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Kim DS, Yoon YI, Kim BK, Choudhury A, Kulkarni A, Park JY, Kim J, Sinn DH, Joo DJ, Choi Y, Lee JH, Choi HJ, Yoon KT, Yim SY, Park CS, Kim DG, Lee HW, Choi WM, Chon YE, Kang WH, Rhu J, Lee JG, Cho Y, Sung PS, Lee HA, Kim JH, Bae SH, Yang JM, Suh KS, Al Mahtab M, Tan SS, Abbas Z, Shresta A, Alam S, Arora A, Kumar A, Rathi P, Bhavani R, Panackel C, Lee KC, Li J, Yu ML, George J, Tanwandee T, Hsieh SY, Yong CC, Rela M, Lin HC, Omata M, Sarin SK. Asian Pacific Association for the Study of the Liver clinical practice guidelines on liver transplantation. Hepatol Int 2024; 18:299-383. [PMID: 38416312 DOI: 10.1007/s12072-023-10629-3] [Citation(s) in RCA: 13] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Accepted: 12/18/2023] [Indexed: 02/29/2024]
Abstract
Liver transplantation is a highly complex and challenging field of clinical practice. Although it was originally developed in western countries, it has been further advanced in Asian countries through the use of living donor liver transplantation. This method of transplantation is the only available option in many countries in the Asia-Pacific region due to the lack of deceased organ donation. As a result of this clinical situation, there is a growing need for guidelines that are specific to the Asia-Pacific region. These guidelines provide comprehensive recommendations for evidence-based management throughout the entire process of liver transplantation, covering both deceased and living donor liver transplantation. In addition, the development of these guidelines has been a collaborative effort between medical professionals from various countries in the region. This has allowed for the inclusion of diverse perspectives and experiences, leading to a more comprehensive and effective set of guidelines.
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Affiliation(s)
- Dong-Sik Kim
- Department of Surgery, Korea University College of Medicine, Seoul, Republic of Korea
| | - Young-In Yoon
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | | | | | - Jun Yong Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jongman Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Dong Hyun Sinn
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Dong Jin Joo
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - YoungRok Choi
- Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jeong-Hoon Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Ho Joong Choi
- Department of Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Ki Tae Yoon
- Department of Internal Medicine, Pusan National University College of Medicine, Yangsan, Republic of Korea
| | - Sun Young Yim
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Cheon-Soo Park
- Department of Surgery, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Deok-Gie Kim
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Hae Won Lee
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea
| | - Won-Mook Choi
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Young Eun Chon
- Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea
| | - Woo-Hyoung Kang
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jinsoo Rhu
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Jae Geun Lee
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Yuri Cho
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Ilsan, Republic of Korea
| | - Pil Soo Sung
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Han Ah Lee
- Department of Internal Medicine, Ewha Womans University, Seoul, Republic of Korea
| | - Ji Hoon Kim
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Si Hyun Bae
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jin Mo Yang
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
| | - Kyung-Suk Suh
- Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
| | - Mamun Al Mahtab
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Soek Siam Tan
- Department of Medicine, Hospital Selayang, Batu Caves, Selangor, Malaysia
| | - Zaigham Abbas
- Sindh Institute of Urology and Transplantation, Karachi, Pakistan
| | - Ananta Shresta
- Department of Hepatology, Alka Hospital, Lalitpur, Nepal
| | - Shahinul Alam
- Crescent Gastroliver and General Hospital, Dhaka, Bangladesh
| | - Anil Arora
- Department of Gastroenterology and Hepatology, Sir Ganga Ram Hospital New Delhi, New Delhi, India
| | - Ashish Kumar
- Department of Gastroenterology and Hepatology, Sir Ganga Ram Hospital New Delhi, New Delhi, India
| | - Pravin Rathi
- TN Medical College and BYL Nair Hospital, Mumbai, India
| | - Ruveena Bhavani
- University of Malaya Medical Centre, Petaling Jaya, Selangor, Malaysia
| | | | - Kuei Chuan Lee
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Jun Li
- College of Medicine, Zhejiang University, Hangzhou, China
| | - Ming-Lung Yu
- Department of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | | | | | | | | | | | - H C Lin
- Endoscopy Center for Diagnosis and Treatment, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Masao Omata
- Department of Gastroenterology, Yamanashi Central Hospital, Yamanashi, Japan
- University of Tokyo, Bunkyo City, Japan
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Drljevic-Nielsen A, Heilskov S, Deleuran MS, Vestergaard C. Immunosuppressive and immunomodulating therapy for atopic dermatitis in pregnancy: an appraisal of the literature. Ital J Dermatol Venerol 2024; 159:23-33. [PMID: 38226937 DOI: 10.23736/s2784-8671.23.07692-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2024]
Abstract
Atopic dermatitis (AD) is the most common dermatological diagnosis during pregnancy. Treatment of AD during pregnancy can be challenging, due to the unpredictable course and the fact that the therapy needs to be safe for both the mother and the fetus. Here we present an up-to-date appraisal of the literature on the treatment options available for AD in patients planning pregnancy, during pregnancy, and during breastfeeding. All patients with AD are recommended to supplement any medical treatment with daily applications of emollients. The first step in the medical treatment for AD during pregnancy are topical corticosteroids, and/or topical tacrolimus. If required, UV-light therapy can also be considered. Treatment with systemic therapy during pregnancy should always rely on a careful risk-benefit assessment and be based on shared-decision making between the treating physician and patient. The first-line systemic treatment option is cyclosporine A, whereas azathioprine may be considered in patients already receiving this treatment prior to pregnancy. Systemic glucocorticoids may also be used. Treatment with systemic JAK inhibitors is not recommended, whereas treatment with mycophenolate mofetil and methotrexate is contraindicated. Targeted therapy with dupilumab is not generally recommended, due to lack of experience in human pregnancies, yet some case-reports on their use are emerging. These recommendations are based on the authors appraisal of existing literature and the current recommendation from the European Task Force on Atopic Dermatitis. It is always the responsibility of the treating physician to stay updated on the newest guidelines and literature when treating patients with AD during pregnancy.
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Affiliation(s)
| | - Sofine Heilskov
- Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark
| | - Mette S Deleuran
- Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark
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Osman KT, Nayfeh T, Alrukby J, Mehta N, Elkhabiry L, Spencer C, Aby ES. Type of donor liver transplant does not affect pregnancy outcomes-a systematic review and meta-analysis. Liver Transpl 2023; 29:1304-1312. [PMID: 37141916 DOI: 10.1097/lvt.0000000000000168] [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] [Received: 02/18/2023] [Accepted: 04/26/2023] [Indexed: 05/06/2023]
Abstract
Liver transplant (LT) has become increasingly common among reproductive-aged women. The effect of the type of liver donor, either a living donor LT (LDLT) or a deceased donor LT, on pregnancy outcomes is unknown. As such, we aim to review the available literature and assess obstetric, pregnancy, or delivery outcomes in LDLT. We conducted a comprehensive literature review of MEDLINE, EMBASE, Cochrane, and Scopus databases. Random-effect meta-regression assessed the association between the percentage of women who underwent LDLT (independent variable) and the proportion of outcomes. Meta-regression results were expressed as a regression coefficient, which transforms the proportion of outcomes of interest associated with a 1% increase in the percentage of LDLT patients. A value of 0 denotes no relationship between the outcomes and LDLT. A total of 6 articles (438 patients) were included, with a total of 806 pregnancies. Eighty-eight (20.09%) patients underwent LDLT. None of the studies segregated the data based on the type of donor LT. The median time from LT to pregnancy was 4.86 (4.62-5.03) years. Twelve (1.5%) stillbirths were reported. LDLT was statistically significantly associated with a higher rate of stillbirths (coefficient 0.002, p < 0.001; I 2 0%). The type of donor LT was not associated with an increased risk of other obstetric, pregnancy, or delivery complications. This is the first meta-analysis to evaluate the effect of the type of donor LT on pregnancy outcomes. This study highlights the lack of robust literature addressing this important topic. The results suggest that pregnancy outcomes after LDLT and deceased donor LT are comparable. Despite LDLT being statistically significantly associated with a higher rate of stillbirths, the association is weak and is unlikely to be clinically significant.
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Affiliation(s)
- Karim T Osman
- Department of Internal Medicine, Lahey Hospital and Medical Center, Burlington, Massachusetts, USA
| | - Tarek Nayfeh
- Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | - Judy Alrukby
- Department of Internal Medicine, Lahey Hospital and Medical Center, Burlington, Massachusetts, USA
| | - Neev Mehta
- Department of Gastroenterology, Lahey Hospital and Medical Center, Burlington, Massachusetts, USA
| | - Lina Elkhabiry
- Department of Internal Medicine, University of Alexandria, Alexandria, Egypt
| | - Carol Spencer
- Department of Library Services, Lahey Hospital and Medical Center, Burlington, Massachusetts, USA
| | - Elizabeth S Aby
- Division of Gastroenterology, Hepatology, and Nutrition, University of Minnesota, Minneapolis, Minnesota, USA
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Williamson C, Nana M, Poon L, Kupcinskas L, Painter R, Taliani G, Heneghan M, Marschall HU, Beuers U. EASL Clinical Practice Guidelines on the management of liver diseases in pregnancy. J Hepatol 2023; 79:768-828. [PMID: 37394016 DOI: 10.1016/j.jhep.2023.03.006] [Citation(s) in RCA: 32] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2023] [Accepted: 03/10/2023] [Indexed: 07/04/2023]
Abstract
Liver diseases in pregnancy comprise both gestational liver disorders and acute and chronic hepatic disorders occurring coincidentally in pregnancy. Whether related to pregnancy or pre-existing, liver diseases in pregnancy are associated with a significant risk of maternal and fetal morbidity and mortality. Thus, the European Association for the Study of Liver Disease invited a panel of experts to develop clinical practice guidelines aimed at providing recommendations, based on the best available evidence, for the management of liver disease in pregnancy for hepatologists, gastroenterologists, obstetric physicians, general physicians, obstetricians, specialists in training and other healthcare professionals who provide care for this patient population.
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Hisano M, Nakagawa K, Ono M, Yoshino O, Saito T, Hirota Y, Inoue E, Kikuchi K, Nakamura H, Yamaguchi K. Multicenter, 2-dose single-group controlled trial of tacrolimus for the severe infertility patients. Medicine (Baltimore) 2023; 102:e34317. [PMID: 37565878 PMCID: PMC10419514 DOI: 10.1097/md.0000000000034317] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2023] [Accepted: 06/22/2023] [Indexed: 08/12/2023] Open
Abstract
INTRODUCTION Infertility is estimated to affect 8% to 12% of reproductive-aged couples worldwide. While approximately 85% of infertile couples have an identified cause, the remaining 15% suffer physically and emotionally from unexplained intractable infertility. In recent years, maternal-to-fetal immunological abnormalities have attracted attention as mechanisms that differ from the conventional factors contributing to infertility and pregnancy loss. A T-helper 2 (Th2)-dominant immune state has been proposed as a maternal immune alteration to eliminate rejection and induce tolerance to a semi-allogeneic fetus. An imbalance in Th1 responses would not induce adequate maternal immune tolerance to the fetus or early embryos. Tacrolimus, widely used as an immunosuppressant agent in solid organ transplant recipients, is expected to suppress maternal rejection and promote tolerance to early embryos after assisted reproductive technology by modulating the immunological environment of the preimplantation endometrium. We planned an exploratory clinical trial to determine the efficacy, safety, and dosage of tacrolimus in women with intractable infertility. METHODS AND ANALYSIS This is a multicenter, 2-dose, single-group controlled trial in infertile women who failed to achieve a chemical pregnancy despite multiple in vitro fertilization (IVF) and embryo transfer (ET) treatment cycles. The following 2 key selection criteria were set: no underlying factors of infertility despite appropriate evaluation and presence of Th1-dominant immune state, defined as a Th1/Th2 cell ratio ≥ 10.3 in the peripheral blood. A total of 26 eligible participants are randomly assigned (in a 2:1 ratio) to receive immunosuppressive therapy with oral tacrolimus at a daily dose of 2 mg or 4 mg. Tacrolimus is administered for 16 days starting from 2 days before ET. The primary endpoint is the presence of clinical pregnancy 3 weeks after IVF/ET treatment, and the secondary endpoint is the presence of biochemical pregnancy 2 weeks after IVF/ET treatment. Safety evaluation and biomarker discovery for tacrolimus treatment in infertile women will be conducted simultaneously. TRIAL REGISTRATION NUMBER Japan Registry of Clinical Trials (jRCT; jRCTs031220235).
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Affiliation(s)
- Michi Hisano
- Center of Maternal-Fetal, Neonatal and Reproductive Medicine, National Center for Child Health and Development, Tokyo, Japan
| | - Koji Nakagawa
- Center for Reproductive Medicine and Implantation Research, Sugiyama Clinic Shinjuku, Tokyo, Japan
| | - Masanori Ono
- Department of Obstetrics and Gynecology, Tokyo Medical University, Tokyo, Japan
| | - Osamu Yoshino
- Department of Obstetrics and Gynecology, Yamanashi University, Yamanashi, Japan
| | - Takakazu Saito
- Center of Maternal-Fetal, Neonatal and Reproductive Medicine, National Center for Child Health and Development, Tokyo, Japan
| | - Yasushi Hirota
- Department of Obstetrics and Gynecology, The University of Tokyo, Tokyo, Japan
| | - Eisuke Inoue
- Showa University Research Administration Center, Showa University, Tokyo, Japan
| | - Kayoko Kikuchi
- Translational Research Headquarters, Fujita Health University, Aichi, Japan
| | - Hidefumi Nakamura
- Department of Research and Development Supervision, National Center for Child Health and Development, Tokyo, Japan
| | - Koushi Yamaguchi
- Center of Maternal-Fetal, Neonatal and Reproductive Medicine, National Center for Child Health and Development, Tokyo, Japan
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Özbilgin M, Egeli T, Ağalar C, Özkardeşler S, Saatli B, Ellidokuz H, Akarsu M, Ünek T, Karademir S, Astarcıoğlu İ. Evaluation of the Effects of Immunosuppressive Drugs Following Liver Transplantation on Pregnancy Outcomes: A Retrospective Study. Transplant Proc 2023; 55:1245-1251. [PMID: 37230900 DOI: 10.1016/j.transproceed.2023.04.023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Revised: 04/05/2023] [Accepted: 04/14/2023] [Indexed: 05/27/2023]
Abstract
BACKGROUND Liver transplantations can be safely performed in women of reproductive age. Women with chronic liver disease may have infertility for various reasons, although fertility returns after recovering >90% of sexual disorders following liver transplantation. The present study examined the effects of immunosuppressive drugs used by women of reproductive age undergoing liver transplantation in our clinic on pregnancy and pregnancy outcomes and evaluated mortality and morbidity in this patient population. METHODS Among the patients undergoing liver transplantation in our clinic between 1997 and 2020, those conceiving after liver transplantation were evaluated in the present study. Demographic data on maternal and newborn health, as well as mortality and morbidity, were recorded. Maternal transplant indications, graft type, the interval between transplantation and pregnancy, maternal age at pregnancy and the number of pregnancies, the number of living children, complications, delivery mode, immunosuppressive drugs, and blood levels were investigated. RESULTS A total of 615 liver transplantations (353 from a living donor, 262 from a cadaveric donor) were performed in our clinic. Furthermore, 33 pregnancies occurred in 22 women following transplantation (17 living donor liver transplantations, 5 deceased donor liver transplantations), and the data of these patients were recorded. Tacrolimus and mycophenolate mofetil were used as immunosuppressive therapy. CONCLUSIONS Liver transplantations can be safely performed in women of reproductive age if indicated, and these patients can be safely followed up throughout the pregnancy and during labor by a multidisciplinary team.
