Monitoring of Thyroid Function after Administration of Iodine-based Contrast Media
Uitgangsvraag
Moet bij kinderen na toediening van een jodiumhoudend contrastmiddel de schildklierfunctie gemonitord worden?
Aanbeveling
Controleer schildklierfunctie (TSH-meting) 2 weken na toediening van intravasculair of gastro-intestinaal jodiumhoudend contrast, bij alle prematuur geboren kinderen (zwangerschapsduur < 37 weken) onder de leeftijd van 3 maanden.
Controleer schildklierfunctie (TSH-meting) 2 weken na toediening van intravasculair jodiumhoudend contrast, bij a term geboren kinderen (zwangerschapsduur ≥ 37 weken) onder de leeftijd van 3 maanden in geval van risicofactoren zoals dysmaturiteit (geboortegewicht voor zwangerschapsduur < -2 SDS), ernstige ziekte, nierinsufficiëntie, cardiale aandoening en in geval van langdurige/veelvuldige blootstelling aan jodiumhoudend contrast zoals bij coronaire CT angiografie en nierdialyse.
Overweeg controle van schildklierfunctie (TSH-meting) 2 weken na toediening van intravasculair jodiumhoudend contrast bij kinderen tussen de leeftijd van 3 maanden en 3 jaar in geval van risicofactoren zoals ernstige ziekte, nierinsufficiëntie, cardiale aandoening en in geval van langdurige/veelvuldige blootstelling aan jodiumhoudend contrast zoals bij coronaire CT angiografie en nierdialyse.
Interpretatie TSH-concentratie:
- TSH ≤ 5 mE/l: geen actie, tenzij het een zeer prematuur kind betreft met een berekende leeftijd van < 32 weken amenorroe duur ten tijde van de bloedafname. Herhaal in dat geval de TSH-meting na 1 week.
- TSH > 5 en ≤ 10 mE/l: herhaal TSH met vrijT4 meting na 1 week
- TSH > 10 en ≤ 20 mE/l: meet vrijT4. Een lage vrij T4 concentratie wijst op hypothyreoïdie en is een behandelindicatie. Overleg met kinderarts-endocrinoloog.*
- TSH > 20 mE/l: meet vrijT4 en start behandeling in overleg met kinderarts-endocrinoloog.*
*Interpretatie van vrij T4 wordt bemoeilijkt door transiënte hypothyroxinemie van prematuren, “non-thyroidal illness” en gebrek aan leeftijdsspecifieke referentie intervallen. Overleg met kinderarts-endocrinoloog wordt geadviseerd voordat met behandeling wordt gestart.
Overwegingen
Advantages and disadvantages of the intervention and quality of evidence
Thyroid hormone is essential for normal brain development in children, especially in the first three years of life. It is well known that untreated congenital hypothyroidism leads to neurodevelopmental problems and that timely treatment initiated within the first weeks of life prevents these developmental problems. Since exposure to ICM may lead to prolonged hypothyroidism the goal of thyroid function monitoring after the use of iodine-based contrast media (ICM) is the prevention of neurodevelopmental delay. However, studies designed to answer the question whether monitoring of thyroid function and the subsequent thyroid hormone supplementation in children exposed to ICM leads to better neurodevelopmental outcome are missing.
A systematic literature search based on the abovementioned did not result in any articles meeting the inclusion criteria. Nine studies were excluded because of missing control groups as defined in the PICO or having a design (and thus population) focused on a different question than the search question. However, these nine studies did report thyroid function monitoring after the use of ICM and are described in table 1.
The studies of Gilligan (2021) and Rath (2019) included a non-iodine exposed control group. Gilligan (2021) compared 114 children £ 24 months with either a single ICM enhanced CT (57 exposed cases) or an abdominal ultrasound (57 unexposed cases) and found no differences in TSH levels measured within three months after imaging. Rath (2019) performed a randomized controlled trial comparing 20 preterm infants receiving iodinated contrast to 21 preterm infants receiving only saline to ascertain peripherally inserted central catheter tip position. No differences in thyroid function were found.
Williams (2016) studied 173 preterm infants (<32 weeks) with exposure to either iodinated contrast or topical iodine during caesarian section and reported thyroid dysfunction mainly in the topical exposure group. The remaining six studies all included cardiac patients undergoing either cardiac CT, angiography, or catheterization. Age groups varied from preterm to eight years. Belloni (2018) reported only transient TSH decrease while the other studies reported hypothyroidism in varying frequencies and duration. Reported rates were highest in infants under three months of age (Jick 2018), low-weight and premature infants (Rosenberg 2018) and in case of renal impairment and multiple iodine exposures (Thaker 2017).
Since these studies include variable age groups, different ICMs, and variable follow-up they do not sufficiently answer the search question.
In 2009 Ahmet and coworkers performed a systematic review in order to determine whether neonates exposed to iodinated contrast media are at risk of hypothyroidism (Ahmet, 2009). They included 11 studies, published between 1986-2000. These were older studies not included in our search. These 11 studies included 182 hospitalized neonates (72 term born, 110 preterm born) exposed to iodinated contrast. Six out of 72 (8.2%) exposed term infants were treated for hypothyroidism and 20 out of 110 (18.2%) exposed preterm infants. The authors concluded that hospitalized neonates exposed to ICM are at risk for abnormal thyroid function and hypothyroidism and that premature infants might be at increased risk. However the studies were however highly affected by bias calling for well-controlled studies.
In the various studies the reported prevalence of hypothyroidism after the use of ICM ranges from 1 to 15%. Overall children in the first three months of life seem most at risk of developing thyroid dysfunction after exposure to ICM. More specifically at high risk seem to be premature neonates, low-birth weight neonates and critically ill infants. Also, renal impairment, cardiac disease, and prolonged/frequent exposure to ICM such as during cardiac bypass and dialysis are risk factors.
An important unanswered question is whether infants between 3 months and 3 years are at risk of developing hypothyroidism after exposure to ICM. Also, whether this is dose dependent and what the duration of the hypothyroidism is and whether this would affect neurodevelopment if left untreated.
Most studies focus on the use of intravascular ICM in neonates, but iatrogenic hypothyroidism has also been described after enteral and lymphatic ICM exposure (Putnins, 2020; Cherella, 2018; Lombard, 2009, Ares 2008).
