|
1
|
Yeaman F, Stritzke A, Kuret V, Sharifi N, Seow CH, Metcalfe A, Leung Y. Thiopurine Exposure During Pregnancy is Not Associated With Anemia in Infants Born to Mothers With IBD. CROHN'S & COLITIS 360 2023; 5:otad066. [PMID: 37941596 PMCID: PMC10629965 DOI: 10.1093/crocol/otad066] [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: 07/26/2023] [Indexed: 11/10/2023] Open
Abstract
Background Thiopurines are commonly used to treat inflammatory bowel disease (IBD). Thiopurines are considered safe throughout pregnancy. However, a published study suggested the risk of neonatal anemia was increased if exposed to thiopurines in utero. This prospective cohort study aimed to determine if there is an increased risk of cytopenia among infants born to pregnant people with IBD, exposed or unexposed to thiopurines, compared to infants born to those without IBD. Methods Pregnant IBD patients, with and without thiopurine exposure, and one cohort of control individuals were recruited over a 5-year period. Consenting individuals completed a questionnaire and infants had a complete blood cell count at the newborn heel prick. Anemia was defined as hemoglobin (Hb) < 140g/L. Descriptive statistics were used to characterize the study population. Fisher exact tests were used to examine differences in outcomes between groups, a P-value of < 0.05 was deemed significant. Results Three cohorts were recruited: 19 IBD patients on thiopurines, 50 IBD patients not on thiopurines, and 37 controls (total of 106). Neonatal median Hb was not different with 177g/L (IQR 38g/L) for the IBD thiopurine group, 180.5g/L (IQR 40g/L) for the IBD non-thiopurine group, and 181g/L (IQR 37g/L) for the controls. Nineteen infants (18%) were cytopenic with 12 (11%) anemic, 6 (5.6%) thrombocytopenic, and 1 (0.94%) lymphopenic. Thiopurine exposure was only in one, mildly anemic, infant. Conclusions These findings further support physicians and IBD patients contemplating pregnancy that current guidelines recommending thiopurine adherence do not lead to increased perinatal risk of anemia or cytopenia.
Collapse
Affiliation(s)
- Fiona Yeaman
- Department of Medicine, University of Calgary, Calgary, AB, Canada
- Internal Medicine, University of Western Australia, Perth, WA, Australia
| | - Amelie Stritzke
- Department of Pediatrics University of Calgary, Calgary, AB, Canada
| | - Verena Kuret
- Department of Obstetrics and Gynecology, University of Calgary, Calgary, AB, Canada
| | - Nastaran Sharifi
- Department of Medicine, University of Calgary, Calgary, AB, Canada
| | - Cynthia H Seow
- Department of Medicine, University of Calgary, Calgary, AB, Canada
- Department of Community Health Sciences; University of Calgary, Calgary, AB, Canada
| | - Amy Metcalfe
- Department of Medicine, University of Calgary, Calgary, AB, Canada
- Department of Obstetrics and Gynecology, University of Calgary, Calgary, AB, Canada
- Department of Community Health Sciences; University of Calgary, Calgary, AB, Canada
| | - Yvette Leung
- Department of Medicine and Division of Gastroenterology, University of British Columbia, Vancouver, BC, Canada
| |
Collapse
|
|
2
|
Yenebere P, Doraiswamy M, Gundroo A. Overview of pregnancy in solid-organ transplantation. Curr Opin Organ Transplant 2023; 28:271-278. [PMID: 37219085 DOI: 10.1097/mot.0000000000001075] [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: 05/24/2023]
Abstract
PURPOSE OF REVIEW Pregnancy in solid organ transplantation (SOT) is a very complex part of transplant medicine wherein there is scarce information available in the literature. Solid organ transplant recipients often have comorbidities, such as hypertension and diabetes, which add additional risk to a pregnancy. RECENT FINDINGS We present this review article on the various aspects of different types of immunosuppressant medications used in pregnancy with added inputs on contraception and fertility after transplant. We described the antepartum and postpartum considerations and discussed the adverse effects of the immunosuppressive medications. Maternal and fetal complications of each SOT have been also discussed in this article. SUMMARY This article will serve as the primary review articles for the use of immunosuppressive medications during pregnancy with consideration during pregnancy after SOT.
Collapse
Affiliation(s)
- Priya Yenebere
- Transplant Nephrology, Department of Internal Medicine, Indiana University, Indianapolis, Indiana
| | - Mohankumar Doraiswamy
- Nephrology - Critical Care, Department of Internal Medicine, Mercy Hospital, Fort Smith, Arkansas
| | - Aijaz Gundroo
- Transplant Nephrology, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| |
Collapse
|
|
3
|
Serati L, Mardigyan V, Dominioni CC, Agozzino F, Bizzi E, Trotta L, Nivuori M, Maestroni S, Negro E, Imazio M, Brucato A. Pericardial Diseases in Pregnancy. Can J Cardiol 2023; 39:1067-1077. [PMID: 37086835 DOI: 10.1016/j.cjca.2023.04.010] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2022] [Revised: 04/13/2023] [Accepted: 04/14/2023] [Indexed: 04/24/2023] Open
Abstract
Pericardial effusion is the most common manifestation of pericardial diseases during pregnancy. This effusion is benign, mild, or moderate, well tolerated, with spontaneous resolution after delivery; no specific treatment is required. Acute pericarditis is the second most common condition, usually requiring medical therapy during pregnancy. Cardiac tamponade and constrictive pericarditis are rare in pregnancy. Pre-pregnancy counselling is essential in women of childbearing age with recurrent pericarditis to plan pregnancy in a phase of disease quiescence and to review therapy. High-dose aspirin or nonselective nonsteroidal anti-inflammatory drugs, such as ibuprofen and indomethacin, can be used up to the 20th week of gestation. Low-dose prednisone (2.5-10 mg/d) can be administered throughout pregnancy. All of these medications, apart from high-dose aspirin, may be used during lactation. Colchicine is compatible with pregnancy and breastfeeding, and it can be continued throughout pregnancy to prevent recurrences. Appropriate follow-up with a multidisciplinary team with experience in the field is recommended throughout pregnancy to ensure good maternal and fetal outcomes.
Collapse
Affiliation(s)
- Lisa Serati
- Department of Internal Medicine, Fatebenefratelli Hospital, Milan, Italy.
| | - Vartan Mardigyan
- Department of Medicine, Jewish General Hospital, Montréal, Québec, Canada
| | | | - Francesco Agozzino
- Department of Internal Medicine, Fatebenefratelli Hospital, Milan, Italy
| | - Emanuele Bizzi
- Department of Internal Medicine, Fatebenefratelli Hospital, Milan, Italy
| | - Lucia Trotta
- Department of Internal Medicine, Fatebenefratelli Hospital, Milan, Italy
| | - Mariangela Nivuori
- Department of Internal Medicine, Fatebenefratelli Hospital, Milan, Italy
| | - Silvia Maestroni
- Department of Internal Medicine, Papa Giovanni XXIII Hospital, Bergamo, Italy
| | - Enrica Negro
- Department of Internal Medicine, Fatebenefratelli Hospital, Milan, Italy
| | - Massimo Imazio
- Cardiology, Cardiothoracic Department, University Hospital "Santa Maria della Misericordia," Udine, Italy
| | - Antonio Brucato
- Department of Biomedical and Clinical Sciences, University of Milan, Fatebenefratelli Hospital, Milan, Italy
| |
Collapse
|
|
4
|
Dar S, Koirala S, Khan A, Bellary MD, Patel AV, Mathew B, Singh R, Baigam N, Razzaq W, Abdin ZU, Khawaja UA. A Comprehensive Literature Review on Managing Systemic Lupus Erythematosus: Addressing Cardiovascular Disease Risk in Females and Its Autoimmune Disease Associations. Cureus 2023; 15:e43725. [PMID: 37727166 PMCID: PMC10505685 DOI: 10.7759/cureus.43725] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2023] [Accepted: 08/18/2023] [Indexed: 09/21/2023] Open
Abstract
This review aimed to evaluate the mechanism of premature cardiovascular disease (CVD) in systemic lupus erythematosus (SLE) patients, particularly in the female population, and emphasize the need for early management interventions; explore the association between SLE and two autoimmune diseases, myasthenia gravis (MG) and antiphospholipid antibody syndrome (APS), and their management strategies; and evaluate the effectiveness of pharmacological and non-pharmacological interventions in managing SLE, focusing on premenopausal females, females of childbearing age, and pregnant patients. We conducted a comprehensive literature review to achieve these objectives using various databases, including PubMed, Google Scholar, and Cochrane. The collected data were analyzed and synthesized to provide an evidence-based overview of SLE, its management strategies as an independent disease, and some disease associations. The treatment should be focused on remission, preventing organ damage, and improving the overall quality of life (QOL). Extensive emphasis should also be focused on diagnosing SLE and concurrent underlying secondary diseases timely and managing them appropriately.
Collapse
Affiliation(s)
- Saleha Dar
- Department of Adult Medicine, Louisiana State University Health Sciences Center, Shreveport, USA
| | - Sabina Koirala
- Department of Medicine, Gandaki Medical College, Pokhara, NPL
| | - Arooba Khan
- Department of Internal Medicine, Khyber Medical College, Peshawar, PAK
| | | | - Arya V Patel
- Department of Internal Medicine, Smt. Nathiba Hargovandas Lakhmichand (NHL) Municipal Medical College, Ahmedabad, IND
| | - Bejoi Mathew
- Department of Internal Medicine, Sri Devaraj Urs Medical College, Kolar, IND
| | - Rahul Singh
- Department of Medicine, Armed Forces Medical College, Pune, IND
| | - Nahida Baigam
- Department of Medicine, Association of Physicians of Pakistani Descent of North America (APPNA), Westmont, USA
| | - Waleed Razzaq
- Department of Internal Medicine, Services Hospital Lahore, Lahore, PAK
| | - Zain U Abdin
- Department of Medicine, District Head Quarter Hospital, Faisalabad, PAK
| | - Uzzam Ahmed Khawaja
- Department of Pulmonary and Critical Care Medicine, Jinnah Medical and Dental College, Karachi, PAK
- Department of Clinical and Translational Research, Dr. Ferrer BioPharma, South Miami, USA
| |
Collapse
|
|
5
|
Brondfield MN, Mahadevan U. Inflammatory bowel disease in pregnancy and breastfeeding. Nat Rev Gastroenterol Hepatol 2023:10.1038/s41575-023-00758-3. [PMID: 37002407 DOI: 10.1038/s41575-023-00758-3] [Citation(s) in RCA: 22] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/20/2023] [Indexed: 06/19/2023]
Abstract
Inflammatory bowel disease (IBD) has a peak age of diagnosis before the age of 35 years. Concerns about infertility, adverse pregnancy outcomes, and heritability of IBD have influenced decision-making for patients of childbearing age and their care providers. The interplay between the complex physiology in pregnancy and IBD can affect placental development, microbiome composition and responses to therapy. Current evidence has shown that effective disease management, including pre-conception counselling, multidisciplinary care and therapeutic agents to minimize disease activity, can improve pregnancy outcomes. This Review outlines the management of IBD in pregnancy and the safety of IBD therapies, including novel agents, with regard to both maternal and fetal health. The vast majority of IBD therapies can be used with low risk during pregnancy and lactation without substantial effects on neonatal outcomes.
