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Mujumdar S, D'Souza M, Abdalla MI. Inflammatory Bowel Disease and Reproductive Health: A Focus on Pregnancy Planning and Outcomes. Semin Reprod Med 2024; 42:228-238. [PMID: 39393792 DOI: 10.1055/s-0044-1791725] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/13/2024]
Abstract
Reproductive counseling is crucial for women's health, especially for those with inflammatory bowel disease (IBD), which often affects younger patients during their childbearing years. Patients with IBD need special considerations when planning for pregnancy. Preconception counseling is important as it helps patients make informed decisions about pregnancy and allows for optimal management of IBD before, during, and after pregnancy. In this review, we aim to provide guidance for managing and treating patients with IBD throughout the preconception, pregnancy, and postpartum period.
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Affiliation(s)
- Sahaj Mujumdar
- Division of Gastroenterology and Hepatology, University of Rochester Medical Center, Rochester, New York
| | - Michelle D'Souza
- Division of Gastroenterology and Hepatology, University of Rochester Medical Center, Rochester, New York
| | - Maisa I Abdalla
- Division of Gastroenterology and Hepatology, University of Rochester Medical Center, Rochester, New York
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2
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Azzam NA, Almutairdi A, Almudaiheem HY, AlAmeel T, Bakkari SA, Alharbi OR, Alenzi KA, AlMolaiki MA, Al-Omari BA, Albarakati RG, Al-Jedai AH, Saadah OI, Almadi MA, Al-Bawardy B, Mosli MH. Saudi consensus guidance for the management of inflammatory bowel disease during pregnancy. Saudi J Gastroenterol 2023:00936815-990000000-00066. [PMID: 38099556 PMCID: PMC11379253 DOI: 10.4103/sjg.sjg_318_23] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2023] [Accepted: 11/08/2023] [Indexed: 09/10/2024] Open
Abstract
ABSTRACT The management of inflammatory bowel disease (IBD) in pregnant women is challenging and must be addressed on a patient-by-patient basis. Optimal patient management requires a multidisciplinary team and clear evidence-based recommendations that cater to this subset of patients. In this article, we provide concise guidelines and clinical care pathway for the management of IBD in pregnant women. Our recommendations were developed by a multidisciplinary working group that includes experts from the Saudi Ministry of Health in collaboration with the Saudi Gastroenterology Association and the Saudi Society of Clinical Pharmacology. All recommendations are based on up-to-date information following an extensive literature review. A total of 23 evidence-based expert opinion recommendations for the management of IBD in pregnant women are herein provided.
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Affiliation(s)
- Nahla A Azzam
- Division of Gastroenterology, Department of Medicine, College of Medicine, King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia
| | - Abdulelah Almutairdi
- Department of Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| | | | - Turki AlAmeel
- Department of Medicine, King Fahad Specialist Hospital, Dammam, Saudi Arabia
| | - Shakir A Bakkari
- Department of Gastroenterology, King Saud Medical City, Riyadh, Saudi Arabia
| | - Othman R Alharbi
- Division of Gastroenterology, Department of Medicine, College of Medicine, King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia
| | - Khalidah A Alenzi
- Executive Director of Transformation, Planning, and Business Development, Tabuk Health Cluster, Tabuk, Saudi Arabia
| | - Maha A AlMolaiki
- Department of Pharmaceutical Care Services, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia
- King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
- Department of Pharmacy Practice, College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
| | - Bedor A Al-Omari
- Department of Pharmaceutical Care Services, Prince Sultan Military Medical City, Riyadh, Saudi Arabia
| | - Rayan G Albarakati
- Department of Obstetrics and Gynecology, Majmaah University, Riyadh, Saudi Arabia
| | - Ahmed H Al-Jedai
- Deputyship of Therapeutic Affairs, Ministry of Health, Riyadh, Saudi Arabia
- Professor, Colleges of Medicine and Pharmacy, Alfaisal University, Riyadh, Saudi Arabia
| | - Omar I Saadah
- Department of Pediatrics, Faculty of Medicine, King Abdulaziz University, Inflammatory Bowel Disease Unit, King Abdulaziz University Hospital, Jeddah, Saudi Arabia
| | - Majid A Almadi
- Division of Gastroenterology, Department of Medicine, College of Medicine, King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia
| | - Badr Al-Bawardy
- Department of Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
- Department of Internal Medicine, Section of Digestive Diseases, Yale School of Medicine, New Haven, CT, USA
| | - Mahmoud H Mosli
- Department of Internal Medicine, King Abdulaziz University, Inflammatory Bowel Disease Unit, King Abdulaziz University Hospital, Jeddah, Saudi Arabia
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3
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Murray J, Kok KB, Ayling RM. Fecal Calprotectin in Gastrointestinal Disease. Clin Chem 2023:7179811. [PMID: 37228058 DOI: 10.1093/clinchem/hvad051] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2023] [Accepted: 03/14/2023] [Indexed: 05/27/2023]
Abstract
BACKGROUND Inflammatory bowel disease (IBD) comprises a group of chronic conditions characterized by relapsing and remitting inflammation of the gastrointestinal tract. The incidence is increasing worldwide, and the therapeutic options for management are expanding. Endoscopy is the gold standard investigation for diagnosis of IBD and for assessing mucosal healing, which is increasingly being used as a measure of disease control. However, it is an invasive procedure that is unpleasant for patients and expensive and time-consuming for hospitals. Fecal calprotectin has been shown to be an accurate surrogate marker of gastrointestinal inflammation in IBD. CONTENT Fecal calprotectin was initially used for the diagnosis of IBD but is now recognized as having a role in assisting in assessment of disease activity, prediction of relapse, and informing decisions around therapy and may help to minimize requirement for endoscopy. However, there are various preanalytical and analytical factors that can affect interpretation of the results; these need to be understood to optimize clinical care. SUMMARY Preanalytical and analytical factors that can potentially influence fecal calprotectin concentrations are examined, and an overview is provided of clinical situations in which fecal calprotectin is commonly measured.