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Affiliation(s)
- Mücahit Özbilgin
- Department of General Surgery, Hepatobiliary Surgery and Liver Transplantation Unit, Dokuz Eylül University Hospital, Izmir, Turkey.
| | - Tufan Egeli
- Department of General Surgery, Hepatobiliary Surgery and Liver Transplantation Unit, Dokuz Eylül University Hospital, Izmir, Turkey
| | - Cihan Ağalar
- Department of General Surgery, Hepatobiliary Surgery and Liver Transplantation Unit, Dokuz Eylül University Hospital, Izmir, Turkey
| | - Sevda Özkardeşler
- Department of Anesthesiology and Reanimation, Dokuz Eylül University Hospital, Izmir, Turkey
| | - Bahadır Saatli
- Department of Gynecology and Obstetrics, Dokuz Eylül University Hospital, Izmir, Turkey
| | - Hülya Ellidokuz
- Department of Preventive Oncology, Dokuz Eylül University Hospital, Izmir, Turkey
| | | | - Tarkan Ünek
- Department of General Surgery, Hepatobiliary Surgery and Liver Transplantation Unit, Dokuz Eylül University Hospital, Izmir, Turkey
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Brondfield MN, Mahadevan U. Inflammatory bowel disease in pregnancy and breastfeeding. Nat Rev Gastroenterol Hepatol 2023:10.1038/s41575-023-00758-3. [PMID: 37002407 DOI: 10.1038/s41575-023-00758-3] [Citation(s) in RCA: 27] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/20/2023] [Indexed: 06/19/2023]
Abstract
Inflammatory bowel disease (IBD) has a peak age of diagnosis before the age of 35 years. Concerns about infertility, adverse pregnancy outcomes, and heritability of IBD have influenced decision-making for patients of childbearing age and their care providers. The interplay between the complex physiology in pregnancy and IBD can affect placental development, microbiome composition and responses to therapy. Current evidence has shown that effective disease management, including pre-conception counselling, multidisciplinary care and therapeutic agents to minimize disease activity, can improve pregnancy outcomes. This Review outlines the management of IBD in pregnancy and the safety of IBD therapies, including novel agents, with regard to both maternal and fetal health. The vast majority of IBD therapies can be used with low risk during pregnancy and lactation without substantial effects on neonatal outcomes.
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Affiliation(s)
- Max N Brondfield
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA
| | - Uma Mahadevan
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
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Shen P, Zhang T, Han R, Xie H, Lv Q. Co-administration of tacrolimus and low molecular weight heparin in patients with a history of implantation failure and elevated peripheral blood natural killer cell proportion. J Obstet Gynaecol Res 2023; 49:649-657. [PMID: 36436504 DOI: 10.1111/jog.15500] [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: 06/29/2022] [Revised: 10/28/2022] [Accepted: 11/03/2022] [Indexed: 11/29/2022]
Abstract
AIM To investigate the therapeutic effect of co-administration of tacrolimus (TAC) and low-molecular-weight heparin (LMWH) or LMWH only on pregnancy outcomes in the female with a history of implantation failure and elevated peripheral blood natural killer (pNK) cell proportion in frozen-thawed embryo transfer cycles. METHODS To evaluate the pregnancy parameters for 249 patients with ≥2 implantation failures and pNK cell proportion ≥12% by analyzing a retrospective observational cohort study. Sixty patients had received the co-administration TAC and LMWH (TAC & LMWH group), 85 others had only taken LMWH (LWMH group), and the rest did not take any particular drugs (control group). RESULTS The experimental finding indicated that the TAC & LMWH group and the LMWH group showed higher clinical pregnancy rates than the control group (p < 0.05), and TAC & LMWH group had a much higher live birth rate. According to the binary logistic regression analysis, the combination of TAC and LMWH was conducive to clinical pregnancy and live birth rate and reduced the possibility of miscarriage. It would not affect the result of spontaneous abortion and live birth, although the LMWH was only beneficial to clinical pregnancy. In addition, these findings were similar for these three groups' obstetrical and neonatal outcomes. CONCLUSIONS The combination of TAC and LMWH can improve clinical pregnancy and live birth rates and reduce the risk of spontaneous miscarriage in patients with a history of implantation failure and elevated pNK ratio. LMWH is also beneficial to clinical pregnancy.
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Affiliation(s)
- Ping Shen
- Department of Obstetrics and Gynecology, The First People's Hospital of Shuangliu District, Chengdu, China
| | - Tao Zhang
- Department of Internal Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, China.,School of Clinical Medicine, Zunyi Medical University, Zunyi, China
| | - Ru Han
- School of Clinical Medicine, Chengdu Medical College, Chengdu, China
| | - Huixia Xie
- Assisted Reproductive Centre, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, China
| | - Qun Lv
- Assisted Reproductive Centre, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, China
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Chung K, Yin O, Kallapur A, Bass L, Coscia L, Constantinescu S, Moritz M, Afshar Y. Emergent prelabor cesarean delivery in solid organ transplant recipients: associated risk factors and outcomes. Am J Obstet Gynecol MFM 2023; 5:100799. [PMID: 36368514 DOI: 10.1016/j.ajogmf.2022.100799] [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: 07/24/2022] [Revised: 10/19/2022] [Accepted: 11/03/2022] [Indexed: 11/11/2022]
Abstract
BACKGROUND Pregnancies after solid organ transplant are at a higher risk of antepartum admission and pregnancy complications including cesarean delivery. Emergent prelabor cesarean delivery is associated with increased maternal and neonatal morbidity in other high-risk populations, but its incidence and impact in transplant recipients is not well-understood. OBJECTIVE This study aimed to characterize the risk factors and outcomes of emergency prelabor cesarean delivery in kidney and liver transplant recipients. STUDY DESIGN This was a retrospective cohort study of all kidney and liver transplant recipients at >20 weeks gestation enrolled in the Transplant Pregnancy Registry International between 1976 and 2019. Participants admitted antepartum who required emergency prelabor cesarean delivery were compared with those admitted antepartum who underwent nonemergent birth. The primary outcomes were severe maternal morbidity and neonatal composite morbidity. Multivariable logistic regression was conducted for neonatal composite morbidity. RESULTS Of 1979 births, 181 pregnancies (188 neonates) with antepartum admission were included. 51 pregnancies (53 neonates, 28%) were delivered by emergent prelabor cesarean delivery compared with 130 pregnancies (135 neonates, 72%) admitted antepartum who subsequently did not require emergent delivery. The most common indication for emergent delivery was nonreassuring fetal heart tracing (44 pregnancies /51 emergent deliveries = 86%). Pregnant people who underwent emergent prelabor cesarean delivery were less likely to deliver at a transplant center (37.3% vs 41.5%; P=.04) and had increased rates of chronic hypertension (33.3% vs 16.2%; P=.02). There was no significant difference in severe maternal morbidity (3.9% vs 4.6%; P=.84), though there was an increase in surgical site infection in the emergent prelabor cesarean delivery cohort (3.9% vs 0%; P=.02). Among those with emergent prelabor cesarean delivery, there was a significant increase in neonatal composite morbidity (43.4% vs 19.3%; P<.001) with earlier gestational age at delivery (33.4 vs 34.7 weeks; P=.02), lower birthweight (1899 g vs 2321 g; P<.001), lower birthweight percentile (30.3% vs 40.6%; P=.03), increased neonatal intensive care unit admission (52.8% vs 35.6%; P=.03), and increased neonatal mortality (11.3% vs 1.5%; P=.002). After adjusting for year of conception, race, hypertensive disorders, and fetal malformations, there was a persistent increased risk of neonatal morbidity (adjusted odds ratio, 3.01; 95% confidence interval, 1.50-6.08; P=.002) associated with emergent prelabor cesarean delivery after transplant. CONCLUSION Almost one-third of kidney and liver transplant recipients admitted antepartum had an emergency prelabor cesarean delivery, and 63% of this cohort delivered outside of a transplant center. Pregnancies after transplantation should involve multidisciplinary transplant-obstetrics collaboration to ensure optimal antepartum disease management, especially for preexisting hypertension, to prevent and mitigate obstetrical and neonatal morbidity in the setting of emergent cesarean delivery.
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Affiliation(s)
- Kathleen Chung
- Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California, Los Angeles, CA (Drs Chung, Yin, and Kallapur, Ms Bass, and Dr Afshar)
| | - Ophelia Yin
- Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California, Los Angeles, CA (Drs Chung, Yin, and Kallapur, Ms Bass, and Dr Afshar)
| | - Aneesh Kallapur
- Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California, Los Angeles, CA (Drs Chung, Yin, and Kallapur, Ms Bass, and Dr Afshar)
| | - Lauren Bass
- Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California, Los Angeles, CA (Drs Chung, Yin, and Kallapur, Ms Bass, and Dr Afshar)
| | - Lisa Coscia
- Transplant Pregnancy Registry International, Gift of Life Institute, Philadelphia, PA (Ms Coscia and Drs Constantinescu and Moritz)
| | - Serban Constantinescu
- Transplant Pregnancy Registry International, Gift of Life Institute, Philadelphia, PA (Ms Coscia and Drs Constantinescu and Moritz); Section of Nephrology, Department of Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA (Dr Constantinescu)
| | - Michael Moritz
- Transplant Pregnancy Registry International, Gift of Life Institute, Philadelphia, PA (Ms Coscia and Drs Constantinescu and Moritz); Department of Surgery, Lehigh Valley Health Network, Allentown, PA (Dr Moritz); Department of Surgery, Morsani College of Medicine, Tampa, FL (Dr Moritz)
| | - Yalda Afshar
- Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California, Los Angeles, CA (Drs Chung, Yin, and Kallapur, Ms Bass, and Dr Afshar).
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Torres J, Chaparro M, Julsgaard M, Katsanos K, Zelinkova Z, Agrawal M, Ardizzone S, Campmans-Kuijpers M, Dragoni G, Ferrante M, Fiorino G, Flanagan E, Gomes CF, Hart A, Hedin CR, Juillerat P, Mulders A, Myrelid P, O'Toole A, Rivière P, Scharl M, Selinger CP, Sonnenberg E, Toruner M, Wieringa J, Van der Woude CJ. European Crohn's and Colitis Guidelines on Sexuality, Fertility, Pregnancy, and Lactation. J Crohns Colitis 2023; 17:1-27. [PMID: 36005814 DOI: 10.1093/ecco-jcc/jjac115] [Citation(s) in RCA: 126] [Impact Index Per Article: 63.0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2022] [Indexed: 02/02/2023]
Affiliation(s)
- Joana Torres
- Division of Gastroenterology, Hospital Beatriz Ângelo, Loures, Portugal
- Division of Gastroenterology, Hospital da Luz, Lisboa, Portugal
- Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal
| | - María Chaparro
- Department of Gastroenterology, Hospital Universitario de La Princesa, IIS-Princesa, UAM, CIBEREHD, Madrid, Spain
| | - Mette Julsgaard
- Department of Hepatology & Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
- Center for Molecular Prediction of Inflammatory Bowel Disease [PREDICT], Department of Clinical Medicine, Aalborg University, Copenhagen, Denmark
| | - Konstantinos Katsanos
- Department of Gastroenterology and Hepatology, University and Medical School of Ioannina, Ioannina, Greece
| | - Zuzana Zelinkova
- Department of Internal Medicine, Svet zdravia, Nemocnica Dunajska Streda, Slovakia
- Firstst Department of Internal Medicine of University Hospital and Slovak Medical University in Bratislava, Bratislava, Slovakia
| | - Manasi Agrawal
- Dr Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Center for Molecular Prediction of Inflammatory Bowel Disease [PREDICT], Department of Clinical Medicine, Aalborg University, Copenhagen, Denmark
| | - Sandro Ardizzone
- Gastrointestinal Unit, Department of Biomedical and Clinical Sciences. University of Milan, Milan, Italy
| | - Marjo Campmans-Kuijpers
- Department of Gastroenterology and Hepatology, University Medical Centre Groningen, Groningen, The Netherlands
| | - Gabriele Dragoni
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences 'Mario Serio', University of Florence, Florence, Italy
- Gastroenterology Department, Careggi University Hospital, Florence, Italy
| | - Marc Ferrante
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
- Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven, Belgium
| | - Gionata Fiorino
- Department of Gastroenterology and Digestive Endoscopy, IRCCS San Raffaele Hospital and Vita-Salute San Raffaele University, Milan, Italy
| | - Emma Flanagan
- Department of Gastroenterology, St Vincent's Hospital Melbourne, Fitzroy, VIC, Australia
| | | | - Ailsa Hart
- Inflammatory Bowel Diseases Unit, St Mark's Hospital, Harrow, UK
| | - Charlotte Rose Hedin
- Karolinska Institutet, Department of Medicine Solna, Stockholm, Sweden
- Karolinska University Hospital, Department of Gastroenterology, Dermatovenereology and Rheumatology, Stockholm, Sweden
| | - Pascal Juillerat
- Clinic for Visceral Surgery and Medicine, Bern University Hospital, Bern, Switzerland
- Crohn's and Colitis Center, Gastroenterology Beaulieu SA, Lausanne, Switzerland
| | - Annemarie Mulders
- Department of Obstetrics and Gynaecology, Division of Obstetrics and Fetal Medicine Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands
| | - Pär Myrelid
- Department of Surgery, Linköping University Hospital, Linköping, Sweden
- Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
| | - Aoibhlinn O'Toole
- Beaumont Hospital, Department of Gastroenterology, Royal College of Surgeons, Dublin, Ireland
| | - Pauline Rivière
- Gastroenterology Unit, Bordeaux University Hospital, Pessac, France
| | - Michael Scharl
- Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | | | - Elena Sonnenberg
- Charité-Universitätsmedizin Berlin, Department of Gastroenterology, Infectious Diseases and Rheumatology, Germany
| | - Murat Toruner
- Department of Gastroenterology, Ankara University School of Medicine, Ankara, Turkey
| | - Jantien Wieringa
- Department of Paediatrics, Haaglanden Medical Center, The Hague, The Netherlands
- Department of Paediatrics, Erasmus Medical Center-Sophia Children's Hospital, Rotterdam, The Netherlands
| | - C Janneke Van der Woude
- Department of Gastroenterology & Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands
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11
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Hisano M, Nakagawa K, Kwak-Kim J, Sugiyama R, Sago H, Yamaguchi K. Changes in the T-helper 1 and 2 cell populations during pregnancy in tacrolimus-treated women with repeated implantation failure and recurrent pregnancy loss. HUM FERTIL 2022; 25:975-982. [PMID: 34304683 DOI: 10.1080/14647273.2021.1955415] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
Tacrolimus has received considerable attention as a treatment approach for infertility associated with maternal-foetal immune abnormalities, such as repeated implantation failure (RIF) and recurrent pregnancy loss (RPL). This study examined the changes in T-helper (Th) 1 and 2 cell populations during pregnancy in peripheral blood of tacrolimus-treated RIF patients who delivered a liveborn infant from August 2012 to February 2020 at the National Centre for Child Health and Development. A total of 58 eligible study subjects were divided into two groups according to the presence of a history of RPL: (i) RIF-alone group (n = 31); and (ii) RIF-plus-RPL group (n = 27). In a flow cytometric analysis, the Th1/Th2 cell ratios were significantly higher before pregnancy than after pregnancy, and during the first trimester than the second trimester in the RIF-alone group (p = 0.0071 and p = 0.0087, respectively). However, no significant differences were present in the RIF-plus-RPL group. Although the Th1 immunity was suppressed under tacrolimus treatment in both groups, a delayed reduction in the Th1 cell percentage after initiation of treatment was observed in the RIF-plus-RPL group. In conclusion, the cellular immune alterations in tacrolimus-treated patients with RIF were different depending on the presence or absence of a history of RPL.
