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Rüegg L, Pluma A, Hamroun S, Cecchi I, Perez-Garcia LF, Anderson PO, Andreoli L, Wirström SB, Boyadhzieva V, Chambers C, Costedoat-Chalumeau N, Dolhain RJEM, Fischer-Betz R, Giles I, Gøtestam-Skorpen C, Hoeltzenbein M, Marchiori F, Mayer-Pickel K, Molto A, Nelson-Piercy C, Nielsen OH, Tincani A, Wallenius M, Zbinden A, Meissner Y, Finckh A, Förger F. EULAR recommendations for use of antirheumatic drugs in reproduction, pregnancy, and lactation: 2024 update. Ann Rheum Dis 2025:S0003-4967(25)00818-0. [PMID: 40287311 DOI: 10.1016/j.ard.2025.02.023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2024] [Revised: 02/11/2025] [Accepted: 02/22/2025] [Indexed: 04/29/2025]
Abstract
OBJECTIVES To update the existing European Alliance of Associations for Rheumatology (EULAR) points to consider (PtC) for use of antirheumatic drugs in reproduction, pregnancy, and lactation, including additional drugs and adverse outcomes as well as paternal drug safety. METHODS According to the EULAR standardised operating procedures, an international task force (TF) defined the questions for a systematic literature review, followed by formulation of the updated statements. A predefined voting process was applied to each overarching principle and statement. Level of evidence and strength of recommendation were assigned, and participants finally provided their level of agreement for each item. RESULTS The TF proposes 5 overarching principles and 12 recommendations for the use of antirheumatic drugs before and during pregnancy, through lactation, and in male patients. The current evidence indicates that synthetic disease-modifying antirheumatic drugs (DMARDs) compatible with pregnancy include antimalarials, azathioprine, colchicine, cyclosporine, sulfasalazine, and tacrolimus. Regarding nonsteroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids, a more restrictive approach to their use during pregnancy is recommended. Based on an individualised risk-benefit assessment, all tumour necrosis factor inhibitor (TNFi) biologic DMARDs (bDMARDs) can be used throughout pregnancy, and non-TNFi bDMARDs may be used if needed. In relation to lactation, compatible drugs include antimalarials, azathioprine, colchicine, cyclosporine, glucocorticoids, intravenous immunoglobulin (IVIG), NSAIDs, sulfasalazine, and tacrolimus. All bDMARDs are considered compatible with breastfeeding. Concerning the use of drugs in men, compatible options include antimalarials, azathioprine, colchicine, cyclosporine, IVIG, leflunomide, methotrexate, mycophenolate, NSAIDs, glucocorticoids, sildenafil, sulfasalazine, tacrolimus, and bDMARDs. CONCLUSIONS The updated recommendations provide consensus guidance and will help to improve the quality of care of patients during the phases of reproduction, pregnancy, and lactation.
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Affiliation(s)
- Linda Rüegg
- Department of Rheumatology and Immunology, Inselspital, Bern University Hospital, University of Bern, Switzerland
| | - Andrea Pluma
- Department of Rheumatology, Vall d'Hebron University Hospital, Barcelona, Spain
| | - Sabrina Hamroun
- Department of Rheumatology, Pontoise Hospital, Pontoise, France
| | - Irene Cecchi
- University Center of Excellence on Nephrologic, Rheumatologic and Rare Diseases (ERK-Net, ERNReconnect and RITA-ERN Member) with Nephrology and Dialysis Unit, Turin, Italy; Center of ImmunoRheumatology and Rare Diseases (CMID), Coordinating Center of the Interregional Network for Rare Diseases of Piedmont and Aosta Valley, San Giovanni Bosco Hub Hospital, Turin, Italy; Department of Clinical and Biological Sciences, University of Turin, Turin, Italy
| | | | - Philip O Anderson
- Division of Clinical Pharmacy, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA
| | - Laura Andreoli
- Rheumatology and Clinical Immunology Unit - ERN ReCONNET, ASST Spedali Civili, Brescia, Italy; Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy; Danish Centre for Expertise in Rheumatology (CeViG), Danish Hospital for Rheumatic Diseases (Dansk Gigthospital), Sønderborg, Denmark; Department of Regional Health Research (IRS), University of Southern Denmark, Odense, Denmark
| | | | - Vladimira Boyadhzieva
- Department of Rheumatology, University Hospital " St. Iv. Rilski", Medical University - Faculty of Medicine, Sofia, Bulgaria
| | - Christina Chambers
- Department of Pediatrics, University of California San Diego, La Jolla, USA
| | | | - Radboud J E M Dolhain
- Department of Rheumatology, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Rebecca Fischer-Betz
- Department of Rheumatology and Hiller Research Unit, University of Düsseldorf, Duesseldorf, Germany
| | - Ian Giles
- Department of Ageing, Rheumatology and Regenerative Medicine, UCL Division of Medicine, London, UK
| | - Carina Gøtestam-Skorpen
- Department of Rheumatology, Ålesund Hospital, Ålesund, Norway; Norwegian University of Science and Technology, Ålesund, Norway
| | - Maria Hoeltzenbein
- Embryotox Center of Clinical Teratology and Drug Safety in Pregnancy, Institute of Clinical Pharmacology and Toxicology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany
| | | | | | - Anna Molto
- AP-HP, Department of Rheumatology, Cochin Hospital, Paris, France; INSERM U-1153, Center for Research in Epidemiology and Statistics, Université Paris Cité, Paris, France
| | | | - Ole Haagen Nielsen
- Department of Gastroenterology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Angela Tincani
- Rheumatology and Clinical Immunology Unit - ERN ReCONNET, ASST Spedali Civili, Brescia, Italy; Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
| | - Marianne Wallenius
- The Norwegian National Network for Pregnancy and Rheumatic Diseases, Department of Rheumatology, St Olavs Hospital, Trondheim, Norway; Institute of Neuromedicine and Movement Science, NTNU, Norwegian University of Science and Technology, Trondheim, Norway
| | - Astrid Zbinden
- Department of Rheumatology and Immunology, Inselspital, Bern University Hospital, University of Bern, Switzerland
| | - Yvette Meissner
- German Rheumatology Research Center Berlin, Epidemiology and Health Services Research, Berlin, Germany; Institute of Social Medicine, Epidemiology and Health Economics, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany
| | - Axel Finckh
- Geneva University Hospital, Rheumatology Division, Geneva, Switzerland
| | - Frauke Förger
- Department of Rheumatology and Immunology, Inselspital, Bern University Hospital, University of Bern, Switzerland; Department of Rheumatology, HOCH Cantonal Hospital St. Gallen, St. Gallen, Switzerland.
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Pluma A, Hamroun S, Rüegg L, Cecchi I, Kramer M, Perez-Garcia LF, Rivero T, Finckh A, Meissner Y, Förger F. Antirheumatic drugs in reproduction, pregnancy, and lactation: a systematic literature review informing the 2024 update of the EULAR recommendations. Ann Rheum Dis 2025:S0003-4967(25)00814-3. [PMID: 40240264 DOI: 10.1016/j.ard.2025.02.021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2024] [Revised: 01/31/2025] [Accepted: 02/22/2025] [Indexed: 04/18/2025]
Abstract
OBJECTIVES This study aimed to summarise and update evidence to inform the 2024 update of the European Alliance of Associations for Rheumatology recommendations for the use of antirheumatic drugs in reproduction, pregnancy, and lactation. METHODS A systematic literature review (SLR) was performed, including keywords on reproduction, adverse pregnancy outcomes (APOs), and lactation. Two appraised SLRs were the basis for the SLR on drug safety in men. If sufficient data were available, a meta-analysis was performed on maternal drug exposure and the risk of APOs. RESULTS Of 6680 screened articles, 255 were included in the final analysis. In pregnancy, most evidence was available for biologic disease-modifying antirheumatic drugs (bDMARDs). Meta-analyses with adjusted risk estimates did not reveal APOs or serious infant infections to be associated with tumour necrosis factor inhibitor (TNFi) use. Data on non-TNFi bDMARDs did not raise concerns. In bDMARD-exposed infants, no serious adverse effects to rotavirus live vaccination were reported. Safety of Bacille Calmette-Guérin vaccination in TNFi-exposed infants could be a concern in the first 6 months of life. Regarding oral glucocorticoids, the SLR and meta-analysis using adjusted risk estimates found a dose-dependent association with an increased risk of preterm birth. Nonsteroidal anti-inflammatory drug use could reversibly reduce fecundability. Concerning lactation, available data on various bDMARDs was reassuring. In male patients, available evidence on methotrexate and most other drugs did not reveal adverse effects on sperm quality or birth outcomes. Cyclophosphamide remains the only drug that causes a dose-dependent irreversible infertility. CONCLUSIONS This SLR provides up-to-date evidence to guide the 2024 update of the European Alliance of Associations for Rheumatology recommendations for the use of antirheumatic drugs in reproduction, pregnancy, and lactation.
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Affiliation(s)
- Andrea Pluma
- Department of Rheumatology, Vall d'Hebron University Hospital, Barcelona, Spain
| | - Sabrina Hamroun
- Department of Rheumatology, Pontoise Hospital, Pontoise, Paris, France
| | - Linda Rüegg
- Department of Rheumatology and Immunology, Inselspital, Bern University Hospital, University of Bern, Switzerland
| | - Irene Cecchi
- University Center of Excellence on Nephrologic, Rheumatologic and Rare Diseases (ERK-Net, ERNReconnect, and RITA-ERN Member) with Nephrology and Dialysis Unit, University of Turin, Turin, Italy; Center of ImmunoRheumatology and Rare Diseases (CMID), Coordinating Center of the Interregional Network for Rare Diseases of Piedmont and Aosta Valley, San Giovanni Bosco Hub Hospital, Turin, Italy; Department of Clinical and Biological Sciences, University of Turin, Turin, Italy
| | - Malte Kramer
- Epidemiology and Health Services Research, German Rheumatology Research Center, Berlin, Germany
| | | | - Tania Rivero
- Universität Bern, Bibliothek Medizin, Bern, Switzerland
| | - Axel Finckh
- Rheumatology Division, Geneva University Hospital, Geneva, Switzerland; Geneva Centre for Inflammation Research (GCIR), University of Geneva, Geneva, Switzerland
| | - Yvette Meissner
- Epidemiology and Health Services Research, German Rheumatology Research Center, Berlin, Germany; Institute for Social Medicine, Epidemiology and Health Economics, Charité - University Medicine Berlin, Berlin, Germany
| | - Frauke Förger
- Department of Rheumatology and Immunology, Inselspital, Bern University Hospital, University of Bern, Switzerland; Department of Rheumatology, HOCH Cantonal Hospital St. Gallen, St. Gallen, Switzerland.
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Bast N, Dost-Kovalsky K, Haben S, Friedmann N, Witt L, Oganowski T, Gold R, Thiel S, Hellwig K. Impact of disease-modifying therapies on pregnancy outcomes in multiple sclerosis: a prospective cohort study from the German multiple sclerosis and pregnancy registry. THE LANCET REGIONAL HEALTH. EUROPE 2025; 48:101137. [PMID: 39811788 PMCID: PMC11732200 DOI: 10.1016/j.lanepe.2024.101137] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/21/2024] [Revised: 11/01/2024] [Accepted: 11/04/2024] [Indexed: 01/16/2025]
Abstract
Background In recent decades, relapsing remitting multiple sclerosis (MS) became more treatable through new disease-modifying therapies (DMTs). Identifying safe treatments with minimal fetal risks for family planning is needed. Methods In this prospective cohort from the German MS and Pregnancy Registry (DMSKW), we analyzed pregnancy and neonatal outcomes in MS-patients using descriptive statistics and logistic/linear regression models to compare DMT-exposed pregnancies to DMT-unexposed pregnancies. Findings In 2885 DMT-exposed and 837 DMT-unexposed pregnancies, exposure was not associated with spontaneous abortions, preterm births or major congenital anomalies (MCAs). Severe infections were rare, but more frequent in the Fumarates-group (11/395: 2.8% vs. 8/837 unexposed-group: 1.0%, p-value: 0.03). Antibiotic-use was associated with 2nd-trimester (OR: 2.47, CI: 1.47, 4.05, p-value: <0.001), 3rd-trimester Natalizumab-exposure (OR: 1.75, CI: 1.15, 2.63, p-value: 0.01), and anti-CD20-exposure (OR: 2.16, CI: 1.41, 3.29, p-value: <0.001). Birthweight was significantly reduced in the Sphingosine-1-phosphate-group (β: -132 g, CI: -205, -60, p-value: <0.001), and 3rd-trimester Natalizumab-subgroup (β: -74 g, CI: -138, -9.4, p-value: 0.02). Small for gestational age (SGA) neonates were common in the Sphingosine-1-phospate- (OR: 1.65, CI: 1.07, 2.50, p-value: 0.02) and anti-CD20-group (OR: 1.54, CI: 1.01, 2.32, p-value: 0.04), and also the entire cohort (651/3459: 18.8%), exceeding the general German population rate (10%) (p-value: <0.001). Interpretation We observed an increased SGA risk, especially following highly-effective DMTs, although the pathomechanisms remain unclear. More research is needed on infection risks and MCAs, perhaps by linking different registries. Funding The DMSKW is partly supported by Almirall, Biogen, Hexal, Merck, Novartis, Roche, Sanofi Genzyme, Teva Pharma and Viatris.
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Affiliation(s)
- Nadine Bast
- Department of Neurology, St. Josef-Hospital – Katholisches Klinikum Bochum, Ruhr University Bochum, Gudrunstr. 56, 44791, Bochum, Germany
- Institute of Clinical Pharmacy and Pharmacotherapy, Heinrich-Heine-Universität Düsseldorf, Universitätsstraße 1, 40225, Düsseldorf, Germany
| | - Karen Dost-Kovalsky
- Department of Neurology, St. Josef-Hospital – Katholisches Klinikum Bochum, Ruhr University Bochum, Gudrunstr. 56, 44791, Bochum, Germany
| | - Sabrina Haben
- Department of Neurology, St. Josef-Hospital – Katholisches Klinikum Bochum, Ruhr University Bochum, Gudrunstr. 56, 44791, Bochum, Germany
| | - Natalia Friedmann
- Department of Neurology, St. Josef-Hospital – Katholisches Klinikum Bochum, Ruhr University Bochum, Gudrunstr. 56, 44791, Bochum, Germany
| | - Laura Witt
- Department of Neurology, St. Josef-Hospital – Katholisches Klinikum Bochum, Ruhr University Bochum, Gudrunstr. 56, 44791, Bochum, Germany
- Institute of Clinical Pharmacy and Pharmacotherapy, Heinrich-Heine-Universität Düsseldorf, Universitätsstraße 1, 40225, Düsseldorf, Germany
| | - Theresa Oganowski
- Department of Neurology, St. Josef-Hospital – Katholisches Klinikum Bochum, Ruhr University Bochum, Gudrunstr. 56, 44791, Bochum, Germany
| | - Ralf Gold
- Department of Neurology, St. Josef-Hospital – Katholisches Klinikum Bochum, Ruhr University Bochum, Gudrunstr. 56, 44791, Bochum, Germany
| | - Sandra Thiel
- Department of Neurology, St. Josef-Hospital – Katholisches Klinikum Bochum, Ruhr University Bochum, Gudrunstr. 56, 44791, Bochum, Germany
| | - Kerstin Hellwig
- Department of Neurology, St. Josef-Hospital – Katholisches Klinikum Bochum, Ruhr University Bochum, Gudrunstr. 56, 44791, Bochum, Germany
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Ayoub M, Muzalyova A, Ebigbo A, Nagl S, Römmele C, Classen J, Wanzl J, Fleischmann C, Ayoub S, Tadic V, Schlottmann J, Schnoy E. Pregnancy in Inflammatory Bowel Disease: Data from a Real-World Cohort in Germany. J Clin Med 2024; 13:7710. [PMID: 39768635 PMCID: PMC11678727 DOI: 10.3390/jcm13247710] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2024] [Revised: 11/18/2024] [Accepted: 12/13/2024] [Indexed: 01/11/2025] Open
Abstract
Background: Inflammatory bowel disease (IBD) frequently manifests at a young age, during the peak fertility years. Understanding the risks of negative pregnancy outcomes associated with IBD is crucial for effective pregnancy management and support. Additionally, it is essential to provide patients with the necessary knowledge to make informed choices and foster their confidence in navigating pregnancy while maintaining effective disease management. Although IBD frequently appears during the peak fertility years, knowledge about managing pregnancy in the context of IBD remains limited and often inaccurate among both physicians and patients. Our study aims to assess the complications occurring during pregnancy in patients with IBD, considering the level of disease activity, and to evaluate the standard of care provided to patients with chronic inflammatory conditions through a cohort analysis. Methods: Patients with IBD who had children were included in this single-center mixed-method (retrospective and prospective) study. Clinical data, disease progression, course of pregnancy, and complications were examined in women. Outcomes for children of men with IBD were also analyzed. To supplement the data, a survey addressing various pregnancy-related topics, including all patients from the university outpatient clinic for IBD, was conducted over a period of six months. Results: A total of 410 patients were screened retrospectively between 2010 and 2021. In total, 134 patients who had children were included in the study: 51.4% (n = 69) had Crohn's disease, 44% (n = 59) had ulcerative colitis, and 4.6% (n = 6) had unclassified inflammatory bowel disease. Of the women, 85% (n = 34) were in remission for at least three months before pregnancy, 14.6% (n = 6) experienced an acute flare-up during pregnancy, and 10.3% (n = 4) and 7.7% (n = 3) had active disease at the time of delivery and during breastfeeding, respectively. Patients with IBD who were in remission before pregnancy did not experience a higher risk of pregnancy complications (no cases of pre-eclampsia or placental abruption were reported in this group). However, the rates of gestational diabetes and fever during pregnancy were 10% for those in remission, compared to 25% for those with active disease. Conclusions: Patients with IBD in remission did not present an increased risk of pregnancy complications. However, our survey indicates that those with active disease at conception were more likely to experience complications such as gestational diabetes and fever. These findings underscore the importance of adequate patient education regarding the safety of various IBD medications during pregnancy in order to avoid pregnancy-related complications.
