant cells following azathioprine exposure. Placenta 2025:S0143-4004(25)00143-2. [PMID: 40413138 DOI: 10.1016/j.placenta.2025.05.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2024] [Revised: 04/14/2025] [Accepted: 05/05/2025] [Indexed: 05/27/2025]
Abstract
Immunosuppressive drugs offer hope for the survival and motherhood of women with various disorders. Although the systemic side effects of these drugs on mothers have been studied, their impact on the placenta remains poorly understood, which can negatively affect fetal and postnatal development. This study investigated the effects of Azathioprine, an immunosuppressive drug, on the chorionic villi of human placentas from healthy pregnancies, focusing on cellular vitality and pro-inflammatory cytokines expression. Chorionic villi from term placentas were cultured and treated with Azathioprine at concentrations ranging from 0 to 100 ng/mL for 24 h. Azathioprine reduced mitochondrial metabolic activity (MTT assay) at all concentrations tested (p < 0.05) and increased cellular injury rates (LDH assay) at 50 and 100 ng/mL (p < 0.05). It also elevated protein (at 12.5 and 25 ng/mL, p < 0.05) and gene expression levels of interleukin (IL)-1β (12.5 ng/mL, p < 0.05). Protein levels of IL-18 increased significantly following Azathioprine exposure (p < 0.05), along with cleaved Caspase-1 (p = 0.003) and phosphorylated NF-κB levels (p < 0.05), compared to controls. IL-18 gene expression was elevated only at 12.5 ng/mL (p < 0.0005). These findings suggest that Azathioprine creates a cytotoxic microenvironment that disrupts the metabolism of chorionic villi, leading to injury and activation of pro-inflammatory cytokine expression. Such changes may contribute to an imbalance in placental homeostasis, potentially associated with adverse maternal and neonatal outcomes that warrant further investigation.
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Affiliation(s)
- Franciele Rodrigues Araújo
- Laboratory for Studies of the Trophoblast Biology, Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, SP, Brazil
| | - Adriana Lopes da Silva
- Laboratory for Studies of the Trophoblast Biology, Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, SP, Brazil
| | - Leandro de Oliveira
- Department of Gynecology and Obstetrics, São Paulo State University (UNESP), Medical School, Botucatu, SP, Brazil
| | - Simone Correa-Silva
- Laboratory for Studies of the Trophoblast Biology, Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, SP, Brazil; Laboratory of Clinical Pediatrics (LIM36), Hospital Das Clinicas HCFMUSP, Faculty of Medicine, University of Sao Paulo, SP, Brazil
| | - Estela Bevilacqua
- Laboratory for Studies of the Trophoblast Biology, Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, SP, Brazil.
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2
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Tarter L, Bermas BL. Expert Perspective on a Clinical Challenge: Lupus and Pregnancy. Arthritis Rheumatol 2024; 76:321-331. [PMID: 37975160 DOI: 10.1002/art.42756] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2023] [Revised: 10/10/2023] [Accepted: 11/13/2023] [Indexed: 11/19/2023]
Abstract
Systemic lupus erythematosus (SLE), a multiorgan systemic inflammatory disorder, predominantly affects women during their reproductive years. In this review, we summarize the state of knowledge about preconception planning and management of SLE during pregnancy. Achieving remission or low disease activity for several months on medications compatible with pregnancy prior to conception is essential to decreasing the risk of disease flare and improving pregnancy outcomes, including pre-eclampsia, preterm birth, and intrauterine growth restriction. With close management and well-controlled disease before and during pregnancy, <10% of patients flare. All patients with SLE should remain on hydroxychloroquine unless contraindicated. Expectant mothers with a history of antiphospholipid syndrome should be treated with anticoagulant therapy during pregnancy. Women with anti-Ro/SSA or anti-La/SSB antibodies require additional monitoring because their offspring are at increased risk for congenital heart block. Patients with SLE should be offered low-dose aspirin starting at the end of the first trimester to reduce the risk of pre-eclampsia. Flares of SLE during pregnancy require escalation of therapy. The immunosuppressives azathioprine, tacrolimus, and cyclosporine are compatible with pregnancy, and biologic agents can also be considered. Glucocorticoid use in pregnancy should be limited to the lowest effective dose. Mycophenolate mofetil/mycophenolic acid, methotrexate, leflunomide, and cyclophosphamide are known to be teratogenic and are contraindicated in pregnancy. Distinguishing a flare of lupus nephritis during pregnancy from pre-eclampsia can be particularly challenging. Overall, outcomes in pregnancy for women with lupus are improving, but gaps in knowledge about optimal management strategies persist.
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Affiliation(s)
- Laura Tarter
- Brigham and Women's Hospital, Boston, Massachusetts
| | - Bonnie L Bermas
- University of Texas Southwestern Medical Center, Dallas, Texas
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3
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Caballero-Mateos AM, Quesada-Caballero M, Cañadas-De la Fuente GA, Caballero-Vázquez A, Contreras-Chova F. IBD and Motherhood: A Journey through Conception, Pregnancy and Beyond. J Clin Med 2023; 12:6192. [PMID: 37834837 PMCID: PMC10573266 DOI: 10.3390/jcm12196192] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2023] [Revised: 09/14/2023] [Accepted: 09/19/2023] [Indexed: 10/15/2023] Open
Abstract
Inflammatory Bowel Disease (IBD) presents distinct challenges during pregnancy due to its influence on maternal health and pregnancy outcomes. This literature review aims to dissect the existing scientific evidence on pregnancy in women with IBD and provide evidence-based recommendations for clinical management. A comprehensive search was conducted across scientific databases, selecting clinical studies, systematic reviews, and other pertinent resources. Numerous studies have underscored an increased risk of complications during pregnancy for women with IBD, including preterm birth, low birth weight, neonates small for gestational age, and congenital malformations. Nevertheless, it's evident that proactive disease management before and throughout pregnancy can mitigate these risks. Continuation of IBD treatment during pregnancy and breastfeeding is deemed safe with agents like thiopurines, anti-TNF, vedolizumab, or ustekinumab. However, there's a call for caution when combining treatments due to the heightened risk of severe infections in the first year of life. For small molecules, their use is advised against in both scenarios. Effective disease management, minimizing disease activity, and interdisciplinary care are pivotal in attending to women with IBD. The emphasis is placed on the continual assessment of maternal and infant outcomes and an expressed need for further research to enhance the understanding of the ties between IBD and adverse pregnancy outcomes.
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4
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Tian X, Zhao J, Song Y, Wang Q, Li M, Liu J, Zeng X. 2022 Chinese guideline for the management of pregnancy and reproduction in systemic lupus erythematosus. RHEUMATOLOGY AND IMMUNOLOGY RESEARCH 2023; 4:115-138. [PMID: 37781682 PMCID: PMC10538620 DOI: 10.2478/rir-2023-0019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/25/2023] [Accepted: 08/19/2023] [Indexed: 10/03/2023]
Abstract
Systemic lupus erythematosus (SLE), a prevalent autoimmune disease predominantly affecting women of childbearing age, presents ongoing challenges despite notable advances in diagnosis and treatment. Although survival rates for SLE patients have significantly improved, pregnancy continues to pose a considerable obstacle. Addressing this critical need for enhanced reproductive and prenatal care, there is a pressing imperative to establish standardized protocols for peri-gestational monitoring and treatment in SLE patients. This guideline is jointly sponsored by the National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), the Chinese Systemic Lupus Erythematosus Treatment and Research Group (CSTAR), and the Chinese Research Committee of Pregnancy and Reproduction in Autoimmune Rheumatic Diseases (CHOPARD). Thirteen pertinent clinical questions have been generated through several rounds of rigorous clinical and methodological expert discussions and selections for a comprehensive understanding of key aspects in this domain. Guided by thorough examination of research evidence and expert perspectives, the formulated recommendations aim to optimize pregnancy success rates, reduce maternal and infant mortality rates, and ultimately enhance the overall well-being of SLE patients.
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Affiliation(s)
- Xinping Tian
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences& Peking Union Medical College; National Clinical Research Center for Dermatologic and Immunologic Diseases, Ministry of Science& Technology; State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College; Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing100730, China
| | - Jiuliang Zhao
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences& Peking Union Medical College; National Clinical Research Center for Dermatologic and Immunologic Diseases, Ministry of Science& Technology; State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College; Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing100730, China
| | - Yijun Song
- Department of Obstetrics, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing100730, China
| | - Qian Wang
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences& Peking Union Medical College; National Clinical Research Center for Dermatologic and Immunologic Diseases, Ministry of Science& Technology; State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College; Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing100730, China
| | - Mengtao Li
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences& Peking Union Medical College; National Clinical Research Center for Dermatologic and Immunologic Diseases, Ministry of Science& Technology; State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College; Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing100730, China
| | - Juntao Liu
- Department of Obstetrics, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing100730, China
| | - Xiaofeng Zeng
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences& Peking Union Medical College; National Clinical Research Center for Dermatologic and Immunologic Diseases, Ministry of Science& Technology; State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College; Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing100730, China
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5
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Kittleson MM, DeFilippis EM, Bhagra CJ, Casale JP, Cauldwell M, Coscia LA, D'Souza R, Gaffney N, Gerovasili V, Ging P, Horsley K, Macera F, Mastrobattista JM, Paraskeva MA, Punnoose LR, Rasmusson KD, Reynaud Q, Ross HJ, Thakrar MV, Walsh MN. Reproductive health after thoracic transplantation: An ISHLT expert consensus statement. J Heart Lung Transplant 2023; 42:e1-e42. [PMID: 36528467 DOI: 10.1016/j.healun.2022.10.009] [Citation(s) in RCA: 26] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2022] [Accepted: 10/10/2022] [Indexed: 11/16/2022] Open
Abstract
Pregnancy after thoracic organ transplantation is feasible for select individuals but requires multidisciplinary subspecialty care. Key components for a successful pregnancy after lung or heart transplantation include preconception and contraceptive planning, thorough risk stratification, optimization of maternal comorbidities and fetal health through careful monitoring, and open communication with shared decision-making. The goal of this consensus statement is to summarize the current evidence and provide guidance surrounding preconception counseling, patient risk assessment, medical management, maternal and fetal outcomes, obstetric management, and pharmacologic considerations.