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Affiliation(s)
- Michi Hisano
- Center of Maternal-Fetal, Neonatal and Reproductive Medicine, National Center for Child Health and Development, Tokyo, Japan
| | - Koji Nakagawa
- Center for Reproductive Medicine and Implantation Research, Sugiyama Clinic Shinjuku, Tokyo, Japan
| | - Joanne Kwak-Kim
- Reproductive Medicine, Department of Obstetrics and Gynecology, Chicago Medical School at Rosalind Franklin University of Medicine and Science, Vernon Hills, IL, USA
| | - Rikikazu Sugiyama
- Center for Reproductive Medicine and Implantation Research, Sugiyama Clinic Shinjuku, Tokyo, Japan
| | - Haruhiko Sago
- Center of Maternal-Fetal, Neonatal and Reproductive Medicine, National Center for Child Health and Development, Tokyo, Japan
| | - Koushi Yamaguchi
- Center of Maternal-Fetal, Neonatal and Reproductive Medicine, National Center for Child Health and Development, Tokyo, Japan
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12
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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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13
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Schulz P, Testa G, York JR, Johannesson L. Children after Uterus Transplantation: 2‐Year Outcomes from the Dallas UtErus Transplant Study (DUETS). BJOG 2022; 129:2117-2124. [DOI: 10.1111/1471-0528.17270] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Revised: 05/26/2022] [Accepted: 05/31/2022] [Indexed: 11/28/2022]
Affiliation(s)
- Philipp Schulz
- Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center Dallas
| | - Giuliano Testa
- Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center Dallas
| | - Jackie R. York
- Department of Neonatology Baylor University Medical Center Dallas
| | - Liza Johannesson
- Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center Dallas
- Department of Obstetrics and Gynecology Baylor University Medical Center Dallas
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14
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Domino liver transplant from a donor with maple syrup urine disease into a recipient with phenylketonuria. Mol Genet Metab Rep 2022; 31:100866. [PMID: 35782613 PMCID: PMC9248231 DOI: 10.1016/j.ymgmr.2022.100866] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2022] [Revised: 03/28/2022] [Accepted: 04/02/2022] [Indexed: 11/23/2022] Open
Abstract
Classical phenylketonuria (PKU) presents a unique challenge for women of child-bearing age. In the context of pregnancy, poorly controlled hyperphenylalaninemia can result in a devastating constellation of outcomes for the baby referred to as the maternal PKU Syndrome. We present the case of a woman with classical PKU unable to maintain a restricted diet and refractory to pharmacological therapies. She elected to undergo a domino liver transplant, receiving an organ from a donor with classical branched chain ketoacid dehydrogenase deficiency (maple syrup urine disease). Plasma phenylalanine concentrations normalized within a few days after transplant and remained so on an unrestricted diet during the first year of follow-up. The patient reports subjective improvements in mood, energy level, and overall quality of life. In the appropriate clinical setting, liver transplant should be considered to provide metabolic stability for PKU patients, particularly women of childbearing age.
This article describes thenovel use of liver transplantation to prevent maternal PKU in a planned pregnancy. Utilization of a domino liver allograft from a patient who was being transplanted for Maple Syrup Urine Disease. Provides a systematic review of the available literature supporting the procedure and discussing the current outcome after transplant.
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15
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Finding the Right Balance in Pregnancy After Liver Transplantation: The Graft Function Should Also Be Taken Into Account. Am J Gastroenterol 2022; 117:1013-1014. [PMID: 35081050 DOI: 10.14309/ajg.0000000000001629] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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16
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Balakirski G, Gerdes S, Beissert S, Ochsendorf F, von Kiedrowski R, Wilsmann-Theis D. Psoriasis-Therapie während Schwangerschaft und Stillzeit. J Dtsch Dermatol Ges 2022; 20:653-685. [PMID: 35578434 DOI: 10.1111/ddg.14789_g] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2021] [Accepted: 03/09/2022] [Indexed: 11/30/2022]
Affiliation(s)
- Galina Balakirski
- Zentrum für Dermatologie, Allergologie und Dermatochirurgie, HELIOS Universitätsklinikum Wuppertal, Universität Witten/Herdecke, Wuppertal
| | - Sascha Gerdes
- Psoriasis-Zentrum, Klinik für Dermatologie, Venerologie und Allergologie, Universitätsklinikum Schleswig- Holstein - Campus Kiel
| | - Stefan Beissert
- Klinik und Poliklinik für Dermatologie, Universitätsklinikum Carl Gustav Carus Dresden
| | - Falk Ochsendorf
- Klinik für Dermatologie, Venerologie und Allergologie, Universitätsklinikum Frankfurt am Main
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17
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Balakirski G, Gerdes S, Beissert S, Ochsendorf F, von Kiedrowski R, Wilsmann-Theis D. Therapy of psoriasis during pregnancy and breast-feeding. J Dtsch Dermatol Ges 2022; 20:653-683. [PMID: 35578438 DOI: 10.1111/ddg.14789] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2021] [Accepted: 03/09/2022] [Indexed: 12/21/2022]
Abstract
There have been multiple systemic drugs approved for the therapy of psoriasis vulgaris and psoriasis arthritis (PsA) in the last decade. However, treatment decisions are difficult to make in women planning a pregnancy and in pregnant and lactating women due to the paucity of data for such cases. The strongest evidence for psoriasis therapy during pregnancy exists for topical corticosteroids. Medically controlled use of UVB-therapy is also considered safe. The best evidence regarding systemic therapy during pregnancy and lactation is available for the group of TNF-alpha inhibitors, which is also reflected in the respective medical product information. This is especially important in cases of psoriatic arthritis. Among traditional systemic therapeutics, the largest clinical experience exists for ciclosporin, which, if medically necessary, may be continued during gestation. However, TNF-alpha inhibitors, especially the pegylated form, should be preferred in case of pregnancy. Furthermore, an elective pregnancy termination is not necessary due to systemic therapy of psoriasis with many further substances during the first pregnancy weeks. The current work provides a comprehensive review of the scientific literature on treatment of psoriasis during pregnancy and lactation. Based on the available scientific information, severity of psoriasis and patient's comorbidities, the best possible therapeutic approach can be found in consensus with the patient.
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Affiliation(s)
- Galina Balakirski
- Center for Dermatology, Allergology and Dermatosurgery, HELIOS University Hospital Wuppertal, Witten/Herdecke University, Wuppertal, Germany
| | - Sascha Gerdes
- Psoriasis Center, Department of Dermatology, Venereology and Allergology, University Hospital Schleswig- Holstein - Campus Kiel, Germany
| | - Stefan Beissert
- Department and Clinic for Dermatology, University Hospital Carl Gustav Carus, Dresden, Germany
| | - Falk Ochsendorf
- Department of Dermatology, Venereology and Allergology, University Hospital Frankfurt am Main, Frankfurt, Germany
| | | | - Dagmar Wilsmann-Theis
- Department and Clinic for Dermatology and Allergology, University Hospital Bonn, Germany
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18
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Sciarrone SS, Ferrarese A, Bizzaro D, Volpato S, Donato FM, Invernizzi F, Trespidi L, Ramezzana IG, Avolio AW, Nure E, Pascale MM, Fagiuoli S, Pasulo L, Merli M, Lapenna L, Toniutto P, Lenci I, Di Donato R, De Maria N, Villa E, Galeota Lanza A, Marenco S, Bhoori S, Mameli L, Cillo U, Boccagni P, Russo FP, Bo P, Cosmi E, Burra P. Safe pregnancy after liver transplantation: Evidence from a multicenter Italian collaborative study. Dig Liver Dis 2022; 54:669-675. [PMID: 34497039 DOI: 10.1016/j.dld.2021.08.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2021] [Revised: 08/17/2021] [Accepted: 08/18/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND Women who have undergone liver transplantation (LT) enjoy better health, and possibility of childbearing. However, maternal and graft risks, optimal immunosuppression, and fetal outcome is still to clarify. AIM Aim of the study was to assess outcomes of pregnancy after LT at national level. METHODS In 2019, under the auspices of the Permanent Transplant Committee of the Italian Association for the Study of the Liver, a multicenter survey including 14 Italian LT-centers was conducted aiming at evaluating the outcomes of recipients and newborns, and graft injury/function parameters during pregnancy in LT-recipients. RESULTS Sixty-two pregnancies occurred in 60 LT-recipients between 1990 and 2018. Median age at the time of pregnancy was 31-years and median time from transplantation to conception was 8-years. During pregnancy, 4 recipients experienced maternal complications with hospital admission. Live-birth-rate was 100%. Prematurity occurred in 25/62 newborns, and 8/62 newborns had low-birth-weight. Cyclosporine was used in 16 and Tacrolimus in 37 pregnancies, with no different maternal or newborn outcomes. Low-birth-weight was correlated to high values of AST, ALT and GGT. CONCLUSION Pregnancy after LT has good outcome; however, maternal complications and prematurity may occur. Compliance with the immunosuppression is fundamental to ensure the stability of graft function and prevent graft-deterioration.