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Affiliation(s)
- Mousa Ayoub
- Internal Medicine III, University Hospital Augsburg, 86156 Augsburg, Germany; (A.E.); (S.N.); (C.R.); (J.C.); (J.W.); (V.T.); (J.S.)
| | - Anna Muzalyova
- Digital Medicine, University Hospital Augsburg, 86156 Augsburg, Germany;
| | - Alanna Ebigbo
- Internal Medicine III, University Hospital Augsburg, 86156 Augsburg, Germany; (A.E.); (S.N.); (C.R.); (J.C.); (J.W.); (V.T.); (J.S.)
| | - Sandra Nagl
- Internal Medicine III, University Hospital Augsburg, 86156 Augsburg, Germany; (A.E.); (S.N.); (C.R.); (J.C.); (J.W.); (V.T.); (J.S.)
| | - Christoph Römmele
- Internal Medicine III, University Hospital Augsburg, 86156 Augsburg, Germany; (A.E.); (S.N.); (C.R.); (J.C.); (J.W.); (V.T.); (J.S.)
| | - Johanna Classen
- Internal Medicine III, University Hospital Augsburg, 86156 Augsburg, Germany; (A.E.); (S.N.); (C.R.); (J.C.); (J.W.); (V.T.); (J.S.)
| | - Julia Wanzl
- Internal Medicine III, University Hospital Augsburg, 86156 Augsburg, Germany; (A.E.); (S.N.); (C.R.); (J.C.); (J.W.); (V.T.); (J.S.)
| | - Carola Fleischmann
- Department of Gastroenterology, Hepatology and Endocrinology, Klinikum Nürnberg, 90419 Nuremberg, Germany;
| | - Sami Ayoub
- Internal Medicine I, University Hospital Augsburg, 86156 Augsburg, Germany;
| | - Vidan Tadic
- Internal Medicine III, University Hospital Augsburg, 86156 Augsburg, Germany; (A.E.); (S.N.); (C.R.); (J.C.); (J.W.); (V.T.); (J.S.)
| | - Jakob Schlottmann
- Internal Medicine III, University Hospital Augsburg, 86156 Augsburg, Germany; (A.E.); (S.N.); (C.R.); (J.C.); (J.W.); (V.T.); (J.S.)
| | - Elisabeth Schnoy
- Internal Medicine III, University Hospital Augsburg, 86156 Augsburg, Germany; (A.E.); (S.N.); (C.R.); (J.C.); (J.W.); (V.T.); (J.S.)
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Chang YC, Kao TE, Chen CL, Lin YC, Hwang DK, Hwang YS, Lin CJ, Chan WC, Lin CP, Chen SN, Sheu SJ. Use of corticosteroids in non-infectious uveitis - expert consensus in Taiwan. Ann Med 2024; 56:2352019. [PMID: 38747459 PMCID: PMC11097703 DOI: 10.1080/07853890.2024.2352019] [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: 01/08/2024] [Accepted: 04/21/2024] [Indexed: 05/18/2024] Open
Abstract
PURPOSE To offer consensus on the utilization of corticosteroids (CS) for treating non-infectious uveitis in the context of clinical practice in Taiwan. This entails examining the different administration methods, their advantages and disadvantages, and considering alternative treatments according to the prevailing evidence and health policies. METHODS Ten ophthalmologists and one rheumatologist convened on December 11, 2022, to review and discuss literature on the topic. The databases explored were the Central Cochrane library, EMBASE, Medline, PUBMED, and Web of Science using relevant keywords. The search spanned from January 1996 to June 2023. After the initial results of the literature review were presented, open voting determined the final statements, with a statement being accepted if it secured more than 70% agreement. This consensus was then presented at significant meetings for further discussions before the final version was established. RESULTS A flow chart and nine statements emerged from the deliberations. They address the importance of CS in uveitis management, guidelines for using topical CS, indications for both periocular or intravitreal and systemic therapies, and tapering and discontinuation methods for both topical and systemic CS. CONCLUSION While CS are a cornerstone for non-infectious uveitis treatment, their administration requires careful consideration, depending on the clinical situation and the specific type of uveitis. The consensus generated from this article provides a guideline for practitioners in Taiwan, taking into account local health policies and the latest research on the subject. It emphasizes the significance of strategic tapering, the potential for alternative therapies, and the importance of patient-centric care.
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Affiliation(s)
- Yo-Chen Chang
- Department of Ophthalmology, School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Ophthalmology, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Ophthalmology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Tzu-En Kao
- Cheng Ching International Eye Hospital, Kaohsiung, Taiwan
| | - Ching-Long Chen
- Department of Ophthalmology, National Defense Medical Center, Taipei, Taiwan
| | - Yu-Chih Lin
- Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - De-Kuang Hwang
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Department of Ophthalmology, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Yih-Shiou Hwang
- College of Medicine, Chang Gung University, Taoyuan City, Taiwan
- Department of Ophthalmology, Chang Gung Memorial Hospital, Taoyuan City, Taiwan
- Department of Ophthalmology, Chang Gung Memorial Hospital, Xiamen Branch, Xiamen, China
- Department of Ophthalmology, Jen-Ai Hospital Dali Branch, Taichung, Taiwan
- Department of Optometry, Asia University, Taichung, Taiwan
| | - Chun-Ju Lin
- Department of Optometry, Asia University, Taichung, Taiwan
- Department of Ophthalmology, China Medical University Hospital, China Medical University, Taichung, Taiwan
- School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan
| | - Wei-Chun Chan
- Department of Ophthalmology, Mackay Memorial Hospital, Taipei, Taiwan
| | - Chang-Ping Lin
- Department of Ophthalmology, National Taiwan University Hospital, Taipei, Taiwan
| | - San-Ni Chen
- Department of Ophthalmology, China Medical University Hospital, China Medical University, Taichung, Taiwan
- School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan
| | - Shwu-Jiuan Sheu
- Department of Ophthalmology, School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Ophthalmology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
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Womack SR, Murphy HR, Arnold MS, Duberstein ZT, Best M, Qiu X, Miller RK, Barrett ES, O'Connor TG. Timing sensitivity of prenatal cortisol exposure and neurocognitive development. Dev Psychopathol 2024:1-14. [PMID: 39501652 DOI: 10.1017/s0954579424001287] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2025]
Abstract
Prenatal glucocorticoid exposure has been negatively associated with infant neurocognitive outcomes. However, questions about developmental timing effects across gestation remain. Participants were 253 mother-child dyads who participated in a prospective cohort study recruited in the first trimester of pregnancy. Diurnal cortisol was measured in maternal saliva samples collected across a single day within each trimester of pregnancy. Children (49.8% female) completed the Bayley Mental Development Scales, Third Edition at 6, 12, and 24 months and completed three observational executive function tasks at 24 months. Structural equation models adjusting for sociodemographic covariates were used to test study hypotheses. There was significant evidence for timing sensitivity. First-trimester diurnal cortisol (area under the curve) was negatively associated with cognitive and language development at 12 months and poorer inhibition at 24 months. Second-trimester cortisol exposure was negatively associated with language scores at 24 months. Third-trimester cortisol positively predicted performance in shifting between task rules (set shifting) at 24 months. Associations were not reliably moderated by child sex. Findings suggest that neurocognitive development is sensitive to prenatal glucocorticoid exposure as early as the first trimester and underscore the importance of assessing developmental timing in research on prenatal exposures for child health outcomes.
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Affiliation(s)
- Sean R Womack
- Department of Psychiatry and Human Behavior, Brown University Warren Alpert Medical School, Providence, USA
- Department of Psychiatry, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA
| | - Hannah R Murphy
- Department of Obstetrics & Gynecology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA
| | - Molly S Arnold
- Department of Psychology, University of Rochester School of Arts and Sciences, Rochester, NY, USA
- Wynne Center for Family Research, University of Rochester, Rochester, NY, USA
| | - Zoe T Duberstein
- Department of Psychology, University of Rochester School of Arts and Sciences, Rochester, NY, USA
- Wynne Center for Family Research, University of Rochester, Rochester, NY, USA
| | - Meghan Best
- Department of Obstetrics & Gynecology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA
| | - Xing Qiu
- Biostatistics and Computational Biology, University of Rochester, Rochester, NY, USA
| | - Richard K Miller
- Department of Obstetrics & Gynecology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA
| | - Emily S Barrett
- Department of Obstetrics & Gynecology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA
- Department of Biostatistics and Epidemiology, Rutgers School of Public Health, Piscataway, NJ, USA
- Environmental and Occupational Health Sciences Institute, Piscataway, NJ, USA
| | - Thomas G O'Connor
- Department of Psychiatry, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA
- Department of Obstetrics & Gynecology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA
- Department of Psychology, University of Rochester School of Arts and Sciences, Rochester, NY, USA
- Wynne Center for Family Research, University of Rochester, Rochester, NY, USA
- Department of Neuroscience, University of Rochester, Rochester, NY, USA
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Cristescu MI, Tutunaru CV, Panaitescu A, Voiculescu VM. Gestational Pemphigoid-From Molecular Mechanisms to Clinical Outcomes: A Case Report and Review of Literature. Life (Basel) 2024; 14:1427. [PMID: 39598226 PMCID: PMC11595257 DOI: 10.3390/life14111427] [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: 09/02/2024] [Revised: 10/26/2024] [Accepted: 10/29/2024] [Indexed: 11/29/2024] Open
Abstract
Gestational pemphigoid is a rare, autoimmune, subepidermal bullous disease with an incidence of 1 in 50,000 pregnancies, displaying itself through pruritic erythema and urticarial papules and plaques that evolve into tense bullae. Histopathological findings consist of subepidermal vesicles with perivascular eosinophils and lymphocytes, and direct immunofluorescence reveals C3 complement and, more rarely, IgG in a linear band along the basement membrane. The course is usually self-limiting within 6 months after delivery but, later, can be triggered by subsequent pregnancies, menstruation, or treatment with oral contraceptives. The newborn can be affected due to the transplacental passage of the maternal immunoglobulins, but, usually, less than 10% of newborns will develop lesions similar to pemphigoid gestationis. The diagnosis and management pose a difficult challenge and should be guided by the severity of the disease. We, therefore, provide a short literature review and discussion plus a case from our clinic, with a typical presentation but a delayed diagnosis and an undulating evolution, with severe manifestations and particularly difficult management due to unexpected complications.
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Affiliation(s)
- Miruna Ioana Cristescu
- Department of Dermatology, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; (M.I.C.); (V.M.V.)
- Elias University Emergency Hospital, 011461 Bucharest, Romania
| | | | - Anca Panaitescu
- Department of Gynecology, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania;
- Filantropia Clinical Hospital, 011132 Bucharest, Romania
| | - Vlad Mihai Voiculescu
- Department of Dermatology, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; (M.I.C.); (V.M.V.)
- Elias University Emergency Hospital, 011461 Bucharest, Romania
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8
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Sousa P, Gisbert JP, Julsgaard M, Selinger CP, Chaparro M. Navigating Reproductive Care in Patients With Inflammatory Bowel Disease: A Comprehensive Review. J Crohns Colitis 2024; 18:ii16-ii30. [PMID: 39475080 PMCID: PMC11523042 DOI: 10.1093/ecco-jcc/jjae048] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Revised: 03/26/2024] [Accepted: 04/27/2024] [Indexed: 11/02/2024]
Abstract
Inflammatory bowel disease [IBD] is often diagnosed in patients during their reproductive years. It is crucial that both healthcare providers and patients are adequately informed to avoid misguided decisions regarding family planning. One of the most important aspects during conception and pregnancy is to maintain disease remission, as disease activity is associated with adverse pregnancy outcomes. Apart from methotrexate, most conventional drugs used in IBD are considered low risk during conception and pregnancy. For newer agents, evidence is still limited. If needed, surgery must not be postponed and should ideally be performed in specialized centres. In most patients, delivery should be vaginal except for patients with complex perianal disease, with an ileoanal pouch anastomosis, or if there is an obstetric contraindication. In children exposed to biological treatments during pregnancy, the risk of infections appears to be low, and psychomotor development is probably not affected. Regarding immunizations, the standard vaccination schedule for inactivated vaccines should be followed for children exposed to biologics in utero. In the case of live vaccines, such as rotavirus, decisions should be individualized and take into consideration the risk-benefit ratio, particularly in developing countries. In this review, we provide a comprehensive and updated overview of aspects related to fertility, pregnancy, breastfeeding, and the impact on the care of children born to mothers with IBD. Both the available evidence and areas of uncertainty are discussed, with the goal of assisting healthcare professionals caring for IBD patients during this important stage of their lives.
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Affiliation(s)
- Paula Sousa
- Department of Gastroenterology, Hospital São Teotónio – Unidade Local de Saúde Dão Lafões, Viseu, Portugal
| | - Javier P Gisbert
- Department of Gastroenterology, Inflammatory Bowel Disease Unit, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa [IIS-Princesa], Universidad Autónoma de Madrid [UAM], Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas [CIBEREHD], Madrid, Spain
| | - Mette Julsgaard
- Department of Hepatology & Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
- Centre for Molecular Prediction of Inflammatory Bowel Disease [PREDICT], Department of Clinical Medicine, Aalborg University, Copenhagen, Denmark
| | | | - María Chaparro
- Department of Gastroenterology, Inflammatory Bowel Disease Unit, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa [IIS-Princesa], Universidad Autónoma de Madrid [UAM], Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas [CIBEREHD], Madrid, Spain
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9
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Ting MYL, Vega-Tapia F, Anguita R, Cuitino L, Valenzuela RA, Salgado F, Valenzuela O, Ibañez S, Marchant R, Urzua CA. Non-Infectious Uveitis and Pregnancy, is There an Optimal Treatment? Uveitis Course and Safety of Uveitis Treatment in Pregnancy. Ocul Immunol Inflamm 2024; 32:1819-1831. [PMID: 38194442 DOI: 10.1080/09273948.2023.2296030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2023] [Revised: 11/23/2023] [Accepted: 12/11/2023] [Indexed: 01/11/2024]
Abstract
In pregnancy, a plethora of factors causes changes in maternal immunity. Uveitis flare-ups are more frequent in the first trimester and in undertreated patients. Management of non-infectious uveitis during pregnancy remains understudied. A bibliographic review to consolidate existing evidence was performed by a multidisciplinary group of Ophthalmologists, Gynaecologists and Rheumatologists. Our group recommends initial management with minimum-required doses of corticosteroids, preferably locally, to treat intraocular inflammation whilst ensuring good neonatal outcomes. If ineffective, clinicians should consider addition of Cyclosporine, Azathioprine or Certolizumab pegol, which are seemingly safe in pregnancy. Other therapies (such as Methotrexate, Mycophenolate Mofetil and alkylating agents) are teratogenic or have a detrimental effect on the foetus. Furthermore, careful multidisciplinary preconception discussions and close follow-up are recommended, monitoring for flare-ups and actively tapering medication doses, with a primary endpoint focused on protecting ocular tissues from inflammation, whilst giving minimal risk of poor pregnancy and foetal outcomes.