Since enteral ICM is regularly used in (premature) newborns with congenital intestinal diseases, this may lead to a high uptake of iodine in the blood system of this vulnerable patient group, particularly in case of prolonged stasis in children with intestinal obstruction (own observation, manuscript in preparation).
Although the causal relationship is not definitive, but with incidental cases of prolonged hypothyroidism after enteral ICM administration having been reported, we advise thyroid function monitoring in preterm infants exposed to intravascular and enteral administration of ICM (Putnins 2020; Lombard, 2009, Ares, 2008). Future studies need to investigate the effect on thyroid function of various modes of administration of ICM, with proper control groups not receiving ICM.
The use of ICM prior to or during pregnancy may also affect neonatal thyroid function. A systematic review on neonatal thyroid function after the use of maternal ICM found a tendency towards an increased risk for hypothyroidism especially in case of higher doses (van Welie 2021). Most ICM are water-soluble and readily cleared from the body. Lipid-based ICM have a delayed excretion. Lipid-based ICM are used for hysterosalpingography but does not seem to affect neonatal thyroid function (Mathews 2023; van Welie 2020).
In March 2022 the FDA issued a drug safety communication recommending thyroid function monitoring of children under three years of age within three weeks of intravascular administration of iodine-based contrast media (FDA, 2022). In a reaction to this recommendation the Pediatric Endocrine Society (PES) and American College of Radiology (ACR) published statements questioning this recommendation due to lack of sufficient evidence (PES 2022). Based on this criticism the FDA issued a revised statement in June 2023 (FDA, 2023).
In the revised statement the FDA states “…decisions about thyroid monitoring following administration to children 3 years and younger should be individualized based on each child’s risk factors. These risk factors may include prematurity, very low birth weight, and underlying medical conditions affecting thyroid function.”
In view of the lack of well-designed studies in this field and to prevent conflicting statements as much as possible, we decided to adopt several of the PES guideline recommendations (PES, 2022).
Screening for primary hypothyroidism consists of a single TSH measurement, included in the guideline. It is important to realize that due to immaturity of the hypothalamic-pituitary axis TSH rise in case of overt hypothyroidism may be delayed or even absent in premature infants, especially in very low birth weight infants (< 32 weeks’ gestation and/or < 1500 grams). This means screening with TSH may miss hypothyroidism in these cases. In addition, premature infants have lower thyroid hormone levels than term born infants (transient hypothyroxinemia of prematurity) and critical illness reduces thyroid hormone concentrations, so-called non-thyroidal illness. These factors make it difficult to certify whether exposure to ICM is the actual cause of the hypothyroidism in hospitalized ill infants.
Patient (and their caretakers) values and preferences
Patients, parents/caretakers and health care professionals want to make decisions based on the best available evidence. A similar case should get equal advice/treatment. The recent FDA advice about monitoring thyroid functioning after iodinated contrast administration makes it necessary to formulate guidelines on whether children in the Netherlands should be monitored. This guideline defines which patients are at increased risk of hypothyroidism after exposure to ICM and provides recommendations on how to apply thyroid monitoring for these populations.
The main benefit of monitoring thyroid functioning is that physicians can identify cases of hypothyroidism that require treatment with daily levothyroxine supplementation to prevent potential brain damage. Monitoring itself involves additional TSH measurements for 2 to 3 weeks after administration of ICM. The populations specified in this guideline are most likely inpatients at neonatology and intensive care wards and are expected to be undergoing frequent blood withdrawals. Blood tests for thyroid monitoring can be combined with other necessary blood tests. The burden of daily levothyroxine supplementation and regular blood withdrawals is considered acceptable in view of the importance of preventing hypothyroxinemia induced brain damage.
In infants and young children pain prevention during blood withdrawal is practiced by the use of local agents such as EMLA or lidocaine and if necessary help of a pedagogical assistant
Costs
Most neonates and infants receiving ICM and at risk for developing prolonged hypothyroidism will most likely be inpatients at neonatology and intensive care wards and are expected to be undergoing frequent blood tests. The costs of an extra blood test are low and may be combined with blood testing for another indication. The costs of levothyroxine supplementation are also low. These relatively low costs are considered acceptable given the importance of preventing hypothyroxinemia-induced brain damage. Since hypothyroxinemia-induced brain damage is associated with significant additional healthcare costs over a longer period, early detection and treatment of cases have the potential to reduce associated health costs.
Acceptance, feasibility and implementation
The monitoring itself requires TSH measurements for 2 to 3 weeks after exposure to ICM, which is currently not standard practice. However, only a small group of children at increased risk of hypothyroidism will require thyroid function monitoring. Early detection of thyroid dysfunction and prevention of hypothyroxinemia-induced brain damage by implementing relatively cheap and easy to administer drugs has clear health benefits. Furthermore, the population at-risk identified in this guideline are often inpatients at neonatology and intensive care wards with frequent blood tests. Thus, for most cases monitoring does not require additional handling. Therefore, the guideline development group does not expect obstructions in terms of acceptance, feasibility and implementation.
The guideline development group advice is to include a reference to this guideline in the radiology report when ICM is used in a child younger than 3 years (since all risk groups defined in this guideline are younger than 3 years).
Rationale of the recommendation: weighing arguments for and against the interventions
Given the importance of thyroid hormone for normal brain development it is necessary to prevent prolonged periods of hypothyroidism in children especially in the first 3 years of life.
To prevent hyperthyroidism in the case of excess iodine exposure the thyroidal Wolff-Chaikoff effect temporarily downregulates thyroid hormone production. After a few weeks an escape from the Wolff-Chaikoff effect occurs and thyroid hormone production is restored. However, prolonged hypothyroidism may occur when the escape from the Wolff-Chaikoff effect fails. Preterm born infants are particularly vulnerable to the suppressive effects of excess iodine due to immaturity of the thyroid gland and inability to escape from the Wolff-Chaikoff effect.
Overall, there is consensus in the field based on earlier studies that children in the first 3 months of life are most at-risk of developing thyroid dysfunction after exposure to ICM in particular:premature neonates, low-birth weight neonates and critically ill infants. Also, renal impairment, cardiac disease, and prolonged/frequent exposure to ICM such as during cardiac bypass and dialysis pose as risk factors.
It remains unclear whether infants between 3 months and 3 years are at risk of developing prolonged hypothyroidism after exposure to ICM and whether this would affect neurodevelopment if left untreated.
