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Gomez-Casado G, Alonso-Titos J, Gonzalez-Mesa E, Ortega-Gomez A. Compatibility of Post-Kidney Transplant Immunosuppression Therapy with Lactation. J Clin Med 2025; 14:2364. [PMID: 40217813 PMCID: PMC11989247 DOI: 10.3390/jcm14072364] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2025] [Revised: 03/08/2025] [Accepted: 03/25/2025] [Indexed: 04/14/2025] Open
Abstract
Breastfeeding after kidney transplantation remains a complex and underexplored topic, primarily due to concerns regarding the safety of immunosuppressive therapies during lactation. Individuals who have received kidney transplants face a higher likelihood of delivering preterm infants and giving birth to babies with a low birth weight when compared with the general population. In this context, breastfeeding is increasingly important because of its advantages for preterm infants. Despite the well-established benefits of breastfeeding for both the mother and infant, the traditional recommendation has been to avoid nursing due to potential drug transmission through breast milk. However, emerging evidence suggests that certain immunosuppressants may be compatible with breastfeeding, challenging long-standing clinical guidelines. In this review, we examine the current literature on the pharmacokinetics, safety profiles, and clinical outcomes associated with key immunosuppressive agents, including cyclosporine, tacrolimus, everolimus, azathioprine, corticosteroids, and belatacept. Our work highlights that all published reports to date on the studied treatments indicate that the amount of the drug reaching breast milk is considered safe for the child's health. These conclusions, however, are derived from very short-term measurements and small numbers of patients. Therefore, we emphasize the need to design structured prospective studies to assess safety in the medium and long term. Our review aims to equip clinicians with the most up-to-date evidence on this topic, enabling them to make informed decisions regarding the compatibility of post-kidney transplant treatments with breastfeeding.
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Affiliation(s)
- Gema Gomez-Casado
- Instituto de Investigación Biomédica de Málaga—IBIMA Plataforma BIONAND, University of Malaga, 29010 Malaga, Spain; (G.G.-C.); (J.A.-T.); (E.G.-M.)
- Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, 29010 Málaga, Spain
| | - Juana Alonso-Titos
- Instituto de Investigación Biomédica de Málaga—IBIMA Plataforma BIONAND, University of Malaga, 29010 Malaga, Spain; (G.G.-C.); (J.A.-T.); (E.G.-M.)
- Nephrology Department, Regional University Hospital of Malaga, RICORS2040 (RD21/0005/0012-RD24/004/0026), 29010 Malaga, Spain
| | - Ernesto Gonzalez-Mesa
- Instituto de Investigación Biomédica de Málaga—IBIMA Plataforma BIONAND, University of Malaga, 29010 Malaga, Spain; (G.G.-C.); (J.A.-T.); (E.G.-M.)
- Department of Surgical Specialties, Biochemistry and Immunology, Faculty of Medicine, University of Malaga, 29010 Malaga, Spain
- Department of Obstetrics and Gynecology Service, Regional University Hospital of Malaga, 29010 Malaga, Spain
| | - Almudena Ortega-Gomez
- Instituto de Investigación Biomédica de Málaga—IBIMA Plataforma BIONAND, University of Malaga, 29010 Malaga, Spain; (G.G.-C.); (J.A.-T.); (E.G.-M.)
- Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, 29010 Málaga, Spain
- CIBER Fisiopatologia Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III, 28029 Madrid, Spain
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Tian X, Zhao J, Song Y, Wang Q, Li M, Liu J, Zeng X. 2022 Chinese guideline for the management of pregnancy and reproduction in systemic lupus erythematosus. RHEUMATOLOGY AND IMMUNOLOGY RESEARCH 2023; 4:115-138. [PMID: 37781682 PMCID: PMC10538620 DOI: 10.2478/rir-2023-0019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/25/2023] [Accepted: 08/19/2023] [Indexed: 10/03/2023]
Abstract
Systemic lupus erythematosus (SLE), a prevalent autoimmune disease predominantly affecting women of childbearing age, presents ongoing challenges despite notable advances in diagnosis and treatment. Although survival rates for SLE patients have significantly improved, pregnancy continues to pose a considerable obstacle. Addressing this critical need for enhanced reproductive and prenatal care, there is a pressing imperative to establish standardized protocols for peri-gestational monitoring and treatment in SLE patients. This guideline is jointly sponsored by the National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), the Chinese Systemic Lupus Erythematosus Treatment and Research Group (CSTAR), and the Chinese Research Committee of Pregnancy and Reproduction in Autoimmune Rheumatic Diseases (CHOPARD). Thirteen pertinent clinical questions have been generated through several rounds of rigorous clinical and methodological expert discussions and selections for a comprehensive understanding of key aspects in this domain. Guided by thorough examination of research evidence and expert perspectives, the formulated recommendations aim to optimize pregnancy success rates, reduce maternal and infant mortality rates, and ultimately enhance the overall well-being of SLE patients.
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Affiliation(s)
- Xinping Tian
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences& Peking Union Medical College; National Clinical Research Center for Dermatologic and Immunologic Diseases, Ministry of Science& Technology; State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College; Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing100730, China
| | - Jiuliang Zhao
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences& Peking Union Medical College; National Clinical Research Center for Dermatologic and Immunologic Diseases, Ministry of Science& Technology; State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College; Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing100730, China
| | - Yijun Song
- Department of Obstetrics, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing100730, China
| | - Qian Wang
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences& Peking Union Medical College; National Clinical Research Center for Dermatologic and Immunologic Diseases, Ministry of Science& Technology; State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College; Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing100730, China
| | - Mengtao Li
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences& Peking Union Medical College; National Clinical Research Center for Dermatologic and Immunologic Diseases, Ministry of Science& Technology; State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College; Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing100730, China
| | - Juntao Liu
- Department of Obstetrics, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing100730, China
| | - Xiaofeng Zeng
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences& Peking Union Medical College; National Clinical Research Center for Dermatologic and Immunologic Diseases, Ministry of Science& Technology; State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College; Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing100730, China
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3
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Laube R, Selinger CP, Seow CH, Christensen B, Flanagan E, Kennedy D, Mountifield R, Seeho S, Shand A, Williams AJ, Leong RW. Australian inflammatory bowel disease consensus statements for preconception, pregnancy and breast feeding. Gut 2023; 72:1040-1053. [PMID: 36944479 DOI: 10.1136/gutjnl-2022-329304] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Accepted: 02/21/2023] [Indexed: 03/23/2023]
Abstract
OBJECTIVE Because pregnancy outcomes tend to be worse in women with inflammatory bowel disease (IBD) than in those without, we aimed to update consensus statements that guide the clinical management of pregnancy in patients with IBD. DESIGN A multidisciplinary working group was established to formulate these consensus statements. A modified RAND/UCLA appropriateness method was used, consisting of a literature review, online voting, discussion meeting and a second round of voting. The overall agreement among the delegates and appropriateness of the statement are reported. RESULTS Agreement was reached for 38/39 statements which provide guidance on management of pregnancy in patients with IBD. Most medications can and should be continued throughout pregnancy, except for methotrexate, allopurinol and new small molecules, such as tofacitinib. Due to limited data, no conclusion was reached on the use of tioguanine during pregnancy. Achieving and maintaining IBD remission before conception and throughout pregnancy is crucial to optimise maternofetal outcomes. This requires a multidisciplinary approach to engage patients, allay anxieties and maximise adherence tomedication. Intestinal ultrasound can be used for disease monitoring during pregnancy, and flexible sigmoidoscopy or MRI where clinically necessary. CONCLUSION These consensus statements provide up-to-date, comprehensive recommendations for the management of pregnancy in patients with IBD. This will enable a high standard of care for patients with IBD across all clinical settings.
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Affiliation(s)
- Robyn Laube
- Faculty of Medicine and Health Sciences, Macquarie University, Sydney, New South Wales, Australia
- Department of Gastroenterology, Macquarie University Hospital, Sydney, New South Wales, Australia
| | | | - Cynthia H Seow
- Department of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Britt Christensen
- Gastroenterology Department, Royal Melbourne Hospital, Melbourne, Victoria, Australia
| | - Emma Flanagan
- Department of Gastroenterology, University of Melbourne, Melbourne, Victoria, Australia
| | - Debra Kennedy
- MotherSafe, Royal Hospital for Women, Sydney, New South Wales, Australia
| | - Reme Mountifield
- Department of Gastroenterology, Flinders Medical Centre, Adelaide, South Australia, Australia
| | - Sean Seeho
- Department of Obstetrics and Gynaecology, Royal North Shore Hospital, St Leonards, New South Wales, Australia
| | - Antonia Shand
- Department of Maternal Foetal Medicine, Royal Hospital for Women, Sydney, New South Wales, Australia
| | - Astrid-Jane Williams
- Department of Gastroenterology, Liverpool Hospital, Liverpool, New South Wales, Australia
| | - Rupert W Leong
- Faculty of Medicine and Health Sciences, Macquarie University, Sydney, New South Wales, Australia
- Department of Gastroenterology, Macquarie University Hospital, Sydney, New South Wales, Australia
- Gastroenterology and Liver Services, Concord Repatriation General Hospital, Concord, New South Wales, Australia
- The University of Sydney Faculty of Medicine and Health, Sydney, New South Wales, Australia
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Habli M, Belal D, Sharma A, Halawa A. Infertility, pregnancy and breastfeeding in kidney transplantation recipients: Key issues. World J Meta-Anal 2023; 11:55-67. [DOI: 10.13105/wjma.v11.i3.55] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2022] [Revised: 01/22/2023] [Accepted: 02/13/2023] [Indexed: 03/01/2023] Open
Abstract
Chronic kidney disease (CKD), especially in advanced stages, is an important cause of infertility. In CKD patients, infertility has been linked to multiple factors. The pathophysiology of infertility related to CKD is complex and forked. Correction of modifiable factors can improve fertility in both genders. In males as well as females, successful kidney transplantation offers good chances of restoration of reproductive function. In female renal allograft recipients, recovery of reproductive functions in the post-transplant period will manifest as restoration of normal menses and ovulation. Owing to this improvement, there is a significant risk of unplanned pregnancy, hence the need to discuss methods of contraception before transplantation. In kidney transplant recipients, different contraceptive options for pregnancy planning, have been used. The selection of one contraception over another is based on preference and tolerability. Pregnancy, in renal transplanted females, is associated with physiologic changes that occur in pregnant women with native kidneys. Immunosuppressive medications during pregnancy, in a recipient with a single functioning kidney, expose the mother and fetus to unwanted complications. Some immunosuppressive drugs are contraindicated during pregnancy. Immunosuppressive medications should be discussed with renal transplant recipients who are planning to breastfeed their babies. In addition to antirejection drugs, other medications should be managed accordingly, whenever pregnancy is planned.