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Affiliation(s)
- Michelle M Kittleson
- Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California.
| | - Ersilia M DeFilippis
- Division of Cardiology, New York Presbyterian-Columbia University Irving Medical Center, New York, New York
| | - Catriona J Bhagra
- Department of Cardiology, Cambridge University and Royal Papworth NHS Foundation Trusts, Cambridge, UK
| | - Jillian P Casale
- Department of Pharmacy Services, University of Maryland Medical Center, Baltimore, Maryland
| | - Matthew Cauldwell
- Department of Obstetrics, Maternal Medicine Service, St George's Hospital, London, UK
| | - Lisa A Coscia
- Transplant Pregnancy Registry International, Gift of Life Institute, Philadelphia, Pennsylvania
| | - Rohan D'Souza
- Division of Maternal and Fetal Medicine, Department of Obstetrics and Gynecology, McMaster University, Hamilton, Ontario, Canada
| | - Nicole Gaffney
- Lung Transplant Service, Alfred Hospital, Melbourne, Australia; Department of Medicine, Central Clinical School, Monash University, Melbourne, Australia
| | | | - Patricia Ging
- Department of Pharmacy, Mater Misericordiae University Hospital, Dublin, Ireland
| | - Kristin Horsley
- Department of Obstetrics and Gynecology, McMaster University, Hamilton, Ontario, Canada
| | - Francesca Macera
- De Gasperis Cardio Center and Transplant Center, Niguarda Hospital, Milan, Italy; Dept of Cardiology, Cliniques Universitaires de Bruxelles - Hôpital Erasme, Brussels, Belgium
| | - Joan M Mastrobattista
- Department of Obstetrics & Gynecology, Division of Maternal-Fetal Medicine, Baylor College of Medicine Houston, Texas
| | - Miranda A Paraskeva
- Lung Transplant Service, Alfred Hospital, Melbourne, Australia; Department of Medicine, Central Clinical School, Monash University, Melbourne, Australia
| | - Lynn R Punnoose
- Vanderbilt Heart and Vascular Institute, Vanderbilt University Medical Center, Nashville, Tennessee
| | | | - Quitterie Reynaud
- Cystic Fibrosis Adult Referral Care Centre, Department of Internal Medicine, Hospices civils de Lyon, Pierre Bénite, France
| | - Heather J Ross
- Peter Munk Cardiac Centre of the University Health Network, Toronto, Ontario, Canada; Ted Rogers Centre for Heart Research, Toronto, Ontario, Canada; University of Toronto, Toronto, Ontario, Canada
| | - Mitesh V Thakrar
- Department of Medicine, Division of Respirology, University of Calgary, Calgary, Alberta, Canada
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6
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Grigorescu RR, Husar-Sburlan IA, Rosulescu G, Bobirca A, Cerban R, Bobirca F, Florescu MM. Pregnancy in Patients with Inflammatory Bowel Diseases-A Literature Review. Life (Basel) 2023; 13:475. [PMID: 36836832 PMCID: PMC9961380 DOI: 10.3390/life13020475] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2022] [Revised: 02/03/2023] [Accepted: 02/04/2023] [Indexed: 02/11/2023] Open
Abstract
In recent years, we have faced an increasing incidence of inflammatory bowel disease (IBD), especially among young people, affecting them during their reproductive years. The paucity of data and reduced knowledge regarding the evolution of the disease during pregnancy and the adverse effects of the therapy on the mother and infant increase voluntary childlessness in this group of patients. Depending on the type of IBD, severity and surgical or medical management, this can negatively affect the pregnancy. C-sections and the risk of low-birth-weight babies are higher in women with IBD, independent of active/inactive disease, while preterm birth, stillbirth and miscarriage are associated with disease activity. In the last period, medicinal therapy has evolved, and new molecules have been developed for better control of the lesions, but the effect on pregnancy and breastfeeding is still controversial. We conducted this review by studying the literature and recent research in order to have a better image of the practical management of IBD during pregnancy.
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Affiliation(s)
| | | | - Georgiana Rosulescu
- Gastroenterology Department, “Sfanta Maria” Hospital, 011172 Bucharest, Romania
| | - Anca Bobirca
- Department of Internal Medicine and Rheumatology, Dr. I. Cantacuzino Clinical Hospital, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania
| | - Razvan Cerban
- Center for Digestive Disease and Liver Transplantation, Fundeni Clinical Institute, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania
| | - Florin Bobirca
- Surgery Department, Dr. Ion Cantacuzino Clinical Hospital, 011437 Bucharest, Romania
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7
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Pregnancy and sex hormone changes after kidney transplant. CLINICA E INVESTIGACION EN GINECOLOGIA Y OBSTETRICIA 2023. [DOI: 10.1016/j.gine.2022.100812] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
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8
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Chowdhury R, Kane SV. Pregnancy and Crohn's disease: concerns and assurance of medical therapy. Gastroenterol Rep (Oxf) 2022; 10:goac055. [PMID: 36225722 PMCID: PMC9550230 DOI: 10.1093/gastro/goac055] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2022] [Revised: 09/19/2022] [Accepted: 09/20/2022] [Indexed: 11/04/2022] Open
Abstract
Approximately 50% of patients with inflammatory bowel disease including both Crohn's disease and ulcerative colitis are female with many being diagnosed and treated during their reproductive years. It is important for women to be in remission prior to and during pregnancy. There have been many advances in the treatment of inflammatory bowel disease, including new therapies. In this review, we summarize the currently approved medications for Crohn's disease and their safety in pregnancy and postpartum. The totality of evidence suggests that the majority of therapies are low-risk before and during pregnancy, and should be continued to control maternal disease.
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Affiliation(s)
- Reezwana Chowdhury
- Division of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA
| | - Sunanda V Kane
- Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN, USA
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9
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Si T, Huang Z, Hegarty R, Ma Y, Heneghan MA. Systematic review with meta-analysis: outcomes of pregnancy in patients with autoimmune hepatitis. Aliment Pharmacol Ther 2022; 55:1368-1378. [PMID: 35393675 PMCID: PMC9324120 DOI: 10.1111/apt.16924] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2021] [Revised: 11/18/2021] [Accepted: 03/25/2022] [Indexed: 02/06/2023]
Abstract
BACKGROUND Autoimmune hepatitis (AIH) is common in females of childbearing age. Although some studies have provided information about the outcomes of pregnancy, there remains uncertainty regarding conclusions. AIM To comprehensively explore the interactions between pregnancy and AIH. METHODS Databases including PubMed, Embase, Cochrane Library and Science Citation Index Expanded were searched to collect available studies in relation to pregnancy in AIH patients (from inception to 28 August 2021). Pooled data were calculated using a random effects model with standardised mean difference (SMD), or risk ratio (RR), and 95% confidence intervals (CI). RESULTS Twelve studies were considered eligible for meta-analysis. Data from 26 case reports/series were extracted for systematic review. AST level in AIH patients was significantly lower during pregnancy (SMD = -0.41, 95% CI = [-0.70, -0.12]; SMD = -1.60, 95% CI = [-2.76, -0.44]) and loss of biochemical remission occurred more frequently in post-partum (RR = 0.31, 95% CI = [0.19, 0.52]). Patients with portal hypertension or without established remission before conception presented as high-risk subgroups and the incidence of pre-term delivery was higher in these groups compared to other AIH patients (RR = 9, 95% CI = [1.22, 51.1]; RR = 0.05, 95% CI = [0.004, 0.38]). In population-based comparison, pre-term birth (RR = 2.45, 95% CI = [1.66, 3.62]) also occurred more often in AIH patients compared with the general population. CONCLUSIONS Successful pregnancy is a reasonable expectation in AIH. However, hepatic biochemistry should be monitored closely in both the puerperium and the post-partum period. Though some patients may present higher risk, with carefully selected therapeutic manipulation and multi-disciplinary care, the majority of mothers and infants should achieve uneventful outcomes.
