Fetal Intracerebral Mass With Major Perinatal Implications

Abstract

A 27-year-old G3A2L0 woman is referred to the Maternal Fetal Medicine clinic after a routine third-trimester ultrasound in a community setting shows an intracerebral mass at 30 weeks’ gestational age (GA). The mother is healthy other than being a chronic carrier of hepatitis B. She is blood type B positive with a negative antibody screen. She previously had two first-trimester therapeutic abortions, and this is her first pregnancy with her current partner. The pregnancy was uneventful with a negative integrated prenatal screen and ultrasounds with normal results at 14 and 20 weeks’ GA. Mild maternal thrombocytopenia was detected throughout the pregnancy (lowest platelet count 97 × 109/L) with reported increased bruising. There is no family history of bleeding disorders in either her or her partner's family.The findings on physical examination are normal with no signs of bleeding, bruising, or petechiae. A complete blood cell count shows a hemoglobin level of 11.3 g/dL (113 g/L) and a platelet count of 124 × 103/μL (124 × 109/L). A repeat ultrasound confirms a large complex intracerebral mass with hypoechoic areas suggestive of cysts as well as echogenic portions that were felt to be either solid or to represent bleeding with clots. The composition of the mass is clarified by maternal MRI at 31 weeks’ GA, which shows a large cystic complex lesion measuring 5.0 × 3.8 × 4.5 cm (Fig 1). There is a solid component that shows blooming on the susceptibility-weighted imaging sequence, suggestive of blood products, clot, or calcification, but an underlying neoplastic process or vascular anomaly cannot be excluded.A repeat ultrasound is performed 10 days later at 32 weeks’ GA in conjunction with a biophysical profile for follow-up of the mass. The mass has increased in size to 5.6 × 4.3 × 4.5 cm with midline shift and possible compression of the left choroid plexus (Fig 2). Parental platelet antigen results are still pending. However, given the increasing mass size, an empirical decision is made to treat the patient as if she had a bleeding disorder. She is hospitalized 3 days later and treated with betamethasone to enhance fetal lung maturity and reduce the risks of neonatal mortality and intraventricular hemorrhage. Intravenous immunoglobulin (IVIG) (1g/kg) and prednisone 50 mg is administered daily for two consecutive days for the management of a probable bleeding disorder.A male infant, weighing 2.179 g, is delivered by caesarean delivery at 33 weeks’ GA with Apgar scores of 8 and 8 at 1 and 5 minutes, respectively. The pediatric team is in attendance and matched, compatible platelets are available for immediate transfusion if necessary. The platelet count at birth is 5 × 103/μL (5 × 109/L). The infant is transferred to the NICU and briefly receives continuous positive airway pressure for transient respiratory distress. Two single-donor, irradiated, platelet transfusions (human platelet antigen [HPA] 1b/1b; 10 mL/kg) are administered on successive days with IVIG (1 g/kg), and the platelet count stabilized at 200 × 103/μL (200 × 109/L).The findings of a complete newborn examination, including a full neurological assessment, are normal. An MRI shows a 5.4 × 6.0 × 4.7 cm intraparenchymal cyst located in the territory of the left middle cerebral artery consistent with an evolving hemorrhage (Fig 3). Midline shift is mild with insignificant parenchymal compression. Multiple, small hematomas are evident, mainly in the cerebellum, and few are noted within the cortical parenchyma. Neurosurgery and neurology are consulted. The risks and benefits of surgical intervention are thoroughly discussed with the parents and the allied health care professional team, but surgical intervention is deemed unnecessary in the absence of raised intracranial pressure and neurological deficits versus the operative risk of further extension and complications from the existing intracranial hemorrhage (ICH). Based on the location and size of the hemorrhage, long-term spastic hemiplegia, right homonymous hemianopia, and epilepsy are prognosticated. The infant is successfully discharged to a level 2 nursery at 13 days of life with planned follow-up.A differential diagnosis of neonatal alloimmune thrombocytopenia, severe idiopathic thrombocytopenia, a hereditary platelet disorder, anatomical abnormality, intracerebral tumor, and a spectrum of congenital infections (toxoplasmosis, rubella, cytomegalovirus, herpes) was considered. The absence of maternal history, negative serology, and