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Affiliation(s)
- Mohamad Habli
- Department of Internal Medicine, Division of Nephrology, Kingdom Hospital, Riyadh 11564, Saudi Arabia
| | - Dawlat Belal
- Kasr El-Ainy School of Medicine, Cairo University, Cairo 11562, Egypt
| | - Ajay Sharma
- Royal Liverpool University Hospital, Royal Liverpool University Hospital, Liverpool L7 8YE, United Kingdom
| | - Ahmed Halawa
- Department of Transplantation, Sheffield Teaching Hospitals, Sheffield S10 2JF, United Kingdom
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Kittleson MM, DeFilippis EM, Bhagra CJ, Casale JP, Cauldwell M, Coscia LA, D'Souza R, Gaffney N, Gerovasili V, Ging P, Horsley K, Macera F, Mastrobattista JM, Paraskeva MA, Punnoose LR, Rasmusson KD, Reynaud Q, Ross HJ, Thakrar MV, Walsh MN. Reproductive health after thoracic transplantation: An ISHLT expert consensus statement. J Heart Lung Transplant 2023; 42:e1-e42. [PMID: 36528467 DOI: 10.1016/j.healun.2022.10.009] [Citation(s) in RCA: 25] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2022] [Accepted: 10/10/2022] [Indexed: 11/16/2022] Open
Abstract
Pregnancy after thoracic organ transplantation is feasible for select individuals but requires multidisciplinary subspecialty care. Key components for a successful pregnancy after lung or heart transplantation include preconception and contraceptive planning, thorough risk stratification, optimization of maternal comorbidities and fetal health through careful monitoring, and open communication with shared decision-making. The goal of this consensus statement is to summarize the current evidence and provide guidance surrounding preconception counseling, patient risk assessment, medical management, maternal and fetal outcomes, obstetric management, and pharmacologic considerations.
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Affiliation(s)
- Michelle M Kittleson
- Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California.
| | - Ersilia M DeFilippis
- Division of Cardiology, New York Presbyterian-Columbia University Irving Medical Center, New York, New York
| | - Catriona J Bhagra
- Department of Cardiology, Cambridge University and Royal Papworth NHS Foundation Trusts, Cambridge, UK
| | - Jillian P Casale
- Department of Pharmacy Services, University of Maryland Medical Center, Baltimore, Maryland
| | - Matthew Cauldwell
- Department of Obstetrics, Maternal Medicine Service, St George's Hospital, London, UK
| | - Lisa A Coscia
- Transplant Pregnancy Registry International, Gift of Life Institute, Philadelphia, Pennsylvania
| | - Rohan D'Souza
- Division of Maternal and Fetal Medicine, Department of Obstetrics and Gynecology, McMaster University, Hamilton, Ontario, Canada
| | - Nicole Gaffney
- Lung Transplant Service, Alfred Hospital, Melbourne, Australia; Department of Medicine, Central Clinical School, Monash University, Melbourne, Australia
| | | | - Patricia Ging
- Department of Pharmacy, Mater Misericordiae University Hospital, Dublin, Ireland
| | - Kristin Horsley
- Department of Obstetrics and Gynecology, McMaster University, Hamilton, Ontario, Canada
| | - Francesca Macera
- De Gasperis Cardio Center and Transplant Center, Niguarda Hospital, Milan, Italy; Dept of Cardiology, Cliniques Universitaires de Bruxelles - Hôpital Erasme, Brussels, Belgium
| | - Joan M Mastrobattista
- Department of Obstetrics & Gynecology, Division of Maternal-Fetal Medicine, Baylor College of Medicine Houston, Texas
| | - Miranda A Paraskeva
- Lung Transplant Service, Alfred Hospital, Melbourne, Australia; Department of Medicine, Central Clinical School, Monash University, Melbourne, Australia
| | - Lynn R Punnoose
- Vanderbilt Heart and Vascular Institute, Vanderbilt University Medical Center, Nashville, Tennessee
| | | | - Quitterie Reynaud
- Cystic Fibrosis Adult Referral Care Centre, Department of Internal Medicine, Hospices civils de Lyon, Pierre Bénite, France
| | - Heather J Ross
- Peter Munk Cardiac Centre of the University Health Network, Toronto, Ontario, Canada; Ted Rogers Centre for Heart Research, Toronto, Ontario, Canada; University of Toronto, Toronto, Ontario, Canada
| | - Mitesh V Thakrar
- Department of Medicine, Division of Respirology, University of Calgary, Calgary, Alberta, Canada
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Grigorescu RR, Husar-Sburlan IA, Rosulescu G, Bobirca A, Cerban R, Bobirca F, Florescu MM. Pregnancy in Patients with Inflammatory Bowel Diseases-A Literature Review. Life (Basel) 2023; 13:475. [PMID: 36836832 PMCID: PMC9961380 DOI: 10.3390/life13020475] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2022] [Revised: 02/03/2023] [Accepted: 02/04/2023] [Indexed: 02/11/2023] Open
Abstract
In recent years, we have faced an increasing incidence of inflammatory bowel disease (IBD), especially among young people, affecting them during their reproductive years. The paucity of data and reduced knowledge regarding the evolution of the disease during pregnancy and the adverse effects of the therapy on the mother and infant increase voluntary childlessness in this group of patients. Depending on the type of IBD, severity and surgical or medical management, this can negatively affect the pregnancy. C-sections and the risk of low-birth-weight babies are higher in women with IBD, independent of active/inactive disease, while preterm birth, stillbirth and miscarriage are associated with disease activity. In the last period, medicinal therapy has evolved, and new molecules have been developed for better control of the lesions, but the effect on pregnancy and breastfeeding is still controversial. We conducted this review by studying the literature and recent research in order to have a better image of the practical management of IBD during pregnancy.
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Affiliation(s)
| | | | - Georgiana Rosulescu
- Gastroenterology Department, “Sfanta Maria” Hospital, 011172 Bucharest, Romania
| | - Anca Bobirca
- Department of Internal Medicine and Rheumatology, Dr. I. Cantacuzino Clinical Hospital, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania
| | - Razvan Cerban
- Center for Digestive Disease and Liver Transplantation, Fundeni Clinical Institute, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania
| | - Florin Bobirca
- Surgery Department, Dr. Ion Cantacuzino Clinical Hospital, 011437 Bucharest, Romania
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Vukusic S, Carra-Dalliere C, Ciron J, Maillart E, Michel L, Leray E, Guennoc AM, Bourre B, Laplaud D, Androdias G, Bensa C, Bigaut K, Biotti D, Branger P, Casez O, Cohen M, Daval E, Deschamps R, Donze C, Dubessy AL, Dulau C, Durand-Dubief F, Guillaume M, Hebant B, Kremer L, Kwiatkowski A, Lannoy J, Maarouf A, Manchon E, Mathey G, Moisset X, Montcuquet A, Pique J, Roux T, Marignier R, Lebrun-Frenay C. Pregnancy and multiple sclerosis: 2022 recommendations from the French multiple sclerosis society. Mult Scler 2023; 29:11-36. [PMID: 36317497 DOI: 10.1177/13524585221129472] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
OBJECTIVE The objective of this study was to develop evidence-based recommendations on pregnancy management for persons with multiple sclerosis (MS). BACKGROUND MS typically affects young women in their childbearing years. Increasing evidence is available to inform questions raised by MS patients and health professionals about pregnancy issues. METHODS The French Group for Recommendations in Multiple Sclerosis (France4MS) reviewed PubMed and university databases (January 1975 through June 2021). The RAND/UCLA appropriateness method was developed to synthesise the scientific literature and expert opinions on healthcare topics; it was used to reach a formal agreement. Fifty-six MS experts worked on the full-text review and initial wording of recommendations. A group of 62 multidisciplinary healthcare specialists validated the final proposal of summarised evidence. RESULTS A strong agreement was reached for all 104 proposed recommendations. They cover diverse topics, such as pregnancy planning, follow-up during pregnancy and postpartum, delivery routes, locoregional analgesia or anaesthesia, prevention of postpartum relapses, breastfeeding, vaccinations, reproductive assistance, management of relapses and disease-modifying treatments. CONCLUSION The 2022 recommendations of the French MS society should be helpful to harmonise counselling and treatment practice for pregnancy in persons with MS, allowing for better and individualised choices.
