Veilig gebruik van contrastmiddelen tijdens de lactatie
Uitgangsvraag
Wat is het veiligheidsprofiel van (jodiumhoudend en gadoliniumhoudend) contrastmiddel (CM) tijdens de lactatieperiode voor moeder en kind?
Aanbeveling
Vanwege de beperkte excretie van CM in de moedermelk, is de werkgroep van mening dat het veilig is om borstvoeding te continueren na toediening van CM.
Als de patiënte de borstvoeding zelf wenst te onderbreken (gezamenlijke besluitvorming met de arts), dan is een tijdsperiode van 24 uur voldoende.
Overwegingen
Data from studies evaluating the safety of the use of contrast media (CM) in the lactation period are very limited (Böhm, 2020). Our search did not find any studies regarding lactation. Therefore, a recommendation based on findings of comparative studies cannot be made. However, we can make a recommendation based on the pharmacokinetics of CM and recommendations of other guidelines. Several reviews found in literature use pharmacokinetics and the results of limited animal studies. Most of their recommendations are also found in other guidelines (Cova, 2014; Lin, 2007; Puac, 2017; Tremblay, 2012; Wang, 2012).
When assessing the risk of CM in the lactation period, information of the excretion of these CM into breast milk and the absorption from the gastrointestinal tract of the new-born is needed. Iodine-based contrast media (ICM) and gadolinium-based contrast agents (GBCA) are water-soluble and therefore excreted in small amounts in breast milk, found in limited animal studies (Bourrinet, 1995; Lorusso, 1994; Okazaki, 1996). Human studies have stated the same, but numbers of patients are also very limited. These studies mention the excretion and later absorption of CM by the newborn, which are also mentioned in the guidelines from The American College of Radiology (ACR) and The American College of Obstetricians and Gynecologists (ACOG). They state that for ICM less than 1% of the administered maternal dose is excreted into breast milk in the first 24 hours. The absorption from the gastrointestinal tract in the newborn is 1%, making the systemic dose less than 0,01%. For GBCA, 0,04% of the administered maternal dose is excreted into breast milk.
Combined with the 1% absorption, the systemic dose is less than 0,0004% (Kubik-Huch, 2007; Nielsen, 1987; Schmiedl, 1990; Tremblay, 2012; Wang, 2012; Webb 2005). Due to the small dose of CM in breast milk, these studies state that it is safe for both mother and newborn to continue breastfeeding after receiving CM. The ACR also states that the decision should be left up to the mother herself. If discontinuation of breastfeeding is wanted, 12-24 hours is enough (ACR, 2022).
The Contrast Media Safety Committee (CMSC) of the European Society of Urogenital Radiology (ESUR) guideline states that breastfeeding may be continued normally with ICM and GBCA (ESUR, 2018; Webb 2005 and 2013).
The guideline regarding GBCA of the Royal College of Radiology (RCR) states that, while no special precaution or cessation of breastfeeding is required, the continuation or cessation of breastfeeding for 24 hours should be at the discretion of the lactating mother in consultation with the clinician (RCR, 2019).
The guideline regarding ICM of the Royal Australian and New Zealand College of Radiologists (RANZCR) states that cessation of breastfeeding or expression and discarding of breast milk after ICM administration are not required (RANZCR, 2018).
The guideline on MRI in the obstetric patient of the Society of Obstetricians and Gynaecologists of Canada states that it is safe to continue breastfeeding after receiving GBCA (Patenaude, 2014).
Recommendations
Our recommendation is in line with other guidelines and the few available data. Due to the limited amount of excretion of CM in breast milk, breastfeeding can be continued without interruption when imaging with CM is needed. If women wish to discontinue, a discontinuation of 24 hours should be enough.
Due to the limited amount of excretion into breast milk, the guideline development group believes it is safe to continue breastfeeding after administration of contrast media. |
If patients wish to discontinue breastfeeding (shared decision making), a discontinuation of 24 hours is sufficient. |
Onderbouwing
Achtergrond
The same questions about the use of contrast media (CM) in pregnancy arise in the puerperium, especially when breastfeeding. Questions arise from mothers, who are administered CM, whether these substances are safe for the new-born during the lactation period. This chapter is intended to provide recommendations regarding this topic.
