CT and MR Pregnancy Guidelines

Relative agreement exists on when to recommend termination of pregnancy after radiation exposure. The so-called "Danish rule" was offered in 1959 by Hammer-Jacobsen, who suggested termination was advisable for a fetal dose of over 10 rads [1]. This guideline has been widely followed. Wagner et al suggest termination should only be considered if a radiation dose of over 5 rad occurs between 2 and 15 weeks of gestation, and is probably indicated only for doses over 15 rad. Hall suggests termination may be considered for a radiation of over 10 rad received between a gestational age of 10 days and 26 weeks [2]. In practice, it is exceptionally unlikely that any single radiological study would deliver a radiation dose sufficient to justify termination. Nonetheless, it is helpful to be aware of the expected radiation dose from common procedures [3, 4], and the magnitude of risk to the fetus per unit dose. This information, which is listed below, can be used to counsel pregnant patients who require a study involving ionizing radiation to the pelvis, or who inadvertently undergo such a study at a time when pregnancy is unsuspected.

Note: 1 rad = 1 cGy = 10 mGy = 10,000 µGy

Key point: In practice, it is exceptionally unlikely that any single diagnostic radiological study would deliver a radiation dose sufficient to justify termination.

References

1. Hammer-Jacobsen E. Therapeutic abortion on account of x-ray examination during pregnancy. Danish Med Bull 1959; 6: 113-122.
2. Hall EJ. Radiobiology for the radiologist, 4th ed. Philadelphia: Lippincott; 1994: 363-452.
3. Wagner LK, Archer BR, Zeck OF. Conceptus dose from two state-of-the-art CT scanners. Radiology 1986; 159: 787-792.
4. Bushberg JT, Seibert JA, Leidholdt EM, Boone JM. The essential physics of medical imaging. Williams and Wilkins, Baltimore, 1994; 694.

In general, intravascular contrast media should be avoided in pregnancy, in order to avoid any possible hazard to the fetus. In vitro experiments have shown iodinated contrast to be mutagenic to human cells [1]. Reassuringly, animal studies have failed to show an in vivo teratogenic effect [2, 3]. The iodine content of contrast media has the potential to produce neonatal hypothyroidism, and this has been observed after the direct instillation of ionic contrast into the amniotic cavity during amniofetography [4]. The intravascular use of non-ionic contrast media has been reported to have no effect on neonatal thyroid function [5]. It is standard pediatric practice to screen all neonates for hypothyroidism, but it is particularly important to perform this test in the infants of mothers who received iodinated contrast during pregnancy [6].

Key point: Despite in vitro concerns, iodinated contrast seems safe to use in pregnancy.

References

1. Nelson JA, Livingston JC, Moon RG. Mutagenic evaluation of radiographic contrast media. Invest Radiol 1982; 17: 183-185.
2. Morisetti A, Tirone P, Luzzani F, de Haen C. Toxicologic safety assessment of iomeprol, a new x-ray contrast agent. Eur J Radiol 1994; 18 (Suppl 1): 21-31.
3. Ralston WH, Robbins MS, James P. Reproductive, developmental, and genetic toxicity of ioversol. Invest Radiol 1989; 24 (Suppl 1): 16-22.
4. desch F, Camus M, Ermans AM, et al. Adverse effects of amniofetography on fetal thyroid function. Am J Obstet Gynecol 1976; 126: 723-726.
5. na G, Zaffaroni M, Defilippi C, et al. Effects of iopamidol on neonatal thyroid function. Eur J Radiol 1992; 12: 22-25.
6. 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: 1234-1240.

The current guidelines of the FDA require labeling of the MRI devices to indicate that the safety of MRI with respect to the fetus "has not been established". Safety concerns arise with respect to both mother and fetus. Maternal safety concerns are the same as for a non-pregnant patient, and are addressed by pre-scan screening. Fetal concerns are twofold; first, the possibility of teratogenic effects, and second, the possibility of acoustic damage. In general, it should be noted that most studies evaluating MRI safety during pregnancy show no ill effects [1-4].