Collapse
Affiliation(s)
- Max N Brondfield
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA
| | - Uma Mahadevan
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
| |
Collapse
|
|
6
|
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: 20] [Impact Index Per Article: 10.0] [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.
Collapse
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
| | | |
Collapse
|
|
7
|
Ishige T, Shimizu T, Watanabe K, Arai K, Kamei K, Kudo T, Kunisaki R, Tokuhara D, Naganuma M, Mizuochi T, Murashima A, Inoki Y, Iwata N, Iwama I, Koinuma S, Shimizu H, Jimbo K, Takaki Y, Takahashi S, Cho Y, Nambu R, Nishida D, Hagiwara SI, Hikita N, Fujikawa H, Hosoi K, Hosomi S, Mikami Y, Miyoshi J, Yagi R, Yokoyama Y, Hisamatsu T. Expert consensus on vaccination in patients with inflammatory bowel disease in Japan. J Gastroenterol 2023; 58:135-157. [PMID: 36629948 PMCID: PMC9838549 DOI: 10.1007/s00535-022-01953-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2022] [Accepted: 12/28/2022] [Indexed: 01/12/2023]
Abstract
Immunosuppressive therapies can affect the immune response to or safety of vaccination in patients with inflammatory bowel disease (IBD). The appropriateness of vaccination should be assessed prior to the initiation of IBD treatment because patients with IBD frequently undergo continuous treatment with immunosuppressive drugs. This consensus was developed to support the decision-making process regarding appropriate vaccination for pediatric and adult patients with IBD and physicians by providing critical information according to the published literature and expert consensus about vaccine-preventable diseases (VPDs) [excluding cervical cancer and coronavirus disease 2019 (COVID-19)] in Japan. This consensus includes 19 important clinical questions (CQs) on the following 4 topics: VPDs (6 CQs), live attenuated vaccines (2 CQs), inactivated vaccines (6 CQs), and vaccination for pregnancy, childbirth, and breastfeeding (5 CQs). These topics and CQs were selected under unified consensus by the members of a committee on intractable diseases with support by a Health and Labour Sciences Research Grant. Physicians should provide necessary information on VPDs to their patients with IBD and carefully manage these patients' IBD if various risk factors for the development or worsening of VPDs are present. This consensus will facilitate informed and shared decision-making in daily IBD clinical practice.
Collapse
Affiliation(s)
- Takashi Ishige
- Department of Pediatrics, Gunma University Graduate School of Medicine, 3-39-22, Showa-Machi, Maebashi, Gunma, 371-8511, Japan.
| | - Toshiaki Shimizu
- Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Kenji Watanabe
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hyogo Medical University, Nishinomiya, Japan
| | - Katsuhiro Arai
- Division of Gastroenterology, Center for Pediatric Inflammatory Bowel Disease, National Center for Child Health and Development, Tokyo, Japan
| | - Koichi Kamei
- Division of Nephrology and Rheumatology, National Center for Child Health and Development, Tokyo, Japan
| | - Takahiro Kudo
- Department of Pediatrics, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Reiko Kunisaki
- Inflammatory Bowel Disease Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Daisuke Tokuhara
- Department of Pediatrics, Wakayama Medical University, Wakayama, Japan
| | - Makoto Naganuma
- Department of Gastroenterology and Hepatology, Kansai Medical University, Osaka, Japan
| | - Tatsuki Mizuochi
- Department of Pediatrics and Child Health, Kurume University School of Medicine, Kurume, Fukuoka, Japan
| | - Atsuko Murashima
- Center for Maternal-Fetal, Neonatal and Reproductive Medicine, National Center of Child Health and Development, Tokyo, Japan
| | - Yuta Inoki
- Division of Nephrology and Rheumatology, National Center for Child Health and Development, Tokyo, Japan
| | - Naomi Iwata
- Department of Infection and Immunology, Aichi Children's Health and Medical Center, Obu, Japan
| | - Itaru Iwama
- Division of Gastroenterology and Hepatology, Saitama Children's Medical Center, Saitama, Japan
| | - Sachi Koinuma
- Japan Drug Information Institute in Pregnancy, National Center of Child Health and Development, Tokyo, Japan
| | - Hirotaka Shimizu
- Division of Gastroenterology, Center for Pediatric Inflammatory Bowel Disease, National Center for Child Health and Development, Tokyo, Japan
| | - Keisuke Jimbo
- Department of Pediatrics, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Yugo Takaki
- Department of Pediatrics, Japanese Red Cross Kumamoto Hospital, Kumamoto, Japan
| | - Shohei Takahashi
- Department of Pediatrics, Kyorin University School of Medicine, Tokyo, Japan
| | - Yuki Cho
- Department of Pediatrics, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Ryusuke Nambu
- Division of Gastroenterology and Hepatology, Saitama Children's Medical Center, Saitama, Japan
| | - Daisuke Nishida
- Inflammatory Bowel Disease Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Shin-Ichiro Hagiwara
- Department of Pediatric Gastroenterology, Nutrition and Endocrinology, Osaka Women's and Children's Hospital, Osaka, Japan
| | - Norikatsu Hikita
- Department of Pediatrics, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Hiroki Fujikawa
- Division of Gastroenterology, Center for Pediatric Inflammatory Bowel Disease, National Center for Child Health and Development, Tokyo, Japan
| | - Kenji Hosoi
- Division of Gastroenterology, Tokyo Metro Children's Medical Center, Tokyo, Japan
| | - Shuhei Hosomi
- Department of Gastroenterology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Yohei Mikami
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Jun Miyoshi
- Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, Tokyo, Japan
| | - Ryusuke Yagi
- Department of Pediatrics, Gunma University Graduate School of Medicine, 3-39-22, Showa-Machi, Maebashi, Gunma, 371-8511, Japan
| | - Yoko Yokoyama
- Department of Intestinal Inflammation Research, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan
| | - Tadakazu Hisamatsu
- Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, Tokyo, Japan
| |
Collapse
|
|
8
|
Meyer A, Taine M, Drouin J, Weill A, Carbonnel F, Dray-Spira R. Serious Infections in Children Born to Mothers With Inflammatory Bowel Disease With In Utero Exposure to Thiopurines and Anti-Tumor Necrosis Factor. Clin Gastroenterol Hepatol 2022; 20:1269-1281.e9. [PMID: 34298191 DOI: 10.1016/j.cgh.2021.07.028] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2021] [Accepted: 07/13/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS We aimed to compare the risk of serious infections in children with in utero exposure to thiopurines and/or anti-tumor necrosis factor (TNF) born to mothers with inflammatory bowel disease (IBD). METHODS Using the French national health database, which covers 99% of the French population (around 66,000,000 people), we identified live births among women with IBD in France between 2010 and 2018. The risks of serious infections in children during the first 5 years of life were compared according to treatment exposures during pregnancy using propensity score-weighted marginal Cox models. RESULTS A total of 26,561 children were included: 3392 were exposed to thiopurine monotherapy, 3399 to anti-TNF monotherapy, 816 to combination therapy, and 18,954 were not exposed to any of these drugs. The risks of serious infections during the first year of life among children exposed to thiopurine monotherapy (adjusted hazard ratio [aHR], 0.94; 95% confidence interval [CI], 0.83-1.07) and anti-TNF monotherapy (aHR, 1.10; 95% CI, 0.95-1.27) were similar to those of unexposed children; a higher risk was observed in children exposed to combination therapy (aHR, 1.36; 95% CI, 1.04-1.79). The highest increased risks were observed for nervous system infections and viral infections. The risk of serious infections during the second to fifth years of life was not associated with IBD treatments. CONCLUSIONS In children born to mothers with IBD, in utero exposure to thiopurine and anti-TNF monotherapies do not increase the risk of serious infections during the first 5 years of life. Combination therapy is associated with an increased risk of serious infections during the first year of life.
Collapse
Affiliation(s)
- Antoine Meyer
- EPIPHARE, Épidémiologie des Produits de Santé, ANSM-CNAM, Saint Denis, France; Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre, Le Kremlin Bicêtre, France & Université Paris Sud, Le Kremlin Bicêtre, France.
| | - Marion Taine
- EPIPHARE, Épidémiologie des Produits de Santé, ANSM-CNAM, Saint Denis, France
| | - Jérôme Drouin
- EPIPHARE, Épidémiologie des Produits de Santé, ANSM-CNAM, Saint Denis, France
| | - Alain Weill
- EPIPHARE, Épidémiologie des Produits de Santé, ANSM-CNAM, Saint Denis, France
| | - Franck Carbonnel
- Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre, Le Kremlin Bicêtre, France & Université Paris Sud, Le Kremlin Bicêtre, France
| | - Rosemary Dray-Spira
- EPIPHARE, Épidémiologie des Produits de Santé, ANSM-CNAM, Saint Denis, France
| |
Collapse
|
|
9
|
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.
Collapse
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
| |
Collapse
|
|
10
|
Mallick B, Malik S. Use of Azathioprine in Ulcerative Colitis: A Comprehensive Review. Cureus 2022; 14:e24874. [PMID: 35698683 PMCID: PMC9184176 DOI: 10.7759/cureus.24874] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/09/2022] [Indexed: 01/10/2023] Open
|
|
11
|
Cytotoxicity of Thiopurine Drugs in Patients with Inflammatory Bowel Disease. TOXICS 2022; 10:toxics10040151. [PMID: 35448412 PMCID: PMC9026123 DOI: 10.3390/toxics10040151] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/11/2022] [Revised: 03/11/2022] [Accepted: 03/17/2022] [Indexed: 02/04/2023]
Abstract
The effectiveness of thiopurine drugs in inflammatory bowel disease (IBD) was confirmed more than a half-century ago. It was proven that these can be essential immunomodulatory medications. Since then, they have been used routinely to maintain remission of Crohn’s disease (CD) and ulcerative colitis (UC). The cytotoxic properties of thiopurines and the numerous adverse effects of the treatment are controversial. However, the research subject of their pharmacology, therapy monitoring, and the search for predictive markers are still very relevant. In this article, we provide an overview of the current knowledge and findings in the field of thiopurines in IBD, focusing on the aspect of their cytotoxicity. Due to thiopurines’ benefits in IBD therapy, it is expected that they will still constitute an essential part of the CD and UC treatment algorithm. More studies are still required on the modulation of the action of thiopurines in combination therapy and their interaction with the gut microbiota.
