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Brain Tumors During Pregnancy


This chapter includes an accompanying lecture presentation that has been prepared by the authors: .

Key Concepts

  • The unique physiologic state of pregnancy creates challenges and affects the timing of treatment for the pregnant patient.

  • The incidence of brain tumors in pregnancy is not different from that in the general population. There is no conclusive evidence suggesting that pregnancy predisposes women to the development of brain tumors.

  • Some brain tumors may increase in size during pregnancy. Meningiomas are notable for this.

  • Imaging is necessary to diagnose brain tumors in general. MRI and CT are safe during pregnancy depending on the timing of imaging and the use of contrast material, and with the appropriate precautions.

  • Surgery for brain tumors during pregnancy is possible and safe. It is best if this can be postponed until delivery; however, if it cannot be postponed, surgery is possible with the appropriate timing and precautions. The decision to proceed with surgery will depend on the nature and location of the lesion, symptoms and neurological status of the patient, and gestational age.

  • Treatment should be aimed at maintaining the health of the patient and of the unborn child.

  • Chemotherapy and radiotherapy should be avoided unless absolutely necessary.

The diagnosis of a brain tumor is challenging for any patient, but stakes can be even further increased in pregnant women. The medical team has to consider both the pregnant patient and her fetus in all of the medical decisions they make. The unique physiologic state of pregnancy creates challenges and influences the timing of treatment for the pregnant patient. Unfortunately, there is a lack of comprehensive data on the care of pregnant patients diagnosed with brain tumors, and this poses challenges in the medical care of these patients. In addition, it is necessary to consider the nature of the tumor, the presentation of the patient, and the timing in pregnancy to determine the best treatment and whether carrying out the pregnancy is feasible. Improved understanding of the optimal medical treatments for pregnant patients and new developments in surgical and anesthetic techniques have resulted in enhanced ability to care for these patients while decreasing pregnancy complications.

In the International Network on Cancer, Infertility and Pregnancy (INCIP) Cancer in Pregnancy Registry, breast cancer, cervical cancer, and hematologic cancers are the three most frequently diagnosed cancers in pregnancy (43%, 14%, and 13%, respectively, in 835 patients registered). It is estimated that the incidence of cancer in pregnant patients ranges from 1 in 1000 to 1 in 2000. Primary intracranial tumors are the fifth leading cause of cancer-related death occurring in women 20 to 39 years old. All types of nervous system tumors have been reported during pregnancy, but no single type is predominant. However, it is known that the hormonal and physiologic changes during pregnancy can affect the biology of certain tumors as well as the development of neurological symptoms. , Many studies have described a relapsing pattern in tumors relative to pregnancy, menstruation, and menopausal status. An example of this is the increased growth of some meningiomas in pregnant women. The incidence of meningioma is similar between pregnant women and nonpregnant women of the same age group. , , However, the physiologic changes of pregnancy such as water retention, engorgement of blood vessels, and the presence of sex hormone receptors on tumor cells may result in volumetric expansion of the meningioma and a flare-up of symptoms such as vomiting, headache, and seizures. , This presentation could potentially be misdiagnosed as hyperemesis gravidarum during early pregnancy or as eclampsia during late pregnancy.

This chapter describes the brain tumors that occur most frequently in women of childbearing age, their common initial signs and symptoms, their impact on gestation, and the medical and surgical management of brain tumors while minimizing the risks to the fetus.