Key point: Most studies evaluating MRI safety during pregnancy show no ill effects.

References

1. Mevissen M, Buntenkotter S, Loscher W. Effects of static and time-varying (50 Hz) magnetic fields on reproduction and fetal development in rats. Teratology 1994; 50: 229-237.
2. Beers GJ. Biological effects of weak electromagnetic fields from 0 Hz to 200 Hz: a survey of the literature with special emphasis on possible magnetic resonance effects. Mag Res Imag 1989; 7: 309-331.
3. Schwartz JL, Crooks LE. NMR imaging produces no observable mutations or cytotoxicity in mammalian cells. AJR 1982; 139: 583-585.
4. Wolff S, Crooks LE, Brown P, Howard R, Painter R. Test for DNA and chromosomal damage induced by nuclear magnetic resonance imaging. Radiology 1980; 136: 707-710.

A small number of studies have raised the possibility of teratogenic effects of MRI exposure in early pregnancy. A reduction in crown-rump length was seen in mice exposed to MRI in midgestation [1]. Exposure to the electromagnetic fields simulating a clinical study caused eye malformations in a genetically predisposed mouse strain [2]. Several hours of exposure of chick embryos in the first 48 hours of life to a strong static magnetic field and rapid electromagnetic gradient fluctuations resulted in an excess number of dead or abnormal chick embryos, when examined at day 5 [3]. Possible mechanisms for apparent deleterious effects include the heating effect of MR gradient changes, and direct non-thermal interaction of the electromagnetic field with biological structures. Tissue heating is greatest at the maternal body surface, and approaches negligible levels near the body center [4], making it unlikely that thermal damage to the fetus is a serious risk. A possible criticism of many of these studies is that they are not applicable to humans. However, they provide sufficient cause for concern such that a cautionary approach should be taken regarding fetal MRI in the first trimester. Accordingly, the guidelines of the National Radiological Protection Board in the United Kingdom is that "it might be prudent to exclude pregnant women during the first three months of pregnancy" [5]. An additional concern in the first trimester is the underlying relatively high rate of spontaneous abortion in this period. An MRI study could be coincidentally followed by a spontaneous abortion, but might give rise to parental concerns regarding causal effect. From a practical viewpoint, first trimester MRI will usually be performed for maternal rather than fetal indications, and in this context MRI is still preferable to any imaging study involving ionizing radiation [6].

Key point: It is good practice to avoid MRI during pregnancy, particularly for elective studies or during the first trimester, but MRI remains preferable to any studies using ionizing radiation.

References

1. Heinrichs WL, Fong P, Flannery M, Heinrichs SC, Crooks LE, Spindle A, Pedersen RA. Midgestational exposure of pregnant balb/c mice to magnetic resonance imaging. Mag Res Imag 1986; 8: 65-69.
2. Tyndall DA, Sulik KK. Effects of magnetic resonance imaging on eye development in the C57BL/6J mouse. Teratology 1991;43: 263-275.
3. Yip YP, Capriotti C, Talagala SL, Yip JW. Effects of MR exposure at 1.5T on early embryonic development of the chick. JMRI 1994; 4: 742-748.
4. Kanal E, Shellock FG, Talagala L. Safety considerations in MR imaging. Radiology 1990; 176: 593-606.
5. National Radiological Protection Board. Principles for the Protection of Patients and Volunteers During Clinical Magnetic Resonance Diagnostic Procedures. Documents of the NRPB, Volume 2, no 1. London: HM Stationery Office, 1991.
6. Shellock FG, Kanal E. Policies, guidelines, and recommendations for MR imaging safety and patient management. JMRI 1991; 1: 97-101.

