Challenges in Interventional Radiology: The Pregnant Patient

Abstract

A pregnant patient presenting to interventional radiology (IR) has a different set of needs from any other patient requiring a procedure. Often, the patient's care can be in direct conflict with the growth and development of the fetus, whether it be optimal fluoroscopic imaging, adequate sedation of the mother, or the timing of the needed procedure. Despite the additional risks and complexities associated with pregnancy, IR procedures can be performed safely for the pregnant patient with knowledge of the special and general needs of the pregnant patient, use of acceptable medications and procedures likely to be encountered during pregnancy, in addition to strategies to protect the patient and her fetus from the hazards of radiation.

Objectives: Upon completion of this article, the reader will be able to reduce radiation exposure to the pregnant patient, identify procedures that might be relevant to the pregnant patient, and select medications that are safer to use in pregnancy.

Accreditation: This activity has been planned and implemented in accordance with the Essential Areas and Policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of Tufts University School of Medicine (TUSM) and Thieme Medical Publishers, New York. TUSM is accredited by the ACCME to provide continuing medical education for physicians.

Credit: Tufts University School of Medicine designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

The Pregnant Patient in Interventional Radiology: General Issues

Managing a pregnant patient in an interventional radiology (IR) practice can come with many challenges.¹ Operators are asked to advocate for two patients, balancing the needs of the sick mother with that of the fetus in her body.

The procedure on the pregnant woman, like any other, requires imaging guidance, sedation and/or analgesics, and other medications including prophylactic antibiotics and antiemetics. However, the physical changes of pregnancy and the presence of the developing fetus make selection of medication and the use of ionizing radiation in the form of fluoroscopic and/or computed tomography (CT) guidance more challenging. In addition, the patients' disease may be more advanced at presentation due to concerns about the pregnancy.²

When consulted to perform a procedure during pregnancy, the interventional radiologist needs to discuss the medical indication and establish medical necessity with both the ordering clinical service and the obstetric service. Elective procedures with relatively little gain for the mother should be postponed if possible until 6 weeks after the delivery.³ In general, a medical emergency threatening the life of the mother such as maternal shock, blunt trauma, and maternal death also threatens the life of the fetus.⁴ Therefore, the primary focus (evaluation, resuscitation, and life-saving treatment) should be the health and well-being of the mother. Fetal assessment and consideration needs are secondary, especially where the fetus might be viable.⁵ In the intermediate semi-urgent but nonemergent setting, delaying treatment until the second or third trimester may reduce the fetal risk of radiation and medication exposure.

The interventionalist must openly discuss with the patient the benefits, risks, and alternatives of the procedure; the use of sedatives and analgesics in addition to other medications needed for the procedure; and potential radiation exposure to properly obtain informed consent.

Beyond 20 weeks of pregnancy, preferential positioning of the patient is in a left lateral decubitus position or with left pelvic tilt to minimize compression of the inferior vena cava (IVC) and aorta by the gravid uterus.^{2 3 6} Electrocautery, if needed, requires careful planning so that the grounding pad and the cautery are not positioned across the uterus for the fear of conducting electricity through the amniotic fluid.⁷

Patients undergoing IR procedures usually require analgesia with or without sedation. A decision should be reached in collaboration with the patient, on the appropriate level of sedation. The physiologic changes that occur during pregnancy can make sedation more challenging. For example, swelling of the nasal mucosa can increase the risk of bleeding if nasal intubation is needed.⁶ Diaphragmatic excursion is decreased due to the enlarged uterus along with an increase in ventilation related to the increased oxygen demands of pregnancy.⁶ The overall blood volume increases as the pregnancy progresses, up to 40% above baseline toward the end of the pregnancy, mostly reflected by an increase in the volume of plasma. This increase in plasma decreases the concentration of water-soluble medications, resulting in a delay of the expected effects of medications such as meperidine. Hypotension can result from the increases in cardiac rate and output, and decrease in systemic resistance. In addition, there is up to a 50% increase in glomerular filtration rates during pregnancy, which can increase the rate of drug clearance. Furthermore, the rate of food absorption slows down and the function of the lower esophageal sphincter decreases, which increases the risks of gastroesophageal reflux⁶ and aspiration. Prophylactic medication for the prevention of reflux should be considered after the end of the first trimester.³