Given the long-lasting and debilitating effect of hypothyroxinemia-induced brain damage and the relatively low-cost easy-to-implement treatment, the recommendation is to also consider thyroid function measurement in children with the specified risk factor aged 3 months to 3 years.
Onderbouwing
Achtergrond
Iodine is essential for thyroid hormone synthesis, and excess iodine exposure may affect thyroid hormone levels. The use of iodine-based contrast media (ICM) for radiological studies leads to excess iodine exposure. In this context it is important to realize that only free iodide is available for uptake by the thyroid gland. ICM mainly contain organically bound iodine that is excreted in the urine unchanged and will not affect thyroid function. However ICM also contain small amounts of free iodide. This concentration varies between different ICM solutions and is batch-dependent with a longer shelf-life leading to a higher free iodine content (van der Molen 2004).
To prevent hyperthyroidism in the case of such excess iodine exposure the thyroid gland temporarily downregulates thyroid hormone production. This is called the Wolff-Chaikoff effect. Within a few days an escape from the Wolff-Chaikoff effect occurs and thyroid hormone production is usually restored to normal within 2 weeks. However, prolonged hypothyroidism may occur when the escape from the Wolff-Chaikoff effect fails. This has been well described in patients with pre-existing thyroid disease. In the fetal period, the thyroid gland is not mature enough to escape from the Wolff-Chaikoff effect until approximately 36 weeks of gestation. This makes the fetus and (premature) neonate particularly vulnerable to the suppressive effects of excess iodine (Lee, 2015). Various studies have shown that intravascular ICM administration reduces thyroid hormone levels in neonates and causes prolonged hypothyroidism. A systematic review including 11 studies with a total of 182 hospitalized neonates exposed to ICM reported hypothyroidism in 8.2% of term infants and 18.2% of premature infants (Ahmet, 2009).
Brain development is critically dependent on thyroid hormone in the first three years of life and therefore prolonged periods of hypothyroidism in infants and young children should be prevented (van Trotsenburg 2021).
In March 2022 the FDA issued a drug safety communication recommending thyroid function monitoring within 3 weeks of intravascular administration of iodine-based contrast media in all children up to 3 years of life. In a reaction to this recommendation the Pediatric Endocrine Society (PES) and American College of Radiology (ACR) published statements questioning this recommendation due to lack of sufficient evidence and proposed a more individualized approach, identifying patient groups who are most at-risk.
In this part of the guideline we address the question whether routine thyroid function monitoring after the use of ICM in children is necessary.
Conclusies / Summary of Findings
|
- GRADE |
No evidence was found regarding the effects of thyroid monitoring in children (<18 years of age) undergoing radiological examinations with intravascular iodine-containing contrast agents on hypothyroidism. |
|
- GRADE |
No evidence was found regarding the effects of thyroid monitoring in children (<18 years of age) undergoing radiological examinations with intravascular iodine-containing contrast agents on hyperthyroidism. |
|
- GRADE |
No evidence was found regarding the effects of thyroid monitoring in children (<18 years of age) undergoing radiological examinations with intravascular iodine-containing contrast agents on irreversible effects of thyroid dysfunction on neurodevelopment of child. |
Samenvatting literatuur
No studies fulfilled our PICO criteria. Therefore, no evidence tables, risk of bias assessment and quality assessment were performed for the studies mentioned in Supplemental Table 1.
Zoeken en selecteren
A systematic review of the literature was performed to answer the following question:
What are the results of thyroid function monitoring after the use of iodinated contrast media in children (<18 years) undergoing radiological examinations?
| P(atients): | Children (<18 years) undergoing radiological examinations with iodinated contrast media (ICM); |
| I(ntervention): | Monitoring of thyroid function after ICM administration. |
| C(ontrol): | No monitoring of thyroid function after ICM administration. |
| O(utcome): |
Hypothyroidism, hyperthyroidism, irreversible effects of thyroid dysfunction on neurological development. |
Relevant outcome measures
The guideline development group considered hypothyroidism and hyperthyroidism as critical outcome measures for decision making; and irreversible effects of thyroid dysfunction on neurodevelopment of children as an important measure for decision making.
A priori, the guideline development group did not define the outcome measures listed above but used the definitions used in the studies.
Per outcome the guideline development group defined the following differences as minimal clinically (patient) important differences:
- Hypothyroidism: RR ≤0.8 or ≥1.25 (dichotomous); 0.5 SD (continuous)
- Hyperthyroidism: RR ≤0.8 or ≥1.25 (dichotomous); 0.5 SD (continuous)
- Irreversible effects of thyroid dysfunction on neurodevelopment of child: RR ≤0.8 or ≥1.25 (dichotomous); 0.5 SD (continuous)
Search and select (Methods)
The databases Medline (via OVID) and Embase (via Embase.com) were searched with relevant search terms from 2000 until 24-07-2023. The detailed search strategy is depicted under the tab Methods. The systematic literature search resulted in 85 hits. Studies were selected based on the following criteria:
- Systematic review, randomized controlled trial or observational research comparing thyroid monitoring to no monitoring in children receiving intravascular iodine-containing contrast.
- Children (<18 years) who underwent radiological examination with iodine-containing contrast media (ICM);
- At least one of the outcome measures was described: hypothyroidism, hyperthyroidism.
- Full-text English language publication.
12 studies were initially selected based on title and abstract screening. After reading the full text, all studies were excluded (see the table with reasons for exclusion under the tab Methods).
Results
Since no studies fulfilled the PICO criteria it was not possible to perform a systematic analysis of the literature. Nine studies did have the correct patient population and performed thyroid function monitoring after the use of iodine-containing contrast. These studies are briefly described in Supplemental Table 1. Since these studies include variable age groups, variable iodine-containing contrast substances and variable follow-up they do not answer the search question, and no quality of evidence analysis or evidence tables were made.
Referenties
- Ahmet, A., Lawson, M. L., Babyn, P., & Tricco, A. C. (2009). Hypothyroidism in neonates post-iodinated contrast media: a systematic review. Acta Paediatrica (Oslo, Norway : 1992), 98(10), 1568-1574.
- Ares SS, de Pipaón Marcos MS, Ruiz-Díaz AI, de Escobar GM, Quero JJ. Hypothyroidism and high plasma and urine iodine levels related to the use of gastrografin. Current Pediatric Reviews. 2008;4:194-197.