A less obvious concern is the potential risk of acoustic damage to the fetus, due to the loud tapping noises generated by the coils of the MR scanner as they are subjected to rapidly oscillating electromagnetic currents, especially with EPI, which is the noisiest sequence in current clinical use. In a follow-up study of 18 patients who had undergone EPI as fetuses, 16 passed their 8 month hearing test, compared to 16.7 expected [1]. In a second study, a microphone was passed through the esophagus into the fluid filled stomach of a volunteer [2]. The aim was to simulate the acoustic environment of the gravid uterus. The sound intensity in the stomach was measured during MRI scanning across a range of radiofrequencies. The attenuation of the transmitted sound was greater than 30 dB, sufficient to reduce sound intensity from near the dangerous level of 120 dB to an acceptable level of under 90 dB. The results of these studies provide reassuring clinical and experimental evidence that there is no significant risk of acoustic injury to the fetus during prenatal MRI.

Key point: Acoustic damage from MRI during pregnancy appears to be a theoretical rather than a real concern.

References

1. Baker PN, Johnson IR, Harvey PR, Gowland PA, Mansfield P. A three-year follow-up of children imaged in utero with echo-planar magnetic resonance. Am J Obstet Gynecol 1994; 170: 32-33.
2. Gover P, Hykin J, Gowland P, Wright J, Johnson I, Mansfield P. An assessment of the intrauterine sound intensity level during obstetric echo-planar magnetic resonance imaging. Br J Radiol 1995; 68: 1090-1094.

Intravenous gadolinium is teratogenic in animal studies, albeit at high and repeated doses [1]. While teratogenic effects have not been observed in a small number of human studies where gadolinium has been given in pregnancy [2, 3], it is clear that gadolinium should not be administered in pregnancy unless there is an absolutely essential clinical indication, particularly during the period of organogenesis. Administration of gadolinium later in pregnancy may be reasonable, although such indication would likely be for a maternal or obstetric indication rather than for evaluation of a fetal abnormality. Examples might include gadolinium enhanced imaging for a maternal brain tumor or suspected placenta accreta. Gadolinium crosses the placenta where it is presumably excreted by the fetal kidneys into the amniotic fluid. In the era of gadolinium-induced nephrogenic systemic fibrosis, this raises theoretical concerns of toxicity related to disassociation and persistence of free gadolinium. Such concerns reinforce the regulatory advice on gadolinium use in pregnancy. The 2007 ACR guidance document for safe MRI practices recommends that intravenous gadolinium should be avoided during pregnancy and should only be used if absolutely essential; furthermore, the risks and benefits of gadolinium use must be discussed with the pregnant patient and referring clinician [4]. Gadolinium is classified as a category C drug by the Food and Drug Administration and can be used if considered critical (only to be administered “if the potential benefit justifies the potential risk to the fetus”).

Key point: Intravenous gadolinium is contra-indicated in pregnancy, and should only be used if absolutely essential, and only after discussion of risks and benefits with the patient and referring clinician.

References

1. 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.
2. Marcos HB, Semelka RC, Worawattanakul S. Normal placenta: gadolinium-enhanced dynamic MR imaging. Radiology. 1997; 205: 493-6.
3. 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: 446-53.
4. Kanal E, Barkovich AJ, Bell C, Borgstede JP, Bradley WG, Jr., Froelich JW, et al. ACR guidance document for safe MR practices: 2007. AJR Am J Roentgenol 2007; 188: 1447-74.

The traditional and standard recommendation is that lactating women who receive intravascular iodinated contrast or gadolinium should discontinue breast-feeding for 24 hours, and the expressed milk during this period should be discarded [1]. The rationale for this recommendation appears weak, for several reasons:

• Only tiny amounts of iodinated or gadolinium-based contrast medium given to a lactating mother reach the milk. For example, a recent study of 20 lactating women found that less than 0.04% of the maternal dose of intravenous gadolinium passes into the breast milk [2].
• Only a tiny fraction of iodinated contrast or gadolinium entering the infant gut is absorbed. For example, only 1-2% of oral iodinated contrast is absorbed into the bloodstream [3].