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Affiliation(s)
- Tengfei Si
- Institute of Liver Studies, King’s College Hospital, Department of Inflammation Biology, Faculty of Life Sciences & MedicineKing’s College LondonLondonUK
| | - Zhenlin Huang
- Institute of Liver Studies, King’s College Hospital, Department of Inflammation Biology, Faculty of Life Sciences & MedicineKing’s College LondonLondonUK,The MOE Key Laboratory for Standardization of Chinese MedicineInstitute of Chinese Materia Medica, Shanghai University of Traditional Chinese MedicineShanghaiChina
| | - Robert Hegarty
- Pediatric Liver, GI and Nutrition CentreKing’s College Hospital NHS Foundation TrustLondonUK
| | - Yun Ma
- Institute of Liver Studies, King’s College Hospital, Department of Inflammation Biology, Faculty of Life Sciences & MedicineKing’s College LondonLondonUK
| | - Michael A. Heneghan
- Institute of Liver Studies, King’s College Hospital, Department of Inflammation Biology, Faculty of Life Sciences & MedicineKing’s College LondonLondonUK
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10
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Andoh A, Kawahara M, Imai T, Tatsumi G, Inatomi O, Kakuta Y. Thiopurine pharmacogenomics and pregnancy in inflammatory bowel disease. J Gastroenterol 2021; 56:881-890. [PMID: 34287682 DOI: 10.1007/s00535-021-01805-z] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Accepted: 06/18/2021] [Indexed: 02/04/2023]
Abstract
The thiopurine drugs azathioprine and 6-mercaptopurine are widely used for the maintenance of clinical remission in steroid-dependent inflammatory bowel disease (IBD). Thiopurines are recommended to be continued throughout pregnancy in IBD patients, but conclusive safety data in pregnant patients remain still insufficient. On the other hand, a strong association between a genetic variant of nucleoside diphosphate-linked moiety X-type motif 15 (NUDT15 p.Arg139Cys) and thiopurine-induced myelotoxicity has been identified. Pharmacokinetic studies have revealed that thiopurine metabolism is altered in pregnant IBD patients and suggested that the fetus may be exposed to the active-thiopurine metabolite, 6-thioguaninetriphosphate, in the uterus. A recent study using knock-in mice harboring the p.Arg138Cys mutation which corresponds to human p.Arg139Cys showed that oral administration of 6-MP at clinical dose induces a severe toxic effect on the fetus harboring the homozygous or heterozygous risk allele. This suggests that NUDT15 genotyping may be required in both women with IBD who are planning pregnancy (or pregnant) and their partner to avoid adverse outcomes for their infant. The risk to the fetus due to maternal thiopurine use is minimal but there are some concerns that are yet to be clarified. In particular, a pharmacogenomic approach to the fetus is considered necessary.
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Affiliation(s)
- Akira Andoh
- Division of Gastroenterology and Hematology, Shiga University of Medical Science, Seta-Tsukinowa, Otsu, Shiga, 520-2192, Japan.
| | - Masahiro Kawahara
- Division of Gastroenterology and Hematology, Shiga University of Medical Science, Seta-Tsukinowa, Otsu, Shiga, 520-2192, Japan
| | - Takayuki Imai
- Division of Gastroenterology and Hematology, Shiga University of Medical Science, Seta-Tsukinowa, Otsu, Shiga, 520-2192, Japan
| | - Goichi Tatsumi
- Division of Gastroenterology and Hematology, Shiga University of Medical Science, Seta-Tsukinowa, Otsu, Shiga, 520-2192, Japan
| | - Osamu Inatomi
- Division of Gastroenterology and Hematology, Shiga University of Medical Science, Seta-Tsukinowa, Otsu, Shiga, 520-2192, Japan
| | - Yoichi Kakuta
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, 980-8574, Japan
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11
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Zhang Y, Li D, Guo H, Wang W, Li X, Shen S. Association between Thiopurines Use and Pregnancy Outcomes in Female Patients with Inflammatory Bowel Disease: A Meta-Analysis. Curr Pharm Des 2021; 27:2317-2324. [PMID: 32938343 DOI: 10.2174/1381612826666200916144249] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2020] [Accepted: 08/18/2020] [Indexed: 11/22/2022]
Abstract
BACKGROUND Conflicting data exist regarding the influence of thiopurines exposure on adverse pregnancy outcomes in female patients with inflammatory bowel disease (IBD). OBJECTIVE The aim of this study was to provide an up-to-date and comprehensive assessment of the safety of thiopurines in pregnant IBD women. METHODS All relevant articles reporting pregnancy outcomes in women with IBD received thiopurines during pregnancy were identified from the databases (PubMed, Embase, Cochrane Library, and ClinicalTrials.gov) with the publication data up to April 2020. Data of included studies were extracted to calculate the relative risk (RR) of multiple pregnancy outcomes: congenital malformations, low birth weight (LBW), preterm birth, small for gestational age (SGA), and spontaneous abortion. The meta-analysis was performed using the random-effects model. RESULTS Eight studies matched with the inclusion criteria and a total of 1201 pregnant IBD women who used thiopurines and 4189 controls comprised of women with IBD received drugs other than thiopurines during pregnancy were included. Statistical analysis results demonstrated that the risk of preterm birth was significantly increased in the thiopurine-exposed group when compared to IBD controls (RR, 1.34; 95% CI, 1.00-1.79; p=0.049; I2 =41%), while no statistically significant difference was observed in the incidence of other adverse pregnancy outcomes. CONCLUSION Thiopurines used in women with IBD during pregnancy is not associated with congenital malformations, LBW, SGA, or spontaneous abortion, but appears to have an association with an increased risk of preterm birth.
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Affiliation(s)
- Yang Zhang
- Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Dandan Li
- Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Heng Guo
- Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Weina Wang
- Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Xingang Li
- Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Su Shen
- Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing, China
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12
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Abstract
Chronic liver disease in pregnancy is rare. Historically, many chronic liver diseases were considered contraindications to pregnancy; however, with current monitoring and treatment strategies, pregnancy may be considered in many cases. Preconception and initial antepartum consultation should focus on disease activity, medication safety, risks of pregnancy, as well as the need for additional monitoring during pregnancy. In most cases, a multidisciplinary approach is necessary to ensure optimal maternal and fetal outcomes. Despite improving outcomes, pregnancy in women with the chronic liver disease remains high risk.
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13
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Pregnancy and Lung Transplantation. CURRENT PULMONOLOGY REPORTS 2021. [DOI: 10.1007/s13665-021-00274-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
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14
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The positive effect of pregnancy in rheumatoid arthritis and the use of medications for the management of rheumatoid arthritis during pregnancy. Inflammopharmacology 2021; 29:987-1000. [PMID: 33844107 DOI: 10.1007/s10787-021-00808-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2021] [Accepted: 03/30/2021] [Indexed: 01/30/2023]
Abstract
Rheumatoid arthritis (RA) is an autoimmune systemic inflammatory disorder that is mostly characterised by progressive symmetrical joint destruction, particularly in the wrist and fingers, while it may also affect additional joints and several organs, such as the skin, heart, blood vessels, and lungs. It is identified by raised anti-rheumatoid factor and anti-cyclic citrullinated peptide antibodies. The chemical mediators involved in the activity of RA are IL-1β, TNF-α, and IL-6. Pregnancy exerts a positive effect on RA that helps to modulate the disease condition. Different hypotheses are recommended to explain the ameliorating effect of pregnancy in RA. RA cannot be completely cured. The treatment goal is the attrition of pain and inflammation and the further progression of the disease. Long-term management of RA is carried out using disease-modifying antirheumatic drugs (DMARDs). Therapy of acute flares can be done with Non-steroidal anti-inflammatory drugs (NSAIDs) accompanied by ad interim usage of glucocorticoids. Biologic response modifiers are also available; they act by abolishing the activity of T- cells. However, it is necessary to select the correct treatment regimen when it comes to the management of RA in pregnancy.
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Laube R, Paramsothy S, Leong RW. Use of medications during pregnancy and breastfeeding for Crohn's disease and ulcerative colitis. Expert Opin Drug Saf 2021; 20:275-292. [PMID: 33412078 DOI: 10.1080/14740338.2021.1873948] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Introduction: The peak age of diagnosis of inflammatory bowel disease (IBD) occurs during childbearing years, therefore management of IBD during pregnancy is a frequent occurrence. Maintenance of disease remission is crucial to optimize pregnancy outcomes, and potential maternal or fetal toxicity from medications must be balanced against the risks of untreated IBD.Areas covered: This review summarizes the literature on safety and use of medications for IBD during pregnancy and lactation.Expert opinion: 5-aminosalicylates, corticosteroids and thiopurines are safe for use during pregnancy, while methotrexate and tofacitinib should only be used with extreme caution. Anti-TNF agents (except certolizumab), vedolizumab, ustekinumab and tofacitinib readily traverse the placenta via active transport, therefore theoretically may affect fetal development. Certolizumab only undergoes passive transfer across the placenta, thus has markedly lower cord blood levels making it likely the safest biologic agent for infants. There is reasonable evidence to support the safety of anti-TNF monotherapy and combination therapy during pregnancy and lactation. Vedolizumab and ustekinumab are also thought to be safe in pregnancy and lactation, while tofacitinib is generally avoided due to teratogenic effects in animal studies.
