2.1 AGENESIS OF THE CORPUS CALLOSUM
Definition Complete or partial agenesis of the corpus callosum (ACC) is a failure of the callosal commissural fibers to cross in the midline and form the corpus callosum between the two cerebral hemispheres. Partial agenesis may also be called hypogenesis, or dysgenesis, of the corpus callosum.
Epidemiology Incidence may be as high as 1%, with many asymptomatic individuals.
Embryology The corpus callosum develops between the 12th and the 22nd week of gestation. Vascular disruption or failure of formation may cause complete or partial agenesis. Associated abnormalities include hydrocephalus, microcephaly, pachygyria, and lissencephaly. More than 80 sporadic, genetic, and chromosomal syndromes have been described with ACC, including trisomies 13 and 18. The incidence of chromosomal abnormalities is approximately 10%. Agenesis of the corpus callosum, combined with intracranial cysts or eye anomalies, should suggest Aicardi syndrome, an X-linked dominant disorder with male lethality.
Inheritance Patterns Most isolated defects are sporadic. Autosomal dominant, recessive, and X-linked syndromes have been described.
Teratogens None known.
Prognosis Isolated ACC may be asymptomatic unless associated with other brain abnormalities. Typically, complete agenesis will have a worse prognosis than partial ACC. Associated brain, or extracranial, abnormalities suggest a guarded prognosis.
Absence of the cavum septum pellucidum
Colpocephaly (teardrop-shaped lateral ventricle)
Widened interhemispheric fissure
Midline interhemispheric cyst
Absence of the corpus callosum
Absent pericallosal artery
Atypical radiating appearance of the median sulci, which converge toward the third ventricle
Medial intracranial lipoma in the third trimester
If ACC is diagnosed, a detailed anatomic survey is required for complete evaluation.
The pericallosal artery follows the superior surface of the corpus callosum. Complete and partial absence of the corpus callosum can be inferred by evaluating the course of the pericallosal artery.
Three-dimensional (3-D) multiplanar imaging can be employed to obtain appropriate sagittal and coronal images of the corpus callosum.
Fetal magnetic resonance imaging (MRI) should be considered as an integral part of the assessment of ACC, particularly when isolated ACC is diagnosed. Fetal MRI may detect additional cerebral anomalies (i.e., heterotopias and migration anomalies).
Isolated absence of the cavum septum pellucidum: There is fusion of the frontal horns of the lateral ventricles with inferior pointing. The corpus callosum is present.
Lobar holoprosencephaly (HPE): There is absence of both the cavum septum pellucidum and the normal interhemispheric fissure.
Septo-optic dysplasia must be distinguished from isolated absence of the cavum septum pellucidum. MRI or 3-D ultrasound can be employed to look at the optic chiasm and nerves. Atrophy of the optic chiasm would indicate a diagnosis of septo-optic dysplasia rather than isolated absence of the cavum septum pellucidum.
Arachnoid cyst: Irregular shape and unlikely to be exactly midline. There is usually no ventricular dilation.
Mild lateral ventriculomegaly: The entire ventricle is dilated. The third ventricle is normal or slightly dilated.
Enlarged cavum septum pellucidum and vergae: The corpus callosum is present. The cavum septum pellicudum extends directly into the cavum vergae.
Aicardi syndrome: This is associated with agenesis or dysgenesis of the corpus callosum and occurs almost exclusively in females.
Investigations and Consultations Required ACC is a difficult diagnosis, and subsequent pregnancy management depends in part on the certainty of the diagnosis. Many cases of ACC are part of a syndrome, and steps to determine whether a case is isolated or syndromic are warranted. Chromosome studies, including microarrays, of the fetus are essential. Evaluation of the parents by a dysmorphologist for signs of autosomal dominant conditions, such as basal cell nevus syndrome and tuberous sclerosis, may be helpful. Fetal echocardiography should be performed to detect congenital heart disease. Maternal serum viral titers should be drawn. Additional consultations will depend on the associated abnormalities found. If uncertainty about the central nervous system (CNS) findings remains, a fetal MRI may be useful to delineate the CNS anatomy.
Monitoring No change in standard obstetric practice is indicated for isolated ACC. The aggressiveness of fetal intervention must be based on the underlying cause, if that can be determined. Isolated ACC should not progress, but if associated with a cyst or with ventriculomegaly or if the diagnosis is in question, a third-trimester examination is desirable to make sure the cyst has not enlarged, the ventricles are stable, and other processes have not been missed.