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Affiliation(s)
- Sandra Vukusic
- Sclérose en Plaques, Pathologies de la Myéline et Neuro-Inflammation, Service de Neurologie, Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Bron, France/INSERM 1028 et CNRS UMR 5292, Observatoire Français de la Sclérose en Plaques, Centre de Recherche en Neurosciences de Lyon, Bron, France/Université Claude Bernard Lyon 1, Université de Lyon, Lyon, France/Eugène Devic EDMUS Foundation against Multiple Sclerosis, State-approved Foundation, Bron, France
| | | | - Jonathan Ciron
- Centre Ressources et Compétences sclérose en plaques (CRC-SEP) et Service de Neurologie B4, Hôpital Pierre-Paul Riquet, CHU Toulouse Purpan, Toulouse, France INSERM UMR1291 - CNRS UMR5051, Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse 3, Toulouse, France
| | - Elisabeth Maillart
- Neurology Department, Pitié-Salpêtrière Hospital, CRC-SEP, Paris, France
| | - Laure Michel
- Neurology Department, CIC_P1414 INSERM, Rennes University Hospital, Rennes, France
| | - Emmanuelle Leray
- EHESP, CNRS, Inserm, Arènes - UMR 6051, RSMS (Recherche sur les Services et Management en Santé) - U 1309, Université de Rennes, Rennes, France
| | | | | | - David Laplaud
- Center for Research in Transplantation and Translational Immunology, UMR 1064, Nantes Université and INSERM, Nantes, France/CIC INSERM 1413, CRC-SEP Pays de la Loire, CHU Nantes, Nantes, France
| | - Géraldine Androdias
- Sclérose en Plaques, Pathologies de la Myéline et Neuro-Inflammation, Service de Neurologie, Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Bron, France/Clinique de la Sauvegarde, Ramsay Santé, Lyon, France
| | - Caroline Bensa
- CRC-SEP, Neurology Department, Hôpital Fondation Adolphe de Rothschild, Paris, France
| | - Kevin Bigaut
- CRC-SEP, Service de Neurologie, Hôpitaux Universitaires de Strasbourg, Strasbourg, France
| | - Damien Biotti
- Centre Ressources et Compétences sclérose en plaques (CRC-SEP) et Service de Neurologie B4, Hôpital Pierre-Paul Riquet, CHU Toulouse Purpan, Toulouse, France INSERM UMR1291 - CNRS UMR5051, Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse 3, Toulouse, France
| | - Pierre Branger
- Service de Neurologie, CHU de Caen Normandie, Caen, France
| | - Olivier Casez
- Pathologies Inflammatoires du Système Nerveux, Neurologie, CHU Grenoble Alpes, Grenoble, France/Translational Research in Autoimmunity and Inflammation Group (T-RAIG), TIMC-IMAG, Université de Grenoble Alpes, Grenoble, France
| | - Mikael Cohen
- CRCSEP Côte d'Azur, CHU de Nice Pasteur 2, Nice, France/Université Nice Côte d'Azur UR2CA-URRIS, Nice, France
| | - Elodie Daval
- Service de Neurologie, CHU de Besançon, Besançon, France
| | - Romain Deschamps
- CRC-SEP, Neurology Department, Hôpital Fondation Adolphe de Rothschild, Paris, France
| | - Cécile Donze
- Hôpital saint Philibert, Groupement des Hôpitaux de l'Institut Catholique de Lille, Faculté de médecine et de maïeutique de Lille, Lomme, France
| | - Anne-Laure Dubessy
- Department of Neurology, Saint-Antoine Hospital, APHP-6, Paris, France/Sorbonne University, Paris, France
| | - Cécile Dulau
- CRC-SEP, Hôpital Pellegrin, CHU de Bordeaux, Bordeaux, France
| | - Françoise Durand-Dubief
- Sclérose en Plaques, Pathologies de la Myéline et Neuro-Inflammation, Service de Neurologie, Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Bron, France
| | | | | | - Laurent Kremer
- CRC-SEP, Service de Neurologie, Hôpitaux Universitaires de Strasbourg, Strasbourg, France
| | - Arnaud Kwiatkowski
- Department of Neurology, Lille Catholic Hospitals, Lille Catholic University, Lille, France
| | - Julien Lannoy
- Service de Neurologie, Centre Hospitalier de Lens, Lens, France
| | - Adil Maarouf
- CRMBM, UMR 7339, CNRS, Aix-Marseille Université, Marseille, France/APHM Hôpital de la Timone, Marseille, France
| | - Eric Manchon
- Department of Neurology, Gonesse Hospital, Gonesse, France
| | - Guillaume Mathey
- Service de neurologie, Centre Hospitalier Régional Universitaire de Nancy - Hôpital Central, Nancy, France
| | - Xavier Moisset
- Neuro-Dol, Inserm, Université Clermont Auvergne, Clermont-Ferrand, France/Department of neurology et CRC-SEP, CHU Clermont-Ferrand, Clermont-Ferrand, France
| | | | - Julie Pique
- Sclérose en Plaques, Pathologies de la Myéline et Neuro-Inflammation, Service de Neurologie, Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Bron, France/INSERM 1028 et CNRS UMR 5292, Centre de Recherche en Neurosciences de Lyon, Bron, France/Université Claude Bernard Lyon 1, Lyon, France
| | - Thomas Roux
- Neurology Department, Pitié-Salpêtrière Hospital, CRC-SEP, Paris, France
| | - Romain Marignier
- Sclérose en Plaques, Pathologies de la Myéline et Neuro-Inflammation, Service de Neurologie, Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Bron, France/INSERM 1028 et CNRS UMR 5292, Centre de Recherche en Neurosciences de Lyon, Lyon, France/Université Claude Bernard Lyon 1, Université de Lyon, Lyon, France
| | - Christine Lebrun-Frenay
- Service de Neurologie, CHU de Besançon, Besançon, France/Université Nice Côte d'Azur UR2CA-URRIS, Nice, France
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8
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Vukusic S, Marignier R, Ciron J, Bourre B, Cohen M, Deschamps R, Guillaume M, Kremer L, Pique J, Carra-Dalliere C, Michel L, Leray E, Guennoc AM, Laplaud D, Androdias G, Bensa C, Bigaut K, Biotti D, Branger P, Casez O, Daval E, Donze C, Dubessy AL, Dulau C, Durand-Dubief F, Hebant B, Kwiatkowski A, Lannoy J, Maarouf A, Manchon E, Mathey G, Moisset X, Montcuquet A, Roux T, Maillart E, Lebrun-Frenay C. Pregnancy and neuromyelitis optica spectrum disorders: 2022 recommendations from the French Multiple Sclerosis Society. Mult Scler 2023; 29:37-51. [PMID: 36345839 DOI: 10.1177/13524585221130934] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Abstract
BACKGROUND In 2020, the French Multiple Sclerosis (MS) Society (SFSEP) decided to develop a national evidence-based consensus on pregnancy in MS. As neuromyelitis optica spectrum disorders (NMOSD) shares a series of commonalities with MS, but also some significant differences, specific recommendations had to be developed. OBJECTIVES To establish recommendations on pregnancy in women with NMOSD. METHODS The French Group for Recommendations in Multiple Sclerosis (France4MS) reviewed PubMed and universities databases (January 1975 through June 2021). The RAND/UCLA appropriateness method, which was developed to synthesise the scientific literature and expert opinions on health care topics, was used to reach a formal agreement. Fifty-six MS experts worked on the full-text review and initial wording of recommendations. A sub-group of nine NMOSD experts was dedicated to analysing available data on NMOSD. A group of 62 multidisciplinary healthcare specialists validated the final proposal of summarised evidence. RESULTS A strong agreement was reached for all 66 proposed recommendations. They cover diverse topics, such as pregnancy planning, follow-up during pregnancy and postpartum, delivery routes, loco-regional analgesia or anaesthesia, prevention of postpartum relapses, breastfeeding, vaccinations, reproductive assistance, management of relapses, and disease-modifying treatments. CONCLUSION Physicians and patients should be aware of the new and specific evidence-based recommendations of the French MS Society for pregnancy in women with NMOSD. They should help harmonise counselling and treatment practise, allowing for better individualised choices.