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Affiliation(s)
- Robyn Laube
- Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Australia.,Department of Gastroenterology, Macquarie University Hospital, Sydney, Australia
| | - Sudarshan Paramsothy
- Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Australia.,Department of Gastroenterology, Macquarie University Hospital, Sydney, Australia.,Department of Gastroenterology and Hepatology, Concord Repatriation General Hospital, Sydney, Australia
| | - Rupert W Leong
- Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Australia.,Department of Gastroenterology, Macquarie University Hospital, Sydney, Australia.,Department of Gastroenterology and Hepatology, Concord Repatriation General Hospital, Sydney, Australia
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16
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Ziogas IA, Hayat MH, Tsoulfas G. Obstetrical and gynecologic challenges in the liver transplant patient. World J Transplant 2020; 10:320-329. [PMID: 33312893 PMCID: PMC7708880 DOI: 10.5500/wjt.v10.i11.320] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2020] [Revised: 10/05/2020] [Accepted: 10/20/2020] [Indexed: 02/06/2023] Open
Abstract
An increasing number of childbearing agewomen undergo liver transplantation (LT) in the United States. Transplantation in this patient subgroup poses a significant challenge regarding the plans for future fertility, particularly in terms of immunosuppression and optimal timing of conception. Intrapartum LT is only rarely performed as the outcome is commonly dismal for the mother or more commonly the fetus. On the other hand, the outcomes of pregnancy in LT recipients are favorable, and children born to LT recipients are relatively healthy. Counseling on pregnancy should start before LT and continue after LT up until pregnancy, while all pregnant LT recipients must be managed by amultidisciplinary team, including both an obstetrician and a transplant hepatologist. Additionally, an interval of at least 1-2 years after successful LT is recommended before considering pregnancy. Pregnancy-induced hypertension, pre-eclampsia, and gestational diabetes mellitus are reported more commonly during the pregnancies of LT recipients than in the pregnancies of non-transplant patients. As adverse fetal outcomes, such asmiscarriage, abortion, stillbirth, or ectopic pregnancy, may occur more often than in the non-transplant population, early planning or delivery either through a planned induction of labor or cesarean section is critical to minimize the risk of complications. No significant long-term physical or phycological abnormalities have been reported in children born to LT recipients.
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Affiliation(s)
- Ioannis A Ziogas
- Medical School, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece
| | - Muhammad H Hayat
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University Medical Center, Nashville, TN 37212, United States
| | - Georgios Tsoulfas
- Department of Surgery, Papageorgiou University Hospital, Aristotle University of Thessaloniki, Thessaloniki 54622, Greece
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17
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Boyle S, Sung-Him Mew T, Lust K, McKenzie S, Javorsky G, Parsonage W. Pregnancy Following Heart Transplantation: A Single Centre Case Series and Review of the Literature. Heart Lung Circ 2020; 30:144-153. [PMID: 33162367 DOI: 10.1016/j.hlc.2020.10.007] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2020] [Revised: 10/03/2020] [Accepted: 10/13/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Maternal and fetal outcomes of pregnancy amongst cardiac transplant recipients are limited in the current literature. METHODS We describe five pregnancies in three cardiac transplant recipients managed between a tertiary centre for obstetric medicine and an associated state-wide transplant centre between 2014-2018, and provide a narrative review of the literature. RESULTS Pre-conception counselling was undertaken. There were no recent rejection episodes and all women demonstrated good baseline cardiac function. Median maternal age was 27 years (range 23-38 yrs.). Median time from transplantation to pregnancy was 5 years (range 2-14 yrs.). All women were managed with modified immunosuppressant regimens and multidisciplinary care. Cardiac function, tacrolimus levels and renal function were closely monitored with frequent monitoring for common complications of pregnancy. There were no maternal or fetal deaths. There was no evidence of graft rejection and no deterioration in cardiac function. Tacrolimus doses were increased to maintain therapeutic targets. Gestational diabetes occurred in three women and cholestasis of pregnancy occurred in one. Each infant was delivered by vaginal delivery. One mother had postpartum haemorrhage in both pregnancies. Pre-eclampsia did not occur. Median gestation at delivery was 37 weeks (range 35+4-40+5 days) with two preterm deliveries. One (1) infant was born with low birth weight. One (1) infant had jaundice requiring phototherapy. All infants were breastfed. CONCLUSION Pregnancy in transplant recipients confers risk to the mother and fetus. Pre-conception counselling, immunosuppressant tailoring and regular monitoring are paramount to avoid rejection and possible teratogenic complications. Favourable pregnancy outcomes are achievable with specialist multidisciplinary care.
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Affiliation(s)
- Siobhan Boyle
- Department of Cardiology, Princess Alexandra Hospital, Brisbane, Qld, Australia; Department of Cardiology, Royal Brisbane and Women's Hospital, Brisbane, Qld, Australia
| | - Thomas Sung-Him Mew
- Department of Cardiology, The Prince Charles Hospital, Brisbane, Qld, Australia; Department of Cardiology, Royal Brisbane and Women's Hospital, Brisbane, Qld, Australia
| | - Karin Lust
- Women's and Newborn's Service, Royal Brisbane and Women's Hospital, Herston, Qld, Australia; Department of Medicine, University of Queensland, Qld, Australia
| | - Scott McKenzie
- Department of Cardiology, The Prince Charles Hospital, Brisbane, Qld, Australia
| | - George Javorsky
- Department of Cardiology, The Prince Charles Hospital, Brisbane, Qld, Australia
| | - William Parsonage
- Department of Cardiology, Royal Brisbane and Women's Hospital, Brisbane, Qld, Australia; Australian Centre for Health Services Innovation, Queensland University of Technology, Brisbane, Qld, Australia.
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18
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Holmøy T, Høglund RA, Illes Z, Myhr KM, Torkildsen Ø. Recent progress in maintenance treatment of neuromyelitis optica spectrum disorder. J Neurol 2020; 268:4522-4536. [PMID: 33011853 PMCID: PMC8563615 DOI: 10.1007/s00415-020-10235-5] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2020] [Revised: 09/16/2020] [Accepted: 09/17/2020] [Indexed: 02/07/2023]
Abstract
Background Treatment of neuromyelitis optica spectrum disorder (NMOSD) has so far been based on retrospective case series. The results of six randomized clinical trials including five different monoclonal antibodies targeting four molecules and three distinct pathophysiological pathways have recently been published. Methods Literature search on clinical trials and case studies in NMOSD up to July 10. 2020. Results We review mechanism of action, efficacy and side effects, and consequences for reproductive health from traditional immunosuppressants and monoclonal antibodies including rituximab, inebilizumab, eculizumab, tocilizumab and satralizumab. Conclusion In NMOSD patients with antibodies against aquaporin 4, monoclonal antibodies that deplete B cells (rituximab and inebilizumab) or interfere with interleukin 6 signaling (tocilizumab and satralizumab) or complement activation (eculizumab) have superior efficacy compared to placebo. Tocilizumab and rituximab were also superior to azathioprine in head-to-head studies. Rituximab, tocilizumab and to some extent eculizumab have well-known safety profiles for other inflammatory diseases, and rituximab and azathioprine may be safe during pregnancy.
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Affiliation(s)
- Trygve Holmøy
- Department of Neurology, Akershus University Hospital, Lørenskog, Norway. .,Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
| | - Rune Alexander Høglund
- Department of Neurology, Akershus University Hospital, Lørenskog, Norway.,Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Zsolt Illes
- Department of Neurology, Odense University Hospital, Odense, Denmark.,Institute of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Kjell-Morten Myhr
- Department of Clinical Medicine, University of Bergen, Bergen, Norway.,Neuro-SysMed, Department of Neurology, Haukeland University Hospital, Bergen, Norway
| | - Øivind Torkildsen
- Department of Clinical Medicine, University of Bergen, Bergen, Norway.,Neuro-SysMed, Department of Neurology, Haukeland University Hospital, Bergen, Norway
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19
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Mao-Draayer Y, Thiel S, Mills EA, Chitnis T, Fabian M, Katz Sand I, Leite MI, Jarius S, Hellwig K. Neuromyelitis optica spectrum disorders and pregnancy: therapeutic considerations. Nat Rev Neurol 2020; 16:154-170. [PMID: 32080393 DOI: 10.1038/s41582-020-0313-y] [Citation(s) in RCA: 66] [Impact Index Per Article: 13.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/15/2020] [Indexed: 12/18/2022]
Abstract
Neuromyelitis optica spectrum disorders (NMOSD) are a type of neurological autoimmune disease characterized by attacks of CNS inflammation that are often severe and predominantly affect the spinal cord and optic nerve. The majority of individuals with NMOSD are women, many of whom are of childbearing age. Although NMOSD are rare, several small retrospective studies and case reports have indicated that pregnancy can worsen disease activity and might contribute to disease onset. NMOSD disease activity seems to negatively affect pregnancy outcomes. Moreover, some of the current NMOSD treatments are known to pose risks to the developing fetus and only limited safety data are available for others. Here, we review published studies regarding the relationship between pregnancy outcomes and NMOSD disease activity. We also assess the risks associated with using disease-modifying therapies for NMOSD during the course of pregnancy and breastfeeding. On the basis of the available evidence, we offer recommendations regarding the use of these therapies in the course of pregnancy planning in individuals with NMOSD.