normal fetal anatomical profile, apart from the localizing lesion, made the diagnosis of viral infection less likely. Congenital brain tumors are rare; the most common are intracranial teratomas, which comprise 50% of all lesions followed by astrocytomas, choroid plexus papillomas, ependymomas, and other primitive tumors. (1) Contrast-enhanced MRI with T1- and T2-weighted imaging helps to define the location, components of the lesion, compression of the ventricular system, midline deviation, and coexisting hydrocephalus. However, differentiation may still prove difficult, and, moreover, hemorrhage can masquerade as a tumor. After maternal treatment was commenced antenatally, the parental HPA status revealed an incompatibility; maternal HPA-1b/1b, paternal HPA-1a/1a, and the infant was later found to have HPA-1a/1b.The incidence of neonatal alloimmune thrombocytopenia (NAIT) is ∼0.7 in 1000 pregnancies. (2) It is the most common cause of severe thrombocytopenia in fetuses and neonates and of ICH in the newborn. (3) NAIT is defined as thrombocytopenia and bleeding in a fetus or neonate caused by maternal antibodies directed against fetal platelet antigens inherited from the father. Human platelet antigen-1a (HPA-1a) is the most frequently involved antigen. Fetal platelet antigens are expressed as early as 16 weeks and enter the maternal circulation through poorly understood mechanisms. Unlike hemolytic disease of the newborn, in which index cases are usually unaffected, NAIT can have severe sequelae even in the initial pregnancy.The incidence of ICH in fetuses with HPA-1a antigen alloimmunization is ∼20%. (4) Most hemorrhages occur antenatally (80%) with 32% presenting before 30 weeks’ GA. (4) NAIT in a first-born child is usually unanticipated and diagnosed at birth because of skin bruising, petechiae, and moderately severe thrombocytopenia (platelet count <50 × 103/μL [50 × 109/L]). ICH is generally identified by cerebral ultrasound as part of the NAIT workup. Our case is unique in that the fetal ICH led to the diagnosis of NAIT rather than vice versa. It is not standard practice with uncomplicated pregnancies to have routine third-trimester ultrasounds and the rationale remained undetermined. Regardless, the intracerebral findings instigated a diagnostic assessment and may have saved this child's life.Antenatal therapy for known NAIT includes fetal transfusion of antigen-compatible platelets, maternal IVIG, and corticosteroids. Recent trends favor the use of the latter two, noninvasive therapies, in the absence of solid evidence from randomized, placebo-controlled trials. With recognized NAIT either apheresis, leuko-reduced, plasma-depleted, irradiated, maternal platelets, or HPA-1a- and HPA-5b-negative stocked platelets are optimum for newborn treatment and should be made immediately available at birth. IVIG (1–2 g/kg total dose) given on successive days with or without steroids is also of benefit but with a slower response time. Random donor platelets have proven useful and are advocated while awaiting the arrival of compatible platelets. (5) Algorithms for the diagnosis of NAIT and neonatal management are summarized in recent reviews. (2)(6)A useful predictor of the severity of thrombocytopenia and future occurrence of ICH with HPA-1a alloimmunization is the presence of fetal ICH in a sibling, (4) but this finding is inconsistent across studies. (7) The rate of ICH recurrence in future pregnancies ranges between 72% and 79%. (4) More recently, blood group A phenotype compared with group O was found to be associated with a 2-fold higher risk of severe NAIT. (8)This case illustrates that, although NAIT is relatively rare, it needs to be considered in any otherwise well fetus or neonate who presents with ICH. Multidisciplinary care involving maternal fetal medicine, radiology, hematology, and the neonatal intensive care team is essential. Major discussion should ensue when NAIT is suspected antenatally but cannot be confirmed in a timely fashion; risks of elective preterm birth must be weighed against the risk of ongoing bleeding in utero. Close monitoring and regular fetal surveillance must be undertaken in a tertiary care service where maternal treatment is optimized and compatible platelets are readily available through the transfusion service to achieve favorable maternal-fetal outcomes. In all cases of ICH, neurodevelopmental follow-up is essential because long-term sequelae are likely. Once a diagnosis of NAIT is established, all future pregnancies should be screened and supervised in an advanced perinatal unit.