- Barr, M. L., Chiu, H. K., Li, N., Yeh, M. W., Rhee, C. M., Casillas, J., Iskander, P. J., & Leung, A. M. (2016). Thyroid Dysfunction in Children Exposed to Iodinated Contrast Media. The Journal of Clinical Endocrinology and Metabolism, 101(6), 2366-2370.
- Belloni, E., Tentoni, S., Puci, M. V., Avogliero, F., Della Latta, D., Storti, S., Alberti, B., Bottoni, A., Bortolotto, C., Fiorina, I., Montomoli, C., & Chiappino, D. (2018). Effect of iodinated contrast medium on thyroid function: a study in children undergoing cardiac computed tomography. Pediatric Radiology, 48(10), 1417-1422.
- Cherella CE, Breault DT, Thaker V, Levine BS, Smith JR. Early Identification of Primary Hypothyroidism in Neonates Exposed to Intralymphatic Iodinated Contrast: A Case Series. J Clin Endocrinol Metab. 2018;103(10):3585-3588.
- Dechant, M. J., van der Werf-Grohmann, N., Neumann, E., Spiekerkoetter, U., Stiller, B., & Grohmann, J. (2016). Thyroidal response following iodine excess for cardiac catheterisation and intervention in early infancy. International Journal of Cardiology, 223, 1014-1018.
- FDA (2022). Iodine-Containing Contrast Media: Drug Safety Communication - FDA Recommends Thyroid Monitoring in Babies and Young Children Who Receive Injections of Iodine-Containing Contrast Media for Medical Imaging.
- FDA (2023). FDA Drug Safety Communication: FDA recommends thyroid monitoring in babies and young children who receive injections of iodine-containing contrast media for medical imaging.
- Gilligan, L. A., Dillman, J. R., Su, W., Zhang, B., Chuang, J., & Trout, A. T. (2021). Primary thyroid dysfunction after single intravenous iodinated contrast exposure in young children: a propensity score matched analysis. Pediatric Radiology, 51(4), 640-648.
- Jick, S. S., Hedderson, M., Xu, F., Cheng, Y., Palkowitsch, P., & Michel, A. (2019). Iodinated Contrast Agents and Risk of Hypothyroidism in Young Children in the United States. Investigative Radiology, 54(5), 296-301.
- Kubicki, R., Grohmann, J., Kunz, K. G., Stiller, B., Schwab, K. O., & van der Werf-Grohmann, N. (2020). Frequency of thyroid dysfunction in pediatric patients with congenital heart disease exposed to iodinated contrast media - a long-term observational study. Journal of pediatric endocrinology & metabolism : JPEM, 33(11), 1409-1415.
- Lee SY, Rhee CM, Leung AM, Braverman LE, Brent GA, Pearce EN. A Review: Radiographic Iodinated Contrast Media-Induced Thyroid Dysfunction, The Journal of Clinical Endocrinology & Metabolism. 2015;100(2) 376-383,
- Lombard F, Dalla-ValeF, Veyrac C, Plan O, Cambonie G, Picaud JC. Severe hypothyroidism after contrast enema in premature infants. Eur J Pediatr. 2018;168:499-500.
- Mathews DM, Peart JM, Sim RG, O'Sullivan S, Derraik JGB, Heather NL, Webster D, Johnson NP, Hofman PL. The impact of prolonged, maternal iodine exposure in early gestation on neonatal thyroid function. Front Endocrinol (Lausanne). 2023;14:1080330. doi: 10.3389/fendo.2023.1080330.
- van der Molen AJ, Thomsen HS, Morcos SK. Effect of iodinated contrast media on thyroid function in adults. Eur Radiol. 2014;14:902-907.
- Pediatriac Endocrine Society (PES) (2022). PES Statement on Thyroid Monitoring in Infants and Young Children Receiving Iodine-Containing Contrast Media.
- Putnins R, Ahmet A, Rigby C, Miller E. Risk of Hypothyroidism After Administration of Iodinated Contrast Material in Neonates: Are You Aware? Can Assoc Radiol J. 2021;72(2):192-193.
- Rath, C. P., Thomas, M., Sullivan, D., & Kluckow, M. (2019). Does the use of an iodine-containing contrast agent to visualise the PICC tip in preterm babies cause hypothyroidism? A randomised controlled trial. Archives of Disease in Childhood. Fetal and neonatal edition, 104(2), F212F214.
- Rosenberg, V., Michel, A., Chodick, G., Cheng, Y., Palkowitsch, P., Koren, G., & Shalev, V. (2018). Hypothyroidism in Young Children Following Exposure to Iodinated Contrast Media: An Observational Study and a Review of the Literature. Pediatric Endocrinology Reviews : PER, 16(2), 256-265.
- Thaker, V. V., Galler, M. F., Marshall, A. C., Almodovar, M. C., Hsu, H. W., Addis, C. J., Feldman, H. A., Brown, R. S., & Levine, B. S. (2017). Hypothyroidism in Infants With Congenital Heart Disease Exposed to Excess Iodine. Journal of the Endocrine Society, 1(8), 1067-1078.
- van Trotsenburg P, Stoupa A, Léger J, Rohrer T, Peters C, Fugazzola L, Cassio A, Heinrichs C, Beauloye V, Pohlenz J, Rodien P, Coutant R, Szinnai G, Murray P, Bartés B, Luton D, Salerno M, de Sanctis L, Vigone M, Krude H, Persani L, Polak M. Congenital Hypothyroidism: A 2020-2021 Consensus Guidelines Update-An ENDO-European Reference Network Initiative Endorsed by the European Society for Pediatric Endocrinology and the European Society for Endocrinology. Thyroid 2021;31(3):387-419.
- 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. European Journal of Endocrinology. 2021;184:189-198.
- van Welie N, Roest I, Portela M, van Rijswijk J, Koks C, Lambalk CB, Dreyer K, Mol BWJ, Finken MJJ, Mijatovic V; H2Oil Study Group. Thyroid function in neonates conceived after hysterosalpingography with iodinated contrast. Hum Reprod. 2020;35(5):1159-1167. doi: 10.1093/humrep/deaa049.
- Williams, F. L., Watson, J., Day, C., Soe, A., Somisetty, S. K., Jackson, L., Velten, E., & Boelen, A. (2017). Thyroid dysfunction in preterm neonates exposed to iodine. Journal of Perinatal edicine, 45(1), 135-143. https://doi.org/10.1515/jpm-2016-0141
Evidence tabellen
Not applicable for this module
Summary of literature that does not answer search question, but includes relevant information for the considerations.
