Veilig gebruik van contrastmiddelen

Initiatief: NVvR Aantal modules: 48

Veilig gebruik van contrastmiddelen tijdens de zwangerschap


Wat is het veiligheidsprofiel van (jodiumhoudend en gadoliniumhoudend) contrastmiddel (CM) tijdens de zwangerschap voor moeder en kind?


Onthoud geen zwangere patiënten van beeldvorming met jodiumhoudend contrastmiddel, wanneer dit medisch geïndiceerd is.


Wees terughoudend met gadoliniumhoudend contrastmiddel vanwege de potentiële risico’s voor de foetus. Gebruik alleen contrastmiddelen wanneer de baten duidelijk groter zijn dan de risico’s.


The use of diagnostic imaging with contrast media (CM) in pregnant patients has always been a topic of debate. It is known that administered CM pass the placenta and enter the foetal circulation in small amounts, but due to lack of hard data on the possible side effects for the foetus, it is difficult to give a solid advice to pregnant patients. Several reviews and papers found in literature use the results of limited data and recommendations of other guidelines (Lin, 2007; Little, 2020; Puac, 2017; Tremblay, 2012; Wang, 2012).


So far, different animal studies reported no congenital malformations with the use of iodine- based contrast media (ICM) (Morisetti, 1994). There are some theoretical concerns that free iodide can cause damage to the foetal thyroid gland (Webb, 2005).


With our search, only one comparative study was included for ICM. In this study no evidence was found that the administration of ICM caused congenital abnormalities or influenced the neonatal thyroid function (Rajaram, 2012). Three other non-comparative studies which were excluded from our search because of missing control groups, but were described in table 2.1, also did not report any congenital abnormalities (Atwell, 2008; Bourjelly, 2010; Kochi, 2012). Based on these findings we found no evidence that ICM cause congenital abnormalities. However, the evidence is uncertain due to the limited data and design of the few studies. Recently, a systematic review (Van Welie, 2021) found the same results regarding ICM with CT. They conducted a systematic review regarding ICM and their effect in pre-conceptional and post-conceptional women and their new-borns. They found five retrospective cohort studies and one case report regarding ICM in CT which reported on 525 neonates. Based on these five cohort studies, they estimated the overall proportion of (transient) neonatal thyroid dysfunction after CT at 0.0% (95% CI: 0.0–0.02% I2=0%).


Due to these limited data, other guidelines were also consulted:


Guidelines from the Contrast Media Safety Committee (CMSC) of the European Society of Urogenital Radiology (ESUR) state that ICM may be given to the pregnant patient and that neonatal thyroid function should be checked during the first week (ESUR, 2018).


The Manual on Contrast Media from the American College of Radiology (ACR) recommends not withholding the use of ICM in pregnant or potentially pregnant patients when it is needed for diagnostic purposes (ACR, 2022).


Guidelines on ICM of the Royal Australian and New Zealand College of Radiologists (RANZCR) state that infants born to women who received ICM while pregnant should have testing for neonatal hypothyroidism (RANZCR, 2021).


Guidelines from The American College of Obstetricians and Gynaecologists (ACOG) state that ICM should only be used if absolutely required to obtain additional diagnostic information that will affect the care of the foetus or woman during the pregnancy (ACOG, 2017).


With gadolinium-based contrast agents (GBCA), animal studies have reported teratogenic effects only when administered in high and repeated doses (Chen, 2008; Novak, 1993; Okuda, 1999). Free gadolinium is toxic, and it is presumed that in high and repeated doses, gadolinium dissociates from its chelation agent. In humans, it is uncertain what the exact risk of gadolinium can be due to the unknown duration of exposure. When CM pass the placenta, it enters the foetal circulation and amniotic fluid. There, it re-enters the circulation due to swallowing of the amniotic fluid by the foetus. Therefore, the exact duration of foetal exposure to gadolinium is not known. The longer it remains in the amniotic fluid, the higher the risk of dissociation and exposure to free gadolinium.


