Spina bifida (SB) is the most common permanently disabling neuro-urological birth defect in the United States, and urological complications of SB are a major source of morbidity. Individuals with SB face a lifelong risk of developing upper tract deterioration, chronic kidney disease and end-stage renal disease due to their neurogenic bladders. ¹ In 2014 the U.S. Centers for Disease Control and Prevention initiated the Urologic Management to Preserve Initial Renal Function Protocol for Young Children with Spina Bifida (UMPIRE) study at multiple centers to define optimal management strategies for newborns and young children with SB (see figure). ² UMPIRE is the first prospective multicenter study to follow a large cohort of newborns with myelomeningocele, a severe form of SB, and monitor their kidney and functional outcomes over time.

We initially examined the baseline imaging characteristics of infants enrolled in UMPIRE. ³ Baseline renal bladder ultrasound (RBUS) data were available for 190 infants, 2 of whom had a solitary kidney. Of these, both had Society of Fetal Ultrasound (SFU) grade 2 hydronephrosis of the solitary kidney. For the 188 infants with both kidneys present, the majority had normal kidneys or low grade hydronephrosis. Specifically, 105 infants (55.9%) had 2 normal kidneys while 41 (21.8%) infants had bilateral SFU grade 1 or greater hydronephrosis. Only 7 (3.7%) infants had SFU grade 3 or 4 dilation in at least 1 kidney. Similarly, 184 infants had a baseline voiding cystourethrogram. Of these, only 28 (15.4%) infants had vesicoureteral reflux (VUR) grade 1 or greater in either kidney and 154 (84.6%) had no VUR whatsoever. Of the 16 infants (8.8%) with bilateral VUR there was 1 infant with grade 5 in both kidneys, 7 infants had grade 3 to 4 in both kidneys, 5 infants had grade 3 to 4 in 1 kidney and 2 infants had grade 1 to 2 in both kidneys. Because of nationwide shortages or institutional policies, results for dimercapto succinic acid renal scan were available for only 66 infants. Of these, only 5 infants (7.6%) had 1 kidney affected by renal scarring, while no infants had bilateral renal scarring. Only 2 infants had VUR into the scarred kidney. In total, we found that infants enrolled in UMPIRE had very low rates of kidney abnormalities at baseline in contrast with previous analyses and frequently cited dogma.

With these data in mind, we then proceeded to examine the frequency of SB surveillance imaging during the first year of life. Newborns enrolled in UMPIRE undergo RBUS every 3 months during the first year of life and annually thereafter. Serial RBUS performed during the first 6 months of life for newborns enrolled in UMPIRE were analyzed. Dilating hydronephrosis (SFU grades 3 to 4) or an increase of 2 SFU grades or greater (eg grade 1 to greater than 3) were deemed positive. In total, 314 patients with RBUS at birth, 3 and 6 months were analyzed, 23 (7.3%) of whom had a total of 49 positive RBUS results. Patients with a negative RBUS at birth had a low probability of positive findings at months 3 (2.0%) and 6 (2.5%). Patients with a positive RBUS at birth had a high probability of remaining positive at months 3 (38.2%) and 6 (43.6%). Taken together these results would seem to suggest that high frequency RBUS screening in infants with SB might be low yield in the setting of a negative initial RBUS, at least in the first 6 months of life.

Figure. UMPIRE study locations.

Urodynamic characteristics of elevated detrusor leak point pressure and detrusor sphincter dyssynergia are associated with renal deterioration in myelomeningocele. Previous analyses have shown that interrater reliability of urodynamics tests is low. ⁴ Therefore, a process to standardize urodynamics interpretation and reconcile discrepancies was developed. In UMPIRE, baseline urodynamics are obtained at 3 months or less and the bladder classified as low risk, intermediate risk or hostile. The multistep standardization of interpretation of urodynamics included review 1) by the original site and 2 of 4 external reviewers (ie 3 pediatric urologists from 3 different clinical sites), 2) if discordant, by 4 external reviewers at an in-person meeting, 3) if classification discordance persisted, by the original site again with reviewer feedback; and 4) if discordance still persisted, by all 9 sites. As of now, 157 baseline urodynamic tests from 9 sites have completed the full review process. Baseline urodynamic tests indicated a hostile bladder in 15% (23/157);,intermediate risk for 61% (96/157), and low risk for 24% (38/157). Initially, reviewers only agreed on 50% (79/157) of the studies. We found variations in interpretation of baseline urodynamics, which could be contributing to decreased interrater reliability. Based on these findings we implemented a standardized review process, which ultimately led to 100% agreement and can inform future urodynamics interpretation.

Guidelines recommend kidney function surveillance for individuals with spina bifida, but there is lack of consensus on surveillance intervals and which specific tests to use, particularly specific for the pediatric population. Most recommend RBUS surveillance, but recommendations for blood testing of kidney function is more variable with RBUS alone often used as a screening tool. In the spina bifida population hydronephrosis has been demonstrated to be of limited use in screening for reduced kidney function. ⁵ Data collected from UMPIRE will help better define specific strategies for kidney surveillance in childhood.

The first infants enrolled in the UMPIRE study will soon be turning 6 years old, and as such the study will soon be examining continence and functional outcomes. However, study investigators remain keenly focused on protecting kidneys from the potential adverse effects of neurogenic bladder in infants with SB, with future studies assessing kidney function and associations with hydronephrosis and urodynamics.