Oversedation can cause maternal hypoxia and hypotension, which ultimately reduce oxygen perfusion to the fetus. There is no autoregulation of fetal blood flow, and fetal blood flow falls in relation to maternal blood pressure. Fetal bradycardia as a result of distress may present as the first indicator of decreased perfusion. Supplemental oxygen should be routinely administered to the mother to maintain oxygenation and to reduce fetal stress.³ Decreasing the level of sedation can also reduce the risk of maternal hypotension and maintain adequate blood flow to the fetus,² but this needs to be balanced with the potential of inducing stress-related complications to the mother and fetus as a result of inadequate pain control.³

Fetal monitoring (confirmation of fetal heart beats) should performed in the latter first trimester and beyond immediately before and after the procedure to ascertain the wellness of the fetus.⁶ In certain circumstances, such as high-risk pregnancy and higher levels of sedation/analgesia, continuous fetal monitoring during the procedure may be appropriate. In the authors' practice, any pregnant patient undergoing sedation receives a full obstetrical consult. An anesthesia consult and postprocedure fetal ultrasound are obtained in the first trimester to evaluate fetal viability (viability is also ascertained just before the procedure). Fetal heart beats are measured by Doppler ultrasound pre- and postprocedure in the second trimester. After 22 weeks of gestation, the patient signs an additional consent for possible emergent cesarean section with the obstetrics service.

All in all, the IR physician should have a low threshold for consulting an anesthesiologist, especially for more complex cases requiring deeper levels of sedation/analgesia and for high-risk pregnancy. In general, monitored anesthesia care with propofol is preferred over regional anesthesia. Regional anesthesia is considered a safer choice for the mother and fetus compared with general anesthesia; however, consideration should be given to significant decreases in maternal blood pressure that can occur with spinal anesthesia.³ Furthermore, the amount and duration of sedation can be minimized by having the most experienced IR physician perform the procedure,² with all the equipment available in the room before stating the procedure.⁸

Pregnancy and Radiation Exposure

In the general population, approximately 50% of conception is not viable and spontaneously lost in women with no exposure to radiation. The risk of non–radiation-related malformation is 3% or higher in this population.¹ On the other hand, thousands of pregnant women are unintentionally exposed to ionizing radiation without knowing their pregnancy status, according to the International Commission on Radiological Protection.⁹

The National Council on Radiation Protection and Measurements states that radiation exposure less than 50 mGy to the fetus is considered negligible in comparison with baseline risks for all developmental abnormalities, but this risk increases significantly when exposure exceeds 150 mGy.¹⁰ The majority of routine diagnostic radiographs (plain film of the chest, extremity, head) delivers less than 20 mGy to the uterus, and CT of the abdomen and pelvis usually delivers less the 35 mGy. Fluoroscopically guided procedures in the pelvis can deliver doses above 100 mGy, and may place the fetus at risk for teratogenicity if exposed during first trimester of pregnancy.^{1 11 12}

There are two main types of radiation effects, deterministic and stochastic. Deterministic effects are not seen below a threshold dose, but above the threshold, the severity of the detrimental effects is dose dependent. Examples of fetal deterministic effects include spontaneous abortion and teratogenicity, depending on the gestational age during which exposure takes place.¹³ The most important prenatal risk and deterministic effects occur at 8 to 15 weeks postconception, when the sensitive cortical cells of the developing brain are exposed to radiation greater than the threshold of 300 mGy. This may result in a decrease of the baby's intelligence quotient and mental retardation. Stochastic effects originate from damage to single cells, enough to cause a mutation but preserving the ability to divide.¹⁴ Carcinogenesis (childhood cancer like leukemia) is an example of stochastic effect. There is no safe level of radiation exposure below which the stochastic effect is eliminated.¹⁰ Such a cancer risk has been determined to be around 5 to 15% per Gy in some series, without a defined dose threshold.⁴ It is associated with exposure of the fetus in later trimesters. Table 1 outlines radiation effects and dose limits for pregnant patients.

Table 1. Radiation effect on fetal development¹⁵ .