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Affiliation(s)
| | - Fabian Vega-Tapia
- Laboratory of Ocular and Systemic Autoimmune Diseases, Department of Ophthalmology, Faculty of Medicine, Universidad de Chile, Santiago, Chile
| | - Rodrigo Anguita
- Moorfields Eye Hospital NHS Foundation Trust, London, UK
- Laboratory of Ocular and Systemic Autoimmune Diseases, Department of Ophthalmology, Faculty of Medicine, Universidad de Chile, Santiago, Chile
- Department of Ophthalmology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Loreto Cuitino
- Laboratory of Ocular and Systemic Autoimmune Diseases, Department of Ophthalmology, Faculty of Medicine, Universidad de Chile, Santiago, Chile
- Servicio de Oftalmología, Hospital Clínico Universidad de Chile, Santiago, Chile
| | - Rodrigo A Valenzuela
- Department of Health Science, Universidad de Aysén, Coyhaique, Chile
- Department of Chemical and Biological Sciences, Faculty of Health, Universidad Bernardo O'Higgins, Santiago, Chile
| | - Felipe Salgado
- Laboratory of Ocular and Systemic Autoimmune Diseases, Department of Ophthalmology, Faculty of Medicine, Universidad de Chile, Santiago, Chile
| | - Omar Valenzuela
- Faculty of Medicine, Clinica Alemana-Universidad del Desarrollo, Santiago, Chile
| | - Sebastian Ibañez
- Faculty of Medicine, Clinica Alemana-Universidad del Desarrollo, Santiago, Chile
| | - Ruben Marchant
- Faculty of Medicine, Clinica Alemana-Universidad del Desarrollo, Santiago, Chile
| | - Cristhian A Urzua
- Laboratory of Ocular and Systemic Autoimmune Diseases, Department of Ophthalmology, Faculty of Medicine, Universidad de Chile, Santiago, Chile
- Faculty of Medicine, Clinica Alemana-Universidad del Desarrollo, Santiago, Chile
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Kothari S, Afshar Y, Friedman LS, Ahn J. AGA Clinical Practice Update on Pregnancy-Related Gastrointestinal and Liver Disease: Expert Review. Gastroenterology 2024; 167:1033-1045. [PMID: 39140906 DOI: 10.1053/j.gastro.2024.06.014] [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: 12/13/2023] [Revised: 06/19/2024] [Accepted: 06/20/2024] [Indexed: 08/15/2024]
Abstract
DESCRIPTION The purpose of this American Gastroenterological Association (AGA) Institute Clinical Practice Update is to review the available published evidence and expert advice regarding the clinical management of patients with pregnancy-related gastrointestinal and liver disease. METHODS This expert review was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership and underwent internal peer review by the Clinical Practice Updates Committee and external peer review through the standard procedures of Gastroenterology. This article provides practical advice for the management of pregnant patients with gastrointestinal and liver disease based on the best available published evidence. The Best Practice Advice statements were drawn from a review of the published literature and from expert opinion. Because formal systematic reviews were not performed, these Best Practice Advice statements do not carry formal ratings regarding the quality of evidence or strength of the presented considerations. Best Practice Advice Statements BEST PRACTICE ADVICE 1: To optimize gastrointestinal and liver disease before pregnancy, preconception and contraceptive care counseling by a multidisciplinary team should be encouraged for reproductive-aged persons who desire to become pregnant. BEST PRACTICE ADVICE 2: Procedures, medications, and other interventions to optimize maternal health should not be withheld solely because a patient is pregnant and should be individualized after an assessment of the risks and benefits. BEST PRACTICE ADVICE 3: Coordination of birth for a pregnant patient with complex inflammatory bowel disease, advanced cirrhosis, or a liver transplant should be managed by a multidisciplinary team, preferably in a tertiary care center. BEST PRACTICE ADVICE 4: Early treatment of nausea and vomiting of pregnancy may reduce progression to hyperemesis gravidarum. In addition to standard diet and lifestyle measures, stepwise treatment consists of symptom control with vitamin B6 and doxylamine, hydration, and adequate nutrition; ondansetron, metoclopramide, promethazine, and intravenous glucocorticoids may be required in moderate to severe cases. BEST PRACTICE ADVICE 5: Constipation in pregnant persons may result from hormonal, medication-related, and physiological changes. Treatment options include dietary fiber, lactulose, and polyethylene glycol-based laxatives. BEST PRACTICE ADVICE 6: Elective endoscopic procedures should be deferred until the postpartum period, whereas nonemergent but necessary procedures should ideally be performed in the second trimester. Pregnant patients with cirrhosis should undergo evaluation for, and treatment of, esophageal varices; upper endoscopy is suggested in the second trimester (if not performed within 1 year before conception) to guide consideration of nonselective β-blocker therapy or endoscopic variceal ligation. BEST PRACTICE ADVICE 7: In patients with inflammatory bowel disease, clinical remission before conception, during pregnancy, and in the postpartum period is essential for improving outcomes of pregnancy. Biologic agents should be continued throughout pregnancy and the postpartum period; use of methotrexate, thalidomide, and ozanimod must be stopped at least 6 months before conception. BEST PRACTICE ADVICE 8: Endoscopic retrograde cholangiopancreatography during pregnancy may be performed for urgent indications, such as choledocholithiasis, cholangitis, and some cases of gallstone pancreatitis. Ideally, endoscopic retrograde cholangiopancreatography should be performed during the second trimester, but if deferring the procedure may be detrimental to the health of the patient and fetus, a multidisciplinary team should be convened to decide on the advisability of endoscopic retrograde cholangiopancreatography. BEST PRACTICE ADVICE 9: Cholecystectomy is safe during pregnancy; a laparoscopic approach is the standard of care regardless of trimester, but ideally in the second trimester. BEST PRACTICE ADVICE 10: The diagnosis of intrahepatic cholestasis of pregnancy is based on a serum bile acid level >10 μmol/L in the setting of pruritus, typically during the second or third trimester. Treatment should be offered with oral ursodeoxycholic acid in a total daily dose of 10-15 mg/kg. BEST PRACTICE ADVICE 11: Management of liver diseases unique to pregnancy, such as pre-eclampsia; hemolysis, elevated liver enzymes, and low platelets syndrome; and acute fatty liver of pregnancy requires planning for delivery and timely evaluation for possible liver transplantation. Daily aspirin prophylaxis for patients at risk for pre-eclampsia or hemolysis, elevated liver enzymes, and low platelets syndrome is advised beginning at week 12 of gestation. BEST PRACTICE ADVICE 12: In patients with chronic hepatitis B virus infection, serum hepatitis B virus DNA and liver biochemical test levels should be ordered. Patients not on treatment but with a serum hepatitis B virus DNA level >200,000 IU/mL during the third trimester of pregnancy should be considered for treatment with tenofovir disoproxil fumarate. BEST PRACTICE ADVICE 13: In patients on immunosuppressive therapy for chronic liver diseases or after liver transplantation, therapy should be continued at the lowest effective dose during pregnancy. Mycophenolate mofetil should not be administered during pregnancy.
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Affiliation(s)
- Shivangi Kothari
- Division of Gastroenterology and Hepatology, University of Rochester, Rochester, New York.
| | - Yalda Afshar
- Division of Maternal Fetal Medicine, University of California Los Angeles, Los Angeles, California
| | - Lawrence S Friedman
- Department of Medicine, Newton-Wellesley Hospital, Boston, Massachusetts; Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts; Department of Medicine, Harvard Medical School, Boston, Massachusetts; Department of Medicine, Tufts University School of Medicine, Boston, Massachusetts
| | - Joseph Ahn
- Division of Gastroenterology and Hepatology, Oregon Health and Science University, Portland, Oregon
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Herman H, Krepelka P, Faridova AT, Trojanova K, Hanacek J, Jaluvkova B, Feyereisl J, Gkalpakiotis S. A severe case of pemphigoid gestationis persisting after labour - case report and review of the literature. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2024; 168:271-275. [PMID: 36919665 DOI: 10.5507/bp.2023.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2022] [Accepted: 02/17/2023] [Indexed: 03/16/2023] Open
Abstract
BACKGROUND AND AIM Pemphigoid gestationis (PG) is a rare skin disease of pregnancy. Given its incidence in pregnant women, physicians and especially obstetricians may not encounter this diagnosis in their entire career. We find this to be a major problem and there is an obligation to report it in as much detail as possible along with recommended treatments with proven efficacy. CASE REPORT We describe the case of a 27 year old patient who was referred to the dermatology department with severe dissemination of blisters in the 9th week of pregnancy. She was diagnosed with pemphigoid gestationis in her first pregnancy. High doses of corticosteroids were initiated but due to inadequate effect cyclosporine was added. The pregnancy was complicated with gestational diabetes. The patient gave birth in her 33rd week by caesarian section due to premature rupture of the membrane. Vesicles were seen on the newborn immediately after birth which diminished spontaneously over 2 weeks. Blisters were still seen on the patient 1 month after labor even with the combination of systemic corticosteroids with cyclosporine. CONCLUSION PG is a rare dermatosis of pregnancy. The course of the disease can be severe, necessitating systemic therapy. As described in this patient, systemic corticosteroids may not be sufficient and adding another immunosuppressive treatment may be needed. If pemphigoid gestationis has occurred during a previous pregnancy it is advised to reconsider another pregnancy.
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Affiliation(s)
- Hynek Herman
- Institute for the Care of Mother and Child, Prague, Czech Republic
- Third Faculty of Medicine, Charles University, Prague, Czech Republic
| | - Petr Krepelka
- Institute for the Care of Mother and Child, Prague, Czech Republic
- Third Faculty of Medicine, Charles University, Prague, Czech Republic
| | - Adela T Faridova
- Institute for the Care of Mother and Child, Prague, Czech Republic
| | - Klara Trojanova
- Institute for the Care of Mother and Child, Prague, Czech Republic
| | - Jiri Hanacek
- Institute for the Care of Mother and Child, Prague, Czech Republic
- Third Faculty of Medicine, Charles University, Prague, Czech Republic
| | | | - Jaroslav Feyereisl
- Institute for the Care of Mother and Child, Prague, Czech Republic
- Third Faculty of Medicine, Charles University, Prague, Czech Republic
| | - Spyridon Gkalpakiotis
- Third Faculty of Medicine, Charles University, Prague, Czech Republic
- Department of Dermatovenereology, University Hospital of Kralovske Vinohrady, Prague, Czech republic
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12
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Caballero-Mateos AM, Quesada-Caballero M, Cañadas-De la Fuente GA, Caballero-Vázquez A, Contreras-Chova F. IBD and Motherhood: A Journey through Conception, Pregnancy and Beyond. J Clin Med 2023; 12:6192. [PMID: 37834837 PMCID: PMC10573266 DOI: 10.3390/jcm12196192] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2023] [Revised: 09/14/2023] [Accepted: 09/19/2023] [Indexed: 10/15/2023] Open
Abstract
Inflammatory Bowel Disease (IBD) presents distinct challenges during pregnancy due to its influence on maternal health and pregnancy outcomes. This literature review aims to dissect the existing scientific evidence on pregnancy in women with IBD and provide evidence-based recommendations for clinical management. A comprehensive search was conducted across scientific databases, selecting clinical studies, systematic reviews, and other pertinent resources. Numerous studies have underscored an increased risk of complications during pregnancy for women with IBD, including preterm birth, low birth weight, neonates small for gestational age, and congenital malformations. Nevertheless, it's evident that proactive disease management before and throughout pregnancy can mitigate these risks. Continuation of IBD treatment during pregnancy and breastfeeding is deemed safe with agents like thiopurines, anti-TNF, vedolizumab, or ustekinumab. However, there's a call for caution when combining treatments due to the heightened risk of severe infections in the first year of life. For small molecules, their use is advised against in both scenarios. Effective disease management, minimizing disease activity, and interdisciplinary care are pivotal in attending to women with IBD. The emphasis is placed on the continual assessment of maternal and infant outcomes and an expressed need for further research to enhance the understanding of the ties between IBD and adverse pregnancy outcomes.
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13
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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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14
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Jølving LR, Nielsen J, Andersen ML, Friedman S, Nørgård BM. Adverse birth outcomes and early-life infections after in utero exposure to corticosteroids for inflammatory bowel disease: a Danish nationwide cohort study. BMC Med 2023; 21:140. [PMID: 37046314 PMCID: PMC10091841 DOI: 10.1186/s12916-023-02817-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Accepted: 03/06/2023] [Indexed: 04/14/2023] Open
Abstract
BACKGROUND Systemic corticosteroids are often used to treat inflammatory bowel disease (IBD) flares during pregnancy as maintenance of disease remission is crucial to optimize pregnancy outcomes. However, there is little data regarding the effect of in utero exposure to corticosteroids on the risk of adverse birth outcomes and early-life infections in the offspring. METHODS We used the Danish national registries to establish a nationwide cohort of all singleton live births in women with IBD from 1995 to 2015. Outcomes in children exposed in utero to corticosteroids were compared to those who were not exposed. In logistic and Cox proportional hazard regression models, we adjusted the outcomes (major congenital malformation, preterm birth, small for gestational age, low 5-min Apgar score, and infections) for confounders such as body mass index, smoking, comorbidity, and additional medical IBD treatment. RESULTS After in utero exposure to corticosteroids at any time between 30 days prior to conception through the first trimester (n = 707), the adjusted hazard ratio of major congenital malformation was 1.28 (95% CI: 0.82-2.00) compared to children born to women with IBD, but not exposed to corticosteroids in utero (n = 9371). After in utero exposure to corticosteroids at any time during pregnancy (n = 1336), the adjusted odds ratios for preterm birth, small for gestational age, and low 5-min Apgar score were 2.45 (95% CI: 1.91-3.13), 1.21 (95% CI: 0.76-1.90), and 0.91 (95% CI: 0.33-2.52), respectively. Finally, the adjusted hazard ratio of overall infections in the first year of life was 1.14 (95% CI: 0.94-1.39). CONCLUSIONS This nationwide cohort study suggests that children of women with IBD exposed to corticosteroids in utero had an almost 2.5-fold increased risk of preterm birth. Use of corticosteroids is closely related to disease activity and we cannot adjust for the independent role of disease activity. It is however reassuring that the other examined birth and early-life outcomes were not statistically significantly increased.
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Affiliation(s)
- Line Riis Jølving
- Center for Clinical Epidemiology, Odense University Hospital, Kløvervænget 30, Entrance 216, 5000, Odense C, Denmark.