Pregnancy Course Obstetric complications are not expected on the basis of ACC alone.
Pregnancy Termination Issues Because many conditions have ACC as a component, an intact fetus should be delivered in an institution with expertise in dysmorphology and fetal pathology.
Delivery Because of the high association with other non-CNS abnormalities, delivery should occur in a tertiary center with full capabilities for diagnosis and management of infants with multiple malformations.
Resuscitation There are no specific issues except in those infants with additional CNS defects, in which case the associated defect will be the dominant factor in decisions regarding intervention.
Transport Referral to a tertiary center after birth is not indicated with an isolated lesion and asymptomatic course. Referral to pediatric neurology as an outpatient is indicated for further evaluation. With any neurologic symptoms present or associated CNS lesions, the infant should be referred promptly to a tertiary perinatal center with pediatric neurology capabilities for definitive evaluation.
Testing and Confirmation Postnatal confirmation of the defect and evaluation for other associated lesions are best achieved with MRI. Screening for inherited metabolic disorders is indicated with isolated lesions of the corpus callosum.
Nursery Management Subsequent course and management are dictated by the associated lesion(s).
Prognosis In cases of isolated ACC, there is variability in neurodevelopmental outcome, ranging from within normal limits to moderate-to-severe disability. The presence of associated CNS malformations is associated with an increased risk of significant neurodevelopmental deficits.
Definition Anencephaly is a defect in closure of the anterior neural tube characterized by complete or partial absence of the forebrain, overlying meninges, skull, and skin.
Epidemiology The incidence is geographically and population dependent and ranges from about 1 in 1000 births in the United States to 1 in 100 in parts of the British Isles (M1:F3). Preconceptual supplementation with folic acid has been shown to decrease the incidence of open neural tube defects.
Embryology Neural tube closure occurs between 20 and 28 days of pregnancy, with abnormalities of cephalic closure, which occurs late, resulting in anencephaly. Anencephaly is characterized by the absence of the cranial vault with exposed neural tissue and is associated with spina bifida, facial and nasal clefts, and omphalocele. Amniotic band disruptions are also an unusual cause of anencephaly. A small number of cases are associated with chromosomal abnormalities, such as trisomy 18.
Inheritance Patterns Multifactorial inheritance with both genetic and environmental factors is implicated. Recurrence risk after one affected pregnancy is 2% to 3% for any open neural tube defect. Rare families have been reported with X-linked inheritance. Periconceptional folic acid supplementation of 0.4 mg/d will decrease the incidence of spina bifida and anencephaly, but a subset of neural tube defects is not prevented by current therapeutic strategies. With folic acid supplementation and food fortification with folic acid, only approximately 50% of cases will be prevented.
Teratogens Valproic acid; folic acid antagonists, such as methotrexate and aminopterin; maternal diabetes; hyperthermia; and folic acid deficiency are associated with an increased risk for neural tube defects.
Screening Maternal serum α-fetoprotein screening or fetal ultrasonographic screening will detect most cases of anencephaly.
Prognosis Anencephaly is invariably lethal, with about 50% of cases being stillborn and the remainder dying in the newborn period.
Skull development is usually completed by 10 weeks’ gestation in a normal fetus.
While early first-trimester crown-rump length may be within the normal range, the mean crown-rump length is lower than expected.
In the first trimester, the brain may appear normal or have varying distorted shapes (“Mickey Mouse” sign of anencephaly at 11-14 weeks’ gestation).
There is gradual degeneration of exposed cerebral tissue, giving rise to the acrania/exencephaly/anencephaly sequence.
The sequence begins with a normal-appearing brain (acrania) that progressively degenerates to amorphous cerebral tissue (exencephaly), and finally to absence of cerebral tissue (anencephaly).
Degenerated cortical tissue is replaced by a vascular mass (area cerebrovasculosa).
On a coronal second-trimester image, the fetus has a “frog-like” appearance.
Anencephaly can be divided into “isolated” anencephaly and anencephaly with “multiple anomalies.” The chromosomal abnormality rate is higher in the multiple-anomaly group.
Late second- and third-trimester polyhydramnios is common, but not invariable.
Acrania: This results from abnormal development of the neurocranium, which ossifies to form the cranial vault.
Cortical tissue is still present.
Acrania is part of the anencephaly spectrum.
