Fetal and neonatal brain tumors are rare. Prenatal ultrasound aids early tumor detection. Nonetheless, we encountered a preterm neonate born at 32 weeks gestation with a massive supratentorial glioma, which was undetected on ultrasound at 19-6/7 weeks gestation. The patient presented at birth with unanticipated massive macrocephaly. Resuscitation and stabilization were difficult, but the medical team felt that futility of care was not established and opted to transfer the baby to an academic center for further imaging and specialist consultations. Diagnosis of an extensive, inoperable tumor was confirmed and support withdrawn. Postmortem histologic examination and immunohistochemical stains identified the majority of tumor cells as glial in origin. This case report illustrates well how a severe and potentially fatal anomaly, which remained undetected prenatally, presented the medical team and family with multiple medical, ethical and emotional challenges at birth; decisions regarding futility of care in the neonatal transport setting are difficult.
Fetal and neonatal brain tumors are rare: less than 10% of perinatal tumors are cranial neoplasms and they account for only 1% of childhood brain tumors.1, 2, 3 Location, biological characteristics and response to therapy are different from that in older children and prognosis is often poor.4, 5, 6, 7, 8 Macrocephaly is a typical clinical finding. Pregnancies are often complicated by a large-for-gestational-age uterus, polyhydramnios and hydrops; dystocia and stillbirth may occur.1, 3, 5, 7, 9 Prenatal ultrasound (US) aids early tumor detection.3, 6, 9, 10, 11 Nonetheless, we encountered a neonate born at 32 weeks of gestation with a massive supratentorial glioma, which was not detected by US at 19-6/7 weeks gestation. The unexpected severe macrocephaly, difficult resuscitation and stabilization presented significant challenges to the medical team and family at birth.
Prenatal history of this Caucasian male neonate was unremarkable; second trimester US showed normal cranial measurements and anatomy at 19-6/7 weeks gestation: head circumference measurement was 17.30 cm (35th percentile) and biparietal diameter was 4.61 cm (48th percentile).
Preterm labor, unresponsive to tocolytics, developed at 32 weeks of gestation and the infant was delivered by cesarean section for breech presentation at the non-tertiary hospital. Delivery of the head was difficult due to unanticipated massive macrocephaly with a head circumference of 46.5 cm (50th percentile for gestational age: 30 cm). Birth weight was 2800 g (above 97th percentile). Both ears were low set and posteriorly rotated, two ear tags on the tragus were noted on the left ear; downslanting palpebral fissures, midface and mandible appeared small possibly secondary to the marked macrocephaly. Apgar scores were 2 at 1 min and 3 at 5 min. The baby required resuscitation and intubation in the delivery room and received surfactant early in his course. At 30 min of age the infant became bradycardic and required chest compressions and epinephrine to recover. Ongoing ventilation, inotrope support and fluid resuscitation were necessary. Poor tone was noted, there was no response to stimulation other than minimal flexion with pain. Spinal reflexes were present, but no pupillary, corneal or gag reflexes could be observed.
Multiple laboratory parameters were abnormal, including a white blood cell count of 31.0 × 109 l−1 with a left shift of 14% immature forms. Nucleated red blood cells were elevated (263, normal 0 to 5), C-reactive protein 25.1 mg dl−1 (upper normal 0.9 mg dl−1), severe anemia with a hemoglobin of 6.32 gm dl−1 (normal 16 to 22 gm dl−1) and a hematocrit of 16.2% (normal 45 to 65%).
Cranial US performed by the neonatologist shortly after birth showed a complete lack of normal intracranial structures with the presence of multiple poorly defined areas of variable echogenicity. After discussion among the medical team and with the parents, decision was made to continue intensive care and transfer the infant to a tertiary-care neonatal intensive care unit at an academic center by a specialized neonatal transport team.
After transfer, computer tomography showed a lack of normal brain structures with exceptions of remnants of a right cerebral hemisphere. An extra-axial fluid collection and subdural hematoma were present. On magnetic resonance imaging (Figure 1), a large-mass distorted intracranial anatomy showing a mantle of brain tissue in the expected location of the right cerebral hemisphere and a partially visualized mantle of tissue in the expected location of the left cerebral hemisphere anteriorly. Ventricular structures were distorted and likely dilated. The majority of the intracranial compartment was replaced by a very large heterogeneous signal: a solid and partially cystic soft tissue mass, measuring 13.3 × 10.3 × 10.4 cm3. The midline falx was thinned and distorted; the posterior fossa appeared small.
A team of neurosurgeons, neonatologists and oncologists assessed that the changes represented an inoperable and incurable tumor. With the parents’ consent, support was withdrawn on the second day of life.
At autopsy the fontanels were widened, the scalp was ‘tense and boggy’. The brain tissue was partially liquefied and hemorrhagic with an increased weight of 750 g (average brain weight at 32 weeks gestation: 209 g). A subarachnoid hemorrhage was noted. Normal cerebral landmarks were entirely obliterated.
