Diagnostic Agent
PREGNANCY RECOMMENDATION: Limited Human Data—Animal Data Suggest Risk
BREASTFEEDING RECOMMENDATION: Limited Human Data—Probably Compatible
PREGNANCY SUMMARY
Available gadolinium-based contrast agents are complexes with chelating agents that lower the potential toxicity in patients receiving the agents by preventing the cellular uptake of free gadolinium. The complexes cross the placenta to the fetus and are excreted by the fetal kidneys into the amniotic fluid, where they remain for long periods. The complexes themselves are relatively nontoxic, but dissociation may occur to release free gadolinium into the amniotic fluid, where it could expose fetal lungs and gut. Presently, the risk of gadolinium-induced toxicity in the fetus is unknown but may be harmful (1–3). A concern has been raised for a risk of gadolinium-induced nephrogenic systemic fibrosis (3). The American College of Radiology recommends that these agents should not be routinely used in pregnancy and, if such use is indicated, a written informed consent be obtained from the patient (1). In addition, the guidelines of the Contrast Media Safety Committee of the European Society of Urogenital Radiology and a review article recommend that gadolinium-based contrast media may be used in pregnancy if such use is important to the mother’s health (4,5).
FETAL RISK SUMMARY
Gadoteridol, a paramagnetic agent, is a nonionic complex formed between a chelating agent and a paramagnetic ion, gadolinium. It is in the same subclass of gadolinium-based contrast agents as gadobenate dimeglumine, gadodiamide, gadofosveset trisodium, gadopentetate dimeglumine, and gadoversetamide. Gadoteridol is indicated for use in MRI in adults and children over 2 years of age to visualize lesions with abnormal vascularity in the brain (intracranial lesions), spine, and associated tissues. It also is indicated for use in MRI in adults to visualize lesions in the head and neck. It is not known if gadoteridol is metabolized or if it binds to plasma proteins. The elimination half-life is about 1.57 hours (6).
Reproduction studies have been conducted in rats and rabbits. In rats, a daily IV dose given for 12 days during gestation that was six times the human dose based on mmol/m2 (HD) doubled the incidence of postimplantation loss. This dose and a daily dose that was 40% lower given for 12 days caused an increase in spontaneous locomotor activity in rat offspring. In rabbits, an increase in the incidence of spontaneous abortions and early delivery was noted at a dose that was seven times the HD (6).
Studies to evaluate the potential for carcinogenicity or potential effects on fertility have not been conducted. Assays for mutagenicity and chromosome aberrations assay were negative. No effect on male and female rat fertility was observed with a low IV dose given three times weekly (6).
BREASTFEEDING SUMMARY
Although no reports describing the administration of gadoteridol during human lactation have been located, reviewers consider gadolinium contrast media to be compatible with breastfeeding because of the very small amounts excreted into milk and potentially being absorbed by a nursing infant (2–4). The American Academy of Pediatrics classifies gadopentetate dimeglumine as compatible with breastfeeding (7) (see Gadopentetate Dimeglumine).
References
1.Kanal E, Barkovich AJ, Bell C, Borgstede JP, Bradley WG Jr, Froelich JW, Gilk T, Gimbel JR, Gosbee J, Kuhni-Kaminski E, Lester JW Jr, Nyenhuis J, Parag Y, Schaefer DJ, Sebek-Scoumis EA, Weinreb J, Zaremba LA, Wilcox P, Lucey L, Sass N, for the ACR Blue Ribbon Panel on MR Safety. ACR guidance document for safe MR practices: 2007. AJR Am J Roentgenol 2007;188:1447–74.
2.Lin SP, Brown JJ. MR contrast agents: physical and pharmacologic basics. J Magn Reson Imaging 2007;25:884–99.
3.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;112:333–40.
4.Webb JAW, Thomsen HS, Morcos SK, and 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;15:1234–40.
5.Garcia-Bournissen F, Shrim A, Koren G. Safety of gadolinium during pregnancy. Can Fam Physician 2006;52:309–10.
6.Product information. Prohance. Bracco Diagnostics, 2007.
7.Committee on Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 2001;106:776–89.