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Affiliation(s)
- Jennifer Murray
- Department of Gastroenterology, Barts Health NHS Trust, Royal London Hospital, London, United Kingdom
| | - Klaartje B Kok
- Department of Gastroenterology, Barts Health NHS Trust, Royal London Hospital, London, United Kingdom
| | - Ruth M Ayling
- Department of Clinical Biochemistry, Barts Health NHS Trust, Royal London Hospital, London, United Kingdom
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Jogendran R, O'Connor K, Jeyakumar A, Tandon P, Nguyen GC, Maxwell C, Huang V. Optimizing maternal and neonatal outcomes through tight control management of inflammatory bowel disease during pregnancy: a pilot feasibility study. Sci Rep 2023; 13:8291. [PMID: 37217778 DOI: 10.1038/s41598-023-35332-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Accepted: 05/16/2023] [Indexed: 05/24/2023] Open
Abstract
A home point-of care FCP test (IBDoc) and a self-reported clinical disease activity program (IBD Dashboard) may improve routine monitoring of IBD activity during pregnancy. We aimed to evaluate the feasibility of tight control management using remote monitoring in pregnant patients with IBD. Pregnant patients (< 20 weeks) with IBD were prospectively enrolled from Mount Sinai Hospital between 2019 and 2020. Patients completed the IBDoc and IBD Dashboard at three core time points. Disease activity was measured clinically using the Harvey-Bradshaw Index (mHBI) for CD and partial Mayo (pMayo) for UC, or objectively using FCP. A feasibility questionnaire was completed in the third trimester. Seventy-seven percent of patients (24 of 31) completed the IBDoc and IBD Dashboard at all core time points. Twenty-four patients completed the feasibility questionnaires. All survey respondents strongly preferred using the IBDoc over standard lab-based testing and would use the home kit in the future. Exploratory analysis identified discordance rates of more than 50% between clinical and objective disease activity. Tight control management using remote monitoring may be feasible among pregnant patients with IBD. A combination of both clinical scores and objective disease markers may better predict disease activity.
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Affiliation(s)
- Rohit Jogendran
- Division of Gastroenterology and Hepatology, IBD Clinical Research Program, Mount Sinai Hospital, Sinai Health System, University of Toronto, Suite 441 - 600 University Avenue, Toronto, ON, M5G 1X5, Canada
| | - Katie O'Connor
- Division of Gastroenterology and Hepatology, IBD Clinical Research Program, Mount Sinai Hospital, Sinai Health System, University of Toronto, Suite 441 - 600 University Avenue, Toronto, ON, M5G 1X5, Canada
| | - Ajani Jeyakumar
- Division of Gastroenterology and Hepatology, IBD Clinical Research Program, Mount Sinai Hospital, Sinai Health System, University of Toronto, Suite 441 - 600 University Avenue, Toronto, ON, M5G 1X5, Canada
| | - Parul Tandon
- Division of Gastroenterology and Hepatology, IBD Clinical Research Program, Mount Sinai Hospital, Sinai Health System, University of Toronto, Suite 441 - 600 University Avenue, Toronto, ON, M5G 1X5, Canada
| | - Geoffrey C Nguyen
- Division of Gastroenterology and Hepatology, IBD Clinical Research Program, Mount Sinai Hospital, Sinai Health System, University of Toronto, Suite 441 - 600 University Avenue, Toronto, ON, M5G 1X5, Canada
| | - Cynthia Maxwell
- Division of Maternal Fetal Medicine, Department of Obstetrics & Gynaecology, Mount Sinai Hospital, Toronto, ON, Canada
- Women's College Hospital Research Institute, Women's College Hospital, Toronto, ON, Canada
| | - Vivian Huang
- Division of Gastroenterology and Hepatology, IBD Clinical Research Program, Mount Sinai Hospital, Sinai Health System, University of Toronto, Suite 441 - 600 University Avenue, Toronto, ON, M5G 1X5, Canada.
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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: 118] [Impact Index Per Article: 59.0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2022] [Indexed: 02/02/2023]
Affiliation(s)
- Joana Torres
- Division of Gastroenterology, Hospital Beatriz Ângelo, Loures, Portugal
- Division of Gastroenterology, Hospital da Luz, Lisboa, Portugal
- Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal
| | - María Chaparro
- Department of Gastroenterology, Hospital Universitario de La Princesa, IIS-Princesa, UAM, CIBEREHD, Madrid, Spain
| | - Mette Julsgaard
- Department of Hepatology & Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
- Center for Molecular Prediction of Inflammatory Bowel Disease [PREDICT], Department of Clinical Medicine, Aalborg University, Copenhagen, Denmark
| | - Konstantinos Katsanos
- Department of Gastroenterology and Hepatology, University and Medical School of Ioannina, Ioannina, Greece
| | - Zuzana Zelinkova
- Department of Internal Medicine, Svet zdravia, Nemocnica Dunajska Streda, Slovakia
- Firstst Department of Internal Medicine of University Hospital and Slovak Medical University in Bratislava, Bratislava, Slovakia
| | - Manasi Agrawal
- Dr Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Center for Molecular Prediction of Inflammatory Bowel Disease [PREDICT], Department of Clinical Medicine, Aalborg University, Copenhagen, Denmark
| | - Sandro Ardizzone
- Gastrointestinal Unit, Department of Biomedical and Clinical Sciences. University of Milan, Milan, Italy
| | - Marjo Campmans-Kuijpers
- Department of Gastroenterology and Hepatology, University Medical Centre Groningen, Groningen, The Netherlands
| | - Gabriele Dragoni
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences 'Mario Serio', University of Florence, Florence, Italy
- Gastroenterology Department, Careggi University Hospital, Florence, Italy
| | - Marc Ferrante
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
- Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven, Belgium
| | - Gionata Fiorino
- Department of Gastroenterology and Digestive Endoscopy, IRCCS San Raffaele Hospital and Vita-Salute San Raffaele University, Milan, Italy
| | - Emma Flanagan
- Department of Gastroenterology, St Vincent's Hospital Melbourne, Fitzroy, VIC, Australia
| | | | - Ailsa Hart
- Inflammatory Bowel Diseases Unit, St Mark's Hospital, Harrow, UK
| | - Charlotte Rose Hedin
- Karolinska Institutet, Department of Medicine Solna, Stockholm, Sweden
- Karolinska University Hospital, Department of Gastroenterology, Dermatovenereology and Rheumatology, Stockholm, Sweden
| | - Pascal Juillerat
- Clinic for Visceral Surgery and Medicine, Bern University Hospital, Bern, Switzerland
- Crohn's and Colitis Center, Gastroenterology Beaulieu SA, Lausanne, Switzerland
| | - Annemarie Mulders
- Department of Obstetrics and Gynaecology, Division of Obstetrics and Fetal Medicine Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands
| | - Pär Myrelid
- Department of Surgery, Linköping University Hospital, Linköping, Sweden
- Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
| | - Aoibhlinn O'Toole
- Beaumont Hospital, Department of Gastroenterology, Royal College of Surgeons, Dublin, Ireland