Postmortem histologic examination and immunohistochemical stains identified the majority of tumor cells as glial, mainly astrocytic, with nodules of neuron-like cells, spindle cell regions, myxoid-like regions and areas of necrosis and palisading as seen in glioblastoma multiforme. Interestingly, the tumor’s mitotic index was low (1 to 3%) despite the apparently rapid growth. Assignment of a final histopathologic diagnosis was difficult and diagnosis of an ‘undifferentiated glioma’ was made.
The patient presented here is remarkable for the fact that the tumor could not be detected on prenatal US at 20 weeks but was massive at birth 12 weeks later resulting in medical and ethical challenges.
The medical staff was surprised by the unexpected presentation of the newborn; they were facing a difficult airway and were struggling to achieve a position appropriate for intubation: multiple blankets were needed to elevate the body to the same level as the head creating a sniffing position to open the airway. The situation was very different from ‘usual’ neonatal resuscitation scenarios and issues beyond those addressed in the standard algorithms of resuscitation were encountered. Neonatologists are well prepared to resuscitate babies with severe malformations (diaphragmatic hernias, etc), which they intermittently encounter in their career, even if undiagnosed at the time of birth. This was a ‘once in your career’ scenario though where ‘airway, breathing, circulation’ (the ABCs of resuscitation) were especially difficult and, although significance of the conditions was evident, its exact nature, best treatment approach and outcome was uncertain.
Owing to the lack of an antenatal diagnosis, team and parents were faced with a sudden and unanticipated extensive resuscitation in a markedly disfigured newborn; the team had to consider the questions of futility of care. As outlined by Wilkinson et al.,12 ‘lethality’ is difficult to define and the question of ‘futility’ of care may be more relevant.13, 14, 15 Guidance on withdrawal of care in situations requiring stabilization and transport is limited and only Dulkerian et al.16 discussed these issues in the context of neonatal transport. In this setting, time to assess futility and ‘best interest’13 is limited. The local neonatologist performed a bedside US but, while recognizing severe abnormalities, was not qualified to give a final interpretation of the imaging study. As the patient was quite ill, a timely transfer to a high-level intensive care unit deemed advisable if care was to be continued; however, it did include a risk of death during transport, which was discussed with the parents. Neonatologists are competent making decisions about futility of care in patients with malformations they encounter regularly during their career, even if the baby is born suddenly and without the diagnosis established prenatally. This scenario is different as the team had not encountered a similar patient before and, while assessing prognosis as likely grim, did not have sufficient information to be certain that care was futile and the condition lethal; specialist input seemed essential. Also, withdrawal of care can be difficult in a non-tertiary setting where teams have limited experience in supporting families and staff when care is redirected. This influenced the decision to stabilize and transport. Including the family in this decision was difficult as the mother was heavily medicated while recovering from surgery and the father appeared to be in shock. Attempts to assess the family wishes and involve them in care decisions had to be abandoned on their request; their level of distress was marked and they had no immediate access to family and friends for support.
Transfer gave the parents time to adapt to the situation and to obtain advice from specialists before final (and non-reversible) decisions were made. But transfer also meant separating mother and child, especially significant as the possibility that the child might die was high. The team felt that transfer did put the interest of the child first as futility was not certain; it was felt that active treatment should thus be continued and optimized.
This did result in expenditures of transport and intensive care, but medical, ethical and emotional aspects of this patient’s care support this decision; Meadow et al.17 outlined that only 6% of cost in the neonatal intensive care unit setting they examined were related to care for non-survivors. Also, in our case, the diagnostic process was very efficient and futility of care was established, communicated to the family and decision to withdraw care was made by the second day of life.
We conclude that advances in prenatal US have improved antenatal detection of fetal tumors, but massive neoplasms with rapid growth may still elude prenatal detection. Parents need to be counseled that US scans, even with many recent advancements, cannot fully exclude the presence of congenital anomalies and diseases that may be encountered at birth. This case illustrates how an unexpected major medical issue, in this case a massive tumor, can present multiple medical challenges for the team treating the mother and infant at the time of birth and can also pose significant emotional and ethical challenges. Scenarios such as the one presented here should be considered for use in health-care simulation training to prepare health-care teams for situations in which they may suddenly encounter these significant medical, emotional and ethical challenges.
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We acknowledge the staff of the referring hospital, transport team and receiving hospital (who are not further named to deidentify the patient). We thank Dr Judith Rossiter for review of the deidentified prenatal US findings.
The authors have not received any support for the work in the form of grants and/or equipment or drugs. The authors declare no conflict of interest.
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Olischar, M., Stavroudis, T., Karp, J. et al. Medical and ethical challenges in the case of a prenatally undiagnosed massive congenital brain tumor. J Perinatol 35, 773–775 (2015). https://doi.org/10.1038/jp.2015.80
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