Large encephalocele: The skull will be visible on close inspection.
Microcephaly: A small skull will be present.
Iniencephaly: This is often present with anencephaly.
Investigations and Consultations Required No specific antenatal evaluations or consultations are necessary.
Monitoring In pregnancies that are continued, clinical assessment for the presence of polyhydramnios is indicated. Symptomatic polyhydramnios is an indication for delivery. Tocolysis is never indicated. The most important component of the prenatal care is emotional support for the family.
Pregnancy Course Anencephaly is always lethal at or shortly after birth.
Pregnancy Termination Issues Suction dilatation and evacuation techniques are appropriate. Karyotyping abortus material is worthwhile to detect the unusual case caused by a chromosome anomaly, such as trisomy 18.
Delivery There are no special conditions regarding delivery. The majority of anencephalic infants will deliver in the breech presentation.
Resuscitation Given the lethal prognosis, neonatal resuscitation is never indicated. Prenatal diagnosis and counseling should focus on preparing the family for nonintervention.
Transport Transport is not an issue.
Testing and Confirmation The abnormality is obvious at birth. Evidence of amniotic band disruptions should be sought. Cord blood should be obtained for genetic testing.
Nursery Management Palliative care with provision of comfort measures and facilitation of parental grief are the principal elements of care. Parents and the health care staff should be counseled that some infants may survive for several days with intermittent periods of stable cardiorespiratory function.
Organ Donation Organ donation from anencephalic infants should not be undertaken due to the serious difficulties surrounding the establishment of brain death in these infants and the lack of evidence to date supporting successful organ transplantation. There can be no modification in the medical criteria of brain death and legal standards of pronouncement of death to include infants with anencephaly. Families who request the opportunity to donate organs from their infant with anencephaly should have information and educational material provided that explains why this practice is not supported. The option of tissue donation from an anencephalic infant, including heart valves, cornea, and liver cells, should be discussed as these tissues may be harvested up to several hours after the death of the infant and can be frozen until a recipient is identified.
2.3 AQUEDUCTAL STENOSIS
Definition Aqueductal stenosis is an obstruction or maldevelopment of the aqueduct of Sylvius, resulting in congenital hydrocephalus.
Epidemiology One in 2000 (M1.8: F1). Ninety percent of cases of congenital hydrocephalus are the result of Arnold-Chiari malformations, whereas 3% to 5% have aqueductal stenosis.
Embryology The aqueduct of Sylvius is the connection between the third and fourth ventricles in the brain and develops at about 6 weeks’ gestation. Histologic evidence of gliosis is found in approximately 50% of cases of aqueductal stenosis, suggesting inflammatory or infectious causes. Some cases may be caused by true congenital atresia. The etiology is heterogeneous and includes congenital tumors, hemorrhage, infections, and genetic syndromes. Flexion and adduction deformities of the thumbs are present in 20% of boys with X-linked aqueductal stenosis.
Inheritance Patterns Most cases are sporadic. Estimates suggest that 2% to 5% of cases of hydrocephalus not associated with neural tube defects have X-linked recessive inheritance. The gene for X-linked aqueductal stenosis has been mapped to Xq28. Because of the rapid progress in mapping of genes and subsequent development of genetic testing, consultation with a medical geneticist or genetic counselor to determine the availability of clinical genetic testing for this disorder is advised.
Teratogens Teratogens are congenital infections, including cytomegalovirus, rubella, and toxoplasmosis.
Prognosis The neonatal detection of aqueductal stenosis is associated with normal development in 24%-86% of cases. However, prenatal diagnosis has a worse prognosis, and “normal” development occurs in only 10% of neonates. There is a 10% to 30% neonatal mortality rate, partly dependent on associated abnormalities. Up to half of fetuses with apparently isolated aqueductal stenosis will have other abnormalities found postnatally or at autopsy. The difference in outcome between a fetal and a neonatal diagnosis of aqueductal stenosis is due to the presence of undetected additional anomalies/chromosomal abnormalities in the fetal group. Approximately 50% of survivors will have an IQ greater than 70. The X-linked recessive form is associated with profound mental retardation and a poor prognosis.
