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Feng J, Xu B, Magnuson JT, Wang J, Gao Y, Qiu W, Xuan R. Exposure of infants to antibiotics via cord blood, breast milk, and formula: A review on exposure level, temporal variation, and risk assessment. JOURNAL OF HAZARDOUS MATERIALS 2025; 494:138665. [PMID: 40403372 DOI: 10.1016/j.jhazmat.2025.138665] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/01/2025] [Revised: 04/26/2025] [Accepted: 05/17/2025] [Indexed: 05/24/2025]
Abstract
The pervasive use of antibiotics across various sectors, including agriculture, medicine, and aquaculture, has led to a notable increase in environmental antibiotic residues. This phenomenon has raised significant public concern regarding the potential health risks antibiotics may pose, particularly to vulnerable populations such as infants. However, the conceptualization of exposure routes of antibiotics to infants and the associated health risks has not been conducted. This review summarized three main pathways infants are exposed to antibiotics, including umbilical cord blood, breast milk, and infant formula. Antibiotic exposure levels in infants were synthesized, examining spatial and temporal trends in antibiotic concentrations across different media through clinical testing. We also analyzed the doses of antibiotics consumed by infants over time through breast milk and formula, evaluating the associated risks. Furthermore, we explored the potential adverse effects of early-life antibiotic exposure on the infant gut microbiota, physical development, and multiple organ systems. Given the global significance of antibiotic distribution, it is pertinent to comprehensively monitor antibiotic concentrations in infants and conduct longitudinal follow-up studies on their growth and development, accurately quantifying and assessing the impacts on fetal and infant health.
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Affiliation(s)
- Jiating Feng
- Gynaecology and obstetrics, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang Province 315020, China; Health Science Center, Ningbo University, Ningbo, Zhejiang Province 315211, China
| | - Bentuo Xu
- National and Local Joint Engineering Research Center of Ecological Treatment Technology for Urban Water Pollution, School of Life and Environmental Science, Wenzhou University, Wenzhou 325035, China
| | - Jason T Magnuson
- US Geological Survey, Columbia Environmental Research Center, Columbia, MO 65201, USA
| | - Jiayi Wang
- Gynaecology and obstetrics, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang Province 315020, China
| | - Yajie Gao
- Gynaecology and obstetrics, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang Province 315020, China
| | - Wenhui Qiu
- Guangdong-Hong Kong Joint Laboratory for Soil and Groundwater Pollution Control, School of Environmental Science and Engineering, Southern University of Science and Technology, Shenzhen 518055, China.
| | - Rongrong Xuan
- Gynaecology and obstetrics, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang Province 315020, China.
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Mou JY, Usman M, Tang JW, Yuan Q, Ma ZW, Wen XR, Liu Z, Wang L. Pseudo-Siamese network combined with label-free Raman spectroscopy for the quantification of mixed trace amounts of antibiotics in human milk: A feasibility study. Food Chem X 2024; 22:101507. [PMID: 38855098 PMCID: PMC11157215 DOI: 10.1016/j.fochx.2024.101507] [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: 03/12/2024] [Revised: 05/16/2024] [Accepted: 05/22/2024] [Indexed: 06/11/2024] Open
Abstract
The utilization of antibiotics is prevalent among lactating mothers. Hence, the rapid determination of trace amounts of antibiotics in human milk is crucial for ensuring the healthy development of infants. In this study, we constructed a human milk system containing residual doxycycline (DXC) and/or tetracycline (TC). Machine learning models and clustering algorithms were applied to classify and predict deficient concentrations of single and mixed antibiotics via label-free SERS spectra. The experimental results demonstrate that the CNN model has a recognition accuracy of 98.85% across optimal hyperparameter combinations. Furthermore, we employed Independent Component Analysis (ICA) and the pseudo-Siamese Convolutional Neural Network (pSCNN) to quantify the ratios of individual antibiotics in mixed human milk samples. Integrating the SERS technique with machine learning algorithms shows significant potential for rapid discrimination and precise quantification of single and mixed antibiotics at deficient concentrations in human milk.
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Affiliation(s)
- Jing-Yi Mou
- Laboratory Medicine, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong Province, China
- Department of Clinical Medicine, School of the 1 Clinical Medicine, Xuzhou Medical University, Xuzhou, Jiangsu Province, China
| | - Muhammad Usman
- School of Medical Informatics and Engineering, Xuzhou Medical University, Xuzhou, Jiangsu Province, China
| | - Jia-Wei Tang
- Laboratory Medicine, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong Province, China
| | - Quan Yuan
- Laboratory Medicine, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong Province, China
- School of Medical Informatics and Engineering, Xuzhou Medical University, Xuzhou, Jiangsu Province, China
| | - Zhang-Wen Ma
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, School of Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu Province, China
- Department of Pharmaceutical Analysis, School of Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu Province, China
| | - Xin-Ru Wen
- School of Medical Informatics and Engineering, Xuzhou Medical University, Xuzhou, Jiangsu Province, China
| | - Zhao Liu
- Department of Clinical Medicine, School of the 1 Clinical Medicine, Xuzhou Medical University, Xuzhou, Jiangsu Province, China
- Department of Thyroid and Breast Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, China
| | - Liang Wang
- Laboratory Medicine, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong Province, China
- Division of Microbiology and Immunology, School of Biomedical Sciences, The University of Western Australia, Crawley, Western Australia, Australia
- School of Agriculture and Food Sustainability, University of Queensland, Brisbane, Queensland, Australia
- Center for Precision Health, School of Medical and Health Sciences, Edith Cowan University, Perth, Western Australia, Australia
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Miao S, Yin J, Liu S, Zhu Q, Liao C, Jiang G. Maternal-Fetal Exposure to Antibiotics: Levels, Mother-to-Child Transmission, and Potential Health Risks. ENVIRONMENTAL SCIENCE & TECHNOLOGY 2024; 58:8117-8134. [PMID: 38701366 DOI: 10.1021/acs.est.4c02018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/05/2024]
Abstract
Due to its widespread applications in various fields, antibiotics are continuously released into the environment and ultimately enter the human body through diverse routes. Meanwhile, the unreasonable use of antibiotics can also lead to a series of adverse outcomes. Pregnant women and developing fetuses are more susceptible to the influence of external chemicals than adults. The evaluation of antibiotic exposure levels through questionnaire surveys or prescriptions in medical records and biomonitoring-based data shows that antibiotics are frequently prescribed and used by pregnant women around the world. Antibiotics may be transmitted from mothers to their offspring through different pathways, which then adversely affect the health of offspring. However, there has been no comprehensive review on antibiotic exposure and mother-to-child transmission in pregnant women so far. Herein, we summarized the exposure levels of antibiotics in pregnant women and fetuses, the exposure routes of antibiotics to pregnant women, and related influencing factors. In addition, we scrutinized the potential mechanisms and factors influencing the transfer of antibiotics from mother to fetus through placental transmission, and explored the adverse effects of maternal antibiotic exposure on fetal growth and development, neonatal gut microbiota, and subsequent childhood health. Given the widespread use of antibiotics and the health threats posed by their exposure, it is necessary to comprehensively track antibiotics in pregnant women and fetuses in the future, and more in-depth biological studies are needed to reveal and verify the mechanisms of mother-to-child transmission, which is crucial for accurately quantifying and evaluating fetal health status.