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Affiliation(s)
- Salvatore Stefano Sciarrone
- Multivisceral Transplant Unit, Department of Surgery Oncology and Gastroenterology, University of Padua, Via Giustiniani 2, Padua 35128, Italy
| | - Alberto Ferrarese
- Multivisceral Transplant Unit, Department of Surgery Oncology and Gastroenterology, University of Padua, Via Giustiniani 2, Padua 35128, Italy
| | - Debora Bizzaro
- Multivisceral Transplant Unit, Department of Surgery Oncology and Gastroenterology, University of Padua, Via Giustiniani 2, Padua 35128, Italy
| | - Sofia Volpato
- Gynaecology and Obstetrics Unit, Department of Women's and Children's Health, University of Padua, Via Giustianini 3, Padua 35128, Italy
| | - Francesca Maria Donato
- Division of Gastroenterology, Maggiore Hospital and IRCCS Foundation, Via Francesco Sforza 35, Milan 20122, Italy
| | - Federica Invernizzi
- Division of Gastroenterology, Maggiore Hospital and IRCCS Foundation, Via Francesco Sforza 35, Milan 20122, Italy
| | - Laura Trespidi
- Gynaecology and Obstetrics Unit, Department of Women's and Children's Health, Fondazione Ospedale Maggiore, Via Francesco Sforza 35, Milan 20122, Italy
| | - Ilaria Giuditta Ramezzana
- Gynaecology and Obstetrics Unit, Department of Women's and Children's Health, Fondazione Ospedale Maggiore, Via Francesco Sforza 35, Milan 20122, Italy
| | - Alfonso Wolfango Avolio
- Liver Unit, Department of Surgery, Agostino Gemelli Hospital, Catholic University, Largo Agostino Gemelli 8, Rome 00168, Italy
| | - Erida Nure
- Liver Unit, Department of Surgery, Agostino Gemelli Hospital, Catholic University, Largo Agostino Gemelli 8, Rome 00168, Italy
| | - Marco Maria Pascale
- Liver Unit, Department of Surgery, Agostino Gemelli Hospital, Catholic University, Largo Agostino Gemelli 8, Rome 00168, Italy
| | - Stefano Fagiuoli
- Gastroenterology, Hepatology and Liver Transplantation Unit, ASST Papa Giovanni XXIII, Piazza OMS 1, Bergamo 24127, Italy
| | - Luisa Pasulo
- Gastroenterology, Hepatology and Liver Transplantation Unit, ASST Papa Giovanni XXIII, Piazza OMS 1, Bergamo 24127, Italy
| | - Manuela Merli
- Gastroenterology, Department of Clinical Medicine, Sapienza University of Rome, Via di Grottarossa 1015, Rome 00189, Italy
| | - Lucia Lapenna
- Gastroenterology, Department of Clinical Medicine, Sapienza University of Rome, Via di Grottarossa 1015, Rome 00189, Italy
| | - Pierluigi Toniutto
- Internal Medicine, Department of Medical Area, University of Udine, via Palladio 8, Udine 33100, Italy
| | - Ilaria Lenci
- Hepatology and Liver Transplant Unit, Department of Medicine, Policlinico Tor Vergata, Viale Oxford 81, Rome 00133, Italy
| | - Roberto Di Donato
- Department of Digestive Disease and Internal Medicine, Azienda Ospedaliero-Universitaria di Bologna Policlinico S.Orsola-Malpighi, Via Giuseppe Massarenti 11, Bologna 40138, Italy
| | - Nicola De Maria
- Department of Internal Medicine, Gastroenterology Unit, Azienda Ospedaliero-Universitaria Policlinico di Modena, Largo del Pozzo 71, Modena 41124, Italy
| | - Erica Villa
- Department of Internal Medicine, Gastroenterology Unit, Azienda Ospedaliero-Universitaria Policlinico di Modena, Largo del Pozzo 71, Modena 41124, Italy
| | | | - Simona Marenco
- Department of Internal Medicine, Gastroenterolgy Unit, Ospedale Policlinico San Martino, Largo Rosanna Benzi 10, Genova 16132, Italy
| | - Sherrie Bhoori
- Department of Surgery and Oncology, Istituto Nazionale Tumori IRCCS, Via Giacomo Venezian, 1, Milan 20133, Italy
| | - Laura Mameli
- Liver and Pancreas Transplant Center, Azienda Ospedaliera Brotzu Piazzale Ricchi 1, Cagliari 09134, Italy
| | - Umberto Cillo
- Hepatobiliary Surgery and Liver Transplantation Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Via Giustiniani 2, Padua 35128, Italy
| | - Patrizia Boccagni
- Hepatobiliary Surgery and Liver Transplantation Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Via Giustiniani 2, Padua 35128, Italy
| | - Francesco Paolo Russo
- Multivisceral Transplant Unit, Department of Surgery Oncology and Gastroenterology, University of Padua, Via Giustiniani 2, Padua 35128, Italy
| | - Patrizio Bo
- Gynaecology and Obstetrics Unit, Cittadella Hospital, Via Riva dell'Ospedale, Cittadella 35013, Italy
| | - Erich Cosmi
- Gynaecology and Obstetrics Unit, Department of Women's and Children's Health, University of Padua, Via Giustianini 3, Padua 35128, Italy
| | - Patrizia Burra
- Multivisceral Transplant Unit, Department of Surgery Oncology and Gastroenterology, University of Padua, Via Giustiniani 2, Padua 35128, Italy.
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19
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Rashidi-Alavijeh J, Frey A, Hörster A, Nguyen BP, Iannaccone A, Saner F, Lange CM, Willuweit K. Safe for Mother, Baby, and Graft? Pregnancy After Liver Transplant: A Single-Center Experience. Transplant Proc 2022; 54:744-748. [DOI: 10.1016/j.transproceed.2022.01.023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Accepted: 01/17/2022] [Indexed: 11/30/2022]
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20
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Balakirski G, Novak N. Atopic Dermatitis and Pregnancy. J Allergy Clin Immunol 2022; 149:1185-1194. [DOI: 10.1016/j.jaci.2022.01.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Revised: 12/28/2021] [Accepted: 01/07/2022] [Indexed: 11/26/2022]
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21
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Dokmak A, Trivedi HD, Bonder A, Wolf J. Pregnancy in Chronic Liver Disease: Before and After Transplantation. Ann Hepatol 2021; 26:100557. [PMID: 34656772 DOI: 10.1016/j.aohep.2021.100557] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2021] [Revised: 05/27/2021] [Accepted: 05/27/2021] [Indexed: 02/04/2023]
Abstract
Chronic liver disease poses various challenges for women of reproductive age. Cirrhosis, particularly if decompensated, and liver transplantation may impact gestation and perinatal outcomes. Tailored management of underlying liver disease is critical to optimize maternal and fetal wellbeing. Early education, timely intervention, close monitoring, and a multidisciplinary approach are key elements required to minimize complications and increase chances of a safe and successful pregnancy. In this review, we focus on the pregnancy-related implications of chronic liver disease and liver transplantation on women of reproductive age and highlight disease-specific management considerations.
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Affiliation(s)
- Amr Dokmak
- Department of Hospital Medicine, Catholic Medical Center, Manchester, NH, USA.
| | - Hirsh D Trivedi
- Department of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Alan Bonder
- Liver Center, Department of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Jacqueline Wolf
- Department of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
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22
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Usage of Tacrolimus and Mycophenolic Acid During Conception, Pregnancy, and Lactation, and Its Implications for Therapeutic Drug Monitoring: A Systematic Critical Review. Ther Drug Monit 2021; 42:518-531. [PMID: 32398419 DOI: 10.1097/ftd.0000000000000769] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Conception, pregnancy, and lactation following solid organ transplantation require appropriate management. The most frequently used immunosuppressive drug combination after solid organ transplantation consists of tacrolimus (Tac) plus mycophenolic acid (MPA). Here, the effects of Tac and MPA on fertility, pregnancy, and lactation are systematically reviewed, and their implications for therapeutic drug monitoring (TDM) are discussed. METHODS A systematic literature search was performed (August 19, 2019) using Ovid MEDLINE, EMBASE, the Cochrane Central Register of controlled trials, Google Scholar, and Web of Science, and 102 studies were included. Another 60 were included from the reference list of the published articles. RESULTS As MPA is teratogenic, women who are trying to conceive are strongly recommended to switch from MPA to azathioprine. MPA treatment in men during conception seems to have no adverse effect on pregnancy outcomes. Nevertheless, in 2015, the drug label was updated with additional risk minimization measures in a pregnancy prevention program. Data on MPA pharmacokinetics during pregnancy and lactation are limited. Tac treatment during conception, pregnancy, and lactation seems to be safe in terms of the health of the mother, (unborn) child, and allograft. However, Tac may increase the risk of hypertension, preeclampsia, preterm birth, and low birth weight. Infants will ingest very small amounts of Tac via breast milk from mothers treated with Tac. However, no adverse outcomes have been reported in children exposed to Tac during lactation. During pregnancy, changes in Tac pharmacokinetics result in increased unbound to whole-blood Tac concentration ratio. To maintain Tac concentrations within the target range, increased Tac dose and intensified TDM may be required. However, it is unclear if dose adjustments during pregnancy are necessary, considering the higher concentration of (active) unbound Tac. CONCLUSIONS Tac treatment during conception, pregnancy and lactation seems to be relatively safe. Due to pharmacokinetic changes during pregnancy, a higher Tac dose might be indicated to maintain target concentrations. However, more evidence is needed to make recommendations on both Tac dose adjustments and alternative matrices than whole-blood for TDM of Tac during pregnancy. MPA treatment in men during conception seems to have no adverse effect on pregnancy outcomes, whereas MPA use in women during conception and pregnancy is strongly discouraged.
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Aljerian K. Uterine transplant: an ethical framework analysis from a Middle Eastern perspective. Curr Med Res Opin 2021; 37:1049-1060. [PMID: 33705236 DOI: 10.1080/03007995.2021.1902296] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
BACKGROUND Significant advances in infertility treatment have been achieved over the past several decades, but women with uterine dysfunction, anomaly, or agenesis still need support to carry a pregnancy to term. Recently, advancements in surgical, anesthetic and immunosuppressive therapy have brought the idea of successful uterine transplant closer to reality, but many challenges must be overcome before uterine transplant can become more common, including ethical challenges related to the study and the conduct of this procedure. METHODS This was an updated ethical analysis of uterine transplant from a Middle Eastern perspective, using an established ethical framework that has been adapted for the analysis of research in non-Western cultures and developing countries. RESULTS Using the ethical framework, this analysis explored research developments in uterine transplant to date, using the following categories: collaborative partnership, social value, scientific validity, a fair selection of study population, favorable risk-benefit ratio, independent review, informed consent, and respect for recruited participants. The analysis revealed a significant need for region- and religion-specific ethical guidelines for uterine transplant procedures. CONCLUSIONS The horizons of research need to expand by addressing and researching the ethical issues related to uterine transplant trials and clinical procedures. LIMITATIONS Limitations included the challenges related to applying ethical analyses to work in developing countries, and the fact that this analysis was based on the views and interpretations of a single researcher.
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Affiliation(s)
- Khaldoon Aljerian
- Forensic and Legal Medicine Unit, Department of Pathology, College of Medicine, King Saud University, Riyadh, Saudi Arabia
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Boulay H, Mazaud-Guittot S, Supervielle J, Chemouny JM, Dardier V, Lacroix A, Dion L, Vigneau C. Maternal, foetal and child consequences of immunosuppressive drugs during pregnancy in women with organ transplant: a review. Clin Kidney J 2021; 14:1871-1878. [PMID: 34345409 PMCID: PMC8323135 DOI: 10.1093/ckj/sfab049] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2020] [Accepted: 03/01/2021] [Indexed: 02/06/2023] Open
Abstract
Although pregnancy remains exceptional in women after heart, liver or lung transplant, obstetricians and nephrologists are regularly confronted with pregnancy in renal transplant recipients. National and international registries have described the epidemiology of maternal, foetal and neonatal complications, and transplantation societies have published recommendations on the monitoring of these high-risk pregnancies. In this review, we summarize the existing data on maternal and foetal complications of pregnancies in women after renal transplant, especially the management of immunosuppression. We also describe the few available data on the middle- and long-term outcomes of their children who were exposed in utero to immunosuppressive drugs.
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Affiliation(s)
- Hugoline Boulay
- University of Rennes, CHU Rennes, INSERM, EHESP, IRSET (Institut de recherche en santé, environnement et travail) - UMR_S 1085, F-35000, Rennes, France
| | - Séverine Mazaud-Guittot
- University of Rennes, CHU Rennes, INSERM, EHESP, IRSET (Institut de recherche en santé, environnement et travail) - UMR_S 1085, F-35000, Rennes, France
| | - Jeanne Supervielle
- University of Rennes, CHU Rennes, INSERM, EHESP, IRSET (Institut de recherche en santé, environnement et travail) - UMR_S 1085, F-35000, Rennes, France
| | - Jonathan M Chemouny
- University of Rennes, CHU Rennes, INSERM, EHESP, IRSET (Institut de recherche en santé, environnement et travail) - UMR_S 1085, F-35000, Rennes, France
| | - Virginie Dardier
- Laboratoire de psychologie, comportement, cognition et communication (LP3 C), Université Rennes-Rennes 2, Rennes, France
| | - Agnes Lacroix
- Laboratoire de psychologie, comportement, cognition et communication (LP3 C), Université Rennes-Rennes 2, Rennes, France
| | - Ludivine Dion
- University of Rennes, CHU Rennes, INSERM, EHESP, IRSET (Institut de recherche en santé, environnement et travail) - UMR_S 1085, F-35000, Rennes, France
| | - Cécile Vigneau
- University of Rennes, CHU Rennes, INSERM, EHESP, IRSET (Institut de recherche en santé, environnement et travail) - UMR_S 1085, F-35000, Rennes, France
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Pregnancy Outcomes After Liver Transplantation: A Systematic Review and Meta-Analysis. Am J Gastroenterol 2021; 116:491-504. [PMID: 33657039 DOI: 10.14309/ajg.0000000000001105] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2020] [Accepted: 11/13/2020] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Liver transplantation (LT) remains the gold standard for treatment of end-stage liver disease. Given the increasing number of liver transplantation in females of reproductive age, our aim was to conduct a systematic review and meta-analysis evaluating pregnancy outcomes after LT. METHODS MEDLINE, Embase, and Scopus databases were searched for relevant studies. Study selection, quality assessment, and data extraction were conducted independently by 2 reviewers. Estimates of pregnancy-related outcomes in LT recipients were generated and pooled across studies using the random-effects model. RESULTS A comprehensive search identified 1,430 potential studies. Thirty-eight studies with 1,131 pregnancies among 838 LT recipients were included in the analysis. Mean maternal age at pregnancy was 27.8 years, with a mean interval from LT to pregnancy of 59.7 months. The live birth rate was 80.4%, with a mean gestational age of 36.5 weeks. The rate of miscarriages (16.7%) was similar to the general population (10%-20%). The rates of preterm birth, preeclampsia, and cesarean delivery (32.1%, 12.5%, and 42.2%, respectively) among LT recipients were all higher than the rates for the general US population (9.9%, 4%, and 32%, respectively). Most analyses were associated with substantial heterogeneity. DISCUSSION Pregnancy outcomes after LT are favorable, but the risk of maternal and fetal complications is increased. Large studies along with consistent reporting to national registries are necessary for appropriate patient counseling and to guide clinical management of LT recipients during pregnancy.
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Sarkar M, Brady CW, Fleckenstein J, Forde KA, Khungar V, Molleston JP, Afshar Y, Terrault NA. Reproductive Health and Liver Disease: Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology 2021; 73:318-365. [PMID: 32946672 DOI: 10.1002/hep.31559] [Citation(s) in RCA: 67] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2020] [Accepted: 09/08/2020] [Indexed: 12/11/2022]
Affiliation(s)
- Monika Sarkar
- University of California, San Francisco, San Francisco, CA
| | | | | | | | | | - Jean P Molleston
- Indiana University and Riley Hospital for Children, Indianapolis, IN
| | - Yalda Afshar
- University of California, Los Angeles, Los Angeles, CA
| | - Norah A Terrault
- Keck School of Medicine, University of Southern California, Los Angeles, CA
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Clark-Snustad K, Butnariu M, Afzali A. Women's Health and Ulcerative Colitis. Gastroenterol Clin North Am 2020; 49:769-789. [PMID: 33121695 DOI: 10.1016/j.gtc.2020.07.004] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Although ulcerative colitis affects males and females at similar rates, certain sex-specific differences influence the disease-related risks and experiences of females with ulcerative colitis. This article reviews topics that affect females with ulcerative colitis, including the impact of disease on the menstrual cycle, fertility, child bearing, sexual health, and recommendations for health care maintenance.