Symmetrical ventricular enlargement
Dilated third ventricle (>2 mm)
Normal posterior fossa
Macrocephaly (head circumference > 2 SD above the mean)
Symmetric parenchymal thinning
Absence of aqueduct distal to the third ventricle
Ventriculomegaly is a descriptive term indicating a lateral ventricle measurement greater than 10 mm at the level of the cavum septum pellucidum. The calipers are positioned on the internal borders of the medial and lateral ventricles at the globus of the choroid plexus.
An atrial width between 10 and 15 mm is considered mild and width greater than 15 mm severe ventriculomegaly.
Ventriculomegaly is associated with different disease processes. Hence, prognosis varies.
Cerebral spinal fluid flows from the lateral ventricles through the foramen of Monro to the third ventricle and then to the fourth ventricle via the aqueduct of Sylvius. The more distal the obstruction is, the greater the involvement of the ventricle system.
The aqueduct of Sylvius is the narrowest passageway in the ventricular system.
While aqueductal stenosis can result in severe ventriculomegaly, brain anatomy may be otherwise preserved.
The sizes of the lateral and third ventricle are not useful predictors of long-term outcome.
Isolated aqueductal stenosis is, by necessity, a diagnosis of exclusion and accounts for only 1%-2% of patients with diagnosed ventriculomegaly.
A 3-D multiplanar view can reconstruct the midsagittal view to evaluate both the corpus callosum and the posterior fossa. The presence of a normal cavum septum pellucidum on a transaxial view is presumptive evidence for an intact corpus callosum.
Investigations and Consultations A family history should be taken and gender determined to evaluate for possible X-linked aqueductal stenosis. In the absence of a previous affected child, the evaluation should exclude other causes of hydrocephalus. Chromosome evaluation and viral studies (both maternal serum and amniotic fluid) should be performed. If ultrasound features are consistent with aqueductal stenosis, gene testing for this disorder should be done. Pediatric neurologic or neurosurgical consultation should be obtained to plan management. Fetal MRI may be helpful to confirm the diagnosis if expertise with this modality is available locally.
Fetal Intervention Theoretically, aqueductal stenosis should be the perfect situation for in utero shunt placement. However, the experience to date has been disappointing. There are many reasons for the relatively poor outcomes that have been seen. Misdiagnosis has been a common finding in all series, as has been failure to detect associated abnormalities. Morbidity has been high, reflecting the difficulties of exact shunt placement in the fetus. For these reasons, and the lack of data to support a clear benefit of fetal surgical intervention, in utero ventriculo-amniotic shunts are not indicated in the management of fetal ventriculomegaly from presumed aqueductal stenosis at the present time.
Monitoring Ventriculomegaly caused by aqueductal stenosis may abruptly increase in severity over a few weeks, so ultrasonographic monitoring is desirable. In addition, follow-up ultrasound may be used to exclude other comorbidities, such as growth delay, and to monitor head size. Otherwise, few pregnancy complications are expected, and pregnancy management should be unchanged.
Pregnancy Termination Issues The method of termination should be a nondestructive one as confirmation of etiology is necessary. Termination should be undertaken at a site with special expertise in neuropathology.
Delivery Although, in theory, early delivery followed by shunt placement could improve outcome, neonatal data do not support the benefit of this approach. Further study is needed before clear recommendations can be made. Mode of delivery can be vaginal if the head is of relatively normal size and the fetus is in a vertex presentation. Macrocephaly or breech presentation are common and often require cesarean section. Delivery should occur in a center where appropriate neonatal and neurologic services are available.
Resuscitation The decision regarding management following the onset of respiration should be discussed with the family prior to delivery. Except in circumstances of extreme enlargement of the head or presence of other severe CNS abnormalities, initial resuscitation is indicated.
Transport Immediate referral to a tertiary perinatal center with pediatric neurology and neurosurgery capabilities is indicated. Precautions during transport are dictated by the maturity of the infant, presence of respiratory distress, and other associated abnormalities.
Testing and Confirmation At the time of delivery, cord blood should be sent for genetic testing if antenatal testing was not performed. Head ultrasound and MRI are useful to establish a definite anatomic diagnosis. Further imaging studies to be considered are echocardiography and abdominal sonography if physical examination findings suggest other abnormalities and studies were not obtained prenatally.
Nursery Management Infants require admission to the neonatal intensive care unit for stabilization and evaluation. Pediatric neurology and pediatric neurosurgery consultation should be obtained to determine management plans.
Preoperative Assessment Issues of importance with respect to the surgical management of aqueductal stenosis are as follows:
The presence of other anomalies (i.e., cardiac, renal, spinal, or limb deformities), which may be associated with a poor overall prognosis.