Collapse
|
|
12
|
Vergani D, Terziroli Beretta-Piccoli B, Mieli-Vergani G. A reasoned approach to the treatment of autoimmune hepatitis. Dig Liver Dis 2021; 53:1381-1393. [PMID: 34162505 DOI: 10.1016/j.dld.2021.05.033] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Revised: 05/15/2021] [Accepted: 05/27/2021] [Indexed: 12/11/2022]
Abstract
Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease affecting all ages, characterised by elevated transaminase and immunoglobulin G levels, positive autoantibodies, interface hepatitis on histology and good response to immunosuppressive treatment. If untreated, it has a poor prognosis. The aim of this review is to analyse AIH therapeutic interventions with reference to our knowledge of the pathogenesis of AIH. Standard treatment, based on steroids and azathioprine, leads to disease remission in 80-90% of patients. Alternative first-line treatment with budesonide is effective in adults, but less so in the juvenile form of AIH; first-line treatment with ciclosporin does not provide convincing advantages compared to standard treatment. Second-line treatments are needed for patients not responding or intolerant to first-line standard management. Mycophenolate mofetil is the most widely used second-line drug, and has good efficacy particularly for patients intolerant to azathioprine, but is teratogenic. Only few and heterogeneous data on calcineurin inhibitors and m-TOR inhibitors are available. Biologicals, including anti-tumour necrosis factor- α and anti-CD20 monoclonal antibodies, have given ambivalent results and may have severe side-effects. Clinical trials with new therapeutic options aiming at targeting B lymphocytes and proinflammatory cytokines, or expanding regulatory T cells to restore tolerance are ongoing.
Collapse
Affiliation(s)
- Diego Vergani
- King's College London Faculty of Life Sciences & Medicine, London, UK; Institute of Liver Studies, MowatLabs, King's College Hospital, London, UK; Epatocentro Ticino, Lugano, Switzerland
| | - Benedetta Terziroli Beretta-Piccoli
- Institute of Liver Studies, MowatLabs, King's College Hospital, London, UK; Epatocentro Ticino, Lugano, Switzerland; Faculty of Biomedical Sciences, Università della Svizzera Italiana, Switzerland
| | - Giorgina Mieli-Vergani
- King's College London Faculty of Life Sciences & Medicine, London, UK; Epatocentro Ticino, Lugano, Switzerland; Paediatric Liver, GI and Nutrition Centre, MowatLabs, King's College Hospital, London, UK.
| |
Collapse
|
|
13
|
Jølving LR, Anru PL, Nielsen J, Friedman S, Nørgård BM. The risk of chronic diseases and congenital malformations during childhood and adolescence after in utero exposure to thiopurines. Aliment Pharmacol Ther 2021; 54:1061-1069. [PMID: 34464467 DOI: 10.1111/apt.16578] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2021] [Revised: 07/05/2021] [Accepted: 08/08/2021] [Indexed: 12/15/2022]
Abstract
BACKGROUND Women with autoimmune diseases, particularly inflammatory bowel disease (IBD), often need to continue immunomodulatory therapies during pregnancy. While the evidence of birth and short-term outcomes in children exposed in utero to these medicines is reassuring, long-term safety data are lacking. AIM To assess any association between in utero exposure to thiopurines and diagnoses of chronic diseases (type 1 diabetes, coeliac disease, thyroid disease, rheumatoid arthritis, IBD and asthma) and congenital malformations during childhood and adolescence. METHODS This nationwide cohort study was based on information using Danish registers and comprised all live-born children from 1995 to 2015 (N = 1 308 778). Children exposed in utero to thiopurines were followed for a median of 8.9 years (25%-75% percentiles 5.5-12.4 years); children not exposed were followed for 13.9 years (25%-75% percentiles 8.7-19.0 years). Analyses were adjusted for a number of confounders including the type of maternal underlying disease. RESULTS A total of 1047 children had been exposed to thiopurines in utero; 96 developed a chronic disease and 126 were diagnosed with congenital malformations during follow-up. The adjusted hazard ratio for rheumatoid arthritis was 0.78 (95% CI 0.35-1.73); for IBD, it was 1.45 (95% CI 0.64-3.27); for asthma 0.94 (95% CI 0.73-1.21), and for congenital malformations, it was 0.95 (95% CI 0.78-1.15). For type 1 diabetes, coeliac disease, thyroid disease and ulcerative colitis, we had insufficient data to perform adjusted analysis. CONCLUSION We found no increased risk of seven common chronic diseases or congenital malformations during childhood and adolescence after gestational exposure to thiopurines.
Collapse
Affiliation(s)
- Line Riis Jølving
- Center for Clinical Epidemiology, Odense University Hospital, Odense, Denmark.,Research Unit of Clinical Epidemiology, Department of Clinical Research, University of Southern Denmark, Odense, Denmark
| | | | - Jan Nielsen
- Center for Clinical Epidemiology, Odense University Hospital, Odense, Denmark.,Research Unit of Clinical Epidemiology, Department of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Sonia Friedman
- Research Unit of Clinical Epidemiology, Department of Clinical Research, University of Southern Denmark, Odense, Denmark.,Division of Gastroenterology, Hepatology and Endoscopy, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA
| | - Bente Mertz Nørgård
- Center for Clinical Epidemiology, Odense University Hospital, Odense, Denmark.,Research Unit of Clinical Epidemiology, Department of Clinical Research, University of Southern Denmark, Odense, Denmark.,Division of Gastroenterology, Hepatology and Endoscopy, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA
| |
Collapse
|
|
14
|
Kanis SL, Modderman S, Escher JC, Erler N, Beukers R, de Boer N, Bodelier A, Depla ACT, Dijkstra G, van Dijk ABRM, Gilissen L, Hoentjen F, Jansen JM, Kuyvenhoven J, Mahmmod N, Mallant-Hent RC, van der Meulen-de Jong AE, Noruzi A, Oldenburg B, Oostenbrug LE, Ter Borg PC, Pierik M, Romberg- Camps M, Thijs W, West R, de Lima A, van der Woude CJ. Health outcomes of 1000 children born to mothers with inflammatory bowel disease in their first 5 years of life. Gut 2021; 70:1266-1274. [PMID: 33046558 PMCID: PMC8223671 DOI: 10.1136/gutjnl-2019-319129] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2019] [Revised: 09/02/2020] [Accepted: 09/05/2020] [Indexed: 12/16/2022]
Abstract
OBJECTIVE The aim of this study was to describe the long-term health outcomes of children born to mothers with inflammatory bowel disease (IBD) and to assess the impact of maternal IBD medication use on these outcomes. DESIGN We performed a multicentre retrospective study in The Netherlands. Women with IBD who gave birth between 1999 and 2018 were enrolled from 20 participating hospitals. Information regarding disease characteristics, medication use, lifestyle, pregnancy outcomes and long-term health outcomes of children was retrieved from mothers and medical charts. After consent of both parents, outcomes until 5 years were also collected from general practitioners. Our primary aim was to assess infection rate and our secondary aims were to assess adverse reactions to vaccinations, growth, autoimmune diseases and malignancies. RESULTS We included 1000 children born to 626 mothers (381 (61%) Crohn's disease, 225 (36%) ulcerative colitis and 20 (3%) IBD unclassified). In total, 196 (20%) had intrauterine exposure to anti-tumour necrosis factor-α (anti-TNF-α) (60 with concomitant thiopurine) and 240 (24%) were exposed to thiopurine monotherapy. The 564 children (56%) not exposed to anti-TNF-α and/or thiopurine served as control group. There was no association between adverse long-term health outcomes and in utero exposure to IBD treatment. We did find an increased rate of intrahepatic cholestasis of pregnancy (ICP) in case thiopurine was used during the pregnancy without affecting birth outcomes and long-term health outcomes of children. All outcomes correspond with the general age-adjusted population. CONCLUSION In our study, we found no association between in utero exposure to anti-TNF-α and/or thiopurine and the long-term outcomes antibiotic-treated infections, severe infections needing hospital admission, adverse reactions to vaccinations, growth failure, autoimmune diseases and malignancies.
Collapse
Affiliation(s)
- Shannon Linda Kanis
- Gastroenterology and Hepatology, Erasmus Medical Center, Rotterdam, The Netherlands
| | - Sanne Modderman
- Gastroenterology and Hepatology, Erasmus Medical Center, Rotterdam, The Netherlands
| | - Johanna C Escher
- Pediatric Gastroenterology, Erasmus MC Sophia Children Hospital, Rotterdam, The Netherlands
| | - Nicole Erler
- Biostatistics, Erasmus Medical Center, Rotterdam, The Netherlands
| | - Ruud Beukers
- Gastroenterology and Hepatology, Albert Schweitzer Ziekenhuis, Dordrecht, The Netherlands
| | - Nanne de Boer
- Gastroenterology and Hepatology, Amsterdam UMC, Amsterdam, The Netherlands
| | - Alexander Bodelier
- Gastroenterology and Hepatology, Amphia Hospital site Molengracht, Breda, The Netherlands
| | | | - Gerard Dijkstra
- Gastroenterology and Hepatology, University of Groningen, Groningen, The Netherlands
| | | | - Lennard Gilissen
- Gastroenterology and Hepatology, Catharina Ziekenhuis, Eindhoven, The Netherlands
| | - Frank Hoentjen
- Gastroenterology and Hepatology, Radboudumc, Nijmegen, The Netherlands
| | - Jeroen M Jansen
- Gastroenterology and Hepatology, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands
| | - Johan Kuyvenhoven
- Gastroenterology and Hepatology, Spaarne Hospital, Haarlem, The Netherlands
| | - Nofel Mahmmod
- Gastroenterology and Hepatology, Sint Antonius Ziekenhuis, Nieuwegein, The Netherlands
| | | | | | - Anahita Noruzi
- Gastroenterology and Hepatology, Erasmus Medical Center, Rotterdam, The Netherlands
| | - Bas Oldenburg
- Gastroenterology and Hepatology, Utrecht Hospital, Utrecht, The Netherlands
| | - Liekele E Oostenbrug
- Gastroenterology and Hepatology, Zuyderland Medisch Centrum Heerlen, Heerlen, The Netherlands
| | | | - Marieke Pierik
- Gastroenterology and Hepatology, Maastricht Universitair Medisch Centrum+, Maastricht, The Netherlands
| | - Mariëlle Romberg- Camps
- Gastroenterology and Hepatology, Zuyderland Medical Centre Sittard-Geleen, Sittard-Geleen, The Netherlands
| | - Willem Thijs
- Gastroenterology and Hepatology, Martini Hospital, Groningen, The Netherlands
| | - Rachel West
- Gastroenterology and Hepatology, Franciscus Gasthuis, Rotterdam, New Caledonia
| | - Alison de Lima
- Gastroenterology and Hepatology, Erasmus Medical Center, Rotterdam, The Netherlands
| | | | | |
Collapse
|
|
15
|
Boulay H, Mazaud-Guittot S, Supervielle J, Chemouny JM, Dardier V, Lacroix A, Dion L, Vigneau C. Maternal, foetal and child consequences of immunosuppressive drugs during pregnancy in women with organ transplant: a review. Clin Kidney J 2021; 14:1871-1878. [PMID: 34345409 PMCID: PMC8323135 DOI: 10.1093/ckj/sfab049] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2020] [Accepted: 03/01/2021] [Indexed: 02/06/2023] Open
Abstract
Although pregnancy remains exceptional in women after heart, liver or lung transplant, obstetricians and nephrologists are regularly confronted with pregnancy in renal transplant recipients. National and international registries have described the epidemiology of maternal, foetal and neonatal complications, and transplantation societies have published recommendations on the monitoring of these high-risk pregnancies. In this review, we summarize the existing data on maternal and foetal complications of pregnancies in women after renal transplant, especially the management of immunosuppression. We also describe the few available data on the middle- and long-term outcomes of their children who were exposed in utero to immunosuppressive drugs.