Given these considerations, and in accordance with the results of a comprehensive review by the European Society of Urogenital Radiology, the very small potential risk associated with absorption of contrast medium may be insufficient to warrant stopping breast-feeding for 24 hours following either iodinated or gadolinium contrast agents [4]. A recent review in the New England Journal of Medicine also concluded that iodinated contrast administered to breast-feeding women posed no risk to the infant [5].

Key point: Lactating women who receive iodinated contrast or gadolinium can continue breast feeding without interruption.

References

1. Omniscan package insert, Nycomed, Princeton, NJ.
2. Kubik-Huch RA, Gottstein-Aalame NM, Frenzel T, et al. Excretion of gadopentetate dimeglumine into human breast milk during lactation. Radiology 2000; 216: 555-558.
3. Mutzel W, Speck U. Pharmacokinetics and biotransformation of iohexol in the rat and the dog. Acta Radiol Suppl. 1980; 362: 87-92.
4. 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: 1234-1240.
5. Ito S. Drug therapy: Drug therapy for breast-feeding women. N Engl J Med 2000; 343: 118-126.

Three large studies showed that the rate of pregnancy associated pulmonary embolism was approximately 1 to 2 per 7000 pregnancies (less than previously supposed), and that the majority occurred post-partum, particularly with pre-eclampsia, Caesarean section, and multiple births [1-3]. Several considerations suggest that CT pulmonary angiography, rather than ventilation perfusion scintigraphy is the preferred technique for imaging suspected pulmonary embolism in pregnancy:

• Available data can be interpreted to support the general superiority of CT pulmonary angiography over ventilation perfusion scintigraphy [4-6].
• Ventilation perfusion scintigraphy is indeterminate in up to 25% of patients imaged during pregnancy [7].
• The fetal radiation dose from CT pulmonary angiography is substantially less than that from ventilation perfusion scintigraphy in all trimesters and even if half-dose perfusion-only scintigraphy is used [8-9].

Key point: CT is the preferred modality for imaging of suspected pulmonary embolism in pregnancy.

References

1. McColl MD, Ramsay JE, Tait RC, et al. Risk factors for pregnancy associated venous thromboembolism. Thromb Haemost 1997;78:1183-8.
2. Gherman RB, Goodwin TM, Leung B, et al. Incidence, clinical characteristics, and timing of objectively diagnosed venous thromboembolism during pregnancy. Obstet Gynecol 1999;94:730-4.
3. Ros HS, Lichtenstein P, Bellocco R, et al. Pulmonary embolism and stroke in relation to pregnancy: how can high-risk women be identified? Am J Obstet Gynecol 2002;186:198-203.
4. British Thoracic Society Standards of Care Committee Pulmonary Embolism Guideline Development Group. British Thoracic Society guidelines for the management of suspected acute pulmonary embolism. Thorax 2003; 58: 470-483.
5. Hayashino Y, Goto M, Noguchi Y, Fukui T. Ventilation-perfusion scanning and helical CT in suspected pulmonary embolism: meta-analysis of diagnostic performance. Radiology 2005; 234: 740-748.
6. Quiroz R, Kucher N, Zou KH, Kipfmueller F, Costello P, Goldhaber SZ, Schoepf UJ. Clinical validity of a negative computed tomography scan in patients with suspected pulmonary embolism: a systematic review. JAMA 2005; 293: 2012-7.
7. Chan WS, Ray JG, Murray S, Coady GE, Coates, G, Ginsberg, JS. Suspected pulmonary embolism in pregnancy: Clinical presentation, results of lung scanning, and subsequent maternal and pediatric outcomes. Arch Intern Med 2002; 162: 1170-1175.
8. Winer-Muram HT, Boone JM, Brown HL, Jennings SG, Mabie WC, Lombardo GT. Pulmonary embolism in pregnant patients: fetal radiation dose with helical CT. Radiology. 2002; 224: 487-92.
9. Russell JR, Stabin MG, Sparks RB, et al. Radiation absorbed dose to the embryo/fetus from radiopharmaceuticals. Health Phys 1997; 73: 756-769.