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Affiliation(s)
- Kindra Clark-Snustad
- Inflammatory Bowel Disease Program, Division of Gastroenterology, University of Washington, 1959 Northeast Pacific Street, Box 356424, Seattle, WA 98195, USA
| | - Madalina Butnariu
- Division of Gastroenterology, Hepatology and Nutrition, The Ohio State University Wexner Medical Center, 410 W. 10(th) Ave. 2(nd) floor, Columbus, OH 43210, USA
| | - Anita Afzali
- Division of Gastroenterology, Hepatology and Nutrition, The Ohio State University Wexner Medical Center, 395 West 12(th) Avenue, Room 280, Columbus, OH 43210, USA.
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Ziogas IA, Hayat MH, Tsoulfas G. Obstetrical and gynecologic challenges in the liver transplant patient. World J Transplant 2020; 10:320-329. [PMID: 33312893 PMCID: PMC7708880 DOI: 10.5500/wjt.v10.i11.320] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2020] [Revised: 10/05/2020] [Accepted: 10/20/2020] [Indexed: 02/06/2023] Open
Abstract
An increasing number of childbearing agewomen undergo liver transplantation (LT) in the United States. Transplantation in this patient subgroup poses a significant challenge regarding the plans for future fertility, particularly in terms of immunosuppression and optimal timing of conception. Intrapartum LT is only rarely performed as the outcome is commonly dismal for the mother or more commonly the fetus. On the other hand, the outcomes of pregnancy in LT recipients are favorable, and children born to LT recipients are relatively healthy. Counseling on pregnancy should start before LT and continue after LT up until pregnancy, while all pregnant LT recipients must be managed by amultidisciplinary team, including both an obstetrician and a transplant hepatologist. Additionally, an interval of at least 1-2 years after successful LT is recommended before considering pregnancy. Pregnancy-induced hypertension, pre-eclampsia, and gestational diabetes mellitus are reported more commonly during the pregnancies of LT recipients than in the pregnancies of non-transplant patients. As adverse fetal outcomes, such asmiscarriage, abortion, stillbirth, or ectopic pregnancy, may occur more often than in the non-transplant population, early planning or delivery either through a planned induction of labor or cesarean section is critical to minimize the risk of complications. No significant long-term physical or phycological abnormalities have been reported in children born to LT recipients.
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Affiliation(s)
- Ioannis A Ziogas
- Medical School, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece
| | - Muhammad H Hayat
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University Medical Center, Nashville, TN 37212, United States
| | - Georgios Tsoulfas
- Department of Surgery, Papageorgiou University Hospital, Aristotle University of Thessaloniki, Thessaloniki 54622, Greece
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Immunosuppressive and Immunomodulating Therapy for Atopic Dermatitis in Pregnancy: An Appraisal of the Literature. Dermatol Ther (Heidelb) 2020; 10:1215-1228. [PMID: 33140290 PMCID: PMC7649192 DOI: 10.1007/s13555-020-00457-w] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2020] [Indexed: 12/27/2022] Open
Abstract
The aim of this appraisal of the literature is to elucidate the effects of immunosuppressive and immunomodulating agents used to treat atopic dermatitis (AD) on risk factors for fertility, pregnancy, and breastfeeding. Negative side effects of the psychological and physical stresses associated to AD flairs and uncontrolled AD are discussed, in order to evaluate the consequences of abstaining from treatment. Research on pregnancies in Danish women suggests a tendency towards an increased use of topical steroids and ultraviolet light therapy during pregnancy, compared to before conception, confirming the need for these patients to receive treatment, as well as decreased use of systemic treatments, suggesting a tendency towards undertreatment in this patient population. It is important that effective treatment be provided to pregnant women with AD. Here we present an appraisal of current knowledge on treatments for AD and the risks of exposure for the fetus and breastfed infant. Since little is known about the association between AD, pregnancy, and systemic treatment, we generalize conclusions based on studies on treatments of pregnant women who have undergone organ transplantation and who have inflammatory bowel disease, rheumatic disease, and autoimmune disease. The majority of recommendations are therefore based on a low or very low quality of evidence according to the GRADE system. The selected studies reflect the authors’ assessment regarding originality and importance in the context of this appraisal. It is always the treating doctor’s responsibility to stay updated on current literature when treating patients, especially pregnant patients.
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Marson EJ, Kamarajah SK, Dyson JK, White SA. Pregnancy outcomes in women with liver transplants: systematic review and meta-analysis. HPB (Oxford) 2020; 22:1102-1111. [PMID: 32636057 DOI: 10.1016/j.hpb.2020.05.001] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2020] [Revised: 04/17/2020] [Accepted: 05/04/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Despite increasing reports of pregnancy in liver transplant recipients, questions remain about the impact of transplantation in pregnancy. METHODS This systematic review was performed according to PRISMA guidelines and eligible studies were identified through a search of PubMed, Scopus and Cochrane CENTRAL databases up to 26th December 2019 for studies reporting pregnancy with liver transplant. A meta-analysis was conducted with the use of random-effects modelling and prospectively registered with the PROSPERO database. RESULTS Of 1239 unique studies, 28 met inclusion criteria, representing 1496 pregnancies in 1073 liver transplant recipients. The live-birth rate was 85.6% (CI95%: 80.5%-90.7%). The rate of other pregnancy outcomes was as follows: induced abortions (5.7%), miscarriages (7.8%) and stillbirths (3.3%). Pooled rates of obstetric complications were hypertension (18.2%), pre-eclampsia (12.8%) and gestational diabetes (7.0%). Pooled rates of delivery outcomes for caesarean section (C-section) and pre-term birth were 42.2% and 27.8%, respectively. CONCLUSION In conclusion, live birth outcomes are good among liver transplant recipients and this favourable trend is consistent at an international level. However, special attention should be given to obstetric complications such as hypertension, pre-eclampsia, and preterm delivery. The high incidence of these complications supports the high-risk classification of post-liver transplant pregnancies and it is necessary for a multidisciplinary team to be involved in the monitoring and counselling of liver transplant recipients both before and during pregnancy. Whilst majority data originate from institutions from high-income countries, data from low-middle income countries (LMIC) are needed owing to rising rates of liver transplantation in LMIC.
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Affiliation(s)
- Ella J Marson
- College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
| | - Sivesh K Kamarajah
- Department of Hepatobiliary, Pancreatic and Transplant Surgery, Freeman Hospital, Newcastle University NHS Foundation Trust Hospitals, Newcastle Upon Tyne, UK; Institute of Cellular Medicine, Newcastle University, Newcastle Upon Tyne, UK.
| | - Jessica K Dyson
- Department of Hepatology, Newcastle Upon Tyne Hospitals NHS Foundation Trust Newcastle Upon Tyne, UK; Newcastle Biomedical Research Centre, Newcastle University, UK
| | - Steven A White
- Department of Hepatobiliary, Pancreatic and Transplant Surgery, Freeman Hospital, Newcastle University NHS Foundation Trust Hospitals, Newcastle Upon Tyne, UK; Institute of Cellular Medicine, Newcastle University, Newcastle Upon Tyne, UK
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Naya I, Sanada Y, Katano T, Miyahara G, Hirata Y, Yamada N, Okada N, Onishi Y, Sakuma Y, Sata N. Pregnancy Outcomes Following Pediatric Liver Transplantation: A Single-Center Experience in Japan. Ann Transplant 2020; 25:e921193. [PMID: 32513910 PMCID: PMC7304366 DOI: 10.12659/aot.921193] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Abstract
Background The number of pregnancies after liver transplantation (LT) is increasing; however, the safety and incidence of complications associated with these pregnancies are still unclear. In this report, we retrospectively assessed the influences and problems associated with post-transplant pregnancy on allografts, recipients, and fetuses. Material/Methods A total of 14 pregnancies were identified in 8 female recipients between 2005 and 2018. The original disease was biliary atresia in all recipients. We provide a basic guide for the management of planned pregnancies in female recipients. Results Of the 7 planned pregnancies, no recipients took mycophenolate mofetil (MMF) or had allograft liver dysfunction. Among the 7 unplanned conceptions, we judged that the pregnancy was inadequate to continue in 4 recipients due to taking MMF and 2 recipients due to allograft liver dysfunction at conception. However, 4 recipients who immediately stopped taking MMF continued with their pregnancies. Ten pregnancies resulted in live 11 births. Among obstetric complications or fetal and neonatal complications, gestational diabetes mellitus in 3 recipients was the most common. There were 3 miscarriages and 1 planned termination because of MMF medication and liver dysfunction. Conclusions Planned pregnancies in LT recipients can lead to the birth of a healthy baby and no influence on either the allograft or the recipient. However, unplanned pregnancies in LT recipients, such as recipients who take MMF or have allograft liver dysfunction, may have an adverse influence on the fetus.
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Affiliation(s)
- Itsuki Naya
- Department of Surgery, Division of Gastroenterological, General and Transplant Surgery, Jichi Medical University, Shimotsuke, Tochigi, Japan
| | - Yukihiro Sanada
- Department of Surgery, Division of Gastroenterological, General and Transplant Surgery, Jichi Medical University, Shimotsuke, Tochigi, Japan
| | - Takumi Katano
- Department of Surgery, Division of Gastroenterological, General and Transplant Surgery, Jichi Medical University, Shimotsuke, Tochigi, Japan
| | - Go Miyahara
- Department of Surgery, Division of Gastroenterological, General and Transplant Surgery, Jichi Medical University, Shimotsuke, Tochigi, Japan
| | - Yuta Hirata
- Department of Surgery, Division of Gastroenterological, General and Transplant Surgery, Jichi Medical University, Shimotsuke, Tochigi, Japan
| | - Naoya Yamada
- Department of Surgery, Division of Gastroenterological, General and Transplant Surgery, Jichi Medical University, Shimotsuke, Tochigi, Japan
| | - Noriki Okada
- Department of Surgery, Division of Gastroenterological, General and Transplant Surgery, Jichi Medical University, Shimotsuke, Tochigi, Japan
| | - Yasuharu Onishi
- Department of Surgery, Division of Gastroenterological, General and Transplant Surgery, Jichi Medical University, Shimotsuke, Tochigi, Japan
| | - Yasunaru Sakuma
- Department of Surgery, Division of Gastroenterological, General and Transplant Surgery, Jichi Medical University, Shimotsuke, Tochigi, Japan
| | - Naohiro Sata
- Department of Surgery, Division of Gastroenterological, General and Transplant Surgery, Jichi Medical University, Shimotsuke, Tochigi, Japan
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A Long-term Evaluation of Treatment Results of Pregnant Patients Following a Liver Transplant. Transplant Proc 2020; 52:2512-2516. [PMID: 32471631 DOI: 10.1016/j.transproceed.2020.03.034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2019] [Revised: 03/05/2020] [Accepted: 03/30/2020] [Indexed: 11/20/2022]
Abstract
INTRODUCTION Transplantation is not only the best method for treating end-stage failure of many organs but also the way to improve the quality of life of patients. For women of childbearing age, an organ transplant often brings a restoration of regular reproductive functions, which means, among other things, the possibility of having biological offspring. OBJECTIVES The aim of the study was to analyze the medical records and assess the impact of a liver transplant on the course of pregnancy and labor. MATERIALS AND METHODS The research was carried out from March to May 2019 in the Nephrology and Transplant Clinic Medical University of Warsaw. The study group consisted of 19 women after liver transplantation. Medical records were analyzed, and laboratory test results routinely performed on patients were also used for the study. RESULTS The mean age of conception of the patients following transplantation was 30 ± 4 years old. In the analyzed period, 6 patients gave birth to 2 children each, and 8 patients to 1 child each. Only 3 patients experienced premature birth. Twelve patients gave birth by caesarean delivery. Fourteen patients took tacrolimus. CONCLUSIONS Pregnancy is possible in patients following a liver transplant and does not appear to have a damaging effect on liver functionality. There is an increased risk of pre-eclampsia, intensified hypertension, and premature birth among patients following a transplant, which is why it is essential for these patients to remain under the care of a specialistic therapeutic team.
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Rahim MN, Long L, Penna L, Williamson C, Kametas NA, Nicolaides KH, Heneghan MA. Pregnancy in Liver Transplantation. Liver Transpl 2020; 26:564-581. [PMID: 31950556 DOI: 10.1002/lt.25717] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2019] [Accepted: 12/26/2019] [Indexed: 02/06/2023]
Abstract
Pregnancy after liver transplantation (LT) is increasingly common and is a frequent scenario that transplant physicians, obstetricians, and midwives encounter. This review summarizes the key issues surrounding preconception, pregnancy-related outcomes, immunosuppression, and breastfeeding in female LT recipients. Prepregnancy counseling in these patients should include recommendations to delay conception for at least 1-2 years after LT and discussions about effective methods of contraception. Female LT recipients are generally recommended to continue immunosuppression during pregnancy to prevent allograft rejection; however, individual regimens may need to be altered. Although pregnancy outcomes are overall favorable, there is an increased risk of maternal and fetal complications. Pregnancy in this cohort remains high risk and should be managed vigilantly in a multidisciplinary setting. We aim to review the available evidence from national registries, population-based studies, and case series and to provide recommendations for attending clinicians.
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Affiliation(s)
- Mussarat N Rahim
- Institute of Liver Studies, King's College Hospital, London, United Kingdom
| | - Lisa Long
- Department of Obstetrics, King's College Hospital, London, United Kingdom
| | - Leonie Penna
- Department of Obstetrics, King's College Hospital, London, United Kingdom
| | | | - Nikos A Kametas
- Fetal Medicine Research Unit, King's College Hospital, London, United Kingdom
| | - Kypros H Nicolaides
- Fetal Medicine Research Unit, King's College Hospital, London, United Kingdom
| | - Michael A Heneghan
- Institute of Liver Studies, King's College Hospital, London, United Kingdom
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Milić S, Tatalović T, Mikolašević I. Pre-existing liver disease in pregnancy: Cirrhosis, autoimmune hepatitis and liver transplantation. Best Pract Res Clin Gastroenterol 2020; 44-45:101668. [PMID: 32359683 DOI: 10.1016/j.bpg.2020.101668] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2019] [Revised: 01/22/2020] [Accepted: 02/18/2020] [Indexed: 01/31/2023]
Abstract
Liver disease during pregnancy is one of the least studied topics, but it links the interests of hepatologists, gynaecologists and family physicians. Approximately 3% of pregnant woman experience some type of liver disease. Liver disease can occur as a result of pregnancy, before pregnancy and coincidence-related during pregnancy. Pregnancy in women with pre-existing liver disease is essential that the clinicians are familiar with this disorder so they can respond promptly and appropriately in all of these situations. So, because of the complications for both mother and child, it is important that liver disease is recognized in a timely manner to avoid undesirable outcomes.