Zoeken en selecteren
A systematic review of the literature was performed to answer the following question: What are the effects of contrast media during the lactation period for mother and new-born regarding safety?
P (Patients): Lactating women with indication for examination with contrast media.
I (Intervention): Contrast media administration.
C (Comparison): No contrast media administration or administration of a different contrast medium.
O (Outcomes): Neonatal adverse effects: gastrointestinal effects, hypersensitivity reactions, thyroid effects, maternal effects: percentage of contrast medium in breast milk, transition into breast milk.
Relevant outcome measures
The guideline working group considered neonatal adverse effects (hypersensitivity reactions, gastrointestinal effects, thyroid effects) of CM in breast milk as crucial outcome measures for decision making; and maternal effects (the percentage of contrast medium in breast milk) as an important outcome measure for decision making.
A priori, the working group did not define the outcome measures listed above but used the definitions used in the studies.
The working group defined the presence of any neonatal adverse effect as a minimal clinically (patient) important difference. Because of the severity of the outcome any statistically significant difference was considered as a clinically important difference between groups.
Search and select (Methods)
The databases Medline (via OVID) and Embase (via Embase.com) were searched with relevant search terms from January 1st, 2000, until January 26th, 2021. The detailed search strategy is depicted under the tab Methods. The systematic literature search resulted in 507 hits.
Studies were selected based on the following criteria:
- Original clinical studies or systematic reviews of original clinical studies; both randomized and observational studies were eligible.
- Patient population consisted of patients who were breastfeeding.
- The safety profile of contrast media administration regarding neonates’ effects and percentage of contrast medium in breast milk was compared between women who received contrast media versus those who received no contrast media or a different contrast medium.
Thirty-one studies were initially selected based on title and abstract screening. After reading the full text, all studies were excluded (see Table of excluded studies in ‘Appendices to modules’).
Results
No studies were included in the analysis of the literature, and therefore no systematic literature analysis was performed.
Referenties
- American College of Radiology. ACR Manual on contrast media, v2022. Available at: [URL].
Accessed: 17 April 2022. - American College of Obstetricians and Gynecologists. Committee Opinion 723: ACOG Guidelines for diagnostic imaging during pregnancy and lactation, 2017. Obstet Gynecol. 2017; 130(4): e210-e216. Available at: [URL] Accessed: 17 April 2022.
- Böhm I, Hungerbühler M. Excretion of iodinated contrast media in human breast milk: surprising results. Eur J Radiol 2020; 128: 109045
- Bourrinet P, Dencausse A, Havard P, Violas X, Bonnemain B. Transplacental passage and milk excretion of iobitridol. Invest Radiol 1995; 30(3):156–158.
- Cova MA, Stacul F, Quaranta R, Guastalla P, Salvatori G, Banderali G, Fonda C, David V, Gregori M, Zuppa AA, Davanzo R. Radiological contrast media in the breastfeeding woman: a position paper of the Italian Society of Radiology (SIRM), the Italian Society of Paediatrics (SIP), the Italian Society of Neonatology (SIN) and the Task Force on Breastfeeding, Ministry of Health, Italy. Eur Radiol. 2014; 24(8):2012-2022.
- European Society of Urogenital Radiology Contrast Media Safety Committee. ESUR Guidelines on contrast safety, v10. 2018. Available at: [URL]. Accessed: 17 April 2022.
- Kubik-Huch RA, Gottstein Alame NM, Frenzel T et al. Gadopentetate diglumine excretion into human breast milk during lactation. Radiology 2000; 216: 555-558.
- Lin SP, Brown JJ. MR contrast agents: physical and pharmacologic basics. J Magn Reson Imaging. 2007; 25(5): 884-899.
- Lorusso V, Luzzani F, Bertani F, Tirone P, de Haën C. Pharmacokinetics and tissue distribution of iomeprol in animals. Eur J Radiol 1994; 18 (Suppl 1): S13-S20.