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Affiliation(s)
- Yang Mao-Draayer
- Department of Neurology, University of Michigan Medical School, Ann Arbor, MI, USA.,Graduate Program in Immunology, Program in Biomedical Sciences, University of Michigan Medical School, Ann Arbor, MI, USA
| | - Sandra Thiel
- Department of Neurology, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany
| | - Elizabeth A Mills
- Department of Neurology, University of Michigan Medical School, Ann Arbor, MI, USA
| | - Tanuja Chitnis
- Department of Neurology, Brigham and Women's Hospital and Massachusetts General Hospital, Boston, MA, USA
| | - Michelle Fabian
- Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Ilana Katz Sand
- Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - M Isabel Leite
- Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK
| | - Sven Jarius
- Molecular Neuroimmunology Group, Department of Neurology, University of Heidelberg, Heidelberg, Germany
| | - Kerstin Hellwig
- Department of Neurology, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany.
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20
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Bayoumy AB, Simsek M, Seinen ML, Mulder CJJ, Ansari A, Peters GJ, De Boer NK. The continuous rediscovery and the benefit-risk ratio of thioguanine, a comprehensive review. Expert Opin Drug Metab Toxicol 2020; 16:111-123. [PMID: 32090622 DOI: 10.1080/17425255.2020.1719996] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2019] [Accepted: 01/16/2020] [Indexed: 12/11/2022]
Abstract
Introduction: In the 1950s, thioguanine (TG), a thiopurine-derivative together with azathioprine (AZA) and mercaptopurine (MP), were developed for the treatment of childhood leukemia. Over the years, the use of TG was also explored for other, mainly immune-mediated and inflammatory, diseases such as in the field of dermatology and rheumatology (e.g. psoriasis, systemic lupus erythematosus (SLE)) and gastroenterology and hepatology (e.g. inflammatory bowel diseases (IBD), autoimmune hepatitis).Areas covered: This review provides a comprehensive overview of all the clinical uses of TG and describes its mechanism of action, pharmacokinetic/pharmacodynamic features, and toxicity.Expert opinion: Thioguanine has shown beneficial clinical effects in hematological (particularly leukemia) and several immune-inflammatory diseases including psoriasis, SLE, polycythemia vera, Churg-Strauss syndrome, IBD, collagenous sprue, refractory celiac disease, and autoimmune hepatitis. Thioguanine is not effective in treating solid-cancers. At relatively low dosages, i.e. 0.2- 0.3mg/kg/day or 20 mg/day, TG has a favorable risk-benefit ratio and is a safe and effective drug in the long-term treatment of amongst other IBD patients. Thioguanine toxicity, especially myelotoxicity, and hepatotoxicity, including nodular regenerative hyperplasia (NRH) of the liver, is limited when dosed adequately. The occurrence of NRH appears dose-dependent and has been especially described during high dose TG above 40 mg/day.
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Affiliation(s)
- Ahmed B Bayoumy
- Amsterdam UMC, Department of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam, Netherlands
| | - Melek Simsek
- Amsterdam UMC, Department of Gastroenterology and Hepatology, VU University Medical Center, AG&M Research Institute, Amsterdam, Netherlands
| | - Margien L Seinen
- Amsterdam UMC, Department of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam, Netherlands
| | - Chris J J Mulder
- Amsterdam UMC, Department of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam, Netherlands
| | - Azhar Ansari
- Department of Gastroenterology, Surrey and Sussex NHS, Easy Surrey Hospital, Surrey, UK
| | - Godefridus J Peters
- Amsterdam UMC, VU University Medical Center, Laboratory Medical Oncology, Cancer Center Amsterdam, Amsterdam, Netherlands
- Department of Biochemistry, Medical University of Gdansk, Gdansk, Poland
| | - Nanne K De Boer
- Amsterdam UMC, Department of Gastroenterology and Hepatology, VU University Medical Center, AG&M Research Institute, Amsterdam, Netherlands
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21
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SARGIN A, KARAMAN S, CEYLAN Ş, AKDEMİR A, HORTU İ. Retrospective evaluation of anesthetic techniques in pregnant women with renal transplantation. Turk J Med Sci 2019; 49:1736-1741. [PMID: 31655526 PMCID: PMC7518678 DOI: 10.3906/sag-1905-59] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2019] [Accepted: 10/17/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND/AIM The aim of this study was to evaluate anesthesia management in cesarean operation of pregnant women who underwent renal transplantation and the effects on postoperative renal function, retrospectively. MATERIALS AND METHODS After obtaining the approval of the ethics committee of our hospital, the records of pregnant women who underwent kidney transplantation and cesarean section between 2007 and 2017 were retrospectively analyzed. The patients’ demographic data, concomitant disease history, the treatment received, and type of anesthesia were retrospectively evaluated and recorded in the follow-up form. RESULTS It was found that a total of 47 women who underwent renal transplantation had 47 live births by cesarean section. The mean age of the pregnant women was 30 ± 5.34 years. The mean time between renal transplantation and conception was 95.34 ± 55.02 months. It was found that 14 (29%) of a total of 47 patients had their first pregnancy. The number of patients with a gravidity of 4 and above was 9 (19%). A total of 21 (44.7%) pregnant women had spontaneous miscarriage. Five (10.6%) patients were treated with curettage for therapeutic purposes. Twenty-two (46%) of the patients whose immunosuppressive therapy was continuing were treated with azathioprine, tacrolimus, and prednisolone. The mean gestational age of delivery was 36.5 ± 1.59 weeks. The rate of prepregnancy hypertension diagnosis was 25.5% (n = 12), while the rate of developing gestational hypertension was 21.3% (n = 10). Spinal anesthesia was administered to 42 (91%) of 47 patients who underwent cesarean section. In the preoperative period, the mean value of serum blood urea nitrogen was 62.88 ± 41.97 mg/dL and the mean serum creatinine level was 3.21 ± 6.17 mg/dL. In the postoperative period, these values were 44.4 ± 29.9 mg/dL and 1.91 ± 1.63 mg/dL, respectively. When the pre- and postoperative serum urea and creatinine levels were compared, they were found to be lower in the postoperative period. However, there was no statistically significant difference (P > 0.05). The mean weight of the newborns was determined as 2707.3 ± 501.5 g. While the number of newborns with a low birth weight (<2500 g) was 18 (38%), among them 3 (0.6%) were below 2000 g. It was found that 36.2% (n = 17) of the newborns required intensive care. None of the patients developed graft rejection. CONCLUSION If there is no contraindication, regional anesthesia may be preferred in the first place for pregnant women with renal transplantation. We suggest that this method of anesthesia has some advantages in terms of maintaining postoperative renal function and higher Apgar scores in newborns with low birth weight.
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Affiliation(s)
- Asuman SARGIN
- Department of Anesthesiology and Reanimation, School of Medicine, Ege University, İzmirTurkey
| | - Semra KARAMAN
- Department of Anesthesiology and Reanimation, School of Medicine, Ege University, İzmirTurkey
| | - Şeyda CEYLAN
- Department of Anesthesiology and Reanimation, School of Medicine, Ege University, İzmirTurkey
| | - Ali AKDEMİR
- Department of Obstetrics and Gynecology, School of Medicine, Ege University, İzmirTurkey
| | - İsmet HORTU
- Department of Obstetrics and Gynecology, School of Medicine, Ege University, İzmirTurkey
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22
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Pregnancy outcome following in utero exposure to azathioprine: A French comparative observational study. Therapie 2018; 73:199-207. [DOI: 10.1016/j.therap.2017.06.006] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2017] [Revised: 05/15/2017] [Accepted: 06/30/2017] [Indexed: 01/05/2023]
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23
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24
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25
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Moaveni DM, Cohn JH, Hoctor KG, Longman RE, Ranasinghe JS. Anesthetic Considerations for the Parturient After Solid Organ Transplantation. Anesth Analg 2017; 123:402-10. [PMID: 27285002 DOI: 10.1213/ane.0000000000001391] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Over the past 40 years, the success of organ transplantation has increased such that female solid organ transplant recipients are able to conceive and carry pregnancies successfully to term. Anesthesiologists are faced with the challenge of providing anesthesia care to these high-risk obstetric patients in the peripartum period. Anesthetic considerations include the effects of the physiologic changes of pregnancy on the transplanted organ, graft function in the peripartum period, and the maternal side effects and drug interactions of immunosuppressive agents. These women are at an increased risk of comorbidities and obstetric complications. Anesthetic management should consider the important task of protecting graft function. Optimal care of a woman with a transplanted solid organ involves management by a multidisciplinary team. In this focused review article, we review the anesthetic management of pregnant patients with solid organ transplants of the kidney, liver, heart, or lung.
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Affiliation(s)
- Daria M Moaveni
- From the Departments of *Clinical Anesthesiology and †Obstetrics and Gynecology, University of Miami Miller School of Medicine/Jackson Memorial Hospital, Miami, Florida
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26
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Mahadevan U, McConnell RA, Chambers CD. Drug Safety and Risk of Adverse Outcomes for Pregnant Patients With Inflammatory Bowel Disease. Gastroenterology 2017; 152:451-462.e2. [PMID: 27769809 DOI: 10.1053/j.gastro.2016.10.013] [Citation(s) in RCA: 63] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2016] [Revised: 10/12/2016] [Accepted: 10/14/2016] [Indexed: 02/07/2023]
Abstract
The management of the pregnant patient with inflammatory bowel disease is complicated by multiple providers, misinformation, and a disease entity that, particularly when active, can adversely affect pregnancy outcomes. This article seeks to frame the debate on medication safety in pregnancy and lactation using the US Food and Drug Administration's new Pregnancy and Lactation Labeling Rule and the most up-to-date safety information to discuss the risks and benefits of using each class of inflammatory bowel disease medication.