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Affiliation(s)
- Sandra Milić
- School of Medicine, University of Rijeka, Rijeka, Croatia; Department of Gastroenterology, University Hospital Center Rijeka, Rijeka, Croatia.
| | | | - Ivana Mikolašević
- School of Medicine, University of Rijeka, Rijeka, Croatia; Department of Gastroenterology, University Hospital Center Rijeka, Rijeka, Croatia.
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Sivaprasadan S, Mathew JS, Surendran S, Padma UD. Pregnancy After Liver Transplantation: Outcomes From a Single-Center Experience. J Clin Exp Hepatol 2020; 10:329-333. [PMID: 32655236 PMCID: PMC7335724 DOI: 10.1016/j.jceh.2019.10.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2019] [Accepted: 10/21/2019] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND/OBJECTIVES Although much has been learnt regarding pregnancy after liver transplantation, data from India are scant. Hence, we evaluated the maternal and fetal outcomes of pregnancies after liver transplantation at our center. METHODS We conducted a retrospective review of all patients who underwent liver transplantation and later conceived at our center between 2006 and 2019. RESULTS Of the 750 liver transplantations performed at our center, 129 were female and 62 of them were in the childbearing age group (15-44 years). A total of seven conceptions occurred in seven patients during the study period. All the pregnancies occurred spontaneously. The median age of the patients at the time of liver transplantation and conception was 25 years (range, 24-33 years) and 29 years (range, 26-36 years), respectively. The median interval between transplantation and conception was 40 months (range, 7-48 months). All patients were on tacrolimus monotherapy. None of the patients had rejection during pregnancy despite a low median tacrolimus trough level of 2.7 ng/mL. Live birth (five cesarean and one normal) occurred in six of seven pregnancies at a median gestation age of 37.5 weeks. Mean birth weight was 3055.8 g (range, 2470-3635 g). Antenatal rubella infection and grade III intrauterine growth restriction resulting in still birth at 29 weeks occurred in one patient. The median postnatal follow-up was 25 months (range, 2-81 months). All babies and mothers were healthy. CONCLUSIONS Pregnancy after liver transplantation has a favorable outcome with a multidisciplinary team approach. There is a physiological reduction of tacrolimus trough levels during pregnancy for which dose augmentation is not usually required.
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Affiliation(s)
- Saraswathy Sivaprasadan
- Department of Pharmacy Practice, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, Kochi, 682041, Kerala, India
| | - Johns S. Mathew
- Department of Gastrointestinal Surgery, Amrita Institute of Medical Sciences and Research Center, Amrita Vishwa Vidyapeetham, Kochi, 682041, Kerala, India
| | - Sudhindran Surendran
- Department of Gastrointestinal Surgery, Amrita Institute of Medical Sciences and Research Center, Amrita Vishwa Vidyapeetham, Kochi, 682041, Kerala, India
| | - Uma D. Padma
- Department of Pharmacology, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, Kochi, 682041, Kerala, India
- Address for correspondence: Dr. Uma Devi P, Associate Professor and Head, Department of Pharmacology, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, Kochi, 682041, Kerala, India.
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Nure E, Pascale MM, Frongillo F, Franco A, Bianco G, Agnes S. Pregnancy After Liver Transplant: Neonatal Outcomes and Long-Term Maternal Follow-up. Transplant Proc 2019; 51:2948-2951. [PMID: 31627912 DOI: 10.1016/j.transproceed.2019.02.071] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2019] [Accepted: 02/17/2019] [Indexed: 11/30/2022]
Abstract
BACKGROUND Today, women who have undergone liver transplantation enjoy better health, so they encounter more frequently the possibility of living pregnancy. Many questions about the safety of pregnancy are pending. This study analyzes pregnancy outcomes in women with a liver transplant managed at Policlinico Universitario "A.Gemelli." RESULTS We identified 17 childbirths in 13 women who had undergone a liver transplant. Causes of transplant include congenital or acquired disorders. The mean age at transplant was 22 ± 9 years, mean maternal age at delivery was 33 ± 5 years, and transplant-to-pregnancy interval was 12 ± 6 years. The mean gestational week was 36.1 ± 3.5. All women had normal liver function after pregnancy. Immunosuppressive therapy before and during pregnancy included tacrolimus (n = 8), cyclosporine (n = 5) and mycophenolate mofetil (n = 1). No maternal death was registered. Maternal complications included increase of aspartate transaminase and alanine transaminase, graft deterioration requiring liver retransplantation, increase of bile acids (n = 1), itch (n = 1), and anemia (n = 1). Twelve women had a high adherence to an immunosuppressive regimen during pregnancy. A woman with poor compliance continued therapy with mycophenolic acid during pregnancy, showing preterm birth (25th week) with fetal respiratory failure. Another woman continued therapy with tacrolimus during breastfeeding without adverse effects. CONCLUSION Liver transplant does not influence women's fertility; during pregnancy, we report low rates of minor graft complications and no major issues. There are no adverse effects on babies. An evaluation by a multidisciplinary team is recommended. Compliance to an immunosuppressive regimen is fundamental to ensure the stability of graft function and to prevent graft deterioration in pregnancy. Moreover, it is suggested to avoid teratogenic drugs, such as mycophenolic acid.
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Affiliation(s)
- Edria Nure
- Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Università Cattolica del Sacro Cuore, Department of General Surgery, General Surgery and Liver Transplant Unit, Rome, Italy
| | - Marco Maria Pascale
- Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Università Cattolica del Sacro Cuore, Department of General Surgery, General Surgery and Liver Transplant Unit, Rome, Italy.
| | - Francesco Frongillo
- Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Università Cattolica del Sacro Cuore, Department of General Surgery, General Surgery and Liver Transplant Unit, Rome, Italy
| | - Antonio Franco
- Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Università Cattolica del Sacro Cuore, Department of General Surgery, General Surgery and Liver Transplant Unit, Rome, Italy
| | - Giuseppe Bianco
- Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Università Cattolica del Sacro Cuore, Department of General Surgery, General Surgery and Liver Transplant Unit, Rome, Italy
| | - Salvatore Agnes
- Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Università Cattolica del Sacro Cuore, Department of General Surgery, General Surgery and Liver Transplant Unit, Rome, Italy
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Zullo F, Saccone G, Donnarumma L, Marino I, Guida M, Berghella V. Pregnancy after liver transplantation: a case series and review of the literature. J Matern Fetal Neonatal Med 2019; 34:3269-3276. [PMID: 31635500 DOI: 10.1080/14767058.2019.1680632] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVE To evaluate maternal and perinatal outcomes in pregnant women after liver transplantation with a case series and literature systematic review. METHODS This was a single-center case-series study performed at University of Naples Federico II. All consecutive women with liver transplantation who reported pregnancy at our institution were included in a dedicated database. In addition, a systematic literature review was performed, including case series, population-based studies, and national registries, including maternal and perinatal outcomes of pregnant women with liver transplant. Studies with fewer than 10 cases and surveys were excluded. The primary outcome was perinatal death, defined as either stillbirth (defined as intrauterine fetal death after 20 weeks of gestation) or neonatal death (death of a live-born infant within the first 28 d of life). RESULTS During the study period, two women who underwent liver transplantation had a pregnancy in our Institution. Both of them underwent liver transplantation for biliary atresia at 1 year of age. One of them received cyclosporin as immunosuppressive regime during pregnancy, while the other one received tacrolimus. Both of them had a pregnancy with no major complications and delivered by cesarean section at term a baby with normal weight. One of them developed thrombocytopenia. Seventeen articles were included in this systematic review. Preterm birth at less than 37 weeks of gestations occurred in 279 women (33.6%). One-hundred women (14.9%) experienced preeclampsia, and 206 women (49.2%) delivered by cesarean delivery. Graft rejection related to pregnancy occurred in 73 women (8.3%). 117 women (12.9%) experienced miscarriage, and 22 (2.3%) IUFD. Fifty-two women (9.52%) underwent elective I-TOP. 195 fetuses (33.4%) were LBW. Eight neonatal deaths were recorded (1.3%). CONCLUSION The maternal and perinatal outcome is usually favorable, but with an increased risk of preeclampsia, preterm birth, and perinatal morbidity and mortality. However, appropriate counseling about risks and complications is essential but women shouldn't be advised against pregnancy.
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Affiliation(s)
- Fabrizio Zullo
- Department of Clinical and Experimental Medicine, School of Medicine, University of Naples Federico II, Naples, Italy
| | - Gabriele Saccone
- Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, University of Naples Federico II, Naples, Italy
| | - Laura Donnarumma
- Department of Clinical and Experimental Medicine, School of Medicine, University of Naples Federico II, Naples, Italy
| | - Ignazio Marino
- Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA
| | - Maurizio Guida
- Department of Clinical and Experimental Medicine, School of Medicine, University of Naples Federico II, Naples, Italy
| | - Vincenzo Berghella
- Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA
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Vestergaard C, Wollenberg A, Barbarot S, Christen-Zaech S, Deleuran M, Spuls P, Flohr C, Trzeciak M, von Kobyletzki L, Seneschal J, Paul C, Bieber T, Werfel T, Fölster-Holst R, Darsow U, Gieler U, Svensson Å, Cork M, Stalder JF, De Raeve L, Kunz B, Simon D, Chernyshov P, Hijnen D, Gelmetti C, Ring J, Taieb A, de Bruin-Weller M, Thyssen JP. European task force on atopic dermatitis position paper: treatment of parental atopic dermatitis during preconception, pregnancy and lactation period. J Eur Acad Dermatol Venereol 2019; 33:1644-1659. [PMID: 31231864 DOI: 10.1111/jdv.15709] [Citation(s) in RCA: 70] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2019] [Accepted: 05/07/2019] [Indexed: 12/14/2022]
Abstract
Atopic dermatitis (AD) is a common inflammatory skin disease that affects both children and adults, including a large number of adults of reproductive age. Several guidelines for the treatment of AD exist, yet specific recommendations for the treatment of pregnant or lactating women and for adults planning to have a child are often lacking. This position paper from the European Task force on Atopic Dermatitis (ETFAD) is based on up-to-date scientific literature on treating pregnant and lactating women as wells as adults with AD planning to have a child. It is based on the expert opinions of members of the ETFAD and on existing safety data on the proposed treatments, many of which are derived from patients with other inflammatory diseases or from transplantation medicine. For treating future parents, as well as pregnant and lactating women with AD, the use of topical treatments including moisturizers, topical corticosteroids, tacrolimus, antiseptics such as chlorhexidine, octenidine, potassium permanganate and sodium hypochlorite (bleach) is deemed to be safe. Ultraviolet (UV) therapy may also be used. Systemic treatment should be prescribed only after careful consideration. According to the opinion of the ETFAD, treatment should be restricted to systemic corticosteroids and cyclosporine A, and, in selected cases, azathioprine.
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Affiliation(s)
- C Vestergaard
- Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark
| | - A Wollenberg
- Department of Dermatology and Allergy, Ludwig-Maximilian University, Munich, Germany.,Hautklinik Thalkirchner Straße, Staedtisches Klinikum Muenchen, Muenchen, Germany
| | - S Barbarot
- Department of Dermatology, CHU Nantes, Nantes, France
| | - S Christen-Zaech
- Pediatric Dermatology Unit, Departments of Dermatology and Pediatrics, Lausanne University Hospital, Lausanne, Switzerland
| | - M Deleuran
- Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark
| | - P Spuls
- Department of Dermatology, Amsterdam Public Health, Infection and Immunity, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - C Flohr
- St. Johns Institute of Dermatology, Kings College and Guy's and St Thomas' NHS Foundation Trust, London, UK
| | - M Trzeciak
- Department of Dermatology, Venereology and Allergology, Medical University of Gdansk, Gdansk, Poland
| | | | - J Seneschal
- Department of dermatology, INSERM, University of Bordeaux, Bordeaux, France
| | - C Paul
- Department of Dermatology, Larrey Hospital, Toulouse University, Toulouse, France
| | - T Bieber
- Department of Dermatology and Allergology, and Christine Kühne-Center for Allergy Research and Education, University of Bonn, Bonn, Germany
| | - T Werfel
- Department of Dermatology and Allergology, Hannover Medical School, Hannover, Germany
| | - R Fölster-Holst
- Department of Dermatology, Venerology and Allergology, University Medical Center Schleswig-Holstein, Kiel, Germany
| | - U Darsow
- Department of Dermatology and Allergology Biederstein, Technical University of Munich, Munich, Germany
| | - U Gieler
- Department of Dermatology, Justus-Liebig-University, Giessen, Germany
| | - Å Svensson
- Department of Dermatology, Lund University, Malmoe, Sweden
| | - M Cork
- Sheffield Dermatology Research, Department of Infection, Immunity & Cardiovascular Disease, University of Sheffield, Sheffield, UK
| | - J-F Stalder
- Department of Dermatology, CHU Nantes, Nantes, France
| | - L De Raeve
- Department of Dermatology, UZ Brussel, Free University of Brussels (VUB), Brussels, Belgium
| | - B Kunz
- Dermatologikum, Hamburg, Germany
| | - D Simon
- Department of Dermatology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - P Chernyshov
- Department of Dermatology, National Medical University, Kiev, Ukraine
| | - D Hijnen
- Department of Dermatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
| | - C Gelmetti
- Department of Pediatric Dermatology, Ospedale Maggiore Policlinico, University of Milan, Milano, Italy
| | - J Ring
- Department of Dermatology and Allergology Biederstein, Technical University of Munich, Munich, Germany.,Christiane-Kühne Center for Allergy Research and Education (CK-Care), Davos, Switzerland
| | - A Taieb
- Department of dermatology, INSERM, University of Bordeaux, Bordeaux, France
| | - M de Bruin-Weller
- Department of Dermatology and Allergology, University Medical Center Utrecht, Utrecht, The Netherlands
| | - J P Thyssen
- Department of Dermatology and Allergy, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
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Nakagawa K, Kwak-Kim J, Hisano M, Kasahara Y, Kuroda K, Sugiyama R, Yamaguchi K. Obstetric and perinatal outcome of the women with repeated implantation failures or recurrent pregnancy losses who received pre- and post-conception tacrolimus treatment. Am J Reprod Immunol 2019; 82:e13142. [PMID: 31081959 DOI: 10.1111/aji.13142] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2019] [Revised: 03/10/2019] [Accepted: 04/09/2019] [Indexed: 12/11/2022] Open
Abstract
PROBLEM Previously, we reported the clinical efficacy of tacrolimus in women with repeated implantation failures (RIF) of immune etiologies. Safety of tacrolimus in pregnant women has been reported in women with organ transplantations. However, the safety of tacrolimus for women with RIF undergoing assisted reproductive technology cycles and their babies has not been reported prior. METHOD OF STUDY This study is a prospective observational study of 109 women with RIF or recurrent pregnancy losses (RPL) who showed elevated peripheral blood Th1/Th2 (CD4+ IFN-γ+ /CD4+ IL-4+ ) cell ratios (≥10.3). All received tacrolimus before and during pregnancy (1-4 mg/d) and delivered a live-born infant(s). Blood concentrations of tacrolimus were measured. Neuromotor development of the babies was also evaluated. RESULTS Total 113 babies were born from 109 women, including four twin pregnancies. Nine pregnancies including four twins were delivered prematurely (8.3%). Two of 109 women showed obstetric complications, such as hypertensive disorder of pregnancy, and only one baby (0.9%) had a congenital abnormality. There were no differences in babies' birthweight, placental weight, and lymphocyte proportion (%) of the umbilical cord among the women with different tacrolimus dosing. Tacrolimus was detected in the maternal plasma, and its concentration did not significantly fluctuate during pregnancy while on daily administration regimen. Neuromotor development of the babies exposed to tacrolimus in utero was comparable with that of babies from the general population. CONCLUSION According to our data, tacrolimus treatment for women with RIF and RPL was not associated with obstetrical and perinatal complications. A large size study is needed to confirm this finding.