- Research Unit of Clinical Epidemiology, Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
| | - Jan Nielsen
- Center for Clinical Epidemiology, Odense University Hospital, Kløvervænget 30, Entrance 216, 5000, Odense C, Denmark
- Research Unit of Clinical Epidemiology, Department of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Mette Louise Andersen
- Center for Clinical Epidemiology, Odense University Hospital, Kløvervænget 30, Entrance 216, 5000, Odense C, Denmark
- Research Unit of Clinical Epidemiology, Department of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Sonia Friedman
- Center for Clinical Epidemiology, Odense University Hospital, Kløvervænget 30, Entrance 216, 5000, Odense C, Denmark
- Division of Gastroenterology, Hepatology, and Endoscopy, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA
- Harvard Medical School, Boston, USA
| | - Bente Mertz Nørgård
- Center for Clinical Epidemiology, Odense University Hospital, Kløvervænget 30, Entrance 216, 5000, Odense C, Denmark
- Research Unit of Clinical Epidemiology, Department of Clinical Research, University of Southern Denmark, Odense, Denmark
- Division of Gastroenterology, Hepatology, and Endoscopy, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA
- Harvard Medical School, Boston, USA
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15
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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: 125] [Impact Index Per Article: 62.5] [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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16
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Wei J, Xia F, Miao J, Wang T, Chen L, Yan X. The risk of congenital heart defects associated with corticosteroids use during the first trimester of pregnancy: a systematic review and meta-analysis. Eur J Clin Pharmacol 2023; 79:1-11. [PMID: 36369382 DOI: 10.1007/s00228-022-03416-w] [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: 05/24/2022] [Accepted: 11/04/2022] [Indexed: 11/13/2022]
Abstract
BACKGROUND Prior studies have suggested that maternal corticosteroids exposure during the first trimester may be associated with an increased risk of congenital heart defects (CHDs) in offspring. However, the findings are discrepant. Moreover, a complete overview of the existing data in the literature is lacking. Our objective was to identify whether such an association exists. METHODS AND RESULTS Relevant studies were identified via searching PubMed, Web of Science, Embase, Chinese databases, and the Cochrane Library databases (search date July 15, 2021) and through checking the reference lists of retrieved articles. The overall pooled risk estimate was calculated using random-effect models. We used the GRADE approach to assess the overall strength of the evidence and the Newcastle-Ottawa Scale to assess study quality. Subgroup analyses were performed to evaluate the association within studies or samples with different characteristics. Sensitivity analyses were performed to assess the robustness of the results. Nine studies involving 1,901,599 participants were included in the final analysis. All studies were evaluated as high quality. In the meta-analysis, no statistically significant association was found between maternal corticosteroids exposure during the first trimester and increased risk of CHDs in offspring (OR = 1.06, 95% CI: 1.00-1.13, P = 0.06, low certainty of evidence). Additionally, we also did not find significant differences in subgroup analyses of corticosteroids exposure patterns, including oral corticosteroids exposure (OR = 1.23, 95% CI: 1.00-1.52), ointment corticosteroids exposure (OR = 1.03, 95% CI: 0.90-1.19), inhalation corticosteroids exposure (OR = 1.06, 95% CI: 0.96-1.17), topical corticosteroids or systemic corticosteroids exposure (OR = 0.95, 95% CI: 0.79-1.15), and nasal corticosteroids exposure (OR = 1.12, 95% CI: 0.80-1.57). CONCLUSIONS Our study does not find an association between maternal corticosteroids exposure during the first trimester and offspring CHDs. However, the existing evidence is of low quality; thus, long-term prospective cohort studies are warranted to verify the safety of corticosteroids in this population, with adequate adjustments for confounding variables.
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Affiliation(s)
- Jiehua Wei
- Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, 110 Xiangya Road, Changsha, 410078, Hunan, China
| | - Fan Xia
- Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, 110 Xiangya Road, Changsha, 410078, Hunan, China
| | - Junxiang Miao
- Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, 110 Xiangya Road, Changsha, 410078, Hunan, China
| | - Tingting Wang
- Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, 110 Xiangya Road, Changsha, 410078, Hunan, China.,NHC Key Laboratory for Birth Defect for Research and Prevention, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, Hunan, China
| | - Lizhang Chen
- Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, 110 Xiangya Road, Changsha, 410078, Hunan, China.
| | - Xuemei Yan
- Department of Internal Medicine, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, 410008, Hunan, China.
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17
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Chen F, Hao L, Zheng K, Zhu S, Dai Z, Shi W, Wang X, Li X, Yang X, Zhao Q. Potential influence of COVID-19 and dexamethasone on the reproductive system: what we know and can expect. HUM FERTIL 2022:1-12. [DOI: 10.1080/14647273.2022.2142919] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Affiliation(s)
- Fei Chen
- Department of Physiology, Jining Medical University, Jining, China
| | - Lanting Hao
- Department of Physiology, Jining Medical University, Jining, China
| | - Kai Zheng
- Department of Physiology, Jining Medical University, Jining, China
| | - Shiheng Zhu
- Department of Physiology, Jining Medical University, Jining, China
| | - Zhiqing Dai
- Department of Physiology, Jining Medical University, Jining, China
| | - Wenhao Shi
- Department of Physiology, Jining Medical University, Jining, China
| | - Xinyi Wang
- Department of Physiology, Jining Medical University, Jining, China
| | - Xinya Li
- Department of Physiology, Jining Medical University, Jining, China
| | - Xinyuan Yang
- Department of Physiology, Jining Medical University, Jining, China
| | - Qian Zhao
- Department of Physiology, Jining Medical University, Jining, China
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18
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Sacks G, Zhang J. Prednisolone and enoxaparin (clexane) therapy ('the Bondi protocol') for repeated IVF failure. Am J Reprod Immunol 2022; 88:e13616. [PMID: 36067527 PMCID: PMC9788304 DOI: 10.1111/aji.13616] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2022] [Revised: 06/13/2022] [Accepted: 08/15/2022] [Indexed: 12/30/2022] Open
Abstract
PROBLEM What is the impact of an empirical immune therapy protocol of prednisolone and enoxaparin (clexane) (the 'Bondi protocol') on women with repeated in vitro fertilization (IVF) failure? METHOD OF STUDY This was a retrospective review of live birth outcomes conducted on all transfer cycles performed by a single clinician (GS) at IVFAustralia between February 2016 and April 2020. This study consisted of 1786 transfer cycles, including 460 cycles treated with the Bondi protocol and 1326 without. Women with repeated IVF failure were given the Bondi protocol based on blood NK cell activity. Primary outcome was live birth and statistical analysis was performed with GraphPad Prism software with significance for P-values < .05. RESULTS Overall 'Bondi' and 'normal' protocol cycles had similar rates of IVF/ICSI, fresh/frozen transfers and use of preimplantation genetic testing (PGT). Women given the Bondi protocol were older, had more previous cycles and had higher blood NK cell activity. There was no significant difference in live birth rates (Bondi 26%, normal 28%). Bondi protocol live birth rates per transfer cycle were as high as 40% in patients under 38 years old. The Bondi protocol was more effective as NK activity increased from 'normal' to 'borderline' to 'high'. For high NK cell activity levels, live birth rates were over four times higher for women on the Bondi protocol (28%) than those on normal protocols (6%, P = .0007). CONCLUSION This study describes a simple and relatively safe immune therapy protocol that may improve IVF success rates in women with evidence of immune dysfunction.
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Affiliation(s)
- Gavin Sacks
- IVFAustraliaSydneyAustralia
- Department of Women’s and Children’s HealthUniversity of New South WalesSydneyAustralia
- St George Hospital and Royal Hospital for WomenSydneyAustralia
| | - Jessica Zhang
- Department of Women’s and Children’s HealthUniversity of New South WalesSydneyAustralia
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19
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Odufalu FD, Long M, Lin K, Mahadevan U. Exposure to corticosteroids in pregnancy is associated with adverse perinatal outcomes among infants of mothers with inflammatory bowel disease: results from the PIANO registry. Gut 2022; 71:1766-1772. [PMID: 34686575 DOI: 10.1136/gutjnl-2021-325317] [Citation(s) in RCA: 43] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2021] [Accepted: 10/09/2021] [Indexed: 12/08/2022]
Abstract
OBJECTIVE Active inflammatory bowel disease (IBD) during pregnancy may require the use of corticosteroids. The aim of this study was to investigate the impact of in utero corticosteroid exposure on adverse pregnancy outcomes, congenital malformations, infections and neurocognitive development among offspring of mothers with IBD. DESIGN Using the prospective Pregnancy in Inflammatory Bowel Disease and Neonatal Outcomes registry, data were collected at each trimester, delivery; and in the 12 months post partum. Bivariate statistics and multivariate logistic regression models compared pregnancy outcomes by corticosteroid exposure. RESULTS A total of 1490 mothers with IBD were enrolled, with 1431 live births recorded. Corticosteroid use was associated with increased risk of preterm birth, small for gestational age, low birth weight (LBW), intrauterine growth restriction and neonatal intensive care unit (NICU) admission. On adjusted multivariate models, corticosteroid use was associated with preterm birth (OR 1.79, 95% CI 1.18 to 2.73), LBW (OR 1.76, 95% CI 1.07 to 2.88) and NICU admission (OR 1.54, 95% CI 1.03 to 2.30). Late corticosteroid use (second and/or third trimester) was associated with serious infections at 9 and 12 months (4% vs 2% and 5% vs 2%, respectively, p=0.03 and p=0.001). There were five newborns with in utero corticosteroid exposure born with orofacial clefts versus one without corticosteroid exposure. Developmental milestones were similar across corticosteroid exposure groups. CONCLUSION In this prospective pregnancy registry, offspring of women exposed to corticosteroids during pregnancy were more likely to have adverse pregnancy outcomes. This emphasises the importance of controlling disease activity before and during pregnancy with steroid-sparing therapy.
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Affiliation(s)
- Florence-Damilola Odufalu
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Francisco, San Francisco, California, USA
| | - Millie Long
- Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Kirk Lin
- Department of Gastroenterology, Palo Alto Medical Foundation, Fremont, California, USA
| | - Uma Mahadevan
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Francisco, San Francisco, California, USA
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20
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Kocatürk E, Podder I, Zenclussen AC, Kasperska Zajac A, Elieh-Ali-Komi D, Church MK, Maurer M. Urticaria in Pregnancy and Lactation. FRONTIERS IN ALLERGY 2022; 3:892673. [PMID: 35873599 PMCID: PMC9300824 DOI: 10.3389/falgy.2022.892673] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2022] [Accepted: 06/09/2022] [Indexed: 11/13/2022] Open
Abstract
Chronic urticaria (CU) is a mast cell-driven chronic inflammatory disease with a female predominance. Since CU affects mostly females in reproductive age, pregnancy is an important aspect to consider in the context of this disease. Sex hormones affect mast cell (MC) biology, and the hormonal changes that come with pregnancy can modulate the course of chronic inflammatory conditions, and they often do. Also, pregnancy-associated changes in the immune system, including local adaptation of innate and adaptive immune responses and skewing of adaptive immunity toward a Th2/Treg profile have been linked to changes in the course of inflammatory diseases. As of now, little is known about the effects of pregnancy on CU and the outcomes of pregnancy in CU patients. Also, there are no real-life studies to show the safety of urticaria medications during pregnancy. The recent PREG-CU study provided the first insights on this and showed that CU improves during pregnancy in half of the patients, whereas it worsens in one-third; and two of five CU patients experience flare-ups of their CU during pregnancy. The international EAACI/GA2LEN/EuroGuiDerm/APAAACI guideline for urticaria recommends adopting the same management strategy in pregnant and lactating CU patients; starting treatment with standard doses of second-generation (non-sedative) H1 antihistamines, to increase the dose up to 4-folds in case of no response, and to add omalizumab in antihistamine-refractory patients; but also emphasizes the lack of evidence-based information on the safety and efficacy of urticaria treatments during pregnancy. The PREG-CU study assessed treatments and their outcomes during pregnancy. Here, we review the reported effects of sex hormones and pregnancy-specific immunological changes on urticaria, we discuss the impact of pregnancy on urticaria, and we provide information and guidance on the management of urticaria during pregnancy and lactation.
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Affiliation(s)
- Emek Kocatürk
- Department of Dermatology, Koç University School of Medicine, Istanbul, Turkey
- *Correspondence: Emek Kocatürk
| | - Indrashis Podder
- Department of Dermatology, Venereology and Leprosy, College of Medicine and Sagore Dutta Hospital, Kolkata, India
| | - Ana C. Zenclussen
- Department of Environmental Immunology, Helmholtz Centre for Environmental Research (UFZ) and Saxonian Incubator for Clinical Translation (SIKT), University of Leipzig, Leipzig, Germany
| | - Alicja Kasperska Zajac
- European Center for Diagnosis and Treatment of Urticaria/Angioedema (GA2LEN UCARE /ACARE Network), Zabrze, Poland
- Department of Clinical Allergology, Urticaria Center of Medical University of Silesia, Katowice, Poland
| | - Daniel Elieh-Ali-Komi
- Institute of Allergology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
- Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Allergology and Immunology, Berlin, Germany
| | - Martin K. Church
- Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Allergology and Immunology, Berlin, Germany
| | - Marcus Maurer
- Institute of Allergology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
- Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Allergology and Immunology, Berlin, Germany
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21
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Thalluri V, Woodman RJ, Vollenhoven B, Tremellen K, Zander-Fox D. Exposure to corticosteroids in the first trimester is associated with an increased risk of urogenital congenital anomalies. Hum Reprod 2022; 37:2167-2174. [PMID: 35734908 DOI: 10.1093/humrep/deac142] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2021] [Revised: 05/03/2022] [Indexed: 01/13/2023] Open
Abstract
STUDY QUESTION Does maternal exposure to first trimester corticosteroids in IVF/ICSI treatment result in an increased risk of congenital anomalies? SUMMARY ANSWER Children born with the aid of IVF/ICSI whose mothers were treated with adjuvant corticosteroids during the first trimester had an increased risk of cryptorchidism, hypospadias and talipes. WHAT IS KNOWN ALREADY Maternal exposure to corticosteroids may increase the risk of congenital anomalies such as cleft palate and neural tube defects. However, the existing studies have conflicting outcomes, are underpowered, and do not study a population undergoing IVF/ICSI, a group known to be at increased risk of abnormalities. STUDY DESIGN, SIZE, DURATION This retrospective cohort analysis covering Monash IVF fertility clinics in Melbourne, Australia assessed the outcomes of 12 426 live births from both fresh and frozen embryo transfers between 2010 and 2016. PARTICIPANTS/MATERIALS, SETTING, METHODS There were 618 live births included in our study group of mothers exposed to corticosteroids (oral prednisolone or dexamethasone) during their IVF/ICSI treatment, with the remainder of births not exposed to steroids (control, n = 11 808). The primary outcome measured was the presence of congenital anomalies and secondary outcomes were birth weight and gestation length. Multivariate binary logistic regression was used to assess the independent effects of corticosteroid exposure and the freezing of embryos, with adjustment for maternal age at oocyte retrieval, smoking status, number of cycles taken, BMI, etiology of the infertility and the use of ICSI. Results are presented as incidence rate ratios (IRRs) with 95% CIs. MAIN RESULTS AND THE ROLE OF CHANCE Amongst 12 426 live births, and 597 birth defects, multivariate logistic regression demonstrated there was an increased incidence in talipes equinovarus (1.33% vs 0.32%, adjusted IRR = 4.30, 95% CI = 1.93, 9.58; P < 0.001), hypospadias (0.66% vs 0.18%, adjusted IRR = 5.90, 95% CI = 2.09, 16.69; P = 0.001) and cryptorchidism (0.83% vs 0.19%, adjusted IRR = 5.53, 95% CI = 1.91, 15.42; P = 0.001) in the offspring of mothers exposed to corticosteroids compared to those who were unexposed. The incidence of neither neural tube defects nor cleft palate were significantly increased in babies exposed to corticosteroids. The sex ratio of infants exposed to corticosteroids during a fresh embryo transfer cycle significantly favored males but reverted to the normal sex ratio in infants conceived in frozen embryo transfer cycles. LIMITATIONS, REASONS FOR CAUTION This was a retrospective observational cohort study using administrative datasets with the potential for measurement error and unobserved confounding. Missing outcome data were obtained from patients using self-report leading to possible ascertainment bias. Given the rare incidence of some of the anomalies assessed, the study was underpowered to identify differences in abnormality rates for some specific anomalies. WIDER IMPLICATIONS OF THE FINDINGS The findings of this study, the largest of its kind, suggest that caution should be heeded when prescribing corticosteroids to women undergoing IVF/ICSI, given that this study has now identified three previously unassociated serious neonatal complications (talipes, hypospadias and cryptorchidism), plus a potential alteration in sex ratio. Physicians should be careful in using corticosteroids in the critical first trimester and should counsel patients regarding the potential risks of this treatment. STUDY FUNDING/COMPETING INTEREST(S) There was no funding sought or obtained for this study. K.T., V.T., B.V. and D.Z.-F. are employees or contractors to Monash IVF and hold a minority stock position in Monash IVF. R.J.W. reports no conflict of interest. TRIAL REGISTRATION NUMBER N/A.