Table 1
Table 1: Brief description of studies that (1) have the same patient population group as the search question but no control group or (2) compare contrast exposure to non-contrast exposure in the context of thyroid dysfunction and thus have a different design and patient population than the search question (Gilligan 2016 and Rath 2019, highlighted in grey below).
|
Study name/design |
Patient population and number |
Type of contrast medium |
Results |
Other remarks |
|
Gilligan, 2021
Retrospective case study with control group |
N =114 Inpatients aged £ 24 months with single CT with ICM or abdominal US and TSH measurement within 90 days after imaging.
57 cases with single CT with ICM (exposed group) 57 cases with abdominal US (unexposed group)
|
Ioversol 320 (Optitray); dose varying between 1,5-2 mL/kg |
Frequency of TSH abnormalities: 8/57 (14%) in exposed group and 4/57 in unexposed group.
Univariable logistic regression: ICM exposure was not a significant predictor of thyroid dysfunction |
Authors’ conclusion: One dose of intravenous ICM likely does not cause prolonged TSH abnormalities; however, larger studies are needed. |
|
Rath, 2019
Prospective study with control group |
N = 41 preterm neonates <30 weeks and >48 hour old; median age 4 days.
Randomized to 0,3 mL of ICM (n=20) or normal saline (n=21) to ascertain certainty of peripherally inserted central catheter (PICC) tip position. Outcome: TSH and fT4 (mIU/L) measured 14 days post PICC insertion and on day 28 of life.
|
0,3mL of Iopamidol containing 300mg iodine/ mL. |
14 days post PICC insertion:
On day 28 of life: TSH level (mIU/L) no contrast group: median 2,25 (IQR 1,2 to 3,3), contrast group: median 1,6 (IQR 0,9 to 3,1) for ICM group. |
Authors’ conclusion: “Use of contrast did not suppress subsequent thyroid function and helped visualize the PICC tip with more certainty.”
RCT for influence contrast exposure on TSH and central catheter tip position.
Comment: only study using ICM for insertion of PICC line. All other studies focus on ICM for cardiac imaging, with higher doses of ICM. |
|
Belloni, 2018
Retrospective |
N=33 Neonates with various congenital heart diseases who underwent iodinated contrast enhanced CT. 10 neonates, mean age 11,2 days. 23 infants/young children, mean age 316.26 days.
Monitoring TSH (mIU/l), fT3 (pg/ml) and fT4 (nmol/l) levels before, 48h after and at discharge from hospital after contrast-enhanced cardiac CT. |
Cardiac CT with IV iopromide administration (1,14±0,17 mL/kg body weight containing 370 mg of iodine/mL). |
Neonates: - Reduced median TSH levels from baseline (mean 10,68, SD 12.12, median 6,88), to 48h post injection (mean 0,77, SD 0,97, median 0,39). At discharge (mean 3,81, SD 2,39, median 3,14) TSH levels were increased compared to 48h, but not lower than baseline (not statistically significant). - No statistically significant differences in fT3 and fT4 levels.
Infants/ young children: - Reduced TSH levels from baseline (mean 2,81, SD 1,17, median 2,68) to 48h post injection (mean 0,88, SD 1,44, median 0,36). At discharge (mean 3,09, SD 2,25, median 2,86) the difference from baseline was not statistically significant. - Reduced fT3 levels from baseline (mean 3,38, SD 0,56, median 3,37) to 48h post injection (mean 2,21, SD 0,70, median 2,07). At discharge (mean 3,15, SD 0,85, median 3,20) levels were not statistically significant from baseline. - No statistically significant differences in fT4 levels. |
Authors’ conclusions: “Intravenous iodinated contrast medium in children with congenital heart disease caused transient thyroid-stimulating hormone decrease 48 h after CT, with thyroid-stimulating hormone returning to normal range at discharge.”
Retrospective observational study. |
|
Dechant, 2016
Prospective |
N=21 10 neonates, 11 infants exposed to iodine during cardiac catheterisation. Median age 30 days (1–180),
Monitoring TSH, fT3 and fT4 levels at four time points before and 3-5 days/ 12-16 days/ 21-35 days after contrast-enhanced cardiac CT.
|
More than 4 ml/kg body weight of iCM (Imeron 400 MCT, Bracco Imaging, Germany). The median administered dose of ICM was 6,8 ml/kg (range 4,5–14,9). |
At baseline, all patients were within normal levels. 3 to 5 days after catheterisation with ICM administration, there was a wide range of TSH values (median 5,01 μg/l, range 0,59–37,73). TSH, fT3 and fT4 levels fluctuated within normal range 6 neonates (60%) presented a TSH imbalance: 5 consistent with latent hypothyroidism; the 6th had a large drop in TSH with borderline-low fT3 and fT4 typical of non-thyroidal illness syndrome. On follow-up, all values returned to normal within a few days without any medical intervention. |
Authors’ conclusions: “Systemic iodine exposure during cardiac catheterization seems to be clinically well tolerated in early infancy. However, exposure to iodine has demonstrable but apparently reversible effects on thyroid hormones during a potentially important developmental period. The implications of this are unclear but warrant further investigation in larger cohorts.”
Single-center prospective observational study |
|
Jick, 2018
Retrospective |
N=2320 patients < 4 years old exposed to a diagnostic procedure with ICM between 2008 and 2016.
Children who within 1 year of ICM exposure had diagnoses based on ICD-9 or ICD-10-DM codes, low laboratory values for thyroid or received thyroid replacement therapy were identified as possible cases of hypothyroidism. All cases were confirmed by chart review. |
1780 (77%) had CT scans with ICM contrast, 544 children had left heart catheterizations including cardioangiography, ventriculography, and coronary angiography, 4 children had both a CT scan and heart catheterization. |
34 out of 2320 met the criteria for hypothyroidism based on ICD-codes. In ICM exposed patients the incidence density rate (IDR) was 1,33 per 1000 person months (CI95% 0,9 to 1,8). 24/34 cases transient and subclinical hypothyroidism. Higher IDRs were present for: (1) probable ICM induced cases (0,90 CI95% 0,58 to 1,33) compared with possible alternate etiology for their hypothyroidism (0,43 CI95% 0,23 to 0,74), (2) males (1,71 CI95% 1,12 to 2,50) versus females (0,86 CI95% 0,44 to 1,53), (3) children with hearth catheterization (2,73 CI95% 1,63 to 4,33) versus CT scan (0,91 CI95% 0,56 to 1,40) and (4) younger children <3 months old (2,61 CI95% 1,34 to 4,63), 3 months to <1 year (2,13 CI95% 1,09 to 3,78) and 1-4 years (0,82 CI95% 0,47 to 1,33). |
Authors’ conclusions: “Our finding of hypothyroidism in young children exposed to iodine contrast agents (1.33 per 1000 person months [95% confidence interval, 0.9–1.8]) is broadly consistent with the sparse literature on this outcome. Rates were highest in the youngest children (< 3 months of age)
Retrospective observational study based on ICD codes using medical records.