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Affiliation(s)
- Koji Nakagawa
- Center for Reproductive Medicine and Implantation Research, Sugiyama Clinic Shinjuku, Tokyo, Japan
| | - Joanne Kwak-Kim
- Reproductive Medicine and Immunology, Department of Obstetrics and Gynecology, Chicago Medical School at Rosalind Franklin University of Medicine and Science, Vernon Hills, Illinois
| | - Michi Hisano
- Department of Maternal-Fetal Biology, National Center for Child Health and Development, Tokyo, Japan
| | | | - Keiji Kuroda
- Center for Reproductive Medicine and Implantation Research, Sugiyama Clinic Shinjuku, Tokyo, Japan
| | - Rikikazu Sugiyama
- Center for Reproductive Medicine and Implantation Research, Sugiyama Clinic Shinjuku, Tokyo, Japan
| | - Koushi Yamaguchi
- Department of Maternal-Fetal Biology, National Center for Child Health and Development, Tokyo, Japan
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Outcomes of Pregnancy in Recipients of Liver Transplants. Clin Gastroenterol Hepatol 2019; 17:1398-1404.e1. [PMID: 30529735 DOI: 10.1016/j.cgh.2018.11.055] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2018] [Revised: 11/07/2018] [Accepted: 11/30/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Despite increasing reports of pregnancy in women who received liver transplants, it is not clear how transplantation and immunosuppression affect pregnancy. We collected data from liver transplant recipients who became pregnant on immunosuppression regimens, pregnancy management, graft morbidity, and outcomes of mothers and neonates. METHODS We searched the liver transplant database in Birmingham, United Kingdom, for women who reported pregnancy after liver transplantation from August 1986 through May 2016. We collected information on morbidities and outcomes of 139 pregnancies in 83 women (median age at conception, 27 y; range, 15-46 y). Fisher exact tests were used to compare categoric variables and Mann-Whitney U and Kruskal-Wallis tests were used to compare continuous variables. The primary outcome was the live birth rate in the entire cohort. Additional outcomes analyzed included differences in immunotherapy regimens, and outcomes associated with exposure to cyclosporine and tacrolimus, time to transplantation (<12 vs >12 mo), and time period of pregnancy (1986-2000 vs 2001-2016). RESULTS Of the pregnancies, 69% resulted in live births, 19% resulted in miscarriages or still births, and 9% were terminated. A higher proportion of patients who conceived more than 1 year after liver transplantation had live births than of women who conceived before this time (98% vs 80%; P = .006). Tacrolimus exposure was associated with higher risks of premature delivery (P = .045) and caesarian section (P = .031) than cyclosporine exposure. Compared with the period from 1986 to 2000, women who conceived from 2001 to 2016 had a significantly shorter time between transplantation and conception (median, 3 vs 7 y; P = .027), frequent use of tacrolimus vs cyclosporine (84% vs 26%; P = .001), and a higher incidence of cesarean section (44% vs 32%; P = .025). CONCLUSIONS Almost 70% of women who conceive after liver transplantation have live births, although this rate is lower than that of women in the overall population. These cases require involvement of hepatologists and obstetricians.
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42
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Yamaguchi K. Tacrolimus treatment for infertility related to maternal-fetal immune interactions. Am J Reprod Immunol 2019; 81:e13097. [PMID: 30689243 DOI: 10.1111/aji.13097] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2018] [Revised: 01/15/2019] [Accepted: 01/16/2019] [Indexed: 12/29/2022] Open
Abstract
Many approaches have been used to achieve successful pregnancies in patients with infertility, though existing treatments remain unsatisfactory in patients with infertility caused by abnormal maternal-fetal immunity. However, our understanding of the immunological aspects of infertility has steadily progressed, aided by recent research into organ transplantation and cancer. The results of these recent analyses have led to the development and evaluation of several candidate immunological treatments, but the use of immunological treatments remains a novel approach. The current paper presents the hypothesis that tacrolimus may have potential as a candidate agent for the treatment of maternal-fetal immunity-related infertility.
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Affiliation(s)
- Koushi Yamaguchi
- Center of Maternal-Fetal, Neonatal and Reproductive Medicine, National Center for Child Health and Development, Tokyo, Japan
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43
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Gülümser Ç, Kinap M, Yanik FB, Sahin Uysal N, Moray G, Haberal M. How safe is pregnancy after liver transplantation? A large case series study at tertiary referral center in Turkey. J Matern Fetal Neonatal Med 2018; 33:1218-1224. [DOI: 10.1080/14767058.2018.1517317] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Affiliation(s)
- Çağrι Gülümser
- Department of Obstetrics and Gynecology, University of Health Sciences, Ankara, Turkey
| | - Mahir Kinap
- Department of General Surgery, Baskent University School of Medicine, Baskent, Turkey
| | | | - Nihal Sahin Uysal
- Department of Obstetrics and Gynecology, University of Health Sciences, Ankara, Turkey
| | - Gokhan Moray
- Department of General Surgery, Baskent University School of Medicine, Baskent, Turkey
| | - Mehmet Haberal
- Department of General Surgery, Baskent University School of Medicine, Baskent, Turkey
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Mikolasevic I, Filipec-Kanizaj T, Jakopcic I, Majurec I, Brncic-Fischer A, Sobocan N, Hrstic I, Stimac T, Stimac D, Milic S. Liver Disease During Pregnancy: A Challenging Clinical Issue. Med Sci Monit 2018; 24:4080-4090. [PMID: 29905165 PMCID: PMC6034557 DOI: 10.12659/msm.907723] [Citation(s) in RCA: 66] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2017] [Accepted: 12/14/2017] [Indexed: 12/15/2022] Open
Abstract
One of the least studied topics in the field of obstetrics is liver disease during pregnancy, which creates a challenge for both gynecologists and hepatologists. Approximately 3% of pregnant women are affected by some form of liver disease during pregnancy. Some of these conditions can be fatal for both the mother and child. In addition, 3 types of liver disease need to be differentiated during pregnancy. One type is liver disease directly related to pregnancy, which can occur at a specific time during pregnancy. Another type is liver disease not related to pregnancy, which can occur at any time, such as viral- or drug-induced hepatitis. Furthermore, pregnancy can occur in women with pre-existing liver disease. It is essential that the clinicians are familiar with this disorder so they can respond promptly and appropriately in all of these situations, especially when emergency delivery is needed and must not be postponed.
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Affiliation(s)
- Ivana Mikolasevic
- Department of Gastroenterology, University Hospital Center (UHC) Rijeka, School of Medicine, University of Rijeka, Rijeka, Croatia
| | - Tajana Filipec-Kanizaj
- Department of Gastroenterology, University Hospital Merkur, School of Medicine, University of Zagreb, Zagreb, Croatia
| | - Ivan Jakopcic
- Department of Gastroenterology, University Hospital Center (UHC) Rijeka, School of Medicine, University of Rijeka, Rijeka, Croatia
| | - Iva Majurec
- Department of Anesthesiology and Intensive Care Unit, University Hospital Merkur, Zagreb, Croatia
| | - Alemka Brncic-Fischer
- Department of Obstetrics and Gynecology, University Hospital Center (UHC) Rijeka, Rijeka, Croatia
| | - Nikola Sobocan
- Department of Gastroenterology, University Hospital Merkur, School of Medicine, University of Zagreb, Zagreb, Croatia
| | - Irena Hrstic
- Department of Internal Medicine, General Hospital Pula, Pula, Croatia
| | - Tea Stimac
- Department of Obstetrics and Gynecology, University Hospital Center (UHC) Rijeka, Rijeka, Croatia
| | - Davor Stimac
- Department of Gastroenterology, University Hospital Center (UHC) Rijeka, School of Medicine, University of Rijeka, Rijeka, Croatia
| | - Sandra Milic
- Department of Gastroenterology, University Hospital Center (UHC) Rijeka, School of Medicine, University of Rijeka, Rijeka, Croatia
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Zaffar N, Soete E, Gandhi S, Sayyar P, Van Mieghem T, D'Souza R. Pregnancy outcomes following single and repeat liver transplantation: An international 2-center cohort. Liver Transpl 2018; 24:769-778. [PMID: 29655314 DOI: 10.1002/lt.25071] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2017] [Revised: 03/22/2018] [Accepted: 03/28/2018] [Indexed: 02/07/2023]
Abstract
Due to advances in obstetric and transplant medicine, women with a history of liver transplantation can have successful pregnancies. However, data on pregnancy outcomes is still limited, especially for women who have had a repeat liver transplant following graft rejection. This retrospective study compares pregnancy outcomes in women with single and repeat liver transplants managed at 2 tertiary hospitals in Toronto, Canada and Leuven, Belgium. We identified 41 pregnancies in 28 transplanted women, 6 of whom conceived following a second liver transplant after the first was rejected. Mean maternal age at delivery was 30 ± 7 years, and transplant-to-pregnancy interval was 8.5 ± 5.1 years. All women had normal liver function upon conception. Immunosuppressants included tacrolimus ± azathioprine (n = 26), cyclosporine (n = 4), and prednisone with immunosuppressants (n = 11). There were no maternal deaths. Maternal complications included hypertensive disorders of pregnancy (n = 10), deterioration in renal function (n = 6), gestational diabetes (n = 4), graft deterioration (n = 2), and anemia requiring blood transfusion (n = 1). Fetal/neonatal adverse outcomes included 2 miscarriages, 3 stillbirths, 1 neonatal death, 5 small-for-gestational-age infants, and 1 minor congenital anomaly. Mean gestational age at delivery was 36.7 ± 4.2 weeks. There were 14 (38.9%) preterm births. Outcomes in women with a second transplant were similar to those with a single transplant, except for a higher incidence of hypertensive disorders. In conclusion, with appropriate multidisciplinary care, stable graft function at pregnancy onset, and adherence to immunosuppressive regimens, women with single and repeat liver transplants have low rates of graft complications but remain at increased risk for pregnancy complications. Immunosuppressants and high-dose glucocorticoids can be safely used for maintenance of graft function and management of graft deterioration in pregnancy. Liver Transplantation 24 769-778 2018 AASLD.
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Affiliation(s)
- Nusrat Zaffar
- Division of Maternal and Fetal Medicine, Department of Obstetrics & Gynaecology, Mount Sinai Hospital, University of Toronto, Canada
| | - Elisabeth Soete
- Department of Obstetrics and Gynecology, University Hospital Leuven, Leuven, Belgium
| | - Shital Gandhi
- Division of Obstetric Medicine, Department of Internal Medicine, Mount Sinai Hospital, University of Toronto, Canada
| | - Parastoo Sayyar
- Division of Maternal and Fetal Medicine, Department of Obstetrics & Gynaecology, Mount Sinai Hospital, University of Toronto, Canada
| | - Tim Van Mieghem
- Division of Maternal and Fetal Medicine, Department of Obstetrics & Gynaecology, Mount Sinai Hospital, University of Toronto, Canada.,Department of Obstetrics and Gynecology, University Hospital Leuven, Leuven, Belgium
| | - Rohan D'Souza
- Division of Maternal and Fetal Medicine, Department of Obstetrics & Gynaecology, Mount Sinai Hospital, University of Toronto, Canada
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Kociszewska-Najman B, Mazanowska N, Pietrzak B, Paczek L, Szpotanska-Sikorska M, Schreiber-Zamora J, Hryniewiecka E, Zochowska D, Samborowska E, Dadlez M, Wielgos M. Low Transfer of Tacrolimus and Its Metabolites into Colostrum of Graft Recipient Mothers. Nutrients 2018; 10:E267. [PMID: 29495430 PMCID: PMC5872685 DOI: 10.3390/nu10030267] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2018] [Revised: 02/18/2018] [Accepted: 02/22/2018] [Indexed: 12/29/2022] Open
Abstract
Currently, the majority of neonates born to organ recipient mothers on chronic immunosuppressive therapy are formula fed. However, over the past few years, evidence has grown, suggesting that breastfeeding might be possible and beneficial. We designed a study assessing the transfer of tacrolimus into the colostrum of posttransplant mothers. We assessed the amount of tacrolimus and its metabolites, M-1 and M-3, that would be ingested by the breastfed neonates. Concentrations of tacrolimus and its metabolites were measured in colostrum from 14 posttransplant mothers as well as in venous cord blood and venous blood of the neonates. Test material analysis was performed by liquid chromatography coupled with mass spectrometry (LC/MS). The amount of ingested formula was registered, which allowed for estimation of the amount of tacrolimus and its metabolites that would be ingested by breastfed infants. The mean amount of tacrolimus that would be ingested by the neonates in maternal milk was 151.4 ng/kg/24 h (standard deviation SD ± 74.39); metabolite M-1: 23.80 ng/kg/24 h (SD ± 14.53); and metabolite M-3: 13.25 ng/kg/24 h (SD ± 9.05). The peak level of tacrolimus and metabolite M-1 in colostrum was noted 8 h after an oral dose (3.219 ng/mL SD ± 2.22 and 0.56 ng/mL SD ± 0.60, respectively) and metabolite M-3 after 6 h (0.29 ng/mL SD ± 0.22). Low concentrations of tacrolimus and its metabolites, M-1 and M-3, in colostrum show that neonates will ingest trace amounts of the drug. Further studies are required to fully assess the safety of breastfeeding by posttransplant mothers.