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Affiliation(s)
- Uma Mahadevan
- Department of Medicine, Division of Gastroenterology, University of California, San Francisco, San Francisco, California.
| | - Ryan A McConnell
- Department of Medicine, Division of Gastroenterology, University of California, San Francisco, San Francisco, California
| | - Christina D Chambers
- Department of Family Medicine and Public Health, University of California San Diego, La Jolla, California
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27
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Mahmoud T, Mujaibel K, Attia H, Zakaria Z, Yagan J, Gheith O, Halim MA, Nair P, Al-Otaibi T. Triplet Pregnancy in a Diabetic Mother With Kidney Transplant: Case Report and Review of the Literature. EXP CLIN TRANSPLANT 2017; 15:139-146. [PMID: 28260455 DOI: 10.6002/ect.mesot2016.p23] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Triplet and higher-order multiple pregnancies can carry increased fetal and maternal complications. Reports of triplet pregnancies after kidney transplant are scarce and have been associated with perinatal complications. Presence of diabetes in such cases worsens both fetal and maternal outcomes. Here, we present a triplet pregnancy in a kidney transplant recipient with diabetes. We also reviewed the literature for causes, prevalence, and outcomes in association with chronic kidney disease, kidney transplant, and diabetes mellitus. The patient, a 31-year-female who received a living-donor kidney transplant, had a first-time pregnancy 6 years after transplant. Pregnancy was complicated by gestational diabetes, preeclampsia, and miscarriage. She continued to have postpartum-impaired glucose tolerance. She became pregnant again after 6 months but required insulin therapy during her third trimester. Pregnancy was terminated by cesarean section for a viable small boy. Two years later, she had triplet pregnancy after ovulation induction with clomiphene. Glycemic control was maintained using intensive insulin therapy guided by frequent home blood glucose monitoring (HbA1c was 5.8% at 22 wk). Both gynecologic care and nephrologic care were carried out through outpatient follow-up. Pregnancy was complicated by hypertension and mild renal dysfunction without proteinuria and ended in elective premature cesarean section at 32 weeks of gestation. She had 3 male babies with low birth weights (1320, 1380, 1275 g), with the largest baby developing sepsis and requiring an intensive care unit stay and then incubator for 49 days. The other 2 required incubators for 36 days. Their weights after 22 months were 9, 16, and 11 kg. The mother is now normotensive with normal renal function and impaired glucose tolerance. Care of diabetic kidney recipients with triplet pregnancy constitutes a special challenge requiring a multispecialty skilled team to ensure the best outcome.
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MESH Headings
- Adult
- Biomarkers/blood
- Blood Glucose/drug effects
- Blood Glucose/metabolism
- Cesarean Section
- Diabetes, Gestational/blood
- Diabetes, Gestational/diagnosis
- Diabetes, Gestational/drug therapy
- Diabetes, Gestational/etiology
- Elective Surgical Procedures
- Female
- Glycated Hemoglobin/metabolism
- Humans
- Hypoglycemic Agents/therapeutic use
- Immunosuppressive Agents/adverse effects
- Infant, Newborn
- Infertility, Female/diagnosis
- Infertility, Female/etiology
- Infertility, Female/physiopathology
- Infertility, Female/therapy
- Insulin/therapeutic use
- Kidney Transplantation/adverse effects
- Live Birth
- Male
- Pregnancy
- Pregnancy, Triplet
- Reproductive Techniques, Assisted
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Affiliation(s)
- Tarek Mahmoud
- Nephrology Department, Hamed Al-Essa Organ Transplant Center, Sabah Area, Kuwait
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28
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Overview of Pregnancy in Renal Transplant Patients. Int J Nephrol 2016; 2016:4539342. [PMID: 28042483 PMCID: PMC5155089 DOI: 10.1155/2016/4539342] [Citation(s) in RCA: 63] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2016] [Revised: 11/05/2016] [Accepted: 11/09/2016] [Indexed: 12/25/2022] Open
Abstract
Kidney transplantation offers best hope to women with end-stage renal disease who wish to become pregnant. Pregnancy in a kidney transplant recipient continues to remain challenging due to side effects of immunosuppressive medication, risk of deterioration of allograft function, risk of adverse maternal complications of preeclampsia and hypertension, and risk of adverse fetal outcomes of premature birth, low birth weight, and small for gestational age infants. The factors associated with poor pregnancy outcomes include presence of hypertension, serum creatinine greater than 1.4 mg/dL, and proteinuria. The recommended maintenance immunosuppression in pregnant women is calcineurin inhibitors (tacrolimus/cyclosporine), azathioprine, and low dose prednisone; and it is considered safe. Sirolimus and mycophenolate mofetil should be stopped 6 weeks prior to conception. The optimal time to conception continues to remain an area of contention. It is important that counseling for childbearing should start as early as prior to getting a kidney transplant and should be done at every clinic visit after transplant. Breast-feeding is not contraindicated and should not be discouraged. This review will help the physicians in medical optimization and counseling of renal transplant recipients of childbearing age.
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29
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Jabiry-Zieniewicz Z, Dabrowski FA, Pietrzak B, Wyzgal J, Bomba-Opoń D, Zieniewicz K, Wielgos M. Pregnancy in the liver transplant recipient. Liver Transpl 2016; 22:1408-17. [PMID: 27197796 DOI: 10.1002/lt.24483] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2016] [Revised: 04/28/2016] [Accepted: 05/12/2016] [Indexed: 12/27/2022]
Abstract
During gestation, the woman's body undergoes various changes, and the line between physiology and pathology is very thin even in healthy women. Today, many of the liver transplant recipients are young women, who at one point in their lives may consider the possibility of pregnancy. Clinicians have to counsel them about the time of conception, the risk of miscarriage, the deterioration of the mother's health status, and the risk of birth defects. This review, based on our 20 years of clinical experience and up-to-date literature, provides comprehensive guidelines on pregnancy management in liver transplant recipients. Pregnancy in liver transplant recipients is possible but never physiological. Proper management and pharmacotherapy lowers the incidence of complications and birth defects. Critical factors for perinatal success include stable graft function before pregnancy, proper preparation for pregnancy, and cautious observation during its course. Liver Transplantation 22 1408-1417 2016 AASLD.
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Affiliation(s)
| | | | - Bronislawa Pietrzak
- 1st Department of Obstetrics and Gynecology, Medical University of Warsaw, Warsaw, Poland
| | - Janusz Wyzgal
- Department of Nephrological Nursing, Medical University of Warsaw, Warsaw, Poland
| | - Dorota Bomba-Opoń
- 1st Department of Obstetrics and Gynecology, Medical University of Warsaw, Warsaw, Poland
| | - Krzysztof Zieniewicz
- Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland
| | - Miroslaw Wielgos
- 1st Department of Obstetrics and Gynecology, Medical University of Warsaw, Warsaw, Poland
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Palosse-Cantaloube L, Hurault-Delarue C, Beau AB, Montastruc JL, Lacroix I, Damase-Michel C. Risk of infections during the first year of life after in utero exposure to drugs acting on immunity: A population-based cohort study. Pharmacol Res 2016; 113:557-562. [PMID: 27697641 DOI: 10.1016/j.phrs.2016.09.028] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2016] [Revised: 09/21/2016] [Accepted: 09/23/2016] [Indexed: 10/20/2022]
Abstract
The aim of the study was to evaluate the association between in utero exposure to drugs that potentially exhibit immunosuppressive activity and occurrence of infections during the first year of life. We conducted a cohort study on the prescription data of pregnant women and their children registered in EFEMERIS cohort (France), during a one-year period. We classified in utero child exposure according to the number of reimbursements for immunosuppressive drugs during pregnancy. The number of infectious episodes during the first year of life was estimated through the number of anti-infective drugs dispensed. The association was estimated by a quasi-Poisson regression with adjustment for confounders. The study population consisted of 9614 children, 3141 of whom had been exposed to immunosuppressive drugs during pregnancy. The most frequently immunosuppressive drugs prescribed were corticosteroids. The mean number of infectious episodes during the first year after birth gradually increased with the number of immunosuppressive drugs dispensed during pregnancy (from 2.38 in controls to 3.88 in the most exposed group). After adjustment for potential confounders, in utero exposure to immunosuppressive drugs was significantly associated with the number of infectious episodes during the first year of life (RR 3ormoreexposuresVS0=1.35, 95% CI 1.24-1.46). Intrauterine exposure to potentially immunosuppressive drugs could be associated with an increased susceptibility to infections in early childhood.