No comparative studies were included with the use of GBCA. Two non-comparative studies shown in table 2.1, reported no adverse outcomes with the use of GBCA (De Santis, 2007; Spencer, 2000). In addition, Ray et al. (Ray 2016), performed a large retrospective study, evaluating the long-term safety of MRI exposure in pregnancy. They identified all births after 20 weeks of gestation in Ontario, Canada, from 2003 to 2015. Women exposed during first trimester of pregnancy to MRI and women exposed later in pregnancy were separately analysed. These were compared to women that were not exposed to MRI and had also no indication for MRI. For this reason, the study was excluded from the literature analysis.


Exposure to MRI during the first trimester of pregnancy (n=1.737), compared with non- exposure (n= 1.418.451), was not associated with increased risk of harm to the foetus. Stillbirths and neonatal deaths occurred among 7/397 (2%) MRI-exposed with gadolinium vs. 9844/1.418.451 (1%) unexposed pregnancies (adjusted RR, 3.70; 95% CI, 1.55 to 8.85) for an adjusted risk difference of 47.5 per 1000 pregnancies (95% CI, 9.7 to 138.2). They also found a significantly increased risk of a broad set of rheumatological, inflammatory, or infiltrative skin conditions. So far, this study is the only longitudinal cohort study with a significant sample size. However, limitations of this study for assessing the risk of gadolinium-based contrast agents are the unavailability of MRI indications of the exposed cohort, a bias towards linear GBCA, a low follow-up rate, no trimester subset analysis, and the lack of a comparable control group with indication for (non-contrast) MRI (Little, 2020; Lum, 2020).


In contrast, a very recent retrospective cohort study (published after our literature search) compared 782 pregnancies that were exposed to MRI with GBCA to 5,209 pregnancies that were exposed to MRI without GBCA out of a population of > 11 million Medicaid-covered pregnancies. The primary endpoint was foetal/neonatal death, and the second endpoint was the infant neonatal intensive care unit admission rate. In both groups the percentage of foetal/neonatal death was 1,4%, with an adjusted relative risk of 0.73 (95% CI 0.34-1.55).


The percentage of infants with a neonatal intensive care unit admission was 7.7% in the GBCA and 8.8% in the non-GBCA group, with an adjusted relative risk of 1.03 (95% CI 0.76- 1.39). These results were considered reassuring for fatal and severe acute effects of GBCA administration during pregnancy, but subacute effects were not studied (Winterstein, 2022).


We also consulted other guidelines for their recommendations concerning GBCA: Guidelines from the CMSC of ESUR state when there is a strong indication for CE MRI, the smallest possible dose of a macrocyclic GBCA may be given to a pregnant female (ESUR, 2018; Webb, 2005 and 2013).


Guidelines from the Royal College of Radiology (RCR) state that GBCA should not be used during pregnancy unless the clinical condition of the patient makes their use absolutely necessary (RCR, 2019).


Guidelines from the ACR state that because it is unclear how GBCA will affect the foetus, these agents should be used with caution to pregnant or potentially pregnant patients. GBCA should only be used if their usage is considered critical and the potential benefits justify the potential unknown risk to the foetus (ACR, 2022).


Guidelines from the ACOG state that the use of GBCA with MRI should be limited. It may be used as a contrast agent in a pregnant woman only if it significantly improves diagnostic performance and is expected to improve foetal or maternal outcome (ACOG, 2021).


Guidelines from the Canadian Association of Radiologists on MRI do not recommend GBCA administration unless absolutely necessary (Jabehdar Maralani, 2022).


Based on our search and the advice from other guidelines, we made recommendations for the use of ICM and GBCA separately. Regarding our second clinical question, no recommendations could be made. None of studies regarding ICM made a distinction in gestational age. For GBCA, only a few studies focussed on the first trimester or women who did not know they were pregnant (Bird, 2019; De Santis, 2007). Their recommendations are like the overall recommendations. The guidelines which are mentioned earlier, also do not have recommendations for specific trimesters. The ACR has a separate document about imaging in potentially pregnant patients, but this document does not address the use of CM. Therefore, a recommendation about a specific trimester cannot be made and our recommendations will be for pregnancy in general.