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Affiliation(s)
| | - Natalia Mazanowska
- First Department of Obstetrics and Gynecology, Medical University of Warsaw, 02-015 Warsaw, Poland.
| | - Bronislawa Pietrzak
- First Department of Obstetrics and Gynecology, Medical University of Warsaw, 02-015 Warsaw, Poland.
| | - Leszek Paczek
- Department of Immunology, Transplant Medicine and Internal Diseases, Transplantation Institute, Medical University of Warsaw, 00-001 Warsaw, Poland.
- Department of Bioinformatics, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, 02-106 Warsaw, Poland.
| | | | - Joanna Schreiber-Zamora
- First Department of Obstetrics and Gynecology, Medical University of Warsaw, 02-015 Warsaw, Poland.
| | - Ewa Hryniewiecka
- Department of Immunology, Transplant Medicine and Internal Diseases, Transplantation Institute, Medical University of Warsaw, 00-001 Warsaw, Poland.
| | - Dorota Zochowska
- Department of Immunology, Transplant Medicine and Internal Diseases, Transplantation Institute, Medical University of Warsaw, 00-001 Warsaw, Poland.
| | - Emilia Samborowska
- Mass Spectrometry Laboratory, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, 02-106 Warsaw, Poland.
| | - Michal Dadlez
- Mass Spectrometry Laboratory, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, 02-106 Warsaw, Poland.
- Institute of Genetics and Biotechnology, Biology Department, Warsaw University, 02-096 Warsaw, Poland.
| | - Miroslaw Wielgos
- First Department of Obstetrics and Gynecology, Medical University of Warsaw, 02-015 Warsaw, Poland.
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47
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Baskiran A, Karakas S, Ince V, Kement M, Ozdemir F, Ozsay O, Kutluturk K, Ersan V, Koc C, Barut B, Yilmaz S. Pregnancy After Liver Transplantation: Risks and Outcomes. Transplant Proc 2017; 49:1875-1878. [PMID: 28923640 DOI: 10.1016/j.transproceed.2017.04.023] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2017] [Revised: 04/05/2017] [Accepted: 04/27/2017] [Indexed: 11/17/2022]
Abstract
OBJECTIVE The aim of this study was to evaluate the outcomes of liver transplant recipients who became pregnant after transplantation. METHODS The clinical data of all patients who underwent liver transplantation between January 2007 and December 2016 in our liver transplantation institute were reviewed. The following data were analyzed: indications for transplantation, recipient age at the beginning of pregnancy, the interval between transplantation and pregnancy, maternal and fetal complications, type of delivery, the health condition of neonates, and modifications in immunosuppressive therapy. RESULTS During the study period, 1890 patients underwent liver transplantation. There were 185 women (9.8%) in childbearing age (15-45 years old), and 18 (9.7%) of them became pregnant during the study period. There were a total of 26 pregnancies. The mean age of patients at the time of operation was 25.3 ± 5.2 years, and the mean interval between operation and conception was 32.7 ± 15.3 months. Seventeen pregnancies (65.4%) ended in a live birth in the study. Six pregnancies (23%) resulted with no maternal or fetal complications. The most frequent maternal complication during pregnancy was pregnancy-induced hypertension (n = 3; 16.6%). CONCLUSIONS Despite advances in immunosuppressive therapy and increasing experience in the management of these patients, pregnancies in liver transplant recipients are still more risky than in the general population for both the mother and the fetus. Thus, the issues related to fertility should be comprehensively discussed with the patients and their partners, preferably before transplantation, and pregnancies in liver transplant recipients should be followed up more carefully by a multidisciplinary team.
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Affiliation(s)
- A Baskiran
- Department of General Surgery, Liver Transplantation Institute of Inonu University, Malatya, Turkey.
| | - S Karakas
- Department of General Surgery, Liver Transplantation Institute of Inonu University, Malatya, Turkey
| | - V Ince
- Department of General Surgery, Liver Transplantation Institute of Inonu University, Malatya, Turkey
| | - M Kement
- University of Health Sciences, Kartal Training and Research Hospital, Istanbul, Turkey
| | - F Ozdemir
- Department of General Surgery, Liver Transplantation Institute of Inonu University, Malatya, Turkey
| | - O Ozsay
- University of Katip Celebi, Ataturk Training and Research Hospital, Izmir, Turkey
| | - K Kutluturk
- Department of General Surgery, Liver Transplantation Institute of Inonu University, Malatya, Turkey
| | - V Ersan
- Department of General Surgery, Liver Transplantation Institute of Inonu University, Malatya, Turkey
| | - C Koc
- Department of General Surgery, Liver Transplantation Institute of Inonu University, Malatya, Turkey
| | - B Barut
- Department of General Surgery, Liver Transplantation Institute of Inonu University, Malatya, Turkey
| | - S Yilmaz
- Department of General Surgery, Liver Transplantation Institute of Inonu University, Malatya, Turkey
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48
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Kociszewska-Najman B, Szpotanska-Sikorska M, Mazanowska N, Wielgos M, Pietrzak B. The comparison of intelligence levels of children born to kidney or liver transplant women with children of healthy mothers. J Matern Fetal Neonatal Med 2017; 31:3160-3165. [DOI: 10.1080/14767058.2017.1365131] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Affiliation(s)
- Bozena Kociszewska-Najman
- Neonatology Ward, 1st Department of Obstetrics and Gynecology, Medical University of Warsaw, Warszawa, Poland
| | | | - Natalia Mazanowska
- 1st Department of Obstetrics and Gynecology, Medical University of Warsaw, Warszawa, Poland
| | - Miroslaw Wielgos
- 1st Department of Obstetrics and Gynecology, Medical University of Warsaw, Warszawa, Poland
| | - Bronislawa Pietrzak
- 1st Department of Obstetrics and Gynecology, Medical University of Warsaw, Warszawa, Poland
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49
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Rademaker M, Agnew K, Andrews M, Armour K, Baker C, Foley P, Frew J, Gebauer K, Gupta M, Kennedy D, Marshman G, Sullivan J. Psoriasis in those planning a family, pregnant or breast-feeding. The Australasian Psoriasis Collaboration. Australas J Dermatol 2017; 59:86-100. [PMID: 28543445 DOI: 10.1111/ajd.12641] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2016] [Accepted: 01/28/2017] [Indexed: 12/20/2022]
Abstract
The Australasian Psoriasis Collaboration has reviewed the evidence for managing moderate to severe psoriasis in those who are pregnant or are breast-feeding, or planning a family. The severity of the psoriasis, associated comorbidities and specific anti-psoriasis treatment, along with other exposures, can have a deleterious effect on pregnancy outcomes. Psoriasis itself increases the risk of preterm and low birthweight babies, along with spontaneous and induced abortions, but no specific birth defects have been otherwise demonstrated. The baseline risk for a live born baby to have a major birth defect is 3%, and significant neuro-developmental problem is 5%. In Australia, pregnant women with psoriasis are more likely to be overweight or obese, depressed, or smoke in their first trimester, and are also less likely to take prenatal vitamins or supplements. Preconception counselling to improve maternal, pregnancy and baby health is therefore strongly encouraged. The topical and systemic therapies commonly used in psoriasis are each discussed separately, with regards to pregnancy exposure, breast-feeding and effects on male fertility and mutagenicity. The systemic therapies included are acitretin, adalimumab, apremilast, certolizumab, ciclosporin, etanercept, infliximab, ixekizumab, methotrexate, NBUVB, prednisone, PUVA, secukinumab and ustekinumab. The topical therapies include dithranol (anthralin), calcipotriol, coal tar, corticosteroids (weak, potent and super-potent), moisturisers, salicylic acid, tacrolimus, and tazarotene. As a general recommendation, effective drugs that have been widely used for years are preferable to newer alternatives with less foetal safety data. It is equally important to evaluate the risks of not treating, as severe untreated disease may negatively impact both mother and the foetus.
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Affiliation(s)
- Marius Rademaker
- Department of Dermatology, Waikato Clinical Campus, Auckland Medical School, Auckland, New Zealand
| | - Karen Agnew
- Department of Dermatology, Greenlane Clinical Centre, Auckland, New Zealand.,Starship Children's Hospital, Auckland, New Zealand
| | - Megan Andrews
- The Skin and Cancer Foundation of Victoria, Melbourne, Victoria, Australia
| | - Katherine Armour
- The Skin and Cancer Foundation of Victoria, Melbourne, Victoria, Australia
| | - Chris Baker
- Department of Medicine (Dermatology), University of Melbourne, St Vincent's Hospital, Melbourne, Victoria, Australia.,University of Melbourne, St Vincent's Hospital, Melbourne, Victoria, Australia
| | - Peter Foley
- Department of Medicine (Dermatology), University of Melbourne, St Vincent's Hospital, Melbourne, Victoria, Australia.,University of Melbourne, St Vincent's Hospital, Melbourne, Victoria, Australia
| | - John Frew
- Department of Dermatology, Prince of Wales Hospital, Sydney, New South Wales, Australia
| | - Kurt Gebauer
- Department of Dermatology, University of Western Australia, Freemantle, Western Australia, Australia
| | - Monisha Gupta
- Department of Dermatology, Liverpool Hospital, Skin Hospital, Sydney, New South Wales, Australia.,University of New South Wales, Sydney, New South Wales, Australia
| | - Debra Kennedy
- Royal Hospital for Women, Sydney, New South Wales, Australia
| | - Gillian Marshman
- Flinders Medical Centre and Repatriation General Hospital, Adelaide, South Australia, Australia
| | - John Sullivan
- Holdsworth House Medical Practice, Sydney, New South Wales, Australia
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50
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Albaghdadi AJH, Hewitt MA, Putos SM, Wells M, Ozolinš TRS, Kan FWK. Tacrolimus in the prevention of adverse pregnancy outcomes and diabetes-associated embryopathies in obese and diabetic mice. J Transl Med 2017; 15:32. [PMID: 28193233 PMCID: PMC5307666 DOI: 10.1186/s12967-017-1137-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2016] [Accepted: 02/03/2017] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND T2DM is a high-risk pregnancy with adverse fetal and maternal outcomes including repeated miscarriages and fetal malformations. Despite the established association between placental insufficiency and poor maternal Th1-adaptability to the development of pregnancy complications in T2DM, there have been no established data to assess benefits of pre-pregnancy immunosuppression relative to gestational outcomes in T2DM. We hypothesized that pre-pregnancy macrolide immune suppression can re-establish normal placental development and uterine vascular adaptation in a mouse model of obesity-associated T2DM. METHODS Fetal live birth rate, postnatal variability, mid-gestational uterine and umbilical flow dynamics and certain morphological features of spiral artery modification were examined in the New Zealand Obese (NONcNZO10/Ltj) female mice (n = 56) weaned to ages of 32 weeks on a 60% calories/g high-fat diet (also referred to as HFD-dNONcNZO), and which received either tacrolimus (0.1 mg/kg s.c. q2d) , its vehicle (castor oil and ethanol) or metformin (in drinking water 200 mg/dL p.o. ad libitum). HFD-BALBc-Rag2/IL2-gc female mice (n = 24) were used as HFD-immunodeficient controls. RESULTS Treatment of the HFD-dNONcNZO female mice with tacrolimus improved live birth rates and postnatal viability scores (p < 0.01), normalized OGTT (p < 0.001), inhibited fetal malformation rates, restored morphology of spiral arterial modification; and improved uterine arterial and umbilical blood flow (p < 0.01). Placental production of TNFαand IL16 in the tacrolimus-treated HFD-dNONcNZO dams were restored to non-diabetic levels and the treatment resulted in the inhibition of aberrant monocyte/macrophage activation during pregnancy in the HFD-dNONcNZO dams. CONCLUSIONS Our present data suggest a casual association between chronic maternal overnutrition and aberrancy in the maternal Th1-immune maladaptation to pregnancy and defective spiral artery modification, placental insufficiency and adverse fetal outcomes in the T2DM subjects. Further safety studies into the use of tacrolimus in the pre-pregnancy glycemic control may be beneficial.
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Affiliation(s)
- Ahmad J. H. Albaghdadi
- Department of Biomedical and Molecular Sciences, Faculty of Health Sciences, Queen’s University, Kingston, ON K7L3N6 Canada
| | - Melanie A. Hewitt
- Department of Biomedical and Molecular Sciences, Faculty of Health Sciences, Queen’s University, Kingston, ON K7L3N6 Canada
| | - Samantha M. Putos
- Department of Biomedical and Molecular Sciences, Faculty of Health Sciences, Queen’s University, Kingston, ON K7L3N6 Canada
| | - Michael Wells
- PARTEQ Innovations, Queen’s University, Kingston, ON K7L 0E9 Canada
| | - Terence R. S. Ozolinš
- Department of Biomedical and Molecular Sciences, Faculty of Health Sciences, Queen’s University, Kingston, ON K7L3N6 Canada
| | - Frederick W. K. Kan
- Department of Biomedical and Molecular Sciences, Faculty of Health Sciences, Queen’s University, Kingston, ON K7L3N6 Canada
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