| | - Pauline Rivière
- Gastroenterology Unit, Bordeaux University Hospital, Pessac, France
| | - Michael Scharl
- Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | | | - Elena Sonnenberg
- Charité-Universitätsmedizin Berlin, Department of Gastroenterology, Infectious Diseases and Rheumatology, Germany
| | - Murat Toruner
- Department of Gastroenterology, Ankara University School of Medicine, Ankara, Turkey
| | - Jantien Wieringa
- Department of Paediatrics, Haaglanden Medical Center, The Hague, The Netherlands
- Department of Paediatrics, Erasmus Medical Center-Sophia Children's Hospital, Rotterdam, The Netherlands
| | - C Janneke Van der Woude
- Department of Gastroenterology & Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands
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Tandon P, Lee EY, Maxwell C, Hitz L, Ambrosio L, Dieleman L, Halloran B, Kroeker K, Huang VM. Fecal Calprotectin May Predict Adverse Pregnancy-Related Outcomes in Patients with Inflammatory Bowel Disease. Dig Dis Sci 2021; 66:1639-1649. [PMID: 32533542 DOI: 10.1007/s10620-020-06381-5] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2020] [Accepted: 05/30/2020] [Indexed: 12/17/2022]
Abstract
BACKGROUND The role of fecal calprotectin in predicting pregnancy-related outcomes in inflammatory bowel disease (IBD) remains unknown. AIM To determine whether increased fecal calprotectin during pregnancy is associated with adverse pregnancy outcomes in IBD. METHODS This is a multicenter cohort study of women with IBD who underwent fecal calprotectin monitoring during pregnancy. Fecal calprotectin levels were stratified by trimester, and adverse pregnancy-related outcomes were recorded. The Mann-Whitney U test assessed differences between continuous variables, whereas categorical variables were compared using the Chi-squared test. RESULTS Eighty-five women with IBD were included. First trimester fecal calprotectin was higher in patients who underwent emergency Cesarean birth compared to those who had a vaginal delivery (503 ug/g, IQR 1554.3 ug/g vs. 130 ug/g, IQR 482 ug/g, p = .030, respectively) and in those who delivered infants with low birth weight compared to normal birth weight (1511 ug/g, IQR 579 ug/g vs. 168 ug/g, IQR 413 ug/g, p = .049, respectively). Third trimester fecal calprotectin was higher in those with non-elective induction of labor (334.5 ug/g, IQR 1411.0 ug/g) compared to those with spontaneous delivery (116.5 ug/g, IQR 227.1 ug/g) (p = .025). Those with a fecal calprotectin ≥ 250 ug/g in the second trimester had an increased incidence of infants with low birth weight (35.3% vs. 3.8%) (p = .049), whereas those with a fecal calprotectin ≥ 250 ug/g in the third trimester had an increased incidence of non-elective induction of labor (43.8% vs. 10.3%, p = .030). CONCLUSIONS Fecal calprotectin may be a useful noninvasive marker to predict adverse pregnancy-related outcomes in patients with IBD.
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Affiliation(s)
- Parul Tandon
- Division of Gastroenterology, Mount Sinai Hospital, Sinai Health System, University of Toronto, Suite 441-600 University Avenue, Toronto, ON, M5G 1X5, Canada.,Department of Medicine, University of Toronto, 441-600 University Avenue, Toronto, ON, M5G 1X5, Canada
| | - Eugenia Y Lee
- Department of Medicine, University of Toronto, 441-600 University Avenue, Toronto, ON, M5G 1X5, Canada
| | - Cynthia Maxwell
- Department of Obstetrics and Gynaecology, University of Toronto, 901-700 University Avenue, Toronto, ON, M5G 1Z5, Canada
| | - Lara Hitz
- Division of Gastroenterology, Mount Sinai Hospital, Sinai Health System, University of Toronto, Suite 441-600 University Avenue, Toronto, ON, M5G 1X5, Canada
| | - Lindsy Ambrosio
- Division of Gastroenterology, University of Alberta, Edmonton, AB, Canada
| | - Levinus Dieleman
- Division of Gastroenterology, University of Alberta, 2-24A Zeidler Building, Edmonton, AB, T6G 2X8, Canada
| | - Brendan Halloran
- Division of Gastroenterology, University of Alberta, 130 University Campus NW, Edmonton, AB, T6G 2X8, Canada
| | - Karen Kroeker
- Division of Gastroenterology, University of Alberta, 8540 112th Street NW, Edmonton, AB, T6G 2X8, Canada
| | - Vivian M Huang
- Division of Gastroenterology, Mount Sinai Hospital, Sinai Health System, University of Toronto, Suite 441-600 University Avenue, Toronto, ON, M5G 1X5, Canada. .,Department of Medicine, University of Toronto, 441-600 University Avenue, Toronto, ON, M5G 1X5, Canada.
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7
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Kim ES, Tarassishin L, Eisele C, Barre A, Nair N, Rendon A, Hawkins K, Debebe A, White S, Thjømøe A, Mørk E, Bento-Miranda M, Panchal H, Agrawal M, Patel A, Chen CL, Kornbluth A, George J, Legnani P, Maser E, Loudon H, Mella MT, Stone J, Dubinsky M, Sabino J, Torres J, Colombel JF, Peter I, Hu J. Longitudinal Changes in Fecal Calprotectin Levels Among Pregnant Women With and Without Inflammatory Bowel Disease and Their Babies. Gastroenterology 2021; 160:1118-1130.e3. [PMID: 33307026 DOI: 10.1053/j.gastro.2020.11.050] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Revised: 11/09/2020] [Accepted: 11/29/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS The effect of pregnancy on inflammatory bowel disease (IBD) remains poorly understood. We aimed to monitor intestinal inflammation using fecal calprotectin (FC) in pregnant women and their babies during early life. METHODS Pregnant women with or without IBD and their infants were prospectively enrolled. FC levels were measured at each trimester of pregnancy and in babies throughout the first 3 years of life. Repeated-measures analysis was applied to investigate changes in FC levels while adjusting for confounders. The FC levels were correlated with the bacterial abundance in both mothers and babies. RESULTS Six hundred and fourteen fecal samples from 358 mothers (98 with IBD) and 1005 fecal samples from 289 infants (76 born to IBD mothers) were analyzed. Pregnant Patients with IBD maintained higher FC levels through pregnancy compared with controls (P = 7.5 × 10-54). FC gradually increased in controls and declined in Patients with IBD throughout pregnancy (P for interaction = 5.8 × 10-7). Babies born to mothers with IBD presented with significantly higher FC levels than those born to controls up to 3 years of age, after adjusting for sex, delivery mode, feeding behavior, and antibiotics exposure (2 weeks to 3 months of age, P = .015; 12-36 months of age, P = .00003). Subdoligranulum, Roseburia, Fusicatenibacter, and Alistipes negatively correlated, and Streptococcus, Prevotella, Escherichia-Shigella, and Bifidobacterium positively correlated with maternal FC levels at T3. Faecalibacterium, Bifidobacterium, and Alistipes showed negative correlations, and Streptococcus were positively correlated with FC levels within 3 months of birth. CONCLUSIONS Pregnancy is associated with decreased inflammatory activity in mothers with IBD. Higher FC levels in babies born to mothers with IBD suggest subclinical inflammation in early life, the long-term consequences of which are uncertain.