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Affiliation(s)
- Shiyu Miao
- State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China
- College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 100049, China
| | - Jia Yin
- State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China
- School of Environment, Hangzhou Institute for Advanced Study, UCAS, Hangzhou 310024, China
- College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 100049, China
| | - Shuang Liu
- State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China
- College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 100049, China
| | - Qingqing Zhu
- State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China
- College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 100049, China
| | - Chunyang Liao
- State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China
- School of Environment, Hangzhou Institute for Advanced Study, UCAS, Hangzhou 310024, China
- Hubei Key Laboratory of Environmental and Health Effects of Persistent Toxic Substances, School of Environment and Health, Jianghan University, Wuhan 430056, China
- College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 100049, China
| | - Guibin Jiang
- State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China
- School of Environment, Hangzhou Institute for Advanced Study, UCAS, Hangzhou 310024, China
- Hubei Key Laboratory of Environmental and Health Effects of Persistent Toxic Substances, School of Environment and Health, Jianghan University, Wuhan 430056, China
- College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 100049, China
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Demarinis G, Tatti F, Taloni A, Giugliano AV, Panthagani J, Myerscough J, Peiretti E, Giannaccare G. Treatments for Ocular Diseases in Pregnancy and Breastfeeding: A Narrative Review. Pharmaceuticals (Basel) 2023; 16:1433. [PMID: 37895903 PMCID: PMC10610321 DOI: 10.3390/ph16101433] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2023] [Revised: 09/30/2023] [Accepted: 10/02/2023] [Indexed: 10/29/2023] Open
Abstract
Pregnancy is a medical condition in which the physiological changes in the maternal body and the potential impact on the developing fetus require a cautious approach in terms of drug administration. Individual treatment, a thorough assessment of the extent of the disease, and a broad knowledge of the therapeutic options and different routes of administration of ophthalmic drugs are essential to ensure the best possible results while minimizing risks. Although there are currently several routes of administration of drugs for the treatment of eye diseases, even with topical administration, there is a certain amount of systemic absorption that must be taken into account. Despite continuous developments and advances in ophthalmic drugs, no updated data are available on their safety profile in these contexts. The purpose of this review is both to summarize the current information on the safety of ophthalmic treatments during pregnancy and lactation and to provide a practical guide to the ophthalmologist for the treatment of eye diseases while minimizing harm to the developing fetus and addressing maternal health needs.
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Affiliation(s)
- Giuseppe Demarinis
- Department of Surgical Sciences, Eye Clinic, University of Cagliari, Via Ospedale 48, 09124 Cagliari, Italy; (G.D.); (F.T.); (E.P.)
| | - Filippo Tatti
- Department of Surgical Sciences, Eye Clinic, University of Cagliari, Via Ospedale 48, 09124 Cagliari, Italy; (G.D.); (F.T.); (E.P.)
| | - Andrea Taloni
- Department of Ophthalmology, University ‘Magna Græcia’ of Catanzaro, Viale Europa, 88100 Catanzaro, Italy;
| | | | - Jesse Panthagani
- Department of Ophthalmology, Southend University Hospital, Southend-on-Sea SS0 0RY, UK; (J.P.); (J.M.)
| | - James Myerscough
- Department of Ophthalmology, Southend University Hospital, Southend-on-Sea SS0 0RY, UK; (J.P.); (J.M.)
| | - Enrico Peiretti
- Department of Surgical Sciences, Eye Clinic, University of Cagliari, Via Ospedale 48, 09124 Cagliari, Italy; (G.D.); (F.T.); (E.P.)
| | - Giuseppe Giannaccare
- Department of Surgical Sciences, Eye Clinic, University of Cagliari, Via Ospedale 48, 09124 Cagliari, Italy; (G.D.); (F.T.); (E.P.)
- Department of Ophthalmology, University ‘Magna Græcia’ of Catanzaro, Viale Europa, 88100 Catanzaro, Italy;
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Murphy CC, Cirillo PM, Krigbaum NY, Singal AG, Jones DP, Zaki T, Cohn BA. In-utero exposure to antibiotics and risk of colorectal cancer in a prospective cohort of 18 000 adult offspring. Int J Epidemiol 2023; 52:1448-1458. [PMID: 36692207 PMCID: PMC10555902 DOI: 10.1093/ije/dyad004] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2022] [Accepted: 01/10/2023] [Indexed: 01/25/2023] Open
Abstract
BACKGROUND Incidence rates of colorectal cancer (CRC) are increasing among younger adults and in mid-life, implicating exposures in early life as risk factors. We examined the association between in-utero exposure to antibiotics and risk of CRC in adult offspring. METHODS The Child Health and Development Studies is a prospective cohort of women receiving prenatal care between 1959 and 1966 in Oakland, California, with deliveries through June 1967. Diagnosed conditions and all prescribed medications were abstracted from mothers' medical records beginning 6 months prior to pregnancy through delivery. We identified mothers who received antibiotics in pregnancy, including penicillins, tetracyclines, short-acting sulfonamides and long-acting sulfonamides. Diagnoses of CRC in adult (age ≥18 years) offspring were ascertained through 2021 by linkage with the California Cancer Registry. Cox proportional models were used to estimate adjusted hazard ratios (aHR), with follow-up accrued from birth through cancer diagnosis, death or last contact. RESULTS Of 18 751 liveborn offspring, about 15% (n = 2635) were exposed in utero to antibiotics: 5.4% (n = 1016) to tetracyclines, 4.9% (n = 918) to penicillins, 4.2% (n = 785) to short-acting sulfonamides and 1.5% (n = 273) to long-acting sulfonamides. Compared with offspring not exposed, associations between in-utero exposure and CRC in adult offspring were: aHR 1.03 (95% CI 0.32, 3.31) for tetracyclines; aHR 1.12 (95% CI 0.35, 3.58) for penicillins; aHR 0.83 (95% CI 0.20, 3.42) for short-acting sulfonamides; and aHR 4.40 (95% CI 1.63, 11.88) for long-acting sulfonamides. CONCLUSION Our findings support an association between in-utero exposure to long-acting sulfonamides and CRC in adulthood.
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Affiliation(s)
- Caitlin C Murphy
- Department of Health Promotion and Behavioral Sciences, University of Texas Health Science Center at Houston (UTHealth Houston), School of Public Health, Houston, TX, USA
| | - Piera M Cirillo
- Child Health and Development Studies, Public Health Institute, Berkeley, CA, USA
| | - Nickilou Y Krigbaum
- Child Health and Development Studies, Public Health Institute, Berkeley, CA, USA
| | - Amit G Singal
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Dean P Jones
- Departments of Medicine and Biochemistry, Emory University School of Medicine, Atlanta, GA, USA
| | - Timothy Zaki
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Barbara A Cohn
- Child Health and Development Studies, Public Health Institute, Berkeley, CA, USA
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Trinh NTH, Hjorth S, Nordeng HME. Use of interrupted time-series analysis to characterise antibiotic prescription fills across pregnancy: a Norwegian nationwide cohort study. BMJ Open 2021; 11:e050569. [PMID: 34880014 PMCID: PMC8655575 DOI: 10.1136/bmjopen-2021-050569] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
OBJECTIVES Antibiotics are the most frequently prescribed medications for pregnant and breastfeeding women. We applied interrupted time-series analysis (ITSA) to describe antibiotic prescription fills patterns in pregnant women and examined recurrent antibiotic fills in subsequent pregnancies. DESIGNS A population-based drug utilisation study. SETTING Norwegian primary care. PARTICIPANTS 653 058 pregnancies derived from Medical Birth Registry of Norway linked to the Norwegian Prescription Database (2006-2016). MAIN OUTCOME MEASURE Proportion of pregnancies exposed to antibiotics aggregated by week in pregnancy time windows. STATISTICAL ANALYSES We descriptively analysed antibiotic prescription fills patterns and components in pregnant women. The changes in antibiotic fills in pregnancy time windows were assessed using ITSA. Interruptions points at week 4 to week 7 into pregnancy and delivery were used. Factors associated with antibiotic fills during pregnancy were identified using generalised estimating equations for Poisson regression. Recurrent antibiotic use was estimated using proportion of women who filled antibiotic prescription in a subsequent pregnancy. RESULTS Antibiotics were filled in 27.6% pregnancies. The ITSA detected an immediate decrease of 0.07 percentage points (95% CI -0.13 to -0.01) in the proportion of exposed pregnancies at 4 weeks after conception, mainly among women taking folic acid before pregnancy. This proportion increased shortly after delivery (immediate change=1.61 percentage points (95% CI 0.31 to 2.91)) then decreased gradually afterwards (change in slope=-0.19 percentage points, 95% CI -0.34 to -0.05)). The strongest factor associated with antibiotic fills during pregnancy was having recurrent urinary tract infections (adjusted OR=2.65, 95% CI 2.59 to 2.72). Women who had filled antibiotics during a pregnancy were up to three times more likely to fill antibiotics in the subsequent pregnancies. CONCLUSIONS ITSA highlighted important impact of pregnancy and delivery on antibiotic fillings. Having antibiotic fills in a pregnancy was associated with recurrent antibiotic fills in subsequent ones.
