Administration of Contrast Media to Pregnant or Potentially Pregnant Patients*

Studies of low-molecular weight water-soluble extracellular substances such as iodinated diagnostic X-ray and computed tomography (CT) and gadolinium-based magnetic resonance imaging (MRI) contrast media in pregnancy have been limited, and their effects on the human embryo or fetus are incompletely understood. Iodinated diagnostic contrast media have been shown to cross the human placenta and enter the fetus in measurable quantities (1, 2). A standard gadolinium-based MRI contrast medium has been shown to cross the placenta in primates and appear within the fetal bladder within 11 minutes after intravenous administration (3). It must be assumed that all iodinated and gadolinium-based contrast media behave in a similar fashion and cross the blood-placental barrier into the fetus.

After entering the fetal blood stream, these agents will be excreted via the urine into the amniotic fluid and be subsequently swallowed by the fetus (4). It is then possible that a small amount will be absorbed from the gut of the fetus with the additional swallowed gadolinium-based contrast agents eliminated back into the amniotic fluid.

In the study in primates, placental enhancement could be detected up to 2 hours following the intravenous (IV) administration of gadopentetate dimeglumine. When gadopentetate dimeglumine was injected directly into the amniotic cavity, it was still conspicuous at 1 hour after administration (3). There are no data available to assess the rate of clearance of contrast media from the amniotic fluid.

Iodinated Low Osmolality Contrast Media

Mutagenic effect of LOCM

Diagnostic iodinated contrast media have been shown to cross the human placenta and enter the fetus when given in usual clinical doses. In-vivo tests in animals have shown no evidence of either mutagenic or teratogenic effects with low-osmolality contrast media (LOCM). No adequate and well-controlled teratogenic studies of the effects of these media in pregnant women have been performed.

Effect of iodinated contrast media on fetal thyroid function

The fetal thyroid plays an important role in the development of the central nervous system. There have been rare reports of hypothyroidism developing in the newborn infant after the administration of iodinated contrast medium during pregnancy; however, this occurred only following amniofetography using fat soluble iodinated contrast medium which was performed in the past to detect congenital malformations.

Intravenous administration of iodinated contrast medium does not affect short-term neonatal TSH, likely because the overall amount of excess iodide in the fetal circulation is small and transient. However, the long term effects are unknown. To date, there has been no documented case of neonatal hypothyroidis from the maternal intravascular injection of water-soluble iodinated contrast agents (5,6). Given the current available data and routine evaluation of all newborns for congenital hypothyroidism by measurement of thyroid stimulating hormone levels at the time of their birth, no extra attention is felt to be necessary (7, 8, 9).

Other adverse effects

There have been no other adverse effects that have been reported in the fetus or neonate following administration of LOCM. However, information in this area is sparse.

Recommendations prior to performing imaging studies requiring iodinated contrast material administration

We recommend that all imaging facilities should have policies and procedures in place to identify pregnant patients prior to the performance of any examination involving administration of iodinated contrast media. If a patient is known to be pregnant, the potential added risks of contrast media should be considered before proceeding with the study (10).

There is insufficient evidence to conclude that LOCM are without any risk with respect to the fetus. Consequently, the Committee on Drugs and Contrast Media recommends the following in patients in whom imaging studies are requested that may require the use of iodinated contrast material:

A. The radiologist should confer with the referring physician and document in the radiology report or the patient’s medical record the following:

1. That the information requested cannot be acquired without contrast administration.

2. That the information needed affects the care of the patient and fetus during the pregnancy.

3. That the referring physician is of the opinion that it is not prudent to wait to obtain this information until after the patient is no longer pregnant.

B. It is recommended that pregnant patients undergoing a diagnostic imaging examination with iodinated contrast media and their referring physicians should indicate that they understand the potential risks and benefits of the procedure to be performed, the potential for risk to the fetus, and the alternative diagnostic options available to them (if any), and that they indicate the desire to proceed.

