The management of congenital neurogenic bladder (CNB) must strike a balance between appropriate and timely diagnostics and therapeutics in order to prevent significant renal damage without negatively affecting caregivers’ and patients’ quality of life. The development of imaging capability and urodynamic (UDS) assessment over the last 50 years has provided insight into the pathophysiology and pathogenesis of this condition. With the advent of clean intermittent catheterization (CIC) and subsequent progress in pharmacological and surgical management, there has been a noticeable improvement in preserving renal function, continence and independence for patients with CNB. However, there remain several unknowns in the management of CNB. For the purposes of this article, we will examine knowledge gaps in CNB due to spinal dysraphism (also referred to as myelomeningocele and spina bifida), the most common etiology of CNB.

Prenatal testing for open neural tube defects and advances in fetal surgery have allowed repair of spinal cord lesions before birth. Early data from the landmark 2011 Management of Myelomeningocele Study (MOMS) demonstrated the benefits of prenatal (ie in utero) repair in reducing hindbrain herniation, reducing shunting for hydrocephalus and improving ambulation, although there was no decrease in the need for CIC in the first 30 months of life (52% among prenatal vs 66% among postnatal repairs; RR 0.78, 95% CI 0.57–1.07).¹ However, recent urological followup has shown more promising results: at a mean age of 7.4 years among 156 children, prenatal repairs appeared to reduce the use of CIC (62% among prenatal vs 87% among postnatal repairs; p <0.001, RR 0.71, 95% CI 0.58–0.86).² In addition, parents of patients in the prenatal group reported lower rates of anticholinergic use, and parents reported that 18 children (24%) in the prenatal group were able to volitionally void, compared to 3 (4%) in the postnatal group (p<0.001, RR 5.8, 95% CI 1.8–18.7). While these results represent subjective benefits of prenatal closure, there remains the potential for significant bias without demonstration of these benefits on UDS. Additional followup of this cohort is needed to determine the durability and efficacy of prenatal closure at decreasing the morbidity of CNB.

Beyond the prenatal setting, questions remain about the ideal management (expectant vs proactive) of patients with CNB in the early postnatal period. Historically, patients with CNB were observed until renal sequelae or other complications occurred, at which point they received urinary diversion. Expectant management, where the patient is followed with renal ultrasound, interval dimercaptosuccinic acid (DMSA) scans and voiding cystography without baseline urodynamics testing, avoids the use of CIC or pharmacotherapy as long as patients do not demonstrate adverse upper tract or clinical findings. The primary benefit of this approach is to decrease the familial/caregiver burden of CIC. The proactive approach involves scheduled CIC immediately from birth, coupled with early urodynamic assessment and continued CIC when parameters are found to be unfavorable. Early catheterization from birth appears to protect the kidneys.³ Early urodynamics allows for risk stratification and enables early intervention for patients with features that may place them at risk for progressive bladder or renal dysfunction.⁴ To evaluate this proactive approach, the Urologic Management to Preserve Initial Renal Function Protocol for Young Children with Spina Bifida (UMPIRE), a prospective iterative quality improvement protocol, was initiated in 2016.⁵ This study follows a cohort of newborns with spina bifida at 9 U.S. centers and aims to demonstrate that specific scheduled imaging, urodynamics and other measured parameters can maintain normal renal function.

Historically, once patients become refractory to oral anticholinergic therapy and CIC, the only option was augmentation cystoplasty or urinary diversion. While typically successful, this operation is associated with long-term morbidity. To this end, there has been uptake of pharmacological treatments for CNB to preserve renal function and reduce urinary incontinence. Besides muscarinic receptor antagonism, activation of β3 adrenergic receptors on the bladder is the main method of bladder relaxation in humans. Mirabegron, the only β3 agonist in clinical use, is the only agent approved by the U.S. Food and Drug Administration (FDA) for nonneurogenic overactive bladder in adults. However, several recent case series of patients with CNB receiving mirabegron have shown improved urodynamic parameters (increased bladder capacity, decreased end filling detrusor pressure, attenuation of detrusor overactivity) and clinical effects (urinary incontinence resolved in more than 70% of patients).^6,7 With limited side effects compared to anticholinergics, β3 agonists warrant further study in patients with CNB as an adjuvant or alternative therapy. OnabotulinumtoxinA intradetrusor injection has also proved to be an effective treatment in refractory neurogenic bladder. While widely used in the pediatric population, it has yet to obtain FDA approval in CNB. Intradetrusor botulinum toxin injection has been shown to improve compliance and capacity on urodynamic studies in patients with CNB.⁸ Due to its efficacy, intradetrusor botulinum toxin injection could delay or diminish indications to initiate complex reconstructive surgical treatments in some patients. There remain, however, questions regarding its long-term durability and safety in CNB.

Management decisions for patients with CNB are often based on diagnostic tests created and validated in normal people. This can result in significant inaccuracies among people with spina bifida, who may have different body mass composition and are frequently nonambulatory. Chu et al have demonstrated that traditional estimated glomerular filtration rate equations result in substantial variability and overestimation of renal function, particularly among creatinine based equations, in children with spina bifida.⁹ This has important implications because clinicians may limit interventions and changes in management if renal function is overestimated. These authors recommend cystatin C based equations due to their improved accuracy. Besides renal function, recent work by Dudley et al has shown substantial variability in the interpretation of UDS studies among 14 pediatric urologists interpreting the same set of urodynamic tracings.¹⁰ This 7-institution study showed that there was very poor agreement regarding detrusor external sphincter dyssynergia and neurogenic detrusor overactivity, and only moderate agreement with regard to determining the detrusor end filling pressure and if a bladder was safe. This sobering work suggests the need to improve the reliability and reproducibility of UDS studies, which will in turn improve management of children with spina bifida.

There remain several unknowns in the management of CNB throughout the natural history of the condition. With early and long-term data from prospective multicenter cohorts such as MOMS, the National Spina Bifida Patient Registry and UMPIRE, together with continued improvements in disease surveillance and diagnostic testing, we can inform progress in the care of these patients that will allow them to live longer and improve their quality of life.