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Affiliation(s)
- Nhung Thi Hong Trinh
- PharmacoEpidemiology and Drug Safety Research Group, Department of Pharmacy, and PharmaTox Strategic Initiative, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway
| | - Sarah Hjorth
- PharmacoEpidemiology and Drug Safety Research Group, Department of Pharmacy, and PharmaTox Strategic Initiative, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway
| | - Hedvig Marie Egeland Nordeng
- PharmacoEpidemiology and Drug Safety Research Group, Department of Pharmacy, and PharmaTox Strategic Initiative, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway
- Department of Child Health and Development, Norwegian Institute of Public Health, Oslo, Norway
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Maternal and Microorganism Characteristics Cannot Predict Adverse Outcome in Pregnancies Complicated With Urinary Tract Infection. INFECTIOUS DISEASES IN CLINICAL PRACTICE 2021. [DOI: 10.1097/ipc.0000000000000900] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Maternal Microbiome and Infections in Pregnancy. Microorganisms 2020; 8:microorganisms8121996. [PMID: 33333813 PMCID: PMC7765218 DOI: 10.3390/microorganisms8121996] [Citation(s) in RCA: 46] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2020] [Revised: 12/09/2020] [Accepted: 12/13/2020] [Indexed: 12/14/2022] Open
Abstract
Pregnancy induces unique changes in maternal immune responses and metabolism. Drastic physiologic adaptations, in an intricately coordinated fashion, allow the maternal body to support the healthy growth of the fetus. The gut microbiome plays a central role in the regulation of the immune system, metabolism, and resistance to infections. Studies have reported changes in the maternal microbiome in the gut, vagina, and oral cavity during pregnancy; it remains unclear whether/how these changes might be related to maternal immune responses, metabolism, and susceptibility to infections during pregnancy. Our understanding of the concerted adaption of these different aspects of the human physiology to promote a successful pregnant remains limited. Here, we provide a comprehensive documentation and discussion of changes in the maternal microbiome in the gut, oral cavity, and vagina during pregnancy, metabolic changes and complications in the mother and newborn that may be, in part, driven by maternal gut dysbiosis, and, lastly, common infections in pregnancy. This review aims to shed light on how dysregulation of the maternal microbiome may underlie obstetrical metabolic complications and infections.
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Pervez H, Usman N, Ahmed MM, Hashmi MS. The Impact of Inflammatory Bowel Disease on Pregnancy and the Fetus: A Literature Review. Cureus 2019; 11:e5648. [PMID: 31700750 PMCID: PMC6822910 DOI: 10.7759/cureus.5648] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023] Open
Abstract
Inflammatory bowel disease (IBD) is a constellation of devastating chronic inflammatory changes in the bowel, either involving the large or small bowel or part of both. As it is widely diagnosed in the fertile age group, this disorder can present itself, very commonly, during pregnancy and thus a better understanding of the disease can be an important factor to influence the maternal and fetal well-being. Medications are what is considered the first line in the management of this disease to control the symptoms or keep the disease in remission. In addition to this, the drugs used to keep the disease in remission can also cause significant adverse effects on the patient and the new nurturing life preparing itself for the outside world. What the fetus gets from the mother will stay for life with the child. We conducted an electronic literature review search which highlights the significance and impact of sustained remission of IBD and the cautious use of various drugs during pregnancy for that purpose. In addition to the influences already mentioned, It is evident that nutritional deficiencies can also prevail with the advancing disease, something to manage as a side note as well. These deficiencies can have a definite effect on the fetus and may cause developmental malformations. In order to avoid this process, a systemic and joint approach should be curtailed. This can reduce the adverse outcomes associated with this ailment during pregnancy.
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Affiliation(s)
- Hira Pervez
- Internal Medicine / Cardiology, Dow University of Health Sciences (DUHS), Karachi, PAK
| | - Norina Usman
- Internal Medicine, Veterans Affairs Palo Alto Health Care System - Stanford University School of Medicine, Palo Alto, USA
| | - Munis M Ahmed
- Internal Medicine, St Mary Mercy Livonia Hospital, Livonia, USA
| | - Mydah S Hashmi
- Internal Medicine, Army Medical College, Rawalpindi, Islamabad, PAK
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van Wattum JJ, Leferink TM, Wilffert B, Ter Horst PGJ. Antibiotics and lactation: An overview of relative infant doses and a systematic assessment of clinical studies. Basic Clin Pharmacol Toxicol 2018; 124:5-17. [PMID: 30015369 DOI: 10.1111/bcpt.13098] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2018] [Accepted: 07/11/2018] [Indexed: 01/10/2023]
Abstract
Breastfeeding is important for the development of the child. Many antibiotics are considered safe during breastfeeding. The aim of the study was to assess the quality of lactation studies with antibiotics using the FDA and International Lactation Consultant Association quality guidelines for lactation studies. The secondary goal was to determine the exposure of the breastfed infant to antibiotics in relation to bacterial resistance and the developing microbiome. A literature search was performed and the included studies were scored on methodology, parameters concerning maternal exposure to antibiotics, maternal plasma and milk sampling. The infant exposure has been calculated and expressed as a percentage of a normal infant therapeutic dose. Sixty-six studies were included in five antibiotic groups (broad-spectrum penicillin, cephalosporins, macrolides and lincosamides, quinolones and sulphonamides). Cephalosporins were the most studied group of antibiotics (n = 21). Fifteen studies met all the criteria of "mother exposure to antibiotic". Six studies met every criterion related to "plasma sampling". Only one case report met all listed criteria for lactation studies. The correct calculation of infant exposure to antibiotics via the milk:plasma ratio (AUC) varies between 13% for macrolides and 38% for broad-spectrum penicillin. The highest assessed exposure as a percentage of infant therapeutic dose was for metronidazole (11%). The studies meet to a limited extent with the quality standards for lactation research. The breastfed infants are exposed to a subtherapeutic concentration of antibiotics.