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Affiliation(s)
- Sandra Vukusic
- Service de Neurologie, Sclérose en Plaques, Pathologies de la Myéline et Neuro-Inflammation, Hospices Civils de Lyon, Hôpital Neurologique Pierre Wertheimer, Bron, France/INSERM 1028 et CNRS UMR 5292, Observatoire Français de la Sclérose en Plaques, Centre de Recherche en Neurosciences de Lyon, Lyon, France/Université de Lyon, Université Claude Bernard Lyon 1, Lyon, France/Eugène Devic EDMUS Foundation against Multiple Sclerosis, State-Approved Foundation, Bron, France
| | - Romain Marignier
- Université de Lyon, Université Claude Bernard Lyon 1, Lyon, France/Hospices Civils de Lyon, Service de Neurologie, Sclérose en Plaques, Pathologies de la Myéline et Neuro-Inflammation, and Centre de Référence des Maladies Inflammatoires Rares du Cerveau et de la Moelle (MIRCEM), Hôpital Neurologique Pierre Wertheimer, Bron, France/FORGETTING Team, INSERM 1028 et CNRS UMR5292, Centre des Neurosciences de Lyon, Lyon, France
| | - Jonathan Ciron
- Centre Ressources et Compétences Sclérose en Plaques (CRC-SEP) et Service de Neurologie B4, Hôpital Pierre-Paul Riquet, CHU Toulouse Purpan, Toulouse, France/INSERM UMR1291 - CNRS UMR5051, Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III, Toulouse, France
| | | | - Mikael Cohen
- CRCSEP Côte d'Azur, CHU de Nice Pasteur 2, Nice, France/UR2CA-URRIS, Université Nice Côte d'Azur, Nice, France
| | - Romain Deschamps
- CRC-SEP, Neurology Department, Hôpital Fondation Adolphe de Rothschild, Paris, France
| | | | - Laurent Kremer
- CRC-SEP, Service de Neurologie, Hôpitaux Universitaires de Strasbourg, Strasbourg, France
| | - Julie Pique
- Hospices Civils de Lyon, Service de Neurologie, Sclérose en Plaques, Pathologies de la Myéline et Neuro-Inflammation, and Centre de Référence des Maladies Inflammatoires Rares du Cerveau et de la Moelle (MIRCEM), Hôpital Neurologique Pierre Wertheimer, Bron, France
| | - Clarisse Carra-Dalliere
- CRC-SEP, Neurology Department, Hôpital Gui de Chauliac, CHU de Montpellier, Montpellier, France
| | - Laure Michel
- CIC_P1414 INSERM, Neurology Department, Rennes University Hospital, Rennes, France
| | - Emmanuelle Leray
- EHESP, CNRS, Inserm, Arènes - UMR 6051, RSMS (Recherche sur les Services et Management en Santé), Université de Rennes, Rennes, France
| | | | - David Laplaud
- INSERM, Center for Research in Transplantation and Translational Immunology, Nantes Université, Nantes, France/CIC INSERM 1413, CRC-SEP Pays de la Loire, CHU Nantes, Nantes, France
| | - Géraldine Androdias
- Service de Neurologie, Sclérose en Plaques, Pathologies de la Myéline et Neuro-Inflammation, Hospices Civils de Lyon, Hôpital Neurologique Pierre Wertheimer, Bron, France/Ramsay Santé, Clinique de la Sauvegarde, Lyon, France
| | - Caroline Bensa
- CRC-SEP, Neurology Department, Hôpital Fondation Adolphe de Rothschild, Paris, France
| | - Kevin Bigaut
- CRC-SEP, Service de Neurologie, Hôpitaux Universitaires de Strasbourg, Strasbourg, France
| | - Damien Biotti
- Centre Ressources et Compétences Sclérose en Plaques (CRC-SEP) et Service de Neurologie B4, Hôpital Pierre-Paul Riquet, CHU Toulouse Purpan, Toulouse, France/INSERM UMR1291 - CNRS UMR5051, Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III, Toulouse, France
| | - Pierre Branger
- Service de Neurologie, CHU de Caen Normandie, Caen, France
| | - Olivier Casez
- Neurologie, Pathologies Inflammatoires du Système Nerveux, CHU Grenoble Alpes, Grenoble, France/TIMC-IMAG, T-RAIG (Translational Research in Autoimmunity and Inflammation Group), Université de Grenoble Alpes, Grenoble, France
| | - Elodie Daval
- Service de Neurologie, CHU de Besançon, Besançon, France
| | - Cécile Donze
- Faculté de Médecine et de Maïeutique de Lille, Groupement des Hôpitaux de l'Institut Catholique de Lille, Hôpital Saint Philibert, Lille, France
| | - Anne-Laure Dubessy
- APHP-6, Department of Neurology, Saint-Antoine Hospital, Paris, France/Sorbonne University, Paris, France
| | - Cécile Dulau
- CRC-SEP, Hôpital Pellegrin, CHU de Bordeaux, Bordeaux, France
| | - Françoise Durand-Dubief
- Service de Neurologie, Sclérose en Plaques, Pathologies de la Myéline et Neuro-Inflammation, Hospices Civils de Lyon, Hôpital Neurologique Pierre Wertheimer, Bron, France
| | | | - Arnaud Kwiatkowski
- Department of Neurology, Lille Catholic Hospitals, Lille Catholic University, Lille, France
| | - Julien Lannoy
- Service de Neurologie, Centre Hospitalier de Lens, Lens, France
| | - Adil Maarouf
- CNRS, CRMBM, UMR 7339, Aix-Marseille Université, Marseille, France/APHM, Hôpital de la Timone, Marseille, France
| | - Eric Manchon
- Department of Neurology, Gonesse Hospital, Gonesse, France
| | - Guillaume Mathey
- Service de Neurologie, Hôpital Central, Centre Hospitalier Régional Universitaire de Nancy, Nancy, France
| | - Xavier Moisset
- Inserm, Neuro-Dol, Université Clermont Auvergne, Clermont-Ferrand, France/Department of Neurology et CRC-SEP, CHU Clermont-Ferrand, Clermont-Ferrand, France
| | | | - Thomas Roux
- CRC-SEP, Neurology Department, Pitié-Salpêtrière Hospital, Paris, France
| | - Elisabeth Maillart
- CRC-SEP, Neurology Department, Pitié-Salpêtrière Hospital, Paris, France
| | - Christine Lebrun-Frenay
- CRCSEP Côte d'Azur, CHU de Nice Pasteur 2, Nice, France/UR2CA-URRIS, Université Nice Côte d'Azur, Nice, France
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9
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Russell MD, Dey M, Flint J, Davie P, Allen A, Crossley A, Frishman M, Gayed M, Hodson K, Khamashta M, Moore L, Panchal S, Piper M, Reid C, Saxby K, Schreiber K, Senvar N, Tosounidou S, van de Venne M, Warburton L, Williams D, Yee CS, Gordon C, Giles I, Roddy E, Armon K, Astell L, Cotton C, Davidson A, Fordham S, Jones C, Joyce C, Kuttikat A, McLaren Z, Merrison K, Mewar D, Mootoo A, Williams E. British Society for Rheumatology guideline on prescribing drugs in pregnancy and breastfeeding: immunomodulatory anti-rheumatic drugs and corticosteroids. Rheumatology (Oxford) 2022; 62:e48-e88. [PMID: 36318966 PMCID: PMC10070073 DOI: 10.1093/rheumatology/keac551] [Citation(s) in RCA: 82] [Impact Index Per Article: 27.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Accepted: 09/15/2022] [Indexed: 11/07/2022] Open
Affiliation(s)
- Mark D Russell
- Centre for Rheumatic Diseases, King's College London, London, UK
| | - Mrinalini Dey
- Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK
| | - Julia Flint
- Department of Rheumatology, Robert Jones and Agnes Hunt Orthopaedic Hospital NHS Foundation Trust, Shropshire, UK
| | - Philippa Davie
- Centre for Rheumatic Diseases, King's College London, London, UK
| | - Alexander Allen
- Clinical Affairs, British Society for Rheumatology, London, UK
| | | | - Margreta Frishman
- Rheumatology, North Middlesex University Hospital NHS Trust, London, UK
| | - Mary Gayed
- Rheumatology, Sandwell and West Birmingham Hospitals, Birmingham, UK
| | | | - Munther Khamashta
- Lupus Research Unit, Division of Women's Health, King's College London, London, UK
| | - Louise Moore
- Rheumatic and Musculoskeletal Disease Unit, Our Lady's Hospice and Care Service, Dublin, Ireland
| | - Sonia Panchal
- Department of Rheumatology, South Warwickshire NHS Foundation Trust, Warwickshire, UK
| | - Madeleine Piper
- Royal National Hospital for Rheumatic Diseases, Royal United Hospital, Bath, UK
| | | | - Katherine Saxby
- Pharmacy, University College London Hospitals NHS Foundation Trust, London, UK
| | - Karen Schreiber
- Thrombosis and Haemostasis, Guy's and St Thomas' NHS Foundation Trust, London, UK.,Department of Rheumatology, Danish Hospital for Rheumatic Diseases, Sonderborg, Denmark.,Department of Regional Health Research (IRS), University of Southern Denmark, Odense, Denmark
| | - Naz Senvar
- Obstetrics and Gynaecology, St George's University Hospitals NHS Foundation Trust, London, UK
| | - Sofia Tosounidou
- Lupus UK Centre of Excellence, Sandwell and West Birmingham Hospitals NHS Trust, Birmingham, UK
| | | | | | - David Williams
- Obstetrics, University College London Hospitals NHS Foundation Trust, London, UK
| | - Chee-Seng Yee
- Department of Rheumatology, Doncaster and Bassetlaw Teaching Hospitals NHS Foundation Trust, Doncaster, UK
| | - Caroline Gordon
- Rheumatology Research Group, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK
| | - Ian Giles
- Centre for Rheumatology, Division of Medicine, University College London, London, UK
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10
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McKinzie CJ, Casale JP, Guerci JC, Prom A, Doligalski CT. Outcomes of Children with Fetal and Lactation Immunosuppression Exposure Born to Female Transplant Recipients. Paediatr Drugs 2022; 24:483-497. [PMID: 35870080 DOI: 10.1007/s40272-022-00525-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/06/2022] [Indexed: 10/16/2022]
Abstract
Solid organ transplantation (SOT) is a lifesaving procedure for those with end-stage kidney, liver, heart, lung, and intestinal diseases, including females of childbearing age who wish to proceed with pregnancy following transplantation. While there is clear risk associated with use of mycophenolate during pregnancy, the risks associated with use of other immunosuppressant agents are less well understood, and the timing of use in pregnancy may be pertinent when considering the risk versus benefit for individual patients. In addition to overall fetal outcomes, including gestational age, birth weight, and mortality, this review summarizes published literature on additional complications that have been examined in association with maternal use during pregnancy and postpartum while breastfeeding. Compared with non-transplant pregnancies, pregnancies in transplant recipients are associated with lower birth weight and earlier gestational age. Effects associated with particular immunosuppressant agents in the infant include renal dysfunction from calcineurin inhibitors, myelosuppression from azathioprine, and decreased circulating immune cells with several agents. However, these effects are noted to primarily be transient, though the decrease in immune cells may predispose the infant to increased infectious complications in the first year of life. Utilizing relative infant dose estimations, nearly all commonly utilized immunosuppressants are likely safe during breastfeeding given the limited exposure to the infant.
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Affiliation(s)
- Cameron J McKinzie
- Department of Pharmacy, University of North Carolina Medical Center, Chapel Hill, NC, USA
| | - Jillian P Casale
- Department of Pharmacy, University of Maryland Medical Center, Baltimore, MD, USA
| | - Jack C Guerci
- Department of Pharmacy, University of North Carolina Medical Center, Chapel Hill, NC, USA
| | - Alyson Prom
- Department of Pharmacy, University of North Carolina Medical Center, Chapel Hill, NC, USA
| | - Christina T Doligalski
- Department of Pharmacy, University of North Carolina Medical Center, Chapel Hill, NC, USA.
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11
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Kim JW, Suh CH. The Safety of Medications During Pregnancy and Lactation in Patients with Inflammatory Rheumatic Diseases. EUROPEAN MEDICAL JOURNAL 2021. [DOI: 10.33590/emj/21-00017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
Abstract
The advances in treatments, including disease-modifying anti-rheumatic drugs and biologic agents, have significantly improved the management of inflammatory rheumatic diseases, allowing females with severe disease to become pregnant and lactate, previously considered as prohibited. Maintaining low disease activity with medications known to be safe from pre-conception to post-partum is a key point in reducing adverse pregnancy outcomes. Numerous observational and case studies have provided a growing amount of evidence on the use of safe anti-rheumatic medications in patients during pregnancy and lactation. Based on this information, this review discusses the safety of medications for patients with inflammatory rheumatic diseases during pregnancy and lactation. Among these, hydroxychloroquine, sulfasalazine, azathioprine, low-dose glucocorticoids, and low-dose aspirin are considered compatible with pregnancy, while methotrexate, cyclophosphamide, mycophenolate mofetil, and leflunomide are contraindicated. Non-steroidal anti-inflammatory drugs are only recommended for use early in pregnancy, as they are reported to cause rare but serious kidney problems in the fetus after 20 weeks or later. Cyclosporin, tacrolimus, and anti-TNF agents can be continued throughout pregnancy if the benefit is greater than the potential risk for the individual patient. Physicians should carefully weigh the risks and benefits of medications in patients with inflammatory rheumatic diseases considering pregnancy.