- Nielsen ST, Matheson I, Rasmussen JN, Skinnemoen K, Andrew E, Hafsahl G. Excretion of iohexol and metrizoate in human breast milk. Acta Radiol. 1987; 28(5): 523-526.
- Okazaki O, Murayama N, Masubuchi N, Nomura H, Hakusui H. Placental transfer and milk secretion of gadodiamide injection in rats. Arzneimittelforschung. 1996; 46(1): 83-86.
- Patenaude Y, Pugash D, Lim K, Morin L; Diagnostic Imaging Committee, Lim K, Bly S, Butt K, Cargill Y, Davies G, Denis N, Hazlitt G, Morin L, Naud K, Ouellet A, Salem S; Society of Obstetricians and Gynaecologists of Canada. The use of magnetic resonance imaging in the obstetric patient. J Obstet Gynaecol Can. 2014; 36(4): 349-363.
- Puac P, Rodríguez A, Vallejo C, Zamora CA, Castillo M. Safety of contrast material use during pregnancy and lactation. Magn Reson Imaging Clin N Am. 2017; 25(4): 787-797.
- Royal Australian and New Zealand College of Radiologists. RANZCR Iodinated Contrast Guidelines, v2.3. 2018. Available at: [URL]. Accessed: 17 April 2022.
- Royal College of Radiologists. RCR Guidance on gadolinium-based contrast agent administration to adult patients. April 2019. Available at: [URL]. Accessed: 17 April 2022.
- Schmiedl U, Maravilla KR, Gerlach R, Dowling CA. Excretion of gadopentetate dimeglumine in human breast milk. AJR Am J Roentgenol. 1990; 154(6): 1305-1306.
- Tremblay E, Therasse E, Thomassin N et al. Quality Initiatives: Guidelines for use of medical imaging during pregnancy and lactation. Radiographics. 2012; 32: 897-911.
- Wang PI, Chong ST, Kielar AZ. Imaging of pregnant and lactating patients: Part 1. Evidence- based review and recommendations. AJR Am J Roentgenol 2012; 198: 778-784.
- Webb JA, Thomsen HS, Morcos SK; Members of Contrast Media Safety Committee of European Society of Urogenital Radiology (ESUR). The use of iodinated and gadolinium contrast media during pregnancy and lactation. Eur Radiol. 2005; 15(6): 1234-1244.
- Webb JA, Thomsen HS. Gadolinium contrast media during pregnancy and lactation. Acta Radiol 2013; 54: 599-600.
Verantwoording
Autorisatiedatum en geldigheid
Laatst beoordeeld : 28-11-2022
Laatst geautoriseerd : 28-11-2022
Geplande herbeoordeling :
Validity
The Radiological Society of the Netherlands (NVvR) will determine around 2027 if this guideline (per module) is still valid and applicable. If necessary, the scientific societies will form a new guideline group to revise the guideline. The validity of a guideline can be shorter than 5 years, if new scientific or healthcare structure developments arise, that could be a reason to commence revisions. The Radiological Society of the Netherlands is the owner of this guideline and thus primarily responsible for the actuality of the guideline. Other scientific societies that have participated in the guideline development share the responsibility to inform the primarily responsible scientific society about relevant developments in their field.
Algemene gegevens
General Information
The Kennisinstituut van de Federatie Medisch Specialisten (www.kennisinstituut.nl) assisted the guideline development group. The guideline was financed by Stichting Kwaliteitsgelden Medisch Specialisten (SKMS) which is a quality fund for medical specialists in The Netherlands.
Samenstelling werkgroep
Guideline development group (GDG)
A multidisciplinary guideline development group (GDG) was formed for the development of the guideline in 2020. The GDG consisted of representatives from all relevant medical specialization fields which were using intravascular contrast administration in their field.
All GDG members have been officially delegated for participation in the GDG by their scientific societies. The GDG has developed a guideline in the period from June 2020 until November 2022. The GDG is responsible for the complete text of this guideline.