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Affiliation(s)
| | - Thomas M Leferink
- Department of PharmacoTherapy, Epidemiology & Economics, Groningen Research Institute of Pharmacy, University of Groningen, Groningen, The Netherlands
| | - Bob Wilffert
- Department of PharmacoTherapy, Epidemiology & Economics, Groningen Research Institute of Pharmacy, University of Groningen, Groningen, The Netherlands
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Abstract
OPINION STATEMENT Inflammatory bowel disease is frequently diagnosed before or during key childbearing years. One of the most important factors for a healthy pregnancy is having quiescent disease prior to conception and maintaining disease remission for the duration of the pregnancy. In order to achieve that, most women will need to continue their inflammatory bowel disease (IBD) treatment during pregnancy. One of the main concerns these women have is whether these medications will have adverse effects on their growing fetus. Aminosalicylates, antibiotics, and steroids are all relatively low risk for use during pregnancy and breastfeeding. Recent studies also support the safety of continuing immunomodulators and anti-tumor necrosis factor agents during pregnancy and with breastfeeding. There seems to be an increased risk for infection, however, with use of combination therapy including both a biologic agent and an immunomodulator. Less evidence is available on the use of anti-integrins in pregnancy; however, the current data suggest they may be safe as well. Conversations about a patient's desire for pregnancy should occur between the patient and provider on a regular basis prior to conception and particularly with any change in disease activity or change in the treatment regimen. This chapter will review the current evidence on the safety of IBD medications during pregnancy and lactation so that providers can more easily discuss the importance of medication adherence for disease remission with their patients who are contemplating conception.
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Pinder M, Lummis K, Selinger CP. Managing inflammatory bowel disease in pregnancy: current perspectives. Clin Exp Gastroenterol 2016; 9:325-335. [PMID: 27789969 PMCID: PMC5072556 DOI: 10.2147/ceg.s96676] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Inflammatory bowel disease (IBD) affects many women of childbearing age. The course of IBD is closely related to pregnancy outcomes with poorly controlled IBD increasing the risk of prematurity, low weight for gestation, and fetal loss. As such, women with IBD face complex decision making weighing the risks of active disease versus those of medical treatments. This review summarizes the current evidence regarding the safety and efficacy of IBD treatments during pregnancy and lactation aiming to provide up-to-date guidance for clinicians. Over 50% of women have poor IBD- and pregnancy-related knowledge, which is associated with views contrary to medical evidence and voluntary childlessness. This review highlights the effects of poor patient knowledge and critically evaluates interventions for improving patient knowledge and outcomes.
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Affiliation(s)
- Matthew Pinder
- Leeds Gastroenterology Institute, Leeds Teaching Hospitals NHS Trust
| | - Katie Lummis
- Leeds Gastroenterology Institute, Leeds Teaching Hospitals NHS Trust
| | - Christian P Selinger
- Leeds Gastroenterology Institute, Leeds Teaching Hospitals NHS Trust
- University of Leeds, Leeds, UK
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Lee Y, Chen C, Chu D, Ko M. Factors associated with potentially harmful antibiotic prescription during pregnancy: a population-based study. J Eval Clin Pract 2016; 22:200-6. [PMID: 26446517 DOI: 10.1111/jep.12454] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/25/2015] [Indexed: 12/18/2022]
Abstract
RATIONALE, AIMS AND OBJECTIVES Inappropriate antibiotic prescriptions during pregnancy may adversely affect the fetus. There were few studies on factors associated with antibiotic prescriptions potentially harmful to the fetus. METHODS This was a population-based cross-sectional study using data from National Health Insurance Research Database. We calculated the frequency of antibiotic prescription according to the status of pregnancy, type of infections, characteristics of patients, doctors and medical institutions. According to the British National Formulary, sulfonamides, trimethoprim, tetracycline and quinolones were classified as antibiotics potentially harmful to the fetus. A multivariate logistic regression analysis was performed to evaluate the independent effect of various characteristic on antibiotic prescriptions, during pregnancy, potentially harmful to the fetus. RESULTS Among the 19 464 pregnant subjects, 6554 (33.67%) received antibiotic prescriptions during pregnancy. Antibiotic prescriptions potentially harmful to the fetus accounted for 6.31% of all antibiotic prescriptions during pregnancy. Pregnant women aged <20 years, in their first trimester, and who were presenting with urogenital infections had the highest risks of receiving antibiotic prescriptions potentially harmful to the fetus. Non-gynaecologists, doctors aged 39-49 or ≥50 years, and doctors at clinics had higher risks of prescribing antibiotics potentially harmful to the fetus. CONCLUSIONS Measures to improve the quality of practices should include efforts to increase awareness of antibiotic prescription guidelines for the treatment of infections in the pregnant population.
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Affiliation(s)
- Yichen Lee
- Department of Health Administration, Tzu-Chi University of Science and Technology, Hualien, Taiwan
| | - Chuchieh Chen
- Department of Health Care Management, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan
| | - Dachen Chu
- Department of Health Care Management, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan.,Department of Emergency Medicine and Surgery, Taipei City Hospital, Taipei, Taiwan.,Institute of Public Health and Community Medicine Research Center, National Yang-Ming University, Taipei, Taiwan
| | - Mingchung Ko
- Department of Health Care Management, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan.,Department of Emergency Medicine and Surgery, Taipei City Hospital, Taipei, Taiwan.,Institute of Public Health and Community Medicine Research Center, National Yang-Ming University, Taipei, Taiwan
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Hosseini-Carroll P, Mutyala M, Seth A, Nageeb S, Soliman D, Boktor M, Sheth A, Chapman J, Morris J, Jordan P, Manas K, Becker F, Alexander JS. Pregnancy and inflammatory bowel diseases: Current perspectives, risks and patient management. World J Gastrointest Pharmacol Ther 2015; 6:156-71. [PMID: 26558150 PMCID: PMC4635156 DOI: 10.4292/wjgpt.v6.i4.156] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2015] [Revised: 06/30/2015] [Accepted: 08/29/2015] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel diseases (IBD) are chronic idiopathic inflammatory conditions characterized by relapsing and remitting episodes of inflammation which can affect several different regions of the gastrointestinal tract, but also shows extra-intestinal manifestations. IBD is most frequently diagnosed during peak female reproductive years, with 25% of women with IBD conceiving after their diagnosis. While IBD therapy has improved dramatically with enhanced surveillance and more abundant and powerful treatment options, IBD disease can have important effects on pregnancy and presents several challenges for maintaining optimal outcomes for mothers with IBD and the developing fetus/neonate. Women with IBD, the medical team treating them (both gastroenterologists and obstetricians/gynecologists) must often make highly complicated choices regarding conception, pregnancy, and post-natal care (particularly breastfeeding) related to their choice of treatment options at different phases of pregnancy as well as post-partum. This current review discusses current concerns and recommendations for pregnancy during IBD and is intended for gastroenterologists, general practitioners and IBD patients intending to become, (or already) pregnant, and their families. We have addressed patterns of IBD inheritance, effects of IBD on fertility and conception (in both men and women), the effects of IBD disease activity on maintenance of pregnancy and outcomes, risks of diagnostic procedures during pregnancy and potential risks and complications associated with different classes of IBD therapeutics. We also have evaluated the clinical experience using "top-down" care with biologics, which is currently the standard care at our institution. Post-partum care and breastfeeding recommendations are also addressed.