Gestational age	Fetal development	Radiation effects
1–2 wk	Fertilization and uterine implantation	Loss of pregnancy (> 50 mGy)
2–8 wk	Formation of organs	Teratogenicity (> 100 mGy)
2–15 wk	Neural development	Microcephaly and mental retardation (> 100 mGy)
2–40 wk	Genetic mutation	Cancer risk: Cancer < 15 years of age (0.06% risk per 10 mGy) cancer later in life (0.4% risk per 10 mGy exposure)

Procedures in the Pregnant Patient

All radiologic tests involving ionizing radiation require a complete pregnancy status questionnaire as part of the initial evaluation. Women of child-bearing age without a history of hysterectomy should be screened for possible pregnancy. If there is any question about whether pregnancy is a possibility, a pregnancy test should be ordered for confirmation (pregnancy tests should be obtained within 72 hours before the procedure). Most states allow minors to have a pregnancy test without parental consent or notification.¹

Since radiation exposure is involved in the majority of IR procedures, it is mandatory to take appropriate actions to limit the dose to the mother and fetus while still accomplishing the goal of the treatment.⁸ This entails limiting the radiation exposure to levels as low as reasonably achievable.¹ Once the need for the procedure is confirmed, the safest way to perform the procedure for the mother and the fetus must be determined. A medical physicist may be consulted to calculate radiation dosage to the fetus and risk related to the procedure.

Multiple strategies can be used to decrease the radiation dose. Fluoroscopy can be avoided if the therapeutic/diagnostic goal can be reach successfully with alternative imaging, such as ultrasound or magnetic resonance. Many procedures, including percutaneous nephrostomy, percutaneous drainage, or percutaneous cholecystostomy, can be achieved with just ultrasound, or requiring a minimal amount of fluoroscopy to confirm catheter position.

An experienced interventionalist should perform the procedure (it is not appropriate to have a trainee as the first operator) to limit not only the radiation exposure but also the time required for sedation. Radiation safety features should be fully utilized.⁸ Strategies in reducing radiation exposure include reducing the rate of pulsed fluoroscopy (adjusted to the lowest rate possible), use of last image hold to position the patient, limiting the beam on time, minimizing digital subtraction angiography (DSA) acquisitions, limiting the use of magnification, using tight collimation, raising the patient away from the X-ray tube, keeping the image intensifier as close to the patient as possible, removing the grid, and reducing the tube current.^{1 4} Use of lead shielding for nonpelvic procedures does not provide significant protection but may impart a positive psychological effect on the patient.

Universally available, the use of multidetector CT can significantly reduce the amount of radiation and improve the diagnostic quality. In addition, the use of low tube current, limiting the length of the scanned area to the minimum required, decreasing the number of acquisitions, increasing the pitch, and avoiding real-time CT fluoroscopy, also limits the radiation exposure to the patient and the fetus.¹⁰

Special Considerations in Commonly Performed IR Procedures

Venous Access

The patient with severe hyperemesis gravidarum in early pregnancy, or chronic inflammatory bowel disease, may require ongoing hydration or nutritional support with durable venous access. Peripherally inserted central catheters (PICC lines), nontunneled and tunneled central lines (e.g., Hohn and Hickman catheters), and even implanted ports may be appropriate solutions, depending on the anticipated duration of the need for IV support, underlying conditions, and patient preference. These procedures can be achieved using ultrasound guidance, with minimal fluoroscopy to confirm the position of the catheter.

Genitourinary Procedures

Hydronephrosis is rare in the first and second trimesters, but may be seen in up to 20% of women in the third trimester with pelvicalyceal diameter greater than 10 mm on ultrasound.¹⁶ In the great majority, the hydronephrosis is located on the right and without symptoms, usually resolving completely within 6 weeks of delivery. A propensity to forming stones may also be exacerbated by the relative stasis of urine (prevalence 0.03–0.4%).¹⁷ Urgent ureteral decompression may be indicated when hydronephrosis is associated with fever or persistent renal colic; IR may be consulted if cystoscopic retrograde stent placement fails, or is contraindicated for other reasons.

Placement of the initial nephrostomy is ideally performed using ultrasound without fluoroscopy as the primary method of guidance.¹⁸ A simple nephrostomy placement avoids prolonged attempts to manipulate wires and stents across an obstruction, as well as lowering the chances of maternal bacteremia from newly established urinary-venous communications.