|
|
Kubicki, 2020
Retrospective |
N=104 (62 male) Aged 1 day to 8 years at inclusion, 24% neonates, 51% infants, 25% children with a median age of 104 days (0 to 8 years)
ICM for conventional angiography in cardiac catheterization (CC-A) or computed tomography angiography (CT-A).
Serum-levels of TSH, fT3 and fT4 were measured at baseline and after ICM (as part of routine screening). At least six months follow-up for incidence of thyroid dysfunction, median = 3 years. |
The mean cumulative ICM load was 6,6 ± 1,6 mL/kg,
75% of patients had more than one event of iodine exposure, mean frequency was three times per patient |
At baseline, all patients were within normal thyroidal levels. 88 patients remained euthyroid. 16 patients developed hypothyroidism (15,4%) after median 11,5 days after ICM exposure. 14 patients recovered, ten required therapy, four recovered spontaneously. 2 patients had long-lasting hypothyroidism, both died.
Patients with thyroid dysfunction had higher frequency of ICM exposure and thyroid disrupting medication. Also, critically ill patients. |
Authors’ conclusions: “The incidence of acquired hypothyroidism after iodine excess was 15.4%. However, most patients developed only transient hypothyroidism.”
Single-center retrospective observational study
Cause of hypothyroidism probably multifactorial in this patient group.
|
|
Rosenberg, 2018
Retrospective |
N= 843 0–3 year-old children exposed to ICM between 1998 and 2015. 816 with at least one year follow-up (461 male and median age 326 days) and 528 with weight data (median 8,9 kg IQR 6,1 to 11,1)). Hypothyroidism defined as either a coded diagnosis, TSH above norm, fT4 below norm, fT3 below norm or new use of thyroid hormone replacement therapy. |
775 children with one examination, usually cardio angiography (N= 481). |
11 children developed hypothyroidism in the year following ICM exposure (828 person years). The incidence rate per 1000 person-years was 13,28 (95% CI: 6,63 to 23,77). Median time between ICM exposure and hypothyroidism was 41 days (IQR 15 to 138). Children with hypothyroidism were exposed at a younger age (median 38 days versus median 329,5 days), had lower weight (median 5,63 kg versus 8,92 kg) and a higher proportion of children with cardio-angiography (10, 90,9% vs 471, 56,6%).
|
Authors’ conclusion: “The risk of ICM- induced hypothyroidism needs to be considered especially in young children with low weight, undergoing cardio-angiography examinations. Systematic monitoring of thyroid function should be conducted in this focused patient population to avoid potential adverse consequences on child development.”
Retrospective observational study |
|
Thaker, 2017
Retrospective |
N= 183 neonates < 1 month with congenital heart disease exposed to iodine during cardiac catheterization or surgery and with at least one TSH value available from routine heel-stick sampling (fT4 also assayed).
Hypothyroidism defined as elevated TSH (>20 mIU/L at 24 to 96 hours of age and >15 mIU/L at >96 hours of age by heel-stick sampling and >9,1 mIU/L at 1 to 20 weeks of age by serum testing). Median postnatal age of the infants on the day of their first procedure was 3 days, and the median gestational age was 38,7 weeks. |
Exposure to only cardiac catheterization in N=73 (40%), both cardiac catheterization and cardiac surgery in N= 89 (49%) and cardiac surgery only in 21 infants (11%).
Exposure period for neonates with hypothyroidism was defined as the period between the date of entry into the cohort and the date of diagnosis of hypothyroidism. Median time to diagnosis was 8.5 days, therefore the end of the exposure period for euthyroid neonates was 8 calendar days after the date of entry into the cohort.
Cumulative ICM dose was median 3,6 mL/kg (IQR 0,3 to 6,9) in hypothyroidism vs median 3,3 mL/kg (IQR 1,3 to 7,2) for euthyroid infants. |
46 infants (25%) developed hypothyroidism of which 18 neonates (39%), had TSH concentration >20 mIU/L.
20 of the 46 infants with hypothyroidism (43%) were treated with levothyroxine; 9 died, 7 successfully withdrawn at 3 years of age, 1 infant successfully discontinued after 26 days, 3 continued to receive through June 2017 (aged 4 years, 2 months; 4 years, 1 month; and 6 years, 8 months). Of the 26 infants who did not receive treatment with levothyroxine: 15 experienced spontaneous resolution of hypothyroidism (median time 15 days; range 4-367), 9 were lost to follow-up and 2 died before initiation of therapy.
Controlling for baseline cardiac risk, postnatal age, and gestational age, the OR was 4,22 (CI95% 1,61 to 11,05) for developing hypothyroidism in neonates with serum creatinine in the highest quartile (>0,9 mg/dL) and OR= 3, 65 (CI95% 1,48 to 9,02) in those who underwent more than three procedures. |
Authors’ conclusion: “Hypothyroidism in neonates with CHD exposed to excess iodine is associated with multiple procedures and impaired renal function. Routine serial monitoring of thyroid function in these neonates is warranted. Future studies should examine the association between hypothyroidism and neurocognitive function in this population.”