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15
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16
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Damas OM, Deshpande AR, Avalos DJ, Abreu MT. Treating Inflammatory Bowel Disease in Pregnancy: The Issues We Face Today. J Crohns Colitis 2015; 9:928-36. [PMID: 26129693 DOI: 10.1093/ecco-jcc/jjv118] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2015] [Accepted: 06/25/2015] [Indexed: 12/12/2022]
Abstract
Many women of childbearing age are living with inflammatory bowel disease [IBD], yet there are limited studies on the use of IBD medications in pregnancy. In this review, we provide a comprehensive update on the safety of these medications during pregnancy, particularly thiopurines and biologicals. Antibiotics, steroids, and aminosalicylates are relatively low risk for use in pregnancy, and growing evidence supports the safety of immunomodulators and anti-tumour necrosis factor agents as well. Available studies on infliximab, adalimumab, and certolizumab pegol show no increase in adverse events during pregnancy or perinatally. Similarly, studies on lactation demonstrate that concentrations of subcutaneous anti-tumour necrosis factor biologicals are undetectable, and levels of thiopurines and infliximab are negligible in breast milk. Less is known about anti-integrins in pregnancy [eg natalizumab and vedolizumab] but currently available data suggest they may be safe as well. Although more studies are needed to examine the long-term effects of these medications on offspring, the available data provide reassuring information for providers caring for women of childbearing age.
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Affiliation(s)
- Oriana M Damas
- University of Miami Miller School of Medicine, Department of Medicine, Division of Gastroenterology, Miami, FL
| | - Amar R Deshpande
- University of Miami Miller School of Medicine, Department of Medicine, Division of Gastroenterology, Miami, FL
| | - Danny J Avalos
- University of Miami Miller School of Medicine Palm Beach Regional Campus, Internal Medicine Division, Department of Medicine, West Palm Beach, FL
| | - Maria T Abreu
- University of Miami Miller School of Medicine, Department of Medicine, Division of Gastroenterology, Miami, FL
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17
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Joergensen JS, Kjær Weile LK, Lamont RF. The early use of appropriate prophylactic antibiotics in susceptible women for the prevention of preterm birth of infectious etiology. Expert Opin Pharmacother 2014; 15:2173-91. [DOI: 10.1517/14656566.2014.950225] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
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18
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Lamont HF, Blogg HJ, Lamont RF. Safety of antimicrobial treatment during pregnancy: a current review of resistance, immunomodulation and teratogenicity. Expert Opin Drug Saf 2014; 13:1569-81. [PMID: 25189188 DOI: 10.1517/14740338.2014.939580] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
INTRODUCTION The extent of antibiotic use in pregnancy remains unknown but may occur in > 40% of pregnant women for various indications, at different gestational ages from different sources. AREAS COVERED Antibiotic resistance, alterations to the neonatal immune system causing allergy, asthma and atopic disease in later life and teratogenicity. EXPERT OPINION Although teratogenesis is not a major concern, it is important, and ignorance and complacency cast a long shadow. Robust evidence exists to guide clinicians in their choice of a safe agent with respect to teratogenicity. Antibiotic resistance is a major safety concern, and together with decreased research and development of new antibiotic agents, it has required legal initiatives to encourage Big Pharma to search for safe alternatives. New information from culture-independent, molecular-based techniques has resulted in a greater understanding of the adverse effects of antepartum/intrapartum antibiotics on the maternal vaginal microbiome and the neonatal gut microbiome. As this might adversely affect the development of the immature immune system and lead to asthma, allergy and atopic disease in later life, new research merits support in scrutinizing the safety of antibiotic use in pregnancy.
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Affiliation(s)
- Harriet F Lamont
- University of Southampton, Southampton General Hospital, Faculty of Medicine , Tremona Road, Southampton, SO16 6YD , UK
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19
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Gwee A, Cranswick N. Anti-infective use in children and pregnancy: current deficiencies and future challenges. Br J Clin Pharmacol 2014; 79:216-21. [PMID: 24588467 DOI: 10.1111/bcp.12363] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2013] [Accepted: 02/11/2014] [Indexed: 12/20/2022] Open
Abstract
There are a number of challenges to using anti-infective agents in children and pregnant women. There is limited understanding of the altered pharmacokinetics of anti-infectives in these populations and as a result, optimized dosing regimens are yet to be established. The potential adverse effects of the drug on pregnancy outcome and the developing foetus is a major consideration, and the long term implications of drug side effects must be taken into account when drug exposure occurs early in life. These factors hinder research and licensing of new anti-infective drugs in these populations. We describe the current deficiencies and future challenges of anti-infective use in children and pregnant women, providing specific examples.
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Affiliation(s)
- Amanda Gwee
- Department of General Medicine, The Royal Children's Hospital Melbourne, Melbourne, Victoria; Murdoch Childrens Research Institute, Melbourne, Victoria
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20
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Abstract
IBD often affects patients during their peak reproductive years. Several drugs are available for the treatment of IBD and new drugs are continuously in the pipeline. As long-term administration of medications is often necessary, the safety of drug therapy during pregnancy and breast-feeding needs to be considered in daily clinical practice. The aim of this Review is to summarize the latest information concerning the safety of medications used to treat IBD during pregnancy and lactation, as well as their effect on fertility. Although only thalidomide and methotrexate are absolutely contraindicated during pregnancy and breast-feeding, alternatives to ciprofloxacin, natalizumab and sodium phosphate should also be considered for pregnant women. Breast-feeding is also discouraged while on treatment with ciclosporin, metronidazole and ciprofloxacin. However, therapy with 5-aminosalicylic acid preparations, glucocorticoids, thiopurines and TNF inhibitors are acceptable during pregnancy and lactation. Pregnant women who have symptomatic IBD or who require therapy should have the opportunity to discuss any associated risks to their pregnancy and infant with the appropriate consultants. By ensuring that the patient and her family are informed, the clinical outcome might be optimized.
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Affiliation(s)
- Ole Haagen Nielsen
- Gastroenterology, Herlev Hospital, University of Copenhagen, Herlev Ringvej 75, DK-2730 Herlev, Denmark
| | - Cynthia Maxwell
- Department of Obstetrics and Gynaecology, Maternal Fetal Medicine Division, Mount Sinai Hospital, University of Toronto, OPG-3, 600 University Avenue, Toronto, ON M5G 1X5, Canada
| | - Jakob Hendel
- Gastroenterology, Herlev Hospital, University of Copenhagen, Herlev Ringvej 75, DK-2730 Herlev, Denmark
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21
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Abstract
When considering whether to administer drugs to women during pregnancy and lactation, we have to take into account that these substances may expose the fetus or neonate to multiple effects. This occurs because there is a unique situation where the maternal compartment is connected with the fetal or neonatal compartment through, respectively, the placental barrier or breast milk. The fetus in utero and the breast-fed neonate are to be considered as organisms exposed and sensitive to the effects of drugs that cross the placenta or enter the breast milk. This review focuses on the most frequently used antibiotics during pregnancy and lactation and presents useful suggestions for daily practice. Drugs that must be avoided are clearly underlined.