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Affiliation(s)
- V Thalluri
- Repromed, Adelaide, Australia.,Department of Obstetrics & Gynaecology, University of Adelaide, Adelaide, Australia
| | - R J Woodman
- Flinders Centre for Epidemiology and Biostatistics, College of Medicine and Public Health, Flinders University, Adelaide, Australia
| | - B Vollenhoven
- Department of Obstetrics & Gynaecology, Flinders University, Adelaide, Australia.,Monash IVF, Melbourne, Australia.,Department of Obstetrics & Gynaecology, Monash University, Melbourne, Australia.,Monash Health, Melbourne, Australia
| | - K Tremellen
- Repromed, Adelaide, Australia.,Department of Obstetrics & Gynaecology, Flinders University, Adelaide, Australia
| | - D Zander-Fox
- Monash IVF, Melbourne, Australia.,University of South Australia, Adelaide, Australia.,Monash University, Adelaide, Australia.,Department of Obstetrics and Gynaecology, University of Adelaide, Adelaide, Australia
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22
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Xie M, Li Y, Meng YZ, Xu P, Yang YG, Dong S, He J, Hu Z. Uterine Natural Killer Cells: A Rising Star in Human Pregnancy Regulation. Front Immunol 2022; 13:918550. [PMID: 35720413 PMCID: PMC9198966 DOI: 10.3389/fimmu.2022.918550] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Accepted: 05/09/2022] [Indexed: 12/28/2022] Open
Abstract
Uterine natural killer (uNK) cells are an immune subset located in the uterus. uNK cells have distinct tissue-specific characteristics compared to their counterparts in peripheral blood and lymphoid organs. Based on their location and the pregnancy status of the host, uNK cells are classified as endometrial NK (eNK) cells or decidua NK (dNK) cells. uNK cells are important in protecting the host from pathogen invasion and contribute to a series of physiological processes that affect successful pregnancy, including uterine spiral artery remodeling, fetal development, and immunity tolerance. Abnormal alterations in uNK cell numbers and/or impaired function may cause pregnancy complications, such as recurrent miscarriage, preeclampsia, or even infertility. In this review, we introduce recent advances in human uNK cell research under normal physiological or pathological conditions, and summarize their unique influences on the process of pregnancy complications or uterine diseases. Finally, we propose the potential clinical use of uNK cells as a novel cellular immunotherapeutic approach for reproductive disorders.
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Affiliation(s)
- Min Xie
- Key Laboratory of Organ Regeneration & Transplantation of Ministry of Education, Department of Obstetrics and Gynecology, The First Hospital of Jilin University, Changchun, China.,National-Local Joint Engineering Laboratory of Animal Models for Human Diseases, The First Hospital of Jilin University, Changchun, China
| | - Yan Li
- Key Laboratory of Organ Regeneration & Transplantation of Ministry of Education, Department of Obstetrics and Gynecology, The First Hospital of Jilin University, Changchun, China.,National-Local Joint Engineering Laboratory of Animal Models for Human Diseases, The First Hospital of Jilin University, Changchun, China
| | - Yi-Zi Meng
- Key Laboratory of Organ Regeneration & Transplantation of Ministry of Education, Department of Obstetrics and Gynecology, The First Hospital of Jilin University, Changchun, China.,National-Local Joint Engineering Laboratory of Animal Models for Human Diseases, The First Hospital of Jilin University, Changchun, China
| | - Peng Xu
- Key Laboratory of Organ Regeneration & Transplantation of Ministry of Education, Department of Obstetrics and Gynecology, The First Hospital of Jilin University, Changchun, China.,National-Local Joint Engineering Laboratory of Animal Models for Human Diseases, The First Hospital of Jilin University, Changchun, China
| | - Yong-Guang Yang
- Key Laboratory of Organ Regeneration & Transplantation of Ministry of Education, Department of Obstetrics and Gynecology, The First Hospital of Jilin University, Changchun, China.,National-Local Joint Engineering Laboratory of Animal Models for Human Diseases, The First Hospital of Jilin University, Changchun, China.,International Center of Future Science, Jilin University, Changchun, China
| | - Shuai Dong
- Key Laboratory of Organ Regeneration & Transplantation of Ministry of Education, Department of Obstetrics and Gynecology, The First Hospital of Jilin University, Changchun, China.,National-Local Joint Engineering Laboratory of Animal Models for Human Diseases, The First Hospital of Jilin University, Changchun, China
| | - Jin He
- Key Laboratory of Organ Regeneration & Transplantation of Ministry of Education, Department of Obstetrics and Gynecology, The First Hospital of Jilin University, Changchun, China
| | - Zheng Hu
- Key Laboratory of Organ Regeneration & Transplantation of Ministry of Education, Department of Obstetrics and Gynecology, The First Hospital of Jilin University, Changchun, China.,National-Local Joint Engineering Laboratory of Animal Models for Human Diseases, The First Hospital of Jilin University, Changchun, China
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23
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Li T, Yuan Y, Liu H, Lu Q, Mu R. Glucocorticoids Improve the Pregnancy Rate and Outcome in Women With Unexplained Positive Autoantibodies: A Systematic Review and Meta-Analysis. Front Med (Lausanne) 2022; 9:819406. [PMID: 35646975 PMCID: PMC9131042 DOI: 10.3389/fmed.2022.819406] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2021] [Accepted: 04/01/2022] [Indexed: 11/16/2022] Open
Abstract
The effect of glucocorticoid therapy on women with unexplained positive autoantibodies is under debate. This systemic review and meta-analysis were performed to evaluate whether glucocorticoid administration can improve the pregnancy outcome of this population. Relevant publications were searched from databases, and a total of seven prospective and retrospective cohort studies that investigated the effects of glucocorticoid administration on women with unexplained positive autoantibodies, were included. The outcomes of our systematic review and meta-analysis were measured in terms of risk ratios (RR) with 95% confidence intervals (CI) using fixed or random effect models. We found that glucocorticoid treatment improved the clinical pregnancy rate (RR 2.19, 95% CI 1.64–2.92) and live birth rate (RR 1.92, 95% CI 1.17–3.16), especially when glucocorticoid administration was started before pregnancy (clinical pregnancy rate: RR 2.30, 95% CI 1.58–3.34; live birth rate: RR 2.30, 95% CI 1.58–3.34). However, no effect of glucocorticoids on the miscarriage rate was found (RR 0.75, 95% CI 0.55–1.02) regardless of the time of drug administration. Our systematic review and meta-analysis support the rational use of glucocorticoids in women with unexplained positive autoantibodies.
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Affiliation(s)
- Ting Li
- Department of Rheumatology and Immunology, Peking University Third Hospital, Beijing, China
| | - Yilin Yuan
- Department of Psychiatry, Peking University Sixth Hospital, Beijing, China
| | - Huixin Liu
- Department of Clinical Epidemiology and Biostatistics, Peking University People's Hospital, Beijing, China
| | - Qun Lu
- Reproductive Medical Center, Peking University People's Hospital, Beijing, China
| | - Rong Mu
- Department of Rheumatology and Immunology, Peking University Third Hospital, Beijing, China
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24
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Abstract
Pregnant women with covid-19 are at greater risk of severe disease than their non-pregnant peers, and yet they are frequently denied investigations or treatments because of unfounded concerns about risk to the fetus. The basic principles of diagnosing and managing covid-19 are the same as for non-pregnant patients, and a multidisciplinary, expert team approach is essential to ensure optimal care. During pregnancy, treatment with corticosteroids should be modified to use non-fluorinated glucocorticoids. Il-6 inhibitors and monoclonal antibodies, together with specific antiviral therapies, may also be considered. Prophylaxis against venous thromboembolism is important. Women may require respiratory support with oxygen, non-invasive ventilation, ventilation in a prone position (either awake or during invasive ventilation), intubation and ventilation, and extracorporeal membrane oxygenation (ECMO). Pregnancy is not a contraindication for any of these supportive therapies, and the criteria for providing them are the same as in the general population. Decisions regarding timing, place, and mode of delivery should be taken with a multidisciplinary team including obstetricians, physicians, anesthetists, and intensivists experienced in the care of covid-19 in pregnancy. Ideally these decisions should take place in consultation with centers that have experience and expertise in all these specialties.
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Affiliation(s)
- Melanie Nana
- Guys and St Thomas' NHS Foundation Trust, London, UK
| | - Kenneth Hodson
- Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
| | | | | | - Marian Knight
- National Perinatal Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, UK
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25
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Wang J, Chen F, Zhu S, Li X, Shi W, Dai Z, Hao L, Wang X. Adverse effects of prenatal dexamethasone exposure on fetal development. J Reprod Immunol 2022; 151:103619. [DOI: 10.1016/j.jri.2022.103619] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Revised: 02/20/2022] [Accepted: 03/24/2022] [Indexed: 12/15/2022]
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26
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Abstract
Pruritus in pregnancy is a common and burdensome symptom that may be a first sign of a pregnancy-specific pruritic disease (atopic eruption of pregnancy, polymorphic eruption of pregnancy, pemphigoid gestationis, and intrahepatic cholestasis in pregnancy) or a dermatosis coinciding with pregnancy by chance. Despite its high prevalence, pruritus is often underrated by physicians, and data regarding the safety profiles of drugs for pruritus are very limited. In this review, we illustrate the epidemiology, possible pathophysiology, clinical characteristics, and diagnostic workup of various pregnancy-related diseases and discuss antipruritic treatments. The prevalence of pruritus in pregnancy demonstrates the importance of symptom recognition and the need for an holistic approach, taking into account both the potential benefits for the patient and the potential risks to the fetus.
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Affiliation(s)
- Aleksandra A Stefaniak
- Department of Dermatology and Center for Chronic Pruritus, University Hospital Münster, Von Esmarch Str 58, 48149, Münster, Germany.
- Department of Dermatology, Venereology and Allergology, Wroclaw Medical University, Wrocław, Poland.
| | - Manuel P Pereira
- Department of Dermatology and Center for Chronic Pruritus, University Hospital Münster, Von Esmarch Str 58, 48149, Münster, Germany
| | - Claudia Zeidler
- Department of Dermatology and Center for Chronic Pruritus, University Hospital Münster, Von Esmarch Str 58, 48149, Münster, Germany
| | - Sonja Ständer
- Department of Dermatology and Center for Chronic Pruritus, University Hospital Münster, Von Esmarch Str 58, 48149, Münster, Germany
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27
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Bove RM, Houtchens MK. Pregnancy Management in Multiple Sclerosis and Other Demyelinating Diseases. Continuum (Minneap Minn) 2022; 28:12-33. [DOI: 10.1212/con.0000000000001108] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
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28
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Tarplin S, Hubbard J, Green S, Whitney R, Wheless L, Barnado A. Women with Rheumatoid Arthritis have similar rates of postpartum maternal outcomes compared to women without autoimmune disease. Semin Arthritis Rheum 2022; 53:151975. [PMID: 35152084 PMCID: PMC8960024 DOI: 10.1016/j.semarthrit.2022.151975] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Revised: 01/07/2022] [Accepted: 01/31/2022] [Indexed: 10/19/2022]
Abstract
OBJECTIVE Limited data exist on the effect of rheumatoid arthritis (RA) on maternal postpartum outcomes. Using a real-world, electronic health record (EHR) cohort, we assessed maternal postpartum outcomes in RA. METHODS In a large, de-identified EHR, we identified possible RA deliveries using ≥1 delivery ICD-9 or ICD-10-CM codes and a validated RA algorithm. RA cases were required to be diagnosed by a rheumatologist on chart review. Maternal postpartum outcomes included rates of blood transfusion, rates of infection up to 6 weeks postpartum defined by a clinician, and length of hospital stay. We also identified deliveries to women without autoimmune diseases. RESULTS We identified 202 deliveries occurring after RA diagnosis and 596 deliveries to controls without autoimmune diseases. Postpartum infection rates were similar among RA patients and controls (8% vs. 4%, p = 0.10), as were red blood cell transfusion rates (2% vs. 2%, p = 1.00). RA case status was not significantly associated with postpartum infection (OR = 2.10, 95% CI 0.88 - 4.98, p = 0.09) but was significantly associated with preterm birth (OR = 2.11, 95% CI 1.38 - 3.23, p = 0.001). Corticosteroid use during pregnancy was common at 41%, while tumor necrosis factor inhibitor use was 13%. After adjusting for age at delivery and race, corticosteroid use at delivery was not associated with postpartum maternal infections but was associated with a significantly lower birthweight in RA cases. CONCLUSION Women with RA have an increased risk of adverse pregnancy outcomes, particularly preterm birth. Our study highlights, however, that maternal postpartum outcomes such as postpartum infection and blood transfusion are not significantly increased in RA patients.
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Effect of perinatal depression on birth and infant health outcomes: a systematic review and meta-analysis of observational studies from Africa. Arch Public Health 2022; 80:34. [PMID: 35057865 PMCID: PMC8772173 DOI: 10.1186/s13690-022-00792-8] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Accepted: 01/07/2022] [Indexed: 01/10/2023] Open
Abstract
Background Antenatal depression is associated with intrauterine growth retardation, preterm birth, and low birth weight. Infants born to mothers with postnatal depression also may suffer from malnutrition and other health problems. Even though there are few single studies conducted so far, a systematic review of these studies is highly important to highlight the effect of antenatal and perinatal depression on adverse birth and infant health outcomes in Africa. Methods We used the Preferred Report Items for Systematic Review and Meta-analysis (PRISMA) when conducting this study. Databases like CINAHL (EBSCO), MEDLINE (via Ovid and PubMed), PsycINFO, Emcare, Psychiatry Online, and Scopus were searched. In addition, Google Scholar and references from a list of eligible studies were explored. We included good quality observational studies based on Newcastle Ottawa Scale which are published in the English language between 2007 and 2018. Heterogeneity and publication bias were assessed. Meta-analysis with a random effect model was employed to determine the pooled effect sizes with a 95% confidence interval. The review protocol is registered in PROSPERO (CRD42018106714). Result We found three studies (1511 participants) and 11 studies (22,254 participants) conducted on the effect of antenatal depression on birth outcomes and perinatal depression on adverse infant health outcomes, respectively. The overall risk of having adverse birth outcomes was 2.26 (95% CI: 1.43, 3.58) times higher among pregnant mothers with depression. The risk of preterm birth and low birth weight was 1.77 (95% CI: 1.03, 3.04) and 2.98 (95% CI: 1.60, 5.55) respectively. Similarly, the risk of having adverse infant health outcomes namely malnutrition and febrile illness was 1.61 (95% CI: 1.34, 1.95) times higher among mothers who had perinatal depression. Conclusions We have found a significant association between antenatal depression and adverse birth outcomes, low birth weight and preterm birth. Similarly, a significant effect of perinatal depression on adverse infant health outcomes namely, malnutrition, and febrile illnesses was observed. The findings highlight that it is time to integrate mental health services with routine maternal health care services to improve birth outcomes and reduce infant morbidity. Supplementary Information The online version contains supplementary material available at 10.1186/s13690-022-00792-8.