Guideline development group
- Dekkers I.A. (Ilona), clinical epidemiologist and radiologist, Leiden University Medical Center, Leiden
- Geenen R.W.F. (Remy), radiologist, Noordwest Ziekenhuisgroep, Alkmaar
- Kerstens M.N. (Michiel), internist-endocrinologist, University Medical Centre Groningen
- Krabbe J.G. (Hans), clinical chemist-endocrinologist, Medisch Spectrum Twente, Enschede
- Rossius M.J.P. (Mariska), radiologist, Erasmus Medical Centre, Rotterdam
- Uyttenboogaart M. (Maarten), neurologist and neuro-interventionalist, University Medical Centre Groningen
- van de Luijtgaarden K.M. (Koen), vascular surgeon, Maasstad Ziekenhuis, Rotterdam
- van der Molen A.J. (Aart), chair guideline development group, radiologist, Leiden University Medical Center, Leiden
- van der Wolk S.L. (Sabine), gynaecologist-obstetrician, Haga Ziekenhuis, Den Haag
- van de Ven A.A.J.M. (Annick), internist-allergologist-immunologist, University Medical Centre Groningen (until 1.7.2022)
- van der Houwen, T.B. (Tim), internist-allergologist-immunologist, Amsterdam University Medical Center (from 1.7.2022)
Invited experts
- van Maaren M.S. (Maurits), internist-allergologist-immunologist, Erasmus MC, Rotterdam
Belangenverklaringen
Conflicts of interest
The GDG members have provided written statements about (financially supported) relations with commercial companies, organisations or institutions that were related to the subject matter of the guideline. Furthermore, inquiries have been made regarding personal financial interests, interests due to personal relationships, interests related to reputation management, interest related to externally financed research and interests related to knowledge valorisation. The statements on conflict of interest can be requested from the administrative office of Kennisinstituut van de Federatie Medisch Specialisten (secretariaat@kennisinstituut.nl) and were summarised below.
Last name |
Function |
Other positions |
Personal financial interests |
Personal relations |
Reputation management |
Externally financed research |
Knowledge valorisation |
Other interests |
Signed |
Actions |
Dekkers IA |
Radiologist, LUMC |
Clinical Epidemiologist
Member of contrast media safety committee, European Society of Urogenital Radiology (no payment)
Member, Gadolinium Research and Education Committee, European Society of Magnetic Resonance in Medicine, and Biology (no payment) |
No |
No |
No |
No |
No |
Received consultancy fees from Guerbet, 2019- 2022 |
July 24th, 2020, Reaffirmed October 12th, 2022 |
No restrictions: received in part 3 of the guideline speaker fees, but this guideline does not mention specific medication, not of working mechanism, nor of side effects. |
Geenen RWF |
Radiologist, Noordwest ziekenhuisgroep /Medisch specialisten Noordwest |
Member of contrast media safety committee, European Society of Urogenital Radiology (no payment) |
No |
No |
No |
No |
No |
No |
April 11th, 2020, Reaffirmed October 12th, 2022 |
No restrictions |
Houwen T, van der |
Internist - Immunologist - Allergologist, Amsterdam UMC, also seconded allergologist in Huid Medisch Centrum |
None |
None |
None |
None |
None |
None |
None |
July 11th, 2022 Reaffirmed October 12th, 2022 |
No restrictions |
Kerstens MN |
Internist- endocrinologist, UMCG |
Chairman Bijniernet (no payment) |
No |
No |
No |
No |
No |
No |
July 1st, 2020, reaffirmed October 25th, 2022 |
No restrictions |
Krabbe JG |
Clinical chemist, Medisch Spectrum Twente |
No |
No |
No |
No |
No |
No |
No |
September 1st, 2020, Reaffirmed October 13th, 2022 |
No restrictions |
Luijtgaarden KM, van de |
Vascular surgeon, Maasland Ziekenhuis |
No |
No |
No |
No |
No |
No |
No |
August 1st, 2020, reaffirmed October 26th, 2022 |
No restrictions |
Molen AJ, van der |
Radiologist LUMC |
Member of contrast media safety committee, European Society of Urogenital Radiology (no payment)
Member, Gadolinium Research and Education Committee, European Society of Magnetic Resonance in Medicine, and Biology (no payment) |