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Affiliation(s)
- A Reali
- Neonatal Pathology and Intensive Care Unit, University of Cagliari, Italy
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22
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de Jonge L, Bos HJ, van Langen IM, de Jong-van den Berg LTW, Bakker MK. Antibiotics prescribed before, during and after pregnancy in the Netherlands: a drug utilization study. Pharmacoepidemiol Drug Saf 2013; 23:60-8. [PMID: 23913654 DOI: 10.1002/pds.3492] [Citation(s) in RCA: 51] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2013] [Revised: 06/28/2013] [Accepted: 07/04/2013] [Indexed: 01/20/2023]
Abstract
PURPOSE To describe the prescription of antibiotics before, during and after pregnancy, and the trends over a 16-year period in the Netherlands, and to determine whether they were prescribed according to national guidelines. METHODS The IADB (http://iadb.nl) contains prescriptions dispensed by community pharmacies in the Netherlands. We extracted information on 18,873 pregnancies for 14,969 women between 1994 and 2009, focusing on antibiotics dispensed in the four trimesters before conception to two trimesters after birth (nine trimesters in total). We calculated trends in prescription rates during pregnancy and over time, and also compared the prescription of antibiotics in the Netherlands with safety category based on the Australian Drug Evaluation Committee. RESULTS During pregnancy 20.8% of the women were prescribed at least one antibiotic. The 'beta-lactam antibacterials/penicillins' group and the specific antibiotic amoxicillin were most commonly prescribed in the nine trimesters covered. The prescription rate of the 'other antibacterials' group during pregnancy increased over the years, in contrast to that of the 'sulphonamides/trimethoprim' group, which decreased. In total, 2.0% of pregnancies were exposed to a 'potentially harmful' antibiotic and 0.8% to a 'harmful' antibiotic. Compared with the period before conception, 'safe' antibiotics were prescribed more often during pregnancy than the other groups. CONCLUSIONS One in five women was prescribed at least one antibiotic during pregnancy in the Netherlands, which is comparable with rates in other European countries. Our results suggest that antibiotics appear to be prescribed to pregnant women generally in accordance with national recommendations.
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Affiliation(s)
- Linda de Jonge
- University of Groningen, University Medical Center Groningen, Department of Genetics, Eurocat Registration Northern Netherlands, Groningen, The Netherlands
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23
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Dréno B, Layton A, Zouboulis C, López-Estebaranz J, Zalewska-Janowska A, Bagatin E, Zampeli V, Yutskovskaya Y, Harper J. Adult female acne: a new paradigm. J Eur Acad Dermatol Venereol 2013; 27:1063-70. [DOI: 10.1111/jdv.12061] [Citation(s) in RCA: 115] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Selinger CP, Leong RWL, Lal S. Pregnancy related issues in inflammatory bowel disease: evidence base and patients' perspective. World J Gastroenterol 2012; 18:2600-8. [PMID: 22690068 PMCID: PMC3369996 DOI: 10.3748/wjg.v18.i21.2600] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2011] [Revised: 09/09/2011] [Accepted: 09/16/2011] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel disease (IBD) affects women of childbearing age and can influence fertility, pregnancy and decisions regarding breastfeeding. Women with IBD need to consider the possible course of disease during pregnancy, the benefits and risks associated with medications required for disease management during pregnancy and breastfeeding and the effects of mode of delivery on their disease. When indicated, aminosalicylates and thiopurines can be safely used during pregnancy. Infliximab and Adalimumab are considered probably safe during the first two trimesters. During the third trimester the placenta can be crossed and caution should be applied. Methotrexate is associated with severe teratogenicity due to its folate antagonism and is strictly contraindicated. Women with IBD tend to deliver earlier than healthy women, but can have a vaginal delivery in most cases. Caesarean sections are generally recommended for women with active perianal disease or after ileo-anal pouch surgery.While the impact of disease activity and medication has been addressed in several studies, there are minimal studies evaluating patients' perspective on these issues. Women's attitudes may influence their decision to have children and can positively or negatively influence the chance of conceiving, and their beliefs regarding therapies may impact on the course of their disease during pregnancy and/or breastfeeding. This review article outlines the impact of IBD and its treatment on pregnancy, and examines the available data on patients' views on this subject.
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25
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Diagnosis and management of bacterial vaginosis and other types of abnormal vaginal bacterial flora: a review. Obstet Gynecol Surv 2010; 65:462-73. [PMID: 20723268 DOI: 10.1097/ogx.0b013e3181e09621] [Citation(s) in RCA: 61] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
UNLABELLED Bacterial vaginosis (BV) is a common cause of abnormal vaginal discharge. It is characterised by an overgrowth of predominantly anaerobic organisms (Gardnerella vaginalis, Prevotella spp., Peptostreptocci, Mobiluncus spp.) in the vagina leading to a replacement of lactobacilli and an increase in vaginal pH. BV can arise and remit spontaneously, but often presents as a chronic or recurrent disease. BV is found most often in women of childbearing age, but may also be encountered in menopausal women, and is rather rare in children. The clinical and microscopic features and diagnosis of BV are herein reviewed, and antibiotic and non-antibiotic treatment approaches discussed. TARGET AUDIENCE Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES After completion of this educational activity, the participant should be better able to analyze bacterial vaginosis clinically, formulate an oral antibiotic treatment regimen for bacterial vaginosis and use vaginal treatments for bacterial vaginosis.
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26
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Kwan LY, Mahadevan U. Inflammatory bowel disease and pregnancy: an update. Expert Rev Clin Immunol 2010; 6:643-57. [PMID: 20594137 DOI: 10.1586/eci.10.35] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
Women with inflammatory bowel disease have similar rates of conception to the general population unless they have had pelvic surgery. Once pregnant, regardless of disease activity, they have an increased risk of adverse pregnancy outcome and should be followed as high-risk obstetric patients. Most medications are compatible with pregnancy and lactation, as described in this article. Ideally, women should discuss their plans for pregnancy with their physician prior to conception so that risks and benefits can be reviewed, medications adjusted and healthcare maintenance updated. Once pregnant, a multidisciplinary team of gastroenterologists, obstetricians and pediatricians should help to ensure the best care for the mother and child.
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Affiliation(s)
- Lola Y Kwan
- University of Rochester Medical Center, Rochester, NY, USA
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27
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Abstract
Acute pyelonephritis is one of the most common indications for antepartum hospitalization. When acute pyelonephritis is diagnosed, conventional treatment includes intravenous fluid and parenteral antibacterial administration. There are limited data by which to assess the superiority of one antibacterial regimen over the other in terms of efficacy, patient acceptance and safety for the developing fetus; however, it is important to consider antimicrobial resistance patterns in the local community when choosing an agent. Moreover, there are growing public health concerns regarding antimicrobial resistance to commonly prescribed medications for urinary tract infections in pregnancy. There is a small body of evidence to support the ambulatory treatment of pregnant women with pyelonephritis in the first and early second trimesters, but the majority of women will be managed as inpatients. This article provides a suggested algorithm for the treatment of pyelonephritis during pregnancy.
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Affiliation(s)
- Jennifer A Jolley
- Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, University of California, Irvine, Orange, California 92868, USA
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28
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Garrido E, Van Domselaar M, Morales S, López-Sanromán A. Enfermedad inflamatoria intestinal y gestación. GASTROENTEROLOGIA Y HEPATOLOGIA 2010; 33:517-29. [DOI: 10.1016/j.gastrohep.2009.11.006] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/28/2009] [Accepted: 11/01/2009] [Indexed: 12/23/2022]
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29
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Abstract
This review covers important questions that arise for physicians caring for women with inflammatory bowel disease. Fertility, pregnancy outcomes and the safety of medications in pregnancy and lactation are discussed.
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Affiliation(s)
- Uma Mahadevan
- Center for Colitis and Crohn's Disease, University of California, San Francisco, 2330 Post Street 610, San Francisco, CA 94115, USA
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30
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Abstract
This review covers important questions that arise for physicians caring for women with inflammatory bowel disease. Fertility, pregnancy outcomes and the safety of medications in pregnancy and lactation are discussed.