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Affiliation(s)
- Lucie Palosse-Cantaloube
- Pharmacologie Médicale et Clinique, UMR INSERM 1027, Centre Hospitalier Universitaire de Toulouse, Faculté de Médecine, Université Toulouse III, 37 Allées Jules Guesde, 31000 Toulouse, France
| | - Caroline Hurault-Delarue
- Pharmacologie Médicale et Clinique, UMR INSERM 1027, Centre Hospitalier Universitaire de Toulouse, Faculté de Médecine, Université Toulouse III, 37 Allées Jules Guesde, 31000 Toulouse, France
| | - Anna-Belle Beau
- Pharmacologie Médicale et Clinique, UMR INSERM 1027, Centre Hospitalier Universitaire de Toulouse, Faculté de Médecine, Université Toulouse III, 37 Allées Jules Guesde, 31000 Toulouse, France
| | - Jean-Louis Montastruc
- Pharmacologie Médicale et Clinique, UMR INSERM 1027, Centre Hospitalier Universitaire de Toulouse, Faculté de Médecine, Université Toulouse III, 37 Allées Jules Guesde, 31000 Toulouse, France
| | - Isabelle Lacroix
- Pharmacologie Médicale et Clinique, UMR INSERM 1027, Centre Hospitalier Universitaire de Toulouse, Faculté de Médecine, Université Toulouse III, 37 Allées Jules Guesde, 31000 Toulouse, France
| | - Christine Damase-Michel
- Pharmacologie Médicale et Clinique, UMR INSERM 1027, Centre Hospitalier Universitaire de Toulouse, Faculté de Médecine, Université Toulouse III, 37 Allées Jules Guesde, 31000 Toulouse, France.
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31
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Casale JP, Doligalski CT. Pharmacologic Considerations for Solid Organ Transplant Recipients Who Become Pregnant. Pharmacotherapy 2016; 36:971-82. [DOI: 10.1002/phar.1800] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
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Abstract
Crohn's disease and ulcerative colitis, referred to as inflammatory bowel disease (IBD), are chronic, relapsing conditions. Patients are often diagnosed at a reproductive age, and therefore questions about fertility and reproductions often arise. Preconceptional counseling is the most important aspect in the management of IBD patients with a pregnancy wish. Patients should be counseled on the influence of IBD and IBD drugs on pregnancy. Most drugs are not related to adverse outcome while used during pregnancy. Active disease is related to adverse outcomes; therefore, it is of utmost importance to strive for remission before conception and during pregnancy.
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Affiliation(s)
| | - C.J. van der Woude
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands
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Schroeder DJ, Tsourounis C. Drug Information Analysis Service. Ann Pharmacother 2016. [DOI: 10.1177/106002809402801206] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
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Abstract
Immunomodulators and biologic medications, alone or in combination, form the core therapeutic strategy for managing moderate-to-severe inflammatory bowel disease (IBD). IBD incidence peaks during the prime reproductive years, raising concerns about the impact of disease and its treatment on fertility, maternal and fetal health during pregnancy, breastfeeding safety, and childhood development. Although IBD increases risk of pregnancy complications independent of disease activity, adverse pregnancy outcomes are more common when disease is active. To mitigate fetal risk, women should conceive while disease is quiescent. Aside from methotrexate, immunomodulators and biologics may be used during pregnancy to achieve and maintain disease control. Based on available safety data, there is no increased risk of congenital anomalies among infants exposed to these medications. Active thiopurine metabolites and most monoclonal antibodies cross the placenta and are detectable in neonates. They are detectable in breast milk in minute levels as well. The impact of this exposure on neonatal outcomes is discussed. Adjusted dosing schedules during gestation may reduce fetal drug exposure, though the maternal risks of such manipulation require careful consideration. Ongoing prospective studies will further inform risk assessment, including for newer medications such as the anti-integrin agents.
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35
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36
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Bermas BL. Drugs and pregnancy. Rheumatology (Oxford) 2015. [DOI: 10.1016/b978-0-323-09138-1.00068-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022] Open
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Hullah EA, Blaker PA, Marinaki AM, Escudier MP, Sanderson JD. A practical guide to the use of thiopurines in oral medicine. J Oral Pathol Med 2014; 44:761-8. [PMID: 25529219 DOI: 10.1111/jop.12274] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/08/2014] [Indexed: 12/11/2022]
Abstract
Thiopurines are widely used as first-line immunosuppressive therapies in the management of chronic inflammatory oral disease. However, despite over half a century of clinical experience, the evidence base for their use is limited. The aims of this paper were to review the evidence for the use of thiopurines in oral medicine and provide a contemporary model of thiopurine metabolism and mechanism of action and a rationale for clinical use and safe practice.
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Affiliation(s)
- E A Hullah
- Oral Medicine, King's College London Dental Institute, London, UK
| | - P A Blaker
- Gastroenterology, Guy's & St Thomas' Hospitals NHS Foundation Trust, Guy's Hospital, Great Maze Pond, London, UK
| | - A M Marinaki
- Purine Research Laboratory, Viapath, Guy's & St Thomas' Hospitals NHS Foundation Trust, Guy's Hospital, Great Maze Pond, London, UK
| | - M P Escudier
- Oral Medicine, King's College London Dental Institute, London, UK
| | - J D Sanderson
- Gastroenterology, Guy's & St Thomas' Hospitals NHS Foundation Trust, Guy's Hospital, Great Maze Pond, London, UK
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38
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Non-steroidal anti inflammatory drugs, glucocorticoids and disease modifying anti-rheumatic drugs for the management of rheumatoid arthritis before and during pregnancy. Curr Opin Rheumatol 2014; 26:334-40. [DOI: 10.1097/bor.0000000000000054] [Citation(s) in RCA: 53] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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39
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Jharap B, de Boer NKH, Stokkers P, Hommes DW, Oldenburg B, Dijkstra G, van der Woude CJ, de Jong DJ, Mulder CJJ, van Elburg RM, van Bodegraven AA. Intrauterine exposure and pharmacology of conventional thiopurine therapy in pregnant patients with inflammatory bowel disease. Gut 2014; 63:451-7. [PMID: 23424097 DOI: 10.1136/gutjnl-2012-303615] [Citation(s) in RCA: 99] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
OBJECTIVE Several studies have demonstrated a favourable safety profile for thiopurine use for inflammatory bowel disease (IBD) during pregnancy. We performed a study in pregnant patients with IBD who were using thiopurines, in order to determine the influence of pregnancy on thiopurine metabolism and to assess intrauterine exposure of the fetus to thiopurines. DESIGN Female patients with IBD receiving steady-state thiopurines and planning a pregnancy were prospectively enrolled. 6-Thioguanine nucleotide (6-TGN) and 6-methylmercaptopurine (6-MMP) concentrations were determined, combined with routine laboratory tests, before, during and after pregnancy. Thiopurine metabolites were measured in umbilical cord blood immediately after delivery. RESULTS Thirty patients who were using azathioprine (28 patients, median dose 1.93 mg/kg) or mercaptopurine (two patients, doses 1.32 and 0.94 mg/kg) were included. During pregnancy, median 6-TGN decreased over time (p=0.001). while 6-MMP increased, without causing myelotoxicity or hepatotoxicity. After delivery, both 6-TGN and 6-MMP levels returned to preconception baseline levels. Fetal 6-TGN concentrations correlated positively with maternal 6-TGN levels (p<0.0001). No 6-MMP was detected in the newborns, except one born with pancytopenia and high alkaline phosphatase activity; the mother of this infant had severe pre-eclampsia. All infants had normal Apgar scores, but 60% had anaemia at birth. No major congenital abnormalities were observed. CONCLUSIONS Pregnancy has a major effect on maternal thiopurine metabolism. In utero the unborn child is exposed to 6-TGN, but not to 6-MMP. Sixty per cent of the infants were born with anaemia, which raises the question whether infants should be tested for possible anaemia immediately after birth.
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Affiliation(s)
- Bindia Jharap
- Department of Gastroenterology and Hepatology, VU University Medical Center, , Amsterdam, The Netherlands
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Ferrero S, Esposito F, Pretta S, Ragni N. Fetal risks related to the treatment of multiple sclerosis during pregnancy and breastfeeding. Expert Rev Neurother 2014; 6:1823-31. [PMID: 17181429 DOI: 10.1586/14737175.6.12.1823] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
In women with multiple sclerosis, pregnancy does not have a long-term adverse effect on lifetime disability; however, there is an increased risk of relapses during the postpartum. Therapies taken during pregnancy may have adverse effects on pregnancy outcome. The small number of pregnancies included in most studies, particularly those evaluating the risks related to the administration of immunomodulating drugs, do not allow firm conclusions to be drawn with regards to their safety. Therefore, until more information regarding safety is available, glatiramer acetate, mitoxantrone and interferon-beta should be discontinued before an anticipated pregnancy. By contrast, glucocorticoids can be used to treat acute relapses during pregnancy.
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Affiliation(s)
- Simone Ferrero
- Department of Obstetrics and Gynaecology, San Martino Hospital and University of Genoa, Largo R. Benzi 1, 16132 Genoa, Italy.
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41
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Josephson MA, McKay DB. Women and transplantation: fertility, sexuality, pregnancy, contraception. Adv Chronic Kidney Dis 2013; 20:433-40. [PMID: 23978550 DOI: 10.1053/j.ackd.2013.06.005] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2013] [Revised: 06/14/2013] [Accepted: 06/17/2013] [Indexed: 01/23/2023]
Abstract
Since 1958, thousands of women with kidney transplants have become pregnant. Although most pregnancies in kidney transplant recipients are successful, they are high-risk endeavors. This seems more a function of the associated issues and comorbidities that often affect individuals with kidney transplants (eg, hypertension) or immunosuppression side effects rather than the kidney transplant per se. Regardless of the underlying pathophysiology, these pregnancies are associated with a high rate of preeclampsia diagnoses, preterm deliveries, Cesarean sections, and small-for-gestational-age babies. Given these risks, it is critical to counsel and inform transplant recipients and prospective transplant recipients of childbearing age and their partners regarding many aspects of pregnancy, including the need for contraception to prevent pregnancy after transplant, immunosuppression concerns, and the potential effect of pregnancy on the outcome of the mother, baby, and kidney transplant.