A particularly challenging situation may arise in the rare event of ureteral injury with ongoing ureteral leak and decompressed renal collecting system. A helpful maneuver in this situation is to perform an on-table intravenous urogram, then rapidly target the transiently visible desired calyx under fluoroscopy (with dose-reducing precautions exercised, as above). Maternal exposure to intravenous nonionic contrast material appears to present a low risk of neonatal hypothyroidism.^{19 20}

Nephrostomy catheters placed during pregnancy tend to collect encrustations of urinary salts more rapidly than catheters placed in nonpregnant patients.²¹ Therefore, routine exchanges should be scheduled every 3 to 4 weeks, or even more frequently, to avoid difficulty in passing wires and consequent increased fluoroscopy time. After delivery, the underlying urologic problem should be addressed definitively.

Biliary Procedures

Gallstones, although uncommon, are the primary cause of biliary obstruction in pregnancy. Acute cholecystitis in pregnancy may be effectively managed with percutaneous cholecystostomy. Ultrasound can be the only imaging guidance as long as there is free aspiration of bile. A drainage catheter should be placed via a transhepatic route, and allowed to drain externally until an optimal time for definitive surgery.^{22 23 24}

Acute pancreatitis in pregnancy is a rare cause of biliary obstruction (∼ 3 in 10,000 pregnancies), but may require biliary decompression via a percutaneous transhepatic approach.²⁵ When endoscopic drainage is unsuccessful or contraindicated, external percutaneous drainage of the biliary tree without complex stenting may be preferred to reduce procedural radiation; however, fluid losses via external drains could risk dehydration and electrolyte imbalance, and therefore require close monitoring.

Venous Thromboembolic Disease in Pregnancy and Postpartum

The incidence of venous thromboembolism (deep venous thrombosis [DVT] and pulmonary embolism [PE]) in pregnancy is four to five times greater than that in the nonpregnant population, secondary to the hypercoagulable state intrinsic to pregnancy.²⁶ This state begins in the first trimester and can increase until 8 weeks postpartum. DVT is easily detectable with ultrasound imaging. The diagnosis of PE in pregnancy may be established with chest X-ray to triage the patient to either a ventilation/perfusion study (after a normal X-ray) or a CT pulmonary angiogram, with a lead shield over the abdomen and pelvis (when PE is suspected).²⁷

The role of IVC filter placement, usually in the suprarenal position, is evolving. The Society of Interventional Radiology lists pregnancy as a potential indication for suprarenal IVC filter placement.²⁸

Peripartum Uterine Bleeding

Abnormal placentation, including placenta previa, accreta, increta, and percreta, poses a risk of significant peripartum hemorrhage. The interventional radiologist may be consulted, often on short notice, to facilitate control of anticipated or ongoing bleeding.²⁹

The technique before delivery involves bilateral femoral artery punctures and selective catheterization of both the right and left internal iliac arteries. Some authors describe selective catheterization of the uterine arteries, which can be challenging and lead to greater radiation exposure to the fetus.²⁹ The 5.5 F compliant balloon catheters are positioned in the internal iliac arteries, and secured at the skin at the inguinal creases in the IR suite. The patient is transferred to the delivery operating room with the deflated balloons in place. The sheath and balloons should be flushed with heparinized saline continuously to prevent thrombotic complications. The balloons can be inflated immediately after the baby is delivered, if needed.

After delivery, persistent hemorrhage may be secondary to uterine atony, uterine arterial injury, arteriovenous (AV) fistula, and rarely to the presence of placenta accreta or increta. Uterine artery embolization (usually with temporary agents such as Gelfoam (Pfizer Injectables, New York, NY)) is effective in arresting postpartum bleeding from these causes. In many cases of accreta, hysterectomy may be pursued; embolization is helpful preoperatively to reduce blood loss.

Trauma in the Pregnant Patient

The priority in the management of the pregnant acute trauma patient is to reestablish and maintain maternal hemodynamic stability.^{30 31} Diagnosis and endovascular techniques for arterial injury management in the extremities are well established, and differ little from those seen in the nonpregnant patient, as the fetus can be isolated from radiation exposure both by distance and shielding. Endovascular treatment of bleeding injuries of the spleen, kidneys, and liver also differs little from that in the nonpregnant patient.³²

High-energy deposition pelvic fractures, which may involve disruption of the pelvic ring and associated internal iliac artery injuries, are highly associated with placental abruption and other potentially lethal fetal injuries. Urgent caesarean delivery may be indicated under conditions of maternal hypotension, as transcatheter embolization of the maternal internal iliac arteries and branches would be deleterious to the fetus. Close collaboration between interventional radiologists, trauma surgeons, and obstetricians is vital in making the best decisions.