Collapse
Affiliation(s)
- Hugoline Boulay
- University of Rennes, CHU Rennes, INSERM, EHESP, IRSET (Institut de recherche en santé, environnement et travail) - UMR_S 1085, F-35000, Rennes, France
| | - Séverine Mazaud-Guittot
- University of Rennes, CHU Rennes, INSERM, EHESP, IRSET (Institut de recherche en santé, environnement et travail) - UMR_S 1085, F-35000, Rennes, France
| | - Jeanne Supervielle
- University of Rennes, CHU Rennes, INSERM, EHESP, IRSET (Institut de recherche en santé, environnement et travail) - UMR_S 1085, F-35000, Rennes, France
| | - Jonathan M Chemouny
- University of Rennes, CHU Rennes, INSERM, EHESP, IRSET (Institut de recherche en santé, environnement et travail) - UMR_S 1085, F-35000, Rennes, France
| | - Virginie Dardier
- Laboratoire de psychologie, comportement, cognition et communication (LP3 C), Université Rennes-Rennes 2, Rennes, France
| | - Agnes Lacroix
- Laboratoire de psychologie, comportement, cognition et communication (LP3 C), Université Rennes-Rennes 2, Rennes, France
| | - Ludivine Dion
- University of Rennes, CHU Rennes, INSERM, EHESP, IRSET (Institut de recherche en santé, environnement et travail) - UMR_S 1085, F-35000, Rennes, France
| | - Cécile Vigneau
- University of Rennes, CHU Rennes, INSERM, EHESP, IRSET (Institut de recherche en santé, environnement et travail) - UMR_S 1085, F-35000, Rennes, France
| |
Collapse
|
|
16
|
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.
Collapse
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
| |
Collapse
|
|
17
|
Ali MF, He H, Friedel D. Inflammatory bowel disease and pregnancy: fertility, complications and treatment. Ann Gastroenterol 2020; 33:579-590. [PMID: 33162735 PMCID: PMC7599341 DOI: 10.20524/aog.2020.0536] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2020] [Accepted: 07/27/2020] [Indexed: 12/30/2022] Open
Abstract
Inflammatory bowel disease (IBD) is commonly diagnosed and treated in the young population. Therefore, it is common that women anticipating or undergoing pregnancy will have to cope with the additional burden of their IBD. Pregnancy in an IBD patient also presents challenges for the practitioner, in that the usual diagnostic and therapeutic armamentarium of potential tests and therapies is disrupted. This review covers the implications of IBD for fertility, pregnancy and offspring, and discusses the management of IBD in pregnancy.
Collapse
Affiliation(s)
- Mohammad Fahad Ali
- Department of Gastroenterology and Hepatology, Guthrie Cortland Medical Center (Mohammad Fahad Ali)
| | - Harry He
- Department of Medicine, NYU Winthrop University Hospital (Harry He)
| | - David Friedel
- Department of Gastroenterology, NYU Winthrop University Hospital (David Friedel), USA
| |
Collapse
|
|
18
|
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.
Collapse
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
| |
Collapse
|
|
19
|
Braga A, Vasconcelos C, Braga J. Autoimmune hepatitis and pregnancy. Best Pract Res Clin Obstet Gynaecol 2020; 68:23-31. [DOI: 10.1016/j.bpobgyn.2020.03.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2020] [Revised: 03/01/2020] [Accepted: 03/05/2020] [Indexed: 02/08/2023]
|
|
20
|
Nørgård BM, Nielsen J, Friedman S. In utero exposure to thiopurines/anti-TNF agents and long-term health outcomes during childhood and adolescence in Denmark. Aliment Pharmacol Ther 2020; 52:829-842. [PMID: 32677731 DOI: 10.1111/apt.15956] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2020] [Revised: 05/15/2020] [Accepted: 06/20/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND Data on long-term health outcomes of children exposed in utero to thiopurines and anti-TNF medications are lacking. AIMS To examine the association between in utero exposure to thiopurines and anti-TNF medications and child health outcomes of site-specific groups of infections, using a composite endpoint including psychiatric diagnoses/autism spectrum disorder (ASD)/attention deficit hyperactivity disorder (ADHD), and malignancies during childhood/adolescence. METHODS A nationwide cohort study based on Danish health registries included 1 311 009 live born children during 1995 through 2015. Outcomes were based on hospital diagnoses (in-patients/out-patients/emergency department contacts). RESULTS In total, 1048 children were exposed in utero to thiopurines and 1 309 961 were unexposed. The adjusted hazard ratios (HRs) for site-specific groups of infections in the first 3 years of life were close to unity. The adjusted HR of psychiatric diagnoses/ASD/ADHD was 1.11 (95% CI 0.81-1.52). The HR of malignancies was not calculated (only two events among the exposed). In total, 493 children were exposed in utero to anti-TNF medications and 728 055 were unexposed. Within the first year of life, the adjusted HR of respiratory, urological/gynaecological infections and other infections were 1.34 (95% CI 1.03-1.74), 2.36 (95% CI 1.15-4.81) and 1.61 (95% CI 1.21-2.13), respectively. We found no increased risk of other adverse outcomes. CONCLUSIONS After in utero exposure to thiopurines, we found no increased risk of infections, psychiatric diagnoses/ASD/ADHD, or malignancies during childhood/adolescence. After in utero exposure to anti-TNF medications, the risk of respiratory, urological/gynaecological infections and other infections was increased during the first year of life.
Collapse
Affiliation(s)
- Bente Mertz Nørgård
- Center for Clinical Epidemiology, Odense University Hospital, and Research Unit of Clinical Epidemiology, University of Southern Denmark, Odense, Denmark.,Center for Crohn's and Colitis, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Jan Nielsen
- Center for Clinical Epidemiology, Odense University Hospital, and Research Unit of Clinical Epidemiology, University of Southern Denmark, Odense, Denmark
| | - Sonia Friedman
- Center for Clinical Epidemiology, Odense University Hospital, and Research Unit of Clinical Epidemiology, University of Southern Denmark, Odense, Denmark.,Center for Crohn's and Colitis, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| |
Collapse
|
|
21
|
Mack CL, Adams D, Assis DN, Kerkar N, Manns MP, Mayo MJ, Vierling JM, Alsawas M, Murad MH, Czaja AJ. Diagnosis and Management of Autoimmune Hepatitis in Adults and Children: 2019 Practice Guidance and Guidelines From the American Association for the Study of Liver Diseases. Hepatology 2020; 72:671-722. [PMID: 31863477 DOI: 10.1002/hep.31065] [Citation(s) in RCA: 507] [Impact Index Per Article: 101.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2019] [Accepted: 11/25/2019] [Indexed: 02/06/2023]
Affiliation(s)
- Cara L Mack
- Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO
| | - David Adams
- Centre for Liver Research, University of Birmingham, Birmingham, UK
| | - David N Assis
- Department of Internal Medicine, Yale School of Medicine, New Haven, CT
| | - Nanda Kerkar
- Golisano Children's Hospital at Strong, University of Rochester Medical Center, New York, NY
| | - Michael P Manns
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Marlyn J Mayo
- Division of Digestive and Liver Diseases, University of Texas SW Medical Center, Dallas, TX
| | - John M Vierling
- Medicine and Surgery, Baylor College of Medicine, Houston, TX
| | | | - Mohammad H Murad
- Mayo Knowledge and Encounter Research Unit, Mayo Clinic College of Medicine, Rochester, MN
| | - Albert J Czaja
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, MN
| |
Collapse
|
|
22
|
Abstract
The disease course of autoimmune diseases such as rheumatoid arthritis is altered during pregnancy, and a similar modulatory role of pregnancy on inflammatory bowel disease (IBD) has been proposed. Hormonal, immunological, and microbial changes occurring during normal pregnancy may interact with the pathophysiology of IBD. IBD consists of Crohn's disease and ulcerative colitis, and because of genetic, immunological, and microbial differences between these disease entities, they may react differently during pregnancy and should be described separately. This review will address the pregnancy-induced physiological changes and their potential effect on the disease course of ulcerative colitis and Crohn's disease, with emphasis on the modulation of epithelial barrier function and immune profiles by pregnancy hormones, microbial changes, and microchimerism.
Collapse
|
|
23
|
Belizna C, Meroni PL, Shoenfeld Y, Devreese K, Alijotas-Reig J, Esteve-Valverde E, Chighizola C, Pregnolato F, Cohen H, Fassot C, Mattera PM, Peretti P, Levy A, Bernard L, Saiet M, Lagarce L, Briet M, Rivière M, Pellier I, Gascoin G, Rakotonjanahary J, Borghi MO, Stojanovich L, Djokovic A, Stanisavljevic N, Bromley R, Elefant-Amoura E, Bahi Buisson N, Pindi Sala T, Kelchtermans H, Makatsariya A, Bidsatze V, Khizroeva J, Latino JO, Udry S, Henrion D, Loufrani L, Guihot AL, Muchardt C, Hasan M, Ungeheuer MN, Voswinkel J, Damian L, Pabinger I, Gebhart J, Lopez Pedrera R, Cohen Tervaert JW, Tincani A, Andreoli L. In utero exposure to Azathioprine in autoimmune disease. Where do we stand? Autoimmun Rev 2020; 19:102525. [PMID: 32240856 DOI: 10.1016/j.autrev.2020.102525] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2020] [Accepted: 01/23/2020] [Indexed: 12/19/2022]
Abstract
Azathioprine (AZA), an oral immunosuppressant, is safe during pregnancy. Some reports suggested different impairments in the offspring of mothers with autoimmune diseases (AI) exposed in utero to AZA. These observations are available from retrospective studies or case reports. However, data with respect to the long-term safety in the antenatally exposed child are still lacking. The aim of this study is to summarize the current knowledge in this field and to focus on the need for a prospective study on this population. We performed a PubMed search using several search terms. The actual data show that although the risk of congenital anomalies in offspring, as well as the infertility risk, are similar to those found in general population, there is a higher incidence of prematurity, of lower weight at birth and an intra-uterine delay of development. There is also an increased risk of materno- fetal infections, especially cytomegalovirus infection. Some authors raise the interrogations about neurocognitive impairment. Even though the adverse outcomes might well be a consequence of maternal illness and disease activity, interest has been raised about a contribution of this drug. However, the interferences between the external agent (in utero exposure to AZA), with the host (child genetic susceptibility, immune system anomalies, emotional status), environment (public health, social context, availability of health care), economic, social, and behavioral conditions, cultural patterns, are complex and represent confounding factors. In conclusion, it is necessary to perform studies on the medium and long-term outcome of children born by mothers with autoimmune diseases, treated with AZA, in order to show the safety of AZA exposure. Only large-scale population studies with long-term follow-up will allow to formally conclude in this field. TAKE HOME MESSAGES.