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Park JS, Chung MK, Lim H, Lee J, Lee CH. Risk of Pregnancy Complications and Low Birth Weight Offsprings in Korean Women With Rheumatic Diseases: A Nationwide Population-Based Study. J Korean Med Sci 2022; 37:e18. [PMID: 35014229 PMCID: PMC8748664 DOI: 10.3346/jkms.2022.37.e18] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2021] [Accepted: 11/18/2021] [Indexed: 11/29/2022] Open
Abstract
BACKGROUND To determine the risk of pregnancy complications and adverse offspring outcomes in Korean women with rheumatic diseases (RDs). METHODS Women aged 20-44 years with pregnancies ending in delivery were identified from the National Health Insurance Service-National Health Information Database (2009-2016). Women with RD including systemic lupus erythematosus (SLE), seropositive rheumatoid arthritis (SPRA), and ankylosing spondylitis (AS) (n = 4,284) were age-matched with controls (n = 26,023). Outcome variables included threatened abortion (TA), preterm birth (PB), preeclampsia/eclampsia (PE/E), intrauterine growth retardation (IGR), urinary tract infection, low birth weight (LBW) offsprings, and offspring death within 1 year of birth. RESULTS Women with RDs had increased risks for cesarean section delivery (odds ratio [OR], 1.5; 95% confidence interval [CI], 1.4-1.6), TA (OR, 1.4; 95% CI, 1.2-1.5), PB (OR, 2.4; 95% CI, 1.9-3.2), PE/E (OR, 4.4; 95% CI, 3.3-5.9), and IGR (OR, 2.4; 95% CI, 2.0-3.1) than the controls. The risk of pregnancy complications was increased in SLE and SPRA pregnancies but not in AS pregnancies. Offsprings of women with RDs had an increased risk of LBW (OR, 4.0; 95% CI, 3.2-4.9). The offspring mortality rate within 1 year of birth was higher in women with RDs (6.2/10,000 persons) than in the controls (4.9/10,000 persons). CONCLUSION Women with RDs are at a risk of developing pregnancy complications, and the risk of LBW offsprings and offspring death within 1 year of birth is increased in these women. Therefore, this population requires special attention during their childbearing years.
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Affiliation(s)
- Jin-Su Park
- Division of Rheumatology, Department of Internal Medicine, National Health Insurance Service Ilsan Hospital, Goyang, Korea
| | - Min Kyung Chung
- Division of Rheumatology, Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
| | - Hyunsun Lim
- Research and Analysis Team, National Health Insurance Service Ilsan Hospital, Goyang, Korea
| | - Jisoo Lee
- Division of Rheumatology, Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea.
| | - Chan Hee Lee
- Division of Rheumatology, Department of Internal Medicine, National Health Insurance Service Ilsan Hospital, Goyang, Korea.
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Shimada H, Wakiya R, Kanenishi K, Miyatake N, Nakashima S, Mansour MMF, Kato M, Miyagi T, Sugihara K, Ushio Y, Mino R, Mizusaki M, Kameda T, Kadowaki N, Dobashi H. Preterm birth is strongly affected by the glucocorticoid dose during pregnancy in women complicated by systemic lupus erythematosus. Arthritis Res Ther 2022; 24:10. [PMID: 34980235 PMCID: PMC8722014 DOI: 10.1186/s13075-021-02699-1] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2021] [Accepted: 12/09/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND This study aimed to investigate the effect of glucocorticoid doses on adverse pregnancy outcomes (APOs) in women complicated by systemic lupus erythematosus (SLE). METHODS We investigated 74 pregnancies complicated by SLE or SLE-dominant mixed connective tissue disease. The pregnancies were managed from conception to delivery in our institution. We retrospectively evaluated whether the mean glucocorticoid dose during pregnancy is associated with APOs, including preterm birth (PB), low birth weight (LBW), and light-for-date (LFD). We also calculated the cut-off dose of glucocorticoid that affected APOs. RESULTS All APOs occurred in 35 (50.7%) patients, with 14 cases of PB, 23 cases of LBW, and 10 cases of LFD. Patients with all APOs or PB had a higher dose of glucocorticoid during pregnancy than patients without all APOs or with full-term birth (P = 0.03, P < 0.01, respectively). Logistic regression analysis for all APOs and PB showed that the cut-off values of the mean glucocorticoid dose were 6.5 and 10.0 mg/day, respectively. Patients who delivered LBW or LFD newborns showed no significant difference in the glucocorticoid dose used during pregnancy than patients without LBW or LFD newborns. Patients who delivered LBW newborns were more likely to have used glucocorticoids during pregnancy (P < 0.01). CONCLUSIONS In pregnancies complicated by SLE, a relatively lower dose of glucocorticoid than previously reported is significantly related to APOs, especially PB. Therefore, the disease activity of patients with SLE should be managed with the appropriate lower dose of glucocorticoid during pregnancy.
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Affiliation(s)
- Hiromi Shimada
- Department of Internal Medicine, Division of Hematology, Rheumatology and Respiratory Medicine, Faculty of Medicine, Kagawa University, 1750-1, Ikenobe, Kida-gun, Miki-cho, Kagawa, Japan.
| | - Risa Wakiya
- Department of Internal Medicine, Division of Hematology, Rheumatology and Respiratory Medicine, Faculty of Medicine, Kagawa University, 1750-1, Ikenobe, Kida-gun, Miki-cho, Kagawa, Japan
| | - Kenji Kanenishi
- Department of Perinatology and Gynecology, Faculty of Medicine, Kagawa University, Kagawa, Japan
| | - Nobuyuki Miyatake
- Department of Hygiene, Faculty of Medicine, Kagawa University, Kagawa, Japan
| | - Shusaku Nakashima
- Department of Internal Medicine, Division of Hematology, Rheumatology and Respiratory Medicine, Faculty of Medicine, Kagawa University, 1750-1, Ikenobe, Kida-gun, Miki-cho, Kagawa, Japan
| | - Mai Mahmoud Fahmy Mansour
- Department of Internal Medicine, Division of Hematology, Rheumatology and Respiratory Medicine, Faculty of Medicine, Kagawa University, 1750-1, Ikenobe, Kida-gun, Miki-cho, Kagawa, Japan
| | - Mikiya Kato
- Department of Internal Medicine, Division of Hematology, Rheumatology and Respiratory Medicine, Faculty of Medicine, Kagawa University, 1750-1, Ikenobe, Kida-gun, Miki-cho, Kagawa, Japan
| | - Taichi Miyagi
- Department of Internal Medicine, Division of Hematology, Rheumatology and Respiratory Medicine, Faculty of Medicine, Kagawa University, 1750-1, Ikenobe, Kida-gun, Miki-cho, Kagawa, Japan
| | - Koichi Sugihara
- Department of Internal Medicine, Division of Hematology, Rheumatology and Respiratory Medicine, Faculty of Medicine, Kagawa University, 1750-1, Ikenobe, Kida-gun, Miki-cho, Kagawa, Japan
| | - Yusuke Ushio
- Department of Internal Medicine, Division of Hematology, Rheumatology and Respiratory Medicine, Faculty of Medicine, Kagawa University, 1750-1, Ikenobe, Kida-gun, Miki-cho, Kagawa, Japan
| | - Rina Mino
- Department of Internal Medicine, Division of Hematology, Rheumatology and Respiratory Medicine, Faculty of Medicine, Kagawa University, 1750-1, Ikenobe, Kida-gun, Miki-cho, Kagawa, Japan
| | - Mao Mizusaki
- Department of Internal Medicine, Division of Hematology, Rheumatology and Respiratory Medicine, Faculty of Medicine, Kagawa University, 1750-1, Ikenobe, Kida-gun, Miki-cho, Kagawa, Japan
| | - Tomohiro Kameda
- Department of Internal Medicine, Division of Hematology, Rheumatology and Respiratory Medicine, Faculty of Medicine, Kagawa University, 1750-1, Ikenobe, Kida-gun, Miki-cho, Kagawa, Japan
| | - Norimitsu Kadowaki
- Department of Internal Medicine, Division of Hematology, Rheumatology and Respiratory Medicine, Faculty of Medicine, Kagawa University, 1750-1, Ikenobe, Kida-gun, Miki-cho, Kagawa, Japan
| | - Hiroaki Dobashi
- Department of Internal Medicine, Division of Hematology, Rheumatology and Respiratory Medicine, Faculty of Medicine, Kagawa University, 1750-1, Ikenobe, Kida-gun, Miki-cho, Kagawa, Japan
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Kim YJ. Glucocorticoid therapy in assisted reproduction. Clin Exp Reprod Med 2021; 48:295-302. [PMID: 34875736 PMCID: PMC8651763 DOI: 10.5653/cerm.2021.04819] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Revised: 07/30/2021] [Accepted: 08/02/2021] [Indexed: 12/02/2022] Open
Abstract
As glucocorticoids are well-known as important regulators of stress and the immune system, their function and clinical use have elicited substantial interest in the field of reproduction. In particular, the effect of glucocorticoid therapy on endometrial receptivity during assisted reproduction, including in vitro fertilization (IVF) cycles, has led to a great deal of interest and controversy. However, previous studies have not been able to provide consistent and reliable evidence due to their small, non-controlled designs and use of different criteria. Considering the potential risk of exposure to glucocorticoids for mothers and fetuses in early pregnancy, the use of glucocorticoids in IVF cycles should be carefully evaluated, including the balance between risk and benefit. To date, there is no conclusive evidence that the use of glucocorticoids improves the pregnancy rate in IVF cycles with unselected subjects, and a further investigation should be considered with a proper study design.
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Affiliation(s)
- Yong Jin Kim
- Department of Obstetrics and Gynecology, Korea University College of Medicine, Seoul, Korea
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Galati A, Brown ES, Bove R, Vaidya A, Gelfand J. Glucocorticoids for therapeutic immunosuppression: Clinical pearls for the practicing neurologist. J Neurol Sci 2021; 430:120004. [PMID: 34598056 DOI: 10.1016/j.jns.2021.120004] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2021] [Revised: 09/19/2021] [Accepted: 09/20/2021] [Indexed: 10/20/2022]
Abstract
Given widespread use of glucocorticoid therapy in neurologic disease, understanding glucocorticoid pharmacology and risk is paramount for the practicing neurologist. While dosing and tapering regimens vary depending on the neurological disease and indication being treated, there are important general principles of glucocorticoid prescribing and monitoring that can guide clinical decision-making. Glucocorticoid-related toxicities can occur across multiple organ systems, including hypertension; dyslipidemia; weight gain; hyperglycemia; osteoporosis and avascular necrosis; myopathy; gastrointestinal bleeding; infection; and neuropsychiatric effects with sleep, mood disturbance and cognition. This narrative review provides a practical framework for safe and responsible prescribing of this therapeutic class of medications, including appreciation of immunosuppressive consequences, risk mitigation strategies, dosing and tapering, and recognition of adrenal insufficiency and glucocorticoid withdrawal.
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Affiliation(s)
- Alexandra Galati
- Division of Neuroimmunology and Glial Biology, Department of Neurology, University of California, San Francisco, USA.
| | - E Sherwood Brown
- Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Riley Bove
- Division of Neuroimmunology and Glial Biology, Department of Neurology, University of California, San Francisco, USA
| | - Anand Vaidya
- Center for Adrenal Disorders, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Jeffrey Gelfand
- Division of Neuroimmunology and Glial Biology, Department of Neurology, University of California, San Francisco, USA.
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Sfakianoudis K, Rapani A, Grigoriadis S, Pantou A, Maziotis E, Kokkini G, Tsirligkani C, Bolaris S, Nikolettos K, Chronopoulou M, Pantos K, Simopoulou M. The Role of Uterine Natural Killer Cells on Recurrent Miscarriage and Recurrent Implantation Failure: From Pathophysiology to Treatment. Biomedicines 2021; 9:biomedicines9101425. [PMID: 34680540 PMCID: PMC8533591 DOI: 10.3390/biomedicines9101425] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Revised: 09/27/2021] [Accepted: 10/05/2021] [Indexed: 01/15/2023] Open
Abstract
Uterine natural killer (uNK) cells constitute a unique uterine leucocyte subpopulation facilitating implantation and maintaining pregnancy. Herein, we critically analyze current evidence regarding the role of uNK cells in the events entailed in recurrent implantation failure (RIF) and recurrent miscarriages (RM). Data suggest an association between RIF and RM with abnormally elevated uNK cells’ numbers, as well as with a defective biological activity leading to cytotoxicity. However, other studies do not concur on these associations. Robust data suggesting a definitive causative relationship between uNK cells and RIF and RM is missing. Considering the possibility of uNK cells involvement on RIF and RM pathophysiology, possible treatments including glucocorticoids, intralipids, and intravenous immunoglobulin administration have been proposed towards addressing uNK related RIF and RM. When considering clinical routine practice, this study indicated that solid evidence is required to report on efficiency and safety of these treatments as there are recommendations that clearly advise against their employment. In conclusion, defining a causative relationship between uNK and RIF–RM pathologies certainly merits investigation. Future studies should serve as a prerequisite prior to proposing the use of uNK as a biomarker or prior to targeting uNK cells for therapeutic purposes addressing RIF and RM.
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Affiliation(s)
- Konstantinos Sfakianoudis
- Centre for Human Reproduction, Genesis Athens Clinic, 14-16, Papanikoli, 15232 Athens, Greece; (K.S.); (A.P.); (M.C.); (K.P.)
| | - Anna Rapani
- Laboratory of Physiology, Medical School, National and Kapodistrian University of Athens, 75, Mikras Asias, 11527 Athens, Greece; (A.R.); (S.G.); (E.M.); (G.K.); (C.T.)
| | - Sokratis Grigoriadis
- Laboratory of Physiology, Medical School, National and Kapodistrian University of Athens, 75, Mikras Asias, 11527 Athens, Greece; (A.R.); (S.G.); (E.M.); (G.K.); (C.T.)
- Assisted Conception Unit, Second Department of Obstetrics and Gynecology, Aretaieion Hospital, Medical School, National and Kapodistrian University of Athens, 76, Vasilisis Sofias Avenue, 11528 Athens, Greece
| | - Agni Pantou
- Centre for Human Reproduction, Genesis Athens Clinic, 14-16, Papanikoli, 15232 Athens, Greece; (K.S.); (A.P.); (M.C.); (K.P.)
- Laboratory of Physiology, Medical School, National and Kapodistrian University of Athens, 75, Mikras Asias, 11527 Athens, Greece; (A.R.); (S.G.); (E.M.); (G.K.); (C.T.)
| | - Evangelos Maziotis
- Laboratory of Physiology, Medical School, National and Kapodistrian University of Athens, 75, Mikras Asias, 11527 Athens, Greece; (A.R.); (S.G.); (E.M.); (G.K.); (C.T.)
- Assisted Conception Unit, Second Department of Obstetrics and Gynecology, Aretaieion Hospital, Medical School, National and Kapodistrian University of Athens, 76, Vasilisis Sofias Avenue, 11528 Athens, Greece
| | - Georgia Kokkini
- Laboratory of Physiology, Medical School, National and Kapodistrian University of Athens, 75, Mikras Asias, 11527 Athens, Greece; (A.R.); (S.G.); (E.M.); (G.K.); (C.T.)
| | - Chrysanthi Tsirligkani
- Laboratory of Physiology, Medical School, National and Kapodistrian University of Athens, 75, Mikras Asias, 11527 Athens, Greece; (A.R.); (S.G.); (E.M.); (G.K.); (C.T.)
| | - Stamatis Bolaris
- Assisted Conception Unit, General-Maternity District Hospital "Elena Venizelou", Elenas Venizelou Avenue, 11521 Athens, Greece;
| | - Konstantinos Nikolettos
- Assisted Reproduction Unit of Thrace “Embryokosmogenesis”, Apalos, 68132 Alexandroupoli, Greece;
| | - Margarita Chronopoulou
- Centre for Human Reproduction, Genesis Athens Clinic, 14-16, Papanikoli, 15232 Athens, Greece; (K.S.); (A.P.); (M.C.); (K.P.)
| | - Konstantinos Pantos
- Centre for Human Reproduction, Genesis Athens Clinic, 14-16, Papanikoli, 15232 Athens, Greece; (K.S.); (A.P.); (M.C.); (K.P.)
| | - Mara Simopoulou
- Laboratory of Physiology, Medical School, National and Kapodistrian University of Athens, 75, Mikras Asias, 11527 Athens, Greece; (A.R.); (S.G.); (E.M.); (G.K.); (C.T.)