The presence of a posterior fossa mass or compressive lesion, such as congenital tumor or tectal mass.
Rate of ventricular enlargement and head growth.
Operative Indications Evidence of progressive ventricular enlargement or accelerated head growth is indication for surgical intervention.
Types of Procedures Standard surgical therapy for aqueductal stenosis is ventricular shunting with either a ventriculoperitoneal (VP) or a ventriculoatrial shunt using a pressure-regulated valve system. An alternative therapy is endoscopic third ventriculostomy (ETV), a procedure that opens an alternative pathway for cerebrospinal fluid (CSF) to exit the third ventricle by a fenestration in the tuber cinereum of the floor of the third ventricle.
Surgical Results/Prognosis In the absence of associated CNS or non-CNS abnormalities, children with aqueductal stenosis have a good overall prognosis.
2.4 ARACHNOID CYST
Definition Arachnoid cysts are membrane-lined, fluid-filled cavities that may occur anywhere within the brain or spinal cord in association with the arachnoid or ventricular lining.
Epidemiology These are relatively rare neonatally because most are asymptomatic, but with prenatal ultrasound screening, more are being detected. They account for 1% of intracranial masses found prenatally and are more common in males than females.
Embryology Arachnoid cysts can occur anywhere in the lining of the brain or spinal cord. They may arise postnatally and are usually associated with trauma or infection, and they may communicate with the subarachnoid space. The cause of congenital cysts is unclear. They most likely represent maldevelopment of the leptomeninges.
Inheritance Patterns Rare autosomal recessive families with isolated arachnoid cysts have been described.
Teratogens Congenital infections.
Prognosis Because these cysts generally compress normal brain structures, the outcome is usually favorable unless associated with other congenital anomalies or there are significant complications related to treatment. The association of intracranial cysts with ACC should suggest the Aicardi syndrome, an X-linked dominant disorder with male lethality.
Unilocular or containing thin septa
Fifty percent occur in the midcranial fossa.
They may also occur in the supracellar cisterna, posterior fossa, or surface of the brain at the level of the fissures.
Most arachnoid cysts are diagnosed between 20 and 30 weeks’ gestation.
When arachnoid cysts are diagnosed after 30 weeks, there is frequently a normal second-trimester examination, indicating that arachnoid cysts may develop quickly.
Occasional diagnoses in the first trimester have been reported.
Interhemispheric fissure cysts may be associated with partial ACC.
With large intrahemispheric cysts, it is difficult to distinguish between compression and ACC.
Associated anomalies increase the likelihood of a karyotypic abnormality.
Arachnoid cysts may spontaneously resolve.
While regression is rare in the fetus, it is common in the neonate.
The cyst regression may result from spontaneous rupture into the subdural or subarachnoid spaces or ventricles.
Of antenatally diagnosed arachnoid cysts, 20% increase in size; approximately 4% regress.
Three-dimensional scanning can show an arachnoid cyst in 3 orthogonal views and confirm its location.
MRI can determine the exact location of arachnoid cysts and their relationship to adjacent brain.
Vein of Galen aneurysm: Utilize color Doppler to distinguish from an arachnoid cyst.
Porencephalic cyst: The cystic area will border on the ventricle.
Intracranial bleed: There will be internal echoes in the apparent cyst if the gain is increased.
Schizencephaly: A disorganized cystic area extends across the midline and involves both hemispheres.
Investigations and Consultations Required Despite the low reported incidence of chromosome abnormalities, cytogenetic studies should be performed. No other diagnostic evaluations are indicated unless the diagnosis is in question. Fetal MRI is a useful tool to confirm the diagnosis if the diagnosis is in doubt. Consultation with a pediatric neurosurgeon should be arranged.
Fetal Intervention Fetal intervention is not indicated because of the relatively benign course of this malformation.
Monitoring Serial ultrasound examinations should be performed to detect or follow ventriculomegaly, to follow the cyst size, and to detect evolving macrocephaly, which could affect delivery mode. If the cyst enlarges, the diagnosis may need to be reevaluated.
Pregnancy Course Obstetric complications are not expected.
Pregnancy Termination Issues The method of termination should be nondestructive as confirmation of etiology is necessary. Termination should be undertaken at a site with special expertise in neuropathology.
Delivery The site of delivery should be at a location with expertise in the management of neonates with CNS malformations.