Medications and the Pregnant Patient

U.S. Food and Drug Administration classifies medications applicable to pregnancy into five categories (A, B, C, D, and X). The majority of the medications used in IR are B and C categories. Group A medications demonstrate no adverse effects in well-controlled studies involving human pregnancies. Group B medications demonstrate no adverse effects in well-controlled studies involving human pregnancies but show adverse effects in animal pregnancies, or are medications that demonstrate no adverse effects in animal pregnancies without well-controlled studies involving human pregnancies. Group C medications demonstrate adverse effects in animal pregnancies without studies involving human pregnancies or are medications where there are no human or animal pregnancy data available. Group D medications demonstrate adverse effects in human pregnancies, but may have benefits that outweigh the risks. Group X medications demonstrate adverse effects in human pregnancies, the risk outweighing possible benefits, and are contraindicated during pregnancy.^{6 33}

Regardless of the category, each medication used during pregnancy should be carefully considered and the benefit should outweigh the risk of its use.

Contrast Agents

Iodinated contrast—Category B. Iodinated contrast does not appear to be teratogenic.^{34 35} Previous experience with direct large dose contrast injection into the amniotic sac has resulted in hypothyroidism of the newborn, although it was not seen with intravenous injection in the pregnant patient,^{35 36} and no teratogenicity was seen in animal pregnancies.³⁵ However, avoiding use of iodinated contrast in the first trimester, if possible, is recommended.³⁴ The American College of Radiology (ACR) recommends the use only when necessary and with informed consent from the patient.³⁶ Diatrizoate meglumine and diatrizoate meglumine sodium are category C (Table 2).³⁷

Table 2. Contrast, topical anesthetics, NSAIDs, reversal agents, and steroids during pregnancy.

Name of medication	Pregnancy category	Special consideration
Iodinated contrast	B	Avoid use in first trimester if possible. Diatrizoate meglumine and diatrizoate meglumine sodium are category C
Gadolinium	C	ACR recommends to avoid in pregnancy
Topical anesthesia (lidocaine, benzocaine, procaine, tetracaine)	B	Cocaine contraindicated in pregnancy
Naloxone	B	Contraindicated in narcotic-dependent patients
Flumazenil	C	Neurobehavioral changes in animals with uterine exposure
Steroids (hydrocortisone, prednisone, methylprednisolone)	C during 2nd and 3rd trimester D during 1st trimester	Prednisone and methylprednisolone more resistant to crossing placental barrier
Diphenhydramine (Benadryl)	B	Overdose can cause uterine contractions
Acetaminophen (Tylenol)	C	Widely used as first-line over-the-counter pain medication in pregnancy
NSAIDs (ibuprofen, naproxen)	C	Premature closure of ductus arteriosus

Abbreviations: ACR, American College of Radiology; NSAIDs, nonsteroidal anti-inflammatory drugs.

Gadolinium—Category C. IV gadolinium crosses the placenta, and in large and frequent doses has been teratogenic in animal studies.³⁵ The ACR recommends avoiding the use of gadolinium during pregnancy unless it is critical, and only after full discussion with the referring clinician and with informed consent from the patient.³⁶

Medications for Sedation and Analgesia

Topical anesthetics (Lidocaine, Benzocaine, Procaine, and Tetracaine)—Category B. No evidence of teratogenic effects exists for topical anesthetics in human pregnancies, but cytotoxicity has been seen in in vitro studies. Cocaine, however, has demonstrated teratogenicity in cocaine users and should be avoided (Tables 2 and 3).^{6 38}

Table 3. Analgesia and sedation during pregnancy.