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Affiliation(s)
- Uma Mahadevan
- Center for Colitis and Crohn's Disease, University of California, San Francisco, 2330 Post Street 610, San Francisco, CA 94115, USA.
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31
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Luginbuehl V, Ruffieux K, Hess C, Reichardt D, von Rechenberg B, Nuss K. Controlled release of tetracycline from biodegradable β-tricalcium phosphate composites. J Biomed Mater Res B Appl Biomater 2009; 92:341-52. [DOI: 10.1002/jbm.b.31520] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
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32
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Prelog M, Grif K, Decristoforo C, Würzner R, Kiechl-Kohlendorfer U, Brunner A, Zimmerhackl LB, Orth D. Tetracycline-resistant Escherichia coli strains are inherited from parents and persist in the infant's intestines in the absence of selective pressure. Eur J Pediatr 2009; 168:1181-7. [PMID: 19096873 DOI: 10.1007/s00431-008-0901-0] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2008] [Accepted: 12/03/2008] [Indexed: 01/15/2023]
Abstract
The study investigated tetracycline (TC), ampicillin (AMP), cefazolin (CEF), and trimethoprim (TMP) resistance in Escherichia coli (E. coli) in the feces of 21 infants up to 6 months of age and in their parents in the absence of selective antimicrobial pressure. Clonality of strains was assessed by pulsed-field gel electrophoresis. Three infants had resistant E. coli strains in their feces identical to the mothers' from week 1 on, which persisted over weeks. From week 2 on, in another four infants, persisting resistant E. coli were found, two of them identical to the mothers'. All of these persisting E. coli strains (except one family) showed at least resistance to TC. In infants, resistant E. coli strains inherited from their mothers tended to persist over months. Therefore, the persistence of resistant E. coli and their possible capacity to cause symptomatic infection or transfer its resistance genes to other bacteria deserves more attention.
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Affiliation(s)
- Martina Prelog
- Department of Pediatrics, Medical University Innsbruck, A-6020 Innsbruck, Austria.
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33
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Cooper WO, Hernandez-Diaz S, Arbogast PG, Dudley JA, Dyer SM, Gideon PS, Hall KS, Kaltenbach LA, Ray WA. Antibiotics potentially used in response to bioterrorism and the risk of major congenital malformations. Paediatr Perinat Epidemiol 2009; 23:18-28. [PMID: 19228311 PMCID: PMC3381893 DOI: 10.1111/j.1365-3016.2008.00978.x] [Citation(s) in RCA: 65] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
This study was designed to assess the association between pregnancy-related exposures to antibiotics recommended for use in the event of a bioterrorism attack and major congenital malformations. A retrospective cohort study included 30 049 infants from Tennessee Medicaid born between 1985 and 2000 identified from computerised state databases. Infants with fetal exposures to ciprofloxacin, azithromycin, doxycycline and amoxicillin (antibiotics recommended for potential bioterrorism attacks) (n = 24 521) and erythromycin (included as a positive control) (n = 2128) were compared with infants with no fetal exposure to any antibiotics (n = 3400). Major congenital malformations identified from computerised records were confirmed through medical record review. Overall, 869 (2.9%) of infants in the cohort had a confirmed major congenital malformation, with major malformations ranging from 2.5% to 3.0% among the antibiotic-specific exposure groups. No increased risk was present in multivariable analyses for any malformations and for malformations of specific organ systems. In conclusion, these data suggest that ciprofloxacin, azithromycin, doxycycline or amoxicillin use by pregnant women should not result in a greater incidence of overall major congenital malformations in infants whose mothers take these medications, though a large increase in risk cannot be ruled out.
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Affiliation(s)
- William O. Cooper
- Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN
| | | | - Patrick G. Arbogast
- Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, TN
| | - Judith A. Dudley
- Department of Preventive Medicine, Vanderbilt University School of Medicine, Nashville, TN
| | - Shannon M. Dyer
- Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN
| | - Patricia S. Gideon
- Department of Preventive Medicine, Vanderbilt University School of Medicine, Nashville, TN
| | - Kathleen S. Hall
- Department of Preventive Medicine, Vanderbilt University School of Medicine, Nashville, TN
| | - Lisa A. Kaltenbach
- Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, TN
| | - Wayne A. Ray
- Department of Preventive Medicine, Vanderbilt University School of Medicine, Nashville, TN
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Abstract
Women with inflammatory bowel disease (IBD) and the physicians who care for them must make difficult decisions on issues of conception, pregnancy, and breastfeeding with very limited and often contradictory information. This review provides the most current information on the inheritance of IBD, fertility, pregnancy outcomes, the management of disease during pregnancy, and the safety of medications in pregnancy and breastfeeding. We would like to emphasize that the information presented here must be individualized to the specific situation of each patient, their acceptance of risk, and their degree of disease severity.
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Affiliation(s)
- Marla Dubinsky
- Department of Pediatrics, Inflammatory Bowel Disease Center, Cedars Sinai Medical Center, Los Angeles, California 90048, USA.
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35
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Mastrobattista JM, Klebanoff MA, Carey JC, Hauth JC, MacPherson CA, Ernest J, Cotroneo M, Leveno KJ, Wapner R, Varner M, Iams JD, Moawad A, Sibai BM, Miodovnik M, Dombrowski M, O'Sullivan MJ, VanDorsten JP, Langer O. The effect of body mass index on therapeutic response to bacterial vaginosis in pregnancy. Am J Perinatol 2008; 25:233-7. [PMID: 18548397 PMCID: PMC2841559 DOI: 10.1055/s-2008-1066875] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
Our objective was to determine the effect of body mass index (BMI) on response to bacterial vaginosis (BV) treatment. A secondary analysis was conducted of two multicenter trials of therapy for BV and TRICHOMONAS VAGINALIS. Gravida were screened for BV between 8 and 22 weeks and randomized between 16 and 23 weeks to metronidazole or placebo. Of 1497 gravida with asymptomatic BV and preconceptional BMI, 738 were randomized to metronidazole; BMI was divided into categories: < 25, 25 to 29.9, and > or = 30. Rates of BV persistence at follow-up were compared using the Mantel-Haenszel chi square. Multiple logistic regression was used to evaluate the effect of BMI on BV persistence at follow-up, adjusting for potential confounders. No association was identified between BMI and BV rate at follow-up ( P = 0.21). BMI was associated with maternal age, smoking, marital status, and black race. Compared with women with BMI of < 25, adjusted odds ratio (OR) of BV at follow-up were BMI 25 to 29.9: OR, 0.66, 95% CI 0.43 to 1.02; BMI > or = 30: OR, 0.83, 95% CI 0.54 to 1.26. We concluded that the persistence of BV after treatment was not related to BMI.