Resuscitation In the majority of cases, arachnoid cysts do not cause symptoms in the immediate newborn period, and resuscitation is not necessary.
Transport Referral to a tertiary center with pediatric neurology and neurosurgery capabilities is indicated.
Testing and Confirmation Although the majority of infants are asymptomatic at birth, infants may present with macrocephaly or a bulging fontanelle with widened sutures. The cysts cause their symptoms through pressure and mass effect. Small-to-moderate cysts are frequently asymptomatic. Postnatal MRI will accurately define these abnormalities.
Nursery Management Infants with asymptomatic arachnoid cysts require no treatment in the immediate newborn period. Consultation with pediatric neurology is recommended with periodic outpatient follow-up. When treatment is necessary, the specific intervention depends on the size of the cyst and the specific location of the cyst within the skull.
Preoperative Assessment Location of the arachnoid cyst with respect to the ventricular system, the basal cisterns, and the structures of the posterior fossa is important for surgical planning. MRI scanning is useful to define the surgical anatomy.
Operative Indications Small arachnoid cysts without mass effect on surrounding neural structures warrant observation only with periodic head ultrasound or MRI. If stable over time, then no surgical intervention is indicated. Larger cysts that present with hydrocephalus, the presence of a neurologic deficit, increase in cyst size, or poorly controlled seizures require surgical intervention.
Shunting of the cyst to the peritoneal cavity or the right atrium.
Marsupialization of the cyst into the basal cisterns or surrounding subarachnoid space. This technique is useful only for arachnoid cysts that present at the skull base adjacent to the basal cisterns.
Fenestration of the cyst into an adjacent ventricle, which may be accomplished endoscopically.
Surgical Results/Prognosis Arachnoid cysts in general have an excellent outcome and are not typically associated with neurologic or cognitive impairment.
Arachnoid cyst seen in Figure 2.4D visualized on MRI.
2.5 CAUDAL APLASIA/DYSPLASIA (REGRESSION) SEQUENCE
Definition Caudal aplasia/dysplasia sequence (caudal regression) is the total or partial agenesis of the distal neural tube resulting in sacral agenesis/dysgenesis with associated abnormalities of the lower extremities and gastrointestinal or genitourinary tracts. It is a continuum from partial agenesis of the sacrococcygeal spine to complete absence of the sacrum, lumbar, and lower thoracic vertebrae.
Epidemiology The sequence occurs in about 1 to 5 of 100,000 births (M1:F1).
Embryology Differentiation of the lower spine is usually complete before the seventh week of pregnancy. The term caudal regression is probably inaccurate, as the caudal defects in this condition are primary malformations rather than the result of regression of structures. Sirenomelia may represent one end of the spectrum of this condition or may be etiologically separate. Heart defects are common associated malformations. This condition may overlap with the VACTERL (vertebral defects, anal atresia, cardiac defects, tracheoesophageal fistula, renal anomalies, limb abnormalities) association, making evaluation for other VACTERL association findings important.
Inheritance Patterns Most often, inheritance is sporadic. Rare families showing autosomal and X-linked dominant inheritance have been reported. It is often seen in association with maternal diabetes.
Teratogens Approximately 16% of cases are seen in infants of diabetic mothers. Individuals with poorly controlled diabetes have an incidence of caudal regression that is 200-fold higher than the general population.
Prognosis Prognosis is dependent on the severity of the defect and presence of associated abnormalities. Bowel and urinary complications are common and may not be compatible with life. If not part of a genetic or chromosomal syndrome, cognitive function is usually normal.
Conical termination of the spine with absent sacral and lower lumbar vertebrae
Disproportion between the upper and lower portions of the body
Shortened lower extremities
Femurs fixed in a V pattern
Decreased/absent movement of the lower extremities
Distal leg atrophy
Absence of the sacrum results in approximation of the iliac blades, giving a “shield-like” appearance.
Single umbilical artery
Congenital heart disease
Incomplete ossification of the sacrum in the first trimester makes the diagnosis difficult, but not impossible.
A 3-D ultrasound can accurately determine the level at which the spine is suddenly interrupted.
Sirenomelia is a related condition in which both legs are fused. In sirenomelia, there is oligohydramnios or absent fluid, and the kidneys may appear to be absent, obstructed, or dysplastic. There may be a single lower extremity, or both legs may be fused and lie alongside each other.