Name of medication	Pregnancy category	Special consideration
Meperidine	B	Preferred over Fentanyl
Fentanyl	C	Favored in patients with seizure history
Morphine	C	Readily crosses to fetal brain
Hydromorphone	C
Propofol	B	First-line medication for deeper sedation
Benzodiazepine	D	Single dose of midazolam likely safe; diazepam contraindicated in pregnancy

The use of nonsteroidal anti-inflammatory drugs (NSAIDs) should be restricted because of risk of premature closure of the ductus arteriosus.³

In a large cohort of pregnant women who used opioid analgesics regularly between 1 month and the end of the first trimester of pregnancy, a positive correlation with certain cardiac defects, spina bifida, and gastroschisis has been noted.³⁹

Meperidine—Category B. Meperidine does not appear to be teratogenic⁷ and is the preferred analgesic compared with fentanyl and morphine in pregnancy. Meperidine used on its own is the preferred drug for sedation in pregnant patients undergoing routine endoscopy, but can cause respiratory depression, and a change in fetal heart rate variability and reactivity in the newborn.^{2 6}

Fentanyl—Category C. Fentanyl does not appear to be teratogenic and is safe in small doses, but found to be embryocidal in rats.⁷ Fentanyl has shorter onset and duration of action than meperidine, and is favored over meperidine in patients with seizure history.^{2 6}

Morphine—Category C. Morphine does not appear to be teratogenic, but is associated with increase in stillbirths and lower birth weight in rats following prolonged exposure³⁸; similar findings have been noted in mothers with chronic methadone exposure. Morphine more readily crosses the blood–brain barrier⁷ when compared with meperidine and fentanyl.

Hydromorphone—Category C. Hydromorphone is teratogenic in animal studies at 600 times the human dose. There is limited literature on hydromorphone use for labor-related pain (the manufacturer recommends against use of medication for obstetric pain), but there is insufficient literature to determine its effect during early pregnancy.

Naloxone—Category B. Naloxone does not appear to be teratogenic.⁷ Given intravenously, naloxone can quickly reverse respiratory depression, hypotension, or unresponsiveness due to narcotic overdose. However, the effect of naloxone can be shorter in duration than the effect of the narcotics given, and continued monitoring after the reversal may be needed to prevent relapse of symptoms. Its use is contraindicated in women who are narcotic dependent, and can exhibit symptoms of withdrawal from reversal of the narcotics.^{6 7}

Propofol—Category B. Propofol does not appear to be teratogenic, although there is paucity of first trimester studies.⁷ It is recommended as first-line medication for patients requiring a deeper level of sedation without the use of a benzodiazepine. Consulting anesthesiology is recommended due to the need for careful titration of the medication and for closely monitoring the patient for respiratory depression.^{2 6 7}

Benzodiazepines (Midazolam, Diazepam, Lorazepam, and Alprazolam)—Category D. Benzodiazepines should be avoided if possible. Midazolam does not appear to be teratogenic⁷ but may be associated with risk of miscarriage during the first and second trimester.⁶ Cleft palate and neurobehavioral effects were seen with the use of diazepam in human pregnancies.^{6 38} Neither should be used in the first trimester (diazepam should not be used at all in pregnancy), and midazolam, which can cause respiratory depression in the newborn, should be used with caution.² Some authors have suggested that a single dose is thought to be safe.³

Flumazenil—Category C. Flumazenil is a benzodiazepine antagonist. It is not well studied in pregnancy, but does not appear to be teratogenic. Animal studies, however, suggest neurobehavioral changes when exposed in utero.⁶

Medications for Prophylactic Antibiotics

Penicillin-based antibiotics (Cefazolin, Ampicillin, Piperacillin–Tazobactam, Ampicillin–Sulbactam, Ceftriaxone)—Category B. Penicillin and its derivatives do not appear to be teratogenic. Increased clearance of the medication along with increase in the plasma volume, especially later in pregnancy, decreases the overall concentration,^{33 40} and may require dose adjustment (Table 4).

Table 4. Antibiotics during pregnancy.

Name of medication	Pregnancy category	Special consideration
Penicillin-based antibiotics: Cefazolin, Ampicillin, Piperacillin–Tazobactam	B	Increased blood clearance later in pregnancy
Erythromycin	B
Clindamycin	B
Aminoglycoside: Vancomycin	C	Potential for nephrotoxicity and sensorineural hearing loss
Quinolones: Ciprofloxacin, Levofloxacin	C	Potential for arthropathy in newborn. Increased clearance later in pregnancy
Tetracyclines: Doxycycline	D	Dental discoloration and maternal liver dysfunction
Gentamycin	D	Potential for ototoxicity and nephrotoxicity

Macrolide (Erythromycin)—Category B. Erythromycin does not appear to be teratogenic (no association with congenital heart defects or pyloric stenosis) in two large studies.^{41 42}

Clindamycin—Category B. Introduced for use in 1968, clindamycin does not appear to be teratogenic when used during pregnancy.⁴³