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Affiliation(s)
- Ji-Won Kim
- Department of Rheumatology, Ajou University School of Medicine, Suwon, Korea
| | - Chang-Hee Suh
- Department of Rheumatology, Ajou University School of Medicine, Suwon, Korea
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12
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The positive effect of pregnancy in rheumatoid arthritis and the use of medications for the management of rheumatoid arthritis during pregnancy. Inflammopharmacology 2021; 29:987-1000. [PMID: 33844107 DOI: 10.1007/s10787-021-00808-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2021] [Accepted: 03/30/2021] [Indexed: 01/30/2023]
Abstract
Rheumatoid arthritis (RA) is an autoimmune systemic inflammatory disorder that is mostly characterised by progressive symmetrical joint destruction, particularly in the wrist and fingers, while it may also affect additional joints and several organs, such as the skin, heart, blood vessels, and lungs. It is identified by raised anti-rheumatoid factor and anti-cyclic citrullinated peptide antibodies. The chemical mediators involved in the activity of RA are IL-1β, TNF-α, and IL-6. Pregnancy exerts a positive effect on RA that helps to modulate the disease condition. Different hypotheses are recommended to explain the ameliorating effect of pregnancy in RA. RA cannot be completely cured. The treatment goal is the attrition of pain and inflammation and the further progression of the disease. Long-term management of RA is carried out using disease-modifying antirheumatic drugs (DMARDs). Therapy of acute flares can be done with Non-steroidal anti-inflammatory drugs (NSAIDs) accompanied by ad interim usage of glucocorticoids. Biologic response modifiers are also available; they act by abolishing the activity of T- cells. However, it is necessary to select the correct treatment regimen when it comes to the management of RA in pregnancy.
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13
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Laube R, Paramsothy S, Leong RW. Use of medications during pregnancy and breastfeeding for Crohn's disease and ulcerative colitis. Expert Opin Drug Saf 2021; 20:275-292. [PMID: 33412078 DOI: 10.1080/14740338.2021.1873948] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Introduction: The peak age of diagnosis of inflammatory bowel disease (IBD) occurs during childbearing years, therefore management of IBD during pregnancy is a frequent occurrence. Maintenance of disease remission is crucial to optimize pregnancy outcomes, and potential maternal or fetal toxicity from medications must be balanced against the risks of untreated IBD.Areas covered: This review summarizes the literature on safety and use of medications for IBD during pregnancy and lactation.Expert opinion: 5-aminosalicylates, corticosteroids and thiopurines are safe for use during pregnancy, while methotrexate and tofacitinib should only be used with extreme caution. Anti-TNF agents (except certolizumab), vedolizumab, ustekinumab and tofacitinib readily traverse the placenta via active transport, therefore theoretically may affect fetal development. Certolizumab only undergoes passive transfer across the placenta, thus has markedly lower cord blood levels making it likely the safest biologic agent for infants. There is reasonable evidence to support the safety of anti-TNF monotherapy and combination therapy during pregnancy and lactation. Vedolizumab and ustekinumab are also thought to be safe in pregnancy and lactation, while tofacitinib is generally avoided due to teratogenic effects in animal studies.
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Affiliation(s)
- Robyn Laube
- Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Australia.,Department of Gastroenterology, Macquarie University Hospital, Sydney, Australia
| | - Sudarshan Paramsothy
- Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Australia.,Department of Gastroenterology, Macquarie University Hospital, Sydney, Australia.,Department of Gastroenterology and Hepatology, Concord Repatriation General Hospital, Sydney, Australia
| | - Rupert W Leong
- Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Australia.,Department of Gastroenterology, Macquarie University Hospital, Sydney, Australia.,Department of Gastroenterology and Hepatology, Concord Repatriation General Hospital, Sydney, Australia
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14
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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.
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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
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15
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Krain RL, Chen KL, Werth VP. Management of autoimmune blistering diseases in pregnancy and the neonate. GIORN ITAL DERMAT V 2019; 154:539-549. [PMID: 31195784 DOI: 10.23736/s0392-0488.19.06375-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
The management of autoimmune blistering diseases (AIBD) is therapeutically challenging, particularly in patients who plan to conceive, or are pregnant or breastfeeding. Not only is a patient's immune system altered by pregnancy-associated hormonal changes, but several medications used for AIBD treatment are not recommended for use in pregnancy or lactation. The data acquired regarding the safety and efficacy of these therapeutic interventions are gathered from studies or case reports from other diseases, as the treatment modalities are similar and randomized controlled trials are typically not performed in the setting of pregnancy. Although some medications for AIBD treatment are considered unsafe for use in pregnancy, many effective and tolerable therapies are able to provide benefit to these patients. In fact, most first-line agents may be used in pregnancy, to a given extent. This article discusses the medications used to treat AIBD prior to conception, during pregnancy, and while breastfeeding, as well as highlights those that are contraindicated. The preferred approach to management in these patients is also discussed. Additionally, we present the available information regarding neonates of mothers with a diagnosis of AIBD, including the likelihood, identification, and management of neonatal blistering and the effects from medication exposure in utero.
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Affiliation(s)
- Rebecca L Krain
- Department of Dermatology, Corporal Michael J. Crescenz VAMC, Philadelphia, PA, USA.,Department of Dermatology, University of Pennsylvania, Philadelphia, PA, USA
| | - Kristen L Chen
- Department of Dermatology, Corporal Michael J. Crescenz VAMC, Philadelphia, PA, USA.,Department of Dermatology, University of Pennsylvania, Philadelphia, PA, USA
| | - Victoria P Werth
- Department of Dermatology, Corporal Michael J. Crescenz VAMC, Philadelphia, PA, USA - .,Department of Dermatology, University of Pennsylvania, Philadelphia, PA, USA
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16
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Sammaritano LR, Bermas BL. Management of pregnancy and lactation. Best Pract Res Clin Rheumatol 2018; 32:750-766. [DOI: 10.1016/j.berh.2019.03.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
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17
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Papp KA, Haraoui B, Kumar D, Marshall JK, Bissonnette R, Bitton A, Bressler B, Gooderham M, Ho V, Jamal S, Pope JE, Steinhart AH, Vinh DC, Wade J. Vaccination Guidelines for Patients With Immune-Mediated Disorders on Immunosuppressive Therapies. J Cutan Med Surg 2018; 23:50-74. [PMID: 30463418 PMCID: PMC6330697 DOI: 10.1177/1203475418811335] [Citation(s) in RCA: 74] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
BACKGROUND: Patients with immune-mediated diseases on immunosuppressive therapies have more infectious episodes than healthy individuals, yet vaccination practices by physicians for this patient population remain suboptimal. OBJECTIVES: To evaluate the safety and efficacy of vaccines in individuals exposed to immunosuppressive therapies and provide evidence-based clinical practice recommendations. METHODS: A literature search for vaccination safety and efficacy in patients on immunosuppressive therapies (2009-2017) was conducted. Results were assessed using the Grading of Recommendation, Assessment, Development, and Evaluation system. RESULTS: Several immunosuppressive therapies attenuate vaccine response. Thus, vaccines should be administered before treatment whenever feasible. Inactivated vaccines can be administered without treatment discontinuation. Similarly, evidence suggests that the live zoster vaccine is safe and effective while on select immunosuppressive therapy, although use of the subunit vaccine is preferred. Caution regarding other live vaccines is warranted. Drug pharmacokinetics, duration of vaccine-induced viremia, and immune response kinetics should be considered to determine appropriate timing of vaccination and treatment (re)initiation. Infants exposed to immunosuppressive therapies through breastmilk can usually be immunized according to local guidelines. Intrauterine exposure to immunosuppressive agents is not a contraindication for inactivated vaccines. Live attenuated vaccines scheduled for infants and children ⩾12 months of age, including measles, mumps, rubella, and varicella, can be safely administered as sufficient time has elapsed for drug clearance. CONCLUSIONS: Immunosuppressive agents may attenuate vaccine responses, but protective benefit is generally maintained. While these recommendations are evidence based, they do not replace clinical judgment, and decisions regarding vaccination must carefully assess the risks, benefits, and circumstances of individual patients.
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Affiliation(s)
- Kim A Papp
- 1 K Papp Clinical Research, Waterloo, ON, Canada.,2 Probity Medical Research, Waterloo, ON, Canada
| | - Boulos Haraoui
- 3 Centre Hospitalier de l'Université de Montréal, Montreal, QC, Canada
| | - Deepali Kumar
- 4 University Health Network, Toronto, ON, Canada.,5 Faculty of Medicine, University of Toronto, Toronto, ON, Canada
| | - John K Marshall
- 6 Department of Medicine and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
| | | | - Alain Bitton
- 8 McGill University Health Centre, Montreal, QC, Canada
| | - Brian Bressler
- 9 Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.,10 St Paul's Hospital, Vancouver, BC, Canada
| | - Melinda Gooderham
- 2 Probity Medical Research, Waterloo, ON, Canada.,11 Faculty of Medicine, Queen's University, Kingston, ON, Canada
| | - Vincent Ho
- 9 Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada
| | - Shahin Jamal
- 12 Vancouver Coastal Health, Vancouver, BC, Canada
| | - Janet E Pope
- 13 Faculty of Medicine, University of Western Ontario, London, ON, Canada.,14 St Joseph's Health Care, London, ON, Canada
| | - A Hillary Steinhart
- 5 Faculty of Medicine, University of Toronto, Toronto, ON, Canada.,15 Mount Sinai Hospital, Toronto, ON, Canada
| | - Donald C Vinh
- 8 McGill University Health Centre, Montreal, QC, Canada.,16 Research Institute, McGill University Health Centre, Montreal, QC, Canada
| | - John Wade
- 9 Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.,17 Vancouver General Hospital, Vancouver, BC, Canada
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18
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Abstract
While much of the existing literature in the field of reproductive rheumatology focuses on fertility, preconception counseling, and pregnancy, there is limited information regarding the postpartum period and lactation. Evidence suggests that many rheumatologic disorders flare after delivery, which, along with limitations in medications compatible with breastfeeding, make this time period challenging for women with rheumatologic conditions. This article discusses rheumatologic disease activity during the postpartum period and reviews the safety during lactation of commonly used medications for the management of rheumatic diseases. Fortunately, many of the commonly used medications are compatible with breastfeeding.