- Assisted Conception Unit, Second Department of Obstetrics and Gynecology, Aretaieion Hospital, Medical School, National and Kapodistrian University of Athens, 76, Vasilisis Sofias Avenue, 11528 Athens, Greece
- Correspondence: ; Tel.: +30-21-0746-2592
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Neykova KK, Milanova M, Ignatov PN. Myasthenia gravis and covid-19 in pregnancy: a review of the literature and case series report. J Matern Fetal Neonatal Med 2021; 35:8308-8316. [PMID: 34582289 DOI: 10.1080/14767058.2021.1973418] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
OBJECTIVES The aim of our study was to investigate the interrelations of symptoms, clinical outcomes and treatment regimens in pregnant women, diagnosed with myasthenia gravis and superimposed COVID-19 infection. METHODS We conducted an observational retrospective study between August, 2020 and July, 2021. Five patients with preexisting MG and superimposed COVID- infection were included in our study. We investigated the duration of MG, the antibody patient status, any present comorbidities, MG baseline treatment and MG severity class prior to the COVID-19 infection, MG severity class and treatment during the COVID-infection, and last but not least, the maternal and fetal clinical outcome. RESULTS None of the participants were hospitalized as they were treated under quarantine at their homes. The most frequently reported complaints were anosmia, headache and fever, which were observed in 3 out of 5 patients. The MG severity was evaluated twice - before and after the quarantine period. Progression to a more advanced stage was found in 2 of our 5 patients. Three of the patients did not require any changes in the prescribed baseline MG treatment. In 2 patients the pyridostigmine dosage had to be increased. One patient received azithromycin and 4 patients were given LMWH (nadroparin) as specific anti-COVID measures. All patients fully recovered and gave birth to healthy newborns. CONCLUSION To our knowledge, this is the first study on pregnant MG patients with superimposed COVID-19 infection. Based on our observations in this study it would seem that the coexistence of MG and COVID-19 infection in pregnancy does not elicit exacerbation in neither of those conditions. Further research is needed to confirm or challenge these findings, especially with the prospects of new virus variants emerging in the future.
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Affiliation(s)
| | - Milena Milanova
- State University Hospital for Treatment of Neurological and Psychiatric Disorders, MBALNP Sv Naum EAD, Sofia, Bulgaria
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Simionescu AA, Danciu BM, Stanescu AMA. State-of-the-Art Review of Pregnancy-Related Psoriasis. MEDICINA (KAUNAS, LITHUANIA) 2021; 57:804. [PMID: 34441010 PMCID: PMC8402069 DOI: 10.3390/medicina57080804] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/18/2021] [Revised: 08/02/2021] [Accepted: 08/04/2021] [Indexed: 12/14/2022]
Abstract
Psoriasis is a chronic immunologic disease involving inflammation that can target internal organs, the skin, and joints. The peak incidence occurs between the age of 30 and 40 years, which overlaps with the typical reproductive period of women. Because of comorbidities that can accompany psoriasis, including metabolic syndrome, cardiovascular involvement, and major depressive disorders, the condition is a complex one. The role of hormones during pregnancy in the lesion dynamics of psoriasis is unclear, and it is important to resolve the implications of this pathology during pregnancy are. Furthermore, treating pregnant women who have psoriasis represents a challenge as most drugs generally prescribed for this pathology are contraindicated in pregnancy because of teratogenic effects. This review covers the state of the art in psoriasis associated with pregnancy. Careful pregnancy monitoring in moderate-to-severe psoriasis vulgaris is required given the high risk of related complications in pregnancy, including pregnancy-induced hypertensive disorders, low birth weight for gestational age, and gestational diabetes. Topical corticosteroids are safe during pregnancy but effective only for localised forms of psoriasis. Monoclonal antibodies targeting cytokines specifically upregulated in psoriasis, such as ustekinumab (IL-12/23 inhibitor), secukinumab (IL-17 inhibitor) can be effective for the severe form of psoriasis during pregnancy. A multidisciplinary team must choose optimal treatment, taking into account fetal and maternal risks and benefits.
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Affiliation(s)
- Anca Angela Simionescu
- Department of Obstetrics and Gynecology, Filantropia Clinical Hospital, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
| | - Bianca Mihaela Danciu
- Department of Obstetrics, Gynecology and Neonatology, “Dr. Alfred Rusescu” National Institute for Maternal and Child Health, 127715 Bucharest, Romania;
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Kieffer TE, Chin PY, Green ES, Moldenhauer LM, Prins JR, Robertson SA. Prednisolone in early pregnancy inhibits regulatory T cell generation and alters fetal and placental development in mice. Mol Hum Reprod 2021; 26:340-352. [PMID: 32159777 DOI: 10.1093/molehr/gaaa019] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2019] [Revised: 02/16/2020] [Indexed: 01/01/2023] Open
Abstract
Corticosteroids have been utilised in the assisted reproduction setting with the expectation of suppressing aberrant immune activation and improving fertility in women. However, the effects of corticosteroids on fertility, and on pregnancy and offspring outcomes, are unclear. In this study, mice were administered prednisolone (1 mg/kg) or PBS daily in the pre-implantation phase, and effects on the adaptive immune response, the implantation rate, fetal development and postnatal outcomes were investigated. Prednisolone disrupted the expected expansion of CD4+ T cells in early pregnancy, inhibiting generation of both regulatory T cells (Treg cells) and effector T cells and suppressing IFNG required for T cell functional competence. Prednisolone caused an 8-20% increase in the embryo implantation rate and increased the number of viable pups per litter. In late gestation, fetal and placental weights were reduced in a litter size-dependent manner, and the canonical inverse relationship between litter size and fetal weight was lost. The duration of pregnancy was extended by ~ 0.5 day and birth weight was reduced by ~ 5% after prednisolone treatment. Viability of prednisolone-exposed offspring was comparable to controls, but body weight was altered in adulthood, particularly in male offspring. Thus, while prednisolone given in the pre-implantation phase in mice increases maternal receptivity to implantation and resource investment in fetal growth, there is a trade-off in long-term consequences for fetal development, birth weight and offspring health. These effects are associated with, and likely caused by, prednisolone suppression of the adaptive immune response at the outset of pregnancy.
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Affiliation(s)
- Tom Ec Kieffer
- Robinson Research Institute & Adelaide Medical School, University of Adelaide, Adelaide, SA 5005, Australia.,Department of Obstetrics and Gynaecology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Peck Y Chin
- Robinson Research Institute & Adelaide Medical School, University of Adelaide, Adelaide, SA 5005, Australia
| | - Ella S Green
- Robinson Research Institute & Adelaide Medical School, University of Adelaide, Adelaide, SA 5005, Australia
| | - Lachlan M Moldenhauer
- Robinson Research Institute & Adelaide Medical School, University of Adelaide, Adelaide, SA 5005, Australia
| | - Jelmer R Prins
- Department of Obstetrics and Gynaecology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Sarah A Robertson
- Robinson Research Institute & Adelaide Medical School, University of Adelaide, Adelaide, SA 5005, Australia
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Peterka M, Heringova LH, Sukop A, Peterkova R. Anti-asthma Drugs Formoterol and Budesonide (Symbicort) Induce Orofacial Clefts, Gastroschisis and Heart Septum Defects in an In Vivo Model. In Vivo 2021; 35:1451-1460. [PMID: 33910822 PMCID: PMC8193330 DOI: 10.21873/invivo.12397] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2021] [Revised: 02/03/2021] [Accepted: 02/05/2021] [Indexed: 01/24/2023]
Abstract
BACKGROUND We had a case in which three consecutive pregnancies resulted in birth of three children with an orofacial cleft. Their mother suffered from bronchial asthma and was treated using symbicort (corticosteroid budesonide plus bronchodilator formoterol) during her pregnancies. A hypothesis was assessed: these anti-asthmatics can induce an orofacial cleft in experimental model. MATERIALS AND METHODS A single administration of one of five increasing doses (including therapeutically used ones) of Symbicort, budesonide or formoterol was injected into the amnion of a chick embryo on day 4 or 5 of incubation. The teratogenic/lethal effects of the anti-asthmatics were assessed on a total of 600 embryos. RESULTS For budesonide, the teratogenic/lethal effect started at a dose 0.003 μg per embryo, for formoterol at 0.3 μg and for Symbicort 0.03 μg. Orofacial clefts and gastroschisis after exposure were found for all three anti-asthmatics. Heart septum defects occurred after exposure to formoterol. CONCLUSION The present results support those clinical/epidemiological studies pointing out that anti-asthmatics have the potential to induce orofacial clefts, gastroschisis and heart malformations during prenatal development in human.
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Affiliation(s)
- Miroslav Peterka
- Cleft Centre, Clinic of Plastic Surgery, Kralovske Vinohrady University Hospital and Third Faculty of Medicine, Charles University, Prague, Czech Republic;
- Institute of Anatomy, First Faculty of Medicine, Charles University, Prague, Czech Republic
| | - Lucie Hubickova Heringova
- Institute of Histology and Embryology, Third Faculty of Medicine, Charles University, Prague, Czech Republic
| | - Andrej Sukop
- Cleft Centre, Clinic of Plastic Surgery, Kralovske Vinohrady University Hospital and Third Faculty of Medicine, Charles University, Prague, Czech Republic
| | - Renata Peterkova
- Institute of Histology and Embryology, Third Faculty of Medicine, Charles University, Prague, Czech Republic
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Palmsten K, Bredesen D, JaKa MM, Kumar PC, Ziegenfuss JY, Kharbanda EO. "I know my body better than you:" patient focus groups to inform a decision aid on oral corticosteroid use during pregnancy. Pharmacoepidemiol Drug Saf 2021; 30:451-461. [PMID: 33314542 PMCID: PMC8686489 DOI: 10.1002/pds.5183] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2020] [Accepted: 12/07/2020] [Indexed: 01/03/2023]
Abstract
PURPOSE There is unmet need for decision support regarding medication use during pregnancy. We aimed to inform the development of a decision aid on oral corticosteroid (OCS) use during pregnancy through focus groups. METHODS We invited patients from one health system who had a recent live birth and a condition for which OCSs may be prescribed (ie, asthma or other autoimmune disease) to participate in focus groups. We conducted conventional qualitative content analysis of verbatim transcripts of the focus groups using inductive coding. RESULTS There were 30 participants across five focus groups from May to June 2019. Women endorsed the need for patient-provider discussions about OCS use during pregnancy in which the provider shares risks and benefits and the patient makes her decision. Furthermore, women generally expressed support for patient-centered handouts about OCS use during pregnancy that the provider discusses with the patient. When considering whether to take OCSs in pregnancy, women had concerns about: the medication's impact on their baby (eg, miscarriage, birth defects, long-term effects), themselves (eg, effects on mood, sleep, weight gain), pregnancy complications (eg, preterm birth, increased blood pressure), and lactation. Women wanted information on OCSs (eg, indications, length of treatment, and cost), alternative treatments, and risks of not taking OCSs. CONCLUSIONS We established patient need for a decision aid on OCS use during pregnancy that providers can discuss with patients. To address patient concerns, the aid should at a minimum describe the medication's impact on baby, including long-term effects, maternal health, pregnancy complications, and lactation.
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Vu T, Harvey B, Suresh N, Farias J, Gooch C. Eculizumab during Pregnancy in a Patient with Treatment-Refractory Myasthenia Gravis: A Case Report. Case Rep Neurol 2021; 13:65-72. [PMID: 33708096 PMCID: PMC7923701 DOI: 10.1159/000511957] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2020] [Accepted: 09/22/2020] [Indexed: 11/23/2022] Open
Abstract
The recombinant humanized monoclonal antibody eculizumab has been shown to be effective and well tolerated in patients with anti-acetylcholine receptor antibody-positive, treatment-refractory generalized myasthenia gravis (gMG). Myasthenia gravis (MG) often affects women of child-bearing potential. However, management can be challenging during pregnancy, and current treatment options are limited due to potential teratogenicity. Data are currently lacking on the use of eculizumab in pregnant women with gMG. This case report describes a successful pregnancy in a young woman with treatment-refractory gMG treated with eculizumab before, during, and after pregnancy. Eculizumab appeared to have a favorable benefit-risk profile in this setting, with no treatment-related adverse effects noted in either the patient or the neonate. The patient remains neurologically stable on eculizumab, which she has now been receiving for 5 years. This first report of the use of eculizumab during pregnancy in a patient with treatment-refractory gMG suggests a potential role for eculizumab in this setting, although further clinical experience is necessary to support its use during pregnancy in women with MG.
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Affiliation(s)
- Tuan Vu
- Department of Neurology, University of South Florida, Tampa, Florida, USA
| | - Brittany Harvey
- Department of Neurology, University of South Florida, Tampa, Florida, USA
| | - Niraja Suresh
- Department of Neurology, University of South Florida, Tampa, Florida, USA
| | - Jerrica Farias
- Department of Neurology, University of South Florida, Tampa, Florida, USA
| | - Clifton Gooch
- Department of Neurology, University of South Florida, Tampa, Florida, USA
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Cao RH, Grimm MC. Pregnancy and medications in inflammatory bowel disease. Obstet Med 2021; 14:4-11. [PMID: 33995565 PMCID: PMC8107959 DOI: 10.1177/1753495x20919214] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2019] [Revised: 01/20/2020] [Accepted: 02/21/2020] [Indexed: 12/27/2022] Open
Abstract
Inflammatory bowel disease (IBD) affects patients at a significant time in their lives, often coinciding with family planning or pregnancy. While advances in IBD therapies have afforded women greater opportunities for successful conception and pregnancy outcomes, there still remains considerable maternal fear surrounding continuation of treatment in pregnancy. With the exception of methotrexate, most IBD drugs are safe and well tolerated during pregnancy and are not associated with significant risk of adverse fetal or pregnancy outcomes. Furthermore, the current evidence overwhelmingly suggests that good control of disease activity and clinical remission at time of conception are the greatest prognostic factors for an uncomplicated pregnancy and maintenance of quiescent disease. Management of pregnant women with IBD should involve discussions with the mother and family about fears or concerns surrounding the impact of IBD on pregnancy. Mothers should be supported and counselled carefully on the safety and importance of adherence to therapy in maintaining remission. Optimal management of these women requires an inter-disciplinary team effort, involving the general practitioner, in close consultation with both gastroenterologists and obstetricians.
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Affiliation(s)
- Rena H Cao
- St George and Sutherland Clinical School,
University of New South Wales, Sydney, Australia
| | - Michael C Grimm
- St George and Sutherland Clinical School,
University of New South Wales, Sydney, Australia
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Vomstein K, Feil K, Strobel L, Aulitzky A, Hofer-Tollinger S, Kuon RJ, Toth B. Immunological Risk Factors in Recurrent Pregnancy Loss: Guidelines Versus Current State of the Art. J Clin Med 2021; 10:869. [PMID: 33672505 PMCID: PMC7923780 DOI: 10.3390/jcm10040869] [Citation(s) in RCA: 47] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2020] [Revised: 02/13/2021] [Accepted: 02/15/2021] [Indexed: 02/06/2023] Open
Abstract
Around 1-5% of all couples experience recurrent pregnancy loss (RPL). Established risk factors include anatomical, genetic, endocrine, and hemostatic alterations. With around 50% of idiopathic cases, immunological risk factors are getting into the scientific focus, however international guidelines hardly take them into account. Within this review, the current state of immunological risk factors in RPL in international guidelines of the European Society of Reproduction and Embryology (ESHRE), American Society of Reproductive Medicine (ASRM), German/Austrian/Swiss Society of Obstetrics and Gynecology (DGGG/OEGGG/SGGG) and the Royal College of Obstetricians and Gynecologists (RCOG) are evaluated. Special attention was drawn to recommendations in the guidelines regarding diagnostic factors such as autoantibodies, natural killer cells, regulatory T cells, dendritic cells, plasma cells, and human leukocyte antigen system (HLA)-sharing as well as treatment options such as corticosteroids, intralipids, intravenous immunoglobulins, aspirin and heparin in RPL. Finally, the current state of the art focusing on both diagnostic and therapeutic options was summarized.