Aminoglycoside (Vancomycin)—Category C. There is potential for nephrotoxicity and sensorineural hearing loss in the newborn following vancomycin use during pregnancy.³³ A small study demonstrated transient auditory brainstem response abnormality in 60% of newborns, exposed to vancomycin during second and third trimester of pregnancy, but this change normalized by age 1.⁴⁴

Quinolones (Ciprofloxacin, Levofloxacin)—Category C. Three studies (38 patients, 549 patients, and 588 patients) failed to show increased teratogenicity for fetuses exposed to quinolones.^{45 46 47} Lower concentration in the pregnant patient suggests an increased clearance and possible need to adjust dosage.³³ There is increased potential for arthropathy in the newborn,³³ and the use of quinolones during pregnancy is discouraged¹ and should not be used as first-line antibiotic in pregnancy.⁴⁶

Tetracyclines (Doxycycline)—Category D. One retrospective study of 1,843 births exposed in utero during the first trimester to doxycycline failed to demonstrate a significant increase in congenital defects.⁴⁷ However, there is risk of dental discoloration and maternal liver dysfunction,³³ so these drugs should be avoided during pregnancy.

Gentamicin—Category D. The possibility for ototoxicity and nephrotoxicity³³ is associated with length of exposure beyond unsafe levels of the medication.⁴⁸ There is increased clearance during pregnancy, requiring higher doses (unless the patient has preeclampsia where the dose must be decreased).^{33 48} Gentamicin exposure in a small group of laboring (end of third trimester) and small group of second trimester patients did not demonstrate hearing loss in the infants.^{48 49} Although gentamicin along with ampicillin is one of the recommended antibiotic regimen for pyelonephritis and chorioamnionitis during pregnancy,⁴⁸ teratogenicity is unknown and to be used as second-line medication for prophylaxis.

Other Medications Used in Interventional Radiology

Metoclopramide (Reglan)—Category B. There is no known significant increased risk of birth defects, low birth weight, preterm delivery, or perinatal deaths, according to a study of 3,458 births in fetuses exposed to metoclopramide during the first trimester.⁵⁰ Metoclopramide is recommended as first-line treatment for HG (Tables 2 and 5).⁵¹

Table 5. Antiemetics during pregnancy.

Name of medication	Pregnancy category	Special consideration
Metoclopramide (Reglan)	B	First-line med for hyperemesis gravida
Ondansetron (Zofran)	B	Contraindicated in patients with liver dysfunction or serious heart disease, including long QT syndrome
Promethazine	C	Possible neonatal platelet dysfunction when given during labor
Prochlorperazine (Compazine)	No category assigned	Avoid in pregnancy

Ondansetron (Zofran)—Category B. Ondansetron does not appear to be teratogenic or associated with increased risk or spontaneous abortion, still birth, preterm labor, or low birth weight.⁵² It should not be used in patients with liver dysfunction or serious heart disease, including long QT syndrome.

Promethazine (Phenergan)—Category C. Promethazine does not appear to be teratogenic,⁵³ but may cause platelet dysfunction in neonates when given to mothers during labor.⁵⁴ Promethazine should be used only if the benefits outweigh the risks, and neither metoclopramide nor ondansetron is available.

Prochlorperazine (Compazine)—No category assigned. There are mixed reports of increased teratogenicity in rats and rabbits versus no significant increase in teratogenicity related to phenothiazine derivatives exposure during pregnancy.³⁸ Prochlorperazine may be best avoided in pregnancy.

Diphenhydramine (Benadryl)—Category B. Diphenhydramine does not appear to be teratogenic in a major study with exposure during early pregnancy.⁵⁵ However, an overdose of diphenhydramine can cause uterine contractions and should be dosed judiciously.⁵⁶

Hydrocortisone, prednisone, methylprednisolone—Category C in second and third trimester, Category D in first trimester. Glucocorticoids are teratogenic in animal studies when used in large doses during organogenesis.⁵⁷ Prednisone and methylprednisolone may be more resistant to crossing the placental barrier (than dexamethasone and betamethasone), but can be oversaturated if large doses are given for long periods of time.^{57 58} Chronic use during pregnancy may lead to low birth weight and adrenal suppression in the newborn^{58 59}; steroids should be used with caution when benefits outweigh risks.