Our recommendation for the use of ICM is in line with the guidelines mentioned above. A discussion of the theoretical potential risks and benefits of the use of ICM should take place but a pregnant patient should not be denied a diagnostic test when it is needed. Because of the heel prick screening test, extra testing of the thyroid is not necessary.


Do not withhold a pregnant patient from imaging with iodine-based contrast media when medically indicated.


Although no adverse outcomes were reported in the two studies mentioned in table 2.1, our recommendation regarding the use of GBCA is in line with other guidelines. The recommendation is based on the study of Ray et al (2016) and the potential teratogenic risks found in animal data.


Be cautious with gadolinium-based contrast agents due to potential risks to the foetus. Only use contrast agents when the benefits clearly outweigh the possible risks.



Little is known about the safety of the use of contrast media (CM) in pregnant patients, both for the mother and the unborn child. Not only the caregiver but also the patients themselves have many questions about the safety of CM. The confusion about this safety can lead to avoidance of a potential crucial diagnostic test. Therefore, an updated search is highly needed.

Iodine-based contrast media




Very low GRADE

Iodine-based contrast medium administration may have little to no effect on neonatal thyroid function when compared with no iodinated contrast medium administration in pregnant patients, but the evidence is very uncertain.


Sources: Rajaram, 2012




No evidence was found regarding the effect of iodine-based contrast medium administration on congenital defects other than thyroid function when compared with no iodine-based contrast medium administration in pregnant patients.


Gadolinium-based contrast agents




No evidence was found regarding the effects of gadolinium-based contrast agent administration on congenital defects when compared with no contrast medium administration, or a different type of contrast medium administration in pregnant patients.


Description of studies


Iodine-based contrast media

Rajaram, 2012 performed a retrospective review of 115 pregnant patients investigated for suspected pulmonary embolism. The patient cohort consisted of two groups: Group A consisted of 73 pregnant females who received iodinated contrast agent for CT-pulmonary angiography (CTPA), and Group B (control group) consisted of 42 pregnant females who were investigated by perfusion imaging only. For group A, a maximum dose of 100 ml of non-ionic iodinated low-molecular-weight agent containing 300 mg/ml iopromide was used as a standard contrast agent. The gestational age at the time of contrast administration was in Group A (median 28 weeks, range 12-40) and Group B (median 29 weeks, range 7-38, p- 0.30). The results of the neonatal thyroid function tests for the babies of the mothers in Groups A and B were compared. The blood samples for TSH levels were obtained from new- borns by heel puncture test at the age of 5–8 days.


Gadolinium-based contrast media

No studies with a control group were found. Descriptive studies without control group can be found in Table 2.1.




Iodine-based contrast media

Rajaram (2012) reported that no significant difference was found in neonatal TSH values between the two groups (p=0.67). The average TSH value for group A, exposure to iodinated contrast agent, was 1.1 mIU/ml. The average TSH value for group B, no exposure to iodinated contrast agent, was 1.07 mIU/ml.


Gadonium-based contrast media


Table 5.1: Brief description of studies that have the same patient population and intervention group as the search question, but no control group

Study name

Patient population and number

Type of contrast medium


Other remarks

Iodine-based contrast media

Atwell, 2008


pregnant patients who underwent CT with iodinated IV

contrast material between February 2000 and October

2006. Mean maternal age at the time of CT was 29 years (range,

19–41 years). Mean gestational age (based on last menstrual period) at the time of CT was 23 weeks

(range, 8–37 weeks). Neonatal patients were born at a mean of 38 weeks of gestation (range, 24–41 weeks of


CT with iodinated IV contrast material (type was not further specified)

For all neonatal patients, serum TSH levels were normal. Mean

serum TSH was 9.7 µIU/mL (range, 2.2–28.8 µIU/mL).