Acute appendicitis complicates approximately 1 in 1500 pregnancies, and is one of the leading indications for surgery in pregnancy [1]. The diagnosis of appendicitis in pregnancy can be clinically difficult, particularly in later pregnancy, as evidenced by a perforation rate of 31% for appendicitis occurring in the first and second trimester but rising to 69% in the third trimester [2]. With respect to imaging, graded compression should be considered the initial modality of choice in the first and second trimesters. In a series of 42 women with suspected appendicitis during pregnancy, ultrasound was found to be 100% sensitive, 96% specific, and 98% accurate in diagnosing appendicitis. [3]. Three patients were unable to be adequately evaluated due to the technical difficulties associated with advanced gestation (over 35 weeks), and the choice of imaging in later pregnancy is more problematic. The only published study on the use of CT for appendicitis in pregnancy showed 100% accuracy in a small series of 7 patients, 2 of whom were found to have appendicitis [4]. More recently, there has been some interest in the use of MRI to diagnose appendicitis in pregnancy. In a Dutch study of 12 suspected cases between 7 and 35 weeks gestation (3 with subsequently proven appendicitis at surgery), MRI correctly identified all 3 cases of acute appendicitis and correctly identified 7 normal cases [5]. The appendix was not seen in two patients (at 17 and 35 weeks gestation). Our institutional experience suggests all modalities (US, CT, and MRI) become problematic in later pregnancy (past 35 weeks gestation) and consultation with on-call faculty may be appropriate in such patients.

Key point: Ultrasound is the preferred modality for imaging of suspected acute appendicitis in pregnancy, except in later pregnancy (> 35 weeks) when CT or MRI may be required (consult with radiology faculty).

References

1. Wittich AC, DeSantis RA, Lockrow EG. Appendectomy during pregnancy: a survey of two army medical activities. Mil Med 1999; 164: 671-674.
2. Weingold AB. Appendicitis in pregnancy. Clin Obstet Gynecol 1983; 26: 801-809.
3. Lim HK, Bae SH, Seo GS. Diagnosis of acute appendicitis in pregnant women: Value of sonography. Am J Roentgenol. 1992; 159:539-542.
4. Castro MA, Shipp TD, Castro EE, et al. The use of helical computed tomography in pregnancy for the diagnosis of acute appendicitis. Am J Obstet Gynecol. 2001; 184:954-957.
5. Cobben LP, Groot I, Haans L, Blickman JG,Puylaert J. MRI for clinically suspected appendicitis during pregnancy. AJR 2004; 183: 671-675.

Obstructive urinary calculi complicate approximately 1 in 3300 pregnancies [1]. Imaging is complicated by the normal physiological hydronephrosis that occurs in pregnancy. Despite this confounding factor, ultrasound correctly visualized 21 of 35 (60%) stones in a retrospective study. This suggests ultrasound remains the initial study of choice, but that additional imaging by non-contrast spiral CT or IVP may be required if ultrasound is negative. Non-contrast CT is probably the more accurate modality, although the radiation dose to the fetus is probably higher [2]. However, radiation dose comparisons between CT and IVP are not straightforward because both can be performed with a wide range of techniques that may or may not incorporate dose-reducing approaches.

Key point: Ultrasound is the preferred modality for imaging of suspected renal colic in pregnancy; if negative, CT or MRI may be required (consult with radiology faculty).

References

1. Butler EL, Cox SM, Eberts EG, Cunningham FG. Symptomatic nephrolithiasis complicating pregnancy. Obstet Gynecol 2000 96: 753-756.
2. Tamm EP, Silverman PM, Shuman WP. Evaluation of the patient with flank pain and possible ureteral calculus. Radiology 2003; 228: 319-29.