Collapse
Affiliation(s)
- Cristina Belizna
- Vascular and Coagulation Department, University Hospital Angers, Angers, France; MITOVASC institute and CARFI facility, University of Angers, UMR CNRS 6015, INSERM U1083, Angers, France; Internal Medicine Department, Clinique de l'Anjou, Angers, France; UMR CNRS 6015, Angers, France; INSERM U1083, Angers, France.
| | - Pier Luigi Meroni
- Clinical Immunology and Rheumatology Research Department Auxologico Institute, Milan, Italy
| | - Yehuda Shoenfeld
- The Zabludowicz Center for Autoimmune Diseases, Affiliated to Sackler Faculty of Medicine, Tel-Aviv University, Israel; I.M. Sechenow First Moscow State Medical University, Moscow, Russia
| | - Katrien Devreese
- Coagulation Laboratory, Department of Clinical Biology, Immunology and Microbiology, Ghent University Hospital, Ghent, Belgium
| | - Jaume Alijotas-Reig
- Systemic Autoimmune Disease Unit, Department of Internal Medicine, Vall d'Hebron University Hospital, Barcelona, Spain; Department of Medicine, Universitat Autonòma, Barcelona, Spain
| | | | - Cecilia Chighizola
- Clinical Immunology and Rheumatology Research Department Auxologico Institute, Milan, Italy
| | - Francesca Pregnolato
- Clinical Immunology and Rheumatology Research Department Auxologico Institute, Milan, Italy
| | - Hannah Cohen
- Haematology Department, University College Hospital, London, UK
| | - Celine Fassot
- Internal Medicine Department, Clinique de l'Anjou, Angers, France
| | - Patrick Martin Mattera
- Faculty of Human and Social Sciences, Laboratory of Research in Psychopathology, 3 place André Leroy, 49008 Angers, France
| | - Pascale Peretti
- Faculty of Human and Social Sciences, Laboratory of Research in Psychopathology, 3 place André Leroy, 49008 Angers, France
| | - Alexandre Levy
- Faculty of Human and Social Sciences, Laboratory of Research in Psychopathology, 3 place André Leroy, 49008 Angers, France
| | - Laurence Bernard
- Faculty of Human and Social Sciences, Laboratory of Research in Psychopathology, 3 place André Leroy, 49008 Angers, France
| | - Mathilde Saiet
- Faculty of Human and Social Sciences, Laboratory of Research in Psychopathology, 3 place André Leroy, 49008 Angers, France
| | - Laurence Lagarce
- Departement of Pharmacovigilance, University Hospital Angers, Angers, France
| | - Marie Briet
- Departement of Pharmacovigilance, University Hospital Angers, Angers, France
| | - Marianne Rivière
- French Lupus and Other Autoimmune Disease Patients Association, AFL+, Cuvry, France
| | - Isabelle Pellier
- Department of Pediatrics, University Hospital Angers, Angers, France
| | - Géraldine Gascoin
- Department of Neonatology, University Hospital Angers, Angers, France
| | | | - Maria Orietta Borghi
- Clinical Immunology and Rheumatology Research Department Auxologico Institute, Milan, Italy
| | - Ljudmila Stojanovich
- Scientific Research Department, Internal Medicine-Rheumatology Bezhanijska Kosa, University Medical Center, Belgrade University, Serbia
| | - Aleksandra Djokovic
- Scientific Research Department, Internal Medicine-Rheumatology Bezhanijska Kosa, University Medical Center, Belgrade University, Serbia
| | - Natasa Stanisavljevic
- Scientific Research Department, Internal Medicine-Rheumatology Bezhanijska Kosa, University Medical Center, Belgrade University, Serbia
| | - Rebecca Bromley
- Manchester University Hospitals NHS Trust, Manchester, UK; Division of Evolution and Genomic Science, School of Biological Sciences, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK
| | - Elisabeth Elefant-Amoura
- Genetical and Medical Embriology, CRAT Reference Center on Teratogenic Agents, Paris Est - Hôpital d'Enfants Armand-Trousseau, 26 avenue du Docteur Arnold Netter, 75571 Paris, France
| | - Nadia Bahi Buisson
- Neurology & Neurodevelopmental disorders Department Necker Enfants Malades University Hospital, APHP, Paris 149 Rue de Sèvres, 75015 Paris; INSERM U1163, Hôpital Necker Enfants Malades, 149 rue de Sèvres, 75015 Paris, France; INSERM U1163, Hôpital Necker Enfants Malades, 149 rue de Sèvres, 75015 Paris, France
| | - Taylor Pindi Sala
- EA 7334, Patient Centered Outcomes Research, University Paris Diderot, Paris, France
| | - Hilde Kelchtermans
- Synapse Research Institute, Maastricht, the Netherlands; Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, the Netherlands
| | - Alexander Makatsariya
- Department of Obstetrics and Gynecology, I.M. Sechenow First Moscow State Medical University, Moscow, Russia
| | - Viktoria Bidsatze
- Department of Obstetrics and Gynecology, I.M. Sechenow First Moscow State Medical University, Moscow, Russia
| | - Jamilya Khizroeva
- Department of Obstetrics and Gynecology, I.M. Sechenow First Moscow State Medical University, Moscow, Russia
| | - Jose Omar Latino
- Autoimmune and thrombophilic disorders Department, Hospital Carlos G. Durand, Buenos Aires, Argentina
| | - Sebastian Udry
- Autoimmune and thrombophilic disorders Department, Hospital Carlos G. Durand, Buenos Aires, Argentina
| | - Daniel Henrion
- Internal Medicine Department, Clinique de l'Anjou, Angers, France
| | - Laurent Loufrani
- Internal Medicine Department, Clinique de l'Anjou, Angers, France
| | | | - Christian Muchardt
- Unit of Epigenetic Regulation, Department of Developmental and Stem Cell Biology, UMR3738 CNRS, Institut Pasteur, Paris, France
| | - Milena Hasan
- Cytometry and Biomarkers Unit of Technology and Service, Center for Translational Science, Institut Pasteur, 28, Rue Doct Roux, 75015 Paris, France
| | - Marie Noelle Ungeheuer
- Clinical Investigation and Acces to Bioresources Department, Institut Pasteur, 28, Rue Doct Roux, 75015 Paris, France
| | - Jan Voswinkel
- Department of Internal Medicine I, Saarland Medical School, University of Saarland, Homburg, Saarland, Germany
| | - Laura Damian
- Department of Rheumatology, County Emergency Hospital Cluj-Napoca, Cluj-Napoca, Romania
| | - Ingrid Pabinger
- Department of Medicine, Division of Hematology and Haemostasis, University Hospital of Vienna, Austria
| | - Johanna Gebhart
- Department of Medicine, Division of Hematology and Haemostasis, University Hospital of Vienna, Austria
| | - Rosario Lopez Pedrera
- Institute Maimónides of Biomedical Investigations, University Hospital Reina Sofía, Cordoba, Spain
| | | | - Angela Tincani
- Rheumatology and Clinical Immunology Unit, University of Brescia, Brescia, Italy; I.M. Sechenow First Moscow State Medical University, Moscow, Russia
| | - Laura Andreoli
- Rheumatology and Clinical Immunology Unit, University of Brescia, Brescia, Italy
| |
Collapse
|
|
24
|
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: 59] [Impact Index Per Article: 11.8] [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.
Collapse
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.
| |
Collapse
|
|
25
|
|
|
26
|
Abstract
PURPOSE OF REVIEW Roughly half of the nearly 1.6 million people with inflammatory bowel disease (IBD) are women of reproductive age. Caring for women with IBD who are also pregnant can be challenging, particularly if with a disease flare or in remission, as there are special considerations needed. RECENT FINDINGS Despite older studies concluding potential risks associated with IBD medical therapies, more recent literature reports healthier maternal and birth outcomes associated with disease control and reduction in the inflammatory burden. Most IBD therapies should generally be continued throughout all three trimesters without interruption as this is associated with better outcomes. SUMMARY Active IBD increases risk of pregnancy complications and adverse pregnancy outcomes. Most medications have a favorable safety profile for use during pregnancy, regardless if in disease flare or remission. Short course corticosteroids for induction and management of flare is permitted. Thiopurines should not be started during pregnancy for a disease flare, but may be continued during pregnancy if previously on monotherapy. Biologics should be continued throughout pregnancy without interruption and timing of third trimester dosing made based on drug levels and estimated date of delivery. Risks/benefit assessment of therapies and disease control is important and should be individualized.
Collapse
|
|
27
|
Puchner A, Gröchenig HP, Sautner J, Helmy-Bader Y, Juch H, Reinisch S, Högenauer C, Koch R, Hermann J, Studnicka-Benke A, Weger W, Puchner R, Dejaco C. Immunosuppressives and biologics during pregnancy and lactation : A consensus report issued by the Austrian Societies of Gastroenterology and Hepatology and Rheumatology and Rehabilitation. Wien Klin Wochenschr 2019; 131:29-44. [PMID: 30643992 PMCID: PMC6342891 DOI: 10.1007/s00508-019-1448-y] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2018] [Accepted: 12/06/2018] [Indexed: 12/14/2022]
Abstract
An increasing and early-onset use of immunosuppressives and biologics has become more frequently seen among patients with inflammatory bowel diseases (IBD) and rheumatic disorders. Many women in their childbearing years currently receive such medications, and some of them in an interdisciplinary setting. Many questions arise in women already pregnant or wishing to conceive with respect to continuing or discontinuing treatment, the risks borne by the newborns and their mothers and long-term safety. Together with the Austrian Society of Rheumatology and Rehabilitation, the IBD working group of the Austrian Society of Gastroenterology and Hepatology has elaborated consensus statements on the use of immunosuppressives and biologics in pregnancy and lactation. This is the first Austrian interdisciplinary consensus on this topic. It is intended to serve as a basis and support for providing advice to our patients and their treating physicians.