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Affiliation(s)
- Eun Soo Kim
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York; The Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York; Division of Gastroenterology, Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, South Korea
| | - Leonid Tarassishin
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Caroline Eisele
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Amelie Barre
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York; Division of Gastroenterology, Cochin Hospital, Université de Paris, Paris, France
| | - Nilendra Nair
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - Alexa Rendon
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Kelly Hawkins
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Anketse Debebe
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Sierra White
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York
| | | | | | - Mario Bento-Miranda
- Division of Gastroenterology, Hospital and University Center of Coimbra, Coimbra, Portugal
| | - Hinaben Panchal
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Manasi Agrawal
- The Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Anish Patel
- Division of Gastroenterology, Brooke Army Medical Center, San Antonio, Texas
| | - Ching-Lynn Chen
- Department of Obstetrics, Gynecology and Reproductive Science, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Asher Kornbluth
- The Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York
| | - James George
- The Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Peter Legnani
- The Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Elana Maser
- The Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Holly Loudon
- Department of Obstetrics, Gynecology and Reproductive Science, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Maria-Teresa Mella
- Division of Maternal Fetal Medicine, Department of Obstetrics, Gynecology and Reproductive Science, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Joanne Stone
- Division of Maternal Fetal Medicine, Department of Obstetrics, Gynecology and Reproductive Science, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Marla Dubinsky
- Department of Pediatric Gastroenterology and Nutrition, Icahn School of Medicine at Mount Sinai, New York, New York
| | - João Sabino
- Department of Gastroenterology, University Hospitals of Leuven, Leuven, Belgium
| | - Joana Torres
- The Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York; Division of Gastroenterology, Surgical Department, Hospital Beatriz Ângelo, Loures, Portugal
| | - Jean-Frederic Colombel
- The Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Inga Peter
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Jianzhong Hu
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.
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D'Amico F, Nancey S, Danese S, Peyrin-Biroulet L. A Practical Guide for Faecal Calprotectin Measurement: Myths and Realities. J Crohns Colitis 2021; 15:152-161. [PMID: 32392336 DOI: 10.1093/ecco-jcc/jjaa093] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND AND AIMS Faecal calprotectin [FC] is a valid and non-invasive marker of mucosal inflammation. It is widely used both in clinical trials and in daily clinical practice for patients with inflammatory bowel diseases, but currently no accepted standardization for FC testing is available. Our primary aim here was to provide a clinician's guide containing all the practical information on FC measurement in order to avoid any confounding factors, to minimize intra- and inter-individual variability in dosage, and to ensure a better and adequate interpretation of the results. METHODS We conducted a detailed search of the scientific literature in the PubMed/MEDLINE, EMBASE and Cochrane databases up to January 2020 to find all relevant and available articles on pre-analytical and analytical phases of FC measurement. RESULTS FC testing is a multi-step procedure consisting of a pre-analytical phase aimed to collect and process the stool sample and a subsequent analytical phase of FC measurement. Several factors can influence test results determining false positives or false negatives. Importantly, this faecal marker is mostly used for patient follow-up and as a predictor of treatment response. For this reason, any altered data may affect the physicians' decisions, negatively impacting on patient management. CONCLUSIONS This review provides for the first time practical advice to minimize dosage variability, although further dedicated studies are needed to compare commercially available tests and identify the best tools for the most precise and accurate FC measurement.
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Affiliation(s)
- Ferdinando D'Amico
- Department of Biomedical Sciences, Humanitas University, Milan, Italy.,Department of Gastroenterology and Inserm NGERE U1256, University Hospital of Nancy, University of Lorraine, Vandoeuvre-lès-Nancy, France
| | - Stéphane Nancey
- Department of Gastroenterology, Hospices Civils de Lyon, Lyon-Sud Hospital, Pierre Benite, and Inserm U1111, CIRI, Lyon, France
| | - Silvio Danese
- Department of Biomedical Sciences, Humanitas University, Milan, Italy.,IBD Center, Department of Gastroenterology, Humanitas Research Hospital, Rozzano -IRCCS-, Milan, Italy
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology and Inserm NGERE U1256, University Hospital of Nancy, University of Lorraine, Vandoeuvre-lès-Nancy, France
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9
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Nuñez F P, Quera R, Sepúlveda E, Simian D, Pizarro G, Lubascher J, Flores L, Ibañez P, Figueroa C, Kronberg U. Pregnancy in Inflammatory Bowel Disease: Experience of a Chilean cohort. GASTROENTEROLOGIA Y HEPATOLOGIA 2020; 44:277-285. [PMID: 33745519 DOI: 10.1016/j.gastrohep.2020.08.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/19/2020] [Revised: 08/12/2020] [Accepted: 08/25/2020] [Indexed: 11/30/2022]
Abstract
BACKGROUND In inflammatory bowel disease (IBD) a high percentage of women are diagnosed during their reproductive age. IBD in remission is the ideal scenario when planning a pregnancy. AIMS To describe the clinical characteristics of pregnancy/newborn and assess disease activity at the time of conception and throughout the pregnancy in patients with IBD treated at a tertiary centre in Chile. METHODS We retrospectively reviewed women diagnosed with IBD who were pregnant or delivered between 2017 and 2020. Demographic, clinical, obstetric and delivery data were obtained from the IBD registry, approved by the local IRB. Descriptive statistics and association tests were performed (χ2, p ≤ 0.05). RESULTS Sixty women with IBD were included. At the beginning of pregnancy, 21 (35%) had active disease and 39 (65%) were in remission. Of those with active disease, 16 (66%) remained active and 6 had spontaneous abortions. In those who were in remission, 26 (69%) remained in this condition. Nine patients (15%) discontinued treatment, and 6 of these had inflammatory activity during pregnancy. Preconception counselling was performed in 23 of the 60 patients, being higher in the group that remained in remission during pregnancy (65% vs. 35%, p = 0.02). Patients who had a flare during pregnancy had more probability of preterm birth (<37 weeks) and newborn with lower weight compared with the group that always remained in remission (89% vs. 74%, p = 0.161) and (2.885 vs 3.370 g; p = 0.0014). CONCLUSION Remission presents better outcomes in pregnancy and preconception counselling would allow a better IBD control during pregnancy.