Neuroimaging in Pregnancy

In general, imaging studies other than ultrasonography should be minimized in pregnant women. However, MRI and CT are important tools in the diagnosis of neurological disease in pregnant women. The use of these two imaging modalities has facilitated the diagnosis of intracranial neoplasms in pregnant patients while minimizing the risk to the patient and the fetus. MRI does not use ionizing radiation and is considered relatively harmless to the fetus. , Furthermore, MRI is the imaging modality of choice to diagnose intracranial neoplasms owing to its excellent soft tissue differentiation. Theoretical concerns regarding the fetus include teratogenic and biologic effects secondary to the alteration of cell migration; however, no formal study has been performed to determine the adverse effect profile in neonates or fetuses to date. Moreover, there is theoretical risk of injury due to the noise during different acquisition sequences. MRI may cause effects at the cellular level from the induction of local electric fields, currents from static and time-varying magnetic fields, and tissue and cellular heating from radiofrequency fields. Most of the adverse biologic effects associated with exposure to radiofrequency fields are thought to be related to thermogenesis. There are class IIIC data suggesting that use of MRI during the first trimester of pregnancy should be restricted to maternal indications to obtain clinically essential information. However, it should be noted that exposure to MRI during the first trimester has not been associated with any long-term sequelae. MRI is safe during any trimester of pregnancy, especially if performed with a 1.5-T scanner. , Much of the trepidation regarding the negative effects associated with MRI in the first trimester comes from very early animal studies that documented effects on the early fetus in terms of growth, miscarriages, and eye malformations. However, the applicability of these animal models to humans has been questioned. According to the 2013 American College of Radiology (ACR) Guidance Document on MR Safe Practices, MRI in pregnant patients should be performed only if the required information cannot be obtained with other, nonionizing imaging modalities; if the information is likely to alter the patient’s care; and if the examination cannot be postponed until delivery. From a practical standpoint, initial diagnostic MRI studies are indicated by a new onset of symptoms suggesting an intracranial neoplasm. However, follow-up MRI during the first trimester is typically avoided unless there is neurological deterioration and depending on the nature of the neoplasm in the initial diagnostic study. Obtaining a timely diagnosis that can appropriately guide the medical and surgical management of the rest of the pregnancy clearly outweighs lesser risks associated with the diagnostic procedures. According to the Society of Obstetricians and Gynaecologists of Canada (SOGC), there is class II evidence that fetal exposure to MRI is safe at 3.0 T or less during the second and third trimesters. One safety consideration regarding MRI studies for the pregnant patient requiring MRI is prolonged supine positioning. A significantly sized gravid uterus may result in hypotension owing to compression of the inferior vena cava in the pregnant woman. This risk can be avoided by placing the pregnant patient in left lateral decubitus or lateral oblique position during the MRI.

CT of the head during pregnancy is relatively harmless to the fetus because the radiation exposure to the fetus is less than 0.005 mGy. The use of CT in pregnant women has increased significantly as we have learned more regarding the safety in and radiation exposure to the fetus. Radiation from a CT scan emanating to a fetus that is 30 cm or more from the scanner results in a dose two orders of magnitude below the maximal permissible dose of 0.5 mSv, , and thus the radiation resulting from CT of the mother’s head presents little risk to the fetus. , Furthermore, the radiation dose that reaches the fetus can be minimized with lead shielding. Nonetheless, CT imaging should be performed judiciously in the pregnant patient, making sure that its benefit outweighs the risk.

On occasion, the administration of iodinated or gadolinium-based contrast material is essential to define the tumor. The administration of a contrast agent can be a concern with regard to possible adverse effects on fetal development. Iodine- or gadolinium-based intravenous contrast agents should be used only when absolutely necessary and only after careful evaluation of the risk-to-benefit ratio.

Iodinated contrast agents are category B drugs in the US Food and Drug Administration classification, which means that they did not pose reproductive risks in animal studies. However, no studies have been performed in humans. Although iodinated contrast material does not have teratogenic effects, it may affect the uptake of iodine by the fetal thyroid gland and lead to hypothyroidism. Furthermore, no teratogenic effects have been reported with iodinated contrast agents used in CT. Considering the lack of literature available to demonstrate that iodinated contrast is completely safe for the fetus, the ACR Manual on Contrast Media recommends that iodinated contrast agents can be administered intravenously only as needed in pregnant women.

Gadolinium is classified as a category C drug by the US Food and Drug Administration, which means that these agents have shown teratogenic effects in animal studies at supraclinical doses. Studies have shown that intravenous gadolinium is teratogenic in animals at high and repeated doses. Gadolinium crosses the placenta and is excreted by the fetal kidneys into the amniotic fluid, where it remains, causing exposure of the developing fetus to it, particularly the lungs and gastrointestinal tract. The 2010 ACR guidelines for safe MRI practices recommend avoiding intravenous gadolinium during pregnancy and using it only if it is judged absolutely essential. It should be noted that despite animal data and concerns about the use of gadolinium in pregnancy, there have been no reported adverse human fetal effects. More research is still needed to determine the safety of MRI gadolinium in pregnancy, but at this time the SOGC recommends that gadolinium contrast material may be used in pregnant women only when the benefits outweigh the potential risks.

Neuroanesthesia in Pregnancy

Although nonobstetric surgery in pregnant patients is fairly common, neurosurgery in these patients is not. The anesthetic management of the pregnant patient undergoing a craniotomy presents challenges because of the anatomic and physiologic changes that occur during pregnancy. Special considerations must be kept in mind and measures taken to make anesthesia safe for the patient and the child. The anesthesia needs to be tailored to the physiologic demands of pregnancy in an attempt to prevent teratogenicity, preterm labor, and fetal hypoxia, as well as to address a multitude of other concerns. There is a paucity of evidence-based neuroanesthesia guidelines for management of pregnant women with intracranial pathologic conditions. This is, at least in part, a result of the rarity of intracranial surgery performed on the pregnant woman.