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42
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Pregnancy following liver transplantation: review of outcomes and recommendations for management. CANADIAN JOURNAL OF GASTROENTEROLOGY = JOURNAL CANADIEN DE GASTROENTEROLOGIE 2013; 26:621-6. [PMID: 22993734 DOI: 10.1155/2012/137129] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Liver transplantation is considered to be the treatment of choice for end-stage liver disease and its success has led to an increase in the number of female liver transplant recipients who are of childbearing age. Several key issues that are noted when counselling patients who are considering pregnancy following liver transplantation include the optimal timing of pregnancy, optimal contraception methods and the management of immunosuppression during pregnancy. The present review summarizes the most recent literature so that the clinician may address these issues with their patient and enable them to make informed decisions about pregnancy planning. The authors review recent studies examining maternal and fetal outcomes, and the rates of complications including risk of graft rejection. Subsequently, the authors provide recommendations for counselling prospective mothers and the management of the pregnant liver transplant recipient.
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43
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Baughman RP, Meyer KC, Nathanson I, Angel L, Bhorade SM, Chan KM, Culver D, Harrod CG, Hayney MS, Highland KB, Limper AH, Patrick H, Strange C, Whelan T. Monitoring of nonsteroidal immunosuppressive drugs in patients with lung disease and lung transplant recipients: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2012; 142:e1S-e111S. [PMID: 23131960 PMCID: PMC3610695 DOI: 10.1378/chest.12-1044] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/06/2012] [Indexed: 01/19/2023] Open
Abstract
OBJECTIVES Immunosuppressive pharmacologic agents prescribed to patients with diffuse interstitial and inflammatory lung disease and lung transplant recipients are associated with potential risks for adverse reactions. Strategies for minimizing such risks include administering these drugs according to established, safe protocols; monitoring to detect manifestations of toxicity; and patient education. Hence, an evidence-based guideline for physicians can improve safety and optimize the likelihood of a successful outcome. To maximize the likelihood that these agents will be used safely, the American College of Chest Physicians established a committee to examine the clinical evidence for the administration and monitoring of immunosuppressive drugs (with the exception of corticosteroids) to identify associated toxicities associated with each drug and appropriate protocols for monitoring these agents. METHODS Committee members developed and refined a series of questions about toxicities of immunosuppressives and current approaches to administration and monitoring. A systematic review was carried out by the American College of Chest Physicians. Committee members were supplied with this information and created this evidence-based guideline. CONCLUSIONS It is hoped that these guidelines will improve patient safety when immunosuppressive drugs are given to lung transplant recipients and to patients with diffuse interstitial lung disease.
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Affiliation(s)
| | - Keith C Meyer
- University of Wisconsin School of Medicine and Public Health, Madison, WI
| | | | - Luis Angel
- University of Texas Health Sciences, San Antonio, TX
| | | | - Kevin M Chan
- University of Michigan Health Systems, Ann Arbor, MI
| | | | | | - Mary S Hayney
- University of Wisconsin School of Pharmacy, Madison, WI
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Taki K, Fukushima T, Ise R, Horii I, Yoshida T. 6-Mercaptopurine-induced histopathological changes and xanthine oxidase expression in rat placenta. J Toxicol Sci 2012; 37:607-15. [PMID: 22688000 DOI: 10.2131/jts.37.607] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022]
Abstract
The placenta secures the embryo and fetus to the endometrium and releases a variety of steroid and peptide hormones that convert the physiology of a female to that of a pregnant female. Chemical-induced alteration or deviation of placental function in the maternal and extraembryonic tissue can ultimately lead to pregnancy loss, congenital malformation and fetal death. The 6-mercaptopurine (6-MP), an anti-leukemic drug, is known to produce undesired effects on some organs, then the placenta/embryo toxicity of 6-MP was investigated in pregnant rats given 60 mg/kg with two intraperitoneal injections on gestation days (GD) 11 and 12. The rats were sacrificed and their placentas were collected on GD13 or 15. On GD15 small and limb-defected embryos were found in the 6-MP-treated rats. Placental weights were significantly reduced on GD15, as well as a reduced number of cells was detected in the labyrinth zone with both the labyrinth and basal zones having thinned. Cleaved caspase-3-positive cells increased in number in the labyrinth zone, while in the basal zone, glycogen cells reduced with cytolysis. The number of spongiotrophoblasts and trophoblastic giant cells also increased by 6-MP treatment. The 6-MP-treatment resulted in the increased xanthine oxidase (Xdh) expression in the placenta, which gene is related to the ischemic condition of tissues. These data suggest that apoptosis of the labyrinth zone cells may lead to decreased materno-fetal exchange. Moreover, subsequent ischemia in the placental tissue may occur and induce Xdh expression.
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Affiliation(s)
- Kenji Taki
- Department of Biochemical Toxicology, School of Pharmacy, Showa University, Tokyo, Japan.
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de Boer NKH, Jharap B, Seinen ML, van Bodegraven AA. Letter: thiopurines during pregnancy and intrauterine exposure to metabolites. Aliment Pharmacol Ther 2012; 35:964-5; author reply 965-6. [PMID: 22436042 DOI: 10.1111/j.1365-2036.2012.05025.x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/08/2022]
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Hutson J, Lubetsky A, Walfisch A, Ballios B, Garcia-Bournissen F, Koren G. The transfer of 6-mercaptopurine in the dually perfused human placenta. Reprod Toxicol 2011; 32:349-53. [DOI: 10.1016/j.reprotox.2011.08.008] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2011] [Revised: 06/15/2011] [Accepted: 08/20/2011] [Indexed: 10/17/2022]
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48
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Walldorf J, Dollinger MM, Seufferlein T. [Pregnancy under immunosuppression]. Internist (Berl) 2011; 52:1178-84. [PMID: 21792600 DOI: 10.1007/s00108-011-2822-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
The desire to have children and pregnancy itself are important topics in the treatment of patients under immunosuppression. In this review the risks of frequently prescribed immunosuppressants are discussed regarding the safety of mother and child during and after pregnancy. Knowledge of the specific risks of immunosuppressants in pregnancy is important to balance the therapy between the patients' desire to be treated most effectively and to deliver a healthy child after an uncomplicated pregnancy. Generally, an interdisciplinary approach is advisable in treating and counseling immunosuppressed patients with a desire to have children and during pregnancy.
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Affiliation(s)
- J Walldorf
- Klinik und Poliklinik für Innere Medizin I, Universitätsklinikum Halle, Ernst-Grube-Straße 40, 06120, Halle, Deutschland.
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Lee NY, Sai Y, Nakashima E, Ohtsuki S, Kang YS. 6-Mercaptopurine transport by equilibrative nucleoside transporters in conditionally immortalized rat syncytiotrophoblast cell lines TR-TBTs. J Pharm Sci 2011; 100:3773-82. [PMID: 21590775 DOI: 10.1002/jps.22631] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2011] [Revised: 04/20/2011] [Accepted: 04/28/2011] [Indexed: 11/07/2022]
Abstract
Recently, more women were provided with 6-mercaptopurine (6-MP) during pregnancy. Therefore, we attempted to clarify the transport mechanisms of 6-MP through blood-placenta barrier using rat conditionally immortalized syncytiotrophoblast cell lines (TR-TBTs). The uptake of 6-MP was time- and ATP dependent, but sodium independent in TR-TBTs. 6-MP was eliminated over 50% from the cells within 30 min. The uptake of 6-MP was saturable with Michaelis-Menten constant values of 198 μM and 250 μM in TR-TBT 18d-1 and TR-TBT 18d-2, respectively. 6-Thioguanine, azathioprine, and hypoxantine, structural analogues of 6-MP, strongly inhibited [(14) C]6-MP uptake. Equilibrative nucleoside transporter (ENT) inhibitors, adenosine and uridine, significantly inhibited [(14) C]6-MP uptake. However, several organic anions and cations had no effect on [(14) C]6-MP uptake in TR-TBTs. These results suggest that sodium-independent transporters, ENTs, may be involved in 6-MP uptake at the placenta. In addition, multidrug resistance protein (MRP) inhibitors, methotrexate, probenecid, cefmetazole, and sulfinpyrazone, significantly increased the accumulation of [(14) C]6-MP in the cells. It is indicated that 6-MP may be eliminated across the blood-placental barrier via MRPs. TR-TBTs expressed mRNA of ENT1, ENT2, MRP4, and MRP5. These findings are important for the therapy of acute lymphoblastic leukemia and autoimmune diseases of pregnant women, and should be useful data in elucidating teratogenicity of 6-MP during pregnancy.
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Affiliation(s)
- Na-young Lee
- College of Pharmacy and Research Institute of Pharmaceutical Science, Sookmyung Women's University, Seoul, Korea
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