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Affiliation(s)
- Paulina Nuñez F
- Universidad de Chile, Facultad de Medicina Occidente, Hospital San Juan de Dios, Universidad de Chile, Santiago, Chile
| | - Rodrigo Quera
- Programa Enfermedad Inflamatoria Intestinal, Departamento Gastroenterología, Clínica Las Condes, Santiago, Chile.
| | - Eduardo Sepúlveda
- Departamento de Ginecología y Obstetricia Universidad de Chile, Santiago, Chile
| | - Daniela Simian
- Dirección Académica, Departamento Gastroenterología, Clínica Las Condes, Santiago, Chile
| | - Gonzalo Pizarro
- Programa Enfermedad Inflamatoria Intestinal, Departamento Gastroenterología, Clínica Las Condes, Santiago, Chile
| | - Jaime Lubascher
- Programa Enfermedad Inflamatoria Intestinal, Departamento Gastroenterología, Clínica Las Condes, Santiago, Chile
| | - Lilian Flores
- Programa Enfermedad Inflamatoria Intestinal, Departamento Gastroenterología, Clínica Las Condes, Santiago, Chile
| | - Patricio Ibañez
- Programa Enfermedad Inflamatoria Intestinal, Departamento Gastroenterología, Clínica Las Condes, Santiago, Chile
| | - Carolina Figueroa
- Unidad de Coloproctología, Departamento de Cirugía, Clínica Las Condes, Santiago, Chile
| | - Udo Kronberg
- Unidad de Coloproctología, Departamento de Cirugía, Clínica Las Condes, Santiago, Chile
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10
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Flanagan E, Wright EK, Begun J, Bryant RV, An YK, Ross AL, Kiburg KV, Bell SJ. Monitoring Inflammatory Bowel Disease in Pregnancy Using Gastrointestinal Ultrasonography. J Crohns Colitis 2020; 14:1405-1412. [PMID: 32343768 DOI: 10.1093/ecco-jcc/jjaa082] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Inflammatory bowel disease [IBD] affects women during their childbearing years. Gastrointestinal ultrasonography [GIUS] accurately identifies disease activity in non-pregnant patients with IBD. The utility of GIUS in pregnancy has not been established. We aimed to determine the feasibility and accuracy of GIUS in the assessment of IBD during pregnancy progression. METHODS A multicentre observational study of women with IBD undergoing GIUS during pregnancy. Clinicians assessed the adequacy of bowel views and disease activity in four colonic segments and the terminal ileum. Location[s] in which views were impeded by the uterus were documented. GIUS disease activity [bowel wall thickness >3 mm] was compared with biochemical disease activity [faecal calprotectin >100 μg/g]. RESULTS Ninety patients and 127 GIUS examinations were included [median gestation 19 weeks, range 4-33]. Adequate colonic views were obtained in 116/127 [91%] scans. Adequate ileal views were obtained in 62/67 [93%] scans <20 weeks and 30/51 [59%] scans at 20-26 weeks. There was a positive correlation between bowel wall thickness and calprotectin [r = 0.26, p = 0.03]. GIUS delivered a specificity of 83%, sensitivity of 74%, and negative predictive value of 90% compared with calprotectin. CONCLUSIONS GIUS is a feasible and accurate modality for monitoring IBD in pregnancy. Adequate GIUS views of the colon and terminal ileum can be obtained in the majority of patients up to 20 weeks of gestation. Beyond 20 weeks, GIUS provides good views of the colon but the terminal ileum becomes difficult to assess.
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Affiliation(s)
- Emma Flanagan
- Department of Gastroenterology, St Vincent's Hospital, University of Melbourne, Melbourne, VIC, Australia
| | - Emily K Wright
- Department of Gastroenterology, St Vincent's Hospital, University of Melbourne, VIC, Australia
| | - Jakob Begun
- Department of Gastroenterology, Mater Hospital, Mater Research Institute, Brisbane, QLD, Australia
| | - Robert V Bryant
- Department of Gastroenterology, Queen Elizabeth Hospital, University of Adelaide, Adelaide, SA, Australia
| | - Yoon-Kyo An
- Department of Gastroenterology, Mater Hospital, Mater Research Institute, Brisbane, QLD, Australia
| | - Alyson L Ross
- Department of Gastroenterology, St Vincent's Hospital, Melbourne, VIC, Australia
| | - Katerina V Kiburg
- Department of Gastroenterology, St Vincent's Hospital, University of Melbourne, Melbourne, VIC, Australia
| | - Sally J Bell
- Department of Gastroenterology, St Vincent's Hospital, Melbourne, VIC, Australia
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11
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Gray JM, Knight K, Nguyen VQ, Rubio MG, Irby L, Boone JH, Sorrentino D. Fecal Lactoferrin and Other Stool Markers during Normal Pregnancy and in Inflammatory Bowel Diseases: A Prospective Study and Review of the Literature. Inflamm Intest Dis 2020; 5:151-157. [PMID: 32999888 DOI: 10.1159/000508970] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2020] [Accepted: 05/25/2020] [Indexed: 12/12/2022] Open
Abstract
Introduction Management of inflammatory bowel diseases (IBDs) - both Crohn's disease (CD) and ulcerative colitis (UC) - during pregnancy can be challenging since most monitoring tools available in nonpregnant patients are contraindicated. Objectives The aim of the study was to test whether fecal inflammatory markers - specifically fecal lactoferrin - physiologically change during normal pregnancy as a prerequisite to use them to monitor IBD activity during pregnancy. Methods Fecal lactoferrin was tested in healthy pregnant and nonpregnant women from the same geographic area and age range (18-40 years) - all negative for clinical gastrointestinal tract inflammation. A retrospective review of fecal lactoferrin levels contrasted with the Simple Endoscopic Score for CD, and the Disease Activity Index for UC was also performed in women with active IBDs within the same age range and geographical area. Results In 30 nonpregnant subjects, fecal lactoferrin levels were 0.87 ± 1.08 μg/g. In 49 pregnant subjects, levels were 0.59 ± 0.83, 0.87 ± 1.13, and 0.85 ± 1.06 μg/g during the first, second, and third trimester, respectively (p = 0.64), with average levels for the 3 trimesters of 0.81 ± 1.04 μg/g (p = 0.61 compared to nonpregnant subjects). Sequential fecal lactoferrin levels (n = 26) did not differ from one trimester to the other in the individual subjects (p = 0.80). In 45 female IBD patients (27 with CD and 18 with UC), fecal lactoferrin levels were correlated with disease activity as defined by the endoscopic scores: 218, 688, and 1,175 μg/g for CD and 931, 2,088, and 2,509 μg/g for UC, respectively, for mild, moderate, and severe activity. Conclusions Fecal lactoferrin levels during normal pregnancy are superimposable to those of nonpregnant women and significantly below levels in women of the same childbearing age with active IBDs. Additional published data - reviewed in this atricle - and our own indicate that fecal lactoferrin and other markers can be potentially used to monitor disease activity in pregnant IBD patients.