To the neurosurgeon, the most relevant anesthetic issues relating to pregnant patients with neurosurgical disorders are (1) the recommended type of anesthesia for those requiring craniotomy and (2) the optimal anesthesia for delivery of the newborn in a patient who has a brain tumor. Planning and decision making need to be based largely on the general principles of neurosurgical and obstetric anesthesia.

When considering whether to perform surgery in an obstetric patient, the surgeon must also consider that mortality in nonobstetric surgeries during pregnancy is approximately 0.25%, and that the in-hospital mortality is fourfold greater than in nonpregnant women (0.82%). In addition, there is increased risk for miscarriage (2.5%), surgery-induced delivery (4.7%), preterm birth (8.2%), and major birth defects (2% in general, but 3.9% if the surgery takes place in the first trimester). The risk of stillbirth or low birth weight increases significantly when preterm delivery has to be induced, which can also affect the survival rate of the child, depending on the gestational age. ,

The decision to proceed with surgery will depend on the nature and location of the lesion, symptoms and neurological status of the patient, and gestational age. Neurosurgical concerns regarding the mother should be among the main factors in deciding whether or not to proceed with surgery; however, this decision should be made by the neurosurgeon, neuroanesthetist, obstetrician, and patient.

Neuroanesthesia for the Pregnant Woman Requiring Craniotomy

Surgery for symptomatic intracranial lesions in pregnant patients presents special challenges to the surgical team. However, several series have suggested that surgical treatment of intracranial masses during pregnancy is well tolerated by both mother and fetus. , Performing surgery for a brain tumor in the pregnant patient is an undertaking that absolutely requires a multidisciplinary approach for best outcomes.

Neurosurgical procedures during pregnancy will take place in one of three possible situations that include neurosurgery in later stages of pregnancy, cesarean section before the neurosurgical procedure, or neurosurgery followed by cesarean section at a later date. Elective surgical procedures during the first trimester should be delayed until the second trimester to avoid the potential fetal risks of perioperative stress, surgery, and the teratogenic effects of anesthetic drugs because the first trimester is the period when most organogenesis occurs. However, it should be noted that no data exist to support the teratogenicity of anesthetic agents in the setting of a clinically relevant anesthesia exposure during first trimester and that most research data originates from multiple exposure paradigms in pregnant rodents. In a large systemic review of pregnancy outcomes following nonobstetric surgical intervention, surgery in the first trimester did not appear to increase major birth defects, and thus it was concluded that it should not be delayed when indicated. Surgery during pregnancy often increases the risk for a first- or second-trimester spontaneous abortion, but it does not increase the incidence of congenital abnormalities, nor does surgery appear to induce premature labor. The second and third trimesters are considered safe for maternal anesthesia primarily because embryogenesis is complete. Human neural embryology suggests that the second trimester is a period of bustling fetal brain development. Animal studies clearly demonstrate that anesthetic agents affect early brain development by altering the anatomic organization of the brain as well as inducing functional consequences in the form of learning and memory deficits. , In addition, anesthetics can disrupt brain development through impairment of neuronal migration, alteration of the chloride gradient, and alterations of the mammalian target of rapamycin (mTOR) pathway. Although data on the fetal brain are limited at this time, most animal studies suggest that the developing fetal brain is at risk from maternal anesthesia, especially during the second trimester.

In addition to the considerations regarding anesthetic agents and management, there are multiple other aspects of the surgery that have to be adapted to the obstetric patient in an attempt to optimize the safety of the patient and the fetus. For example, surgical positioning and dosage of anesthetic agents should be modified appropriately. Plasma volume and total blood volume are increased in pregnancy, resulting in dilutional anemia. Cardiac output is also increased by as much as 50%. As a result of many of these changes, anesthetic requirements are often decreased in pregnant patients undergoing surgery. Minute ventilation and tidal volume are increased, whereas the functional residual capacity and expiratory reserve volume are decreased. , Ventilation also increases in pregnancy. At term, respiratory rate is increased by 15%, tidal volume is increased by 40%, and net minute ventilation is increased 50% above nonpregnant levels. Pregnant patients are also at increased risk for vomiting and aspiration at induction because gastric motility is decreased in pregnancy.