Investigations and Consultations Required Evaluation of the mother for diabetes should be performed. Fetal echocardiography should be performed to evaluate for associated cardiac defects. Pediatric surgical consultations should be obtained to plan neonatal management with the family.
Monitoring No specific alterations in obstetric care are necessary unless diabetes is diagnosed. The diagnosis is difficult to make, so repeat ultrasound examinations may be worthwhile. In addition, following fetal growth and amniotic fluid volume may be helpful in ongoing cases.
Pregnancy Termination Issues In the patient with known diabetes, no special autopsy requirements are necessary. In the absence of maternal diabetes, full autopsy of an intact fetus should be performed to establish the diagnosis.
Delivery Breech presentation is common and may warrant cesarean section, particularly as marked body/head discrepancy may be present. The complex neonatal issues that will be encountered require delivery at a tertiary center.
Resuscitation Except for the issues related to prematurity and to infants of diabetic mothers, there are no special concerns in planning for resuscitation. In a small number of cases, there may be other serious anomalies (CNS or cardiac) that could govern approach. If other life-threatening and potentially uncorrectable defects are known to be present, prenatal discussion with the parents regarding nonintervention is appropriate. If caudal regression is associated with bilateral renal agenesis, the defect is lethal.
Transport Referral to a tertiary center with multiple pediatric subspecialty capabilities is indicated.
Testing and Confirmation The physical findings are apparent at birth. Imaging studies, including echocardiography, to exclude concomitant cardiac anomalies, skeletal survey, abdominal ultrasound, head ultrasound, or cranial MRI should be obtained prior to invasive interventions.
Nursery Management Approach and management are governed by the suspected cause (i.e., maternal diabetes), associated anomalies, and the location of the defect. Caudal regression syndromes with lumbosacral agenesis may range from absent coccyx, as an isolated finding without neurologic sequelae, to sacral or lumbosacral agenesis. There are five types of caudal regression sequence. Types I and II are considered mild forms with coccyx absence, but without deficits in functionality. Type I involves total or partial unilateral sacral agenesis. Type II involves total sacral agenesis with variable lumbar agenesis. Types III and IV are the most severe, with total absence of the sacrum and systemic and neurological complications. Type III involves variable lumbar and total sacral agenesis, with the caudal end plate of the lowest vertebra often resting above fused ilia. Type IV involves fusion of soft tissues of both the lower limbs. Type V, also known as “sirenomelia” or “mermaid syndrome,” is associated with a single femur and tibia and may not have the same etiology as the other types. Depending on the type of sacral agenesis, bowel or urinary bladder deficiencies may be present. Associated orthopedic anomalies may include deformities of the feet, flexion contractures of the lower extremities, dislocation of the hips, kyphoscoliosis, and absence of ribs.
Management requires a multidisciplinary approach by neurosurgeons, urologists, nephrologists, physical therapists, and psychologists. Surgical interventions, such as transureteroureterostomy and cutaneous vesicostomy, may be necessary if clean intermittent catheterization or anticholinergic drug administration is not adequate to treat urological disorders. Colostomy is performed to treat an imperforate anus. Depending on the severity of the syndrome, orthopedic interventions may also be required. Treatment is supportive only when the primary pathology is irreversible.
Prognosis is poor in many cases. Early neonatal death in the severe forms occurs from cardiac, renal, and respiratory complications. Surviving infants usually have normal cognitive function.
2.6 INTRACRANIAL TUMORS
Definition There are over 100 types of intracranial tumors, but the majority of antenatally detected cranial tumors are teratomas derived from totipotent cells, including embryonic ectodermal, endodermal, and mesodermal tissue derivatives. Other more common fetal brain tumors are astrocytoma, ependymoma, choroid plexus papilloma, medulloblastoma, craniopharyngioma, and meningioma. It is difficult, however, to reliably separate these tumors from other intracranial neoplasms and benign cystic lesions.
Epidemiology Intracranial tumors are rare, with 50% of antenatally detected tumors being teratomas that show a very high male-to-female preponderance.
Embryology Teratomas occur most often in a midline location and have mixed solid and cystic areas. Only 3% of all teratomas occur intracranially. Other brain tumors form from specific areas of the developing nervous system. Most are located supratentorially.
Inheritance Patterns Sporadic.
Differential Diagnosis Benign intracranial lesions such as arachnoid cysts and lipomas. Teratomas and other intracranial neoplasms generally show progression and distortion of normal structures.