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Affiliation(s)
- James M Gray
- IBD Center, Division of Gastroenterology, Virginia Tech Carilion School of Medicine, Roanoke, Virginia, USA
| | - Kristin Knight
- IBD Center, Division of Gastroenterology, Virginia Tech Carilion School of Medicine, Roanoke, Virginia, USA
| | - Vu Q Nguyen
- IBD Center, Division of Gastroenterology, Virginia Tech Carilion School of Medicine, Roanoke, Virginia, USA
| | - Marrieth G Rubio
- IBD Center, Division of Gastroenterology, Virginia Tech Carilion School of Medicine, Roanoke, Virginia, USA
| | - Lauren Irby
- TechLab Research and Development, Blacksburg, Virginia, USA
| | - James H Boone
- TechLab Research and Development, Blacksburg, Virginia, USA
| | - Dario Sorrentino
- IBD Center, Division of Gastroenterology, Virginia Tech Carilion School of Medicine, Roanoke, Virginia, USA.,Department of Clinical and Experimental Medical Sciences, University of Udine School of Medicine, Udine, Italy
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12
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Laserna-Mendieta EJ, Lucendo AJ. Faecal calprotectin in inflammatory bowel diseases: a review focused on meta-analyses and routine usage limitations. Clin Chem Lab Med 2020; 57:1295-1307. [PMID: 30785706 DOI: 10.1515/cclm-2018-1063] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2018] [Accepted: 11/28/2018] [Indexed: 12/12/2022]
Abstract
A growing body of evidence has been published about the usefulness of measuring calprotectin in faecal samples (FCAL) in inflammatory bowel disease (IBD) assessment, including diagnosis, monitoring of disease activity and relapse prediction. Several systematic reviews with meta-analyses compiling studies for each particular clinical setting have been carried out in recent years. Most of these were focused on the use of FCAL in IBD diagnosis and showed a relevant role for this marker in selecting patients with gastrointestinal symptoms who would not need a further examination by endoscopy. Although a lesser number of meta-analyses have been performed on the use of FCAL as a surrogate marker of disease activity, a close correlation between FCAL and endoscopic activity of IBD has been shown. With respect to the predictive capacity of FCAL for IBD relapse, a single meta-analysis published indicates that this role is more limited. Furthermore, FCAL thresholds vary considerably depending on the clinical setting and, what is more concerning, among different commercially available assays due to a lack of FCAL concentration interchangeability. Here, we summarise recent publications about the role and limitations of FCAL in IBD, with a special focus on meta-analyses, and give an overview of alternative faecal biomarkers.
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Affiliation(s)
- Emilio J Laserna-Mendieta
- Department of Gastroenterology, Hospital General de Tomelloso, Tomelloso, Spain.,Clinical Laboratory, Hospital General de Villarrobledo, Villarrobledo, Spain
| | - Alfredo J Lucendo
- Department of Gastroenterology, Hospital General de Tomelloso, Tomelloso, Spain.,Biomedical Research Network Centre for Liver and Digestive Diseases (CIBEREHD), Madrid, Spain
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13
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Rottenstreich A, Mishael T, Granovsky SG, Koslowsky B, Schweistein H, Abitbol G, Goldin E, Shitrit ABG. Clinical utility of fecal calprotectin in monitoring disease activity and predicting relapse in pregnant patients with inflammatory bowel diseases. Eur J Intern Med 2020; 77:105-110. [PMID: 32197833 DOI: 10.1016/j.ejim.2020.03.015] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2019] [Accepted: 03/12/2020] [Indexed: 12/28/2022]
Abstract
OBJECTIVES Inflammatory bowel diseases (IBDs) are commonly diagnosed in reproductive-aged women and can substantially affect pregnancy outcomes. Non-invasive monitoring of IBD during the prenatal course is particularly challenging as traditional laboratory biomarkers are often affected by pregnancy-related physiologic changes. We aimed to evaluate the role of fecal calprotectin (FC) in monitoring disease activity and predicting relapse among IBD women throughout gestation. METHODS Women with IBD attending a multidisciplinary clinic for the preconception, antenatal and postnatal treatment were prospectively recruited during 2014-2018. FC levels were determined with an enzyme-linked immunoassay. RESULTS A total of 265 FC (preconception, n = 41; 1st trimester, n = 48; 2nd trimester, n = 84; 3rd trimester, n = 76; postpartum, n = 16) measurements were obtained in 157 pregnancies. Higher FC concentrations were found in all time points in those with active disease than those in remission as assessed by either physician global assessment or disease clinical scores. FC levels were significantly correlated with physician global assessment and disease activity indices in all 5 periods of investigation. Excluding those with disease flare at the time of conception, disease relapse was encountered during the prenatal course in 40 (31.5%) of the remaining 127 pregnancies. FC levels were significantly higher in those who experienced a disease flare later in the course of gestation as compared to those who maintained clinical remission (median 341 vs. 224 μg/g, P = 0.04). CONCLUSION FC appears to be a reliable marker of ongoing disease activity throughout the prenatal course as well as a predictor of imminent disease flare among IBD pregnant patients.
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Affiliation(s)
- Amihai Rottenstreich
- Department of Obstetrics and Gynecology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
| | - Tali Mishael
- IBD MOM Unit, Digestive Diseases Institute, Shaare Zedek Medical Center, Affiliated with the Medical School, Hebrew University, Jerusalem, Israel
| | - Sorina Grisaru Granovsky
- IBD MOM Unit, Digestive Diseases Institute, Shaare Zedek Medical Center, Affiliated with the Medical School, Hebrew University, Jerusalem, Israel
| | - Benjamin Koslowsky
- IBD MOM Unit, Digestive Diseases Institute, Shaare Zedek Medical Center, Affiliated with the Medical School, Hebrew University, Jerusalem, Israel
| | - Hagai Schweistein
- IBD MOM Unit, Digestive Diseases Institute, Shaare Zedek Medical Center, Affiliated with the Medical School, Hebrew University, Jerusalem, Israel
| | - Guila Abitbol
- IBD MOM Unit, Digestive Diseases Institute, Shaare Zedek Medical Center, Affiliated with the Medical School, Hebrew University, Jerusalem, Israel
| | - Eran Goldin
- IBD MOM Unit, Digestive Diseases Institute, Shaare Zedek Medical Center, Affiliated with the Medical School, Hebrew University, Jerusalem, Israel
| | - Ariella Bar-Gil Shitrit
- IBD MOM Unit, Digestive Diseases Institute, Shaare Zedek Medical Center, Affiliated with the Medical School, Hebrew University, Jerusalem, Israel
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14
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Noninvasive Methods For Assessing Inflammatory Bowel Disease Activity in Pregnancy: A Systematic Review. J Clin Gastroenterol 2019; 53:574-581. [PMID: 31306343 DOI: 10.1097/mcg.0000000000001244] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Active inflammatory bowel disease (IBD) may increase the risk of adverse outcomes during pregnancy. Our aim was to systematically review the role of noninvasive fecal tests, such as fecal calprotectin (FCP) and lactoferrin (FL), and laboratory tests including C-reactive protein (CRP), hemoglobin, and albumin in the assessment of IBD during pregnancy. A systematic search of electronic databases was performed through October 2018 for studies assessing the utility of fecal and laboratory tests in predicting IBD activity in pregnant patients. Active disease was defined based on routinely used clinical criteria such as the Harvey-Bradshaw Index or Mayo score for ulcerative colitis. Noninvasive test levels were stratified by the presence of active disease and by gestational period (preconception, first trimester, second trimester, and third trimester). Thirteen studies were included. Both FCP and FL levels were significantly higher in pregnant patients with IBD compared with those without IBD. FCP levels were also significantly higher in patients with active disease compared with those with the inactive disease during all gestational periods. Furthermore, 3 studies demonstrated no consistent correlation with serum CRP and active IBD during pregnancy. Similarly, serum albumin and hemoglobin levels did not correlate with disease activity in pregnant patients with IBD. Given the lack of high-quality evidence, only FCP appears to correlate with IBD activity in all gestational periods of pregnancy. The utility of the other noninvasive tests such as serum CRP, hemoglobin, and albumin remains to be determined in this population.