Collapse
Affiliation(s)
- Antonia Puchner
- Division of Rheumatology, Third Medical Department, Medical University of Vienna/Vienna General Hospital, Vienna, Austria
| | - Hans Peter Gröchenig
- Medical Department, Hospital of the Brothers of Mercy, St. Veit an der Glan, Austria
| | - Judith Sautner
- Second Medical Department, Korneuburg-Stockerau Hospital/Lower Austrian Center for Rheumatology, Stockerau, Austria
| | - Yvonne Helmy-Bader
- Department of Obstetrics and Gynecology, Medical University of Vienna, Vienna, Austria
| | - Herbert Juch
- Department of Cell Biology, Histology and Embryology, Medical University of Graz, Graz, Austria
| | - Sieglinde Reinisch
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Christoph Högenauer
- Division of Gastroenterology and Hepatology, Medical Department, Medical University of Graz, Graz, Austria
| | - Robert Koch
- Division of Gastroenterology, First Medical Department, Medical University of Innsbruck, Innsbruck, Austria
| | - Josef Hermann
- Division of Rheumatology and Immunology, Medical Department, Medical University of Graz, Graz, Austria
| | | | - Wolfgang Weger
- Department of Dermatology and Venereology, Medical University of Graz, Graz, Austria
| | - Rudolf Puchner
- Division of Rheumatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Clemens Dejaco
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria.
| |
Collapse
|
|
28
|
Fava A, Petri M. Systemic lupus erythematosus: Diagnosis and clinical management. J Autoimmun 2019; 96:1-13. [PMID: 30448290 PMCID: PMC6310637 DOI: 10.1016/j.jaut.2018.11.001] [Citation(s) in RCA: 377] [Impact Index Per Article: 62.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2018] [Revised: 11/01/2018] [Accepted: 11/01/2018] [Indexed: 12/12/2022]
Abstract
Systemic lupus erythematosus (SLE) is a worldwide chronic autoimmune disease which may affect every organ and tissue. Genetic predisposition, environmental triggers, and the hormonal milieu, interplay in disease development and activity. Clinical manifestations and the pattern of organ involvement are widely heterogenous, reflecting the complex mosaic of disrupted molecular pathways converging into the SLE clinical phenotype. The SLE complex pathogenesis involves multiple cellular components of the innate and immune systems, presence of autoantibodies and immunocomplexes, engagement of the complement system, dysregulation of several cytokines including type I interferons, and disruption of the clearance of nucleic acids after cell death. Use of immunomodulators and immunosuppression has altered the natural course of SLE. In addition, morbidity and mortality in SLE not only derive from direct immune mediated tissue damage but also from SLE and treatment associated complications such as accelerated coronary artery disease and increased infection risk. Here, we review the diagnostic approach as well as the etiopathogenetic rationale and clinical evidence for the management of SLE. This includes 1) lifestyle changes such as avoidance of ultraviolet light; 2) prevention of comorbidities including coronary artery disease, osteoporosis, infections, and drug toxicities; 3) use of immunomodulators (i.e. hydroxychloroquine and vitamin D); and 4) immunosuppressants and targeted therapy. We also review new upcoming agents and regimens currently under study.
Collapse
Affiliation(s)
- Andrea Fava
- Johns Hopkins University School of Medicine, 1830 East Monument Street, Suite 7500, Baltimore, MD 21205, USA
| | - Michelle Petri
- Johns Hopkins University School of Medicine, 1830 East Monument Street, Suite 7500, Baltimore, MD 21205, USA.
| |
Collapse
|
|
29
|
Gomes SZ, Araujo F, Bandeira CL, Oliveira LG, Hoshida MS, Zugaib M, Francisco RPV, Bevilacqua E. The Impact of Immunosuppressive Drugs on Human Placental Explants. Reprod Sci 2018; 26:1225-1234. [DOI: 10.1177/1933719118812739] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
The use of immunosuppressive drugs guarantees the vitality of the graft and allows gestation in spite of intercurrences such as prematurity and intrauterine growth restriction. However, little is known about the direct effects of immunosuppressive drugs on placental cells. We investigated the effects of immunosuppressive drugs in the chorionic villous explants from human term placentas of healthy gestations. Human placental explants from term gestations (37-39 week gestational age, n = 12) were exposed to cyclosporine A (CSA, 0, 62.5, 125, 1250 ng/mL) or azathioprine (AZA, 0, 5, 10, 100 ng/mL) separately or, in combination for up to 48 hours. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays showed a significant decrease in the explant metabolic activity between AZA and the control group (24 hours, 100 ng/mL, 48 hours, all concentrations, P < .005). Cyclosporin A (CsA) reduced cell activity when associated with AZA (48 hours, P < .005). Fibrinoid deposits increased in AZA-treated explants alone (5 ng/mL, 48 hours; 10 ng/mL, 24-48 hours; P < .005) or when associated with CsA (10 AZA/125 CsA, P < .05), whereas in CsA treatment alone, there was an augment in syncytial knots (24-48 hours, P < .005). The sFLT1 gene (24 hours, P < .05) and protein ( P < .005) expression increased in AZA and CsA-treatments separately or in combination ( P < .05). Placental growth factor increased in AZA (24 hours, 10 ng/mL) and CsA (125 ng/mL; P < .05). In conclusion, our data indicate that AZA primarily acts on the villous metabolism, perturbing placental homeostasis. Since these drugs may alter the balance of angiogenic factors in its selection for clinical application, their impact on the behavior of placental villous should be considered.
Collapse
Affiliation(s)
- Sara Z. Gomes
- Department of Cellular and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
| | - Franciele Araujo
- Department of Cellular and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
| | - Carla L. Bandeira
- Department of Cellular and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
| | - Leandro G. Oliveira
- Gynecology and Obstetrics Department, Botucatu Medical School, Sao Paulo State University, São Paulo, Brazil
| | - Mara S. Hoshida
- Obstetrics and Gynecology Department, University of São Paulo Medical School, São Paulo, Brazil
| | - Marcelo Zugaib
- Obstetrics and Gynecology Department, University of São Paulo Medical School, São Paulo, Brazil
| | - Rossana P. V. Francisco
- Obstetrics and Gynecology Department, University of São Paulo Medical School, São Paulo, Brazil
| | - Estela Bevilacqua
- Department of Cellular and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
| |
Collapse
|
|
30
|
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]
|
|
31
|
Use of Thiopurines During Conception and Pregnancy Is Not Associated With Adverse Pregnancy Outcomes or Health of Infants at One Year in a Prospective Study. Clin Gastroenterol Hepatol 2017; 15:1232-1241.e1. [PMID: 28342949 DOI: 10.1016/j.cgh.2017.02.041] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2016] [Revised: 02/28/2017] [Accepted: 02/28/2017] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Most data on the safety of thiopurine therapy for inflammatory bowel disease (IBD) during pregnancy come from retrospective studies, which makes it difficult to adjust for confounding factors. We performed a prospective cohort study to determine whether thiopurine use affects pregnancy outcomes or health outcomes of children. METHODS We performed a prospective study of all women who visited the IBD preconception outpatient clinic at our tertiary health center in The Netherlands from December 2008 through May 2016. Patients were counseled before pregnancy and seen bimonthly during pregnancy. We collected and analyzed data on medication use, as well as lifestyle and clinical factors, during conception and pregnancy. Pregnancy outcomes (live birth, spontaneous abortion, elective abortion, and stillbirth), birth outcomes (gestational age, birth weight, and congenital abnormalities), and health outcomes of infants 1 year after birth were compared between women who did and did not use a thiopurine during conception and pregnancy. In addition, health outcomes of infants 1 year after birth were compared with infants born to mothers without IBD from the same geographic region. RESULTS Our study comprised 309 women with confirmed IBD (216 with Crohn's disease, 85 with ulcerative colitis, and 8 with IBD unclassified). During the study period, 311 pregnancies of 232 women resulted in a live birth; a thiopurine was used during 108 pregnancies (35%). After correction for diagnosis, fertility treatment, and disease activity, there was no association between thiopurine use and spontaneous abortions. Birth outcomes were similar between women who did and did not use a thiopurine. Among infants 1 year of age, there were no differences in median growth, number of infections, allergies, adverse reactions to vaccinations, or chronic diseases between those born to women who did and did not use a thiopurine or between women with and without IBD. CONCLUSIONS In this prospective cohort study, we found no association between maternal thiopurine use during pregnancy and increased spontaneous abortions, adverse birth outcomes, or adverse health outcomes of infants 1 year after birth.
Collapse
|
|
32
|
Dauti A, Gerstl B, Chong S, Chisholm O, Anazodo A. Improvements in Clinical Trials Information Will Improve the Reproductive Health and Fertility of Cancer Patients. J Adolesc Young Adult Oncol 2017; 6:235-269. [PMID: 28207285 DOI: 10.1089/jayao.2016.0084] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
There are a number of barriers that result in cancer patients not being referred for oncofertility care, which include knowledge about reproductive risks of antineoplastic agents. Without this information, clinicians do not always make recommendations for oncofertility care. The objective of this study was to describe the level of reproductive information and recommendations that clinicians have available in clinical trial protocols regarding oncofertility management and follow-up, and the information that patients may receive in clinical trials patient information sheets or consent forms. A literature review of the 71 antineoplastic drugs included in the 68 clinical trial protocols showed that 68% of the antineoplastic drugs had gonadotoxic animal data, 32% had gonadotoxic human data, 83% had teratogenic animal data, and 32% had teratogenic human data. When the clinical trial protocols were reviewed, only 22% of the protocols reported the teratogenic risks and 32% of the protocols reported the gonadotoxic risk. Only 56% of phase 3 protocols had gonadotoxic information and 13% of phase 3 protocols had teratogenic information. Nine percent of the protocols provided fertility preservation recommendations and 4% provided reproductive information in the follow-up and survivorship period. Twenty-six percent had a section in the clinical trials protocol, which identified oncofertility information easily. When gonadotoxic and teratogenic effects of treatment were known, they were not consistently included in the clinical trial protocols and the lack of data for new drugs was not reported. Very few protocols gave recommendations for oncofertility management and follow-up following the completion of cancer treatment. The research team proposes a number of recommendations that should be required for clinicians and pharmaceutical companies developing new trials.