No |
No |
No |
No |
No |
Received consultancy fees from Guerbet, 2019- 2022 |
July, 24th, 2020 Reaffirmed October 12th, 2022 |
No restrictions: received in part 3 of the guideline speaker fees, but this guideline does not mention Specific medication, not of working mechanism, nor of side effects. |
Rossius MJP |
Radiologist Erasmus Medical Centre |
Medical coordinator (no payment) |
No |
No |
No |
No |
No |
No |
April 7th, 2020, Reaffirmed October 13th, 2022 |
No restrictions |
Uyttenboogaart M |
Neurologist and neuro- interventionalist UMCG |
Advisor International Federation of Orthopaedic Manipulative Physical Therapist / Nederlandse Vereniging Manuele Therapie |
No |
No |
Subsidy Hart Stichting for CONTRAST (Consortium of New Treatments in Acute Stroke): WP8 Stroke logistics and Epidemiology: financing of 2 PhD students by the Hart Stichting / PPS Allowance |
Work package leader CONTRAST (Consortium of New Treatments in Acute Stroke): WP8 Stroke logistics and Epidemiology |
No |
No |
June 30th, 2020, reaffirmed October 26th, 2022 |
No restrictions: the CONTRAST consortium wp8 is only about organisation and treatment of stroke. Stroke is not in this guideline. |
Ven AAJM, van de |
Internist- allergologist- immunologist, UMCG |
Education and research related to work as internist- allergist |
No |
No |
No |
No |
No |
No |
April 7th, 2020, Reaffirmed October 19th, 2022 |
No restrictions |
Wolk S, van der |
Gynaecologist- obstetrician, Haga Ziekenhuis |
No |
No |
No |
No |
No |
No |
No |
June 30th, 2021, reaffirmed October 25th, 2022 |
No restrictions |
Inbreng patiëntenperspectief
Input of patient’s perspective
The guideline does not address a specific adult patient group, but a diverse set of diagnoses. Therefore, it was decided to invite a broad spectrum of patient organisations for the stakeholder consultation. The stakeholder consultation was performed at the beginning of the process for feedbacking on the framework of subjects and clinical questions addressed in the guideline, and during the commentary phase to provide feedback on the concept guideline. The list of organisations which were invited for the stakeholder consultation can be requested from the Kennisinstituut van de Federatie Medisch Specialisten (secretariaat@kennisinstituut.nl). In addition, patient information on safe use of contrast media in pregnancy and lactation was developed for Thuisarts.nl, a platform to inform patients about health and disease.
Implementatie
Implementation
During different phases of guideline development, implementation and practical enforceability of the guideline were considered. The factors that could facilitate or hinder the introduction of the guideline in clinical practice have been explicitly considered. The implementation plan can be found in the ‘Appendices to modules’. Furthermore, quality indicators were developed to enhance the implementation of the guideline. The indicators can also be found in the ‘Appendices to modules’.
Werkwijze
Methodology
AGREE
This guideline has been developed conforming to the requirements of the report of Guidelines for Medical Specialists 2.0 by the advisory committee of the Quality Counsel (www.kwaliteitskoepel.nl). This report is based on the AGREE II instrument (Appraisal of Guidelines for Research & Evaluation II) (www.agreetrust.org), a broadly accepted instrument in the international community and based on the national quality standards for guidelines: “Guidelines for guidelines” (www.zorginstituutnederland.nl).
Identification of subject matter
During the initial phase of the guideline development, the GDG identified the relevant subject matter for the guideline. The framework is consisted of both new matters, which were not yet addressed in part 1 and 2 of the guideline, and an update of matters that were subject to modification (for example in case of new published literature). Furthermore, a stakeholder consultation was performed, where input on the framework was requested.