Prognosis Prognosis depends on the size and location of the tumor. The majority of antenatally detected tumors have been lethal.
Distortion of brain anatomy
Cystic or solid appearance
Tumor occupies a variable volume of the intracranial cavity
Size may result in dystocia at time of delivery
Hydrops from high output failure
Hemorrhage into the cerebral mass
Sonographic detection usually occurs in the third trimester. However, detection in the second trimester has been reported.
Rapid growth results in necrotic components that appear cystic.
This is the second most common brain tumor.
Glioblastoma is a type of astrocytoma and develops rapidly.
Arises from the fourth ventricle
Has a poor prognosis
Choroid plexus papilloma
Rapid onset of ventriculomegaly and macrocephaly
Extends into the lateral ventricle
Secretes a large amount of CSF
Less commonly arises in third and fourth ventricles
Originates from vermis
Tumor inception: 14-23 weeks’ gestation
Arises from Rathke’s pouch—an extodermal extension from the roof of the mouth
When large, sonographically similar to a teratoma
Prenatal ultrasound cannot accurately diagnosis tumor histology.
Ultrasound can distinguish the few potentially curable lesions (i.e., a localized choroid plexus papilloma) from a rapidly expanding fatal tumor.
A neonatal brain biopsy is required to obtain a definitive diagnosis.
Color Doppler can evaluate an intracranial mass for vascularity and displacement of normal vessels.
Choroid plexus papillomas and astrocytomas demonstrate internal vascular flow.
Gangliomas generally present as an avascular mass.
To determine the extent of an intracranial tumor, MRI should be considered.
Investigations and Consultations Required Because of the inability to make a precise diagnosis in some cases, other causes must be considered for the sonographic features, particularly intracranial hemorrhage. Consultation with a neurosurgeon or neurologist and with a neonatologist is essential to provide the family full information regarding the grave prognosis for the neonate and to develop a plan of management.
Fetal Intervention None is indicated.
Monitoring These tumors tend to grow quickly, and there may be massive macrocephaly. In addition to being a part of the differential diagnosis, intracranial hemorrhage may occur within a tumor, contributing to both uncertainty in interpreting the ultrasonographic findings and rapid head growth. Fetal hydrops and polyhydramnios are common complications of intracranial tumors. Serial ultrasound examinations are useful to monitor for the development of these complications, as well as to assess fetal head size.
Pregnancy Course The pregnancy may be complicated by polyhydramnios and resulting preterm labor. Symptomatic polyhydramnios is an indication for delivery, and tocolysis is not indicated.
Pregnancy Termination Issues The excessive growth of the head may complicate both forms of pregnancy termination. An intact fetus is not necessary for confirmation of the diagnosis.
Delivery The significant head size reported in these infants may require elective cesarean section for maternal indications, despite the grave prognosis. Attempts at cranial decompression are not likely to be successful. The decision to use a vertical or horizontal incision on the uterus will depend on the fetal lie and the status of the lower uterine segment. Spontaneous rupture of the fetal head has been reported.
Resuscitation Because progressive cranial enlargement is the primary fetal manifestation of an intracranial tumor, operative delivery prior to full gestation may be indicated. Assistance with the onset of respiration will be determined by both the gestational age at delivery and the difficulties encountered intrapartum. The most common intracranial mass presenting in fetal life is a teratoma, which has an almost uniform perinatal mortality. Therefore, if prenatal diagnosis suggests that the mass is a teratoma, it is appropriate for the option of nonintervention to be presented to the parents.
Transport Transfer to a tertiary center with neonatology, pediatric neurosurgery, pediatric neurology, and pediatric oncology subspecialty capabilities is essential.
Testing and Confirmation MRI is used to determine tumor location, morphology, relationship to surrounding structures, and presence of ventricular enlargement. On occasion, Doppler flow studies are useful to define the impact on cerebral vasculature. Biochemical markers obtained from CSF may aid in making a diagnosis. The definitive diagnosis requires tissue histopathologic examination from either tumor resection or biopsy.
Nursery Management The management of a neonate with an intracranial tumor in general involves three issues beyond those that are relative to preterm delivery, if such has been required. These are as follows:
hydrocephalus—if and when to place a shunt
tumor removal—timing, approach, and feasibility of complete resection
adjuvant therapy—chemotherapy, radiotherapy, or both