Collapse
Affiliation(s)
- Angela Dauti
- 1 College of Arts and Sciences, Department of Chemistry, New York University , New York City, New York.,2 Population Sciences Department, Dana-Farber Cancer Institute , Boston, Massachusetts.,3 Department of Women's and Children's Medicine, School of Medical Sciences, University of New South Wales , Sydney, Australia
| | - Brigitte Gerstl
- 4 Kids Cancer Centre, Sydney Children's Hospital , Sydney, Australia
| | - Serena Chong
- 3 Department of Women's and Children's Medicine, School of Medical Sciences, University of New South Wales , Sydney, Australia
| | - Orin Chisholm
- 5 Department of Pharmaceutical Medicine, School of Medical Sciences, University of New South Wales , Sydney, Australia
| | - Antoinette Anazodo
- 3 Department of Women's and Children's Medicine, School of Medical Sciences, University of New South Wales , Sydney, Australia .,4 Kids Cancer Centre, Sydney Children's Hospital , Sydney, Australia .,6 Nelune Comprehensive Cancer Centre, Prince of Wales Hospital , Randwick, Australia
| |
Collapse
|
|
33
|
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.
Collapse
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
| |
Collapse
|
|
34
|
Danielsson Borssén Å, Wallerstedt S, Nyhlin N, Bergquist A, Lindgren S, Almer S, Werner M. Pregnancy and childbirth in women with autoimmune hepatitis is safe, even in compensated cirrhosis. Scand J Gastroenterol 2016; 51:479-85. [PMID: 26631429 DOI: 10.3109/00365521.2015.1115893] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
INTRODUCTION Autoimmune hepatitis (AIH) is a liver disease that primarily affects women. Many become ill during childbearing age, and medication can be lifelong. Few studies exist on pregnancy outcome in women with AIH. Objectives The aim was to assess the outcome of women with AIH and their children during pregnancy and postpartum. MATERIALS AND METHODS Sixty-four women from a well-characterised cohort with AIH filled out a questionnaire with information about their disease, miscarriage/abortion, pregnancies and potential birth defects in 2012. In 2004, 106 women answered the same questionnaire and their results were analysed along with the new questionnaires. RESULTS One hundred and thirty-eight women have completed the questionnaire and 100 children have been born by 58 women. Fifty-seven women (41%) had cirrhosis. In 84% of the pregnancies, the AIH was stable or milder, 32% had an increase in activity postpartum. The proportion of preterm births (before week 38) was 22%, caesarean sections 17%, malformations 3%, and two children died. Twenty-three women with cirrhosis had children after diagnosis of cirrhosis but without more complications than for non-cirrhotic mothers. However, they did have a higher prevalence of caesarean sections. CONCLUSION Pregnancy and childbirth in AIH appear to be safe for both child and mother, even in women with compensated liver cirrhosis.
Collapse
Affiliation(s)
- Åsa Danielsson Borssén
- a Department of Medicine, Sections for Hepatology and Gastroenterology , Umeå University , Umeå , Sweden
| | - Sven Wallerstedt
- b Department of Medicine, Sections for Hepatology and Gastroenterology , Sahlgrenska University Hospital at Östra Sjukhuset, Gothenburg, Sweden
| | - Nils Nyhlin
- c Department of Medicine, Sections for Hepatology and Gastroenterology , Örebro University Hospital , Örebro , Sweden
| | - Annika Bergquist
- d Department of Medicine, Sections for Hepatology and Gastroenterology , Karolinska University Hospital , Stockholm , Sweden
| | - Stefan Lindgren
- e Department of Medicine, Sections for Hepatology and Gastroenterology , University Hospital of Skåne, Malmö, Sweden
| | - Sven Almer
- d Department of Medicine, Sections for Hepatology and Gastroenterology , Karolinska University Hospital , Stockholm , Sweden
| | - Mårten Werner
- a Department of Medicine, Sections for Hepatology and Gastroenterology , Umeå University , Umeå , Sweden
| |
Collapse
|
|
35
|
Experts Opinion on the Practical Use of Azathioprine and 6-Mercaptopurine in Inflammatory Bowel Disease. Inflamm Bowel Dis 2016; 22:2733-2747. [PMID: 27760078 DOI: 10.1097/mib.0000000000000923] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The relevance of azathioprine and 6-mercaptopurine therapy in inflammatory bowel disease, Crohn's disease, and ulcerative colitis, has been challenged in recent publications. In this article, a panel of experts gives advice, based on the relevant literature, on indications and practical use of azathioprine/6-mercaptopurine, prevention, and management of drug adverse reactions and special situations such as vaccination, pregnancy, and lactation.
Collapse
|
|
36
|
Bar-Gil Shitrit A, Grisaru-Granovsky S, Ben Ya'acov A, Goldin E. Management of Inflammatory Bowel Disease During Pregnancy. Dig Dis Sci 2016; 61:2194-2204. [PMID: 27068171 DOI: 10.1007/s10620-016-4139-9] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2015] [Accepted: 03/21/2016] [Indexed: 02/08/2023]
Abstract
Inflammatory bowel disease (IBD) usually affects women during their reproductive years and many concerns arise among these young patients. Pre-pregnancy consultation with a multi-disciplinary team is very important. The team should make patients aware of the critical importance of ensuring that conception occurs during a period of disease remission. Conception during an IBD flare-up results in disease activity or even exacerbates disease in two-thirds of women. Exacerbation of the disease is associated with increased frequency of maternal and fetal complications. Drug therapy constitutes a considerable source of patient anxiety but most drugs used for treating IBD are considered safe. Therefore, continuing pharmacological therapy during pregnancy is necessary to maintain disease control. Optimization of pre-conception nutritional status and smoking cessation are also emphasized. The general guideline for most patients, except for active perianal disease patients, is to aim for vaginal delivery in the absence of obstetric contraindications. Consistent, ongoing follow-up, as detailed in this review, should allay the anxieties and fears surrounding continuing immunosuppressive drugs during pregnancy, allowing each patient to attain the optimal conditions for achieving her goal of holding a healthy baby.
Collapse
Affiliation(s)
| | - Sorina Grisaru-Granovsky
- Fetal Maternal Medicine, Obstetrics and Gynecology Department, Shaare Zedek Medical Center, Jerusalem, Israel
| | - Ami Ben Ya'acov
- IBD Center, Digestive Diseases Institute, Shaare Zedek Medical Center, Jerusalem, Israel
| | - Eran Goldin
- IBD Center, Digestive Diseases Institute, Shaare Zedek Medical Center, Jerusalem, Israel
| |
Collapse
|
|
37
|
Czaja AJ. Diagnosis and Management of Autoimmune Hepatitis: Current Status and Future Directions. Gut Liver 2016; 10:177-203. [PMID: 26934884 PMCID: PMC4780448 DOI: 10.5009/gnl15352] [Citation(s) in RCA: 98] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2015] [Accepted: 11/04/2015] [Indexed: 02/06/2023] Open
Abstract
Autoimmune hepatitis is characterized by autoantibodies, hypergammaglobulinemia, and interface hepatitis on histological examination. The features lack diagnostic specificity, and other diseases that may resemble autoimmune hepatitis must be excluded. The clinical presentation may be acute, acute severe (fulminant), or asymptomatic; conventional autoantibodies may be absent; centrilobular necrosis and bile duct changes may be present; and the disease may occur after liver transplantation or with features that suggest overlapping disorders. The diagnostic criteria have been codified, and diagnostic scoring systems can support clinical judgment. Nonstandard autoantibodies, including antibodies to actin, α-actinin, soluble liver antigen, perinuclear antineutrophil antigen, asialoglycoprotein receptor, and liver cytosol type 1, are tools that can support the diagnosis, especially in patients with atypical features. Prednisone or prednisolone in combination with azathioprine is the preferred treatment, and strategies using these medications in various doses can ameliorate treatment failure, incomplete response, drug intolerance, and relapse after drug withdrawal. Budesonide, mycophenolate mofetil, and calcineurin inhibitors can be considered in selected patients as frontline or salvage therapies. Molecular (recombinant proteins and monoclonal antibodies), cellular (adoptive transfer and antigenic manipulation), and pharmacological (antioxidants, antifibrotics, and antiapoptotic agents) interventions constitute future directions in management. The evolving knowledge of the pathogenic pathways and the advances in technology promise new management algorithms.
Collapse
Affiliation(s)
- Albert J. Czaja
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, MN,
USA
| |
Collapse
|
|
38
|
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.
Collapse
|
|
39
|
Vierling JM. Autoimmune Hepatitis and Overlap Syndromes: Diagnosis and Management. Clin Gastroenterol Hepatol 2015; 13:2088-108. [PMID: 26284592 DOI: 10.1016/j.cgh.2015.08.012] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2015] [Revised: 08/11/2015] [Accepted: 08/11/2015] [Indexed: 12/14/2022]
Affiliation(s)
- John M Vierling
- Departments of Medicine and Surgery, Baylor College of Medicine, Baylor-St Luke's Medical Center, Houston, Texas.
| |
Collapse
|
|
40
|
Damas OM, Deshpande AR, Avalos DJ, Abreu MT. Treating Inflammatory Bowel Disease in Pregnancy: The Issues We Face Today. J Crohns Colitis 2015; 9:928-36. [PMID: 26129693 DOI: 10.1093/ecco-jcc/jjv118] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2015] [Accepted: 06/25/2015] [Indexed: 12/12/2022]
Abstract
Many women of childbearing age are living with inflammatory bowel disease [IBD], yet there are limited studies on the use of IBD medications in pregnancy. In this review, we provide a comprehensive update on the safety of these medications during pregnancy, particularly thiopurines and biologicals. Antibiotics, steroids, and aminosalicylates are relatively low risk for use in pregnancy, and growing evidence supports the safety of immunomodulators and anti-tumour necrosis factor agents as well. Available studies on infliximab, adalimumab, and certolizumab pegol show no increase in adverse events during pregnancy or perinatally. Similarly, studies on lactation demonstrate that concentrations of subcutaneous anti-tumour necrosis factor biologicals are undetectable, and levels of thiopurines and infliximab are negligible in breast milk. Less is known about anti-integrins in pregnancy [eg natalizumab and vedolizumab] but currently available data suggest they may be safe as well. Although more studies are needed to examine the long-term effects of these medications on offspring, the available data provide reassuring information for providers caring for women of childbearing age.