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Affiliation(s)
- Joan M. Mastrobattista
- Department of Obstetrics, Gynecology and Reproductive Sciences, The University of Texas Medical School at Houston, 6431 Fannin Street, Suite 3.274, Houston, Texas 77030, , (713) 500-6412, Fax: (713) 500-7860
| | - Mark A. Klebanoff
- National Institute of Child Health and Human Development, Division of Epidemiology, Statistics & Prevention Research (DESPR), 6100 Executive Boulevard, Room 7B05F, MSC 7510, Bethesda, MD 20892-7510, , (301) 496-5267, Fax: (301) 496-3790
| | - J. Christopher Carey
- Denver Health and Professor, University of Colorado School of Medicine, 777 Bannock St. MC 0660, Denver, CO, 80204, , (303) 602-9715, Fax: (303) 602-9734
| | - John C. Hauth
- Department of Obstetrics and Gynecology, University of Alabama, Birmingham, 618 South 20 Street, Birmingham, AL 35233-7333, , (205) 934-9414, Fax: (205) 975-5723
| | - Cora A. MacPherson
- Department of Epidemiology and Biostatistics, The George Washington University Biostatistics Center, 6110 Executive Boulevard, Suite 750, Rockville, MD, 20852, , (301) 881-9260, Fax: (301) 816-0385
| | - J.M Ernest
- Department of Obstetrics and Gynecology, Wake Forest University, Medical Center Boulevard, Winston-Salem, NC 27157, , (336) 716-1025, Fax: (336) 716-6937
| | - Margaret Cotroneo
- Magee Women's Hospital, Department of Obstetrics, Gynecology and Reproductive Sciences, 300 Halket Street, Pittsburgh, PA 15213, , (412) 641-4055, Fax: (412) 641-5518
| | - Kenneth J. Leveno
- Department of Obstetrics and Gynecology, The University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX 75390-9032, , (214) 648-2316, Fax: (214) 648-4763
| | - Ronald Wapner
- Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Columbia Medical University, 16 East 60 Street, Room 480, New York, NY 10021, , (212) 305-6293, Fax: (212) 305-4380
| | - Michael Varner
- University of Utah Health Sciences Center Department of Obstetrics and Gynecology, 30 North 1900 East, Suite 2B200, Salt Lake City, UT 84132, , (801) 585-5156, Fax: (801) 585-2594
| | - Jay D. Iams
- Ohio State University, Department of Obstetrics and Gynecology, 563 Means Hall, 1654 Upham Drive, Columbus, OH 43210-1228, , (614) 293-8736, Fax: (614) 293-8993
| | - Atef Moawad
- Department of Obstetrics and Gynecology, University of Chicago Medical Center, 5841 S. Maryland MC 2050, Chicago, IL 60637, , (773) 702-5200, Fax: (773) 702-5160
| | - Baha M. Sibai
- University of Cincinnati, Department of Obstetrics and Gynecology, 231 Albert Sabin Way, Cincinnati, OH 45267-0526, , (513) 558-8448, Fax: (513) 558-6138
| | - Menachem Miodovnik
- Department of Obstetrics and Gynecology, Washington Hospital Center, 110 Irving Street, NW, Room 5B-63, Washington, DC 20010, , (202) 877-9663, Fax: (202) 877-5435
| | - Mitchell Dombrowski
- Department of Obstetrics and Gynecology, St. John Hospital, 22151 Moross, Detroit, MI, 48236, , (313) 343-7798, Fax: (313) 343-4932
| | - Mary J. O'Sullivan
- University of Miami, Department of Obstetrics and Gynecology, Division of Research, R 136, Miami, FL, 33123, , (305) 243-7364
| | - J. Peter VanDorsten
- Medical University of South Carolina, Department of Obstetrics and Gynecology, 96 Jonathan Lucas Street, Suite 634, Charleston, SC 29425, , (843) 792-1668, Fax: 843-792-0533
| | - Oded Langer
- Department of Obstetrics and Gynecology, St. Luke's-Roosevelt Hospital Center, 1000 10 Avenue, Suite 10C-01, New York, NY 10019, , (212) 523-5750, Fax: (212) 523-8066
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Abstract
Management of the pregnant patient presents unique challenges to the treating physician. Current Food and Drug Administration classifications do not necessarily reflect clinical experience or recent literature. Ideally, one should use the lowest-risk drug possible, with attention to the appropriate level of efficacy for the patient's condition, the stage of pregnancy and dose adjustment. Every treatment decision should be fully discussed with the patient and a multidisciplinary team that should include the obstetrician and, if appropriate, the paediatrician. This review will cover the medications commonly used to treat gastrointestinal disease. The majority of medications can be categorised as 'low risk' or 'should be avoided'. The following medications should never be used during pregnancy due to the clear risk of teratogenicity or adverse events: bismuth, castor oil, sodium bicarbonate, methotrexate, ribavirin, doxycycline, tetracycline, and thalidomide.
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Affiliation(s)
- Uma Mahadevan
- Division of Gastroenterology, Department of Medicine, University of California, UCSF Center for Colitis and Crohn's Disease, 2330 Post Street #610, San Francisco, CA 94115, USA.
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Mahadevan U, Kane S. American gastroenterological association institute technical review on the use of gastrointestinal medications in pregnancy. Gastroenterology 2006; 131:283-311. [PMID: 16831611 DOI: 10.1053/j.gastro.2006.04.049] [Citation(s) in RCA: 103] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
This literature review and the recommendations therein were prepared for the American Gastroenterological Association Institute Clinical Practice and Economics Committee. The paper was approved by the Committee on February 22, 2006 and by the AGA Institute Governing Board on April 20, 2006.
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Affiliation(s)
- Uma Mahadevan
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, USA
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38
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Abstract
The physiologic changes of pregnancy and risks to the fetus require attention during dermatologic surgery. Elective surgery should be performed in the second trimester or the postpartum period. Cosmetic work should occur after delivery to avoid hypertrophic or hyperpigmented scars. Skin preparatory agents and anesthetics may have fetal implications and should be chosen with care. Antibiotic selection for any infections must take into account possible maternal and fetal risks. Attention to detail and awareness of the changes in pregnancy should lead to safe surgery in the pregnant patient.
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Affiliation(s)
- Susan M Sweeney
- Division of Dermatology, University of Massachusetts Medical School, and Dermatologic Surgery, University of Massachusetts Memorial Health Care, Worcester, MA 01655, USA.
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39
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Amann U, Egen-Lappe V, Strunz-Lehner C, Hasford J. Antibiotics in pregnancy: analysis of potential risks and determinants in a large German statutory sickness fund population. Pharmacoepidemiol Drug Saf 2006; 15:327-37. [PMID: 16557603 DOI: 10.1002/pds.1225] [Citation(s) in RCA: 45] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
PURPOSE Antibiotics are frequently prescribed drugs in pregnancy. The purpose of the study was to analyse the use, the potential risks and the determinants of systemic antibiotic prescriptions during pregnancy. METHODS A large, nation-wide acting German statutory sickness fund provided prescription data and personal data of 41,293 pregnant women. For this study, all prescriptions of systemic antibiotics (ATC: J01) dispensed to each woman during a 21-month period were analysed. We used the FDA risk classification system and enrolled a literature search to identify potentially harmful antibiotics. To investigate the impact of geographical and socio-economic determinants in antibiotic prescribing, a multivariate logistic regression model was performed. RESULTS Of the 41,293 women, 19.7% received at least one antibiotic drug during pregnancy. There was a shift to relatively safe and reduced antibiotic drug use during pregnancy. Prescribing of contraindicated antibactericals or potentially harmful drugs was seen in 521 women (1.3% of all women). In the logistic regression, being younger than 21 years (adjusted OR 2.14, 95%CI 1.80-2.53) or being welfare recipient (adjusted OR 1.57, CI 1.25-2.00) was strongly associated with higher antibiotic use. Significantly lower antibiotic use was seen in 5 of 16 German federal states (OR 0.74-0.83). CONCLUSIONS About 20% of pregnant women received antibiotics, and 1.3% received a harmful drug. To minimise the risks, detailed guidelines are needed for the antibiotic treatment during pregnancy.
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Affiliation(s)
- Ute Amann
- Institute for Medical Informatics, Biometry and Epidemiology, University of Munich, Munich, Germany.
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