Gadolinium-Based Contrast Agents (GBCAs)

Mutagenic effect of GBCAs

To date, there have been no known adverse effects to human fetuses reported when clinically recommended dosages of GBCAs have been given to pregnant women. A single cohort study of 26 women exposed to gadolinium chelates during the first trimester of pregnancy showed no evidence of teratogenesis or mutagenesis in their progeny (11). However, no adequate and well-controlled teratogenic studies of the effects of these media in pregnant women have been performed.

Risk of nephrogenic systemic fibrosis

There are no known cases of NSF linked to the use of GBCAs in pregnant patients to date. However, gadolinium chelates may accumulate in the amniotic fluid. Therefore, there is the potential for dissociation of the toxic free gadolinium ion, conferring a potential risk for the development of nephrogenic systemic fibrosis (NSF) in the child or mother. Because the risk is unknown, it is generally recommended that gadolinium chelates not be used routinely in pregnant patients.

Recommendations for the use of GBCA-enhanced MRI examinations in pregnant patients

Because it is unclear how GBCAs will affect the fetus, these agents should be administered only with caution. They should only be used if their usage is considered critical and the potential benefits justify the potential risk to the unborn fetus. If a GBCA is to be used in a pregnant patient, one of the agents believed to be at low risk for the development of NSF (12) should be used at the lowest possible dose to achieve diagnostic results. In pregnant patients with severely impaired renal function, the same precautions should be observed as in non-pregnant patients.

At the present time, the Committee on Drugs and Contrast Media recommends the following concerning the performance of contrast-enhanced MRI examinations in pregnant patients.

Each case should be reviewed carefully and gadolinium-based contrast agent administered only when there is a potential significant benefit to the patient or fetus that outweighs the possible risk of exposure of the fetus to free gadolinium ions.

A. The radiologist should confer with the referring physician and document the following in the radiology report or the patient’s medical record:

1. That information requested from the MRI study cannot be acquired without the use of IV contrast or by using other imaging modalities.

2. That the information needed affects the care of the patient and/or fetus during the pregnancy.

3. That the referring physician is of the opinion that it is not prudent to wait to obtain this information until after the patient is no longer pregnant.

B. It is recommended that both pregnant patients undergoing an MRI examination and their referring physicians should indicate that they understand the potential risks and benefits of the MRI procedure to be performed, and the alternative diagnostic options available (if any), and that they wish to proceed.

Premedication of pregnant patients (with prior allergic-like reactions to iodinated or gadolinium-based contrast media

Diphenhydramine and corticosteroids (most commonly prednisone and methyl-prednisolone) are commonly used for prophylaxis in patients at risk for allergic-like contrast reactions to contrast media. Diphenhydramine is classified as FDA category B. (FDA category B: Animal reproductive studies have failed to demonstrate a risk to the fetus and there are no adequate well-controlled studies in pregnant women.) Prednisone (FDA category C) and dexamethasone (FDA category C) traverse the placenta; however most of these agents are metabolized within the placenta before reaching the fetus and therefore are not associated with teratogenicity in humans. (FDA category C: Animal reproduction studies have shown an adverse effect on fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.) However, sporadic cases of fetal adrenal suppression have been reported. Methylprednisolone also classified as a class C drug, carries a small risk of cleft lip if used before 10 weeks of gestation (16, 17).

REFERENCES

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12. Thomsen HS, Morcos SK, Almen T et al. Nephrogenic systemic fibrosis and gadolinium- based contrast media: Update ESUR Contrast Medium Safety Committeee Guidelines. Eur Radiol June 2012. Online

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15. MuhlerMR, Clement O, Salomon LJ et al. Maternofetal pharmacokinetics of gadolinium chelate in mice. Radiology. 2011; 258: 455-460.

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17. Niebyl JR. Clinical Practice: Nausea and vomiting in pregnancy. N Engl J Med 2010;363:1544-1550.

*ACR Manual on Contrast Media – Version 8, 2012, www.ACR.org. Reprinted with permission of the American College of Radiology. No other representation of this article is authorized without express, written permission from the American College of Radiology.