It is paramount to maintain normal uterine blood flow to avoid fetal hypoxia. Cardiotocography to monitor the fetal heart rate and potential contractions in patients past the 16th week of gestation provides information regarding the adequacy of oxygen delivery to the fetus. In addition to fetal hypoxia, decreased uterine perfusion may lead to premature contractions and preterm labor. Hyperventilation and vasoconstrictors during surgery are often needed to maintain adequate uterine perfusion. A reduction in Pa co 2 from 32 mm Hg, the normal level in pregnancy, to 25 mm Hg, a goal that occasionally may be necessary during craniotomy procedures owing to the presence of brain edema surrounding a brain tumor, can decrease uterine artery blood flow by 25%. ,

Positioning of the pregnant patient is also critical, and certain considerations must be kept in mind to avoid mechanical compression of the vena cava by the gravid uterus. The supine position increases intrathoracic and intra-abdominal pressures, which may decrease uterine blood flow and result in a condition called supine hypotension syndrome . To prevent this, a bump can be placed under the right hip of the pregnant patient to tilt the patient closer to left lateral position to minimize vena cava compression by the fetus. Park bench and sitting positions have been found to have milder detrimental effect on uterine blood flow compared with other positions, and the latter allows better respiratory function. The prone position, on the other hand, should be avoided in the pregnant patient.

Blood pressure should be kept normotensive in the pregnant patient under anesthesia; however, controlled hypotension may be necessary in certain instances. Several case reports of medically induced hypotension during aneurysm clipping in pregnant patients suggest that a mean arterial blood pressure of 40 to 50 mm Hg for up to 40 minutes does not result in harm to the fetus. This measure should be avoided unless absolutely needed.

Newborn Delivery in Patients With Cranial Lesions

The diagnosis of a brain tumor in a pregnant woman generates a challenge regarding when and how to deliver the newborn and the route of delivery. Historically, delivery has been postponed until after 36 to 38 weeks of pregnancy to decrease the chances of respiratory distress syndrome and other preterm syndromes in the fetus. Improvements in the use of surfactant and other medical therapies have demonstrated that safe delivery at 32 weeks of pregnancy may be a possible option. , Developments in neonatal intensive care in the past 20 years have pushed the boundaries of medicine to the point of being able to keep children alive with prematurity as great as 22 to 26 weeks’ gestational age. Nevertheless, these children are at very high risk of neurodevelopmental sequelae as well as other preterm syndromes. It is advisable to try to carry the pregnancy to as close to term as possible.

The presence of intracranial pathology in the pregnant patient greatly affects the anesthetic plan and the plan for delivery of the newborn. If the treatment team decides to accomplish delivery and craniotomy concurrently, the anesthetic management plan will be heavily influenced by the anesthetic requirements for a craniotomy. If delivery is to be performed before the brain tumor resection, the medical team must be acutely cognizant of the precautions necessary in the presence of an intracranial lesion causing a mass effect and elevated intracranial pressure, because this, compounded with the physiologic stress of delivery, can result in catastrophic outcomes. , Therefore the anesthetic and delivery strategy should be modified according to the situation of the patient. There is a paucity of data on the effect of active labor on brain tumors, but there are concerns that this may lead to elevated intracranial pressure or higher chances of tumor hemorrhage. Furthermore, there are even fewer data on the effect of vaginal delivery or cesarean delivery after craniotomy for resection of brain tumors. Thus, it is believed that in patients with brain tumors who are ready to deliver, it is better to perform general endotracheal anesthesia and a cesarean section to prevent sudden elevations in intracranial pressure that can lead to significant neurological complications in the presence of an intracranial lesion causing mass effect. Regional anesthesia should be avoided in patients with brain lesions that present with significant intracranial mass effect. The placement of an epidural catheter may result in loss of cerebrospinal fluid and the consequent risk of tonsillar herniation or development of acute subdural hematoma. , Regional anesthesia may be appropriate during a cesarean section after an uncomplicated neurosurgical procedure and for lesions that do not exert a mass effect. In this scenario, the patient must be awake and cooperative. The main advantage of this approach is to decrease the risk of general anesthesia during delivery. However, in instances in which a vaginal delivery is being attempted, the obstetrician should have a low threshold to consider instrumented delivery if necessary to shorten and facilitate the delivery process in case there are any difficulties during labor. In general, unless absolutely dictated by a deteriorating clinical or neurological condition, craniotomies at the time of or shortly after the delivery are not recommended because of the transient coagulopathy that frequently develops during the immediate postpartum period. , Whenever possible, craniotomy for resection of brain tumor should be performed after the newborn has been delivered and the mother has recovered.

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