Rationale for the use of fetal ventriculosubgaleal shunts for the treatment of aqueduct stenosis
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Shohra Qaderi
Abstract
Fetal hydrocephalus causes irreversible neural injury in utero, yet no prenatal therapy currently exists. Postnatal treatments such as ventriculoperitoneal shunts and endoscopic third ventriculostomy with choroid plexus cauterization cannot reverse pre-existing brain injury. We propose that the ventriculosubgaleal shunt (VSGS), widely used as a temporizing measure in severely premature neonates, may offer a feasible and ethically justifiable approach for in utero treatment. VSGS placement avoids the complications of ventriculoamniotic shunts and leverages a closed system that can relieve intracranial pressure and potentially preserve brain tissue integrity. Given its technical simplicity, established safety profile, and alignment with core ethical principles – including maternal autonomy and proportional risk-benefit, we argue for consideration of VSGS as an investigational fetal therapy in selected cases of progressive hydrocephalus. Given its investigational status, implementation should be limited to clinical trials with stringent IRB supervision and ethical safeguards.
Introduction
Infant hydrocephalus is characterized by the abnormal, progressive accumulation of cerebrospinal fluid (CSF) within the brain’s ventricular system [1], 2]. It is a relatively common diagnosis, with a global incidence estimated at 8.5 per 10,000 live births and can develop postnatally secondary to other conditions such as infection and hemorrhage. Higher prevalence rates are observed in Africa, Asia, and South America compared to other continents, with an approximate global prevalence of about 400,000 new cases of infant hydrocephalus annually [3], 4].
The brain normally contains fluid-filled spaces called ventricles. This fluid (cerebrospinal fluid, or CSF) has a normal pattern of production, circulation, and absorption that, when disturbed, can lead to accumulation of CSF within the ventricles, causing them to expand and put pressure on the surrounding brain. This condition, hydrocephalus, can result from congenital anomalies or can develop secondary to such things as inflammation (from infection or hemorrhage), venous dysfunction, or an obstructing mass [5]. Progressive hydrocephalus is sometimes detected prior to birth on fetal imaging. Aqueduct stenosis is among the most common congenital causes of hydrocephalus and can cause progressive ventriculomegaly in the fetus. This can result in excess transependymal movement of CSF into the perventricular white matter, ependymal disruption, mechanical compression and shearing of brain tissue, and decreased cerebral blood flow with tissue hypoxia and ischemia. Unchecked, this can cause significant and irreversible brain injury with negative neurodevelopmental consequences and, sometimes, even death [2].
In utero intervention to arrest progressive ventriculomegaly has the potential to improve outcomes for affected infants. Evidence suggests that a lateral ventricular atrium (LVA) width of ≥15 mm and progressive ventriculomegaly with cortical thinning during pregnancy are associated with poorer neurological outcomes and a higher neonatal mortality rate [6], with a greater likelihood of irreversible brain damage when present beyond 32 weeks [7]. The 10-year survival rate following postnatal surgical treatment is approximately 60 % [8]. Furthermore, severe ventriculomegaly at term can complicate the child’s delivery, with severe macrocephaly necessitating delivery by Caesarean section. It even has implications for its postnatal treatment. Severe ventriculomegaly increases the complication risks for VP shunt placement. It also decreases the chance of success with the alternative treatment, endoscopic third ventriculostomy combined with choroid plexus cauterization (ETV/CPC), [9]. Thus, early intervention to prevent severe fetal ventriculomegaly offers potential benefits for both mother and child.
Unfortunately, there is no currently available treatment for fetal hydrocephalus [10], 11]. Postnatal treatment options include ventriculoperitoneal (VP) shunt placement, ventriculosubgaleal shunt (VSGS) placement as a temporary treatment in the prematurely born [12], [13], [14], [15], [16], [17] and endoscopic third ventriculostomy with choroid plexus cauterization (ETV/CPC), [18]. While these treatments stop the progressive hydrocephalus and relieve the pressure, they do not impact any pre-existing irreversible brain injury.
This paper examines the clinical and ethical implications of in utero intervention, presenting the VSGS as a potential option for prenatal treatment in cases of severe, progressive ventriculomegaly specifically secondary to isolated congenital aqueduct stenosis.
Rationale for treating fetal hydrocephalus secondary to isolated aqueduct stenosis
The underlying cause of fetal hydrocephalus critically influences prognosis and treatment strategy. Aqueduct stenosis – specifically when unassociated with other obvious congenital brain anomalies – is a logical target for prenatal intervention because the progressive ventriculomegaly is itself the primary agent of brain injury [19], [20], [21]. In contrast, hydrocephalus due to genetic syndromes, severe CNS malformations (e.g., holoprosencephaly), or congenital infections (e.g., CMV, toxoplasmosis) or intracerebral hemorrhage is predictably associated with primary brain dysfunction or injury separate from that caused by the hydrocephalus itself, and therefore less likely to substantially benefit from in utero intervention. Etiology-specific assessment – including genetic testing, TORCH screening, and fetal MRI – would be essential for appropriate patient selection [22], 23].
Rationale for treating fetal hydrocephalus by VSGS implantation
For severely premature infants, the postnatal development of hydrocephalus secondary to intraventricular hemorrhage is common in developed countries [24]. Definitive treatment, such as placement of a VP shunt or endoscopic intervention, is often infeasible due to the infant’s small size and weight [14], 25], 26]. In these cases, a long-standing and commonly used temporizing measure has been the placement of a VSGS, which effectively controls hydrocephalus until the child reaches a greater weight and can tolerate more definitive intervention. Given the effectiveness of this postpartum intervention in severely premature infants it could logically be an effective treatment for eligible fetal patients prior to birth.
