Guidelines for the Use of CT and MRI During Pregnancy and Lactation

Guidelines for the Use of CT and MRI During

Pregnancy and Lactation

Introduction

The increasing use of imaging in the population will inevitably result in an increase in requests for imaging in women who are pregnant or lactating. The objectives of these guidelines are to review:

The safety issues related to CT and MRI during pregnancy and lactation
The obstetric and non-obstetric applications of CT and MRI in pregnancy
The appropriate use of imaging and contrast agents during pregnancy and lactation

Teratogenesis After Exposure to Ionizing Radiation

Organogenesis occurs predominantly between 2 and 15 weeks gestation. This is the period when the fetus is most susceptible to the teratogenic effects of ionizing radiation, which include microcephaly, microphthalmia, mental retardation, growth retardation, behavioral defects, and cataracts. Teratogenic effects are extremely unlikely in fetuses before 2 weeks of gestation and after 15 weeks of gestation [1]. Teratogenesis is considered a non-stochastic effect of radiation (i.e., a threshold dose exists below which there is no risk). The threshold radiation dose below which no teratogenic effects occur is not known, but is estimated to range from 5 to 15 rad [2]. The radiation dose to the fetus from a spiral CT study of the maternal pelvis using typical technical parameters is variable and depends on gestational age and scanning parameters such as slice thickness and mAs. That said, estimated doses range from 2.4 rad in the first trimester to 4.6 rad in the third trimester [3, 4]. An older study that is probably not representative of current technology suggested fetal doses of up to 5-10 rad [5]. Therefore, the radiation dose of pelvic CT is likely at or below the estimated threshold level for induction of congenital malformations. In practice, studies have shown the incidence of malformations is not measurably increased after in utero irradiation in humans [6].

Key point: Teratogenesis is not a major concern after diagnostic CT studies of the pelvis in pregnancy, because the radiation dose is generally too low to cause such effects.

Carcinogenesis After Exposure to Ionizing Radiation

Carcinogenesis is believed to be a stochastic effect of radiation (i.e., no threshold dose). The risk of childhood malignancy after in utero irradiation was first reported in 1956 [1], though the association was not widely accepted until the early 1960s. The existing data, derived from different sources, are relatively consistent. These data (which utilize several different end-points) are shown below:

End-point	Risk
Baseline risk of childhood cancer	19/10,000
Baseline risk of fatal childhood (0-15 yrs) cancer [2]	5/10,000
Excess risk of fatal childhood cancer per rad of fetal whole body dose [3]	4.6/10,000
Excess risk of childhood cancer per rad of fetal whole body dose [4]	6.4/10,000
Excess risk of childhood cancer per rad of fetal whole body dose [5]:	6/10,000
Relative risk of childhood cancer after fetal radiation exposure of 5 rad [6]:	2

Using a fetal dose estimate from pelvic CT of 2-5 rad [7, 8], this implies an increased risk of childhood cancer of up to 2 times baseline for a standard pelvic CT. The relationship between the risk of carcinogenesis and gestational age at the time of radiation exposure is more controversial [9]. The OSCC study suggests the risk is higher with exposure in the first trimester than with exposure in the second or third trimesters, with relative risks of 3.19, 1.29 and 1.30, respectively [10]. However, this may be an artifactual result, since radiographic studies in the first trimester may have included a disproportionately high fraction of high dose non-obstetric studies such as IVPs and barium enemas. Also, experimental work in dogs suggests exposure later in gestation is more carcinogenic [11]. Nonetheless, the possibility of pre-malignant change in the first trimester remains, leading the NRPB to assume that some risk exists after irradiation in the first weeks of pregnancy.

Assuming a relatively high fetal dose estimate of 5 rads for a pelvic CT during pregnancy, the relative risk of fatal childhood cancer may be doubled. This relative risk may appear substantial, but it should be remembered that the baseline risk is very low, so that the odds of dying of childhood cancer go from 1 in 2000 (baseline) to 2 in 2000 (after 5 rads). To assist with patient counseling, some practical risk comparisons may be helpful. The excess risk (of 1 in 2000) is equivalent to driving 20,000 miles in a car or living in New York City for 3 years [12]. It should also be noted that the guidelines of the American College of Obstetricians and Gynecologists [13] are superficial in their discussion of the carcinogenic risk of radiation during pregnancy, describing it as "very small" and concluding "abortion should not be recommended". The ACOG guidelines do not indicate what information or risk estimates should be provided during parental counseling, if any.