Clinical questions and outcomes
The outcome of the stakeholder consultation was discussed with the GDG, after which definitive clinical questions were formulated. Subsequently, the GDG formulated relevant outcome measures (both beneficial and harmful effects). The GDG rated the outcome measures as critical, important and of limited importance (GRADE method). Furthermore, where applicable, the GDG defined relevant clinical differences.
Search and select
For clinical questions, specific search strategies were formulated, and scientific articles published in several electronic databases were searched. First, the studies that potentially had the highest quality of research were reviewed. The GDG selected literature in pairs (independently of each other) based on the title and abstract. A second selection was performed by the methodological advisor based on full text. The databases used, selection criteria and number of included articles can be found in the modules, the search strategy in the appendix.
Quality assessment of individual studies
Individual studies were systematically assessed, based on methodological quality criteria that were determined prior to the search. For systematic reviews, a combination of the AMSTAR checklist and PRISMA checklist was used. For RCTs the Cochrane risk of bias tool and suggestions by the CLARITY Group at McMaster University were used, and for cohort studies/observational studies the risk of bias tool by the CLARITY Group at McMaster University was used. The risk of bias tables can be found in the separate document Appendices to modules.
Summary of literature
The relevant research findings of all selected articles were shown in evidence tables. The evidence tables can be found in the separate document Appendices to modules. The most important findings in literature were described in literature summaries. When there were enough similarities between studies, the study data were pooled.
Grading quality of evidence and strength of recommendations
The strength of the conclusions of the included studies was determined using the GRADE- method. GRADE stands for Grading Recommendations Assessment, Development and Evaluation (see http://www.gradeworkinggroup.org) (Atkins, 2004). GRADE defines four levels for the quality of scientific evidence: high, moderate, low, or very low. These levels provide information about the certainty level of the literature conclusions (http://www.guidelinedevelopment.org/handbook).
The evidence was summarized in the literature analysis, followed by one or more conclusions, drawn from the body of evidence. The level of evidence for the conclusions can be found above the conclusions. Aspects such as expertise of GDG members, local expertise, patient preferences, costs, availability of facilities and organisation of healthcare aspects are important to consider when formulating a recommendation. These aspects are discussed in the paragraph justifications. The recommendations provide an answer to the clinical question or help to increase awareness and were based on the available scientific evidence and the most relevant justifications.
Appendices
Internal (meant for use by scientific society or its members) quality indicators were developed with the guideline and can be found in the separate document Appendices to modules. In most cases, indicators were not applicable. For most questions, additional scientific research on the subject is warranted. Therefore, the GDG formulated knowledge gaps to aid in future research, which can be found in the separate document Appendices to modules.
Commentary and authorisation phase
The concept guideline was subjected to commentaries by the involved scientific societies. The list of parties that participated in the commentary phase can be requested from the Kennisinstituut van de Federatie Medisch Specialisten (secretariaat@kennisinstituut.nl). The commentaries were collected and discussed with the GDG. The feedback was used to improve the guideline; afterwards the GDG made the guideline definitive. The final version of the guideline was offered to the involved scientific societies for authorization and was authorized.
Literature
Brouwers MC, Kho ME, Browman GP, et al. AGREE Next Steps Consortium. AGREE II: advancing guideline development, reporting and evaluation in health care. CMAJ. 2010; 182(18): E839-E842.
Medisch Specialistische Richtlijnen 2.0. Adviescommissie Richtlijnen van de Raad Kwaliteit, 2012. Available at: [URL].
Schünemann H, Brożek J, Guyatt G, et al. GRADE handbook for grading quality of evidence and strength of recommendations. Updated October 2013. The GRADE Working Group, 2013. Available at: [URL].
Schünemann HJ, Oxman AD, Brozek J, et al. Grading quality of evidence and strength of recommendations for diagnostic tests and strategies. BMJ. 2008;336(7653):1106- 1110. Erratum published in: BMJ 2008;336(7654).
Ontwikkeling van Medisch Specialistische Richtlijnen: stappenplan. Kennisinstituut van Medisch Specialisten, 2020.