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19
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Pinder M, Lummis K, Selinger CP. Managing inflammatory bowel disease in pregnancy: current perspectives. Clin Exp Gastroenterol 2016; 9:325-335. [PMID: 27789969 PMCID: PMC5072556 DOI: 10.2147/ceg.s96676] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Inflammatory bowel disease (IBD) affects many women of childbearing age. The course of IBD is closely related to pregnancy outcomes with poorly controlled IBD increasing the risk of prematurity, low weight for gestation, and fetal loss. As such, women with IBD face complex decision making weighing the risks of active disease versus those of medical treatments. This review summarizes the current evidence regarding the safety and efficacy of IBD treatments during pregnancy and lactation aiming to provide up-to-date guidance for clinicians. Over 50% of women have poor IBD- and pregnancy-related knowledge, which is associated with views contrary to medical evidence and voluntary childlessness. This review highlights the effects of poor patient knowledge and critically evaluates interventions for improving patient knowledge and outcomes.
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Affiliation(s)
- Matthew Pinder
- Leeds Gastroenterology Institute, Leeds Teaching Hospitals NHS Trust
| | - Katie Lummis
- Leeds Gastroenterology Institute, Leeds Teaching Hospitals NHS Trust
| | - Christian P Selinger
- Leeds Gastroenterology Institute, Leeds Teaching Hospitals NHS Trust
- University of Leeds, Leeds, UK
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20
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Abstract
There are currently limited data on the management of eosinophilic esophagitis (EoE) during pregnancy. At our center, however, we have followed several pregnant women with EoE and others have asked pertinent questions in pre-pregnancy counseling. The relatively young age of patients with EoE implies that many practitioners will also encounter patients with these questions. In this review, we use four cases to prompt a discussion about concerns focused on the safety of steroids and diet therapy during pregnancy and breast-feeding, potential nutritional risks with dietary elimination, how to optimize therapy, and whether endoscopic evaluation for monitoring of disease activity is safe during pregnancy and breast-feeding. An additional concern is whether the disease could progress during pregnancy and breast-feeding if no therapies are used. Although there are no studies specifically examining pregnant EoE patients, we have reviewed the literature relevant to this population as informed by the treatment of inflammatory bowel disease patients during pregnancy, where these issues have been studied in more depth. Providers who care for EoE patients who could become pregnant should familiarize themselves with these issues.
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21
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Krause ML, Makol A. Management of rheumatoid arthritis during pregnancy: challenges and solutions. Open Access Rheumatol 2016; 8:23-36. [PMID: 27843367 PMCID: PMC5098768 DOI: 10.2147/oarrr.s85340] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Rheumatoid arthritis, a chronic inflammatory autoimmune disease with significant physical disability, affects women three times more frequently than men, often in their childbearing years. Parenthood decisions can be challenging, often affected by perceptions of their disease state, health care needs, and complex pharmacological treatments. Many women struggle to find adequate information to guide them on pregnancy planning, lactation, and early parenting in relation to their chronic condition. The expanded availability and choice of pharmacotherapies have supported optimal disease control prior to conception and enhanced physical capabilities for women to successfully overcome the challenges of raising children but require a detailed understanding of their risks and safety in the setting of pregnancy and breastfeeding. This review outlines the various situational challenges faced by rheumatologists in providing care to men and women in the reproductive age group interested in starting a family. Up to date evidence-based solutions particularly focusing on the safe use of disease-modifying antirheumatic drugs and biologic response modifiers to assist rheumatologists in the care of pregnant and lactating women with RA are reviewed.
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Affiliation(s)
- Megan L Krause
- Division of Rheumatology, Department of Internal Medicine, Mayo Clinic, MN, USA
| | - Ashima Makol
- Division of Rheumatology, Department of Internal Medicine, Mayo Clinic, MN, USA
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22
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Nguyen GC, Seow CH, Maxwell C, Huang V, Leung Y, Jones J, Leontiadis GI, Tse F, Mahadevan U, van der Woude CJ. The Toronto Consensus Statements for the Management of Inflammatory Bowel Disease in Pregnancy. Gastroenterology 2016; 150:734-757.e1. [PMID: 26688268 DOI: 10.1053/j.gastro.2015.12.003] [Citation(s) in RCA: 339] [Impact Index Per Article: 37.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS The management of inflammatory bowel disease (IBD) poses a particular challenge during pregnancy because the health of both the mother and the fetus must be considered. METHODS A systematic literature search identified studies on the management of IBD during pregnancy. The quality of evidence and strength of recommendations were rated using the Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach. RESULTS Consensus was reached on 29 of the 30 recommendations considered. Preconception counseling and access to specialist care are paramount in optimizing disease management. In general, women on 5-ASA, thiopurine, or anti-tumor necrosis factor (TNF) monotherapy for maintenance should continue therapy throughout pregnancy. Discontinuation of anti-TNF therapy or switching from combination therapy to monotherapy may be considered in very select low-risk patients. Women who have a mild to moderate disease flare while on optimized 5-ASA or thiopurine therapy should be managed with systemic corticosteroid or anti-TNF therapy, and those with a corticosteroid-resistant flare should start anti-TNF therapy. Endoscopy or urgent surgery should not be delayed during pregnancy if indicated. Decisions regarding cesarean delivery should be based on obstetric considerations and not the diagnosis of IBD alone, with the exception of women with active perianal Crohn's disease. With the exception of methotrexate, the use of medications for IBD should not influence the decision to breast-feed and vice versa. Live vaccinations are not recommended within the first 6 months of life in the offspring of women who were on anti-TNF therapy during pregnancy. CONCLUSIONS Optimal management of IBD before and during pregnancy is essential to achieving favorable maternal and neonatal outcomes.
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Affiliation(s)
- Geoffrey C Nguyen
- Mount Sinai Hospital Centre for Inflammatory Bowel Disease, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
| | - Cynthia H Seow
- Departments of Medicine & Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
| | - Cynthia Maxwell
- Department of Obstetrics and Gynecology, University of Toronto, Toronto, Ontario, Canada
| | - Vivian Huang
- Division of Gastroenterology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
| | - Yvette Leung
- Division of Gastroenterology, University of Calgary, Calgary, Alberta, Canada
| | - Jennifer Jones
- Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada
| | | | - Frances Tse
- Department of Medicine, McMaster University, Hamilton, Ontario, Canada
| | - Uma Mahadevan
- Department of Medicine, University of California, San Francisco, San Francisco, California
| | - C Janneke van der Woude
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands
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23
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Almas S, Vance J, Baker T, Hale T. Management of Multiple Sclerosis in the Breastfeeding Mother. Mult Scler Int 2016; 2016:6527458. [PMID: 26966579 PMCID: PMC4757692 DOI: 10.1155/2016/6527458] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2015] [Revised: 12/30/2015] [Accepted: 12/31/2015] [Indexed: 12/12/2022] Open
Abstract
Multiple Sclerosis (MS) is an autoimmune neurological disease characterized by inflammation of the brain and spinal cord. Relapsing-Remitting MS is characterized by acute attacks followed by remission. Treatment is aimed at halting these attacks; therapy may last for months to years. Because MS disproportionately affects females and commonly begins during the childbearing years, clinicians treat pregnant or nursing MS patients. The intent of this review is to perform an in-depth analysis into the safety of drugs used in breastfeeding women with MS. This paper is composed of several drugs used in the treatment of MS and current research regarding their safety in breastfeeding including immunomodulators, immunosuppressants, monoclonal antibodies, corticosteroids, and drugs used for symptomatic treatment. Typically, some medications are large polar molecules which often do not pass into the milk in clinically relevant amounts. For this reason, interferon beta is likely safe for the infant when given to a breastfeeding mother. However, other drugs with particularly dangerous side effects may not be recommended. While treatment options are available and some data from clinical studies does exist, there continues to be a need for investigation and ongoing review of the medications used in breastfeeding mothers.
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Affiliation(s)
- Saneea Almas
- Department of Pediatrics, School of Medicine, Texas Tech University Health Sciences Center, 1400 Wallace Boulevard, Amarillo, TX 79106, USA
| | - Jesse Vance
- Infant Risk Center, Texas Tech University Health Sciences Center, 1400 Wallace Boulevard, Amarillo, TX 79106, USA
| | - Teresa Baker
- Department of Obstetrics & Gynecology, School of Medicine, Texas Tech University Health Sciences Center, 1400 Coulter Street, Amarillo, TX 79106, USA
| | - Thomas Hale
- Department of Pediatrics, School of Medicine, Texas Tech University Health Sciences Center, 1400 Wallace Boulevard, Amarillo, TX 79106, USA
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24
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Abstract
Immunomodulators and biologic medications, alone or in combination, form the core therapeutic strategy for managing moderate-to-severe inflammatory bowel disease (IBD). IBD incidence peaks during the prime reproductive years, raising concerns about the impact of disease and its treatment on fertility, maternal and fetal health during pregnancy, breastfeeding safety, and childhood development. Although IBD increases risk of pregnancy complications independent of disease activity, adverse pregnancy outcomes are more common when disease is active. To mitigate fetal risk, women should conceive while disease is quiescent. Aside from methotrexate, immunomodulators and biologics may be used during pregnancy to achieve and maintain disease control. Based on available safety data, there is no increased risk of congenital anomalies among infants exposed to these medications. Active thiopurine metabolites and most monoclonal antibodies cross the placenta and are detectable in neonates. They are detectable in breast milk in minute levels as well. The impact of this exposure on neonatal outcomes is discussed. Adjusted dosing schedules during gestation may reduce fetal drug exposure, though the maternal risks of such manipulation require careful consideration. Ongoing prospective studies will further inform risk assessment, including for newer medications such as the anti-integrin agents.