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Affiliation(s)
- Kilian Vomstein
- Department of Gynecological Endocrinology and Reproductive Medicine, Medical University Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria; (K.F.); (L.S.); (A.A.); (S.H.-T.); (B.T.)
| | - Katharina Feil
- Department of Gynecological Endocrinology and Reproductive Medicine, Medical University Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria; (K.F.); (L.S.); (A.A.); (S.H.-T.); (B.T.)
| | - Laura Strobel
- Department of Gynecological Endocrinology and Reproductive Medicine, Medical University Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria; (K.F.); (L.S.); (A.A.); (S.H.-T.); (B.T.)
| | - Anna Aulitzky
- Department of Gynecological Endocrinology and Reproductive Medicine, Medical University Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria; (K.F.); (L.S.); (A.A.); (S.H.-T.); (B.T.)
| | - Susanne Hofer-Tollinger
- Department of Gynecological Endocrinology and Reproductive Medicine, Medical University Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria; (K.F.); (L.S.); (A.A.); (S.H.-T.); (B.T.)
| | - Ruben-Jeremias Kuon
- Department of Gynecological Endocrinology and Fertility Disorders, Ruprecht-Karls University Heidelberg, Im Neuenheimer Feld 440, 69120 Heidelberg, Germany;
| | - Bettina Toth
- Department of Gynecological Endocrinology and Reproductive Medicine, Medical University Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria; (K.F.); (L.S.); (A.A.); (S.H.-T.); (B.T.)
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Intravenous Immunoglobulin Therapy for Gestational Pemphigoid Refractory to Conventional Treatment. ACTAS DERMO-SIFILIOGRAFICAS 2021. [DOI: 10.1016/j.adengl.2020.12.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] Open
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44
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Je G, Ghasemi M. Myasthenia gravis and pregnancy. World J Obstet Gynecol 2020; 9:1-10. [DOI: 10.5317/wjog.v9.i1.1] [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: 05/22/2020] [Revised: 11/09/2020] [Accepted: 11/17/2020] [Indexed: 02/06/2023] Open
Abstract
Myasthenia gravis (MG) is an autoimmune disorder of neuromuscular junction that has higher incidence in younger women than men, which could be related to differences in sex hormones physiology and immune system functioning between males and females. MG can first present during pregnancy and variably affect pregnancy, labor, and postpartum period. In this paper, we had an updated overview on our understanding about MG presentation and its effect on pregnancy and vice versa, therapeutic options for MG pregnant women, management of pregnancy or labor complications in MG patients, and finally fetal and neonatal considerations in MG pregnant women. A multidisciplinary approach, involving obstetricians/gynecologists, neurologists, and anes-thesiologists, plays a pivotal role in improving the clinical outcomes in both MG mothers and their infants during pregnancy, delivery and postpartum.
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Affiliation(s)
- Goun Je
- Department of Neurology, University of Massachusetts Medical School, Worcester, MA 01655, United States
| | - Mehdi Ghasemi
- Department of Neurology, University of Massachusetts Medical School, Worcester, MA 01655, United States
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Hashimoto Y, Michihata N, Yamana H, Shigemi D, Morita K, Matsui H, Yasunaga H, Aihara M. Ophthalmic Corticosteroids in Pregnant Women with Allergic Conjunctivitis and Adverse Neonatal Outcomes: Propensity Score Analyses. Am J Ophthalmol 2020; 220:91-101. [PMID: 32681904 DOI: 10.1016/j.ajo.2020.07.011] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2020] [Revised: 06/03/2020] [Accepted: 07/08/2020] [Indexed: 12/23/2022]
Abstract
PURPOSE The risks of topical ophthalmic corticosteroids during pregnancy remain unclear. This study investigated the association between exposure to topical ophthalmic corticosteroids during pregnancy and adverse neonatal outcomes. DESIGN Retrospective, cohort, database study. METHODS Pregnant women with allergic conjunctivitis in the JMDC claims database (JMDC, Tokyo, Japan) between 2005 and 2018 were included. Adverse neonatal outcomes (congenital anomalies [CA], preterm birth [PB], low birthweight [LB], and the composite of these 3 outcomes) were compared between mothers who did and did not receive topical ophthalmic corticosteroids during the first trimester. Controls were women who were not prescribed topical ophthalmic corticosteroids during the first trimester. First, propensity scores were calculated with known confounders, including disorders during pregnancy, other chronic comorbidities, and use of antihistamines. Logistic regression was then conducted with propensity score adjustment. RESULTS A total of 6,847 eligible women were identified of whom 898 (13%) had received topical ophthalmic corticosteroids. CA occurred in 5.5% and 4.9%, respectively; PB in 3.4% and 3.9%, respectively; LB in 5.9% and 7.0%, respectively; and the composite outcome in 11.7% and 11.7% of unexposed and exposed mothers, respectively. Corticosteroid eye drops were not significantly associated with an increase in CA (adjusted odds ratio [aOR], 0.78; 95% confidence interval [CI], 0.54-1.14; P = .20); PB (aOR, 1.23; 95% CI, 0.80-1.88; P = .35); LB (aOR, 1.17; 95% CI, 0.84-1.61; P = .35), or composite outcome (aOR, 0.95; 95% CI, 0.73-1.22; P = .68). CONCLUSIONS The use of topical ophthalmic corticosteroids in pregnant women with allergic conjunctivitis was not associated with any increase in CA, PB, or LB.
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Affiliation(s)
- Yohei Hashimoto
- Department of Ophthalmology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, Tokyo, Japan.
| | - Nobuaki Michihata
- Department of Health Services Research, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Hayato Yamana
- Department of Health Services Research, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Daisuke Shigemi
- Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, Tokyo, Japan
| | - Kojiro Morita
- Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, Tokyo, Japan
| | - Hiroki Matsui
- Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, Tokyo, Japan
| | - Hideo Yasunaga
- Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, Tokyo, Japan
| | - Makoto Aihara
- Department of Ophthalmology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
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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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47
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Boria F, Maseda R, Albízuri F, de la Calle M. Intravenous Immunoglobulin Therapy for Gestational Pemphigoid Refractory to Conventional Treatment. ACTAS DERMO-SIFILIOGRAFICAS 2020; 112:83-85. [PMID: 32986975 DOI: 10.1016/j.ad.2019.04.016] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2019] [Revised: 03/29/2019] [Accepted: 04/15/2019] [Indexed: 10/23/2022] Open
Affiliation(s)
- F Boria
- Unidad de Medicina Materno-Fetal, Servicio de Obstetricia, Hospital Universitario La Paz, Madrid, España.
| | - R Maseda
- Servicio de Dermatología, Hospital Universitario La Paz, Madrid, España
| | - F Albízuri
- Servicio de Dermatología, Hospital Universitario La Paz, Madrid, España
| | - M de la Calle
- Unidad de Medicina Materno-Fetal, Servicio de Obstetricia, Hospital Universitario La Paz, Madrid, España
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48
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Woon EV, Day A, Bracewell-Milnes T, Male V, Johnson M. Immunotherapy to improve pregnancy outcome in women with abnormal natural killer cell levels/activity and recurrent miscarriage or implantation failure: A systematic review and meta-analysis. J Reprod Immunol 2020; 142:103189. [PMID: 32889304 DOI: 10.1016/j.jri.2020.103189] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2020] [Accepted: 08/12/2020] [Indexed: 12/14/2022]
Abstract
There is a trend towards offering immunotherapy to women with unexplained reproductive failure based on abnormal Natural Killer (NK) cell levels. Previous systematic reviews evaluating immunotherapy usage have not focused on women with abnormal level of NK cells. To address the gap in literature, this systematic review aims to evaluate the efficacy of immunotherapy to improve pregnancy outcome in women with recurrent miscarriage (RM) or implantation failure (RIF) specifically selected based on abnormal levels and/or activity of NK cells. Six databases were searched for peer-reviewed studies following PRISMA guidelines. Risk of bias assessment was conducted using RoB2 for randomized controlled trials (RCT) and ROBINS-I for non-RCT. Of 1025 studies identified, seven studies on intravenous immunoglobulin (IVIG) (four), prednisolone (one), etanercept (one) and intralipid (one) were included. Meta-analysis of the non-RCT IVIG studies (557 participants; 312 intervention, 245 controls) showed livebirth in favour of intervention (RR 2.57; 95 % CI = 1.79-3.69; p < 0.05), however there were significant heterogeneity (I2 = 62 %) and moderate to severe risk of bias in these studies. Individual RCTs reported improved livebirth outcome in etanercept, intralipid and prednisolone and this was significant in the former two (p < 0.05). In conclusion, there may be some benefit of immunotherapy, but paucity of high quality evidence means that it is not possible to support the use of immunotherapy even when selected based on abnormal NK cell level/activity. Further research with application of scientifically validated immunological biomarkers in well-planned large scale RCTs will determine whether immunotherapy is beneficial in this subpopulation of women.
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Affiliation(s)
- Ee Von Woon
- Department of Metabolism, Digestion and Reproduction, Institute of Developmental Reproductive & Developmental Biology, Imperial College London, Chelsea and Westminster Hospital Campus, 369 Fulham Roadd, London, UK.
| | - Andrea Day
- Department of Obstetrics and Gynaecology, Chelsea and Westminster Hospital NHS Foundation Trust, West Middlesex University Hospital, Twickenham Road, Isleworth, London UK
| | - Timothy Bracewell-Milnes
- Department of Metabolism, Digestion and Reproduction, Institute of Developmental Reproductive & Developmental Biology, Imperial College London, Chelsea and Westminster Hospital Campus, 369 Fulham Roadd, London, UK
| | - Victoria Male
- Department of Metabolism, Digestion and Reproduction, Institute of Developmental Reproductive & Developmental Biology, Imperial College London, Chelsea and Westminster Hospital Campus, 369 Fulham Roadd, London, UK
| | - Mark Johnson
- Department of Metabolism, Digestion and Reproduction, Institute of Developmental Reproductive & Developmental Biology, Imperial College London, Chelsea and Westminster Hospital Campus, 369 Fulham Roadd, London, UK
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Palmsten K, Bandoli G, Vazquez-Benitez G, Xi M, Johnson DL, Xu R, Chambers CD. Oral corticosteroid use during pregnancy and risk of preterm birth. Rheumatology (Oxford) 2020; 59:1262-1271. [PMID: 31566229 DOI: 10.1093/rheumatology/kez405] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2019] [Revised: 07/30/2019] [Indexed: 01/23/2023] Open
Abstract
OBJECTIVE To evaluate the associations between oral corticosteroid (OCS) dose early and late in pregnancy and preterm birth (PTB) among women with RA. METHODS Pregnant women in the MotherToBaby Pregnancy Studies (2003-2014) with RA (n = 528) were included in the primary analysis. Information was collected by phone interview and from medical records. We estimated risk ratios (RR) for OCS dose trajectories and other disease-related medications before gestational day 140 and hazard ratios (HR) for time-varying exposures after gestational day 139. RESULTS PTB risk was 15.5% overall. Compared with no OCS, PTB risk was increased in high (adjusted (a)RR: 4.77 (95% CI: 2.76, 8.26)) and medium (aRR: 1.81 (95% CI: 1.10, 2.97)) cumulative OCS dose trajectories during the first 139 gestational days. The low cumulative trajectory group was associated with an increased risk of PTB that was not statistically significant (aRR: 1.38 (95% CI: 0.79, 2.38)), and DMARDs were not associated with PTB (biologic DMARDs aHR: 1.08 (95% CI: 0.70, 1.66); non-biologic DMARDs aHR: 0.87 (95% CI: 0.55, 1.38)). OCS exposure to ⩾10 mg of prednisone equivalent daily dose after gestational day 139 vs none was associated with increased PTB rate (aHR: 2.45 (95% CI: 1.32, 4.56)), whereas <10 mg was associated with a modestly increased rate of PTB that was not statistically significant (aHR: 1.18 (95% CI: 0.60, 2.30)). CONCLUSION Higher OCS doses vs no OCS use, both earlier and later in pregnancy, were associated with an increase in PTB among women with RA.
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Affiliation(s)
- Kristin Palmsten
- HealthPartners Institute, Minneapolis, MN.,Department of Pediatrics, University of California, CA, USA
| | - Gretchen Bandoli
- Department of Pediatrics, University of California, CA, USA.,Department of Family Medicine and Public Health, University of California, CA, USA
| | | | - Min Xi
- HealthPartners Institute, Minneapolis, MN
| | | | - Ronghui Xu
- Department of Family Medicine and Public Health, University of California, CA, USA.,Department of Mathematics, University of California, CA, USA
| | - Christina D Chambers
- Department of Pediatrics, University of California, CA, USA.,Department of Family Medicine and Public Health, University of California, CA, USA
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50
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Palmsten K, Bandoli G, Watkins J, Vazquez-Benitez G, Gilmer TP, Chambers CD. Oral Corticosteroids and Risk of Preterm Birth in the California Medicaid Program. THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE 2020; 9:375-384.e5. [PMID: 32791247 DOI: 10.1016/j.jaip.2020.07.047] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 02/06/2020] [Revised: 07/03/2020] [Accepted: 07/27/2020] [Indexed: 12/15/2022]
Abstract
BACKGROUND There is limited information regarding the impact of dose and gestational timing of oral corticosteroid (OCS) use on preterm birth (PTB), especially among women with asthma. OBJECTIVES To evaluate OCS dose and timing on PTB for asthma and, as a comparison, systemic lupus erythematosus (SLE). METHODS We used health care data from California Medicaid enrollees linked to birth certificates (2007-2013), identifying women with asthma (n = 22,084) and SLE (n = 1174). We estimated risk ratios (RR) for OCS cumulative dose trajectories and other disease-related medications before gestational day 140 and hazard ratios (HR) for time-varying exposures after day 139. RESULTS For asthma, PTB risk was 14.0% for no OCS exposure and 14.3%, 16.8%, 20.5%, and 32.7% in low, medium, medium-high, and high cumulative dose trajectory groups, respectively, during the first 139 days. The high-dose group remained associated with PTB after adjustment (adjusted RR [aRR]: 1.46; 95% confidence interval [CI]: 1.00, 2.15). OCS dose after day 139 was not clearly associated with PTB, nor were controller medications. For SLE, PTB risk for no OCS exposure was 24.9%, and it was 39.1% in low- and 61.2% in high-dose trajectory groups. aRR were 1.80 (95% CI: 1.34, 2.40) for high and 1.24 (95% CI: 0.97, 1.58) for low groups. Only prednisone equivalent dose >20 mg/day after day 139 was associated with increased PTB (adjusted HR: 2.54; 95% CI: 1.60, 4.03). CONCLUSIONS For asthma, higher OCS doses early in pregnancy, but not later, were associated with increased PTB. For SLE, higher doses early and later in pregnancy were associated with PTB.
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Affiliation(s)
- Kristin Palmsten
- Research Division, HealthPartners Institute, Minneapolis, Minn; Department of Pediatrics, University of California, San Diego, Calif.
| | - Gretchen Bandoli
- Department of Pediatrics, University of California, San Diego, Calif; Department of Family Medicine and Public Health, University of California, San Diego, Calif
| | - Jim Watkins
- Research and Analytic Studies Division, California Department of Health Services, Sacramento, Calif
| | | | - Todd P Gilmer
- Department of Family Medicine and Public Health, University of California, San Diego, Calif
| | - Christina D Chambers
- Department of Pediatrics, University of California, San Diego, Calif; Department of Family Medicine and Public Health, University of California, San Diego, Calif
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