No maternal patient reported thyroid problems in her child

Author’s conclusion: Based on neonatal TSH measurements in a small number of

patients, we found no ill effect of iodinated contrast agents on neonatal thyroid function after in utero exposure.


Retrospective observational study.

Bourjelly, 2010


All pregnant women who underwent multidetector pulmonary computed tomographic angiography because they were suspected of having pulmonary embolism between 2004 and 2008 and new-borns resulting from the index pregnancy were included.

Mean gestational age at the time of administration of the contrast material was 27.8

weeks 6 7.4.


The mean dose of total iodine administered was 45

000 mg/L 6 7321.

All new-borns had a normal T 4 level at birth; only one new-born had a transiently abnormal TSH level at birth, which normalized at day 6 of life.

This new-born was born to a mother who had many drug exposures during pregnancy.

Author’s conclusion: A single, high-dose in utero exposure to water-soluble, low- osmolar, iodinated intravenous products, such as iohexol, is unlikely to have a clinically important effect on thyroid function at birth.


Retrospective observational study.

Kochi, 2012

N=61 (64

neonates) pregnant women receiving iodinated contrast during a CT scan procedure, and their neonates.

The mean age of mothers in this group was 27.6 years at the time that they underwent a CT scan procedure. The mean GA at the time of the procedure was

25.6 weeks. The earliest GA was 8 weeks and the latest was 37 weeks. The mean GA at delivery was

37.5 weeks. Eight women had hypothyroidism.


A control group of 6 pregnant patients that received an CT scan without iodinated contrast was included. (Since the control group contained

<10 patients, this study was excluded from the literature


Iodinated contrast


The mean amount of non-ionic radioiodine contrast material used was

103.5 mL of Ultravist 300, which is approximately equal to 30 g of iodine. The range was between 21 and 46 g of iodine.

The TSH and T4 levels for all neonates, except one in this group, were within the reference range of

0.5 to 6.0 KIU/mL

for TSH and 7 to 14 Kg/dL for T4. One neonate had a T4 level of less than 6 Kg/dL and a normal TSH level. This patient was a preterm infant being born at the 25th week of gestational age

who also developed respiratory distress syndrome and sepsis.

Author’s conclusion: This study concludes that there is no significant adverse clinical risk of thyroid function abnormalities to the foetus after IV iodinated contrast material to their mothers. 


Retrospective observational study.

Gadolinium-based contrast agents

De Santis, 2007


Pregnant women exposed to gadopentetate dimeglumine in the periconceptional and first trimester period who had undergone an MRI owing to other clinical indications. Age: 31 ± 4 years The mean menstrual age at exposure was

29.78 days and 24/26 exposures were in the postconceptional period.

Gadopentetate dimeglumine

Two pregnancies, exposed at 15 and 18 days of menstrual age were complicated by low-birth- weight infants (LBW) but without any neonatal complications.

One congenital anomaly at birth in a baby that had two haemangiomas born at 38 weeks to a woman exposed at 31 days of menstrual age through an MRI for a pituitary


Author’s conclusion: In this prospective cohort study, we found no maternal or neonatal complications and only one congenital anomaly at birth.


Prospective observational study.

Spencer, 2000


Women with symptomatic hydronephrosis during pregnancy

(1) clinical features of loin pain in pregnancy as assessed by an obstetrician and urologist; (2) ipsilateral dilatation of the renal pelvis shown by routine abdominal sonography; and

(3) informed consent of the patient.

19–34 weeks of gestation.

Patient age not reported.

IV bolus of 0.1 mmol/kg of gadopentatate dimeglumine

There were no adverse obstetric or infant outcomes.

Author’s conclusion: MR excretory urography is a promising technique which affords equivalent functional and additional anatomical information to isotope renography.


Prospective study.

Ray, 2016

N= 397 exposed to gadolinium MRI and N=1 418 451

not exposed. Women with first trimester exposure to MRI.