Pelvimetry is occasionally requested when vaginal delivery is being considered for breech presentation (especially in a primagravida) or for patients with suspected cephalopelvic disproportion, although reports on the utility of pelvimetry are conflicting and the reproducibility of pelvimetry measurements has also been questioned [1-3]. Pelvimetry can be performed by conventional radiography, CT, or MRI [4]. While MRI has the theoretical advantage of not using ionizing radiation, the fetal dose from a limited CT pelvimetry study (low doses lateral and frontal digital radiographs with a single axial slice through the femoral heads to measure interspinous diameter) is under 0.1 rad. Even assuming the worse case scenario that the dose is 0.1 rad and that such a dose is as dangerous as radiation earlier in pregnancy, the risk of fatal childhood cancer would only be increased by 2%, a minimal risk. For such reasons, if pelvimetry is considered appropriate, it is reasonable to perform pelvimetry by CT rather than MRI.

Key point: Pelvimetry can be performed either by low dose CT or by MRI, and written informed consent is not required.

References

1. Anderson N. X-ray pelvimetry: helpful or harmful? J Fam Pract 1983; 17: 405-12.
2. Sibony O, Alran S, Oury JF. Vaginal birth after cesarean section: X-ray pelvimetry at term is informative. J Perinat Med. 2006; 34: 212-5.
3. Keller TM, Rake A, Michel SC, Seifert B, Efe G, Treiber K, Huch R, Marincek B, Kubik-Huch RA. Obstetric MR pelvimetry: reference values and evaluation of inter- and intraobserver error and intraindividual variability. Radiology. 2003; 227:37-43.
4. Stark DD, McCarthy SM, Filly RA, Parer JT, Hricak H, Callen PW. Pelvimetry by magnetic resonance imaging. AJR Am J Roentgenol 1985; 144:947-950.

General points:

• CT of the fetus should be avoided in all trimesters of pregnancy, because it may cause up to a doubling of the risk of fatal childhood cancer.
• No radiological procedure involving ionizing radiation to the pelvis should be undertaken in a patient who declares she may be pregnant without consultation with radiology faculty.
• MRI poses no known risk to the fetus in the second and third trimester. MRI in the first trimester should only be performed after consultation with radiology faculty.
• Breast feeding can be continued without interruption after administration of iodinated contrast or gadolinium to a lactating patient
• It is advisable to obtain written informed consent for CT of the abdomen or pelvis in a pregnant patient. For studies that pose minimal risk (including CT pelvimetry, CT of other body parts, and MRI) it is advisable to explain the negligible nature of the risk to the patient and document this discussion in either the chart or the radiology report.

Specific points:

• The most common indications for urgent CT during pregnancy are:

1. Appendicitis - For first and second trimester pregnancies US and/or MR should be performed prior to obtaining a CT
2. Pulmonary embolism - In this case a CT pulmonary angiogram exposes the fetus to less radiation than a VQ scan. Therefore, CT should be the initial modality.
3. Renal colic - US is the initial study of choice.
4. Trauma. US may be sufficient for the initial imaging evaluation of a pregnant patient who has sustained trauma, but CT should be performed if serious injury is suspected.

• All patients undergoing CT of the abdomen or pelvis during pregnancy should sign the written informed consent form available at (consent form). The consent form can be completed by either the referring physician or the involved radiologist (including the radiology resident on-call). Patients referred from the Department of Obstetrics, Gynecology and Reproductive Sciences will be consented by the referring physician.
• For studies that pose minimal risk (including CT pelvimetry, CT of other body parts, and MRI) it is advisable to explain the negligible nature of the risk to the patient and document this discussion in either the chart or the radiology report. This discussion can be undertaken by either the referring physician or the involved radiologist.
• CT contrast seems safe to use in pregnancy and should be administered in the usual fashion ñ this is far preferable to repeating a study because the initial examination was non-diagnostic due to lack of intravenous contrast.
• Intravenous gadolinium is contra-indicated in pregnancy, and should only be used if absolutely essential and only after discussion of risks and benefits with the patient and referring clinician and radiology faculty.
• Pelvimetry can be performed either by low dose CT or by MRI, and written informed consent is not required.