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25
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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.
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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
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26
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Spencer B. Medications and Breastfeeding for Mothers With Chronic Illness. J Obstet Gynecol Neonatal Nurs 2015; 44:543-552. [DOI: 10.1111/1552-6909.12663] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
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27
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Kavanaugh A, Cush JJ, Ahmed MS, Bermas BL, Chakravarty E, Chambers C, Clowse M, Curtis JR, Dao K, Hankins GDV, Koren G, Kim SC, Lapteva L, Mahadevan U, Moore T, Nolan M, Ren Z, Sammaritano LR, Seymour S, Weisman MH. Proceedings From the American College of Rheumatology Reproductive Health Summit: The Management of Fertility, Pregnancy, and Lactation in Women With Autoimmune and Systemic Inflammatory Diseases. Arthritis Care Res (Hoboken) 2015; 67:313-25. [DOI: 10.1002/acr.22516] [Citation(s) in RCA: 64] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2014] [Accepted: 11/04/2014] [Indexed: 01/31/2023]
Affiliation(s)
| | | | | | | | | | | | - Megan Clowse
- Duke University Medical Center; Durham North Carolina
| | | | | | | | - Gideon Koren
- The Hospital for Sick Children, Toronto; Ontario Canada
| | | | | | | | - Thomas Moore
- School of Medicine, University of California at San Diego
| | - Martha Nolan
- Society for Women's Health Research; Washington DC
| | - Zhaoxia Ren
- National Institute of Child Health and Human Development, National Institutes of Health; Bethesda Maryland
| | - Lisa R. Sammaritano
- Hospital for Special Surgery, Weill Medical College of Cornell University; New York New York
| | - Sally Seymour
- US Food and Drug Administration; Silver Spring Maryland
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28
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van der Woude CJ, Ardizzone S, Bengtson MB, Fiorino G, Fraser G, Katsanos K, Kolacek S, Juillerat P, Mulders AGMGJ, 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; 9:107-124. [PMID: 25602023 DOI: 10.1093/ecco-jcc/jju006] [Citation(s) in RCA: 331] [Impact Index Per Article: 33.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [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.
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29
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30
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Schulze H, Esters P, Dignass A. Review article: the management of Crohn's disease and ulcerative colitis during pregnancy and lactation. Aliment Pharmacol Ther 2014; 40:991-1008. [PMID: 25200000 DOI: 10.1111/apt.12949] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2014] [Revised: 02/24/2014] [Accepted: 08/14/2014] [Indexed: 12/14/2022]
Abstract
BACKGROUND Inflammatory bowel diseases (IBD) commonly affect young patients in the reproductive phase of their lives. The chronic and relapsing nature of IBD and the potential need for medical or surgical interventions raise concerns about family planning issues. AIM To review the current knowledge on IBD management in pregnant and nursing IBD patients. METHODS A PubMed literature search was performed using the search terms 'reproduction' and 'inflammatory bowel disease' and using the headers and main subjects of each section of this article as search terms. RESULTS Male and female fertility are not impaired in the majority of IBD patients. In IBD patients with quiescent disease pregnancy outcomes are not impaired in comparison to the general population, however, an increased incidence of pregnancy complications is observed in active IBD patients. As methotrexate (MTX) has been demonstrated to be teratogenic, the use of MTX is contraindicated in patients, who wish to conceive, throughout pregnancy and when nursing. However, normal pregnancies following MTX treatment at conception and later have been reported. Most of the other currently approved IBD medications are not associated with adverse pregnancy outcomes and may be used to maintain quiescent disease or to induce a rapid remission in patients with flares and active disease. Breast-feeding in IBD patients is possible and recommended. CONCLUSIONS The overall outcome of pregnancies in IBD patients is favourable and not different to healthy controls, thus patients with IBD should not be discouraged from having children.
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Affiliation(s)
- H Schulze
- Department of Medicine I - Gastroenterology, Hepatology, Oncology and Nutrition, Agaplesion Markus Hospital, Goethe University, Frankfurt, Germany
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31
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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.
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32
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33
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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: 19] [Impact Index Per Article: 1.7] [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.
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34
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Butler DC, Heller MM, Murase JE. Safety of dermatologic medications in pregnancy and lactation. J Am Acad Dermatol 2014; 70:417.e1-10; quiz 427. [DOI: 10.1016/j.jaad.2013.09.009] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2013] [Revised: 08/29/2013] [Accepted: 09/07/2013] [Indexed: 10/25/2022]
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35
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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.
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Ng SW, Mahadevan U. Management of inflammatory bowel disease in pregnancy. Expert Rev Clin Immunol 2013; 9:161-73; quiz 174. [PMID: 23390947 DOI: 10.1586/eci.12.103] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
The management of inflammatory bowel disease (IBD) in women who are pregnant or contemplating pregnancy requires special considerations. Although many of the medications in IBD treatment are generally low risk, this is not the case for all agents, and substitution of medications or adjustments in dosage or dose timing may be needed. Furthermore, while women with IBD who have not had prior pelvic surgery are as likely to conceive as non-IBD counterparts, there is evidence to suggest that pregnancy outcomes may be worse in women with IBD, particularly if they have active disease during conception or pregnancy. Therefore, a thoughtful discussion between the patient and her healthcare team is critical to ensure awareness of the possible risks of pregnancy to the mother and her infant and how these risks can be minimized with a coordinated effort in counseling, monitoring and medication adherence.
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Affiliation(s)
- Susie W Ng
- Department of Gastroenterology, University of California, San Francisco, CA 94122, USA
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Selinger CP, Leong RWL, Lal S. Pregnancy related issues in inflammatory bowel disease: evidence base and patients' perspective. World J Gastroenterol 2012; 18:2600-8. [PMID: 22690068 PMCID: PMC3369996 DOI: 10.3748/wjg.v18.i21.2600] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2011] [Revised: 09/09/2011] [Accepted: 09/16/2011] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel disease (IBD) affects women of childbearing age and can influence fertility, pregnancy and decisions regarding breastfeeding. Women with IBD need to consider the possible course of disease during pregnancy, the benefits and risks associated with medications required for disease management during pregnancy and breastfeeding and the effects of mode of delivery on their disease. When indicated, aminosalicylates and thiopurines can be safely used during pregnancy. Infliximab and Adalimumab are considered probably safe during the first two trimesters. During the third trimester the placenta can be crossed and caution should be applied. Methotrexate is associated with severe teratogenicity due to its folate antagonism and is strictly contraindicated. Women with IBD tend to deliver earlier than healthy women, but can have a vaginal delivery in most cases. Caesarean sections are generally recommended for women with active perianal disease or after ileo-anal pouch surgery.While the impact of disease activity and medication has been addressed in several studies, there are minimal studies evaluating patients' perspective on these issues. Women's attitudes may influence their decision to have children and can positively or negatively influence the chance of conceiving, and their beliefs regarding therapies may impact on the course of their disease during pregnancy and/or breastfeeding. This review article outlines the impact of IBD and its treatment on pregnancy, and examines the available data on patients' views on this subject.
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Habal FM, Huang VW. Review article: a decision-making algorithm for the management of pregnancy in the inflammatory bowel disease patient. Aliment Pharmacol Ther 2012; 35:501-15. [PMID: 22221203 DOI: 10.1111/j.1365-2036.2011.04967.x] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2011] [Revised: 12/07/2011] [Accepted: 12/09/2011] [Indexed: 12/16/2022]
Abstract
BACKGROUND Inflammatory bowel disease affects patients who are in their reproductive years. There are many questions regarding the management of IBD patients who are considering or who are already pregnant. These include the effect of the disease and the medications on fertility and on the pregnancy outcome. AIM To create an evidence-based decision-making algorithm to help guide physicians through the management of pregnancy in the IBD patient. METHODS A literature review using phrases that include: 'inflammatory bowel disease', 'Crohn's disease', 'ulcerative colitis', 'pregnancy', 'fertility', 'breast feeding', 'delivery', 'surgery', 'immunomodulators', 'azathioprine', 'mercaptopurine', 'biologics', 'infliximab', 'adalimumab', 'certolizumab'. CONCLUSIONS The four decision-making nodes in the algorithm for the management of pregnancy in the IBD patient, and the key points for each one are as follows: (i) preconception counselling - pregnancy outcome is better if patients remain in remission during pregnancy, (ii) contemplating pregnancy or is already pregnant - drugs used to treat IBD appear to be safe during pregnancy, with the exception of methotrexate and thalidomide, (iii) delivery and (iv) breast feeding - drugs used to treat IBD appear to be safe during lactation, except for ciclosporin. Another key point is that biological agents may be continued up to 30 weeks gestation. The management of pregnancy in the IBD patient should be multi-disciplinary involving the patient and her partner, the family physician, the gastroenterologist and the obstetrician.
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Affiliation(s)
- F M Habal
- Department of Medicine, University Health Network, University of Toronto, ON, Canada.