Gadolinium- enhanced MRI during first trimester

“There were 7 stillbirths or neonatal deaths (17.6 per 1000)

following gadolinium- enhanced MRI exposure (cohort 2) vs 9844

events (6.9 per

1000) in

nonexposed women, an adjusted RR

of 3.70 (95% CI,

1.55-8.85) and an adjusted risk difference of

47.5 per 1000

(95% CI, 9.7-


Author’s conclusion: “Exposure to gadolinium enhanced MRI at any gestation was not associated with a greater risk of congenital anomalies. Although the NSF-like outcome was extremely rare, gadolinium- enhanced MRI was associated with an adjusted HR of 1.36 for any rheumatological, inflammatory or infiltrative skin condition up to age 4 years, and an adjusted RR of 3.70 for stillbirth or neonatal death, albeit with just 7 events in the gadolinium MRI



Level of evidence of the literature


Iodine-based contrast media

The level of evidence regarding the outcome measure thyroid function started as GRADE low due to the observational nature of the included study was downgraded by one level to very low due to the small number of included patients (imprecision).


Gadolinium-based contrast agents

No studies with a control group were found. Therefore, no evidence tables, risk of bias assessment and quality assessment were performed for the studies mentioned in Table 2.1.

A systematic review of the literature was performed to answer the following question: What are the effects of contrast media during pregnancy for mother and child regarding safety?


P (Patients): Pregnant women with indication for examination with contrast media.

I (Intervention): Contrast media administration (iodine-based or gadolinium-based).

C (Comparison): No contrast media administration or different contrast media administration.

O (Outcomes): Foetal: congenital malformation (e.g., thyroid), maternal: adverse events.


Relevant outcome measures

The guideline working group considered congenital malformations as a critical 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 a congenital malformation 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 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 pregnant patients
  • The safety profile of contrast media administration regarding foetal congenital malformations was compared between women who received contrast media versus those who received no contrast media or a different contrast medium
  • Iodine-based contrast media (ICM) or gadolinium-based contrast agent (GBCA)

Initially, thirty-one studies were selected based on title and abstract screening. After reading the full text, thirty studies were excluded (see Table of excluded studies in ‘Appendices to modules’) and one study was included.



One study (Rajaram, 2012) about iodine-based contrast media was included in the analysis of the literature. Important study characteristics and results are summarized in the evidence tables and the assessment of the risk of bias is summarized in the risk of bias tables

(‘Appendices to modules’). Six studies were found that had the correct patient population and intervention group, but no control group, or no ICM or GBCA. These studies are briefly described in Table 2.1. Since the studies do not answer the search question, no quality of evidence analysis or evidence tables have been made for them.