Key point: 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.

Avoiding Exposure in Pregnancy

No law or professional standard requires that radiologists determine in advance whether a patient of childbearing-age is pregnant [1]. However, it is clearly good practice to implement the following guidelines:

Signs should be prominently displayed in all radiology departments asking each patient to notify a technologist or physician if she is, or thinks she could be, pregnant.
All technologists should ask women of childbearing-age if they might be pregnant prior to performing a radiologic procedure.
Radiology requisition forms filled out by referring physicians should include a section dealing with the possibility of pregnancy.
No radiological procedure involving exposure to the pelvis should be undertaken in a patient who declares she may be pregnant without consultation with a radiologist. The radiologist should discuss risks and benefits with the patient, and determine if it is appropriate to proceed, perform an alternative procedure, or delay the study to allow performance of a pregnancy test.

It should be noted that current recommendations do not recognize a safe period during the menstrual cycle, and so the concept of the "ten day rule" is obsolete. A patient who thinks she may be pregnant should be discussed with the referring physician, in order to determine the appropriate course of action (e.g., rescheduling after pregnancy testing, proceeding with the test after counseling, or changing to another modality).

Key point: It is the responsibility of the patient to disclose any possibility of pregnancy, although appropriate signage and questioning of all women of reproductive age is also critical. The supervising radiologist should discuss any cases of possible pregnancy with the referring physician.

Managing Pregnant Patients Who Are Irradiated

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.

Procedure	*Conceptus radiation dose (rads)**
Abdominal radiograph	0.25
Intravenous pyelogram	0.8
Barium enema	0.8
Lumbar spine radiographs	0.6
CT pelvis	1-10

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.

Iodinated Contrast Media in Pregnancy

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 . Reassuringly, animal studies have failed to show an in vivo teratogenic effect . 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 . 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 .

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

Introduction to Risks From MRI During Pregnancy

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 fora 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 .

Risk of Teratogensis From MRI During Pregnancy

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.

Risk of Acoustic Damage From MRI During Pregnancy

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.

RISK OF TERATOGENESIS FROM GADOLINIUM

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.

USE OF CONTRAST MEDIA DURING LACTATION

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.

Imaging Of Suspected Pulmonary Embolism in Pregnancy

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.

Imaging of Suspected Acute Appendicitis in Pregnancy

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).

Imaging of Suspected Renal Colic in Pregnancy

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).

Imaging of Trauma in Pregnancy

Trauma and accidental injuries complicate 6-7% of all pregnancies [1], and are usually due to motor vehicle accidents, domestic abuse or assaults, and falls. Common adverse consequences include uterine contractions, preterm labor or delivery, and placental abruption. Fetal or maternal demise is rare. In many cases, external fetal monitoring and ultrasound may be adequate for assessment, including detection of placental abruption or uterine rupture (the most serious complication) and documentation of fetal well being [1-3]. That said, trauma to the pregnant patient must be considered with the utmost seriousness because even minor trauma can cause fetal demise [4]. The cardinal principle in the management of trauma in pregnancy is that there can be no fetal survival without maternal survival, with the rare exception of the gravely injured mother late in pregnancy where urgent Cesarean section may allow for fetal survival. From an imaging perspective, ultrasound is an excellent tool for initial evaluation of the traumatized pregnant patient, but CT is the preferred modality when clinical or ultrasound findings suggest visceral injuries unaccompanied by intraperitoneal hemorrhage, or injuries of the chest, mediastinum, aorta, spine, retroperitoneum, bowel, bladder, and bones [5]. MRI is not a practical option for rapid evaluation of all these body parts in an unstable patient after trauma. Placental infarction or abruption typically appears at CT as a single avascular area of varying size that extends from the placental base to the placental surface [6]. High attenuation in the nonplacental portion of the uterus indicates contusion, tear, or partial uterine disruption Loss of amniotic fluid into the maternal peritoneum or free fetal parts in the maternal abdomen indicate an obstetric catastrophe, but it may be difficult to determine if free intraperitoneal fluid is amniotic fluid or hemorrhage from a maternal visceral injury [6].

Key point: Ultrasound 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.

CT Pelvimetry

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.

Summary and Key Points

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:

Appendicitis - For first and second trimester pregnancies US and/or MR should be performed prior to obtaining a CT

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.
Renal colic - US is the initial study of choice.
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.

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