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Singh M, Qualie J, Currie A, Howarth ES, Khare MM. Is breastfeeding safe with azathioprine? Obstet Med 2011; 4:104-7. [PMID: 27579102 DOI: 10.1258/om.2011.110013] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/20/2011] [Indexed: 11/18/2022] Open
Abstract
BACKGROUND Azathioprine is commonly used as an immunosuppressant during pregnancy in the management of various conditions such as connective tissue disorders, inflammatory bowel disease and pregnant women with organ transplant. Continuation of azathioprine through pregnancy and postpartum is vital for maternal reasons. However, there is limited evidence regarding safety of use of azathioprine with breastfeeding. METHODS AND RESULTS We report an observational case series of 10 mother-baby pairs managed at a tertiary teaching hospital. Mothers on azathioprine who were keen to breastfeed were counselled antenatally regarding limited short-term and long-term safety data for the babies. Mothers participating in this study completed a questionnaire at every visit. At follow-up visits, babies were examined by a neonatologist for clinical signs of infection and checked for adverse effects on haematological profile. CONCLUSION There was no clinically significant adverse effect on haematological profile or immunosuppression in these babies. Our case series supports safety of azathioprine in the short term. However, large numbers are needed to determine long-term safety of azathioprine and breastfeeding.
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Affiliation(s)
- Mandeep Singh
- Women's and Perinatal Services, Leicester Royal Infirmary, University Hospital Leicester, Leicester , UK
| | - Jan Qualie
- Women's and Perinatal Services, Leicester Royal Infirmary, University Hospital Leicester, Leicester , UK
| | - Andrew Currie
- Women's and Perinatal Services, Leicester Royal Infirmary, University Hospital Leicester, Leicester , UK
| | - Edmund S Howarth
- Women's and Perinatal Services, Leicester Royal Infirmary, University Hospital Leicester, Leicester , UK
| | - Manjiri M Khare
- Women's and Perinatal Services, Leicester Royal Infirmary, University Hospital Leicester, Leicester , UK
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Abstract
Crohn disease and ulcerative colitis commonly affect women in their childbearing years. Fortunately, advances in the field of inflammatory bowel disease have made successful pregnancy outcomes a reality for many women. These advances have led to family planning as a common discussion between gastroenterologists and inflammatory bowel disease patients. Common discussion topics are fertility, conception, medication safety, pregnancy, delivery, and breastfeeding although there are limited available data. Education and patient awareness have become vital factors in successful pregnancy outcomes.
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Affiliation(s)
- Dawn B Beaulieu
- Division of Gastroenterology, Hepatology and Nutrition, Inflammatory Bowl Disease Center, Vanderbilt University, 1211 21st Avenue South, Suite 220 MAB, Nashville, TN 37232, USA
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Angelberger S, Reinisch W, Messerschmidt A, Miehsler W, Novacek G, Vogelsang H, Dejaco C. Long-term follow-up of babies exposed to azathioprine in utero and via breastfeeding. J Crohns Colitis 2011; 5:95-100. [PMID: 21453877 DOI: 10.1016/j.crohns.2010.10.005] [Citation(s) in RCA: 83] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2010] [Revised: 09/22/2010] [Accepted: 10/15/2010] [Indexed: 12/13/2022]
Abstract
BACKGROUND Recommendations on breastfeeding under thiopurines are inconsistent due to limited data. AIM To assess the risk of infections in offspring breastfed by mothers receiving azathioprine (AZA) for inflammatory bowel disease (IBD). METHODS Babies, who were breastfed from their mothers treated either with or without AZA were included from a local pregnancy-registry. Women were asked by structured personal interview on general development, infections, hospitalisations and vaccinations of their offspring. RESULTS A group of 11 mothers taking AZA (median 150 mg/d) during pregnancy and lactation and another of 12 patients without using any immunosuppressive therapy breastfed 15 babies each for median 6 months and 8 months, respectively. Median age of children at time of interview was 3.3 and 4.7 years, respectively. All offspring showed age-appropriate mental and physical development. Infections were commonly seen childhood diseases. Similar rates were observed for most of the various infections between offspring with and without azathioprine exposure during breastfeeding. However, common cold more than two episodes/year and conjunctivitis were numerically more often reported in the group without AZA exposure. In an exploratory analysis no difference in the rate of hospitalisations was seen between exposed (0.06 hospitalisations/patient year) versus non-exposed children (0.12 hospitalisations/patient year, p=0.8) CONCLUSION Our study which reports the largest number of babies breastfed with exposure to AZA suggests that breastfeeding does not increase the risk of infections.
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Affiliation(s)
- Sieglinde Angelberger
- Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Austria
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Abstract
Historically, pregnancy in women with many inflammatory rheumatic diseases was not considered safe and was discouraged. Combined care allows these pregnancies to be managed optimally, with the majority of outcomes being favorable. Disease activity at the time of conception and anti-phospholipid antibodies are responsible for most complications. Disease flares, pre-eclampsia, and thrombosis are the main maternal complications, whereas fetal loss and intrauterine growth restriction are the main fetal complications. Antirheumatic drugs used during pregnancy and lactation to control disease activity are corticosteroids, hydroxychloroquine, sulphasalzine, and azathioprine. Vaginal delivery is possible in most circumstances, with cesarean section being reserved for complications.
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European evidenced-based consensus on reproduction in inflammatory bowel disease. J Crohns Colitis 2010; 4:493-510. [PMID: 21122553 DOI: 10.1016/j.crohns.2010.07.004] [Citation(s) in RCA: 103] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2010] [Accepted: 07/12/2010] [Indexed: 02/08/2023]
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Kwan LY, Mahadevan U. Inflammatory bowel disease and pregnancy: an update. Expert Rev Clin Immunol 2010; 6:643-57. [PMID: 20594137 DOI: 10.1586/eci.10.35] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
Women with inflammatory bowel disease have similar rates of conception to the general population unless they have had pelvic surgery. Once pregnant, regardless of disease activity, they have an increased risk of adverse pregnancy outcome and should be followed as high-risk obstetric patients. Most medications are compatible with pregnancy and lactation, as described in this article. Ideally, women should discuss their plans for pregnancy with their physician prior to conception so that risks and benefits can be reviewed, medications adjusted and healthcare maintenance updated. Once pregnant, a multidisciplinary team of gastroenterologists, obstetricians and pediatricians should help to ensure the best care for the mother and child.
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Affiliation(s)
- Lola Y Kwan
- University of Rochester Medical Center, Rochester, NY, USA
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Garrido E, Van Domselaar M, Morales S, López-Sanromán A. Enfermedad inflamatoria intestinal y gestación. GASTROENTEROLOGIA Y HEPATOLOGIA 2010; 33:517-29. [DOI: 10.1016/j.gastrohep.2009.11.006] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/28/2009] [Accepted: 11/01/2009] [Indexed: 12/23/2022]
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Gisbert JP. Safety of immunomodulators and biologics for the treatment of inflammatory bowel disease during pregnancy and breast-feeding. Inflamm Bowel Dis 2010; 16:881-95. [PMID: 19885906 DOI: 10.1002/ibd.21154] [Citation(s) in RCA: 98] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
The aim of this article is to critically review available data regarding the safety of immunomodulators and biological therapies during pregnancy and breast-feeding in women with inflammatory bowel disease. Methotrexate and thalidomide can cause congenital anomalies and are contraindicated during pregnancy (and breast-feeding). Although thiopurines have a Food and Drug Administration (FDA) rating D, available data suggest that these drugs are safe and well tolerated during pregnancy. Although traditionally women receiving azathioprine or mercaptopurine have been discouraged from breast-feeding because of theoretical potential risks, it seems that these drugs may be safe in this scenario. Treatment with cyclosporine for steroid-refractory ulcerative colitis (UC) during pregnancy can be considered safe and effective, and the use of this drug should be considered in cases of severe UC as a means of avoiding urgent surgery. Breast-feeding is contraindicated for patients receiving cyclosporine. Biological therapies appear to be safe in pregnancy, as no increased risk of malformations has been demonstrated. Therefore, the limited clinical results available suggest that the benefits of infliximab and adalimumab in attaining response and maintaining remission in pregnant patients might outweigh the theoretical risks of drug exposure to the fetus. Stopping therapy in the third trimester may be considered, as it seems that transplacental transfer of infliximab is low prior to this. Certolizumab differs from infliximab and adalimumab in that it is a Fab fragment of an antitumor necrosis factor alpha monoclonal antibody, and therefore it may not be necessary to stop certolizumab in the third trimester. The use of infliximab is probably compatible with breast-feeding.
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Affiliation(s)
- Javier P Gisbert
- Gastroenterology Unit, Hospital Universitario de la Princesa and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Madrid, Spain.
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Van Assche G, Dignass A, Reinisch W, van der Woude CJ, Sturm A, De Vos M, Guslandi M, Oldenburg B, Dotan I, Marteau P, Ardizzone A, Baumgart DC, D'Haens G, Gionchetti P, Portela F, Vucelic B, Söderholm J, Escher J, Koletzko S, Kolho KL, Lukas M, Mottet C, Tilg H, Vermeire S, Carbonnel F, Cole A, Novacek G, Reinshagen M, Tsianos E, Herrlinger K, Oldenburg B, Bouhnik Y, Kiesslich R, Stange E, Travis S, Lindsay J. The second European evidence-based Consensus on the diagnosis and management of Crohn's disease: Special situations. J Crohns Colitis 2010; 4:63-101. [PMID: 21122490 DOI: 10.1016/j.crohns.2009.09.009] [Citation(s) in RCA: 528] [Impact Index Per Article: 35.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2009] [Revised: 09/28/2009] [Accepted: 09/28/2009] [Indexed: 02/08/2023]
Affiliation(s)
- Gert Van Assche
- Division of Gastroenterology, Leuven University Hospitals, 49 Herestraat, BE 3000, Leuven, Belgium.
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49
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Abstract
This review covers important questions that arise for physicians caring for women with inflammatory bowel disease. Fertility, pregnancy outcomes and the safety of medications in pregnancy and lactation are discussed.
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Affiliation(s)
- Uma Mahadevan
- Center for Colitis and Crohn's Disease, University of California, San Francisco, 2330 Post Street 610, San Francisco, CA 94115, USA
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50
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Abstract
This review covers important questions that arise for physicians caring for women with inflammatory bowel disease. Fertility, pregnancy outcomes and the safety of medications in pregnancy and lactation are discussed.
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Affiliation(s)
- Uma Mahadevan
- Center for Colitis and Crohn's Disease, University of California, San Francisco, 2330 Post Street 610, San Francisco, CA 94115, USA.
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