  1. 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.
  2. Atwell TD, Lteif AN, Brown DL, McCann M, Townsend JE, Leroy AJ. Neonatal thyroid function after administration of IV iodinated contrast agent to 21 pregnant patients. AJR Am J Roentgenol. 2008; 191(1): 268-271.
  3. Bird ST, Gelperin K, Sahin L, Bleich KB, Fazio-Eynullayeva E, Woods C, Radden E, Greene P, McCloskey C, Johnson T, Shinde M, Krefting I. First-trimester exposure to gadolinium- based contrast agents: a utilization study of 4.6 million U.S. pregnancies. Radiology. 2019; 293(1): 193-200.
  4. Bourjeily G, Chalhoub M, Phornphutkul C, Alleyne TC, Woodfield CA, Chen KK. Neonatal thyroid function: effect of a single exposure to iodinated contrast medium in utero. Radiology. 2010; 256(3): 744-750.
  5. Chen MM, Coakley FV, Kaimal A, Laros RK Jr. Guidelines for computed tomography and magnetic resonance imaging use during pregnancy and lactation. Obstet Gynecol. 2008; 112(2 Pt 1): 333-340.
  6. De Santis M, Straface G, Cavaliere AF, Carducci B, Caruso A. Gadolinium periconceptional exposure: pregnancy and neonatal outcome. Acta Obstet Gynecol Scand. 2007; 86(1): 99-101.
  7. European Society of Urogenital Radiology Contrast Media Safety Committee. ESUR Guidelines on contrast safety, v10. 2018. Available at: [URL] Accessed: 17 April 2022.
  8. Han BH, Lee KS, Han JY, Choi JS, Ahn HK, Ryu HM, Yang JH, Han HW, Nava-Ocampo AA. Pregnancy outcome after 1st-trimester inadvertent exposure to barium sulphate as a contrast media for upper gastrointestinal tract radiography. J Obstet Gynaecol. 2011; 31(7): 586-588.
  9. Jabehdar Maralani P, Kapadia A, Liu G, Moretti F, Ghandehari H, Clarke SE, Wiebe S, Garel J, Ertl-Wagner B, Hurrell C, Schieda N. Canadian Association of Radiologists recommendations for the safe use of MRI during pregnancy. Can Assoc Radiol J. 2022; 73(1): 56-67.
  10. Kochi MH, Kaloudis EV, Ahmed W, Moore WH. Effect of in utero exposure of iodinated intravenous contrast on neonatal thyroid function. J Comput Assist Tomogr. 2012; 36(2): 165-169.
  11. Lin SP, Brown JJ. MR contrast agents: physical and pharmacologic basics. J Magn Reson Imaging. 2007; 25(5): 884-899.
  12. Little JT, Bookwalter CA. Magnetic resonance safety: Pregnancy and lactation. Magn Reson Imaging Clin N Am. 2020; 28(4): 509-516.
  13. Lum M, Tsiouris AJ. MRI safety considerations during pregnancy. Clin Imaging. 2020; 62: 69- 75.
  14. Morisetti A, Tirone P, Luzzani F, de Haën C. Toxicological safety assessment of iomeprol, a new X-ray contrast agent. Eur J Radiol. 1994; 18 (Suppl 1): S21-S31.
  15. Novak Z, Thurmond AS, Ross PL, Jones MK, Thornburg KL, Katzberg RW. Gadolinium-DTPA transplacental transfer and distribution in fetal tissue in rabbits. Invest Radiol. 1993; 28(9): 828-830.
  16. Okuda Y, Sagami F, Tirone P, Morisetti A, Bussi S, Masters RE. [Reproductive and developmental toxicity study of gadobenate dimeglumine formulation (E7155) (3)-- Study of embryo-fetal toxicity in rabbits by intravenous administration]. J Toxicol Sci. 1999; 24 (Suppl 1): 79-87.
  17. 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.
  18. Rajaram S, Exley CE, Fairlie F, Matthews S. Effect of antenatal iodinated contrast agent on neonatal thyroid function. Br J Radiol. 2012; 85(1015): e238-e242.
  19. Royal Australian and New Zealand College of Radiologists. RANZCR Iodinated Contrast Guidelines, v2.3. 2018. Available at: [URL] Accessed: 17 April 2022.
  20. Ray JG, Vermeulen MJ, Bharatha A, Montanera WJ, Park AL. Association between MRI exposure during pregnancy and fetal and childhood outcomes. JAMA. 2016; 316(9): 952-961.
  21. Royal College of Radiologists. Guidance on gadolinium-based contrast agent administration to adult patients. April 2019. Available at: [URL]. Accessed: 17 April 2022.
  22. Spencer JA, Tomlinson AJ, Weston MJ, Lloyd SN. Early report: comparison of breath-hold MR excretory urography, Doppler ultrasound, and isotope renography in evaluation of symptomatic hydronephrosis in pregnancy. Clin Radiol. 2000; 55(6): 446-453.
  23. 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.
  24. Van Welie N, Portela M, Dreyer K, Schoonmade LJ, van Wely M, Mol BWJ, van Trotsenburg ASP, Lambalk CB, Mijatovic V, Finken MJJ. Iodine contrast prior to or during pregnancy and neonatal thyroid function: a systematic review. Eur J Endocrinol. 2021; 184(1): 189-198.
  25. 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.
  26. 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): 1234-1240.
  27. Webb JA, Thomsen HS. Gadolinium contrast media during pregnancy and lactation. Acta Radiol. 2013; 54: 599-600.
  28. Winterstein AG, Thai TN, Nduguba S, Smolinski NE, Wang X, Sahin L, et al. Risk of fetal/neonatal death or neonatal intensive care unit admission associated with gadolinium magnetic resonance imaging exposure during pregnancy. Am J Obstet Gynecol. 2022 Oct 11:S0002-9378(22)00809-2. doi: 10.1016/j.ajog.2022.10.005.