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15
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The Influence of Maternal-Foetal Parameters on Concentrations of Zonulin and Calprotectin in the Blood and Stool of Healthy Newborns during the First Seven Days of Life. An Observational Prospective Cohort Study. J Clin Med 2019; 8:jcm8040473. [PMID: 30959960 PMCID: PMC6517987 DOI: 10.3390/jcm8040473] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2019] [Revised: 04/03/2019] [Accepted: 04/04/2019] [Indexed: 12/19/2022] Open
Abstract
Background: It can be hypothetically assumed that maternal and perinatal factors influence the intestinal barrier. Methods: The study was conducted with 100 healthy, full-term newborns breastfed in the first week of life, with similar analyses for their mothers. Zonulin and calprotectin levels were used as intestinal permeability markers. Results: The median (range) zonulin concentrations (ng/mL) were in mothers: serum, 21.39 (6.39–57.54); stool, 82.23 (42.52–225.74); and newborns: serum cord blood, 11.14 (5.82–52.34); meconium, 54.15 (1.36–700.65); and stool at age seven days, 114.41 (29.38–593.72). Calprotectin median (range) concentrations (µg/mL) in mothers were: stool, 74.79 (3.89–211.77); and newborns: meconium, 154.76 (6.93–8884.11); and stool at age seven days 139.12 (11.89–627.35). The use of antibiotics during pregnancy resulted in higher zonulin concentrations in umbilical-cord serum and calprotectin concentrations in newborn stool at seven days, while antibiotic therapy during labour resulted in higher zonulin concentrations in the stool of newborns at seven days. Zonulin concentrations in the stool of newborns (at seven days) who were born via caesarean section were higher compared to with vaginal birth. With further analyses, caesarean section was found to have a greater effect on zonulin concentrations than prophylactic administration of antibiotics in the perinatal period. Pregnancy mass gain >18 kg was associated with higher calprotectin concentrations in maternal stool. Body Mass Index (BMI) increase >5.7 during pregnancy was associated with decreased zonulin concentrations in maternal stool and increased calprotectin concentrations in stool of mothers and newborns at seven days. There was also a negative correlation between higher BMI increase in pregnancy and maternal zonulin stool concentrations and a positive correlation between BMI increase in pregnancy and maternal calprotectin stool concentrations. Conclusion: Maternal-foetal factors such as caesarean section, antibiotic therapy during pregnancy, as well as change in mother’s BMI during pregnancy may increase intestinal permeability in newborns. Changes in body mass during pregnancy can also affect intestinal permeability in mothers. However, health consequences associated with increased intestinal permeability during the first days of life are unknown. Additionally, before the zonulin and calprotectin tests can be adopted as universal diagnostic applications to assess increased intestinal permeability, validation of these tests is necessary.
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16
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Calprotectin in pregnancy and pregnancy-associated diseases: a systematic review and prospective cohort study. Arch Gynecol Obstet 2019; 299:1567-1577. [PMID: 30953184 DOI: 10.1007/s00404-019-05134-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2018] [Accepted: 03/25/2019] [Indexed: 12/17/2022]
Abstract
PURPOSE Calprotectin, a marker of acute and chronic inflammation, may play a role in pregnancy-associated disorders. We aimed to summarize available clinical data on calprotectin in pregnancy and to establish normal values of calprotectin during the course of pregnancy. METHODS We performed a systematic review of the databases PubMed and Cochrane Central Register of Controlled Trials to identify experimental and clinical evidence assessing the role of calprotectin in pregnancy. In addition, we performed a prospective cohort study assessing serum and urine calprotectin throughout pregnancy. RESULTS We identified 17 studies investigating 1638 pregnant women, 151 newborns, and 99 non-pregnant controls, measuring calprotectin in different compartments. Calprotectin was present in meconium and elevated in fecal samples of pregnant women with active inflammatory bowel disease. In women with pregnancy-induced hypertension, mild and severe preeclampsia (PE), calprotectin was significantly elevated in maternal plasma and serum, but not in fetal serum, amniotic fluid, and umbilical cord blood. For the cohort study, we recruited 196 pregnant women. PE and concomitant renal disease were present in 6/196 (3%) and 11/196 (5.6%) of women, respectively. Throughout pregnancy, median serum and urine levels of calprotectin largely exceed reported concentrations of the healthy non-pregnant population, but showed no significant variations between trimesters 1-3 and post-partum. Calprotectin in serum was correlated with systolic blood pressure and in urine with leukocytes and total protein. No significant differences were found in subgroup analyses of smokers vs. non-smokers, PE vs. none, and renal disease (kidney stones, reflux) vs. none. CONCLUSION Calprotectin concentrations in amnion fluid and stools serve as potential indicators of inflammatory states during pregnancy. Urinary calprotectin concentrations are continuously high during pregnancy and show no significant variations between trimesters 1-3 and post-partum.
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17
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Gomes CF, Sousa M, Lourenço I, Martins D, Torres J. Gastrointestinal diseases during pregnancy: what does the gastroenterologist need to know? Ann Gastroenterol 2018; 31:385-394. [PMID: 29991883 PMCID: PMC6033757 DOI: 10.20524/aog.2018.0264] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2018] [Accepted: 02/26/2018] [Indexed: 12/15/2022] Open
Abstract
Pregnancy is characterized by numerous physiological changes that may lead to a diversity of symptoms and frequently to gastrointestinal complaints, such as heartburn, nausea and vomiting, or constipation. Chronic gastrointestinal diseases require treatment maintenance during this period, raising the challenging question whether outcomes beneficial to the mother may be harmful for the fetus. In addition, certain diseases, such as acute fatty liver of pregnancy, only develop during pregnancy and may require urgent procedures, such as fetus delivery. Even though they are not present in our day-to-day practice, knowledge of pregnancy-related diseases is fundamental and collaboration between gastroenterologists and obstetricians is often necessary. Herein, we review pregnancy-related diseases and systematize the most appropriate treatment choices according to the recent literature and guidelines, so that the article can serve as a guide to the gastroenterologist regarding the medical approach to pregnancy-related gastrointestinal and liver diseases and their therapeutic management.