Single-center retrospective observational study based on medical records to examine the risk factors for the development of hypothyroidism. |
|
Williams, 2017
Prospective |
N= 173 Premature infants < 32 weeks’ gestation with serious congenital anomaly. 125 exposed to topical iodine or ICM of which 95 exposed to ICM only, 16 exposed to only topical iodine prior to C-section, 14 mixed exposure source. 48 unexposed to iodine
TSH and fT4 levels were measured on postnatal days 7, 14, 28 and at the equivalent of 36 weeks’ gestation from heel-prick blood. TSH levels ≥ 6 mU/L was the threshold for suspicion of thyroid dysfunction. Hypothyroidism was classified if treatment with Levothyroxine was required. Hyperthyrotropinaemia was classified for TSH levels between 10,1 and 19,9 mU/L. |
ICM was used for verification of central venous catheter position. Three ICM types: Optiray 300 (used for 15% population), Omnipaque 240/250 (used for 33% population) and Ultravist 300 (used for 52% of the population). Doses ranged from 0,2 to 1,0 mL per application, with a mode of 0,3 ml. 86 infants received a single ICM dose, 18 two doses and 4 infants received three doses. The median days for receipt of the 1st , 2nd and 3rd ICM doses were 3, 17 and 21 days, respectively. |
13/173 infants had TSH ≥ 6 mU/L 6/95 (6%) in group exposed to ICM only, 3/16(19%) in group exposed to topical iodine only and 4/48 in unexposed group.
No infant was diagnosed with hypothyroidism;
3 infants (all in exposed group) had transient hyperthyrotropinaemia that normalized by the 36th week.
Overall thyroid dysfunction incidence in exposed group 7,2%, in unexposed group 8,3%
Infants in topical iodine exposure group had significantly higher TSH and fT4 levels than unexposed infants |
Authors’ conclusion:” Neonatal thyroid dysfunction was seen following exposure to iodine via caesarean section but not via exposure to contrast media.”
Observational cohort study |
Abbreviations: IQR = interquartile range, ICM = iodine-based contrast media, OR = odds ratio, CI= confidence interval, TSH = thyroid stimulating hormone, fT3= free triiodothyronine, fT4= free thyroxine.
Table of excluded studies
|
Reference |
Reason for exclusion |
|
Ahmet, A., Lawson, M. L., Babyn, P., & Tricco, A. C. (2009). Hypothyroidism in neonates post-iodinated contrast media: a systematic review. Acta paediatrica (Oslo, Norway : 1992), 98(10), 1568–1574. https://doi.org/10.1111/j.1651-2227.2009.01412.x |
wrong publication type |
|
Barr, M. L., Chiu, H. K., Li, N., Yeh, M. W., Rhee, C. M., Casillas, J., Iskander, P. J., & Leung, A. M. (2016). Thyroid Dysfunction in Children Exposed to Iodinated Contrast Media. The Journal of clinical endocrinology and metabolism, 101(6), 2366–2370. https://doi.org/10.1210/jc.2016-1330 |
wrong population/ design (monitoring of thyroid function is not focus, not all children exposed to ICM) |
|
Belloni, E., Tentoni, S., Puci, M. V., Avogliero, F., Della Latta, D., Storti, S., Alberti, B., Bottoni, A., Bortolotto, C., Fiorina, I., Montomoli, C., & Chiappino, D. (2018). Effect of iodinated contrast medium on thyroid function: a study in children undergoing cardiac computed tomography. Pediatric radiology, 48(10), 1417–1422. https://doi.org/10.1007/s00247-018-4163-3 |
wrong design (no control population, monitoring of thyroid functioning is not focus) |
|
Dechant, M. J., van der Werf-Grohmann, N., Neumann, E., Spiekerkoetter, U., Stiller, B., & Grohmann, J. (2016). Thyroidal response following iodine excess for cardiac catheterisation and intervention in early infancy. International journal of cardiology, 223, 1014–1018. https://doi.org/10.1016/j.ijcard.2016.08.292 |
wrong design (no control population, monitoring of thyroid functioning is not focus) |
|
Gilligan, L. A., Dillman, J. R., Su, W., Zhang, B., Chuang, J., & Trout, A. T. (2021). Primary thyroid dysfunction after single intravenous iodinated contrast exposure in young children: a propensity score matched analysis. Pediatric radiology, 51(4), 640–648. https://doi.org/10.1007/s00247-020-04881-0 |
wrong design (comparing contrast exposure to non-contrast exposure, PICO about monitoring in contrast exposed group) |
|
Jick, S. S., Hedderson, M., Xu, F., Cheng, Y., Palkowitsch, P., & Michel, A. (2019). Iodinated Contrast Agents and Risk of Hypothyroidism in Young Children in the United States. Investigative radiology, 54(5), 296–301. https://doi.org/10.1097/RLI.0000000000000541 |
wrong design (no control population, monitoring of thyroid functioning is not focus) |
|
Kubicki, R., Grohmann, J., Kunz, K. G., Stiller, B., Schwab, K. O., & van der Werf-Grohmann, N. (2020). Frequency of thyroid dysfunction in pediatric patients with congenital heart disease exposed to iodinated contrast media - a long-term observational study. Journal of pediatric endocrinology & metabolism : JPEM, 33(11), 1409–1415. https://doi.org/10.1515/jpem-2020-0032 |
wrong design (no control population, monitoring of thyroid functioning is not focus) |
|
Lee, S. Y., Rhee, C. M., Leung, A. M., Braverman, L. E., Brent, G. A., & Pearce, E. N. (2015). A review: Radiographic iodinated contrast media-induced thyroid dysfunction. The Journal of clinical endocrinology and metabolism, 100(2), 376–383. https://doi.org/10.1210/jc.2014-3292 |
wrong study design, wrong publication type |
|
Rath, C. P., Thomas, M., Sullivan, D., & Kluckow, M. (2019). Does the use of an iodine-containing contrast agent to visualise the PICC tip in preterm babies cause hypothyroidism? A randomised controlled trial. Archives of disease in childhood. Fetal and neonatal edition, 104(2), F212–F214. https://doi.org/10.1136/archdischild-2017-314665 |
wrong design (comparing contrast exposure to non-contrast exposure, PICO about monitoring in contrast exposed group) |
|
Rosenberg, V., Michel, A., Chodick, G., Cheng, Y., Palkowitsch, P., Koren, G., & Shalev, V. (2018). Hypothyroidism in Young Children Following Exposure to Iodinated Contrast Media: An Observational Study and a Review of the Literature. Pediatric endocrinology reviews : PER, 16(2), 256–265. https://doi.org/10.17458/per.vol16.2018.hypothyroidism |
wrong design (no control population, monitoring of thyroid functioning is not focus) |
|
Thaker, V. V., Galler, M. F., Marshall, A. C., Almodovar, M. C., Hsu, H. W., Addis, C. J., Feldman, H. A., Brown, R. S., & Levine, B. S. (2017). Hypothyroidism in Infants With Congenital Heart Disease Exposed to Excess Iodine. Journal of the Endocrine Society, 1(8), 1067–1078. https://doi.org/10.1210/js.2017-00174 |
wrong design (monitoring thyroid functioning is not focus, but identification risk factors) |
|
Williams, F. L., Watson, J., Day, C., Soe, A., Somisetty, S. K., Jackson, L., Velten, E., & Boelen, A. (2017). Thyroid dysfunction in preterm neonates exposed to iodine. Journal of perinatal medicine, 45(1), 135–143. https://doi.org/10.1515/jpm-2016-0141 |
wrong design (comparing contrast exposure to non-contrast exposure, PICO about monitoring in contrast exposed group) |
Verantwoording
Autorisatiedatum en geldigheid
Laatst beoordeeld : 01-12-2024
Laatst geautoriseerd : 01-12-2024
Geplande herbeoordeling : 01-12-2027
Validity
The Radiological Society of the Netherlands (NVvR) will determine if this guideline (per module) is still valid and applicable around 2029. 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, asking for a revision of the guideline. The Radiological Society of the Netherlands is the owner of this guideline and therefore 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 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
A multidisciplinary guideline development group (GDG) was formed for the development of the guideline in 2022. 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 2022 until July 2024. The GDG is responsible for the complete text of this guideline.