Autorisatiedatum en geldigheid

Laatst beoordeeld  : 28-11-2022

Laatst geautoriseerd  : 28-11-2022

Geplande herbeoordeling  :


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.

Initiatief en autorisatie

  • Nederlandse Vereniging voor Radiologie
Geautoriseerd door:
  • Nederlandse Internisten Vereniging
  • Nederlandse Vereniging van Maag-Darm-Leverartsen
  • Nederlandse Vereniging voor Cardiologie
  • Nederlandse Vereniging voor Heelkunde
  • Nederlandse Vereniging voor Neurologie
  • Nederlandse Vereniging voor Obstetrie en Gynaecologie
  • Nederlandse Vereniging voor Radiologie
  • Nederlandse Vereniging voor Klinische Chemie en Laboratoriumgeneeskunde
  • Patiëntenfederatie Nederland
  • Nederlandse Vereniging voor Allergologie en Klinische Immunologie
  • Nederlandse Vereniging voor Endocrinologie
  • Nederlandse Vereniging voor Vaatchirurgie

Algemene gegevens

General Information

The Kennisinstituut van de Federatie Medisch Specialisten ( 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


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 ( and were summarised below.


Last name


Other positions

Personal financial


Personal relations

Reputation management

Externally financed


Knowledge valorisation

Other interests



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







Received consultancy fees from Guerbet, 2019-


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


Member of contrast media safety

committee, European

Society of Urogenital

Radiology (no payment)







April 11th, 2020, Reaffirmed October 12th,


No restrictions

Houwen T, van der

Internist - Immunologist - Allergologist, Amsterdam UMC, also seconded allergologist in Huid Medisch









July 11th, 2022 Reaffirmed October 12th, 2022

No restrictions

Kerstens MN

Internist- endocrinologist, UMCG

Chairman Bijniernet (no payment)







July 1st, 2020, reaffirmed October 25th,


No restrictions

Krabbe JG

Clinical chemist, Medisch Spectrum Twente








September 1st, 2020,

Reaffirmed October 13th, 2022

No restrictions

Luijtgaarden KM, van de

Vascular surgeon, Maasland Ziekenhuis








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



Member, Gadolinium Research and Education Committee, European Society of Magnetic Resonance in Medicine, and Biology (no







Received consultancy fees from Guerbet, 2019-


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)







April 7th, 2020, Reaffirmed October 13th,


No restrictions

Uyttenboogaart M

Neurologist and neuro- interventionalist UMCG

Advisor International Federation of Orthopaedic Manipulative Physical Therapist / Nederlandse Vereniging Manuele Therapie



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


Work package leader CONTRAST

(Consortium of New Treatments in Acute Stroke): WP8 Stroke logistics and Epidemiology



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-








April 7th, 2020, Reaffirmed October 19th, 2022

No restrictions

Wolk S, van der

Gynaecologist- obstetrician, Haga Ziekenhuis








June 30th, 2021, reaffirmed October 25th,


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 ( In addition, patient information on safe use of contrast media in pregnancy and lactation was developed for, a platform to inform patients about health and disease.



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’.




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 ( This report is based on the AGREE II instrument (Appraisal of Guidelines for Research & Evaluation II) (, a broadly accepted instrument in the international community and based on the national quality standards for guidelines: “Guidelines for guidelines” (


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 (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 (


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.



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 ( 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.



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.

Zeldzame ziekten