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Affiliation(s)
- Catarina Frias Gomes
- Surgical Department, Gastroenterology Division (Catarina Frias Gomes, Joana Torres), Hospital Beatriz Ângelo, Loures, Portugal
| | - Mónica Sousa
- Medicine Department, Internal Medicina Division (Mónica Sousa);), Hospital Beatriz Ângelo, Loures, Portugal
| | - Inês Lourenço
- Surgical Department, Gynaecology and Obstetrics Division (Inês Lourenço, Diana Martins), Hospital Beatriz Ângelo, Loures, Portugal
| | - Diana Martins
- Surgical Department, Gynaecology and Obstetrics Division (Inês Lourenço, Diana Martins), Hospital Beatriz Ângelo, Loures, Portugal
| | - Joana Torres
- Surgical Department, Gastroenterology Division (Catarina Frias Gomes, Joana Torres), Hospital Beatriz Ângelo, Loures, Portugal
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18
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Kammerlander H, Nielsen J, Kjeldsen J, Knudsen T, Gradel KO, Friedman S, Nørgård BM. Fecal Calprotectin During Pregnancy in Women With Moderate-Severe Inflammatory Bowel Disease. Inflamm Bowel Dis 2018; 24:839-848. [PMID: 29506137 DOI: 10.1093/ibd/izx055] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Fecal calprotectin (FC) is a biomarker used for assessing disease activity among IBD patients. Sparse knowledge exists as to whether FC correlates with clinical disease activity during pregnancy. Our aim was to assess FC and selected biomarkers in women with moderate-severe IBD and correlate them with clinical disease activity scores in pregnant women. METHODS We identified a nationwide cohort of 219 singleton pregnancies in women with moderate-severe disease (all treated with anti-tumor recrosis factor-α [anti-TNF-α] therapy during pregnancy), and we reviewed the medical records to extract clinical details and information on biomarkers. FC, C-reactive protein (CRP), hemoglobin, and albumin were collected according to each trimester. RESULTS A total of 346 FC measurements were obtained throughout the gestational periods. FC values were between 80-120, 259-349, and 778-1277 mg/kg in women with clinically inactive, mild, and moderate-severe disease activity, respectively, and were significantly higher among the women with clinical disease activity. ROC curves for disease activity were computed according to the preconception period: 0.81 (95% confidence interval [CI], 0.69-0.93), first trimester: 0.73 (95% CI, 0.60-0.86), second trimester: 0.74 (95% CI, 0.62-0.86), and third trimester: 0.76 (95% CI, 0.64-0.88), respectively. We found a sensitivity of 69.7%-80.0%, a specificity of 66.7%-73.3%, and a positive predictive value of 66.7%-74.4% over the 4 gestational periods when a cutoff of 200 mg/kg was used. We found no clinically significant differences in CRP, albumin, or hemoglobin. CONCLUSIONS FC in pregnant women with moderate-severe IBD treated with anti-TNF-α therapy was significantly higher in women with clinical disease activity compared with the women without. FC correlated with the level of clinical disease activity in all gestational periods.
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Affiliation(s)
- Heidi Kammerlander
- Center for Clinical Epidemiology, Odense University Hospital, and Research Unit of Clinical Epidemiology, Institute of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Jan Nielsen
- Center for Clinical Epidemiology, Odense University Hospital, and Research Unit of Clinical Epidemiology, Institute of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Jens Kjeldsen
- Department of Medical Gastroenterology, Odense University Hospital, Odense, Denmark
| | - Torben Knudsen
- Department of Medical Gastroenterology, Hospital of Southwest Jutland, Esbjerg, Denmark
| | - Kim Oren Gradel
- Center for Clinical Epidemiology, Odense University Hospital, and Research Unit of Clinical Epidemiology, Institute of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Sonia Friedman
- Center for Clinical Epidemiology, Odense University Hospital, and Research Unit of Clinical Epidemiology, Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.,Crohn's and Colitis Center, Brigham and Women's Hospital, Boston, Massachusetts and Harvard Medical School, Boston, Massachusetts
| | - Bente Mertz Nørgård
- Center for Clinical Epidemiology, Odense University Hospital, and Research Unit of Clinical Epidemiology, Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.,Crohn's and Colitis Center, Brigham and Women's Hospital, Boston, Massachusetts and Harvard Medical School, Boston, Massachusetts
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19
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Choden T, Mandaliya R, Charabaty A, Mattar MC. Monitoring inflammatory bowel disease during pregnancy: Current literature and future challenges. World J Gastrointest Pharmacol Ther 2018; 9:1-7. [PMID: 29430322 PMCID: PMC5797976 DOI: 10.4292/wjgpt.v9.i1.1] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2017] [Revised: 10/13/2017] [Accepted: 10/30/2017] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel disease has a high prevalence in women of childbearing age and can have a significant impact on pregnancy, from conceiving to carrying the pregnancy. Active disease during pregnancy is known to have negative effects on pregnancy outcomes; therefore, careful monitoring during this period is an important but challenging aspect of care and is crucial as it affects important management decisions. Recent data seems to suggest that endoscopy is a relatively safe procedure during all trimesters of pregnancy. Serum biomarkers such as C-reactive protein and fecal calprotectin are helpful non-invasive markers, but have shown conflicting results for correlation with disease activity in some initial studies. Further work is necessary to establish standard of care monitoring during pregnancy.
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Affiliation(s)
- Tenzin Choden
- Department of Internal Medicine, MedStar Georgetown University Hospital, Washington, DC 20007, United States
| | - Rohan Mandaliya
- Division of Gastroenterology, MedStar Georgetown University Hospital, Washington, DC 20007, United States
| | - Aline Charabaty
- Division of Gastroenterology, MedStar Georgetown University Hospital, Washington, DC 20007, United States
| | - Mark C Mattar
- Division of Gastroenterology, MedStar Georgetown University Hospital, Washington, DC 20007, United States
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20
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Abstract
Calprotectin is a 36kDa member of the S100 family of proteins. It is derived predominantly from neutrophils and has direct antimicrobial effects and a role within the innate immune response. Calprotectin is found in various body fluids in proportion to the degree of any existing inflammation and its concentration in feces is about six times that of plasma. Measurement of fecal calprotectin is a useful surrogate marker of gastrointestinal inflammation. It has a high negative predictive value in ruling out inflammatory bowel disease (IBD) in undiagnosed, symptomatic patients and a high sensitivity for diagnosing the disease making it useful as a tool for prioritising endoscopy. In patients with known IBD, fecal calprotectin can be a useful tool to assist management, providing evidence of relapse or mucosal healing to enable therapy to be intensified or reduced. There are a number of commercial calprotectin assays with marked difference in performance as judged by external quality assessment and at present no standardised reference material exists. Various factors may affect results including age, medication and day to day variation. Laboratories should therefore be mindful of the characteristics of their own assay and factors that may affect results.
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Affiliation(s)
- Ruth M Ayling
- FRCPath Consultant Chemical Pathologist, Clinical Biochemistry, Pathology and Pharmacy Building, Royal London Hospital, London, United Kingdom
| | - Klaartje Kok
- MRCP Consultant Gastroenterologist, Barts Health NHS Trust, London, United Kingdom
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