Collapse
Affiliation(s)
- Oriana M Damas
- University of Miami Miller School of Medicine, Department of Medicine, Division of Gastroenterology, Miami, FL
| | - Amar R Deshpande
- University of Miami Miller School of Medicine, Department of Medicine, Division of Gastroenterology, Miami, FL
| | - Danny J Avalos
- University of Miami Miller School of Medicine Palm Beach Regional Campus, Internal Medicine Division, Department of Medicine, West Palm Beach, FL
| | - Maria T Abreu
- University of Miami Miller School of Medicine, Department of Medicine, Division of Gastroenterology, Miami, FL
| |
Collapse
|
|
41
|
|
|
42
|
Lee KM, Kim YS, Seo GS, Kim TO, Yang SK. Use of Thiopurines in Inflammatory Bowel Disease: A Consensus Statement by the Korean Association for the Study of Intestinal Diseases (KASID). Intest Res 2015; 13:193-207. [PMID: 26130993 PMCID: PMC4479733 DOI: 10.5217/ir.2015.13.3.193] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2015] [Revised: 04/29/2015] [Accepted: 05/06/2015] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND/AIMS For decades, thiopurines have been the mainstay of inflammatory bowel disease (IBD) treatment and will play an important role in the future. However, complex metabolism and various side effects limit the use of these potent drugs in clinical practice. The Korean Association for the Study of Intestinal Diseases developed a set of consensus statements with the aim of guiding clinicians on the appropriate use of thiopurines in the management of IBD. METHODS Sixteen statements were initially drafted by five committee members. The quality of evidence and classification of recommendation were assessed according to the Grading of Recommendations Assessment, Development and Evaluation system. The statements were then circulated to IBD experts in Korea for review, feedback, and then finalized and accepted by voting at the consensus meeting. RESULTS The consensus statements comprised four parts: (1) pre-treatment evaluation and management strategy, including value of thiopurine S-methyltransferase screening, dosing schedule, and novel biomarkers for predicting thiopurine-induced leukopenia; (2) treatment with thiopurines with regards to optimal duration of thiopurine treatment and long-term outcomes of combination therapy with anti-tumor necrosis factors; (3) safety of thiopurines, especially during pregnancy and lactation; and (4) monitoring side effects or efficacy of therapy using biomarkers. CONCLUSIONS Thiopurines are an effective treatment option for patients with IBD. Management decisions should be individualized according to the risk of relapse and adverse events.
Collapse
Affiliation(s)
- Kang-Moon Lee
- Department of Internal Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Suwon, Korea
| | - You Sun Kim
- Department of Internal Medicine, Seoul Paik Hospital, Inje University College of Medicine, Seoul, Korea
| | - Geom Seog Seo
- Department of Internal Medicine, Digestive Disease Research Institute, Wonkwang University College of Medicine, Iksan, Korea
| | - Tae Oh Kim
- Department of Internal Medicine, Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea
| | - Suk-Kyun Yang
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | | |
Collapse
|
|
43
|
|
|
44
|
van der Woude C, Ardizzone S, Bengtson M, Fiorino G, Fraser G, Katsanos K, Kolacek S, Juillerat P, Mulders A, Pedersen N, Selinger C, Sebastian S, Sturm A, Zelinkova Z, Magro F. The second European evidenced-based consensus on reproduction and pregnancy in inflammatory bowel disease. J Crohns Colitis 2015; 9:107-24. [PMID: 25602023 DOI: 10.1093/ecco-jcc/jju006] [Citation(s) in RCA: 328] [Impact Index Per Article: 32.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Trying to conceive and being pregnant is an emotional period for those involved. In the majority of patients suffering from inflammatory bowel disease, maintenance therapy is required during pregnancy to control the disease, and disease control might necessitate introduction of new drugs during a vulnerable period. In this updated consensus on the reproduction and pregnancy in inflammatory bowel disease reproductive issues including fertility, the safety of drugs during pregnancy and lactation are discussed.
Collapse
Affiliation(s)
- C.J. van der Woude
- Department of Gastroenterology and Hepatology, Erasmus MC, Rotterdam, The Netherlands
| | - S. Ardizzone
- Inflammatory Bowel Disease Unit, Department of Gastroenterology, ‘Luigi Sacco’ University Hospital, Milan, Italy
| | - M.B. Bengtson
- Department of Medicine, Vestfold Hospital Trust, Tønsberg, Norway
| | - G. Fiorino
- Department of Gastroenterology, IBD Center, IRCCS Istituto Clinico Humanitas, Rozzano, Italy
| | - G. Fraser
- eIBD Unit, Department of Gastroenterology, Rabin Medical Center and University of Tel-Aviv, Petah Tikva, Israel
| | - K. Katsanos
- Department of Gastroenterology and Hepatology, University and Medical School of Ioannina, Ioannina, Greece
| | - S. Kolacek
- Children’s Hospital Zagreb, Zagreb University Medical School, Zagreb, Croatia
| | - P. Juillerat
- Department of Gastroenterology, Clinic for Visceral Surgery and Medicine, Bern University Hospital, Bern, Switzerland
| | - A.G.M.G.J. Mulders
- Department of Obstetrics and Gynecology, Erasmus MC, Rotterdam, The Netherlands
| | - N. Pedersen
- Gastroenterological Unit, Herlev University Hospital, Herlev, Denmark
| | - C. Selinger
- Department of Gastroenterology, St James’ University Hospital Leeds, Leeds, UK
| | - S. Sebastian
- Hull & East Yorkshire Hospitals and Hull & York Medical School, Hull, UK
| | - A. Sturm
- Department of Internal Medicine and Gastroenterology, Hospital Waldfriede, Berlin, Germany
| | - Z. Zelinkova
- Gastroenterology Unit, 5th Department of Internal Medicine, University Hospital, Bratislava, Slovakia
| | - F. Magro
- Department of Pharmacology & Therapeutics, University of Porto, Porto, Portugal
- MedInUP, Center for Drug Discovery and Innovative Medicines, University of Porto, Porto, Portugal
- Department of Gastroenterology, Hospital de São João, Porto, Portugal
| | | |
Collapse
|
|
45
|
Abstract
Current therapeutic options for patients with inflammatory bowel disease (IBD) include several agents that can alter their immune response to infections. Effective vaccines exist and offer protection against a number of infectious diseases. However, recent data has shown that IBD patients are inadequately vaccinated and, as a result, at risk to develop certain preventable infections. Furthermore, gastroenterologists' knowledge regarding the appropriate immunizations to administer to their IBD patients is suboptimal. This review article focuses on the current immunization schedule for the IBD patient and stresses the important role of the gastroenterologist as an active participant in the management of vaccination in their IBD patients.
Collapse
Affiliation(s)
- Athanasios P Desalermos
- Section of Gastroenterology, Boston Medical Center, Boston University School of Medicine, 85 East Concord Street, Boston, MA 02118, USA
| | | | | |
Collapse
|
|
46
|
Abstract
PURPOSE OF REVIEW Inflammatory bowel disease (IBD) often affects women in their peak reproductive years, and therapy is often continued during pregnancy to maintain stable disease activity. Therapeutic options have expanded over the last 2 decades with the advent of new biologic options. It is, therefore, important for the gastroenterologists and other clinicians caring for patients with IBD to understand safety data regarding the treatment options, both biologic and nonbiologic, in pregnant IBD patients. RECENT FINDINGS In general, quality of evidence in this area remains low. However, larger prospective studies are beginning to provide evidence regarding the potential safety of biologics both alone and in conjunction with nonbiologic therapy. SUMMARY The majority of treatment options for IBD appears to be of low risk and may often be continued through pregnancy and lactation. Not treating IBD, for example, by discontinuing therapy prior to or with pregnancy, may pose a greater risk to mother and fetus in many cases.
Collapse
|
|
47
|
Pregnancy after heart and lung transplantation. Best Pract Res Clin Obstet Gynaecol 2014; 28:1146-62. [PMID: 25179291 DOI: 10.1016/j.bpobgyn.2014.07.019] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2014] [Revised: 07/18/2014] [Accepted: 07/21/2014] [Indexed: 12/31/2022]
Abstract
Patients awaiting transplantation should be counseled regarding posttransplant contraception and the potential adverse outcomes associated with posttransplant conception. Pregnancy should be avoided for at least 1-2 years post transplant to minimize the risks to allograft function and fetal well-being. Transplant patients, particularly lung transplant recipients, have an increased risk of maternal and neonatal pregnancy-related complications, including prematurity and low birth weight, postpartum graft loss, and long-term morbidity and mortality compared to other solid-organ recipients. Therefore, careful monitoring by a specialized transplant team is crucial. Maintenance of immunosuppression is recommended, except for mycophenolate and mammalian target of rapamycin inhibitors (mTORi), which should be replaced before conception. Immunosuppressants must be regularly monitored and dosing adjusted to avoid graft rejection. Monitoring during labor is mandatory and epidural anesthesia recommended. Vaginal delivery should be standard and cesarean delivery only performed for obstetric reasons. Breastfeeding poses risks of neonatal exposure to immunosuppressants and is generally contraindicated.
Collapse
|
|
48
|
Huang VW, Habal FM. From conception to delivery: managing the pregnant inflammatory bowel disease patient. World J Gastroenterol 2014; 20:3495-506. [PMID: 24707132 PMCID: PMC3974516 DOI: 10.3748/wjg.v20.i13.3495] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2013] [Revised: 01/12/2014] [Accepted: 02/26/2014] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel disease (IBD) typically affects patients during their adolescent and young adult years. As these are the reproductive years, patients and physicians often have concerns regarding the interaction between IBD, medications and surgery used to treat IBD, and reproduction, pregnancy outcomes, and neonatal outcomes. Studies have shown a lack of knowledge among both patients and physicians regarding reproductive issues in IBD. As the literature is constantly expanding regarding these very issues, with this review, we provide a comprehensive, updated overview of the literature on the management of the IBD patient from conception to delivery, and provide action tips to help guide the clinician in the management of the IBD patient during pregnancy.
Collapse
|
|
49
|
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.
Collapse
Affiliation(s)
- Bindia Jharap
- Department of Gastroenterology and Hepatology, VU University Medical Center, , Amsterdam, The Netherlands
| | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
50
|
Thiagarajan KMF, Arakali SR, Mealey KJ, Cardonick EH, Gaughan WJ, Davison JM, Moritz MJ, Armenti VT. Safety considerations: breastfeeding after transplant. Prog Transplant 2013; 23:137-46. [PMID: 23782661 DOI: 10.7182/pit2013803] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Organ transplant is an effective treatment for end-stage organ failure. For women, restoration of organ function can restore fertility and the ability to successfully carry a pregnancy. Posttransplant pregnancies have been reported among recipients of all types of solid organ transplants via case and center reports plus registry data. Stable graft function is dependent on prevention of rejection, currently accomplished by using maintenance immunosuppressant medications, to which the fetus is exposed in utero. Common among neonatal outcomes in transplant recipients are preterm and low-birth-weight infants. Emotional, nutritional, and immunologic benefits of breastfeeding have been well-documented and could be valuable for these newborns. Concern must be directed at the effects of the child's exposure to immunosuppressive agents excreted into the breast milk. Breastfeeding could be considered in transplant recipients if it can be shown that the level of exposure does not result in risks to the newborn, immediately and throughout childhood. Despite concerns of health care professionals, some recipients have chosen to breastfeed. Breastfeeding after transplant must be approached with consideration of many issues, and the potential risks require further study. This review focuses on benefits of breastfeeding, common immunosuppressive agents used in organ transplant recipients, a summary of the reports of women who have breastfed their infants while on immunosuppressive therapy and the published studies on breastfeeding and immunosuppressive agents. Recommendations are provided to guide health care professionals to help mothers receiving immunosuppressive agents to make informed choices about breastfeeding their infants.
Collapse
|