Prior attempts to treat fetal hydrocephalus in utero have included placement of a ventriculo-amniotic shunt tube [27], [28], [29], [30]. This exposes the tube to the risks of migration or even removal by the fetus itself as well as direct exposure of the ventricle CSF to amniotic fluid. Consequently, amniotic fluid reflux could occur and potentially cause ventriculitis [27], 31], 32]. The VSGS is a closed system, thus avoiding this. Ventricular CSF decompresses into and accumulates within a subgaleal pocket. This may act by the absorption of CSF into the scalp vasculature or lymph system, or by acting to directly relieve the intraventricular pressure or dampen the intraventricular pressure waves [16], 25]. In some cases, the subgaleal pocket fills with CSF under pressure to the extent that the pocket needs to be percutaneously decompressed by removing CSF [33]. This could also be done in utero under ultrasound guidance if necessary.
Fetal endoscopic third ventriculostomy (ETV) has been reported [34]. But ETV is not only technically challenging, and thus risky, but the failure rate is unacceptably high. Peralta and co-authors reported a series in which the failure rate was 80 % [35]. ETV alone (without choroid plexus cauterization) even in a full-term neonate with aqueduct stenosis has a predicted failure rate of 60 %, according to the ETV Success Score [9].
Of all available options to treat severe fetal hydrocephalus, placement of a VSGS is arguably the most plausible in terms of technical ease, safety, and likelihood of success in protecting the fetal brain from injury during this crucial time in brain development. Our premise is that a widely used procedure, which has been successfully performed on premature infants as small as 750 g and as young as 24 weeks of gestation postnatally, can be employed prior to birth without undue risk to the fetal or pregnant patient compared to other fetal interventions [14], 25]. Given the severity of the complications of the untreated condition in terms of both morbidity and mortality, the anticipated relative risk-to-benefit ratio makes a sound clinical and ethical case for conducting a trial of fetal VSGS implantation in cases of severe, progressive ventriculomegaly from isolated congenital aqueduct stenosis.
Ethical considerations
The introduction of this, or any other fetal intervention raises important ethical considerations. These primarily revolve around respect for maternal autonomy, informed consent, risk-benefit assessment to the fetal patient, experimental justification, and equitable access to fetal interventions. The use of fetal surgery or interventions to mitigate neurological damage must carefully balance beneficence and autonomy-based obligations to the pregnant patient and beneficence-based obligations to the fetal patient [36].
Fetal intervention introduces unique challenges as the pregnant patient is the sole decision-maker on behalf of the fetus. It also raises the ethical question of whether the pregnant patient should be exposed to the potential surgical risks of a procedure from which she may not, herself, benefit. The decision to proceed must consider whether the risks to the pregnant patient (infection, preterm labor, uterine rupture, and the possible need for cesarean delivery in subsequent pregnancies) are sufficiently proportionate to the anticipated benefits for the fetus (preventing irreversible brain damage to mitigate significant morbidity or mortality) [37]. Furthermore, unlike fetal myelomeningocele repair, which now has a well-documented history of improved postnatal outcomes, the putative benefit of fetal hydrocephalus treatment is as yet unproven [38].
Given the experimental nature of in utero VSGS placement, ensuring properly informed consent is paramount. Pregnant patients may feel pressured into accepting the intervention due to strong emotional attachments to the fetus, pressure from healthcare providers, or fear of guilt if they decline the procedure. Ensuring that patients fully understand the uncertainties of any meaningful benefit as well as the known potential risks to themselves as well as the child is crucial in maintaining ethical integrity in decision-making.
Additionally, the equity of in utero interventions must be addressed. Access to fetal surgery is limited to highly specialized centers, potentially exacerbating disparities in healthcare access. Pregnant patients from lower socioeconomic backgrounds, inadequate insurance coverage, rural areas, or countries with limited fetal surgery expertise may lack access to innovative treatments, raising concerns about whether such interventions will only benefit a privileged subset of patients. And, although the cost of neurocognitive disability to patients, their families and society is substantial, the cost of fetal interventions is also significant, and healthcare systems should carefully evaluate whether funding an experimental procedure is ethically justified prior to data that demonstrate its safety and efficacy.
To ensure ethical integrity, fetal interventions should adhere to the guidelines set forth by the International Fetal Medicine and Surgery Society (IFMSS), which emphasize strong institutional oversight, multidisciplinary involvement, patient advocacy, and regulatory compliance. Moving forward, ethical and clinical support for using the VSGS to treat fetal hydrocephalus must be investigated by rigorous research and a commitment to upholding the principles of beneficence, non-maleficence, and autonomy [39], 40].
Conclusions
Severe progressive fetal ventriculomegaly causes irreversible brain damage which postnatal therapies cannot address. We have proposed fetal VSGS placement to mitigate brain injury and improve outcomes for these infants. Given its feasibility and alignment with ethical principles, we advocate for its application in specialized centers, as an investigational measure in cases of isolated aqueduct stenosis. Further investigation into its safety and efficacy under strict investigational review board (IRB) supervision is warranted.
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Research ethics: Not applicable.
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Informed consent: Not applicable.
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Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
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Use of Large Language Models, AI and Machine Learning Tools: None declared.
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Conflict of interest: The authors state no conflict of interest.
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Research funding: None declared.
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Data availability: Not applicable.
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