Guideline development group
- de Graaf N. (Nanko), chair guideline development group, radiologist, Erasmus Medical Center, Rotterdam
- Den Dekker M.A.M. (Martijn), radiologist, Ziekenhuis ZorgSaam
- Emons J.A.M. (Joyce), paediatric allergist, Sophia Children’s Hospital, Erasmus Medical Center, Rotterdam
- Geenen R.W.F. (Remy), radiologist, Noordwest Ziekenhuisgroep, Alkmaar
- Jöbsis, J.J. (Jasper), paediatrician and nephrologist, Onze Lieve Vrouwe Gasthuis, Amsterdam
- Liebrand C.A. (Chantal), anaesthesiologist, Erasmus Medical Centre, Rotterdam
- Sloots C.E.J. (Pim), surgeon, Erasmus Medical Centre, Rotterdam
- Zwaveling-Soonawala N. (Nitash), paediatrician -endocrinologist, Amsterdam University Medical Center, Amsterdam.
Advisory group
- Doganer E.C. (Esen), Kind & Ziekenhuis, Patient representative
- Riedijk M.A. (Maaike), paediatrician and intensive care physician, Emma Hospital, Amsterdam University Medical Centre
- Van der Molen A.J. (Aart), radiologist, Leiden University Medical Centre, Leiden
Methodological support
• Houtepen L.C. (Lotte), advisor, Knowledge Institute of the Federation Medical Specialists
• Mostovaya I.M. (Irina), senior advisor, Knowledge Institute of the Federation Medical Specialists
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 is 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 |
|
De Graaf |
Radiologist, Erasmus Medical Centre Rotterdam, |
Board member of the Technology section, Netherlands. Far. for Radiology (unpaid) Board member Ned. Comm. Radiation dosimetry (NCS) (unpaid) |
None |
None |
None |
None |
None |
None |
July 14th, 2022
|
No restrictions. |
|
Geenen RWF |
Radiologist, Noordwest ziekenhuisgroep/medisch specialisten Noordwest |
Member of contrast media safety committee, European Society of Urogenital Radiology (no payment) |
None |
None |
None |
None |
None |
None |
September 2nd, 2022 |
No restrictions |
|
Emons |
Pediatrician-allergologist, Erasmus MC-Sophia, paid |
Editorial board NTvAAKI, unpaid NVvAKI communications committee, unpaid |
None |
None |
None |
Epitope study, cutaneous immunotherapy for peanut, DBV BAT cow's milk study, NWO Itulizax study, tree pollen immunotherapy, ALK |
None |
None |
July 7th, 2022
|
No restrictions, research has no link with hypersensitivity reactions after administration of contrast agents in children. |
|
Jöbsis |
Pediatrician, pediatric nephrologist |
None |
None |
None |
None |
None |
None |
None |
July 2nd, 2022 |
No restrictions |
|
Sloots |
Pediatric surgeon Erasmus MC Sophia Children's Hospital |
None |
None |
None |
None |
None |
None |
None |
August, 15th, 2022
|
No restrictions |
|
Liebrand |
Anaesthesiologist Sophia Children's Hospital/Erasmus MC Pediatrician St. Antonius Hospital, Kleve |
Notarzt Kreis Kleve |
None |
None |
None |
None |
None |
None |
December, 20th, 2022
|
No restrictions |
|
Zwaveling-Soonawala |
Pediatrician-endocrinologist, Emma Children's Hospital, Amsterdam UMC |
None |
None |
None |
None |
None |
None |
None |
June, 13th, 2023
|
No restrictions |
|
Advisory group |
||||||||||
|
Molen AJ, van der |
Radiologist LUMC |
Member of contrast media safety committee, European Society of Urogenital Radiology (no payment). |
None |
None |
None |
None |
None |
Received speaker fees from Guerbet, 2019-2022 |
June, 5th, 2023
|
No restrictions (given the role as a sounding board group member, no active contribution to texts and the mandate for decisions rests with the guideline development group, no further restrictions have been formulated for the ancillary activities at the gadopiclenol expert group) |
|
Riedijk |
Pediatrician Amsterdam UMC - Emma Children's Hospital |
Board member SICK: unpaid. PICE board member: unpaid. |
None |
None |
None |
None |
None |
None |
December, 6th, 2022
|
No restrictions |
|
Doganer |
Junior project manager/policy officer at the Child and Hospital Foundation |
None |
None |
None |
None |
None |
None |
None |
July, 25th, 2023
|
No restrictions |
Inbreng patiëntenperspectief
Input of patient’s perspective
The guideline does not address a specific child patient group, but a diverse set of diagnoses. Therefore, it was decided to invite a broad spectrum of patient organisations for the stakeholder consultation, and invite the patient organisation Kind & Ziekenhuis (translated as Child and Hospital Foundation) in the Advisory group. 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 children was developed for Thuisarts.nl, a platform to inform patients about health and disease.
Implementatie
Implementation
During different phases of the 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, 2 and 3 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, whre 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 can be found 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 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 during the conception of 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 guideline was made definitive by the GDG. 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.
Zoekverantwoording
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